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Sample records for proximal nhe3 promoter

  1. 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.

  2. 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

  3. Selective knockdown of AT1 receptors by RNA interference inhibits Val5-ANG II endocytosis and NHE-3 expression in immortalized rabbit proximal tubule cells

    PubMed Central

    Li, Xiao C.; Zhuo, Jia L.

    2008-01-01

    Receptor-mediated endocytosis of extracellular ANG II has been suggested to play an important role in the regulation of proximal tubule cell (PTC) function. Using immortalized rabbit PTCs as an in vitro cell culture model, we tested the hypothesis that extracellular ANG II is taken up by PTCs through angiotensin type 1 receptor (AT1; or AT1a) receptor-mediated endocytosis and that inhibition of ANG II endocytosis using a selective AT1 receptor small-interfering RNA (siRNA; AT1R siRNA) or endocytotic inhibitors exerts a physiological effect on total and apical sodium and hydrogen exchanger isoform 3 (NHE-3) protein abundance. Western blots and live cell imaging with FITC-labeled ANG II confirmed that transfection of PTCs with a human specific AT1R siRNA for 48 h selectively knocked down AT1 receptor protein by 76 ± 5% (P < 0.01), whereas transfection with a scrambled siRNA had little effect. In nontransfected PTCs, exposure to extracellular ANG II (1 nM) for 60 min at 37°C increased intracellular ANG II accumulation by 67% (control: 566 ± 55 vs. ANG II: 943 ± 160 pg/mg protein, P < 0.05) and induced mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (163 ± 15% of control, P < 0.01). AT1R siRNA reduced ANG II endocytosis to a level similar to losartan, which blocks cell surface AT1 receptors (557 ± 37 pg/mg protein, P < 0.05 vs. ANG II), or to colchicine, which disrupts cytoskeleton microtubules (613 ± 12 pg/mg protein, P < 0.05 vs. ANG II). AT1R siRNA, losartan, and colchicine all attenuated ANG II-induced ERK1/2 activation and total cell lysate and apical membrane NHE-3 abundance. The scrambled siRNA had no effect on ANG II endocytosis, ERK1/2 activation, or NHE-3 expression. These results suggest that AT1 receptor-mediated endocytosis of extracellular ANG II may regulate proximal tubule sodium transport by increasing total and apical NHE-3 proteins. PMID:17428839

  4. 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.

  5. Renal NHE expression and activity in neonatal NHE3- and NHE8-null mice.

    PubMed

    Pirojsakul, Kwanchai; Gattineni, Jyothsna; Dwarakanath, Vangipuram; Baum, Michel

    2015-01-01

    Na(+)/H(+) exchanger (NHE)3 is the predominant NHE on the brush-border membrane of the proximal tubule in adult animals. NHE8 has been localized to the brush-border membrane of proximal tubules and is more highly expressed in neonates than in adult animals. However, the relative role of NHE8 in neonatal renal acidification is unclear. The present study examined if there was a compensatory increase in NHE3 in NHE8-null neonatal mice and whether there was a compensatory increase in NHE8 in NHE3-null neonatal mice. In addition, we examined whether wild-type, NHE3-null, and NHE8-null mice had an increase in NHE activity in response to metabolic acidosis. We found that at baseline, there was comparable renal NHE3 mRNA, total protein, and brush-border membrane protein abundance as in neonatal control and NHE8-null mice. There was comparable renal NHE8 mRNA, total protein, and brush-border membrane protein abundance in NHE3-null neonatal and control mice. Both NHE3- and NHE8-null mice had a comparable but lower rate of NHE activity than control mice. We next imposed metabolic acidosis in wild-type, NHE3-null, and NHE8-null mice. Acidemic NHE8-null mice had an increase in brush-border membrane vesicle NHE3 protein abundance and NHE activity compared with vehicle-treated mice. Likewise, NHE3-null mice had an increase in NHE8 brush-border membrane protein abundance and NHE activity in response to metabolic acidosis. In conclusion, both NHE3 and NHE8 likely play a role in neonatal acidification.

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

    PubMed

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

    2015-06-15

    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.

  7. Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II.

    PubMed

    He, Peijian; Klein, Janet; Yun, C Chris

    2010-09-01

    Angiotensin II (ANG II) stimulates renal tubular reabsorption of NaCl by targeting Na(+)/H(+) exchanger NHE3. We have shown previously that inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) plays a critical role in stimulation of NHE3 in response to elevated intracellular Ca(2+) concentration ([Ca(2+)](i)). In this study, we investigated the role of IRBIT in mediating NHE3 activation by ANG II. IRBIT is abundantly expressed in the proximal tubules where NHE3 is located. ANG II at physiological concentrations stimulates NHE3 transport activity in a model proximal tubule cell line. ANG II-induced activation of NHE3 was abrogated by knockdown of IRBIT, whereas overexpression of IRBIT enhanced the effect of ANG II on NHE3. ANG II transiently increased binding of IRBIT to NHE3 at 5 min but became dissociated by 45 min. In comparison, it took at least 15 min of ANG II treatment for an increase in NHE3 activity and NHE3 surface expression. The stimulation of NHE3 by ANG II was dependent on changes in [Ca(2+)](i) and Ca(2+)/calmodulin-dependent protein kinases II. Inhibition of CaMKII completely blocked the ANG II-induced binding of IRBIT to NHE3 and the increase in NHE3 surface abundance. Several serine residues of IRBIT are thought to be important for IRBIT binding. Mutations of Ser-68, Ser-71, and Ser-74 of IRBIT decreased binding of IRBIT to NHE3 and its effect on NHE3 activity. In conclusion, our current findings demonstrate that IRBIT is critically involved in mediating activation of NHE3 by ANG II via a Ca(2+)/calmodulin-dependent protein kinases II-dependent pathway.

  8. 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.

  9. Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site.

    PubMed

    Chen, Tiane; Kocinsky, Hetal S; Cha, Boyoung; Murtazina, Rakhilya; Yang, Jianbo; Tse, C Ming; Singh, Varsha; Cole, Robert; Aronson, Peter S; de Jonge, Hugo; Sarker, Rafiquel; Donowitz, Mark

    2015-01-23

    The epithelial brush-border Na(+)/H(+) exchanger NHE3 is acutely inhibited by cGKII/cGMP, but how cGKII inhibits NHE3 is unknown. This study tested the hypothesis that cGMP inhibits NHE3 by phosphorylating it and altering its membrane trafficking. Studies were carried out in PS120/NHERF2 and in Caco-2/Bbe cells overexpressing HA-NHE3 and cGKII, and in mouse ileum. NHE3 activity was measured with 2',7'-bis(carboxyethyl)-S-(and 6)carboxyfluorescein acetoxy methylester/fluorometry. Surface NHE3 was determined by cell surface biotinylation. Identification of NHE3 phosphorylation sites was by iTRAQ/LC-MS/MS with TiO2 enrichment and immunoblotting with specific anti-phospho-NHE3 antibodies. cGMP/cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3. cGMP/cGKII increased NHE3 phosphorylation at three sites (rabbit Ser(554), Ser(607), and Ser(663), equivalent to mouse Ser(552), Ser(605), and Ser(659)), all of which had to be present at the same time for cGMP to inhibit NHE3. NHE3-Ser(663) phosphorylation was not necessary for cAMP inhibition of NHE3. Dexamethasone (4 h) stimulated wild type NHE3 activity and increased surface expression but failed to stimulate NHE3 activity or increase surface expression when NHE3 was mutated to either S663A or S663D. We conclude that 1) cGMP inhibition of NHE3 is associated with phosphorylation of NHE3 at Ser(554), Ser(607), and Ser(663), all of which are necessary for cGMP/cGKII to inhibit NHE3. 2) Dexamethasone stimulates NHE3 by phosphorylation of a single site, Ser(663). The requirement for three phosphorylation sites in NHE3 for cGKII inhibition, and for phosphorylation of one of these sites for dexamethasone stimulation of NHE3, is a unique example of regulation by phosphorylation.

  10. 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

  11. Myosin VI mediates the movement of NHE3 down the microvillus in intestinal epithelial cells

    PubMed Central

    Chen, Tiane; Hubbard, Ann; Murtazina, Rakhilya; Price, Jennifer; Yang, Jianbo; Cha, Boyoung; Sarker, Rafiquel; Donowitz, Mark

    2014-01-01

    ABSTRACT The intestinal brush border Na+/H+ exchanger NHE3 is tightly regulated through changes in its endocytosis and exocytosis. Myosin VI, a minus-end-directed actin motor, has been implicated in endocytosis at the inter-microvillar cleft and during vesicle remodeling in the terminal web. Here, we asked whether myosin VI also regulates NHE3 movement down the microvillus. The basal NHE3 activity and its surface amount, determined by fluorometry of the ratiometric pH indicator BCECF and biotinylation assays, respectively, were increased in myosin-VI-knockdown (KD) Caco-2/Bbe cells. Carbachol (CCH) and forskolin (FSK) stimulated NHE3 endocytosis in control but not in myosin VI KD cells. Importantly, immunoelectron microscopy results showed that NHE3 was preferentially localized in the basal half of control microvilli but in the distal half in myosin VI KD cells. Treatment with dynasore duplicated some aspects of myosin VI KD: it increased basal surface NHE3 activity and prevented FSK-induced NHE3 endocytosis. However, NHE3 had an intermediate distribution along the microvillus (between that in myosin VI KD and untreated cells) in dynasore-treated cells. We conclude that myosin VI is required for basal and stimulated endocytosis of NHE3 in intestinal cells, and suggest that myosin VI also moves NHE3 down the microvillus. PMID:24928903

  12. Cyclic AMP-mediated endocytosis of intestinal epithelial NHE3 requires binding to synaptotagmin 1

    PubMed Central

    Musch, Mark W.; Arvans, Donna L.; Wang, Yunwei; Nakagawa, Yasushi; Solomaha, Elena

    2010-01-01

    The apical membrane Na+-H+ exchanger (NHE)3 is regulated by cAMP-dependent phosphorylation, which inhibits its activity through membrane endocytosis. The clathrin complex adaptor protein synaptotagmin 1 (Syt 1) appears to be essential to this process, but little is known about its expression in intestinal epithelial cells or interaction with NHE3. The intestinal epithelial expression and apical location of Syt 1 were determined by Syt 1 mRNA profiling and immunolocalization. Tandem mass spectrometry was used for protein identification. Bis(sulfosuccinimidyl) suberate (BS3) cross linking suggested that NHE3 and Syt 1 were in a membrane complex following cAMP stimulation of Caco2BBE (Brush Border Expressions) cells. To investigate the regulation of NHE3 appearance in a Syt 1-containing membrane compartment, doxycycline-inducible hemaglutinin (HA)-tagged NHE3 was expressed in Caco2BBE cells. HA-NHE3 correctly targeted to the apical membrane, where, upon cAMP stimulation, it was internalized with a Syt 1-containing compartment. Site-directed mutagenesis of NHE3 showed that serine 605 (S605) was pivotal to NHE3 and Syt 1 association and internalization. Direct Syt 1 interaction with NHE3 was suggested by fluorescence resonance energy transfer (FRET) analysis. The physiological role of S552 was less clear. By FRET, this serine residue appeared to be involved in cAMP-induced Syt 1 binding of NHE3. However, when HA-tagged NHE3 S552A was expressed in Caco2 cells, the mutated construct was not inserted into the apical membrane. We conclude that intestinal epithelial Syt 1 plays an important role in cAMP-stimulated endocytosis of apical NHE3 through cAMP-dependent phosphorylation of S605 that is required for NHE3 and Syt 1 association. PMID:19926819

  13. 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

  14. 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

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

    2015-11-01

    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.

  15. IRBIT, Inositol 1,4,5-Triphosphate (IP3) Receptor-binding Protein Released with IP3, Binds Na+/H+ Exchanger NHE3 and Activates NHE3 Activity in Response to Calcium*

    PubMed Central

    He, Peijian; Zhang, Huanchun; Yun, C. Chris

    2008-01-01

    Calcium (Ca2+) is a highly versatile second messenger that regulates various cellular processes. Previous studies showed that elevation of intracellular Ca2+ regulates the activity of Na+/H+ exchanger 3 (NHE3). However, the effect of Ca2+-dependent signaling on NHE3 activity varies depending on cell types. In this study, we report the identification of IP3 receptor-binding protein released with IP3 (IRBIT) as a NHE3 interacting protein and its role in regulation of NHE3 activity. IRBIT bound to the carboxyl-terminal domain of NHE3, which is necessary for acute regulation of NHE3. Ectopic expression of IRBIT resulted in Ca2+-dependent activation of NHE3 activity, whereas silencing of endogenous IRBIT resulted in inhibition of NHE3 activity. Ca2+-dependent stimulation of NHE3 activity was dependent on the binding of IRBIT to NHE3. Previously Ca2+-dependent inhibition of NHE3 was demonstrated in the presence of NHERF2. Co-expression of IRBIT was able to reverse the NHERF2-dependent inhibition of NHE3. We also showed that IRBIT-dependent activation of NHE3 involves exocytic trafficking of NHE3 to the plasma membrane and this activation was blocked by inhibition of calmodulin (CaM) or CaM-dependent kinase II. These results suggest that the overall effect of Ca2+ on NHE3 activity is balanced by IRBIT-dependent activation and NHERF2-dependent inhibition. PMID:18829453

  16. 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.

  17. Elevated calcium acutely regulates dynamic interactions of NHERF2 and NHE3 proteins in opossum kidney (OK) cell microvilli.

    PubMed

    Zhu, Xinjun; Cha, Boyoung; Zachos, Nicholas C; Sarker, Rafiquel; Chakraborty, Molee; Chen, Tian-E; Kovbasnjuk, Olga; Donowitz, Mark

    2011-10-01

    The brush border (BB) Na(+)/H(+) exchanger NHE3 is rapidly activated or inhibited by changes in trafficking, which mimics renal and intestinal physiology. However, there is a paradox in that NHE3 has limited mobility in the BB due to its binding to the multi-PDZ domain containing the NHERF family. To allow increased endocytosis, as occurs with elevated intracellular Ca(2+), we hypothesized that NHE3 had to be, at least transiently, released from the BB cytoskeleton. Because NHERF1 and -2 are localized at the BB, where they bind NHE3 as well as the cytoskeleton, we tested whether either or both might dynamically interact with NHE3 as part of Ca(2+) signaling. We employed FRET to study close association of NHE3 and these NHERFs and fluorescence recovery after photobleaching to monitor NHE3 mobility in the apical domain in polarized opossum kidney cells. Under basal conditions, NHERF2 and NHE3 exhibited robust FRET signaling. Within 1 min of A23187 (0.5 μm) exposure, the NHERF2-NHE3 FRET signal was abolished, and BB NHE3 mobility was transiently increased. The dynamics in FRET signal and NHE3 mobility correlated well with a change in co-precipitation of NHE3 and NHERF2 but not NHERF1. We conclude the following. 1) Under basal conditions, NHE3 closely associates with NHERF2 in opossum kidney cell microvilli. 2) Within 1 min of elevated Ca(2+), the close association of NHE3-NHERF2 is abolished but is re-established in ∼60 min. 3) The change in NHE3-NHERF2 association is accompanied by an increased BB mobile fraction of NHE3, which contributes to inhibition of NHE3 transport activity via increased endocytosis.

  18. SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells.

    PubMed

    Musch, M W; Bookstein, C; Xie, Y; Sellin, J H; Chang, E B

    2001-04-01

    Short-chain fatty acids (SCFA), produced by colonic bacterial flora fermentation of dietary carbohydrates, promote colonic Na absorption through mechanisms not well understood. We hypothesized that SCFA promote increased expression of apical membrane Na/H exchange (NHE), serving as luminal physiological cues for regulating colonic Na absorptive capacity. Studies were performed in human colonic C2/bbe (C2) monolayers and in vivo. In C2 cells exposed to butyrate, acetate, proprionate, or the poorly metabolized SCFA isobutyrate, apical membrane NHE3 activity and protein expression increased in a time- and concentration-dependent manner, whereas no changes were observed for NHE2. In contrast, no significant changes in brush-border hydrolase or villin expression were noted. Analogous to the in vitro findings, rats fed the soluble fiber pectin exhibited a time-dependent increase in colonic NHE3, but not NHE2, protein, mRNA, and brush-border activity. These changes were region-specific, as no changes were observed in the ileum. We conclude that luminal SCFA are important physiological cues for regulating colonic Na absorptive function, allowing the colon to adapt to chronic changes in dietary carbohydrate and Na loads.

  19. Ezrin regulates NHE3 translocation and activation after Na+-glucose cotransport

    PubMed Central

    Zhao, Huiren; Shiue, Harn; Palkon, Sara; Wang, Yingmin; Cullinan, Patrick; Burkhardt, Janis K.; Musch, Mark W.; Chang, Eugene B.; Turner, Jerrold R.

    2004-01-01

    Initiation of Na+-glucose cotransport in intestinal epithelial cells leads to activation of the apical Na+-H+ exchanger NHE3 and subsequent increases in cytoplasmic pH (pHi). This process requires activation of p38 mitogen-activated protein (MAP) kinase, but additional signaling intermediates have not been identified. One candidate is the cytoskeletal linker protein ezrin, which interacts with NHE3 via specific regulatory proteins. The data show that initiation of Na+-glucose cotransport resulted in rapid increases in both apical membrane-associated NHE3 and cytoskeletal-associated ezrin and occurred in parallel with ezrin phosphorylation at threonine 567. Phosphorylation at this site is known to activate ezrin and increase its association with actin. Consistent with a central role for ezrin activation in this NHE3 regulation, an N-terminal dominant negative ezrin construct inhibited both NHE3 recruitment and pHi increases after Na+-glucose cotransport. Ezrin phosphorylation occurred in parallel with p38 MAP kinase activation, and the latter proceeded normally in cells expressing dominant negative ezrin. In contrast, inhibition of p38 MAP kinase prevented increases in ezrin phosphorylation after initiation of Na+-glucose cotransport. Thus, ezrin phosphorylation after Na+-glucose cotransport requires p38 MAP kinase activity, but p38 MAP kinase activation does not require ezrin function. These data describe a specific role for ezrin in the coordinate regulation of Na+-glucose cotransport and Na+-H+ exchange. Intact ezrin function is necessary for NHE3 recruitment to the apical membrane and NHE3-dependent pHi increases triggered by Na+-glucose cotransport. The data also define a pathway of p38 MAP kinase-dependent ezrin activation. PMID:15197272

  20. Evidence for NHE3-mediated Na transport in sheep and bovine forestomach.

    PubMed

    Rabbani, Imtiaz; Siegling-Vlitakis, Christiane; Noci, Bardhyl; Martens, Holger

    2011-08-01

    Na absorption across the cornified, multilayered, and squamous rumen epithelium is mediated by electrogenic amiloride-insensitive transport and by electroneutral Na transport. High concentrations of amiloride (>100 μM) inhibit Na transport, indicating Na(+)/H(+) exchange (NHE) activity. The underlying NHE isoform for transepithelial Na absorption was characterized by mucosal application of the specific inhibitor HOE642 for NHE1 and S3226 for NHE3 in Ussing chamber studies with isolated epithelia from bovine and sheep forestomach. S3226 (1 μM; NHE3 inhibitor) abolished electroneutral Na transport under control conditions and also the short-chain fatty acid-induced increase of Na transport via NHE. However, HOE642 (30 μM; NHE1 inhibitor) did not change Na transport rates. NHE3 was immunohistochemically localized in membranes of the upper layers toward the lumen. Expression of NHE1 and NHE3 has been previously demonstrated by RT-PCR, and earlier experiments with isolated rumen epithelial cells have shown the activity of both NHE1 and NHE3. Obviously, both isoforms are involved in the regulation of intracellular pH, pH(i). However, transepithelial Na transport is only mediated by apical uptake via NHE3 in connection with extrusion of Na by the basolaterally located Na-K-ATPase. The missing involvement of NHE1 in transepithelial Na transport suggests that the proposed "job sharing" in epithelia between these two isoforms probably also applies to forestomach epithelia: NHE3 for transepithelial transport and NHE1 for, among others, pH(i) and volume regulation. PMID:21613579

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

    PubMed

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

    2013-11-15

    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.

  2. Chronic noradrenaline increases renal expression of NHE-3, NBC-1, BSC-1 and aquaporin-2.

    PubMed

    Sonalker, Prajakta A; Tofovic, Stevan P; Bastacky, Sheldon I; Jackson, Edwin K

    2008-05-01

    1. Because chronic activation of the renal sympathetic nervous system promotes sodium and water retention, it is conceivable that long-term exposure of the kidney to the sympathetic neurotransmitter noradrenaline upregulates the expression of key renal epithelial transport systems. 2. To test this hypothesis, we used immunoblotting of renal cortical and medullary tissue to investigate the abundance of major transport systems expressed along the renal tubule in response to long-term (15 days) infusions of noradrenaline (600 ng/min) in rats. 3. Mean arterial blood pressure and heart rate were significantly elevated in rats receiving chronic infusions of noradrenaline (128 +/- 10 mmHg and 492 +/- 16 b.p.m., respectively) compared with animals treated with saline only (89 +/- 3 mmHg and 376 +/- 14 b.p.m., respectively). 4. Chronic infusions of noradrenaline also increased the protein abundance of the cortical Na(+)/H(+) exchanger isoform 3 (NHE-3; 2.5-fold; P = 0.0142), the cortical sodium-bicarbonate cotransporter NBC-1 (2.5-fold; P = 0.0067), the bumetanide-sensitive sodium-potassium-chloride cotransporter BSC-1/NKCC2 in the inner stripe of outer medulla (threefold; P = 0.0020) and aquaporin-2 in the inner medulla (twofold; P = 0.0039). 5. In contrast, noradrenaline did not significantly affect expression of the thiazide-sensitive Na(+)-Cl(-) cotransporter in the cortex, Na(+)/K(+)-ATPase-alpha(1) in the cortex and inner stripe of the outer or inner medulla, the inwardly rectifying K(+) channel (ROMK-1) in the inner stripe of the outer medulla or aquaporin-1 in the cortex or inner medulla. Noradrenaline did significantly, but modestly (less than twofold), increase aquaporin-1 in the inner stripe of the outer medulla. 6. We conclude that noradrenaline-induced increases in the expression of NHE-3, NBC-1, BSC-1 and aquaporin-2 are likely to play an important role in the regulation of salt and water transport by noradrenaline in the kidney and may explain, at least in

  3. AKT and GSK-3 Are Necessary for Direct Ezrin Binding to NHE3 as Part of a C-terminal Stimulatory Complex

    PubMed Central

    Singh, Varsha; Lin, Rong; Yang, Jianbo; Cha, Boyoung; Sarker, Rafiquel; Tse, Chung Ming; Donowitz, Mark

    2014-01-01

    Basal activity of the BB Na+/H+ exchanger NHE3 requires multiprotein complexes that form on its C terminus. One complex stimulates basal NHE3 activity and contains ezrin and phosphoinositides as major components; how it stimulates NHE3 activity is not known. This study tested the hypothesis that ezrin dynamically associates with this complex, which sets ezrin binding. NHE3 activity was reduced by an Akti. This effect was eliminated if ezrin binding to NHE3 was inhibited by a point mutant. Recombinant AKT phosphorylated NHE3 C terminus in the domain ezrin directly binds. This domain (amino acids 475–589) is predicted to be α-helical and contains a conserved cluster of three serines (Ser515, Ser522, and Ser526). Point mutations of two of these (S515A, S515D, or S526A) reduced basal NHE3 activity and surface expression and had no Akti inhibition. S526D had NHE3 activity equal to wild type with normal Akti inhibition. Ezrin binding to NHE3 was regulated by Akt, being eliminated by Akti. NHE3-S515A and -S526D did not bind ezrin; NHE3-S515D had reduced ezrin binding; NHE3-S526D bound ezrin normally. NHE3-Ser526 is predicted to be a GSK-3 kinase phosphorylation site. A GSK-3 inhibitor reduced basal NHE3 activity as well as ezrin-NHE3 binding, and this effect was eliminated in NHE3-S526A and -S526D mutants. The conclusions were: 1) NHE3 basal activity is regulated by a signaling complex that is controlled by sequential effects of two kinases, Akt and GSK-3, which act on a Ser cluster in the same NHE3 C-terminal domain that binds ezrin; and 2) these kinases regulate the dynamic association of ezrin with NHE3 to affect basal NHE3 activity. PMID:24398676

  4. Akt2 Phosphorylates Ezrin to Trigger NHE3 Translocation and Activation*

    PubMed Central

    Shiue, Harn; Musch, Mark W.; Wang, Yingmin; Chang, Eugene B.; Turner, Jerrold R.

    2005-01-01

    Initiation of Na+-glucose cotransport in intestinal absorptive epithelia causes NHE3 to be translocated to the apical plasma membrane, leading to cytoplasmic alkalinization. We reported recently that this NHE3 translocation requires ezrin phosphorylation. However, the kinase that phosphorylates ezrin in this process has not been identified. Because Akt has also been implicated in NHE3 translocation, we investigated the hypothesis that Akt phosphorylates ezrin. After initiation of Na+-glucose cotransport, Akt is activated with kinetics that parallel those of ezrin phosphorylation. Inhibition of p38 MAP kinase, which blocks ezrin phosphorylation, also prevents Akt activation. Purified Akt directly phosphorylates recombinant ezrin at threonine 567 in vitro in an ATP-dependent manner. This in vitro phosphorylation can be prevented by Akt inhibitors. In intact cells, inhibition of either phosphoinositide 3-kinase, an upstream regulator of Akt, or inhibition of Akt itself using inhibitors validated in vitro prevents ezrin phosphorylation after initiation of Na+-glucose cotransport. Specific small interfering RNA knockdown of Akt2 prevented ezrin phosphorylation in intact cells. Pharmacological Akt inhibition or Akt2 knockdown also prevented NHE3 translocation and activation after initiation of Na+-glucose cotransport, confirming the functional role of Akt2. These studies therefore identify Akt2 as a critical kinase that regulates ezrin phosphorylation and activation. This Akt2-dependent ezrin phosphorylation leads to NHE3 translocation and activation. PMID:15531580

  5. Akt2 phosphorylates ezrin to trigger NHE3 translocation and activation.

    PubMed

    Shiue, Harn; Musch, Mark W; Wang, Yingmin; Chang, Eugene B; Turner, Jerrold R

    2005-01-14

    Initiation of Na(+)-glucose cotransport in intestinal absorptive epithelia causes NHE3 to be translocated to the apical plasma membrane, leading to cytoplasmic alkalinization. We reported recently that this NHE3 translocation requires ezrin phosphorylation. However, the kinase that phosphorylates ezrin in this process has not been identified. Because Akt has also been implicated in NHE3 translocation, we investigated the hypothesis that Akt phosphorylates ezrin. After initiation of Na(+)-glucose cotransport, Akt is activated with kinetics that parallel those of ezrin phosphorylation. Inhibition of p38 MAP kinase, which blocks ezrin phosphorylation, also prevents Akt activation. Purified Akt directly phosphorylates recombinant ezrin at threonine 567 in vitro in an ATP-dependent manner. This in vitro phosphorylation can be prevented by Akt inhibitors. In intact cells, inhibition of either phosphoinositide 3-kinase, an upstream regulator of Akt, or inhibition of Akt itself using inhibitors validated in vitro prevents ezrin phosphorylation after initiation of Na(+)-glucose cotransport. Specific small interfering RNA knockdown of Akt2 prevented ezrin phosphorylation in intact cells. Pharmacological Akt inhibition or Akt2 knockdown also prevented NHE3 translocation and activation after initiation of Na(+)-glucose cotransport, confirming the functional role of Akt2. These studies therefore identify Akt2 as a critical kinase that regulates ezrin phosphorylation and activation. This Akt2-dependent ezrin phosphorylation leads to NHE3 translocation and activation.

  6. PLC-γ directly binds activated c-Src, which is necessary for carbachol-mediated inhibition of NHE3 activity in Caco-2/BBe cells.

    PubMed

    Zachos, Nicholas C; Lee, Luke J; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark

    2013-08-01

    Elevated levels of intracellular Ca(2+) ([Ca(2+)]i) inhibit Na(+)/H(+) exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca(2+)]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca(2+) signaling proteins necessary for regulation of NHE3 activity. [Ca(2+)]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca(2+)]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y(416) phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca(2+)]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca(2+)]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca(2+)]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3.

  7. Variation in the ADH1B proximal promoter affects expression.

    PubMed

    Pochareddy, Sirisha; Edenberg, Howard J

    2011-05-30

    The primary pathway of metabolism of dietary alcohol is via its oxidation in liver by alcohol dehydrogenases (ADH). Differences in the ADH enzyme activity or levels of enzyme present could affect the risk for alcoholism. Regulatory variations have been shown to affect the promoter activity and thereby affect the risk for alcoholism. In this study the functional effects of the two SNPs (rs1159918 and rs1229982) in the proximal promoter region of ADH1B that were associated with alcoholism were explored. We examined the effects of five naturally occurring haplotypes on the promoter activity. We observed that a C to A change at rs1229982 increased promoter activity 1.4-fold.

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

    PubMed

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

    2015-03-31

    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.

  9. 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

  10. Genome-wide proximal promoter analysis and interpretation.

    PubMed

    Guruceaga, Elizabeth; Segura, Victor; Corrales, Fernando J; Rubio, Angel

    2010-01-01

    High-throughput gene expression technologies based on DNA microarrays allow the examination of biological systems. However, the interpretation of the complex molecular descriptions generated by these approaches is still challenging. The development of new methodologies to identify common regulatory mechanisms involved in the control of the expression of a set of co-expressed genes might enhance our capacity to extract functional information from genomic data sets. In this chapter, we describe a method that integrates different sources of information: gene expression data, genome sequence information, described transcription factor binding sites (TFBSs), functional information, and bibliographic data. The starting point of the analysis is the extraction of promoter sequences from a whole genome and the detection of TFBSs in each gene promoter. This information allows the identification of enriched TFBSs in the proximal promoter of differentially expressed genes. The functional and bibliographic interpretation of the results improves our biological insight into the regulatory mechanisms involved in a microarray experiment. PMID:19957149

  11. Characterization of developmental Na(+) uptake in rainbow trout larvae supports a significant role for Nhe3b.

    PubMed

    Boyle, David; Blair, Salvatore D; Chamot, Danuta; Goss, Greg G

    2016-11-01

    Developing freshwater fish must compensate for the loss of ions, including sodium (Na(+)), to the environment. In this study, we used a radiotracer flux approach and pharmacological inhibitors to investigate the role of sodium/hydrogen exchange proteins (Nhe) in Na(+) uptake in rainbow trout (Oncorhynchus mykiss) reared from fertilization in soft water (0.1mM Na(+)). For comparison, a second group of embryos/larvae reared in hard water (2.2mM Na(+), higher pH and [Ca(2+)]) were also included in the experiment but were fluxed in soft water, only. Unidirectional rates of Na(+) uptake increased throughout development and were significantly higher in embryos/larvae reared in soft water. However, the mechanisms of Na(+) uptake in both groups of larvae were not significantly different, either in larvae immediately post-hatch or later in development: the broad spectrum Na(+) channel blocker amiloride inhibited 85-90% of uptake and the Nhe-inhibitor EIPA also caused near maximal inhibitions of Na(+) uptake. These data indicated Na(+) uptake was Nhe-mediated in soft water. A role of Nhe3b (but not Nhe2 or Nhe3a) in Na(+) uptake in soft water was also supported through gene expression analyses: expression of nhe3b increased throughout development in whole embryos/larvae in both groups and was significantly higher in those reared in soft water. This pattern of expression correlated well with measurements of Na(+) uptake. Together these data indicate that in part, rainbow trout embryos/larvae reared in low Na(+) soft water maintained Na(+) homeostasis by an EIPA sensitive component of Na(+) uptake, and support a primary role for Nhe3b.

  12. 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

  13. Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats.

    PubMed

    Elkjaer, Marie-Louise; Kwon, Tae-Hwan; Wang, Weidong; Nielsen, Jakob; Knepper, Mark A; Frøkiaer, Jørgen; Nielsen, Søren

    2002-12-01

    The purpose of this study was to examine whether hypokalemia is associated with altered abundance of major renal Na+ transporters that may contribute to the development of urinary concentrating defects. We examined the changes in the abundance of the type 3 Na+/H+ exchanger (NHE3), Na+ - K+-ATPase, the bumetanide-sensitive Na+ - K+ - 2Cl- cotransporter (BSC-1), the thiazide-sensitive Na+ - Cl- cotransporter (TSC), and epithelial sodium channel (ENaC) subunits in kidneys of hypokalemic rats. Semiquantitative immunoblotting revealed that the abundance of BSC-1 (57%) and TSC (46%) were profoundly decreased in the inner stripe of the outer medulla (ISOM) and cortex/outer stripe of the outer medulla (OSOM), respectively. These findings were confirmed by immunohistochemistry. Moreover, total kidney abundance of all ENaC subunits was significantly reduced in response to the hypokalemia: alpha-subunit (61%), beta-subunit (41%), and gamma-subunit (60%), and this was confirmed by immunohistochemistry. In contrast, the renal abundance of NHE3 in hypokalemic rats was dramatically increased in cortex/OSOM (736%) and ISOM (210%). Downregulation of BSC-1, TSC, and ENaC may contribute to the urinary concentrating defect, whereas upregulation of NHE3 may be compensatory to prevent urinary Na+ loss and/or to maintain intracellular pH levels.

  14. 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

  15. The presence of distal and proximal promoters for rat mitochondrial glycerol-3-phosphate acyltransferase

    PubMed Central

    Aneja, Kawalpreet K; Guha, Prajna; Shilpi, Rasheda Y.; Chakraborty, Sanjoy; Schramm, Laura M.; Haldar, Dipak

    2008-01-01

    Sequence analysis using the Promoser program predicted two promoter like regions for rat mtGPAT: a distal promoter ∼30 kb upstream and a proximal promoter near the first translational codon. Rat liver cells transfected with pGL3-basic vector containing the distal and proximal promoter resulted in 10.8 and 4.8 fold increase in the luciferase activity, respectively. Results of electromobility shift assay and chromatin immunoprecipitation suggested binding of transcription factors to the distal and proximal promoter regions. 5′RACE PCR showed two transcripts with different transcriptional start sites. When transfected rat liver cells were starved and refed, there was about 2.7 fold increase in the luciferase activity with cells transfected with the distal promoter while the proximal promoter showed no change. Thus, the two promoters could be functionally distinguished. Taken together, we conclude that there are two promoters for rat mtGPAT gene and that the transcriptional regulation is mediated through the distal promoter. PMID:18021946

  16. The presence of distal and proximal promoters for rat mitochondrial glycerol-3-phosphate acyltransferase.

    PubMed

    Aneja, Kawalpreet K; Guha, Prajna; Shilpi, Rasheda Y; Chakraborty, Sanjoy; Schramm, Laura M; Haldar, Dipak

    2008-02-01

    Sequence analysis using the Promoser program predicted two promoter-like regions for rat mtGPAT: a distal promoter approximately 30kb upstream and a proximal promoter near the first translational codon. Rat liver cells transfected with pGL3-basic vector containing the distal and proximal promoter resulted in 10.8- and 4.8-fold increase in the luciferase activity, respectively. Results of electromobility shift assay and chromatin immunoprecipitation suggested binding of transcription factors to the distal and proximal promoter regions. 5' RACE PCR showed two transcripts with different transcriptional start sites. When transfected rat liver cells were starved and refed, there was about 2.7-fold increase in the luciferase activity with cells transfected with the distal promoter while the proximal promoter showed no change. Thus, the two promoters could be functionally distinguished. Taken together, the results suggest that there are two promoters for rat mtGPAT gene and that the transcriptional regulation is mediated through the distal promoter.

  17. Close Association of Carbonic Anhydrase (CA2a and CA15a), Na+/H+ Exchanger (Nhe3b), and Ammonia Transporter Rhcg1 in Zebrafish Ionocytes Responsible for Na+ Uptake

    PubMed Central

    Ito, Yusuke; Kobayashi, Sayako; Nakamura, Nobuhiro; Miyagi, Hisako; Esaki, Masahiro; Hoshijima, Kazuyuki; Hirose, Shigehisa

    2013-01-01

    Freshwater (FW) fishes actively absorb salt from their environment to tolerate low salinities. We previously reported that vacuolar-type H+-ATPase/mitochondrion-rich cells (H-MRCs) on the skin epithelium of zebrafish larvae (Danio rerio) are primary sites for Na+ uptake. In this study, in an attempt to clarify the mechanism for the Na+ uptake, we performed a systematic analysis of gene expression patterns of zebrafish carbonic anhydrase (CA) isoforms and found that, of 12 CA isoforms, CA2a and CA15a are highly expressed in H-MRCs at larval stages. The ca2a and ca15a mRNA expression were salinity-dependent; they were upregulated in 0.03 mM Na+ water whereas ca15a but not ca2a was down-regulated in 70 mM Na+ water. Immunohistochemistry demonstrated cytoplasmic distribution of CA2a and apical membrane localization of CA15a. Furthermore, cell surface immunofluorescence staining revealed external surface localization of CA15a. Depletion of either CA2a or CA15a expression by Morpholino antisense oligonucleotides resulted in a significant decrease in Na+ accumulation in H-MRCs. An in situ proximity ligation assay demonstrated a very close association of CA2a, CA15a, Na+/H+ exchanger 3b (Nhe3b), and Rhcg1 ammonia transporter in H-MRC. Our findings suggest that CA2a, CA15a, and Rhcg1 play a key role in Na+uptake under FW conditions by forming a transport metabolon with Nhe3b. PMID:23565095

  18. The proximal J kappa germline-transcript promoter facilitates receptor editing through control of ordered recombination.

    PubMed

    Vettermann, Christian; Timblin, Greg A; Lim, Vivian; Lai, Ernest C; Schlissel, Mark S

    2015-01-01

    V(D)J recombination creates antibody light chain diversity by joining a Vκ gene segment with one of four Jκ segments. Two Jκ germline-transcript (GT) promoters control Vκ-Jκ joining, but the mechanisms that govern Jκ choice are unclear. Here, we show in gene-targeted mice that the proximal GT promoter helps targeting rearrangements to Jκ1 by preventing premature DNA breaks at Jκ2. Consequently, cells lacking the proximal GT promoter show a biased utilization of downstream Jκ segments, resulting in a diminished potential for receptor editing. Surprisingly, the proximal--in contrast to the distal--GT promoter is transcriptionally inactive prior to Igκ recombination, indicating that its role in Jκ choice is independent of classical promoter function. Removal of the proximal GT promoter increases H3K4me3 levels at Jκ segments, suggesting that this promoter could act as a suppressor of recombination by limiting chromatin accessibility to RAG. Our findings identify the first cis-element critical for Jκ choice and demonstrate that ordered Igκ recombination facilitates receptor editing.

  19. 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

  20. Regulation of intestinal hPepT1 (SLC15A1) activity by phosphodiesterase inhibitors is via inhibition of NHE3 (SLC9A3)

    PubMed Central

    Anderson, Catriona M.H.; Thwaites, David T.

    2007-01-01

    The H+-coupled transporter hPepT1 (SLC15A1) mediates the transport of di/tripeptides and many orally-active drugs across the brush-border membrane of the small intestinal epithelium. Incubation of Caco-2 cell monolayers (15 min) with the dietary phosphodiesterase inhibitors caffeine and theophylline inhibited Gly–Sar uptake across the apical membrane. Pentoxifylline, a phosphodiesterase inhibitor given orally to treat intermittent claudication, also decreased Gly–Sar uptake through a reduction in capacity (Vmax) without any effect on affinity (Km). The reduction in dipeptide transport was dependent upon both extracellular Na+ and apical pH but was not observed in the presence of the selective Na+/H+ exchanger NHE3 (SLC9A3) inhibitor S1611. Measurement of intracellular pH confirmed that caffeine was not directly inhibiting hPepT1 but rather having an indirect effect through inhibition of NHE3 activity. NHE3 maintains the H+-electrochemical gradient which, in turn, acts as the driving force for H+-coupled solute transport. Uptake of β-alanine, a substrate for the H+-coupled amino acid transporter hPAT1 (SLC36A1), was also inhibited by caffeine. The regulation of NHE3 by non-nutrient components of diet or orally-delivered drugs may alter the function of any solute carrier dependent upon the H+-electrochemical gradient and may, therefore, be a site for both nutrient–drug and drug–drug interactions in the small intestine. PMID:17498647

  1. Transcription factor binding and spacing constraints in the human beta-actin proximal promoter.

    PubMed Central

    Danilition, S L; Frederickson, R M; Taylor, C Y; Miyamoto, N G

    1991-01-01

    The human beta-actin promoter, including its 5' flanking region and 5' untranslated region, is ubiquitously active in mammalian cells in culture. In this report we investigated the transcriptional activity of, and the protein-DNA interactions that occur within, the proximal region of the human beta-actin promoter. Efficient beta-actin promoter activity in transfected human HeLa cells requires only 114bp of 5' flanking sequences. Two of the cis-actin regulatory elements within this region of the beta-actin promoter, the CCAAT box and proximal CCArGG box, are specific in vitro binding sites for the transcription factors, nuclear factor Y (NF-Y) and serum response factor (p67SRF), respectively. These two elements are required together to stimulate in vivo transcription from the homologous as well as a heterologous promoter. Finally, a particular spatial alignment between the CCAAT box and proximal CCArGG box is required for trans-activation in vivo. The above provides strong evidence for a functional interaction between NF-Y and p67SRF when bound to their respective binding sites in the beta-actin promoter. Images PMID:1762920

  2. 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

  3. Grouper tshβ promoter-driven transgenic zebrafish marks proximal kidney tubule development.

    PubMed

    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.

  4. 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

  5. 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

  6. 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.

  7. Activity of proximal promoter of the human beta(1)-integrin gene was increased in Sézary syndrome.

    PubMed

    Paulin, Y; Boukhelifa, M; Derappe, C; Giner, M; Font, J; Aubery, M

    2001-06-01

    Changes in beta1-integrin expression have been involved in abnormal cellular interactions between malignant lymphocytes from Sézary (Sz) patients and keratinocytes. In this paper, we compare the activity of both distal and proximal promoters of the beta1-integrin gene in malignant lymphocytes from Sz patients with human normal lymphocytes. Activity of both beta1-integrin promoters was also analysed in human normal keratinocytes. Northern blot analysis shows that beta1-integrin mRNA expression is higher in malignant Sz lymphocytes than in normal lymphocytes. CAT assays show that the activity of proximal beta1-integrin promoter is markedly increased (up to 6-fold) in malignant lymphocytes from Sz patients, in comparison to normal lymphocytes. These results suggest that changes in activity of the proximal promoter of beta1-integrin subunit could be, in part, responsible for the abnormal cellular interactions between malignant lymphocytes and keratinocytes observed in Sz syndrome.

  8. Higher frequency of intron loss from the promoter proximally paused genes of Drosophila melanogaster.

    PubMed

    Jiang, Li; Li, Xue-Nan; Niu, Deng-Ke

    2014-01-01

    Although intron losses have been widely reported, it is not clear whether they are neutral and therefore random or driven by positive selection. Intron transcription and splicing are time-consuming and can delay the expression of its host gene. For genes that must be activated quickly to respond to physiological or stress signals, intron delay may be deleterious. Promoter proximally paused (PPP) genes are a group of rapidly expressed genes. To respond quickly to activation signals, they generally initiate transcription competently but stall after synthesizing a short RNA. In this study, performed in Drosophila melanogaster, the PPP genes were found to have a significantly higher rate of intron loss than control genes. However, further analysis did not find more significant shrinkage of intron size in PPP genes. Referring to previous studies on the rates of transcription and splicing and to the time saved by deletion of the introns from mouse gene Hes7, it is here suggested that transcription delay is comparable to splicing delay only when the intron is 28.5 kb or larger, which is greater in size than 95% of vertebrate introns, 99.5% of Drosophila introns, and all the annotated introns of Saccharomyces cerevisiae and Arabidopsis thaliana. Delays in intron splicing are probably a selective force, promoting intron loss from quickly expressed genes. In other genes, it may have been an exaptation during the emergency of developmental clocks.

  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. 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

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

    PubMed

    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.

  12. 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

  13. Hormone-specific regulation of the kidney androgen-regulated gene promoter in cultured mouse renal proximal-tubule cells.

    PubMed Central

    Soler, Montse; Tornavaca, Olga; Solé, Esther; Menoyo, Anna; Hardy, Dianne; Catterall, James F; Vandewalle, Alain; Meseguer, Anna

    2002-01-01

    The kidney androgen-regulated protein (KAP) is specifically expressed and differentially regulated by androgens and tri-iodothyronine (T(3)) in intact mouse early (PCT) and late (PR) proximal-tubule cells. Until now, detailed characterization of the molecular elements mediating androgen-responsive gene expression in the kidney has been hampered by the lack of appropriate cultured cell systems suitable for DNA transfection studies. In the present study we have analysed the hormone-dependent transactivation of the KAP gene promoter in immortalized differentiated PCT and PR proximal-tubule cells derived from L-PK/Tag1 transgenic mice. Transient transfection studies with different KAP promoter constructs indicated that a 224 bp-truncated fragment was sufficient to mediate cell-specific expression of the KAP promoter. Dihydrotestosterone (DHT) stimulated in an androgen-dependent manner the transactivation of KAP in PCT and PR cells, while mutation of a putative androgen-response element (ARE) sequence located at -39 bp from the transcription initiation site abolished the transactivation induced by DHT. Furthermore, insulin-like growth factor 1 (IGF-1), but not T(3), enhanced the androgen-dependent transactivation of KAP in cultured PCT cells. These results demonstrate that the short 224 bp fragment of the KAP promoter is sufficient to drive the proximal-tubule androgen-specific regulated expression of KAP and reveal synergistic interactions between IGF-1 and androgens for KAP regulation in PCT cells. PMID:12030848

  14. A proximal promoter region of Arabidopsis DREB2C confers tissue-specific expression under heat stress.

    PubMed

    Chen, Huan; Je, Jihyun; Song, Chieun; Hwang, Jung Eun; Lim, Chae Oh

    2012-09-01

    The dehydration-responsive element-binding factor 2C (DREB2C) is a member of the CBF/DREB subfamily of proteins, which contains a single APETALA2/Ethylene responsive element-binding factor (AP2/ERF) domain. To identify the expression pattern of the DREB2C gene, which contains multiple transcription cis-regulatory elements in its promoter, an approximately 1.4 kb upstream DREB2C sequence was fused to the β-glucuronidase reporter gene (GUS) and the recombinant p1244 construct was transformed into Arabidopsis thaliana (L.) Heynh. The promoter of the gene directed prominent GUS activity in the vasculature in diverse young dividing tissues. Upon applying heat stress (HS), GUS staining was also enhanced in the vasculature of the growing tissues. Analysis of a series of 5'-deletions of the DREB2C promoter revealed that a proximal upstream sequence sufficient for the tissue-specific spatial and temporal induction of GUS expression by HS is localized in the promoter region between -204 and -34 bps relative to the transcriptional start site. Furthermore, electrophoretic mobility shift assay (EMSA) demonstrated that nuclear protein binding activities specific to a -120 to -32 bp promoter fragment increased after HS. These results indicate that the TATA-proximal region and some latent trans-acting factors may cooperate in HS-induced activation of the Arabidopsis DREB2C promoter.

  15. 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

  16. 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

  17. A functional study of proximal goat β-casein promoter and intron 1 in immortalized goat mammary epithelial cells.

    PubMed

    Kung, M H; Lee, Y J; Hsu, J T; Huang, M C; Ju, Y T

    2015-06-01

    Goat β-casein (CSN2) promoter has been extensively used to derive expression of recombinant therapeutic protein in transgenic goats; however, little direct evidence exists for signaling molecules and the cis-elements of goat CSN2 promoter in response to lactogenic hormone stimulation in goat mammary epithelial cells. Here, we use an immortalized caprine mammary epithelial cell line (CMC) to search for evidence of the above. Serial 5'-flanking regions deleted of promoter and intron 1 in goat CSN2 (-4,047 to +2,054) driven by firefly luciferase reporter gene were constructed and applied to measure promoter activity in CMC. The intron 1 region (+393 to +501) significantly decreased basal activity of the promoter. This finding contradicts other studies of the role of intron 1. The signal transducer and activator of transcription (STAT)5a played a significant role in activating promoter activity by prolactin stimulation. Hydrocortisone enhanced and prolonged the activity of STAT5a and promoter in CMC, but was independent of the glucocorticoid receptor response element. The minimum length of the CSN2 promoter segment in response to lactogenic stimulation was confirmed by 5' serial deletions. A cis-element located from -300 to -90 in proximal goat CSN2 promoter that is absent in bovine and human CSN2 promoter was newly identified. We demonstrated the presence of a STAT5a binding site (-102 to -82) and preservation of the guanosine nucleotide at position -90 based on responses to the presence of lactogenic hormone using internal deletions and point mutations of the predicted STAT5a binding site, and chromatin immunoprecipitation assay. Together, these findings demonstrate that the proximal -300 bp of goat CSN2 promoter containing the STAT5a binding site (-102 to -82) is the response element for lactogenic hormone stimulation. Additionally, intron 1 may be required for tissue or developmental stage-specific expression in mammary gland. The role of the far-distal regions of

  18. An evolutionarily conserved Myostatin proximal promoter/enhancer confers basal levels of transcription and spatial specificity in vivo.

    PubMed

    Grade, Carla Vermeulen Carvalho; Salerno, Mônica Senna; Schubert, Frank R; Dietrich, Susanne; Alvares, Lúcia Elvira

    2009-10-01

    Myostatin (Mstn) is a negative regulator of skeletal muscle mass, and Mstn mutations are responsible for the double muscling phenotype observed in many animal species. Moreover, Mstn is a positive regulator of adult muscle stem cell (satellite cell) quiescence, and hence, Mstn is being targeted in therapeutic approaches to muscle diseases. In order to better understand the mechanisms underlying Mstn regulation, we searched for the gene's proximal enhancer and promoter elements, using an evolutionary approach. We identified a 260-bp-long, evolutionary conserved region upstream of tetrapod Mstn and teleost mstn b genes. This region contains binding sites for TATA binding protein, Meis1, NF-Y, and for CREB family members, suggesting the involvement of cAMP in Myostatin regulation. The conserved fragment was able to drive reporter gene expression in C2C12 cells in vitro and in chicken somites in vivo; both normally express Mstn. In contrast, the reporter construct remained silent in the avian neural tube that normally does not express Mstn. This suggests that the identified element serves as a minimal promoter, harboring some spatial specificity. Finally, using bioinformatic approaches, we identified additional genes in the human genome associated with sequences similar to the Mstn proximal promoter/enhancer. Among them are genes important for myogenesis. This suggests that Mstn and these genes may form a synexpression group, regulated by a common signaling pathway.

  19. Expression of Steroidogenic Factor 1 in the Testis Requires an Interactive Array of Elements Within Its Proximal Promoter1

    PubMed Central

    Scherrer, Serge P.; Rice, Daren A.; Heckert, Leslie L.

    2006-01-01

    Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that is important for expression of genes involved in sexual differentiation, testicular and adrenal development, and hormone synthesis and regulation. To better understand the mechanisms required for SF-1 production, we employed transient transfec-tion analysis and electrophoretic mobility shift assays to characterize the elements and proteins required for transcriptional activity of the SF-1 proximal promoter in testicular Sertoli and Leydig cells and adrenocortical cells. Direct comparison of SF-1-promoter activity in testis and adrenal cell types established that a similar set of regulatory elements (an E box, CCAAT box, and Sp1-binding sites) is required for proximal promoter activity in these cells. Further evaluation of the E box and CCAAT box revealed a novel synergism between the two elements and iden-tified functionally important bases within the elements. Importantly, DNA/protein-binding studies uncovered new proteins interacting with the E box and CCAAT box. Thus, in addition to the previously identified USF and NF-Y proteins, newly described complexes, having migration properties that differed between Sertoli and Leydig cells, were observed bound to the E box and CCAAT box. Transient transfection analysis also identified several Sp1/Sp3-binding elements important for expression of SF-1 in the testis, one of which was previously described for expression in the adrenal gland whereas the other two were newly disclosed elements. PMID:12390883

  20. Binding of Sp1/Sp3 to the proximal promoter of the hMOR gene is enhanced by DAMGO.

    PubMed

    Xu, Y; Carr, L G

    2001-08-22

    The major binding site for morphine is the mu opioid receptor (MOR), which mediates morphine's analgesic and euphoric effects. The MOR gene is highly regulated at the level of transcription. The present study examined DNA-protein interactions in the human MOR (hMOR) -500 to -292 promoter region, and tested whether chronic opioid drug treatment could modulate these DNA-protein interactions. 5'-deletion and transient transfection assays in SK-N-SH cells revealed four regions that activated hMOR gene transcription. A 60 bp sequence (-351 to -292) upstream of the proximal transcription initiation site (-252) contained cis-elements required for basal promoter activity. Sp1 and Sp3 bound to this 60 bp region, which was confirmed by electromobility shift assays using a Sp1 consensus oligo as competitor and specific antibodies against Sp1 and Sp3. Methylation interference analysis localized the Sp1 binding site to the sequence CCCTCCTCCC (-310 to -301) and also suggested that additional transcription factors, other than Sp1-related proteins, contacted the -321 to -301 sequence. Moreover, the binding of Sp1/Sp3 to the hMOR promoter was significantly enhanced by chronic exposure to [D-Ala(2), N-Me-Phe(4), Gly(5)-ol] enkephalin (DAMGO), a selective MOR agonist, and this effect was attenuated specifically by pretreatment with a MOR antagonist, naloxone. Taken together, the present studies demonstrated, for the first time, that the binding of Sp1/Sp3 to the hMOR proximal promoter could be modulated by chronic DAMGO treatment. Such enhanced binding of Sp1/Sp3 to the promoter may lead to a functional change in hMOR gene transcription.

  1. 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

  2. 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

  3. Expression of a novel isoform of Na(+)/H(+) exchanger 3 in the kidney and intestine of banded houndshark, Triakis scyllium.

    PubMed

    Li, Shanshan; Kato, Akira; Takabe, Souichirou; Chen, An-Ping; Romero, Michael F; Umezawa, Takahiro; Nakada, Tsutomu; Hyodo, Susumu; Hirose, Shigehisa

    2013-05-15

    Na(+)/H(+) exchanger 3 (NHE3) provides one of the major Na(+) absorptive pathways of the intestine and kidney in mammals, and recent studies of aquatic vertebrates (teleosts and elasmobranchs) have demonstrated that NHE3 is expressed in the gill and plays important roles in ion and acid-base regulation. To understand the role of NHE3 in elasmobranch osmoregulatory organs, we analyzed renal and intestinal expressions and localizations of NHE3 in a marine elasmobranch, Japanese banded houndshark (Triakis scyllium). mRNA for Triakis NHE3 was most highly expressed in the gill, kidney, spiral intestine, and rectum. The kidney and intestine expressed a transcriptional isoform of NHE3 (NHE3k/i), which has a different amino terminus compared with that of NHE3 isolated from the gill (NHE3g), suggesting that NHE3k/i and NHE3g arise from a single gene by alternative promoter usage. Immunohistochemical analyses of the Triakis kidney demonstrated that NHE3k/i is expressed in the apical membrane of a part of the proximal and late distal tubules in the sinus zone. In the bundle zone of the kidney, NHE3k/i was expressed in the apical membrane of the early distal tubules known as the diluting segment. In the spiral intestine and rectum, NHE3k/i was localized toward the apical membrane of the epithelial cells. The transcriptional levels of NHE3k/i were increased in the kidney when Triakis was acclimated in 130% seawater, whereas those in the spiral intestine were increased in fish acclimated in diluted seawater. These results suggest that NHE3 is involved in renal Na(+) reabsorption, urine acidification, and intestinal Na(+) absorption in elasmobranchs.

  4. Identification and characterization of proximal promoter polymorphisms in the human concentrative nucleoside transporter 2 (SLC28A2).

    PubMed

    Yee, Sook Wah; Shima, James E; Hesselson, Stephanie; Nguyen, Loan; De Val, Sarah; Lafond, Rachel J; Kawamoto, Michiko; Johns, Susan J; Stryke, Doug; Kwok, Pui-Yan; Ferrin, Thomas E; Black, Brian L; Gurwitz, David; Ahituv, Nadav; Giacomini, Kathleen M

    2009-03-01

    The human concentrative nucleoside transporter 2 (CNT2) plays an important role in the absorption, disposition, and biological effects of endogenous nucleosides and nucleoside analog drugs. We identified genetic variation in the basal promoter region of CNT2 and characterized the function of the variants. We screened DNA from an ethnically diverse population and identified five basal promoter variants in CNT2. Three major haplotypes in the CNT2 basal promoter region were identified and were found at different allele frequencies in various ethnic groups. The common promoter variants and haplotypes were constructed and characterized for their promoter activity using luciferase reporter assays. One polymorphic variant, rs2413775 (-146T>A), with an allele frequency >20% in all populations, showed a gain of function in luciferase activity. Furthermore, in vivo mouse promoter assays of these nucleotide variants using the hydrodynamic tail vein injection, leading to their expression in the liver, demonstrated similar results. Transcription factor binding site (TFBS) analysis indicated this variant alters a hepatic nuclear factor (HNF) 1 TFBS. Electrophoretic mobility shift assay demonstrated stronger binding of HNF1alpha and weaker binding of HNF1beta to the -146T and -146A regions, whereas the single nucleotide polymorphism (SNP), -146A, exhibited enhanced binding to both HNF1alpha and HNF1beta, consistent with its greater activity in reporter assays. The data collectively suggest that the common variant, -146T>A, in the proximal promoter of CNT2 may result in an enhanced transcription rate of the gene and, thus, expression levels of CNT2. This SNP may play a role in variation in the pharmacokinetics and pharmacological effects of nucleoside analogs.

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

    PubMed

    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)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)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n=2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n=4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)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)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility.

  6. 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…

  7. Physical Proximity May Promote Lateral Acquisition of Bacterial Symbionts in Vesicomyid Clams

    PubMed Central

    Decker, Carole; Olu, Karine; Arnaud-Haond, Sophie; Duperron, Sébastien

    2013-01-01

    Vesicomyid clams harbor intracellular sulfur-oxidizing bacteria that are predominantly maternally inherited and co-speciate with their hosts. Genome recombination and the occurrence of non-parental strains were recently demonstrated in symbionts. However, mechanisms favoring such events remain to be identified. In this study, we investigated symbionts in two phylogenetically distant vesicomyid species, Christineconcha regab and Laubiericoncha chuni, which sometimes co-occur at a cold-seep site in the Gulf of Guinea. We showed that each of the two species harbored a single dominant bacterial symbiont strain. However, for both vesicomyid species, the symbiont from the other species was occasionally detected in the gills using fluorescence in situ hybridization and gene sequences analyses based on six symbiont marker genes. Symbiont strains co-occurred within a single host only at sites where both host species were found; whereas one single symbiont strain was detected in C. regab specimens from a site where no L. chuni individuals had been observed. These results suggest that physical proximity favored the acquisition of non-parental symbiont strains in Vesicomyidae. Over evolutionary time, this could potentially lead to genetic exchanges among symbiont species and eventually symbiont displacement. Symbiont densities estimated using 3D fluorescence in situ hybridization varied among host species and sites, suggesting flexibility in the association despite the fact that a similar type of metabolism is expected in all symbionts. PMID:23861734

  8. A gene-type-specific enhancer regulates the carbamyl phosphate synthetase I promoter by cooperating with the proximal GAG activating element.

    PubMed Central

    Goping, I S; Lamontagne, S; Shore, G C; Nguyen, M

    1995-01-01

    The rat carbamyl phosphate synthetase I gene is expressed in two cell types: hepatocytes and epithelial cells of the intestinal mucosa. The proximal promoter contains a single activating element, GAG, two repressor elements (sites I and III) and an anti-repressor element (site II). Although these elements together exhibit the potential for complex regulation, they are unable to confer tissue-specific promoter activity. Here we have identified a cell-type-specific enhancer that lies 10 kilobases upstream of the promoter. Unexpectedly, the enhancer also functioned in a gene-type-specific manner. The enhancer stimulated promoter activity exclusively through the proximal GAG element. Abrogation of GAG, either directly by mutation of GAG or indirectly by sites I and III repressors, abolished enhancer activation. Conversely, activation of the heterologous thymidine kinase promoter by the enhancer required the introduction of GAG. The requirement for GAG, therefore, functions to constrain the enhancer to a specific target promoter. PMID:7784176

  9. 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

  10. PHF8 and REST/NRSF co-occupy gene promoters to regulate proximal gene expression.

    PubMed

    Wang, Juan; Lin, Xueqiu; Wang, Su; Wang, Chenfei; Wang, Qixuan; Duan, Xikun; Lu, Peng; Wang, Qian; Wang, Chengyang; Liu, X Shirley; Huang, Jinyan

    2014-01-01

    Chromatin regulators play an important role in the development of human diseases. In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a chromatin regulator that has attracted special concern recently. PHF8 is a histone lysine demethylase ubiquitously expressed in nuclei. Mutations of PHF8 are associated with X-linked mental retardation. It usually functions as a transcriptional co-activator by associating with H3K4me3 and RNA polymerase II. We found that PHF8 may associate with another regulator, REST/NRSF, predominately at promoter regions via studying several published PHF8 chromatin immunoprecipitation-sequencing (ChIP-Seq) datasets. Our analysis suggested that PHF8 not only activates but may also repress gene expression. PMID:24852203

  11. 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

  12. Association of the CpG methylation pattern of the proximal insulin gene promoter with type 1 diabetes.

    PubMed

    Fradin, Delphine; Le Fur, Sophie; Mille, Clémence; Naoui, Nadia; Groves, Chris; Zelenika, Diana; McCarthy, Mark I; Lathrop, Mark; Bougnères, Pierre

    2012-01-01

    The insulin (INS) region is the second most important locus associated with Type 1 Diabetes (T1D). The study of the DNA methylation pattern of the 7 CpGs proximal to the TSS in the INS gene promoter revealed that T1D patients have a lower level of methylation of CpG -19, -135 and -234 (p = 2.10(-16)) and a higher methylation of CpG -180 than controls, while methylation was comparable for CpG -69, -102, -206. The magnitude of the hypomethylation relative to a control population was 8-15% of the corresponding levels in controls and was correlated in CpGs -19 and -135 (r = 0.77) and CpG -135 and -234 (r = 0.65). 70/485 (14%) of T1D patients had a simultaneous decrease in methylation of CpG -19, -135, -234 versus none in 317 controls. CpG methylation did not correlate with glycated hemoglobin or with T1D duration. The methylation of CpG -69, -102, -180, -206, but not CpG -19, -135, -234 was strongly influenced by the cis-genotype at rs689, a SNP known to show a strong association with T1D. We hypothesize that part of this genetic association could in fact be mediated at the statistical and functional level by the underlying changes in neighboring CpG methylation. Our observation of a CpG-specific, locus-specific methylation pattern, although it can provide an epigenetic biomarker of a multifactorial disease, does not indicate whether the reported epigenetic pattern preexists or follows the establishment of T1D. To explore the effect of chronic hyperglycemia on CpG methylation, we studied non obese patients with type 2 diabetes (T2D) who were found to have decreased CpG-19 methylation versus age-matched controls, similar to T1D (p = 2.10(-6)) but increased CpG-234 methylation (p = 5.10(-8)), the opposite of T1D. The causality and natural history of the different epigenetic changes associated with T1D or T2D remain to be determined. PMID:22567146

  13. The Ewing sarcoma protein (EWS) binds directly to the proximal elements of the macrophage-specific promoter of the CSF-1 receptor (csf1r) gene.

    PubMed

    Hume, David A; Sasmono, Tedjo; Himes, S Roy; Sharma, Sudarshana M; Bronisz, Agnieszka; Constantin, Myrna; Ostrowski, Michael C; Ross, Ian L

    2008-05-15

    Many macrophage-specific promoters lack classical transcriptional start site elements such as TATA boxes and Sp1 sites. One example is the CSF-1 receptor (CSF-1R, CD115, c-fms), which is used as a model of the transcriptional regulation of macrophage genes. To understand the molecular basis of start site recognition in this gene, we identified cellular proteins binding specifically to the transcriptional start site (TSS) region. The mouse and human csf1r TSS were identified using cap analysis gene expression (CAGE) data. Conserved elements flanking the TSS cluster were analyzed using EMSAs to identify discrete DNA-binding factors in primary bone marrow macrophages as candidate transcriptional regulators. Two complexes were identified that bind in a highly sequence-specific manner to the mouse and human TSS proximal region and also to high-affinity sites recognized by myeloid zinc finger protein 1 (Mzf1). The murine proteins were purified by DNA affinity isolation from the RAW264.7 macrophage cell line and identified by mass spectrometry as EWS and FUS/TLS, closely related DNA and RNA-binding proteins. Chromatin immunoprecipitation experiments in bone marrow macrophages confirmed that EWS, but not FUS/TLS, was present in vivo on the CSF-1R proximal promoter in unstimulated primary macrophages. Transfection assays suggest that EWS does not act as a conventional transcriptional activator or repressor. We hypothesize that EWS contributes to start site recognition in TATA-less mammalian promoters.

  14. Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region

    PubMed Central

    2004-01-01

    The transcription of the human UCP3 (uncoupling protein-3) gene in skeletal muscle is tightly regulated by metabolic signals related to fatty acid availability. However, changes in thyroid status also modulate UCP3 gene expression, albeit by unknown mechanisms. We created transgenic mice bearing the entire human UCP3 gene to investigate the effect of thyroid hormones on human UCP3 gene expression. Treatment of human UCP3 transgenic mice with thyroid hormones induced the expression of the human gene in skeletal muscle. In addition, transient transfection experiments demonstrate that thyroid hormones activate the transcription of the human UCP3 gene promoter when MyoD and the TR (thyroid hormone receptor) were co-transfected. The action of thyroid hormones on UCP3 gene transcription is mediated by the binding of the TR to a proximal region in the UCP3 gene promoter that contains a direct repeat structure. An intact DNA sequence of this site is required for thyroid hormone responsiveness and TR binding. Chromatin immunoprecipitation assays revealed that the TR binds this element in vivo. The murine Ucp3 gene promoter was also dependent on MyoD and responsive to thyroid hormone in transient transfection assays. However, it was much less sensitive to thyroid hormone than the human UCP3 promoter. In summary, UCP3 gene transcription is activated by thyroid hormone treatment in vivo, and this activation is mediated by a TRE (thyroid hormone response element) in the proximal promoter region. Such regulation suggests a link between UCP3 gene expression and the effects of thyroid hormone on mitochondrial function in skeletal muscle. PMID:15496137

  15. Transcriptional regulation of the human mu opioid receptor (hMOR) gene: evidence of positive and negative cis-acting elements in the proximal promoter and presence of a distal promoter.

    PubMed

    Xu, Y; Carr, L G

    2001-07-01

    The mu opioid receptor (MOR), the primary binding site for morphine, is an important target for treating pain and drug addiction. The MOR gene is tightly regulated at the level of transcription, and potential polymorphisms in its 5' regulatory region can cause individual variation in MOR gene expression, nociception, and opiate responses. To study the 5' regulatory region of the human MOR gene (hMOR), we further investigated our previous finding of two regulatory regions and have localized a 40-bp positive cis-acting element and a 35-bp negative cis-acting element that regulate hMOR transcription in SK-N-SH cells. Electromobility shift assays and methylation interference assay with the 40-bp probe suggested that protein contacts were made with the core recognition sequence GCC (-510 to -508). The 35-bp sequence (-694 to -660) was the hMOR homolog of the mMOR negative regulatory element, and it suppressed proximal promoter activity of the hMOR gene. Additionally, the presence of an hMOR distal promoter was confirmed using RT-PCR. However, the activity of the distal promoter construct (-2325 to -777) was weak compared with the activity of the proximal promoter construct (-776 to -212).

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

    PubMed Central

    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

  17. 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

  18. 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

  19. Sp1 and Sp3 control constitutive expression of the human NHE2 promoter by interactions with the proximal promoter and the transcription initiation site

    PubMed Central

    Pearse, Ian; Zhu, Ying X.; Murray, Eleanor J.; Dudeja, Pradeep K.; Ramaswamy, Krishnamurthy; Malakooti, Jaleh

    2007-01-01

    We have previously cloned the human Na+/H+ exchanger NHE2 gene and its promoter region. In the present study, the regulatory elements responsible for the constitutive expression of NHE2 were studied. Transient transfection assays revealed that the −40/+150 promoter region contains the core promoter responsible for the optimal promoter activity. A smaller fragment, −10/+40, containing the TIS (transcription initiation site) showed minimal activity. We identified a palindrome that overlaps the TIS and binds to the transcription factors Sp1 and Sp3. Mutations in the 5′ flank of the palindrome abolished the Sp1/Sp3 interaction and reduced promoter activity by approx. 45%. In addition, a conserved GC-box centered at −25 was found to play a critical role in basal promoter activity and also interacted with Sp1 and Sp3. An internal deletion in the GC-box severely reduced the promoter activity. Sp1/Sp3 binding to these elements was established using gel-mobility shift assays, confirmed by chromatin immunoprecipitation and co-transfections in Drosophila SL2 cells. Furthermore, we identified two positive regulatory elements in the DNA region corresponding to the 5′-UTR (5′-untranslated region). The results in the present study indicate that Sp1 and Sp3 are required for constitutive NHE2 expression and that the positive regulatory elements of the 5′-UTR may co-operate with the 5′-flanking region to achieve the optimal promoter activity. PMID:17561809

  20. Carbohydrate-binding modules promote the enzymatic deconstruction of intact plant cell walls by targeting and proximity effects.

    PubMed

    Hervé, Cécile; Rogowski, Artur; Blake, Anthony W; Marcus, Susan E; Gilbert, Harry J; Knox, J Paul

    2010-08-24

    Cell wall degrading enzymes have a complex molecular architecture consisting of catalytic modules and noncatalytic carbohydrate-binding modules (CBMs). The function of CBMs in cell wall degrading processes is poorly understood. Here, we have evaluated the potential enzyme-targeting function of CBMs in the context of intact primary and secondary cell wall deconstruction. The capacity of a pectate lyase to degrade pectic homogalacturonan in primary cell walls was potentiated by cellulose-directed CBMs but not by xylan-directed CBMs. Conversely, the arabinofuranosidase-mediated removal of side chains from arabinoxylan in xylan-rich and cellulose-poor wheat grain endosperm cell walls was enhanced by a xylan-binding CBM but less so by a crystalline cellulose-specific module. The capacity of xylanases to degrade xylan in secondary cell walls was potentiated by both xylan- and cellulose-directed CBMs. These studies demonstrate that CBMs can potentiate the action of a cognate catalytic module toward polysaccharides in intact cell walls through the recognition of nonsubstrate polysaccharides. The targeting actions of CBMs therefore have strong proximity effects within cell wall structures, explaining why cellulose-directed CBMs are appended to many noncellulase cell wall hydrolases.

  1. Frequency and Prognostic Impact of CEBPA Proximal, Distal and Core Promoter Methylation in Normal Karyotype AML: A Study on 623 Cases

    PubMed Central

    Fasan, Annette; Alpermann, Tamara; Haferlach, Claudia; Grossmann, Vera; Roller, Andreas; Kohlmann, Alexander; Eder, Christiane; Kern, Wolfgang; Haferlach, Torsten; Schnittger, Susanne

    2013-01-01

    The clinical impact of aberrant CEBPA promoter methylation (PM) in AML is controversially discussed. The aim of this study was to clarify the significance of aberrant CEBPA PM with regard to clinical features in a cohort of 623 cytogenetically normal (CN) de novo AML. 555 cases had wild-type CEBPA, 68 cases harbored CEBPA mutations. The distal promoter was methylated in 238/623 cases (38.2%), the core promoter in 8 of 326 cases (2.5%), whereas proximal PM was never detected. CEBPA PM and CEBPA mutations were mutually exclusive. CEBPA distal PM positive cases were characterized by reduced CEBPA mRNA expression levels and elevated white blood cell counts. CEBPA distal PM was less frequent in patients with mutations in FLT3, NPM1 and TET2 and more frequent in cases with RUNX1 and IDH2R140 mutations. Overall, no association of methylation to prognosis was seen. However CEBPA distal PM was associated with inferior outcome in cases with low FLT3-ITD ratio or TET2 mutations. A distinct gene expression profile of CEBPA distal PM positive cases compared to CEBPA mutated and CEBPA distal PM negative cases was observed. In conclusion, the presence of aberrant CEBPA PM is associated with distinct biological features but impact on outcome is weak. PMID:23383300

  2. PTEN mutation and epidermal growth factor receptor activation regulate vascular endothelial growth factor (VEGF) mRNA expression in human glioblastoma cells by transactivating the proximal VEGF promoter.

    PubMed

    Pore, Nabendu; Liu, Shuang; Haas-Kogan, Daphne A; O'Rourke, Donald M; Maity, Amit

    2003-01-01

    Our previous work showed that, compared with parental U87MG human glioblastoma cells, vascular endothelial growth factor (VEGF) mRNA levels are decreased in U87/T691, a derivative line in which epidermal growth factor receptor (EGFR) signaling is inhibited by introduction of a truncated p185(Neu) protein (A. Maity et al., Cancer Res., 60: 5879-5886, 2000). The effect of EGFR activation on VEGF was mediated at the level of transcription via a phosphatidylinositol 3'-kinase (PI3K)-dependent pathway. In the current study we investigated the effect of PTEN, a negative regulator of PI3K signaling commonly mutated in glioblastoma cells, on VEGF expression. Several glioblastoma cell lines containing mutant PTEN, including U87MG, U87/T691, and U251MG, were infected with adenovirus expressing wild-type PTEN. This led to a decrease in the levels of both VEGF mRNA and phosphorylated Akt, a marker for PI3K activation. Treatment of U87MG cells with LY294002, a PI3K inhibitor, or cotransfection with a vector expressing wild-type PTEN decreased VEGF promoter activity using reporters containing either 1.5 kb of the promoter or a fragment extending from -88 to +54 bp. Activity of the -88/+54 VEGF promoter was down-regulated by dominant negative Akt and up-regulated by constitutively active myristoylated Akt. Introduction of wild-type PTEN and pharmacological inhibition of EGFR decreased VEGF mRNA expression and VEGF promoter activity in U87MG cells to a greater extent that did either manipulation by itself. Therefore, in human glioblastoma cells, PTEN mutation can cooperate with EGFR activation to increase VEGF mRNA levels by transcriptionally up-regulating the proximal VEGF promoter via the PI3K/Akt pathway.

  3. Characterization of the cis elements in the proximal promoter regions of the anthocyanin pathway genes reveals a common regulatory logic that governs pathway regulation

    PubMed Central

    Zhu, Zhixin; Wang, Hailong; Wang, Yiting; Guan, Shan; Wang, Fang; Tang, Jingyu; Zhang, Ruijuan; Xie, Lulu; Lu, Yingqing

    2015-01-01

    Cellular activities such as compound synthesis often require the transcriptional activation of an entire pathway; however, the molecular mechanisms underlying pathway activation have rarely been explained. Here, the cis regulatory architecture of the anthocyanin pathway genes targeted by the transcription factor (TF) complex including MYB, bHLH, and WDR was systematically analysed in one species and the findings extended to others. In Ipomoea purpurea, the IpMYB1-IpbHLH2-IpWDR1 (IpMBW) complex was found to be orthologous to the PAP1-GL3-TTG1 (AtPGT) complex of Arabidopsis thaliana, and interacted with a 7-bp MYB-recognizing element (MRE) and a 6-bp bHLH-recognizing element (BRE) at the proximal promoter region of the pathway genes. There was little transcription of the gene in the absence of the MRE or BRE. The cis elements identified experimentally converged on two syntaxes, ANCNNCC for MREs and CACN(A/C/T)(G/T) for BREs, and our bioinformatic analysis showed that these were present within anthocyanin gene promoters in at least 35 species, including both gymnosperms and angiosperms. For the anthocyanin pathway, IpMBW and AtPGT recognized the interspecific promoters of both early and later genes. In A. thaliana, the seed-specific TF complex (TT2, TT8, and TTG1) may regulate all the anthocyanin pathway genes, in addition to the proanthocyanidin-specific BAN. When multiple TF complexes in the anthocyanin pathway were compared, the cis architecture played a role larger than the TF complex in determining the variation in promoter activity. Collectively, a cis logic common to the pathway gene promoters was found, and this logic is essential for the trans factors to regulate the pathway. PMID:25911741

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

    PubMed Central

    Welch, William 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

  5. Expression of steroidogenic factor 1 in the testis requires an E box and CCAAT box in its promoter proximal region.

    PubMed

    Daggett, M A; Rice, D A; Heckert, L L

    2000-03-01

    Steroidogenic factor 1 (SF-1), also known as adrenal 4-binding protein, is a member of the nuclear hormone receptor family that regulates transcription of genes encoding hormones and steroidogenic enzymes important to the function of the hypothalamic-pituitary-gonadal axis. The mammalian Ftz-F1 gene encodes SF-1 and is required for development of adrenal glands and gonads. To better understand the mechanisms regulating this gene in the gonads, we have examined its expression in the testis and characterized the promoter region for SF-1 in two testicular cell types. SF-1 promoter activity was examined in primary cultures of Sertoli cells and cell lines representative of Sertoli and Leydig cells. Deletion mutagenesis of the promoter identified several regions: both 5' and 3' to the transcriptional start sites that are important for transcriptional activity. Two elements, an E box and a CCAAT box, were found to be important for SF-1 transcription in the testis. An oligodeoxynucleotide containing both of these elements bound three specific protein complexes. The binding of one complex required only sequences within the E box and cross-reacted with antibodies against the basic helix-loop-helix ZIP proteins USF1 and USF2. A second specific complex required sequences within both the E box and CCAAT box for efficient binding, while a third complex predominantly interacted with sequences within the CCAAT motif. The presence of multiple protein complexes binding these sites suggests that regulation through these elements may involve interactions with different factors that depend on the state of the cell and its environment.

  6. 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

  7. 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

  8. 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

  9. Characterization of the proximal region of the goat NANOG promoter that is used for monitoring cell reprogramming and early embryo development.

    PubMed

    Guo, Yanjie; Lei, Lei; Ma, Xiaoling; Wang, Huayan

    2014-01-01

    Nanog is a key transcription regulatory molecule that plays an important role in maintaining stem cell pluripotency. However, the molecular features and transcription regulation of the NANOG gene in domestic animals are not well investigated. In this study, the 751-base pairs (bp) fragment of the proximal region of the goat NANOG promoter (GNP), which has a 572-bp promoter sequence retaining multiple transcription binding sites and a 179-bp 5' untranslated region of the goat NANOG gene, was cloned and characterized. The recombinant construct of pGNP-EGFP (enhanced green fluorescent protein) was solely activated in pluripotent cells and could be upregulated by the Oct4/Sox2 complex. The construct was stably transfected into goat fetal fibroblast (GFF) cells that were then used as the recipient cells to generate the induced pluripotent stem (iPS) cells. GNP-directed EGFP expression could be used to monitor the progression of cell reprogramming and the formation of iPS cells. The pGNP-EGFP construct was also delivered into goat oocytes cultured in vitro by microinjection. Interestingly, NANOG expression pattern in early stage goat embryos matured in vitro was asymmetrical. In two-cell embryos, the expression level of NANOG was uneven with one blastomere expressing EGFP and the next blastomere with no expression of EGFP. This was also observed in four-cell embryos. This asymmetrical expression may be due to the heterozygous expression of NANOG because of the quality of embryos and the culture environment. In conclusion, the GNP-EGFP reporter system represents a useful tool to monitor endogenous NANOG activation and for research with goat pluripotent stem cells. PMID:24183713

  10. Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain

    PubMed Central

    2014-01-01

    Background The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood. Results The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency of morphine analgesia was significantly reduced in nerve-injured mice compared with control sham-operated mice. After peripheral nerve injury, we observed a decreased expression of MOR protein and mRNA, accompanied by an increased methylation status of MOR gene PP, in DRG. However, peripheral nerve injury could not induce a decreased expression of MOR mRNA in the spinal cord. Treatment with 5-aza-2′-deoxycytidine (5-aza-dC), inhibited the increased methylation of MOR gene PP and prevented the decreased expression of MOR in DRG, thereby improved systemic, spinal and periphery morphine analgesia. Conclusions Altogether, our results demonstrate that increased methylation of the MOR gene PP in DRG is required for the decreased morphine analgesia in neuropathic pain. PMID:25118039

  11. Hepatitis B virus X protein promotes renal epithelial-mesenchymal transition in human renal proximal tubule epithelial cells through the activation of NF-κB.

    PubMed

    Li, Mei; Hu, Liping; Zhu, Fengxin; Zhou, Zhangmei; Tian, Jianwei; Ai, Jun

    2016-08-01

    Hepatitis B virus (HBV)-associated glomerulo-nephritis is the most common extra-hepatic disorder occurring with hepatitis B virus infection. In the present study, we hypothesized that HBV X protein (HBx) may play a critical role in renal interstitial fibrosis, as HBx has been shown to induce epithelial-mesenchymal transition (EMT) in renal cells. For this purpose, we successfully transfected HBx plasmid into human renal proximal tubule epithelial cells (HK-2 cells). We found that transfection with HBx plasmid significantly downregulated E-cadherin expression and upregulated α-smooth muscle actin, collagen I and fibronectin expression in a time- and concentration-dependent manner (at the lower concentrations and earlier time points). HBx also increased nuclear factor-κB (NF-κB) phosphorylation in a time- and concentration-dependent manner (again at the lower concentrations and earlier time points); however, it did not alter the phosphorylation of Smad2, Smad3, p38, phosphoinositide 3-kinase (PI3K) or extracellular signal-regulated kinase (ERK). Thus, the findings of this study demonstrate that HBx promotes EMT in renal HK-2 cells, and the potential underlying mechanisms may involve the activation of the NF-κB signaling pathway.

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

    PubMed

    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

    2012-04-01

    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.

  13. The Retroviruses Human Immunodeficiency Virus Type 1 and Moloney Murine Leukemia Virus Adopt Radically Different Strategies To Regulate Promoter-Proximal Polyadenylation

    PubMed Central

    Furger, Andre; Monks, Joan; Proudfoot, Nick J.

    2001-01-01

    Maximal gene expression in retroviruses requires that polyadenylation in the 5′ long terminal repeat (LTR) is suppressed. In human immunodeficiency virus type 1 (HIV-1) the promoter-proximal poly(A) site is blocked by interaction of U1 snRNP with the closely positioned major splice donor site (MSD) 200 nucleotides downstream. Here we investigated whether the same mechanism applies to down-regulate 5′ LTR polyadenylation in Moloney murine leukemia virus (MoMLV). Although the same molecular architecture is present in both viruses, the MoMLV poly(A) signal in the 5′ LTR is active whether or not the MSD is mutated. This surprising difference between the two retroviruses is not due to their actual poly(A) signals or MSD sequences, since exchange of either element between the two viral sequences does not alter their ability to regulate 5′ LTR poly(A) site use. Instead we demonstrate that sequence between the cap and AAUAAA is required for MSD-dependent poly(A) regulation in HIV-1, indicating a key role for this part of the LTR in poly(A) site suppression. We also show that the MoMLV poly(A) signal is an intrinsically weak RNA-processing signal. This suggests that in the absence of a poly(A) site suppression mechanism, MoMLV is forced to use a weak poly(A) signal. PMID:11689654

  14. Differential regulation of Na+ transporters along nephron during ANG II-dependent hypertension: distal stimulation counteracted by proximal inhibition.

    PubMed

    Nguyen, Mien T X; Lee, Donna H; Delpire, Eric; McDonough, Alicia A

    2013-08-15

    During angiotensin II (ANG II)-dependent hypertension, ANG II stimulates, while hypertension inhibits, Na(+) transporter activity to balance Na(+) output to input. This study tests the hypothesis that ANG II infusion activates Na(+) transporters in the distal nephron while inhibiting transporters along the proximal nephron. Male Sprague-Dawley rats were infused with ANG II (400 ng·kg(-1)·min(-1)) or vehicle for 2 wk. Kidneys were dissected (cortex vs. medulla) or fixed for immunohistochemistry (IHC). ANG II increased mean arterial pressure by 40 mmHg, urine Na(+) by 1.67-fold, and urine volume by 3-fold, evidence for hypertension and pressure natriuresis. Na(+) transporters' abundance and activation [assessed by phosphorylation (-P) or proteolytic cleavage] were measured by immunoblot. During ANG II infusion Na(+)/H(+) exchanger 3 (NHE3) abundance decreased in both cortex and medulla; Na-K-2Cl cotransporter 2 (NKCC2) decreased in medullary thick ascending loop of Henle (TALH) and increased, along with NKCC2-P, in cortical TALH; Na-Cl cotransporter (NCC) and NCC-P increased in the distal convoluted tubule; and epithelial Na(+) channel subunits and their cleaved forms were increased in both cortex and medulla. Like NKCC2, STE20/SPS1-related proline alanine-rich kinase (SPAK) and SPAK-P were decreased in medulla and increased in cortex. By IHC, during ANG II NHE3 remained localized to proximal tubule microvilli at lower abundance, and the differential regulation of NKCC2 and NKCC2-P in cortex versus medulla was evident. In summary, ANG II infusion increases Na(+) transporter abundance and activation from cortical TALH to medullary collecting duct while the hypertension drives a natriuresis response evident as decreased Na(+) transporter abundance and activation from proximal tubule through medullary TALH. PMID:23720346

  15. 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

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

    PubMed

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

    2015-09-01

    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

  17. Activation of the rat follicle-stimulating hormone receptor promoter by steroidogenic factor 1 is blocked by protein kinase a and requires upstream stimulatory factor binding to a proximal E box element.

    PubMed

    Heckert, L L

    2001-05-01

    The receptor for the pituitary glycoprotein hormone FSH (FSHR) and the nuclear hormone receptor steroidogenic factor 1 (SF-1) play important roles in control of the hypothalamic-pituitary- gonadal axis. FSHR is essential for integrating the pituitary FSH signal to gonadal response, while SF-1 is an important transcriptional regulator of many genes that function within this axis and is essential for the development of gonads and adrenal glands. Given the critical role of SF-1 in regulation of the gonads and the coexpression of FSHR and SF-1 in Sertoli and granulosa cells, we examined the ability of SF-1 to regulate transcription of the FSHR gene. We found that SF-1 stimulated rat FSHR promoter activity in a dose-dependent and promoter-specific manner. Examination of various promoter deletion mutants indicated that SF-1 acts through the proximal promoter region and upstream promoter sequences. An E box element within the proximal promoter is essential for activation of the FSHR promoter by SF-1. This element binds the transcriptional regulators USF1 and USF2 (upstream stimulatory factors 1 and 2) but not SF-1, as shown by electrophoretic mobility shift assays. In addition, functional studies identified a requirement for the USF proteins in SF-1 activation of FSHR and mapped an important regulatory domain within exons 4 and 5 of USF2. Cotransfection studies revealed that activation of protein kinase A leads to inhibition of SF-1-stimulated transcription of FSHR, while it synergized with SF-1 to activate the equine LH beta-promoter (ebeta). Thus, stimulation of the cAMP pathway differentially regulates SF-1 activation of the FSHR and ebeta-promoters.

  18. 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

  19. 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.

  20. 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.

  1. ras oncogene-dependent activation of the P4 promoter of minute virus of mice through a proximal P4 element interacting with the Ets family of transcription factors.

    PubMed Central

    Fuks, F; Deleu, L; Dinsart, C; Rommelaere, J; Faisst, S

    1996-01-01

    The P4 promoter of parvovirus minute virus of mice (MVMp) directs transcription of the genes coding for nonstructural proteins. The activity of promoter P4 is regulated by several cis-acting DNA elements. Among these, a promoter-proximal GC box was shown to be essential for P4 activity (J.K. Ahn, B.J. Gavin, G. Kumar, and D.C. Ward, J. Virol. 63:5425-5439, 1989). In this study, a motif homologous to an Ets transcription factor-binding site (EBS), located immediately upstream from the GC box, was found to be required for the full activity of promoter P4 in the ras-transformed rat fibroblast cell line FREJ4. In normal parental FR3T3 cells, the transcriptional function of P4 EBS was insignificant but could be restored by transient cell transfection with the c-Ha-ras oncogene. P4 EBS may thus contribute to the stimulation of promoter P4 in ras-transformed cells. Electrophoretic mobility shift assays using crude extracts from FREJ4 cells revealed the binding of a member(s) of the Ets family of transcription factors to the P4 EBS, as well as the interaction of two members of the Sp1 family, Sp1 and Sp3, with the adjacent GC box. When produced in Drosophila melanogaster SL2 cells, Ets-1 and Sp1 proteins acted synergistically to transactivate promoter P4 through their respective cognate sites. PMID:8627649

  2. Proximal promoter elements of the human zeta-globin gene confer embryonic-specific expression on a linked reporter gene in transgenic mice.

    PubMed

    Pondel, M D; Sharpe, J A; Clark, S; Pearson, L; Wood, W G; Proudfoot, N J

    1996-11-01

    We have investigated the transcriptional regulation of the human embryonic zeta-globin gene promoter. First, we examined the effect that deletion of sequences 5' to zeta-globin's CCAAT box have on zeta-promoter activity in erythroid cell lines. Deletions of sequences between -116 and -556 (cap = 0) had little effect while further deletion to -84 reduced zeta-promoter activity by only 2-3-fold in both transiently and stably transfected erythroid cells. Constructs containing 67, 84 and 556 bp of zeta-globin 5' flanking region linked to a beta-galactosidase reporter gene (lacZ) and hypersensitive site -40 (HS-40) of the human alpha-globin gene cluster were then employed for the generation of transgenic mice. LacZ expression from all constructs, including a 67 bp zeta-globin promoter, was erythroid-specific and most active between 8.5 and 10.5 days post-fertilisation. By 16.5 days gestation, lacZ expression dropped 40-100-fold. These results suggest that embryonic-specific activation of the human zeta-globin promoter is conferred by a 67 bp zeta-promoter fragment containing only a CCAAT and TATA box. PMID:8932366

  3. Melatonin synthesis in retina: cAMP-dependent transcriptional regulation of chicken arylalkylamine N-acetyltransferase by a CRE-like sequence and a TTATT repeat motif in the proximal promoter.

    PubMed

    Haque, Rashidul; Chong, Nelson W; Ali, Fatima; Chaurasia, Shyam S; Sengupta, Trisha; Chun, Eugene; Howell, Jennifer C; Klein, David C; Iuvone, P Michael

    2011-10-01

    Arylalkylamine N-acetyltransferase (AANAT) is the key regulatory enzyme controlling the daily rhythm of melatonin biosynthesis. In chicken retinal photoreceptor cells, Aanat transcription and AANAT activity are regulated in part by cAMP-dependent mechanisms. The purpose of this study was to identify regulatory elements within the chicken Aanat promoter responsible for cAMP-dependent induction. Photoreceptor-enriched retinal cell cultures were transfected with a luciferase reporter construct containing up to 4 kb of 5'-flanking region and the first exon of Aanat. Forskolin treatment stimulated luciferase activity driven by the ∼4 kb promoter construct and by all 5'-deletion constructs except the smallest, Aanat (-217 to +120)luc. Maximal basal and forskolin-stimulated expression levels were generated by the Aanat (-484 to +120)luc construct. This construct lacks a canonical cyclic AMP-response element (CRE), but contains two other potentially important elements in its sequence: an eight times TTATT repeat (TTATT₈) and a CRE-like sequence. Electrophoretic mobility shift assays, luciferase reporter assays, chromatin immunoprecipitation, and siRNA experiments provide evidence that these elements bind c-Fos, JunD, and CREB to enhance basal and forskolin-stimulated Aanat transcription. We propose that the CRE-like sequence and TTATT₈ elements in the 484 bp proximal promoter interact to mediate cAMP-dependent transcriptional regulation of Aanat.

  4. Expression of Steroidogenic Factor 1 in the Testis Requires an E Box and CCAAT Box in its Promoter Proximal Region1

    PubMed Central

    Daggett, Melissa A.F.; Rice, Daren A.; Heckert, Leslie L.

    2006-01-01

    Steroidogenic factor 1 (SF-1), also known as adrenal 4-binding protein, is a member of the nuclear hormone receptor family that regulates transcription of genes encoding hormones and steroidogenic enzymes important to the function of the hypothalamic-pituitary-gonadal axis. The mammalian Ftz-F1 gene encodes SF-1 and is required for development of adrenal glands and gonads. To better understand the mechanisms regulating this gene in the gonads, we have examined its expression in the testis and characterized the promoter region for SF-1 in two testicular cell types. SF-1 promoter activity was examined in primary cultures of Sertoli cells and cell lines representative of Sertoli and Leydig cells. Deletion mutagenesis of the promoter identified several regions: both 5′ and 3′ to the transcriptional start sites that are important for transcriptional activity. Two elements, an E box and a CCAAT box, were found to be important for SF-1 transcription in the testis. An oligodeoxynucleotide containing both of these elements bound three specific protein complexes. The binding of one complex required only sequences within the E box and cross-reacted with antibodies against the basic helix-loop-helix ZIP proteins USF1 and USF2. A second specific complex required sequences within both the E box and CCAAT box for efficient binding, while a third complex predominantly interacted with sequences within the CCAAT motif. The presence of multiple protein complexes binding these sites suggests that regulation through these elements may involve interactions with different factors that depend on the state of the cell and its environment. PMID:10684809

  5. 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 ...

  6. 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

  7. Cellular effect evaluation of micropollutants using transporter functions of renal proximal tubule cells.

    PubMed

    Ren, Xianghao; Lee, Yu Jin; Han, Ho Jae; Kim, In S

    2009-11-01

    Issues pertaining to the effects of micropollutants in reclaimed water are arising in terms of their effect on human health. However, current cellular methodologies face some difficulties to detect subtle effects of waterborne micropollutants at environmental concentrations (ngL(-1)-microgL(-1)) on human and animal cells. In this study, an appropriate cellular model capable of detecting the subtle effects of aquatic micropollutants at environmental concentrations using the functions of primary cultured rabbit renal proximal tubule cells (PTCs) is proposed. Tris-(2-chloroethyl)-phosphate (TCEP) was chosen as the representative micropollutant from eight typical micropollutants via lactate dehydrogenase assay. TCEP significantly decreased not only ion (sodium, calcium, and phosphate) uptake from 10(-2) mg L(-1) (64.8-82.5%, 60.4-68.8%, and 91.9-93.8% of the control, respectively), but also the expression of ion transporters (NHE-3 and L-type Ca channel) from 10(-2) mg L(-1) (53.9-87.4% and 38.6-63.6% of the control, respectively). Moreover, TCEP significantly decreased both the non-ion (glucose, fructose, and l-arginine) uptake and the expression of non-ion transporters (SGLT 1, GLUT 5, and rBAT) from 10(-2) mg L(-1). Therefore, the results demonstrated that the function of PTCs as a cellular model can be used to determine subtle effects of environmental micropollutants at low concentrations. PMID:19729184

  8. 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.

  9. Proximal humerus fractures.

    PubMed

    Price, Matthew C; Horn, Pamela L; Latshaw, James C

    2013-01-01

    Proximal humerus fractures are among the most common fractures associated with osteoporosis. With an aging population, incidence of these fractures will only increase. The proximal humerus not only forms the lateral portion of the shoulder articulation but also has significant associations with musculoskeletal and neurovascular structures. As a result, fractures of the proximal humerus can significantly impact not only the function of the shoulder joint, but the health and function of the entire upper extremity as well. Understanding of these fractures, the management options, and associated nursing care, can help reduce morbidity rate and improve functional outcomes.

  10. Bulk Topological Proximity Effect.

    PubMed

    Hsieh, Timothy H; Ishizuka, Hiroaki; Balents, Leon; Hughes, Taylor L

    2016-02-26

    Existing proximity effects stem from systems with a local order parameter, such as a local magnetic moment or a local superconducting pairing amplitude. Here, we demonstrate that despite lacking a local order parameter, topological phases also may give rise to a proximity effect of a distinctively inverted nature. We focus on a general construction in which a topological phase is extensively coupled to a second system, and we argue that, in many cases, the inverse topological order will be induced on the second system. To support our arguments, we rigorously establish this "bulk topological proximity effect" for all gapped free-fermion topological phases and representative integrable models of interacting topological phases. We present a terrace construction which illustrates the phenomenological consequences of this proximity effect. Finally, we discuss generalizations beyond our framework, including how intrinsic topological order may also exhibit this effect.

  11. Proximal fifth metatarsal fractures.

    PubMed

    Ramponi, Denise R

    2013-01-01

    The most common fracture of the foot is a fracture of the proximal fifth metatarsal. In general, there are 3 types of fractures involving the proximal fifth metatarsal area, including a proximal diaphyseal stress fracture, a Jones fracture, and an avulsion fracture of the tuberosity. Some fractures of the fifth metatarsal heal without difficulty, whereas some have the potential for nonunion or delayed healing. Each fracture has some variation in the anatomical location on the fifth metatarsal, the mechanism of injury, the radiographic findings, and the treatment plan. Avulsion fractures of the tuberosity often heal without difficulty, yet fractures distal to the area of insertion of the peroneus brevis tendon are prone to nonunion and delayed healing (). Differential diagnosis of a fifth metatarsal midfoot injury includes ankle sprains, midfoot sprains, plantar facial ruptures, peroneus tendon ruptures, and other foot fractures.

  12. 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.

  13. 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.

  14. 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

  15. 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)

  16. Traumatic proximal tibiofibular dislocation.

    PubMed

    Burgos, J; Alvarez-Montero, R; Gonzalez-Herranz, P; Rapariz, J M

    1997-01-01

    Proximal tibiofibular dislocation is an exceptional lesion. Rarer still is its presentation in childhood. We describe the clinical case of a 6-year-old boy, the victim of a road accident. He had a tibiofibular dislocation associated with a metaphyseal fracture of the tibia.

  17. 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,…

  18. 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

  19. 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.

  20. 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.

  1. Proximate Composition Analysis.

    PubMed

    2016-01-01

    The proximate composition of foods includes moisture, ash, lipid, protein and carbohydrate contents. These food components may be of interest in the food industry for product development, quality control (QC) or regulatory purposes. Analyses used may be rapid methods for QC or more accurate but time-consuming official methods. Sample collection and preparation must be considered carefully to ensure analysis of a homogeneous and representative sample, and to obtain accurate results. Estimation methods of moisture content, ash value, crude lipid, total carbohydrates, starch, total free amino acids and total proteins are put together in a lucid manner.

  2. 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).

  3. 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.

  4. The reduction of Na/H exchanger-3 protein and transcript expression in acute ischemia–reperfusion injury is mediated by extractable tissue factor(s)

    PubMed Central

    Zhang, Jianning; Babich, Victor; Bobulescu, I. Alexandru; Shi, Mingjun; McLeroy, Paul; Rogers, Thomas E.; Moe, Orson W.

    2014-01-01

    Ischemic renal injury is a formidable clinical problem, the pathophysiology of which is incompletely understood. As the Na/H exchanger-3 (NHE3) mediates the bulk of apical sodium transport and a significant fraction of oxygen consumption in the proximal tubule, we examined mechanisms by which ischemia–reperfusion affects the expression of NHE3. Ischemia–reperfusion dramatically decreased NHE3 protein and mRNA (immunohistochemistry, immunoblot, and RNA blot) in rat kidney cortex and medulla. The decrease in NHE3 protein was uniform throughout all tubules, including those appearing morphologically intact. In the kidney cortex, a decrease in NHE3 surface protein preceded that of NHE3 total protein and mRNA. Kidney homogenates from rats exposed to mild renal ischemia-reduced cell surface NHE3 protein expression in opossum kidney cells in vitro, whereas homogenates from animals with moderate-to-severe ischemia reduced both total NHE3 protein and mRNA. The decrease in total NHE3 protein was dependent on the proteasomal degradation associated with NHE3 ubiquitylation measured by coimmunoprecipitation. The transferable factor(s) from the ischemic homogenate that reduce NHE3 expression were found to be heat sensitive and to be associated with a lipid-enriched fraction, and did not include regulatory RNAs. Thus, transferable factor(s) mediate the ischemia–reperfusion injury-induced decrease in NHE3 of the kidney. PMID:21814178

  5. 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

  6. 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

  7. Hirayama Disease with Proximal Involvement

    PubMed Central

    2016-01-01

    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

  8. 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...

  9. Sodium butyrate stimulates NHE8 expression via its role on activating NHE8 basal promoter activity.

    PubMed

    Xu, Hua; McCoy, Anthony; Li, Jing; Zhao, Yang; Ghishan, Fayez K

    2015-09-15

    Butyrate is a major metabolite in colonic lumen. It is produced from bacterial fermentation of dietary fiber. Butyrate has been shown to stimulate electroneutral sodium absorption through its regulation on sodium/hydrogen exchanger 3 (NHE3). Although NHE8, the newest addition of intestinal NHE family, is involved in sodium absorption in the intestinal tract, whether butyrate modulates NHE8 expression in the intestinal epithelial cells is not known. In the current study, we showed that butyrate treatment strongly induced NHE8 protein and NHE8 mRNA expression in human intestinal epithelial cells. Transfection with the human NHE8 promoter reporter constructs showed that butyrate treatment stimulated reporter gene expression at an amount comparable with its stimulation of NHE8 mRNA expression. Interestingly, a similar result was also observed in human NHE8 promoter transfected cells after trichostatin (TSA) treatment. Gel mobility shift assay identified an enhanced Sp3 protein binding on the human NHE8 basal promoter region upon butyrate stimulation. Furthermore, Sp3 acetylation modification is involved in butyrate-mediated NHE8 activation in Caco-2 cells. Our findings suggest that the mechanism of butyrate action on NHE8 expression involves enhanced Sp3 interaction at the basal promoter region of the human NHE8 gene promoter to activate NHE8 gene transcription. Thus butyrate is involved in intestinal regulation of NHE8 resulting enhanced sodium absorption.

  10. [Management of proximal ureteral stones].

    PubMed

    Lechevallier, E; Taxer, O; Saussine, C

    2008-12-01

    Proximal ureteral stone less than 4-6mm may initially be treated by surveillance. Generally, extracorporeal shockwave lithotripsy (ESWL) is the first line treatment for proximal ureteral stones, specially for stones less than 1cm. For stones greater than 1cm, the results of ureteroscopy (URS) are better than the results of ESWL and in these cases URS may be an option. In case of failure of ESWL, URS can be proposed. URS can be the first line treatment in case of severe ureteral obstruction with no urinary infection. Proximal ureteroscopy must be careful because severe complications are not infrequent. Open surgery has very rare indication. Metabolic check-up and annually follow-up with at least a renal imaging at three months are recommended.

  11. 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.

  12. Proximal Rectus Femoris Avulsion Repair.

    PubMed

    Dean, Chase S; Arbeloa-Gutierrez, Lucas; Chahla, Jorge; Pascual-Garrido, Cecilia

    2016-06-01

    Proximal rectus femoris tendon avulsions are rare and occur mostly in male athletes. Currently, the standard of care for complete tendinous avulsions of the direct arm of the rectus femoris is nonoperative treatment. However, surgical repair may be considered in high-level athletes who have a high demand for repetitive hip flexion performed in an explosive manner or in patients in whom nonoperative treatment has failed. The purpose of this technical note is to describe the method for surgical repair of the proximal direct arm of the rectus femoris to its origin at the anterior inferior iliac spine using suture anchors. PMID:27656376

  13. 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.

  14. 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.…

  15. 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

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

    PubMed

    Campennì, Marco; Schino, Gabriele

    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.

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

    PubMed

    Campennì, Marco; Schino, Gabriele

    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

  18. Foot anomalies and proximal symphalangism.

    PubMed

    Shaw, Lauren; McCaul, Janet; Irwin, Greg J; Huntley, James S

    2012-09-01

    We report the case of a 2-week-old girl born at term (by vaginal delivery and without antenatal or perinatal events) who was referred as having "bilateral talipes and bilateral proximal symphalangism of little and ring fingers." The "talipes" was atypical with marked equinus and varus, but no cavus or adductus of the midfoot. Her mother had both symphalangism (absence of proximal interphalangeal joints) of middle, ring, and little fingers bilaterally and fixed pes planus with a rigid fixed hindfoot-and these deformities had also been present from birth. The maternal grandmother was similarly affected. However, the neonatal subject has an unaffected older sibling; maternal siblings are also unaffected. The three affected people did not have other obvious musculoskeletal abnormalities. Because of the coalitions, the child's atypical talipes was managed by a modified Kite's procedure. Symphalangism-coalition syndromes may be associated with conductive deafness because of fusion of the auditory ossicles.

  19. Fractures of the proximal humerus.

    PubMed

    Brorson, Stig

    2013-10-01

    Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate. The bandages were further supported by splints made of wood or coarse grass. Healing was expected in forty days. Different fracture patterns have been discussed and classified since Ancient Greece. Current classification of proximal humeral fractures mainly relies on the classifications proposed by Charles Neer and the AO/OTA classification. Since the late 1980's it has been known that intra- and inter-observer variation was high within the two systems. I conducted a series of observer studies to qualify the disagreement further and to study to what extent improvement of agreement could be obtained. No clinically significant differences in observer agreement were found at different levels of clinical experience, by reducing the number of categories, or by adding high quality radiographs, CT or 3D CT scans. A consistently low agreement on the Neer classification within and between untrained orthopaedic doctors was found. However, we also found that inter-observer agreement on treatment recommendation was higher than the agreement on the Neer classification. In a randomized trial we found that agreement could improve significantly by training of doctors, especially among specialists. However, classification of proximal humeral fractures remains a challenge for the conduct, reporting, and interpretation of clinical trials. The evidence for the benefits of surgery in complex fractures of the proximal humerus is weak. In three systematic reviews I studied the outcome after locking plate osteosynthesis or reverse arthroplasty in complex fractures patterns. No randomized trials or well-conducted comparative studies were identified. High failure rates suggest that the use of these

  20. 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.

  1. 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.

  2. 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.

  3. 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 ...

  4. 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.

  5. Proximal Biceps in Overhead Athletes.

    PubMed

    Chalmers, Peter N; Verma, Nikhil N

    2016-01-01

    The proximal long head of the biceps tendon and its attachment at the superior glenoid tubercle and labrum are subject to a spectrum of disorders in overhead athletes. Biceps disorders are commonly characterized by intermittent anterior or deep-seated shoulder pain exacerbated by activity. Diagnosis is reached via various physical examination maneuvers; MRI can be uncertain. Nonsteroidal anti-inflammatory medications, targeted ultrasound-guided corticosteroid injections, and supervised physical therapy are the mainstays of nonoperative treatment. Operative treatment, which remains controversial, provides reliable pain relief, restoration of function for activities of daily living, and low complication rates, but return to play can be unpredictable.

  6. Biomass proximate analysis using thermogravimetry.

    PubMed

    García, Roberto; Pizarro, Consuelo; Lavín, Antonio G; Bueno, Julio L

    2013-07-01

    This work proposes a 25 min-last thermogravimetric method as a tool to determine biomass sample's proximate analysis data (moisture, ash, volatile matter and fixed carbon contents) just by direct measure of weight changes on each sample's TG chart. Compared with international standards commonly used to that aim, TG is a faster and easier to develop technique. Obtained results were satisfactory, with AEE under 6% for moisture and volatile matter, close to 10% for fixed carbon determination and AAD of 1.6 points for ash content.

  7. The HTV Proximity Communication System

    NASA Astrophysics Data System (ADS)

    Harada, Motoyuki; Takahashi, Tetsuo; Tanaka, Tetsuo

    2002-01-01

    National Space Development Agency of Japan (NASDA) is developing the H-II Transfer Vehicle (HTV) as an unmanned logistic support vehicle for the International Space Station (ISS). The HTV, which is launched by the H-IIA rocket, transports both pressurized and un-pressurized cargoes to the ISS, reloads disposal items from the ISS and performs destructive reentry over ocean area. NASDA plans the first flight of HTV in 2005 for demonstration. The HTV will contribute the ISS assembly and logistic re-supply operations with international commonality. For unmanned vehicle operation, communication link is critical with commanding and control, especially in proximity region to the ISS. As for the HTV operation, NASDA is developing dedicated communication system installed on the Japanese Experiment Module (JEM) of the ISS, which is called the Proximity Communication System (PROX). The HTV receives commands and transmits telemetry data through the PROX in its proximity operation to the ISS. To achieve this, the PROX can communicate with the HTV on its nominal trajectory within 23km of the ISS. Especially within 3km of the ISS, the PROX has capability to perform omni-directional communication to the HTV. The PROX also has GPS receiver and send GPS data to the HTV to support the HTV navigation for relative GPS navigation used in "far" range (500m away from the ISS). In addition to the above fundamental functions, the PROX has a capability of range and range-rate measurement between the ISS and the HTV by the pseudo noise (PN) code epoch and the Doppler shift frequency. This provides a reference data independent of "main" navigation methods (rendezvous sensor navigation or GPS navigation) of the HTV. The PROX also assists the ISS crew with its commanding device, called the Hardware Command Panel (HCP), to issue time-dependent safety-related critical commands for HTV berthing/un-berthing operation. When a failure occurs somewhere on "communication path" from the PROX Base Band

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Proximal outcomes matter: a multilevel examination of the processes by which coordinating councils produce change.

    PubMed

    Javdani, Shabnam; Allen, Nicole E

    2011-03-01

    Communities are engaged in efforts to create a coordinated response to intimate partner violence. Though coordinating councils are commonly employed vehicles for such efforts, research provides only equivocal support regarding their effectiveness. These mixed findings may reflect methodological and conceptual challenges. Specifically, there is an over-reliance on conceptualizing council effectiveness in terms of distal outcomes (e.g., behavior change), rather than the intermediary processes by which councils affect change. A direct assessment of councils' proximal outcomes may highlight change mechanisms. To that end, this study investigates the extent to which councils impact proximal outcomes and examines the processes through which proximal outcomes are interrelated and linked to distal community change. Study findings suggest that perceived proximal outcomes do significantly predict variability in perceived distal community change across councils. Specifically, promotion of social capital and institutionalized change predict achievement of distal community change, and promotion of social capital also predicts achievement of institutionalized change.

  15. Proximity effect correction sensitivity analysis

    NASA Astrophysics Data System (ADS)

    Zepka, Alex; Zimmermann, Rainer; Hoppe, Wolfgang; Schulz, Martin

    2010-05-01

    Determining the quality of a proximity effect correction (PEC) is often done via 1-dimensional measurements such as: CD deviations from target, corner rounding, or line-end shortening. An alternative approach would compare the entire perimeter of the exposed shape and its original design. Unfortunately, this is not a viable solution as there is a practical limit to the number of metrology measurements that can be done in a reasonable amount of time. In this paper we make use of simulated results and introduce a method which may be considered complementary to the standard way of PEC qualification. It compares simulated contours with the target layout via a Boolean XOR operation with the area of the XOR differences providing a direct measure of how close a corrected layout approximates the target.

  16. Proximity and emergency department use

    PubMed Central

    Bergeron, Patrick; Courteau, Josiane; Vanasse, Alain

    2015-01-01

    Abstract Objective To determine if geographic proximity to an emergency department (ED) is related to ED use in a metropolitan population of patients with cardiovascular risk factors. Design Population-based, retrospective cohort study. Setting The census metropolitan area of Montreal, Que. Participants Cohort of 99 400 patients with diabetes, hypertension, or dyslipidemia in 2007 without a history of cardiovascular disease. Each patient was spatially referred to 1 of 5857 dissemination areas (DAs). Main outcome measures Annual number of visits to an ED with respect to the distance between the centroid of a patient’s DA and the closest ED, controlling for age, sex, comorbidities, and neighbourhood immigration, social, and material characteristics. Multilevel logistic and negative binomial regressions were used to determine if the proximity to the closest ED was related to ED use, frequent ED use (≥ 4 visits in a year), and number of ED visits. Results A total of 25 889 (26.0%) patients in the cohort visited an ED at least once during a 1-year period, among which 4563 (4.6%) were frequent users with at least 4 visits. These frequent users were responsible for 28 249 (45.5%) of all 62 021 visits to EDs. The distance between a DA and its closest ED was significantly and negatively correlated with ED use (P < .001), even after controlling for confounding variables. Patients living in a DA close to an ED were also more likely to be frequent users, but the extent of use among them (range from 4 to 82 ED visits) was not related to the distance to the closest ED. Conclusion These results suggest that patients at risk of cardiovascular disease living in a metropolitan area are more likely to seek a medical encounter at the ED if they live closer to it. PMID:26505061

  17. 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.

  18. 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.

  19. 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.

  20. 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…

  1. Grouping by proximity in haptic contour detection.

    PubMed

    Overvliet, Krista E; Krampe, Ralf Th; Wagemans, Johan

    2013-01-01

    We investigated the applicability of the Gestalt principle of perceptual grouping by proximity in the haptic modality. To do so, we investigated the influence of element proximity on haptic contour detection. In the course of four sessions ten participants performed a haptic contour detection task in which they freely explored a haptic random dot display that contained a contour in 50% of the trials. A contour was defined by a higher density of elements (raised dots), relative to the background surface. Proximity of the contour elements as well as the average proximity of background elements was systematically varied. We hypothesized that if proximity of contour elements influences haptic contour detection, detection will be more likely when contour elements are in closer proximity. This should be irrespective of the ratio with the proximity of the background elements. Results showed indeed that the closer the contour elements were, the higher the detection rates. Moreover, this was the case independent of the contour/background ratio. We conclude that the Gestalt law of proximity applies to haptic contour detection.

  2. 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…

  3. [Robot-assisted coelioscopic proximal tubal reanastomosis].

    PubMed

    Carbonnel, M; Roulot, A; Fay, S; Ayoubi, J-M

    2013-01-01

    We report two cases of robot-assisted coelioscopic proximal tubal reanastomosis after proximal tubal ligature. Patients were aged 43 and 34 years respectively and had previously undergone proximal tubal ligation by coagulation section at 37 years of age for the first patient, and by Filshie clip at 24 years for the second one. Both had regular menstrual cycles and their ovarian reserve was good. Their partners were presenting with normal sperm criteria. Proximal tubal reanastomosis was carried out in September 2010 by robotic coelioscopy with five extramucous vicryl 5-0 stitches on each tube and positive blue testing. Total durations of the interventions were 200 and 220minutes respectively. Postoperative outcomes were simple and patients had spontaneous pregnancy at 4 and 2.5 months respectively. Both pregnancies show normal progress currently. This is a contribution to literature data meant to determine the role of robotics in proximal tubal reanastomosis. PMID:22521989

  4. Proximity hybridization-triggered signal switch for homogeneous chemiluminescent bioanalysis.

    PubMed

    Zong, Chen; Wu, Jie; Liu, Mengmeng; Yang, Linlin; Liu, Lin; Yan, Feng; Ju, Huangxian

    2014-06-01

    A proximity hybridization-triggered signal switch was presented for convenient homogeneous chemiluminescent detection of a wide range of affinity target biomolecules, such as oligonucleotides, protein biomarkers, and aptamer-recognized targets. The presence of the target promoted the formation of a proximate complex via the proximity hybridization of two help DNA strands or the DNA strands labeled to affinity ligands, which subsequently unfolded the self-reporting molecular beacon to switch on the chemiluminescence signal. The response could be further amplified with an in situ enzymatic recycling strategy for highly sensitive chemiluminescence detection. By using an antibody as the affinity ligand, this simple protocol could sensitively detect protein biomarker in a concentration range of 6 orders of magnitude with a detection limit down to 80 fM. With the use of an aptamer as the affinity ligand, a method for homogeneous chemiluminescent detection of thrombin was proposed. The one-step and wash-free assay showed good selectivity and required only 1 μL of sample. Its high sensitivity, acceptable accuracy, and satisfactory versatility of analytes led to various applications in bioanalysis.

  5. Fast optical proximity correction: analytical method

    NASA Astrophysics Data System (ADS)

    Shioiri, Satomi; Tanabe, Hiroyoshi

    1995-05-01

    In automating optical proximity correction, calculation speed becomes important. In this paper we present a novel method for calculating proximity corrected features analytically. The calculation will take only several times the amount it takes to calculate intensity of one point on wafer. Therefore, the calculation will become extremely faster than conventional repetitive aerial image calculations. This method is applied to a simple periodic pattern. The simulated results show great improvement on linearity after correction and have proved the effectiveness of this analytical method.

  6. [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

  7. 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.

  8. Locking plates in proximal humerus fractures.

    PubMed

    Strohm, P C; Helwig, P; Konrad, G; Südkamp, N P

    2007-12-01

    It is well known that proximal humerus fractures are among the three most frequent fracture types. Epidemiological invetsigations show that in people elder than 60 years the fracture of the proximal humerus is more frequent than fractures of the hip region (17). Over the last decades several techniques have been applied for treatment of proximal humerus fractures. Widely accepted is the initiation of a conservative treatment regimen for undisplaced fractures, however, the standard treatment for displaced fractures, especially three and four part fractures, is still the center of scientific debate. Many different implants have been tested and investigated, thus demonstrating lack of sufficient results. Over the last years the development of angle stable, locking implants started and clinical studies demonstrated encouraging results. In our clinic the locking proximal humerus plate and the PHILOS plate advanced to the implant of choice for treatment of displaced proximal humerus fractures. There are still cases of implant failure and humerus head necrosis, but most of these complications were caused by the fracture type and not an implant specific problem. However the overall results with these new implants are encouraging. Key words: locking plates, proximal humerus fracture, humerus, humerus fracture, PHILOS, PHP.

  9. 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…

  10. Maturation of rat proximal tubule chloride permeability.

    PubMed

    Baum, Michel; Quigley, Raymond

    2005-12-01

    We have previously shown that neonate rabbit tubules have a lower chloride permeability but comparable mannitol permeability compared with adult proximal tubules. The surprising finding of lower chloride permeability in neonate proximals compared with adults impacts net chloride transport in this segment, which reabsorbs 60% of the filtered chloride in adults. However, this maturational difference in chloride permeability may not be applicable to other species. The present in vitro microperfusion study directly examined the chloride and mannitol permeability using in vitro perfused rat proximal tubules during postnatal maturation. Whereas there was no maturational change in mannitol permeability, chloride permeability was 6.3 +/- 1.3 x 10(-5) cm/s in neonate rat proximal convoluted tubule and 16.1 +/- 2.3 x 10(-5) cm/s in adult rat proximal convoluted tubule (P < 0.01). There was also a maturational increase in chloride permeability in the rat proximal straight tubule (5.1 +/- 0.6 x 10(-5) cm/s vs. 9.3 +/- 0.6 x 10(-5) cm/s, P < 0.01). There was no maturational change in bicarbonate-to-chloride permeabilities (P(HCO3)/P(Cl)) in the rat proximal straight tubules (PST) and proximal convoluted tubules (PCT) or in the sodium-to-chloride permeability (P(Na)/P(Cl)) in the proximal straight tubule; however, there was a significant maturational decrease in proximal convoluted tubule P(Na)/P(Cl) with postnatal development (1.31 +/- 0.12 in neonates vs. 0.75 +/- 0.06 in adults, P < 0.001). There was no difference in the transepithelial resistance measured by current injection and cable analysis in the PCT, but there was a maturational decrease in the PST (7.2 +/- 0.8 vs. 4.6 +/- 0.1 ohms x cm2, P < 0.05). These studies demonstrate there are maturational changes in the rat paracellular pathway that impact net NaCl transport during development. PMID:16051720

  11. 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

  12. 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

  13. 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

  14. Existence and convergence of best proximity points

    NASA Astrophysics Data System (ADS)

    Eldred, A. Anthony; Veeramani, P.

    2006-11-01

    Consider a self map T defined on the union of two subsets A and B of a metric space and satisfying T(A)[subset of or equal to]B and T(B)[subset of or equal to]A. We give some contraction type existence results for a best proximity point, that is, a point x such that d(x,Tx)=dist(A,B). We also give an algorithm to find a best proximity point for the map T in the setting of a uniformly convex Banach space.

  15. 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…

  16. 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

  17. [Novel treatment possibilities for proximal caries].

    PubMed

    Meyer-Lueckel, Hendrik; Fejerskov, Ole; Paris, Sebastian

    2009-01-01

    So far approaches for caries treatment follow a dichotomized scheme: Non invasive options of primary and secondary prevention are contrasted to invasive treatment of caries lesions. Depending on the treatment philosophy of dentists and dental schools an early or late invasive treatment threshold is recommended. Sealing of proximal lesions as done in pit and fissures has only been established in some dental schools, so far. Moreover, infiltration of the enamel part of lesions could close the gap between preventive and invasive measures. Most of these novel treatment options for proximal surfaces are currently in the last stages of product development. With respect to the good clinical results of proximal sealing with conventional sealants, this regimen seems already be recommendable to hamper further lesion progression in clinical practice. Caries infiltration of lesions situated on proximal and other smooth surfaces might even be a more promising approach, if clinical studies corroborate the recent in vitro findings. All these novel limited invasive strategies might be suitable to complete the current dichotomized way of caries treatment.

  18. 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

  19. Vortices in normal part of proximity system

    SciTech Connect

    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.

  20. Factors affecting proximal tubular reabsorption during development

    SciTech Connect

    Kaskel, F.J.; Kumar, A.M.; Lockhart, E.A.; Evan, A.; Spitzer, A.

    1987-01-01

    Studies performed in several animal species have demonstrated that glomerulotubular balance is maintained throughout development despite the many changes that occur in the factors known to control it. In an attempt to understand the nature of this phenomenon the authors quantified the magnitude and described the profile of these changes in guinea pigs. The changes in physical forces were assessed from measurements of hydrostatic and oncotic pressures, whereas those in the permeability characteristics of the proximal tubule epithelium were estimated from permanence to radioactivity-labelled macromolecules of graded radii, histologic measurements of the intercellular channels, and measurements of end-proximal ratio of tubular fluid-to-plasma osmolality (TF/P/sub osm/). Between 1 and 50 days of age the net pressure for reabsorption increased from 15.0 to 30.9 mmHg with the major change occurring during the first 2-3 wk of postnatal life. The urinary recovery of (/sup 3/H)inulin, (/sup 14/C)sucrose, and (/sup 14/C)creatinine, injected in the early segment of proximal tubules did not vary with age. The urinary recovery of (/sup 14/C)mannitol increased from 92% at birth to 100% at 49 days of age. The length of the zonulae occludens and the width of the intercellular channels did not change during this period. The findings support the hypothesis that during early postnatal life glomerulotubular balance is made possible by a high permeability of the proximal tubule, which compensates for the low net reabsorptive pressure. As the animal matures and the proximal tubule epithelium becomes tighter, for glomerulotubular balance to be maintained, an increase in the number of intercellular channels and in the active transport of sodium need to be postulated.

  1. 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

  2. Juvenile xanthogranuloma of the proximal nail fold.

    PubMed

    Piraccini, Bianca Maria; Fanti, Pier Alessandro; Iorizzo, Matilde; Tosti, Antonella

    2003-01-01

    An 18-month-old Caucasian boy presented with a firm 0.5 mm nodule, pink-red in color, with a yellow hue and some telangiectases on the surface, localized on the right thumbnail. The nodule involved all of the proximal nail fold and covered the proximal third of the nail. Pathology showed a dense dermal infiltrate of histiocytes, some of which had foamy nuclei, and multinucleated Touton giant cells. The lesion progressively decreased in size and had completely disappeared after 3 years. Periodic follow-up was important not only to monitor evolution of the juvenile xanthogranuloma, but also to avoid excessive growth of the lesion with possible definitive nail matrix damage.

  3. 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

  4. Children's memory and proximity to violence.

    PubMed

    Pynoos, R S; Nader, K

    1989-03-01

    The study examined 133 school-age children's memory of a sniper attack at their elementary school. Researchers analyzed the role that spatial representation, memory markers, inner plans of action, and strategies of recall played in the memory process. In recalling the event, exposed children reduced their degree of life threat, while nonexposed children increased their proximity to the violence. Clinical and forensic implications are discussed.

  5. Endoscopic proximal hamstring repair and ischial bursectomy.

    PubMed

    Dierckman, Brian D; Guanche, Carlos A

    2012-12-01

    With the significant increase in use of the arthroscope around the hip have come several less invasive techniques to manage pathologies around this joint. This technical note with a video details one such technique that allows for the endoscopic management of proximal hamstring tears and chronic ischial bursitis, which until now have been managed exclusively with much larger open approaches. This procedure allows for complete exposure of the posterior aspect of the hip in a safe, minimally invasive fashion. PMID:23766996

  6. 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

  7. 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

  8. 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

  9. 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

  10. Bilateral Brodie's abscess at the proximal tibia.

    PubMed

    Buldu, Halil; Bilen, Fikri Erkal; Eralp, Levent; Kocaoglu, Mehmet

    2012-08-01

    Brodie's abscess is a form of subacute osteomyelitis, which typically involves the metaphyses of the long tubular bones, particularly in the tibia. The diagnosis is usually made incidentally, as there are no accompanying symptoms or laboratory studies. Bilateral involvement at the proximal tibia is unusual. However, orthopaedic surgeons should be aware of this entity, as it may present without symptoms. Checking the contralateral limb for concomitant Brodie's abscess is recommended.

  11. 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

  12. Bilateral, atraumatic, proximal tibiofibular joint instability.

    PubMed

    Morrison, Troy D; Shaer, James A; Little, Jill E

    2011-01-01

    Dislocation of the tibiofibular joint is rare and usually results from a traumatic event. Only 1 case of atraumatic proximal tibiofibular joint instability in a 14-year-old girl has been reported in the literature, however this condition might occur more frequently than once thought. A wide range of treatment options exist for tibiofibular dislocations. Currently, the first choice is a conservative approach, and when this fails, surgical means such as resection of the fibula head, arthrodesis, and reconstruction are considered. However, no consensus exists on the most effective treatment. This article reports a unique case of bilateral, atraumatic, proximal tibia and fibular joint instability involving a 30-year-old man with a 20-year history of pain and laxity in the right knee. The patient had no trauma to his knees; he reported 2 immediate family members with similar complaints, which suggests that this case is likely congenital. After conservative approaches proved to be ineffective, the patient underwent capsular reconstruction using free autologous gracilis tendon. At 6-month postoperative follow-up, the patient was pain free with no locking and instability. He then underwent surgery on the left knee. At 1-year follow-up after the second surgery, the patient had no symptoms or restrictions in mobility. We provide an alternative surgical approach to arthrodesis and resection for the treatment of chronic proximal tibiofibular instability. In the treatment of chronic tibiofibular instability, we believe that reconstruction of the tibiofibular joint is a safe and effective choice.

  13. Management of proximal humerus fractures in adults

    PubMed Central

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

    2014-01-01

    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

  14. 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.

  15. 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.

  16. Proximal myopathy: diagnostic approach and initial management.

    PubMed

    Suresh, Ernest; Wimalaratna, Sunil

    2013-08-01

    Proximal myopathy presents as symmetrical weakness of proximal upper and/or lower limbs. There is a broad range of underlying causes including drugs, alcohol, thyroid disease, osteomalacia, idiopathic inflammatory myopathies (IIM), hereditary myopathies, malignancy, infections and sarcoidosis. Clinical assessment should aim to distinguish proximal myopathy from other conditions that can present similarly, identify patients who need prompt attention, like those with cardiac, respiratory or pharyngeal muscle involvement, and determine underlying cause of myopathy. Initial evaluation should include simple tests, like creatine kinase, thyroid function and (25)OH vitamin D levels, but further evaluation including neurophysiological studies, muscle imaging and muscle biopsy should be considered for patients in whom no toxic, metabolic or endocrine cause is found, and in those with clinical features suggestive of inflammatory or hereditary myopathy. Additionally, screening for malignancy and testing for anti-Jo1 antibody is indicated for selected patients with IIM. Management depends on underlying cause, and includes measures, such as removal of offending agent, correction of endocrine or metabolic problem, corticosteroids and immunosuppressive therapy for IIM, and physical therapy, rehabilitation and genetic counselling for muscular dystrophies.

  17. 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

  18. 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.

  19. 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.

  20. Optical system for proximity operations in aerospace

    NASA Astrophysics Data System (ADS)

    Zhang, Yong-Liang; Liu, Xiao-Chun; Lu, Huan-Zhang

    2008-12-01

    Satellite serving offers a potential for extending the life of satellites and reducing launching and operating costs. Proximity operations are necessary for purpose of satellite serving. As the primary measurement system, optical system can provide the information of relative navigation in near field. The paper has two main contributions. Firstly, we summarize use of optical systems for guidance and navigation in the missions of proximity operations in aerospace. Their characteristics vary from the manned missions, which are performed by astronauts on-orbit, through semi-autonomous missions, wherein human operators on the ground segment issue high level directives and sensor-guided systems on the space segment guide the execution, to the full-autonomous missions, which are executed using unmanned space robotic systems. It comes to light that future space operations will be more autonomous. Secondly, we present a concept and framework of a vision system for satellite proximity operations, which is semi-autonomous and can treat with uncooperative satellites. The vision system uses visible and infrared sensors synchronously to acquire images, which solves the problem of data integrity introduced by ambient illumination and direct sunlight for visible sensor. The vision system uses natural features on the satellite surfaces instead of artificial markers for its operation, computes relative motion and structure of the target, and tracks features in image sequences. Selected algorithms of the system have been characterized in ground environment; they are undergoing systematic sets of adaptation for space.

  1. Analytical parametrization of fusion barriers using proximity potentials

    NASA Astrophysics Data System (ADS)

    Dutt, Ishwar; Puri, Rajeev K.

    2010-06-01

    Using the three versions of proximity potentials, namely proximity 1977, proximity 1988, and proximity 2000, we present a pocket formula for fusion barrier heights and positions. This was achieved by analyzing as many as 400 reactions with mass between 15 and 296. Our parametrized formula can reproduced the exact barrier heights and positions within an accuracy of ±1%. A comparison with the experimental data is also in good agreement.

  2. Proximity and Interactive Learning in University-Firm Relationships

    ERIC Educational Resources Information Center

    Thune, Taran

    2009-01-01

    This paper addresses the question of whether proximity is always necessary for interactive learning, as proposed by recent European innovation theory. Recent research has provided a refined conceptualization of proximity, but there is little empirically-based knowledge about the actual role that proximity plays in relationships intended to foster…

  3. 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.

  4. 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

  5. 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

  6. Characterization of glucose transport by cultured rabbit kidney proximal convoluted and proximal straight tubule cells.

    PubMed

    Del Valle, Pedro L; Trifillis, Anna; Ruegg, Charles E; Kane, Andrew S

    2002-04-01

    Rabbit kidney proximal convoluted tubule (RPCT) and proximal straight tubule (RPST) cells were independently isolated and cultured. The kinetics of the sodium-dependent glucose transport was characterized by determining the uptake of the glucose analog alpha-methylglucopyranoside. Cell culture and assay conditions used in these experiments were based on previous experiments conducted on the renal cell line derived from the whole kidney of the Yorkshire pig (LLC-PK1). Results indicated the presence of two distinct sodium-dependent glucose transporters in rabbit renal cells: a relatively high-capacity, low-affinity transporter (V(max) = 2.28 +/- 0.099 nmoles/mg protein min, Km = 4.1 +/- 0.27 mM) in RPCT cells and a low-capacity, high-affinity transporter (V(max) = 0.45 +/- 0.076 nmoles/mg protein min, K(m) = 1.7 +/- 0.43 mM) in RPST cells. A relatively high-capacity, low-affinity transporter (V(max) = 1.68 +/- 0.215 nmoles/mg protein min, Km = 4.9 +/- 0.23 mM) was characterized in LLC-PK1 cells. Phlorizin inhibited the uptake of alpha-methylglucopyranoside in proximal convoluted, proximal straight, and LLC-PK1 cells by 90, 50, and 90%, respectively. Sodium-dependent glucose transport in all three cell types was specific for hexoses. These data are consistent with the kinetic heterogeneity of sodium-dependent glucose transport in the S1-S2 and S3 segments of the mammalian renal proximal tubule. The RPCT-RPST cultured cell model is novel, and this is the first report of sodium-dependent glucose transport characterization in primary cultures of proximal straight tubule cells. Our results support the use of cultured monolayers of RPCT and RPST cells as a model system to evaluate segment-specific differences in these renal cell types.

  7. 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.

  8. Ewing's sarcoma of proximal humeral epiphysis.

    PubMed

    Esmaili, Heydar Ali; Niknejad, Mohammad Taghi; Mohajeri, Shiva

    2015-02-01

    Ewing's sarcoma is one of the most common primary bone tumors of childhood. The tumor is almost always metaphyseal or diaphyseal, within long bones. In children, lesions of the epiphysis are often benign, with the most common diagnosis being chondroblastoma. Rarely, 1%-2% of Ewing sarcomas may involve epiphysis. We present a case of Ewing's sarcoma of the proximal humeral epiphysis in a 13-year-old boy. This case adds to previously reported cases of epiphyseal Ewing sarcoma and suggests that the diagnosis should be considered for pediatric epiphyseal lesions. PMID:25644805

  9. Fractures of the proximal humeral epiphysis.

    PubMed

    Burgos-Flores, J; Gonzalez-Herranz, P; Lopez-Mondejar, J A; Ocete-Guzman, J G; Amaya-Alarcón, S

    1993-01-01

    Twenty-two patients with marked displacement of a fracture of the proximal humeral epiphysis have been treated with closed or open reduction and fixation by Kirschner wires. At an average follow-up of 6.8 years there have been good functional results in almost all patients (91.1), with better results in patients under 13 years of age particularly with less residual displacement or angulation. Since there is a greater occurrence of residual deformity and symmetria and limitation of motion in older patients, a more aggressive approach to correct the initial displacement and angulation is warranted in those over the age of 13 years.

  10. 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

  11. Proximal monomelic amyotrophy of the upper limb.

    PubMed

    Amir, D; Magora, A; Vatine, J J

    1987-07-01

    A 30-year-old patient of Central European origin, suffering from monomelic amyotrophy, is presented. The disease was characterized by proximal weakness of one upper limb, mainly of the shoulder girdle, accompanied by atrophy. The electrodiagnostic examination revealed signs of partial denervation in the presence of normal motor and sensory conduction. The disease, which is probably of the anterior horn cells, had a benign course and good prognosis, as evident from repeated examinations during a follow-up of eight years. PMID:3606370

  12. 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

  13. Carbon nanotube proximity influences rice DNA

    NASA Astrophysics Data System (ADS)

    Katti, Dinesh R.; Sharma, Anurag; Pradhan, Shashindra Man; Katti, Kalpana S.

    2015-07-01

    The uptake of carbon nanotubes (CNT) influences the output of plants, potentially through interactions between the DNA and CNTs. However, little is known about the changes in the plant DNA due to CNT proximity. We report changes in rice plant DNA in the proximity of single walled CNT (SWCNT) using molecular dynamics simulations. The DNA experiences breaking and forming of hydrogen bonds due to unzipping of Watson-Crick (WC) nucleobase pairs and wrapping onto SWCNT. The number of hydrogen bonds between water and DNA nucleobases decreases due to the presence of SWCNT. A higher number of guanine-cytosine (Gua-Cyt) WC hydrogen bonds break as compared to adenine-thymine (Ade-Thy), which suggests that Gua and Cyt bases play a dominant role in DNA-SWCNT interactions. We also find that changes to non-WC nucleobase pairs and van der Waals attractive interactions between WC nucleobase pairs and SWCNT cause significant changes in the conformation of the DNA.

  14. Testing simple indices of habitat proximity.

    PubMed

    Winfree, Rachael; Dushoff, Jonathan; Crone, Elizabeth E; Schultz, Cheryl B; Budny, Robert V; Williams, Neal M; Kremen, Claire

    2005-06-01

    Simple measures of habitat proximity made primarily on the basis of land cover are widely used in the ecological literature to infer habitat connectivity, or the potential for animal movement among resource patches. However, such indices rarely have been tested against observations of animal movement or against more detailed biological models. We developed a priori expectations as to the types of study systems and organisms for which various habitat proximity indices would be best suited. We then used data from three study systems and four species to test which, if any, of the indices were good predictors of population-level responses. Our a priori expectations about index performance were not upheld. The indices that consider both habitat area and distance from the focal patch were highly correlated with each other, suggesting that they do index similar quantities. However, none of the indices performed well in predicting population response variables. The results suggest that the pattern of habitat cover alone may be insufficient to predict the process of animal movement.

  15. Fast proximity algorithm for MAP ECT reconstruction

    NASA Astrophysics Data System (ADS)

    Li, Si; Krol, Andrzej; Shen, Lixin; Xu, Yuesheng

    2012-03-01

    We arrived at the fixed-point formulation of the total variation maximum a posteriori (MAP) regularized emission computed tomography (ECT) reconstruction problem and we proposed an iterative alternating scheme to numerically calculate the fixed point. We theoretically proved that our algorithm converges to unique solutions. Because the obtained algorithm exhibits slow convergence speed, we further developed the proximity algorithm in the transformed image space, i.e. the preconditioned proximity algorithm. We used the bias-noise curve method to select optimal regularization hyperparameters for both our algorithm and expectation maximization with total variation regularization (EM-TV). We showed in the numerical experiments that our proposed algorithms, with an appropriately selected preconditioner, outperformed conventional EM-TV algorithm in many critical aspects, such as comparatively very low noise and bias for Shepp-Logan phantom. This has major ramification for nuclear medicine because clinical implementation of our preconditioned fixed-point algorithms might result in very significant radiation dose reduction in the medical applications of emission tomography.

  16. Proximal intentional neglect: a case study.

    PubMed Central

    Gold, M; Shuren, J; Heilman, K M

    1994-01-01

    Although neglect has been demonstrated in the horizontal, vertical, and radial planes of space and has been attributed to sensory-attentional, motor-intentional, and representational deficits, motor intentional neglect in the radial plane has not been previously described. A patient who had a right parietal infarct was tested with a modified cancellation task that uses a fixed window, thereby controlling attentional demands and allowing one to dissociate between intentional and representational neglect. This patient showed proximal (radial) intentional neglect (a failure to move towards or in proximal space). Unlike controls whose search times decreased with increasing window size, our patient showed no change in search time as a function of window size. This pattern of behaviour suggests that the patient's search strategy does not incorporate factors such as the relation between a fixed target space and a variably sized aperture, but rather was based on the allocation of a certain amount of resources for a fixed period of time after which, regardless of performance, the patient would stop searching. PMID:7964818

  17. Updated Classification System for Proximal Humeral Fractures

    PubMed Central

    Guix, José M. Mora; Pedrós, Juan Sala; Serrano, Alejandro Castaño

    2009-01-01

    Proximal humeral fractures can restrict daily activities and, therefore, deserve efficient diagnoses that minimize complications and sequels. For good diagnosis and treatment, patient characteristics, variability in the forms of the fractures presented, and the technical difficulties in achieving fair results with surgical treatment should all be taken into account. Current classification systems for these fractures are based on anatomical and pathological principles, and not on systematic image reading. These fractures can appear in many different forms, with many characteristics that must be identified. However, many current classification systems lack good reliability, both inter-observer and intra-observer for different image types. A new approach to image reading, following a well-designed set and sequence of variables to check, is needed. We previously reported such an image reading system. In the present study, we report a classification system based on this image reading system. Here we define 21 fracture characteristics and apply them along with classical Codman approaches to classify fractures. We base this novel classification system for classifying proximal humeral fractures on a review of scientific literature and improvements to our image reading protocol. Patient status, fracture characteristics and surgeon circumstances have been important issues in developing this system. PMID:19574487

  18. 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.

  19. 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

  20. Obesity and Supermarket Access: Proximity or Price?

    PubMed Central

    Aggarwal, Anju; Hurvitz, Philip M.; Monsivais, Pablo; Moudon, Anne V

    2012-01-01

    Objectives. We examined whether physical proximity to supermarkets or supermarket price was more strongly associated with obesity risk. Methods. The Seattle Obesity Study (SOS) collected and geocoded data on home addresses and food shopping destinations for a representative sample of adult residents of King County, Washington. Supermarkets were stratified into 3 price levels based on average cost of the market basket. Sociodemographic and health data were obtained from a telephone survey. Modified Poisson regression was used to test the associations between obesity and supermarket variables. Results. Only 1 in 7 respondents reported shopping at the nearest supermarket. The risk of obesity was not associated with street network distances between home and the nearest supermarket or the supermarket that SOS participants reported as their primary food source. The type of supermarket, by price, was found to be inversely and significantly associated with obesity rates, even after adjusting for individual-level sociodemographic and lifestyle variables, and proximity measures (adjusted relative risk = 0.34; 95% confidence interval = 0.19, 0.63) Conclusions. Improving physical access to supermarkets may be one strategy to deal with the obesity epidemic; improving economic access to healthy foods is another. PMID:22698052

  1. Proximal interphalangeal joint dislocations without fractures.

    PubMed

    Vicar, A J

    1988-02-01

    Injuries to the proximal interphalangeal joint are extremely common. An understanding of the complex anatomy of this joint is essential for diagnosis and treatment of proximal interphalangeal joint sprains and dislocations. Lateral injuries are among the commonest injuries in the hand. These are often stable after reduction, requiring only closed treatment. Occasionally, however, the collateral ligament can be trapped in the joint and require open reduction. Dorsal dislocations represent the most common dislocation in the hand. These, too, are usually stable after reduction and can be treated by closed methods. On occasion, however, these dislocations will be open or irreducible by closed means, requiring surgical intervention and repair of damaged structures. Complex rotary dislocations are exactly that: complex. An exact understanding of the damaged structures and causes of irreducibility frequently makes this an injury often requiring open reduction and selective repair of damaged soft tissue structures. Fortunately, prompt diagnosis, reduction, and institution of appropriate treatment can usually afford the patient good function after these injuries. It must be noted that stiffness is more common than instability, and active range-of-motion exercises instituted at the proper time are essential. These joints will often remain permanently thicker after injury in spite of optimal care, and tenderness and soreness with use may persist for 6 to 12 months.

  2. Ecology: the proximate cause of frog declines?

    PubMed

    Di Rosa, Ines; Simoncelli, Francesca; Fagotti, Anna; Pascolini, Rita

    2007-05-31

    Pounds et al. argue that global warming contributes to amphibian declines by encouraging outbreaks of the chytrid fungus Batrachochytrium dendrobatidis. Although our findings agree with the climate-linked epidemic hypothesis, this pathogen is probably not the only proximate factor in such cases: in the Trasimeno Lake area of Umbria in central Italy, for example, the water frog Rana lessonae first declined in the late 1990s, yet chytridiomycosis was not observed until 2003 (refs 5, 6). Here we show that the chytrid was common there throughout 1999-2002, in a previously unknown form that did not cause disease. We therefore think that the focus by Pounds et al. on a single pathogen is hard to justify because the host-parasite ecology is at present so poorly understood.

  3. 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.

  4. 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.

  5. [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

  6. [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.

  7. Novel superconducting proximized heterostructures for ultrafast photodetection

    NASA Astrophysics Data System (ADS)

    Pepe, G. P.; Parlato, L.; Marrocco, N.; Pagliarulo, V.; Peluso, G.; Barone, A.; Tafuri, F.; Uccio, U. Scotti di; Miletto, F.; Radovic, M.; Pan, D.; Sobolewski, Roman

    2009-11-01

    Weak ferromagnet/superconductor (F/S) proximity bilayers have been fabricated and characterized for basic physics studies concerning the ultrafast carrier dynamics in layered materials. The normalized reflectivity change (Δ R/ R) as a function of the time delay between the pump and the probe laser beams has been measured in F/S heterostructures formed by a low critical temperature superconductor (Nb) with a NiCu overlayer, and a high Tc superconductor (YBCO) covered by Au/NiCu and manganite (LSMO) overlayers. The attention is mainly focused to the investigation of nonequilibrium excitation dynamics inside different bilayers in the low temperature region. The presence of the weak ferromagnetic overlayer produces faster optical relaxation times with respect to sole superconducting films. The results are promising in view of potential applications as ultrafast kinetic inductance superconducting photodetectors as confirmed by preliminary time-resolved photoimpedance experiments on both Nb and NiCu(21 nm)/Nb(70 nm) samples.

  8. Protein structure alignment beyond spatial proximity.

    PubMed

    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.

  9. Proximity to mining industry and cancer mortality.

    PubMed

    Fernández-Navarro, Pablo; García-Pérez, Javier; Ramis, Rebeca; Boldo, Elena; López-Abente, Gonzalo

    2012-10-01

    Mining installations are releasing toxic substances into the environment which could pose a health problem to populations in their vicinity. We sought to investigate whether there might be excess cancer-related mortality in populations residing in towns lying in the vicinity of Spanish mining industries governed by the Integrated Pollution Prevention and Control Directive, and the European Pollutant Release and Transfer Register Regulation, according to the type of extraction method used. An ecologic study was designed to examine municipal mortality due to 32 types of cancer, across the period 1997 through 2006. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Poisson regression models, using the Bayesian conditional autoregressive model proposed by Besag, York and Molliè and Integrated Nested Laplace Approximations for Bayesian inference, were used: to analyze risk of dying from cancer in a 5-kilometer zone around mining installations; effect of type of industrial activity; and to conduct individual analyses within a 50-kilometer radius of each installation. Excess mortality (relative risk, 95% credible interval) of colorectal cancer (1.097, 1.041-1.157), lung cancer (1.066, 1.009-1.126) specifically related with proximity to opencast coal mining, bladder cancer (1.106, 1.016-1.203) and leukemia (1.093, 1.003-1.191) related with other opencast mining installations, was detected among the overall population in the vicinity of mining installations. Other tumors also associated in the stratified analysis by type of mine, were: thyroid, gallbladder and liver cancers (underground coal installations); brain cancer (opencast coal mining); stomach cancer (coal and other opencast mining installations); and myeloma (underground mining installations). The results suggested an association between risk of dying due to digestive, respiratory, hematologic and thyroid cancers and proximity to Spanish mining

  10. Fixation of proximal humeral prostheses and rotational micromotion.

    PubMed

    Harris, T E; Jobe, C M; Dai, Q G

    2000-01-01

    Twenty pairs of cadaveric humeri were used to compare the rotational stability of proximal humeral prostheses fixed by proximal cementation with the stability offered by press fit or full cementation. For each proximally cemented specimen, only the upper portion of the prosthesis was coated with cement. For the fully cemented specimens, a cement restrictor was used just distal to the prosthesis, and a finger-packing technique was used to fill the proximal humeral medullary canal. Torque was applied to the Morse taper of the prostheses, and rotational micromotion was measured at the level of the osteotomy. In each of 11 pairs of cadaveric humeri, one side was press fit and the contralateral side was proximally cemented; in each of 9 pairs, proximal cementation was compared with full cementation. Proximally cemented prostheses' micromotion was significantly less than that of press-fit prostheses (P = .0016). There was no difference in micromotion between proximal cementation and full cementation (P = .82). Proximal cementation increased initial fixation over press fit. Full cementation did not increase rotational stability.

  11. 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

  12. Loss of tubular creatinine secretion as the only sign of tubular proximal cell dysfunction in light chain proximal tubulopathy

    PubMed Central

    Stehlé, Thomas; Vignon, Marguerite; Flamant, Martin; Figueres, Marie-Lucile; Rabant, Marion; Rodenas, Anita; Noël, Laure-Hélène; Arnulf, Bertrand; Vidal-Petiot, Emmanuelle

    2016-01-01

    Abstract Light chain proximal tubulopathy (LCPT) is a rare disease, characterized by cytoplasmic inclusions of light chain (usually kappa) immunoglobulins. Clinical presentation is usually a Fanconi syndrome. The proximal tubular dysfunction can be incomplete, and exceptional cases of LCPT without any tubular dysfunction have even been described. Here, we report a case of LCPT in which the only sign of proximal tubulopathy is the absence of secretion of creatinine, as assessed by the simultaneous measurement of renal clearance of creatinine and 51CrEDTA. The loss of tubular creatinine secretion as a sign of tubular proximal cell dysfunction ought to be identified in patients with light chain proximal tubulopathy as it leads to a clinically relevant underestimation of GFR by the creatinine-derived equations. The prevalence and prognostic significance of this particular proximal tubular damage in LCPT remain to be determined. PMID:27367983

  13. 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

  14. Regulation of Drosophila Adh promoter switching by an initiator-targeted repression mechanism.

    PubMed Central

    Ren, B; Maniatis, T

    1998-01-01

    The stage-specific expression of the Drosophila alcohol dehydrogenase (Adh) gene is achieved through the alternate activation of two tandem promoters. The proximal promoter is active primarily during late embryonic development and early larval stages, while the distal promoter is active in late third instar larvae and adults. Here, we provide evidence that this Adh promoter switch is regulated by a zinc finger repressor protein (AEF-1) that is expressed predominantly in adult flies and targets the initiator region of the proximal promoter. We propose that AEF-1 plays a critical role in Adh promoter switching by blocking interactions between a component of the general transcription machinery and the initiator region of the proximal promoter. PMID:9463385

  15. 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.

  16. Anatomic Reconstruction of the Proximal Tibiofibular Joint.

    PubMed

    Warner, Brent T; Moulton, Samuel G; Cram, Tyler R; LaPrade, Robert F

    2016-02-01

    Proximal tibiofibular joint (PTFJ) instability can be easily missed or confused for other, more common lateral knee pathologies such as meniscal tears, fibular collateral ligament injury, biceps femoris pathology, or iliotibial band syndrome. Because of this confusion, some authors believe that PTFJ instability is more common than initially appreciated. Patients with PTFJ subluxation may have no history of inciting trauma or injury, and it is not uncommon for these patients to have bilateral symptoms and generalized ligamentous laxity. Currently, the optimal surgical treatment for patients with chronic PTFJ instability is unknown. Historically, a variety of surgical treatments have been reported. Initially, joint arthrodesis and fibular head resection were recommended. More recently, temporary screw fixation, nonanatomic reconstruction with strips of the biceps femoris tendon or iliotibial band, and reconstruction with free hamstring autograft have been described. The purpose of this report is to present our surgical technique for treatment of chronic PTFJ instability using an anatomic reconstruction of the posterior ligamentous structures of the PTFJ with a semitendinosus autograft. PMID:27274455

  17. 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.

  18. 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.

  19. Effects of thrust reversing in ground proximity

    NASA Technical Reports Server (NTRS)

    Joshi, P. B.; Hughes, R. V.

    1987-01-01

    The changes in stability and control characteristics encountered by a thrust reversing aircraft during its final approach, landing, and ground roll are described. These changes include a strong pitch-up accompanied by the loss of horizontal tail and aileron control effectiveness. The magnitude of reverser induced changes in ground effect are much larger than corresponding changes in free air. Some unexpected unsteady motions exhibited in wind tunnel by an aircraft model with reversers operating in ground proximity are also described. The cause of this oscillatory behavior was determined to be an unsteady interaction between the wall jets formed by impingement of reverser jets on the ground and the on-coming free stream. Time histories of rolling moments measured by the wind tunnel balance or support system were removed and frequencies were scaled by Strouhal number to full scale. Corrected time series were used to simulate the motion of a fighter aircraft with thrust reversers in ground effect. The simulation predicted large roll angles and nose down attitude at touchdown. Some phenomena of jet attachment to solid surfaces are discussed and areas for future research are recommended.

  20. 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.

  1. 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.

  2. Scintillation Proximity Assay of Arginine Methylation

    PubMed Central

    Wu, Jiang; Xie, Nan; Feng, You; Zheng, Y. George

    2011-01-01

    Methylation of arginine residues, catalyzed by protein arginine methyltransferases (PRMTs), is one important protein post-translational modification involved in epigenetic regulation of gene expression. A fast and effective assay for PRMT can provide valuable information for dissecting the biological functions of PRMTs, as well as for screening small-molecule inhibitors of arginine methylation. Currently, among the methods used for PRMT activity measurement, many contain laborious separation procedures, which restrict the applications of these assays for high-throughput screening (HTS) in drug discovery. The authors report here a mix-and-measure method to measure PRMT activity based on the principle of scintillation proximity assay (SPA). In this assay, 3H-AdoMet was used as methyl donor, and biotin-modified histone H4 peptide served as a methylation substrate. Following the methylation reaction catalyzed by PRMTs, streptavidin-coated SPA beads were added to the reaction solution, and SPA signals were detected by a MicroBeta scintillation counter. No separation step is needed, which simplifies the assay procedure and greatly enhances the assay speed. Particularly, the miniaturization and robustness suggest that this method is suited for HTS of PRMT inhibitors. PMID:21821785

  3. 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

  4. Dynamic proximity of spatio-temporal sequences.

    PubMed

    Horn, David; Dror, Gideon; Quenet, Brigitte

    2004-09-01

    Recurrent networks can generate spatio-temporal neural sequences of very large cycles, having an apparent random behavior. Nonetheless a proximity measure between these sequences may be defined through comparison of the synaptic weight matrices that generate them. Following the dynamic neural filter (DNF) formalism we demonstrate this concept by comparing teacher and student recurrent networks of binary neurons. We show that large sequences, providing a training set well exceeding the Cover limit, allow for good determination of the synaptic matrices. Alternatively, assuming the matrices to be known, very fast determination of the biases can be achieved. Thus, a spatio-temporal sequence may be regarded as spatio-temporal encoding of the bias vector. We introduce a linear support vector machine (SVM) variant of the DNF in order to specify an optimal weight matrix. This approach allows us to deal with noise. Spatio-temporal sequences generated by different DNFs with the same number of neurons may be compared by calculating correlations of the synaptic matrices of the reconstructed DNFs. Other types of spatio-temporal sequences need the introduction of hidden neurons, and/or the use of a kernel variant of the SVM approach. The latter is being defined as a recurrent support vector network (RSVN).

  5. Proximate and elemental analysis of infant formula.

    PubMed

    Tanner, J T

    1982-11-01

    The Nutrient Surveillance Branch has been conducting a survey of infant formula products for Fiscal Year 1981. Each product has been carefully analyzed and the results compared to the label declaration and the minimum-maximum limits specified by the American Academy of Pediatrics' Committee on Nutrition (CON/AAP). Proximate and elemental analyses were made. Protein, fat, ash, and total solids (moisture) were determined by AOAC methods. Osmolality, density, and fatty acids (linoleic) were also determined. Carbohydrates were calculated by difference and caloric content was calculated by using the general Atwater factors. Elemental analysis for Ca, P, Mg, Fe, Zn, Cu, Mn, Na, and K were performed by induction coupled plasma absorption spectroscopy. Chloride was assayed by potentiometric titration with AgNO3. A summary of the findings from the infant formula survey have been compared with CON/AAP recommendations. In general, there were only a few exceptions where the label claims and the CON/AAP requirements were not met. However, in none of these cases was the difference considered to be of public health significance.

  6. Proximity Navigation of Highly Constrained Spacecraft

    NASA Technical Reports Server (NTRS)

    Scarritt, S.; Swartwout, M.

    2007-01-01

    Bandit is a 3-kg automated spacecraft in development at Washington University in St. Louis. Bandit's primary mission is to demonstrate proximity navigation, including docking, around a 25-kg student-built host spacecraft. However, because of extreme constraints in mass, power and volume, traditional sensing and actuation methods are not available. In particular, Bandit carries only 8 fixed-magnitude cold-gas thrusters to control its 6 DOF motion. Bandit lacks true inertial sensing, and the ability to sense position relative to the host has error bounds that approach the size of the Bandit itself. Some of the navigation problems are addressed through an extremely robust, error-tolerant soft dock. In addition, we have identified a control methodology that performs well in this constrained environment: behavior-based velocity potential functions, which use a minimum-seeking method similar to Lyapunov functions. We have also adapted the discrete Kalman filter for use on Bandit for position estimation and have developed a similar measurement vs. propagation weighting algorithm for attitude estimation. This paper provides an overview of Bandit and describes the control and estimation approach. Results using our 6DOF flight simulator are provided, demonstrating that these methods show promise for flight use.

  7. Proximate and ultimate causes of punishment and strong reciprocity.

    PubMed

    Barclay, Pat

    2012-02-01

    While admirable, Guala's discussion of reciprocity suffers from a confusion between proximate causes (psychological mechanisms triggering behaviour) and ultimate causes (evolved function of those psychological mechanisms). Because much work on "strong reciprocity" commits this error, I clarify the difference between proximate and ultimate causes of cooperation and punishment. I also caution against hasty rejections of "wide readings" of experimental evidence.

  8. Analysis of pattern density on process proximity compensation

    NASA Astrophysics Data System (ADS)

    Jung, Sunwook; Lo, Fred; Yang, Tien-Chu; Yang, Ta-Hong; Chen, Kuang-Chao; Lu, Chih-Yuan

    2007-03-01

    The challenges of ever-smaller CD (Critical Dimension) budget for advanced memory product requires tight ACLV (Across-Chip Line-width Variation) control. In addition to the lithographic MOPC (Model-based Optical Proximity Correction) for DCD (photo CD) control, the process correction for etch proximity effect can no longer be ignored. To meet on our requirement on final CD accuracy for critical layer, a set of test pattern, that represents memory array in one of our critical layers, has been generated for both photo and etch process characterizations. Through the combination of different pattern-coverage areas in the test mask and wafer map design, various local (chip-level) pattern densities of 40%~70% and global (wafer-level) pattern densities of 35%~65% were achieved for optical and etch proximity study. The key contributors to the process proximity effect were identified and voluminous data has been extracted from the memory block like patterns for statistical analysis. The photo and etch proximity effects were hence modeled as function of memory block separation, local pattern density as well as global pattern density. Finally, the respective photo and etch proximity effects through model-based proximity correction and rule-based proximity correction were applied in a multi-step flow to products.

  9. 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

  10. 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

  11. Interactive orbital proximity operations planning system

    NASA Technical Reports Server (NTRS)

    Grunwald, Arthur J.; Ellis, Stephen R.

    1990-01-01

    An interactive graphical planning system for on-site planning of proximity operations in the congested multispacecraft environment about the space station is presented. The system shows the astronaut a bird's eye perspective of the space station, the orbital plane, and the co-orbiting spacecraft. The system operates in two operational modes: (1) a viewpoint mode, in which the astronaut is able to move the viewpoint around in the orbital plane to range in on areas of interest; and (2) a trajectory design mode, in which the trajectory is planned. Trajectory design involves the composition of a set of waypoints which result in a fuel-optimal trajectory which satisfies all operational constraints, such as departure and arrival constraints, plume impingement constraints, and structural constraints. The main purpose of the system is to present the trajectory and the constraints in an easily interpretable graphical format. Through a graphical interactive process, the trajectory waypoints are edited until all operational constraints are satisfied. A series of experiments was conducted to evaluate the system. Eight airline pilots with no prior background in orbital mechanics participated in the experiments. Subject training included a stand-alone training session of about 6 hours duration, in which the subjects became familiar with orbital mechanics concepts and performed a series of exercises to familiarize themselves with the control and display features of the system. They then carried out a series of production runs in which 90 different trajectory design situations were randomly addressed. The purpose of these experiments was to investigate how the planning time, planning efforts, and fuel expenditures were affected by the planning difficulty. Some results of these experiments are presented.

  12. 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

  13. 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.

  14. Novel Biosensor of Membrane Protein Proximity Based on Fluorogen Activated Proteins.

    PubMed

    Vasilev, Kalin V; Gallo, Eugenio; Shank, Nathaniel; Jarvik, Jonathan W

    2016-01-01

    We describe a novel biosensor system for reporting proximity between cell surface proteins in live cultured cells. The biosensor takes advantage of recently developed fluorogen-activating proteins (FAPs) that display fluorescence only when bound to otherwise-nonfluorescent fluorogen molecules. To demonstrate feasibility for the approach, two recombinant rapamycin-binding proteins were expressed as single-pass plasma membrane proteins in HeLa cells; one of the proteins (scAvd- FRB) carried an extracellular avidin tag; the other (HL1-TO1-FKBP) carried an extracellular FAP. Cells were incubated with a membrane-impermeable bivalent ligand (biotin-PEG2000-DIR) consisting of biotin joined to a dimethyl-indole red (DIR) fluorogen by a polyethylene glycol linker, thus tethering the fluorogen to the scAvd-FRB fusion protein. Addition of rapamycin, which promotes FKBP-FRB dimerization and thereby brings the FAP in close proximity to the tethered fluorogen, led to a significant increase in DIR fluorescence. We call the new proximity assay TEFLA, for tethered fluorogen assay. PMID:27055753

  15. Detecting pairing symmetry in Fe-based superconductors: Solitons and proximity patch

    NASA Astrophysics Data System (ADS)

    Vakaryuk, Victor; Stanev, Valentin; Lee, Wei-Cheng; Levchenko, Alex

    2013-03-01

    We suggest a mechanism which promotes the existence of a phase soliton - topological defect formed in the relative phase of superconducting gaps of a two-band superconductor with s+ - type of pairing. This mechanism exploits the proximity effect with a conventional s-wave superconductor which favors the alignment of the phases of the two-band superconductor which, in the case of s+ - pairing, are π-shifted in the absence of proximity. In the case of a strong proximity such effect can be used to reduce soliton's energy below the energy of a soliton-free state thus making the soliton thermodynamically stable. Based on this observation we consider an experimental setup, applicable both for stable and metastable solitons, which can be used to distinguish between s+ - and s+ + types of pairing in the iron-based multiband superconductors. The financial support was provided by the Center of Emergent Superconductivity funded by the U.S. DOE, Award No. DE-AC0298CH1088. W.C.L. acknowledges Roving Postdoc Program sponsored by CES. AL acknowledges support from Michigan State University.

  16. 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

  17. Neurogenic regulation of proximal bicarbonate and chloride reabsorption.

    PubMed

    Cogan, M G

    1986-01-01

    Although a change in renal nerve activity is known to alter proximal reabsorption, it is unclear whether reabsorption of NaHCO3 or NaCl or both are affected. Sprague-Dawley rats (n = 10) were studied using free-flow micropuncture techniques during euvolemia and following acute ipsilateral denervation. Glomerular filtration rate and single nephron glomerular filtration rate were stable. Absolute proximal bicarbonate reabsorption fell following denervation (933 +/- 40 to 817 +/- 30 pmol/min) with a parallel reduction in chloride reabsorption (1,643 +/- 116 to 1,341 +/- 129 peq/min). Urinary sodium, potassium, bicarbonate, and chloride excretion all increased significantly. To further assess the physiological significance of neurogenic modulation of proximal transport, other rats (n = 6) were subjected to acute unilateral nephrectomy (AUN). There is evidence that AUN induces a contralateral natriuresis (renorenal reflex) at least partially by causing inhibition of efferent renal nerve traffic. AUN caused significant changes in proximal NaHCO3 and NaCl reabsorption as well as in whole kidney electrolyte excretion in the same pattern as had denervation. Prior denervation of the remaining kidney prevented the proximal and whole kidney response to AUN (n = 6). In conclusion, depression of renal nerve activity inhibits both NaHCO3 and NaCl reabsorption in the rat superficial proximal convoluted tubule. The data are consistent with the hypothesis that changes in renal nerve activity modify whole kidney electrolyte excretion under physiological conditions at least partially by regulating proximal transport.

  18. Open reduction and internal fixation of proximal humerus fractures.

    PubMed

    Drosdowech, Darren S; Faber, Kenneth J; Athwal, George S

    2008-10-01

    Open reduction of proximal humeral fractures has the advantage of providing direct control over each fracture fragment and permitting anatomic reduction and fixation with advanced devices. Modern fixed-angle locking plates designed specifically for proximal humerus fractures have allowed the expansion of surgical indications permitting surgeons to address more complicated fractures. Advanced preoperative imaging and fluoroscopy allow a better understanding of fracture patterns and permit the surgeon to use this knowledge intraoperatively. Research is required to further validate fracture classification systems, to develop surgical guidelines for decision making, and to compare the outcomes of the various treatments options for proximal humerus fractures.

  19. Split biceps femoris tendon reconstruction for proximal tibiofibular joint instability.

    PubMed

    Mena, H; Brautigan, B; Johnson, D L

    2001-07-01

    Recurrent instability of the proximal tibiofibular joint is an infrequently diagnosed abnormality. We present a new technique for reconstructing the joint using a split biceps femoris tendon passed through a bone tunnel in both the proximal tibial metaphysis and fibular head. The case report is also presented. The procedure offers an anatomic reconstruction and firm stabilization. It allows normal motion of the proximal tibiofibular joint and preserves the normal mechanics of the ankle. This procedure is an excellent alternative to resection of the fibular head, transarticular arthrodesis, or pseudoarthrosis focus at the fibular head.

  20. Inhibitory interactions among olfactory glomeruli do not necessarily reflect spatial proximity.

    PubMed

    Reisenman, Carolina E; Heinbockel, Thomas; Hildebrand, John G

    2008-08-01

    Inhibitory interactions shape the activity of output neurons in primary olfactory centers and promote contrast enhancement of odor representations. Patterns of interglomerular connectivity, however, are largely unknown. To test whether the proximity of glomeruli to one another is correlated with interglomerular inhibitory interactions, we used intracellular recording and staining methods to record the responses of projection (output) neurons (PNs) associated with glomeruli of known olfactory tuning in the primary olfactory center of the moth Manduca sexta. We focused on Toroid I, a glomerulus in the male-specific macroglomerular complex (MGC) specialized to one of the two key components of the conspecific females' sex pheromone, and the adjacent, sexually isomorphic glomerulus 35, which is highly sensitive to Z-3-hexenyl acetate (Z3-6:OAc). We used the two odorants to activate these reference glomeruli and tested the effects of olfactory activation in other glomeruli. We found that Toroid-I PNs were not inhibited by input to G35, whereas G35 PNs were inhibited by input to Toroid-I PNs. We also recorded the responses of PNs arborizing in other sexually isomorphic glomeruli to stimulation with the sex pheromone and Z3-6:OAc. We found that inhibitory responses were not related to proximity to the MGC and G35: both distant and adjacent PNs were inhibited by stimulation with the sex pheromone, some others were affected by only one odorant, and yet others by neither. Similar results were obtained in female PNs recorded in proximity to female-specific glomeruli. Our findings indicate that inhibitory interactions among glomeruli are widespread and independent of their spatial proximity.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Proportional proximity sensing for telerobots using Coherent Laser Radar

    NASA Technical Reports Server (NTRS)

    Vazquez, Sixto L.; Goode, Plesent W.; Slotwinski, Anthony R.

    1992-01-01

    The ability of a telerobotic manipulator to operate in confined spaces while avoiding unwanted collisions is enhanced by the accurate sensing of its proximate environment. To achieve the fidelity required for precise manipulator control, a proportional proximity sensor system with a sufficiently large measurement envelope is required. Current proximity sensors provide a binary indication of the presence of obstacles within a small envelope with coarse or no proportional measurement of their location. A proportional proximity sensor system configured as a Frequency Modulated Continuous Wave (FMCW) Coherent Laser Radar (CLR) using a semiconductor laser as the energy source is described and analyzed. The source and reflected energies mix coherently to generate a radio frequency (RF) signal whose frequency is proportional to the range. The system is tested for accuracy, range, depth of range, speed, and sensitivity and the results are presented. Techniques to derive orientation information and an application to telerobotic control are also described.

  8. 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

  9. View to northeast, showing west elevation and south side. Proximity ...

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

    View to northeast, showing west elevation and south side. Proximity of fence of adjacent subdivision precluded photography of north side. - Drew-Sherwood Farm, Barn, 7927 Elk Grove Boulevard, Elk Grove, Sacramento County, CA

  10. Evaluation and management of pediatric proximal humerus fractures.

    PubMed

    Popkin, Charles A; Levine, William N; Ahmad, Christopher S

    2015-02-01

    In the pediatric population, sports participation, falls, and motor vehicle accidents can result in proximal humerus fractures. Because the proximal humeral growth plate is responsible for up to 80% of the growth of the humerus, the remodeling of these fractures in children is tremendous. Most of these injuries can be treated with a sling or hanging arm cast, although older children with decreased remodeling capacity may require surgery. Special considerations should be taken for management of proximal humerus fractures that occur in the context of Little League shoulder, lesser tuerosity avulsion fractures, fracture-dislocations, birth fractures, and fractures associated with cysts. Most pediatric patients with proximal humerus fractures have favorable results, and complications are infrequent.

  11. 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)

  12. Analysis on the characteristics of pulsed laser proximity fuze's echo

    NASA Astrophysics Data System (ADS)

    Wang, Kun; Chen, Huimin

    2011-06-01

    With the rapid development of semiconductor technology and laser technology, a kind of proximity fuze named pulsed laser proximity fuze has been applied. Compared with other fuzes, pulsed laser proximity fuze has high ranging precision and strong resistance to artificial active interference. It is an important development tendency of proximity fuze. The paper analyze the characteristic of target echo of laser signal, and then make theoretical analysis and calculation on the laser signal transmission in the smog. Firstly, use the pulse width of 10ns semiconductor laser fuze to do typical targets experiment, to get the echo information of target distance is 5m; then to do smog interference experiment, by comparing the pulse width amplitude and backscattering signal amplitude of laser fuze in simulation and experiment, analyzing the effect of anti-clutter, providing the evidence for the subsequent of circuit of signal amplification and processing.

  13. Proximal row carpectomy with or without postoperative immobilisation.

    PubMed

    Jacobs, R; Degreef, I; De Smet, L

    2008-12-01

    Previously published reports have shown good results after proximal row carpectomy in all cases that had a postoperative immobilisation period from 1 to 4 weeks. Immobilisation is thought to be necessary because of the risk of postoperative subluxation of the carpus and for pain relief. There is, however, no evidence of its value. The results in 13 patients who underwent proximal row carpectomy without postoperative immobilisation were compared with those in 25 patients who underwent proximal row carpectomy with postoperative immobilisation for 4 weeks. After a mean follow-up period of 27 months, no significant differences were found for pain, range of motion or return to work between the two groups. We conclude that postoperative immobilisation is not necessary after proximal row carpectomy.

  14. [Merle D'Aubigne's oblique proximal femoral osteotomy. Surgical technique].

    PubMed

    López Sosa, Francisco H; Valentín-Guerrero, Santiago; Miranda-López, Eduardo

    2008-01-01

    Proximal femoral osteotomy with the technique described by Merle D'AubignC and Valliant was used in the treatment of adult patients with osteoarthritis or idiopathic avascular necrosis. Dr. Antonio Flores applied this technique to children with subluxation and acetabular dysplasia, identified with exaggerated anteversion and valgus of the proximal femur. He reported correction of the deformity in 75% of patients. The purpose of this paper is to describe the technique, its indications and complications.

  15. 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.

  16. 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

  17. Four year Evaluation of Proximal Resin Infiltration in Adolescents

    PubMed Central

    Kuscu, Ozgur Onder; Hysi, Dorian

    2015-01-01

    Aim Resin infiltration of proximal lesions is a new approach to stopping caries progression. Therefore, the aim of the present study was to evaluate four-year efficacy of proximal infiltrates in adolescents. Materials and methods In ten adolescents, a total of 21 proximal infiltrates (ICON® (DMG, Germany) were applied to initial proximal lesions of permanent incisors and premolars according to the manufacturer’s instruction. The clinical quality of resin infiltration was assessed at 1 week, 1, 2, 3 and 4 years after the treatment and the evaluation of the therapeutic effect was analyzed by radiographs. Results Ten patients were followed up clinically for four years. The majority of the infiltrated lesions were located on permanent incisors. Teeth which were proximally infiltrated did not exhibit dental plaque and gingival bleeding in most cases. At annual recalls, plaque scores remained constant. The gingival status remained steady and no differences in tooth shape and contour were detected. Discoloration was detected in four teeth (19%) in 1st year recall and was constant at annual intervals. The radiographic evaluation of the bitewing radiographs showed no progression in 21 lesions (100%) from baseline to the 4-year recall. Overall oral hygiene of the patients was satisfactory. Conclusion In conclusion, proximal infiltration is an effective prophylactic measure in adolescents.

  18. Four year Evaluation of Proximal Resin Infiltration in Adolescents

    PubMed Central

    Kuscu, Ozgur Onder; Hysi, Dorian

    2015-01-01

    Aim Resin infiltration of proximal lesions is a new approach to stopping caries progression. Therefore, the aim of the present study was to evaluate four-year efficacy of proximal infiltrates in adolescents. Materials and methods In ten adolescents, a total of 21 proximal infiltrates (ICON® (DMG, Germany) were applied to initial proximal lesions of permanent incisors and premolars according to the manufacturer’s instruction. The clinical quality of resin infiltration was assessed at 1 week, 1, 2, 3 and 4 years after the treatment and the evaluation of the therapeutic effect was analyzed by radiographs. Results Ten patients were followed up clinically for four years. The majority of the infiltrated lesions were located on permanent incisors. Teeth which were proximally infiltrated did not exhibit dental plaque and gingival bleeding in most cases. At annual recalls, plaque scores remained constant. The gingival status remained steady and no differences in tooth shape and contour were detected. Discoloration was detected in four teeth (19%) in 1st year recall and was constant at annual intervals. The radiographic evaluation of the bitewing radiographs showed no progression in 21 lesions (100%) from baseline to the 4-year recall. Overall oral hygiene of the patients was satisfactory. Conclusion In conclusion, proximal infiltration is an effective prophylactic measure in adolescents. PMID:27688414

  19. 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.

  20. 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.

  1. 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

  2. Regulation of human prohormone convertase 2 promoter activity by the transcription factor EGR-1.

    PubMed Central

    Jansen, E; Ayoubi, T A; Meulemans, S M; Van De Ven, W J

    1997-01-01

    Prohormone convertases are involved in the tissue-specific endoproteolytic processing of prohormones and neuropeptide precursors within the secretory pathway. In the present study, we have isolated genomic clones comprising the 5'-terminal region of the human prohormone convertase 2 (PC2) gene and established characteristics of the PC2 promoter region. The proximal promoter region is very G+C-rich and does not contain a canonical TATA box or a CAAT box. Transient expression assays with a set of human PC2 gene fragments containing progressive 5' deletions demonstrate that the proximal promoter region is capable of directing high levels of neuroendocrine-specific expression of reporter gene constructs. In addition, we show that the transcription factor EGR-1 interacts with two distinct elements within the proximal human PC2 promoter region. Transfection experiments also demonstrate that EGR-1 is able to enhance PC2 promoter activity. PMID:9359835

  3. Induced spectral gap and pairing correlations from superconducting proximity effect

    NASA Astrophysics Data System (ADS)

    Chiu, Ching-Kai; Cole, William S.; Das Sarma, S.

    2016-09-01

    We theoretically consider superconducting proximity effect, using the Bogoliubov-de Gennes (BdG) theory, in heterostructure sandwich-type geometries involving a normal s -wave superconductor and a nonsuperconducting material with the proximity effect being driven by Cooper pairs tunneling from the superconducting slab to the nonsuperconducting slab. Applications of the superconducting proximity effect may rely on an induced spectral gap or induced pairing correlations without any spectral gap. We clarify that in a nonsuperconducting material the induced spectral gap and pairing correlations are independent physical quantities arising from the proximity effect. This is a crucial issue in proposals to create topological superconductivity through the proximity effect. Heterostructures of three-dimensional topological insulator (TI) slabs on conventional s -wave superconductor (SC) substrates provide a platform, with proximity-induced topological superconductivity expected to be observed on the "naked" top surface of a thin TI slab. We theoretically study the induced superconducting gap on this naked surface. In addition, we compare against the induced spectral gap in heterostructures of SC with a normal metal or a semiconductor with strong spin-orbit coupling and a Zeeman splitting potential (another promising platform for topological superconductivity). We find that for any model for the non-SC metal (including metallic TI) the induced spectral gap on the naked surface decays as L-3 as the thickness (L ) of the non-SC slab is increased in contrast to the slower 1 /L decay of the pairing correlations. Our distinction between proximity-induced spectral gap (with its faster spatial decay) and pairing correlation (with its slower spatial decay) has important implications for the currently active search for topological superconductivity and Majorana fermions in various superconducting heterostructures.

  4. PROMOTING RESILIENCE.

    PubMed

    Desjardins, Eric; Barker, Gillian; Lindo, Zoë; Dieleman, Catherine; Dussault, Antoine C

    2015-06-01

    Broadening contingents of ecologists and environmental scientists have recently begun to promote ecological resilience both as a conceptual framework and as a practical goal. As some critics have noted, this growing interest has brought with it a multiplication of notions of ecological resilience. This paper reviews how and why the notion of ecological resilience has been adopted, used, and defended in ecology since its introduction by C. S. Holling in 1973. We highlight the many faces of ecological resilience, but unlike other reviewers who see these as disunified and confused, we interpret ecological resilience as an evolving, multidimensional, theoretical concept unified by its role in guiding practical response to ecological and environmental challenges. This perspective informs a review of some of the factors often recognized as favoring resilience (structural and response diversity, functional redundancy, modularity, and spatial heterogeneity); we show how the roles and relationships of these factors can be clarified by considering them in the theoretical framework of Complex Adaptive Systems (CASs).

  5. Long-range superconducting proximity effect in polycrystalline Co nanowires

    SciTech Connect

    Kompaniiets, M.; Porrati, F.; Huth, M.; Dobrovolskiy, O. V.; Neetzel, C.; Brötz, J.; Ensinger, W.

    2014-02-03

    We report experimental evidence of a long-range superconducting proximity effect in polycrystalline Co nanowires in contact with a superconducting W-based floating electrode (inducer). For electrical resistance measurements, voltage leads were connected to the Co nanowire on both sides of the superconducting inducer at a distance of 7.2 μm. We observed a 28% reduction of the nanowire resistance when sweeping the temperature below the inducer's transition temperature T{sub c} = 5.2 K. Our analysis of the resistance data shows that the superconducting proximity length in polycrystalline Co is as large as 1 μm at 2.4 K, attesting to a long-range proximity effect. Moreover, this long-range proximity effect is insusceptible to magnetic fields up to 11 T, which is indicative of spin-triplet pairing. Our results provide evidence that magnetic inhomogeneity of the ferromagnet enlarges the spatial extend of the spin-triplet superconducting proximity effect.

  6. Proximal femur fractures: the pioneer era of 1818 to 1925.

    PubMed

    Bartonícek, Jan

    2004-02-01

    The foundations of the modern era of the treatment of proximal femur fractures were laid by Cooper who in 1819 published the first therapeutically oriented classification of these fractures. During the following 100 years the clinical diagnostics were further developed; five classifications of proximal femur fractures were formulated including the terminology used until now (peritrochanteric, intertrochanteric), and surgical treatment was started. The first attempt at internal fixation of the proximal femur in the 1850s was by Langenbeck. His patient died of sepsis. The first successful internal fixation of proximal femur fractures was done in 1875 by König. At the beginning of the twentieth century the method of surgical treatment for proximal femur fractures was improved by Lambotte, Delbet, and Putti. However, the time was not ready yet for this method of treatment. Only technologic progress (stainless steel, new technology), the additional development of anesthesia and asepsis, improvement of xray apparatus, and introduction of the traction table created the prerequisites for successful gradation of Smith-Petersen's method from 1925 to 1931, and which a few years later was used worldwide. PMID:15021169

  7. Orthopaedic Approaches to Proximal Humeral Fractures Following Trauma

    PubMed Central

    Mafi, Reza; Khan, Wasim; Mafi, Pouya; Hindocha, Sandip

    2014-01-01

    Proximal humeral fractures have been a topic of discussion in medical literature dating back as far as 3rd century BC. Today, these fractures are the most common type of humeral fractures and account for about 5-6% of all fractures in adults with the incidence rising rapidly with age. In broad terms the management of proximal humeral fractures can be divided into two categories: conservative versus surgical intervention. The aim of treatment is to stabilize the fracture, aid better union and reduce pain during the healing process. Failure to achieve this can result in impairment of function, and significantly weaken the muscles inserting onto the proximal humerus. With the rising incidence of proximal humeral fractures, especially among the elderly, the short and long term burden for patients as well as the wider society is increasing. Furthermore, there is a lack of consistency in the definitive treatment and management of displaced fractures. This systematic review of literature compares the surgical treatment of proximal humeral fractures with their conservative management, by evaluating the available randomised controlled trials on this topic. PMID:25408786

  8. Treatment of Hostile Proximal Necks During Endovascular Aneurysm Repair

    PubMed Central

    Navarro, Tulio Pinho; Bernardes, Rodrigo de Castro; Procopio, Ricardo Jayme; Leite, Jose Oyama; Dardik, Alan

    2014-01-01

    Endovascular aneurysm repair (EVAR) is a therapy that continues to evolve rapidly as advances in technology are incorporated into new generations of devices and surgical practice. Although EVAR has emerged as a safe and effective treatment for patients with favorable anatomy, treatment of patients with unfavorable anatomy remains controversial and is still an off-label indication for endovascular treatment with some current stent-grafts. The proximal neck of the aneurysm remains the most hostile anatomic barrier to successful endovascular repair with long-term durability. Open surgery for unfavorable necks is still considered the gold standard treatment in contemporary practice, despite the increased mortality and morbidity attributed to suprarenal cross-clamping, particularly in high-risk patients. Evolving technology may overcome the obstacles preventing endovascular treatment of unfavorable proximal neck anatomy; current approaches include purely endovascular as well as hybrid approaches, and generally include strategies that either extend the length of the short neck, move the proximal neck more proximally, or keep the short neck intact. These approaches include the use of debranching techniques, banding, chimneys, fenestrated and branched devices, filling the sac with endobags, endoanchors, and other novel devices. These newer-generation devices appear to have promising short- and midterm results. However, lack of good evidence of efficacy with long-term results for these newer approaches still precludes wide dissemination of endovascular solutions for the hostile proximal neck. PMID:26798712

  9. Treatment of Hostile Proximal Necks During Endovascular Aneurysm Repair.

    PubMed

    Navarro, Tulio Pinho; Bernardes, Rodrigo de Castro; Procopio, Ricardo Jayme; Leite, Jose Oyama; Dardik, Alan

    2014-02-01

    Endovascular aneurysm repair (EVAR) is a therapy that continues to evolve rapidly as advances in technology are incorporated into new generations of devices and surgical practice. Although EVAR has emerged as a safe and effective treatment for patients with favorable anatomy, treatment of patients with unfavorable anatomy remains controversial and is still an off-label indication for endovascular treatment with some current stent-grafts. The proximal neck of the aneurysm remains the most hostile anatomic barrier to successful endovascular repair with long-term durability. Open surgery for unfavorable necks is still considered the gold standard treatment in contemporary practice, despite the increased mortality and morbidity attributed to suprarenal cross-clamping, particularly in high-risk patients. Evolving technology may overcome the obstacles preventing endovascular treatment of unfavorable proximal neck anatomy; current approaches include purely endovascular as well as hybrid approaches, and generally include strategies that either extend the length of the short neck, move the proximal neck more proximally, or keep the short neck intact. These approaches include the use of debranching techniques, banding, chimneys, fenestrated and branched devices, filling the sac with endobags, endoanchors, and other novel devices. These newer-generation devices appear to have promising short- and midterm results. However, lack of good evidence of efficacy with long-term results for these newer approaches still precludes wide dissemination of endovascular solutions for the hostile proximal neck.

  10. Influence of surround proximity on induction of brown and darkness.

    PubMed

    Buck, Steven L; Shelton, Andrew; Stoehr, Brooke; Hadyanto, Vina; Tang, Miaolu; Morimoto, Takuma; DeLawyer, Tanner

    2016-03-01

    A bright white surround makes a yellow long-wavelength target look both browner and darker. We explored the parallel between these two types of induction by examining their dependence on the proximity of the bright surround to the target at two different time scales with 27 ms and 1 s stimulus durations. We assessed (a) brown induction by adjustment of target luminance to perceptual brown and yellow boundaries and (b) darkness induction by a successive matching procedure. We found that brown induction is a quick process that is robust even for 27 ms stimuli. For darkness induction, there was a strong, spatially localized surround proximity effect for the 27 ms stimuli and much weaker proximity effect for the 1 s stimuli. For brown induction, proximity effects were generally weaker but still showed relatively stronger localized proximity effects for 27 ms stimuli than for 1 s stimuli. For these stimuli, darkness induction predicts the relative pattern but not the magnitudes of brown induction. Both brown and darkness inductions show the operation of quick, spatially localized processes that are apparently superseded by other processes for extended stimulus presentations.

  11. 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.

  12. Tenofovir renal toxicity targets mitochondria of renal proximal tubules

    PubMed Central

    Kohler, James J; Hosseini, Seyed H; Hoying-Brandt, Amy; Green, Elgin; Johnson, David M; Russ, Rodney; Tran, Dung; Raper, C Michael; Santoianni, Robert; Lewis, William

    2009-01-01

    Tenofovir disoproxil fumarate (TDF) is an analog of adenosine monophosphate that inhibits HIV reverse transcriptase in HIV/AIDS. Despite its therapeutic success, renal tubular side effects are reported. The mechanisms and targets of tenofovir toxicity were determined using ‘2 × 2’ factorial protocols, and HIV transgenic (TG) and wild-type (WT) littermate mice with or without TDF (5 weeks). A parallel study used didanosine (ddI) instead of TDF. At termination, heart, kidney, and liver samples were retrieved. Mitochondrial DNA (mtDNA) abundance, and histo- and ultrastructural pathology were analyzed. Laser-capture microdissection (LCM) was used to isolate renal proximal tubules for molecular analyses. Tenofovir increased mtDNA abundance in TG whole kidneys, but not in their hearts or livers. In contrast, ddI decreased mtDNA abundance in the livers of WTs and TGs, but had no effect on their hearts or kidneys. Histological analyses of kidneys showed no disruption of glomeruli or proximal tubules with TDF or ddI treatments. Ultrastructural changes in renal proximal tubules from TDF-treated TGs included an increased number and irregular shape of mitochondria with sparse fragmented cristae. LCM-captured renal proximal tubules from TGs showed decreased mtDNA abundance with tenofovir. The results indicate that tenofovir targets mitochondrial toxicity on the renal proximal tubule in an AIDS model. PMID:19274046

  13. 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

  14. 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

  15. 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.

  16. The thermometer of social relations: mapping social proximity on temperature.

    PubMed

    Ijzerman, Hans; Semin, Gün R

    2009-10-01

    "Holding warm feelings toward someone" and "giving someone the cold shoulder" indicate different levels of social proximity. In this article, we show effects of temperature that go beyond these metaphors people live by. In three experiments, warmer conditions, compared with colder conditions, induced (a) greater social proximity, (b) use of more concrete language, and (c) a more relational focus. Different temperature conditions were created by either handing participants warm or cold beverages (Experiment 1) or placing them in comfortable warm or cold ambient conditions (Experiments 2 and 3). These studies corroborate recent findings in the field of grounded cognition revealing that concrete experiences ground abstract concepts with which they are coexperienced. Our studies show a systemic interdependence among language, perception, and social proximity: Environmentally induced conditions shape not only language use, but also the perception and construal of social relationships.

  17. Methodology for proximal wear evaluation in posterior resin composites.

    PubMed

    Ziemiecki, T L; Wendt, S L; Leinfelder, K F

    1992-08-01

    The purpose of this study was to utilize a methodology to measure proximal wear of posterior resin composites with respect to time. A group of 10 teeth (5 premolars and 5 molars) were restored with P-30, a posterior resin composite restorative. At placement the proximal contacts were judged to be closed visually, and with unwaxed dental floss. The patients were then recalled at intervals of 6, 12, and 36 months for indirect wear evaluations. Resin composite transfer copings were made and indexed on baseline models. A zoom stereomicroscope, at 20 microns resolution, was used to determine proximal wear. For the posterior restorative material the premolar and molar teeth wore at the same rate. The amount of wear was statistically greater for premolar teeth at 6 and 12-month evaluation periods than molar teeth. At 36 months, there was no statistical difference in wear between premolar and molar teeth.

  18. Pyrocarbon proximal interphalangeal joint arthroplasty: outcomes of a cohort study.

    PubMed

    McGuire, D T; White, C D; Carter, S L; Solomons, M W

    2012-07-01

    Pyrocarbon arthroplasty of the proximal interphalangeal joint is a relatively new concept. Early studies have been encouraging, reporting improved pain and function, but a largely unchanged arc of motion. Subsidence of the implant is common, but how it relates to outcome has not been analyzed. This study was performed to review the results of 57 pyrocarbon proximal interphalangeal implanted joints. Results showed a statistically significant increase in the arc of motion, excellent pain relief, and improved function. Subsidence was observed on radiographs in 40% of joints, but no correlation was found compared with arc of motion or function. The incidence of complications is fairly high and usually related to the peri-articular soft tissues, but they are usually minor and do not require further treatment. From this review, we can recommend the use of this implant for treatment of arthritis of the proximal interphalangeal joint.

  19. The thermometer of social relations: mapping social proximity on temperature.

    PubMed

    Ijzerman, Hans; Semin, Gün R

    2009-10-01

    "Holding warm feelings toward someone" and "giving someone the cold shoulder" indicate different levels of social proximity. In this article, we show effects of temperature that go beyond these metaphors people live by. In three experiments, warmer conditions, compared with colder conditions, induced (a) greater social proximity, (b) use of more concrete language, and (c) a more relational focus. Different temperature conditions were created by either handing participants warm or cold beverages (Experiment 1) or placing them in comfortable warm or cold ambient conditions (Experiments 2 and 3). These studies corroborate recent findings in the field of grounded cognition revealing that concrete experiences ground abstract concepts with which they are coexperienced. Our studies show a systemic interdependence among language, perception, and social proximity: Environmentally induced conditions shape not only language use, but also the perception and construal of social relationships. PMID:19732385

  20. 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

  1. Bringing proximate neighbours into the study of US residential segregation.

    PubMed

    Friedman, Samantha

    2011-01-01

    The race and ethnicity of neighbours are thought to be critical in shaping household mobility underlying residential segregation. However, studies on this topic have used data at the census-tract level of analysis rather than at the proximate-neighbour level. Using a non-publicly available version of the neighbour-cluster sample within the American Housing Survey, this study incorporates data on the race, ethnicity and socioeconomic characteristics of the proximate neighbours of White, Black and Latino households and examines their impact on household residential satisfaction, out- and in-mobility. Results indicate that proximate-neighbour race and ethnicity matter in influencing endpoints of the mobility process and do not necessarily parallel those at the census-tract level. Implications of these findings are discussed as they relate to the study of residential segregation.

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

    PubMed

    Weiner, M W; Weinman, E J; Kashgarian, M; Hayslett, J P

    1971-07-01

    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.

  3. Proximal arm kinematics affect grip force-load force coordination.

    PubMed

    Vermillion, Billy C; Lum, Peter S; Lee, Sang Wook

    2015-10-01

    During object manipulation, grip force is coordinated with load force, which is primarily determined by object kinematics. Proximal arm kinematics may affect grip force control, as proximal segment motion could affect control of distal hand muscles via biomechanical and/or neural pathways. The aim of this study was to investigate the impact of proximal kinematics on grip force modulation during object manipulation. Fifteen subjects performed three vertical lifting tasks that involved distinct proximal kinematics (elbow/shoulder), but resulted in similar end-point (hand) trajectories. While temporal coordination of grip and load forces remained similar across the tasks, proximal kinematics significantly affected the grip force-to-load force ratio (P = 0.042), intrinsic finger muscle activation (P = 0.045), and flexor-extensor ratio (P < 0.001). Biomechanical coupling between extrinsic hand muscles and the elbow joint cannot fully explain the observed changes, as task-related changes in intrinsic hand muscle activation were greater than in extrinsic hand muscles. Rather, between-task variation in grip force (highest during task 3) appears to contrast to that in shoulder joint velocity/acceleration (lowest during task 3). These results suggest that complex neural coupling between the distal and proximal upper extremity musculature may affect grip force control during movements, also indicated by task-related changes in intermuscular coherence of muscle pairs, including intrinsic finger muscles. Furthermore, examination of the fingertip force showed that the human motor system may attempt to reduce variability in task-relevant motor output (grip force-to-load force ratio), while allowing larger fluctuations in output less relevant to task goal (shear force-to-grip force ratio). PMID:26289460

  4. Proximal arm kinematics affect grip force-load force coordination

    PubMed Central

    Vermillion, Billy C.; Lum, Peter S.

    2015-01-01

    During object manipulation, grip force is coordinated with load force, which is primarily determined by object kinematics. Proximal arm kinematics may affect grip force control, as proximal segment motion could affect control of distal hand muscles via biomechanical and/or neural pathways. The aim of this study was to investigate the impact of proximal kinematics on grip force modulation during object manipulation. Fifteen subjects performed three vertical lifting tasks that involved distinct proximal kinematics (elbow/shoulder), but resulted in similar end-point (hand) trajectories. While temporal coordination of grip and load forces remained similar across the tasks, proximal kinematics significantly affected the grip force-to-load force ratio (P = 0.042), intrinsic finger muscle activation (P = 0.045), and flexor-extensor ratio (P < 0.001). Biomechanical coupling between extrinsic hand muscles and the elbow joint cannot fully explain the observed changes, as task-related changes in intrinsic hand muscle activation were greater than in extrinsic hand muscles. Rather, between-task variation in grip force (highest during task 3) appears to contrast to that in shoulder joint velocity/acceleration (lowest during task 3). These results suggest that complex neural coupling between the distal and proximal upper extremity musculature may affect grip force control during movements, also indicated by task-related changes in intermuscular coherence of muscle pairs, including intrinsic finger muscles. Furthermore, examination of the fingertip force showed that the human motor system may attempt to reduce variability in task-relevant motor output (grip force-to-load force ratio), while allowing larger fluctuations in output less relevant to task goal (shear force-to-grip force ratio). PMID:26289460

  5. Glomerulotubular balance in a mathematical model of the proximal nephron.

    PubMed

    Weinstein, A M

    1990-03-01

    A nonelectrolyte model of proximal tubule epithelium has been extended by the inclusion of a compliant tight junction. Here "compliance" signifies that both the junctional salt and water permeability increase and the salt reflection coefficient decreases in response to small pressure differences from lateral interspace to tubule lumen. In previous models of rat proximal tubule, there has been virtually no sensitivity of isotonic salt transport to changes in peritubular oncotic force. With the inclusion of junctional compliance, decreases in peritubular protein can open the junction and produce a secretory salt flux. Thus the model can represent the "backflux hypothesis," as it was originally put forth (J. E. Lewy and E. E. Windhager, Am. J. Physiol. 214: 943-954, 1968). Additional calculations, simulating a tight junction with negligible water permeability, reveal that the quantitative impact of peritubular protein can be realized whether or not there is substantial junctional water flux. The epithelial model of proximal tubule has also been incorporated into a model of the proximal nephron, complete with glomerulus, peritubular capillary, and interstitium. The interstitial compartment is well mixed and interstitial pressure and osmolality are determined iteratively to achieve balance between tubule reabsorption and capillary uptake. For this model, two domains of operation are identified. When interstitial pressures are low, junctions are closed, and filtration fraction has no effect on proximal reabsorption. When interstitial pressures are relatively elevated, epithelial junctions are open, and proximal salt reabsorption changes in proportion to changes in filtration fraction. In neither domain, however, does the model tubule augment salt flux with isolated increases in luminal flow rate (at constant filtration fraction). The absence of a separate effect of tubule fluid flow on salt transport precludes perfect glomerulotubular balance.

  6. 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.

  7. Proximal aortic dissection (dissecting aortic aneurysm) in a mature ostrich.

    PubMed

    Ferreras, M C; González, J; Pérez, V; Reyes, L E; Gómez, N; Pérez, C; Corpa, J M; García-Marín, J F

    2001-01-01

    The gross and histopathologic lesions observed in a case of spontaneous proximal aortic dissection (dissecting aortic aneurysm) in a mature ostrich are reported. At necropsy, a dissecting intramural hematoma was seen in the proximal aorta, extended about 12 cm distally from the aortic valves. Histopathologic changes in aortic dissection included fragmentation and disruption of elastic laminae, presence of cystic extracellular spaces, and pooling of ground substance in the tunica media. Hepatic copper levels were measured, and the low concentration found suggested that a copper deficiency together with other risk factors such as the elevation of blood pressure may have been implicated in the development of the aortic dissection seen in this ostrich.

  8. Proximal Periprosthetic Femur Fractures: Strategies for Internal Fixation.

    PubMed

    Moloney, Gele B; Toro, Jose B; Helfet, David L; Wellman, David S

    2016-01-01

    As the number of patients living with total hip arthroplasty continues to rise, there will be an increase in periprosthetic fractures requiring surgical treatment. Treatment of periprosthetic femur fractures below a well-fixed hip arthroplasty stem presents a unique set of challenges. A review of the existing literature on surgical technique, including plate selection and configuration, proximal fixation options, and use of allograft, can serve to guide treatment of these challenging injuries. While not conclusive, the literature supports using soft tissue preserving techniques, bicortical proximal fixation, and fixation spanning the length of the femur. PMID:27327912

  9. Metatarsal shaft fractures and fractures of the proximal fifth metatarsal.

    PubMed

    Fetzer, Gary B; Wright, Rick W

    2006-01-01

    Metatarsal fractures represent a relatively common injury, especially in athletes. The pertinent anatomy, evaluation, diagnosis, classification, and treatment of acute and chronic (stress) metatarsal shaft fractures are discussed. Fractures of the proximal fifth metatarsal, which are unique and important injuries, are also discussed. Treatment remains relatively straightforward for the traumatic metatarsal injury, whereas traditional stress fractures typically heal with decreased activity. The problematic proximal fifth metatarsal fracture (Jones fracture) frequently requires surgical intervention in patients who want to avoid non-weight-bearing cast immobilization. The authors' current treatment for this fracture includes the option of intramedullary fixation versus cast immobilization.

  10. 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.

  11. 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.

  12. 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].

  13. ACUTE ISOLATED ANTEROLATERAL DISLOCATION OF THE PROXIMAL TIBIOFIBULAR JOINT.

    PubMed

    Almeida Silvares, Paulo Roberto de; Fernandes Guerreiro, Joao Paulo; Müller, Sergio Swain; Pereira, Ricardo Violante; Vannini, Rodrigo

    2010-01-01

    Isolated traumatic dislocation of the proximal tibiofibular joint is rare. This injury may go unrecognized or be misdiagnosed at the initial presentation. Lack of clinical suspicion can cause diagnostic problems. The diagnosis requires an accurate history of the mechanism and symptoms of the injury, and adequate clinical and radiographic evaluation of both knees. Unrecognized cases are a source of chronic abnormalities. The treatment consists of closed reduction and immobilization or, in non-reducible or unstable cases, open reduction with temporary internal fixation. A rare case of isolated proximal tibiofibular dislocation in a basketball player is reported to illustrate this injury.

  14. 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

  15. Molecular dissection of cis-acting regulatory elements from 5'-proximal regions of a vaccinia virus late gene cluster.

    PubMed

    Miner, J N; Weinrich, S L; Hruby, D E

    1988-01-01

    Promoter elements responsible for directing the transcription of six tightly clustered vaccinia virus (VV) late genes (open reading frames [ORFs] D11, D12, D13, A1, A2, and A3) from the HindIII D/A region of the viral genome were identified within the upstream sequences proximal to each individual locus. These regions were identified as promoters by excising them from the VV genome, abutting them to the bacterial chloramphenicol acetyl transferase gene, and demonstrating their ability to drive expression of the reporter gene in transient-expression assays in an orientation-specific manner. To delineate the 5' boundary of the upstream elements, two of the VV late gene (A1 and D13) promoter: CAT constructs were subjected to deletion mutagenesis procedures. A series of 5' deletions of the ORF A1 promoter from -114 to -24 showed no reduction in promoter activity, whereas additional deletion of the sequences from -24 to +2 resulted in the complete loss of activity. Deletion of the ORF A1 fragment from -114 to -104 resulted in a 24% increase in activity, suggesting the presence of a negative regulatory region. In marked contrast to previous 5' deletion analyses which have identified VV late promoters as 20- to 30-base-pair cap-proximal sequences, 5' deletions to define the upstream boundary of the ORF D13 promoter identified two positive regulatory regions, the first between -235 and -170 and the second between -123 and -106. Background levels of chloramphenicol acetyltransferase expression were obtained with deletions past -88. Significantly, this places the ORF D13 regulatory regions within the upstream coding sequences of the ORF A1. A high-stringency computer search for homologies between VV late promoters that have been thus far characterized was carried out. Several potential consensus sequences were found just upstream from RNA start sites of temporally related promoter elements. Three major conclusions are drawn from these experiments. (i) The presence of

  16. 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

  17. 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

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

    PubMed

    Long, Marcus J C; Poganik, Jesse R; Aye, Yimon

    2016-03-23

    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

  19. 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

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

    PubMed

    Long, Marcus J C; Poganik, Jesse R; Aye, Yimon

    2016-03-23

    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.

  1. 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

  2. Paternal relatedness and age proximity regulate social relationships among adult female rhesus macaques.

    PubMed

    Widdig, A; Nürnberg, P; Krawczak, M; Streich, W J; Bercovitch, F B

    2001-11-20

    Kin selection promotes the evolution of social behavior that increases the survival and reproductive success of close relatives. Among primates, maternal kinship frequently coincides with a higher frequency of grooming and agonistic aiding, but the extent to which paternal kinship influences adult female social relationships has not yet been investigated. Here, we examine the effect of both maternal and paternal kinship, as well as age proximity, on affiliative interactions among semifree-ranging adult female rhesus macaques, Macaca mulatta. Kinship was assessed by using both microsatellites and DNA-fingerprinting. Our study confirms that the closest affiliative relationships characterize maternal half-sisters. We provide evidence that adult females are significantly more affiliative with paternal half-sisters than with nonkin. Furthermore, paternal kin discrimination was more pronounced among peers than among nonpeers, indicating that age proximity has an additional regulatory effect on affiliative interactions. We propose that kin discrimination among cercopithecine primates emerges from ontogenetic processes that involve phenotype matching based on shared behavioral traits, such as inherited personality profiles, rather than physiological or physical characteristics.

  3. Reviewing employee turnover: focusing on proximal withdrawal states and an expanded criterion.

    PubMed

    Hom, Peter W; Mitchell, Terence R; Lee, Thomas W; Griffeth, Rodger W

    2012-09-01

    We reconceptualize employee turnover to promote researchers' understanding and prediction of why employees quit or stay in employing institutions. A literature review identifies shortcomings with prevailing turnover dimensions. In response, we expand the conceptual domain of the turnover criterion to include multiple types of turnover (notably, involuntary quits) and multiple types of staying. Guided by the premise that "everyone eventually leaves; no one stays with an organization forever," we also suggest considering where leavers end up-or post-exit destinations, such as another job, full-time parenting, or educational pursuits. We propose "proximal withdrawal states" that motivate members to participate or withdraw from organizations as an expanded criterion. These motivational states precede turnover and are derived from 2 overarching dimensions: desired employment status (whether employees want to stay or leave) and perceived volitional control (whether quit or stay decisions are completely up to them or at least partially under external regulation). Crossing these dimensions yields 4 prime states: enthusiastic leavers and stayers and reluctant leavers and stayers. We further subdivide these mind-sets into subtypes by differentiating employer from other forms of external control (e.g., family). Focusing on more common subtypes, we explain how they arise from particular motivational forces and profile how they differ by attitudes, behaviors, and turnover speed and destinations. We further discuss ways to measure this expanded criterion and proximal states (and subtypes) and investigate the latter's profiled differences. Finally, we discuss scientific and practical implications and future research directions.

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

    PubMed

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

    2013-06-01

    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 the speed of subsequent flexible approach responses, but not those 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

  5. 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

  6. 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

  7. 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.

  8. 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.…

  9. 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…

  10. 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…

  11. Three-part inventions: intracellular signaling and induced proximity.

    PubMed

    Crabtree, G R; Schreiber, S L

    1996-11-01

    Everyone has had the experience of stoking a fire; putting the logs close together causes flames to appear from previously dying embers. In a similar way, mere proximity might mediate qualitative biological responses. We discuss natural molecules that appear to have arisen to bring two proteins together and illustrate how this simple mechanism can be used to control a wide variety of biological processes.

  12. 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.

  13. 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.

  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. Conservative Treatment for Bilateral Displaced Proximal Humerus Head Fracture.

    PubMed

    Rodriguez-Corlay, Ruy E; 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

  16. 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…

  17. 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.

  18. 75 FR 33198 - Co-Location/Proximity Hosting Services

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ...; ] COMMODITY FUTURES TRADING COMMISSION 17 CFR Parts 36, 37, and 38 Co-Location/Proximity Hosting Services AGENCY: Commodity Futures Trading Commission. ACTION: Proposed rule. SUMMARY: The Commodity Futures... third-parties to carry out their self-regulatory obligations and other obligations under the...

  19. 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.

  20. 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.

  1. 75 FR 5009 - Proximity Detection Systems for Underground Mines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    ... operators at mine sites from 2002 to 2006. The National Institute for Occupational Safety and Health (NIOSH... Safety and Health Administration 30 CFR Parts 57 and 75 RIN 1219-AB65 Proximity Detection Systems for Underground Mines AGENCY: Mine Safety and Health Administration, Labor. ACTION: Request for...

  2. 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.

  3. Residential proximity to major roads and obstetrical complications.

    PubMed

    Yorifuji, Takashi; Naruse, Hiroo; Kashima, Saori; Murakoshi, Takeshi; Doi, Hiroyuki

    2015-03-01

    Exposure to air pollution is linked with an increased risk of preterm births. To provide further evidence on this relationship, we evaluated the association between proximity to major roads--as an index for air pollution exposure--and various obstetrical complications. Data were extracted from a database maintained by the perinatal hospital in Shizuoka, Japan. We restricted the analysis to mothers with singleton pregnancies of more than 22 weeks of gestation from 1997 to 2012 (n=19,077). Using the geocoded residential information, each mother was assigned proximity to major roads. We then estimated multivariate adjusted odds ratios and their 95% confidence intervals (CIs) for the effects of proximity to major roads on various obstetrical complications (preeclampsia, gestational diabetes mellitus, placenta abruption, placenta previa, preterm premature rupture of membrane (pPROM), preterm labor, and preterm births). We found positive associations of proximity to major roads with preeclampsia and pPROM. Living within 200 m increased the odds of preeclampsia by 1.3 times (95% CI, 1.0-1.8) and pPROM by 1.6 times (95% CI, 1.1-2.2). Furthermore, living within 200 m increased the odds of preterm births by 1.4 fold (95% CI, 1.2-1.7). Exposure to traffic-related air pollution increased the risk of preeclampsia and pPROM in this study. We propose a mechanism responsible for the association between air pollution and preterm births.

  4. 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.

  5. On the Surprising Salience of Curvature in Grouping by Proximity

    ERIC Educational Resources Information Center

    Strother, Lars; Kubovy, Michael

    2006-01-01

    The authors conducted 3 experiments to explore the roles of curvature, density, and relative proximity in the perceptual organization of ambiguous dot patterns. To this end, they developed a new family of regular dot patterns that tend to be perceptually grouped into parallel contours, dot-sampled structured grids (DSGs). DSGs are similar to the…

  6. West and south elevations, view to northeast. Proximity of house ...

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

    West and south elevations, view to northeast. Proximity of house and trees precluded photography of north and east elevations, but building is symmetrical. Entry is in east elevation; windmill was mounted at third story level on north elevation. - Drew-Sherwood Farm, Tank House, 7927 Elk Grove Boulevard, Elk Grove, Sacramento County, CA

  7. 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.

  8. 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…

  9. Unconventional oil and gas: The role of politics and proximity

    NASA Astrophysics Data System (ADS)

    Schelly, Chelsea

    2016-10-01

    Political divisions are important in understanding public perceptions of unconventional oil and natural gas development, but so is proximity to drilling activities. New research highlights that, as geographical distance from development areas increases, political ideology becomes more influential in explaining diverging perceptions.

  10. The Grammaticalization of the Proximative in Tok Pisin.

    ERIC Educational Resources Information Center

    Romaine, Suzanne

    1999-01-01

    Discusses grammaticalization of "laik" in Tok Pisin, meaning "want/like/desire" (from English "like") and "klostu," meaning "near" (from English "close to") as markers of proximative. Shows although "klostu" was more generally a feature of Pacific Pidgin English and began to grammaticalize in mid-19th century, is now in competition with "laik," a…

  11. 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

  12. 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…

  13. 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…

  14. 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

  15. Trabecular bone ontogeny in the human proximal femur.

    PubMed

    Ryan, Timothy M; Krovitz, Gail E

    2006-12-01

    Ontogenetic changes in the human femur associated with the acquisition of bipedal locomotion, especially the development of the bicondylar angle, have been well documented. The purpose of this study is to quantify changes in the three-dimensional structure of trabecular bone in the human proximal femur in relation to changing functional and external loading patterns with age. High-resolution X-ray computed tomography scan data were collected for 15 juvenile femoral specimens ranging in age from prenatal to approximately nine years of age. Serial slices were collected for the entire proximal femur of each individual with voxel resolutions ranging from 0.017 to 0.046 mm depending on the size of the specimen. Spherical volumes of interest were defined within the proximal femur, and the bone volume fraction, trabecular thickness, trabecular number, and fabric anisotropy were calculated in three dimensions. Bone volume fraction, trabecular number, and degree of anisotropy decrease between the age of 6 months and 12 months, with the lowest values for these parameters occurring in individuals near 12 months of age. By age 2-3 years, the bone volume, thickness, and degree of anisotropy increase slightly, and regions in the femoral neck become more anisotropic corresponding to the thickening of the inferior cortical bone of the neck. These results suggest that trabecular structure in the proximal femur reflects the shift in external loading patterns associated with the initiation of unassisted walking in infants.

  16. Isolated musculocutaneous neuropathy caused by a proximal humeral exostosis.

    PubMed

    Juel, V C; Kiely, J M; Leone, K V; Morgan, R F; Smith, T; Phillips, L H

    2000-01-25

    We report an isolated musculocutaneous neuropathy caused by a proximal humeral osteochondroma that became symptomatic after the patient played recreational basketball. Lesion resection resulted in complete deficit resolution. Mass lesions involving the musculocutaneous nerve should be considered in patients with atraumatic, isolated musculocutaneous neuropathies that are recurrent or fail to recover, even in the setting of strenuous exercise.

  17. Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling.

    PubMed

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

    2014-11-01

    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 posttranslational 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.

  18. Indices of risk assessment of fracture of the proximal humerus

    PubMed Central

    Giannotti, Stefano; Bottai, Vanna; Dell’osso, Giacomo; Donati, Daniela; Bugelli, Giulia; De Paola, Gaia; Guido, Giulio

    2012-01-01

    Summary Osteoporotic fractures are now a social problem for incidence and costs. Fractures of the proximal humerus events are frequent and constantly increasing. It is estimated that they are 20% of all osteoporotic fractures. Bone densitometry in most cases underestimates the real humeral bone density. There is little information about osteoporotic changes in the proximal humerus and their association with the cortical thickness of the humeral shaft. The ratio between the thickness of the cortical and the total diameter of the humeral diaphysis is the cortical index. Fracture risk limit value is 0.231. Convinced of the need to quantify in a reproducible way the real local humerus bone density, we performed a comparative evaluation of bone density of the humerus and femur in patients admitted to our clinic for fractures of the humerus and femur. We evaluated 28 women treated surgically for a fragility fracture of the proximal humerus or femur neck in 2010. All cortical index obtained were lower than the limit for fracture risk set at 0.231, so the IC was more predictive of neck medial fractures of the femur than had DEXA and the U.S. The information about the cortical index may provide a simple way of determining the bone quality of the proximal humerus and of facilitating decision-making in the surgical treatment of patients with fractures of the humerus. So we want to emphasize the importance of therapy for osteoporosis even in patients with fractures of the proximal humerus, which often have not critical densitometric values of femur or column, but they are at risk of new fractures. PMID:22783334

  19. 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.

  20. A procedure to estimate proximate analysis of mixed organic wastes.

    PubMed

    Zaher, U; Buffiere, P; Steyer, J P; Chen, S

    2009-04-01

    In waste materials, proximate analysis measuring the total concentration of carbohydrate, protein, and lipid contents from solid wastes is challenging, as a result of the heterogeneous and solid nature of wastes. This paper presents a new procedure that was developed to estimate such complex chemical composition of the waste using conventional practical measurements, such as chemical oxygen demand (COD) and total organic carbon. The procedure is based on mass balance of macronutrient elements (carbon, hydrogen, nitrogen, oxygen, and phosphorus [CHNOP]) (i.e., elemental continuity), in addition to the balance of COD and charge intensity that are applied in mathematical modeling of biological processes. Knowing the composition of such a complex substrate is crucial to study solid waste anaerobic degradation. The procedure was formulated to generate the detailed input required for the International Water Association (London, United Kingdom) Anaerobic Digestion Model number 1 (IWA-ADM1). The complex particulate composition estimated by the procedure was validated with several types of food wastes and animal manures. To make proximate analysis feasible for validation, the wastes were classified into 19 types to allow accurate extraction and proximate analysis. The estimated carbohydrates, proteins, lipids, and inerts concentrations were highly correlated to the proximate analysis; correlation coefficients were 0.94, 0.88, 0.99, and 0.96, respectively. For most of the wastes, carbohydrate was the highest fraction and was estimated accurately by the procedure over an extended range with high linearity. For wastes that are rich in protein and fiber, the procedure was even more consistent compared with the proximate analysis. The new procedure can be used for waste characterization in solid waste treatment design and optimization.

  1. TRANSCRIPTIONAL REGULATION OF MITOCHONDRIAL GLYCEROPHOSPHATE ACYLTRANSFERASE IS MEDIATED BY DISTAL PROMOTER VIA ChREBP AND SREBP-1

    PubMed Central

    Guha, Prajna; Aneja, Kawalpreet K.; Shilpi, Rasheda Y.; Haldar, Dipak

    2009-01-01

    We have recently identified two promoters, distal and proximal for rat mitochondrial glycerophosphate acyltransferase (mtGPAT). Here we are reporting further characterization of the promoters. Insulin and epidermal growth factor (EGF) stimulated while leptin and glucagon inhibited the luciferase activity of the distal promoter and the amounts of the distal transcript. Conversely, luciferase activity of the proximal promoter and proximal transcript remained unchanged due to these treatments. Only the distal promoter has binding sites for carbohydrate response element binding protein (ChREBP) and sterol regulatory element binding protein-1 (SREBP-1). Electromobility shift assays and chromatin immunoprecipitation assays demonstrated that ChREBP and SREBP-1 bind to the mtGPAT distal promoter. Insulin and EGF increased while glucagon and leptin decreased the binding of SREBP-1 and ChREBP to the distal promoter. Thus, the distal promoter is the regulatory promoter while the proximal promoter acts constitutively for rat mtGPAT gene under the influence of hormones and growth factor. PMID:19682972

  2. 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

  3. 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

  4. 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

  5. Functional study of the equine beta-casein and kappa-casein gene promoters.

    PubMed

    Lenasi, Tina; Kokalj-Vokac, Nadja; Narat, Mojca; Baldi, Antonella; Dovc, Peter

    2005-01-01

    Casein genes are expressed in a tissue-specific and highly coordinated manner. The main goals of casein gene promoter studies are to unravel cis- and trans-acting factors involved in the complex signalling pathway controlling milk production, and to explore the possibility of using these promoters for tissue-specific production of heterologous proteins in the mammary gland. Here we present a comparative study of the equine beta-casein and kappa-casein gene proximal promoters. In order to confirm the assumption that in the horse, as in other mammalian species, casein genes are organized in a cluster located on a single chromosome, we performed in situ hybridization of pro-metaphase chromosomes with two BAC clones containing different equine casein genes. Sequence analysis of the beta-casein and kappa-casein gene proximal promoters revealed binding sites for activators (STAT5, GRE, NF1, MAF) and repressors (YY1, PMF), characteristic for casein genes. The alignments of casein gene promoters revealed the highest sequence identity in the proximal promoter region between the equine and human beta-casein gene promoters. We directly compared the activity of equine beta-casein and kappa-casein gene promoters in vitro using bovine mammary gland cell line BME-UV1. In this system, the kappa-casein gene proximal promoter activated the reporter gene expression more efficiently than the beta-casein gene promoter of approximately the same length. The 810 bp of beta-casein promoter activated the reporter gene expression more efficiently than the long fragment (1920 bp) and the 1206 bp fragment of the same promoter, which included also 396 bp of 5' UTR.

  6. 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

  7. 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

  8. 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

  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.

    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.

  10. 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.

  11. 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.

  12. 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.

  13. Proximal humeral osteoarticular allografts: technique, pearls and pitfalls, outcomes.

    PubMed

    Farfalli, German L; Ayerza, Miguel A; Muscolo, D Luis; Aponte-Tinao, Luis A

    2015-12-01

    Allograft transplantation is a biologic reconstruction option for massive bone defects after resection of bone sarcomas. This type of reconstruction not only restores bone stock but it also allows us to reconstruct the joint anatomically. These factors are a major concern, especially in a young and active population.We are describing indications, surgical techniques, pearls and pitfalls, and outcomes of proximal humeral osteoarticular allografts, done at present time in our institution.We found that allograft fractures and articular complications, as epiphyseal resorption and subchondral fracture, are the main complications observed in proximal humerus osteoarticular allograft reconstructions. Nevertheless, only fractures need a reconstruction revision. Joint complications may adversely affect the limb function, but for this reason, an allograft revision is rarely performed.

  14. Perceptual grouping in Gabor lattices: proximity and alignment.

    PubMed

    Claessens, Peter M; Wagemans, Johan

    2005-11-01

    We propose the Gabor lattice as a new stimulus designed to deal with multiple organizations in perceptual grouping, allowing both comparison between psychophysical data and neural findings and a systematic investigation of grouping based on several low-level characteristics and their interactions. A Gabor lattice is a geometric lattice with Gabor patches, evoking a multistable global orientation percept. Visual grouping in Gabor lattices with elements aligned in a global orientation was compared with grouping of nonaligned Gabor patches and of Gaussian blobs. The effect sizes of proximity and alignment were estimated in logistic regression analyses. The results confirmed the importance of proximity and local element alignment as factors in dynamic grouping. We also found a small but consistent enhancement of grouping along the global vector orthogonal to the local patch orientations. In light of these results, we further motivate the relevance of these stimuli and the associated experimental paradigm.

  15. Elements of proximal formative assessment in learners' discourse about energy

    NASA Astrophysics Data System (ADS)

    Harrer, Benedikt W.; Scherr, Rachel E.; Wittmann, Michael C.; Close, Hunter G.; Frank, Brian W.

    2012-02-01

    Proximal formative assessment, the just-in-time elicitation of students' ideas that informs ongoing instruction, is usually associated with the instructor in a formal classroom setting. However, the elicitation, assessment, and subsequent instruction that characterize proximal formative assessment are also seen in discourse among peers. We present a case in which secondary teachers in a professional development course at SPU are discussing energy flow in refrigerators. In this episode, a peer is invited to share her thinking (elicitation). Her idea that refrigerators move heat from a relatively cold compartment to a hotter environment is inappropriately judged as incorrect (assessment). The "instruction" (peer explanation) that follows is based on the second law of thermodynamics, and acts as corrective rather than collaborative.

  16. Anterolateral Biplanar Proximal Tibial Opening-Wedge Osteotomy.

    PubMed

    Dean, Chase S; Chahla, Jorge; Moulton, Samuel G; Nitri, Marco; Serra Cruz, Raphael; LaPrade, Robert F

    2016-06-01

    Proximal tibial anterolateral opening-wedge osteotomies have been reported to achieve successful biplanar lower-extremity realignment. Indications for a proximal tibial anterolateral osteotomy include symptomatic genu recurvatum with genu valgus alignment, usually in patients with a flat sagittal-plane tibial slope. The biplanar approach is able to simultaneously address both components of a patient's malalignment with a single procedure. The correction amount is verified with spacers and intraoperative imaging, while correction of the patient's heel height is simultaneously measured. A plate is secured into the osteotomy site, and the site is filled with bone allograft. The anterolateral tibial osteotomy has been reported to be an effective surgical procedure for correcting concomitant genu recurvatum and genu valgus malalignment. PMID:27656374

  17. 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

  18. Half-TV format MWIR sensor module incorporating proximity electronics

    NASA Astrophysics Data System (ADS)

    Ashcroft, A. P.; Richardson, L.; Harji, J.; Giuliano, F.

    2012-06-01

    The Osprey-E sensor module consists of an integrated detector-cooler assembly (IDCA) and custom proximity electronics mounted in a lightweight, ruggedized housing. Based on the half-TV format Osprey FPA, it implements recent improvement in SELEX Galileo's array hybridization technique. Ongoing tests have shown that performance is not significantly degraded after more than 5000 cooldown cycles. The FPA exploits SELEX Galileo's High Operating Temperature (HOT) HgCdTe (MCT) and is optimized for operation at 110K. Very low levels of defective pixels (<0.003%) have been achieved at this temperature. The proximity electronics are a new design that originates from SELEX Galileo's Centre of Excellence in Infrared Detectors. The electronics provide all the necessary supplies and signals for detector operation and digitize the detector output into 14-bit digital video. The sensor has been developed to offer a very lightweight, rugged camera core particularly suited to airborne applications.

  19. Ultimate and proximate mechanisms of reciprocal altruism in rats.

    PubMed

    Dolivo, Vassilissa; Rutte, Claudia; Taborsky, Michael

    2016-09-01

    The reciprocal exchange of goods and services among social partners is a conundrum in evolutionary biology because of its proneness to cheating, but also the behavioral and cognitive mechanisms involved in such mutual cooperation are hotly debated. Extreme viewpoints range from the assumption that, at the proximate level, observed cases of "direct reciprocity" can be merely explained by basic instrumental and Pavlovian association processes, to the other extreme implying that "cultural factors" must be involved, as is often attributed to reciprocal cooperation among humans. Here we argue that neither one nor the other extreme conception is likely to explain proximate mechanisms underlying reciprocal altruism in animals. In particular, we outline that Pavlovian association processes are not sufficient to explain the documented reciprocal cooperation among Norway rats, as has been recently argued. PMID:27495930

  20. A Surviving Child With Complete Proximal Tracheal Atresia

    PubMed Central

    Haight, Ken; Sankaran, Koravangattu; Shokeir, Mohamed

    1984-01-01

    An infant was born with an unusual combination of primitive foregut anomalies consisting of complete proximal tracheal atresia, proximal esophageal atresia and distal tracheoesophageal fistula. Before the birth, the family physician suspected an anomaly of the upper airway or esophageal occlusion on the basis of hydramnios evident at the thirty-third to thirty-fourth week of gestation, and earlier amniocentesis which indicated a normal level of α-fetoprotein. He consulted the hospital obstetrics and neonatology departments, which were thus prepared to deal with a potential airway problem at the birth. At birth, prompt airway management, including tracheostomy, prevented anoxic damage to the child. Features which should alert the physician to tracheal obstruction include antenatal polyhydramnios; severe respiratory distress without an audible cry and palpable distal trachea in the newborn; and failure to advance the endotracheal tube beyond the infant's vocal cords. PMID:21279046

  1. 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.

  2. 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.

  3. Do people remember the temporal proximity of unrelated events?

    PubMed

    Friedman, William J; Janssen, Steve M J

    2010-12-01

    In the present study, we tested the ability to remember the temporal proximity of two unrelated events that had happened within 7 days of one another. In three experiments, 1,909 participants judged whether pairs of news events, ranging in age from 1 month to about 6 years, had occurred within a week of each other and, if not, how far apart they had occurred. Some event pairs were related, and others were unrelated. For unrelated event pairs, same-week and separation judgments were very poor. Accuracy was much greater for both kinds of judgments when the events were related. Participants often guessed the separation of unrelated event pairs, whereas they frequently deduced the separation or remembered the proximity of related event pairs. For both types of pairs, the participants reported using the strength of the memories or the general period in which the events had occurred.

  4. 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.

  5. 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.

  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. 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)

  8. 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

  9. 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

  10. 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

  11. 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

  12. Moulded cement-prosthesis for osteosarcoma of the proximal humerus.

    PubMed

    Pan, K L; Ong, G B; Potukuchi, A P

    2006-12-01

    We report a case of an 11-year-old boy with osteosarcoma of the proximal humerus treated with wide excision and reconstruction with a cement spacer-prosthesis. After seven years of follow-up, the patient is now almost a young adult. We present his current physical and functional status, which seems to defray the initial doubts regarding long-term problems when we chose this method of reconstruction. PMID:17600994

  13. Prevalence of rotator cuff tears in operative proximal humerus fractures.

    PubMed

    Choo, Andrew; Sobol, Garret; Maltenfort, Mitchell; Getz, Charles; Abboud, Joseph

    2014-11-01

    Proximal humerus fractures and rotator cuff tears have been shown to have increasing rates with advancing age, theoretically leading to significant overlap in the 2 pathologies. The goal of this study was to examine the prevalence, associated factors, and effect on treatment of rotator cuff tears in surgically treated proximal humerus fractures. A retrospective review was performed of all patients who had surgery for a proximal humerus fracture from January 2007 to June 2012 in the shoulder department of a large academic institution. Patient demographics, the presence and management of rotator cuff tears, and surgical factors were recorded. Regression analysis was performed to determine which factors were associated with rotator cuff tears. This study reviewed 349 fractures in 345 patients. Of these, 30 (8.6%) had concomitant rotator cuff tears. Those with a rotator cuff tear were older (average age, 68.7 vs 63.1 years), were more likely to have had a dislocation (40% vs 12.5%), and were more likely to have undergone subsequent arthroscopic repair or reverse total shoulder arthroplasty than those without a rotator cuff tear. Most (22 of 30) were treated with suture repair at the time of surgery, but 5 patients underwent reverse total shoulder arthroplasty based primarily on the intraoperative finding of a significant rotator cuff tear. A concomitant rotator cuff tear in association with a proximal humerus fracture is relatively common. Rotator cuff tears are associated with older patients and those with a fracture-dislocation. In rare cases, these cases may require the availability of a reverse shoulder prosthesis. PMID:25361372

  14. 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

  15. 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

  16. 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

  17. 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

  18. PROXIMITY TO AN EXERCISE FACILITY AND PHYSICAL ACTIVITY IN CHINA.

    PubMed

    Ani, Ruopeng; Zheng, Jiakun

    2014-11-01

    Physical inactivity is a major risk factor for premature morbidity and mortality. We studied the relationship between proximity to an exercise facility and leisure time physical activity in China. We conducted a questionnaire-based survey of 10 provinces in China during 2012 among 5,000 respondents with a completion rate of 82.1%. Respondents were asked about leisure time physical activity, defined as any exercise during the week. Respondents were also asked if they lived within 10 minutes walking distance from an exercise facility. The association between proximity to an exercise facility and physical activity were examined with multivariate regression analysis while attempting to control for sociodemographic factors and province of residence. Proximity to an exercise facility was found to be positively associated with leisure time physical activity. Individuals living within 10 minutes walking distance from an exercise facility were 6.79% (95% confidence interval: 3.67-10.01) more likely to have any leisure time physical activity than those who lived more than 10 minutes walking distance from an exercise facility. Physical exercise among females, younger adults, people with a higher education and urban residents appeared to have a greater association with distance to an exercise facility. Improving accessibility to an exercise facility might increase the likelihood of leisure time physical activity, especially among working-age urban Chinese.

  19. 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

  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

    2015-12-14

    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.

  1. 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

  2. Scheduling in Heterogeneous Computing Environments for Proximity Queries.

    PubMed

    Kim, Duksu; Lee, Jinkyu; Lee, Junghwan; Shin, Insik; Kim, John; Yoon, Sunggeui

    2013-04-01

    We present a novel, Linear Programming (LP) based scheduling algorithm that exploits heterogeneous multi-core architectures such as CPUs and GPUs to accelerate a wide variety of proximity queries. To represent complicated performance relationships between heterogeneous architectures and different computations of proximity queries, we propose a simple, yet accurate model that measures the expected running time of these computations. Based on this model, we formulate an optimization problem that minimizes the largest time spent on computing resources, and propose a novel, iterative LP-based scheduling algorithm. Since our method is general, we are able to apply our method into various proximity queries that have different characteristics. Our method achieves an order of magnitude performance improvement by using four different GPUs and two hexa-core CPUs over using a hexa-core CPU only. Unlike prior scheduling methods, our method continually improves the performance, as we add more computing resources. Also, our method achieves much higher performance improvement compared with prior methods as heterogeneity of computing resources is increased. We also show that our method provides results that are close to the performance provided by a conservative upper bound of the ideal throughput. These results demonstrate the efficiency and robustness of our algorithm that have not been achieved by prior methods.

  3. Progenitor Cells in Proximal Airway Epithelial Development and Regeneration

    PubMed Central

    Lynch, Thomas J.; Engelhardt, John F.

    2015-01-01

    Multiple distinct epithelial domains are found throughout the airway that are distinguishable by location, structure, function, and cell-type composition. Several progenitor cell populations in the proximal airway have been identified to reside in confined microenvironmental niches including the submucosal glands (SMGs), which are embedded in the tracheal connective tissue between the surface epithelium and cartilage, and basal cells that reside within the surface airway epithelium (SAE). Current research suggests that regulatory pathways that coordinate development of the proximal airway and establishment of progenitor cell niches may overlap with pathways that control progenitor cell responses during airway regeneration following injury. SMGs have been shown to harbor epithelial progenitor cells, and this niche is dysregulated in diseases such as cystic fibrosis. However, mechanisms that regulate progenitor cell proliferation and maintenance within this glandular niche are not completely understood. Here we discuss glandular progenitor cells during development and regeneration of the proximal airway and compare properties of glandular progenitors to those of basal cell progenitors in the SAE. Further investigation into glandular progenitor cell control will provide a direction for interrogating therapeutic interventions to correct aberrant conditions affecting the SMGs in diseases such as cystic fibrosis, chronic bronchitis, and asthma. PMID:24818588

  4. Proximal Rectus Femoris Avulsion: Ultrasonic Diagnosis and Nonoperative Management

    PubMed Central

    Esser, Stephan; Jantz, David; Hurdle, Mark F.; Taylor, Walter

    2015-01-01

    Objective To present a case of ultrasonic diagnosis and nonoperative management of a complete proximal rectus femoris avulsion in a National Collegiate Athletic Association Division 1 soccer goalkeeper. Background While delivering a goal kick, a previously uninjured 24-year-old collegiate soccer goalkeeper had the sudden onset of right anterior thigh pain. He underwent rehabilitation with rapid resolution of his presenting pain but frequent intermittent recurrence of anterior thigh pain. After he was provided a definitive diagnosis with musculoskeletal ultrasound, he underwent an extended period of rehabilitation and eventually experienced complete recovery without recurrence. Differential Diagnosis Rectus femoris avulsion, rectus femoris strain or partial tear, inguinal hernia, or acetabular labral tear. Treatment Operative and nonoperative options were discussed. In view of the player's recovery, nonoperative options were pursued with a good result. Uniqueness Complete proximal rectus femoris avulsions are rare. Our case contributes to the debate on whether elite-level kicking and running athletes can return to full on-field performance without surgery. Conclusions Complete proximal rectus femoris avulsions can be treated effectively using nonoperative measures with good preservation of function even in the elite-level athlete. In addition, musculoskeletal ultrasound is an excellent tool for on-site evaluation and may help guide prognosis and management. PMID:25978099

  5. 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.

  6. Scheduling in Heterogeneous Computing Environments for Proximity Queries.

    PubMed

    Kim, Duksu; Lee, Jinkyu; Lee, Junghwan; Shin, Insik; Kim, John; Yoon, Sunggeui

    2013-04-01

    We present a novel, Linear Programming (LP) based scheduling algorithm that exploits heterogeneous multi-core architectures such as CPUs and GPUs to accelerate a wide variety of proximity queries. To represent complicated performance relationships between heterogeneous architectures and different computations of proximity queries, we propose a simple, yet accurate model that measures the expected running time of these computations. Based on this model, we formulate an optimization problem that minimizes the largest time spent on computing resources, and propose a novel, iterative LP-based scheduling algorithm. Since our method is general, we are able to apply our method into various proximity queries that have different characteristics. Our method achieves an order of magnitude performance improvement by using four different GPUs and two hexa-core CPUs over using a hexa-core CPU only. Unlike prior scheduling methods, our method continually improves the performance, as we add more computing resources. Also, our method achieves much higher performance improvement compared with prior methods as heterogeneity of computing resources is increased. We also show that our method provides results that are close to the performance provided by a conservative upper bound of the ideal throughput. These results demonstrate the efficiency and robustness of our algorithm that have not been achieved by prior methods. PMID:23568962

  7. SLAP tear associated with a minimally displaced proximal humerus fracture.

    PubMed

    Kendall, Corey B; Tanner, Stephanie L; Tolan, Stefan J

    2007-12-01

    Nondisplaced proximal humerus fracture may be associated with soft tissue injury. This case report examines 2 cases of superior labral anterior-posterior (SLAP) tears in association with nondisplaced fractures of the proximal humerus. In the first case, the patient fell from a jet ski, causing a traction injury to his arm. A greater tuberosity fracture was identified. Magnetic resonance imaging (MRI) did not reveal a definitive labral tear. After conservative management had failed, a type IV SLAP tear and a small rotator cuff tear were arthroscopically identified and repaired. In the second case, a power company lineman fell from a lift and attempted to hold on with his dominant arm. A nondisplaced greater tuberosity and a surgical neck fracture were discovered. MR arthrography revealed no evidence of SLAP tear. Four months after injury, a type II SLAP tear was arthroscopically identified and repaired. In these 2 cases, the presence of the fracture likely slowed operative intervention because pain was attributed to the fracture itself, and not to the SLAP tear. If patients do not follow the usual course of improvement after a proximal humerus fracture from a superior traction mechanism, consideration should be given to associated superior labral tears that may require surgical intervention.

  8. Links between casino proximity and gambling participation, expenditure, and pathology.

    PubMed

    Sévigny, Serge; Ladouceur, Robert; Jacques, Christian; Cantinotti, Michael

    2008-06-01

    Two studies investigated the relationship between casino proximity and gambling participation, expenditure, and pathology. In Study 1, 8,842 participants were categorized into 1 of 4 driving distances from their home to the nearest casino in the province of Quebec: 0-100 km, 100.01-200 km, 200.01-300 km, or 300.01-981 km. In Study 2, 5,158 participants, who lived within a 100-km driving distance from the Montreal casino, were classified into 1 of 5 equidistant, 20-km driving distances. A survey company interviewed participants regarding their gambling habits. Results indicated a positive link between casino proximity and gambling participation (at the provincial and Montreal levels) and expenditure (at the provincial level only) but no link with the current prevalence rate of probable pathological gambling or of problem gambling. In a setting in which many types of gambling activities are available, casino proximity in itself does not appear to explain the rate of gambling-related problems. It is necessary to continue prospective research on exposure and adaptation theories as potential explanations for the development of pathological gambling.

  9. Proximity hybridization regulated DNA biogate for sensitive electrochemical immunoassay.

    PubMed

    Ren, Kewei; Wu, Jie; Zhang, Yue; Yan, Feng; Ju, Huangxian

    2014-08-01

    An electrochemical DNA biogate was designed for highly sensitive homogeneous electrochemical immunoassay by combining target-induced proximity hybridization with a mesoporous silica nanoprobe (MSN). The electroactive methylene blue (MB) was sealed in the inner pores of MSN with single-stranded DNA. In the presence of target protein and two DNA-labeled antibodies, the formed proximate complex could hybridize with the DNA strand to form a rigid double-stranded structure and thus open the biogate, which led to the release of MB entrapped in the MSN. The target protein-dependent amount of released MB could be conveniently monitored with a screen-printed carbon electrode. Moreover, the detachment process of MB could be further amplified with an in situ enzymatic recycling binding of the proximate complex with the single-stranded DNA. Using prostate-specific antigen as a model target, the proposed assay showed a wide detection range from 0.002 to 100 ng mL(-1) with a detection limit of 1.3 pg mL(-1). This strategy was simple and universal for various analytes with different affinity ligands. This method possessed great potential for convenient point-of-care testing and commercial application.

  10. 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.

  11. Isolated acute dislocation of the proximal tibiofibular joint.

    PubMed

    Iosifidis, Michael I; Giannoulis, Ioannis; Tsarouhas, Alexandros; Traios, Stavros

    2008-06-01

    Lesions of knee's lateral side are less common than medial injuries. The anatomy of the lateral ligaments and the presence of additional structures (eg, fibula head) can cause diagnostic problems. Isolated dislocation of the proximal tibiofibular joint is unusual; therefore, it may be overlooked in the emergency department. Many cases are missed due to failure of diagnosis. This type of injury is common in athletes whose sports require twisting motions of the flexed knee (eg, wrestling, parachute jumping, judo, gymnastics, skiing, rugby, football, soccer, track, baseball, basketball, racquetball, and roller-skating). Anterolateral dislocation of the proximal tibiofibular joint is seemingly rare in soccer players, as less than a handful cases have been reported in the literature. The diagnosis can be made by clinical examination, plain knee radiographs, and, sometimes, computed tomography (CT) scanning for further confirmation. Treatment usually consists of closed or open reduction. In complicated cases, however, arthrodesis or resection of the fibular head may be required. This article reports a rare case of acute isolated anterolateral dislocation of the proximal tibiofibular joint in a soccer player and discusses the joint anatomy, types of dislocations, mechanisms of injury, and treatment options.

  12. Correction for etch proximity: new models and applications

    NASA Astrophysics Data System (ADS)

    Granik, Yuri

    2001-09-01

    Short-range etch proximity effects increase intra-die CD variability and degrade the IC performance and yield. Tight control of the etch bias is an increasingly critical factor in realizing the ITRS technology nodes. The 2000 technology nodes revision added a new category, the post-etch 'physical' gate length metric, that is 9 - 17% smaller than 'in-resist' gate length. We present new etch proximity correction methods and models designed to reduce negative impact of etch-induced CD variability and increase uniformity of the controlled over- etching. Resolution Enhancement Technologies (RET) design correction methods typically employ 'lumped' process models. We found that an alternative methodology based upon separation of the process factors and the related models may yield better accuracy, performance, and better suit the design and process optimization flows. The contributions from the reticle, the optics, the wafer, and etch are individually determined and then used either separately or in aggregation for the most flexible and optimum correction of their respective contributions. The etch corrections are based on the Variable Etch Bias model (VEB model). This semi-empirical model requires experimental CD information to be collected from the test patterns under fixed process conditions (point-process model). It demonstrates excellent fit to the early experimental CD-SEM data gathered to date, which spans a variety of layout features and process conditions. The VEB model works in conjunction with CalibreR software system's Variable Threshold Resist-Extended (VTR-E) model, however the etching is modeled separately from the optics and the resist processing. This yields better understanding and more accurate explanation of the experiments than those that are produced by the 'lumped' process modeling. The VEB model explains etch- induced bias in terms of the following three proximity characteristics or variables: effective trench width (or pattern separation), pattern

  13. Proximal clamping levels in abdominal aortic aneurysm surgery.

    PubMed Central

    Büket, S; Atay, Y; Islamoğlu, F; Yağdi, T; Posacioğlu, H; Alat, I; Cikirikçioğlu, M; Yüksel, M; Durmaz, I

    1999-01-01

    In the surgical treatment of abdominal aortic aneurysm, the single proximal cross-clamp can be placed at 3 alternative aortic levels: infrarenal, hiatal, and thoracic. We performed this retrospective study to evaluate the advantages and disadvantages of the 3 main aortic clamping locations. Eighty patients presented at our institution with abdominal aortic aneurysms from March 1993 through May 1998. Fifty of these patients had intact aneurysms and underwent elective surgery, and 30 had ruptured aneurysms that necessitated emergency surgery. Proximal aortic clamping was applied at the infrarenal level in 24 patients (22 from the intact aneurysm group, 2 from the ruptured group), at the hiatal level in 34 patients (22 intact, 12 ruptured), and at the thoracic level (descending aorta) via a limited left lateral thoracotomy in 22 patients (6 intact, 16 ruptured). Early mortality rates (within 30 days) were 4% (2 of 50 patients) among patients with intact aneurysms and 40% (12 of 30 patients) among those with ruptured aneurysms. In the 2 patients from the intact aneurysm group, proximal aortic clamps were applied at the hiatal level. In the ruptured aneurysm group, proximal aortic clamps were placed at the thoracic level in 10 patients, the infrarenal level in 1, and the hiatal level in 1. According to our study, the clinical status of the patient and the degree of operative urgency--as determined by the extent of the aneurysm--generally dictate the proximal clamp location. Patients who present with aneurysmal rupture or hypovolemic shock benefit from thoracic clamping, because it restores the blood pressure and allows time to replace the volume deficit. Infrarenal placement is advantageous in patients with intact aneurysms if there is sufficient space for the clamp between the renal arteries and the aortic aneurysm. In patients with juxtarenal aneurysms, hiatal clamping enables safe and easy anastomosis to the healthy aorta. Clamping at this level also helps prevent

  14. Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle

    PubMed Central

    Cardozo, Marcos Julián; Sánchez-Arrones, Luisa; Sandonis, África; Sánchez-Camacho, Cristina; Gestri, Gaia; Wilson, Stephen W.; Guerrero, Isabel; Bovolenta, Paola

    2014-01-01

    Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hedgehog (Hh) signalling, which promotes stalk specification. In the absence of Hh signalling, the stalks are not specified, causing cyclopia. Recent studies showed that the cell adhesion molecule Cdon forms a heteromeric complex with the Hh receptor Patched 1 (Ptc1). This receptor complex binds Hh and enhances signalling activation, indicating that Cdon positively regulates the pathway. Here we show that in the developing zebrafish and chick optic vesicle, in which cdon and ptc1 are expressed with a complementary pattern, Cdon acts as a negative Hh signalling regulator. Cdon predominantly localizes to the basolateral side of neuroepithelial cells, promotes the enlargement of the neuroepithelial basal end-foot and traps Hh protein, thereby limiting its dispersion. This Ptc-independent function protects the retinal primordium from Hh activity, defines the stalk/retina boundary and thus the correct proximo-distal patterning of the eye. PMID:25001599

  15. Clinical results of using the proximal humeral internal locking system plate for internal fixation of displaced proximal humeral fractures.

    PubMed

    Norouzi, Masoud; Naderi, Mohammad Nasir; Komasi, Mehdi Hemmati; Sharifzadeh, Seyyed Reza; Shahrezaei, Mostafa; Eajazi, Alireza

    2012-05-01

    Proximal humerus fractures are accounting for 4-5% of all fractures with increasing incidence. Proximal Humeral Internal Locking System (PHILOS) plate is a new plate which permits early mobility and lowers the risk of complications. The aim of this study was to evaluate the functional outcome and the complication rate after using this plate. Between 2006-2008, 37 patients with displaced 2-, 3-, and 4-part fractures of the proximal humerus underwent surgery using PHILOS plate. The mean range of follow-up was 12 months. Twenty patients were aged 60 years and younger, and 17 were aged older than 60 years. The average American Shoulder and Elbow Surgeons (ASES) score at the final follow-up was 77.62. According to Michener and colleagues classification, 5.4% of patients had an excellent outcome, 72.9% were minimally functionally limited, 16.2% were moderately functionally limited, and 5.4% were maximally functionally limited. The average ASES score between patients 60 years and older and those 60 years and younger was not different significantly. One patient developed avascular necrosis of the humeral head, 2 patients developed an infection, and no patients developed a nonunion. Fixation with PHILOS plate can be considered a good method with high union rates for this kind of fracture, especially in the older population with osteoporotic bone.

  16. Parathyroid hormone decreases HCO3 reabsorption in the rat proximal tubule by stimulating phosphatidylinositol metabolism and inhibiting base exit.

    PubMed Central

    Pastoriza-Munoz, E; Harrington, R M; Graber, M L

    1992-01-01

    The mechanism of inhibition of HCO3 transport by parathyroid hormone (PTH) in the proximal tubule is not clearly defined. Previous studies in vitro have suggested that this effect is mediated via cAMP generation, which acts to inhibit Na/H exchange, resulting in cell acidification. To examine this question in vivo, intracellular pH (pHi) was measured in the superficial proximal tubule of the rat using the pH-sensitive fluoroprobes 4-methylumbelliferone (4MU) and 2',7'-bis(carboxyethyl)-(5, and 6)-carboxyfluorescein (BCECF). PTH was found to alkalinize the cell. This alkalinization suggested inhibition of basolateral base exit, which was confirmed by in situ microperfusion studies: lowering HCO3 in peritubular capillaries acidified the cell, an effect blunted by PTH. Removal of luminal Na promoted basolateral base entry, alkalinizing the cell. This response was also blunted by PTH. Readdition of luminal Na stimulated the luminal Na/H exchanger, causing an alkalinization overshoot that was partially inhibited by PTH. cAMP inhibited luminal H secretion but did not alkalinize the cell. Stimulation of phosphatidylinositol-bis-phosphate turnover by PTH was suggested by the effect to the hormone to increase cell Ca. Blocking the PTH-induced rise in cell Ca blunted the effect of the hormone to alkalinize the cell, as did inhibition of phosphatidylinositol breakdown. Furthermore, stimulation of protein kinase C by a phorbol ester and a diacylglycerol applied basolaterally alkalinized the cell and inhibited luminal H secretion. The findings indicate that both arms of the phosphatidylinositol-bis-phosphate cascade play a role in mediating the effect of PTH on the cell pH. The results are consistent with the view that PTH inhibits base exit in the proximal tubule by activation of the phosphatidylinositol cascade. The resulting alkalinization may contribute, with cAMP, to inhibit apical Na/H exchange and the PTH-induced depression of proximal HCO3 reabsorption. PMID:1314850

  17. 14 CFR 121.360 - Ground proximity warning-glide slope deviation alerting 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-glide slope... Equipment Requirements § 121.360 Ground proximity warning-glide slope deviation alerting system. (a) No... turbine-powered airplane unless it is equipped with a ground proximity warning/glide slope...

  18. The functional importance of a cap site-proximal region of the human prointerleukin 1[beta] gene is defined

    SciTech Connect

    Hunninghake, G.W.; Geist, L.J.; Monick, M.M.; Stinski, M.F. ); Monks, B.G.; Monroy, M.A.; Fenton, M.J. ); Webb, A.C. ); Dayer, J.M. ); Auron, P.E. )

    1992-08-01

    Prointerleukin 1[beta] (IL-1[beta]) is a cytokine that mediates a broad range of biological activities. Genomic sequences that regulate IL-1[beta] transcription include both inducible regulatory elements located more than 2,700 bp upstream of the transcriptional start site (cap site) and proximal elements located near the TATA box of this gene. In this study, we focused on the identification and characterization of trans-acting nuclear regulatory proteins that bind to the cap site-proximal region of the human IL-1[beta] gene. We identified a protein, termed NFIL-1[beta]A (NF[beta]A), that binds to a highly conserved 12-bp DNA sequence (-49 to -38) located upstream of the TATA box motif in both the human and murine IL-1[beta] genes. The IL-1[alpha] gene, which lacks a TATA motif, does not possess an NF[beta]A-binding sequence within the promoter region, suggesting that NF[beta]A may selectively regulate IL-1[beta] expression. Using electrophoretic mobility shift assays, we identified several distinct DNA-protein complexes that are expressed in a cell-type-specific manner. In monocytic cell lines, the relative abundance of these complexes varied rapidly following stimulation of the cells with phorbol esters or lipopolysaccharide. UV cross-linking analysis identified two distinct DNA-binding polypeptides that comprise distinct complexes. The functional role of NF[beta]A was assessed in transient transfection assays. These data indicate the NF[beta]A is required for both basal and inducible promoter activity in monocytic cells. Furthermore, the human cytomegalovirus immediate-early 1 gene product requires the presence of NF[beta]A in order to trans-activate the proximal IL-1[beta] promoter in a monocytic cell line. We propose that NF[beta]A is a factor that mediates either direct or indirect activation by the immediate-early 1 gene product. The proximity of this essential factor to the TATA motif suggests a possible role in transcriptional initiation.

  19. Structural and functional analysis of the bovine Mx1 promoter.

    PubMed

    Yamada, Kohji; Nakatsu, Yuichiro; Onogi, Akio; Takasuga, Akiko; Sugimoto, Yoshikazu; Ueda, Junji; Watanabe, Tomomasa

    2009-04-01

    The bovine Mx1 promoter region was found to contain 4 IFN-stimulated response elements (ISREs), 7 GC boxes, 2 IL-6 responsive elements, 2 NFκB-binding sites and 2 AP-1-binding sites. Among Holstein, Charolai, and Brahman breeds, 5 nucleotide substitutions were detected in the promoter region. After the Mx1 promoter region from Holstein had been constructed with pGL-basic expression vector, the transfected cells showed promoter activity after IFN induction. Several artificial deletion mutants were prepared to determine the important regulatory elements responsible for the promoter activity, and it was found that ISRE has a key function in IFN response. The proximal ISRE1 showed potential induction by IFN. Furthermore, the proximal GC boxes were found to be essential for IFN response in the bovine Mx1 promoter with the deletion mutants. In this case, the 2 GC boxes exhibited a synergistic activation in the IFN response. Mithramycin A, an agent that inhibits gene expression selectively by coating GC boxes, was used, and Mx mRNA expression in MDBK cells was suppressed by this chemical. Therefore, GC boxes were also shown to be essential for IFN response in the bovine Mx1 gene. PMID:19203250

  20. Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury.

    PubMed

    Sekine, Michiko; Monkawa, Toshiaki; Morizane, Ryuji; Matsuoka, Kunie; Taya, Choji; Akita, Yoshiko; Joh, Kensuke; Itoh, Hiroshi; Hayashi, Matsuhiko; Kikkawa, Yoshiaki; Kohno, Kenji; Suzuki, Akemi; Yonekawa, Hiromichi

    2012-02-01

    The proximal straight tubule (S3 segment) of the kidney is highly susceptible to ischemia and toxic insults but has a remarkable capacity to repair its structure and function. In response to such injuries, complex processes take place to regenerate the epithelial cells of the S3 segment; however, the precise molecular mechanisms of this regeneration are still being investigated. By applying the "toxin receptor mediated cell knockout" method under the control of the S3 segment-specific promoter/enhancer, Gsl5, which drives core 2 β-1,6-N-acetylglucosaminyltransferase gene expression, we established a transgenic mouse line expressing the human diphtheria toxin (DT) receptor only in the S3 segment. The administration of DT to these transgenic mice caused the selective ablation of S3 segment cells in a dose-dependent manner, and transgenic mice exhibited polyuria containing serum albumin and subsequently developed oliguria. An increase in the concentration of blood urea nitrogen was also observed, and the peak BUN levels occurred 3-7 days after DT administration. Histological analysis revealed that the most severe injury occurred in the S3 segments of the proximal tubule, in which tubular cells were exfoliated into the tubular lumen. In addition, aquaporin 7, which is localized exclusively to the S3 segment, was diminished. These results indicate that this transgenic mouse can suffer acute kidney injury (AKI) caused by S3 segment-specific damage after DT administration. This transgenic line offers an excellent model to uncover the mechanisms of AKI and its rapid recovery.

  1. Effects of Lightpipe Proximity on Si Wafer Temperature in Rapid Thermal Processing Tools

    NASA Astrophysics Data System (ADS)

    Kreider, K. G.; Chen, D. H.; DeWitt, D. P.; Kimes, W. A.; Tsai, B. K.

    2003-09-01

    Lightpipe radiation thermometers (LPRTs) are used as temperature monitoring sensors in most rapid thermal processing (RTP) tools for semiconductor fabrication. These tools are used for dopant anneal, gate oxide formation, and other high temperature processing. In order to assure uniform wafer temperatures during processing these RTP tools generally have highly reflecting chamber walls to promote a uniform heat flux on the wafer. Therefore, only minimal disturbances in the chamber reflectivity are permitted for the sensors, and the small 2 mm diameter sapphire lightpipe is generally the temperature sensor of choice. This study was undertaken to measure and model the effect of LPRT proximity on the wafer temperature. Our experiments were performed in the NIST RTP test bed using a NIST thin-film thermocouple (TFTC) calibration wafer. We measured the spectral radiance temperature with the center lightpipe and compared these with the TFTC junctions and with the three LPRTs at the mid-radius of the wafer. We measured LPRT outputs from a position flush with the reflecting plate to within 2 mm of the stationary wafer under steady-state conditions with wafer-to-cold plate separation distances of 6 mm, 10 mm and 12.5 mm. Depressions in the wafer temperature up to 25 °C were observed. A finite-element radiation model of the wafer-chamber-lightpipe was developed to predict the temperature depression as a function of proximity distance and separation distance. The experimental results were compared with those from a model that accounts for lightpipe geometry and radiative properties, wafer emissivity and chamber cold plate reflectivity.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  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. Perceptual organization by proximity and similarity in schizophrenia.

    PubMed

    Kurylo, Daniel D; Pasternak, Roey; Silipo, Gail; Javitt, Daniel C; Butler, Pamela D

    2007-09-01

    Perceptual organization represents a basic and essential function that occurs at an intermediate level of visual processing. Much of the previous research on perceptual organization in schizophrenia employed indirect measurements, or included factors beyond sensory processing. The aims of the present study were to determine the integrity of perceptual organization in schizophrenia, as well as to determine the stimulus duration necessary to perform perceptual organization. Psychophysical measurements were compared between patients with schizophrenia and matched control subjects. Participants viewed dot patterns briefly presented on a computer monitor, and indicated whether stimuli appeared grouped as vertical or horizontal lines. Grouping was based upon either relative proximity or similarity in color. Across trials, relative proximity or color similarity was progressively reduced until stimuli became bi-stable (perceived as either of two patterns of grouping), establishing the grouping threshold. In separate conditions, stimuli were immediately followed by a mask to limit processing. Stimulus duration was progressively reduced until stimuli became bi-stable, establishing the critical stimulus duration (CSD). Schizophrenia patients demonstrated elevated grouping thresholds for grouping by proximity as well as color similarity. In addition, CSD was significantly extended for the schizophrenia group, with a nearly four-fold increase in duration of processing. These results provide direct evidence of impairment in schizophrenia for perceptual organization based upon spatial relationships and feature similarity, and suggest deficits in low-level perceptual organization processes. Although this study did not directly investigate the physiological correlates underlying perceptual impairments, these results are consistent with a theory of impaired lateral connections within visual cortical areas in schizophrenia. PMID:17681736

  10. Scheduling in heterogeneous computing environments for proximity queries.

    PubMed

    Kim, Duksu; Lee, Jinkyu; Lee, Junghwan; Shin, Insik; Kim, John; Yoon, Sung-Eui

    2013-09-01

    We present a novel, linear programming (LP)-based scheduling algorithm that exploits heterogeneous multicore architectures such as CPUs and GPUs to accelerate a wide variety of proximity queries. To represent complicated performance relationships between heterogeneous architectures and different computations of proximity queries, we propose a simple, yet accurate model that measures the expected running time of these computations. Based on this model, we formulate an optimization problem that minimizes the largest time spent on computing resources, and propose a novel, iterative LP-based scheduling algorithm. Since our method is general, we are able to apply our method into various proximity queries used in five different applications that have different characteristics. Our method achieves an order of magnitude performance improvement by using four different GPUs and two hexa-core CPUs over using a hexa-core CPU only. Unlike prior scheduling methods, our method continually improves the performance, as we add more computing resources. Also, our method achieves much higher performance improvement compared with prior methods as heterogeneity of computing resources is increased. Moreover, for one of tested applications, our method achieves even higher performance than a prior parallel method optimized manually for the application. We also show that our method provides results that are close (e.g., 75 percent) to the performance provided by a conservative upper bound of the ideal throughput. These results demonstrate the efficiency and robustness of our algorithm that have not been achieved by prior methods. In addition, we integrate one of our contributions with a work stealing method. Our version of the work stealing method achieves 18 percent performance improvement on average over the original work stealing method. This result shows wide applicability of our approach.

  11. Nonequilibrium thermodynamic model of the rat proximal tubule epithelium.

    PubMed

    Weinstein, A M

    1983-11-01

    The rat proximal tubule epithelium is represented as well-stirred, compliant cellular and paracellular compartments bounded by mucosal and serosal bathing solutions. With a uniform pCO2 throughout the epithelium, the model variables include the concentrations of Na, K, Cl, HCO3, H2PO4, HPO4, and H, as well as hydrostatic pressure and electrical potential. Except for a metabolically driven Na-K exchanger at the basolateral cell membrane, all membrane transport within the epithelium is passive and is represented by the linear equations of nonequilibrium thermodynamics. In particular, this includes the cotransport of Na-Cl and Na-H2PO4 and countertransport of Na-H at the apical cell membrane. Experimental constraints on the choice of ionic conductivities are satisfied by allowing K-Cl cotransport at the basolateral membrane. The model equations include those for mass balance of the nonreacting species, as well as chemical equilibrium for the acidification reactions. Time-dependent terms are retained to permit the study of transient phenomena. In the steady state the energy dissipation is computed and verified equal to the sum of input from the Na-K exchanger plus the Gibbs free energy of mass addition to the system. The parameter dependence of coupled water transport is studied and shown to be consistent with the predictions of previous analytical models of the lateral intercellular space. Water transport in the presence of an end-proximal (HCO3-depleted) luminal solution is investigated. Here the lower permeability and higher reflection coefficient of HCO3 enhance net sodium and water transport. Due to enhanced flux across the tight junction, this process may permit proximal tubule Na transport to proceed with diminished energy dissipation.

  12. 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

  13. Scheduling in heterogeneous computing environments for proximity queries.

    PubMed

    Kim, Duksu; Lee, Jinkyu; Lee, Junghwan; Shin, Insik; Kim, John; Yoon, Sung-Eui

    2013-09-01

    We present a novel, linear programming (LP)-based scheduling algorithm that exploits heterogeneous multicore architectures such as CPUs and GPUs to accelerate a wide variety of proximity queries. To represent complicated performance relationships between heterogeneous architectures and different computations of proximity queries, we propose a simple, yet accurate model that measures the expected running time of these computations. Based on this model, we formulate an optimization problem that minimizes the largest time spent on computing resources, and propose a novel, iterative LP-based scheduling algorithm. Since our method is general, we are able to apply our method into various proximity queries used in five different applications that have different characteristics. Our method achieves an order of magnitude performance improvement by using four different GPUs and two hexa-core CPUs over using a hexa-core CPU only. Unlike prior scheduling methods, our method continually improves the performance, as we add more computing resources. Also, our method achieves much higher performance improvement compared with prior methods as heterogeneity of computing resources is increased. Moreover, for one of tested applications, our method achieves even higher performance than a prior parallel method optimized manually for the application. We also show that our method provides results that are close (e.g., 75 percent) to the performance provided by a conservative upper bound of the ideal throughput. These results demonstrate the efficiency and robustness of our algorithm that have not been achieved by prior methods. In addition, we integrate one of our contributions with a work stealing method. Our version of the work stealing method achieves 18 percent performance improvement on average over the original work stealing method. This result shows wide applicability of our approach. PMID:23846096

  14. [Proximate analysis of straw by near infrared spectroscopy (NIRS)].

    PubMed

    Huang, Cai-jin; Han, Lu-jia; Liu, Xian; Yang, Zeng-ling

    2009-04-01

    Proximate analysis is one of the routine analysis procedures in utilization of straw for biomass energy use. The present paper studied the applicability of rapid proximate analysis of straw by near infrared spectroscopy (NIRS) technology, in which the authors constructed the first NIRS models to predict volatile matter and fixed carbon contents of straw. NIRS models were developed using Foss 6500 spectrometer with spectra in the range of 1,108-2,492 nm to predict the contents of moisture, ash, volatile matter and fixed carbon in the directly cut straw samples; to predict ash, volatile matter and fixed carbon in the dried milled straw samples. For the models based on directly cut straw samples, the determination coefficient of independent validation (R2v) and standard error of prediction (SEP) were 0.92% and 0.76% for moisture, 0.94% and 0.84% for ash, 0.88% and 0.82% for volatile matter, and 0.75% and 0.65% for fixed carbon, respectively. For the models based on dried milled straw samples, the determination coefficient of independent validation (R2v) and standard error of prediction (SEP) were 0.98% and 0.54% for ash, 0.95% and 0.57% for volatile matter, and 0.78% and 0.61% for fixed carbon, respectively. It was concluded that NIRS models can predict accurately as an alternative analysis method, therefore rapid and simultaneous analysis of multicomponents can be achieved by NIRS technology, decreasing the cost of proximate analysis for straw.

  15. 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

  16. Efficiency of the Lausanne Clinical Pathway for Proximal Femoral Fractures

    PubMed Central

    Fleury, Nicole; Chevalley, François; Rubli, Eve; Coti, Pauline; Farron, Alain; Jolles, Brigitte M.

    2015-01-01

    Purpose/Introduction: The number of hip fractures is rising, due to increases in life expectancy. In such cases, patients are at risk from post-operative complications and subsequently the average length of hospitalization may be extended. In 2011, we established a clinical pathway (CP), a specific model of care for patient-care management, to improve the clinical and economic outcomes of proximal femoral fracture management in elderly patients. The goal was to evaluate the CP using clinical, process, and financial indicators. Methods: We included all surgical patients aged 65 and over, admitted to the emergency department with a fracture of the proximal femur following a fall. Assessment parameters included three performance indicators: clinical, process, and financial. The clinical indicators were the presence or absence of acute delirium on the third post-operative day, diagnosis of nosocomial pneumonia, and the number of patients fulfilling at least 75% of their nutritional requirements at the end of the hospitalization period. The process indicator was the time interval between arrival at the emergency department and surgery. The financial indicator was based on the number of days spent in hospital. Results: From 2011 to 2013, 669 patients were included in the CP. We observed that the average length of stay in hospital decreased as soon as the CP was implemented and stabilized afterwards. The goal of 90% of patients undergoing surgery within 48 h of arrival in the emergency department was surpassed in 2013 (93.1%). Furthermore, we observed an improvement in the clinical indicators. Conclusion: The application of a CP allowed an improvement in the qualitative and quantitative efficiency of proximal femoral fracture management in elderly patients, in terms of clinical, process, and financial factors. PMID:25745631

  17. 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

  18. 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

  19. Arteriovenous graft with outflow in the proximal axillary vein.

    PubMed

    Teruya, Theodore H; Schaeffer, David; Abou-Zamzam, Ahmed M; Bianchi, Christian

    2009-01-01

    Arteriovenous access can result in complications including extremity ischemia and swelling. Use of the nondominant upper extremity is preferred because complications will result in less severe disability. The distal axillary vein in the axilla is usually considered to be the end point for arteriovenous access in the upper extremity. Vascular surgeons are familiar with exposure of the proximal axillary artery via an infraclavicular incision. The axillary vein is also easily exposed through this technique. Use of this vein for arteriovenous graft outflow can preserve the dominant arm for future use. Nine patients with arteriovenous grafts with venous outflow in the proximal arm for future use. All patients had exposure to the proximal axillary vein via an infraclavicular incision. There were six women and three men. All patients had multiple failed access in the ipsilateral extremity. One patient had a loop configuration graft, while the six others had a straight graft with arterial inflow via the brachial artery. One patient had a bovine mesenteric vein graft, while the remaining six had expanded polytetrafluoroethylene grafts. Six of the seven patients had ambulatory surgery, while one patient was admitted postoperatively with mental status changes. Patency rates were 78%, with mean follow-up of 16 months. One patient had early failure due to steal and one patient failed at 22 months. Six of seven patients are alive at current follow-up. Three patients required secondary procedures including venous angioplasty (n=2) and subclavian artery stenting (n=1). The infraclavicular axillary vein can be used as an effective outflow for arteriovenous grafts. This procedure can be done as an outpatient surgery with a low complication rate. This procedure can preserve the dominant arm for future access and provides a possible alternative to surgery on another extremity.

  20. Proximity effects on H absorption in ultrathin V layers

    NASA Astrophysics Data System (ADS)

    Pálsson, Gunnar K.; Eriksson, A. K.; Amft, M.; Xin, X.; Liebig, A.; Ólafsson, Sveinn; Hjörvarsson, Björgvin

    2014-07-01

    We discuss proximity effects on the hydrogen uptake in 14 atomic layers of vanadium. The enthalpy and entropy of solution were measured and compared to ab initio density functional calculations. We show that there exists a large difference in the hydrogen uptake of V in Cr/V and Fe/V superlattices, in which the V is under close to identical strain states. The calculations show that neither local strain effects nor charge redistributions can be the cause for the observed effect. This leaves magnetic and long ranged elastic strain fields—neither captured by the current calculations—as possible mechanisms for the observed effects.

  1. 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.

  2. 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.

  3. [Tomodensitometry measurements of proximal tibia and acceleration in marathon athletes].

    PubMed

    Gremion, Gérald; Cordey, Jacques; Leyvraz, Pierre-François; Rizzoli, René; Crettenand, Antoinette; Gobelet, Charles; Dériaz, Olivier; Crettenand, Andre

    2004-02-01

    We evaluated bone adaptation of the tibia to mechanical stresses in male marathon runners and in sedentary controls in function of the ground impact measured by accelerometry and of the bone mineral density assessed by peripheral quantitative computed tomography (QCT). Sixty-three subjects (51 runners and 12 controls) were enrolled. All had measurements of bone mineral density of the proximal tibia and of acceleration at the same site during a jogging at 9 km/hour. The results show a significant higher cortical BMD in runners with the higher value of late accelerations (at 50 ms after the contact with the ground). The late acceleration might be related to muscle contraction.

  4. 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

  5. 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

  6. Outcome Analysis of Locking Plate Fixation in Proximal Humerus Fracture

    PubMed Central

    Pathak, Abhishek; Gaur, Sanjiv

    2016-01-01

    Introduction Proximal humerus fractures account for approximately 5% of all fractures. Stable minimally displaced fractures can be treated nonoperatively but the management of displaced fractures remain controversial with various modalities of treatment available. Locking plates provide stable fixation and enable early postoperative mobilization specially in osteoporotic proximal humerus fracture. Aim To evaluate the functional outcome of locking plate fixation and to compare the results of two approaches used for fixation. Materials and Methods This prospective study was conducted at a tertiary level hospital between September 2011 to December 2013. PHILOS plates were used for internal fixation of displaced proximal humerus fractures Neer’s type 2 part, 3 part and 4 part fractures on 26 patients (M/F ratio 1.36:1; mean age 46 years). According to Neer classification, 5,12 and 9 patients had displaced 2, 3 and 4 part fractures respectively. Deltopectoral and deltoid splitting approaches were used for fixation on 13 patients each. Functional outcome was assessed using Constant-Murley shoulder score. Graphpad software version 6.0 was used with Chi-square test and Fisher-exact test are used to compare data. The p-value< 0.05 is considered significant. Results Of the 26 patients, all fractures united radiologically and clinically and average constant score at final follow-up was 72.5. At the final follow-up 8 patients had good score, 10 patients had moderate score, 6 patients had excellent outcome and 2 patients had poor outcome according to Constant score. Mean time to union was 12.3 weeks (9 –15 weeks). Four complications (15.4%) were encountered, 2 cases of varus malunion, 1 case of wound infection which required wound debridement and 1 case of screw cut-out in which screw removal was done. Mean constant score in delto splitting approach was 70.9 and 74 in deltopectoral group (p-value= 0.54). No significant difference existed in constant score in 2 approaches

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Early proximal junctional failure in patients with preoperative sagittal imbalance.

    PubMed

    Smith, Micah W; Annis, Prokopis; Lawrence, Brandon D; Daubs, Michael D; Brodke, Darrel S

    2013-10-01

    Study Type Retrospective review. Introduction Sagittal imbalance has been associated with lower health-related quality of life outcomes, and restoration of imbalance is associated with improved outcomes.123 The long constructs used in adult spinal deformity have potential consequences such as proximal junctional kyphosis (PJK). Clinically, the development of PJK may not be as important as failure of the construct or vertebrae at the proximal end. As PJK does not lead to worse clinical outcomes,45 we define the term early proximal junctional failure (EPJF) as fracture, implant failure, or myelopathy due to stenosis at the upper instrumental vertebra (UIV) or UIV + 1 within 6 months of surgery. Objective The purpose of this study is to report the incidence of EPJF in patients who are sagittally imbalanced preoperatively and to identify risk factors postoperatively that correlate with EPJF using commonly reported sagittal balance parameters. Methods We reviewed 197 patients with preoperative sagittal imbalance by at least one of the following: sagittal vertical axis more than 5 cm, global sagittal alignment more than 45 degrees, pelvic incidence-lumbar lordosis more than 10 degrees, or spine-sacral angle less than 120 degrees. Radiographic measurements also included proximal junctional angle, thoracic kyphosis, lumbar lordosis, pelvic parameters, and sagittal balance parameters/formulas, as well as UIV angle, UIV spinosacral angle, and UIV plumb line to assess as potential risk factors. EPJF incidence was calculated postoperatively for each of the accepted sagittal balance parameters/formulas. Results EPJF was observed in 49 of 197 patients (25%) with preoperative sagittal imbalance and was more common in fusions with UIV in the lower thoracic spine (TS) (35%) than in those with UIV in the upper TS (10%) or lumbar (25%) (p = 0.007). Of the 49 EPJF patients, 16 patients (33%) required revision surgery within the first year, for an overall early revision

  12. Retained Urethral Catheter Secondary to Placement in Proximal Ureter.

    PubMed

    McGregor, Thomas B; 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.

  13. Nonequilibrium and proximity effects in superconductor-normal metal junctions

    NASA Astrophysics Data System (ADS)

    Kauppila, V. J.; Nguyen, H. Q.; Heikkilä, T. T.

    2013-08-01

    We study the consequences of nonequilibrium heating and inverse proximity effect in normal metal-insulator-superconductor-insulator-normal metal (NISIN) junctions with a simple quasi-one-dimensional model. We especially focus on observables and parameter regions that are of interest in the design of SINIS coolers with quasiparticle traps. We present numerical results calculated by solving the Usadel equation and also present analytical approximations in two limiting cases: a short junction with a non-negligible resistance in both ends and a long junction with a transparent contact at one end.

  14. 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

  15. Diabetic neuropathy part 2: proximal and asymmetric phenotypes.

    PubMed

    Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J

    2013-05-01

    Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is the most common type of diabetic neuropathy, many other subtypes have been defined since the 1800s, including proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most 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 however are controversial.

  16. 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

  17. 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

  18. 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.

  19. [Fibrocartilaginous mesenchymoma of the proximal humerus: case report].

    PubMed

    Masquijo, Julio Javier; Sartori, Federico; Innocenti, Sergio

    2014-10-01

    Fibrocartilaginous mesenchymoma (FCM) is a rare tumor that primarily affects the long bones. Few cases have been reported since its description. A case of a 4-year-old boy with FCM located in the humerus is presented. Radiological examination showed an expansive lytic lesion located in the metaphyseal proximal humerus. Magnetic resonance imaging showed soft tissue expansion. Histopathological diagnosis was confirmatory of FCM. Curettage, adjuvant phenolization, and bone grafting with bone substitute, and autologous bone marrow was performed. During a follow-up period of 2 years, there was no evidence of disease progression. FCM should be considered in the differential diagnosis of lytic bone lesions in children and adolescents.

  20. 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

  1. 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.

  2. 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.

  3. Groups as units of functional analysis, individuals as proximate mechanisms.

    PubMed

    Wilson, David Sloan

    2014-06-01

    Whenever selection operates at a given level of a multitier hierarchy, units at that level should become the object of functional analysis, and units at lower levels should be studied as proximate mechanisms. This intuition already exists for the study of genes in individuals, when individuals are the unit of selection. It is only beginning to be applied for the study of individuals in groups, when groups are the unit of selection. Smaldino's target article is an important step in this direction with an emphasis on human cultural evolution, but the same algorithm applies to all multilevel evolutionary processes.

  4. 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.

  5. 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

  6. An unusual presentation of hemophilia B: pseudotumor of proximal tibia.

    PubMed

    Mittal, Saurav; Arora, Sumit; Khanna, Shilpa; Maini, Lalit; Gautam, V K

    2011-07-01

    Hemophilia is one of the most common genetically inherited causes of bleeding disorders. The usual presentation is continuous bleeding from a wound. Very seldom, it presents as a pseudotumor of bone. When left untreated, it may induce compression and pressure necrosis of adjacent structures. Careful evaluation and a high index of suspicion are usually required to arrive at the correct diagnosis. In this article, we report the case of a 10-year-old boy with hemophilia B (Christmas disease) that presented as a pseudotumor producing a large defect in the proximal tibia.

  7. Proximity effects in a topological-insulator/Mott-insulator heterostructure

    NASA Astrophysics Data System (ADS)

    Ueda, Suguru; Kawakami, Norio; Sigrist, Manfred

    2013-04-01

    We investigate proximity effects in a correlated heterostructure of a two-dimensional Mott insulator (MI) and a topological insulator (TI) by employing inhomogeneous dynamical mean-field theory. We show that the edge state of the TI induces strongly renormalized midgap states inside the MI region, which still have a remnant of the helical energy spectrum. The penetration of low-energy electrons, which is controlled by the interface tunneling V, largely enhances the electron mass inside the MI and also splits a single Dirac cone at edge sites into the spatially separated two Dirac cones in the strong V region.

  8. Expression of sodium/hydrogen exchanger 3 and cation-chloride cotransporters in the kidney of Japanese eel acclimated to a wide range of salinities.

    PubMed

    Teranishi, Keitaro; Mekuchi, Miyuki; Kaneko, Toyoji

    2013-02-01

    Reabsorption of monovalent ions in the kidney is essential for adaptation to freshwater and seawater in teleosts. To assess a possible role of Na(+)/H(+) exchanger 3 (NHE3) in renal osmoregulation, we first identified a partial sequence of cDNA encoding NHE3 from the Japanese eel kidney. For comparison, we also identified cDNAs encoding kidney specific Na(+)-K(+)-2Cl(-) cotransporter 2 (NKCC2α) and Na(+)-Cl(-) cotransporter (NCCα). In eels acclimated to a wide range of salinities from deionized freshwater to full-strength seawater, the expression of NHE3 in the kidney was the highest in eel acclimated to full-strength seawater. Meanwhile, the NCCα expression exhibited a tendency to increase as the environmental salinity decreased, whereas the NKCC2α expression was not significantly different among the experimental groups. Immunohistochemical studies showed that NHE3 was localized to the apical membrane of epithelial cells composing the second segments of the proximal renal tubule in seawater-acclimated eel. Meanwhile, the apical membranes of epithelial cells in the distal renal tubule and collecting duct showed more intense immunoreactions of NKCC2α and NCCα, respectively, in freshwater eel than in seawater eel. These findings suggest that renal monovalent-ion reabsorption is mainly mediated by NKCC2α and NCCα in freshwater eel and by NHE3 in seawater eel.

  9. Bilateral traumatic proximal humerus fractures managed by open reduction and internal fixation with locked plates.

    PubMed

    Jaiswal, Atin; Kachchhap, Naiman Deepak; Chaterjee, Rupak; Tanwar, Yashwant Singh; Habib, Masood; Singh, Satya Prakash

    2013-01-01

    Fractures of the proximal humerus are uncommon in young patients. Although bilateral fracture of proximal humerus itself is rare, association with epilepsy and electrocution is frequent. Only one case of traumatic bilateral proximal humerus fracture has been reported in the literature. We report a rare case of bilateral traumatic displaced proximal humerus fractures in a 40 years old male patient, which was treated by means of open reduction and internal fixation with proximal humerus locked pates on both sides and obtained a good functional outcome.

  10. 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.

  11. 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.

  12. 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.

  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. 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.

  15. Proximity to Pollution Sources and Risk of Amphibian Limb Malformation

    PubMed Central

    Taylor, Brynn; Skelly, David; Demarchis, Livia K.; Slade, Martin D.; Galusha, Deron; Rabinowitz, Peter M.

    2005-01-01

    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

  16. 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

  17. Parkinson's Disease Prevalence and Proximity to Agricultural Cultivated Fields.

    PubMed

    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 km(2) 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.

  18. 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

  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. 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).

  1. 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

  2. Visualization of Calcium Dynamics in Kidney Proximal Tubules.

    PubMed

    Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Csohány, Rózsa; Prókai, Ágnes; Kis-Petik, Katalin; Szabó, Attila; Bősze, Zsuzsanna; Bender, Balázs; Tóvári, József; Enyedi, Ágnes; Orbán, Tamás I; Apáti, Ágota; Sarkadi, Balázs

    2015-11-01

    Intrarenal changes in cytoplasmic calcium levels have a key role in determining pathologic and pharmacologic responses in major kidney diseases. However, cell-specific delivery of calcium-sensitive probes in vivo remains problematic. We generated a transgenic rat stably expressing the green fluorescent protein-calmodulin-based genetically encoded calcium indicator (GCaMP2) predominantly in the kidney proximal tubules. The transposon-based method used allowed the generation of homozygous transgenic rats containing one copy of the transgene per allele with a defined insertion pattern, without genetic or phenotypic alterations. We applied in vitro confocal and in vivo two-photon microscopy to examine basal calcium levels and ligand- and drug-induced alterations in these levels in proximal tubular epithelial cells. Notably, renal ischemia induced a transient increase in cellular calcium, and reperfusion resulted in a secondary calcium load, which was significantly decreased by systemic administration of specific blockers of the angiotensin receptor and the Na-Ca exchanger. The parallel examination of in vivo cellular calcium dynamics and renal circulation by fluorescent probes opens new possibilities for physiologic and pharmacologic investigations.

  3. Designing and Applying Proximity-Dependent Hybridization Chain Reaction.

    PubMed

    Koos, Björn; Söderberg, Ola

    2016-01-01

    Proximity-dependent hybridization chain reaction (proxHCR) is a novel technique for detection of protein interaction, post-translational modifications (PTMs), or protein expression. The method is based upon antibodies targeting the proteins of interest that are covalently conjugated to DNA oligonucleotides, which enables the induction of a hybridization chain reaction (HCR) to generate a fluorescent signal visible under a microscope. In contrast to the in situ proximity ligation assay (in situ PLA), which is another method that utilizes antibody-DNA conjugates to detect protein interactions, proxHCR does not require enzymatic steps. This makes proxHCR an inexpensive alternative to in situ PLA. Another potential advantage might be that proxHCR could more readily be adapted for use in automated staining procedures and in point-of-care devices, as all reagents can be stored at room temperature. This unit describes how the oligonucleotide system for proxHCR can be designed and a protocol for how to perform proxHCR is presented. © 2016 by John Wiley & Sons, Inc.

  4. 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.

  5. 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.

  6. ADAM17 substrate release in proximal tubule drives kidney fibrosis

    PubMed Central

    Kefaloyianni, Eirini; Muthu, Muthu Lakshmi; Kaeppler, Jakob; Sun, Xiaoming; Sabbisetti, Venkata; Chalaris, Athena; Rose-John, Stefan; Wong, Eitan; Sagi, Irit; Waikar, Sushrut S.; Rennke, Helmut; Bonventre, Joseph V.

    2016-01-01

    Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates’ receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis. ADAM17 hypomorphic mice, specific ADAM17 inhibitor–treated WT mice, or mice with inducible KO of ADAM17 in proximal tubule (Slc34a1-Cre) were significantly protected against these effects. In vitro, in proximal tubule cells, we show that AREG has unique profibrotic actions that are potentiated by TNFα-induced AREG cleavage. In vivo, in acute kidney injury (AKI) and chronic kidney disease (CKD, fibrosis) patients, soluble AREG is indeed highly upregulated in human urine, and both ADAM17 and AREG expression show strong positive correlation with fibrosis markers in related kidney biopsies. Our results indicate that targeting of the ADAM17 pathway represents a therapeutic target for human kidney fibrosis. PMID:27642633

  7. Probing nuclear pore complex architecture with proximity-dependent biotinylation.

    PubMed

    Kim, Dae In; Birendra, K C; Zhu, Wenhong; Motamedchaboki, Khatereh; Doye, Valérie; Roux, Kyle J

    2014-06-17

    Proximity-dependent biotin identification (BioID) is a method for identifying protein associations that occur in vivo. By fusing a promiscuous biotin ligase to a protein of interest expressed in living cells, BioID permits the labeling of proximate proteins during a defined labeling period. In this study we used BioID to study the human nuclear pore complex (NPC), one of the largest macromolecular assemblies in eukaryotes. Anchored within the nuclear envelope, NPCs mediate the nucleocytoplasmic trafficking of numerous cellular components. We applied BioID to constituents of the Nup107-160 complex and the Nup93 complex, two conserved NPC subcomplexes. A strikingly different set of NPC constituents was detected depending on the position of these BioID-fusion proteins within the NPC. By applying BioID to several constituents located throughout the extremely stable Nup107-160 subcomplex, we refined our understanding of this highly conserved subcomplex, in part by demonstrating a direct interaction of Nup43 with Nup85. Furthermore, by using the extremely stable Nup107-160 structure as a molecular ruler, we defined the practical labeling radius of BioID. These studies further our understanding of human NPC organization and demonstrate that BioID is a valuable tool for exploring the constituency and organization of large protein assemblies in living cells.

  8. QCL-based standoff and proximal chemical detectors

    NASA Astrophysics Data System (ADS)

    Dupuis, Julia R.; Hensley, Joel; Cosofret, Bogdan R.; Konno, Daisei; Mulhall, Phillip; Schmit, Thomas; Chang, Shing; Allen, Mark; Marinelli, William J.

    2016-05-01

    The development of two longwave infrared quantum cascade laser (QCL) based surface contaminant detection platforms supporting government programs will be discussed. The detection platforms utilize reflectance spectroscopy with application to optically thick and thin materials including solid and liquid phase chemical warfare agents, toxic industrial chemicals and materials, and explosives. Operation at standoff (10s of m) and proximal (1 m) ranges will be reviewed with consideration given to the spectral signatures contained in the specular and diffusely reflected components of the signal. The platforms comprise two variants: Variant 1 employs a spectrally tunable QCL source with a broadband imaging detector, and Variant 2 employs an ensemble of broadband QCLs with a spectrally selective detector. Each variant employs a version of the Adaptive Cosine Estimator for detection and discrimination in high clutter environments. Detection limits of 5 μg/cm2 have been achieved through speckle reduction methods enabling detector noise limited performance. Design considerations for QCL-based standoff and proximal surface contaminant detectors are discussed with specific emphasis on speckle-mitigated and detector noise limited performance sufficient for accurate detection and discrimination regardless of the surface coverage morphology or underlying surface reflectivity. Prototype sensors and developmental test results will be reviewed for a range of application scenarios. Future development and transition plans for the QCL-based surface detector platforms are discussed.

  9. ADAM17 substrate release in proximal tubule drives kidney fibrosis

    PubMed Central

    Kefaloyianni, Eirini; Muthu, Muthu Lakshmi; Kaeppler, Jakob; Sun, Xiaoming; Sabbisetti, Venkata; Chalaris, Athena; Rose-John, Stefan; Wong, Eitan; Sagi, Irit; Waikar, Sushrut S.; Rennke, Helmut; Humphreys, Benjamin D.; Bonventre, Joseph V.; Herrlich, Andreas

    2016-01-01

    Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates’ receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis. ADAM17 hypomorphic mice, specific ADAM17 inhibitor–treated WT mice, or mice with inducible KO of ADAM17 in proximal tubule (Slc34a1-Cre) were significantly protected against these effects. In vitro, in proximal tubule cells, we show that AREG has unique profibrotic actions that are potentiated by TNFα-induced AREG cleavage. In vivo, in acute kidney injury (AKI) and chronic kidney disease (CKD, fibrosis) patients, soluble AREG is indeed highly upregulated in human urine, and both ADAM17 and AREG expression show strong positive correlation with fibrosis markers in related kidney biopsies. Our results indicate that targeting of the ADAM17 pathway represents a therapeutic target for human kidney fibrosis.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Quantitive analysis of the proximity effect in optical lithographic process

    NASA Astrophysics Data System (ADS)

    Bae, Sang-Man; Kim, Hung-Eil; Ham, Young-Mog; Moon, Seung-Chan; Choi, Soo-Han

    1994-05-01

    As the density of VLSI circuits increases, the proximity effect has been one of the critical issues in optical lithography. In general, the linewidth difference between dense and isolated patterns corresponds to 0.08 micrometers when a conventional i-line single resist process using a 0.54 NA is applied to the half-micron geometry on a flat wafer. Therefore, this linewidth difference has significantly affected the process stability in the real process applications. This paper describes the dependency of the proximity effects on the pattern size, line and space duty ratio, kinds of substrate film, defocus effect during exposure, and resist process conditions related to the variation of the resist thickness and develop time. Critical dimension (CD) deviation caused by the different latent image contrast is also experimentally monitored using two different photoresists. A simulation is performed for the purpose of obtaining the optimum resist thickness to reduce CD difference caused by the variations of resist thickness in the real topography.

  16. Two Proximal Skin Electrodes — A Respiration Rate Body Sensor

    PubMed Central

    Trobec, Roman; Rashkovska, Aleksandra; Avbelj, Viktor

    2012-01-01

    We propose a new body sensor for extracting the respiration rate based on the amplitude changes in the body surface potential differences between two proximal body electrodes. The sensor could be designed as a plaster-like reusable unit that can be easily fixed onto the surface of the body. It could be equipped either with a sufficiently large memory for storing the measured data or with a low-power radio system that can transmit the measured data to a gateway for further processing. We explore the influence of the sensor's position on the quality of the extracted results using multi-channel ECG measurements and considering all the pairs of two neighboring electrodes as potential respiration-rate sensors. The analysis of the clinical measurements, which also include reference thermistor-based respiration signals, shows that the proposed approach is a viable option for monitoring the respiration frequency and for a rough classification of breathing types. The obtained results were evaluated on a wireless prototype of a respiration body sensor. We indicate the best positions for the respiration body sensor and prove that a single sensor for body surface potential difference on proximal skin electrodes can be used for combined measurements of respiratory and cardiac activities. PMID:23202022

  17. 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

  18. 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

  19. Transcriptional regulation of the lactase-phlorizin hydrolase promoter by PDX-1.

    PubMed

    Wang, Zhi; Fang, Rixun; Olds, Lynne C; Sibley, Eric

    2004-09-01

    Lactase-phlorizin hydrolase gene expression is spatially restricted along the anterior-posterior gut axis. Lactase gene transcription is maximal in the distal duodenum and jejunum in adult mammals and is barely detectable in the proximal duodenum. By contrast, pancreatic duodenal homeobox-1 (PDX-1) protein is expressed maximally in the proximal duodenum. This study aimed to determine the role of PDX-1 in regulating lactase gene promoter activity in intestinal epithelial cells. Caco-2 cells were cotransfected with lactase promoter-reporter constructs in the presence of a PDX-1 expression vector and assayed for luciferase activity. PDX-1 cotransfection results in repression of lactase promoter activity. Sequence analysis of the lactase promoter revealed a putative PDX-1 DNA binding site in the proximal 100-bp lactase gene promoter. EMSAs demonstrated that PDX-1 can interact with the lactase promoter binding site but not with a site in which the core PDX-1 binding sequence TAAT is mutated. Site-directed mutagenesis of the PDX-1 core binding site in the lactase promoter-reporter construct suggests that PDX-1 can function independently of DNA binding to its consensus binding site. Stable overexpression of PDX-1 results in repression of the endogenous human lactase gene in differentiated Caco-2 cells. Given the contrasting spatial expression pattern, PDX-1 may function to specify the anterior boundary of lactase expression in the small intestine and is thus a candidate regulator of anterior spatial restriction in the gut.

  20. Heat-Shock Promoters: Targets for Evolution by P Transposable Elements in Drosophila

    PubMed Central

    Walser, Jean-Claude; Chen, Bing; Feder, Martin E

    2006-01-01

    Transposable elements are potent agents of genomic change during evolution, but require access to chromatin for insertion—and not all genes provide equivalent access. To test whether the regulatory features of heat-shock genes render their proximal promoters especially susceptible to the insertion of transposable elements in nature, we conducted an unbiased screen of the proximal promoters of 18 heat-shock genes in 48 natural populations of Drosophila. More than 200 distinctive transposable elements had inserted into these promoters; greater than 96% are P elements. By contrast, few or no P element insertions segregate in natural populations in a “negative control” set of proximal promoters lacking the distinctive regulatory features of heat-shock genes. P element transpositions into these same genes during laboratory mutagenesis recapitulate these findings. The natural P element insertions cluster in specific sites in the promoters, with up to eight populations exhibiting P element insertions at the same position; laboratory insertions are into similar sites. By contrast, a “positive control” set of promoters resembling heat-shock promoters in regulatory features harbors few P element insertions in nature, but many insertions after experimental transposition in the laboratory. We conclude that the distinctive regulatory features that typify heat-shock genes (in Drosophila) are especially prone to mutagenesis via P elements in nature. Thus in nature, P elements create significant and distinctive variation in heat-shock genes, upon which evolutionary processes may act. PMID:17029562