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Sample records for proximal nhe3 promoter

  1. Cell confluency-induced Stat3 activation regulates NHE3 expression by recruiting Sp1 and Sp3 to the proximal NHE3 promoter region during epithelial dome formation.

    PubMed

    Su, Hsiao-Wen; Wang, Shainn-Wei; Ghishan, Fayez K; Kiela, Pawel R; Tang, Ming-Jer

    2009-01-01

    Activation of signal transducer and activator of transcription-3 (Stat3) during cell confluency is related to its regulatory roles in cell growth arrest- or survival-related physiological or developmental processes. We previously demonstrated that this signaling event triggers epithelial dome formation by transcriptional augmentation of sodium hydrogen exchanger-3 (NHE3) expression. However, the detailed molecular mechanism remained unclear. By using serial deletions, site-directed mutagenesis, and EMSA analysis, we now demonstrate Stat3 binding to an atypical Stat3-response element in the rat proximal NHE3 promoter, located adjacent to a cluster of Sp cis-elements (SpA/B/C), within -77/-36 nt of the gene. SpB (-58/-55 nt) site was more effective than SpA (-72/-69 nt) site for cooperative binding of Sp1/Sp3. Increasing cell density had no effect on Sp1/Sp3 expression but resulted in their increased binding to the SpA/B/C probe along with Stat3 and concurrently with enhanced nuclear pTyr705-Stat3 level. Immunoprecipitation performed with the nuclear extracts demonstrated physical interaction of Stat3 and Sp1/Sp3 triggered by cell confluency. Stat3 inhibition by overexpression of dominant-negative Stat3-D mutant in MDCK cells or by small interfering RNA-mediated knockdown in Caco-2 cells resulted in inhibition of the cell density-induced NHE3 expression, Sp1/Sp3 binding, and NHE3 promoter activity and in decreased dome formation. Thus, during confluency, ligand-independent Stat3 activation leads to its interaction with Sp1/Sp3, their recruitment to the SpA/B/C cluster in a Stat3 DNA-binding domain-dependent fashion, increased transcription, and expression of NHE3, to coordinate cell density-mediated epithelial dome formation.

  2. Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and phosphorylation in proximal tubule cells.

    PubMed

    Crajoinas, Renato O; Polidoro, Juliano Z; Carneiro de Morais, Carla P A; Castelo-Branco, Regiane C; Girardi, Adriana C C

    2016-11-01

    Binding of angiotensin II (ANG II) to the AT1 receptor (AT1R) in the proximal tubule stimulates Na(+)/H(+) exchanger isoform 3 (NHE3) activity through multiple signaling pathways. However, the effects of ANG II/AT1R-induced inihibitory G protein (Gi) activation and subsequent decrease in cAMP accumulation on NHE3 regulation are not well established. We therefore tested the hypothesis that ANG II reduces cAMP/PKA-mediated phosphorylation of NHE3 on serine 552 and, in doing so, stimulates NHE3 activity. Under basal conditions, ANG II stimulated NHE3 activity but did not affect PKA-mediated NHE3 phosphorylation at serine 552 in opossum kidney (OKP) cells. However, in the presence of the cAMP-elevating agent forskolin (FSK), ANG II blocked FSK-induced NHE3 inhibition, reduced intracellular cAMP concentrations, lowered PKA activity, and prevented the FSK-mediated increase in NHE3 serine 552 phosphorylation. All effects of ANG II were blocked by pretreating OKP cells with the AT1R antagonist losartan, highlighting the contribution of the AT1R/Gi pathway in ANG II-mediated NHE3 upregulation under cAMP-elevating conditions. Accordingly, Gi inhibition by pertussis toxin treatment decreased NHE3 activity both in vitro and in vivo and, more importantly, prevented the stimulatory effect of ANG II on NHE3 activity in rat proximal tubules. Collectively, our results suggest that ANG II counteracts the effects of cAMP/PKA on NHE3 phosphorylation and inhibition by activating the AT1R/Gi pathway. Moreover, these findings support the notion that NHE3 dephosphorylation at serine 552 may represent a key event in the regulation of renal proximal tubule sodium handling by ANG II in the presence of natriuretic hormones that promote cAMP accumulation and transporter phosphorylation.

  3. Local pH domains regulate NHE3-mediated Na+ reabsorption in the renal proximal tubule

    PubMed Central

    Burford, James L.; McDonough, Alicia A.; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, Janos

    2014-01-01

    The proximal tubule Na+/H+ exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na+ reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution. PMID:25298526

  4. Local pH domains regulate NHE3-mediated Na⁺ reabsorption in the renal proximal tubule.

    PubMed

    Brasen, Jens Christian; Burford, James L; McDonough, Alicia A; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, Janos

    2014-12-01

    The proximal tubule Na(+)/H(+) exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na(+) reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution.

  5. Thyroid hormone stimulates the renal Na/H exchanger NHE3 by transcriptional activation

    PubMed Central

    CANO, ADRIANA; BAUM, MICHEL; MOE, ORSON W.

    2014-01-01

    Thyroid hormone stimulates renal proximal tubule NaCl and NaHCO3 absorption in part by activating the apical membrane Na/H exchanger NHE3. We used a renal epithelial cell line, the opossum kidney (OK) cell, to define the mechanism by which 3,5,3′-triiodothyronine (T3) increases NHE3 activity. T3 stimulated NHE3 activity, an effect that was blocked by inhibition of cellular transcription or translation. The increase in activity was associated with increases in steady-state cell surface and total cellular NHE3 protein and NHE3 transcript abundance. T3 stimulated transcription of the NHE3 gene and had no effect on NHE3 transcript stability. The transcriptional activity of the 5′-flanking region of the rat NHE3 gene was stimulated by T3 when expressed in OK cells. When heterologously expressed rat NHE3 transcript levels were clamped constant with a constitutive promoter in OK cells, T3 has no effect on rat NHE3 protein abundance, suggesting the absence of regulation of NHE3 protein stability or translation. These studies demonstrate that T3 stimulates NHE3 activity by activating NHE3 gene transcription and increasing NHE3 transcript and protein abundance. PMID:9886925

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

    PubMed Central

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

    2016-01-01

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

  7. 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.

  8. 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.

  9. 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.

  10. Molecular cloning of NHE3 from LLC-PK1 cells and localization in pig kidney.

    PubMed

    Shugrue, C A; Obermüller, N; Bachmann, S; Slayman, C W; Reilly, R F

    1999-08-01

    LLC-PK1 cells, an established line from pig kidney, express basolateral and apical Na+/H+ exchangers that can be distinguished by their differing sensitivities to the amiloride analog N-ethyl-N-isopropylamiloride (EIPA). It has been shown previously that the basolateral exchanger is encoded by NHE1. In the present study, a combination of reverse transcription-PCR, 5' RACE, and genomic library screening was used to clone the coding region of the porcine NHE3 gene. There was significant homology between the LLC-PK1 sequence and the previously reported rabbit and rat NHE3 genes, with nucleotide and deduced amino acid identities of 87 and 85% in rabbit, and 85 and 87% in rat, respectively. To study expression patterns, Northern analysis was carried out using an NHE3 cDNA to probe poly(A)+ RNA isolated from LLC-PK1 cells, and from pig kidney cortex. In all three cases, a major transcript of 6.1 kb was detected along with two minor transcripts of 4.7 and 3.8 kb. In situ hybridization with two different NHE3 probes gave intense labeling of the distal convoluted tubule in pig kidney but (unexpectedly) no detectable labeling of the proximal tubule. These studies suggest that there are marked species differences in NHE3 expression in the distal nephron.

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

    PubMed Central

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

    2015-01-01

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

  12. 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.

  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. Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis.

    PubMed

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

    2017-04-03

    The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney, where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3(loxloxCre)) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium, or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine, and pH were significantly elevated in NHE3(loxloxCre) mice, while urine osmolality and GFR were significantly lower. Water deprivation revealed a small urinary concentrating defect in NHE3(loxloxCre) mice on a control diet, exaggerated on low sodium chloride. Ten days of low or high sodium chloride diet did not affect plasma sodium in control mice; however, NHE3(loxloxCre) mice were susceptible to low sodium chloride (about -4 mM) or high sodium chloride intake (about +2 mM) versus baseline, effects without differences in plasma aldosterone between groups. Blood pressure was significantly lower in NHE3(loxloxCre) mice and was sodium chloride sensitive. In control mice, the expression of the sodium/phosphate co-transporter Npt2c was sodium chloride sensitive. However, lack of tubular NHE3 blunted Npt2c expression. Alterations in the abundances of sodium/chloride cotransporter and its phosphorylation at threonine 58 as well as the abundances of the α-subunit of the epithelial sodium channel, and its cleaved form, were also apparent in NHE3(loxloxCre) mice. Thus, renal NHE3 is required to maintain blood pressure and steady-state plasma sodium levels when dietary sodium chloride intake is modified.

  15. 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

    2011-10-07

    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.

  16. Reduced colonic microbial diversity is associated with colitis in NHE3-deficient mice

    PubMed Central

    Larmonier, Claire B.; Laubitz, Daniel; Hill, Faihza M.; Shehab, Kareem W.; Lipinski, Leszek; Midura-Kiela, Monica T.; McFadden, Rita-Marie T.; Ramalingam, Rajalakshmy; Hassan, Kareem A.; Golebiewski, Marcin; Besselsen, David G.; Ghishan, Fayez K.

    2013-01-01

    Chronic inflammation and enteric infections are frequently associated with epithelial Na+/H+ exchange (NHE) inhibition. Alterations in electrolyte transport and in mucosal pH associated with inflammation may represent a key mechanism leading to changes in the intestinal microbial composition. NHE3 expression is essential for the maintenance of the epithelial barrier function. NHE3−/− mice develop spontaneous distal chronic colitis and are highly susceptible to dextran sulfate (DSS)-induced mucosal injury. Spontaneous colitis is reduced with broad-spectrum antibiotics treatment, thus highlighting the importance of the microbiota composition in NHE3 deficiency-mediated colitis. We herein characterized the colonic microbiome of wild-type (WT) and NHE3−/− mice housed in a conventional environment using 454 pyrosequencing. We demonstrated a significant decrease in the phylogenetic diversity of the luminal and mucosal microbiota of conventional NHE3−/− mice compared with WT. Rederivation of NHE3−/− mice from conventional to a barrier facility eliminated the signs of colitis and decreased DSS susceptibility. Reintroduction of the conventional microflora into WT and NHE3−/− mice from the barrier facility resulted in the restoration of the symptoms initially described in the conventional environment. Interestingly, qPCR analysis of the microbiota composition in mice kept in the barrier facility compared with reconventionalized mice showed a significant reduction of Clostridia classes IV and XIVa. Therefore, the gut microbiome plays a prominent role in the pathogenesis of colitis in NHE3−/− mice, and, reciprocally, NHE3 also plays a critical role in shaping the gut microbiota. NHE3 deficiency may be a critical contributor to dysbiosis observed in patients with inflammatory bowel disease. PMID:24029465

  17. Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile

    PubMed Central

    Engevik, Melinda A.; Engevik, Kristen A.; Yacyshyn, Mary Beth; Wang, Jiang; Hassett, Daniel J.; Darien, Benjamin; Yacyshyn, Bruce R.

    2014-01-01

    Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na+/H+ exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na+ and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na+ and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile. PMID:25552580

  18. Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile.

    PubMed

    Engevik, Melinda A; Engevik, Kristen A; Yacyshyn, Mary Beth; Wang, Jiang; Hassett, Daniel J; Darien, Benjamin; Yacyshyn, Bruce R; Worrell, Roger T

    2015-03-15

    Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na(+)/H(+) exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na(+) and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na(+) and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile.

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

    PubMed

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

    2015-12-01

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

  20. Immunolocalization of NBC3 and NHE3 in the rat epididymis: colocalization of NBC3 and the vacuolar H+-ATPase.

    PubMed

    Pushkin, A; Clark, I; Kwon, T H; Nielsen, S; Kurtz, I

    2000-01-01

    In the male reproductive tract, the epididymis plays an important role in mediating transepithelial bicarbonate transport and luminal acidification. In the proximal vas deferens, a significant component of luminal acidification is Na+-independent, and mediated by specific cells that possess apical vacuolar proton pumps. In contrast, luminal acidification in the cauda epididymidis is an Na+-dependent process. The specific apical Na+-dependent H+/base transport process(es) responsible for luminal acidification have not been identified. A potential clue as to the identity of these apical Na+-dependent H+/base transporter(s) is provided by similarities between the transport properties of the epididymis and the mammalian nephron. Specifically, the H+/base transport properties of caput epididymidis resemble the mammalian renal proximal tubule, whereas the distal epididymis and vas deferens have characteristics in common with renal collecting duct intercalated cells. Given the known expression of the Na+/H+ antiporter, NHE3, in the proximal tubule, and of the electroneutral sodium bicarbonate cotransporter, NBC3, in renal intercalated cells, we determined the localization of NHE3 and NBC3 in various regions of rat epididymis. NBC3 was highly expressed on the apical membrane of apical (narrow) cells in caput epididymidis, and light (clear) cells in corpus and cauda epididymidis. The number of cells expressing apical NBC3 was highest in cauda epididymidis. The localization of NBC3 in the epididymis was identical to the vacuolar H+-ATPase. The results indicate that colocalization of NBC3 and the vacuolar H+-ATPase is not restricted to kidney intercalated cells. Moreover, the close association of the two transporters appears to be a more generalized phenomenon in cells that express high levels of vacuolar H+-ATPase. Unlike NBC3, NHE3 was most highly expressed on the apical membrane of all epithelial cells in caput epididymidis, with less expression in the corpus, and no

  1. Na+/H+ and Na+/NH4+ exchange activities of zebrafish NHE3b expressed in Xenopus oocytes

    PubMed Central

    Ito, Yusuke; Kato, Akira; Hirata, Taku; Hirose, Shigehisa

    2014-01-01

    Zebrafish Na+/H+ exchanger 3b (zNHE3b) is highly expressed in the apical membrane of ionocytes where Na+ is absorbed from ion-poor fresh water against a concentration gradient. Much in vivo data indicated that zNHE3b is involved in Na+ absorption but not leakage. However, zNHE3b-mediated Na+ absorption has not been thermodynamically explained, and zNHE3b activity has not been measured. To address this issue, we overexpressed zNHE3b in Xenopus oocytes and characterized its activity by electrophysiology. Exposure of zNHE3b oocytes to Na+-free media resulted in significant decrease in intracellular pH (pHi) and intracellular Na+ activity (aNai). aNai increased significantly when the cytoplasm was acidified by media containing CO2-HCO3− or butyrate. Activity of zNHE3b was inhibited by amiloride or 5-ethylisopropyl amiloride (EIPA). Although the activity was accompanied by a large hyperpolarization of ∼50 mV, voltage-clamp experiments showed that Na+/H+ exchange activity of zNHE3b is electroneutral. Exposure of zNHE3b oocytes to medium containing NH3/NH4+ resulted in significant decreases in pHi and aNai and significant increase in intracellular NH4+ activity, indicating that zNHE3b mediates the Na+/NH4+ exchange. In low-Na+ (0.5 mM) media, zNHE3b oocytes maintained aNai of 1.3 mM, and Na+-influx was observed when pHi was decreased by media containing CO2-HCO3− or butyrate. These results provide thermodynamic evidence that zNHE3b mediates Na+ absorption from ion-poor fresh water by its Na+/H+ and Na+/NH4+ exchange activities. PMID:24401990

  2. PDZ Domain Dependent Regulation of NHE3 Occurs by Both Internal Class II and C-terminal Class I PDZ Binding Motifs.

    PubMed

    Cha, Boyoung; Yang, Jianbo; Singh, Varsha; Zachos, Nicholas C; Sarker, Rafiquel I; Chen, Tian-E; Chakraborty, Molee; Tse, Chung-Ming; Donowitz, Mark

    2017-03-10

    NHE3 directly binds NHERF family scaffolding proteins that are required for many aspects of NHE3 regulation. The NHERFs bind both to an internal region (aa. 586-660) of the NHE3 C-terminus and to the NHE3 C-terminal four amino acids. The internal NHERF binding region contains both putative Class I (-592SAV-) and Class II (-595CLDM-) PDZ binding motifs (PBM). Point mutagenesis showed that only the Class II motif contributes to NHERF binding. In this study, the roles in regulation of NHE3 activity of these two PBMs were investigated, revealing: 1) Interaction between these binding sites since mutation of either removed nearly all NHERF binding. 2) Mutations in either significantly reduced basal NHE3 activity. Total and percent plasma membrane (PM) NHE3 protein expression were reduced in the C-terminal but not in the internal PBD mutation. 3) cGMP and Ca2+-mediated inhibition of NHE3 were impaired both in the internal and in the C-terminal PBM mutations. 4) A significant reduction in half-life of the PM pool of NHE3 in only the internal PBM mutation but no change in total NHE3 half-life in either. 5) Some difference in NHE3 associating proteins in the two PBM mutations. In conclusion, NHE3 binds to NHERF proteins via both an internal Class II and C-terminal Class I PBM, which interact. The former appears to determine NHE3 stability of a pool in the PM and the letter determines total expression and percent PM expression.

  3. 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.

  4. Promoter-proximal polyadenylation sites reduce transcription activity

    PubMed Central

    Andersen, Pia K.; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500 base pairs of the promoter. In contrast, promoter-proximal positioning of a pA site-independent histone gene terminator supports high transcription levels. We propose that optimal communication between a pA site-dependent gene terminator and its promoter critically depends on gene length and that short RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels. PMID:23028143

  5. 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

  6. Phosphorylation and subcellular localization of Na(+)/H(+) exchanger isoform 3 (NHE3) are associated with altered gallbladder absorptive function after formation of cholesterol gallstones.

    PubMed

    Chen, Yongsheng; Wu, Shuodong; Tian, Yu; Kong, Jing

    2017-02-01

    Na(+)/H(+) exchanger isoform 3 (NHE3) dysfunction is thought to contribute to the altered gallbladder absorption that occurs in cholesterol gallstone disease, but the mechanism is unknown. The current study was undertaken to examine the expression, phosphorylation, and subcellular localization of NHE3 in gallbladder epithelium cells (GBECs) of male C57BL/6 mice on a control or lithogenic diet. Thirty-six 8-week-old male C57BL/6 mice were randomly assigned to receive a high cholesterol diet or a regular diet for 8 weeks. Gallstone formation was recorded. Gallbladder bile cholesterol, phospholipid, and total bile acids were examined. RT-PCR was used to measure NHE3 mRNA expression. NHE3 protein expression and subcellular localization were examined by Western blotting and immunofluorescence microscopy, respectively. Gallstones were formed in all mice fed the lithogenic diet. Despite higher NHE3 mRNA expression in gallbladders of the mice on the lithogenic diet than in those on the control diet, there was no significant difference in expression of total NHE3 protein. However, a higher level of NHE3 phosphorylated at serine-552 (P-NHE3) was seen on the lithogenic diet. In immunofluorescence studies, NHE3 protein was expressed both on the apical membrane and in the cytoplasm of mouse GBEC. This pattern of subcellular distribution of NHE3 strongly corroborates an exchanger trafficking mechanism in NHE3 activity regulation in mouse GBEC. We conclude that increased phosphorylation of NHE3 following gallstone formation leads to turnover of the exchanger, resulting in decreased gallbladder concentrating function.

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

    PubMed Central

    Erb, Ionas; van Nimwegen, Erik

    2011-01-01

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

  8. Transcription factor binding site positioning in yeast: proximal promoter motifs characterize TATA-less promoters.

    PubMed

    Erb, Ionas; van Nimwegen, Erik

    2011-01-01

    The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of 6 'proximal promoter motifs' (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters.

  9. 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.

  10. D-Glucose Acts via SGLTI to Increase NHE3 in Mouse Jejunal Brush Border by a NHERF2-Dependent Process

    PubMed Central

    Lin, Rong; Murtazina, Rakhilya; Cha, Boyoung; Chakraborty, Molee; Sarker, Rafiquel; Chen, Tian-e; Lin, Zhihong; Hogema, Boris M.; de Jonge, Hugo R.; Seidler, Ursula; Turner, Jerrold R.; Li, Xuhang; Kovbasnjuk, Olga; Donowitz, Mark

    2010-01-01

    Background & Aims Oral rehydration solutions (ORS) reduce diarrhea-associated mortality by unclear mechanisms. Sodium absorption is mediated by the Na+/H+ hydrogen exchanger NHE3 and is increased by Na+-glucose co-transport in vitro, but the mechanisms of this process are only partially understood and its in vivo relevance has not been determined. Methods Intracellular pH was measured in jejunal enterocytes of wild-type mice and mice with disrupted Na+/H+ exchange regulatory co-factor 2 (NHERF2−/− mice) by multi-photon microscopy. Diarrhea was induced by cholera toxin. Caco-2BBe cells that express NHE3 and the sodium/glucose cotransporter (SGLT)1 were studied by fluorometery, before and after siRNA-mediated knockdown of NHERF1 or NHERF2. NHE3 distribution was assessed by cell-surface biotinylation and confocal microscopy. Brush border mobility was determined by fluorescence recovery after photobleaching and confocal microscopy. Results The non-metabolized SGLT1 substrate α-methyl-D-Glu (α-MD-G) activated jejunal NHE3; this process required Akt and NHERF2. α-MD-G normalized NHE3 activity after cholera toxin-induced diarrhea. α-MD-G–stimulated jejunal NHE3 activity was: defective in NHERF2−/− mice and cells with NHERF2 knockdown, but occurred normally with NHERF1 knockdown; associated with increased NHE3 surface expression in Caco-2 cells, which was also NHERF2-dependent; associated with dissociation of NHE3 from NHERF2 and an increase in the NHE3 mobile fraction from the brush border; and accompanied by a NHERF2 ezrin-radixin-moesin–binding domain-dependent increase in co-precipitation of ezrin with NHE3. Conclusions SGLT1-mediated Na-glucose co-transport stimulates NHE3 activity in vivo by an Akt- and NHERF2-dependent signaling pathway. It is associated with increased brush border NHE3 and association between ezrin and NHE3. Activation of NHE3 corrects cholera toxin-induced defects in Na absorption and might mediate efficacy of ORS. PMID:20977906

  11. Berberine increases the expression of NHE3 and AQP4 in sennosideA-induced diarrhoea model.

    PubMed

    Zhang, Yongguo; Wang, Xin; Sha, Sumei; Liang, Shuli; Zhao, Lina; Liu, Lin; Chai, Na; Wang, Honghong; Wu, Kaichun

    2012-09-01

    Berberine, a compound isolated from Chinese Goldthread Rhizome, has been widely used as a non-prescription drug to treat diarrhoea in China. Previous studies have demonstrated multiple pharmacological activities for berberine, including its significant role in antimicrobial activity. However, its effect on ion exchange and water transfer remains unclear. The present study aims to explore the effect of berberine on the expression of Na(+)/H(+) exchanger3 (NHE3) and aquaporin4 (AQP4) in both diarrhoea mouse model induced by sennosideA and human intestinal epithelium cell line (HIEC). Semi-quantitative RT-PCR, immunohistochemistry and western blotting were adopted to detect the mRNA and protein expression levels of NHE3 and AQP4. Furthermore, the absorption of berberine and the PKC activity were detected by HPLC and PepTag® Assay to elucidate the underlying mechanisms. It was shown that the expression levels of NHE3 and AQP4 were significantly increased in the diarrhoea mice treated with berberine compared with the untreated diarrhoea mice. Similarly, the expression levels of NHE3 and AQP4 were strikingly enhanced in HIEC co-treated with sennosideA and berberine compared with samples treated with sennosideA only. We also found the maximal absorption of berberine to be approximately 0.01%. In addition, no significant change of PKC activity was observed in the different HIEC treated groups. These results showed that berberine was able to increase the expression of NHE3 and AQP4, suggesting that berberine might exhibit its anti-diarrhoeal effect partially by enhancing the absorption of Na(+) and water.

  12. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    PubMed

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.

  13. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    PubMed Central

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative. PMID:8566861

  14. 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.

  15. 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

  16. The Proximal J Kappa Germline-Transcript Promoter Facilitates Receptor Editing through Control of Ordered Recombination

    PubMed Central

    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. PMID:25559567

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. An unmethylated 3' promoter-proximal region is required for efficient transcription initiation.

    PubMed

    Appanah, Ruth; Dickerson, David R; Goyal, Preeti; Groudine, Mark; Lorincz, Matthew C

    2007-02-16

    The promoter regions of approximately 40% of genes in the human genome are embedded in CpG islands, CpG-rich regions that frequently extend on the order of one kb 3' of the transcription start site (TSS) region. CpGs 3' of the TSS of actively transcribed CpG island promoters typically remain methylation-free, indicating that maintaining promoter-proximal CpGs in an unmethylated state may be important for efficient transcription. Here we utilize recombinase-mediated cassette exchange to introduce a Moloney Murine Leukemia Virus (MoMuLV)-based reporter, in vitro methylated 1 kb downstream of the TSS, into a defined genomic site. In a subset of clones, methylation spreads to within approximately 320 bp of the TSS, yielding a dramatic decrease in transcript level, even though the promoter/TSS region remains unmethylated. Chromatin immunoprecipitation analyses reveal that such promoter-proximal methylation results in loss of RNA polymerase II and TATA-box-binding protein (TBP) binding in the promoter region, suggesting that repression occurs at the level of transcription initiation. While DNA methylation-dependent trimethylation of H3 lysine (K)9 is confined to the intragenic methylated region, the promoter and downstream regions are hypo-acetylated on H3K9/K14. Furthermore, DNase I hypersensitivity and methylase-based single promoter analysis (M-SPA) experiments reveal that a nucleosome is positioned over the unmethylated TATA-box in these clones, indicating that dense DNA methylation downstream of the promoter region is sufficient to alter the chromatin structure of an unmethylated promoter. Based on these observations, we propose that a DNA methylation-free region extending several hundred bases downstream of the TSS may be a prerequisite for efficient transcription initiation. This model provides a biochemical explanation for the typical positioning of TSSs well upstream of the 3' end of the CpG islands in which they are embedded.

  20. Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans

    PubMed Central

    Adelman, Karen; Lis, John T.

    2013-01-01

    Recent years have witnessed a sea change in our understanding of transcription regulation: whereas traditional models focused solely on the events that brought RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging evidence points to the pausing of Pol II during early elongation as a widespread regulatory mechanism in higher eukaryotes. Current data indicate that pausing is particularly enriched at genes in signal-responsive pathways. Here the evidence for pausing of Pol II from recent high-throughput studies will be discussed, as well as the potential interconnected functions of promoter-proximally paused Pol II. PMID:22986266

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2006-12-08

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

  3. Transcriptional regulation: effects of promoter proximal pausing on speed, synchrony and reliability.

    PubMed

    Boettiger, Alistair N; Ralph, Peter L; Evans, Steven N

    2011-05-01

    Recent whole genome polymerase binding assays in the Drosophila embryo have shown that a substantial proportion of uninduced genes have pre-assembled RNA polymerase-II transcription initiation complex (PIC) bound to their promoters. These constitute a subset of promoter proximally paused genes for which mRNA elongation instead of promoter access is regulated. This difference can be described as a rearrangement of the regulatory topology to control the downstream transcriptional process of elongation rather than the upstream transcriptional initiation event. It has been shown experimentally that genes with the former mode of regulation tend to induce faster and more synchronously, and that promoter-proximal pausing is observed mainly in metazoans, in accord with a posited impact on synchrony. However, it has not been shown whether or not it is the change in the regulated step per se that is causal. We investigate this question by proposing and analyzing a continuous-time Markov chain model of PIC assembly regulated at one of two steps: initial polymerase association with DNA, or release from a paused, transcribing state. Our analysis demonstrates that, over a wide range of physical parameters, increased speed and synchrony are functional consequences of elongation control. Further, we make new predictions about the effect of elongation regulation on the consistent control of total transcript number between cells. We also identify which elements in the transcription induction pathway are most sensitive to molecular noise and thus possibly the most evolutionarily constrained. Our methods produce symbolic expressions for quantities of interest with reasonable computational effort and they can be used to explore the interplay between interaction topology and molecular noise in a broader class of biochemical networks. We provide general-purpose code implementing these methods.

  4. Distal and proximal promoters co-regulate pqsR expression in Pseudomonas aeruginosa.

    PubMed

    Farrow, John M; Pesci, Everett C

    2016-12-23

    The ubiquitous bacterium Pseudomonas aeruginosa is an opportunistic pathogen that can cause serious infections in immunocompromised individuals. P. aeruginosa virulence is controlled partly by intercellular communication, and the transcription factor PqsR is a necessary component in the P. aeruginosa cell-to-cell signaling network. PqsR acts as the receptor for the Pseudomonas quinolone signal, and it controls the production of 2-alkyl-4-quinolone molecules which are important for pathogenicity. Previous studies showed that the expression of pqsR is positively controlled by the quorum-sensing regulator LasR, but it was unclear how LasR is able to induce pqsR transcription. In this report, we further investigated the control of pqsR, and discovered two separate promoter sites that contribute to pqsR expression. LasR-mediated activation occurs at the distal promoter site, but this activation can be antagonized by the regulator CysB. The proximal promoter site also contributes to pqsR transcription, but initiation at this site is inhibited by a negative regulatory sequence element, and potentially by the H-NS family members MvaT and MvaU. We propose a model where positive and negative regulatory influences at each promoter site are integrated to modify pqsR expression. This arrangement could allow for information from both environmental signals and cell-to-cell communication to influence PqsR levels.

  5. Endothelial Cell–Specific Expression of Roundabout 4 Is Regulated by Differential DNA Methylation of the Proximal Promoter

    PubMed Central

    Okada, Yoshiaki; Funahashi, Nobuaki; Tanaka, Toru; Nishiyama, Yuji; Yuan, Lei; Shirakura, Keisuke; Turjman, Alexis S.; Kano, Yoshihiro; Naruse, Hiroki; Suzuki, Ayano; Sakai, Miki; Zhixia, Jiang; Kitajima, Kenji; Ishimoto, Kenji; Hino, Nobumasa; Kondoh, Masuo; Mukai, Yohei; Nakagawa, Shinsaku; García-Cardeña, Guillermo; Aird, William C.; Doi, Takefumi

    2017-01-01

    Objective The molecular basis of endothelial cell (EC)–specific gene expression is poorly understood. Roundabout 4 (Robo4) is expressed exclusively in ECs. We previously reported that the 3-kb 5′-flanking region of the human Robo4 gene contains information for lineage-specific expression in the ECs. Our studies implicated a critical role for GA-binding protein and specificity protein 1 (SP1) in mediating overall expression levels. However, these transcription factors are also expressed in non-ECs. In this study, we tested the hypothesis that epigenetic mechanisms contribute to EC-specific Robo4 gene expression. Methods and Results Bisulfite sequencing analysis indicated that the proximal promoter of Robo4 is methylated in non-ECs but not in ECs. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine increased Robo4 gene expression in non-ECs but not in ECs. Proximal promoter methylation significantly decreased the promoter activity in ECs. Electrophoretic mobility shift assays showed that DNA methylation of the proximal promoter inhibited SP1 binding to the −42 SP1 site. In DNase hypersensitivity assays, chromatin condensation of the Robo4 promoter was observed in some but not all nonexpressing cell types. In Hprt (hypoxanthine phosphoribosyltransferase)-targeted mice, a 0.3-kb proximal promoter directed cell-type–specific expression in the endothelium. Bisulfite sequencing analysis using embryonic stem cell–derived mesodermal cells and ECs indicated that the EC-specific methylation pattern of the promoter is determined by demethylation during differentiation and that binding of GA-binding protein and SP1 to the proximal promoter is not essential for demethylation. Conclusions The EC-specific DNA methylation pattern of the Robo4 proximal promoter is determined during cell differentiation and contributes to regulation of EC-specific Robo4 gene expression. PMID:24855053

  6. T-cell functional regions of the human IL-3 proximal promoter.

    PubMed

    Ryan, G R; Vadas, M A; Shannon, M F

    1994-10-01

    The human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells. Its expression is regulated at both the transcriptional and post-transcriptional level. We have previously shown that treatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene. To define the regions of the gene required for transcription activation, we generated a series of reporter constructs containing different regions of the IL-3 gene 5' and 3' flanking sequences. Both positive and negative regulatory elements were identified in the proximal 5' flanking region of the IL-3 gene. The promoter region between -173 and -60 contained the strongest activating elements. The transcription factor AP-1 could bind to this positive activator region of the promoter. We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA/PHA.

  7. Transcription elongation factors DSIF and NELF: promoter-proximal pausing and beyond.

    PubMed

    Yamaguchi, Yuki; Shibata, Hirotaka; Handa, Hiroshi

    2013-01-01

    DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) were originally identified as factors responsible for transcriptional inhibition by 5,6-dichloro-1-beta-d-ribofuranosyl-benzimidazole (DRB) and were later found to control transcription elongation, together with P-TEFb, at the promoter-proximal region. Although there is ample evidence that these factors play roles throughout the genome, other data also suggest gene- or tissue-specific roles for these factors. In this review, we discuss how these apparently conflicting data can be reconciled. In light of recent findings, we also discuss the detailed mechanism by which these factors control the elongation process at the molecular level. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.

  8. Argonaute-bound small RNAs from promoter-proximal RNA polymerase II.

    PubMed

    Zamudio, Jesse R; Kelly, Timothy J; Sharp, Phillip A

    2014-02-27

    Argonaute (Ago) proteins mediate posttranscriptional gene repression by binding guide miRNAs to regulate targeted RNAs. To confidently assess Ago-bound small RNAs, we adapted a mouse embryonic stem cell system to express a single epitope-tagged Ago protein family member in an inducible manner. Here, we report the small RNA profile of Ago-deficient cells and show that Ago-dependent stability is a common feature of mammalian miRNAs. Using this criteria and immunopurification, we identified an Ago-dependent class of noncanonical miRNAs derived from protein-coding gene promoters, which we name transcriptional start site miRNAs (TSS-miRNAs). A subset of promoter-proximal RNA polymerase II (RNAPII) complexes produces hairpin RNAs that are processed in a DiGeorge syndrome critical region gene 8 (Dgcr8)/Drosha-independent but Dicer-dependent manner. TSS-miRNA activity is detectable from endogenous levels and following overexpression of mRNA constructs. Finally, we present evidence of differential expression and conservation in humans, suggesting important roles in gene regulation.

  9. 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.

  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. Deferasirox-induced iron depletion promotes BclxL downregulation and death of proximal tubular cells.

    PubMed

    Martin-Sanchez, Diego; Gallegos-Villalobos, Angel; Fontecha-Barriuso, Miguel; Carrasco, Susana; Sanchez-Niño, Maria Dolores; Lopez-Hernandez, Francisco J; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belén

    2017-01-31

    Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis. However, despite inhibiting caspase-3 activation, the pan-caspase inhibitor zVAD-fmk failed to prevent deferasirox-induced cell death. Moreover, zVAD increased deferasirox-induced cell death, a feature sometimes found in necroptosis. Electron microscopy identified mitochondrial injury and features of necrosis. However, neither necrostatin-1 nor RIP3 knockdown prevented deferasirox-induced cell death. Deferasirox caused BclxL depletion and BclxL overexpression was protective. Preventing iron depletion protected from BclxL downregulation and deferasirox cytotoxicity. In conclusion, deferasirox promoted iron depletion-dependent cell death characterized by BclxL downregulation. BclxL overexpression was protective, suggesting a role for BclxL downregulation in iron depletion-induced cell death. This information may be used to develop novel nephroprotective strategies. Furthermore, it supports the concept that monitoring kidney tissue iron depletion may decrease the risk of deferasirox nephrotoxicity.

  12. Deferasirox-induced iron depletion promotes BclxL downregulation and death of proximal tubular cells

    PubMed Central

    Martin-Sanchez, Diego; Gallegos-Villalobos, Angel; Fontecha-Barriuso, Miguel; Carrasco, Susana; Sanchez-Niño, Maria Dolores; Lopez-Hernandez, Francisco J; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belén

    2017-01-01

    Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis. However, despite inhibiting caspase-3 activation, the pan-caspase inhibitor zVAD-fmk failed to prevent deferasirox-induced cell death. Moreover, zVAD increased deferasirox-induced cell death, a feature sometimes found in necroptosis. Electron microscopy identified mitochondrial injury and features of necrosis. However, neither necrostatin-1 nor RIP3 knockdown prevented deferasirox-induced cell death. Deferasirox caused BclxL depletion and BclxL overexpression was protective. Preventing iron depletion protected from BclxL downregulation and deferasirox cytotoxicity. In conclusion, deferasirox promoted iron depletion-dependent cell death characterized by BclxL downregulation. BclxL overexpression was protective, suggesting a role for BclxL downregulation in iron depletion-induced cell death. This information may be used to develop novel nephroprotective strategies. Furthermore, it supports the concept that monitoring kidney tissue iron depletion may decrease the risk of deferasirox nephrotoxicity. PMID:28139717

  13. 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.

  14. The CpG Island in the Murine Foxl2 Proximal Promoter Is Differentially Methylated in Primary and Immortalized Cells

    PubMed Central

    Tran, Stella; Wang, Ying; Lamba, Pankaj; Zhou, Xiang; Boehm, Ulrich; Bernard, Daniel J.

    2013-01-01

    Forkhead box L2 (Foxl2), a member of the forkhead transcription factor family, plays important roles in pituitary follicle-stimulating hormone synthesis and in ovarian maintenance and function. Mutations in the human FOXL2 gene cause eyelid malformations and premature ovarian failure. FOXL2/Foxl2 is expressed in pituitary gonadotrope and thyrotrope cells, the perioptic mesenchyme of the developing eyelid, and ovarian granulosa cells. The mechanisms governing this cell-restricted expression have not been described. We mapped the Foxl2 transcriptional start site in immortalized murine gonadotrope-like cells, LβT2, by 5’ rapid amplification of cDNA ends and then PCR amplified approximately 1 kb of 5’ flanking sequence from murine genomic DNA. When ligated into a reporter plasmid, the proximal promoter conferred luciferase activity in both homologous (LβT2) and, unexpectedly, heterologous (NIH3T3) cells. In silico analyses identified a CpG island in the proximal promoter and 5’ untranslated region, suggesting that Foxl2 transcription might be regulated epigenetically. Indeed, pyrosequencing and quantitative analysis of DNA methylation using real-time PCR revealed Foxl2 proximal promoter hypomethylation in homologous compared to some, though not all, heterologous cell lines. The promoter was also hypomethylated in purified murine gonadotropes. In vitro promoter methylation completely silenced reporter activity in heterologous and homologous cells. Collectively, the data suggest that differential proximal promoter DNA methylation may contribute to cell-specific Foxl2 expression in some cellular contexts. However, gonadotrope-specific expression of the gene cannot be explained by promoter hypomethylation alone. PMID:24098544

  15. 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

  16. The enrichment of TATA box and the scarcity of depleted proximal nucleosome in the promoters of duplicated yeast genes.

    PubMed

    Kim, Yuseob; Lee, Jang H; Babbitt, Gregory A

    2010-01-01

    Population genetic theory of gene duplication suggests that the preservation of duplicate copies requires functional divergence upon duplication. Genes that can be readily modified to produce new gene expression patterns may thus be duplicated often. In yeast, genes exhibit dichotomous expression patterns based on their promoter architectures. The expression of genes that contain TATA box or occupied proximal nucleosome (OPN) tends to be variable and respond to external signals. On the other hand, genes without TATA box or with depleted proximal nucleosome (DPN) are expressed constitutively. We find that recent duplicates in the yeast genome are heavily biased to be TATA box containing genes and not to be DPN genes. This suggests that variably expressed genes, due to the functional organization in their promoters, have higher duplicability than constitutively expressed genes.

  17. Analyses of promoter-proximal pausing by RNA polymerase II on the hsp70 heat shock gene promoter in a Drosophila nuclear extract.

    PubMed Central

    Li, B; Weber, J A; Chen, Y; Greenleaf, A L; Gilmour, D S

    1996-01-01

    Analyses of Drosophila cells have revealed that RNA polymerase II is paused in a region 20 to 40 nucleotides downstream from the transcription start site of the hsp70 heat shock gene when the gene is not transcriptionally active. We have developed a cell-free system that reconstitutes this promoter-proximal pausing. The paused polymerase has been detected by monitoring the hyperreactivity of thymines in the transcription bubble toward potassium permanganate. The pattern of permanganate reactivity for the hsp70 promoter in the reconstituted system matches the pattern found on the promoter after it has been introduced back into files by P-element-mediated transposition. Matching patterns of permanganate reactivity are also observed for a non-heat shock promoter, the histone H3 promoter. Further analysis of the hsp70 promoter in the reconstituted system reveals that pausing does not depend on sequence-specific interactions located immediately downstream from the pause site. Sequences upstream from the TATA box influence the recruitment of polymerase rather than the efficiency of pausing. Kinetic analysis indicates that the polymerase rapidly enters the paused state and remains stably in this state for at least 25 min. Further analysis shows that the paused polymerase will initially resume elongation when Sarkosyl is added but loses this capacity within minutes of pausing. Using an alpha-amanitin-resistant polymerase, we provide evidence that promoter-proximal pausing does not require the carboxy-terminal domain of the polymerase. PMID:8816456

  18. Increased Renal Proximal Convoluted Tubule Transport Contributes to Hypertension in Cyp4a14 Knockout Mice

    PubMed Central

    Quigley, Raymond; Chakravarty, Sumana; Zhao, Xueying; Imig, John D.; Capdevila, Jorge H.

    2009-01-01

    Background/Aims Disrupting the enzyme Cyp4a14 in mice leads to hypertension, which is more severe in the male mice and appears to be due to androgen excess. Because the Cyp4a14 enzyme is located in the proximal tubule of the kidney, we hypothesized that there could be dysregulation of transport in this segment that could contribute to the hypertension. Methods Wild-type (SV/129) mice and mice that had targeted disruption of the Cyp4a14 gene were studied. Proximal convoluted tubules (PCT) from knockout and wild-type mice were dissected and perfused in vitrofor measurement of volume absorption (JV). Expression of the sodium-hydrogen exchanger 3 (NHE3), the predominant transporter responsible for sodium transport in this segment, was measured by immunoblot. Renal vascular (afferent arteriole) responses to angiotensin and endothelin were also measured. Results PCT volume absorption was elevated in tubules from the Cyp4a14 knockout mice as compared to the wild-type mice. Brush border membrane NHE3 expression was almost 2-fold higher in Cyp4a14 knockout mice than in wild-type mice. No difference was found in the afferent arteriolar response. Conclusion Thus, hypertension in the Cyp4a14 knockout mice appears to be driven by excessive fluid reabsorption in the proximal tubule, which is secondary to overexpression of NHE3. PMID:19713718

  19. The mammalian Na+/H+ antiporters NHE-1, NHE-2, and NHE-3 are electroneutral and voltage independent, but can couple to an H+ conductance

    PubMed Central

    1995-01-01

    Na+/H+ exchange in vertebrates is thought to be electroneutral and insensitive to the membrane voltage. This basic concept has been challenged by recent reports of antiport-associated currents in the turtle colon epithelium (Post and Dawson, 1992, 1994). To determine the electrogenicity of mammalian antiporters, we used the whole-cell patch clamp technique combined with microfluorimetric measurements of intracellular pH (pHi). In murine macrophages, which were found by RT- PCR to express the NHE-1 isoform of the antiporter, reverse (intracellular Na(+)-driven) Na+/H+ exchange caused a cytosolic acidification and activated an outward current, whereas forward (extracellular Na(+)-driven) exchange produced a cytosolic alkalinization and reduced a basal outward current. The currents mirrored the changes in pHi, were strictly dependent on the presence of a Na+ gradient and were reversibly blocked by amiloride. However, the currents were seemingly not carried by the Na+/H+ exchanger itself, but were instead due to a shift in the voltage dependence of a preexisting H+ conductance. This was supported by measurements of the reversal potential (Erev) of tail currents, which identified H+ (equivalents) as the charge carrier. During Na+/H+ exchange, Erev changed along with the measured changes in pHi (by 60-69 mV/pH). Moreover, the current and Na+/H+ exchange could be dissociated. Zn2+, which inhibits the H+ conductance, reversibly blocked the currents without altering Na+/H+ exchange. In Chinese hamster ovary (CHO) cells, which lack the H+ conductance, Na+/H+ exchange produced pHi changes that were not accompanied by transmembrane currents. Similar results were obtained in CHO cells transfected with either the NHE-1, NHE-2, or NHE-3 isoforms of the antiporter, indicating that exchange through these isoforms is electroneutral. In all the isoforms tested, the amplitude and time- course of the antiport-induced pHi changes were independent of the holding voltage. We conclude that

  20. 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

  1. A 350 bp region of the proximal promoter of Rds drives cell-type specific gene expression

    PubMed Central

    Cai, Xue; Conley, Shannon M.; Cheng, Tong; Al-Ubaidi, Muayyad R.; Naash, Muna I.

    2010-01-01

    RDS (retinal degeneration slow) is a photoreceptor-specific tetraspanin protein required for the biogenesis and maintenance of rod and cone outer segments. Mutations in the Rds gene are associated with multiple forms of rod- and cone-dominant retinal degeneration. To gain more insight into the mechanisms underlying the regulation of this gene the identification of regulatory sequences within the promoter of Rds was undertaken. A 3.5kb fragment of the 5′ flanking region of the mouse Rds gene was isolated and binding sites for Crx, Otx2, Nr2e3, RXR family members, Mef2C, Esrrb, NF1, AP1, and SP1 in addition to several E-boxes, GC-boxes and GAGA-boxes were identified. Crx binding sequences were conserved in all mammalian species examined. Truncation expression analysis of the Rds promoter region in Y-79 retinoblastoma cells showed maximal activity in the 350bp proximal promoter region. We also show that inclusion of more distal fragments reduced promoter activity to the basal level, and that the promoter activities are cell-type and direction specific. Co-transfection with Nrl increased promoter activity, suggesting that this gene positively regulates Rds expression. Based on these findings, a relatively small fragment of the Rds promoter may be useful in future gene transfer studies to drive gene expression in photoreceptors. PMID:20447394

  2. 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.

  3. 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

  4. Clustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies

    PubMed Central

    Colebatch, Andrew J.; Di Stefano, Leon; Wong, Stephen Q.; Hannan, Ross D.; Waring, Paul M.; Dobrovic, Alexander

    2016-01-01

    Most cancer DNA sequencing studies have prioritized recurrent non-synonymous coding mutations in order to identify novel cancer-related mutations. Although attention is increasingly being paid to mutations in non-coding regions, standard approaches to identifying significant mutations may not be appropriate and there has been limited analysis of mutational clusters in functionally annotated non-coding regions. We sought to identify clustered somatic mutations (hotspot regions across samples) in functionally annotated regions in melanoma and other cutaneous malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma). Sliding window analyses revealed numerous recurrent clustered hotspot mutations in proximal promoters, with some specific clusters present in up to 25% of cases. Mutations in melanoma were clustered within ETS and Sp1 transcription factor binding motifs, had a UV signature and were identified in other cutaneous malignancies. Clinicopathologic correlation and mutation analysis support a causal role for chronic UV irradiation generating somatic mutations in transcription factor binding motifs of proximal promoters. PMID:27611953

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

    PubMed Central

    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 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. PMID:25447411

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

    PubMed Central

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

    2013-01-01

    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. PMID:23485868

  8. 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.

  9. 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…

  10. Regulation of glomerulotubular balance: flow-activated proximal tubule function.

    PubMed

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

    2017-03-07

    The purpose of this review is to summarize our knowledge and understanding of the physiological importance and the mechanisms underlying flow-activated proximal tubule transport. Since the earliest micropuncture studies of mammalian proximal tubule, it has been recognized that tubular flow is an important regulator of sodium, potassium, and acid-base transport in the kidney. Increased fluid flow stimulates Na(+) and HCO3(-) absorption in the proximal tubule via stimulation of Na/H-exchanger isoform 3 (NHE3) and H(+)-ATPase. In the proximal tubule, brush border microvilli are the major flow sensors, which experience changes in hydrodynamic drag and bending moment as luminal flow velocity changes and which transmit the force of altered flow to cytoskeletal structures within the cell. The signal to NHE3 depends upon the integrity of the actin cytoskeleton; the signal to the H(+)-ATPase depends upon microtubules. We have demonstrated that alterations in fluid drag impact tubule function by modulating ion transporter availability within the brush border membrane of the proximal tubule. Beyond that, there is evidence that transporter activity within the peritubular membrane is also modulated by luminal flow. Secondary messengers that regulate the flow-mediated tubule function have also been delineated. Dopamine blunts the responsiveness of proximal tubule transporters to changes in luminal flow velocity, while a DA1 antagonist increases flow sensitivity of solute reabsorption. IP3 receptor-mediated intracellular Ca(2+) signaling is critical to transduction of microvillus drag. In this review, we summarize our findings of the regulatory mechanism of flow-mediated Na(+) and HCO3(-) transport in the proximal tubule and review available information about flow sensing and regulatory mechanism of glomerulotubular balance.

  11. 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

  12. NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly

    PubMed Central

    Gilchrist, Daniel A.; Nechaev, Sergei; Lee, Chanhyo; Ghosh, Saikat Kumar B.; Collins, Jennifer B.; Li, Leping; Gilmour, David S.; Adelman, Karen

    2008-01-01

    The Negative Elongation Factor (NELF) is a transcription regulatory complex that induces stalling of RNA polymerase II (Pol II) during early transcription elongation and represses expression of several genes studied to date, including Drosophila Hsp70, mammalian proto-oncogene junB, and HIV RNA. To determine the full spectrum of NELF target genes in Drosophila, we performed a microarray analysis of S2 cells depleted of NELF and discovered that NELF RNAi affects many rapidly inducible genes involved in cellular responses to stimuli. Surprisingly, only one-third of NELF target genes were, like Hsp70, up-regulated by NELF-depletion, whereas the majority of target genes showed decreased expression levels upon NELF RNAi. Our data reveal that the presence of stalled Pol II at this latter group of genes enhances gene expression by maintaining a permissive chromatin architecture around the promoter-proximal region, and that loss of Pol II stalling at these promoters is accompanied by a significant increase in nucleosome occupancy and a decrease in histone H3 Lys 4 trimethylation. These findings identify a novel, positive role for stalled Pol II in regulating gene expression and suggest that there is a dynamic interplay between stalled Pol II and chromatin structure. PMID:18628398

  13. The ATP-dependent chromatin remodeling enzyme Fun30 represses transcription by sliding promoter-proximal nucleosomes.

    PubMed

    Byeon, Boseon; Wang, Wei; Barski, Artem; Ranallo, Ryan T; Bao, Kan; Schones, Dustin E; Zhao, Keji; Wu, Carl; Wu, Wei-Hua

    2013-08-09

    The evolutionarily conserved ATP-dependent chromatin remodeling enzyme Fun30 has recently been shown to play important roles in heterochromatin silencing and DNA repair. However, how Fun30 remodels nucleosomes is not clear. Here we report a nucleosome sliding activity of Fun30 and its role in transcriptional repression. We observed that Fun30 repressed the expression of genes involved in amino acid and carbohydrate metabolism, the stress response, and meiosis. In addition, Fun30 was localized at the 5' and 3' ends of genes and within the open reading frames of its targets. Consistent with its role in gene repression, we observed that Fun30 target genes lacked histone modifications often associated with gene activation and showed an increased level of ubiquitinated histone H2B. Furthermore, a genome-wide nucleosome mapping analysis revealed that the length of the nucleosome-free region at the 5' end of a subset of genes was changed in Fun30-depleted cells. In addition, the positions of the -1, +2, and +3 nucleosomes at the 5' end of target genes were shifted significantly, whereas the position of the +1 nucleosome remained largely unchanged in the fun30Δ mutant. Finally, we demonstrated that affinity-purified, single-component Fun30 exhibited a nucleosome sliding activity in an ATP-dependent manner. These results define a role for Fun30 in the regulation of transcription and indicate that Fun30 remodels chromatin at the 5' end of genes by sliding promoter-proximal nucleosomes.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-01

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

  16. Gastrin induces sodium-hydrogen exchanger 3 phosphorylation and mTOR activation via a phosphoinositide 3-kinase-/protein kinase C-dependent but AKT-independent pathway in renal proximal tubule cells derived from a normotensive male human.

    PubMed

    Liu, Tianbing; Jose, Pedro A

    2013-02-01

    Gastrin is natriuretic, but its renal molecular targets and signal transduction pathways are not fully known. In this study, we confirmed the existence of CCKBR (a gastrin receptor) in male human renal proximal tubule cells and discovered that gastrin induced S6 phosphorylation, a downstream component of the phosphatidylinositol 3 kinase (PI3 kinase)-mammalian target of rapamycin pathway. Gastrin also increased the phosphorylation of sodium-hydrogen exchanger 3 (NHE3) at serine 552, caused its internalization, and decreased its expression at the cell surface and NHE activity. The phosphorylation of NHE3 and S6 was dependent on PI3 kinases because it was blocked by 2 different PI3-kinase inhibitors, wortmannin and LY294,002. The phosphorylation of NHE3 and S6 was not affected by the protein kinase A inhibitor H-89 but was blocked by a pan-PKC (chelerythrine) and a conventional PKC (cPKC) inhibitor (Gö6976) (10 μM) and an intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The cPKC involved was probably PKCα because it was phosphorylated by gastrin. The gastrin-mediated phosphorylation of NHE3, S6, and PKCα was via phospholipase C because it was blocked by a phospholipase C inhibitor, U73122 (10 μM). The phosphorylation (activation) of AKT, which is usually upstream of mammalian target of rapamycin in the classic PI3 kinase-AKT-p70S6K signaling pathway, was not affected, suggesting that the gastrin-induced phosphorylation of NHE3 and S6 is dependent on both PI3 kinase and PKCα but not AKT.

  17. Transcriptional activation of heat shock protein 90 mediated via a proximal promoter region as trigger of caspofungin resistance in Aspergillus fumigatus.

    PubMed

    Lamoth, Frédéric; Juvvadi, Praveen R; Gehrke, Christopher; Asfaw, Yohannes G; Steinbach, William J

    2014-02-01

    Invasive aspergillosis is a deadly infection for which new antifungal therapies are needed. Heat shock protein 90 (Hsp90) is an essential chaperone in Aspergillus fumigatus representing an attractive antifungal target. Using a thiamine-repressible promoter (pthiA), we showed that genetic repression of Hsp90 significantly reduced virulence in a murine model of invasive aspergillosis. Moreover, substituting the A. fumigatus hsp90 promoter with 2 artificial promoters (potef, pthiA) and the Candida albicans hsp90 promoter resulted in hypersensitivity to caspofungin and abolition of the paradoxical effect (resistance at high caspofungin concentrations). By inducing truncations in the hsp90 promoter, we identified a 100-base pair proximal sequence that triggers a significant increase of hsp90 expression (≥1.5-fold) and is essential for the paradoxical effect. Preventing this increase of hsp90 expression was sufficient to abolish the paradoxical effect and therefore optimize the antifungal activity of caspofungin.

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

    PubMed Central

    Salero, Enrique; Giménez, Cecilio; Zafra, Francisco

    2003-01-01

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

  19. Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments.

    PubMed

    Watanabe, Sumiyo; Ogasawara, Toru; Tamura, Yoshifuru; Saito, Taku; Ikeda, Toshiyuki; Suzuki, Nobuchika; Shimosawa, Tatsuo; Shibata, Shigeru; Chung, Ung-Il; Nangaku, Masaomi; Uchida, Shunya

    2017-01-01

    Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct. The promoters of the three genes were linked to a GFP-coding fragment, the final constructs were then incorporated into an adenovirus vector, and this was then used to generate gene-manipulated viruses. After flushing circulating blood, viruses were directly injected into the renal arteries of rats and were allowed to site-specifically expression in tubule cells, and rats were then euthanized to obtain kidney tissues for immunohistochemistry. Double staining with adenovirus-derived EGFP and endogenous proteins were examined to verify orthotopic expression, i.e. "adenovirus driven NPT2a-EGFP and endogenous NHE3 protein", "adenovirus driven NKCC2-EGFP and endogenous NKCC2 protein" and "adenovirus driven AQP2-EGFP and endogenous AQP2 protein". Owing to a lack of finding good working anti-NPT2a antibody, an antibody against a different protein (sodium-hydrogen exchanger 3 or NHE3) that is also specifically expressed in the proximal tubule was used. Kidney structures were well-preserved, and other organ tissues did not show EGFP staining. Our gene transfer method is easier than using genetically engineered animals, and it confers the advantage of allowing the manipulation of gene transfer after birth. This is the first method to successfully target gene expression to specific cells in the kidney tubules. This study may serve as the first step for safe and effective gene

  20. Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments

    PubMed Central

    Watanabe, Sumiyo; Ogasawara, Toru; Tamura, Yoshifuru; Saito, Taku; Ikeda, Toshiyuki; Suzuki, Nobuchika; Shimosawa, Tatsuo; Shibata, Shigeru; Chung, Ung-il; Nangaku, Masaomi; Uchida, Shunya

    2017-01-01

    Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct. The promoters of the three genes were linked to a GFP-coding fragment, the final constructs were then incorporated into an adenovirus vector, and this was then used to generate gene-manipulated viruses. After flushing circulating blood, viruses were directly injected into the renal arteries of rats and were allowed to site-specifically expression in tubule cells, and rats were then euthanized to obtain kidney tissues for immunohistochemistry. Double staining with adenovirus-derived EGFP and endogenous proteins were examined to verify orthotopic expression, i.e. “adenovirus driven NPT2a-EGFP and endogenous NHE3 protein”, “adenovirus driven NKCC2-EGFP and endogenous NKCC2 protein” and “adenovirus driven AQP2-EGFP and endogenous AQP2 protein”. Owing to a lack of finding good working anti-NPT2a antibody, an antibody against a different protein (sodium-hydrogen exchanger 3 or NHE3) that is also specifically expressed in the proximal tubule was used. Kidney structures were well-preserved, and other organ tissues did not show EGFP staining. Our gene transfer method is easier than using genetically engineered animals, and it confers the advantage of allowing the manipulation of gene transfer after birth. This is the first method to successfully target gene expression to specific cells in the kidney tubules. This study may serve as the first step for safe and

  1. 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.

  2. Osterix induces Col1a1 gene expression through binding to Sp1 sites in the bone enhancer and proximal promoter regions.

    PubMed

    Ortuño, Maria José; Susperregui, Antonio R G; Artigas, Natalia; Rosa, José Luis; Ventura, Francesc

    2013-02-01

    Bone-specific transcription factors promote differentiation of mesenchymal precursors toward the osteoblastic cell phenotype. Among them, Runx2 and Osterix have been widely accepted as master osteogenic factors, since neither Runx2 nor Osterix null mice form mature osteoblasts. Recruitment of Osterix to a number of promoters of bone-specific genes has been shown. However, little is known about the functional interactions between Osterix and the Col1a1 promoter. In this study we determined in several mesenchymal and osteoblastic cell types that either BMP-2 or Osterix overexpression increased Col1a1 transcription. We identified consensus Sp1 sequences, located in the proximal promoter and in the bone-enhancer, as Osterix binding regions in the Col1a1 promoter in vitro and in vivo. Furthermore, we show that p38 or Erk MAPK signaling is required for maximal transcriptional effects on Col1a1 expression. Runx2 has been shown to activate Col1a1 expression through binding to sites which are located close to the Sp1 sites where Osterix binds. Our data show that overexpression of Runx2 and Osterix leads to a cooperative effect on the expression of the Col1a1 endogenous gene and its promoter reporter construct. These effects mainly affect the long isoform of Osterix which suggest that the two Osterix isoforms might display some differential effects on the transactivation of bone-specific genes.

  3. 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

  4. Notch signaling proteins HES-1 and Hey-1 bind to insulin degrading enzyme (IDE) proximal promoter and repress its transcription and activity: implications for cellular Aβ metabolism.

    PubMed

    Leal, María C; Surace, Ezequiel I; Holgado, María P; Ferrari, Carina C; Tarelli, Rodolfo; Pitossi, Fernando; Wisniewski, Thomas; Castaño, Eduardo M; Morelli, Laura

    2012-02-01

    Cerebral amyloid β (Aβ) accumulation is pathogenically associated with sporadic Alzheimer's disease (SAD). BACE-1 is involved in Aβ generation while insulin-degrading enzyme (IDE) partakes in Aβ proteolytic clearance. Vulnerable regions in AD brains show increased BACE-1 protein levels and enzymatic activity while the opposite occurs with IDE. Another common feature in SAD brains is Notch1 overexpression. Here we demonstrate an increase in mRNA levels of Hey-1, a Notch target gene, and a decrease of IDE transcripts in the hippocampus of SAD brains as compared to controls. Transient transfection of Notch intracellular domain (NICD) in N2aSW cells, mouse neuroblastoma cells (N2a) stably expressing human amyloid precursor protein (APP) Swedish mutation, reduce IDE mRNA levels, promoting extracellular Aβ accumulation. Also, NICD, HES-1 and Hey-1 overexpression result in decreased IDE proximal promoter activity. This effect was mediated by 2 functional sites located at -379/-372 and -310-303 from the first translation start site in the -575/-19 (556 bp) fragment of IDE proximal promoter. By site-directed mutagenesis of the IDE promoter region we reverted the inhibitory effect mediated by NICD transfection suggesting that these sites are indeed responsible for the Notch-mediated inhibition of the IDE gene expression. Intracranial injection of the Notch ligand JAG-1 in Tg2576 mice, expressing the Swedish mutation in human APP, induced overexpression of HES-1 and Hey-1 and reduction of IDE mRNA levels, respectively. Our results support our theory that a Notch-dependent IDE transcriptional modulation may impact on Aβ metabolism providing a functional link between Notch signaling and the amyloidogenic pathway in SAD.

  5. Sp7/Osterix induces the mouse pro-α2(I) collagen gene (Col1a2) expression via the proximal promoter in osteoblastic cells.

    PubMed

    Yano, Hiroyuki; Hamanaka, Ryoji; Nakamura-Ota, Miki; Adachi, Sawako; Zhang, Juan Juan; Matsuo, Noritaka; Yoshioka, Hidekatsu

    2014-09-26

    Bone is essentially composed of two components, hydroxyapatite and extracellular matrix proteins. The extracellular matrix of bone is primary composed of collagen, mostly type I collagen, with lesser amounts of other types of collagen such as type V collagen. Osteoblast differentiation is a multi-step process in which many classes of factors function in a coordinated manner. Sp7/Osterix, which binds to G/C-rich sequences, is a transcription factor that contributes to osteoblast differentiation. The present study aimed to clarify the involvement of Sp7/Osterix with the proximal promoter region of the mouse Col1a2 gene containing multiple G/C-rich sequences exist. Consequently, a functional analysis of the proximal mouse Col1a2 promoter showed that a substitution mutation of the second G/C-rich sequence from the transcription site specifically decreased the activity of osteoblastic cells. In addition, the experiments of overexpression of Sp7/Osterix and treatment with its specific siRNA showed that this G/C-rich sequence is responsible for the specific expression in osteoblastic cells. Consistent with these data, Sp7/Osterix bound to the region and increased the expression of the Col1a2 gene in association with osteoblast differentiation in the culture system.

  6. 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

  7. Binding and functional effects of transcription factors Sp1 and Sp3 on the proximal human lecithin:cholesterol acyltransferase promoter.

    PubMed

    Hoppe, K L; Francone, O L

    1998-05-01

    Human lecithin:cholesterol acyltransferase (LCAT) circulates in plasma bound to high density lipoproteins (HDL) and modulates the rate by which cholesteryl ester is transported to the liver. So far, little is known about the regulation of the expression of the LCAT gene. In this study we have defined the cis-elements, identified the trans-acting factors and demonstrated their functional effects and significance in determining transcriptional activity of the proximal LCAT promoter. Using deletion mutants having 5' variable ends (from nucleotides -72 to -27), we have identified the presence of two non-consensus GC-rich regions that stimulate transcription in HepG2 and HeLa cells. These regions designated sites A (-29 to -47) and B (-49 to -65) contain the CCTCC core sequence which in electromobility shift analysis is critical for the formation of two DNA-protein complexes designated I and II. Site-directed mutagenesis suggests that both sites are equally important in promoter activity, and that cooperative interactions between both sites are not required for activity. Electromobility shift and supershift experiments using oligonucleotides spanning sites A and B identified Sp1 and Sp3 as the transcription factors interacting at these sites. To determine the significance and functional effects that Sp1 and Sp3 have in regulating LCAT promoter activity, we performed transfection experiments in Drosophila SL-2 cells as they lack endogenous Sp1 and Sp3. Sp1 but not Sp3 activates the human LCAT promoter and when Sp1 is co-transfected along with Sp3, Sp3 functions as a dose-dependent repressor of Sp1-mediated activation. These findings indicate that Sp1 is capable of transactivating a reporter gene linked to the LCAT promoter containing Sp binding sites and suggests that the levels of Sp3 or the nuclear Sp1/Sp3 ratio may play an important role in determining the transcriptional activity of the LCAT promoter in vivo.

  8. A Leader Intron of a Soybean Elongation Factor 1A (eEF1A) Gene Interacts with Proximal Promoter Elements to Regulate Gene Expression in Synthetic Promoters.

    PubMed

    Zhang, Ning; McHale, Leah K; Finer, John J

    2016-01-01

    Introns, especially the first intron in the 5' untranslated region (5'UTR), can significantly impact gene expression via intron-mediated enhancement (IME). In this study, we demonstrate the leader intron of a soybean elongation factor 1A (eEF1A) gene (GmScreamM8) was essential for the high activity of the native promoter. Furthermore, the interaction of the GmScreamM8 leader intron with regulatory element sequences from several soybean eEF1A promoters was studied using synthetic promoters, which consisted of element tetramers upstream of a core promoter used to regulate a green fluorescent protein (gfp) reporter gene. Element tetramers, placed upstream of a GmScreamM8 core promoter, showed very high activity using both transient expression in lima bean cotyledons and stable expression in soybean hairy roots, only if the native leader intron was included, suggesting an interaction between intronic sequences and promoter elements. Partial deletions of the leader intron showed that a 222 bp intronic sequence significantly contributed to very high levels of GFP expression. Generation of synthetic intron variants with a monomeric or trimeric repeat of the 222 bp intronic sequence, yielded almost two-fold higher expression compared to the original intron, while partial deletion of the 222 bp intronic repeated sequence significantly decreased gene expression, indicating that this intronic sequence was essential for the intron-element interaction enhancement.

  9. A Leader Intron of a Soybean Elongation Factor 1A (eEF1A) Gene Interacts with Proximal Promoter Elements to Regulate Gene Expression in Synthetic Promoters

    PubMed Central

    Zhang, Ning; McHale, Leah K.; Finer, John J.

    2016-01-01

    Introns, especially the first intron in the 5’ untranslated region (5’UTR), can significantly impact gene expression via intron-mediated enhancement (IME). In this study, we demonstrate the leader intron of a soybean elongation factor 1A (eEF1A) gene (GmScreamM8) was essential for the high activity of the native promoter. Furthermore, the interaction of the GmScreamM8 leader intron with regulatory element sequences from several soybean eEF1A promoters was studied using synthetic promoters, which consisted of element tetramers upstream of a core promoter used to regulate a green fluorescent protein (gfp) reporter gene. Element tetramers, placed upstream of a GmScreamM8 core promoter, showed very high activity using both transient expression in lima bean cotyledons and stable expression in soybean hairy roots, only if the native leader intron was included, suggesting an interaction between intronic sequences and promoter elements. Partial deletions of the leader intron showed that a 222 bp intronic sequence significantly contributed to very high levels of GFP expression. Generation of synthetic intron variants with a monomeric or trimeric repeat of the 222 bp intronic sequence, yielded almost two-fold higher expression compared to the original intron, while partial deletion of the 222 bp intronic repeated sequence significantly decreased gene expression, indicating that this intronic sequence was essential for the intron-element interaction enhancement. PMID:27806110

  10. 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.

  11. Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter.

    PubMed

    Xiao, Lin; Kovac, Suzana; Chang, Mike; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

    2014-02-01

    Gastrin and its precursors act as growth factors for the normal and neoplastic gastrointestinal mucosa. As the hypoxia mimetic cobalt chloride upregulates the gastrin gene, the effect of other metal ions on gastrin promoter activity was investigated. Gastrin mRNA was measured by real-time PCR, gastrin peptides by RIA, and gastrin promoter activity by dual-luciferase reporter assay. Exposure to Zn(2)(+) ions increased gastrin mRNA concentrations in the human gastric adenocarcinoma cell line AGS in a dose-dependent manner, with a maximum stimulation of 55 ± 14-fold at 100 μM (P<0.05). Significant stimulation was also observed with Cd(2)(+) and Cu(2)(+), but not with Ca(2)(+), Mg(2)(+), Ni(2)(+), or Fe(3)(+) ions. Activation of MAPK and phosphatidylinositol 3-kinase pathways is necessary but not sufficient for gastrin induction by Zn(2)(+). Deletional mutation of the gastrin promoter identified an 11 bp DNA sequence, which contained an E-box motif, as necessary for Zn(2)(+)-dependent gastrin induction. The fact that E-box binding transcription factors play a crucial role in the epithelial-mesenchymal transition (EMT), together with our observation that Zn(2)(+) ions upregulate the gastrin gene in AGS cells by an E-box-dependent mechanism, suggests that Zn(2)(+) ions may induce an EMT, and that gastrin may be involved in the transition.

  12. 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

  13. Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: role of the proximal promoter GC-rich region

    PubMed Central

    Englert, Neal A.; Turesky, Robert J.; Han, Weiguo; Bessette, Erin E.; Spivack, Simon D.; Caggana, Michele; Spink, David C.; Spink, Barbara C.

    2014-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, contributes to carcinogenesis through its role in the regulation of cytochrome P450 1 (CYP1)-catalyzed metabolism of carcinogens. Here, we investigated genetic and epigenetic mechanisms that affect AhR expression. Analyses of the human AHR proximal promoter in MCF-7 human breast cancer cells using luciferase assays and electrophoretic mobility shift assays revealed multiple specificity protein (Sp) 1 binding sequences that are transcriptional activators in vitro. The regulation of AhR expression was evaluated in long-term estrogen exposed (LTEE) MCF-7 cells, which showed increased AhR expression, enhanced CYP1 inducibility, and increased capacity to form DNA adducts when exposed to the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. The increased AhR expression in LTEE cells was found not to result from increased mRNA stability, differential RNA processing, or decreased DNA methylation. Analysis of the AHR proximal promoter region using chromatin immunoprecipitation confirmed that enhanced expression of AhR in LTEE cells involves changes in histone modifications, notably decreased trimethylation of histone 3, lysine 27. Upon further examination of the GC-rich Sp1-binding region, we confirmed that it contains a polymorphic (GGGGC)n repeat. In a population of newborns from New York State, the allele frequency of (GGGGC)n was n = 4>5≫6, 2. Circular dichroism spectroscopy revealed the ability of sequences of this GC-rich region to form guanine-quadruplex structures in vitro. These studies revealed multiple levels at which AhR expression may be controlled, and offer additional insights into mechanisms regulating AhR expression that can ultimately impact carcinogenesis. PMID:22728919

  14. Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: role of the proximal promoter GC-rich region.

    PubMed

    Englert, Neal A; Turesky, Robert J; Han, Weiguo; Bessette, Erin E; Spivack, Simon D; Caggana, Michele; Spink, David C; Spink, Barbara C

    2012-09-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, contributes to carcinogenesis through its role in the regulation of cytochrome P450 1 (CYP1)-catalyzed metabolism of carcinogens. Here, we investigated genetic and epigenetic mechanisms that affect AhR expression. Analyses of the human AHR proximal promoter in MCF-7 human breast cancer cells using luciferase assays and electrophoretic mobility shift assays revealed multiple specificity protein (Sp) 1 binding sequences that are transcriptional activators in vitro. The regulation of AhR expression was evaluated in long-term estrogen exposed (LTEE) MCF-7 cells, which showed increased AhR expression, enhanced CYP1 inducibility, and increased capacity to form DNA adducts when exposed to the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. The increased AhR expression in LTEE cells was found not to result from increased mRNA stability, differential RNA processing, or decreased DNA methylation. Analysis of the AHR proximal promoter region using chromatin immunoprecipitation confirmed that enhanced expression of AhR in LTEE cells involves changes in histone modifications, notably decreased trimethylation of histone 3, lysine 27. Upon further examination of the GC-rich Sp1-binding region, we confirmed that it contains a polymorphic (GGGGC)(n) repeat. In a population of newborns from New York State, the allele frequency of (GGGGC)(n) was n = 4 > 5 ≫ 6, 2. Circular dichroism spectroscopy revealed the ability of sequences of this GC-rich region to form guanine-quadruplex structures in vitro. These studies revealed multiple levels at which AhR expression may be controlled, and offer additional insights into mechanisms regulating AhR expression that can ultimately impact carcinogenesis.

  15. 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

  16. The COOH terminus of megalin regulates gene expression in opossum kidney proximal tubule cells

    PubMed Central

    Li, Yuanli; Cong, Rong; Biemesderfer, Daniel

    2008-01-01

    We recently reported that megalin is subjected to regulated intramembrane proteolysis (RIP) and includes 1) protein kinase C (PKC)-regulated, metalloprotease-mediated ectodomain shedding producing a membrane-bound megalin COOH-terminal fragment (MCTF) and 2) γ-secretase-mediated cleavage of the MCTF producing a soluble megalin intracellular domain (MICD). Based on studies of RIP of other receptors, the MICD is predicted to target to the nucleus and regulate gene expression. To determine whether RIP of megalin regulates proximal tubule gene expression, we stably expressed the transfected MCTF (tMCTF) or transfected MICD (tMICD) in opossum kidney proximal tubule (OKP) cells and examined the resulting phenotype. Immunoblotting and immunocytochemical analysis of tMCTF cells showed the tMCTF was expressed and constitutively processed by γ-secretase. Analysis of specific protein expression in tMCTF- and tMICD-transfected cells using Western blot showed endogenous megalin and Na+/H+ exchanger 3 (NHE3) protein expression to be dramatically lower than that of control cells. Expression of other proteins including myosin VI, β-adaptin, and the Na-K-ATPase appeared unchanged. Analysis of specific mRNA expression using quantitative real-time PCR showed megalin and NHE3 mRNA levels were significantly lower in tMCTF- and tMICD-transfected cells compared with controls. Inhibition of γ-secretase activity in tMCTF cells resulted in an 8- to 10-fold recovery of megalin mRNA within 4 h. These data show that the COOH-terminal domain of megalin regulates expression of specific proteins in OKP cells and provides the first evidence that RIP of megalin may be part of a signaling pathway linking protein absorption and gene expression in proximal tubule. PMID:18495814

  17. Retroviral insertions 90 kilobases proximal to the Evi-1 myeloid transforming gene activate transcription from the normal promoter.

    PubMed Central

    Bartholomew, C; Ihle, J N

    1991-01-01

    The inappropriate production of the Evi-1 zinc finger protein occurs in retrovirus-induced murine myeloid leukemias and human acute myelogenous leukemias. In murine leukemias, expression of the Evi-1 gene is associated with retroviral insertions either in the Evi-1 locus, which is immediately 5' of the coding region of the gene, or in the genetically linked Cb-1/fim-3 locus. In these studies, we demonstrate by chromosomal walking and pulse field electrophoresis that the Cb-1/fim-3 locus is located 90 kb 5' of the Evi-1 locus. Primary structure analysis of Evi-1 cDNA clones from a Cb-1/fim-3 rearranged cell line (DA-3) demonstrates that transcription initiates 5' of the Evi-1 locus and that the first noncoding exon of the gene is 681 bp larger than previously defined. S1 nuclease protection studies reveal multiple transcription initiation sites within this region. Comparable transcriptional initiation sites were identified in RNA from kidney and ovary, in which the gene is normally expressed, suggesting that retroviral insertions in the Cb-1/fim-3 locus activate transcription from the normal promoter. In one myeloid cell line (DA-3), a single long terminal repeat (LTR) is present in the Cb-1/fim-3 locus. No stable transcripts were detectable from this LTR. In cells with retroviral insertions in the Cb-1/fim-3 locus, one allele of the Evi-1 locus becomes hypermethylated in the 5' region of the gene. Together, these results are most consistent with an LTR-mediated, long-range cis activation of Evi-1 gene expression. Images PMID:1848663

  18. Polyamine-modulated c-Myc expression in normal intestinal epithelial cells regulates p21Cip1 transcription through a proximal promoter region

    PubMed Central

    Liu, Lan; Guo, Xin; Rao, Jaladanki N.; Zou, Tongtong; Marasa, Bernard S.; Chen, Jie; Greenspon, Jose; Casero, Robert A.; Wang, Jian-Ying

    2006-01-01

    Maintenance of intestinal mucosal epithelial integrity requires cellular polyamines that regulate expression of various genes involved in cell proliferation, growth arrest and apoptosis. Our previous studies have shown that polyamines are essential for expression of the c-myc gene and that polyamine-induced c-Myc plays a critical role in stimulation of normal IEC (intestinal epithelial cell) proliferation, but the exact downstream targets of induced c-Myc are still unclear. The p21Cip1 protein is a major player in cell cycle control, which is primarily regulated at the transcriptional level. The current study was designed to determine whether induced c-Myc stimulates normal IEC proliferation by repressing p21Cip1 transcription following up-regulation of polyamines. Overexpression of the ODC (ornithine decarboxylase) gene increased levels of cellular polyamines, induced c-Myc expression and inhibited p21Cip1 transcription, as indicated by repression of p21Cip1 promoter activity and a decrease in p21Cip1 protein levels. In contrast, depletion of cellular polyamines by inhibiting ODC enzyme activity with α-difluoromethylornithine decreased c-Myc, but increased p21Cip1 transcription. Ectopic expression of wild-type c-myc not only inhibited basal levels of p21Cip1 transcription in control cells, but also prevented increased p21Cip1 in polyamine-deficient cells. Experiments using different p21Cip1 promoter mutants showed that transcriptional repression of p21Cip1 by c-Myc was mediated through Miz-1- and Sp1-binding sites within the proximal region of the p21Cip1 promoter in normal IECs. These findings confirm that p21Cip1 is one of the direct mediators of induced c-Myc following increased polyamines and that p21Cip1 repression by c-Myc is implicated in stimulation of normal IEC proliferation. PMID:16706751

  19. Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress

    PubMed Central

    Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka

    2017-01-01

    Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress. DOI: http://dx.doi.org/10.7554/eLife.21907.001 PMID:28177284

  20. Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress.

    PubMed

    Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka

    2017-02-08

    Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.

  1. Verification of the in vivo activity of three distinct cis-acting elements within the Gata1 gene promoter-proximal enhancer in mice.

    PubMed

    Shimizu, Ritsuko; Hasegawa, Atsushi; Ottolenghi, Sergio; Ronchi, Antonella; Yamamoto, Masayuki

    2013-11-01

    The transcription factor GATA1 is essential for erythroid and megakaryocytic cell differentiation. Gata1 hematopoietic regulatory domain (G1HRD) has been shown to recapitulate endogenous Gata1 gene expression in transgenic mouse assays in vivo. G1HRD contains a promoter-proximal enhancer composed of a GATA-palindrome motif, four CP2-binding sites and two CACCC boxes. We prepared transgenic reporter mouse lines in which green fluorescent protein and β-galactosidase expression are driven by wild-type G1HRD (as a positive control) and the G1HRD harboring mutations within these cis-acting elements (as the experimental conditions), respectively. Exploiting this transgenic dual reporter (TDR) assay, we show here that in definitive erythropoiesis, G1HRD activity was markedly affected by individual mutations in the GATA-palindrome motif and the CACCC boxes. Mutation of CP2-binding sites also moderately decreased G1HRD activity. The combined mutation of the CP2-binding sites and the GATA-palindrome motif resulted in complete loss of G1HRD activity. In contrast, in primitive erythroid cells, individual mutations of each element did not affect G1HRD activity; G1HRD activity was abolished only when these three mutations were combined. These results thus show that all three elements independently and cooperatively contribute to G1HRD activity in vivo in definitive erythropoiesis, although these are contributing redundantly to primitive erythropoiesis.

  2. Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites.

    PubMed

    Hashimoto, Ko; Otero, Miguel; Imagawa, Kei; de Andrés, María C; Coico, Jonathan M; Roach, Helmtrud I; Oreffo, Richard O C; Marcu, Kenneth B; Goldring, Mary B

    2013-04-05

    The role of DNA methylation in the regulation of catabolic genes such as MMP13 and IL1B, which have sparse CpG islands, is poorly understood in the context of musculoskeletal diseases. We report that demethylation of specific CpG sites at -110 bp and -299 bp of the proximal MMP13 and IL1B promoters, respectively, detected by in situ methylation analysis of chondrocytes obtained directly from human cartilage, strongly correlated with higher levels of gene expression. The methylation status of these sites had a significant impact on promoter activities in chondrocytes, as revealed in transfection experiments with site-directed CpG mutants in a CpG-free luciferase reporter. Methylation of the -110 and -299 CpG sites, which reside within a hypoxia-inducible factor (HIF) consensus motif in the respective MMP13 and IL1B promoters, produced the most marked suppression of their transcriptional activities. Methylation of the -110 bp CpG site in the MMP13 promoter inhibited its HIF-2α-driven transactivation and decreased HIF-2α binding to the MMP13 proximal promoter in chromatin immunoprecipitation assays. In contrast to HIF-2α, MMP13 transcriptional regulation by other positive (RUNX2, AP-1, ELF3) and negative (Sp1, GATA1, and USF1) factors was not affected by methylation status. However, unlike the MMP13 promoter, IL1B was not susceptible to HIF-2α transactivation, indicating that the -299 CpG site in the IL1B promoter must interact with other transcription factors to modulate IL1B transcriptional activity. Taken together, our data reveal that the methylation of different CpG sites in the proximal promoters of the human MMP13 and IL1B genes modulates their transcription by distinct mechanisms.

  3. Protein kinase C-α interaction with iHSP70 in mitochondria promotes recovery of mitochondrial function after injury in renal proximal tubular cells.

    PubMed

    Nowak, Grazyna; Soundararajan, Sridharan; Mestril, Ruben

    2013-09-01

    This study determined the role of PKC-α and associated inducible heat shock protein 70 (iHSP70) in the repair of mitochondrial function in renal proximal tubular cells (RPTCs) after oxidant injury. Wild-type PKC-α (wtPKC-α) and an inactive PKC-α [dominant negative dn; PKC-α] mutant were overexpressed in primary cultures of RPTCs, and iHSP70 levels and RPTC regeneration were assessed after treatment with the oxidant tert-butylhydroperoxide (TBHP). TBHP exposure increased ROS production and induced RPTC death, which was prevented by ferrostatin and necrostatin-1 but not by cyclosporin A. Overexpression of wtPKC-α maintained mitochondrial levels of active PKC-α, reduced cell death, and accelerated proliferation without altering ROS production in TBHP-injured RPTCs. In contrast, dnPKC-α blocked proliferation and monolayer regeneration. Coimmunoprecipitation and proteomic analysis demonstrated an association between inactive, but not active, PKC-α and iHSP70 in mitochondria. Mitochondrial iHSP70 levels increased as levels of active PKC-α decreased after injury. Overexpression of dnPKC-α augmented, whereas overexpression of wtPKC-α abrogated, oxidant-induced increases in mitochondrial iHSP70 levels. iHSP70 overexpression (1) maintained mitochondrial levels of phosphorylated PKC-α, (2) improved the recovery of state 3 respiration and ATP content, (3) decreased RPTC death (an effect abrogated by cyclosporine A), and (4) accelerated proliferation after oxidant injury. In contrast, iHSP70 inhibition blocked the recovery of ATP content and exacerbated RPTC death. Inhibition of PKC-α in RPTC overexpressing iHSP70 blocked the protective effects of iHSP70. We conclude that active PKC-α maintains mitochondrial function and decreases cell death after oxidant injury. iHSP70 is recruited to mitochondria in response to PKC-α dephosphorylation and associates with and reactivates inactive PKC-α, which promotes the recovery of mitochondrial function, decreases RPTC

  4. 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.

  5. 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.

  6. Proximity fuze

    SciTech Connect

    Harrison, T.R.

    1989-08-22

    A proximity fuze system is described. It 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.

  7. Furin gene (fur) regulation in differentiating human megakaryoblastic Dami cells: involvement of the proximal GATA recognition motif in the P1 promoter and impact on the maturation of furin substrates.

    PubMed

    Laprise, Marie-Hélène; Grondin, Francine; Cayer, Pauline; McDonald, Patrick P; Dubois, Claire M

    2002-11-15

    The convertase furin is involved in the maturation of key growth/aggregation mediators synthesized by the platelet producers, megakaryocytes, but the regulation of furin in these cells remains unknown. Computer-assisted search of the furin promoter sequence revealed multiple potential binding motifs for GATA-1, suggesting that furin is expressed and regulated in these cells. Using megakaryoblastic Dami cells, we observed that fur mRNA expression increased gradually on phorbol 12-myristate 13-acetate-induced differentiation, reaching maximum levels (8.3-fold increase) at 10 days. Transient transfections with P1, P1A, or P1B fur-LUC-promoter constructs revealed that in Dami cells, the P1 promoter is the strongest and the most sensitive to forced expression of GATA-1. Coexpression of GATA-1 and its comodulator, Friend of GATA-1 (FOG-1), resulted in a cooperative increase in P1 activity. Deletion analysis indicated that important GATA-1-regulated sequences are located in the most proximal region of the P1 promoter. Further analysis revealed 2 potential GATA-binding motifs at positions -66 and +62. Point mutation of each of the 2 motifs indicated that the intactness of the first GATA site is required for full basal and GATA-1-stimulated promoter activity. Finally, the inhibition of furin activity through gene transfer of the inhibitor alpha1-AT-PDX led to a block in maturation of the furin substrates transforming growth factor-beta1 and platelet-derived growth factor. Taken together, these results indicate that the most proximal GATA element in the P1 promoter is needed for fur gene expression in megakaryoblastic cells. They also suggest that proper regulation of the fur gene in megakaryocytes has an impact on the activation of furin substrates involved in megakaryocyte maturation and platelet functions.

  8. Transcriptional activation of the SH2D2A gene is dependent on a cyclic adenosine 5'-monophosphate-responsive element in the proximal SH2D2A promoter.

    PubMed

    Dai, Ke-Zheng; Johansen, Finn-Eirik; Kolltveit, Kristin Melkevik; Aasheim, Hans-Christian; Dembic, Zlatko; Vartdal, Frode; Spurkland, Anne

    2004-05-15

    The SH2D2A gene, encoding the T cell-specific adapter protein (TSAd), is rapidly induced in activated T cells. In this study we investigate the regulation of the SH2D2A gene in Jurkat T cells and in primary T cells. Reporter gene assays demonstrated that the proximal 1-kb SH2D2A promoter was constitutively active in Jurkat TAg T cells and, to a lesser extent, in K562 myeloid cells, Reh B cells, and 293T fibroblast cells. The minimal SH2D2A promoter was located between position -236 and -93 bp from the first coding ATG, and transcriptional activity in primary T cells depended on a cAMP response element (CRE) centered around position -117. Nuclear extracts from Jurkat TAg cells and activated primary T cells contained binding activity to this CRE, as observed in an EMSA. Consistent with this observation, we found that a cAMP analog was a very potent inducer of SH2D2A mRNA expression in primary T cells as measured by real-time RT-PCR. Furthermore, activation of SH2D2A expression by CD3 stimulation required cAMP-dependent protein kinase activity. Thus, transcriptional regulation of the SH2D2A gene in activated T cells is critically dependent on a CRE in the proximal promoter region.

  9. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

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

  10. Exon-specific northern analysis and rapid amplification of cDNA ends (RACE) reveal that the proximal promoter II (PII) is responsible for aromatase cytochrome P450 (CYP19) expression in human ovary.

    PubMed

    Jenkins, C; Michael, D; Mahendroo, M; Simpson, E

    1993-11-01

    Estrogens are synthesized from C19 steroids by a unique form of cytochrome P450, aromatase cytochrome P-450 (P-450AROM; the product of the CYP19 gene). We have shown that tissue-specific expression of human P-450AROM is determined, in part, by the use of alternative promoters. Previous methods of analysis for determining the specific 5'-termini of the different transcripts included S1 nuclease protection, primer extension, and Northern analysis. In the present study we have used the RACE procedure (rapid amplification of cDNA ends) to amplify and clone the 5' termini of P-450AROM transcripts expressed in human corpus luteum (CL). Sequencing of the resulting clones supports the results of the previously performed studies. Specifically, the proximal promoter, PII, is the predominant promoter utilized in CL, such that the start of transcription occurs 26 bp downstream of the putative TATA sequence. A minority of the clones possess an alternative 5'-end, namely I.3. Exon-specific Northern analysis confirms that the majority of the P-450AROM transcripts in CL tissue contain sequence specific for promoter II. Similarly, exon-specific Northern analysis indicates that transcripts in human follicles, as well as granulosa cells in culture, contain primarily sequence specific for promoter II.

  11. DEC1 binding to the proximal promoter of CYP3A4 ascribes to the downregulation of CYP3A4 expression by IL-6 in primary human hepatocytes

    PubMed Central

    Gang, Cao; Wei, Liu; Jing, Xiong; Gang, Hu; Ruini, Chen; Rui, Ning; Wei, Shang; Jian, Yang; Bingfang, Yan

    2014-01-01

    In this study, we provided molecular evidences that IL-6 contributed to the decreased capacity of oxidative biotransformation in human liver by suppressing the expression of CYP3A4. After human hepatocytes were treated with IL-6, DEC1 expression rapidly increased, and subsequently, the CYP3A4 expression decreased continuously. Furthermore, the repression of CYP3A4 by IL-6 occurred after the increase of DEC1 in primary human hepatocytes. In HepG2 cells, knockdown of DEC1 increased the CYP3A4 expression and its enzymatic activity. In addition, it partially abolished the decreased CYP3A4 expression as well as its enzymatic activity induced by IL-6. Consistent with this, overexpression of DEC1 markedly reduced the CYP3A4 promoter activity and the CYP3A4 expression as well as its enzymatic activity. Using sequential truncation and site directed mutagenesis of CYP3A4 proximal promoter with DEC1 construct, we showed that DEC1 specifically bound to CCCTGC sequence in the proximal promoter of CYP3A4, which was validated by EMSA and ChIP assay. These findings suggest that the repression of CYP3A4 by IL-6 is achieved through increasing the DEC1 expression in human hepatocytes, the increased DEC1 binds to the CCCTGC sequence in the promoter of CYP3A4 to form CCCTGC-DEC1 complex, and the complex downregulates the CYP3A4 expression and its enzymatic activity. PMID:22728071

  12. Proximal Tibial Bone Graft

    MedlinePlus

    ... All Site Content AOFAS / FootCareMD / Treatments Proximal Tibial Bone Graft Page Content What is a bone graft? Bone grafts may be needed for various ... the proximal tibia. What is a proximal tibial bone graft? Proximal tibial bone graft (PTBG) is a ...

  13. Chromatin immunoprecipitation scanning identifies glucocorticoid receptor binding regions in the proximal promoter of a ubiquitously expressed glucocorticoid target gene in brain.

    PubMed

    van der Laan, Siem; Sarabdjitsingh, R Angela; Van Batenburg, Marcel F; Lachize, Servane B; Li, Hualing; Dijkmans, Thomas F; Vreugdenhil, Erno; de Kloet, E Ron; Meijer, Onno C

    2008-09-01

    While the actions of glucocorticoids on brain functions have been comprehensively studied, the underlying genomic mechanisms are poorly understood. In this study, we show that glucocorticoid-induced leucine zipper (GILZ) mRNA is strongly and ubiquitously induced in rat brain. To decipher the molecular mechanisms underlying these genomic effects, it is of interest to identify the regulatory sites in the promoter region. Alignment of the rat GILZ promoter with the well-characterized human promoter resulted in poor sequence homology. Consequently, we analyzed the rat 5' flanking sequence by Matrix REDUCE and identified two high-affinity glucocorticoid response elements (GRE) located 2 kb upstream of the transcription start site. These findings were corroborated using the glucocorticoid receptor (GR) expressing Ns-1 PC12 rat cell-line. In these cells, dexamethasone treatment leads to a progressive increase of GILZ mRNA expression levels via a GR-dependent mechanism. Subsequently, using chromatin immunoprecipitation assays we show that the two high-affinity GREs are located within the GR-binding regions. Lastly, we demonstrate using multiple tissue in situ hybridization a marked increase in mRNA expression levels in spleen, thymus, heart, lung, liver, muscle, testis, kidney, colon, ileum, as well as in brain and conclude that the GILZ gene can be used to study glucocorticoid effects in many additional rodent tissues.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Proximal Hamstring Repair Strength

    PubMed Central

    Harvey, Margaret Ann; Singh, Hardeep; Obopilwe, Elifho; Charette, Ryan; Miller, Suzanne

    2015-01-01

    Background: Proximal hamstring repair for complete ruptures has become a common treatment. There is no consensus in the literature about postoperative rehabilitation protocols following proximal hamstring repair. Some protocols describe bracing to prevent hip flexion or knee extension while others describe no immobilization. There are currently no biomechanical studies evaluating proximal hamstring repairs; nor are there any studies evaluating the effect of different hip flexion angles on these repairs. Hypothesis: As hip flexion increases from 0° to 90°, there will be a greater gap with cyclical loading. Study Design: Controlled laboratory study. Methods: Proximal hamstring insertions were detached from the ischial tuberosity in 24 cadavers and were repaired with 3 single-loaded suture anchors in the hamstring footprint with a Krakow suture technique. Cyclic loading from 10 to 125 N at 1 Hz was then performed for 0°, 45°, and 90° of hip flexion for 1500 cycles. Gap formation, stiffness, yield load, ultimate load, and energy to ultimate load were compared between groups using paired t tests. Results: Cyclic loading demonstrated the least amount of gap formation (P < .05) at 0° of hip flexion (2.39 mm) and most at 90° of hip flexion (4.19 mm). There was no significant difference in ultimate load between hip flexion angles (326, 309, and 338 N at 0°, 45°, and 90°, respectively). The most common mode of failure occurred with knot/suture failure (n = 17). Conclusion: Increasing hip flexion from 0° to 90° increases the displacement across proximal hamstring repairs. Postoperative bracing that limits hip flexion should be considered. Clinical Relevance: Repetitive motion involving hip flexion after a proximal hamstring repair may cause compromise of the repair. PMID:26665049

  19. 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.

  20. Steerable Capacitive Proximity Sensor

    NASA Technical Reports Server (NTRS)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

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

  1. 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,…

  2. 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

  3. 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.

  4. 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.

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

    PubMed

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

    2016-04-01

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

  6. 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

  7. Some properties of fuzzy soft proximity spaces.

    PubMed

    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.

  8. The proximal islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen promoter is sufficient to initiate but not maintain transgene expression in mouse islets in vivo.

    PubMed

    Frigeri, Claudia; Martin, Cyrus C; Svitek, Christina A; Oeser, James K; Hutton, John C; Gannon, Maureen; O'Brien, Richard M

    2004-07-01

    We have previously reported the discovery of an islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that is predominantly expressed in islet beta-cells. IGRP has recently been identified as a major autoantigen in a mouse model of type 1 diabetes. The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression in transiently transfected islet-derived hamster insulinoma tumor and betaTC-3 cells revealed that the promoter region located between -306 and +3 confers high-level reporter gene expression. To determine whether this same promoter region is sufficient to confer islet beta-cell-specific gene expression in vivo, it was ligated to a beta-galactosidase reporter gene, and transgenic mice expressing the resulting fusion gene were generated. In two independent founder lines, this -306 to +3 promoter region was sufficient to drive beta-galactosidase expression in newborn mouse islets, predominantly in beta-cells, which was initiated during the expected time in development, around embryonic day 12.5. However, unlike the endogenous IGRP gene, beta-galactosidase expression was also detected in the cerebellum. Moreover, beta-galactosidase expression was almost completely absent in adult mouse islets, suggesting that cis-acting elements elsewhere in the IGRP gene are required for determining appropriate IGRP tissue-specific expression and for the maintenance of IGRP gene expression in adult mice.

  9. Proximity of Radiation Desiccation Response Motif to the core promoter is essential for basal repression as well as gamma radiation-induced gyrB gene expression in Deinococcus radiodurans.

    PubMed

    Anaganti, Narasimha; Basu, Bhakti; Mukhopadhyaya, Rita; Apte, Shree Kumar

    2017-03-02

    The radioresistant D. radiodurans regulates its DNA damage regulon (DDR) through interaction between a 17bp palindromic cis-regulatory element called the Radiation Desiccation Response Motif (RDRM), the DdrO repressor and a protease IrrE. The role of RDRM in regulation of DDR was dissected by constructing RDRM sequence-, position- or deletion-variants of Deinococcal gyrB gene (DR0906) promoter and by RDRM insertion in the non-RDRM groESL gene (DR0606) promoter, and monitoring the effect of such modifications on the basal as well as gamma radiation inducible promoter activity by quantifying fluorescence of a GFP reporter. RDRM sequence-variants revealed that the conservation of sequence at the 5th and 13th position and the ends of RDRM is essential for basal repression by interaction with DdrO. RDRM position-variants showed that the sequence acts as a negative regulatory element only when located around transcription start site (TSS) and within the span of RNA polymerase (RNAP) binding region. RDRM deletion-variants indicated that the 5' sequence of RDRM possibly possesses an enhancer-like element responsible for higher expression yields upon repressor clearance post-irradiation. The results suggest that RDRM plays both a negative as well as a positive role of in the regulation of DDR in D. radiodurans.

  10. 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

  11. 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...

  12. 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.

  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. Proximity Sensors Make Robot Dexterous

    NASA Technical Reports Server (NTRS)

    Hess, Cliff; Li, Larry C. H.

    1990-01-01

    Control system enables robot hand to grasp objects of varied shapes. Key features of system: reflective proximity sensors furnishing data on position, orientation, and distance of object and software protocol controlling sequence of operations in approaching and grasping objects. Reflected-beam sensing concept applied to simple opposed-jaw industrial grippers as well as to dexterous robot hands.

  15. Proximity and Anti-proximity effects in nanowires

    NASA Astrophysics Data System (ADS)

    Chan, Moses

    Near a superconductor/normal-metal interface, the leakage of Cooper pairs extends superconducting behavior into the metal. The spatial range of this proximity effect in a normal metal can be as long as 1 µm. However, when a ferromagnet is placed in contact with a superconductor, the Cooper pairs from the superconductor are not expected to survive beyond at most a few nanometers into the ferromagnet. Surprisingly we find when a cobalt nanowire as long as 600 nm is sandwiched between superconducting electrodes, it attains zero resistance at low temperature. For even longer wires, the transition to incomplete superconductivity via this (long range) proximity effect is foreshadowed by a large resistance peak (1). On the other hand when Zn nanowires of 40 nm diameter are contacted by superconducting electrodes, their superconductivity is unexpectedly suppressed (2). Worked supported by Penn State MRSEC.

  16. 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.

  17. 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.

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

    ERIC Educational Resources Information Center

    van Compernolle, Remi A.; Williams, Lawrence

    2012-01-01

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

  19. 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 ...

  20. Active Targets For Capacitive Proximity Sensors

    NASA Technical Reports Server (NTRS)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

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

  1. 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

  2. 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.

  3. Protein Neighbors and Proximity Proteomics.

    PubMed

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

    2015-11-01

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

  4. Fibrosis: ultimate and proximate causes

    PubMed Central

    Thannickal, Victor J.; Zhou, Yong; Gaggar, Amit; Duncan, Steven R.

    2014-01-01

    Fibrotic disorders account for an increasing burden of disease-associated morbidity and mortality worldwide. Although numerous risk factors have been recognized, the etiologies of many of these clinical syndromes have not been identified, and they are often termed idiopathic or cryptogenic. Here, we provide an evolutionary perspective on fibrosis aimed at elucidating its etiopathogenesis. By asking the ultimate question of “why” this process evolved in multicellular organisms, we hope to uncover proximate explanations for “how” it causes disease in humans. We posit that physiological fibrosis-like reactions evolved as an essential process in host defense against pathogens and in normal wound healing. Based on this premise, we reason that pathological fibrosis is related to one or more of the following: unidentified infectious or noninfectious antigens, autoimmunity, impaired regenerative responses, and the antagonistically pleiotropic action of genes involved in wound healing or development. The importance of genetic susceptibility, epigenetics, aging, and the modern-day environment are highlighted. Consideration of both ultimate and proximate causation goes beyond philosophical cogitations, as it will better inform pathobiological mechanisms of disease and aid in the prevention and treatment of fibrotic diseases. PMID:25365073

  5. 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

  6. Using Valsiner's Zone Theory To Interpret Change in Classroom Practice: Beyond the Zone of Proximal Development.

    ERIC Educational Resources Information Center

    Blanton, Maria L.; Westbrook, Susan L.; Carter, Glenda

    This study explores the use of Valsiner's zone theory as a way to interpret the zones of proximal development of three secondary school teachers in mathematics and science. Specifically, researchers used classroom discourse to identify what the participating teachers promoted (zone of promoted action) or allowed (zone of free movement) in the…

  7. Deformed proximity potential for heavy ion reactions

    SciTech Connect

    Baltz, A.J.

    1989-09-01

    The proximity potential is discussed for the inelastic scattering of a spherical nucleus on a deformed nucleus or the mutual interaction of two deformed nuclei. It is shown that the proximity potential is, in general, geometrically more correct than the usual centerline prescription used in inelastic scattering analyses. For the cases where the proximity potential is inadequate a folding model approach is advocated. Techniques to facilitate the coupled channels analysis are presented. 11 refs., 6 figs.

  8. 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.

  9. 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.

  10. 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.

  11. Human Promoters Are Intrinsically Directional

    PubMed Central

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

    2015-01-01

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

  12. 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.

  13. 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.

  14. Sugar proximity and human grip strength.

    PubMed

    Quintanar, A F; Hill, T V

    1988-12-01

    In a double-blind experiment with 90 undergraduate students the hypothesis was tested that proximity to sugar reduces human grip strength. An earlier study indicated that sugar proximity does indeed significantly reduce human grip strength. When additional controls were added to this design to reduce random sampling error, the hypothesis was not supported.

  15. Grouping by Proximity in Haptic Contour Detection

    PubMed Central

    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. PMID:23762364

  16. 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…

  17. A Brief Index for Proximity Searching

    NASA Astrophysics Data System (ADS)

    Téllez, Eric Sadit; Chávez, Edgar; Camarena-Ibarrola, Antonio

    Many pattern recognition tasks can be modeled as proximity searching. Here the common task is to quickly find all the elements close to a given query without sequentially scanning a very large database.

  18. Polarization proximity effect in isolator crystal pairs.

    PubMed

    Linzon, Y; Ferrera, M; Razzari, L; Pignolet, A; Morandotti, R

    2008-12-01

    We experimentally study the polarization dynamics (orientation and ellipticity) of near-infrared light transmitted through magneto-optical yttrium iron garnet isolator crystal pairs using a modified balanced detection scheme. When the pair separation is in the submillimeter range, we observed a proximity effect in which the saturation field is reduced by up to 20%. One-dimensional calculations suggest that the proximity effect originates from magnetostatic interactions between the dipole moments of the isolator crystals.

  19. A proximal activator of transcription in epithelial-mesenchymal transition

    PubMed Central

    Venkov, Christo D.; Link, Andrew J.; Jennings, Jennifer L.; Plieth, David; Inoue, Tsutomu; Nagai, Kojiro; Xu, Carol; Dimitrova, Yoana N.; Rauscher, Frank J.; Neilson, Eric G.

    2007-01-01

    Epithelial-mesenchymal transition (EMT) is an important mechanism for phenotypic conversion in normal development and disease states such as tissue fibrosis and metastasis. While this conversion of epithelia is under tight transcriptional control, few of the key transcriptional proteins are known. Fibroblasts produced by EMT express a gene encoding fibroblast-specific protein 1 (FSP1), which is regulated by a proximal cis-acting promoter element called fibroblast transcription site–1 (FTS-1). In mass spectrometry, chromatin immunoprecipitation, and siRNA studies, we used FTS-1 as a unique probe for mediators of EMT and identified a complex of 2 proteins, CArG box–binding factor–A (CBF-A) and KRAB-associated protein 1 (KAP-1), that bind this site. Epithelial cells engineered to conditionally express recombinant CBF-A (rCBF-A) activate the transcription of FSP1 and undergo EMT. The FTS-1 response element also exists in the promoters modulating a broader EMT transcriptome, including Twist, and Snail, as well as E-cadherin, β-catenin, ZO 1, vimentin, α1(I) collagen, and α–smooth muscle actin, and the induction of rCBF-A appropriately alters their expression as well. We believe formation of the CBF-A/KAP-1/FTS-1 complex is sufficient for the induction of FSP1 and a novel proximal activator of EMT. PMID:17273560

  20. A proximal activator of transcription in epithelial-mesenchymal transition.

    PubMed

    Venkov, Christo D; Link, Andrew J; Jennings, Jennifer L; Plieth, David; Inoue, Tsutomu; Nagai, Kojiro; Xu, Carol; Dimitrova, Yoana N; Rauscher, Frank J; Neilson, Eric G

    2007-02-01

    Epithelial-mesenchymal transition (EMT) is an important mechanism for phenotypic conversion in normal development and disease states such as tissue fibrosis and metastasis. While this conversion of epithelia is under tight transcriptional control, few of the key transcriptional proteins are known. Fibroblasts produced by EMT express a gene encoding fibroblast-specific protein 1 (FSP1), which is regulated by a proximal cis-acting promoter element called fibroblast transcription site-1 (FTS-1). In mass spectrometry, chromatin immunoprecipitation, and siRNA studies, we used FTS-1 as a unique probe for mediators of EMT and identified a complex of 2 proteins, CArG box-binding factor-A (CBF-A) and KRAB-associated protein 1 (KAP-1), that bind this site. Epithelial cells engineered to conditionally express recombinant CBF-A (rCBF-A) activate the transcription of FSP1 and undergo EMT. The FTS-1 response element also exists in the promoters modulating a broader EMT transcriptome, including Twist, and Snail, as well as E-cadherin, beta-catenin, ZO 1, vimentin, alpha1(I) collagen, and alpha-smooth muscle actin, and the induction of rCBF-A appropriately alters their expression as well. We believe formation of the CBF-A/KAP-1/FTS-1 complex is sufficient for the induction of FSP1 and a novel proximal activator of EMT.

  1. 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.

  2. Proximity operations considerations affecting spacecraft design

    NASA Technical Reports Server (NTRS)

    Staas, Steven K.

    1991-01-01

    Experience from several recent spacecraft development programs, such as Space Station Freedom (SSF) and the Orbital Maneuvering Vehicle (OMV) has shown the need for factoring proximity operations considerations into the vehicle design process. Proximity operations, those orbital maneuvers and procedures which involve operation of two or more spacecraft at ranges of less than one nautical mile, are essential to the construction, servicing, and operation of complex spacecraft. Typical proximity operations considerations which drive spacecraft design may be broken into two broad categories; flight profile characteristics and concerns, and use of various spacecraft systems during proximity operations. Proximity operations flight profile concerns include the following: (1) relative approach/separation line; (2) relative orientation of the vehicles; (3) relative translational and rotational rates; (4) vehicle interaction, in the form of thruster plume impingement, mating or demating operations, or uncontrolled contact/collision; and (5) active vehicle piloting. Spacecraft systems used during proximity operations include the following: (1) sensors, such as radar, laser ranging devices, or optical ranging systems; (2) effector hardware, such as thrusters; (3) flight control software; and (4) mating hardware, needed for docking or berthing operations. A discussion of how these factors affect vehicle design follows, addressing both active and passive/cooperative vehicles.

  3. 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…

  4. Evaluation and Management of Proximal Humerus Fractures

    PubMed Central

    Khmelnitskaya, Ekaterina; Lamont, Lauren E.; Taylor, Samuel A.; Lorich, Dean G.; Dines, David M.; Dines, Joshua S.

    2012-01-01

    Proximal humerus fractures are common injuries, especially among older osteoporotic women. Restoration of function requires a thorough understanding of the neurovascular, musculotendinous, and bony anatomy. This paper addresses the relevant anatomy and highlights various management options, including indication for arthroplasty. In the vast majority of cases, proximal humerus fractures may be treated nonoperatively. In the case of displaced fractures, when surgical intervention may be pursued, numerous constructs have been investigated. Of these, the proximal humerus locking plate is the most widely used. Arthroplasty is generally reserved for comminuted 4-part fractures, head-split fractures, or fractures with significant underlying arthritic changes. Reverse total shoulder arthroplasty is reserved for patients with a deficient rotator cuff, or highly comminuted tuberosities. PMID:23316376

  5. Two-Dimensional Optical Proximity Effects

    NASA Astrophysics Data System (ADS)

    Flanner, Philip D.; Subramanian, Shankar; Neureuther, Andrew R.

    1986-08-01

    In projection printing the proximity effects between adjacent two-dimensional features such as concentric elbows can be the limiting factor in designing layout rules. An aerial image simulation code based on the imaging algorithms in SAMPLE has been developed and used to investigate these proximity effects. The program accepts arbitrary polygonal shapes constructed of rectangular and triangular patches. The image is calculated using Hopkins transmission cross coefficient formulation and uses rapid integral evaluation techniques. The cpu time for this FORTRAN F77 program depends on the size of the mask and the partial coherence factor as 0.25[(1 + σ) 2A(NA/λ)2]2 seconds on a DEC VAX 11/780 using double precision, where A is the mask area, σ the coherence factor, NA the numerical aperture and λ the wavelength. The output intensity can be displayed with graphics tools such as UNIGRAFIX or cross-sectioned for input to SAMPLE development simulation along critical paths. Proximity effects in critical regions between features such as nested elbows, contacts near contacts and lines, and lines near large pads are studied. For small contacts studies show that a contact hole can be placed as close as 0.5λ/NA microns to another contact hole. For nested elbows the critical effect is the variation in intensity in the straight regions just adjacent to the corner. This undesirable variation is primarily due to the intrafeature intensity interactions and is not greatly influenced by the proximity of another nested elbow. For general feature shapes the proximity effects are reduced by increasing the partial coherence factor to 0.5 or higher but at the cost of reducing contrast and peak intensity. For contact masks a partial coherence of 0.3 is recommended for higher edge slope and peak intensities. Proximity effects of small defects are also illustrated.

  6. Strategy for photostable proximity bioassays using lanthanides

    PubMed Central

    Haushalter, Jeanne P.; Faris, Gregory W.

    2011-01-01

    We report initial findings for research aimed at creating photostable lanthanide chelate reporters for proximity assays. These reporters take advantage of the nanometer scale distance dependence of fluorescence enhancement for molecules in the vicinity of noble metal nanoparticles and also capitalize on some unique properties of lanthanide chelates. This approach promises to lead to proximity assays that do not suffer from photobleaching and offer very high on/off enhancement ratios. Results for lanthanide chelates on silver island films and in colloidal suspensions are reported. Enhancement factors range from 1 to 2 orders of magnitude, with larger enhancements for strongly quenched lanthanides. PMID:17356638

  7. [Proximity and breastfeeding at the maternity hospital].

    PubMed

    Fradin-Charrier, Anne-Claire

    2015-01-01

    The establishment of breastfeeding, as well as its duration, are facilitated through the proximity of the mother with her new baby. However, in maternity hospitals, breastfeeding mothers very often leave their baby in the nursery at night time. A study carried out in 2014 in several maternity hospitals put forward suggestions and highlighted areas to improve in everyday practice.

  8. Vortices in normal part of proximity system

    DOE PAGES

    Kogan, V. G.

    2015-05-26

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

  9. 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

  10. Encoding Direction when Interpreting Proximal Terms

    ERIC Educational Resources Information Center

    Ashley, Aaron; Carlson, Laura A.

    2007-01-01

    The location of an object is often described by spatially relating it to a known landmark. The spatial terms used in such descriptions can provide various types of information. For example, projective terms such as "above" indicate direction but not distance, whereas proximal terms such as "near" indicate distance but not direction. Previous…

  11. Object detection system using SPAD proximity detectors

    NASA Astrophysics Data System (ADS)

    Stark, Laurence; Raynor, Jeffrey M.; Henderson, Robert K.

    2011-10-01

    This paper presents an object detection system based upon the use of multiple single photon avalanche diode (SPAD) proximity sensors operating upon the time-of-flight (ToF) principle, whereby the co-ordinates of a target object in a coordinate system relative to the assembly are calculated. The system is similar to a touch screen system in form and operation except that the lack of requirement of a physical sensing surface provides a novel advantage over most existing touch screen technologies. The sensors are controlled by FPGA-based firmware and each proximity sensor in the system measures the range from the sensor to the target object. A software algorithm is implemented to calculate the x-y coordinates of the target object based on the distance measurements from at least two separate sensors and the known relative positions of these sensors. Existing proximity sensors were capable of determining the distance to an object with centimetric accuracy and were modified to obtain a wide field of view in the x-y axes with low beam angle in z in order to provide a detection area as large as possible. Design and implementation of the firmware, electronic hardware, mechanics and optics are covered in the paper. Possible future work would include characterisation with alternative designs of proximity sensors, as this is the component which determines the highest achievable accur1acy of the system.

  12. 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

  13. 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…

  14. Proximity correction for electron beam lithography

    NASA Astrophysics Data System (ADS)

    Marrian, Christie R.; Chang, Steven; Peckerar, Martin C.

    1996-09-01

    As the critical dimensions required in mask making and direct write by electron beam lithography become ever smaller, correction for proximity effects becomes increasingly important. Furthermore, the problem is beset by the fact that only a positive energy dose can be applied with an electron beam. We discuss techniques such as chopping and dose shifting, which have been proposed to meet the positivity requirement. An alternative approach is to treat proximity correction as an optimization problem. Two such methods, local area dose correction and optimization using a regularizer proportional to the informational entropy of the solution, are compared. A notable feature of the regularized proximity correction is the ability to correct for forward scattering by the generation of a 'firewall' set back from the edge of a feature. As the forward scattering width increases, the firewall is set back farther from the feature edge. The regularized optimization algorithm is computationally time consuming using conventional techniques. However, the algorithm lends itself to a microelectronics integrated circuit coprocessor implementation, which could perform the optimization faster than even the fastest work stations. Scaling the circuit to larger number of pixels is best approached with a hybrid serial/parallel digital architecture that would correct for proximity effects over 108 pixels in about 1 h. This time can be reduced by simply adding additional coprocessors.

  15. Proximity correction for e-beam lithography

    NASA Astrophysics Data System (ADS)

    Marrian, Christie R.; Chang, Steven; Peckerar, Martin C.

    1995-12-01

    As the critical dimensions required for masks and e-beam direct write become ever smaller, the correction of proximity effects becomes more necessary. Furthermore, the problem is beset by the fact that only a positive energy dose can be applied with the e-beam. We discuss here approaches such as chopping and dose shifting which have been proposed to meet the positivity requirement. An alternative approach is to treat proximity correction as an optimization problem. Two such methods, local area dose correction and optimization using a regularizer proportional to the informational entropy of the solution, are compared. A notable feature of the regularized proximity correction is the ability to correct for forward scattering by the generation of a 'firewall' set back from the edge of a feature. As the forward scattering width increases, the firewall is set back further from the feature edge. The regularized optimization algorithm is computationally time consuming using conventional techniques. However, the algorithm lends itself to a microelectronics integrated circuit coprocessor implementation which could perform the optimization much faster than even the fastest work stations. Scaling the circuit to larger number of pixels is best approached with a hybrid serial/parallel digital architecture which would correct for proximity effects over 108 pixels about one hour. This time can be reduced by simply adding additional coprocessors.

  16. Proximal Contact Repair of Complex Amalgam Restorations.

    PubMed

    Zguri, M N; Casey, J A; Jessup, J P; Vandewalle, K S

    2017-01-12

    The carving of a complex amalgam restoration may occasionally result in light proximal contact with the adjacent tooth. The purpose of this study was to investigate the strength of complex amalgam restorations repaired with a proximal slot amalgam preparation. Extracted human third molars of similar coronal size were sectioned 1 mm apical to the height of the contour using a saw and were randomly distributed into 9 groups of 10 teeth each. One pin was placed at each line angle of the flattened dentinal tooth surface. A metal matrix band was placed and an admixed alloy was condensed and carved to create a full crown contour but with a flat occlusal surface. A proximal slot was prepared with or without a retention groove and repaired using a single-composition spherical amalgam 15 minutes, 24 hours, one week, or six months after the initial crown condensation. The specimens were stored for 24 hours in 37°C water before fracture at the marginal ridge using a round-ended blade in a universal testing machine. The control group was not repaired. The mean maximum force in newtons and standard deviation were determined per group. Data were analyzed with a 2-way analysis of variance as well as Tukey and Dunnett tests (α=0.05). Significant differences were found between groups based on type of slot preparation (p=0.017) but not on time (p=0.327), with no significant interaction (p=0.152). No significant difference in the strength of the marginal ridge was found between any repair group and the unrepaired control group (p>0.076). The proximal repair strength of a complex amalgam restoration was not significantly different from an unrepaired amalgam crown. Placing a retention groove in the proximal slot preparation resulted in significantly greater fracture strength than a slot with no retention grooves. Time of repair had no significant effect on the strength of the repair.

  17. Characteristics of He II Proximity Profiles

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  18. Clinical Impact of Proximal Autosomal Imbalances

    PubMed Central

    Hamid, AB; Weise, A; Voigt, M; Bucksch, M; Kosyakova, N; Liehr, T; Klein, E

    2012-01-01

    Centromere-near gain of copy number can be induced by intra- or inter-chromosomal rearrangements or by the presence of a small supernumerary marker chromosome (sSMC). Interestingly, partial trisomy to hexasomy of euchromatic material may be present in clinically healthy or affected individuals, depending on origin and size of chromosomal material involved. Here we report the known minimal sizes of all centromere-near, i.e., proximal auto-somal regions in humans, which are tolerated; over 100 Mb of coding DNA are comprised in these regions. Additionally, we have summarized the typical symptoms for nine proximal autosomal regions including genes obviously sensitive to copy numbers. Overall, studying the carriers of specific chromosomal imbalances using genomics-based medicine, combined with single cell analysis can provide the genotype-phenotype correlations and can also give hints where copy-number-sensitive genes are located in the human genome. PMID:24052727

  19. 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

  20. Space robotic system for proximity operations

    NASA Technical Reports Server (NTRS)

    Magnani, P. G.; Colomba, M.

    1989-01-01

    Key to an efficient accomplishment of space station servicing operations is the development of a scenario where the presence of man in space is well integrated with the capability of teleoperated and automatic robot system outside the stations. Results focusing on mission requirements, trajectory sequences, propulsion subsystem features, and manipulative kit characteristics relevant to proximity servicing during a Man Tended Free Flyers Robotic Mission (MTFF-RM) are illustrated.

  1. Capacitive Proximity Sensor Has Longer Range

    NASA Technical Reports Server (NTRS)

    Vranish, John M.

    1992-01-01

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

  2. 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.

  3. 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.

  4. Endoscopic Proximal Hamstring Repair and Ischial Bursectomy

    PubMed Central

    Dierckman, Brian D.; Guanche, Carlos A.

    2012-01-01

    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

  5. Technical implications in proximal forearm transplantation.

    PubMed

    Haddock, Nicholas T; Chang, Benjamin; Bozentka, David J; Steinberg, David R; Levin, Lawrence Scott

    2013-12-01

    The field of vascularized composite allotransplantation has developed for more than a decade. Investigators are defining patient selection criteria, transplant indications, immunologic regimens, and tolerance. The majority of the current reported hand transplantations have been for treatment of distal forearm or hand amputations. In more proximal amputees, the functional outcome of the transplanted arm has some unique variables that require a different surgical approach. We present a single case of bilateral proximal forearm transplantation in effort to describe the unique technical considerations in this complex procedure. The surgical procedure is described in detail. At 19 months, our patient had 4/5 strength of finger and thumb flexors and protective extensor as well as 4/5 wrist flexors and extensors. Our patient had recovery of sensation. Our patient now lives independently and does her lower extremity prosthesis independently using her hands. These results are expected to continue to improve with more time. In hand transplantation, functional results have been very promising. The described approach of forearm transplantation allows the transfer of the entire functional unit, which should optimize the ultimate outcome for these more proximal injuries.

  6. 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.

  7. 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

  8. Proximity effect correction concerning forward scattering

    NASA Astrophysics Data System (ADS)

    Tsunoda, Dai; Shoji, Masahiro; Tsunoe, Hiroyuki

    2010-09-01

    The Proximity Effect is a critical problem in EB Lithography which is used in Photomask writing. Proximity Effect means that an electron shot by gun scatters by collided with resist molecule or substrate atom causes CD variation depending on pattern density [1]. Scattering by collision with resist molecule is called as "forward scattering", that affects in dozens of nanometer range, and with substrate atom is called as "backward scattering, that affects approximately 10 micrometer in 50keV acceleration voltage respectively. In conventional Proximity Effect Correction (PEC) for mask writing, we don't need to think forward scattering effect. However we should think about forward scattering because of smaller feature size. We have proposed a PEC software product named "PATACON PC-Cluster"[2], which can concern forward scattering and calculate optimum dose modulation. In this communication, we explain the PEC processing throughput when the that takes forward scattering into account. The key technique is to use different processing field size for forward scattering calculation. Additionally, the possibility is shown that effective PEC may be available by connecting forward scattering and backward scattering.

  9. Calibrating animal-borne proximity loggers.

    PubMed

    Rutz, Christian; Morrissey, Michael B; Burns, Zackory T; Burt, John; Otis, Brian; St Clair, James J H; James, Richard

    2015-06-01

    Growing interest in the structure and dynamics of animal social networks has stimulated efforts to develop automated tracking technologies that can reliably record encounters in free-ranging subjects. A particularly promising approach is the use of animal-attached 'proximity loggers', which collect data on the incidence, duration and proximity of spatial associations through inter-logger radio communication. While proximity logging is based on a straightforward physical principle - the attenuation of propagating radio waves with distance - calibrating systems for field deployment is challenging, since most study species roam across complex, heterogeneous environments.In this study, we calibrated a recently developed digital proximity-logging system ('Encounternet') for deployment on a wild population of New Caledonian crows Corvus moneduloides. Our principal objective was to establish a quantitative model that enables robust post hoc estimation of logger-to-logger (and, hence, crow-to-crow) distances from logger-recorded signal-strength values. To achieve an accurate description of the radio communication between crow-borne loggers, we conducted a calibration exercise that combines theoretical analyses, field experiments, statistical modelling, behavioural observations, and computer simulations.We show that, using signal-strength information only, it is possible to assign crow encounters reliably to predefined distance classes, enabling powerful analyses of social dynamics. For example, raw data sets from field-deployed loggers can be filtered at the analysis stage to include predominantly encounters where crows would have come to within a few metres of each other, and could therefore have socially learned new behaviours through direct observation. One of the main challenges for improving data classification further is the fact that crows - like most other study species - associate across a wide variety of habitats and behavioural contexts, with different signal

  10. 14 CFR 135.153 - Ground proximity warning system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  11. 14 CFR 135.153 - Ground proximity warning system.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  12. Proximity Labeling Reveals Molecular Determinants of FGFR4 Endosomal Transport.

    PubMed

    Haugsten, Ellen Margrethe; Sørensen, Vigdis; Kunova Bosakova, Michaela; de Souza, Gustavo Antonio; Krejci, Pavel; Wiedlocha, Antoni; Wesche, Jørgen

    2016-10-07

    The fibroblast growth factor receptors (FGFRs) are important oncogenes promoting tumor progression in many types of cancer, such as breast, bladder, and lung cancer as well as multiple myeloma and rhabdomyosarcoma. However, little is known about how these receptors are internalized and down-regulated in cells. We have here applied proximity biotin labeling to identify proteins involved in FGFR4 signaling and trafficking. For this purpose we fused a mutated biotin ligase, BirA*, to the C-terminal tail of FGFR4 (FGFR4-BirA*) and the fusion protein was stably expressed in U2OS cells. Upon addition of biotin to these cells, proteins in proximity to the FGFR4-BirA* fusion protein became biotinylated and could be isolated and identified by quantitative mass spectrometry. We identified in total 291 proteins, including 80 proteins that were enriched in samples where the receptor was activated by the ligand (FGF1), among them several proteins previously found to be involved in FGFR signaling (e.g., FRS2, PLCγ, RSK2 and NCK2). Interestingly, many of the identified proteins were implicated in endosomal transport, and by precise annotation we were able to trace the intracellular pathways of activated FGFR4. Validating the data by confocal and three-dimensional structured illumination microscopy analysis, we concluded that FGFR4 uses clathrin-mediated endocytosis for internalization and is further sorted from early endosomes to the recycling compartment and the trans-Golgi network. Depletion of cells for clathrin heavy chain led to accumulation of FGFR4 at the cell surface and increased levels of active FGFR4 and PLCγ, while AKT and ERK signaling was diminished, demonstrating that functional clathrin-mediated endocytosis is required for proper FGFR4 signaling. Thus, this study reveals proteins and pathways involved in FGFR4 transport and signaling that provide possible targets and opportunities for therapeutic intervention in FGFR4 aberrant cancer.

  13. Superconductivity in Magnetic and Proximity Effect Systems.

    NASA Astrophysics Data System (ADS)

    Stephan, Walter Hugo

    Some aspects of the theory of superconductors containing paramagnetic impurities in the model of Shiba and Rusinov (SR) are examined. The critical magnetic field deviation function is shown to be very sensitive to the SR scattering parameter varepsilon_0 , with improved agreement with experiment for Zn -Mn as compared to the theory of Abrikosov and Gor'Kov (AG). Optical absorption and thermal conductivity experiments involving a variety of transition metal alloys are reanalyzed including up to three scattering phase shifts, with no significant improvement found over the agreement obtained with only a single phase shift. The electromagnetic coherence length with SR impurities is also considered. Model calculations for superconducting spin-glasses show that systems such as Gd{_ {x}Ce}_{1-{rm x} }{rm Ru_2}, which exhibit significant deviations from the AG prediction for the reduction of the critical temperature with impurity concentration, are also expected to exhibit significant deviations from AG behavior for properties such as the thermodynamic critical field and the electromagnetic penetration depth. The model of Lee for reentrant ferromagnetic superconductors is shown to be only in qualitative agreement with the free energy difference and thermal conductivity determined experimentally for ErRh_{4}B _{4}. A variety of properties of proximity effect junctions are considered within the McMillan model. The temperature dependence of the free energy difference differs significantly from that of a BCS superconductor, with the deviation function becoming much more negative than the BCS prediction. The optical absorption and the low temperature magnetic penetration depth of the normal side of a proximity effect junction with magnetic impurities are also calculated. Finally, the temperature dependence of the zero bias tunneling conductance of a proximity effect induced superconducting spin glass is calculated and found to be in reasonable agreement with experiments

  14. 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

  15. Periprosthetic proximal femur fractures: current concepts.

    PubMed

    Parvizi, Javad; Vegari, David N

    2011-06-01

    With the increase in demand for total hip and knee arthroplasty, the orthopaedic community has seen a dramatic increase in periprosthetic fractures. Given the high morbidity and mortality associated with these fractures, the orthopaedic surgeon needs to be prepared to deal with this difficult problem. The purpose of this article is to provide the surgeon with an algorithmic approach that allows for easy classification and treatment options for periprosthetic fractures of the proximal femur. Such an approach should prevent the mismanagement of these complications.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Management of posttraumatic proximal interphalangeal joint contracture.

    PubMed

    Houshian, Shirzad; Jing, Shan Shan; Chikkamuniyappa, Chandrasekar; Kazemian, Gholam Hussein; Emami-Moghaddam-Tehrani, Mohammad

    2013-08-01

    Chronic flexion contracture of the proximal interphalangeal (PIP) joint presents a common yet challenging problem to hand surgeons. Over the years, multiple treatment modalities have been described for this problem, producing limited results. Nonoperative treatment using serial casting and splints should be tried before attempting open surgical release, which should be done in selected patients. The use of external fixation for treating PIP contracture has been encouraging and can be a useful alterative. This review provides an update on the current management of PIP joint contractures and presents a flowchart of treatment to aid decision making.

  1. Fiber optical ranging sensor for proximity fuse

    NASA Astrophysics Data System (ADS)

    Du, Fang; Chi, Zeying; You, Mingjun; Chen, Wenjian

    1996-09-01

    A fiber optical ranging sensor used in laser proximity fuze is described in this paper. In the fuze, pulse laser diode (LD) is used as light source and trigger signal is generated by comparing the reflected light pulses with the reference pulses by a correlator after they were converted into electric signals by PIN photodiodes. Multi-mode fibers and integrated optical devices are used in the system so that the structure can be more compact. Optical fiber delay line is used to offer precise delay time for reference channel.

  2. Open Subpectoral Tenodesis of the Proximal Biceps.

    PubMed

    Voss, Andreas; Cerciello, Simone; Yang, Justin; Beitzel, Knut; Cote, Mark P; Mazzocca, Augustus D

    2016-01-01

    This article summarizes both the various techniques for an open subpectoral biceps tenodesis as well as the biomechanics associated with these procedures. It provides information regarding the indications and contraindications to support the surgeon's decision. Furthermore, a postoperative protocol as well as an outcome overview is presented to address postoperative care. A short summary of the recent literature regarding potential complications is included to provide further insight on this technique. The open subpectoral tenodesis of the long head of the biceps is a safe and reproducible technique with a low complication rate for patients with pathologies of the proximal biceps.

  3. Complications of Proximal Biceps Tenotomy and Tenodesis.

    PubMed

    Virk, Mandeep S; Nicholson, Gregory P

    2016-01-01

    The long head of biceps tendon (LHBT) is a well-recognized cause of anterior shoulder pain. Tenotomy or tenodesis of the LHBT is an effective surgical solution for relieving pain arising from the LHBT. Cosmetic deformity of the arm, cramping or soreness in the biceps muscle, and strength deficits in elbow flexion and supination are the three most common adverse events associated with tenotomy of the LHBT. Complications associated with tenodesis of the LHBT include loss of fixation resulting in cosmetic deformity, residual groove pain, pain or soreness in the biceps muscle, infection, stiffness, hematoma, neurologic injury, vascular injury, proximal humerus fracture, and reflex sympathetic dystrophy.

  4. Space station proximity operations and window design

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

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

  5. The role of proximal-enhancer elements in the glucocorticoid regulation of carbamoylphosphate synthetase gene transcription from the upstream response unit.

    PubMed

    Schoneveld, Onard J L M; Gaemers, Ingrid C; Hoogenkamp, Maarten; Lamers, Wouter H

    2005-11-01

    As part of the urea cycle, carbamoylphosphate synthetase (CPS) converts toxic ammonia resulting from amino-acid catabolism into urea. Liver-specific and glucocorticoid-dependent expression of the gene involves a distal enhancer, a promoter-proximal enhancer, and the minimal promoter itself. When challenged with glucocorticoids, the glucocorticoid-responsive unit (GRU) in the distal enhancer of the carbamoylphosphate-synthetase gene can only activate gene expression if, in addition to the minimal promoter, the proximal enhancer is present. Here, we identify and characterise two elements in the proximal CPS enhancer that are involved in glucocorticoid-dependent gene activation mediated by the GRU. A purine-rich stretch forming a so-called GAGA-box and a glucocorticoid-response element (GRE) are both crucial for the efficacy of the GRU and appear to constitute a promoter-proximal response unit that activates the promoter. The glucocorticoid response of the CPS gene is, therefore, dependent on the combined action of a distal and a promoter-proximal response unit.

  6. 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.

  7. Phylogenetic proximity revealed by neurodevelopmental event timings.

    PubMed

    Nagarajan, Radhakrishnan; Clancy, Barbara

    2008-01-01

    Statistical properties such as distribution and correlation signatures were investigated using a temporal database of common neurodevelopmental events in the three species most frequently used in experimental studies, rat, mouse, and macaque. There was a fine nexus between phylogenetic proximity and empirically derived dates of the occurrences of 40 common events including the neurogenesis of cortical layers and outgrowth milestones of developing axonal projections. Exponential and power-law approximations to the distribution of the events reveal strikingly similar decay patterns in rats and mice when compared to macaques. Subsequent hierarchical clustering of the common event timings also captures phylogenetic proximity, an association further supported by multivariate linear regression data. These preliminary results suggest that statistical analyses of the timing of developmental milestones may offer a novel measure of phylogenetic classifications. This may have added pragmatic value in the specific support it offers for the reliability of rat/mouse comparative modeling, as well as in the broader implications for the potential of meta-analyses using databases assembled from the extensive empirical literature.

  8. Synostosis of the Proximal Tibiofibular Joint

    PubMed Central

    Sferopoulos, Nikolaos K.

    2010-01-01

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

  9. 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.

  10. Proteomics of Primary Cilia by Proximity Labeling

    PubMed Central

    Mick, David U.; Rodrigues, Rachel B.; Leib, Ryan D.; Adams, Christopher M.; Chien, Allis S.; Gygi, Steven P.; Nachury, Maxence V.

    2015-01-01

    SUMMARY While cilia are recognized as important signaling organelles, the extent of ciliary functions remains unknown because of difficulties in cataloguing proteins from mammalian primary cilia. We present a method that readily captures rapid snapshots of the ciliary proteome by selectively biotinylating ciliary proteins using a cilia-targeted proximity labeling enzyme (cilia-APEX). Besides identifying known ciliary proteins, cilia-APEX uncovered several ciliary signaling molecules. The kinases PKA, AMPK and LKB1 were validated as bona fide ciliary proteins and PKA was found to regulate Hedgehog signaling in primary cilia. Furthermore, proteomics profiling of Ift27/Bbs19 mutant cilia correctly detected BBSome accumulation inside Ift27−/− cilia and revealed that β-arrestin 2 and the viral receptor CAR are candidate cargoes of the BBSome. This work demonstrates that proximity labeling can be applied to proteomics of non-membrane-enclosed organelles and suggests that proteomics profiling of cilia will enable a rapid and powerful characterization of ciliopathies. PMID:26585297

  11. 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.

  12. Empathy: Its ultimate and proximate bases.

    PubMed

    Preston, Stephanie D; de Waal, Frans B M

    2002-02-01

    There is disagreement in the literature about the exact nature of the phenomenon of empathy. There are emotional, cognitive, and conditioning views, applying in varying degrees across species. An adequate description of the ultimate and proximate mechanism can integrate these views. Proximately, the perception of an object's state activates the subject's corresponding representations, which in turn activate somatic and autonomic responses. This mechanism supports basic behaviors (e.g., alarm, social facilitation, vicariousness of emotions, mother-infant responsiveness, and the modeling of competitors and predators) that are crucial for the reproductive success of animals living in groups. The Perception-Action Model (PAM), together with an understanding of how representations change with experience, can explain the major empirical effects in the literature (similarity, familiarity, past experience, explicit teaching, and salience). It can also predict a variety of empathy disorders. The interaction between the PAM and prefrontal functioning can also explain different levels of empathy across species and age groups. This view can advance our evolutionary understanding of empathy beyond inclusive fitness and reciprocal altruism and can explain different levels of empathy across individuals, species, stages of development, and situations.

  13. The convergence rate of the proximal alternating direction method of multipliers with indefinite proximal regularization.

    PubMed

    Sun, Min; Liu, Jing

    2017-01-01

    The proximal alternating direction method of multipliers (P-ADMM) is an efficient first-order method for solving the separable convex minimization problems. Recently, He et al. have further studied the P-ADMM and relaxed the proximal regularization matrix of its second subproblem to be indefinite. This is especially significant in practical applications since the indefinite proximal matrix can result in a larger step size for the corresponding subproblem and thus can often accelerate the overall convergence speed of the P-ADMM. In this paper, without the assumptions that the feasible set of the studied problem is bounded or the objective function's component [Formula: see text] of the studied problem is strongly convex, we prove the worst-case [Formula: see text] convergence rate in an ergodic sense of the P-ADMM with a general Glowinski relaxation factor [Formula: see text], which is a supplement of the previously known results in this area. Furthermore, some numerical results on compressive sensing are reported to illustrate the effectiveness of the P-ADMM with indefinite proximal regularization.

  14. Role of proximal tubules in the pathogenesis of kidney disease.

    PubMed

    Nakhoul, Nazih; Batuman, Vecihi

    2011-01-01

    The proximal tubules make up a significant portion of the kidneys; proximal tubule epithelial cells are the most populous cell type in the kidney, and carry out diverse regulatory and endocrine functions where numerous transporters are located. Under normal circumstances, more than two thirds of filtered salt and water, and all filtered bicarbonate is reabsorbed in the proximal tubule. A number of inherited and acquired acid-base and tubule disorders are linked to impaired transporters in the proximal tubule cells. Equally important is the intrinsic immune characteristics of proximal tubule cells that give them the ability to also function as immune responders to a wide range of immunologic, ischemic or toxic injury. It is therefore not surprising that proximal tubule-related phenomena are closely related to the pathogenesis of a vast array of kidney diseases. Many kidney diseases, acute and chronic, first manifest with proximal tubule disorders. Recent insight into molecular characteristics of transport functions in the proximal tubules, and the recognition that proximal tubule cells possess intrinsic immune responses have contributed to an improved understanding of important areas in nephrology, such as Fanconi's syndrome, renal tubular acidosis, phosphate wasting syndromes, Dent's disease, cystinuria and other amino acid transport disorders, acute kidney injury, and the role of proximal tubules in progressive kidney disease. Megalin/ cubilin-mediated endocytosis by proximal tubule cells of increased quantities of filtered proteins (protein overloading) in glomerular diseases appears to evoke cell stress responses resulting in increased inflammatory cytokines leading to tubulointerstitial inflammation and fibrosis. Finally, the proximal tubule may be the site of both active vitamin D synthesis through the action of 1-α-hydroxylase, and the site where erythropoietin synthesis takes place. Thus, proximal tubule injury also contributes to two distressing

  15. Proximity effects in ferromagnet-superconductor structures

    NASA Astrophysics Data System (ADS)

    Halterman, Klaus Byron

    I present an extensive theoretical investigation of the proximity effects that occur in ferromagnet/superconductor systems. I use a numerical method to solve self consistently the Bogoliubov-de Gennes equations in the continuum. I obtain the pair amplitude and the local density of states (DOS), and use these results to extract the relevant lengths characterizing both the leakage of superconductivity into the magnet and to study spin splitting induced in the superconductor. These phenomena are investigated as a function of parameters such as temperature, magnet polarization, interfacial scattering, sample size and Fermi wave vector mismatch, all of which turn out to have an important influence on the results. These comprehensive results should help characterize and analyze future data, and are shown to be in agreement with existing experiments.

  16. 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.

  17. 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.

  18. [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.

  19. Isosmotic volume reabsorption in rat proximal tubule

    PubMed Central

    1980-01-01

    A theoretical model incorporation both active and passive forces has been developed for fluid reabsorption from split oil droplets in rat intermediate and late proximal tubule. Of necessity, simplifying assumptions have been introduced; we have assumed that the epithelium can be treated as a single membrane and that the membrane "effective" HCO3 permeability is near zero. Based on this model with its underlying assumptions, the following conclusions are drawn. Regardless of the presence or absence of active NaCl transport, fluid reabsorption from the split oil droplet is isosmotic. The reabsorbate osmolarity can be affected by changes in tubular permeability parameters and applied forces but is not readily altered from an osmolarity essentially equal to that of plasma. In a split droplet, isosmotic flow need not be a special consequence of active Na transport, is not the result of a particular set of permeability properties, and is not merely a trivial consequence of a very high hydraulic conductivity; isosmotic flow can be obtained with hydraulic conductivity nearly an order of magnitude lower than that previously measured in the rat proximal convoluted tubule. Isosmotic reabsorption is, in part, the result of the interdependence of salt and water flows, their changing in parallel, and thus their ratio, the reabsorbate concentration being relatively invariant. Active NaCl transport can cause osmotic water flow by reducing the luminal fluid osmolarity. In the presence of passive forces the luminal fluid can be hypertonic to plasma, and active NaCl transport can still exert its osmotic effect on volume flow. There are two passive forces for volume flow: the Cl gradient and the difference in effective osmotic pressure; they have an approximately equivalent effect on volume flow. Experimentally, we have measured volume changes in a droplet made hyperosmotic by the addition of 50 mM NaCl; the experimental results are predicted reasonably well by our theoretical model

  20. Isosmotic volume reabsorption in rat proximal tubule.

    PubMed

    Warner, R R; Lechene, C

    1980-11-01

    A theoretical model incorporation both active and passive forces has been developed for fluid reabsorption from split oil droplets in rat intermediate and late proximal tubule. Of necessity, simplifying assumptions have been introduced; we have assumed that the epithelium can be treated as a single membrane and that the membrane "effective" HCO3 permeability is near zero. Based on this model with its underlying assumptions, the following conclusions are drawn. Regardless of the presence or absence of active NaCl transport, fluid reabsorption from the split oil droplet is isosmotic. The reabsorbate osmolarity can be affected by changes in tubular permeability parameters and applied forces but is not readily altered from an osmolarity essentially equal to that of plasma. In a split droplet, isosmotic flow need not be a special consequence of active Na transport, is not the result of a particular set of permeability properties, and is not merely a trivial consequence of a very high hydraulic conductivity; isosmotic flow can be obtained with hydraulic conductivity nearly an order of magnitude lower than that previously measured in the rat proximal convoluted tubule. Isosmotic reabsorption is, in part, the result of the interdependence of salt and water flows, their changing in parallel, and thus their ratio, the reabsorbate concentration being relatively invariant. Active NaCl transport can cause osmotic water flow by reducing the luminal fluid osmolarity. In the presence of passive forces the luminal fluid can be hypertonic to plasma, and active NaCl transport can still exert its osmotic effect on volume flow. There are two passive forces for volume flow: the Cl gradient and the difference in effective osmotic pressure; they have an approximately equivalent effect on volume flow. Experimentally, we have measured volume changes in a droplet made hyperosmotic by the addition of 50 mM NaCl; the experimental results are predicted reasonably well by our theoretical model.

  1. 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

  2. Health Promotion

    DTIC Science & Technology

    1986-03-11

    Department of Defense DIRECTIVEAD-A269 638 , , AD-A29 638March 11, 1986 IIIIii!IN 111111111,11 Ii1111,111111[NUMBER 1010.10 SUBJECT: Health Promotion ...34 March 13, 1985 INC A. URPOSE SThis Directive establishes a health promotion policy within the Department of Defense to improve and maintain military...civilian employees. C. DEFINITIONS 1. Health Promotion . Any combination of health education and related organizational, social, economic or health care

  3. 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

  4. Role of the Na+/H+ exchanger 3 in angiotensin II-induced hypertension

    PubMed Central

    Li, Xiao C.; Shull, Gary E.; Miguel-Qin, Elisa

    2015-01-01

    The renal mechanisms responsible for angiotensin II (ANG II)-induced hypertension remain incompletely understood. The present study tested the hypothesis that the Na+/H+ exchanger 3 (NHE3) is required for ANG II-induced hypertension in mice. Five groups of wild-type (Nhe3+/+) and Nhe3−/− mice were treated with vehicle or high pressor doses of ANG II (1.5 mg/kg/day ip, via minipump for 2 wk, or 10 pmol/min iv for 30 min). Under basal conditions, Nhe3−/− mice had significantly lower systolic blood pressure (SBP) and mean intra-arterial pressure (MAP) (P < 0.01), 24 h urine (P < 0.05), urinary Na+ (P < 0.01) and urinary K+ excretion (P < 0.01). In response to ANG II, SBP and MAP markedly increased in Nhe3+/+ mice in a time-dependent manner, as expected (P < 0.01). However, these acute and chronic pressor responses to ANG II were significantly attenuated in Nhe3−/− mice (P < 0.01). Losartan blocked ANG II-induced hypertension in Nhe3+/+ mice but induced marked mortality in Nhe3−/− mice. The attenuated pressor responses to ANG II in Nhe3−/− mice were associated with marked compensatory humoral and renal responses to genetic loss of intestinal and renal NHE3. These include elevated basal plasma ANG II and aldosterone and kidney ANG II levels, salt wasting from the intestines, increased renal AQP1, Na+/HCO3−, and Na+/K+-ATPase expression, and increased PKCα, mitogen-activated protein kinases ERK1/2, and glycogen synthase kinase 3αβ signaling proteins in the proximal tubules (P < 0.01). We concluded that NHE3 in proximal tubules of the kidney, along with NHE3 in intestines, is required for maintaining basal blood pressure as well as the full development of ANG II-induced hypertension. PMID:26242933

  5. 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

  6. Morphometry of Proximal Femur in Indian Population

    PubMed Central

    Joshi, Sheetal; Tuli, Anita; Raheja, Shashi; Jain, Priyanka; Srivastava, Priyanka

    2017-01-01

    Introduction Total hip arthroplasty is a commonly performed surgery now-a-day. There are regional and racial variations in the stature of the population worldwide. So there is always need of population specific data for making best fit prosthesis. Aim The present study was done to measure the parameters of proximal femur and to analyse their correlation by using standard statistical analysis. Materials and Methods Ninety one dry bones (44 left and 47 right) were used. Femur Head Diameter (FHD), Femur Neck Length (FNL), Femur Neck Diameter (FND), Femur Neck Thickness (FNT), Cervicodiaphyseal Angle (CDA) was directly measured with the help of anthropometric instruments. Femur Head Offset (FHO) and Vertical Offset (VO) were measured in the anteroposterior digital photographs. Results Normally distributed variables were compared using Student’s t-test (Unpaired data) to analyse significant effect. There was a significant difference between right and left side of FND and CDA. Pearson correlation coefficient was used to analyse the relationship among variables. FHO had high correlation with the VO (0.687, p<0.001). Conclusion These parameters can be used for designing the prosthesis and plates for hip joint reconstructive surgeries suitable for Indian population. PMID:28384844

  7. 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.

  8. Proximal Row Carpectomy Combined with Wrist Hemiarthroplasty

    PubMed Central

    Culp, Randall W.; Bachoura, Abdo; Gelman, Scott E.; Jacoby, Sidney M.

    2012-01-01

    Proximal row carpectomy (PRC) combined with distal radius hemiarthroplasty is a relatively novel procedure that rivals total wrist arthrodesis and offers a new surgical treatment option for select patients with painful, end-stage wrist disease. We present our early experience with this procedure. A retrospective chart review was conducted for nonrheumatoid patients diagnosed with wrist arthritis and subsequently treated with wrist hemiarthroplasty combined with PRC. The minimum follow-up duration was 12 months. Preoperative and postoperative flexion, extension, and grip strength were recorded. Postoperative radiographic findings were assessed. The Patient-Rated Wrist Evaluation (PRWE) questionnaire was administered to gauge postoperative pain and function. The records of 10 patients were reviewed. The mean age was 64 years and the mean postoperative follow-up duration was 19 months. Postoperative flexion, extension, and grip strength were all found to be less than the preoperative levels. The mean postoperative PRWE score for pain and function were 26 and 23, respectively. The complications were diverse and occurred at a relatively high rate. PRC combined with distal radius hemiarthroplasty is a novel procedure that offers a potential surgical option for the treatment of wrist arthritis in select patients. Our early experience has lead us to modify our technique with regard to the implant material, and at this stage, the surgical technique and the most appropriate implant may require further optimization. The level of evidence for this study is IV (therapeutic). PMID:23904978

  9. Distal radius fracture after proximal row carpectomy

    PubMed Central

    Igeta, Yuka; Naito, Kiyohito; Sugiyama, Yoichi; Obata, Hiroyuki; Aritomi, Kentaro; Kaneko, Kazuo; Obayashi, Osamu

    2015-01-01

    Introduction We encountered a patient with distal radius fracture (DRF) after proximal row carpectomy (PRC). The mechanism of the DRF after PRC is discussed in this report. Presentation of case The patient was a 73-year-old female who had undergone PRC due to Kienböck disease before. The wrist range of motion was: 45° on dorsiflexion and 20° on flexion. DRF has occurred at 3 years after PRC. The fracture type was extra-articular fracture. Osteosynthesis was performed using a volar locking plate. No postoperative complication developed, the Mayo score was excellent at 6 months after surgery, and the daily living activity level recovered to that before injury. Discussion Since the wrist range of motion decreased and the lunate fitted into the joint surface after PRC, making the forearm join with the hand like a single structure, pressure may have been loaded on the weak distal end of the radius from the dorsal side, causing volar displacement and fracture. Conclusion The pressure distribution and range of motion of the radiocarpal joint after PRC are different from those of a normal joint, and the mechanism of fracture also changes due to PRC. PMID:25623755

  10. 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.

  11. 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.

  12. Effective proximity retrieval by ordering permutations.

    PubMed

    Chavez, Edgar; Figueroa, Karina; Navarro, Gonzalo

    2008-09-01

    We introduce a new probabilistic proximity search algorithm for range and K-nearest neighbor (K-NN) searching in both coordinate and metric spaces. Although there exist solutions for these problems, they boil down to a linear scan when the space is intrinsically high-dimensional, as is the case in many pattern recognition tasks. This, for example, renders the K-NN approach to classification rather slow in large databases. Our novel idea is to predict closeness between elements according to how they order their distances towards a distinguished set of anchor objects. Each element in the space sorts the anchor objects from closest to farthest to it, and the similarity between orders turns out to be an excellent predictor of the closeness between the corresponding elements. We present extensive experiments comparing our method against state-of-the-art exact and approximate techniques, both in synthetic and real, metric and non-metric databases, measuring both CPU time and distance computations. The experiments demonstrate that our technique almost always improves upon the performance of alternative techniques, in some cases by a wide margin.

  13. 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.

  14. 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.

  15. Proximity effects in cold atom artificial graphene

    NASA Astrophysics Data System (ADS)

    Graß, Tobias; Chhajlany, Ravindra W.; Tarruell, Leticia; Pellegrini, Vittorio; Lewenstein, Maciej

    2017-03-01

    Cold atoms in an optical lattice with brick-wall geometry have been used to mimic graphene, a two-dimensional material with characteristic Dirac excitations. Here we propose to bring such artificial graphene into the proximity of a second atomic layer with a square lattice geometry. For non-interacting fermions, we find that such bilayer system undergoes a phase transition from a graphene-like semi-metal phase, characterized by a band structure with Dirac points, to a gapped band insulator phase. In the presence of attractive interactions between fermions with pseudospin-1/2 degree of freedom, a competition between semi-metal and superfluid behavior is found at the mean-field level. Using the quantum Monte Carlo method, we also investigate the case of strong repulsive interactions. In the Mott phase, each layer exhibits a different amount of long-range magnetic order. Upon coupling both layers, a valence-bond crystal is formed at a critical coupling strength. Finally, we discuss how these bilayer systems could be realized in existing cold atom experiments.

  16. 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.

  17. 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.

  18. The Proximal Tubule and Albuminuria: Really!

    PubMed Central

    Dickson, Landon E.; Wagner, Mark C.; Sandoval, Ruben M.

    2014-01-01

    Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative techniques and approaches have provided exciting insights into these processes, and numerous investigators have shown that selective PT cell defects lead to significant albuminuria, even reaching nephrotic range in animal models. Thus, the mechanisms of albumin reabsorption and transcytosis are undergoing intense study. Working in concert with megalin and cubilin, a nonselective multireceptor complex that predominantly directs proteins for lysosomal degradation, the neonatal Fc receptor (FcRn) located at the brush border of the apical membrane has been implicated as the “receptor” mediating albumin transcytosis. The FcRn pathway facilitates reabsorption and mediates transcytosis by its pH-dependent binding affinity in endosomal compartments. This also allows for selective albumin sorting within the PT cell. This reclamation pathway minimizes urinary losses and catabolism of albumin, thus prolonging its serum half-life. It may also serve as a molecular sorter to preserve and reclaim normal albumin while allowing “altered” albumin to be catabolized via lysosomal pathways. Here, we critically review the data supporting this novel mechanism. PMID:24408874

  19. Topological defect-phase soliton and the pairing symmetry of a two-band superconductor: role of the proximity effect.

    PubMed

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

    2012-11-30

    We suggest a mechanism which promotes the existence of a phase soliton--a 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 an effect can be used to reduce the 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 for both stable and metastable solitons, which can be used to distinguish between ss(+-) and s(++) types of pairing in the iron-based multiband superconductors.

  20. Health Promotion

    PubMed Central

    Wilson, Ron

    1992-01-01

    How physicians address issues of disease prevention and health promotion is discussed and current standards of screening for disease and counseling practices are reviewed. Collaboration among all health professionals is necessary if preventive medicine is to be effective. PMID:21221259

  1. 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.

  2. Wrist level and proximal-upper extremity replantation.

    PubMed

    Hanel, Douglas P; Chin, Simon H

    2007-02-01

    Since Malt and McKhan's first successful arm replantation in 1962, upper extremity replantation surgery techniques have been refined and spread worldwide. Nevertheless, replantation at or proximal to the wrist, referred to as wrist-proximal replants, remains a daunting challenge that presents the hand surgeon with an array of difficulties distinct from digital replantation.

  3. Proximal and distal muscle fatigue differentially affect movement coordination

    PubMed Central

    Cowley, Jeffrey C.

    2017-01-01

    Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor) or distal (finger flexor) muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p < 0.005) in trunk lean and velocity, reduced humeral elevation (11°, p < 0.005), and increased elbow flexion (4°, p < 0.01). In contrast, distal fatigue caused small but significant changes in trunk angles (2°, p < 0.05), increased velocity of wrench movement relative to the hand (17°/s, p < 0.001), and earlier wrist extension (4%, p < 0.005). Movement variability increased at proximal joints but not distal joints after both fatigue protocols (p < 0.05). Varying movements at proximal joints may help people adapt to fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks. PMID:28235005

  4. Comparative studies for different proximity potentials applied to α decay

    NASA Astrophysics Data System (ADS)

    Yao, Y. J.; Zhang, G. L.; Qu, W. W.; Qian, J. Q.

    2015-09-01

    Half-lives of α decay of even-even nuclei calculated by using fourteen different versions of proximity potentials are compared to experimental data. The results show that the results of the generalized proximity potential 1977 are very much in agreement with the experimental data. In comparison with the distributions of nuclear potentials at small distances and the distributions of total potentials above the released energy Q α , it is found that at small distances the distributions of nuclear potentials have large difference and the distributions of total potentials are different among the listed proximity potentials. The different potential distributions affect the penetration probability of α, which is related to the half-life of the α decay for each nucleus. The generalized proximity potential 1977 is also used to calculate the half-lives of α decay of nuclei with odd mass numbers. The results show that the generalized proximity potential 1977 can calculate the half-lives of the α decay of almost all nuclei, which underlines and supports the use of the generalized proximity potential 1977 by Santhosh et al. in the Coulomb and proximity potential model (CPPM) and the Coulomb and proximity potential model for deformed nuclei (CPPMDN).

  5. Menin and JunD regulate gastrin gene expression through proximal DNA elements.

    PubMed

    Mensah-Osman, Edith J; Veniaminova, Natalia A; Merchant, Juanita L

    2011-11-01

    Mutations in the MEN1 gene correlate with multiple endocrine neoplasia I (MEN1). Gastrinomas are the most malignant of the neuroendocrine tumors associated with MEN1. Because menin and JunD proteins interact, we examined whether JunD binds to and regulates the gastrin gene promoter. Both menin and JunD are ubiquitous nuclear proteins that we showed colocalize in the gastrin-expressing G cells of the mouse antrum. Transfection with a JunD expression vector alone induced endogenous gastrin mRNA in AGS human gastric cells, and the induction was blocked by menin overexpression. We mapped repression by menin to both a nonconsensus AP-1 site and proximal GC-rich elements within the human gastrin promoter. Chromatin immunoprecipitation assays, EMSAs, and DNA affinity precipitation assays documented that JunD and Sp1 proteins bind these two elements and are both targets for menin regulation. Consistent with menin forming a complex with histone deacetylases, we found that repression of gastrin gene expression by menin was reversed by trichostatin A. In conclusion, proximal DNA elements within the human gastrin gene promoter mediate interactions between JunD, which induces gastrin gene expression and menin, which suppresses JunD-mediated activation.

  6. Hypospadias and Residential Proximity to Pesticide Applications

    PubMed Central

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

    2013-01-01

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

  7. 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.

  8. 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.

  9. Proximal humeral reconstruction using nail cement spacer in primary and metastatic tumours of proximal humerus.

    PubMed

    Kundu, Zile Singh; Gogna, Paritosh; Gupta, Vinay; Kamboj, Pradeep; Singla, Rohit; Sangwan, Sukhbir Singh

    2013-11-01

    Limb salvage surgery for malignant tumours of proximal humerus is an operative challenge, where the surgeon has to preserve elbow and hand functions and retain shoulder stability with as much function as possible. We treated 14 consecutive patients with primary malignant or isolated metastasis of proximal humerus with surgical resection and reconstruction by nail cement spacer. There were 8 females and 6 males, with a mean age of 28.92 years (range 16-51 years) and a mean follow-up of 30.14 months (range 12-52 months). The diagnosis was osteosarcoma in 8 patients, chondrosarcoma in 4 patients and metastasis from thyroid and breast carcinoma in 1 patient each. One of our patients had radial nerve neuropraxia, 1 developed inferior subluxation and 3 developed distant metastasis. Two patients died of disease and one developed local recurrence leading to forequarter amputation, leaving a total of 11 patients with functional extremities for assessment at the time of final follow-up which was done using the Musculoskeletal Tumour Society (MSTS) score. Though we were able to preserve the elbow, wrist and hand functions in all patients, the abductor mechanism, deltoid muscle and axillary nerve were not salvageable in any of cases. The mean MSTS score at the time of final follow-up was 19.09. Thus, proximal humeral reconstruction using nail cement spacer is a technical simple, cost-effective and reproducible procedure which makes it a reliable option in subset of patients where the functions around the shoulder cannot be preserved despite costlier prosthesis.

  10. 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.

  11. Modeling tunneling for the unconventional superconducting proximity effect

    NASA Astrophysics Data System (ADS)

    Zareapour, Parisa; Xu, Jianwei; Zhao, Shu Yang F.; Jain, Achint; Xu, Zhijun; Liu, T. S.; Gu, G. D.; Burch, Kenneth S.

    2016-12-01

    Recently there has been reinvigorated interest in the superconducting proximity effect, driven by predictions of the emergence of Majorana fermions. To help guide this search, we have developed a phenomenological model for the tunneling spectra in anisotropic superconductor-normal metal proximity devices. We combine successful approaches used in s-wave proximity and standard d-wave tunneling to reproduce tunneling spectra in d-wave proximity devices, and clarify the origin of various features. Different variations of the pair potential are considered, resulting from the proximity-induced superconductivity. Furthermore, the effective pair potential felt by the quasiparticles is momentum-dependent in contrast to s-wave superconductors. The probabilities of reflection and transmission are calculated by solving the Bogoliubov equations. Our results are consistent with experimental observations of the unconventional proximity effect and provide important experimental parameters such as the size and length scale of the proximity induced gap, as well as the conditions needed to observe the reduced and full superconducting gaps.

  12. Health Promotion

    PubMed Central

    Karmali-Rawji, Shameela; Kassim-Lakha, Shaheen; Taylor, Karmel

    1992-01-01

    Perceived lack or loss of control, stress, a rapidly again population and rising costs of health care necessitate effective health promotion and disease prevention in the elderly. In a collaborative health promotion effort, the private sector, public sector, and community partners have joined to increase the South Asian elders' sense of control over the decisions and circumstances that affect their everyday lives. The project was designed to help elders come to terms with the fragmentation of their extended families, cultural alienation, decreased autonomy, need for information, and greater risk of cardiovascular disease. Imagesp622-a

  13. Non-Melanoma-Associated Dyschromia of the Proximal Nail Fold

    PubMed Central

    Cohen, Philip R

    2016-01-01

    Subungual melanoma with pigmentation beneath the nail that extends to involve the proximal nail fold is referred to as Hutchinson’s sign. Black or brown subungual discoloration involving the proximal nail fold secondary to other etiologies has been referred to as pseudo-Hutchinson’s sign. Three patients with nail discoloration and concurrent dyschromia of the proximal nail fold are described: a female with a chronic subungual hematoma and pseudo-Hutchinson’s sign, a male with culture-confirmed Pseudomonas aeruginosa (P. aeruginosa) of the nail with green discoloration involving the proximal nail fold, and a male with an acute subungual hematoma with red-purple subungual discoloration affecting the proximal nail fold. PubMed was searched for the following: black, brown, chloronychia, discoloration, dyschromia, green, hematoma, Hutchinson’s sign, nail, nail fold, proximal, pseudo-Hutchinson’s sign, red, subungual melanoma, syndrome. The papers were reviewed and appropriate references evaluated. In conclusion, melanoma-associated black proximal nail fold pigmentation is referred to as Hutchinson’s sign, and non-melanoma-associated black pigmentation has been designated as pseudo-Hutchinson’s sign. Subungual nail plate discoloration extending to involve the proximal nail fold may be black, green, or red-purple in patients with melanocytic and non-melanocytic lesions, bacterial infection (Pseudomonas), and acute subungual hematoma, respectively. Instead of creating a new terminology, we suggest that non-black subungual discoloration (green or red-purple) extending to involve the proximal nail fold be referred to as pseudo pseudo-Hutchinson’s sign. PMID:28090415

  14. Axillary artery injury as a complication of proximal humerus fractures.

    PubMed

    McLaughlin, J A; Light, R; Lustrin, I

    1998-01-01

    Proximal humerus fractures are common injuries and represent approximately 5% of all fractures. These fractures are infrequently associated with neurovascular injuries. Brachial plexus injuries are uncommon, whereas axillary artery injuries are rare. A review of 19 previously reported cases of axillary artery injury after proximal humerus fracture revealed that 84% occurred in patients older than 50 years, 53% were associated with brachial plexus injury, and 21% resulted in upper extremity amputation. This study describes a case of axillary artery injury after proximal humerus fracture and, on the basis of a literature review, offers suggestions for the early diagnosis and effective treatment of this uncommon injury.

  15. 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.

  16. 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.

  17. An unusual case of glipizide-induced proximal myopathy

    PubMed Central

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

    2016-01-01

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

  18. 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

  19. 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

  20. Abnormalities of proximal femoral growth after severe Perthes' disease.

    PubMed

    Sponseller, P D; Desai, S S; Millis, M B

    1989-08-01

    We studied the pattern of proximal femoral growth after severe Perthes' disease (Catterall grade III or IV) by retrospective analysis of serial radiographs in 52 hips (46 patients). Our aim was to determine the relationship between proximal femoral growth abnormalities and metaphyseal cysts, epiphyseal extrusion, physeal narrowing, and extensive epiphyseal necrosis. The average follow-up after treatment was 9.8 years (range 4 to 16 years), and 37 of the hips were followed to skeletal maturity. Slowing of proximal femoral growth was common: symmetrical abnormality was seen in 26 hips and asymmetrical abnormality in nine. However, definite premature closure of the proximal femoral physis was seen in only three hips. Abnormality seemed to be due to altered growth velocity rather than to bar formation in most cases. Metaphyseal cysts, epiphyseal extrusion and physeal narrowing during the active stage of the disease, alone or in combination, were found to be neither sensitive nor specific predictors of the subsequent growth pattern.

  1. Differential permeability of the proximal and distal rabbit small bowel

    PubMed Central

    Ross, Allan; Rubin, Allen W.; Deren, Julius J.

    1972-01-01

    The permeability of the proximal and distal rabbit intestine for two to six carbon polyhydric alcohols was compared. Intestinal segments were mounted in chambers that permitted the measurement of the unidirectional flux across the brush border membrane. For both proximal and distal intestine, the permeability for a series of polyhydric alcohols decreased with increasing size. The proximal intestine was more permeable for four, five, and six carbon polyhydric alcohols than distal intestine. This regional permeability difference can be attributed to variations in the permeability characteristics of the brush border specifically. The uptake of alcohols was nonsaturable and was not inhibited by phlorizine or n-ethylmaleimide. The results are compatible with the concept that the brush border membrane has properties similar to artificial porous membranes and that the equivalent radius of the pores of the proximal intestine exceeds that of the distal gut. PMID:4639025

  2. 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.

  3. Post-traumatic osteonecrosis of the proximal humerus.

    PubMed

    Patel, Shelain; Colaco, Henry B; Elvey, Michael E; Lee, Marcus H

    2015-10-01

    Post-traumatic osteonecrosis of the proximal humerus represents a challenging problem to the surgeon. It is commonly seen following multi-fragmentary fractures of the proximal humerus which may affect the long-term functional recovery after such injuries. This review summarises the current evidence on risk factors, reasons why estimating its epidemiology is difficult, the vascular supply of the humeral head, classification, and management options.

  4. [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.

  5. Hemiarthroplasty for proximal humeral fracture: restoration of the Gothic arch.

    PubMed

    Krishnan, Sumant G; Bennion, Phillip W; Reineck, John R; Burkhead, Wayne Z

    2008-10-01

    Proximal humerus fractures are the most common fractures of the shoulder girdle, and initial management of these injuries often determines final outcome. When arthroplasty is used to manage proximal humeral fractures, surgery remains technically demanding, and outcomes have been unpredictable. Recent advances in both technique and prosthetic implants have led to more successful and reproducible results. Key technical points include restoration of the Gothic arch, anatomic tuberosity reconstruction, and minimal soft tissue dissection.

  6. 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.

  7. 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.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2012-12-01

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

  10. 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.

  11. RADIOGRAPHIC ASSESSMENT OF THE OPENING WEDGE PROXIMAL TIBIAL OSTEOTOMY

    PubMed Central

    Silva, Carlos Francisco Bittencourt; Camara, Eduardo Kastrup Bittencourt; Vieira, Luiz Antonio; Adolphsson, Fernando; Rodarte, Rodrigo Ribeiro Pinho

    2015-01-01

    Objective: To radiographically evaluate individuals who underwent opening wedge proximal tibial osteotomy, with the aim of analyzing the proximal tibial slope in the frontal and sagittal planes, and the patellar height. Method: The study included 22 individuals who were operated at the National Traumatology and Orthopedics Institute (INTO) for correction of varus angular tibial deviation using the opening wedge osteotomy (OWO) technique with the Orthofix monolateral external fixator. Patients with OWO whose treatment was completed between January 2000 and December 2006 were analyzed. The measurement technique consisted of using anteroposterior radiographs with loading and lateral views with the operated knees flexed at 30°. Results: There were no statistically significant differences between the pre and postoperative tibial slope and patellar height values in the patients evaluated. Conclusion: Opening wedge proximal tibial osteotomy is a technique that avoids the problems presented by high proximal tibial osteotomy, since it is done without causing changes to the extensor mechanism, ligament imbalance or distortions in the proximal tibia. PMID:27022577

  12. Developmental Changes in Proximal Tubule Tight Junction Proteins

    PubMed Central

    HADDAD, MAHA; LIN, FANGMING; DWARAKANATH, VANGIPURAM; CORDES, KIMBERLY; BAUM, MICHEL

    2014-01-01

    We demonstrated previously that neonatal proximal tubules have a lower passive paracellular permeability to chloride ions and higher resistance than that of adult proximal tubules. In addition, administration of thyroid hormone to neonates, before the normal maturational increase in serum thyroid hormone levels, prematurely accelerates the developmental increase in chloride permeability to adult levels. To test the hypothesis that there is a maturational change in tight junction proteins and that thyroid hormone mediates these changes, we examined the two known tight junction proteins present in proximal tubules, occludin and claudin 2. Using immunoblot and immunohistochemistry, we demonstrated that claudin 2 has a 4-fold greater abundance in neonatal proximal tubules than in adult tubules. Occludin, however, has a 4-fold greater expression in adult tubules than in neonatal tubules. Administration of thyroid hormone to neonates did not affect claudin 2 expression, occludin expression, or the transepithelial resistance in rat proximal tubule cells in vitro. In conclusion, there are postnatal maturational changes in tight junction proteins. The factors that cause these maturational changes are unknown but unlikely to be due solely to the maturational increase in thyroid hormone. PMID:15585672

  13. Intramedullary Nailing for Pathological Fractures of the Proximal Humerus

    PubMed Central

    Choi, Eun-Seok; Han, Ilkyu; Cho, Hwan Seong; Park, In Woong; Park, Jong Woong

    2016-01-01

    Background Endoprosthetic reconstruction is widely applied for pathological fractures of the proximal humerus; however, functional impairment is usually unsatisfactory. The aims of the current study are to evaluate the reliability of interlocking intramedullary (IM) nailing with cement augmentation as a fixation method in proximal humeral lesions and to assess functional outcomes. Methods We reviewed 32 patients with pathological fractures of the proximal humerus who underwent interlocking IM nailing and cement augmentation. Functional scores and pain relief were assessed as outcomes. Results The mean follow-up period was 14.2 months. The mean Musculoskeletal Tumor Society functional score and Karnofsky performance status scale score were 27.7 and 75.6, respectively. Improvement of pain assessed using the visual analogue scale was 6.2 on average. Thirty-one patients (97%) experienced no pain after surgery. The mean ranges of forward flexion and abduction were 115° and 112.6°, respectively. All patients achieved stability and had no local recurrence without failure of fixation until the last follow-up. Conclusions Proximal interlocking IM nailing with cement augmentation appears to be a reliable treatment option for pathological or impending fractures of the proximal humerus in selected patients with metastatic tumors, even with extensive bone destruction. PMID:27904730

  14. Fluoroscopically Guided Peritendinous Corticosteroid Injection for Proximal Hamstring Tendinopathy

    PubMed Central

    Nicholson, Luke T.; DiSegna, Steven; Newman, Joel S.; Miller, Suzanne L.

    2014-01-01

    Background: Proximal hamstring tendinopathy is an uncommon but debilitating cause of posterior thigh pain in athletes subjected to repetitive eccentric hamstring contraction, such as runners. Minimal data exist evaluating treatment options for proximal hamstring tendinopathy. Purpose: This retrospective study evaluates the effectiveness of fluoroscopically guided corticosteroid injections in treating proximal hamstring tendinopathy. Study Design: Case series; Level of evidence, 4. Methods: Eighteen athletes with 22 cases of magnetic resonance imaging–confirmed proximal hamstring tendinopathy were treated with corticosteroid injection and later contacted to evaluate the efficacy of the injection with the use of a questionnaire. Results: The visual analog score decreased from 7.22 preinjection to 3.94 postinjection (P < .001), level of athletic participation increased from 28.76% to 68.82% (P < .001) at a mean follow-up of 21 months, and 38.8% of patients experienced complete resolution at a mean follow-up of 24.8 months. The mean lower extremity function score at the time of follow-up was 60. Conclusion: A trial of fluoroscopically guided corticosteroid injection is warranted in patients presenting with symptoms of proximal hamstring tendinopathy refractory to conservative therapy. PMID:26535310

  15. A biomechanical comparison of proximal femoral nails and locking proximal anatomic femoral plates in femoral fracture fixation

    PubMed Central

    Ozkan, Korhan; Türkmen, İsmail; Sahin, Adem; Yildiz, Yavuz; Erturk, Selim; Soylemez, Mehmet Salih

    2015-01-01

    Background: The incidence of fractures in the trochanteric area has risen with the increasing numbers of elderly people with osteoporosis. Although dynamic hip screw fixation is the gold standard for the treatment of stable intertrochanteric femur fractures, treatment of unstable intertrochanteric femur fractures still remains controversial. Intramedullary devices such as Gamma nail or proximal femoral nail and proximal anatomic femur plates are in use for the treatment of intertrochanteric femur fractures. There are still many investigations to find the optimal implant to treat these fractures with minimum complications. For this reason, we aimed to perform a biomechanical comparison of the proximal femoral nail and the locking proximal anatomic femoral plate in the treatment of unstable intertrochanteric fractures. Materials and Methods: Twenty synthetic, third generation human femur models, obtained for this purpose, were divided into two groups of 10 bones each. Femurs were provided as a standard representation of AO/Orthopedic Trauma Associationtype 31-A2 unstable fractures. Two types of implantations were inserted: the proximal femoral intramedullary nail in the first group and the locking anatomic femoral plate in the second group. Axial load was applied to the fracture models through the femoral head using a material testing machine, and the biomechanical properties of the implant types were compared. Result: Nail and plate models were locked distally at the same level. Axial steady load with a 5 mm/m velocity was applied through the mechanical axis of femur bone models. Axial loading in the proximal femoral intramedullary nail group was 1.78-fold greater compared to the plate group. All bones that had the plate applied were fractured in the portion containing the distal locking screw. Conclusion: The proximal femoral intramedullary nail provides more stability and allows for earlier weight bearing than the locking plate when used for the treatment of

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. VCSEL-based microsensors for photonic proximity fuzing of munitions

    NASA Astrophysics Data System (ADS)

    Keeler, G. A.; Mar, A.; Geib, K. M.; Hsu, A. Y.; Serkland, D. K.; Peake, G. M.

    2008-08-01

    This paper describes technologies developed at Sandia National Laboratories to support a joint DoD/DoE initiative to create a compact, robust, and affordable photonic proximity sensor for munitions fuzing. The proximity fuze employs high-power vertical-cavity surface-emitting laser (VCSEL) arrays, resonant-cavity photodetectors (RCPDs), and refractive micro-optics that are integrated within a microsensor whose volume is approximately 0.01 cm3. Successful development and integration of these custom photonic components should enable a g-hard photonic proximity fuze that replaces costly assemblies of discrete lasers, photodetectors, and bulk optics. Additional applications of this technology include void sensing, ladar and short-range 3-D imaging.

  1. Modular endoprosthetic replacement for metastatic tumours of the proximal femur

    PubMed Central

    Chandrasekar, Coonoor R; Grimer, Robert J; Carter, Simon R; Tillman, Roger M; Abudu, Adesegun T

    2008-01-01

    Background and aims Endoprosthetic replacements of the proximal femur are commonly required to treat destructive metastases with either impending or actual pathological fractures at this site. Modular prostheses provide an off the shelf availability and can be adapted to most reconstructive situations for proximal femoral replacements. The aim of this study was to assess the clinical and functional outcomes following modular tumour prosthesis reconstruction of the proximal femur in 100 consecutive patients with metastatic tumours and to compare them with the published results of patients with modular and custom made endoprosthetic replacements. Methods 100 consecutive patients who underwent modular tumour prosthetic reconstruction of the proximal femur for metastases using the METS system from 2001 to 2007 were studied. The patient, tumour and treatment factors in relation to overall survival, local control, implant survival and complications were analysed. Functional scores were obtained from surviving patients. Results and conclusion There were 45 male and 55 female patients. The mean age was 60.2 years. The indications were metastases. Seventy five patients presented with pathological fracture or with failed fixation and 25 patients were at a high risk of developing a fracture. The mean follow up was 15.9 months [range 0–77]. Three patients died within 2 weeks following surgery. 69 patients have died and 31 are alive. Of the 69 patients who were dead 68 did not need revision surgery indicating that the implant provided single definitive treatment which outlived the patient. There were three dislocations (2/5 with THR and 1/95 with unipolar femoral heads). 6 patients had deep infections. The estimated five year implant survival (Kaplan-Meier analysis) was 83.1% with revision as end point. The mean TESS score was 64% (54%–82%). We conclude that METS modular tumour prosthesis for proximal femur provides versatility; low implant related complications and

  2. 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).

  3. Expression of Arabidopsis LINEs from two promoters.

    PubMed

    Ohta, Yoshizu; Noma, Kenichi; Tsuchimoto, Suguru; Ohtsubo, Eiichi; Ohtsubo, Hisako

    2002-12-01

    Most Arabidopsis long interspersed elements (LINEs, called ATLNs) have two open reading frames, orf1 and orf2. In the 5' untranslated regions (UTRs) located upstream of orf1, the most proximal segments of tens of base pairs long are not homologous even in two ATLN members with almost identical sequences. In this study, we first show that RT-PCR products from ATLN39, a member of ATLN, can be detected only in total RNA from the hypomethylation mutant ddm1 or from suspension-cultured cells treated with a DNA methylation inhibitor 5-azacytidine, indicating that the expression of ATLN39 is negatively regulated by DNA methylation. We then show that orf1 fused in frame with the luciferase (luc) gene is expressed in suspension-cultured cells of A. thaliana when the 5' UTR is present in the region upstream of orf1. Analysis of deletion in the 5' UTR revealed that the 5' UTR has two promoters, designated here as P1 and P2. Analysis of transcripts by 5' RACE showed that their 5' ends were located at sites immediately upstream of the P1 region or at sites downstream of the P2 region. This observation and the fact that the P1 region contains no TATA sequence indicate that P1 is an internal promoter that initiates transcription from sites upstream of the promoter. A sequence containing GGCGA with a CpG methylatable site is conserved in the P1 regions in members closely related to ATLN39. The P2 region, however, contains the TATA sequence as well as another sequence with a CpG site. The TATA sequence is conserved in members closely related to ATLN39 but not in the other ATLN members, suggesting that P2 is the promoter uniquely present in the ATLN39-related members. Transcripts from promoter P1 can be used as templates to give new copies proficient in retroposition, but those from promoter P2 cannot because of the lack of the proximal half region of the 5' UTR sequence. Transcripts from promoter P2, as well as those from promoter P1 can, however, be used for the production of a

  4. Evolution and proximate expression of human paternal investment.

    PubMed

    Geary, D C

    2000-01-01

    In more than 95% of mammalian species, males provide little direct investment in the well-being of their offspring. Humans are one notable exception to this pattern and, to date, the factors that contributed to the evolution and the proximate expression of human paternal care are unexplained (T. H. Clutton-Brock, 1989). The nature, extent, and influence of human paternal investment on the physical and social well-being of children are reviewed in light of the social and ecological factors that are associated with paternal investment in other species. On the basis of this review, discussion of the evolution and proximate expression of human paternal investment is provided.

  5. Investigation of proximity effects in electron microscopy and lithography

    SciTech Connect

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

    2012-01-30

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

  6. 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.

  7. Longitudinal spin Seebeck effect free from the proximity Nernst effect.

    PubMed

    Kikkawa, T; Uchida, K; Shiomi, Y; Qiu, Z; Hou, D; Tian, D; Nakayama, H; Jin, X-F; Saitoh, E

    2013-02-08

    This Letter provides evidence for intrinsic longitudinal spin Seebeck effects (LSSEs) that are free from the anomalous Nernst effect (ANE) caused by an extrinsic proximity effect. We report the observation of LSSEs in Au/Y(3)Fe(5)O(12) (YIG) and Pt/Cu/YIG systems, showing that the LSSE appears even when the mechanism of the proximity ANE is clearly removed. In the conventional Pt/YIG structure, furthermore, we separate the LSSE from the ANE by comparing the voltages in different magnetization and temperature-gradient configurations; the ANE contamination was found to be negligibly small even in the Pt/YIG structure.

  8. Inverse Proximity Effect in Superconductor-ferromagnet Bilayer Structures

    SciTech Connect

    Xia, Jing

    2010-04-05

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

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

    NASA Astrophysics Data System (ADS)

    Cole, William; Sau, Jay

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

  10. 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

  11. Promoting Retention

    PubMed Central

    Hall, LaToya N.; Ficker, Lisa J.; Chadiha, Letha A.; Green, Carmen R.; Jackson, James S.; Lichtenberg, Peter A.

    2016-01-01

    Objectives: The objectives of this study were to evaluate the capability of a research volunteer registry to retain community-dwelling African American older adults, and to explore demographic and health factors associated with retention. Method: A logistic regression model was used to determine the influence of demographics, health factors, and registry logic model activities on retention in a sample of 1,730 older African American adults. Results: Almost 80% of participants active in the volunteer research registry between January 2012 and June 2015 were retained. Employment, being referred to research studies, a higher number of medical conditions, and more follow-up contacts were associated with an increased likelihood of retention. Older age, more months in the registry, and more mobility problems decreased the likelihood of retention. Discussion: These results suggest the Michigan Center for Urban African American Aging Research logic model promotes retention through involving older African American adults in research through study referrals and intensive follow-up. The loss of participants due to age- and mobility-related issues indicate the registry may be losing its most vulnerable participants. PMID:28138501

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  13. A theory for the evolution of other-regard integrating proximate and ultimate perspectives.

    PubMed

    Akçay, Erol; Van Cleve, Jeremy; Feldman, Marcus W; Roughgarden, Joan

    2009-11-10

    Although much previous work describes evolutionary mechanisms that promote or stabilize different social behaviors, we still have little understanding of the factors that drive animal behavior proximately. Here we present a modeling approach to answer this question. Our model rests on motivations to achieve objectives as the proximate determinants of behavior. We develop a two-tiered framework by first modeling the dynamics of a social interaction at the behavioral time scale and then find the evolutionarily stable objectives that result from the outcomes these dynamics produce. We use this framework to ask whether "other-regarding" motivations, which result from a kind of nonselfish objective, can evolve when individuals are engaged in a social interaction that entails a conflict between their material payoffs. We find that, at the evolutionarily stable state, individuals can be other-regarding in that they are motivated to increase their partners' payoff as well as their own. In contrast to previous theories, we find that such motivations can evolve because of their direct effect on fitness and do not require kin selection or a special group structure. We also derive general conditions for the evolutionary stability of other-regarding motivations. Our conditions indicate that other-regarding motivations are more likely to evolve when social interactions and behavioral objectives are both synergistic.

  14. 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

  15. 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.

  16. 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

  17. Performance characteristics of proximity focused ultraviolet image converters

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

    Performance characteristics of Bendix type BX 8025-4522 proximity focused image tubes for 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.

  18. 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…

  19. 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.…

  20. 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.

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

    PubMed Central

    2015-01-01

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

  2. Housing Projects and Crime: Testing a Proximity Hypothesis.

    ERIC Educational Resources Information Center

    Roncek, Dennis W.; And Others

    1981-01-01

    Proximity to public housing projects has a small but statistically significant effect on the incidence of violent crime. However, adjacency to public housing is a weak predictor of violent crime once the socioeconomic and housing characteristics of the adjacent blocks are taken into account. (Author/GC)

  3. 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…

  4. Vygotsky's Zone of Proximal Development: Implications for Gifted Education.

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.

    This paper reviews Lev Vygotsky's theories concerning optimizing of potential through assistance, support, or instruction. The paper notes that there is a "zone of proximal development" or a band around intelligence quotient (IQ) scores reflecting one's true potential. IQ tests are generally well-standardized and "static,"…

  5. A pedunculated intraluminal foregut reduplication cyst of the proximal esophagus.

    PubMed

    Craig, S R; Wallace, W H; Scott, D J; Cameron, E W

    1998-06-01

    A 66-year-old woman with a 3-month history of progressive dysphagia underwent transoral excision of a pedunculated cyst arising in the proximal esophagus. Histologic examination confirmed a pedunculated intraluminal foregut reduplication cyst. She remains well 1 year after excision with no recurrence of dysphagia.

  6. A Region of Proximal Learning Model of Study Time Allocation

    ERIC Educational Resources Information Center

    Metcalfe, J.; Kornell, N.

    2005-01-01

    A Region of Proximal Learning model is proposed emphasizing two components to people's study time allocation, controlled by different metacognitive indices. The first component is choice, which is further segmented into two stages: (1) a decision of whether to study or not and (2) the order of priority of items chosen. If the people's Judgments of…

  7. 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…

  8. 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…

  9. 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

  10. 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.

  11. Osteosynthesis of the proximal femur anchorage of a cervical nail.

    PubMed

    el Banna, S; Burny, F; Bourgois, R; Donkerwolcke, M; Moulart, F

    1994-01-01

    One of the factors determining the stability of osteosynthesis is the mechanical strength of the bone fragments required for the anchorage of the implant. The aim is to study the driving of a Thornton nail in the proximal epiphysis of a human femur as a way to measure the strength of the trabecular bone and to predict the stability of the implanted system.

  12. Distal and variably proximal causes: education, obesity, and health.

    PubMed

    Schafer, Markus H; Ferraro, Kenneth F

    2011-11-01

    Medical sociologists hold that social conditions generate disparities across a host of health conditions through exposure to a variety of more proximate risk factors. Though distal and proximal causes jointly influence disease, the nature of risk accumulation may differ appreciably by the link of a proximal cause to the outcome in question. This paper employs a representative sample of over 3000 American older adults to examine whether position in the educational gradient amplifies the effect of obesity on two health outcomes. Results indicate that educational inequalities amplify the effect of high body mass index on disability (unstandardized coefficients across education groups range from -.05 [ns] to .26 [p < .01] among overweight respondents yet reach .17 [ns] to .73 [p < .001] among severely obese adults), but fail to amplify the consequences of severe obesity in the case of C-reactive protein (CRP) levels. Instead, educational gradients in CRP are most pronounced at lower levels of body mass. Sex-specific analyses further clarify these patterns, as the connections between CRP and body mass are particularly strong among women. We conclude that risk accumulation processes differ based on the proximity of causes to the health outcome under examination.

  13. Constructing a MEZOPED (Multiple Electronic Zone of Proximal Development).

    ERIC Educational Resources Information Center

    Murfin, Brian

    1994-01-01

    This paper presents the theoretical background for using computer-mediated communication to link children and scientists in a multiple electronic zone of proximal development. It is postulated that students will be able to perform at higher cognitive levels as a result of this increased interment contact with many adults. (LZ)

  14. 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…

  15. Proximal dup(10q): Case report and literature review

    SciTech Connect

    Barritt, J.A.; Teague, K.E.; Bodurtha, J.N.

    1994-09-01

    We report a case of a proximal dir dup(10q) in a female with multiple congenital anomalies. During infancy she was noted to gave growth retardation, microcephaly, microphthalmia, coloboma, a long, beaked nose, posteriorly rotated ears with simple helices, full bowed lips, widely-spaced nipples, broad first toes, hypermobile and proximally placed thumbs, a heart murmur, PDA, and coarctation of the aorta. Additional findings at age 13 included a full columella, short philtrum, thin limbs, bilateral blindness, and mental retardation, as well as continued growth retardation. Her medical history included precocious puberty at age 8 and a diagnosis of hyperactivity. Using FISH with multiple probes combined with GTG-banding, the aberrant chromosome was determined to be a dir dup(10)(q21{r_arrow}q22). Parental chromosomes were normal and the family history was unremarkable. The parental origin of the dir dup(10) is being assessed using DNA markers. Five similar cases of proximal dup(10q) have been reported previously. Consistent characteristics include low birth weight, developmental and psychomotor delay, growth retardation, and microcephaly. Also found in most cases were short prominent philtrum, bowed mouth, PDA, thin limbs, coloboma, micropthalmia, deep set eyes, and other ocular anomalies. Our case is unique in that she has a long, beaked nose, precocious puberty, and hyperactivity. Future studies such as this, using molecular cytogenetic techniques to better define the chromatin involved in proximal dup(10q), may lead to its recognition as a distinct clinical phenotype.

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

    PubMed Central

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

    2011-01-01

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

  17. 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.

  18. Approximate proximal point methods for convex programming problems

    SciTech Connect

    Eggermont, P.

    1994-12-31

    We study proximal point methods for the finite dimensional convex programming problem minimize f(x) such that x {element_of} C, where f : dom f {contained_in} RIR is a proper convex function and C {contained_in} R is a closed convex set.

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

    ERIC Educational Resources Information Center

    Hyland, Ken

    2010-01-01

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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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…

  5. 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…

  6. Proximity effects and pair currents in cuprate junctions

    NASA Astrophysics Data System (ADS)

    Koren, Gad

    2017-04-01

    Proximity effects and pair currents were measured in epitaxial trilayer c-axis junctions comprised of a {{{PrBa}}}2{{{Cu}}}3{{{O}}}7-δ barrier sandwiched in between an overdoped {{{Y}}}0.94{{{Ca}}}0.06{{{Ba}}}2{{{Cu}}}3{{{O}}}7-δ layer and underdoped {{{YBa}}}2{{{Cu}}}2.7{{{Co}}}0.3{{{O}}}{y} layer. These junctions had two T c values of {{T}}{{c}}({high})=84{--}86 K and {{T}}{{c}}({low})=50{--}55 K, allowing investigation when both electrodes are superconducting, or when only one is superconducting while the other is in its pseudogap regime. For T below T c(high) but much above T c(low), two distinct proximity effect transitions were observed in the resistance at two temperature regimes, between 80 and 84 K, and 76 to 80 K. The first is a conventional proximity effect with the T c(high) electrode, while the second is a second order proximity effect of this electrode with uncorrelated pairs in the pseudogap regime. Conductance spectra measured between 2 and 86 K showed four different I c pair currents which were attributed to coherent pairs tunneling through the barrier below 42 K, to a fluctuating pairs current up to ∼77 K, and to a proximity pairs current between 77 and 84 K. All pair currents were suppressed under magnetic fields, with two distinct decay parameters that originated in the two different electrodes, with a significant suppression observed in the pseudogap regime.

  7. Proximal Scaphoid Arthroplasty Using the Medial Femoral Trochlea Flap

    PubMed Central

    Higgins, James P.; Burger, Heinze K.

    2013-01-01

    Background The medial trochlea of the femur (medial femoral trochlea, MFT) provides a source of convex osteocartilaginous vascularized bone that has been demonstrated to have a similar contour to the proximal scaphoid. This provides a potential solution for difficult recalcitrant proximal pole scaphoid nonunions. Materials and Methods Sixteen consecutive patients who underwent MFT proximal scaphoid arthroplasty were reviewed. Follow-up data were recorded at a minimum of 6 months, with an average of 14 months. The results of this cohort were previously reported in detail but are summarized herein. Description of Technique The ability to reconstruct both bone and cartilage of the nonunion enables the surgeon to resect the nonunited proximal pole to prepare for scaphoid reconstruction. A segment of osteocartilaginous MFT is harvested in dimensions required by the scaphoid defect. The MFT segment is harvested on the transverse branch of the descending geniculate vessels. Fixation may be achieved with ease due to the size of the reconstructed segment. Results Computed tomography imaging demonstrated 15 of 16 reconstructed scaphoids achieving osseous union. Follow-up range of motion (ROM) of the wrist averaged 46.0° extension (range 28-80°) and 43.8° flexion (range 10-80°), which was similar to preoperative (average 45.7° extension and 43.0° flexion). Scapholunate angles remained unaffected (51.6° preoperatively and 48.6° postoperatively), indicating preservation of carpal relationships. Conclusions Vascularized MFT flaps provide a useful tool in the treatment of difficult proximal pole scaphoid nonunions. Early follow-up demonstrates high rate of achieving union with acceptable ROM and good pain relief. PMID:24436821

  8. 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.

  9. SGLT2 mediates glucose reabsorption in the early proximal tubule.

    PubMed

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

    2011-01-01

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

  10. Studies of the electrical potential difference in rat proximal tubule.

    PubMed

    Seely, J F; Chirito, E

    1975-07-01

    The electrical potential difference (PD) in the rat proximal convoluted tubule was investigated in vivo as a function of distance from the glomerulus. The PD was found to be invariably negative (up to -4.5 mV) in the earliest segments (less than 0.5 mm from the glomerulus) and rose to positive values (+2 to +4) in the later segments (1 mm beyond the glomerulus). This change in PD correlated with the bubule fluid-to-plasma (TF/P) chloride ratios, which rose from unity in the early segments to approximately 1.3 in the late. Corresponding changes in PD and chloride ratios could be elicited by single-nephron stop-flow techniques in the early segments. Luminal perfusion techniques demonstrated a direct relationship between PD and tubule fluid chloride concentration. Acetazolamide was found to significantly reduce both late proximal PD (less than +2 mV) and TF/P chloride ratios (less than 1.06). Split-drop studies demonstrated that the negative PD in the early proximal tubule was dependent on the presence of glucose and alanine and the absence of a chloride gradient, whereas in the late proximal tubule under the same conditions the PD was not significantly different from zero. In this segment of the nephron the positive PD in free flow appeared to result from the chloride diffusion potential generated by preferential HCO3 reabsorption. These results provide further demonstration of intrinsic differences in the transport properties along the length of the proximal convoluted tubule.

  11. Proximal Fifth Metatarsal Fractures: Anatomy, Classification, Treatment and Complications

    PubMed Central

    Cheung, Chi Nok; Lui, Tun Hing

    2016-01-01

    Context Fractures of proximal fifth metatarsal are one of the most common fractures of the foot. Evidence Acquisition A search of PubMed for studies on proximal fifth metatarsal fracture and Jones fracture focusing on the classification and management was performed. The reference list of the retrieved articles was searched for additional related studies. Results The vascular supply and soft tissue anatomy of the fifth metatarsal explains the increased risk of delayed union and non-union in fractures at the metaphyseal-diaphyseal junction. Lawrence and Botte classify proximal fifth metatarsal fractures according to their location: tuberosity avulsion fractures (zone 1), fractures at metaphyseal-diaphyseal junction extending into the fourth-fifth intermetatarsal joint (zone 2) and proximal diaphyseal fractures (zone 3). Zone 1 fractures are treated conservatively with functional immobilization and early mobilization with excellent outcome. For zone 2 and zone 3 fractures, acute forms can be treated conservatively but with a risk of delayed union time and time for return to function. Therefore, early surgical fixation with intramedullary screw is advised in athletic individuals. For cases presented with signs of delayed union and non-union, surgical treatment with or without bone grafting is recommended. Complications of these fractures and their management are discussed in this report. Conclusions Lawrence and Botte’s classification of proximal fifth metatarsal fractures is recommended by experts, due to its implication on prognosis and treatment strategy. Zone 1 fractures should be treated conservatively due to their excellent healing potential. Early operative treatment is advised for zone 2 and zone 3 fractures, especially in the athletic group. Complications of delayed union, non-union and refractures should be treated by revision fixation and bone grafting. PMID:28144601

  12. 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.

  13. CFTR mediated chloride secretion in the avian renal proximal tubule.

    PubMed

    Laverty, Gary; Anttila, Ashley; Carty, Jenava; Reddy, Varudhini; Yum, Jamie; Arnason, Sighvatur S

    2012-01-01

    In primary cell cultures of the avian (Gallus gallus) renal proximal tubule parathyroid hormone and cAMP activation generate a Cl(-)-dependent short circuit current (I(SC)) response, consistent with net transepithelial Cl(-) secretion. In this study we investigated the expression and physiological function of the Na-K-2Cl (NKCC) transporter and CFTR chloride channel, both associated with Cl(-) secretion in a variety of tissues, in these proximal tubule cells. Using both RT-PCR and immunoblotting approaches, we showed that NKCC and CFTR are expressed, both in proximal tubule primary cultures and in a proximal tubule fraction of non-cultured (native tissue) fragments. We also used electrophysiological methods to assess the functional contribution of NKCC and CFTR to forskolin-activated I(SC) responses in filter grown cultured monolayers. Bumetanide (10 μM), a specific blocker of NKCC, inhibited forskolin activated I(SC) by about 40%, suggesting that basolateral uptake of Cl(-) is partially mediated by NKCC transport. In monolayers permeabilized on the basolateral side with nystatin, forskolin activated an apical Cl(-) conductance, manifested as bidirectional diffusion currents in the presence of oppositely directed Cl(-) gradients. Under these conditions the apical conductance appeared to show some bias towards apical-to-basolateral Cl(-) current. Two selective CFTR blockers, CFTR Inhibitor 172 and GlyH-101 (both at 20 μM) inhibited the forskolin activated diffusion currents by 38-68%, with GlyH-101 having a greater effect. These data support the conclusion that avian renal proximal tubules utilize an apical CFTR Cl(-) channel to mediate cAMP-activated Cl(-) secretion.

  14. The Utility of Proximal-Accretion Stratigraphy in Lateral Moraines

    NASA Astrophysics Data System (ADS)

    Samolczyk, M. A.; Osborn, G.

    2010-12-01

    Lateral-moraine stratigraphy is a valuable tool that can be used to constrain the timing and magnitude of alpine glacier fluctuations. Numerous lateral moraines, conventionally thought to have been constructed during the Little Ice Age (LIA), have been shown to be composite landforms that contain multiple till layers deposited by successively larger glacier advances. Organic matter and/or tephra sandwiched between the till layers constrain times of advance and retreat; wood fragments within till may provide the age of the till. Observation of contemporary lateral moraines has lead to the recognition of two means of lateral moraine construction: (1) accretion of tills onto the distal flank of the pre-existing lateral moraine, and (2) accretion or plastering of tills onto the proximal flank of the pre-existing moraine. In composite lateral moraines, distal and proximal accretion result in paleosurfaces that trend parallel to the current distal and proximal slope, respectively. Published work using lateral-moraine stratigraphy, for example at Bugaboo and Stutfield glaciers in the Canadian Rockies, has used evidence only from distal-accretion moraines. However, proximal-accretion moraines that provide chronological information have been found at Nisqually Glacier on Mount Rainier in Washington State, USA, and Columbia Glacier, an outlet of the Columbia Icefield in the Canadian Rockies. A gully cut into the left-lateral moraine at Nisqually Glacier exposes a sandy seam, with associated wood fragments, that runs parallel to the proximal moraine flank for ~20 m. Wood collected from different elevations along the seam have radiocarbon ages of 1715±15, 1700±15, and 1670±50 14C yr BP, indicating that the seam is similar in age along its extent and likely marks a paleosurface separating older till below and till of the First Millennium advance above. At Columbia Glacier, some till exposures in the prominent right-lateral moraine show a fissility dipping variably 40 to 50

  15. 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

  16. 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

  17. 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

  18. Cryptosporidium, chronic diarrhoea and the proximal small intestinal mucosa.

    PubMed Central

    Phillips, A D; Thomas, A G; Walker-Smith, J A

    1992-01-01

    The association between Cryptosporidium, chronic diarrhoea and a proximal small intestinal mucosal enteropathy was reviewed over a six and a half year period. One hundred and twenty three children with cryptosporidiosis and no clinical evidence of immune deficiency were identified. 50% of children excreting only Cryptosporidium had chronic diarrhoea. Most cases (63%) of chronic diarrhoea occurred in the first two years of life. A mild to moderate enteropathy was present in all nine children undergoing a small intestinal biopsy and seven showed the presence of Cryptosporidium adhering to villous epithelium. All patients eventually recovered spontaneously. Cryptosporidium is a cause of chronic diarrhoea and a proximal small intestinal mucosal enteropathy in children without immune deficiency. Screening for the parasite should be part of the investigative procedures in children with chronic diarrhoea. Images Figure 4 PMID:1398230

  19. Ionic requirements of proximal tubular sodium transport. II. Hydrogen ion.

    PubMed

    Green, R; Giebisch, G

    1975-11-01

    Simultaneous perfusion to proximal convoluted tubules and peritubular capillaries was used to study the effects of different perfusion fluids on sodium reabsorption and hydrogen secretion, which was calculated as bicarbonate reabsorption and titratable acid. Results show that sodium reabsorption was not tightly coupled to hydrogen secretion. Bicarbonate stimulates both sodium reabsorption and hydrogen secretion, but Tris stimulates only sodium reabsorption. Imposing an adverse chloride gradient across the proximal tubule (C1- peritubular greater than C1- luminal) decreased sodium reabsorption but did not diminish hydrogen secretion. Diamox inhibited both net sodium and hydrogen transport. It is concluded that there is not firm linkage between sodium reabsorption and hydrogen secretion and that bicarbonate probably stimulates sodium transport by a number of mechanisms, including an effect on the sodium transport unrelated to its ability to increase hydrogen ion secretion.

  20. Upgrade of the proximity focusing RICH at Jlab

    SciTech Connect

    Cisbani, Evaristo; Colilli, Stefano; Cusanno, Francesco; Fratoni, Rolando; Frullani, Salvatore; Garibaldi, Franco; Giuliani, Fausto; Gricia, Massimo; Lucentini, Maurizio; Santavenere, Fabio; Urciuoli, Guido; Iodice, Mauro; Argentieri, A.; de Cataldo, Giacinto; De Leo, Raffaele; Lagamba, Luigi; Marrone, Stefano; Nappi, E.; Camsonne, Alexandre; Kross, Brian; Michaels, Robert; Reitz, Bodo; Segal, John; Wojtsekhowski, Bogdan; Zorn, Carl; Monno, E.; Breuer, Herbert

    2009-09-01

    The Hall A RICH at Jefferson Lab is undergoing an upgrade to adapt to the higher momentum kinematics of the neutron spin structure Transversity experiments planned to run in 2008. The JLab RICH is a proximity focusing detector using liquid C6F14 as Cherenkov radiator, a thin layer of CsI as photon converter, evaporated on segmented pad panels of a proportional chamber. The original RICH had a superior hadron identification up to 2 GeV/c with pion/kaon rejection at the level of 1:1000 at ~ similar90% intrinsic efficiency. The upgrade will extend this performance above 2.4 GeV/c by means of a larger photon detector (a multiwire-multipad proportional chamber) and a longer proximity gap which will improve the photon detection geometrical efficiency and the angular resolution, respectively.

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

    NASA Astrophysics Data System (ADS)

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

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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Proximal symphalangism: Evidence of linkage to 17q

    SciTech Connect

    Francomano, C.A.; Rubenstein, J.R.; Polymeropoulos, M.H.

    1994-09-01

    Proximal symphalangism (PS; OMIM 185800) is an autosomal dominant disorder which is characterized by ankylosis of the proximal interphalangeal joints and an increased incidence of conductive deafness in some families. A large American kindred with PS was originally described by Cushing in 1916, segregating for this disorder in many generations. Several follow-up studies have confirmed the disorder in members of this kindred and have also suggested that conductive deafness is a pleiotropic effect of the mutant gene in this family. In an effort to localize the gene, we have studied 55 members of Cushing`s kindred with 85 microsatellite repeat polymorphisms spanning the human genome. Genetic linkage analysis with data for marker D17S809 gave significant evidence for linkage with Zmax=3.4 at recombination fraction {theta}=0.05.

  7. 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.

  8. Synostosis of proximal phalangeal bases for loss of distal metacarpal

    PubMed Central

    Jindal, Pankaj

    2016-01-01

    A finger rendered unstable due to loss of metacarpal head can be stabilized by creating a synostosis at the base of the proximal phalanx of the affected finger with the adjacent normal finger. A cortico cancellous graft bridges the two adjacent proximal phalanges at their bases which are temporarily stabilized with an external fixator. The procedure can be done for, recurrence of giant cell tumor of metacarpal and for traumatic metacarpal loss. The procedure and long term follow up of one patient is presented who had giant cell tumor. This option should be considered before offering ray amputation. There is no micro vascular surgery involved, nor is there any donor site morbidity. The graft heals well without any absorption. The affected finger shows excellent function in the long term followup. PMID:27904227

  9. Reverse shoulder arthroplasty for the management of proximal humerus fractures.

    PubMed

    Jobin, Charles M; Galdi, Balazs; Anakwenze, Oke A; Ahmad, Christopher S; Levine, William N

    2015-03-01

    The use of reverse shoulder arthroplasty is becoming increasingly popular for the treatment of complex three- and four-part proximal humerus fractures in the elderly compared with the often unpredictable and poor outcomes provided by open reduction and internal fixation and by hemiarthroplasty. Inferior results with plate osteosynthesis are often a result of complications of humeral head osteonecrosis, loss of fixation, and screw penetration through the humeral head, whereas major concerns with hemiarthroplasty are tuberosity resorption, malunion, and nonunion resulting in pseudoparalysis. Comparative studies support the use of reverse shoulder arthroplasty in elderly patients with complex proximal humerus fractures because the functional outcomes and relief of pain are reliably improved. Repair and union of the greater tuberosity fragment during reverse shoulder arthroplasty demonstrates improved external rotation, clinical outcomes, and patient satisfaction compared with outcomes after tuberosity resection, nonunion, or resorption. Satisfactory results can be obtained with careful preoperative planning and attention to technical details.

  10. 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.

  11. Adamantinoma of the proximal femur: a case report.

    PubMed

    Ii, Sadao; Tsuchiya, Hiroyuki; Takazawa, Koutaro; Minato, Hiroshi; Tomita, Katsuro

    2004-01-01

    Adamantinoma is a rare low-grade malignant bone tumor with an indolent course. The tibia is involved in 85%-90% of long-bone cases. We encountered a patient with primary adamantinoma of the proximal femur. A 60-year-old woman fell and fractured her proximal left femur in the area of a cystic lesion. She underwent an osteosynthesis procedure, and bone union was obtained. After 3 years she developed pain in the left thigh, and a radiographic abnormality was found at the fracture site. A metastatic bone tumor was suspected, and curettage and cementing were carried out. Histologically, we found an epithelial component but failed to detect any primary cancer. Local recurrence became evident after another 6 years. A marginal excision was performed and a bipolar femoral prosthesis was implanted. We finally diagnosed the patient with adamantinoma. In this report we describe the characteristics of this tumor and discuss the reasoning concerning the differential diagnosis and therapeutic plan.

  12. 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

  13. 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.

  14. 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.

  15. Long range p -wave proximity effect into a disordered metal

    NASA Astrophysics Data System (ADS)

    Keser, Aydin Cem; Stanev, Valentin; Galitski, Victor

    2015-03-01

    We use quasiclassical methods of superconductivity to study the superconducting proximity effect from a topological p -wave superconductor into a disordered quasi-one-dimensional metallic wire. We demonstrate that the corresponding Eilenberger equations with disorder reduce to a closed nonlinear equation for the superconducting component of the matrix Green's function. Remarkably, this equation is formally equivalent to a classical mechanical system (i.e., Newton's equations), with the Green function corresponding to a coordinate of a fictitious particle and the coordinate along the wire corresponding to time. This mapping allows us to obtain exact solutions in the disordered nanowire in terms of elliptic functions. A surprising result that comes out of this solution is that the p -wave superconductivity proximity induced into the disordered metal remains long range, decaying as slowly as the conventional s -wave superconductivity. It is also shown that impurity scattering leads to the appearance of a zero-energy peak.

  16. Longitudinal proximity effects in superconducting transition-edge sensors.

    PubMed

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

    2010-01-29

    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{c} of the TES is current dependent and at fixed current scales as 1/L{2}. We have also 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 microm, 1450 times the mean-free path.

  17. Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

    SciTech Connect

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

    2010-01-29

    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 have also 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 {micro}m, 1450 times the mean-free path.

  18. [Pathological proximal femur fracture: consider also primary bone tumour].

    PubMed

    van de Sande, Michiel A J; van Rijswijk, Carla S P; Dijkstra, P D Sander; Taminiau, Antonie M H

    2010-01-01

    Two male and one female patient, aged 64, 70 and 51 respectively, were surgically treated for pathological fracture of the proximal femur without preoperative biopsy. In contrast to their benign radiological diagnosis, all three patients were finally diagnosed as having a malignant primary bone tumour. The proximal femur is the primary location of pathological fractures in the appendicular skeleton. Metastases to bone are the most common cause of a destructive lesion of the skeleton in an adult. Although rare, a primary bone tumour must be included in differential diagnosis of a pathological fracture. A systematic diagnostic strategy is critical to avoid complications that make curative treatment impossible. A solitary bone lesion seen on radiography should never be assumed to be a bone metastasis. Without further diagnostic research, surgical treatment for a pathological fracture should never be commenced before a definitive diagnosis is made.

  19. 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

  20. Copper in silicon: Quantitative analysis of internal and proximity gettering

    SciTech Connect

    McHugo, S.A.; Flink, C.; Weber, E.R.

    1997-08-01

    The behavior of copper in the presence of a proximity gettering mechanism and a standard internal gettering mechanism in silicon was studied. He implantation-induced cavities in the near surface region were used as a proximity gettering mechanism and oxygen precipitates in the bulk of the material provided internal gettering sites. Moderate levels of copper contamination were introduced by ion implantation such that the copper was not supersaturated during the anneals, thus providing realistic copper contamination/gettering conditions. Copper concentrations at cavities and internal gettering sites were quantitatively measured after the annealings. In this manner, the gettering effectiveness of cavities was measured when in direct competition with internal gettering sites. The cavities were found to be the dominant gettering mechanism with only a small amount of copper gettered at the internal gettering sites. These results reveal the benefits of a segregation-type gettering mechanism for typical contamination conditions.

  1. Pediatric Scaphoid Proximal Pole Nonunion With Avascular Necrosis.

    PubMed

    Jernigan, Edward W; Smetana, Brandon S; Patterson, J Megan M

    2016-12-24

    A 13-year-old, right hand-dominant, otherwise healthy boy presented with left wrist pain 19 months after a nonmotorized scooter injury. Radiographs and magnetic resonance imaging at presentation demonstrated proximal pole scaphoid nonunion with avascular necrosis of the proximal fragment. Operative and nonsurgical treatment options were discussed and the family elected for an attempt at nonsurgical management. The patient was placed in a short-arm thumb spica cast, with a window for a bone stimulator, for 14 weeks. At the conclusion of the treatment, the pain had resolved and x-ray and computed tomography scan demonstrated bony union. The authors recommend considering an initial trial of nonsurgical management for treatment of all pediatric scaphoid nonunions.

  2. Proximity- and Astigmatism-Tolerant Testsites For Electrical Linewidth Measurement

    NASA Astrophysics Data System (ADS)

    Lin, Burn J.

    1989-07-01

    Electrical linewidth measurement is well-known for high precision and throughput. However, the standard four-point probe testsite is only useful for measuring the width of an isolated conducting line. Line-and-space and isolated spaces can be simulated satisfactorily by adding dummy lines parallel to the active line but weak links or potential electrical shorting situations often prematurely cause these structures to fail before their true limits are reached. In this paper, fully wrapped proximity- and astigmatism-tolerant designs for line-and-space and isolated spaces are shown. They have been successfully demonstrated with printed images. An application in evaluating the exposure-defocus window of a one-layer i-line resist using the proximity-tolerant testsites is given.

  3. [Proximal and distal rupture of the m. biceps brachii].

    PubMed

    Lorbach, O; Kieb, M; Grim, C; Engelhardt, M

    2010-12-01

    Ruptures of the biceps tendon account for a high percentage of tendon ruptures. The aetiology of proximal ruptures of the long head of the biceps tendon is often degenerative and they are frequently associated with lesions of the rotator cuff. The clinical findings are often not specific and long lasting. Distal ruptures of the biceps tendon mostly occur during eccentric contraction of the biceps muscle.Clinical tests, the associated haematoma and a distalisation or proximalisation of the muscle belly in combination with ultrasound or MRI to rule out combined diseases lead to the diagnosis. The possible options include conservative and operative treatment. Tenotomy and tenodesis lead to comparable results in the literature. Therefore, conservative treatment is mostly recommended in proximal ruptures. Operative treatment is preferred in distal ruptures of the biceps tendon in order to achieve an anatomical reconstruction of the muscle function. Chronic ruptures of the distal biceps tendon can be successfully treated with free autografts or allografts.

  4. 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.

  5. 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)

  6. Superconducting proximity effect for in situ and model layered systems

    SciTech Connect

    Finnemore, D.K.

    1980-01-01

    The primary drawback for in situ composites is that the ac losses are higher than for mechanically produced multifilamentary wire. To develop an understanding of the proximity effect so that analytical expressions will be available for design, a model system is developed based on PbCd. Items discussed include boundary conditions at SN interface, phonon spectral function, supercurrents through normal barriers, flux entry fields, and implications for in situ composites. (GHT)

  7. Surgical outcome of delayed presentation of congenital proximal radioulnar synostosis

    PubMed Central

    Garg, Gaurav; Gupta, Som P.

    2015-01-01

    Background: Presentation of proximal radioulnar synostosis varies from cosmetic concerns with no functional limitations to significant pronation deformity which hampers activities of daily living. Surgical management must be considered based on the position of the forearm and functional limitations. We describe the surgical technique, results, and complications of excision of the radial head along with the proximal radius up to the distal extent of the synostosis site and securing the osteotomized radial shaft with a tensor fascia lata graft. Materials and methods: Four patients having six affected elbows with delayed presentation of congenital proximal radioulnar synostosis with dislocated radial head managed surgically were included in the study. There were three males and one female with an average age of 20.25 years (ranging from 16 to 25 years). Preoperatively wrists were locked in the mean pronation position of 51.6° (ranging from 30° to 70°). The indications for surgery were limitation in activities of daily living and an obvious cosmetic deformity. Results: All patients were satisfied with the surgery and showed significant improvement in functional status. Mean active supination was 15° (ranging from 5 to 32°) with passive supination was a mean of 24.8° (ranging from 11° to 44°). Similarly, mean active pronation was 58.5° (ranging from 50° to 71°) with further passive correction up to a mean of 64.16° (ranging from 57° to 87°) at last follow up. Conclusions: This procedure is simple, cost effective, and a reasonable option for treatment of proximal radioulnar synostosis with a dislocated radial head in adult patients. The operation does not require any specialized team or implants, and can be performed in a moderately equipped hospital. PMID:27163088

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

    PubMed

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

    2016-04-22

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

  9. 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

  10. Effect of Shock Proximity on Richtmyer-Meshkov Growth

    SciTech Connect

    Glendinning, S G; Bolstad, J; Braun, D G; Edwards, M J; Hsing, W W; Lasinski, B F; Louis, H; Miles, A; Moreno, J; Peyser, T A; Remington, B A; Robey, H F; Turano, E J; Verdon, C P; Zhou, Y

    2002-10-31

    We report here experiments, conducted on the Omega laser [T.R. Boehly et al., Optics Commun. 133, 495 (1997)], and simulations that show reduced Richtmyer-Meshkov growth rates in a strongly shocked system with linear initial amplitudes (k{eta}{sub 0} {le} 0.9). The growth rate at early time is less than half the impulsive model prediction, rising at later time to near the impulsive prediction. An analytical model that accounts for shock proximity agrees with the results.

  11. A Proximate Biological Survey of San Diego Bay, California

    DTIC Science & Technology

    1975-01-01

    smoothhound) Carcharhinidac Galeorhinus zyoptems (soupfin sliark) Prionace glaum (blue sliark) Sphyrnidae Sphyrna zygaena ( hammerhead shark ...1 and 2, but an isolated group is also indicated in the south bay around station 10. The 28 Midshipman Bonito Sharks Croaker Bonito Figure 13...Species of fish most often collected at individual stat ions during Proximate Survey. 29 bonito and the sharks were taken, for the most part, at

  12. A fossil hominoid proximal femur from Kikorongo Crater, southwestern Uganda.

    PubMed

    DeSilva, Jeremy; Shoreman, Eleanor; MacLatchy, Laura

    2006-06-01

    The external morphology of a fragmentary right proximal femur from southwestern Uganda is described here. Discovered in the Kikorongo Crater of Queen Elizabeth National Park in 1961, this specimen was informally assigned to Homo sapiens (although never described) and tentatively dated to the late Pleistocene. However, because aspects of the external morphology of the femur align the fossil with the African great apes, we suggest that the Kikorongo femur may be the first postcranial fossil of the genus Pan. Like the African apes, the Kikorongo specimen lacks both an obturator externus groove and an intertrochanteric line. It has a short femoral neck with a circular cross section, and a narrow and deep superior notch. Using resampling statistics and discriminant function analysis, the Kikorongo femur clustered with the genus Pan, as opposed to Gorilla or Homo. However, if the specimen is from Pan, it would be large for this taxon. Furthermore, features that clearly distinguish the external morphology of Plio-Pleistocene hominin proximal femora from African ape femora, such as the shape of the femoral neck in cross section and femoral neck length, have converged in Holocene humans and African apes. Unfortunately, the internal morphology of the femoral neck of the Kikorongo fossil was not discernable. Although we hypothesize that the Kikorongo femur is from the genus Pan, there is such variability in the proximal femora of modern humans that, although it would be an unusual human, it remains possible that this fossil represents H. sapiens.

  13. The role of physical proximity in nosocomial diarrhea.

    PubMed

    Chang, V T; Nelson, K

    2000-09-01

    To examine physical proximity as a risk factor for the nosocomial acquisition of Clostridium difficile-associated diarrhea (CDAD) and of antibiotic-associated diarrhea (AAD), we assessed a retrospective cohort of 2859 patients admitted to a community hospital from 1 March 1987 through 31 August 1987. Of these patients, 68 had nosocomial CDAD and 54 had nosocomial AAD. In multivariate analysis, physical proximity to a patient with CDAD (relative risk [RR], 1.86; 95% confidence interval [CI], 1.06-3.28), exposure to clindamycin (RR, 4.22; 95% CI, 2.11-8.45), and the number of antibiotics taken (RR, 1.49; 95% CI, 1.23-1.81) were significant. For patients with nosocomial AAD, exposure to a roommate with AAD (RR, 3.94; 95% CI, 1. 27-12.24), a stay in an intensive care unit or cardiac care unit (RR, 1.93; 95% CI, 1.05-3.53), and the number of antibiotics taken (RR, 2.01; 95% CI, 1.67-2.40) were significant risk factors. Physical proximity may be an independent risk factor for acquisition of nosocomial CDAD and AAD.

  14. Risk factors and predictors of mortality for proximal humeral fractures

    PubMed Central

    Gooding, Benjamin WT; Manning, Paul A; Wallace, W Angus; Geoghegan, John M

    2014-01-01

    Background Risk factors for mortality after proximal humeral fracture, including socioeconomic status, are poorly defined. This retrospective review of prospectively collected data defines the epidemiology and predictors of mortality in association with proximal humeral fractures. Methods Patients who sustained proximal humeral fractures were identified from fragility fracture and trauma databases between May 2001 and September 2012. Results In total, 1880 patients with a mean age of 69 years and a male to female ratio of 2 : 3 were identified. Socioeconomic distribution is skewed towards the lowest and highest quintiles. Low-energy mechanisms caused 88% of fractures. Men sustain fractures when they are aged 10 years younger and via higher-energy mechanisms. In total, 536 patients (29%) died within the study period with a 1-year mortality of 9.8%, rising to 28.2% at 5 years. Female gender, increasing age, pathological fracture and increased number of co-morbidities were independent variables for increased mortality. Conclusions The present study, which was conducted over an 11-year period, is the first to combine the epidemiology and risk factors for mortality with socioeconomic rank. One-year mortality risk is twice that of the background matched population. Patient counselling with respect to increased mortality should be considered, especially in higher-risk elderly females with multiple co-morbidities. PMID:27582921

  15. Proximate and mineral content of restaurant steak meals.

    PubMed

    Green, E M; Appledorf, H

    1983-02-01

    Restaurant steak meals were analyzed for proximate and mineral composition by standard methodology. Nutritional adequacy of the meals was determined by comparing analyzed values with Recommended Dietary Allowances for adults. The meals were considered to be adequate in a nutrient if they provided at least one-third the RDA for that nutrient. Analyzed values were also compared with values obtained from food composition tables. The results of this study indicate that: 1. Restaurant steak meals differ significantly in weight of meal components, proximate components, and mineral components. 2. Although the meals were adequate in kilocalories and protein, they could be considered to be excessive since they provided more than 50% of the RDA for energy and more than 100% of the RDA for protein. 3. The meals can be considered inadequate in calcium for both men and women (only 16% of the RDA) and in iron for women (only 25% of the RDA). 4. Tables of food composition are useful in predicting the proximate and mineral composition of restaurant steak meals.

  16. 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.

  17. Reconstruction of the extensor mechanism after proximal tibia endoprosthetic replacement.

    PubMed

    Bickels, J; Wittig, J C; Kollender, Y; Neff, R S; Kellar-Graney, K; Meller, I; Malawer, M M

    2001-10-01

    The proximal tibia is a difficult area in which to perform a wide resection of a bone tumor. This difficulty is due to the intimate relationship of tumor in this location to the nerves and blood vessels of the leg, inadequate soft tissue coverage after endoprosthetic reconstruction, and the need to reconstruct the extensor mechanism. Competence of the extensor mechanism is the major determinant of functional outcome of these patients. Between 1980 and 1997, 55 patients underwent proximal tibia resection with endoprosthetic reconstruction for a variety of malignant and benign-aggressive tumors. Reconstruction of the extensor mechanism included reattachment of the patellar tendon to the prosthesis with a Dacron tape, reinforcement with autologous bone-graft, and attachment of an overlying gastrocnemius flap. All patients were followed for a minimum of 2 years; 6 patients (11%) had a transient peroneal nerve palsy, 4 patients (7.2%) had a fasciocutaneous flap necrosis, and 2 patients (3.6%) had a deep wound infection. Full extension to extension lag of 20 degrees was achieved in 44 patients, and 8 patients required secondary reinforcement of the patellar tendon. Function was estimated to be good to excellent in 48 patients (87%). Reattachment of the patellar tendon to the prosthesis and reinforcement with an autologous bone-graft and a gastrocnemius flap are reliable means to restore extension after proximal tibia endoprosthetic reconstruction.

  18. Using Protein-Confined Proximity To Determine Chemical Reactivity.

    PubMed

    Kobayashi, Tomonori; Hoppmann, Christian; Yang, Bing; Wang, Lei

    2016-11-16

    Chemical reactivity is essential for functional modification of biomolecules with small molecules and the development of covalent drugs. The reactivity between a chemical functional group of a small molecule and that of a large biomolecule cannot be reliably predicted from the reactivity of the corresponding functional groups separately installed on two small molecules, because the proximity effect on reactivity resulting from the binding of the small molecule to the biomolecule is challenging to achieve by mixing two small molecules. Here we present a new strategy to determine the chemical reactivity of two functional groups in the context of close proximity afforded by proteins. The functional groups to be tested were separately installed at the interface of two interacting proteins in the format of amino acid side chains via the expansion of the genetic code. Reaction of the two functional groups resulted in covalent cross-linking of interacting proteins, readily detectable by gel electrophoresis. Using this strategy, we evolved new synthetases to genetically encode N(ε)-fluoroacetyllysine (FAcK), an isosteric fluorine analogue of acetyllysine. We demonstrated that fluoroacetamide installed on FAcK, previously thought inert to biological functional groups, actually reacted with the thiol group of cysteine when in proximity. This strategy should be valuable for accurately evaluating chemical reactivity of small molecules toward large biomolecules, which will help avoid undesired side reactions of drugs and expand the repertoire of functional groups to covalently target biomolecules.

  19. 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

  20. 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

  1. Calcium transport in the rabbit superficial proximal convoluted tubule

    SciTech Connect

    Ng, R.C.; Rouse, D.; Suki, W.N.

    1984-09-01

    Calcium transport was studied in isolated S2 segments of rabbit superficial proximal convoluted tubules. 45Ca was added to the perfusate for measurement of lumen-to-bath flux (JlbCa), to the bath for bath-to-lumen flux (JblCa), and to both perfusate and bath for net flux (JnetCa). In these studies, the perfusate consisted of an equilibrium solution that was designed to minimize water flux or electrochemical potential differences (PD). Under these conditions, JlbCa (9.1 +/- 1.0 peq/mm X min) was not different from JblCa (7.3 +/- 1.3 peq/mm X min), and JnetCa was not different from zero, which suggests that calcium transport in the superficial proximal convoluted tubule is due primarily to passive transport. The efflux coefficient was 9.5 +/- 1.2 X 10(-5) cm/s, which was not significantly different from the influx coefficient, 7.0 +/- 1.3 X 10(-5) cm/s. When the PD was made positive or negative with use of different perfusates, net calcium absorption or secretion was demonstrated, respectively, which supports a major role for passive transport. These results indicate that in the superficial proximal convoluted tubule of the rabbit, passive driving forces are the major determinants of calcium transport.

  2. Hand proximity facilitates spatial discrimination of auditory tones

    PubMed Central

    Tseng, Philip; Yu, Jiaxin; Tzeng, Ovid J. L.; Hung, Daisy L.; Juan, Chi-Hung

    2014-01-01

    The effect of hand proximity on vision and visual attention has been well documented. In this study we tested whether such effect(s) would also be present in the auditory modality. With hands placed either near or away from the audio sources, participants performed an auditory-spatial discrimination (Experiment 1: left or right side), pitch discrimination (Experiment 2: high, med, or low tone), and spatial-plus-pitch (Experiment 3: left or right; high, med, or low) discrimination task. In Experiment 1, when hands were away from the audio source, participants consistently responded faster with their right hand regardless of stimulus location. This right hand advantage, however, disappeared in the hands-near condition because of a significant improvement in left hand's reaction time (RT). No effect of hand proximity was found in Experiments 2 or 3, where a choice RT task requiring pitch discrimination was used. Together, these results that the perceptual and attentional effect of hand proximity is not limited to one specific modality, but applicable to the entire “space” near the hands, including stimuli of different modality (at least visual and auditory) within that space. While these findings provide evidence from auditory attention that supports the multimodal account originally raised by Reed et al. (2006), we also discuss the possibility of a dual mechanism hypothesis to reconcile findings from the multimodal and magno/parvocellular account. PMID:24966839

  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. 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.

  5. 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

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

    PubMed

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

    2014-07-08

    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.

  7. 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...

  8. 14 CFR 121.360 - Ground proximity warning-glide slope deviation alerting system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Ground proximity warning-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...

  9. Proximity association in polygynous western black crested gibbons (Nomascus concolor jingdongensis): network structure and seasonality.

    PubMed

    Guan, Zhen-Hua; Huang, Bei; Ning, Wen-He; Ni, Qing-Yong; Jiang, Xue-Long

    2013-01-01

    We investigated the structure and seasonality of the proximity network in a group of polygynous western black crested gibbons (Nomascus concolor) using social network analysis. The spatial proximity changed seasonally and was affected by temperature and rainfall. Preferred proximity association was not distributed randomly among individuals. Kinship was one explanation for the social structure, as offspring preferred to maintain close proximity with their mothers. The proximity of infants to mothers decreased with age, and independent offspring had lower proximity to mothers than dependent ones. We found that the adult male had different proximity relationships with two different adult females. The frequency of proximity between the male and the infant-carrying female was significantly higher than that between the male and the female who had immigrated carrying one offspring of uncertain paternity into the group. Infanticide avoidance and/or predation protection for dependent infants might explain the proximity relationship differences. Temperature influenced group proximity association, with individual proximity increasing in the cold months and decreasing in the hot months. Group proximity decreased in months with higher anthropogenic disturbance.

  10. 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.

  11. [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.

  12. Functional results after proximal row carpectomy to salvage a wrist.

    PubMed

    Kremer, Thomas; Sauerbier, Michael; Trankle, Markus; Dragu, Adrian; Germann, Guenter; Baumeister, Steffen

    2008-01-01

    Proximal row carpectomy is a movement-preserving procedure in the treatment of arthrosis of the wrist. We have retrospectively assessed the objective and subjective functional results after proximal row carpectomy. Assessment of outcome included measurement of range of movement (ROM), grip strength and self-assessment of pain relief with a visual analogue scale (VAS) and the Disabilities of arm, shoulder, and hand (DASH) questionnaire. Results were graded using the Mayo and Krimmer wrist scores. Fourty-five patients (mean age 48 (30-67) years) were evaluated with a follow-up of 32 (8-115) months. Underlying conditions included: degenerative arthritis secondary to scapholunate advanced collapse deformity, or chronic scaphoid non-union (n=35), Kienbock disease stage III (n=4), chronic perilunate dislocation and fracture-dislocation (n=4), avascular necrosis of the scaphoid (n=1), and severe radiocarpal arthrosis secondary to distal radial fracture (n=1). Active ROM for wrist extension and flexion was 70 degrees and mean radial and ulnar deviation 30.8 degrees . Grip strength was 51% of the unaffected side. The average DASH score was 26. The intensity of the pain, measured by VAS, was reduced by 44% after strenuous activities and by 71% at rest. The Mayo and Krimmer wrist scores were 55 and 62 points indicating good results; 32 patients returned to work and 25 patients to their former occupation. Our results show that proximal row carpectomy is a technically easy operation that preserves a satisfying ROM and pain relief, and is recommended when the head of the capitate and the lunate fossa are not affected by arthrosis.

  13. 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.

  14. Dynamic knee loads during gait predict proximal tibial bone distribution.

    PubMed

    Hurwitz, D E; Sumner, D R; Andriacchi, T P; Sugar, D A

    1998-05-01

    This study tested the validity of the prediction of dynamic knee loads based on gait measurements. The relationship between the predicted loads at the knee and the distribution of bone between the medial and lateral sides of the tibia was examined. The motion and external forces and moments at the knee were measured during gait and a statically determinate muscle model was used to predict the corresponding forces on the medial and lateral tibial plateaus. In particular, the relationship between the knee adduction moment during gait and the ratio or distribution of medial to lateral tibial bone mineral content was studied. Bone mineral content was measured with dual energy X-ray absorptiometry in four regions, two proximal regions 20 mm in height, one medial and one lateral and two distal regions 20 mm in height, one medial and one lateral. The best single predictor of the medial lateral ratio of proximal bone mineral content (bone distribution) was the adduction moment (R2=0.31, p=0.003). Adding weight (negative coefficient. p=0.0004) and the ratio of the average predicted peak force on the medial plateau to the predicted peak force on the lateral plateau (positive coefficient, p=0.0033) to the regression model significantly increased the ability to predict the proximal medial lateral bone distribution (R2=0.72, p=0.0001). Distally neither the subject characteristics nor the gait moments and predicted forces were significant predictors of the bone distribution. The lack of a correlation distally may be reflective of the forces being more evenly distributed further from the tibial plateau. While it has long been suggested that the adduction moment is the primary determinate of the distribution of load between the medial and lateral plateaus, this is the first evidence of its relationship to the underlying bone distribution.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Size and shape variation in Australopithecus afarensis proximal femora.

    PubMed

    Harmon, Elizabeth H

    2006-09-01

    The degree of size and shape variation in the A. afarensis fossil sample has been interpreted in a variety of ways. Size variation has been described as exceeding that of extant hominoids, similar to that of strongly sexually dimorphic hominoids, and best matched to modern humans. The degree of shape variation has been characterized both as great and negligible. Recent fieldwork has increased the proximal femoral sample, providing new data with which to examine variation. The proximal femur of A. afarensis is analyzed in a comparative framework in order to gauge the magnitude of size and shape variation in this element. Seven of the best-preserved A. afarensis proximal femora contribute to the analysis (A.L. 128-1, A.L. 152-2, A.L. 211-1, A.L. 288-1ap, A.L. 333-3, A.L. 333-123, A.L. 827-1). Comparative samples from Pan, Pongo, Gorilla, and Homo provide context for interpreting variation among the fossils. The coefficient of variation (CV) of linear measurements is used to estimate size variation. Bootstrap resampling of CVs from extant hominoids provides distributions for comparison to A. afarensis CVs. Ratios of linear measurements provide scale-free shape variables that are used in pairwise comparisons. The Euclidean distance between pairs of A. afarensis are compared to the Euclidean distances between extant hominoid pairs. As found in some earlier analyses, size variation in A. afarensis is accommodated best in gorillas and orangutans. The magnitude of difference in shape between A. afarensis pairs is exceeded by most taxa, indicating that shape variation is not extreme. These general findings are contradicted by a few instances of excessive size and shape variation. These are uncharacteristic results and could point to temporal bias, although other alternatives are explored. The signal from the proximal femur is that size variation in A. afarensis is like that of the strongly sexually dimorphic apes, and shape variation is well within the range of most

  1. 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.

  2. [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.

  3. 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.

  4. 4. MESOSCOPIC SUPERCONDUCTIVITY: Proximity Action theory of superconductive nanostructures

    NASA Astrophysics Data System (ADS)

    Skvortsov, M. A.; Larkin, A. I.; Feigel'man, M. V.

    2001-10-01

    We review a novel approach to the superconductive proximity effect in disordered normal-superconducting (N-S) structures. The method is based on the multicharge Keldysh action and is suitable for the treatment of interaction and fluctuation effects. As an application of the formalism, we study the subgap conductance and noise in two-dimensional N-S systems in the presence of the electron-electron interaction in the Cooper channel. It is shown that singular nature of the interaction correction at large scales leads to a nonmonotonuos temperature, voltage and magnetic field dependence of the Andreev conductance.

  5. Tractable Algorithms for Proximity Search on Large Graphs

    DTIC Science & Technology

    2010-07-01

    bounds enable us to expand the neighborhood in an adaptive fashion, i.e. include “potential” nearest neigh- bors . As the neighborhood is expanded these...All these applications require ranking, i.e. computing nearest neigh- bors under a given measure. While random walk based proximity measures like...assume that we want to find the k nearest neigh- bors of node i within T ′. In Figure 3.2 we plot the lower and upper bounds of hi,j , in the order of

  6. 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.

  7. Cascading failures in networks with proximate dependent nodes

    NASA Astrophysics Data System (ADS)

    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.

  8. [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.

  9. Outcome of closed proximal phalangeal fractures of the hand

    PubMed Central

    Singh, Jaswinder; Jain, Karun; Mruthyunjaya; Ravishankar, R

    2011-01-01

    Background: The proximal phalanx (PP) of the fingers is fractured more frequently than the middle or even distal phalanges. The problems of malunion, stiffness and sometimes loss of skin or other soft tissues associated with PP fracture increases the disability. The optimum treatment depends on fracture location, fracture geometry and fracture stability. The objective of the study was to analyse the treatment outcome in a series of closed proximal phalangeal fractures of the hand. Materials and Methods: Eighty-four proximal phalangeal fractures in 68 patients were enrolled from 2007 to 2009. The treatment modalities were broadly categorised into two groups, Group A consisted of conservative treatment, and Group B consisted of surgical treatment. Group A included 47 digits treated with closed reduction (CR) with immobilization (n=43), extension block cast and dynamic traction (n=4), while 37 digits were treated in Group B, which included closed or open reduction (OR) and internal fixation (IF) with K-wires (n=31), OR and IF with stainless-steel wiring (n=2), and mini external-fixator (n=4). Belsky's criteria and Gingrass’ criteria were used for assessment of finger injuries and to assess the efficacy of conservative and surgical modalities for closed proximal phalangeal fractures of the hand. Results: Average period of follow-up was 1 year (range 10-14 months). The excellent to good results seen in Groups A and B were 89% and 92%, respectively. Six complications were seen in Group A, which included four cases with malunion and two cases with digital stiffness. Three complications were seen in Group B, which included one each of malunion, digital stiffness and extensor lag. Overall, maximum poor results (n=4) were seen with CR and buddy strapping. Conclusion: Conservative treatment is an inexpensive method, particularly suitable for stable fractures, and in patients who are poor candidates for surgery, Surgical modalities have distinct advantage of stable fixation

  10. 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.

  11. 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

  12. Endoluminal vacuum therapy for iatrogenic perforation of the proximal oesophagus.

    PubMed

    Möschler, O; Müller, M K

    2014-03-01

    Iatrogenic perforation of the upper gastrointestinal tract is one of the most serious complications of upper gastrointestinal endoscopy, with high rates of morbidity and mortality. Treatment is challenging because stent placement or surgical repair of the perforation in this area is often impossible. We report on two cases of iatrogenic perforations of the very proximal oesophagus and distal hypopharynx which could be successfully closed by using an endoluminal vacuum sponge treatment for 5 days. Thus, the endoluminal vacuum therapy may be a useful alternative to surgery in such cases of difficultly managable perforations of the upper oesophagus.

  13. Benign monomelic amyotrophy with proximal upper limb involvement: case report.

    PubMed

    Neves, Marco Antonio Orsini; Freitas, Marcos R G de; Mello, Mariana Pimentel de; Dumard, Carlos Henrique; Freitas, Gabriel R de; Nascimento, Osvaldo J M

    2007-06-01

    Monomelic amyotrophy (MA) is a rare condition in which neurogenic amyotrophy is restricted to an upper or lower limb. Usually sporadic, it usually has an insidious onset with a mean evolution of 2 to 4 years following first clinical manifestations, which is, in turned, followed by stabilization. We report a case of 20-years-old man who presented slowly progressive amyotrophy associated with proximal paresis of the right upper limb, which was followed by clinical stabilization 4 years later. Eletroneuromyography revealed denervation along with myofasciculations in various muscle groups of the right upper limb. We call attention to this rare location of MA, as well as describe some theories concerning its pathophysiology .

  14. Pseudocontractions in the intermediate sense: Fixed and best proximity points

    NASA Astrophysics Data System (ADS)

    De la Sen, Manuel

    2013-09-01

    This paper studies a general contractive condition for a class of two-cyclic self-maps on the union of a finite number of subsets of a metric space which are allowed to have a finite number of successive images in the same subsets of its domain. If the space is uniformly convex and the subsets are non-empty, closed and convex then all the iterated sequences are proved to converge to a unique closed limiting finite sequence. Such a sequence contains the best proximity points of adjacent subsets which coincide with a unique fixed point if all such subsets intersect.

  15. STM/STS on proximity-coupled superconducting graphene

    NASA Astrophysics Data System (ADS)

    Ovadia, Maoz; Ji, Yu; Lee, Gil-Ho; Fang, Wenjing; Hoffman, Jennifer; Jarillo-Herrero, Pablo; Kong, Jing; Kim, Philip

    Graphene in good electrical contact with a superconductor has been observed to have an enhanced proximity effect. Application of a magnetic field is expected to generate an Abrikosov lattice of superconducting vortices, each containing Andreev bound states in its core. With our versatile, homebuilt, low temperature scanning tunneling force microscope (STM/SFM), we investigate the electronic properties of graphene on superconducting NbSe2 in a magnetic field and search for signatures of these vortex core states. This work was supported by the STC Center for Integrated Quantum Materials, NSF Grant No. DMR-1231319.

  16. PlantProm: a database of plant promoter sequences

    PubMed Central

    Shahmuradov, Ilham A.; Gammerman, Alex J.; Hancock, John M.; Bramley, Peter M.; Solovyev, Victor V.

    2003-01-01

    PlantProm DB, a plant promoter database, is an annotated, non-redundant collection of proximal promoter sequences for RNA polymerase II with experimentally determined transcription start site(s), TSS, from various plant species. The first release (2002.01) of PlantProm DB contains 305 entries including 71, 220 and 14 promoters from monocot, dicot and other plants, respectively. It provides DNA sequence of the promoter regions (−200 : +51) with TSS on the fixed position +201, taxonomic/promoter type classification of promoters and Nucleotide Frequency Matrices (NFM) for promoter elements: TATA-box, CCAAT-box and TSS-motif (Inr). Analysis of TSS-motifs revealed that their composition is different in dicots and monocots, as well as for TATA and TATA-less promoters. The database serves as learning set in developing plant promoter prediction programs. One such program (TSSP) based on discriminant analysis has been created by Softberry Inc. and the application of a support ftp: vector machine approach for promoter identification is under development. PlantProm DB is available at http://mendel.cs.rhul.ac.uk/ and http://www.softberry.com/. PMID:12519961

  17. 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.

  18. Proximity-Induced Shiba States in a Molecular Junction

    NASA Astrophysics Data System (ADS)

    Island, Joshua O.; Gaudenzi, Rocco; de Bruijckere, Joeri; Burzurí, Enrique; Franco, Carlos; Mas-Torrent, Marta; Rovira, Concepció; Veciana, Jaume; Klapwijk, Teun M.; Aguado, Ramón; van der Zant, Herre S. J.

    2017-03-01

    Superconductors containing magnetic impurities exhibit intriguing phenomena derived from the competition between Cooper pairing and Kondo screening. At the heart of this competition are the Yu-Shiba-Rusinov (Shiba) states which arise from the pair breaking effects a magnetic impurity has on a superconducting host. Hybrid superconductor-molecular junctions offer unique access to these states but the added complexity in fabricating such devices has kept their exploration to a minimum. Here, we report on the successful integration of a model spin 1 /2 impurity, in the form of a neutral and stable all organic radical molecule, in proximity-induced superconducting break junctions. Our measurements reveal excitations which are characteristic of a spin-induced Shiba state due to the radical's unpaired spin strongly coupled to a superconductor. By virtue of a variable molecule-electrode coupling, we access both the singlet and doublet ground states of the hybrid system which give rise to the doublet and singlet Shiba excited states, respectively. Our results show that Shiba states are a robust feature of the interaction between a paramagnetic impurity and a proximity-induced superconductor where the excited state is mediated by correlated electron-hole (Andreev) pairs instead of Cooper pairs.

  19. 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.

  20. 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.

  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. 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

  3. 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.

  4. Rotor Vortex Wake in Close Proximity of Walls in Hover

    NASA Astrophysics Data System (ADS)

    Konus, Mehmet Fatih; Savas, Omer

    2014-11-01

    Expanding flight envelopes of rotorcraft raise concerns about their behavior in very close proximity of walls or corners where the separation between the wall and the rotor disk can almost vanish. A series of experiments are conducted in a water tank to study the hover behavior of the wake of a 25-cm diameter three-bladed rotor at 8 rev/s. Particle image velocimetry, strain gage force balance measurements and flow visualization are employed. The vortex wake, which is axisymmetric on the average in an unbounded surrounding, is distorted increasingly with decreasing separation from a wall or corner. The vortex wake bends toward the wall and into the corner. The individual helical filaments off the rotor tips are distorted and closely follow the wall. Intermittent reversed vortical flow regions appear upstream of the rotor disk in the proximity of the wall. The mean streamlines indicate that the wake is bent toward the wall or into the corner. The component of the thrust vector along the axis of the rotor decreases. These observation suggest that the thrust vector progressively deviates from the geometric axis of the rotor.

  5. Conductances, diffusion and streaming potentials in the rat proximal tubule.

    PubMed Central

    De Mello, G B; Lopes, A G; Malnic, G

    1976-01-01

    1. Transtubular potential differences and specific resistances were measured in rat proximal tubules by means of single and double barrelled glass micro-electrodes. 2. Tip localization was made by observation of effective resistance changes measured with double barrelled micro-electrodes upon passage of oil droplets, and by perfusion with choline C1. 3. Mean early proximal p.d.s. of the order of -1 to -2 mV, and late values of +0-5 to +1mV were found. Mean specific resistances ranged from 12 to 15 omega cm2. 4. Diffusion potentials and single ion relative conductances were evaluated, perfusing the lumen with solutions differing only with respect to one salt concentration. Na and K conductances were similar and greater than those of C1. 5. Luminal and peritubular perfusions with hypotonic solutions showed the occurrence of streaming potentials in this structure suggesting the existence of pores lined with negative charges. The effective diameter of these pores appeared to be reduced by hypotonic perfusion, as evidenced by a significant increase in resistance, indicating that the main ion path across this structure is represented by intercellular spaces. PMID:10433

  6. 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.

  7. Pyrazinoate transport in the isolated perfused rabbit proximal tubule.

    PubMed

    Besseghir, K; Roch-Ramel, F

    1986-12-01

    The bidirectional tubular transport of pyrazinoate (PZA) was studied in the isolated perfused proximal S2 segment of rabbit kidney. PZA reabsorption was a mechanism of large capacity, temperature-dependent and requiring a normal Na+/K+-ATPase activity. PZA reabsorption was reversibly decreased when lactate was added to the perfusate, indicating that it might occur through the sodium-lactate cotransport. The addition of PAH to the bath had a slight stimulatory effect on PZA reabsorption, suggesting a component of anion exchange in the overall PZA reabsorption. However, SITS added to either the perfusate or the bathing medium induced a non-significant decrease in PZA reabsorption, confirming the minor part of an anion exchange mechanism in this reabsorptive process. PZA reabsorption was not affected by the establishment of a bath-to-lumen H+ gradient, and was only moderately decreased after carbonic anhydrase inhibition by ethoxyzolamide, in opposition to what is known for the reabsorbed anion salicylate. The secretory transport of PZA was saturable and also dependent on a normal Na+/K+-ATPase activity. It is concluded that PZA is bidirectionally transported by facilitated mechanisms in the rabbit proximal S2 segment, one major reabsorptive mechanism appearing to be a sodium-anion cotransport, which might be the sodium-lactate reabsorbing mechanism.

  8. 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

  9. 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).

  10. Analysis of standing droplets in rat proximal tubules

    PubMed Central

    1982-01-01

    Volume, osmolality, and concentrations for Na, Cl, and raffinose have been measured as a function of time in standing droplets within rat intermediate and late proximal tubules. Standing droplet reabsorption proceeds without the development of a measurable osmotic difference across the epithelium. After 140 s of tubular exposure, droplet-to- plasma concentration differences are observed for raffinose, Na, and Cl with the observed Na concentration difference, usually referred to as limiting gradient, being approximately 9 mM. It is possible that a smaller or even no limiting difference would be attained with longer exposure times. Previous values measured for the limiting Na concentration in the rat proximal tubule were determined before the attainment of constant concentrations. Assuming that the Na concentration we measured is the limiting value, we estimate that active NaCl transport accounts for a very small fraction, less than 6%, of the volume reabsorption; using an alternative approach of fitting a theoretical model to our experimental data, active NaCl transport is again estimated to account for only 6% of the total reabsorbate. The previous interpretation that a limiting Na concentration gradient constitutes the most direct evidence for active Na transport may be in error; the gradient we measure can be modeled without incorporating active NaCl transport. PMID:7069399

  11. Scaphoid Proximal Pole Fracture Following Headless Screw Fixation

    PubMed Central

    Rancy, Schneider K.; Zelken, Jonathan A.; Lipman, Joseph D.; Wolfe, Scott W.

    2015-01-01

    Background Headless screw fixation of scaphoid fractures and nonunions yields predictably excellent outcomes with a relatively low complication profile. However, intramedullary implants affect the load to failure and stress distribution within bone and may be implicated in subsequent fracture. Case Description We describe a posttraumatic fracture pattern of the scaphoid proximal pole originating at the previous headless screw insertion site in three young male patients with healed scaphoid nonunions. Each fracture was remarkably similar in shape and size, comprised the volar proximal pole, and was contiguous with the screw entry point. Treatment was challenging but successful in all cases. Literature Review Previous reports have posited that stress-raisers secondary to screw orientation may be implicated in subsequent peri-implant fracture of the femoral neck. Repeat scaphoid fracture after screw fixation has also been reported. However, the shape and locality of secondary fracture have not been described, nor has the potential role of screw fixation in the production of distinct fracture patterns. Clinical Relevance Hand surgeons must be aware of this difficult complication that may follow antegrade headless screw fixation of scaphoid fracture nonunion, and of available treatment strategies. PMID:26855840

  12. 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.

  13. Uncertainty quantification for personalized analyses of human proximal femurs.

    PubMed

    Wille, Hagen; Ruess, Martin; Rank, Ernst; Yosibash, Zohar

    2016-02-29

    Computational models for the personalized analysis of human femurs contain uncertainties in bone material properties and loads, which affect the simulation results. To quantify the influence we developed a probabilistic framework based on polynomial chaos (PC) that propagates stochastic input variables through any computational model. We considered a stochastic E-ρ relationship and a stochastic hip contact force, representing realistic variability of experimental data. Their influence on the prediction of principal strains (ϵ1 and ϵ3) was quantified for one human proximal femur, including sensitivity and reliability analysis. Large variabilities in the principal strain predictions were found in the cortical shell of the femoral neck, with coefficients of variation of ≈40%. Between 60 and 80% of the variance in ϵ1 and ϵ3 are attributable to the uncertainty in the E-ρ relationship, while ≈10% are caused by the load magnitude and 5-30% by the load direction. Principal strain directions were unaffected by material and loading uncertainties. The antero-superior and medial inferior sides of the neck exhibited the largest probabilities for tensile and compression failure, however all were very small (pf<0.001). In summary, uncertainty quantification with PC has been demonstrated to efficiently and accurately describe the influence of very different stochastic inputs, which increases the credibility and explanatory power of personalized analyses of human proximal femurs.

  14. Visualization of Calcium Dynamics in Kidney Proximal Tubules

    PubMed Central

    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.

    2015-01-01

    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. PMID:25788535

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

    PubMed

    Koos, Björn; Söderberg, Ola

    2016-08-01

    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.

  16. Proximal humeral replacement using a fixed-fulcrum endoprosthesis.

    PubMed

    Griffiths, D; Gikas, P D; Jowett, C; Bayliss, L; Aston, W; Skinner, J; Cannon, S; Blunn, G; Briggs, T W R; Pollock, R

    2011-03-01

    Between 1997 and 2007, 68 consecutive patients underwent replacement of the proximal humerus for tumour using a fixed-fulcrum massive endoprosthesis. Their mean age was 46 years (7 to 87). Ten patients were lost to follow-up and 16 patients died. The 42 surviving patients were assessed using the Musculoskeletal Tumor Society (MSTS) Score and the Toronto Extremity Salvage Score (TESS) at a mean follow-up of five years and 11 months (one year to ten years and nine months). The mean MSTS score was 72.3% (53.3% to 100%) and the mean TESS was 77.2% (58.6% to 100%). Four of 42 patients received a new constrained humeral liner to reduce the risk of dislocation. This subgroup had a mean MSTS score of 77.7% and a mean TESS of 80.0%. The dislocation rate for the original prosthesis was 25.9; none of the patients with the new liner had a dislocation at a mean of 14.5 months (12 to 18). Endoprosthetic replacement for tumours of the proximal humerus using this prosthesis is a reliable operation yielding good results without the documented problems of unconstrained prostheses. The performance of this prosthesis is expected to improve further with a new constrained humeral liner, which reduces the risk of dislocation.

  17. Structure and Regulation of the Versican Promoter

    PubMed Central

    Domenzain-Reyna, Clelia; Hernández, Daniel; Miquel-Serra, Laia; Docampo, María José; Badenas, Celia; Fabra, Angels; Bassols, Anna

    2009-01-01

    Versican is a large chondroitin sulfate proteoglycan of the extracellular matrix that is involved in a variety of cellular processes. We showed previously that versican, which is overexpressed in cutaneous melanomas as well as in premalignant lesions, contributes to melanoma progression, favoring the detachment of cells and the metastatic dissemination. Here, we investigated the transcriptional regulation of the versican promoter in melanoma cell lines with different levels of biological aggressiveness and stages of differentiation. We show that versican promoter up-regulation accounts for the differential expression levels of mRNA and protein detected in the invasive SK-mel-131 human melanoma cells. The activity of the versican promoter increased 5-fold in these cells in comparison with that measured in non-invasive MeWo melanoma cells. Several transcriptional regulatory elements were identified in the proximal promoter, including AP-1, Sp1, AP-2, and two TCF-4 sites. We show that promoter activation is mediated by the ERK/MAPK and JNK signaling pathways acting on the AP-1 site, suggesting that BRAF mutation present in SK-mel-131 cells impinge upon the up-regulation of the versican gene through signaling elicited by the ERK/MAPK pathway. This is the first time the AP-1 transcription factor family has been shown to be related to the regulation of versican expression. Furthermore, deletion of the TCF-4 binding sites caused a 60% decrease in the promoter activity in SK-mel-131 cells. These results showing that AP-1 and TCF-4 binding sites are the main regulatory regions directing versican production provide new insights into versican promoter regulation during melanoma progression. PMID:19269971

  18. Nucleotide sequence conservation of novel and established cis-regulatory sites within the tyrosine hydroxylase gene promoter

    PubMed Central

    Wang, Meng; Banerjee, Kasturi; Baker, Harriet; Cave, John W.

    2015-01-01

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis and its gene proximal promoter ( < 1 kb upstream from the transcription start site) is essential for regulating transcription in both the developing and adult nervous systems. Several putative regulatory elements within the TH proximal promoter have been reported, but evolutionary conservation of these elements has not been thoroughly investigated. Since many vertebrate species are used to model development, function and disorders of human catecholaminergic neurons, identifying evolutionarily conserved transcription regulatory mechanisms is a high priority. In this study, we align TH proximal promoter nucleotide sequences from several vertebrate species to identify evolutionarily conserved motifs. This analysis identified three elements (a TATA box, cyclic AMP response element (CRE) and a 5′-GGTGG-3′ site) that constitute the core of an ancient vertebrate TH promoter. Focusing on only eutherian mammals, two regions of high conservation within the proximal promoter were identified: a ∼250 bp region adjacent to the transcription start site and a ∼85 bp region located approximately 350 bp further upstream. Within both regions, conservation of previously reported cis-regulatory motifs and human single nucleotide variants was evaluated. Transcription reporter assays in a TH -expressing cell line demonstrated the functionality of highly conserved motifs in the proximal promoter regions and electromobility shift assays showed that brain-region specific complexes assemble on these motifs. These studies also identified a non-canonical CRE binding (CREB) protein recognition element in the proximal promoter. Together, these studies provide a detailed analysis of evolutionary conservation within the TH promoter and identify potential cis-regulatory motifs that underlie a core set of regulatory mechanisms in mammals. PMID:25774193

  19. 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.

  20. Childhood leukemia and residential proximity to industrial and urban sites

    SciTech Connect

    García-Pérez, Javier; López-Abente, Gonzalo; Gómez-Barroso, Diana; Morales-Piga, Antonio; Pardo Romaguera, Elena; Tamayo, Ibon; Fernández-Navarro, Pablo; and others

    2015-07-15

    Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in

  1. 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

  2. Mass inversion in graphene by proximity to dichalcogenide monolayer

    NASA Astrophysics Data System (ADS)

    Alsharari, Abdulrhman M.; Asmar, Mahmoud M.; Ulloa, Sergio E.

    2016-12-01

    Proximity effects resulting from depositing a graphene layer on a transition-metal dichalcogenide substrate layer change the dynamics of the electronic states in graphene, inducing spin-orbit coupling and staggered potential effects. An effective Hamiltonian that describes different symmetry-breaking terms in graphene, while preserving time-reversal invariance, shows that an inverted mass band-gap regime is possible. The competition of different perturbation terms causes a transition from an inverted mass phase to a staggered gap in the bilayer heterostructure as seen in its phase diagram. A tight-binding calculation of the bilayer validates the effective model parameters. A relative gate voltage between the layers may produce such a phase transition in experimentally accessible systems. The phases are characterized in terms of Berry curvature and valley Chern numbers, demonstrating that the system may exhibit quantum spin Hall and valley Hall effects.

  3. Residential Proximity to Environmental Hazards and Adverse Health Outcomes

    PubMed Central

    Maantay, Juliana A.; Chakraborty, Jayajit

    2011-01-01

    How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses. PMID:22028451

  4. Variable reluctance proximity sensors for cryogenic valve position indication

    NASA Technical Reports Server (NTRS)

    Cloyd, R. A.

    1982-01-01

    A test was conducted to determine the performance of a variable reluctance proximity sensor system when installed in a space shuttle external tank vent/relief valve. The sensors were used as position indicators. The valve and sensors were cycled through a series of thermal transients; while the valve was being opened and closed pneumatically, the sensor's performance was being monitored. During these thermal transients, the vent valve was cooled ten times by liquid nitrogen and two times by liquid hydrogen. It was concluded that the sensors were acceptable replacements for the existing mechanical switches. However, the sensors need a mechanical override for the target similar to what is presently used with the mechanical switches. This override could insure contact between sensor and target and eliminate any problems of actuation gap growth caused by thermal gradients.

  5. Analytic-domain lens design with proximate ray tracing.

    PubMed

    Zheng, Nan; Hagen, Nathan; Brady, David J

    2010-08-01

    We have developed an alternative approach to optical design which operates in the analytical domain so that an optical designer works directly with rays as analytical functions of system parameters rather than as discretely sampled polylines. This is made possible by a generalization of the proximate ray tracing technique which obtains the analytical dependence of the rays at the image surface (and ray path lengths at the exit pupil) on each system parameter. The resulting method provides an alternative direction from which to approach system optimization and supplies information which is not typically available to the system designer. In addition, we have further expanded the procedure to allow asymmetric systems and arbitrary order of approximation, and have illustrated the performance of the method through three lens design examples.

  6. Sensitive detection of aggregated prion protein via proximity ligation

    PubMed Central

    Hammond, Maria; Wik, Lotta; Deslys, Jean-Philippe; Comoy, Emmanuel; Linné, Tommy; Landegren, Ulf; Kamali-Moghaddam, Masood

    2014-01-01

    The DNA assisted solid-phase proximity ligation assay (SP-PLA) provides a unique opportunity to specifically detect prion protein (PrP) aggregates by investigating the collocation of 3 or more copies of the specific protein. We have developed an SP-PLA that can detect PrP aggregates in brain homogenates from infected hamsters even after a 107-fold dilution. In contrast, brain homogenate from uninfected animals did not generate a detectable signal at 100-fold higher concentration. Using either of the 2 monoclonal anti-PrP antibodies, 3F4 and 6H4, we successfully detected low concentrations of aggregated PrP. The presented results provide a proof of concept that this method might be an interesting tool in the development of diagnostic approaches of prion diseases. PMID:25482604

  7. Intraoperative Proximal Femoral Fracture in Primary Cementless Total Hip Arthroplasty.

    PubMed

    Ponzio, Danielle Y; Shahi, Alisina; Park, Andrew G; Purtill, James J

    2015-08-01

    Intraoperative proximal femoral fracture is a complication of primary cementless total hip arthroplasty (THA) at rates of 2.95-27.8%. A retrospective review of 2423 consecutive primary cementless THA cases identified 102 hips (96 patients) with fracture. Multivariate analysis compared fracture incidences between implants, Accolade (Stryker Orthopaedics) and Tri-Lock (DePuy Orthopaedics, Inc.), and evaluated potential risk factors using a randomized control group of 1150 cases without fracture. The fracture incidence was 4.4% (102/2423), 3.7% (36/1019) using Accolade and 4.9% using Tri-Lock (66/1404) (P=0.18). Female gender (OR=1.96; 95% CI 1.19-3.23; P=0.008) and smaller stem size (OR=1.64; 95% CI 1.04-2.63; P=0.03) predicted increased odds of fracture. No revisions of the femoral component were required in the fracture cohort.

  8. Sensitive detection of aggregated prion protein via proximity ligation.

    PubMed

    Hammond, Maria; Wik, Lotta; Deslys, Jean-Philippe; Comoy, Emmanuel; Linné, Tommy; Landegren, Ulf; Kamali-Moghaddam, Masood

    2014-01-01

    The DNA assisted solid-phase proximity ligation assay (SP-PLA) provides a unique opportunity to specifically detect prion protein (PrP) aggregates by investigating the collocation of 3 or more copies of the specific protein. We have developed an SP-PLA that can detect PrP aggregates in brain homogenates from infected hamsters even after a 10(7)-fold dilution. In contrast, brain homogenate from uninfected animals did not generate a detectable signal at 100-fold higher concentration. Using either of the 2 monoclonal anti-PrP antibodies, 3F4 and 6H4, we successfully detected low concentrations of aggregated PrP. The presented results provide a proof of concept that this method might be an interesting tool in the development of diagnostic approaches of prion diseases.

  9. Proximal and point detection of contaminated surfaces using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Guicheteau, Jason A.; Christesen, Steven D.; Tripathi, Ashish; Emmons, Erik D.; Wilcox, Phillip G.; Emge, Darren K.; Pardoe, Ian J.; Fountain, Augustus W., III

    2011-11-01

    We are actively investigating the use of Raman spectroscopy for proximal standoff detection of chemicals and explosive materials on surfaces. These studies include Raman Chemical Imaging of contaminated fingerprints for forensic attribution and the assessments of commercial handheld or portable Raman instruments operating with near-infrared (IR) as well as ultraviolet (UV) laser excitation specifically developed for on-the-move reconnaissance of chemical contamination. As part of these efforts, we have measured the Raman cross sections of chemical agents, toxic industrial chemicals, and explosives from the UV to NIR. We have also measured and modeled the effect interrogation angle has on the Raman return from droplets on man-made surfaces. Realistic droplet distributions have been modeled and tested against variations in surface scan patterns and laser spot size for determining the optimum scan characteristics for detection of relevant surface contamination.

  10. Detection of Protein SUMOylation In Situ by Proximity Ligation Assays.

    PubMed

    Sahin, Umut; Jollivet, Florence; Berthier, Caroline; de Thé, Hugues; Lallemand-Breitenbach, Valérie

    2016-01-01

    Sumoylation is a posttranslational process essential for life and concerns a growing number of crucial proteins. Understanding the influence of this phenomenon on individual proteins or on cellular pathways in which they function has become an intense area of research. A critical step in studying protein sumoylation is to detect sumoylated forms of a particular protein. This has proven to be a challenging task for a number of reasons, especially in the case of endogenous proteins and in vivo studies or when studying rare cells such as stem cells. Proximity ligation assays that allow detection of closely interacting protein partners can be adapted for initial detection of endogenous sumoylation or ubiquitination in a rapid, ultrasensitive, and cheap manner. In addition, modified forms of a given protein can be detected in situ in various cellular compartments. Finally, the flexibility of this technique may allow rapid screening of drugs and stress signals that may modulate protein sumoylation.

  11. Endovascular treatment of proximal arsastomotic aneurysms after aortic prosthetic reconstruction

    SciTech Connect

    Tiesenhausen, Kurt; Hausegger, Klaus A.; Tauss, Josef; Amann, Wilfried; Koch, Guenter

    2001-01-15

    Purpose: To describe the efficacy and value of endovascular stent-grafts for the treatment of aortic anastomotic pseudo-aneurysms.Methods: Three patients with proximal aortic anastomotic pseudoaneurysms 8-15 years after prosthetic reconstruction were treated by transfemoral stent-graft implantation. In two patients the pseudoaneurysms were excluded by Talent prostheses [tube graft (n=1), bifurcated graft (n=s1)]. In one patient an uniiliac Zenith stent-graft was implanted and an extra-anatomic crossover bypass for revascularization of the contralateral lower extremity was performed.Results: All procedures were successful with primary exclusion of the pseudoaneurysms. During the follow-up (mean 16 months) one endoleak occurred due to migration of the tube stent-graft. The endoleak was sealed successfully by implanting an additional bifurcated stent-graft.Conclusion: Stent-graft exclusion of aortic pseudoaneurysms offers a minimally invasive and safe alternative to open surgical reconstruction.

  12. Endovascular Treatment of Proximal Anastomotic Aneurysms After Aortic Prosthetic Reconstruction

    SciTech Connect

    Tiesenhausen, Kurt; Hausegger, Klaus A.; Tauss, Josef; Amann, Wilfried; Koch, Guenter

    2001-01-15

    Purpose: To describe the efficacy and value of endovascular stent-grafts for the treatment of aortic anastomotic pseudoaneurysms.Methods: Three patients with proximal aortic anastomotic pseudoaneurysms 8-15 years after prosthetic reconstruction were treated by transfemoral stent-graft implantation. In two patients the pseudoaneurysms were excluded by Talent prostheses [tube graft (n = 1), bifurcated graft (n = 1)]. In one patient an uni iliac Zenith stent-graft was implanted and an extra-anatomic crossover bypass for revascularization of the contralateral lower extremity was performed.Results: All procedures were successful with primary exclusion of the pseudoaneurysms. During the follow-up (mean 16 months) one endoleak occurred due to migration of the tube stent-graft. The endoleak was sealed successfully by implanting an additional bifurcated stent-graft.Conclusion: Stent-graft exclusion of aortic pseudoaneurysms offers a minimally invasive and safe alternative to open surgical reconstruction.

  13. Factors affecting minority population proximity to hazardous facilities

    SciTech Connect

    Nieves, L.A.; Nieves, A.L. |

    1995-04-01

    Disproportionate exposure of minority groups to environmental hazards has been attributed to ``environmental racism`` by some authors, without systematic investigation of the factors underlying this exposure pattern. This study examines regional differences in the proximity of African-Americans, Hispanics, Asians, and non-Hispanic Whites to a broad range of facility types and explores the effects of urban and income factors. A statistically significant inverse relationship is found between the percentage of non-Hispanic Whites and virtually all facility categories in all regions. Except for Hispanics in the South, all such associations for minority groups show a direct relationship, though some are nonsignificant. The geographic concentration of facilities is more closely tied to urbanization than to economic factors. Controlling for both urban and economic factors, minority population concentration is still a significant explanatory variable for some facility types in some regions. This finding is most consistent for African-Americans.

  14. Fundamental Proximity Effects in Focused electron Beam Induced Deposition

    SciTech Connect

    Plank, Harald; Smith, Daryl; Haber, Thomas; Rack, Philip D; Hofer, Ferdinand

    2012-01-01

    Fundamental proximity effects for electron beam induced deposition processes on nonflat surfaces were studied experimentally and via simulation. Two specific effects were elucidated and exploited to considerably increase the volumetric growth rate of this nanoscale direct write method: (1) increasing the scanning electron pitch to the scale of the lateral electron straggle increased the volumetric growth rate by 250% by enhancing the effective forward scattered, backscattered, and secondary electron coefficients as well as by strong recollection effects of adjacent features; and (2) strategic patterning sequences are introduced to reduce precursor depletion effects which increase volumetric growth rates by more than 90%, demonstrating the strong influence of patterning parameters on the final performance of this powerful direct write technique.

  15. Proximity fingerprint of s{plus_minus} superconductivity.

    SciTech Connect

    Koshelev, A. E.; Stanev, V.

    2011-01-01

    We suggest a straightforward and unambiguous test to identify possible opposite signs of the superconducting order parameter in different bands proposed for iron-based superconductors (s{sub {+-}}-state). We consider the proximity effect in a weakly coupled sandwich composed of a s{sub {+-}}-superconductor and a thin layer of the s-wave superconductor. In such system the s-wave order parameter is coupled differently with different s{sub {+-}}-gaps and it typically aligns with one of these gaps. This forces the other s{sub {+-}}-gap to be anti-aligned with the s-wave gap. In such situation the aligned band induces a peak in the s-wave density of states (DoS), while the anti-aligned band induces a dip. Observation of such contact-induced negative feature in the s-wave DoS would provide a definite proof for s{sub {+-}}-superconductivity.

  16. Implicit learning of arithmetic regularities is facilitated by proximal contrast.

    PubMed

    Prather, Richard W

    2012-01-01

    Natural number arithmetic is a simple, powerful and important symbolic system. Despite intense focus on learning in cognitive development and educational research many adults have weak knowledge of the system. In current study participants learn arithmetic principles via an implicit learning paradigm. Participants learn not by solving arithmetic equations, but through viewing and evaluating example equations, similar to the implicit learning of artificial grammars. We expand this to the symbolic arithmetic system. Specifically we find that exposure to principle-inconsistent examples facilitates the acquisition of arithmetic principle knowledge if the equations are presented to the learning in a temporally proximate fashion. The results expand on research of the implicit learning of regularities and suggest that contrasting cases, show to facilitate explicit arithmetic learning, is also relevant to implicit learning of arithmetic.

  17. Orion Rendezvous, Proximity Operations, and Docking Design and Analysis

    NASA Technical Reports Server (NTRS)

    D'Souza, Christopher; Hanak, F. Chad; Spehar, Pete; Clark, Fred D.; Jackson, Mark

    2007-01-01

    The Orion vehicle will be required to perform rendezvous, proximity operations, and docking with the International Space Station (ISS) and the Earth Departure Stage (EDS)/Lunar Landing Vehicle (LLV) stack in Low Earth Orbit (LEO) as well as with the Lunar Landing Vehicle in Low Lunar Orbit (LLO). The RPOD system, which consists of sensors, actuators, and software is being designed to be flexible and robust enough to perform RPOD with different vehicles in different environments. This paper will describe the design and the analysis which has been performed to date to allow the vehicle to perform its mission. Since the RPOD design touches on many areas such as sensors selection and placement, trajectory design, navigation performance, and effector performance, it is inherently a systems design problem. This paper will address each of these issues in order to demonstrate how the Orion RPOD has been designed to accommodate and meet all the requirements levied on the system.

  18. Magnetic proximity effect in perovskite superconductor/ferromagnet multilayers

    NASA Astrophysics Data System (ADS)

    Stahn, J.; Chakhalian, J.; Niedermayer, Ch.; Hoppler, J.; Gutberlet, T.; Voigt, J.; Treubel, F.; Habermeier, H.-U.; Cristiani, G.; Keimer, B.; Bernhard, C.

    2005-04-01

    Multilayers of superconducting/ferromagnetic (SC/FM) YBa2Cu3O7/La2/3Ca1/3MnO3 have been studied by neutron reflectometry. The occurrence of a structurally forbidden Bragg peak in the FM state highlights a significant difference between the nuclear and magnetic depth profiles. From comparison with simulated reflectivity curves we identify two possible magnetization profiles: (i) a magnetic moment within the SC layer antiparallel to the one in the FM layer (antiphase magnetic proximity effect) or (ii) a “dead” region in the FM layer with zero net magnetic moment. In addition, we observe an anomalous enhancement of the off-specular reflection in the SC state which signals a strong mutual interaction between SC and FM order parameters.

  19. Rendezvous, proximity operations and capture quality function deployment report

    NASA Astrophysics Data System (ADS)

    Lamkin, Stephen L.

    1991-12-01

    Rendezvous, Proximity Operations, and Capture (RPOC) is a missions operations area which is extremely important to present and future space initiatives and must be well planned and coordinated. To support this, a study team was formed to identify a specific plan of action using the Quality Function Deployment (QFD) process. This team was composed of members from a wide spectrum of engineering and operations organizations which are involved in the RPOC technology area. The key to this study's success is an understanding of the needs of potential programmatic customers and the technology base available for system implementation. To this end, the study team conducted interviews with a variety of near term and future programmatic customers and technology development sponsors. The QFD activity led to a thorough understanding of the needs of these customers in the RPOC area, as well as the relative importance of these needs.

  20. Studying Cerebral Vasculature Using Structure Proximity and Graph Kernels

    PubMed Central

    Kwitt, Roland; Pace, Danielle; Niethammer, Marc; Aylward, Stephen

    2014-01-01

    An approach to study population differences in cerebral vasculature is proposed. This is done by 1) extending the concept of encoding cerebral blood vessel networks as spatial graphs and 2) quantifying graph similarity in a kernel-based discriminant classifier setup. We argue that augmenting graph vertices with information about their proximity to selected brain structures adds discriminative information and consequently leads to a more expressive encoding. Using graph-kernels then allows us to quantify graph similarity in a principled way. To demonstrate our approach, we assess the hypothesis that gender differences manifest as variations in the architecture of cerebral blood vessels, an observation that previously had only been tested and confirmed for the Circle of Willis. Our results strongly support this hypothesis, i.e, we can demonstrate non-trivial, statistically significant deviations from random gender classification in a cross-validation setup on 40 healthy patients. PMID:24579182

  1. Solute-Solvent Energetics Based on Proximal Distribution Functions.

    PubMed

    Ou, Shu-Ching; Pettitt, B Montgomery

    2016-08-25

    We consider the hydration structure and thermodynamic energetics of solutes in aqueous solution. On the basis of the dominant local correlation between the solvent and the chemical nature of the solute atoms, proximal distribution functions (pDF) can be used to quantitatively estimate the hydration pattern of the macromolecules. We extended this technique to study the solute-solvent energetics including the van der Waals terms representing excluded volume and tested the method with butane and propanol. Our results indicate that the pDF-reconstruction algorithm can reproduce van der Waals solute-solvent interaction energies to useful kilocalorie per mole accuracy. We subsequently computed polyalanine-water interaction energies for a variety of conformers, which also showed agreement with the simulated values.

  2. Extracorporeal shockwave therapy for chronic proximal plantar fasciitis.

    PubMed

    Strash, Walter W; Perez, Richard R

    2002-10-01

    Although much enthusiasm surrounds applying extracorporeal shock wave therapy for various musculoskeletal conditions, its effects are not well understood and warrant continued study. Certain body tissues or organs may be damaged either acutely or chronically by ESWT; however, it is unequivocal that lung tissue may be damaged. It is theorized that neovascularization is responsible for improvement in symptoms of plantar fasciitis. Neovascularization is the direct effect of macrophage stimulation through cytokines. ESWT has effects at the cellular level--does it interfere with metabolic activity or enhance it? The noninvasive nature and minimal complications of appropriately applied ESWT are its primary advantages. Symptoms may continue to improve for three weeks to six months after treatment; the effects of shock wave therapy seem to be time dependent. ESWT is an effective form of treatment for proximal insertional plantar fasciitis after exhaustive, conservative forms of treatment have failed.

  3. Rendezvous, proximity operations and capture quality function deployment report

    NASA Technical Reports Server (NTRS)

    Lamkin, Stephen L. (Editor)

    1991-01-01

    Rendezvous, Proximity Operations, and Capture (RPOC) is a missions operations area which is extremely important to present and future space initiatives and must be well planned and coordinated. To support this, a study team was formed to identify a specific plan of action using the Quality Function Deployment (QFD) process. This team was composed of members from a wide spectrum of engineering and operations organizations which are involved in the RPOC technology area. The key to this study's success is an understanding of the needs of potential programmatic customers and the technology base available for system implementation. To this end, the study team conducted interviews with a variety of near term and future programmatic customers and technology development sponsors. The QFD activity led to a thorough understanding of the needs of these customers in the RPOC area, as well as the relative importance of these needs.

  4. [Apophyseal avulsions of the pelvis and proximal femur].

    PubMed

    Jacobsen, S

    1993-07-05

    Avulsion fractures of the pelvic and proximal femoral apophyseal centres are not uncommonly seen in adolescent athletes engaged in vigorous sports. They are the result of strong or uncoordinated muscular traction, and are the equivalents of muscle or tendon pulls in mature athletes. They are particularly seen in athletics, soccer, rugby, ice hockey and break dance. They involve the anterior third of the iliac crest, the anterior iliac spines, the tuber ischiadicum, the symphysis pubis and the trochanter minor. The radiographic and clinical diagnosis, symptoms and signs, treatment and prognosis are well described in the orthopaedic literature and this literature is evaluated here. The fractures are easily and almost exclusively treated conservatively, and will only in a few cases result in a lasting functional disability.

  5. Induced gap in topological materials from the superconducting proximity effect

    NASA Astrophysics Data System (ADS)

    Chiu, Ching-Kai; Cole, William

    Topological superconductivity has been of considerable interest lately, with several proposed experimental realizations in solid state systems. A heterostructure of s-wave superconductor and 3D topological insulator is one of the more promising platforms, with topological superconductivity realized on the ''naked'' surface of the topological insulator through the superconducting proximity effect. We theoretically study the induced superconducting gap on the naked surface. Adjusting the Fermi level above the bulk gap (which is the case in experiments), our results for the induced superconducting gap are in agreement with that probed in thin topological insulators (<10nm) in the experiments (Nat. Phys. 10, 943-950 (2014) and Phys. Rev. Lett. 112, 217001 (2014)). We further predict the gap in thick topological insulators (>10nm). This work is supported by LPS-MPO-CMTC, Microsoft Q, and JQI-NSF-PFC.

  6. Isovolumetric regulation of renal proximal tubules in hypotonic medium.

    PubMed

    Lohr, J W

    1990-01-01

    Isolated nonperfused proximal tubules maintained their cell volume at a constant level (isovolumetric regulation, IVR), when osmolality of the bathing medium was gradually decreased from 290 to 190 mosm at 1.5 and 5.0 mosm/min. Hypotonic IVR was blocked by inhibiting the Na(+)-K+ pump with ouabain (10(-4) M) when osmolality was decreased at 1.5 or 5 mosm/min. Concentration-dependent inhibition of cell volume maintenance was observed in the presence of the K+ channel blocker barium (10(-3)-10(-2) M) when osmolality decreased at 5 mosm/min. Quinine (10(-3) M), another K+ channel blocker, also inhibited IVR at osmolality decreases of 1.5 and 5 mosm/min. These results suggest that the maintenance of constant cell volume during gradual hypoosmotic exposure involves mechanisms that depend on intact Na-K-ATPase and the controlled loss of intracellular K+.

  7. Proximal Tubule Cell Hypothesis for Cardiorenal Syndrome in Diabetes

    PubMed Central

    Saito, Akihiko; Kaseda, Ryohei; Hosojima, Michihiro; Sato, Hiroyoshi

    2011-01-01

    Incidence of cardiovascular disease (CVD) is remarkably high among patients with chronic kidney disease (CKD), even in the early microalbuminuric stages with normal glomerular filtration rates. Proximal tubule cells (PTCs) mediate metabolism and urinary excretion of vasculotoxic substances via apical and basolateral receptors and transporters. These cells also retrieve vasculoprotective substances from circulation or synthesize them for release into the circulation. PTCs are also involved in the uptake of sodium and phosphate, which are critical for hemodynamic regulation and maintaining the mineral balance, respectively. Dysregulation of PTC functions in CKD is likely to be associated with the development of CVD and is linked to the progression to end-stage renal disease. In particular, PTC dysfunction occurs early in diabetic nephropathy, a leading cause of CKD. It is therefore important to elucidate the mechanisms of PTC dysfunction to develop therapeutic strategies for treating cardiorenal syndrome in diabetes. PMID:21197105

  8. Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply

    PubMed Central

    O'Brien, Maria; McEvoy, Niall; Hallam, Toby; Kim, Hye-Young; Berner, Nina C.; Hanlon, Damien; Lee, Kangho; Coleman, Jonathan N.; Duesberg, Georg S.

    2014-01-01

    Reliable chemical vapour deposition (CVD) of transition metal dichalcogenides (TMDs) is currently a highly pressing research field, as numerous potential applications rely on the production of high quality films on a macroscopic scale. Here, we show the use of liquid phase exfoliated nanosheets and patterned sputter deposited layers as solid precursors for chemical vapour deposition. TMD monolayers were realized using a close proximity precursor supply in a CVD microreactor setup. A model describing the growth mechanism, which is capable of producing TMD monolayers on arbitrary substrates, is presented. Raman spectroscopy, photoluminescence, X-ray photoelectron spectroscopy, atomic force microscopy, transmission electron microscopy, scanning electron microscopy and electrical transport measurements reveal the high quality of the TMD samples produced. Furthermore, through patterning of the precursor supply, we achieve patterned growth of monolayer TMDs in defined locations, which could be adapted for the facile production of electronic device components. PMID:25487822

  9. Granger causality stock market networks: Temporal proximity and preferential attachment

    NASA Astrophysics Data System (ADS)

    Výrost, Tomáš; Lyócsa, Štefan; Baumöhl, Eduard

    2015-06-01

    The structure of return spillovers is examined by constructing Granger causality networks using daily closing prices of 20 developed markets from 2nd January 2006 to 31st December 2013. The data is properly aligned to take into account non-synchronous trading effects. The study of the resulting networks of over 94 sub-samples revealed three significant findings. First, after the recent financial crisis the impact of the US stock market has declined. Second, spatial probit models confirmed the role of the temporal proximity between market closing times for return spillovers, i.e. the time distance between national stock markets matters. Third, a preferential attachment between stock markets exists, i.e. the probability of the presence of spillover effects between any given two markets increases with their degree of connectedness to others.

  10. Automobile proximity and indoor residential concentrations of BTEX and MTBE

    SciTech Connect

    Corsi, Dr. Richard; Morandi, Dr. Maria; Siegel, Dr. Jeffrey; Hun, Diana E

    2011-01-01

    Attached garages have been identified as important sources of indoor residential air pollution. However, the literature lacks information on how the proximity of cars to the living area affects indoor concentrations of gasoline-related compounds, and the origin of these pollutants. We analyzed data from the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study and evaluated 114 residences with cars in an attached garage, detached garage or carport, or without cars. Results indicate that homes with cars in attached garages were affected the most. Concentrations in homes with cars in detached garages and residences without cars were similar. The contribution from gasoline-related sources to indoor benzene and MTBE concentrations appeared to be dominated by car exhaust, or a combination of tailpipe and gasoline vapor emissions. Residing in a home with an attached garage could lead to benzene exposures ten times higher than exposures from commuting in heavy traffic.

  11. Probing dynamic protein ensembles with atomic proximity measures.

    PubMed

    Gáspári, Zoltán; Angyán, Annamária F; Dhir, Somdutta; Franklin, Dino; Perczel, András; Pintar, Alessandro; Pongor, Sándor

    2010-11-01

    The emerging role of internal dynamics in protein fold and function requires new avenues of structure analysis. We analyzed the dynamically restrained conformational ensemble of ubiquitin generated from residual dipolar coupling data, in terms of protruding and buried atoms as well as interatomic distances, using four proximity-based algorithms, CX, DPX, PRIDE and PRIDE-NMR (http://hydra.icgeb.trieste.it/protein/). We found that Ubiquitin, this relatively rigid molecule has a highly diverse dynamic ensemble. The environment of protruding atoms is highly variable across conformers, on the other hand, only a part of buried atoms tends to fluctuate. The variability of the ensemble cautions against the use of single conformers when explaining functional phenomena. We also give a detailed evaluation of PRIDE-NMR on a wide dataset and discuss its usage in the light of the features of available NMR distance restraint sets in public databases.

  12. Etch modeling for accurate full-chip process proximity correction

    NASA Astrophysics Data System (ADS)

    Beale, Daniel F.; Shiely, James P.

    2005-05-01

    The challenges of the 65 nm node and beyond require new formulations of the compact convolution models used in OPC. In addition to simulating more optical and resist effects, these models must accommodate pattern distortions due to etch which can no longer be treated as small perturbations on photo-lithographic effects. (Methods for combining optical and process modules while optimizing the speed/accuracy tradeoff were described in "Advanced Model Formulations for Optical and Process Proximity Correction", D. Beale et al, SPIE 2004.) In this paper, we evaluate new physics-based etch model formulations that differ from the convolution-based process models used previously. The new models are expressed within the compact modeling framework described by J. Stirniman et al. in SPIE, vol. 3051, p469, 1997, and thus can be used for high-speed process simulation during full-chip OPC.

  13. Determination of muscle effort at the proximal femur rotation osteotomy

    NASA Astrophysics Data System (ADS)

    Sachenkov, O.; Hasanov, R.; Andreev, P.; Konoplev, Yu

    2016-11-01

    The paper formulates the problem of biomechanics of a new method for treatment of Legg-Calve-Perthes disease. Numerical calculations of the rotational flexion osteotomy have been carried out for a constructed mathematical model of the hip joint, taking into account the main set of muscles. The work presents the results of the calculations and their analysis. The results have been compared with the clinical data. The calculations of the reactive forces arising in the acetabulum and the proximal part of the femur allowed us to reveal that this reactive force changes both in value and direction. These data may be useful for assessing the stiffness of an external fixation device used in orthopedic intervention and for evaluating the compression in the joint.

  14. Meniscal Allograft Interposition Combined with Proximal Row Carpectomy.

    PubMed

    Steiner, Murphy M; Willsey, Matthew R; Werner, Frederick W; Harley, Brian J; Klein, Shay; Setter, Kevin J

    2017-02-01

    Background Proximal row carpectomy (PRC) is contraindicated in wrists with preexisting arthritis of the proximal capitate or radiolunate fossa. Patients with these conditions frequently pursue wrist arthrodesis with its associated functional limitations. Questions/Purposes The purpose of this study was to evaluate the results of using lateral meniscal allograft interposition (LMAI), in combination with PRC, in patients with symptomatic wrist arthritis. The primary question is whether this allograft will allow wrist function comparable to that in patients having only a PRC. A secondary question was to determine the short-term longevity of the allograft. Patients/Method Between 2006 and 2012, nine wrists underwent PRC with LMAI. Patient demographics and rates of complication or graft failure were determined. During independent clinical exams, functional outcomes were reviewed, patients completed a Disabilities of the Arm, Shoulder, and Hand (DASH) scores, and radiographs were taken. Results Four patients met the inclusion criteria, having clinical follow-up at an average of 4.2 years. DASH scores at the time of follow-up ranged from 9 to 33, with an average of 24. Average radiocapitate joint space in the first postoperative radiograph was 2.8 mm compared with 1.8 mm at the time of final follow-up. No wrists went on to arthrodesis. Conclusion Early outcomes of PRC with LMAI are comparable to those results found in the literature of PRC alone. LMAI with PRC may be a valid short-term option as a motion-preserving procedure in those patients contraindicated to having a PRC alone. Level of Evidence Level IV.

  15. Phase holograms in PMMA with proximity effect correction

    NASA Technical Reports Server (NTRS)

    Maker, Paul D.; Muller, R. E.

    1993-01-01

    Complex computer generated phase holograms (CGPH's) have been fabricated in PMMA by partial e-beam exposure and subsequent partial development. The CGPH was encoded as a sequence of phase delay pixels and written by the JEOL JBX-5D2 E-beam lithography system, a different dose being assigned to each value of phase delay. Following carefully controlled partial development, the pattern appeared rendered in relief in the PMMA, which then acts as the phase-delay medium. The exposure dose was in the range 20-200 micro-C/sq cm, and very aggressive development in pure acetone led to low contrast. This enabled etch depth control to better than plus or minus lambda(sub vis)/60. That result was obtained by exposing isolated 50 micron square patches and measuring resist removal over the central area where the proximity effect dose was uniform and related only to the local exposure. For complex CGPH's with pixel size of the order of the e-beam proximity effect radius, the patterns must be corrected for the extra exposure caused by electrons scattered back up out of the substrate. This has been accomplished by deconvolving the two-dimensional dose deposition function with the desired dose pattern. The deposition function, which plays much the same role as an instrument response function, was carefully measured under the exact conditions used to expose the samples. The devices fabricated were designed with 16 equal phase steps per retardation cycle, were up to 1 cm square, and consisted of up to 100 million 0.3-2.0 micron square pixels. Data files were up to 500 MB long and exposure times ranged to tens of hours. A Fresnel phase lens was fabricated that had diffraction limited optical performance with better than 85 percent efficiency.

  16. Shock wave therapy for chronic proximal plantar fasciitis.

    PubMed

    Ogden, J A; Alvarez, R; Levitt, R; Cross, G L; Marlow, M

    2001-06-01

    Three hundred two patients with chronic heel pain caused by proximal plantar fasciitis were enrolled in a study to assess the treatment effects consequent to administration of electrohydraulicall-generated extracorporeal shock waves. Symptoms had been present from 6 months to 18 years. Each treated patient satisfied numerous inclusion and exclusion criteria before he or she was accepted into this study, which was approved by the Food and Drug Administration as a randomized, double-blind evaluation of the efficacy of shock wave therapy for this disorder. Overall, at the predetermined evaluation period 3 months after one treatment, 56% more of the treated patients had a successful result by all four of the evaluation criteria when compared with the patients treated with a placebo. This difference was significant and corroborated the fact that this difference in the results was specifically attributable to the shock wave treatment, rather than any natural improvement caused by the natural history of the condition. The current study showed that the directed application of electrohydraulic-generated shock waves to the insertion of the plantar fascia onto the calcaneus is a safe and effective nonsurgical method for treating chronic, recalcitrant heel pain syndrome that has been present for at least 6 months and has been refractory to other commonly used nonoperative therapies. This technology, when delivered using the OssaTron (High Medical Technology, Kreuz-lingen, Switzerland), has been approved by the Food and Drug Administration specifically for the treatment of chronic proximal plantar fasciitis. The results suggest that this therapeutic modality should be considered before any surgical options, and even may be preferable to cortisone injection, which has a recognized risk of rupture of the plantar fascia and recurrence of symptoms.

  17. Crown dimensions and proximal enamel thickness of mandibular second bicuspids.

    PubMed

    Fernandes, Sérgio Augusto; Vellini-Ferreira, Flávio; Scavone-Junior, Helio; Ferreira, Rívea Inês

    2011-01-01

    To achieve proper recontouring of anterior and posterior teeth, to obtain optimal morphology during enamel stripping, it is important to be aware of dental anatomy. This study aimed at evaluating crown dimensions and proximal enamel thickness in a sample of 40 extracted sound, human, mandibular, second bicuspids (20 right and 20 left). Mesiodistal, cervico-occlusal and buccolingual crown dimensions were measured using a digital caliper, accurate to 0.01 mm. Teeth were embedded in acrylic resin and cut along their long axes through the proximal surfaces to obtain 0.7 mm-thick central sections. Enamel thickness on the cut sections was measured using a perfilometer. Comparative analyses were carried out using the Student's-t test (α= 5%). The mean mesiodistal crown widths for right and left teeth were 7.79 mm (± 0.47) and 7.70 mm (± 0.51), respectively. Mean cervico-occlusal heights ranged from 8.31 mm (± 0.75) on the right to 8.38 mm (± 0.85) on the left teeth. The mean values for the buccolingual dimension were 8.67 mm (± 0.70) on the right and 8.65 mm (± 0.54) on the left teeth. The mean enamel thickness on the mesial surfaces ranged from 1.35 mm (± 0.22) to 1.40 mm (± 0.17), on the left and right sides, respectively. On the distal surfaces, the corresponding values were 1.44 mm (± 0.21) and 1.46 mm (± 0.12). No significant differences were found between measurements for right and left teeth. However, enamel thickness was significantly greater on the distal surfaces, compared with the mesial surfaces.

  18. [Osteoporotic fractures of the proximal femur. What's new?].

    PubMed

    Bonnaire, F; Straßberger, C; Kieb, M; Bula, P

    2012-10-01

    Proximal femoral fractures in the elderly are still increasing and are almost always associated with osteoporosis. Especially the over 80-year-olds are increasing and at risk in this respect. In the treatment of these patients new knowledge has been achieved over the last years. An interdisciplinary, multimodal approach with early involvement of internists, geriatricians, anesthetists, osteologists, social workers, care facilities and outpatient trauma and orthopedic surgeons seems to generate a better outcome with fewer complications. In cases of suspected proximal femoral fracture diagnostic imaging should include a computed tomography scan of the posterior pelvic ring to detect commonly occurring fragility fractures of the lateral mass of the sacrum. Early surgery within the first 48 h has a significant positive effect with respect to general and local complications and early mortality. Medical and organizational barriers to an early operation, such as anticoagulant medication, limited capability of communication due to mental dysfunction and lack of operation capacity are continuously declining and subsequently complication rates are decreasing annually in Germany. Endoprosthetics are still associated with higher perioperative mortality than osteosynthesis (4.4 % versus 5.8 %). The innovations in the field of implants and surgical technique also contribute to these lower complication rates. While endoprosthetic treatment is still the gold standard for severely dislocated femoral neck fractures, non-dislocated or slightly dislocated fractures should be fixed with a stable extramedullary implant. For pertrochanteric fractures extramedullary stabilization can only be recommended for stable types of fractures. Every instable trochanteric fracture should be fixed with an intramedullary implant. The use of third generation nails has implicated a significant reduction of complication rates regarding cut-out and reoperations. Rotational fixing of the head

  19. Treatment of proximal humerus fractures in the elderly

    PubMed Central

    Launonen, Antti P; Lepola, Vesa; Flinkkilä, Tapio; Laitinen, Minna; Paavola, Mika; Malmivaara, Antti

    2015-01-01

    Background and purpose There is no consensus on the treatment of proximal humerus fractures in the elderly. Patients and methods We conducted a systematic search of the medical literature for randomized controlled trials and controlled clinical trials from 1946 to Apr 30, 2014. Predefined PICOS criteria were used to search relevant publications. We included randomized controlled trials involving 2- to 4-part proximal humerus fractures in patients over 60 years of age that compared operative treatment to any operative or nonoperative treatment, with a minimum of 20 patients in each group and a minimum follow-up of 1 year. Outcomes had to be assessed with functional or disability measures, or a quality-of-life score. Results After 2 independent researchers had read 777 abstracts, 9 publications with 409 patients were accepted for the final analysis. No statistically significant differences were found between nonoperative treatment and operative treatment with a locking plate for any disability, for quality-of-life score, or for pain, in patients with 3- or 4-part fractures. In 4-part fractures, 2 trials found similar shoulder function between hemiarthroplasty and nonoperative treatment. 1 trial found slightly better health-related quality of life (higher EQ-5D scores) at 2-year follow-up after hemiarthroplasty. Complications were common in the operative treatment groups (10–29%). Interpretation Nonoperative treatment over locking plate systems and tension banding is weakly supported. 2 trials provided weak to moderate evidence that for 4-part fractures, shoulder function is not better with hemiarthroplasty than with nonoperative treatment. 1 of the trials provided limited evidence that health-related quality of life may be better at 2-year follow-up after hemiarthroplasty. There is a high risk of complications after operative treatment. PMID:25574643

  20. Oropharyngeal acid reflux and motility abnormalities of the proximal esophagus

    PubMed Central

    Passaretti, Sandro; Mazzoleni, Giorgia; Vailati, Cristian; Testoni, Pier Alberto

    2016-01-01

    AIM To investigate the relationship between pathological oropharyngeal (OP) acid exposure and esophageal motility in patients with extra-esophageal syndromes. METHODS In this prospective study we enrolled consecutive outpatients with extra-esophageal symptoms suspected to be related to gastroesophageal reflux disease (GERD). We enrolled only patients with a reflux symptom index (RSI) score-higher than 13 and with previous lung, allergy and ear, nose and throat evaluations excluding other specific diagnoses. All patients underwent 24-h OP pH-metry with the Dx probe and esophageal high-resolution manometry (HRM). Patients were divided into two groups on the basis of a normal or pathological pH-metric finding (Ryan Score) and all manometric characteristics of the two groups were compared. RESULTS We examined 135 patients with chronic extra-esophageal syndromes. Fifty-one were considered eligible for the study. Of these, 42 decided to participate in the protocol. Patients were divided into two groups on the basis of normal or pathological OP acid exposure. All the HRM parameters were compared for the two groups. Significant differences were found in the median upper esophageal sphincter resting pressure (median 71 mmHg vs 126 mmHg, P = 0.004) and the median proximal contractile integral (median 215.5 cm•mmHg•s vs 313.5 cm•mmHg•s, P = 0.039), both being lower in the group with pathological OP acid exposure, and the number of contractions with small or large breaks, which were more frequent in the same group. This group also had a larger number of peristaltic contractions with breaks in the 20 mmHg isobaric contour (38.7% vs 15.38%, P < 0.0001). CONCLUSION In patients with suspected GERD-related extra-esophageal syndromes pathological OP acid exposure was associated with weaker proximal esophageal motility. PMID:27833390

  1. Mesiodistal width and proximal enamel thickness of maxillary first bicuspids.

    PubMed

    Macha, Aurélio de Carvalho; Vellini-Ferreira, Flávio; Scavone-Junior, Helio; Ferreira, Rívea Inês

    2010-01-01

    This study aimed at evaluating measurements relative to the mesiodistal crown width and enamel thickness of maxillary first bicuspids. The sample consisted of 40 extracted sound bicuspids (20 right and 20 left), selected from white patients (mean age: 23.7 +/- 4.2 years), who were treated orthodontically with tooth extraction at a private clinic in São Paulo, SP, Brazil. All teeth were embedded in acrylic resin and cut along their long axis through the proximal surfaces, parallel to the buccal side, to obtain 0.6-mm central sections. The mesiodistal crown width and proximal enamel thickness were measured using a stereoscopic microscope connected to a computer. Measurements for right and left teeth, as well as the mesial and distal enamel thicknesses in the total sample, were compared by the Wilcoxon test (alpha = 0.05). The mesiodistal crown width mean values found were 7.51 mm (+/- 0.54) on the right side and 7.53 mm (+/- 0.35) on the left side. The mean enamel thickness on the distal surfaces for both sides was 1.29 mm (right: s.d. = 0.12 and left: s.d. = 0.18). The mean values for the mesial surfaces were 1.08 mm (+/- 0.14) and 1.19 mm (+/- 0.25), on the right and the left sides, respectively. No significant differences were found between the crown measurements and enamel thicknesses on the left and right sides. However, enamel thickness was significantly greater on the distal surfaces. Reliable measurements of enamel thickness are useful to guide stripping, which may be an attractive alternative to tooth extraction because it allows the transverse arch dimension to be maintained.

  2. p-Cresol mediates autophagic cell death in renal proximal tubular cells.

    PubMed

    Lin, Hsin-Hung; Huang, Chiu-Ching; Lin, Tze-Yi; Lin, Ching-Yuang

    2015-04-02

    Higher serum level of p-cresol (PC) in chronic kidney disease (CKD) patients has been linked with CKD progression. The toxic effect of PC on diverse cells has been reported by prior studies, except for renal tubular cells. Both autophagy and apoptosis contribute to renal tubular cell death, yet evidence of its response to PC is limited and their crosstalk is still unclear. Autophagy is an important cellular process involved in toxin-induced cell death. Renal tubular cell death in tubular injury is thought to be one of the key events causing the progression of CKD. Thus, we treated rat (NRK-52E) and human (HRPTEC) renal proximal tubular cells (RPTC) with PC and found the cell proliferation was significantly decreased. Cell apoptosis was significantly increased and accompanied with the activation of autophagy as evidenced by increases in LC3-II, beclin 1 and Atg 4. We also found an increase of p62 by c-Jun activation. p62 accumulation could mediate the activation of caspase 8-dependent cell apoptosis. Conversely, knockdown of p62 by siRNA of p62 had the opposite effect by arresting LC3-II accumulation and promoting increasing cell viability. We conclude that PC triggered autophagic RPTC death via JNK-mediated p62 accumulation and then activated caspase 8-dependent cell death pathway. PC can be considered as one of the key events causing progression of CKD, which might affect drug disposition in CKD cases.

  3. Proximate causes of natal dispersal in female yellow-bellied marmots, Marmota flaviventris.

    PubMed

    Armitage, Kenneth B; Van Vuren, Dirk H; Ozgul, Arpat; Oli, Madan K

    2011-01-01

    We investigated factors influencing natal dispersal in 231 female yearling yellow-bellied marmots (Marmota flaviventris) using comprehensive analysis of 10 years (1983-1993) of radiotelemetry and 37 years (1963-1999) of capture-mark-recapture data. Only individuals whose dispersal status was verified, primarily by radiotelemetry, were considered. Univariate analyses revealed that six of the 24 variables we studied significantly influenced dispersal: dispersal was less likely when the mother was present, amicable behavior with the mother and play behavior were more frequent, and spatial overlap was greater with the mother, with matriline females, and with other yearling females. Using both univariate and multivariate analyses, we tested several hypotheses proposed as proximate causes of dispersal. We rejected inbreeding avoidance, population density, body size, social intolerance, and kin competition as factors influencing dispersal. Instead, our results indicate that kin cooperation, expressed via cohesive behaviors and with a focus on the mother, influenced dispersal by promoting philopatry. Kin cooperation may be an underappreciated factor influencing dispersal in both social and nonsocial species.

  4. Deleting the TGF-β receptor in proximal tubules impairs HGF signaling.

    PubMed

    Nlandu Khodo, Stellor; Neelisetty, Surekha; Woodbury, Luke; Green, Elizabeth; Harris, Raymond C; Zent, Roy; Gewin, Leslie

    2016-03-15

    Transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) play key roles in regulating the response to renal injury but are thought to mediate divergent effects on cell behavior. However, how TGF-β signaling alters the response to HGF in epithelia, the key site of HGF signaling in the injured kidney, is not well studied. Contrary to our expectation, we showed that deletion of the TGF-β type II receptor in conditionally immortalized proximal tubule (PT) cells impaired HGF-dependent signaling. This reduced signaling was due to decreased transcription of c-Met, the HGF receptor, and the TGF-β-dependent c-Met transcription and increased response to HGF in PT cells were mediated by the Notch pathway. The interactions of TGF-β, HGF, and Notch pathways had biologically significant effects on branching morphogenesis, cell morphology, migration, and proliferation. In conclusion, epithelial TGF-β signaling promotes HGF signaling in a Notch-dependent pathway. These findings suggest that TGF-β modulates PT responses not only by direct effects, but also by affecting other growth factor signaling pathways.

  5. Proximal ADMM for multi-channel image reconstruction in spectral X-ray CT.

    PubMed

    Sawatzky, Alex; Xu, Qiaofeng; Schirra, Carsten O; Anastasio, Mark A

    2014-08-01

    The development of spectral X-ray computed tomography (CT) using binned photon-counting detectors has received great attention in recent years and has enabled selective imaging of contrast agents loaded with K-edge materials. A practical issue in implementing this technique is the mitigation of the high-noise levels often present in material-decomposed sinogram data. In this work, the spectral X-ray CT reconstruction problem is formulated within a multi-channel (MC) framework in which statistical correlations between the decomposed material sinograms can be exploited to improve image quality. Specifically, a MC penalized weighted least squares (PWLS) estimator is formulated in which the data fidelity term is weighted by the MC covariance matrix and sparsity-promoting penalties are employed. This allows the use of any number of basis materials and is therefore applicable to photon-counting systems and K-edge imaging. To overcome numerical challenges associated with use of the full covariance matrix as a data fidelity weight, a proximal variant of the alternating direction method of multipliers is employed to minimize the MC PWLS objective function. Computer-simulation and experimental phantom studies are conducted to quantitatively evaluate the proposed reconstruction method.

  6. Involvement of the proximal tibiofibular joint in osteoarthritis of the knee.

    PubMed

    Oztuna, Volkan; Yildiz, Altan; Ozer, Caner; Milcan, Abtullah; Kuyurtar, Fehmi; Turgut, Akin

    2003-12-01

    This study was performed to evaluate the possible involvement of the proximal tibiofibular joint in primary osteoarthritis of the knee. A total of 40 patients with primary osteoarthritis of the knee who had magnetic resonance imaging scans were reexamined for proximal tibiofibular joint involvement. The patient was questioned if pain was present in the proximal tibiofibular joint while at rest, when walking and climbing stairs. Symptoms were evaluated by applying moderate compression over the proximal tibiofibular joint during active ankle and knee motions. Magnetic resonance imaging scans were reexamined by two radiologists. Three of the 40 patients had minimal or moderate pain in the proximal tibiofibular joint during stair-climbing and on clinical examination. Magnetic resonance imaging scans of these three patients revealed osteophyte or subchondral cyst formation, or both. Degenerative changes in the proximal tibiofibular joint may be evident in association with osteoarthritis of the knee and may result in lateral-sided pain at the knee.

  7. Successful treatment of proximal renal tubular acidosis and Fanconi syndrome with vitamin D replacement.

    PubMed

    Ali, Syed Ahsan; Tariq, Muhammad

    2016-01-01

    Proximal renal tubular acidosis (RTA), also known as Type II RTA, is characterized by a defect in the ability to reabsorb bicarbonate (HCO 3 ) in the proximal tubule. It is usually associated with generalized dysfunction of the proximal tubule as part of Fanconi syndrome. Very few case reports in the literature support Vitamin D deficiency as a cause of proximal RTA. We present a case of a young female who presented with proximal RTA and Fanconi syndrome and excellently responded to Vitamin D replacement. Thus, work-up for the etiology of proximal RTA should include Vitamin D levels since replacement of this vitamin in those who are deficient can lead to cure of such patients.

  8. Developing a Promotional Video

    ERIC Educational Resources Information Center

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  9. A comprehensive promoter landscape identifies a novel promoter for CD133 in restricted tissues, cancers, and stem cells

    PubMed Central

    Sompallae, Ramakrishna; Hofmann, Oliver; Maher, Christopher A.; Gedye, Craig; Behren, Andreas; Vitezic, Morana; Daub, Carsten O.; Devalle, Sylvie; Caballero, Otavia L.; Carninci, Piero; Hayashizaki, Yoshihide; Lawlor, Elizabeth R.; Cebon, Jonathan; Hide, Winston

    2013-01-01

    PROM1 is the gene encoding prominin-1 or CD133, an important cell surface marker for the isolation of both normal and cancer stem cells. PROM1 transcripts initiate at a range of transcription start sites (TSS) associated with distinct tissue and cancer expression profiles. Using high resolution Cap Analysis of Gene Expression (CAGE) sequencing we characterize TSS utilization across a broad range of normal and developmental tissues. We identify a novel proximal promoter (P6) within CD133+ melanoma cell lines and stem cells. Additional exon array sampling finds P6 to be active in populations enriched for mesenchyme, neural stem cells and within CD133+ enriched Ewing sarcomas. The P6 promoter is enriched with respect to previously characterized PROM1 promoters for a HMGI/Y (HMGA1) family transcription factor binding site motif and exhibits different epigenetic modifications relative to the canonical promoter region of PROM1. PMID:24194746

  10. Analysis of Proximity-1 Space Link Interleaved Time Synchronization (PITS) Protocol

    NASA Technical Reports Server (NTRS)

    Woo, Simon S.

    2011-01-01

    To synchronize clocks between spacecraft in proximity, the Proximity-1 Space Link Interleaved Time Synchronization (PITS) Protocol has been proposed. PITS is based on the NTP Interleaved On-Wire Protocol and is capable of being adapted and integrated into CCSDS Proximity-1 Space Link Protocol with minimal modifications. In this work, we will discuss the correctness and liveness of PITS. Further, we analyze and evaluate the performance of time synchronization latency with various channel error rates in different PITS operational modes.

  11. A dual-mode proximity sensor with integrated capacitive and temperature sensing units

    NASA Astrophysics Data System (ADS)

    Qiu, Shihua; Huang, Ying; He, Xiaoyue; Sun, Zhiguang; Liu, Ping; Liu, Caixia

    2015-10-01

    The proximity sensor is one of the most important devices in the field of robot application. It can accurately provide the proximity information to assistant robots to interact with human beings and the external environment safely. In this paper, we have proposed and demonstrated a dual-mode proximity sensor composed of capacitive and resistive sensing units. We defined the capacitive type proximity sensor perceiving the proximity information as C-mode and the resistive type proximity sensor detecting as R-mode. Graphene nanoplatelets (GNPs) were chosen as the R-mode sensing material because of its high performance. The dual-mode proximity sensor presents the following features: (1) the sensing distance of the dual-mode proximity sensor has been enlarged compared with the single capacitive proximity sensor in the same geometrical pattern; (2) experiments have verified that the proposed sensor can sense the proximity information of different materials; (3) the proximity sensing capability of the sensor has been improved by two modes perceive collaboratively, for a plastic block at a temperature of 60 °C: the R-mode will perceive the proximity information when the distance d between the sensor and object is 6.0-17.0 mm and the C-mode will do that when their interval is 0-2.0 mm additionally two modes will work together when the distance is 2.0-6.0 mm. These features indicate our transducer is very valuable in skin-like sensing applications.

  12. Double Stent Assist Coiling of Ruptured Large Saccular Aneurysm in Proximal Basilar Artery Fenestration

    PubMed Central

    Park, Woong Bae; Huh, Joon; Cho, Chul Bum; Yang, Seung Ho; Kim, Il Sup; Hong, Jae Taek; Lee, Sang Won

    2015-01-01

    Basilar artery fenestration is infrequent and even rarer in association with a large aneurysm. With proximity to brain stem and vital perforators, endovascular coiling can be considered first. If the large ruptured aneurysm with a wide neck originated from fenestra of the proximal basilar artery and the fenestration loop has branches of posterior circulation, therapeutic consideration should be thorough and fractionized. We report endovascular therapeutic details for a case of a ruptured large saccular aneurysm in proximal basilar artery fenestration. PMID:26523257

  13. [Nutritional characterization of carbohydrates and proximal composition of cooked tropical roots and tubers produced in Costa Rica].

    PubMed

    Blanco-Metzler, Adriana; Tovar, Juscelino; Fernández-Piedra, Mireya

    2004-09-01

    Tropical roots and tubers (TRT) are important staple foods in the tropics. TRT are produced by small farmers and have received only limited attention. The objective of this paper was to evaluate nutritionally important carbohydrate fractions and proximal composition of cooked cassava (Manihot esculenta), cocoyam- or tannia- (Xantosoma sp) and yam (Dioscorea alata) grown in Costa Rica. Twenty boiled samples of each TRT were analyzed for proximal composition, following AOAC protocols. Carbohydrate fractions (dietary fiber, available and resistant starch) and alpha-amylolysis rate were assessed by enzymatic methods. All TRT analyzed consisted mainly of water and carbohydrates, representing moderate dietary fiber and energy sources. They show a low protein level and contain no fat. Moisture, protein, ashes and dietary fiber contents vary significantly (p<0.01) among the three species. In terms of their proximal composition, these locally grown TRT differ from TRTs cultivated in the South Pacific area, but appear similar to other Latin American varieties. In all samples most of the dietary fiber (84-88%) is insoluble; available starch ranges between 74 and 84% of the dry matter, whereas resistant starch content varied between 0.7 and 1.7%. Amylolysis rate was similar for cassava and cocoyam, whereas a significantly slower digestion (p<0.01) was recorded for yam. Compared to values reported in the literature for other starchy foods and to gelatinized potato starch, used as reference sample, the studied TRT showed intermediate amylolysis rates. It is concluded that consumption of these TRT may be promoted in Costa Rica and other countries with a similar nutritional situation.

  14. Proximal and distal regulation of the HYAL1 gene cluster by the estrogen receptor α in breast cancer cells

    PubMed Central

    Edjekouane, Lydia; Benhadjeba, Samira; Jangal, Maïka; Fleury, Hubert; Gévry, Nicolas; Carmona, Euridice; Tremblay, André

    2016-01-01

    Chromosomal and genome abnormalities at the 3p21.3 locus are frequent events linked to epithelial cancers, including ovarian and breast cancers. Genes encoded in the 3p21.3 cluster include HYAL1, HYAL2 and HYAL3 members of hyaluronidases involved in the breakdown of hyaluronan, an abundant component of the vertebrate extracellular matrix. However, the transcriptional regulation of HYAL genes is poorly defined. Here, we identified the estrogen receptor ERα as a negative regulator of HYAL1 expression in breast cancer cells. Integrative data mining using METABRIC dataset revealed a significant inverse correlation between ERα and HYAL1 gene expression in human breast tumors. ChIP-Seq analysis identified several ERα binding sites within the 3p21.3 locus, supporting the role of estrogen as an upstream signal that diversely regulates the expression of 3p21.3 genes at both proximal and distal locations. Of these, HYAL1 was repressed by estrogen through ERα binding to a consensus estrogen response element (ERE) located in the proximal promoter of HYAL1 and flanked by an Sp1 binding site, required to achieve optimal estrogen repression. The repressive chromatin mark H3K27me3 was increased at the proximal HYAL1 ERE but not at other EREs contained in the cluster, providing a mechanism to selectively downregulate HYAL1. The HYAL1 repression was also specific to ERα and not to ERβ, whose expression did not correlate with HYAL1 in human breast tumors. This study identifies HYAL1 as an ERα target gene and provides a functional framework for the direct effect of estrogen on 3p21.3 genes in breast cancer cells. PMID:27764788

  15. Coxa vara with proximal femoral growth arrest in patients who had neonatal extracorporeal membrane oxygenation.

    PubMed

    DiFazio, Rachel L; Kocher, Minider S; Berven, Sigurd; Kasser, James

    2003-01-01

    This is a retrospective review of four patients in whom a pattern of coxa vara with proximal femoral growth arrest and metaphyseal irregularities developed. These patients were all treated with neonatal extracorporeal membrane oxygenation and presented with a progressive gait disturbance and pain, leg-length discrepancy, and limited abduction. Imaging revealed coxa vara with proximal femoral growth arrest. Two patients (three hips) underwent proximal femoral valgus osteotomy, one patient underwent fixation of a femoral neck fracture with subsequent greater trochanter transfer, and one patient is being observed. This case series suggests an association between neonatal extracorporeal membrane oxygenation and this unusual pattern of coxa vara with proximal femoral growth arrest.

  16. A pathway-centric view of spatial proximity in the 3D nucleome across cell lines

    PubMed Central

    Karathia, Hiren; Kingsford, Carl; Girvan, Michelle; Hannenhalli, Sridhar

    2016-01-01

    In various contexts, spatially proximal genes have been shown to be functionally related. However, the extent to which spatial proximity of genes in a pathway contributes to the pathway’s context-specific activity is not known. Leveraging Hi-C data in six human cell-lines, we show that spatial proximity of genes in a pathway is highly correlated with the pathway’s context-specific expression and function. Furthermore, spatial proximity of pathway genes correlates with interactions of their protein products, and the specific pathway genes that are proximal to one another tend to occupy higher levels in the regulatory hierarchy. In addition to intra-pathway proximity, related pathways are spatially proximal to one another and housekeeping-genes tend to be proximal to several other pathways suggesting their coordinating role. Substantially extending previous works, our study reveals a pathway-centric organization of 3D-nucleome, whereby, functionally related interacting driver genes tend to be in spatial-proximity in a context-specific manner. PMID:27976707

  17. The functional results of tibial shaft fractures treated with intramedullary nail compressed by proximal tube.

    PubMed

    Karaarslan, Ahmet Adnan; Acar, Nihat; Aycan, Hakan; Sesli, Erhan

    2016-04-01

    Nailing of tibial shaft fractures is considered the gold standard surgical method by many surgeons. The aim of this retrospective study was to investigate and compare the clinical outcome of tibial shaft fractures treated with intramedullary nails compressed by proximal tube and conventional intramedullary interlocking nails. Fifty-seven patients with tibial shaft fractures, treated with intramedullary nails compressed by proximal tube (n = 32) and the conventional interlocking nails (n = 25), were reviewed. All fractures except for one were united without any additional surgical intervention in the proximal compression tube nail group, whereas in the conventional interlocking nail group, six patients needed dynamization surgery (p = 0.005) and three cases of nonunion were recorded. In the proximal compression tube nail group, faster union occurred in 20 ± 2 (16-24) weeks (mean ± SD; range) without failure of locking screws and proximal nail migration, whereas in the conventional interlocking nail group, union occurred in 22 ± 2.5 (17-27) weeks (p = 0.001) with two failures of locking screws and two proximal nail migration. The proximal compression tube nail system is safer than the conventional nailing methods for the treatment for transverse and oblique tibial shaft fractures with a less rate of nonunion, proximal locking screw failure and proximal nail migration.

  18. A Model for Promoting Student Interaction on Community College (Commuter) Campuses.

    ERIC Educational Resources Information Center

    Ridge, Richard A.

    The planning and development of a program to promote interaction among commuter students at Germanna Community College and to provide for their various needs are described. The program involved establishing an Interaction Center (IC) in 1974, centrally located in proximity to the college's learning resources center and library. The center was to…

  19. Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

    PubMed Central

    Baena, Andres; Ligeiro, Filipa; Diop, Ousmane M.; Brieva, Claudia; Gagneux, Pascal; O'Brien, Stephen J.; Ryder, Oliver A.; Goldfeld, Anne E.

    2007-01-01

    Background Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF. PMID:17637837

  20. Proximal Blade Twist Feedback Control for Heliogyro Solar Sails

    NASA Astrophysics Data System (ADS)

    Smith, Sarah Mitchell

    mode is on the order of 0.005%, meaning there is almost no inherent damping in the blade. Next, the proximal blade twist feedback control design was successful in overcoming friction in the root actuator and added damping to the blade. The damping ratio for the lowest frequency torsional mode was increased from 0.001% to 0.09%, which is a significant amount for a heliogyro spacecraft. Finally, the camera sensor used for the proximal differential twist measurement proved to be feasible and quantization from these measurements only decreased the damping ratio to 0.075%. This research provides the first indication that a physically realizable blade root controller can deal with friction in an effective way, thus taking a step towards advancing the technology readiness level of the heliogyro spacecraft.