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Sample records for enhancing glut-2 glucokinase

  1. Rosiglitazone stimulates the release and synthesis of insulin by enhancing GLUT-2, glucokinase and BETA2/NeuroD expression

    SciTech Connect

    Kim, Hyo-Sup; Noh, Jung-Hyun; Hong, Seung-Hyun; Hwang, You-Cheol; Yang, Tae-Young; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu

    2008-03-14

    Peroxisome proliferator-activated receptor (PPAR)-{gamma} is a member of the nuclear receptor superfamily, and its ligands, the thiazolidinediones, might directly stimulate insulin release and insulin synthesis in pancreatic {beta}-cells. In the present study, we examined the effects of rosiglitazone (RGZ) on insulin release and synthesis in pancreatic {beta}-cell (INS-1). Insulin release and synthesis were stimulated by treatment with RGZ for 24 h. RGZ upregulated the expressions of GLUT-2 and glucokinase (GCK). Moreover, it was found that RGZ increased the expression of BETA2/NeuroD gene which could regulate insulin gene expression. These results suggest that RGZ could stimulate the release and synthesis of insulin through the upregulation of GLUT-2, GCK, and BETA2/NeuroD gene expression.

  2. Glucose-induced toxicity in insulin-producing pituitary cells that coexpress GLUT2 and glucokinase. Implications for metabolic engineering.

    PubMed

    Faradji, R N; Havari, E; Chen, Q; Gray, J; Tornheim, K; Corkey, B E; Mulligan, R C; Lipes, M A

    2001-09-28

    We have shown that intermediate lobe (IL) pituitary cells can be engineered to produce sufficient amounts of insulin (ins) to cure diabetes in nonobese diabetic mice but, unlike transplanted islets, ILins cells evade immune attack. To confer glucose-sensing capabilities into these cells, they were further modified with recombinant adenoviruses to express high levels of GLUT2 and the beta-cell isoform of glucokinase (GK). Although expression of GLUT2 alone had negligible effects on glucose usage and lactate production, expression of GK alone resulted in approximately 2-fold increase in glycolytic flux within the physiological (3-20 mm) glucose range. GLUT2/GK coexpression further increased glycolytic flux at 20 mm glucose but disproportionately increased flux at 3 mm glucose. Despite enhanced glycolytic fluxes, GLUT2/GK-coexpressing cells showed glucose dose-dependent accumulation of hexose phosphates, depletion of intracellular ATP, and severe apoptotic cell death. These studies demonstrate that glucose-sensing properties can be introduced into non-islet cells by the single expression of GK and that glucose responsiveness can be augmented by the coexpression of GLUT2. However, in the metabolic engineering of surrogate beta cells, it is critical that the levels of the components be closely optimized to ensure their physiological function and to avoid the deleterious consequences of glucose-induced toxicity.

  3. mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2

    PubMed Central

    Yang, Guangrui; Kakizoe, Yutaka; Liu, Mi; Yang, Kevin T.; Liu, Ying; Yang, Baoxue; Yang, Tianxin

    2015-01-01

    Background & Aims Microsomal prostaglandin E synthase-2 (mPGES-2) deletion does not influence in vivo PGE2 production and the function of this enzyme remains elusive. The present study was undertaken to investigate the role of mPGES-2 in streptozotocin (STZ)-induced type-1 diabetes and organ injuries. Methods mPGES-2 wild type (WT) and knockout (KO) mice were treated by a single intraperitoneal injection of STZ at the dose of 120 mg/kg to induce type-1 diabetes. Subsequently, glycemic status and organ injuries were evaluated. Results Following 4 days of STZ administration, mPGES-2 KO mice exhibited severe lethality in contrast to the normal phenotype observed in WT control mice. In a separate experiment, the analysis was performed at day 3 of the STZ treatment in order to avoid lethality. Blood glucose levels were similar between STZ-treated KO and WT mice. However, the livers of KO mice were yellowish with severe global hepatic steatosis, in parallel with markedly elevated liver enzymes and remarkable stomach expansion. However, the morphology of the other organs was largely normal. The STZ-treated KO mice displayed extensive hepatocyte apoptosis compared with WT mice in parallel with markedly enhanced inflammation and oxidative stress. More interestingly, a liver-specific 50% upregulation of GLUT2 was found in the KO mice accompanied with a markedly enhanced STZ accumulation and this induction of GLUT2 was likely to be associated with the insulin/SREBP-1c pathway. Primary cultured hepatocytes of KO mice exhibited an increased sensitivity to STZ-induced injury and higher cellular STZ content, which was markedly blunted by the selective GLUT2 inhibitor phloretin. Conclusions mPGES-2 deletion enhanced STZ-induced liver toxicity possibly via GLUT2-mediated STZ uptake, independently of diabetes mellitus. PMID:25076362

  4. Effects of isoleucine on glucose uptake through the enhancement of muscular membrane concentrations of GLUT1 and GLUT4 and intestinal membrane concentrations of Na+/glucose co-transporter 1 (SGLT-1) and GLUT2.

    PubMed

    Zhang, Shihai; Yang, Qing; Ren, Man; Qiao, Shiyan; He, Pingli; Li, Defa; Zeng, Xiangfang

    2016-08-01

    Knowledge of regulation of glucose transport contributes to our understanding of whole-body glucose homoeostasis and human metabolic diseases. Isoleucine has been reported to participate in regulation of glucose levels in many studies; therefore, this study was designed to examine the effect of isoleucine on intestinal and muscular GLUT expressions. In an animal experiment, muscular GLUT and intestinal GLUT were determined in weaning pigs fed control or isoleucine-supplemented diets. Supplementation of isoleucine in the diet significantly increased piglet average daily gain, enhanced GLUT1 expression in red muscle and GLUT4 expression in red muscle, white muscle and intermediate muscle (P<0·05). In additional, expressions of Na+/glucose co-transporter 1 and GLUT2 were up-regulated in the small intestine when pigs were fed isoleucine-supplemented diets (P<0·05). C2C12 cells were used to examine the expressions of muscular GLUT and glucose uptake in vitro. In C2C12 cells supplemented with isoleucine in the medium, cellular 2-deoxyglucose uptake was increased (P<0·05) through enhancement of the expressions of GLUT4 and GLUT1 (P<0·05). The effect of isoleucine was greater than that of leucine on glucose uptake (P<0·05). Compared with newborn piglets, 35-d-old piglets have comparatively higher GLUT4, GLUT2 and GLUT5 expressions. The results of this study demonstrated that isoleucine supplementation enhanced the intestinal and muscular GLUT expressions, which have important implications that suggest that isoleucine could potentially increase muscle growth and intestinal development by enhancing local glucose uptake in animals and human beings. PMID:27464458

  5. Glucokinase activators.

    PubMed

    Filipski, Kevin J; Futatsugi, Kentaro; Pfefferkorn, Jeffrey A; Stevens, Benjamin D

    2012-07-01

    In this review we highlight recently disclosed progress in the field of small-molecule activators of the human glucokinase enzyme. Several of the reported chemotypes possess structural features that diverge from known leads; some of these modifications appear to be specifically designed to modulate tissue selectivity or discrete parameters of enzyme function (e.g., S0.5 v Vmax). This review will inform the reader of the extent of continued effort being directed toward discovery of a first-in-class drug for Type II diabetes mellitus that functions through this target. Patents were selected from those published in December 2009 up to November 2011; foreign filings were translated where possible to understand the claims and biological techniques utilized to characterize the reported glucokinase activators. Overall, there appears to be a recent trend leading to reduced patent filings for small-molecule glucokinase activators. There are many possible explanations for this trend; however, it is likely that the field has reached maturity and that the downturn of new disclosures represents the transition of many of these programs to the clinic.

  6. Water transport by GLUT2 expressed in Xenopus laevis oocytes.

    PubMed

    Zeuthen, Thomas; Zeuthen, Emil; Macaulay, Nanna

    2007-03-01

    The glucose transporter GLUT2 has been shown to also transport water. In the present paper we investigated the relation between sugar and water transport in human GLUT2 expressed in Xenopus oocytes. Sugar transport was determined from uptakes of non-metabolizable glucose analogues, primarily 3-O-methyl-D-glucopyranoside; key experimental results were confirmed using D(+)-glucose. Water transport was derived from changes in oocyte volume monitored at a high resolution (20 pl, 1 s). Expression of GLUT2 induced a sugar permeability, P(S), of about 5 x 10(-6) cm s(-1) and a passive water permeability, L(p), of 5.5 x 10(-5) cm s(-1). Accordingly, the passive water permeability of a GLUT2 protein is about 10 times higher than its sugar permeability. Both permeabilities were abolished by phloretin. Isosmotic addition of sugar to the bathing solution (replacing mannitol) induced two parallel components of water influx in GLUT2, one by osmosis and one by cotransport. The osmotic driving force arose from sugar accumulation at the intracellular side of the membrane and was given by an intracellular diffusion coefficient for sugar of 10(-6) cm(2) s(-1), one-fifth of the free solution value. The diffusion coefficient was determined in oocytes coexpressing GLUT2 and the water channel AQP1 where water transport was predominantly osmotic. By the cotransport mechanism about 35 water molecules were transported for each sugar molecule by a mechanism within the GLUT2. These water molecules could be transported uphill, against an osmotic gradient, energized by the flux of sugar. This capacity for cotransport is 10 times smaller than that of the Na(+)-coupled glucose transporters (SGLT1). The physiological role of GLUT2 for intestinal transport under conditions of high luminal sugar concentrations is discussed. PMID:17158169

  7. Does apical membrane GLUT2 have a role in intestinal glucose uptake?

    PubMed Central

    Naftalin, Richard J

    2014-01-01

    It has been proposed that the non-saturable component of intestinal glucose absorption, apparent following prolonged exposure to high intraluminal glucose concentrations, is mediated via the low affinity glucose and fructose transporter, GLUT2, upregulated within the small intestinal apical border. The evidence that the non-saturable transport component is mediated via an apical membrane sugar transporter is that it is inhibited by phloretin, after exposure to phloridzin. Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route. As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface. These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments. The model demonstrates that uphill glucose transport via SGLT1 into enterocytes, when short-circuited by any passive glucose carrier in the apical membrane, such as GLUT2, will reduce transcellular glucose absorption and thereby lead to increased paracellular flow. The model also illustrates that apical GLUT2 may usefully act as an osmoregulator to prevent excessive enterocyte volume change with altered luminal glucose concentrations. PMID:25671087

  8. Evolution of glucose utilization: Glucokinase and glucokinase regulator protein

    PubMed Central

    Irwin, David M.; Tan, Huanran

    2014-01-01

    Glucose is an essential nutrient that must be distributed throughout the body to provide energy to sustain physiological functions. Glucose is delivered to distant tissues via be blood stream, and complex systems have evolved to maintain the levels of glucose within a narrow physiological range. Phosphorylation of glucose, by glucokinase, is an essential component of glucose homeostasis, both from the regulatory and metabolic point-of-view. Here we review the evolution of glucose utilization from the perspective of glucokinase. We discuss the origin of glucokinase, its evolution within the hexokinase gene family, and the evolution of its interacting regulatory partner, glucokinase regulatory protein (GCKR). Evolution of the structure and sequence of both glucokinase and GCKR have been necessary to optimize glucokinase in its role in glucose metabolism. PMID:24075984

  9. Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in polarized epithelial cysts.

    PubMed

    Cohen, Merav; Kitsberg, Daniel; Tsytkin, Sabina; Shulman, Maria; Aroeti, Benjamin; Nahmias, Yaakov

    2014-07-01

    GLUT2 is a facilitative glucose transporter, expressed in polarized epithelial cells of the liver, intestine, kidney and pancreas, where it plays a critical role in glucose homeostasis. Together with SGLT1/2, it mediates glucose absorption in metabolic epithelial tissues, where it can be translocated apically upon high glucose exposure. To track the subcellular localization and dynamics of GLUT2, we created an mCherry-hGLUT2 fusion protein and expressed it in multicellular kidney cysts, a major site of glucose reabsorption. Live imaging of GLUT2 enabled us to avoid the artefactual localization of GLUT2 in fixed cells and to confirm the apical GLUT2 model. Live cell imaging showed a rapid 15 ± 3 min PKC-dependent basal-to-apical translocation of GLUT2 in response to glucose stimulation and a fourfold slower basolateral translocation under starvation. These results mark the physiological importance of responding quickly to rising glucose levels. Importantly, we show that phloretin, an apple polyphenol, inhibits GLUT2 translocation in both directions, suggesting that it exerts its effect by PKC inhibition. Subcellular localization studies demonstrated that GLUT2 is endocytosed through a caveolae-dependent mechanism, and that it is at least partly recovered in Rab11A-positive recycling endosome. Our work illuminates GLUT2 dynamics, providing a platform for drug development for diabetes and hyperglycaemia. PMID:25056286

  10. GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish

    PubMed Central

    Marín-Juez, Rubén; Rovira, Mireia; Crespo, Diego; van der Vaart, Michiel; Spaink, Herman P; Planas, Josep V

    2015-01-01

    Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing. PMID:25294126

  11. Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in polarized epithelial cysts.

    PubMed

    Cohen, Merav; Kitsberg, Daniel; Tsytkin, Sabina; Shulman, Maria; Aroeti, Benjamin; Nahmias, Yaakov

    2014-07-01

    GLUT2 is a facilitative glucose transporter, expressed in polarized epithelial cells of the liver, intestine, kidney and pancreas, where it plays a critical role in glucose homeostasis. Together with SGLT1/2, it mediates glucose absorption in metabolic epithelial tissues, where it can be translocated apically upon high glucose exposure. To track the subcellular localization and dynamics of GLUT2, we created an mCherry-hGLUT2 fusion protein and expressed it in multicellular kidney cysts, a major site of glucose reabsorption. Live imaging of GLUT2 enabled us to avoid the artefactual localization of GLUT2 in fixed cells and to confirm the apical GLUT2 model. Live cell imaging showed a rapid 15 ± 3 min PKC-dependent basal-to-apical translocation of GLUT2 in response to glucose stimulation and a fourfold slower basolateral translocation under starvation. These results mark the physiological importance of responding quickly to rising glucose levels. Importantly, we show that phloretin, an apple polyphenol, inhibits GLUT2 translocation in both directions, suggesting that it exerts its effect by PKC inhibition. Subcellular localization studies demonstrated that GLUT2 is endocytosed through a caveolae-dependent mechanism, and that it is at least partly recovered in Rab11A-positive recycling endosome. Our work illuminates GLUT2 dynamics, providing a platform for drug development for diabetes and hyperglycaemia.

  12. Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8.

    PubMed

    Corpe, Christopher P; Eck, Peter; Wang, Jin; Al-Hasani, Hadi; Levine, Mark

    2013-03-29

    Intestinal vitamin C (Asc) absorption was believed to be mediated by the Na(+)-dependent ascorbic acid transporter SVCT1. However, Asc transport across the intestines of SVCT1 knock-out mice is normal indicating that alternative ascorbic acid transport mechanisms exist. To investigate these mechanisms, rodents were gavaged with Asc or its oxidized form dehydroascorbic acid (DHA), and plasma Asc concentrations were measured. Asc concentrations doubled following DHA but not Asc gavage. We hypothesized that the transporters responsible were facilitated glucose transporters (GLUTs). Using Xenopus oocyte expression, we investigated whether facilitative glucose transporters GLUT2 and GLUT5-12 transported DHA. Only GLUT2 and GLUT8, known to be expressed in intestines, transported DHA with apparent transport affinities (Km) of 2.33 and 3.23 mm and maximal transport rates (Vmax) of 25.9 and 10.1 pmol/min/oocyte, respectively. Maximal rates for DHA transport mediated by GLUT2 and GLUT8 in oocytes were lower than maximal rates for 2-deoxy-d-glucose (Vmax of 224 and 32 pmol/min/oocyte for GLUT2 and GLUT8, respectively) and fructose (Vmax of 406 and 116 pmol/min/oocyte for GLUT2 and GLUT8, respectively). These findings may be explained by differences in the exofacial binding of substrates, as shown by inhibition studies with ethylidine glucose. DHA transport activity in GLUT2- and GLUT8-expressing oocytes was inhibited by glucose, fructose, and by the flavonoids phloretin and quercetin. These studies indicate intestinal DHA transport may be mediated by the facilitative sugar transporters GLUT2 and GLUT8. Furthermore, dietary sugars and flavonoids in fruits and vegetables may modulate Asc bioavailability via inhibition of small intestinal GLUT2 and GLUT8.

  13. Calcium absorption by Cav1.3 induces terminal web myosin II phosphorylation and apical GLUT2 insertion in rat intestine.

    PubMed

    Mace, Oliver J; Morgan, Emma L; Affleck, Julie A; Lister, Norma; Kellett, George L

    2007-04-15

    Glucose absorption in rat jejunum involves Ca(2+)- and PKC betaII-dependent insertion of GLUT2 into the apical membrane. Ca(2+)-induced rearrangement of the enterocyte cytoskeleton is thought to enhance paracellular flow. We have therefore investigated the relationships between myosin II regulatory light chain phosphorylation (RLC(20)), absorption of glucose, water and calcium, and mannitol clearance. ML-7, an inhibitor of myosin light chain kinase, diminished the phloretin-sensitive apical GLUT2 but not the phloretin-insensitive SGLT1 component of glucose absorption in rat jejunum perfused with 75 mM glucose. Western blotting and immunocytochemistry revealed marked decreases in RLC(20) phosphorylation in the terminal web and in the levels of apical GLUT2 and PKC betaII, but not SGLT1. Perfusion with phloridzin or 75 mM mannitol, removal of luminal Ca(2+), or inhibition of unidirectional (45)Ca(2+) absorption by nifedipine exerted similar effects. ML-7 had no effect on the absorption of 10 mM Ca(2+), nor clearance of [(14)C]-mannitol, which was less than 0.7% of the rate of glucose absorption. Water absorption did not correlate with (45)Ca(2+) absorption or mannitol clearance. We conclude that the Ca(2+) necessary for contraction of myosin II in the terminal web enters via an L-type channel, most likely Ca(v)1.3, and is dependent on SGLT1. Moreover, terminal web RLC(20) phosphorylation is necessary for apical GLUT2 insertion. The data confirm that glucose absorption by paracellular flow is negligible, and show further that paracellular flow makes no more than a minimal contribution to jejunal Ca(2+) absorption at luminal concentrations prevailing after a meal.

  14. Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance

    PubMed Central

    Li, Xinhua; Ho, Sherry SY; Leong, Sai Mun; Wong, Reuben K; Koay, Evelyn SC; Ferraris, Ronaldo P

    2014-01-01

    Background Gastrointestinal symptoms and malabsorption following fructose ingestion (fructose intolerance) are common in functional gastrointestinal disorders (FGID). The underlying mechanism is unclear, but is hypothesized to be related an abnormality of intestinal fructose transporter proteins. Objective To assess the expression of the main intestinal fructose transporter proteins, glucose transport protein 5 (GLUT5) and 2 (GLUT2), in FGID. Methods The expression of GLUT5 and GLUT2 protein and mRNA in small intestinal biopsy tissue was investigated using real-time reverse-transcription PCR and Western immunoblotting in 11 adults with FGID and fructose intolerance ascertained by breath testing and in 15 controls. Results Median expression levels of GLUT5 mRNA normalized to beta-actin were 0.18 (interquartile range, IQR, 0.13–0.21) in patients and 0.17 (IQR 0.12–0.19) in controls (p > 0.05). Respective levels of GLUT2 mRNA were 0.26 (IQR 0.20–0.31) and 0.26 (IQR 0.19–0.31) (p > 0.05). Median expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR 0.52–1.68) in patients and 0.95 (IQR 0.59–1.15) in controls (p > 0.05). Respective protein expression levels for GLUT2 were 1.56 (IQR 1.06–2.14) and 1.35 (IQR 0.96–1.79) (p > 0.05). Conclusions Human fructose intolerance may not be associated with marked changes in GLUT5 and GLUT2 expression. Replication of these results in a larger subject group, including measures of transporter activation and membrane and subcellular localization, is warranted. PMID:24918004

  15. Insights into the role of neuronal glucokinase

    PubMed Central

    De Backer, Ivan; Hussain, Sufyan S.; Gardiner, James V.

    2016-01-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. PMID:27189932

  16. Insights into the role of neuronal glucokinase.

    PubMed

    De Backer, Ivan; Hussain, Sufyan S; Bloom, Stephen R; Gardiner, James V

    2016-07-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. PMID:27189932

  17. Insights into Mechanism of Glucokinase Activation

    PubMed Central

    Liu, Shenping; Ammirati, Mark J.; Song, Xi; Knafels, John D.; Zhang, Jeff; Greasley, Samantha E.; Pfefferkorn, Jeffrey A.; Qiu, Xiayang

    2012-01-01

    Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk. PMID:22298776

  18. Structure-Activity Relationship of Azaindole-Based Glucokinase Activators.

    PubMed

    Paczal, Attila; Bálint, Balázs; Wéber, Csaba; Szabó, Zoltán B; Ondi, Levente; Theret, Isabelle; De Ceuninck, Frédéric; Bernard, Catherine; Ktorza, Alain; Perron-Sierra, Francoise; Kotschy, András

    2016-01-28

    7-Azaindole has been identified as a novel bidentate anchor point for allosteric glucokinase activators. A systematic investigation around three principal parts of the new small molecule glucokinase activators led to a robust SAR in agreement with structural data that also helped to assess the conformational flexibility of the allosteric activation site. The increase in glucose uptake resulting from glucokinase activation in hepatocytes in vitro translated into the efficient lowering of glucose levels in vivo with the best compounds. PMID:26685731

  19. Zonation of glucokinase in rat liver changes during postnatal development.

    PubMed

    Kirchner, G; Harbers, M; Bünsch, A; Seitz, H J; Höppner, W

    1993-08-01

    In the liver many metabolic pathways are preferentially localized in different zones of the acinus. It is assumed that this zonation allows an efficient adaptation to different states of nutrition, because alternative pathways can be regulated independently. It is reported that the rate limiting enzyme for the glycolytic pathway, glucokinase (EC 2.7.1.2), is predominantly located in the pericentral zone. The gene expression of glucokinase is induced to a maximum level after a carbohydrate-rich diet. In starved or diabetic rats glucokinase gene expression is barely detectable. In postnatal development glucokinase is induced to significant levels only from day 14 onwards. The distribution of the glucokinase protein in the rat liver lobule in the first 4 weeks of postnatal life was investigated by immunohistochemistry and compared to the distribution observed in adult rats. In adult rats considerably high levels of glucokinase are measureable as shown by immunoblotting utilizing a monospecific antibody and a photometric assay of glucokinase enzyme activity, respectively. Immunohistochemically the hepatic glucokinase protein is detected in the perivenous area. During postnatal development, the quantities of hepatic glucokinase protein and glucokinase enzyme activity start to increase significantly from day 15 onwards. Subsequently, glucokinase levels rise further until day 29. In contrast to the results obtained by immunoblotting, glucokinase is already detectable in some liver cells in sections from 6-day-old rats by immunohistochemistry. The liver lobule structure at this age is not completely developed, therefore it is not possible to definitely assign these cells to periportal or pericentral areas. At day 10 post partum the number of glucokinase expressing cells, which appear to be localized preferentially in the periportal zone, increases. In agreement with the immunoblotting, an immense increase in glucokinase activity was observed at day 14. The periportal

  20. GLUT2 proteins and PPARγ transcripts levels are increased in liver of ovariectomized rats: reversal effects of resistance training

    PubMed Central

    Tomaz, Luciane M.; Barbosa, Marina R.; Farahnak, Zahra; Lagoeiro, Cristiani G.; Magosso, Natalia S.S; Lavoie, Jean-Marc; Perez, Sérgio E. A.

    2016-01-01

    [Purpose] This study investigated the effects of ovariectomy (Ovx) and 12 weeks of resistance training (RT) on gene expression of GLUT2, the main glucose transporter in the liver, and on PPARγ, a transcription factor known to target GLUT2 expression. [Methods] Forty Holtzman rats were divided into 5 groups: Sham-sedentary (Sed), Sham- RT, Ovx-Sed, Ovx-RT, and Ovx-Sed with hormone replacement (E2). The RT protocol consisted of sessions held every 72 h for 12 weeks, during which the animals performed 4 to 9 vertical climbs (1.1 m) at 2 min intervals with progressively heavier weights (30 g after the fourth climb) tied to the tail. The E2 silastic capsule was inserted into the rats’ backs 48 hours before the first RT session. [Results] In addition to liver fat, GLUT2 protein levels and PPARγ transcripts were increased (P < 0.05) in Ovx compared to Sham-Sed animals, suggesting increased hepatic glucose uptake under estrogen deficient conditions. RT and E2 in Ovx rats decreased liver fat accumulation as well as GLUT2 and PPARγ gene expression to the level of Sham- Sed animals. [Conclusion] The results of this study suggest that liver GLUT2 as well as PPARγ expression in Ovx rats are accompanied by increased fat accumulation and glucose uptake, thus providing a substrate for increased de novo lipogenesis. RT appears to be an appropriate exercise model to circumvent these effects. PMID:27508154

  1. SUMOylation of Pancreatic Glucokinase Regulates Its Cellular Stability and Activity*

    PubMed Central

    Aukrust, Ingvild; Bjørkhaug, Lise; Negahdar, Maria; Molnes, Janne; Johansson, Bente B.; Müller, Yvonne; Haas, Wilhelm; Gygi, Steven P.; Søvik, Oddmund; Flatmark, Torgeir; Kulkarni, Rohit N.; Njølstad, Pål R.

    2013-01-01

    Glucokinase is the predominant hexokinase expressed in hepatocytes and pancreatic β-cells, with a pivotal role in regulating glucose-stimulated insulin secretion, illustrated by glucokinase gene mutations causing monogenic diabetes and congenital hyperinsulinemic hypoglycemia. A complex tissue-specific network of mechanisms regulates this enzyme, and a major unanswered question in glucokinase biology is how post-translational modifications control the function of the enzyme. Here, we show that the pancreatic isoform of human glucokinase is SUMOylated in vitro, using recombinant enzymes, and in insulin-secreting model cells. Three N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform. SUMO-1 and E2 overexpression stabilized preferentially the wild-type human pancreatic enzyme in MIN6 β-cells, and SUMOylation increased the catalytic activity of recombinant human glucokinase in vitro and also of glucokinase in target cells. Small ubiquitin-like modifier conjugation represents a novel form of post-translational modification of the enzyme, and it may have an important regulatory function in pancreatic β-cells. PMID:23297408

  2. Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity

    PubMed Central

    Park, Joo-Man; Kim, Tae-Hyun; Jo, Seong-Ho; Kim, Mi-Young; Ahn, Yong-Ho

    2015-01-01

    Glucokinase (GK), mainly expressed in the liver and pancreatic β-cells, is critical for maintaining glucose homeostasis. GK expression and kinase activity, respectively, are both modulated at the transcriptional and post-translational levels. Post-translationally, GK is regulated by binding the glucokinase regulatory protein (GKRP), resulting in GK retention in the nucleus and its inability to participate in cytosolic glycolysis. Although hepatic GKRP is known to be regulated by allosteric mechanisms, the precise details of modulation of GKRP activity, by post-translational modification, are not well known. Here, we demonstrate that GKRP is acetylated at Lys5 by the acetyltransferase p300. Acetylated GKRP is resistant to degradation by the ubiquitin-dependent proteasome pathway, suggesting that acetylation increases GKRP stability and binding to GK, further inhibiting GK nuclear export. Deacetylation of GKRP is effected by the NAD+-dependent, class III histone deacetylase SIRT2, which is inhibited by nicotinamide. Moreover, the livers of db/db obese, diabetic mice also show elevated GKRP acetylation, suggesting a broader, critical role in regulating blood glucose. Given that acetylated GKRP may affiliate with type-2 diabetes mellitus (T2DM), understanding the mechanism of GKRP acetylation in the liver could reveal novel targets within the GK-GKRP pathway, for treating T2DM and other metabolic pathologies. PMID:26620281

  3. Determination of endopolyphosphatase using polyphosphate glucokinase.

    PubMed

    Kowalczyk, T H; Phillips, N F

    1993-07-01

    A method has been developed for determining endopolyphosphatase (polyphosphate depolymerase, EC 3.6.1.10) activity. The enzyme catalyzes the hydrolysis of inorganic polyphosphates [poly(Ps)] by cleaving internal phosphoanhydride bonds without removal of terminal phosphate residues. During the reaction, shorter poly(P) chains are formed and the molar concentration of poly(P) increases. This enzymatic activity is difficult to quantitate, because the substrates and products of the reaction are chemically identical. The commonly used viscometric method lacks sensitivity and cannot be used with shorter poly(P) substrates. The method described here overcomes these problems, and in addition is rapid, simple, and can be used for distinguishing between the endopolyphosphatase and exopolyphosphatase (EC 3.6.1.11) activities. It is based on monitoring the increase in the number of poly(P) chains generated by endopolyphosphatase. For this purpose, the method takes advantage of the specific property of poly(P) glucokinase (EC 2.7.1.63) which utilizes poly(Ps) of different sizes present in the endopolyphosphatase reaction mixture and reduces them to fairly uniform very short-chain product, poly(P)m. The concentration of poly(P)m is expressed in terms of acid-labile phosphorus and is proportional to the duration of the endopolyphosphatase reaction (i.e., the number of original poly(P) chains) and to protein concentration. The increase in the poly(P)m concentration is a relative measure of the endopolyphosphatase activity. Under certain conditions, m equals 3.5 and the activity can be expressed in standard units, since the exact number of poly(P) chains formed by endopolyphosphatase can be calculated from the increase in molar concentration of poly(P)3.5. Accuracy and advantages of the assay are discussed. PMID:8396361

  4. Familial adult onset hyperinsulinism due to an activating glucokinase mutation: Implications for pharmacological glucokinase activation

    PubMed Central

    Challis, Benjamin G.; Harris, Julie; Sleigh, Alison; Isaac, Iona; Orme, Steve M.; Seevaratnam, Nandini; Dhatariya, Ketan; Simpson, Helen L.; Semple, Robert K.

    2016-01-01

    Context Glucokinase (GCK) phosphorylates and thereby “traps” glucose in cells, thus serving as a gatekeeper for cellular glucose metabolism, particularly in hepatocytes and pancreatic beta cells. In humans, activating GCK mutations cause familial hyperinsulinaemic hypoglycaemia (GCK-HH), leading to keen interest in the potential of small molecule glucokinase activators (GKAs) as treatments for diabetes mellitus. Many such agents have been developed, however observation of side effects including hypertriglyceridaemia and hepatic steatosis have delayed their clinical development. Objective To describe the clinical presentation and metabolic profiles of affected family members in a kindred with familial hyperinsulinism of adult presentation due to a known activating mutation in GCK. Design Clinical, biochemical and metabolic assessment, and GCK sequencing in affected family members. Results In the 60 year-old female proband, hyperinsulinaemic hypoglycaemia (blood glucose 2.1mmol/mol, insulin 18pmol/l) was confirmed following 34 hours of fasting, however abdominal computed tomography (CT), pancreatic MRI, endoscopic ultrasound, octreotide scintigraphy and selective arterial calcium stimulation failed to localise an insulinoma. A prolonged OGTT revealed fasting hypoglycaemia that was exacerbated after glucose challenge, consistent with dysregulated glucose-stimulated insulin release. A heterozygous activating mutation, p.Val389Leu, in the glucokinase gene (GCK) was found in the proband and four other family members. Of these, two had been investigated elsewhere for recurrent hypoglycaemia in adulthood, while the other two adult relatives were asymptomatic despite profound hypoglycaemia. All three of the available family members with the p.Val389Leu mutation had normal serum lipid profiles, normal rates of fasting hepatic de novo lipogenesis and had hepatic triglyceride levels commensurate with their degree of adiposity. Conclusion Activating GCK mutations may

  5. Oat β-glucan depresses SGLT1- and GLUT2-mediated glucose transport in intestinal epithelial cells (IEC-6).

    PubMed

    Abbasi, Nazanin N; Purslow, Peter P; Tosh, Susan M; Bakovic, Marica

    2016-06-01

    Oat β-glucan consumption is linked to reduced risk factors associated with diabetes and obesity by lowering glycemic response and serum level of low-density lipoproteins. The purpose of this study was to identify the mechanism of action of oat β-glucan at the interface between the gut wall and the lumen responsible for attenuating glucose levels. We proposed that viscous oat β-glucan acts as a physical barrier to glucose uptake in normally absorptive gut epithelial cells IEC-6 by affecting the expression of intestinal glucose transporters. Concentration and time-dependent changes in glucose uptake were established by using a nonmetabolizable glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose. The effectiveness of nutrient transport in IEC-6 cells was shown by significant differences in glucose uptake and corresponding transporter expression. The expressions of glucose transporters sodium-glucose-linked transport protein 1 (SGLT1) and glucose transporter 2 (GLUT2) increased with time (0-60 minutes) and glucose levels (5-25 mmol/L). The suppression of glucose uptake and SGLT1 and GLUT2 expression by increasing concentrations (4-8 mg/mL) of oat β-glucan demonstrated a direct effect of the physical properties of oat β-glucan on glucose transport. These results affirmed oat β-glucan as a dietary agent for minimizing postprandial glucose and showed that modulating the activity of the key intestinal glucose transporters with oat β-glucan could be an effective way of lowering blood glucose levels in patients with diabetes. PMID:27188900

  6. The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine.

    PubMed

    Mace, Oliver J; Schindler, Marcus; Patel, Sonal

    2012-06-15

    Intestinal enteroendocrine cells (IECs) secrete gut peptides in response to both nutrients and non-nutrients. Glucose and amino acids both stimulate gut peptide secretion. Our hypothesis was that the facilitative glucose transporter, GLUT2, could act as a glucose sensor and the calcium-sensing receptor, CasR, could detect amino acids in the intestine to modify gut peptide secretion. We used isolated loops of rat small intestine to study the secretion of gluco-insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) secretion stimulated by luminal perfusion of nutrients or bile acid. Inhibition of the sodium-dependent glucose cotransporter 1 (SGLT1) with phloridzin partially inhibited GIP, GLP-1 and PYY secretion by 45%, suggesting another glucose sensor might be involved in modulating peptide secretion. The response was completely abolished in the presence of the GLUT2 inhibitors phloretin or cytochalasin B. Given that GLUT2 modified gut peptide secretion stimulated by glucose, we investigated whether it was involved in the secretion of gut peptide by other gut peptide secretagogues. Phloretin completely abolished gut peptide secretion stimulated by artificial sweetener (sucralose), dipeptide (glycylsarcosine), lipid (oleoylethanolamine), short chain fatty acid (propionate) and major rat bile acid (taurocholate) indicating a fundamental position for GLUT2 in the gut peptide secretory mechanism. We investigated how GLUT2 was able to influence gut peptide secretion mediated by a diverse range of stimulators and discovered that GLUT2 affected membrane depolarisation through the closure of K+(ATP)-sensitive channels. In the absence of SGLT1 activity (or presence of phloridzin), the secretion of GIP, GLP-1 and PYY was sensitive to K+(ATP)-sensitive channel modulators tolbutamide and diazoxide. L-amino acids phenylalanine (Phe), tryptophan (Trp), asparagine (Asn), arginine (Arg) and glutamine (Gln) also stimulated GIP, GLP-1 and

  7. Control of liver glucokinase activity: A potential new target for incretin hormones?

    PubMed

    Francini, Flavio; Massa, María Laura; Polo, Mónica Patricia; Villagarcía, Hernán; Castro, María Cecilia; Gagliardino, Juan José

    2015-12-01

    We tested the exendin-4 and des-fluoro-sitagliptin effects on fructose-induced increase in liver glucokinase activity in rats with impaired glucose tolerance and the exendin-4 effect on glucokinase activity in HepG2 cells incubated with fructose in the presence/absence of exendin-9-39. After 3 weeks of in vivo fructose administration we measured: (1) serum glucose, insulin and triglyceride levels; (2) liver and HepG2 cells glucokinase activity and (3) liver glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase mRNA and protein levels. Fructose fed rats had: hypertriglyceridemia, hyperinsulinemia and high liver glucokinase activity (mainly located in the cytosolic fraction) together with higher glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase mRNA and protein concentrations compared to control rats. Co-administration of either exendin-4 or des-fluoro-sitagliptin prevented serum and liver changes except glucokinase protein expression. Exendin-4 also prevented fructose-induced increase in glucokinase activity in cultured HepG2 cells, effect blunted by co-incubation with exendin-9-36. In conclusion exendin-4/des-fluro-sitagliptin prevented fructose-induced effect on glucokinase activity, mainly affecting enzyme activity modulators. Exendin 9-39 blunted in vitro protective exendin-4 effect on glucokinase activity, thus suggesting a direct effect of the later on hepatocytes through GLP-1 receptor. Alterations of glucokinase activity modulators could play a role in the pathogenesis of liver dysfunction, becoming a potential new treatment target for GLP-1 receptor agonists.

  8. Atherogenic, fibrotic and glucose utilising actions of glucokinase activators on vascular endothelium and smooth muscle

    PubMed Central

    2014-01-01

    Background Pharmaceutical interventions for diabetes aim to control glycaemia and to prevent the development of complications, such as cardiovascular diseases. Some anti-hyperglycaemic drugs have been found to have adverse cardiovascular effects in their own right, limiting their therapeutic role. Glucokinase activity in the pancreas is critical in enhancing insulin release in response to hyperglycaemia. Glucokinase activators (GKAs) are novel agents for diabetes which act by enhancing the formation of glucose-6-phosphate leading to increased insulin production and subsequent suppression of blood glucose. Little, however, is known about the direct effects of GKAs on cardiovascular cells. Methods The effect of the GKAs RO28-1675 and Compound A on glucose utilisation in bovine aortic endothelial cells (BAEC) and rat MIN6 was observed by culturing the cells at high and low glucose concentration in the presence and absence of the GKAs and measuring glucose consumption. The effect of RO28-1675 at various concentrations on glucose-dependent signalling in BAEC was observed by measuring Smad2 phosphorylation by Western blotting. The effect of RO28-1675 on TGF-β stimulated proteoglycan synthesis was measured by 35S-SO4 incorporation and assessment of proteoglycan size by SDS-PAGE. The effects of RO28-1675 on TGF-β mediated Smad2C phosphorylation in BAEC was observed by measurement of pSmad2C levels. The direct actions of RO28-1675 on vascular reactivity were observed by measuring arteriole tone and lumen diameter. Results GKAs were demonstrated to increase glucose utilisation in pancreatic but not endothelial cells. Glucose-activated Smad2 phosphorylation was decreased in a dose-dependent fashion in the presence of RO28-1675. No effect of RO28-1675 was observed on TGF-β stimulated proteoglycan production. RO28-1675 caused a modest dilation in arteriole but not contractile sensitivity. Conclusions GKA RO28-1675 did not increase glucose consumption in endothelial cells

  9. Insulin-positive, Glut2-low cells present within mouse pancreas exhibit lineage plasticity and are enriched within extra-islet endocrine cell clusters.

    PubMed

    Beamish, Christine A; Strutt, Brenda J; Arany, Edith J; Hill, David J

    2016-04-18

    Regeneration of insulin-producing β-cells from resident pancreas progenitors requires an understanding of both progenitor identity and lineage plasticity. One model suggested that a rare β-cell sub-population within islets demonstrated multi-lineage plasticity. We hypothesized that β-cells from young mice (postnatal day 7, P7) exhibit such plasticity and used a model of islet dedifferentiation toward a ductal epithelial-cell phenotype to test this theory. RIPCre;Z/AP(+/+) mice were used to lineage trace the fate of β-cells during dedifferentiation culture by a human placental alkaline phosphatase (HPAP) reporter. There was a significant loss of HPAP-expressing β-cells in culture, but remaining HPAP(+) cells lost insulin expression while gaining expression of the epithelial duct cell marker cytokeratin-19 (Ck19). Flow cytometry and recovery of β-cell subpopulations from whole pancreas vs. islets suggest that the HPAP(+)Ck19(+) cells had derived from insulin-positive, glucose-transporter-2-low (Ins(+)Glut2(LO)) cells, representing 3.5% of all insulin-expressing cells. The majority of these cells were found outside of islets within clusters of <5 β-cells. These insulin(+)Glut2(LO) cells demonstrated a greater proliferation rate in vivo and in vitro as compared to insulin(+)Glut2(+) cells at P7, were retained into adulthood, and a subset differentiated into endocrine, ductal, and neural lineages, illustrating substantial plasticity. Results were confirmed using RIPCre;ROSA- eYFP mice. Quantitative PCR data indicated these cells possess an immature β-cell phenotype. These Ins(+)Glut2(LO) cells may represent a resident population of cells capable of forming new, functional β-cells, and which may be potentially exploited for regenerative therapies in the future.

  10. Insulin-positive, Glut2-low cells present within mouse pancreas exhibit lineage plasticity and are enriched within extra-islet endocrine cell clusters.

    PubMed

    Beamish, Christine A; Strutt, Brenda J; Arany, Edith J; Hill, David J

    2016-04-18

    Regeneration of insulin-producing β-cells from resident pancreas progenitors requires an understanding of both progenitor identity and lineage plasticity. One model suggested that a rare β-cell sub-population within islets demonstrated multi-lineage plasticity. We hypothesized that β-cells from young mice (postnatal day 7, P7) exhibit such plasticity and used a model of islet dedifferentiation toward a ductal epithelial-cell phenotype to test this theory. RIPCre;Z/AP(+/+) mice were used to lineage trace the fate of β-cells during dedifferentiation culture by a human placental alkaline phosphatase (HPAP) reporter. There was a significant loss of HPAP-expressing β-cells in culture, but remaining HPAP(+) cells lost insulin expression while gaining expression of the epithelial duct cell marker cytokeratin-19 (Ck19). Flow cytometry and recovery of β-cell subpopulations from whole pancreas vs. islets suggest that the HPAP(+)Ck19(+) cells had derived from insulin-positive, glucose-transporter-2-low (Ins(+)Glut2(LO)) cells, representing 3.5% of all insulin-expressing cells. The majority of these cells were found outside of islets within clusters of <5 β-cells. These insulin(+)Glut2(LO) cells demonstrated a greater proliferation rate in vivo and in vitro as compared to insulin(+)Glut2(+) cells at P7, were retained into adulthood, and a subset differentiated into endocrine, ductal, and neural lineages, illustrating substantial plasticity. Results were confirmed using RIPCre;ROSA- eYFP mice. Quantitative PCR data indicated these cells possess an immature β-cell phenotype. These Ins(+)Glut2(LO) cells may represent a resident population of cells capable of forming new, functional β-cells, and which may be potentially exploited for regenerative therapies in the future. PMID:27010375

  11. Insulin secretion impairment in Sirt6 knockout pancreatic β cells is mediated by suppression of the FoxO1-Pdx1-Glut2 pathway

    PubMed Central

    Song, Mi-Young; Wang, Jie; Ka, Sun-O; Bae, Eun Ju; Park, Byung-Hyun

    2016-01-01

    Sirtuin 6 (Sirt6), a chromatin associated class III deacetylase, controls whole-body energy homeostasis and has a critical role in glucose-stimulated insulin secretion (GSIS) in pancreatic β cells. However, its underlying molecular mechanism remains poorly understood. To gain further insights, we studied the pathway by which Sirt6 regulates GSIS utilizing mice lacking Sirt6 in their β cells (βS6KO). Further, we overexpressed wild type or deacetylase-inactive mutant Sirt6 in isolated islets as well as in MIN6 cells. We confirmed that βS6KO mice developed glucose intolerance with severely impaired GSIS. Gene expression analysis of knockout islets and overexpression studies demonstrated that Sirt6 deacetylates forkhead box protein O1 (FoxO1) to trigger its nuclear export and releases its transcriptional repression of key glucose sensing genes such as Pdx1 and Glut2. Ectopic overexpression of Sirt6 in knockout islets resulted in rescue of the defective insulin secretion and restoration of the expression of Pdx1 and Glut2. These results show that Sirt6 in pancreatic β cells deacetylates FoxO1 and subsequently increases the expression of Pdx1 and Glut2 to maintain the glucose-sensing ability of pancreatic β cells and systemic glucose tolerance. PMID:27457971

  12. The Hepatoselective Glucokinase Activator PF-04991532 Ameliorates Hyperglycemia without Causing Hepatic Steatosis in Diabetic Rats

    PubMed Central

    Erion, Derek M.; Lapworth, Amanda; Amor, Paul A.; Bai, Guoyun; Vera, Nicholas B.; Clark, Ronald W.; Yan, Qingyun; Zhu, Yimin; Ross, Trenton T.; Purkal, Julie; Gorgoglione, Matthew; Zhang, Guodong; Bonato, Vinicius; Baker, Levenia; Barucci, Nicole; D’Aquila, Theresa; Robertson, Alan; Aiello, Robert J.; Yan, Jiangli; Trimmer, Jeff; Rolph, Timothy P.; Pfefferkorn, Jeffrey A.

    2014-01-01

    Hyperglycemia resulting from type 2 diabetes mellitus (T2DM) is the main cause of diabetic complications such as retinopathy and neuropathy. A reduction in hyperglycemia has been shown to prevent these associated complications supporting the importance of glucose control. Glucokinase converts glucose to glucose-6-phosphate and determines glucose flux into the β-cells and hepatocytes. Since activation of glucokinase in β-cells is associated with increased risk of hypoglycemia, we hypothesized that selectively activating hepatic glucokinase would reduce fasting and postprandial glucose with minimal risk of hypoglycemia. Previous studies have shown that hepatic glucokinase overexpression is able to restore glucose homeostasis in diabetic models; however, these overexpression experiments have also revealed that excessive increases in hepatic glucokinase activity may also cause hepatosteatosis. Herein we sought to evaluate whether liver specific pharmacological activation of hepatic glucokinase is an effective strategy to reduce hyperglycemia without causing adverse hepatic lipids changes. To test this hypothesis, we evaluated a hepatoselective glucokinase activator, PF-04991532, in Goto-Kakizaki rats. In these studies, PF-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. During a hyperglycemic clamp in Goto-Kakizaki rats, the glucose infusion rate was increased approximately 5-fold with PF-04991532. This increase in glucose infusion can be partially attributed to the 60% reduction in endogenous glucose production. While PF-04991532 induced dose-dependent increases in plasma triglyceride concentrations it had no effect on hepatic triglyceride concentrations in Goto-Kakizaki rats. Interestingly, PF-04991532 decreased intracellular AMP concentrations and increased hepatic futile cycling. These data suggest that hepatoselective glucokinase

  13. The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats.

    PubMed

    Erion, Derek M; Lapworth, Amanda; Amor, Paul A; Bai, Guoyun; Vera, Nicholas B; Clark, Ronald W; Yan, Qingyun; Zhu, Yimin; Ross, Trenton T; Purkal, Julie; Gorgoglione, Matthew; Zhang, Guodong; Bonato, Vinicius; Baker, Levenia; Barucci, Nicole; D'Aquila, Theresa; Robertson, Alan; Aiello, Robert J; Yan, Jiangli; Trimmer, Jeff; Rolph, Timothy P; Pfefferkorn, Jeffrey A

    2014-01-01

    Hyperglycemia resulting from type 2 diabetes mellitus (T2DM) is the main cause of diabetic complications such as retinopathy and neuropathy. A reduction in hyperglycemia has been shown to prevent these associated complications supporting the importance of glucose control. Glucokinase converts glucose to glucose-6-phosphate and determines glucose flux into the β-cells and hepatocytes. Since activation of glucokinase in β-cells is associated with increased risk of hypoglycemia, we hypothesized that selectively activating hepatic glucokinase would reduce fasting and postprandial glucose with minimal risk of hypoglycemia. Previous studies have shown that hepatic glucokinase overexpression is able to restore glucose homeostasis in diabetic models; however, these overexpression experiments have also revealed that excessive increases in hepatic glucokinase activity may also cause hepatosteatosis. Herein we sought to evaluate whether liver specific pharmacological activation of hepatic glucokinase is an effective strategy to reduce hyperglycemia without causing adverse hepatic lipids changes. To test this hypothesis, we evaluated a hepatoselective glucokinase activator, PF-04991532, in Goto-Kakizaki rats. In these studies, PF-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. During a hyperglycemic clamp in Goto-Kakizaki rats, the glucose infusion rate was increased approximately 5-fold with PF-04991532. This increase in glucose infusion can be partially attributed to the 60% reduction in endogenous glucose production. While PF-04991532 induced dose-dependent increases in plasma triglyceride concentrations it had no effect on hepatic triglyceride concentrations in Goto-Kakizaki rats. Interestingly, PF-04991532 decreased intracellular AMP concentrations and increased hepatic futile cycling. These data suggest that hepatoselective glucokinase

  14. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 1. Discovery of a novel tool compound for in vivo proof-of-concept.

    PubMed

    Ashton, Kate S; Andrews, Kristin L; Bryan, Marian C; Bryan, Marion C; Chen, Jie; Chen, Kui; Chen, Michelle; Chmait, Samer; Croghan, Michael; Cupples, Rod; Fotsch, Christopher; Helmering, Joan; Jordan, Steve R; Kurzeja, Robert J M; Michelsen, Klaus; Pennington, Lewis D; Poon, Steve F; Sivits, Glenn; Van, Gwyneth; Vonderfecht, Steve L; Wahl, Robert C; Zhang, Jiandong; Lloyd, David J; Hale, Clarence; St Jean, David J

    2014-01-23

    Small molecule activators of glucokinase have shown robust efficacy in both preclinical models and humans. However, overactivation of glucokinase (GK) can cause excessive glucose turnover, leading to hypoglycemia. To circumvent this adverse side effect, we chose to modulate GK activity by targeting the endogenous inhibitor of GK, glucokinase regulatory protein (GKRP). Disrupting the GK-GKRP complex results in an increase in the amount of unbound cytosolic GK without altering the inherent kinetics of the enzyme. Herein we report the identification of compounds that efficiently disrupt the GK-GKRP interaction via a previously unknown binding pocket. Using a structure-based approach, the potency of the initial hit was improved to provide 25 (AMG-1694). When dosed in ZDF rats, 25 showed both a robust pharmacodynamic effect as well as a statistically significant reduction in glucose. Additionally, hypoglycemia was not observed in either the hyperglycemic or normal rats.

  15. Effect of GLP-1 treatment on GLUT2 and GLUT4 expression in type 1 and type 2 rat diabetic models.

    PubMed

    Villanueva-Peñacarrillo, M L; Puente, J; Redondo, A; Clemente, F; Valverde, I

    2001-07-01

    Glucagon-like peptide-1 (G LP-1) is an incretin with glucose-dependent insulinotropic and insulin-independent antidiabetic properties that exerts insulin-like effects on glucose metabolism in rat liver, skeletal muscle, and fat. This study aimed to search for the effect of a prolonged treatment, 3 ds, with GLP-1 on glucotransporter GLUT2 expression in liver, and on that of GLUT4 in skeletal muscle and fat, in rats. Normal rats and streptozotocin-induced type 1 and type 2 diabetic models were used; diabetic rats were also treated with insulin for comparison. In normal rats, GLP-1 treatment reduced in the three tissues the corresponding glucotransporter protein level, without modifying their mRNA. In the type 2 diabetic model, GLP-1, like insulin, stimulated in liver and fat only the glucotransporter translational process, while in the muscle an effect at the GLUT4 transcriptional level was also observed. In the type 1 diabetic model, GLP-1 apparently exerted in the liver only a posttranslational effect on GLUT2 expression; in muscle and fat, while insulin was shown to have an action on GLUT4 at both transcriptional and translational levels, the effect of GLP-1 was restricted to glucotransporter translation. In normal and diabetic rats, exogenous GLP-1 controlled the glucotransporter expression in extrapancreatic tissues participating in the overall glucose homeostasis-liver, muscle, and fat-where the effect of the peptide seems to be exerted only at the translational and/or posttranslational level; in muscle and fat, the presence of insulin seems to be required for GLP-1 to activate the transcriptional process. The stimulating action of GLP-1 on GLUT2 and GLUT4 expression, mRNA or protein, could be a mechanism by which, at least in part, the peptide exerts its lowering effect on blood glucose.

  16. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx.

    PubMed

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette; Holst, Jens Juul

    2015-06-15

    Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans, but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide, which causes hyperpolarization, eliminated the response. Luminal inhibition of the sodium-glucose cotransporter 1 (SGLT1) (by phloridzin) eliminated glucose-stimulated release as well as secretion stimulated by luminal methyl-α-D-glucopyranoside (20% wt/vol), a metabolically inactive SGLT1 substrate, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct KATP channel closure by sulfonylureas stimulated secretion. Therefore, glucose stimulates NT secretion by uptake through SGLT1 and GLUT2, both causing depolarization either as a consequence of sodium-coupled uptake (SGLT1) or by closure of KATP channels (GLUT2 and SGLT1) secondary to the ATP-generating metabolism of glucose.

  17. Chard (Beta vulgaris L. var. cicla) extract ameliorates hyperglycemia by increasing GLUT2 through Akt2 and antioxidant defense in the liver of rats.

    PubMed

    Gezginci-Oktayoglu, Selda; Sacan, Ozlem; Bolkent, Sehnaz; Ipci, Yesim; Kabasakal, Levent; Sener, Goksel; Yanardag, Refiye

    2014-01-01

    Chard is a plant used as an alternative hypoglycemic agent by diabetic people in Turkey. The aim of this study was to examine the molecular mechanism of hypoglycemic effects of chard extract. Male Sprague-Dawley rats (6-7 months old) were divided into five groups for this investigation: (1) control, (2) hyperglycemic, (3) hyperglycemic+chard, (4) hyperglycemic+insulin, (5) hyperglycemic+chard+insulin. Fourteen days after animals were rendered hyperglycemic by intraperitoneal injection of 60 mg/kg streptozotocin, the chard water extract (2 g/kg/day) or/and insulin (6 U/kg/day) was administered for 45 days. Hypoglycemic effect of chard extract was demonstrated by a significant reduction in the fasting blood glucose and increased glycogen levels in liver of chard extract-treated hyperglycemic rats. Moreover, activity of adenosine deaminase, which is suggested as an important enzyme for modulating the bioactivity of insulin, was decreased by chard treatment. Immunostaining analysis showed increased nuclear translocation of Akt2 and synthesis of GLUT2 in the hepatocytes of chard or/and insulin-treated hyperglycemic rats. The oxidative stress was decreased and antioxidant defense was increased by chard extract or/and insulin treatment to hyperglycemic rats according to the decreased malondialdehyde formation, the activities of catalase, superoxide dismutase, myeloperoxidase and increased glutathione levels. These findings suggest that chard extract might improve glucose response by increasing GLUT2 through Akt2 and antioxidant defense in the liver.

  18. Chronic Ethanol Consumption Inhibits Glucokinase Transcriptional Activity by Atf3 and Triggers Metabolic Syndrome in Vivo*

    PubMed Central

    Kim, Ji Yeon; Hwang, Joo-Yeon; Lee, Dae Yeon; Song, Eun Hyun; Park, Keon Jae; Kim, Gyu Hee; Jeong, Eun Ae; Lee, Yoo Jeong; Go, Min Jin; Kim, Dae Jin; Lee, Seong Su; Kim, Bong-Jo; Song, Jihyun; Roh, Gu Seob; Gao, Bin; Kim, Won-Ho

    2014-01-01

    Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from −287 to −158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3 siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis. PMID:25074928

  19. All1371 is a polyphosphate-dependent glucokinase in Anabaena sp. PCC 7120.

    PubMed

    Klemke, Friederike; Beyer, Gabriele; Sawade, Linda; Saitov, Ali; Korte, Thomas; Maldener, Iris; Lockau, Wolfgang; Nürnberg, Dennis J; Volkmer, Thomas

    2014-12-01

    The polyphosphate glucokinases can phosphorylate glucose to glucose 6-phosphate using polyphosphate as the substrate. ORF all1371 encodes a putative polyphosphate glucokinase in the filamentous heterocyst-forming cyanobacterium Anabaena sp. PCC 7120. Here, ORF all1371 was heterologously expressed in Escherichia coli, and its purified product was characterized. Enzyme activity assays revealed that All1371 is an active polyphosphate glucokinase that can phosphorylate both glucose and mannose in the presence of divalent cations in vitro. Unlike many other polyphosphate glucokinases, for which nucleoside triphosphates (e.g. ATP or GTP) act as phosphoryl group donors, All1371 required polyphosphate to confer its enzymic activity. The enzymic reaction catalysed by All1371 followed classical Michaelis-Menten kinetics, with kcat = 48.2 s(-1) at pH 7.5 and 28 °C and KM = 1.76 µM and 0.118 mM for polyphosphate and glucose, respectively. Its reaction mechanism was identified as a particular multi-substrate mechanism called the 'bi-bi ping-pong mechanism'. Bioinformatic analyses revealed numerous polyphosphate-dependent glucokinases in heterocyst-forming cyanobacteria. Viability of an Anabaena sp. PCC 7120 mutant strain lacking all1371 was impaired under nitrogen-fixing conditions. GFP promoter studies indicate expression of all1371 under combined nitrogen deprivation. All1371 might play a substantial role in Anabaena sp. PCC 7120 under these conditions.

  20. All1371 is a polyphosphate-dependent glucokinase in Anabaena sp. PCC 7120.

    PubMed

    Klemke, Friederike; Beyer, Gabriele; Sawade, Linda; Saitov, Ali; Korte, Thomas; Maldener, Iris; Lockau, Wolfgang; Nürnberg, Dennis J; Volkmer, Thomas

    2014-12-01

    The polyphosphate glucokinases can phosphorylate glucose to glucose 6-phosphate using polyphosphate as the substrate. ORF all1371 encodes a putative polyphosphate glucokinase in the filamentous heterocyst-forming cyanobacterium Anabaena sp. PCC 7120. Here, ORF all1371 was heterologously expressed in Escherichia coli, and its purified product was characterized. Enzyme activity assays revealed that All1371 is an active polyphosphate glucokinase that can phosphorylate both glucose and mannose in the presence of divalent cations in vitro. Unlike many other polyphosphate glucokinases, for which nucleoside triphosphates (e.g. ATP or GTP) act as phosphoryl group donors, All1371 required polyphosphate to confer its enzymic activity. The enzymic reaction catalysed by All1371 followed classical Michaelis-Menten kinetics, with kcat = 48.2 s(-1) at pH 7.5 and 28 °C and KM = 1.76 µM and 0.118 mM for polyphosphate and glucose, respectively. Its reaction mechanism was identified as a particular multi-substrate mechanism called the 'bi-bi ping-pong mechanism'. Bioinformatic analyses revealed numerous polyphosphate-dependent glucokinases in heterocyst-forming cyanobacteria. Viability of an Anabaena sp. PCC 7120 mutant strain lacking all1371 was impaired under nitrogen-fixing conditions. GFP promoter studies indicate expression of all1371 under combined nitrogen deprivation. All1371 might play a substantial role in Anabaena sp. PCC 7120 under these conditions. PMID:25320362

  1. Mutations in the glucokinase gene of the fetus result in reduced birth weight.

    PubMed

    Hattersley, A T; Beards, F; Ballantyne, E; Appleton, M; Harvey, R; Ellard, S

    1998-07-01

    Low birth weight and fetal thinness have been associated with non-insulin dependent diabetes mellitus (NIDDM) and insulin resistance in childhood and adulthood. It has been proposed that this association results from fetal programming in response to the intrauterine environment. An alternative explanation is that the same genetic influences alter both intrauterine growth and adult glucose tolerance. Fetal insulin secretion in response to maternal glycaemia plays a key role in fetal growth, and adult insulin secretion is a primary determinant of glucose tolerance. We hypothesized that a defect in the sensing of glucose by the pancreas, caused by a heterozygous mutation in the glucokinase gene, could reduce fetal growth and birth weight in addition to causing hyperglycaemia after birth. In 58 offspring, where one parent has a glucokinase mutation, the inheritance of a glucokinase mutation by the fetus resulted in a mean reduction of birth weight of 533 g (P=0.002). In 19 of 21 sibpairs discordant for the presence of a glucokinase mutation, the child with the mutation had a lower birth weight, with a mean difference of 521 g (P=0.0002). Maternal hyperglycaemia due to a glucokinase mutation resulted in a mean increase in birth weight of 601 g (P=0.001). The effects of maternal and fetal glucokinase mutations on birth weight were additive. We propose that these changes in birth weight reflect changes in fetal insulin secretion which are influenced directly by the fetal genotype and indirectly, through maternal hyperglycaemia, by the maternal genotype. This observation suggests that variation in fetal growth could be used in the assessment of the role of genes which modify either insulin secretion or insulin action.

  2. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

    NASA Astrophysics Data System (ADS)

    Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

    2013-12-01

    Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

  3. Pyrimidone-based series of glucokinase activators with alternative donor-acceptor motif.

    PubMed

    Filipski, Kevin J; Guzman-Perez, Angel; Bian, Jianwei; Perreault, Christian; Aspnes, Gary E; Didiuk, Mary T; Dow, Robert L; Hank, Richard F; Jones, Christopher S; Maguire, Robert J; Tu, Meihua; Zeng, Dongxiang; Liu, Shenping; Knafels, John D; Litchfield, John; Atkinson, Karen; Derksen, David R; Bourbonais, Francis; Gajiwala, Ketan S; Hickey, Michael; Johnson, Theodore O; Humphries, Paul S; Pfefferkorn, Jeffrey A

    2013-08-15

    Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor-acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor-acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor-acceptor motifs may find utility in other glucokinase activator series or beyond.

  4. Insights into mechanism of glucokinase activation: observation of multiple distinct protein conformations.

    PubMed

    Liu, Shenping; Ammirati, Mark J; Song, Xi; Knafels, John D; Zhang, Jeff; Greasley, Samantha E; Pfefferkorn, Jeffrey A; Qiu, Xiayang

    2012-04-20

    Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk.

  5. Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation.

    PubMed

    Baldini, Steffi F; Steenackers, Agata; Olivier-Van Stichelen, Stéphanie; Mir, Anne-Marie; Mortuaire, Marlène; Lefebvre, Tony; Guinez, Céline

    2016-09-16

    Blood glucose fluctuates with the fasting-feeding cycle. One of the liver's functions is to maintain blood glucose concentrations within a physiological range. Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. In hepatocytes, GCK catalyzes the phosphorylation of glucose into glucose-6-phosphate. This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver. PMID:27520373

  6. Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation.

    PubMed

    Baldini, Steffi F; Steenackers, Agata; Olivier-Van Stichelen, Stéphanie; Mir, Anne-Marie; Mortuaire, Marlène; Lefebvre, Tony; Guinez, Céline

    2016-09-16

    Blood glucose fluctuates with the fasting-feeding cycle. One of the liver's functions is to maintain blood glucose concentrations within a physiological range. Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. In hepatocytes, GCK catalyzes the phosphorylation of glucose into glucose-6-phosphate. This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver.

  7. Tissue and subcellular distribution of glucokinase in rat liver and their changes during fasting-refeeding.

    PubMed

    Toyoda, Y; Miwa, I; Kamiya, M; Ogiso, S; Nonogaki, T; Aoki, S; Okuda, J

    1995-01-01

    The distribution of glucokinase in rat liver under both normal feeding and fasting-refeeding conditions was investigated immunohistochemically. Under normal feeding conditions, glucokinase immunoreactivity was observed in both nuclei and cytoplasm of parenchymal cells. The nuclei were stained intensely and evenly, whereas the cytoplasm showed weak immunoreactivity of different degrees of staining intensity depending on the location of the cells. The cytoplasm of perivenous hepatocytes was stained more intensely, though not so much more, than that of periportal hepatocytes. The cytoplasm of hepatocytes surrounding the terminal hepatic venule (THV), of hepatocytes surrounding the portal triad, and of some other hepatocytes showed a stronger immunoreactivity than that of residual hepatocytes. The nuclear immunoreactivity in hepatocytes surrounding the portal triad and in some other hepatocytes was weak or absent, and positive immunoreactivity was detected at the plasma membrane of some of these cells. After 72 h of fasting, glucokinase immunoreactivity was markedly decreased in all hepatocytes. After the start of refeeding, the cytoplasmic immunoreactivity began to increase first in the parenchymal cells surrounding the THV and extended to those in the intermediate zone followed by those in the periportal zone. In contrast, the increase in nuclear immunoreactivity started in hepatocytes situated in the intermediate zone adjacent to the perivenous zone and then extended to those in the perivenous zone followed by those in the periportal zone. Hepatocytes surrounding either THV or portal triad showed a distinctive change in immunoreactivity during the refeeding period. After 10 h of refeeding, strong immunoreactivity was observed in both the cytoplasm and the nuclei of all hepatocytes, and appreciable glucokinase immunoreactivity was detected at the plasma membrane of some hepatocytes. These findings are discussed from the standpoint of a functional role of glucokinase

  8. Reciprocal distribution of hexokinase and glucokinase in the periportal and perivenous zone of the rat liver acinus.

    PubMed

    Fischer, W; Ick, M; Katz, N R

    1982-04-01

    Glucokinase and hexokinase activities were measured in the periportal and perivenous zone of the liver acinus separated by microdissection. A microfluorimetric assay was established for the separate determination of both enzyme activities. Glucokinase activity was about 3.5-fold higher in the perivenous than in the periportal zone in fed male and female rats. after 24 h starvation this gradient was only slightly changed. Hexokinase showed an inverse gradient with about 1.5-fold higher activities in the periportal than in the perivenous zone in both fed and fasted animals. Since glucokinase is restricted to parenchymal cells and hexokinase is present predominantly or even exclusively in non-parenchymal cells, the heterogeneous distribution of glucokinase activity supports the model of a "metabolic zonation of liver parenchyma" with a predominance of glucose uptake in the perivenous and glucose release in the periportal hepatocytes.

  9. Hyperglycemia Induced by Glucokinase Deficiency Accelerates Atherosclerosis Development and Impairs Lesion Regression in Combined Heterozygous Glucokinase and the Apolipoprotein E-Knockout Mice

    PubMed Central

    Adingupu, Damilola D.; Andréasson, Anne-Christine; Ahnmark, Andrea

    2016-01-01

    Aim. Models combining diabetes and atherosclerosis are important in evaluating the cardiovascular (CV) effects and safety of antidiabetes drugs in the development of treatments targeting CV complications. Our aim was to evaluate if crossing the heterozygous glucokinase knockout mouse (GK+/−) and hyperlipidemic mouse deficient in apolipoprotein E (ApoE−/−) will generate a disease model exhibiting a diabetic and macrovascular phenotype. Methods. The effects of defective glucokinase on the glucose metabolism and on the progression and regression of atherosclerosis on high-fat diets were studied in both genders of GK+/−ApoE−/− and ApoE−/− mice. Coronary vascular function of the female GK+/−ApoE−/− and ApoE−/− mice was also investigated. Results. GK+/−ApoE−/− mice show a stable hyperglycemia which was increased on Western diet. In oral glucose tolerance test, GK+/−ApoE−/− mice showed significant glucose intolerance and impaired glucose-stimulated insulin secretion. Plasma lipids were comparable with ApoE−/− mice; nevertheless the GK+/−ApoE−/− mice showed slightly increased atherosclerosis development. Conclusions. The GK+/−ApoE−/− mice showed a stable and reproducible hyperglycemia, accelerated atherosclerotic lesion progression, and no lesion regression after lipid lowering. This novel model provides a promising tool for drug discovery, enabling the evaluation of compound effects against both diabetic and cardiovascular endpoints simultaneously in one animal model. PMID:27774459

  10. Theoretical investigations on the interactions of glucokinase regulatory protein with fructose phosphates.

    PubMed

    Ling, Baoping; Yan, Xueyuan; Sun, Min; Bi, Siwei

    2016-02-01

    Glucokinase (GK) plays a critical role in maintaining glucose homeostasis in the human liver and pancreas. In the liver, the activity of GK is modulated by the glucokinase regulatory protein (GKRP) which functions as a competitive inhibitor of glucose to bind to GK. Moreover, the inhibitory intensity of GKRP-GK is suppressed by fructose 1-phosphate (F1P), and reinforced by fructose 6-phosphate (F6P). Here, we employed a series of computational techniques to explore the interactions of fructose phosphates with GKRP. Calculation results reveal that F1P and F6P can bind to the same active site of GKRP with different binding modes, and electrostatic interaction provides a major driving force for the ligand binding. The presence of fructose phosphate severely influences the motions of protein and the conformational space, and the structural change of sugar phosphate influences its interactions with GKRP, leading to a large conformational rearrangement of loop2 in the SIS2 domain. In particular, the binding of F6P to GKRP facilitates the protruding loop2 contacting with GK to form the stable GK-GKRP complex. The conserved residues 179-184 of GKRP play a major role in the binding of phosphate group and maintaining the stability of GKRP. These results may provide deep insight into the regulatory mechanism of GKRP to the activity of GK. PMID:26629747

  11. Selection and characterization of a glucokinase-deficient mutant of Tetrahymena thermophila

    SciTech Connect

    Roberts, C.T. Jr.; Lavine, J.E.; Morse, D.E.

    1982-04-01

    The authors isolated a mutant of Tetrahymena thermophila that is resistant to inhibition of growth by the glucose analog 2-deoxyglucose. The mutant exhibits a deficiency in a cytoplasmic glucokinase. This enzymatic defect and the attendant inability to convert 2-deoxyglucose to toxic phosphorylated derivatives is apparently the sole basis for the mutant phenotype since transport of glucose and 2-deoxyglucose is unimpaired; there is no elevation of glucose-6-phosphatase activity, which could decrease the level of toxic 2-deoxyglucose metabolites. Genetic analyses have shown that the mutant allele is recessive and inherited as a single Mendelian mutation. The glucokinase-deficient strain described here is useful for the selection of other mutants in this organism and for the investigation of various cellular processes initiated or modulated by glucose and its analogs. The authors have exploited the molecular defect in this strain to investigate the initial steps in the cyclic AMP-mediated repression of galactokinase gene expression which is caused by glucose.

  12. Enantioselective synthesis of tatanans A-C and reinvestigation of their glucokinase-activating properties

    NASA Astrophysics Data System (ADS)

    Xiao, Qing; Jackson, Jeffrey J.; Basak, Ashok; Bowler, Joseph M.; Miller, Brian G.; Zakarian, Armen

    2013-05-01

    The tatanans are members of a novel class of complex sesquilignan natural products recently isolated from the rhizomes of Acorus tatarinowii Schott plants. Tatanans A, B and C have previously been reported to have potent glucokinase-activating properties that exceed the in vitro activity of known synthetic antidiabetic agents. Here, using a series of sequential [3,3]-sigmatropic rearrangements, we report the total synthesis of tatanan A in 13 steps and 13% overall yield. We also complete a concise enantioselective total synthesis of more complex, atropisomeric tatanans B and C via a distinct convergent strategy based on a palladium-catalysed diastereotopic aromatic group differentiation (12 steps, 4% and 8% overall yield, respectively). A plausible biosynthetic relationship between acyclic tatanan A and spirocyclic tatanans B and C is proposed and probed experimentally. With sufficient quantities of the natural products in hand, we undertake a detailed functional characterization of the biological activities of tatanans A-C. Contrary to previous reports, our assays utilizing pure recombinant human enzyme demonstrate that tatanans do not function as allosteric activators of glucokinase.

  13. Glucokinase regulatory proten genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3...

  14. Relevant associations of the glucokinase regulatory protein/glucokinase gene variation with TAG concentrations in a high-cardiovascular risk population: modulation by the Mediterranean diet.

    PubMed

    Sotos-Prieto, Mercedes; Guillén, Marisa; Vicente Sorli, Jose; Portolés, Olga; Guillem-Saiz, Patricia; Ignacio Gonzalez, Jose; Qi, Lu; Corella, Dolores

    2013-01-28

    The SNP rs1260326 (P446L) and rs1799884 (-30G>A) for the glucokinase regulatory protein (GCKR) and glucokinase (GCK) genes, respectively, have been associated with opposing effects on TAG and glucose concentrations. However, their genetic modulation by diet (dietary patterns or foods) remains to be investigated. We studied 945 high-cardiovascular risk subjects aged 67 (sd 6) years who participated in the PREvención con DIeta MEDiterránea-Valencia Study. Demographic, clinical, biochemical and genetic data were obtained. Adherence to the Mediterranean diet (MD) and food intake were measured by validated questionnaires. Carriers of the L allele of GKCR had significantly higher TAG concentrations (PP: 1.34 (SD 0.05) mmol/l v. PL+LL: 1.54 (SD 0.03) mmol/l; P= 0.014) and LL carriers had lower glucose concentrations (PL+PP: 6.85 (SD 0.08) mmol/l v. LL: 6.40 (SD 0.16) mmol/l; P= 0.032) after multivariate adjustment. Conversely, homozygous subjects for the variant allele (A) in the GCK gene had significantly lower TAG (GG+GA: 1.48 (SD 0.03) mmol/l v. AA: 1.17 (SD 0.18) mmol/l; P= 0.033) and a higher risk of diabetes (OR 3.3, 95 % CI 1.2, 9.2). Combined effects for both SNP increased TAG concentrations by 37 % (P= 0.033). Adherence to the MD modulated the effects of GCKR polymorphism on TAG: subjects with genetic risk had lower TAG (L-allele carriers; PP: 1.48 (SD 0.14) mmol/l v. PL+LL: 1.51 (SD 0.08) mmol/l; P= 0.917) compared with those with a higher adherence. Analysis of the joint effects of the GCKR and individual food items identified significant associations (olive oil (P= 0.035), vegetables (P= 0.012), red meat (P= 0.017), butter (P= 0.039), sweetened carbonated beverages (P= 0.036) and nuts (P= 0.038)). In conclusion, we found that rs1260326 (GCKR) is significantly associated with higher TAG concentrations, but is modulated by adherence to the MD. PMID:22716779

  15. Modulation of glucokinase by glucose, small-molecule activator and glucokinase regulatory protein: steady-state kinetic and cell-based analysis.

    PubMed

    Bourbonais, Francis J; Chen, Jing; Huang, Cong; Zhang, Yanwei; Pfefferkorn, Jeffrey A; Landro, James A

    2012-02-01

    GK (glucokinase) is an enzyme central to glucose metabolism that displays positive co-operativity to substrate glucose. Small-molecule GKAs (GK activators) modulate GK catalytic activity and glucose affinity and are currently being pursued as a treatment for Type 2 diabetes. GK progress curves monitoring product formation are linear up to 1 mM glucose, but biphasic at 5 mM, with the transition from the lower initial velocity to the higher steady-state velocity being described by the rate constant kact. In the presence of a liver-specific GKA (compound A), progress curves at 1 mM glucose are similar to those at 5 mM, reflecting activation of GK by compound A. We show that GKRP (GK regulatory protein) is a slow tight-binding inhibitor of GK. Analysis of progress curves indicate that this inhibition is time dependent, with apparent initial and final Ki values being 113 and 12.8 nM respectively. When GK is pre-incubated with glucose and compound A, the inhibition observed by GKRP is time dependent, but independent of GKRP concentration, reflecting the GKA-controlled transition between closed and open GK conformations. These data are supported by cell-based imaging data from primary rat hepatocytes. This work characterizes the modulation of GK by a novel GKA that may enable the design of new and improved GKAs.

  16. Discovery of an intravenous hepatoselective glucokinase activator for the treatment of inpatient hyperglycemia.

    PubMed

    Stevens, Benjamin D; Litchfield, John; Pfefferkorn, Jeffrey A; Atkinson, Karen; Perreault, Christian; Amor, Paul; Bahnck, Kevin; Berliner, Martin A; Calloway, Jessica; Carlo, Anthony; Derksen, David R; Filipski, Kevin J; Gumkowski, Mike; Jassal, Charanjeet; MacDougall, Margit; Murphy, Brendan; Nkansah, Paul; Pettersen, John; Rotter, Charles; Zhang, Yan

    2013-12-15

    Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties.

  17. Substrate-induced Nuclear Export and Peripheral Compartmentalization of Hepatic Glucokinase Correlates with Glycogen Deposition

    PubMed Central

    Shiota, Masa; Knobel, Susan M.; Piston, David W.; Cherrington, Alan D.; Magnuson, Mark A.

    2001-01-01

    Hepatic glucokinase (GK) is acutely regulated by binding to its nuclear-anchored regulatory protein (GKRP). Although GK release by GKRP is tightly coupled to the rate of glycogen synthesis, the nature of this association is obscure. To gain insight into this coupling mechanism under physiological stimulating conditions in primary rat hepatocytes, we analyzed the subcellular distribution of GK and GKRP with immunofluorescence, and glycogen deposition with glycogen cytochemical fluorescence, using confocal microscopyand quantitative image analysis. Following stimulation, a fraction of the GK signal translocated from the nucleus to the cytoplasm. The reduction in the nuclear to cytoplasmic ratio of GK, an index of nuclear export, correlated with a >50% increase in glycogen cytochemical fluorescence over a 60min stimulation period. Furthermore, glycogen accumulation was initially deposited in a peripheral pattern in hepatocytes similar to that of GK. These data suggest that a compartmentalization exists of both active GK and the initial sites of glycogen deposition at the hepatocyte surface. PMID:12369705

  18. Features for instantaneous emissions of low-level infrared signals of glucokinase enzyme from Pyrococcus furiosus.

    PubMed

    Torres, Sergio; Mella, Héctor; Reyes, Claudio; Meza, Pablo; Gallardo, Maria J; Staforelli, Juan P

    2015-03-10

    A noncontact infrared (IR) imaging-based methodology and signal recovery tools are applied on an enzyme reaction as a test target. The method is implemented by a long-wave (8-12 μm) IR microbolometer imaging array and a germanium-based IR optical vision. The reaction is carried out by the glucokinase, which produces a rapid exothermal release of energy that is weak, and, even worse, the IR video captured by the uncooled microbolometer detector is affected by spatial and temporal noise with specific complexities. Hitherto, IR-based signal recovery tools have worked with a standard acquisition frequency, which is clearly beyond the time scale of a real scenario. The implications of this (and similar) rapid reactions motivate the designs of a signal recovery method using prior information of the processes to extract and quantify the spontaneity of the enzymatic reaction in a three-dimensional (space and time) single and noncontact online measurement. PMID:25968383

  19. A Fresh View of Glycolysis and Glucokinase Regulation: History and Current Status*

    PubMed Central

    Lenzen, Sigurd

    2014-01-01

    This minireview looks back at a century of glycolysis research with a focus on the mechanisms of flux regulation. Traditionally, glycolysis is regarded as a feeder pathway that prepares glucose for further catabolism and energy production. However, glycolysis is much more than that, in particular in those tissues that express the low affinity glucose-phosphorylating enzyme glucokinase. This enzyme equips the glycolytic pathway with a special steering function for the regulation of intermediary metabolism. In beta cells, glycolysis acts as a transducer for triggering and amplifying physiological glucose-induced insulin secretion. On the basis of these considerations, I have defined a glycolytic flux regulatory unit composed of the two fructose ester steps of this pathway with various enzymes and metabolites that regulate glycolysis. PMID:24637025

  20. Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus

    SciTech Connect

    Sakura, Hiroshi; Eto, Kazuhiro; Ueno, Hirohisa; Yazaki, Yoshio; Kadowaki, Takashi ); Kadowaki, Hiroko; Simokawa, Kotaro; Akanuma, Yasuo ); Koda, Naoya; Fukushima, Yoshimitsu )

    1992-12-01

    Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. The authors isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, they identified a missense mutation substituting ariginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM). 12 refs., 3 figs., 2 tabs.

  1. The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of type 2 diabetes mellitus.

    PubMed

    Pfefferkorn, Jeffrey A; Tu, Meihua; Filipski, Kevin J; Guzman-Perez, Angel; Bian, Jianwei; Aspnes, Gary E; Sammons, Matthew F; Song, Wei; Li, Jian-Cheng; Jones, Christopher S; Patel, Leena; Rasmusson, Tim; Zeng, Dongxiang; Karki, Kapil; Hamilton, Michael; Hank, Richard; Atkinson, Karen; Litchfield, John; Aiello, Robert; Baker, Levenia; Barucci, Nicole; Bourassa, Patricia; Bourbonais, Francis; Bourbounais, Francis; D'Aquila, Theresa; Derksen, David R; MacDougall, Margit; Robertson, Alan

    2012-12-01

    Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy.

  2. Metabolites in safety testing assessment in early clinical development: a case study with a glucokinase activator.

    PubMed

    Sharma, Raman; Litchfield, John; Atkinson, Karen; Eng, Heather; Amin, Neeta B; Denney, William S; Pettersen, John C; Goosen, Theunis C; Di, Li; Lee, Esther; Pfefferkorn, Jeffrey A; Dalvie, Deepak K; Kalgutkar, Amit S

    2014-11-01

    The present article summarizes Metabolites in Safety Testing (MIST) studies on a glucokinase activator, N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (PF-04937319), which is under development for the treatment of type 2 diametes mellitus. Metabolic profiling in rat, dog, and human hepatocytes revealed that PF-04937319 is metabolized via oxidative (major) and hydrolytic pathways (minor). N-Demethylation to metabolite M1 [N-methyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide] was the major metabolic fate of PF-04937319 in human (but not rat or dog) hepatocytes, and was catalyzed by CYP3A and CYP2C isoforms. Qualitative examination of circulating metabolites in humans at the 100- and 300-mg doses from a 14-day multiple dose study revealed unchanged parent drug and M1 as principal components. Because M1 accounted for 65% of the drug-related material at steady state, an authentic standard was synthesized and used for comparison of steady-state exposures in humans and the 3-month safety studies in rats and dogs at the no-observed-adverse-effect level. Although circulating levels of M1 were very low in beagle dogs and female rats, adequate coverage was obtained in terms of total maximal plasma concentration (∼7.7× and 1.8×) and area under the plasma concentration-time curve (AUC; 3.6× and 0.8× AUC) relative to the 100- and 300-mg doses, respectively, in male rats. Examination of primary pharmacology revealed M1 was less potent as a glucokinase activator than the parent drug (compound PF-04937319: EC50 = 0.17 μM; M1: EC50 = 4.69 μM). Furthermore, M1 did not inhibit major human P450 enzymes (IC50 > 30 μM), and was negative in the Salmonella Ames assay, with minimal off-target pharmacology, based on CEREP broad ligand profiling. Insights gained from this analysis should lead to a more efficient and focused development plan for fulfilling MIST requirements with

  3. Role of Sp1 and SREBP-1a in the insulin-mediated regulation of glucokinase transcription in the liver of gilthead sea bream (Sparus aurata).

    PubMed

    Egea, Miriam; Metón, Isidoro; Córdoba, Marlon; Fernández, Felipe; Baanante, Isabel V

    2008-01-15

    Insulin induction of glucokinase (GCK) transcription in the liver is essential for maintaining glucose homeostasis. To study the molecular mechanism underlying the regulation of hepatic GCK expression in the carnivorous fish gilthead sea bream (Sparus aurata), we analysed the role of sterol regulatory element binding protein-1a (SREBP-1a) and specificity protein (Sp) 1 in insulin-dependent GCK transcription. Transient transfection experiments performed in HepG2 cells and electrophoretic mobility shift assays allowed us to identify a cis-element in the proximal region of GCK promoter implicated in transactivation by SREBP-1a. Consistently, mutations in the SRE binding site completely abolished the enhancing effect of SREBP-1a. These results and previous findings suggest that SREBP-1a plays a role in the transcriptional regulation of key enzymes in glycolysis-gluconeogenesis. Since SREBP-1a and Sp1 may mediate insulin action on S. aurata GCK transcription, we analysed the effect of insulin on HepG2 cells transfected with GCK promoter reporter constructs carrying intact or mutated SRE or Sp boxes. Insulin transactivated GCK irrespective of the presence of an intact or mutated SRE box. However, insulin failed to induce GCK transcription when using reporter constructs that had either a mutated Sp site or no Sp site. Our findings indicate that Sp1, rather than SREBP-1a, mediates the insulin-dependent induction of S. aurata GCK.

  4. Dynamic Localization of Glucokinase and Its Regulatory Protein in Hypothalamic Tanycytes

    PubMed Central

    Ordenes, Patricio; Millán, Carola; Yañez, María José; Llanos, Paula; Villagra, Marcos; Elizondo-Vega, Roberto; Martínez, Fernando; Nualart, Francisco; Uribe, Elena; de los Angeles García-Robles, María

    2014-01-01

    Glucokinase (GK), the hexokinase involved in glucose sensing in pancreatic β cells, is also expressed in hypothalamic tanycytes, which cover the ventricular walls of the basal hypothalamus and are implicated in an indirect control of neuronal activity by glucose. Previously, we demonstrated that GK was preferentially localized in tanycyte nuclei in euglycemic rats, which has been reported in hepatocytes and is suggestive of the presence of the GK regulatory protein, GKRP. In the present study, GK intracellular localization in hypothalamic and hepatic tissues of the same rats under several glycemic conditions was compared using confocal microscopy and Western blot analysis. In the hypothalamus, increased GK nuclear localization was observed in hyperglycemic conditions; however, it was primarily localized in the cytoplasm in hepatic tissue under the same conditions. Both GK and GKRP were next cloned from primary cultures of tanycytes. Expression of GK by Escherichia coli revealed a functional cooperative protein with a S0.5 of 10 mM. GKRP, expressed in Saccharomyces cerevisiae, inhibited GK activity in vitro with a Ki 0.2 µM. We also demonstrated increased nuclear reactivity of both GK and GKRP in response to high glucose concentrations in tanycyte cultures. These data were confirmed using Western blot analysis of nuclear extracts. Results indicate that GK undergoes short-term regulation by nuclear compartmentalization. Thus, in tanycytes, GK can act as a molecular switch to arrest cellular responses to increased glucose. PMID:24739934

  5. Glucosensing in liver and Brockmann bodies of rainbow trout through glucokinase-independent mechanisms.

    PubMed

    Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2016-09-01

    We hypothesize that glucosensor mechanisms other than that mediated by glucokinase (GK) are present in the liver and Brockmann bodies (BB) of rainbow trout, and are affected by stress. We evaluated in these tissues changes in parameters related to putative glucosensor mechanisms based on liver X receptor (LXR), mitochondrial activity, sweet taste receptor, and SGLT-1 6h after intraperitoneal injection of saline solution alone (normoglycaemic treatment) or containing insulin (hypoglycaemic treatment), or d-glucose (hyperglycaemic treatment). Half of tanks were kept at normal stocking density (NSD; 10kgfishmass·m(-3)) whereas the remaining tanks were kept at high stocking density (HSD; 70kgfishmass·m(-3)). The results provide for the first time in fish evidence for the presence of putative glucosensor systems based on mitochondrial activity and sweet taste receptor in liver whereas in BB systems based on LXR, mitochondrial activity, sweet taste receptor, and SGLT-1 could be operative. We also obtained for the first time in fish evidence for the functioning of integrative metabolic sensors in response to changes in nutrient levels since changes in the mRNA abundance of sirtuin 1 (SIRT-1) were observed in response to increased glucose levels. The stress conditions elicited by HSD altered the response of the glucosensor systems based on mitochondrial activity, sweet taste receptor, and SGLT-1 in the liver, and LXR and SGLT-1 in the BB.

  6. Production of glucose-6-phosphate by glucokinase coupled with an ATP regeneration system.

    PubMed

    Yan, Bingkun; Ding, Qingbao; Ou, Ling; Zou, Zhi

    2014-03-01

    A process of glucose-6-phosphate (G-6-P) production coupled with an adenosine triphosphate (ATP) regeneration system was constructed that utilized acetyl phosphate (ACP) via acetate kinase (ACKase). The genes glk and ack from Escherichia coli K12 were amplified and cloned into pET-28a(+), then transformed into E. coli BL21 (DE3) and the recombinant strains were named pGLK and pACK respectively. Glucokinase (glkase) in pGLK and ACKase in pACK were both overexpressed in soluble form. G-6-P was efficiently produced from glucose and ACP using a very small amount of ATP. The conversion yield was greater than 97 % when the reaction solution containing 10 mM glucose, 20 mM ACP-Na₂, 0.5 mM ATP, 5 mM Mg²⁺, 50 mM potassium phosphate buffer (pH 7.0), 4.856 U glkase and 3.632 U ACKase were put into 37 °C water bath for 1 h. PMID:24165747

  7. Overexpression of a glucokinase point mutant in the treatment of diabetes mellitus.

    PubMed

    Lu, G; Teng, X; Zheng, Z; Zhang, R; Peng, L; Zheng, F; Liu, J; Huang, H; Xiong, H

    2016-04-01

    Glucokinase (GCK) is an important enzyme critical for glucose metabolism, and has been targeted as such in the pursuit of a cure for diabetes mellitus. We show that streptozotocin (STZ)-induced diabetic murine model exhibits low GCK expression with high blood glucose levels; moreover, aggravated glomerulonephritis is observed in the model when there is IL10 deficiency. Although T cells infiltrate into the liver and pancreas in STZ-induced diabetes mice, T helper 1 (Th1) and T helper 17 (Th17) cells decrease significantly with STZ addition in in vitro polarization. Using a mutant GCK gene (GCK 262) with a knocked out cytosine at position 2643 results in lower protein expression and more ubiquitination-led protein degradation compared with wild-type GCK (GCK 261). We further observed that hsa-mir-1302 can bind to 3'-untranslated region of mutant GCK, which can decrease GCK mRNA translation. Finally, delivery of mutant GCK by subcutaneous injection is more effective at decreasing blood glucose in the STZ-treated (STZ) murine diabetes model than insulin treatment alone. Similarly, mutant GCK consistently and moderately decreases blood glucose levels in GK rats over a period of 12 and 70 days without inducing hypoglycemia, whereas insulin is only effective over 12 h. These results suggest that mutant GCK may be a future cure for diabetes.

  8. Sex-Specific Control of Fat Mass and Counterregulation by Hypothalamic Glucokinase.

    PubMed

    Steinbusch, Laura K M; Picard, Alexandre; Bonnet, Marion S; Basco, Davide; Labouèbe, Gwenaël; Thorens, Bernard

    2016-10-01

    Glucokinase (Gck) is a critical regulator of glucose-induced insulin secretion by pancreatic β-cells. It has been suggested to also play an important role in glucose signaling in neurons of the ventromedial hypothalamic nucleus (VMN), a brain nucleus involved in the control of glucose homeostasis and feeding. To test the role of Gck in VMN glucose sensing and physiological regulation, we studied mice with genetic inactivation of the Gck gene in Sf1 neurons of the VMN (Sf1Gck(-/-) mice). Compared with control littermates, Sf1Gck(-/-) mice displayed increased white fat mass and adipocyte size, reduced lean mass, impaired hypoglycemia-induced glucagon secretion, and a lack of parasympathetic and sympathetic nerve activation by neuroglucopenia. However, these phenotypes were observed only in female mice. To determine whether Gck was required for glucose sensing by Sf1 neurons, we performed whole-cell patch clamp analysis of brain slices from control and Sf1Gck(-/-) mice. Absence of Gck expression did not prevent the glucose responsiveness of glucose-excited or glucose-inhibited Sf1 neurons in either sex. Thus Gck in the VMN plays a sex-specific role in the glucose-dependent control of autonomic nervous activity; this is, however, unrelated to the control of the firing activity of classical glucose-responsive neurons.

  9. Hepatocellular adenoma showing high uptake of (18)F-fluorodeoxyglucose (FDG) via an increased expression of glucose transporter 2 (GLUT-2).

    PubMed

    Nakashima, Takaaki; Takayama, Yukihisa; Nishie, Akihiro; Asayama, Yoshiki; Baba, Shingo; Yamashita, Youichi; Shirabe, Ken; Kubo, Yuichiro; Hida, Tomoyuki; Honda, Hiroshi

    2014-01-01

    Hepatocellular adenoma (HCA) is a benign liver neoplasm composed of hepatocytes. We experienced HCA demonstrating a high uptake of (18)F-fluorodeoxyglucose (FDG) on positron emission tomography-computed tomography, mimicking a malignant tumor. The mechanism underlying the uptake of FDG has not been identified. Here, we discuss that an enhancement of glucose metabolism via an increased expression of glucose transporter 2 may have a role in the high uptake of FDG shown by HCAs.

  10. Lactose metabolism in Streptococcus lactis: studies with a mutant lacking glucokinase and mannose-phosphotransferase activities

    SciTech Connect

    Thompson, J.; Chassy, B.M.; Egan, W.

    1985-04-01

    A mutant of Streptococcus lactis 133 has been isolated that lacks both glucokinase and phosphoenolpyruvate-dependent mannose- phosphotransferase (mannose-PTS) activities. The double mutant S. lactis 133 mannose-PTSd GK- is unable to utilize either exogenously supplied or intracellularly generated glucose for growth. Fluorographic analyses of metabolites formed during the metabolism of (/sup 14/C)lactose labeled specifically in the glucose or galactosyl moiety established that the cells were unable to phosphorylate intracellular glucose. However, cells of S. lactis 133 mannose-PTSd GK- readily metabolized intracellular glucose 6-phosphate, and the growth rates and cell yield of the mutant and parental strains on sucrose were the same. During growth on lactose, S. lactis 133 mannose-PTSd GK- fermented only the galactose moiety of the disaccharide, and 1 mol of glucose was generated per mol of lactose consumed. For an equivalent concentration of lactose, the cell yield of the mutant was 50% that of the wild type. The specific rate of lactose utilization by growing cells of S. lactis 133 mannose-PTSd GK- was ca. 50% greater than that of the wild type, but the cell doubling times were 70 and 47 min, respectively. High-resolution /sup 31/P nuclear magnetic resonance studies of lactose transport by starved cells of S. lactis 133 and S. lactis 133 mannose-PTSd GK- showed that the latter cells contained elevated lactose-PTS activity. Throughout exponential growth on lactose, the mutant maintained an intracellular steady-state glucose concentration of 100 mM.

  11. Regulation of glucokinase activity in liver of hibernating ground squirrel Spermophilus undulatus.

    PubMed

    Khu, L Ya; Storey, K B; Rubtsov, A M; Goncharova, N Yu

    2014-07-01

    The kinetic properties of glucokinase (GLK) from the liver of active and hibernating ground squirrels Spermophilus undulatus have been studied. Entrance of ground squirrels into hibernation from their active state is accompanied by a sharp decrease in blood glucose (Glc) level (from 14 to 2.9 mM) and with a significant (7-fold) decrease of GLK activity in the liver cytoplasm. Preparations of native GLK practically devoid of other molecular forms of hexokinase were obtained from the liver of active and hibernating ground squirrels. The dependence of GLK activity upon Glc concentration for the enzyme from active ground squirrel liver showed a pronounced sigmoid character (Hill coefficient, h=1.70 and S0.5=6.23 mM; the experiments were conducted at 25°C in the presence of enzyme stabilizers, K+ and DTT). The same dependence of enzyme activity on Glc concentration was found for GLK from rat liver. However, on decreasing the temperature to 2°C (simulation of hibernation conditions), this dependency became almost hyperbolic (h=1.16) and GLK affinity for substrate was reduced (S0.5=23 mM). These parameters for hibernating ground squirrels (body temperature 5°C) at 25°C were found to be practically equal to the corresponding values obtained for GLK from the liver of active animals (h=1.60, S0.5=9.0 mM, respectively); at 2°C sigmoid character was less expressed and affinity for Glc was drastically decreased (h=1.20, S0.5=45 mM). The calculations of GLK activity in the liver of hibernating ground squirrels based on enzyme kinetic characteristics and seasonal changes in blood Glc concentrations have shown that GLK activity in the liver of hibernating ground squirrels is decreased about 5500-fold.

  12. Role of connecting loop I in catalysis and allosteric regulation of human glucokinase

    PubMed Central

    Martinez, Juliana A; Larion, Mioara; Conejo, Maria S; Porter, Carol M; Miller, Brian G

    2014-01-01

    Glucokinase (GCK, hexokinase IV) is a monomeric enzyme with a single glucose binding site that displays steady-state kinetic cooperativity, a functional characteristic that affords allosteric regulation of GCK activity. Structural evidence suggests that connecting loop I, comprised of residues 47–71, facilitates cooperativity by dictating the rate and scope of motions between the large and small domains of GCK. Here we investigate the impact of varying the length and amino acid sequence of connecting loop I upon GCK cooperativity. We find that sequential, single amino acid deletions from the C-terminus of connecting loop I cause systematic decreases in cooperativity. Deleting up to two loop residues leaves the kcat value unchanged; however, removing three or more residues reduces kcat by 1000-fold. In contrast, the glucose K0.5 and KD values are unaffected by shortening the connecting loop by up to six residues. Substituting alanine or glycine for proline-66, which adopts a cis conformation in some GCK crystal structures, does not alter cooperativity, indicating that cis/trans isomerization of this loop residue does not govern slow conformational reorganizations linked to hysteresis. Replacing connecting loop I with the corresponding loop sequence from the catalytic domain of the noncooperative isozyme human hexokinase I (HK-I) eliminates cooperativity without impacting the kcat and glucose K0.5 values. Our results indicate that catalytic turnover requires a minimal length of connecting loop I, whereas the loop has little impact upon the binding affinity of GCK for glucose. We propose a model in which the primary structure of connecting loop I affects cooperativity by influencing conformational dynamics, without altering the equilibrium distribution of GCK conformations. PMID:24723372

  13. Role of connecting loop I in catalysis and allosteric regulation of human glucokinase.

    PubMed

    Martinez, Juliana A; Larion, Mioara; Conejo, Maria S; Porter, Carol M; Miller, Brian G

    2014-07-01

    Glucokinase (GCK, hexokinase IV) is a monomeric enzyme with a single glucose binding site that displays steady-state kinetic cooperativity, a functional characteristic that affords allosteric regulation of GCK activity. Structural evidence suggests that connecting loop I, comprised of residues 47-71, facilitates cooperativity by dictating the rate and scope of motions between the large and small domains of GCK. Here we investigate the impact of varying the length and amino acid sequence of connecting loop I upon GCK cooperativity. We find that sequential, single amino acid deletions from the C-terminus of connecting loop I cause systematic decreases in cooperativity. Deleting up to two loop residues leaves the kcat value unchanged; however, removing three or more residues reduces kcat by 1000-fold. In contrast, the glucose K0.5 and KD values are unaffected by shortening the connecting loop by up to six residues. Substituting alanine or glycine for proline-66, which adopts a cis conformation in some GCK crystal structures, does not alter cooperativity, indicating that cis/trans isomerization of this loop residue does not govern slow conformational reorganizations linked to hysteresis. Replacing connecting loop I with the corresponding loop sequence from the catalytic domain of the noncooperative isozyme human hexokinase I (HK-I) eliminates cooperativity without impacting the kcat and glucose K0.5 values. Our results indicate that catalytic turnover requires a minimal length of connecting loop I, whereas the loop has little impact upon the binding affinity of GCK for glucose. We propose a model in which the primary structure of connecting loop I affects cooperativity by influencing conformational dynamics, without altering the equilibrium distribution of GCK conformations. PMID:24723372

  14. A Common Missense Variant in the Glucokinase Regulatory Protein Gene (GCKR) Is Associated with Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE-Using the genome-wide-association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metaboli...

  15. Studies on the use of sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucopyranose for the large-scale purification of hepatic glucokinase.

    PubMed Central

    Holroyde, M J; Chesher, J M; Trayer, I P; Walker, D G

    1976-01-01

    The synthesis of N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucose is described and it was shown to be a competitive inhibitor (Ki, 0.75 mM) with respect to glucose of rat hepatic glucokinase (EC 2.7.1.2). After attachment to CNBr-activated Sepharose 4B, this derivative was able to remove glucokinase quantitatively from crude liver extracts and release it when the columns were developed with glucose, glucosamine, N-acetyl-glucosamine or KC1. Repeated exposure of the columns to liver extracts led to rapid loss in their effectiveness as affinity matrices because proteins other than glucokinase are bound to the columns. The nature of such protein binding and methods for the rejuvenation of "used" columns are discussed along with the effect of the mode of preparation of the Sepharose-ligand conjugate and the concentration of bound ligand on the purification of glucokinase. Glucose 6-phosphate dehydrogenase is cited as an example of both non-specific protein binding to the affinity column and of the importance of the control of ligand concentration in removing such non-specifically bound proteins. Some guidelines emerged that should be generally applicable to other systems, particularly those which involve affinity chromatography of enzymes that are present in tissue extracts in very low amounts and possess only a relatively low association constant for the immobilized ligand. PMID:1275893

  16. Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. Objective: We investigated the combined effects of the GCKR rs780094C-->T,...

  17. Characterization of the heterozygous glucokinase knockout mouse as a translational disease model for glucose control in type 2 diabetes

    PubMed Central

    Baker, D J; Atkinson, A M; Wilkinson, G P; Coope, G J; Charles, A D; Leighton, B

    2014-01-01

    Background and Purpose The global heterozygous glucokinase (GK) knockout (gkwt/del) male mouse, fed on a high-fat (60% by energy) diet, has provided a robust and reproducible model of hyperglycaemia. This model could be highly relevant to some facets of human type 2 diabetes (T2D). We aimed to investigate the ability of standard therapeutic agents to lower blood glucose at translational doses, and to explore the glucose-lowering potential of novel glucokinase activators (GKAs) in this model. Experimental Approach We measured the ability of insulin, metformin, glipizide, exendin-4 and sitagliptin, after acute or repeat dose administration, to lower free-feeding glucose levels in gkwt/del mice. Further, we measured the ability of novel GKAs, GKA23, GKA71 and AZD6370 to control glucose either alone or in combination with some standard agents. Key Results A single dose of insulin (1 unit·kg−1), metformin (150, 300 mg·kg−1), glipizide (0.1, 0.3 mg·kg−1), exendin-4 (2, 20 μg·kg−1) and GKAs reduced free-feeding glucose levels. Sitagliptin (10 mg·kg−1), metformin (300 mg·kg−1) and AZD6370 (30, 400 mg·kg−1) reduced glucose excursions on repeat dosing. At a supra-therapeutic dose (400 mg·kg−1), AZD6370 also lowered basal levels of glucose without inducing hypoglycaemia. Conclusion and Implications Standard glucose-lowering therapeutic agents demonstrated significant acute glucose lowering in male gkwt/del mice at doses corresponding to therapeutic free drug levels in man, suggesting the potential of these mice as a translatable model of human T2D. Novel GKAs also lowered glucose in this mouse model. PMID:24772483

  18. Low glucokinase activity and high rates of gluconeogenesis contribute to hyperglycemia in barn owls (Tyto alba) after a glucose challenge.

    PubMed

    Myers, M R; Klasing, K C

    1999-10-01

    Barn owls (Tyto alba) and leghorn chickens were fed a low protein high glucose (33.44% protein, 23.67% glucose) or a high protein low glucose (55.35% protein, 1.5% glucose) diet. After an intravenous glucose infusion, the peak in plasma glucose was not affected by diet in either species and was 22.6 and 39.4 mmol/L in chickens and barn owls, respectively. Glucose levels returned to normal within 30 min in chickens, but remained elevated for 3.5 h in barn owls. An oral glucose challenge also resulted in greater and longer hyperglycemia in barn owls than in chickens. The activities of hepatic glucokinase, malic enzyme and phosphoenolpyruvate carboxykinase of barn owls were 16, 35, and 333% of the levels in chickens. Malic enzyme (P = 0.024) was less affected by dietary glucose level in barn owls than in chickens. Cultured hepatocytes from chickens produced 43% more glucose from lactate than hepatocytes from barn owls and, conversely, barn owl hepatocytes produced 87% more glucose from threonine than chickens (P = 0.001). Gluconeogenesis from lactate was greatly suppressed by high media glucose in chicken hepatocytes but not in those of barn owls (P = 0.0001 for species by glucose level interaction). When threonine was the substrate, gluconeogenesis was suppressed by increased glucose in both species but to a greater relative extent in chickens (P = 0.007 for species by glucose level interaction). Owls were glucose intolerant at least in part because of low hepatic glucokinase activity and an inadequate suppression of gluconeogenesis in the presence of exogenous glucose, apparently because they evolved with large excesses of amino acids and limited glucose in their normal diet. PMID:10498765

  19. Unique phylogenetic relationships of glucokinase and glucosephosphate isomerase of the amitochondriate eukaryotes Giardia intestinalis, Spironucleus barkhanus and Trichomonas vaginalis.

    PubMed

    Henze, K; Horner, D S; Suguri, S; Moore, D V; Sánchez, L B; Müller, M; Embley, T M

    2001-12-27

    Glucokinase (GK) and glucosephosphate isomerase (GPI), the first two enzymes of the glycolytic pathway of the diplomonads Giardia intestinalis and Spironucleus barkhanus, Type I amitochondriate eukaryotes, were sequenced. GPI of the parabasalid Trichomonas vaginalis was also sequenced. The diplomonad GKs belong to a family of specific GKs present in cyanobacteria, in some proteobacteria and also in T. vaginalis, a Type II amitochondriate protist. These enzymes are not part of the hexokinase family, which is broadly distributed among eukaryotes, including the Type I amitochondriate parasite Entamoeba histolytica. G. intestinalis GK expressed in Escherichia coli was specific for glucose and glucosamine, as are its eubacterial homologs. The sequence of diplomonad and trichomonad GPIs formed a monophyletic group more closely related to cyanobacterial and chloroplast sequences than to cytosolic GPIs of other eukaryotes and prokaryotes. The findings show that certain enzymes of the energy metabolism of these amitochondriate protists originated from sources different than those of other eukaryotes. The observation that the two diplomonads and T. vaginalis share the same unusual GK and GPI is consistent with gene trees that suggest a close relationship between diplomonads and parabasalids. The intriguing relationships of these enzymes to cyanobacterial (and chloroplast) enzymes might reflect horizontal gene transfer between the common ancestor of the diplomonad and parabasalid lineages and the ancestor of cyanobacteria. PMID:11750134

  20. The relationship of glucokinase activator-induced hypoglycemia with arteriopathy, neuronal necrosis, and peripheral neuropathy in nonclinical studies.

    PubMed

    Pettersen, John C; Litchfield, John; Neef, Natasha; Schmidt, Stephen P; Shirai, Norimitsu; Walters, Karen M; Enerson, Bradley E; Chatman, Linda A; Pfefferkorn, Jeffrey A

    2014-06-01

    Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All compounds produced varying degrees of hypoglycemia in all species. Brain neuronal necrosis and/or peripheral neuropathy were observed with most compounds. These findings are consistent with literature reports linking hypoglycemia with nervous system effects. Arteriopathy, mainly of cardiac vessels, was observed at a low frequency in monkey and/or dog. Arteriopathy occurred only at doses that produced severe and prolonged periods of repeated hypoglycemia. Since this lesion occurred in multiple studies with structurally distinct GKAs, these results suggested arteriopathy was related to GKA pharmacology. The morphological characteristics of the arteriopathy were consistent with that produced by experimental catecholamine administration. We hypothesize that the prolonged periods of hypoglycemia resulted in increased local and/or systemic concentrations of catecholamines via a counterregulatory and/or stress-related mechanism. Alternatively, prolonged hypoglycemia may have resulted in endothelial dysfunction leading to arteriopathy. This risk can be managed in human patients in clinical studies by careful glucose monitoring and intervention to avoid prolonged episodes of hypoglycemia.

  1. Unique phylogenetic relationships of glucokinase and glucosephosphate isomerase of the amitochondriate eukaryotes Giardia intestinalis, Spironucleus barkhanus and Trichomonas vaginalis.

    PubMed

    Henze, K; Horner, D S; Suguri, S; Moore, D V; Sánchez, L B; Müller, M; Embley, T M

    2001-12-27

    Glucokinase (GK) and glucosephosphate isomerase (GPI), the first two enzymes of the glycolytic pathway of the diplomonads Giardia intestinalis and Spironucleus barkhanus, Type I amitochondriate eukaryotes, were sequenced. GPI of the parabasalid Trichomonas vaginalis was also sequenced. The diplomonad GKs belong to a family of specific GKs present in cyanobacteria, in some proteobacteria and also in T. vaginalis, a Type II amitochondriate protist. These enzymes are not part of the hexokinase family, which is broadly distributed among eukaryotes, including the Type I amitochondriate parasite Entamoeba histolytica. G. intestinalis GK expressed in Escherichia coli was specific for glucose and glucosamine, as are its eubacterial homologs. The sequence of diplomonad and trichomonad GPIs formed a monophyletic group more closely related to cyanobacterial and chloroplast sequences than to cytosolic GPIs of other eukaryotes and prokaryotes. The findings show that certain enzymes of the energy metabolism of these amitochondriate protists originated from sources different than those of other eukaryotes. The observation that the two diplomonads and T. vaginalis share the same unusual GK and GPI is consistent with gene trees that suggest a close relationship between diplomonads and parabasalids. The intriguing relationships of these enzymes to cyanobacterial (and chloroplast) enzymes might reflect horizontal gene transfer between the common ancestor of the diplomonad and parabasalid lineages and the ancestor of cyanobacteria.

  2. Evidence for the Presence of Glucosensor Mechanisms Not Dependent on Glucokinase in Hypothalamus and Hindbrain of Rainbow Trout (Oncorhynchus mykiss)

    PubMed Central

    Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; López-Patiño, Marcos A.; Míguez, Jesús M.; Soengas, José L.

    2015-01-01

    We hypothesize that glucosensor mechanisms other than that mediated by glucokinase (GK) operate in hypothalamus and hindbrain of the carnivorous fish species rainbow trout and stress affected them. Therefore, we evaluated in these areas changes in parameters which could be related to putative glucosensor mechanisms based on liver X receptor (LXR), mitochondrial activity, sweet taste receptor, and sodium/glucose co-transporter 1 (SGLT-1) 6h after intraperitoneal injection of 5 mL.Kg-1 of saline solution alone (normoglycaemic treatment) or containing insulin (hypoglycaemic treatment, 4 mg bovine insulin.Kg-1 body mass), or D-glucose (hyperglycaemic treatment, 500 mg.Kg-1 body mass). Half of tanks were kept at a 10 Kg fish mass.m-3 and denoted as fish under normal stocking density (NSD) whereas the remaining tanks were kept at a stressful high stocking density (70 kg fish mass.m-3) denoted as HSD. The results obtained in non-stressed rainbow trout provide evidence, for the first time in fish, that manipulation of glucose levels induce changes in parameters which could be related to putative glucosensor systems based on LXR, mitochondrial activity and sweet taste receptor in hypothalamus, and a system based on SGLT-1 in hindbrain. Stress altered the response of parameters related to these systems to changes in glycaemia. PMID:25996158

  3. Bifunctional ADP-dependent phosphofructokinase/glucokinase activity in the order Methanococcales--biochemical characterization of the mesophilic enzyme from Methanococcus maripaludis.

    PubMed

    Castro-Fernandez, Victor; Bravo-Moraga, Felipe; Herrera-Morande, Alejandra; Guixe, Victoria

    2014-04-01

    In some archaea, the phosphorylation of glucose and fructose 6-phosphate (fructose 6P) is carried out by enzymes that are specific for either substrate and that use ADP as phosphoryl donor. In the hyperthermophilic archaeon Methanocaldococcus jannaschii, a bifunctional enzyme able to phosphorylate glucose and fructose 6P has been described. To determine whether the ability to phosphorylate both glucose and fructose 6P is a common feature for all enzymes of the order Methanococcales, we expressed, purified and characterized the unique homologous protein of the mesophilic archaea Methanococcus maripaludis. Assay of the enzyme activity with different sugars, metals and nucleotides allows us to conclude that the enzyme is able to phosphorylate both fructose 6P and glucose in the presence of ADP and a divalent metal cation. Kinetic characterization of the enzyme revealed complex regulation by the free Mg(2+) concentration and AMP, with the latter appearing to be a key metabolite. To determine whether this enzyme could have a role in gluconeogenesis, we evaluated the reversibility of both reactions and found that glucokinase activity is reversible, whereas phosphofructokinase activity is not. To determine the important residues for glucose and fructose 6P binding, we modeled the bifunctional phosphofructokinase/glucokinase enzyme from M. maripaludis and its interactions with both sugar substrates using protein–ligand docking. Comparison of the active site of the phosphofructokinase/glucokinase enzyme from M. maripaludis with the structural models constructed for all the homology sequences present in the order Methanococcales shows that all of the ADP-dependent kinases from this order would be able to phosphorylate glucose and fructose 6P, which rules out the current annotation of these enzymes as specific phosphofructokinases.

  4. Studies on recombinant glucokinase (r-glk) protein of Brucella abortus as a candidate vaccine molecule for brucellosis.

    PubMed

    Vrushabhendrappa; Singh, Amit Kumar; Balakrishna, Konduru; Sripathy, Murali Harishchandra; Batra, Harsh Vardhan

    2014-09-29

    Brucellosis is one of the most prevalent zoonotic diseases of worldwide distribution caused by the infection of genus Brucella. Live attenuated vaccines such as B. abortus S19, B. abortus RB51 and B. melitensis Rev1 are found most effective against brucellosis infection in animals, contriving a number of serious side effects and having chances to revert back into their active pathogenic form. In order to engineer a safe and effective vaccine candidate to be used in both animals and human, a recombinant subunit vaccine molecule comprising the truncated region of glucokinase (r-glk) gene from B. abortus S19 was cloned and expressed in Escherichia coli BL21DE3 host. Female BALB/c mice immunized with purified recombinant protein developed specific antibody titer of 1:64,000. The predominant IgG2a and IgG2b isotypes signified development of Th1 directed immune responses. In vitro cell cytotoxicity assay using anti-r-glk antibodies incubated with HeLa cells showed 81.20% and 78.5% cell viability against lethal challenge of B. abortus 544 and B. melitensis 16M, respectively. The lymphocyte proliferative assay indicated a higher splenic lymphocyte responses at 25μg/ml concentration of protein which implies the elevated development of memory immune responses. In contrast to control, the immunized group of mice intra-peritoneal (I.P.) challenged with B. abortus 544 were significantly protected with no signs of necrosis and vacuolization in their liver and spleen tissue. The elevated B-cell response associated with Th1 adopted immunity, significant in vitro cell viability as well as protection afforded in experimental animals after challenge, supplemented with histopathological analysis are suggestive of r-glk protein as a prospective candidate vaccine molecule against brucellosis.

  5. Intrinsic electrophilicity of the 4-methylsulfonyl-2-pyridone scaffold in glucokinase activators: role of glutathione-S-transferases and in vivo quantitation of a glutathione conjugate in rats.

    PubMed

    Litchfield, John; Sharma, Raman; Atkinson, Karen; Filipski, Kevin J; Wright, Stephen W; Pfefferkorn, Jeffrey A; Tan, Beijing; Kosa, Rachel E; Stevens, Benjamin; Tu, Meihua; Kalgutkar, Amit S

    2010-11-01

    Previous studies on the in vitro metabolism of 4-alkylsulfonyl-2-pyridone-based glucokinase activators revealed a facile, non-enzymatic displacement of the 4-alkylsulfonyl group by glutathione. In the present studies, a role for glutathione-S-transferases (GST) as catalysts in the desulfonylation reaction was demonstrated using a combination of human liver microsomes, human liver cytosol and human GSTs. The identification of a glutathione conjugate in circulation following intravenous administration of a candidate 4-methylsulfonyl-2-pyridone to rats confirmed the relevance of the in vitro findings.

  6. Identification of 21 novel glucokinase (GCK) mutations in UK and European Caucasians with maturity-onset diabetes of the young (MODY).

    PubMed

    Thomson, K L; Gloyn, A L; Colclough, K; Batten, M; Allen, L I S; Beards, F; Hattersley, A T; Ellard, S

    2003-11-01

    Maturity-onset diabetes of the young (MODY) resulting from mutations in the glucokinase (GCK) gene accounts for approximately 20% of MODY in the UK. We have performed fluorescent single stranded conformation polymorphism (F-SSCP) analysis or direct sequencing of the GCK gene in 212 patients referred as part of a research cohort or for diagnostic molecular genetic testing. Mutation screening has identified 43 different mutations in 61 individuals, of which 21 are novel. This report details the mutations identified and their associated clinical features.

  7. Post-prandial regulation of hepatic glucokinase and lipogenesis requires the activation of TORC1 signalling in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Mennigen, Jan A; Terrier, Frédéric; Dias, Karine; Seiliez, Iban; Skiba-Cassy, Sandrine

    2013-12-01

    To assess the potential involvement of TORC1 (target of rapamycin complex 1) signalling in the regulation of post-prandial hepatic lipid and glucose metabolism-related gene expression in trout, we employed intraperitoneal administration of rapamycin to achieve an acute inhibition of the TOR pathway. Our results reveal that rapamycin inhibits the phosphorylation of TORC1 and its downstream effectors (S6K1, S6 and 4E-BP1), without affecting Akt and the Akt substrates Forkhead-box Class O1 (FoxO1) and glycogen synthase kinase 3α/β (GSK 3α/β). These results indicate that acute administration of rapamycin in trout leads to the inhibition of TORC1 activation. No effect is observed on the expression of genes involved in gluconeogenesis, glycolysis and fatty acid oxidation, but hepatic TORC1 inhibition results in decreased sterol regulatory element binding protein 1c (SREBP1c) gene expression and suppressed fatty acid synthase (FAS) and glucokinase (GK) at gene expression and activity levels, indicating that FAS and GK activity is controlled at a transcriptional level in a TORC1-dependent manner. This study demonstrates for the first time in fish that post-prandial regulation of hepatic lipogenesis and glucokinase in rainbow trout requires the activation of TORC1 signalling. PMID:24031053

  8. Toward a unified model of passive drug permeation II: the physiochemical determinants of unbound tissue distribution with applications to the design of hepatoselective glucokinase activators.

    PubMed

    Ghosh, Avijit; Maurer, Tristan S; Litchfield, John; Varma, Manthema V; Rotter, Charles; Scialis, Renato; Feng, Bo; Tu, Meihua; Guimaraes, Cris R W; Scott, Dennis O

    2014-10-01

    In this work, we leverage a mathematical model of the underlying physiochemical properties of tissues and physicochemical properties of molecules to support the development of hepatoselective glucokinase activators. Passive distribution is modeled via a Fick-Nernst-Planck approach, using in vitro experimental data to estimate the permeability of both ionized and neutral species. The model accounts for pH and electrochemical potential across cellular membranes, ionization according to Henderson-Hasselbalch, passive permeation of the neutral species using Fick's law, and passive permeation of the ionized species using the Nernst-Planck equation. The mathematical model of the physiochemical system allows derivation of a single set of parameters governing the distribution of drug molecules across multiple conditions both in vitro and in vivo. A case study using this approach in the development of hepatoselective glucokinase activators via organic anion-transporting polypeptide-mediated hepatic uptake and impaired passive distribution to the pancreas is described. The results for these molecules indicate the permeability penalty of the ionized form is offset by its relative abundance, leading to passive pancreatic exclusion according to the Nernst-Planck extension of Fickian passive permeation. Generally, this model serves as a useful construct for drug discovery scientists to understand subcellular exposure of acids or bases using specific physiochemical properties.

  9. Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus.

    PubMed

    Pfefferkorn, Jeffrey A; Guzman-Perez, Angel; Litchfield, John; Aiello, Robert; Treadway, Judith L; Pettersen, John; Minich, Martha L; Filipski, Kevin J; Jones, Christopher S; Tu, Meihua; Aspnes, Gary; Risley, Hud; Bian, Jianwei; Stevens, Benjamin D; Bourassa, Patricia; D'Aquila, Theresa; Baker, Levenia; Barucci, Nicole; Robertson, Alan S; Bourbonais, Francis; Derksen, David R; Macdougall, Margit; Cabrera, Over; Chen, Jing; Lapworth, Amanda Lee; Landro, James A; Zavadoski, William J; Atkinson, Karen; Haddish-Berhane, Nahor; Tan, Beijing; Yao, Lili; Kosa, Rachel E; Varma, Manthena V; Feng, Bo; Duignan, David B; El-Kattan, Ayman; Murdande, Sharad; Liu, Shenping; Ammirati, Mark; Knafels, John; Dasilva-Jardine, Paul; Sweet, Laurel; Liras, Spiros; Rolph, Timothy P

    2012-02-01

    Glucokinase is a key regulator of glucose homeostasis, and small molecule allosteric activators of this enzyme represent a promising opportunity for the treatment of type 2 diabetes. Systemically acting glucokinase activators (liver and pancreas) have been reported to be efficacious but in many cases present hypoglycaemia risk due to activation of the enzyme at low glucose levels in the pancreas, leading to inappropriately excessive insulin secretion. It was therefore postulated that a liver selective activator may offer effective glycemic control with reduced hypoglycemia risk. Herein, we report structure-activity studies on a carboxylic acid containing series of glucokinase activators with preferential activity in hepatocytes versus pancreatic β-cells. These activators were designed to have low passive permeability thereby minimizing distribution into extrahepatic tissues; concurrently, they were also optimized as substrates for active liver uptake via members of the organic anion transporting polypeptide (OATP) family. These studies lead to the identification of 19 as a potent glucokinase activator with a greater than 50-fold liver-to-pancreas ratio of tissue distribution in rodent and non-rodent species. In preclinical diabetic animals, 19 was found to robustly lower fasting and postprandial glucose with no hypoglycemia, leading to its selection as a clinical development candidate for treating type 2 diabetes.

  10. Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

    PubMed Central

    García-Herrero, Carmen-María; Rubio-Cabezas, Oscar; Azriel, Sharona; Gutierrez-Nogués, Angel; Aragonés, Angel; Vincent, Olivier; Campos-Barros, Angel; Argente, Jesús; Navas, María-Angeles

    2012-01-01

    Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing. PMID:22291974

  11. Importance of glucokinase −258G/A polymorphism in Asian Indians with post-transplant and type 2 diabetes mellitus

    PubMed Central

    Khan, Imran Ali; Vattam, Kiran Kumar; Jahan, Parveen; Hasan, Qurratulain; Rao, Pragna

    2016-01-01

    Summary Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) are non-synonymous forms of diabetes. Glucokinase (GCK) plays a key role in glucose metabolism. The relationship between the GCK promoter and specific types of diabetes, such as PTDM and T2DM, in the Asian Indian population is unknown. We examined the occurrence of a specific GCK promoter variant (−258G/A) in patients with T2DM and PTDM. The case-control study enrolled 640 Asian Indian subjects, including controls (n = 250) and T2DM (n = 250), PTDM (n = 42), and non-post-transplant diabetes mellitus (non-PTDM) (n = 98) patients. Purified Deoxyribonucleic acid (DNA) was genotyped with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The digested PCR products were analyzed on 12% polyacrylamide gels. The anthropometric, biochemical, and clinical details of each group were documented. GCK −258G/A alleles and genotypes were not associated with T2DM. However, among PTDM subjects, we detected a higher frequency of heterozygotes (52.4%) and a positive association with alleles/genotypes. The results suggest that the promoter region (−258G/A) of GCK plays an important role in PTDM in Asian Indians. PMID:26989645

  12. Molecular and Functional Changes in Glucokinase Expression in the Brainstem Dorsal Vagal Complex in a Murine Model of Type 1 Diabetes

    PubMed Central

    Halmos, Katalin Cs.; Gyarmati, Peter; Xu, Hong; Maimaiti, Shaniya; Jancso, Gabor; Benedek, Gyorgy; Smith, Bret N

    2015-01-01

    Glucose concentration changes in the nucleus tractus solitarius (NTS) affect visceral function and metabolism by influencing central vagal circuits, especially inhibitory, GABAergic NTS neurons. Acutely elevated glucose can alter NTS neuron activity, and prolonged hyperglycemia and hypoinsulemia in animal models of type 1 diabetes results in plasticity of neural responses in the NTS. NTS neurons contributing to metabolic regulation therefore act as central glucose sensors and are functionally altered in type 1 diabetes. Glucokinase (GCK) mediates cellular utilization of glucose, linking increased glucose concentration to excitability changes mediated by ATP-sensitive K+ channels (KATP). Using quantitative RT-PCR, Western blot, and in vitro electrophysiology, we tested the hypothesis that changes in GCK expression in the NTS accompanied development of diabetes symptoms in the streptozotocin (STZ)-treated mouse model of type 1 diabetes. After several days of hyperglycemia in STZ-treated mice, RNA expression of GCK, but not Kir6.2 or SUR1, was decreased versus controls in the dorsal vagal complex. Electrophysiological recordings in vitro indicated that neural responses to acute hyperglycemia, and synaptic responsiveness to blockade of GCK with glucosamine, were attenuated in GABAergic NTS neurons from STZ-treated mice, consistent with reduced molecular and functional expression of GCK in the vagal complex of hyperglycemic, STZ-treated mice. Altered autonomic responses to glucose in type 1 diabetes may therefore involve reduced functional GCK expression in the dorsal vagal complex. PMID:26297899

  13. Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model.

    PubMed

    Saito, Mikako; Kaneda, Asako; Sugiyama, Tae; Iida, Ryousuke; Otokuni, Keiko; Kaburagi, Misako; Matsuoka, Hideaki

    2015-01-01

    Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk(+/-)) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk(+/-) mice ranged from 0.41-0.68 versus that in wild (Gk(+/+)) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95-1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk(+/-) strain fed the CD, and Gk(+/-) strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk(+/-) strain developed in this study. PMID:25765873

  14. Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model

    PubMed Central

    SAITO, Mikako; KANEDA, Asako; SUGIYAMA, Tae; IIDA, Ryousuke; OTOKUNI, Keiko; KABURAGI, Misako; MATSUOKA, Hideaki

    2015-01-01

    Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk+/−) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk+/− mice ranged from 0.41–0.68 versus that in wild (Gk+/+) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95–1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk+/− strain fed the CD, and Gk+/− strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk+/− strain developed in this study. PMID:25765873

  15. Zonal expression of the glucokinase gene in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization.

    PubMed

    Eilers, F; Bartels, H; Jungermann, K

    1993-02-01

    The abundance and zonal distribution of glucokinase (GK) mRNA were studied in rat liver during a normal 12 h day/12 h night rhythm (dark from 1900 to 0700 hours) and during refeeding after 60 h of starvation. Zonation of GK gene expression was examined by in situ hybridization with a radiolabelled cRNA probe and GK mRNA abundance was determined by Northern blot analysis with a digoxigenin-labelled cRNA probe. GK mRNA appeared to be almost homogeneously distributed throughout the whole daily feeding cycle; yet it was predominantly localized in the perivenous and intermediate zone during refeeding after 60 h of starvation. During the daily feeding rhythm, the total amount of GK mRNA increased quickly with the beginning of the feeding period at 1900 hours reaching a maximum at midnight and then decreased continuously to a basal level at noon. Virtually no GK mRNA was detected after 60 h of starvation. Refeeding caused a rapid increase in GK mRNA to a maximum at 2400 hours followed by a decrease to approximately two-thirds of the maximum value at 0700 hours. If the homogeneous distribution of GK mRNA during the daily feeding rhythm was real rather than apparent because of too low a sensitivity of the cRNA probe, the present results suggest that during the normal circadian cycle the mainly perivenous distribution of GK enzyme activity and protein is regulated preferentially at a translational level. The findings clearly show that during refeeding after 60 h of starvation the GK distribution is controlled predominantly at a pretranslational level.

  16. The glucokinase locus is an important contributor to glucose variation in the Chinese population at high risk for type II diabetes

    SciTech Connect

    Wu, D.A. |; Warden, C.H.; Lusis, A.J.

    1994-09-01

    Recently, major advances have been achieved in the genetics of maturity onset diabetes of the young (MODY) with two loci identified: the glucokinase (GCK) gene on chromosome (chr.) 7p and a locus near the adenosine deaminase (ADA) gene on chr. 20q. However, it is not known whether either of these MODY loci contribute to variation in glucose metabolism in populations other than MODY families. To examine this question, we have studied 94 Chinese nuclear families; 54 have both parents affected with type II diabetes, 22 have only one parent affected, and 18 have both normal parents. None of the affected diabetic probands were diagnosed prior to adulthood. Nondiabetic offspring were phenotyped by measuring plasma glucose and insulin responses to an oral glucose challenge. Parents and nondiabetic offspring were genotyped for dinucleotide repeat markers. two near the GCK locus and one near the ADA locus. Prior to linkage analysis, both glucose and insulin response variables were adjusted for the effects of age, sex, and body mass index. By non-parametric quantitative sib-pair linkage analysis, we found no evidence for linkage of glucose response variables with the ADA locus on chr. 20q (p=0.64-0.92, 146 sibpairs). However, significant evidence for linkage of log-transformed integrated glucose response area was observed with the GCK locus (haplotypes based on two tightly linked GCK markers) on chr. 7p (p=0.001, N=127). Linkage with the GCK locus was also demonstrated. In contrast, insulin variables, including integrated response area and responses at different time points, showed no evidence of linkage with either the ADA or GCK loci, despite the positive correlation between glucose and insulin responses in these families. These data raise the possibility that the GCK gene may be involved as one of the contributing genes in the etiology of type II diabetes in the Chinese population.

  17. Dose selection using a semi-mechanistic integrated glucose-insulin-glucagon model: designing phase 2 trials for a novel oral glucokinase activator.

    PubMed

    Zhang, Xin; Schneck, Karen; Bue-Valleskey, Juliana; Yeo, Kwee Poo; Heathman, Michael; Sinha, Vikram

    2013-02-01

    Selecting dosing regimens for phase 2 studies for a novel glucokinase activator LY2599506 is challenging due to the difficulty in modeling and assessing hypoglycemia risk. A semi-mechanistic integrated glucose-insulin-glucagon (GIG) model was developed in NONMEM based on pharmacokinetic, glucose, insulin, glucagon, and meal data obtained from a multiple ascending dose study in patients with Type 2 diabetes mellitus treated with LY2599506 for up to 26 days. The series of differential equations from the NONMEM model was translated into an R script to prospectively predict 24-h glucose profiles following LY2599506 treatment for 3 months for a variety of doses and dosing regimens. The reduction in hemoglobin A1c (HbA1c) at the end of the 3-month treatment was estimated using a transit compartment model based on the simulated fasting glucose values. Two randomized phase 2 studies, one with fixed dosing and the other employing conditional dose titration were conducted. The simulation suggested that (1) Comparable HbA1c lowering with lower hypoglycemia risk occurs with titration compared to fixed-dosing; and (2) A dose range of 50-400 mg BID provides either greater efficacy or lower hypoglycemia incidence or both than glyburide. The predictions were in reasonable agreement with the observed clinical data. The model predicted HbA1c reduction and hypoglycemia risk provided the basis for the decision to focus on the dose-titration trial and for the selection of doses for the demonstration of superiority of LY2599506 to glyburide. The integrated GIG model represented a valuable tool for the evaluation of hypoglycemia incidence. PMID:23263772

  18. Comparison of the circulating metabolite profile of PF-04991532, a hepatoselective glucokinase activator, across preclinical species and humans: potential implications in metabolites in safety testing assessment.

    PubMed

    Sharma, Raman; Litchfield, John; Bergman, Arthur; Atkinson, Karen; Kazierad, David; Gustavson, Stephanie M; Di, Li; Pfefferkorn, Jeffrey A; Kalgutkar, Amit S

    2015-02-01

    A previous report from our laboratory disclosed the identification of PF-04991532 [(S)-6-(3-cyclopentyl-2-(4-trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid] as a hepatoselective glucokinase activator for the treatment of type 2 diabetes mellitus. Lack of in vitro metabolic turnover in microsomes and hepatocytes from preclinical species and humans suggested that metabolism would be inconsequential as a clearance mechanism of PF-04991532 in vivo. Qualitative examination of human circulating metabolites using plasma samples from a 14-day multiple ascending dose clinical study, however, revealed a glucuronide (M1) and monohydroxylation products (M2a and M2b/M2c) whose abundances (based on UV integration) were greater than 10% of the total drug-related material. Based on this preliminary observation, mass balance/excretion studies were triggered in animals, which revealed that the majority of circulating radioactivity following the oral administration of [¹⁴C]PF-04991532 was attributed to an unchanged parent (>70% in rats and dogs). In contrast with the human circulatory metabolite profile, the monohydroxylated metabolites were not detected in circulation in either rats or dogs. Available mass spectral evidence suggested that M2a and M2b/M2c were diastereomers derived from cyclopentyl ring oxidation in PF-04991532. Because cyclopentyl ring hydroxylation on the C-2 and C-3 positions can generate eight possible diastereomers, it was possible that additional diastereomers may have also formed and would need to be resolved from the M2a and M2b/M2c peaks observed in the current chromatography conditions. In conclusion, the human metabolite scouting study in tandem with the animal mass balance study allowed early identification of PF-04991532 oxidative metabolites, which were not predicted by in vitro methods and may require additional scrutiny in the development phase of PF-04991532.

  19. Effects of dietary glucose and dextrin on activity and gene expression of glucokinase and fructose-1,6-bisphosphatase in liver of turbot Scophthalmus maximus.

    PubMed

    Nie, Qin; Miao, Huijun; Miao, Shuyan; Zhou, Huihui; Zhang, Yanjiao; Zhang, Wenbing; Mai, Kangsen

    2015-06-01

    Glucokinase (GK) and fructose-1,6-bisphosphatase (FBPase) play crucial role in glucose metabolism. In the present study, the cDNA encoding GK and FBPase was cloned from the liver of turbot Scophthalmus maximus by rapid amplification of cDNA end technique. Effects of dietary glucose and dextrin on the activities and gene expressions of these two enzymes were also studied. Results showed that the full length of GK cDNA was 2226 bp, consisting of an open reading frame (ORF) of 1434 bp. The full-length cDNA coding FBPase was 1314 bp with a 1014 bp ORF encoding 337 amino acids. Analyses of gene expression of GK and FBPase were conducted in gill, liver, the whole intestine, the whole kidney, heart, the dorsal white muscle and brain. The highest expression of GK was found in liver, followed by muscle. The expression of FBPase was found higher in liver than heart and gill. Both hepatic GK activity and mRNA expression were highly induced in turbot after being fed with dietary carbohydrates (p < 0.05). However, the GK activity and mRNA expression in the group with dietary glucose did not significantly differ from those in the group with dietary dextrin (p > 0.05). Compared with the control group, there were no significant differences in FBPase activity and mRNA expression in the glucose as well as dextrin group (p > 0.05). The increased hepatic GK activity and gene expression indicated that the first step of glycolysis was activated in turbot by dietary carbohydrates.

  20. Zinc Finger Nuclease Mediated Knockout of ADP-Dependent Glucokinase in Cancer Cell Lines: Effects on Cell Survival and Mitochondrial Oxidative Metabolism

    PubMed Central

    Richter, Susan; Morrison, Shona; Connor, Tim; Su, Jiechuang; Print, Cristin G.; Ronimus, Ron S.; McGee, Sean L.; Wilson, William R.

    2013-01-01

    Zinc finger nucleases (ZFN) are powerful tools for editing genes in cells. Here we use ZFNs to interrogate the biological function of ADPGK, which encodes an ADP-dependent glucokinase (ADPGK), in human tumour cell lines. The hypothesis we tested is that ADPGK utilises ADP to phosphorylate glucose under conditions where ATP becomes limiting, such as hypoxia. We characterised two ZFN knockout clones in each of two lines (H460 and HCT116). All four clones had frameshift mutations in all alleles at the target site in exon 1 of ADPGK, and were ADPGK-null by immunoblotting. ADPGK knockout had little or no effect on cell proliferation, but compromised the ability of H460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions, with clonogenic survival falling from 21±3% for the parental line to 6.4±0.8% (p = 0.002) and 4.3±0.8% (p = 0.001) for the two knockouts. A similar increased sensitivity to clonogenic cell killing was observed under anoxia. No such changes were found when ADPGK was knocked out in HCT116 cells, for which the parental line was less sensitive than H460 to anoxia and to hexokinase-2 silencing. While knockout of ADPGK in HCT116 cells caused few changes in global gene expression, knockout of ADPGK in H460 cells caused notable up-regulation of mRNAs encoding cell adhesion proteins. Surprisingly, we could discern no consistent effect on glycolysis as measured by glucose consumption or lactate formation under anoxia, or extracellular acidification rate (Seahorse XF analyser) under oxic conditions in a variety of media. However, oxygen consumption rates were generally lower in the ADPGK knockouts, in some cases markedly so. Collectively, the results demonstrate that ADPGK can contribute to tumour cell survival under conditions of high glycolytic dependence, but the phenotype resulting from knockout of ADPGK is cell line dependent and appears to be unrelated to priming of glycolysis in these lines. PMID:23799003

  1. The association between Mediterranean Diet Score and glucokinase regulatory protein gene variation on the markers of cardiometabolic risk: an analysis in the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

    PubMed

    Sotos-Prieto, Mercedes; Luben, Robert; Khaw, Kay-Tee; Wareham, Nicholas J; Forouhi, Nita G

    2014-07-14

    Consumption of a Mediterranean diet (MD) and genetic variation in the glucokinase regulatory protein (GCKR) gene have been reported to be associated with TAG and glucose metabolism. It is uncertain whether there is any interaction between these factors. Therefore, the aims of the present study were to test the association of adherence to a MD and rs780094 (G>A) SNP in the GCKR gene with the markers of cardiometabolic risk, and to investigate the interaction between genetic variation and MD adherence. We studied 20 986 individuals from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The relative Mediterranean Diet Score (rMED: range 0-18) was used to assess MD adherence. Linear regression was used to estimate the association between the rMED, genotype and cardiometabolic continuous traits, adjusting for potential confounders. In adjusted analyses, we observed independent associations of MD adherence and genotype with cardiometabolic risk, with the highest risk group (AA genotype; lowest rMED) having higher concentrations of TAG, total cholesterol and apoB (12·5, 2·3 and 3·1%, respectively) v. those at the lowest risk (GG genotype; highest rMED). However, the associations of MD adherence with metabolic markers did not differ by genotype, with no significant gene-diet interactions for lipids or for glycated Hb. In conclusion, we found independent associations of the rMED and of the GCKR genotype with cardiometabolic profile, but found no evidence of interaction between them.

  2. Hypoglycemic effects of Zanthoxylum alkylamides by enhancing glucose metabolism and ameliorating pancreatic dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    You, Yuming; Ren, Ting; Zhang, Shiqi; Shirima, Gerald Gasper; Cheng, YaJiao; Liu, Xiong

    2015-09-01

    This study aimed to evaluate the hypoglycemic effect of Zanthoxylum alkylamides and explore the potential mechanism in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were orally treated with 3, 6, and 9 mg per kg bw alkylamides daily for 28 days. As the alkylamide dose increased, the relative weights of the liver and kidney, fasting blood glucose, and fructosamine levels were significantly decreased. The alkylamides also significantly increased the body weight and improved the oral glucose tolerance of the rats. Likewise, the alkylamides significantly increased the levels of liver and muscle glycogen and plasma insulin. These substances further alleviated the histopathological changes in the pancreas of the diabetic rats. The beneficial effects of high-dose alkylamides showed a comparable activity to the anti-diabetic drug glibenclamide. Western blot and real-time PCR results revealed that the alkylamide treatment significantly decreased the expression levels of the key enzymes (phosphoenolpyruvate caboxykinase and glucose-6-phosphatase) involved in gluconeogenesis and increased the glycolysis enzyme (glucokinase) in the liver, and enhanced the expression levels of pancreatic duodenal homeobox-1, glucokinase, and glucose transporter 2 in the pancreas. In addition, it was also observed that the alkylamides, unlike glibenclamide, increased the transient receptor potential cation channel subfamily V member 1 and decreased cannabinoid receptor 1 expressions in the liver and pancreas. Therefore, alkylamides can prevent STZ-induced hyperglycemia by altering the expression levels of the genes related to glucose metabolism and by ameliorating pancreatic dysfunction.

  3. Collagen esterification enhances the function and survival of pancreatic β cells in 2D and 3D culture systems

    SciTech Connect

    Ko, Jae Hyung; Kim, Yang Hee; Jeong, Seong Hee; Lee, Song; Park, Si-Nae; Shim, In Kyong; Kim, Song Cheol

    2015-08-07

    Collagen, one of the most important components of the extracellular matrix (ECM), may play a role in the survival of pancreatic islet cells. In addition, chemical modifications that change the collagen charge profile to a net positive charge by esterification have been shown to increase the adhesion and proliferation of various cell types. The purpose of this study was to characterize and compare the effects of native collagen (NC) and esterified collagen (EC) on β cell function and survival. After isolation by the collagenase digestion technique, rat islets were cultured with NC and EC in 2 dimensional (2D) and 3 dimensional (3D) environments for a long-term duration in vitro. The cells were assessed for islet adhesion, morphology, viability, glucose-induced insulin secretion, and mRNA expression of glucose metabolism-related genes, and visualized by scanning electron microscopy (SEM). Islet cells attached tightly in the NC group, but islet cell viability was similar in both the NC and EC groups. Glucose-stimulated insulin secretion was higher in the EC group than in the NC group in both 2D and 3D culture. Furthermore, the mRNA expression levels of glucokinase in the EC group were higher than those in the NC group and were associated with glucose metabolism and insulin secretion. Finally, SEM observation confirmed that islets had more intact component cells on EC sponges than on NC sponges. These results indicate that modification of collagen may offer opportunities to improve function and viability of islet cells. - Highlights: • We changed the collagen charge profile to a net positive charge by esterification. • Islets cultured on esterified collagen improved survival in both 2D and 3D culture. • Islets cultured on esterified collagen enhanced glucose-stimulated insulin release. • High levels of glucokinase mRNA may be associated with increased insulin release.

  4. Moral Enhancement

    PubMed Central

    Douglas, Thomas

    2008-01-01

    Opponents of biomedical enhancement often claim that, even if such enhancement would benefit the enhanced, it would harm others. But this objection looks unpersuasive when the enhancement in question is a moral enhancement — an enhancement that will expectably leave the enhanced person with morally better motives than she had previously. In this article I (1) describe one type of psychological alteration that would plausibly qualify as a moral enhancement, (2) argue that we will, in the medium-term future, probably be able to induce such alterations via biomedical intervention, and (3) defend future engagement in such moral enhancements against possible objections. My aim is to present this kind of moral enhancement as a counter-example to the view that biomedical enhancement is always morally impermissible. PMID:19132138

  5. 3,5,3'-Triiodo-L-thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC-1) towards a beta-cell-Like phenotype.

    PubMed

    Misiti, Silvia; Anastasi, Emanuela; Sciacchitano, Salvatore; Verga Falzacappa, Cecilia; Panacchia, Laura; Bucci, Barbara; Khouri, Daniele; D'Acquarica, Ilaria; Brunetti, Ercole; Di Mario, Umberto; Toscano, Vincenzo; Perfetti, Riccardo

    2005-07-01

    The thyroid hormone, 3,5,3'-Triiodo-L-thyronine (T3), is essential for growth, differentiation, and regulation of metabolic functions in multicellular organisms, although the specific mechanisms of this control are still unknown. In this study, treatment of a human pancreatic duct cell line (hPANC-1) with T3 blocks cell growth by an increase of cells in G(0)/G(1) cell cycle phase and enhances morphological and functional changes as indicated by the marked increase in the synthesis of insulin and the parallel decrease of the ductal differentiation marker cytokeratin19. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent increase in insulin and glut2 mRNA levels in response to T3. As last step of the acquisition of a beta-cell-like phenotype, we present evidence that thyroid hormones are able to increase the release of insulin into the culture medium. In conclusion, our results suggest, for the first time, that thyroid hormones induce cell cycle perturbations and play an important role in the process of transdifferentiation of a human pancreatic duct line (hPANC-1) into pancreatic-beta-cell-like cells. These findings have important implications in cell-therapy based treatment of diabetes and may provide important insights in the designing of novel therapeutic agents to restore normal glycemia in subjects with diabetes.

  6. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

    SciTech Connect

    Kandasamy, Neelamegam; Ashokkumar, Natarajan

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

  7. Subchronic alpha-linolenic acid treatment enhances brain plasticity and exerts an antidepressant effect: a versatile potential therapy for stroke.

    PubMed

    Blondeau, Nicolas; Nguemeni, Carine; Debruyne, David N; Piens, Marie; Wu, Xuan; Pan, Hongna; Hu, XianZhang; Gandin, Carine; Lipsky, Robert H; Plumier, Jean-Christophe; Marini, Ann M; Heurteaux, Catherine

    2009-11-01

    Omega-3 polyunsaturated fatty acids are known to have therapeutic potential in several neurological and psychiatric disorders. However, the molecular mechanisms of action underlying these effects are not well elucidated. We previously showed that alpha-linolenic acid (ALA) reduced ischemic brain damage after a single treatment. To follow-up this finding, we investigated whether subchronic ALA treatment promoted neuronal plasticity. Three sequential injections with a neuroprotective dose of ALA increased neurogenesis and expression of key proteins involved in synaptic functions, namely, synaptophysin-1, VAMP-2, and SNAP-25, as well as proteins supporting glutamatergic neurotransmission, namely, V-GLUT1 and V-GLUT2. These effects were correlated with an increase in brain-derived neurotrophic factor (BDNF) protein levels, both in vitro using neural stem cells and hippocampal cultures and in vivo, after subchronic ALA treatment. Given that BDNF has antidepressant activity, this led us to test whether subchronic ALA treatment could produce antidepressant-like behavior. ALA-treated mice had significantly reduced measures of depressive-like behavior compared with vehicle-treated animals, suggesting another aspect of ALA treatment that could stimulate functional stroke recovery by potentially combining acute neuroprotection with long-term repair/compensatory plasticity. Indeed, three sequential injections of ALA enhanced protection, either as a pretreatment, wherein it reduced post-ischemic infarct volume 24 h after a 1-hour occlusion of the middle cerebral artery or as post-treatment therapy, wherein it augmented animal survival rates by threefold 10 days after ischemia. PMID:19641487

  8. Biocatalyst Enhancement

    EPA Science Inventory

    The increasing availability of enzyme collections has assisted attempts by pharmaceutical producers to adopt green chemistry approaches to manufacturing. A joint effort between an enzyme producer and a pharmaceutical manufacturer has been enhanced over the past three years by ena...

  9. Soy Leaf Extract Containing Kaempferol Glycosides and Pheophorbides Improves Glucose Homeostasis by Enhancing Pancreatic β-Cell Function and Suppressing Hepatic Lipid Accumulation in db/db Mice.

    PubMed

    Li, Hua; Ji, Hyeon-Seon; Kang, Ji-Hyun; Shin, Dong-Ha; Park, Ho-Yong; Choi, Myung-Sook; Lee, Chul-Ho; Lee, In-Kyung; Yun, Bong-Sik; Jeong, Tae-Sook

    2015-08-19

    This study investigated the molecular mechanisms underlying the antidiabetic effect of an ethanol extract of soy leaves (ESL) in db/db mice. Control groups (db/+ and db/db) were fed a normal diet (ND), whereas the db/db-ESL group was fed ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The pancreatic insulin content of the db/db-ESL group was significantly greater than that of the db/db group. ESL supplementation altered pancreatic IRS1, IRS2, Pdx1, Ngn3, Pax4, Ins1, Ins2, and FoxO1 expression. Furthermore, ESL suppressed lipid accumulation and increased glucokinase activity in the liver. ESL primarily contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of kaempferol glycosides, improved β-cell proliferation through IRS2-related FoxO1 signaling, whereas pheophorbide a, a product of chlorophyll breakdown, improved insulin secretion and β-cell proliferation through IRS1-related signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose homeostasis by enhancing IRS-mediated β-cell insulin signaling and suppressing SREBP-1-mediated hepatic lipid accumulation in db/db mice. PMID:26211813

  10. Soy Leaf Extract Containing Kaempferol Glycosides and Pheophorbides Improves Glucose Homeostasis by Enhancing Pancreatic β-Cell Function and Suppressing Hepatic Lipid Accumulation in db/db Mice.

    PubMed

    Li, Hua; Ji, Hyeon-Seon; Kang, Ji-Hyun; Shin, Dong-Ha; Park, Ho-Yong; Choi, Myung-Sook; Lee, Chul-Ho; Lee, In-Kyung; Yun, Bong-Sik; Jeong, Tae-Sook

    2015-08-19

    This study investigated the molecular mechanisms underlying the antidiabetic effect of an ethanol extract of soy leaves (ESL) in db/db mice. Control groups (db/+ and db/db) were fed a normal diet (ND), whereas the db/db-ESL group was fed ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The pancreatic insulin content of the db/db-ESL group was significantly greater than that of the db/db group. ESL supplementation altered pancreatic IRS1, IRS2, Pdx1, Ngn3, Pax4, Ins1, Ins2, and FoxO1 expression. Furthermore, ESL suppressed lipid accumulation and increased glucokinase activity in the liver. ESL primarily contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of kaempferol glycosides, improved β-cell proliferation through IRS2-related FoxO1 signaling, whereas pheophorbide a, a product of chlorophyll breakdown, improved insulin secretion and β-cell proliferation through IRS1-related signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose homeostasis by enhancing IRS-mediated β-cell insulin signaling and suppressing SREBP-1-mediated hepatic lipid accumulation in db/db mice.

  11. Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling in isolated rat islets.

    PubMed

    Rafacho, Alex; Marroquí, Laura; Taboga, Sebastião R; Abrantes, Júlia L F; Silveira, Leonardo R; Boschero, Antonio C; Carneiro, Everardo M; Bosqueiro, José R; Nadal, Angel; Quesada, Ivan

    2010-01-01

    Although glucocorticoids are widely used as antiinflammatory agents in clinical therapies, they may cause serious side effects that include insulin resistance and hyperinsulinemia. To study the potential functional adaptations of the islet of Langerhans to in vivo glucocorticoid treatment, adult Wistar rats received dexamethasone (DEX) for 5 consecutive days, whereas controls (CTL) received only saline. The analysis of insulin release in freshly isolated islets showed an enhanced secretion in response to glucose in DEX-treated rats. The study of Ca(2+) signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca(2+) signals were found between both groups with tolbutamide or KCl, indicating that the alterations were probably related to metabolism. Thus, mitochondrial function was explored by monitoring oxidation of nicotinamide dinucleotide phosphate autofluorescence and mitochondrial membrane potential. Both parameters revealed a higher response to glucose in islets from DEX-treated rats. The mRNA and protein content of glucose transporter-2, glucokinase, and pyruvate kinase was similar in both groups, indicating that changes in these proteins were probably not involved in the increased mitochondrial function. Additionally, we explored the status of Ca(2+)-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase C alpha as well as an increased response of the phospholipase C/inositol 1,4,5-triphosphate pathway in DEX-treated rats. Finally, an increased number of docked secretory granules were observed in the beta-cells of DEX animals using transmission electron microscopy. Thus, these results demonstrate that islets from glucocorticoid-treated rats develop several adaptations that lead to an enhanced stimulus-secretion coupling and secretory capacity.

  12. Enhancing Opportunities.

    ERIC Educational Resources Information Center

    Meyers, Michelle J.

    1994-01-01

    Hispanics can enhance their professional career by finding jobs with corporations that offer to pay for graduate tuition. This opportunity has positively influenced the careers of many Hispanics and has proven advantageous for corporations as well by increasing the knowledge and skills of their employees. (LP)

  13. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

    PubMed

    Kandasamy, Neelamegam; Ashokkumar, Natarajan

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats.

  14. Endothelial cells in co-culture enhance embryonic stem cell differentiation to pancreatic progenitors and insulin-producing cells through BMP signaling.

    PubMed

    Talavera-Adame, Dodanim; Wu, Gordon; He, Yao; Ng, Tina T; Gupta, Ankur; Kurtovic, Silvia; Hwang, Jae Y; Farkas, Daniel L; Dafoe, Donald C

    2011-09-01

    Endothelial cells (ECs) represent the major component of the embryonic pancreatic niche and play a key role in the differentiation of insulin-producing β cells in vivo. However, it is unknown if ECs promote such differentiation in vitro. We investigated whether interaction of ECs with mouse embryoid bodies (EBs) in culture promotes differentiation of pancreatic progenitors and insulin-producing cells and the mechanisms involved. We developed a co-culture system of mouse EBs and human microvascular ECs (HMECs). An increase in the expression of the pancreatic markers PDX-1, Ngn3, Nkx6.1, proinsulin, GLUT-2, and Ptf1a was observed at the interface between EBs and ECs (EB-EC). No expression of these markers was found at the periphery of EBs cultured without ECs or those co-cultured with mouse embryonic fibroblasts (MEFs). At EB-EC interface, proinsulin and Nkx6.1 positive cells co-expressed phospho-Smad1/5/8 (pSmad1/5/8). Therefore, EBs were treated with HMEC conditioned media (HMEC-CM) suspecting soluble factors involved in bone morphogenetic protein (BMP) pathway activation. Upregulation of PDX-1, Ngn3, Nkx6.1, insulin-1, insulin-2, amylin, SUR1, GKS, and amylase as well as down-regulation of SST were detected in treated EBs. In addition, higher expression of BMP-2/-4 and their receptor (BMPR1A) were also found in these EBs. Recombinant human BMP-2 (rhBMP-2) mimicked the effects of the HMEC-CM on EBs. Noggin (NOG), a BMP antagonist, partially inhibited these effects. These results indicate that the differentiation of EBs to pancreatic progenitors and insulin-producing cells can be enhanced by ECs in vitro and that BMP pathway activation is central to this process.

  15. Cooking enhances beneficial effects of pea seed coat consumption on glucose tolerance, incretin, and pancreatic hormones in high-fat-diet-fed rats.

    PubMed

    Hashemi, Zohre; Yang, Kaiyuan; Yang, Han; Jin, Alena; Ozga, Jocelyn; Chan, Catherine B

    2015-04-01

    Pulses, including dried peas, are nutrient- and fibre-rich foods that improve glucose control in diabetic subjects compared with other fibre sources. We hypothesized feeding cooked pea seed coats to insulin-resistant rats would improve glucose tolerance by modifying gut responses to glucose and reducing stress on pancreatic islets. Glucose intolerance induced in male Sprague-Dawley rats with high-fat diet (HFD; 10% cellulose as fibre) was followed by 3 weeks of HFD with fibre (10%) provided by cellulose, raw-pea seed coat (RP), or cooked-pea seed coat (CP). A fourth group consumed low-fat diet with 10% cellulose. Oral and intraperitoneal glucose tolerance tests (oGTT, ipGTT) were done. CP rats had 30% and 50% lower glucose and insulin responses in oGTT, respectively, compared with the HFD group (P < 0.05) but ipGTT was not different. Plasma islet and incretin hormone concentrations were measured. α- and β-cell areas in the pancreas and density of K- and L-cells in jejunum and ileum were quantified. Jejunal expression of hexose transporters was measured. CP feeding increased fasting glucagon-like peptide 1 and glucose-stimulated gastric inhibitory polypeptide responses (P < 0.05), but K- and L-cells densities were comparable to HFD, as was abundance of SGLT1 and GLUT2 mRNA. No significant difference in β-cell area between diet groups was observed. α-cell area was significantly smaller in CP compared with RP rats (P < 0.05). Overall, our results demonstrate that CP feeding can reverse adverse effects of HFD on glucose homeostasis and is associated with enhanced incretin secretion and reduced α-cell abundance.

  16. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    SciTech Connect

    Rashid, Kahkashan; Sil, Parames C.

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  17. Enhancing bioremediation

    SciTech Connect

    Koenigsberg, S.

    1997-02-01

    Oxygen is often the limiting factor in aerobic bioremediation. Without adequate oxygen, contaminant degradation will either cease or proceed by highly inefficient anaerobic processes. Researchers at Regenesis Bioremediation Products recently develope a technology to combat this problem, Oxygen Release Compound (ORC) a unique formulation of magnesium peroxide release oxygen slowly when hydrated. ORC is idea for supporting bioremediation of underground storage tank releases. ORC treatment represents a low intensity approach to remediation - simple, passive, low-cost, long term enhancement of a natural attenuation. 1 fig.

  18. Taurine supplementation modulates glucose homeostasis and islet function.

    PubMed

    Carneiro, Everardo M; Latorraca, Marcia Q; Araujo, Eliana; Beltrá, Marta; Oliveras, Maria J; Navarro, Mónica; Berná, Genoveva; Bedoya, Francisco J; Velloso, Licio A; Soria, Bernat; Martín, Franz

    2009-07-01

    Taurine is a conditionally essential amino acid for human that is involved in the control of glucose homeostasis; however, the mechanisms by which the amino acid affects blood glucose levels are unknown. Using an animal model, we have studied these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT). Islet cell function was determined by insulin secretion, cytosolic Ca2+ measurements and glucose metabolism from isolated islets. Islet cell gene expression and translocation was examined via immunohistochemistry and quantitative real-time polymerase chain reaction. Insulin signaling was studied by Western blot. Islets from taurine-supplemented mice had: (i) significantly higher insulin content, (ii) increased insulin secretion at stimulatory glucose concentrations, (iii) significantly displaced the dose-response curve for glucose-induced insulin release to the left, (iv) increased glucose metabolism at 5.6 and 11.1-mmol/L concentrations; (v) slowed cytosolic Ca2+ concentration ([Ca2+]i) oscillations in response to stimulatory glucose concentrations; (vi) increased insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression in the nucleus. Moreover, taurine supplementation significantly increased both basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an improved IPGTT. These results indicate that taurine controls glucose homeostasis by regulating the expression of genes required for glucose-stimulated insulin secretion. In addition, taurine enhances peripheral insulin sensitivity. PMID:18708284

  19. EDITORIAL: Enhancing nanolithography Enhancing nanolithography

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2012-01-01

    Lithography was invented in late 18th century Bavaria by an ambitious young playwright named Alois Senefelder. Senefelder experimented with stone, wax, water and ink in the hope of finding a way of reproducing text so that he might financially gain from a wider distribution of his already successful scripts. His discovery not only facilitated the profitability of his plays, but also provided the world with an affordable printing press that would ultimately democratize the dissemination of art, knowledge and literature. Since Senefelder, experiments in lithography have continued with a range of innovations including the use of electron beams and UV that allow increasingly higher-resolution features [1, 2]. Applications for this have now breached the limits of paper printing into the realms of semiconductor and microelectronic mechanical systems technology. In this issue, researchers demonstrate a technique for fabricating periodic features in poly(3,4-ethylene dioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) [3]. Their method combines field enhancements from silica nanospheres with laser-interference lithography to provide a means of patterning a polymer that has the potential to open the market of low-end, high-volume microelectronics. Laser-interference lithography has already been used successfully in patterning. Researchers in Korea used laser-interference lithography to generate stamps for imprinting a two-dimensional photonic crystal structure into green light emitting diodes (LEDs) [4]. The imprinted patterns comprised depressions 100 nm deep and 180 nm wide with a periodicity of 295 nm. In comparison with unpatterned LEDs, the intensity of photoluminescence was enhanced by a factor of seven in the LEDs that had the photonic crystal structures imprinted in them. The potential of exploiting field enhancements around nanostructures for new technologies has also attracted a great deal of attention. Researchers in the USA and Australia have used the field

  20. Can stock enhancement enhance stocks?

    NASA Astrophysics Data System (ADS)

    Støttrup, J. G.; Sparrevohn, C. R.

    2007-02-01

    Successful stock enhancement or restocking requires a thorough understanding of the ecological processes that provide a potential for stocking within different ecosystems, i.e. determine which factors define the potential for stocking, such as population dynamics, economic cost-benefits, fisheries management and socio-economic impacts. Stocking is not simply a question of aquaculture logistics (i.e. the ability to produce a sufficient number of fry relative to the magnitude of the natural recruitment within the system), nor should it be a new outlet for aquaculture production. Quantitative targets should be set and the expected performance of the stocking tested. Potential loopholes, such as post-release mortality and habitat requirements related to the release, should be examined and resolved. If properly managed, stocking may lead to an increase in population, contribute to the local fishery and/or lead to an increase in the spawning stock biomass. The criteria for stocking are discussed in this paper using examples from flatfish and cod stocking programmes within specific ecosystems.

  1. Dietary supplementation of a mixture of Lactobacillus strains enhances performance of broiler chickens raised under heat stress conditions

    NASA Astrophysics Data System (ADS)

    Faseleh Jahromi, Mohammad; Wesam Altaher, Yassir; Shokryazdan, Parisa; Ebrahimi, Roohollah; Ebrahimi, Mahdi; Idrus, Zulkifli; Tufarelli, Vincenzo; Liang, Juan Boo

    2016-07-01

    High ambient temperature is a major problem in commercial broiler production in the humid tropics because high producing broiler birds consume more feed, have higher metabolic activity, and thus higher body heat production. To evaluate the effects of two previously isolated potential probiotic strains ( Lactobacillus pentosus ITA23 and Lactobacillus acidophilus ITA44) on broilers growing under heat stress condition, a total of 192 chicks were randomly allocated into four treatment groups of 48 chickens each as follows: CL, birds fed with basal diet raised in 24 °C; PL, birds fed with basal diet plus 0.1 % probiotic mixture raised in 24 °C; CH, birds fed with basal diet raised in 35 °C; and PH, birds fed with basal diet plus 0.1 % probiotic mixture raised in 35 °C. The effects of probiotic mixture on the performance, expression of nutrient absorption genes of the small intestine, volatile fatty acids (VFA) and microbial population of cecal contents, antioxidant capacity of liver, and fatty acid composition of breast muscle were investigated. Results showed that probiotic positively affected the final body weight under both temperature conditions (PL and PH groups) compared to their respective control groups (CL and CH). Probiotic supplementation numerically improved the average daily gain (ADG) under lower temperature, but significantly improved ADG under the higher temperature ( P < 0.05) by sustaining high feed intake. Under the lower temperature environment, supplementation of the two Lactobacillus strains significantly increased the expression of the four sugar transporter genes tested (GLUT2, GLUT5, SGLT1, and SGLT4) indicating probiotic enhances the absorption of this nutrient. Similar but less pronounced effect was also observed under higher temperature (35 °C) condition. In addition, the probiotic mixture improved bacterial population of the cecal contents, by increasing beneficial bacteria and decreasing Escherichia coli population, which could be

  2. Dietary supplementation of a mixture of Lactobacillus strains enhances performance of broiler chickens raised under heat stress conditions.

    PubMed

    Faseleh Jahromi, Mohammad; Wesam Altaher, Yassir; Shokryazdan, Parisa; Ebrahimi, Roohollah; Ebrahimi, Mahdi; Idrus, Zulkifli; Tufarelli, Vincenzo; Liang, Juan Boo

    2016-07-01

    High ambient temperature is a major problem in commercial broiler production in the humid tropics because high producing broiler birds consume more feed, have higher metabolic activity, and thus higher body heat production. To evaluate the effects of two previously isolated potential probiotic strains (Lactobacillus pentosus ITA23 and Lactobacillus acidophilus ITA44) on broilers growing under heat stress condition, a total of 192 chicks were randomly allocated into four treatment groups of 48 chickens each as follows: CL, birds fed with basal diet raised in 24 °C; PL, birds fed with basal diet plus 0.1 % probiotic mixture raised in 24 °C; CH, birds fed with basal diet raised in 35 °C; and PH, birds fed with basal diet plus 0.1 % probiotic mixture raised in 35 °C. The effects of probiotic mixture on the performance, expression of nutrient absorption genes of the small intestine, volatile fatty acids (VFA) and microbial population of cecal contents, antioxidant capacity of liver, and fatty acid composition of breast muscle were investigated. Results showed that probiotic positively affected the final body weight under both temperature conditions (PL and PH groups) compared to their respective control groups (CL and CH). Probiotic supplementation numerically improved the average daily gain (ADG) under lower temperature, but significantly improved ADG under the higher temperature (P < 0.05) by sustaining high feed intake. Under the lower temperature environment, supplementation of the two Lactobacillus strains significantly increased the expression of the four sugar transporter genes tested (GLUT2, GLUT5, SGLT1, and SGLT4) indicating probiotic enhances the absorption of this nutrient. Similar but less pronounced effect was also observed under higher temperature (35 °C) condition. In addition, the probiotic mixture improved bacterial population of the cecal contents, by increasing beneficial bacteria and decreasing Escherichia coli population, which could

  3. Cognitive Enhancement and Education

    ERIC Educational Resources Information Center

    Buchanan, Allen

    2011-01-01

    Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

  4. Enhancement and Civic Virtue

    PubMed Central

    Jefferson, Will; Douglas, Thomas; Kahane, Guy; Savulescu, Julian

    2014-01-01

    Opponents of biomedical enhancement frequently adopt what Allen Buchanan has called the Personal Goods Assumption. On this assumption, the benefits of biomedical enhancement will accrue primarily to those individuals who undergo enhancements, not to wider society. Buchanan has argued that biomedical enhancements might in fact have substantial social benefits by increasing productivity. We outline another way in which enhancements might benefit wider society: by augmenting civic virtue and thus improving the functioning of our political communities. We thus directly confront critics of biomedical enhancement who argue that it will lead to a loss of social cohesion and a breakdown in political life. PMID:24882886

  5. Chemical penetration enhancers.

    PubMed

    Newton, Stephen J

    2013-01-01

    Chemical penetration enhancers are utilized in topical preparations as a method for enhancing permeation of drugs across the skin. In particular, they are utilized for transdermal delivery of medications in an attempt to produce a systemic response, to avoid first-pass metabolism, and to decrease the gastrointestinal transit time observed with oral medications. A review of the selection of chemical penetration enhancers, their mechanism of action, the most common chemical penetration enhancers in each class, and alternatives will be discussed in detail.

  6. Thermal Stabilty of Glucokinase (GK) as Influenced by the Substrate Glucose, an Allosteric Glucokinase Activator Drug (GKA) and the Osmolytes Glycerol and Urea

    PubMed Central

    Zelent, B.; Buettger, C.; Grimsby, J.; Sarabu, R.; Vanderkooi, J.M.; Wand, A.J.; Matschinsky, F. M.

    2014-01-01

    We investigated how glycerol, urea, glucose and a GKA influence kinetics and stability of wildtype and mutant GK. Glycerol and glucose stabilized GK additively. Glycerol barely affected the TF spectra of all GKs but decreased kcat, glucose S0.5 and KD values and ATP KM while leaving cooperativity unchanged. Glycerol sensitized all GKs to GKA as shown by TF. Glucose increased TF of GKs without influence of glycerol on the effect. Glycerol and GKA affected kinetics and binding additively. The activation energies for thermal denaturation of GK were a function of glucose with KDs of 3 and 1mM without and with glycerol, respectively. High urea denatured wild type GK reversibly at 20 and 60 °C and urea treatment of irreversibly heat denatured GK allowed refolding as demonstrated by TF including glucose response. We concluded: Glycerol stabilizes GK indirectly without changing the folding structure of the apoenzyme, by restructuring the surface water of the protein, whereas glucose stabilizes GK directly by binding to its substrate site and inducing a compact conformation. Glucose or glycerol (alone or combined) are unable to prevent irreversible heat denaturation above 40 °C. However, urea denatures GK reversibly even at 60 °C by binding to the protein backbone and directly interacting with hydrophobic side chains. It prevents irreversible aggregation allowing complete refolding when urea is removed. This study establishes the foundation for exploring numerous instability mutants among the more than 600 variant GKs causing diabetes in animals and humans. PMID:22446163

  7. Smart Image Enhancement Process

    NASA Technical Reports Server (NTRS)

    Jobson, Daniel J. (Inventor); Rahman, Zia-ur (Inventor); Woodell, Glenn A. (Inventor)

    2012-01-01

    Contrast and lightness measures are used to first classify the image as being one of non-turbid and turbid. If turbid, the original image is enhanced to generate a first enhanced image. If non-turbid, the original image is classified in terms of a merged contrast/lightness score based on the contrast and lightness measures. The non-turbid image is enhanced to generate a second enhanced image when a poor contrast/lightness score is associated therewith. When the second enhanced image has a poor contrast/lightness score associated therewith, this image is enhanced to generate a third enhanced image. A sharpness measure is computed for one image that is selected from (i) the non-turbid image, (ii) the first enhanced image, (iii) the second enhanced image when a good contrast/lightness score is associated therewith, and (iv) the third enhanced image. If the selected image is not-sharp, it is sharpened to generate a sharpened image. The final image is selected from the selected image and the sharpened image.

  8. Suboptimization of developmental enhancers.

    PubMed

    Farley, Emma K; Olson, Katrina M; Zhang, Wei; Brandt, Alexander J; Rokhsar, Daniel S; Levine, Michael S

    2015-10-16

    Transcriptional enhancers direct precise on-off patterns of gene expression during development. To explore the basis for this precision, we conducted a high-throughput analysis of the Otx-a enhancer, which mediates expression in the neural plate of Ciona embryos in response to fibroblast growth factor (FGF) signaling and a localized GATA determinant. We provide evidence that enhancer specificity depends on submaximal recognition motifs having reduced binding affinities ("suboptimization"). Native GATA and ETS (FGF) binding sites contain imperfect matches to consensus motifs. Perfect matches mediate robust but ectopic patterns of gene expression. The native sites are not arranged at optimal intervals, and subtle changes in their spacing alter enhancer activity. Multiple tiers of enhancer suboptimization produce specific, but weak, patterns of expression, and we suggest that clusters of weak enhancers, including certain "superenhancers," circumvent this trade-off in specificity and activity. PMID:26472909

  9. Credit Enhancement Overview Guide

    SciTech Connect

    Financing Solutions Working Group

    2014-01-01

    Provides considerations for state and local policymakers and energy efficiency program administrators designing and implementing successful credit enhancement strategies for residential and commercial buildings.

  10. Beta-cell gene expression and functional characterisation of the human insulinoma cell line CM.

    PubMed

    Baroni, M G; Cavallo, M G; Mark, M; Monetini, L; Stoehrer, B; Pozzilli, P

    1999-04-01

    Animal insulinoma cell lines are widely used to study physiological and pathophysiological mechanisms involved in glucose metabolism and to establish in vitro models for studies on beta-cells. In contrast, human insulinoma cell lines are rarely used because of difficulties in obtaining and culturing them for long periods. The aim of our study was to investigate, under different experimental conditions, the capacity of the human insulinoma cell line CM to retain beta-cell function, particularly the expression of constitutive beta-cell genes (insulin, the glucose transporters GLUT1 and GLUT2, glucokinase), intracellular and secreted insulin, beta-cell granules, and cAMP content. Results showed that CM cells from an early-passage express specific beta-cell genes in response to glucose stimulation, in particular the insulin and GLUT genes. Such capacity is lost at later passages when cells are cultured at standard glucose concentrations. However, if cultured at lower glucose concentration (0.8 mM) for a longer time, CM cells re-acquire the capacity to respond to glucose stimulation, as shown by the increased expression of beta-cell genes (insulin, GLUT2, glucokinase). Nonetheless, insulin secretion could not be restored under such experimental conditions despite the presence of intracellular insulin, although cAMP response to a potent activator of adenylate cyclase, forskolin, was present indicating a viable system. In conclusion, these data show that the human insulinoma cell line CM, at both early-passage and late-passage, posseses a functional glucose-signalling pathway and insulin mRNA expression similar to normal beta-cells, representing, therefore, a good model for studies concerning the signalling and expression of beta-cells. Furthermore, we have previously shown that it is also a good model for immunological studies. In this respect it is important to note that the CM cell line is one of the very few existing human beta-cell lines in long-term culture.

  11. A low-protein diet during pregnancy alters glucose metabolism and insulin secretion.

    PubMed

    Souza, Denise de Fátima I; Ignácio-Souza, Letícia M; Reis, Sílvia Regina de L; Reis, Marise Auxiliadora de B; Stoppiglia, Luiz Fabrizio; Carneiro, Everardo Magalhães; Boschero, Antonio Carlos; Arantes, Vanessa Cristina; Latorraca, Márcia Queiroz

    2012-03-01

    In pancreatic islets, glucose metabolism is a key process for insulin secretion, and pregnancy requires an increase in insulin secretion to compensate for the typical insulin resistance at the end of this period. Because a low-protein diet decreases insulin secretion, this type of diet could impair glucose homeostasis, leading to gestational diabetes. In pancreatic islets, we investigated GLUT2, glucokinase and hexokinase expression patterns as well as glucose uptake, utilization and oxidation rates. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. The insulin secretion in 2.8 mmol l(-1) of glucose was higher in islets from LPP rats than that in islets from CP, CNP and LPNP rats. Maximal insulin release was obtained at 8.3 and 16.7 mmol l(-1) of glucose in LPP and CP groups, respectively. The glucose dose-response curve from LPNP group was shifted to the right in relation to the CNP group. In the CP group, the concentration-response curve to glucose was shifted to the left compared with the CNP group. The LPP groups exhibited an "inverted U-shape" dose-response curve. The alterations in the GLUT2, glucokinase and hexokinase expression patterns neither impaired glucose metabolism nor correlated with glucose islet sensitivity, suggesting that β-cell sensitivity to glucose requires secondary events other than the observed metabolic/molecular events. PMID:22034157

  12. Constitutively active heat shock factor 1 enhances glucose-driven insulin secretion.

    PubMed

    Uchiyama, Tsuyoshi; Tomono, Shoichi; Utsugi, Toshihiro; Ohyama, Yoshio; Nakamura, Tetsuya; Tomura, Hideaki; Kawazu, Shoji; Okajima, Fumikazu; Kurabayashi, Masahiko

    2011-06-01

    Weak pancreatic β-cell function is a cause of type 2 diabetes mellitus. Glucokinase regulates insulin secretion via phosphorylation of glucose. The present study focused on a system for the self-protection of pancreatic cell by expressing heat shock factor (HSF) and heat shock protein (HSP) to improve insulin secretion without inducing hypoglycemia. We previously generated a constitutively active form of human HSF1 (CA-hHSF1). An adenovirus expressing CA-hHSF1 using the cytomegalovirus promoter was generated to infect mouse insulinoma cells (MIN6 cells). An adenovirus expressing CA-hHSF1 using a human insulin promoter (Ins-CA-hHSF1) was also generated to infect rats. We investigated whether CA-hHSF1 induces insulin secretion in MIN6 cells and whether Ins-CA-hHSF1 can improve blood glucose and serum insulin levels in healthy Wister rats and type 2 diabetes mellitus model rats. CA-hHSF1 expression increased insulin secretion 1.27-fold compared with the overexpression of wild-type hHSF1 in MIN6 cells via induction of HSP90 expression and subsequent activation of glucokinase. This mechanism is associated with activation of both glucokinase and neuronal nitric oxide synthase. Ins-CA-hHSF1 improved blood glucose levels in neonatal streptozotocin-induced diabetic rats. Furthermore, Ins-CA-hHSF1 reduced oral glucose tolerance testing results in healthy Wister rats because of an insulin spike at 15 minutes; however, it did not induce hypoglycemia. CA-hHSF1 induced insulin secretion both in vitro and in vivo. These findings suggest that gene therapy with Ins-CA-hHSF1 will be able to be used to treat patients with type 2 diabetes mellitus and impaired glucose tolerance without causing hypoglycemia at fasting. PMID:20817212

  13. Enhancing Drug Court Success

    ERIC Educational Resources Information Center

    Deschenes, Elizabeth Piper; Ireland, Connie; Kleinpeter, Christine B.

    2009-01-01

    This study evaluates the impact of enhanced drug court services in a large county in Southern California. These enhanced services, including specialty counseling groups, educational/employment resources, and increased Residential Treatment (RT) beds, were designed to increase program retention and successful completion (graduation) of drug court.…

  14. Enhanced oil recovery update

    SciTech Connect

    Smith, R.V

    1989-03-01

    Technology continues to grow in the realm of enhanced oil recovery. Since 1950 several processes have proven economic for oil recovery. Others are still in their infancy and must be custom designed for each reservoir. This paper gives a general overview of these processes. The author focuses on the latest technology and the outlook for enhanced oil recovery operations.

  15. Enhancing Individual Readiness.

    ERIC Educational Resources Information Center

    1997

    This document contains three papers from a symposium on enhancing individual readiness through human resource development (HRD). "Secondary School Administrator's Perception of Enhancing Self-Worth through Service" (Thomas Li-Ping Tang, Emily James Weatherford) presents results of a study to examine secondary school administrators' endorsement of…

  16. Electrostatic precipitator efficiency enhancement

    SciTech Connect

    Polizzotti, D.M.; Steelhammer, J.C.

    1983-05-24

    Method for enhancing the removal of particles from a particleladen gas stream utilizing an electrostatic precipitator, which comprises treating the gas with morpholine or derivatives thereof. Treated particles are found to also have desirable flow characteristics. Particularly effective compositions for the purpose comprise a combination of the morpholine, or derivative thereof, with an electrostatic precipitator efficiency enhancer, and in particular an alkanolamine.

  17. Should we enhance animals?

    PubMed Central

    Chan, Sarah

    2012-01-01

    Much bioethical discussion has been devoted to the subject of human enhancement through various technological means such as genetic modification. Although many of the same technologies could be, indeed in many cases already have been, applied to non-human animals, there has been very little consideration of the concept of “animal enhancement”, at least not in those specific terms. This paper addresses the notion of animal enhancement and the ethical issues surrounding it. A definition of animal enhancement is proposed that provides a framework within which to consider these issues; and it is argued that if human enhancement can be considered to be a moral obligation, so too can animal enhancement. PMID:19880704

  18. EDITORIAL: Nano-enhanced! Nano-enhanced!

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-08-01

    In the early 19th century, a series of engineering and scientific breakthroughs by Nicolas Léonard Sadi Carnot, James Watt and many others led to the foundations of thermodynamics and a new pedigree of mechanical designs that reset the standards of engineering efficiency. The result was the industrial revolution. In optical- and electronics- based nanotechnology research, a similarly subtle bargain is being made; we cannot alter the fact that systems have a finite response to external excitations, but what we can do is enhance that response. The promising attributes of ZnO have long been recognised; its large band gap and high exciton binding energy lend it to a number of applications from laser diodes, LEDs, optical waveguides and switches, and acousto-optic applications to sun cream. When this material is grown into nanowires and nanorods, the material gains a whole new dimension, as quantum confinement effects come into play. Discovery of the enhanced radiative recombination, which has potential for exploitation in many optical and opto-electronic applications, drove intensive research into investigating these structures and into finding methods to synthesise them with optimised properties. This research revealed further subtleties in the properties of these materials. One example is the work by researchers in the US reporting synthesis procedures that produced a yield—defined as the weight ratio of ZnO nanowires to the original graphite flakes—of 200%, and which also demonstrated, through photoluminescence analysis of nanowires grown on graphite flakes and substrates, that graphite induces oxygen vacancies during annealing, which enhances the deep-level to near-band-edge emission ratio [1]. Other one-dimensional materials that provide field emission enhancements include carbon nanotubes, and work has been performed to find ways of optimising the emission efficiency from these structures, such as through control of the emitter density [2]. One of the

  19. Hierarchical image enhancement

    NASA Astrophysics Data System (ADS)

    Qi, Wei; Han, Jing; Zhang, Yi; Bai, Lian-fa

    2016-05-01

    Image enhancement is an important technique in computer vision. In this paper, we propose a hierarchical image enhancement approach based on the structure layer and texture layer. In the structure layer, we propose a structure-based method based on GMM, which better exploits structure details with fewer noise. In the texture layer, we present a structure-filtering method to filter unwanted texture with keeping completeness of detected salient structure. Next, we introduce a structure constraint prior to integrate them, leading to an improved enhancement result. Extensive experiments demonstrate that the proposed approach achieves higher quality results than previous approaches.

  20. LIGNITE FUEL ENHANCEMENT

    SciTech Connect

    Charles Bullinger

    2005-07-07

    This 4th quarterly Technical Progress Report for the Lignite Fuel Enhancement Project summarizes activities from April 1st through June 30th of 2005. It also summarizes the subsequent purchasing activity and dryer/process construction.

  1. LIGNITE FUEL ENHANCEMENT

    SciTech Connect

    Charles Bullinger

    2005-06-07

    This 3rd quarterly Technical Progress Report for the Lignite Fuel Enhancement Project summarizes activities from January 1st through March 31st of 2005. It also summarizes the subsequent purchasing activity and final dryer/process design.

  2. Enhanced metabolite generation

    DOEpatents

    Chidambaram, Devicharan

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  3. Resonance enhanced tunneling

    NASA Astrophysics Data System (ADS)

    Matsumoto, S.; Yoshimura, M.

    2000-12-01

    Time evolution of tunneling in thermal medium is examined using the real-time semiclassical formalism previously developed. Effect of anharmonic terms in the potential well is shown to give a new mechanism of resonance enhanced tunneling. If the friction from environment is small enough, this mechanism may give a very large enhancement for the tunneling rate. The case of the asymmetric wine bottle potential is worked out in detail.

  4. MORAL ENHANCEMENT AND FREEDOM

    PubMed Central

    Harris, John

    2011-01-01

    This paper identifies human enhancement as one of the most significant areas of bioethical interest in the last twenty years. It discusses in more detail one area, namely moral enhancement, which is generating significant contemporary interest. The author argues that so far from being susceptible to new forms of high tech manipulation, either genetic, chemical, surgical or neurological, the only reliable methods of moral enhancement, either now or for the foreseeable future, are either those that have been in human and animal use for millennia, namely socialization, education and parental supervision or those high tech methods that are general in their application. By that is meant those forms of cognitive enhancement that operate across a wide range of cognitive abilities and do not target specifically ‘ethical’ capacities. The paper analyses the work of some of the leading contemporary advocates of moral enhancement and finds that in so far as they identify moral qualities or moral emotions for enhancement they have little prospect of success. PMID:21133978

  5. Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet.

    PubMed

    Kang, Jian; Ge, Chongyang; Yu, Lei; Li, Longlong; Ma, Haitian

    2016-01-01

    Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg·kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway. PMID:27410429

  6. Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet

    PubMed Central

    Kang, Jian; Ge, Chongyang; Yu, Lei; Li, Longlong; Ma, Haitian

    2016-01-01

    Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg·kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway. PMID:27410429

  7. In vitro differentiation potential of human haematopoietic CD34(+) cells towards pancreatic β-cells.

    PubMed

    Sunitha, Manne Mudhu; Srikanth, Lokanathan; Santhosh Kumar, Pasupuleti; Chandrasekhar, Chodimella; Sarma, Potukuchi Venkata Gurunadha Krishna

    2016-10-01

    Haematopoietic stem cells (HSCs) possess multipotent ability to differentiate into various types of cells on providing appropriate niche. In the present study, the differentiating potential of human HSCs into β-cells of islets of langerhans was explored. Human HSCs were apheretically isolated from a donor and cultured. Phenotypic characterization of CD34 glycoprotein in the growing monolayer HSCs was confirmed by immunocytochemistry and flow cytometry techniques. HSCs were induced by selection with beta cell differentiating medium (BDM), which consists of epidermal growth factor (EGF), fibroblast growth factor (FGF), transferrin, Triiodo-l-Tyronine, nicotinamide and activin A. Distinct morphological changes of differentiated cells were observed on staining with dithizone (DTZ) and expression of PDX1, insulin and synaptophysin was confirmed by immunocytochemistry. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed distinct expression of specific β-cell markers, pancreatic and duodenal homeobox-1 (PDX1), glucose transporter-2 (GLUT-2), synaptophysin (SYP) and insulin (INS) in these differentiated cells compared to HSCs. Further, these cells exhibited elevated expression of INS gene at 10 mM glucose upon inducing with different glucose concentrations. The prominent feature of the obtained β-cells was the presence of glucose sensors, which was determined by glucokinase activity and high glucokinase activity compared with CD34(+) stem cells. These findings illustrate the differentiation of CD34(+) HSCs into β-cells of islets of langerhans. PMID:27514733

  8. Antidiabetic activity of zinc oxide and silver nanoparticles on streptozotocin-induced diabetic rats.

    PubMed

    Alkaladi, Ali; Abdelazim, Aaser Mohamed; Afifi, Mohamed

    2014-01-01

    The use of nanoparticles in medicine is an attractive proposition. In the present study, zinc oxide and silver nanoparticles were evaluated for their antidiabetic activity. Fifty male albino rats with weight 120 ± 20 and age 6 months were used. Animals were grouped as follows: control; did not receive any type of treatment, diabetic; received a single intraperitoneal dose of streptozotocin (100 mg/kg), diabetic + zinc oxide nanoparticles (ZnONPs), received single daily oral dose of 10 mg/kg ZnONPs in suspension, diabetic + silver nanoparticles (SNPs); received a single daily oral dose of SNP of 10 mg/kg in suspension and diabetic + insulin; received a single subcutaneous dose of 0.6 units/50 g body weight. Zinc oxide and silver nanoparticles induce a significant reduced blood glucose, higher serum insulin, higher glucokinase activity higher expression level of insulin, insulin receptor, GLUT-2 and glucokinase genes in diabetic rats treated with zinc oxide, silver nanoparticles and insulin. In conclusion, zinc oxide and sliver nanoparticles act as potent antidiabetic agents. PMID:24477262

  9. Human nature and enhancement.

    PubMed

    Buchanan, Allen

    2009-03-01

    Appeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good. I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.

  10. Mechanisms of memory enhancement.

    PubMed

    Stern, Sarah A; Alberini, Cristina M

    2013-01-01

    The ongoing quest for memory enhancement is one that grows necessary as the global population increasingly ages. The extraordinary progress that has been made in the past few decades elucidating the underlying mechanisms of how long-term memories are formed has provided insight into how memories might also be enhanced. Capitalizing on this knowledge, it has been postulated that targeting many of the same mechanisms, including CREB activation, AMPA/NMDA receptor trafficking, neuromodulation (e.g., via dopamine, adrenaline, cortisol, or acetylcholine) and metabolic processes (e.g., via glucose and insulin) may all lead to the enhancement of memory. These and other mechanisms and/or approaches have been tested via genetic or pharmacological methods in animal models, and several have been investigated in humans as well. In addition, a number of behavioral methods, including exercise and reconsolidation, may also serve to strengthen and enhance memories. By utilizing this information and continuing to investigate these promising avenues, memory enhancement may indeed be achieved in the future.

  11. Surface Enhanced Quantum Control

    NASA Astrophysics Data System (ADS)

    Rangan, Chitra

    2013-05-01

    Miniaturization of quantum technologies have led to physics that require the marriage of atomic physics and nanomaterials science. Some of the resulting areas of research are hybrid quantum devices, single-molecule spectroscopies, table-top intense field generators, etc. I will present an area of research that I dub ``Surface-enhanced quantum control'' that is an exciting way of controlling light and nanomatter. By combining the electromagnetic enhancement properties of plasmonic nanomaterials with the modification of the atomic properties, we can achieve an unprecedented level of control over quantum dynamics. I will present examples of surface-enhanced state purification, in which quantum states near metal nanostructures can be rapidly purified by the application of a weak near-resonant control field. We gratefully acknowledge support from the NSERC Discovery Grant Program and the NSERC Strategic Network for Bioplasmonic Systems.

  12. Rituals enhance consumption.

    PubMed

    Vohs, Kathleen D; Wang, Yajin; Gino, Francesca; Norton, Michael I

    2013-09-01

    Four experiments tested the novel hypothesis that ritualistic behavior potentiates and enhances ensuing consumption--an effect found for chocolates, lemonade, and even carrots. Experiment 1 showed that participants who engaged in ritualized behavior, compared with those who did not, evaluated chocolate as more flavorful, valuable, and deserving of behavioral savoring. Experiment 2 demonstrated that random gestures do not boost consumption as much as ritualistic gestures do. It further showed that a delay between a ritual and the opportunity to consume heightens enjoyment, which attests to the idea that ritual behavior stimulates goal-directed action (to consume). Experiment 3 found that performing a ritual oneself enhances consumption more than watching someone else perform the same ritual, suggesting that personal involvement is crucial for the benefits of rituals to emerge. Finally, Experiment 4 provided direct evidence of the underlying process: Rituals enhance the enjoyment of consumption because of the greater involvement in the experience that they prompt.

  13. Biomedical enhancements as justice.

    PubMed

    Nam, Jeesoo

    2015-02-01

    Biomedical enhancements, the applications of medical technology to make better those who are neither ill nor deficient, have made great strides in the past few decades. Using Amartya Sen's capability approach as my framework, I argue in this article that far from being simply permissible, we have a prima facie moral obligation to use these new developments for the end goal of promoting social justice. In terms of both range and magnitude, the use of biomedical enhancements will mark a radical advance in how we compensate the most disadvantaged members of society.

  14. Measuring and Enhancing Creativity

    ERIC Educational Resources Information Center

    Mahboub, Kamyar C.; Portillo, Margaret B.; Liu, Yinhui; Chandraratna, Susantha

    2004-01-01

    The purpose of this study was to assess ways by which creativity may be enhanced in a design-oriented course. In order to demonstrate the validity of the approach, a statistically based study was employed. Additionally, the experiment was replicated in two design-oriented fields at the University of Kentucky. These fields were civil engineering…

  15. Investigations into Character Enhancement.

    ERIC Educational Resources Information Center

    Hartoonian, H. Michael

    2001-01-01

    Presents six different investigations of character enhancement that attempts to answer three questions: (1) who are you; (2) what is your destination; and (3) who is your captain? Intends to build relationships among ideas such as perspective taking, seeing and making connections with the other, and understanding more about ethical development.…

  16. Teaching to Enhance Research

    ERIC Educational Resources Information Center

    Harland, Tony

    2016-01-01

    In this paper, I present a conceptual argument for "teaching-led research" in which university lecturers construct courses that directly and positively influence their research, while at the same time, safeguard and enhance the student experience. A research-pedagogy for higher education considers the link between teaching and research,…

  17. Enhancing Employee Skills.

    ERIC Educational Resources Information Center

    1999

    This document contains four symposium papers on enhancing employee skills. "The Effect of Study Skills Training Intervention on United States Air Force Aeromedical Apprentices" (John C. Griffith) demonstrates how study skills intervention resulted in a significant increase in the end-of-course scores of a sample of 90 randomly selected Air Force…

  18. Enhancing Workgroup Performance.

    ERIC Educational Resources Information Center

    1998

    This document contains four papers from a symposium on enhancing workgroup performance in human resource development (HRD). "Formation of Cross-Cultural Global Teams: Making Informed Choices on Team Composition" (Robert L. Dilworth) describes how a mixed class of U.S. and international students identified their cultural and learning styles and…

  19. Cognition-Enhancing Drugs

    PubMed Central

    Mehlman, Maxwell J

    2004-01-01

    New drugs that enhance cognition in cognitively healthy individuals present difficult public policy challenges. While their use is not inherently unethical, steps must be taken to ensure that they are safe, that they are widely available to promote equality of opportunity, and that individuals are free to decide whether or not to use them. PMID:15330974

  20. Graphically Enhanced Science Notebooks

    ERIC Educational Resources Information Center

    Minogue, James; Wiebe, Eric; Madden, Lauren; Bedward, John; Carter, Mike

    2010-01-01

    A common mode of communication in the elementary classroom is the science notebook. In this article, the authors outline the ways in which "graphically enhanced science notebooks" can help engage students in complete and robust inquiry. Central to this approach is deliberate attention to the efficient and effective use of student-generated…

  1. Competence Enhancement Behavior Management

    ERIC Educational Resources Information Center

    Farmer, Thomas W.; Goforth, Jennifer B.; Hives, Jacqueline; Aaron, Annie; Jackson, Frances; Sgammato, Adrienne

    2006-01-01

    Competence Enhancement Behavior Management is presented as a framework for supporting students with challenging behaviors in general education classrooms. This approach emphasizes classroom management and discipline strategies that (a) help to build positive relations with students, (b) communicate to students that they are important, and (c)…

  2. Does Powerpoint enhance learning?

    PubMed

    Penciner, Rick

    2013-03-01

    The ubiquitous nature of PowerPoint begs the question, does PowerPoint enhance learning? This narrative explores the evidence for the effectiveness of PowerPoint and multimedia presentations in learning and information processing. Practical recommendations are provided for presentations.

  3. Music Enhances Learning.

    ERIC Educational Resources Information Center

    Campabello, Nicolette; De Carlo, Mary Jane; O'Neil, Jean; Vacek, Mary Jill

    An action research project implemented musical strategies to affect and enhance student recall and memory. The target population was three suburban elementary schools near a major midwestern city: (1) a kindergarten classroom contained 32-38 students; (2) a second grade classroom contained 23 students and five Individualized Education Program…

  4. Piezoelectrically Enhanced Photocathodes

    NASA Technical Reports Server (NTRS)

    Beach, Robert A.; Nikzad, Shouleh; Bell, Lloyd Douglas; Strittmatter, Robert

    2011-01-01

    Doping of photocathodes with materials that have large piezoelectric coefficients has been proposed as an alternative means of increasing the desired photoemission of electrons. Treating cathode materials to increase emission of electrons is called "activation" in the art. It has been common practice to activate photocathodes by depositing thin layers of suitable metals (usually, cesium). Because cesium is unstable in air, fabrication of cesiated photocathodes and devices that contain them must be performed in sealed tubes under vacuum. It is difficult and costly to perform fabrication processes in enclosed, evacuated spaces. The proposed piezoelectrically enhanced photocathodes would have electron-emission properties similar to those of cesiated photocathodes but would be stable in air, and therefore could be fabricated more easily and at lower cost. Candidate photocathodes include nitrides of elements in column III of the periodic table . especially compounds of the general formula Al(x)Ga(1.x)N (where 0< or = x < or =.1). These compounds have high piezoelectric coefficients and are suitable for obtaining response to ultraviolet light. Fabrication of a photocathode according to the proposal would include inducement of strain in cathode layers during growth of the layers on a substrate. The strain would be induced by exploiting structural mismatches among the various constituent materials of the cathode. Because of the piezoelectric effect in this material, the strain would give rise to strong electric fields that, in turn, would give rise to a high concentration of charge near the surface. Examples of devices in which piezoelectrically enhanced photocathodes could be used include microchannel plates, electron- bombarded charge-coupled devices, image tubes, and night-vision goggles. Piezoelectrically enhanced photocathode materials could also be used in making highly efficient monolithic photodetectors. Highly efficient and stable piezoelectrically enhanced

  5. Tea enhances insulin activity.

    PubMed

    Anderson, Richard A; Polansky, Marilyn M

    2002-11-20

    The most widely known health benefits of tea relate to the polyphenols as the principal active ingredients in protection against oxidative damage and in antibacterial, antiviral, anticarcinogenic, and antimutagenic activities, but polyphenols in tea may also increase insulin activity. The objective of this study was to determine the insulin-enhancing properties of tea and its components. Tea, as normally consumed, was shown to increase insulin activity >15-fold in vitro in an epididymal fat cell assay. Black, green, and oolong teas but not herbal teas, which are not teas in the traditional sense because they do not contain leaves of Camellia senensis, were all shown to increase insulin activity. High-performance liquid chromatography fractionation of tea extracts utilizing a Waters SymmetryPrep C18 column showed that the majority of the insulin-potentiating activity for green and oolong teas was due to epigallocatechin gallate. For black tea, the activity was present in several regions of the chromatogram corresponding to, in addition to epigallocatechin gallate, tannins, theaflavins, and other undefined compounds. Several known compounds found in tea were shown to enhance insulin with the greatest activity due to epigallocatechin gallate followed by epicatechin gallate, tannins, and theaflavins. Caffeine, catechin, and epicatechin displayed insignificant insulin-enhancing activities. Addition of lemon to the tea did not affect the insulin-potentiating activity. Addition of 5 g of 2% milk per cup decreased the insulin-potentiating activity one-third, and addition of 50 g of milk per cup decreased the insulin-potentiating activity approximately 90%. Nondairy creamers and soy milk also decreased the insulin-enhancing activity. These data demonstrate that tea contains in vitro insulin-enhancing activity and the predominant active ingredient is epigallocatechin gallate. PMID:12428980

  6. Surface-enhanced spectroscopy

    NASA Astrophysics Data System (ADS)

    Moskovits, Martin

    1985-07-01

    In 1978 it was discovered, largely through the work of Fleischmann, Van Duyne, Creighton, and their coworkers that molecules adsorbed on specially prepared silver surfaces produce a Raman spectrum that is at times a millionfold more intense than expected. This effect was dubbed surface-enhanced Raman scattering (SERS). Since then the effect has been demonstrated with many molecules and with a number of metals, including Cu, Ag, Au, Li, Na, K, In, Pt, and Rh. In addition, related phenomena such as surface-enhanced second-harmonic generation, four-wave mixing, absorption, and fluorescence have been observed. Although not all fine points of the enhancement mechanism have been clarified, the majority view is that the largest contributor to the intensity amplification results from the electric field enhancement that occurs in the vicinity of small, interacting metal particles that are illuminated with light resonant or near resonant with the localized surface-plasmon frequency of the metal structure. Small in this context is gauged in relation to the wavelength of light. The special preparations required to produce the effect, which include among other techniques electrochemical oxidation-reduction cycling, deposition of metal on very cold substrates, and the generation of metal-island films and colloids, is now understood to be necessary as a means of producing surfaces with appropriate electromagnetic resonances that may couple to electromagnetic fields either by generating rough films (as in the case of the former two examples) or by placing small metal particles in close proximity to one another (as in the case of the latter two). For molecules chemisorbed on SERS-active surface there exists a "chemical enhancement" in addition to the electromagnetic effect. Although difficult to measure accurately, the magnitude of this effect rarely exceeds a factor of 10 and is best thought to arise from the modification of the Raman polarizability tensor of the adsorbate

  7. Enhanced coalbed methane recovery

    SciTech Connect

    Mazzotti, M.; Pini, R.; Storti, G.

    2009-01-15

    The recovery of coalbed methane can be enhanced by injecting CO{sub 2} in the coal seam at supercritical conditions. Through an in situ adsorption/desorption process the displaced methane is produced and the adsorbed CO{sub 2} is permanently stored. This is called enhanced coalbed methane recovery (ECBM) and it is a technique under investigation as a possible approach to the geological storage of CO{sub 2} in a carbon dioxide capture and storage system. This work reviews the state of the art on fundamental and practical aspects of the technology and summarizes the results of ECBM field tests. These prove the feasibility of ECBM recovery and highlight substantial opportunities for interdisciplinary research at the interface between earth sciences and chemical engineering.

  8. Superposition Enhanced Nested Sampling

    NASA Astrophysics Data System (ADS)

    Martiniani, Stefano; Stevenson, Jacob D.; Wales, David J.; Frenkel, Daan

    2014-07-01

    The theoretical analysis of many problems in physics, astronomy, and applied mathematics requires an efficient numerical exploration of multimodal parameter spaces that exhibit broken ergodicity. Monte Carlo methods are widely used to deal with these classes of problems, but such simulations suffer from a ubiquitous sampling problem: The probability of sampling a particular state is proportional to its entropic weight. Devising an algorithm capable of sampling efficiently the full phase space is a long-standing problem. Here, we report a new hybrid method for the exploration of multimodal parameter spaces exhibiting broken ergodicity. Superposition enhanced nested sampling combines the strengths of global optimization with the unbiased or athermal sampling of nested sampling, greatly enhancing its efficiency with no additional parameters. We report extensive tests of this new approach for atomic clusters that are known to have energy landscapes for which conventional sampling schemes suffer from broken ergodicity. We also introduce a novel parallelization algorithm for nested sampling.

  9. Enhanced Microfluidic Electromagnetic Measurements

    NASA Technical Reports Server (NTRS)

    Giovangrandi, Laurent (Inventor); Ricco, Antonio J. (Inventor); Kovacs, Gregory (Inventor)

    2015-01-01

    Techniques for enhanced microfluidic impedance spectroscopy include causing a core fluid to flow into a channel between two sheath flows of one or more sheath fluids different from the core fluid. Flow in the channel is laminar. A dielectric constant of a fluid constituting either sheath flow is much less than a dielectric constant of the core fluid. Electrical impedance is measured in the channel between at least a first pair of electrodes. In some embodiments, enhanced optical measurements include causing a core fluid to flow into a channel between two sheath flows of one or more sheath fluids different from the core fluid. An optical index of refraction of a fluid constituting either sheath flow is much less than an optical index of refraction of the core fluid. An optical property is measured in the channel.

  10. Enhanced magnetocaloric effect material

    DOEpatents

    Lewis, Laura J. H.

    2006-07-18

    A magnetocaloric effect heterostructure having a core layer of a magnetostructural material with a giant magnetocaloric effect having a magnetic transition temperature equal to or greater than 150 K, and a constricting material layer coated on at least one surface of the magnetocaloric material core layer. The constricting material layer may enhance the magnetocaloric effect by restriction of volume changes of the core layer during application of a magnetic field to the heterostructure. A magnetocaloric effect heterostructure powder comprising a plurality of core particles of a magnetostructural material with a giant magnetocaloric effect having a magnetic transition temperature equal to or greater than 150 K, wherein each of the core particles is encapsulated within a coating of a constricting material is also disclosed. A method for enhancing the magnetocaloric effect within a giant magnetocaloric material including the step of coating a surface of the magnetocaloric material with a constricting material is disclosed.

  11. Image enhancement by holography.

    NASA Technical Reports Server (NTRS)

    Stroke, G. W.

    1973-01-01

    The speed of the holographic image deblurring method has recently been further enhanced by a new speed in the realization of the powerful holographic image-deblurring filter. The filter makes it possible to carry out the deblurring, in the optical computer used, in times of the order of one second. The experimental achievements using the holographic image-enhancement method are illustrated with examples ranging from out-of-focus or motion-blurred photographs, including 'amateur' photos recorded on Polaroid film, to the sharpening of the best available electron micrographs of viruses. Images recorded with X-rays, notably from rocket-borne photos of the sun, and out-of-focus photographs from cameras in NASA satellites have been similarly deblurred.

  12. Enhancing genetic virtue.

    PubMed

    Walker, Mark

    2009-09-01

    The Genetic Virtue Project (GVP) is a proposed interdisciplinary effort between philosophers, psychologists and geneticists to discover and enhance human ethics using biotechnology genetic correlates of virtuous behavior. The empirical plausibility that virtues have biological correlates is based on the claims that (a) virtues are a subset of personality, specifically, personality traits conceived of as "enduring behaviors," and (b) that there is ample evidence that personality traits have a genetic basis. The moral necessity to use the GVP for moral enhancement is based on the claims that we should eliminate evil (as understood generically, not religiously), as some evil is a function of human nature. The GVP is defended against several ethical and political criticisms.

  13. Digital Enhancement Of Pneumothoraces

    NASA Astrophysics Data System (ADS)

    Cocklin, M.; Kaye, G.; Kerr, I.; Lams, P.

    1982-11-01

    If a patient presents with symptoms indicative of a pneumothorax it is improbable that it would not be detected in a chest radiograph. However, detection on the radiograph can be difficult and a small pneumothorax may be missed when there is no clinical suspicion of its presence. This report presents some methods by which the characteristic pneumothorax edge may be enhanced by digital image processing. Various examples are given.

  14. Lignite Fuel Enhancement

    SciTech Connect

    Charles Bullinger

    2006-02-03

    This 6th quarterly Technical Progress Report for the Lignite Fuel Enhancement Project summarizes activities from October 1st through December 31st of 2005. It also summarizes the subsequent purchasing activity and dryer/process construction. Hypothesis remains the same. We will be able to dry lignite an increment to benefit the performance of and reduce emissions from a coal burning electric power generating station.

  15. Enhanced Rescue Lift Capability

    NASA Technical Reports Server (NTRS)

    Young, Larry A.

    2007-01-01

    The evolving and ever-increasing demands of emergency response and disaster relief support provided by rotorcraft dictate, among other things, the development of enhanced rescue lift capability for these platforms. This preliminary analysis is first-order in nature but provides considerable insight into some of the challenges inherent in trying to effect rescue using a unique form of robotic rescue device deployed and operated from rotary-wing aerial platforms.

  16. [About moral enhancement].

    PubMed

    Goffi, Jean-Yves

    2015-01-01

    First, a short summary of the moral enhancement debate is drawn up. Then an argument first put forward by J. Harris is explored: this argument is directly related to I. Perrson's and J. Savulescu's conception of moral life. To conclude, it is suggested that they advocate a naïve idea of technology, conceived as a neutral means for value loaded ends. PMID:26238765

  17. Enhanced airglow at Titan

    NASA Astrophysics Data System (ADS)

    Royer, Emilie; Esposito, Larry; Wahlund, Jan-Erik

    2016-06-01

    The Cassini Ultraviolet Imaging Spectrograph (UVIS) instrument made thousand of observations of Titan since its arrival in the Saturnian system in 2004, but only few of them have been analyzed yet. Using the imaging capability of UVIS combined to a big data analytics approach, we have been able to uncover an unexpected pattern in this observations: on several occasions the Titan airglow exhibits an enhanced brightness by approximately a factor of 2, generally combined with a lower altitude of the airglow emission peak. These events typically last from 10 to 30 minutes and are followed and preceded by an airglow of regular and expected level of brightness and altitude. Observations made by the Cassini Plasma Spectrometer (CAPS) instrument onboard Cassini allowed us to correlate the enhanced airglow observed on T-32 with an electron burst. The timing of the burst and the level of energetic electrons (1 keV) observed by CAPS correspond to a brighter and lower than typical airglow displayed on the UVIS data. Furthermore, during T-32 Titan was inside the Saturn's magnetosheath and thus more subject to bombardment by energetic particles. However, our analysis demonstrates that the presence of Titan inside the magnetosheath is not a necessary condition for the production of an enhanced airglow, as we detected other similar events while Titan was within Saturn's magnetosphere. The study presented here aims to a better understanding of the interactions of Titan's upper atmosphere with its direct environment.

  18. Sleep for cognitive enhancement

    PubMed Central

    Diekelmann, Susanne

    2014-01-01

    Sleep is essential for effective cognitive functioning. Loosing even a few hours of sleep can have detrimental effects on a wide variety of cognitive processes such as attention, language, reasoning, decision making, learning and memory. While sleep is necessary to ensure normal healthy cognitive functioning, it can also enhance performance beyond the boundaries of the normal condition. This article discusses the enhancing potential of sleep, mainly focusing on the domain of learning and memory. Sleep is known to facilitate the consolidation of memories learned before sleep as well as the acquisition of new memories to be learned after sleep. According to a widely held model this beneficial effect of sleep relies on the neuronal reactivation of memories during sleep that is associated with sleep-specific brain oscillations (slow oscillations, spindles, ripples) as well as a characteristic neurotransmitter milieu. Recent research indicates that memory processing during sleep can be boosted by (i) cueing memory reactivation during sleep; (ii) stimulating sleep-specific brain oscillations; and (iii) targeting specific neurotransmitter systems pharmacologically. Olfactory and auditory cues can be used, for example, to increase reactivation of associated memories during post-learning sleep. Intensifying neocortical slow oscillations (the hallmark of slow wave sleep (SWS)) by electrical or auditory stimulation and modulating specific neurotransmitters such as noradrenaline and glutamate likewise facilitates memory processing during sleep. With this evidence in mind, this article concludes by discussing different methodological caveats and ethical issues that should be considered when thinking about using sleep for cognitive enhancement in everyday applications. PMID:24765066

  19. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes.

  20. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  1. Enhancement and Obsolescence: Avoiding an "Enhanced Rat Race".

    PubMed

    Sparrow, Robert

    2015-09-01

    A claim about continuing technological progress plays an essential, if unacknowledged, role in the philosophical literature on "human enhancement." I argue that-should it eventuate-continuous improvement in enhancement technologies may prove more bane than benefit. A rapid increase in the power of available enhancements would mean that each cohort of enhanced individuals will find itself in danger of being outcompeted by the next in competition for important social goods-a situation I characterize as an "enhanced rat race." Rather than risk the chance of being rendered technologically and socially obsolete by the time one is in one's early 20s, it may be rational to prefer that a wide range of enhancements that would generate positional disadvantages that outweigh their absolute advantages be prohibited altogether. The danger of an enhanced rat race therefore constitutes a novel argument in favor of abandoning the pursuit of certain sorts of enhancements. PMID:26412737

  2. Metamaterials enhancing optical forces

    NASA Astrophysics Data System (ADS)

    Ginis, Vincent; Tassin, Philippe; Soukoulis, Costas M.; Veretennicoff, Irina

    2014-05-01

    The interaction between light and matter involves not only an energy transfer, but also the transfer of linear momentum. In everyday life applications this linear momentum of light is too small to play any significant role. However, in nanoscale dimensions, the associated optical forces start to play an increasingly important role. These forces are, e.g., large enough for exiting experiments in the fields of cavity-optomechanics, laser cooling and optical trapping of small particles. Recently, it has been suggested that optical gradient forces can also be employed for all-optical actuation in micro- and nanophotonic systems. The typical setup consists of two slab waveguides positioned in each others vicinity such that they are coupled through the interaction of the evanescent tails. Although the gradient forces between these waveguides can be enhanced considerably using electromagnetic resonators or slow-light techniques, the resulting displacements remain relatively small. In this contribution, we present an alternative approach to enhance optical gradient forces between waveguides using a combination of transformation optics and metamaterials. Our design starts from the observation that gradient forces exponentially decay with the separation distance between the waveguides. Therefore, we employ transformation optics to annihilate the apparent distance for light between the waveguides. Analytical calculations confirm that the resulting forces indeed increase when such an annihilating cladding is inserted. Subsequently, we discuss the metamaterial implementation of this annihilating medium. Such lensing media automatically translate into anisotropic metamaterials with negative components in the permittivity and permeability tensors. Our full-wave numerical simulations show that the overall amplification is highly limited by the loss-tangent of the metamaterial cladding. However, as this cladding only needs to operate in the near-field for a specific polarization

  3. Cell Growth Enhancement

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Exogene Corporation uses advanced technologies to enhance production of bio-processed substances like proteins, antibiotics and amino acids. Among them are genetic modification and a genetic switch. They originated in research for Jet Propulsion Laboratory. Extensive experiments in cell growth through production of hemoglobin to improve oxygen supply to cells were performed. By improving efficiency of oxygen use by cells, major operational expenses can be reduced. Greater product yields result in decreased raw material costs and more efficient use of equipment. A broad range of applications is cited.

  4. Optical waveguide enhanced photovoltaics.

    PubMed

    Rühle, Sven; Greenwald, Shlomit; Koren, Elad; Zaban, Arie

    2008-12-22

    Enhanced light to electric power conversion efficiency of photovoltaic cells with a low absorbance was achieved using waveguide integration. We present a proof of concept using a very thin dye-sensitized solar cell which absorbed only a small fraction of the light at normal incidence. The glass substrate in conjunction with the solar cells reflecting back contact formed a planar waveguide, which lead to more than four times higher conversion efficiency compared to conventional illumination at normal incidence. This illumination concept leads to a new type of multi-junction PV systems based on enforced spectral splitting along the waveguide.

  5. Plasma enhanced microwave joining

    SciTech Connect

    Yiin, T.; Barmatz, M.; Sayir, A.

    1995-12-31

    A new method for plasma enhanced microwave joining of high purity (99.8%) alumina has been developed. The controlled application of a plasma between the adjoining surfaces of two rods initially heats the microwave-low-absorbing alumina rods to temperatures high enough for them to absorb microwave energy efficiently. With this technology, the adjacent surfaces of alumina rods can be melted and welded together in less than three minutes using approximately 400 watts of microwave energy. Four point bending tests measured fracture strengths of up to 130 MPa at the joined interface. Optical and SEM micrographs indicated that exaggerated grain growth prevailed for all joints studied.

  6. Enhanced by Frost

    NASA Technical Reports Server (NTRS)

    2005-01-01

    30 September 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows outcrops of south polar layered terrain. Their appearance in this July 2005 springtime image is enhanced by bright patches of carbon dioxide frost. The frost is left over from the previous southern winter season; by summer, the frost would be gone.

    Location near: 84.6oS, 203.5oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

  7. Cognitive diversity and moral enhancement.

    PubMed

    Gyngell, Chris; Easteal, Simon

    2015-01-01

    One debate in contemporary bioethics centers on whether the development of cognitive enhancement technologies (CETs) will hasten the need for moral enhancement. In this article we provide a new argument in favor of pursuing these enhancement technologies together. The widespread availability of CETs will likely increase population-level cognitive diversity. Different people will choose to enhance different aspects of their cognition, and some won't enhance themselves at all. Although this has the potential to be beneficial for society, it could also result in harms as people become more different from one another. Aspects of our moral psychology make it difficult for people to cooperate and coordinate actions with those who are very different from themselves. These moral failings could be targeted by moral enhancement technologies, which may improve cooperation among individuals. Moral enhancement technologies will therefore help society maximize the benefits, and reduce the costs, associated with widespread access to cognitive enhancements.

  8. Computer enhancement of radiographs

    NASA Technical Reports Server (NTRS)

    Dekaney, A.; Keane, J.; Desautels, J.

    1973-01-01

    Examination of three relevant noise processes and the image degradation associated with Marshall Space Flight Center's (MSFC) X-ray/scanning system was conducted for application to computer enhancement of radiographs using MSFC's digital filtering techniques. Graininess of type M, R single coat and R double coat X-ray films was quantified as a function of density level using root-mean-square (RMS) granularity. Quantum mottle (including film grain) was quantified as a function of the above film types, exposure level, specimen material and thickness, and film density using RMS granularity and power spectral density (PSD). For various neutral-density levels the scanning device used in digital conversion of radiographs was examined for noise characteristics which were quantified by RMS granularity and PSD. Image degradation of the entire pre-enhancement system (MG-150 X-ray device; film; and optronics scanner) was measured using edge targets to generate modulation transfer functions (MTF). The four parameters were examined as a function of scanning aperture sizes of approximately 12.5 25 and 50 microns.

  9. Telemetry-Enhancing Scripts

    NASA Technical Reports Server (NTRS)

    Maimone, Mark W.

    2009-01-01

    Scripts Providing a Cool Kit of Telemetry Enhancing Tools (SPACKLE) is a set of software tools that fill gaps in capabilities of other software used in processing downlinked data in the Mars Exploration Rovers (MER) flight and test-bed operations. SPACKLE tools have helped to accelerate the automatic processing and interpretation of MER mission data, enabling non-experts to understand and/or use MER query and data product command simulation software tools more effectively. SPACKLE has greatly accelerated some operations and provides new capabilities. The tools of SPACKLE are written, variously, in Perl or the C or C++ language. They perform a variety of search and shortcut functions that include the following: Generating text-only, Event Report-annotated, and Web-enhanced views of command sequences; Labeling integer enumerations with their symbolic meanings in text messages and engineering channels; Systematic detecting of corruption within data products; Generating text-only displays of data-product catalogs including downlink status; Validating and labeling of commands related to data products; Performing of convenient searches of detailed engineering data spanning multiple Martian solar days; Generating tables of initial conditions pertaining to engineering, health, and accountability data; Simplified construction and simulation of command sequences; and Fast time format conversions and sorting.

  10. Surfactant-enhanced bioremediation

    SciTech Connect

    Churchill, P.F.; Dudley, R.J.; Churchill, S.A.

    1995-12-31

    This study was undertaken to examine the effect of three structurally related, non-ionic surfactants, Triton X-45, Triton X-100 and Triton X-165, as well as the oleophilic fertilizer, Inipol EAP 22, on the rate of biodegradation of phenanthrene by pure bacterial cultures. Each surfactant dramatically increased the apparent aqueous solubility of phenanthrene. Model studies were conducted to investigate the ability of these surfactants to enhance the rate of transport and uptake of polycyclic aromatic hydrocarbons into bacterial cells, and to assess the impact that increasing the aqueous solubility of hydrocarbons has on their rate of biodegradation. The results indicate that increasing the apparent aqueous solubility of hydrocarbons can lead to enhanced biodegradation rates by two Pseudomonas saccharophila strains. However, the experiments also suggest that some surfactants can inhibit aromatic hydrocarbon biodegradation by certain bacteria. The data also support the hypothesis that surface-active components present in the oleophilic fertilizer formulation, Inipol EAP 22, may have significantly contributed to the positive results reported in tests of remedial agent impact on bioremediation, which was used as a supplemental clean-up technology on Exxon Valdez crude oil-contaminated Alaskan beaches.

  11. Direct vs. Indirect Moral Enhancement.

    PubMed

    Schaefer, G Owen

    2015-09-01

    Moral enhancement is an ostensibly laudable project. Who wouldn't want people to become more moral? Still, the project's approach is crucial. We can distinguish between two approaches for moral enhancement: direct and indirect. Direct moral enhancements aim at bringing about particular ideas, motives or behaviors. Indirect moral enhancements, by contrast, aim at making people more reliably produce the morally correct ideas, motives or behaviors without committing to the content of those ideas, motives and/or actions. I will argue, on Millian grounds, that the value of disagreement puts serious pressure on proposals for relatively widespread direct moral enhancement. A more acceptable path would be to focus instead on indirect moral enhancements while staying neutral, for the most part, on a wide range of substantive moral claims. I will outline what such indirect moral enhancement might look like, and why we should expect it to lead to general moral improvement.

  12. Digitally Enhanced Heterodyne Interferometry

    NASA Technical Reports Server (NTRS)

    Shaddock, Daniel; Ware, Brent; Lay, Oliver; Dubovitsky, Serge

    2010-01-01

    Spurious interference limits the performance of many interferometric measurements. Digitally enhanced interferometry (DEI) improves measurement sensitivity by augmenting conventional heterodyne interferometry with pseudo-random noise (PRN) code phase modulation. DEI effectively changes the measurement problem from one of hardware (optics, electronics), which may deteriorate over time, to one of software (modulation, digital signal processing), which does not. DEI isolates interferometric signals based on their delay. Interferometric signals are effectively time-tagged by phase-modulating the laser source with a PRN code. DEI improves measurement sensitivity by exploiting the autocorrelation properties of the PRN to isolate only the signal of interest and reject spurious interference. The properties of the PRN code determine the degree of isolation.

  13. Photon enhanced thermionic emission

    SciTech Connect

    Schwede, Jared; Melosh, Nicholas; Shen, Zhixun

    2014-10-07

    Photon Enhanced Thermionic Emission (PETE) is exploited to provide improved efficiency for radiant energy conversion. A hot (greater than 200.degree. C.) semiconductor cathode is illuminated such that it emits electrons. Because the cathode is hot, significantly more electrons are emitted than would be emitted from a room temperature (or colder) cathode under the same illumination conditions. As a result of this increased electron emission, the energy conversion efficiency can be significantly increased relative to a conventional photovoltaic device. In PETE, the cathode electrons can be (and typically are) thermalized with respect to the cathode. As a result, PETE does not rely on emission of non-thermalized electrons, and is significantly easier to implement than hot-carrier emission approaches.

  14. Plant performance enhancement program

    SciTech Connect

    Munchausen, J.H.

    1995-09-01

    The Plant Performance Enhancement Program (P{sup 2}EP), an initiative of the Electric Power Research Institute (EPRI), responds to strong industry incentives to improve nuclear plant thermal efficiency and electrical output. Launched by EPRI`s Nuclear Power Division, P{sup 2}EP operates within the purview of the Plant Support Engineering (PSE) Program, with day-to-day activities conducted out of the P{sup 2}EP office headquartered at EPRI`s facility in Charlotte, North Carolina. This alignment is consistent with EPFU`s strategic targets in support of industry goals, keeping P{sup 2}EP`s mission in clear focus: Helping utility thermal performance engineers improve the heat rate of nuclear power plants, thereby increasing unit average capacity and reducing plant operations and maintenance costs per kilowatt-hour.

  15. Structure Size Enhanced Histogram

    NASA Astrophysics Data System (ADS)

    Wesarg, Stefan; Kirschner, Matthias

    Direct volume visualization requires the definition of transfer functions (TFs) for the assignment of opacity and color. Multi-dimensional TFs are based on at least two image properties, and are specified by means of 2D histograms. In this work we propose a new type of a 2D histogram which combines gray value with information about the size of the structures. This structure size enhanced (SSE) histogram is an intuitive approach for representing anatomical features. Clinicians — the users we are focusing on — are much more familiar with selecting features by their size than by their gradient magnitude value. As a proof of concept, we employ the SSE histogram for the definition of two-dimensional TFs for the visualization of 3D MRI and CT image data.

  16. Global Enhanced Vegetation Index

    NASA Technical Reports Server (NTRS)

    2002-01-01

    By carefully measuring the wavelengths and intensity of visible and near-infrared light reflected by the land surface back up into space, the Moderate-resolution Imaging Spectroradiometer (MODIS) Team can quantify the concentrations of green leaf vegetation around the world. The above MODIS Enhanced Vegetation Index (EVI) map shows the density of plant growth over the entire globe. Very low values of EVI (white and brown areas) correspond to barren areas of rock, sand, or snow. Moderate values (light greens) represent shrub and grassland, while high values indicate temperate and tropical rainforests (dark greens). The MODIS EVI gives scientists a new tool for monitoring major fluctuations in vegetation and understanding how they affect, and are affected by, regional climate trends. For more information, read NASA Unveils Spectacular Suite of New Global Data Products from MODIS. Image courtesy MODIS Land Group/Vegetation Indices, Alfredo Huete, Principal Investigator, and Kamel Didan, University of Arizona

  17. Cavity enhanced atomic magnetometry

    PubMed Central

    Crepaz, Herbert; Ley, Li Yuan; Dumke, Rainer

    2015-01-01

    Atom sensing based on Faraday rotation is an indispensable method for precision measurements, universally suitable for both hot and cold atomic systems. Here we demonstrate an all-optical magnetometer where the optical cell for Faraday rotation spectroscopy is augmented with a low finesse cavity. Unlike in previous experiments, where specifically designed multipass cells had been employed, our scheme allows to use conventional, spherical vapour cells. Spherical shaped cells have the advantage that they can be effectively coated inside with a spin relaxation suppressing layer providing long spin coherence times without addition of a buffer gas. Cavity enhancement shows in an increase in optical polarization rotation and sensitivity compared to single-pass configurations. PMID:26481853

  18. Plasmonic enhanced ultrafast switch.

    SciTech Connect

    Subramania,Ganapathi Subramanian; Reno, John Louis; Passmore, Brandon Scott; Harris, Tom.; Shaner, Eric Arthur; Barrick, Todd A.

    2009-09-01

    Ultrafast electronic switches fabricated from defective material have been used for several decades in order to produce picosecond electrical transients and TeraHertz radiation. Due to the ultrashort recombination time in the photoconductor materials used, these switches are inefficient and are ultimately limited by the amount of optical power that can be applied to the switch before self-destruction. The goal of this work is to create ultrafast (sub-picosecond response) photoconductive switches on GaAs that are enhanced through plasmonic coupling structures. Here, the plasmonic coupler primarily plays the role of being a radiation condenser which will cause carriers to be generated adjacent to metallic electrodes where they can more efficiently be collected.

  19. Delta launcher enhanced

    NASA Astrophysics Data System (ADS)

    1987-08-01

    The next-generation, 'Delta II' version of the Delta expendable launch vehicle will be able to launch over 4000 lbs into geosynchronous transfer orbit (GTO), as required by the USAF's Navstar GPS; the current Delta 3920 configuration can loft only 2800 lbs into GEO. Three distinct growth configurations of the Delta II are planned: the 6925, whose booster propellant tanks will be extended by 12 ft; the 7925, whose improved booster engine will increase nozzle expansion ratio from 8:1 to 12:1; and the 'enhanced ' Delta II, with stretched graphite-epoxy solid rocket motor cases. In this final form, Delta II will boost 4010 lbs into GTO, or 11,110 lbs into LEO.

  20. Enhancing multiple disciplinary teamwork.

    PubMed

    Weaver, Terri E

    2008-01-01

    Multiple disciplinary research provides an opportunity to bring together investigators across disciplines to provide new views and develop innovative approaches to important questions. Through this shared experience, novel paradigms are formed, original frameworks are developed, and new language is generated. Integral to the successful construction of effective cross-disciplinary teams is the recognition of antecedent factors that affect the development of the team such as intrapersonal, social, physical environmental, organizational, and institutional influences. Team functioning is enhanced with well-developed behavioral, affective, interpersonal, and intellectual processes. Outcomes of effective multiple disciplinary research teams include novel ideas, integrative models, new training programs, institutional change, and innovative policies that can also influence the degree to which antecedents and processes contribute to team performance. Ongoing evaluation of team functioning and achievement of designated outcomes ensures the continued development of the multiple disciplinary team and confirmation of this approach as important to the advancement of science.

  1. Enhanced oil recovery system

    DOEpatents

    Goldsberry, Fred L.

    1989-01-01

    All energy resources available from a geopressured geothermal reservoir are used for the production of pipeline quality gas using a high pressure separator/heat exchanger and a membrane separator, and recovering waste gas from both the membrane separator and a low pressure separator in tandem with the high pressure separator for use in enhanced oil recovery, or in powering a gas engine and turbine set. Liquid hydrocarbons are skimmed off the top of geothermal brine in the low pressure separator. High pressure brine from the geothermal well is used to drive a turbine/generator set before recovering waste gas in the first separator. Another turbine/generator set is provided in a supercritical binary power plant that uses propane as a working fluid in a closed cycle, and uses exhaust heat from the combustion engine and geothermal energy of the brine in the separator/heat exchanger to heat the propane.

  2. Enhanced Geothermal Systems

    SciTech Connect

    Jeanloz, R.; Stone, H.

    2013-12-31

    DOE, through the Geothermal Technologies Office (GTO) within the Office of Energy Efficiency and Renewable Energy, requested this study, identifying a focus on: i) assessment of technologies and approaches for subsurface imaging and characterization so as to be able to validate EGS opportunities, and ii) assessment of approaches toward creating sites for EGS, including science and engineering to enhance permeability and increase the recovery factor. Two days of briefings provided in-depth discussion of a wide range of themes and challenges in EGS, and represented perspectives from industry, government laboratories and university researchers. JASON also contacted colleagues from universities, government labs and industry in further conversations to learn the state of the field and potential technologies relevant to EGS.

  3. Teacher Enhancement Institute

    NASA Technical Reports Server (NTRS)

    Marshall-Bradley, Tina

    1994-01-01

    During the 1980's, a period of intense concern over educational quality in the United States, few indicators of U.S. student achievement garnered the interest of policy makers and pundits as successfully as the results of international testing in mathematics and science. This concern was so great that as a part of the Goals 2000 initiative, President George Bush indicated that 'By the year 2000, U.S. students should be first in the world in mathematics and science.' The Clinton Administration is placing a major emphasis, not only on rigorous academic standards and creating a new system for assessing students' progress, but also including professional development as a major focus. The argument being that teachers need more sustained, intensive training to prepare them to teach to higher standards. Executive order 12821 mandates that national laboratories 'assist in the mathematics and science education of our Nation's students, teachers, parents and the public by establishing programs at their agency to provide for training elementary and secondary school teachers to improve their knowledge of mathematics and science'. These and other issues led to the development of ideas for a project that addresses the need for excellence in mathematics, science and technology instruction. In response to these initiatives the NASA/LaRC Teacher Enhancement Institute was proposed. The TEI incorporated systemic reform perspectives, enhanced content knowledge for teachers, and teacher preparation. Emphasis was also placed on recruiting those educators who teach in impoverished urban school districts with at-risk student populations who have been traditionally under represented in science, mathematics, technology and engineering. Participants in the Teacher Enhancement Institute were 37 teachers from grades K-8, teaching in Region 2 in the state of Virginia, as well as 2 preservice teachers from Norfolk State University and one teacher from Dublin, Virginia, where a Science

  4. Lignite Fuel Enhancement

    SciTech Connect

    Charles Bullinger; Nenad Sarunac

    2010-03-31

    Pulverized coal power plants which fire lignites and other low-rank high-moisture coals generally operate with reduced efficiencies and increased stack emissions due to the impacts of high fuel moisture on stack heat loss and pulverizer and fan power. A process that uses plant waste heat sources to evaporate a portion of the fuel moisture from the lignite feedstock in a moving bed fluidized bed dryer (FBD) was developed in the U.S. by a team led by Great River Energy (GRE). The demonstration was conducted with Department of Energy (DOE) funding under DOE Award Number DE-FC26-04NT41763. The objectives of GRE's Lignite Fuel Enhancement project were to demonstrate reduction in lignite moisture content by using heat rejected from the power plant, apply technology at full scale at Coal Creek Station (CCS), and commercialize it. The Coal Creek Project has involved several stages, beginning with lignite drying tests in a laboratory-scale FBD at the Energy Research Center (ERC) and development of theoretical models for predicting dryer performance. Using results from these early stage research efforts, GRE built a 2 ton/hour pilot-scale dryer, and a 75 ton/hour prototype drying system at Coal Creek Station. Operated over a range of drying conditions, the results from the pilot-scale and prototype-scale dryers confirmed the performance of the basic dryer design concept and provided the knowledge base needed to scale the process up to commercial size. Phase 2 of the GRE's Lignite Fuel Enhancement project included design, construction and integration of a full-scale commercial coal drying system (four FBDs per unit) with Coal Creek Units 1 and 2 heat sources and coal handling system. Two series of controlled tests were conducted at Coal Creek Unit 1 with wet and dried lignite to determine effect of dried lignite on unit performance and emissions. Wet lignite was fired during the first, wet baseline, test series conducted in September 2009. The second test series was performed

  5. Enhanced preliminary assessment

    SciTech Connect

    Not Available

    1992-02-01

    An Enhanced Preliminary Assessment was conducted at Fort Benjamin Harrison (FBH) Indiana, which is located approximately 12 miles from downtown Indianapolis in Lawrence Township, Marion County. FBH contains 2,501 acres, of which approximately 1,069 acres is covered by woodlands. Activities at FBH include administration, training, housing, and support. Sensitive environments at FBH include wetlands, habitat areas for the endangered Indiana bat, endangered plants, and historically and archeologically significant areas. FBH is a U.S. Army Soldier Support Center under the jurisdiction of the U.S. Army Training and Doctrine Command (TRADOC). Based on information obtained during and subsequent to a site visit (15 through 18 October 1991), 36 types of Areas Requiring Environmental Evaluation (AREEs) were identified and grouped by the following categories: Facility Operations; Maintenance/Fueling Operations; Water Treatment Operations; Training Areas; Hazardous Materials Storage/Waste Handling Areas; Sanitary Wastewater Treatment Plants; Storage Tanks; Landfills/Incinerators; Medical Facilities; Burn Pit Areas; Spill Areas; Ammunition Storage; Coal Storage; and Facility-wide AREEs. This report presents a summary of findings for each AREE and recommendations for further action.

  6. Enhanced Design Alternative IV

    SciTech Connect

    N. E. Kramer

    1999-05-18

    This report evaluates Enhanced Design Alternative (EDA) IV as part of the second phase of the License Application Design Selection (LADS) effort. The EDA IV concept was compared to the VA reference design using criteria from the ''Design Input Request for LADS Phase II EDA Evaluations'' (CRWMS M&O 1999b) and (CRWMS M&O 1999f). Briefly, the EDA IV concept arranges the waste packages close together in an emplacement configuration known as ''line load''. Continuous pre-closure ventilation keeps the waste packages from exceeding the 350 C cladding and 200 C (4.3.13) drift wall temperature limits. This EDA concept keeps relatively high, uniform emplacement drift temperatures (post-closure) to drive water away from the repository and thus dry out the pillars between emplacement drifts. The waste package is shielded to permit human access to emplacement drifts and includes an integral filler inside the package to reduce the amount of water that can contact the waste form. Closure of the repository is desired 50 years after first waste is emplaced. Both backfill and a drip shields will be emplaced at closure to improve post-closure performance.

  7. Enhanced Micellar Catalysis LDRD.

    SciTech Connect

    Betty, Rita G.; Tucker, Mark D; Taggart, Gretchen; Kinnan, Mark K.; Glen, Crystal Chanea; Rivera, Danielle; Sanchez, Andres; Alam, Todd Michael

    2012-12-01

    The primary goals of the Enhanced Micellar Catalysis project were to gain an understanding of the micellar environment of DF-200, or similar liquid CBW surfactant-based decontaminants, as well as characterize the aerosolized DF-200 droplet distribution and droplet chemistry under baseline ITW rotary atomization conditions. Micellar characterization of limited surfactant solutions was performed externally through the collection and measurement of Small Angle X-Ray Scattering (SAXS) images and Cryo-Transmission Electron Microscopy (cryo-TEM) images. Micellar characterization was performed externally at the University of Minnesotas Characterization Facility Center, and at the Argonne National Laboratory Advanced Photon Source facility. A micellar diffusion study was conducted internally at Sandia to measure diffusion constants of surfactants over a concentration range, to estimate the effective micelle diameter, to determine the impact of individual components to the micellar environment in solution, and the impact of combined components to surfactant phase behavior. Aerosolized DF-200 sprays were characterized for particle size and distribution and limited chemical composition. Evaporation rates of aerosolized DF-200 sprays were estimated under a set of baseline ITW nozzle test system parameters.

  8. Enhanced target factor analysis.

    PubMed

    Rostami, Akram; Abdollahi, Hamid; Maeder, Marcel

    2016-03-10

    Target testing or target factor analysis, TFA, is a well-established soft analysis method. TFA answers the question whether an independent target test vector measured at the same wavelengths as the collection of spectra in a data matrix can be excluded as the spectrum of one of the components in the system under investigation. Essentially, TFA cannot positively prove that a particular test spectrum is the true spectrum of one of the components, it can, only reject a spectrum. However, TFA will not reject, or in other words TFA will accept, many spectra which cannot be component spectra. Enhanced Target Factor Analysis, ETFA addresses the above problem. Compared with traditional TFA, ETFA results in a significantly narrower range of positive results, i.e. the chance of a false positive test result is dramatically reduced. ETFA is based on feasibility testing as described in Refs. [16-19]. The method has been tested and validated with computer generated and real data sets.

  9. Enhanced membrane gas separations

    SciTech Connect

    Prasad, R.

    1993-07-13

    An improved membrane gas separation process is described comprising: (a) passing a feed gas stream to the non-permeate side of a membrane system adapted for the passage of purge gas on the permeate side thereof, and for the passage of the feed gas stream in a counter current flow pattern relative to the flow of purge gas on the permeate side thereof, said membrane system being capable of selectively permeating a fast permeating component from said feed gas, at a feed gas pressure at or above atmospheric pressure; (b) passing purge gas to the permeate side of the membrane system in counter current flow to the flow of said feed gas stream in order to facilitate carrying away of said fast permeating component from the surface of the membrane and maintaining the driving force for removal of the fast permeating component through the membrane from the feed gas stream, said permeate side of the membrane being maintained at a subatmospheric pressure within the range of from about 0.1 to about 5 psia by vacuum pump means; (c) recovering a product gas stream from the non-permeate side of the membrane; and (d) discharging purge gas and the fast permeating component that has permeated the membrane from the permeate side of the membrane, whereby the vacuum conditions maintained on the permeate side of the membrane by said vacuum pump means enhance the efficiency of the gas separation operation, thereby reducing the overall energy requirements thereof.

  10. Enhancing chemical reactions

    DOEpatents

    Morrey, John R.

    1978-01-01

    Methods of enhancing selected chemical reactions. The population of a selected high vibrational energy state of a reactant molecule is increased substantially above its population at thermal equilibrium by directing onto the molecule a beam of radiant energy from a laser having a combination of frequency and intensity selected to pump the selected energy state, and the reaction is carried out with the temperature, pressure, and concentrations of reactants maintained at a combination of values selected to optimize the reaction in preference to thermal degradation by transforming the absorbed energy into translational motion. The reaction temperature is selected to optimize the reaction. Typically a laser and a frequency doubler emit radiant energy at frequencies of .nu. and 2.nu. into an optical dye within an optical cavity capable of being tuned to a wanted frequency .delta. or a parametric oscillator comprising a non-centrosymmetric crystal having two indices of refraction, to emit radiant energy at the frequencies of .nu., 2.nu., and .delta. (and, with a parametric oscillator, also at 2.nu.-.delta.). Each unwanted frequency is filtered out, and each desired frequency is focused to the desired radiation flux within a reaction chamber and is reflected repeatedly through the chamber while reactants are fed into the chamber and reaction products are removed therefrom.

  11. Waste water filtration enhancement

    SciTech Connect

    Martin, H.L.

    1989-01-01

    Removal of submicron particles from process solutions and waste water is now economically achievable using a new Tyvek{reg sign} media in conventional filtration equipment. This new product greatly enhances filtration and allows use of the much improved filter aids and polymers which were recently developed. It has reduced operating costs and ensures a clean effluent discharge to the environment. This significant technical development is especially important to those who discharge to a small stream with low 7Q10 flow and must soon routinely pass the Toxicity tests that are being required by many States for NPDES permit renewal. The Savannah River Plant produces special nuclear materials for the US Government. Aluminum forming and metal finishing operations in M-Area, that manufacture fuel and target assemblies for the nuclear reactors, discharge to a waste water treatment facility using BAT hydroxide precipitation and filtration. The new Tyvek{reg sign} media and filter aids have achieved 55% less solids in the filtrate discharged to Tims Branch Creek, 15% less hazardous waste (dry filter cake), 150%-370% more filtration capacity, 74% lower materials purchase cost, 10% lower total M-Area manufacturing cost, and have improved safety. Performance with the improved polymers is now being evaluated.

  12. Enhancing young people's awareness.

    PubMed

    Doan Thi Tien

    1995-01-01

    The role of the Vietnam Youth Union (21 million members) is to educate the youth aged 14-28 years about the movement at the grassroots level. Since 1995, it has been entrusted with information, education, and communication (IEC) activities (implemented through the Educational Center for Population, Health, and Development) concerning family planning, the environment, human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Mass media, direct communication, Youth Union leading staff, Youth Union cultural and arts activities, and advertisement have been used. 16 newspapers and magazines, a radio program, and a TV program disseminate information for the group. 1000 motivators' groups, 1370 Youth Clubs, and Youth Villages at the commune level work to enhance awareness and to change biased attitudes and habits. Leading staff speak at conferences and seminars that are attended by target groups. Art troupes perform at special local events; plays are organized and videos are shown. The HIV/AIDS information and prevention campaign is of great importance because research findings indicate that many young people believe that only prostitutes and drug addicts can be infected, and that condoms are bad and only for use with prostitutes. There are about 2300 persons infected with HIV in 14 provinces, mostly in the south and central regions. 131 are reported to have developed AIDS. PMID:12320323

  13. Enhanced local tomography

    DOEpatents

    Katsevich, Alexander J.; Ramm, Alexander G.

    1996-01-01

    Local tomography is enhanced to determine the location and value of a discontinuity between a first internal density of an object and a second density of a region within the object. A beam of radiation is directed in a predetermined pattern through the region of the object containing the discontinuity. Relative attenuation data of the beam is determined within the predetermined pattern having a first data component that includes attenuation data through the region. In a first method for evaluating the value of the discontinuity, the relative attenuation data is inputted to a local tomography function .function..sub..LAMBDA. to define the location S of the density discontinuity. The asymptotic behavior of .function..sub..LAMBDA. is determined in a neighborhood of S, and the value for the discontinuity is estimated from the asymptotic behavior of .function..sub..LAMBDA.. In a second method for evaluating the value of the discontinuity, a gradient value for a mollified local tomography function .gradient..function..sub..LAMBDA..epsilon. (x.sub.ij) is determined along the discontinuity; and the value of the jump of the density across the discontinuity curve (or surface) S is estimated from the gradient values.

  14. Backside configured surface plasmonic enhancement

    SciTech Connect

    Gu, Guiru; Lu, Xuejun; Vaillancourt, Jarrod

    2014-03-31

    In this work, we fabricated, measured and compared the quantum dots infrared photodetector enhancement by the top- and backside- configured plasmonic structures. The backside configured plasmonic structure can provide much higher device performance enhancement. Furthermore, the excitation of the surface plasmonic waves by the top- and backside- configured plasmonic structures was analyzed. Detailed simulation results of the electric field at different wavelength from top illumination and backside illumination were provided. The stronger electric field from the backside illumination attributed to the higher enhancement.

  15. Cognitive Enhancement: Treating or Cheating?

    PubMed

    Whetstine, Leslie M

    2015-09-01

    In this article I provide an overview of the moral and medical questions surrounding the use of cognitive enhancers. This discussion will be framed in light of 4 key considerations: (1) is there a difference between therapy and enhancement? (2) How safe are these interventions? (3) Is the use of nootropics cheating? (4) Would enhancers create a further divide of social inequality where only the very wealthy have access to them?

  16. Performance-enhancing supplements.

    PubMed

    Pecci, M A; Lombardo, J A

    2000-11-01

    Supplements that are marketed as ergogenic aids have achieved widespread use in the United States. In image-conscious society, these agents are not only being consumed by athletes, but also by those looking for a quick fix to enhance their appearance. Many assume that the performance claims made by the manufacturers are based on actual data, and that these agents must be safe because they are sold to the general public. Unfortunately, in most cases these assumptions are false. Creatine has become very popular, particularly among college and high school athletes. Studies within the last 5 years have shown that creatine does seem to have certain ergogenic benefits in a laboratory setting. It is not currently known whether these benefits actually can be transferred to the playing field. Although creatine has not consistently been shown to cause any major side effects, there is some question regarding creatine's effect on the kidneys, particularly with long-term use. Also, the safety of supplementation in children and adolescents has not been examined at all; its use in this population should be discouraged until there are more data. Androstenedione is an agent that has received a large amount of popular press in the last year, and this has led to an surge in its usage. It is believed to exert its ergogenic effects through conversion to testosterone. But what limited data are available suggest that at the recommended dosage, it does not cause any measurable change in testosterone levels, or provide any ergogenic benefit in inexperienced weight lifters. Also, it has yet to be determined whether androstenedione causes any of the side effects often attributed to use of the illegal anabolic steroids. Its mechanism of action suggests it has the potential to cause many of these negative effects. Studies are just beginning to appear in the literature, and certainly more data need to be gathered before androstenedione supplementation can be recommended for use as an ergogenic

  17. Lignite Fuel Enhancement

    SciTech Connect

    Charles Bullinger

    2007-03-31

    This 11th quarterly Technical Progress Report for the Lignite Fuel Enhancement Project summarizes activities from January 1st through March 31st of 2007. It summarizes the completion of the Prototype testing activity and initial full-scale dryer design, Budget Period 2 activity during that time period. The Design Team completed process design and layouts of air, water, and coal systems. Heyl-Patterson completed dryer drawings and has sent RFPs to several fabricators for build and assembly. Several meetings were held with Barr engineers to finalize arrangement of the drying, air jig, and coal handling systems. Honeywell held meetings do discuss the control system logic and hardware location. By the end of March we had processed nearly 300,000 tons of lignite through the dryer. Outage preparation maintenance activities on a coal transfer hopper restricted operation of the dryer in February and March. The Outage began March 17th. We will not dry coal again until early May when the Outage on Unit No.2 completes. The Budget Period 1 (Phase 1) final report was submitted this quarter. Comments were received from NETL and are being reviewed. The Phase 2 Project Management Plan was submitted to NETL in January 2007. This deliverable also included the Financing Plan. An application for R&D 100 award was submitted in February. The project received an award from the Minnesota Professional Engineering Society's Seven Wonders of Engineering Award and Minnesota ACEC Grand Award in January. To further summarize, the focus this quarter has been on finalizing commercial design and the layout of four dryers behind each Unit. The modification to the coal handling facilities at Coal Creek and incorporation of air jigs to further beneficiate the segregated material the dryers will reject 20 to 30 % of the mercury and sulfur is segregated however this modification will recover the carbon in that stream.

  18. Enhancers, enhancers - from their discovery to today's universe of transcription enhancers.

    PubMed

    Schaffner, Walter

    2015-04-01

    Transcriptional enhancers are short (200-1500 base pairs) DNA segments that are able to dramatically boost transcription from the promoter of a target gene. Originally discovered in simian virus 40 (SV40), a small DNA virus, transcription enhancers were soon also found in immunoglobulin genes and other cellular genes as key determinants of cell-type-specific gene expression. Enhancers can exert their effect over long distances of thousands, even hundreds of thousands of base pairs, either from upstream, downstream, or from within a transcription unit. The number of enhancers in eukaryotic genomes correlates with the complexity of the organism; a typical mammalian gene is likely controlled by several enhancers to fine-tune its expression at different developmental stages, in different cell types and in response to different signaling cues. Here, I provide a personal account of how enhancers were discovered more than 30 years ago, and also address the amazing development of the field since then.

  19. Plasmon Enhanced Photoemission

    SciTech Connect

    Polyakov, Aleksandr

    2012-05-08

    this work, the structure consisted of rectangular nano-grooves (NGs) arranged in a subwavelength grating on a metal surface is presented that provides a dramatic increase in the metal’s absorption, field localization, and field enhancement. When light is polarized perpendicular to the orientation of the grooves a standing SPP wave is excited along the vertical walls in the NGs, that act as Fabry-Perot resonators. By adjusting the geometry of the NGs and the period of the subwavelength grating the resonance can be fine tuned to a desired position, for example, the laser fundamental wavelength, anywhere from the UV to the near infrared (NIR). Two types of gratings are presented: (a) a gold grating with period of 600 nm, and (b) an aluminum-gold grating with a period of 100 nm; both with resonance at 720 nm. In each case, strong on-resonance absorption was observed, with over 98% for grating (b). Unlike the grating-coupled SPP waves, where the angle is well defined by the momentum matching condition, the resonant NGs allow coupling to the standing modes at a range of angles of incidence, referred to as the angular bandwidth. A new model for the on-resonance absorption based on the ensamble action of the NGs is presented that serves as the basis for a design of an NG grating with an ultrawide spectral as well as angular bandwidth. For sample (b), the angular bandwidth is 80 degrees, corresponding to an opening angle of 160 degrees. The photoemission enhancement for such a grating was measured to be seven orders of magnitude for a four-photon photoemission. This is an incredible result demonstrating the power of the plasmonic grating presented, which is an efficient light trapper and field enhancer for a non-linear processes. These results demonstrate that the metal photocathode prepared with a NG grating on the metal surface will provide sufficient pulse charge driven by a 1 μJ 15fs pulsed laser at 800 nm for the optimum FEL operation.

  20. Enhancing Motivation in Physical Education

    ERIC Educational Resources Information Center

    Alderman, Brandon L.; Beighle, Aaron; Pangrazi, Robert P.

    2006-01-01

    Increasing motivation towards physical activity through quality physical education has recently gained considerable attention. Several investigators have outlined specific models or theories to illustrate how motivation can be enhanced in physical education. Enhancing a youngster's perceived physical competence, promoting intrinsic motivation…

  1. Enhancing Self Esteem. Second Edition.

    ERIC Educational Resources Information Center

    Frey, Diane; Carlock, C. Jesse

    This book takes the theory of self-esteem and translates that theory into practice. It presents a systematic approach to enhancing self-esteem, suggesting a specific sequence and phase-wise progression of enhancing self-esteem. Cognitive, emotional, and behavioral aspects of individuals are all incorporated into the theory and practice outlined in…

  2. Performance-enhancing drug use.

    PubMed

    Green, Gary A

    2009-09-01

    According to Gary Green, MD, everyone who deals with athletes is a "stakeholder" in the issue of performance-enhancing drugs and can influence athletes in a positive or negative role. In this issue of ORTHOPEDICS, Dr Green shares his thoughts on testing, prevention, and education of performance-enhancing drug use.

  3. Resolution Enhancement of Multilook Imagery

    SciTech Connect

    Galbraith, Amy E.

    2004-07-01

    This dissertation studies the feasibility of enhancing the spatial resolution of multi-look remotely-sensed imagery using an iterative resolution enhancement algorithm known as Projection Onto Convex Sets (POCS). A multi-angle satellite image modeling tool is implemented, and simulated multi-look imagery is formed to test the resolution enhancement algorithm. Experiments are done to determine the optimal con guration and number of multi-angle low-resolution images needed for a quantitative improvement in the spatial resolution of the high-resolution estimate. The important topic of aliasing is examined in the context of the POCS resolution enhancement algorithm performance. In addition, the extension of the method to multispectral sensor images is discussed and an example is shown using multispectral confocal fluorescence imaging microscope data. Finally, the remote sensing issues of atmospheric path radiance and directional reflectance variations are explored to determine their effect on the resolution enhancement performance.

  4. The Misfortunes of Moral Enhancement.

    PubMed

    Azevedo, Marco Antonio

    2016-10-01

    In Unfit for the Future, Ingmar Persson and Julian Savulescu present a sophisticated argument in defense of the imperative of moral enhancement. They claim that without moral enhancement, the future of humanity is seriously compromised. The possibility of ultimate harm, caused by a dreadful terrorist attack or by a final unpreventable escalation of the present environmental crisis aggravated by the availability of cognitive enhancement, makes moral enhancement a top priority. It may be considered optimistic to think that our present moral capabilities can be successfully improved by means of moral education, moral persuasion, and fear of punishment. So, without moral enhancement, drastic restrictions on human freedom would become the only alternative to prevent those dramatic potential outcomes. In this article, I will try to show that we still have reason to be less pessimistic and that Persson & Savulescu's arguments are fortunately unconvincing.

  5. The Misfortunes of Moral Enhancement.

    PubMed

    Azevedo, Marco Antonio

    2016-10-01

    In Unfit for the Future, Ingmar Persson and Julian Savulescu present a sophisticated argument in defense of the imperative of moral enhancement. They claim that without moral enhancement, the future of humanity is seriously compromised. The possibility of ultimate harm, caused by a dreadful terrorist attack or by a final unpreventable escalation of the present environmental crisis aggravated by the availability of cognitive enhancement, makes moral enhancement a top priority. It may be considered optimistic to think that our present moral capabilities can be successfully improved by means of moral education, moral persuasion, and fear of punishment. So, without moral enhancement, drastic restrictions on human freedom would become the only alternative to prevent those dramatic potential outcomes. In this article, I will try to show that we still have reason to be less pessimistic and that Persson & Savulescu's arguments are fortunately unconvincing. PMID:27473409

  6. Lignite Fuel Enhancement

    SciTech Connect

    Charles Bullinger

    2006-04-03

    This 7th quarterly Technical Progress Report for the Lignite Fuel Enhancement Project summarizes activities from January 1st through March 31st of 2006. It also summarizes the subsequent purchasing activity, dryer/process construction, and testing. The Design Team began conferencing again as construction completed and the testing program began. Primary focus this quarter was construction/installation completion. Phase 1 extension recommendation, and subsequent new project estimate, Forms 424 and 4600 were accepted by DOE headquarters. DOE will complete the application and amended contract. All major mechanical equipment was run, checked out, and tested this quarter. All water, air, and coal flow loops were run and tested. The system was run on January 30th, shut down to adjust equipment timing in the control system on the 31st, and run to 75 ton//hour on February 1st. It ran for seven to eight hours per day until March 20th when ''pairs'' testing ( 24 hour running) began. ''Pairs'' involves comparative testing of unit performance with seven ''wet'' pulverizers versus six ''wet'' and one ''dry''. During the interim, more operators were brought up to speed on system operation and control was shifted to the main Unit No.2 Control Room. The system is run now from the Unit control board operator and an equipment operator checks the system during regular rounds or when an alarm needs verification. The flawless start-up is unprecedented in the industry and credit should be made to the diligence and tenacity of Coal Creek maintenance/checkout staff. Great River Energy and Headwaters did not meet to discuss the Commercialization Plan this quarter. The next meeting is pending data from the drying system. Discussions with Basin Electric, Otter Tail, and Dairyland continue and confidentiality secured as we promote dryers in their stations. Lighting and fire protection were completed in January. Invoices No.12 through No.20 are completed and forwarded following preliminary

  7. Enhanced Elliptic Grid Generation

    NASA Technical Reports Server (NTRS)

    Kaul, Upender K.

    2007-01-01

    An enhanced method of elliptic grid generation has been invented. Whereas prior methods require user input of certain grid parameters, this method provides for these parameters to be determined automatically. "Elliptic grid generation" signifies generation of generalized curvilinear coordinate grids through solution of elliptic partial differential equations (PDEs). Usually, such grids are fitted to bounding bodies and used in numerical solution of other PDEs like those of fluid flow, heat flow, and electromagnetics. Such a grid is smooth and has continuous first and second derivatives (and possibly also continuous higher-order derivatives), grid lines are appropriately stretched or clustered, and grid lines are orthogonal or nearly so over most of the grid domain. The source terms in the grid-generating PDEs (hereafter called "defining" PDEs) make it possible for the grid to satisfy requirements for clustering and orthogonality properties in the vicinity of specific surfaces in three dimensions or in the vicinity of specific lines in two dimensions. The grid parameters in question are decay parameters that appear in the source terms of the inhomogeneous defining PDEs. The decay parameters are characteristic lengths in exponential- decay factors that express how the influences of the boundaries decrease with distance from the boundaries. These terms govern the rates at which distance between adjacent grid lines change with distance from nearby boundaries. Heretofore, users have arbitrarily specified decay parameters. However, the characteristic lengths are coupled with the strengths of the source terms, such that arbitrary specification could lead to conflicts among parameter values. Moreover, the manual insertion of decay parameters is cumbersome for static grids and infeasible for dynamically changing grids. In the present method, manual insertion and user specification of decay parameters are neither required nor allowed. Instead, the decay parameters are

  8. Utilizing scattering to further enhance integrating cavity-enhanced spectroscopy

    NASA Astrophysics Data System (ADS)

    Bixler, Joel N.; Winkler, Chase A.; Hokr, Brett H.; Mason, John D.; Yakovlev, Vladislav V.

    2016-01-01

    Spectroscopic optical characterization and identification of molecular structures and complex systems would greatly benefit from new technologies capable of analyzing molecular species in small quantities with maximum sensitivity and specificity. Integrating cavity-enhanced spectroscopy has recently been shown as a viable tool for achieving this goal. This technique could greatly benefit from methods for further enhancing the desired spectroscopic signal, allowing for lower detection limits. Here, we present a simple method to further enhance fluorescence signal generated inside an integrating cavity by introducing additional scattering to the sample of interest.

  9. Environmental engineering education enhancement

    NASA Astrophysics Data System (ADS)

    Caporali, E.

    2012-04-01

    Since higher education plays a central role in the development of both human beings and modern societies, enhancing social, cultural and economic development, active citizenship, ethical values and expertises for a sustainable growth, environment respectful, the European Commission promotes a wide range of programmes. Among the EC programmes, the TEMPUS - Trans European Mobility Programme for University Studies, with the support of the DG EAC of the European Commission, has contributed to many aspects of general interest for higher education. Curricula harmonization, LifeLong Learning Programme development, ICT use, quality assessment, accreditation, innovation learning methods, growth of networks of institutions trusting each other, are the focused aspects. Such a solid cooperation framework is surely among the main outcomes of the TEMPUS Projects leaded by the University of Firenze UNIFI (Italy), DEREC - Development of Environment and Resources Engineering Curriculum (2005-2008), and its spin-off DEREL - Development of Environment and Resources Engineering Learning (2010-2013), and VICES - Videoconferencing Educational Services (2009-2012). DEREC and DEREL TEMPUS projects, through the co-operation of Universities in Italy, Austria, Germany, Greece, Macedonia, Albania and Serbia, are aimed at the development of first and second level curricula in "Environment and Resources Engineering" at the Ss. Cyril and Methodius University - UKIM Skopje (MK). In the DEREC Project the conditions for offering a joint degree title in the field of Environmental Engineering between UNIFI and UKIM Skopje were fulfilled and a shared educational programme leading to the mutual recognition of degree titles was defined. The DEREL project, as logical continuation of DEREC, is aimed to introduce a new, up-to-date, postgraduate second level curriculum in Environment and Resources Engineering at UKIM Skopje, University of Novi Sad (RS) and Polytechnic University of Tirana (AL). following

  10. Excitation enhancement and extraction enhancement with photonic crystals

    SciTech Connect

    Shapira, Ofer; Soljacic, Marin; Zhen, Bo; Chua, Song-Liang; Lee, Jeongwon; Joannopoulos, John

    2015-03-03

    Disclosed herein is a system for stimulating emission from at least one an emitter, such as a quantum dot or organic molecule, on the surface of a photonic crystal comprising a patterned dielectric substrate. Embodiments of this system include a laser or other source that illuminates the emitter and the photonic crystal, which is characterized by an energy band structure exhibiting a Fano resonance, from a first angle so as to stimulate the emission from the emitter at a second angle. The coupling between the photonic crystal and the emitter may result in spectral and angular enhancement of the emission through excitation and extraction enhancement. These enhancement mechanisms also reduce the emitter's lasing threshold. For instance, these enhancement mechanisms enable lasing of a 100 nm thick layer of diluted organic molecules solution with reduced threshold intensity. This reduction in lasing threshold enables more efficient organic light emitting devices and more sensitive molecular sensing.

  11. Resolution enhancement in tilted coordinates

    NASA Astrophysics Data System (ADS)

    Hariri Naghadeh, Diako; Keith Morley, Christopher

    2016-11-01

    Deconvolution is applied to remove source wavelet effects from seismograms. The results are resolution enhancement that enables detection of thin layers. Following enhancement of resolution, low frequency and high angle reflectors, particularly at great depth, appear as low amplitude and semi-invisible reflectors that are difficult to track and pick. A new approach to enhance resolution is introduced that estimates a derivative using continuous wavelet transform in tilted coordinates. The results are compared with sparse spike deconvolution, curvelet deconvolution and inverse quality filtering in wavelet domain. The positive consequence of the new method is to increase sampling of high dip features by changing the coordinate system from Cartesian to tilted. To compare those methods a complex data set was chosen that includes high angle faults and chaotic mass transport complex. Image enhancement using curvelet deconvolution shows a chaotic system as a non-chaotic one. The results show that sparse spike deconvolution and inverse quality filtering in wavelet domain are able to enhance resolution more than curvelet deconvolution especially at great depth but it is impossible to follow steep dip reflectors after resolution enhancement using these methods, especially when their apparent dips are more than 45°. By estimating derivatives in a continuous wavelet transform from tilted data sets similar resolution enhancement as the other deconvolution methods is achieved but additionally steep dipping reflectors are imaged much better than others. Subtracted results of the enhanced resolution data set using new method and the other introduced methods show that steeply dipping reflectors are highlighted as a particular ability of the new method. The results show that high frequency recovery in Cartesian co-ordinate is accompanied by inability to image steeply dipping reflectors especially at great depths. Conversely recovery of high frequency data and imaging of the data

  12. WEATHERABILITY OF ENHANCED DEGRADABLE PLASTICS

    EPA Science Inventory

    The main objective of this study was to assess the performance and the asociated variability of several selected enhanced degradable plastic materials under a variety of different exposure conditions. Other objectives were to identify the major products formed during degradation ...

  13. Geothermal Permeability Enhancement - Final Report

    SciTech Connect

    Joe Beall; Mark Walters

    2009-06-30

    The overall objective is to apply known permeability enhancement techniques to reduce the number of wells needed and demonstrate the applicability of the techniques to other undeveloped or under-developed fields. The Enhanced Geothermal System (EGS) concept presented in this project enhances energy extraction from reduced permeability zones in the super-heated, vapor-dominated Aidlin Field of the The Geysers geothermal reservoir. Numerous geothermal reservoirs worldwide, over a wide temperature range, contain zones of low permeability which limit the development potential and the efficient recovery of heat from these reservoirs. Low permeability results from poorly connected fractures or the lack of fractures. The Enhanced Geothermal System concept presented here expands these technologies by applying and evaluating them in a systematic, integrated program.

  14. Ultrasonic enhancement of battery diffusion.

    PubMed

    Hilton, R; Dornbusch, D; Branson, K; Tekeei, A; Suppes, G J

    2014-03-01

    It has been demonstrated that sonic energy can be harnessed to enhance convection in Galvanic cells during cyclic voltammetry; however, the practical value of this approach is limited due to the lack of open volumes for convection patterns to develop in most batteries. This study evaluates the ability of ultrasonic waves to enhance diffusion in membrane separators commonly used in sandwich-architecture batteries. Studies include the measuring of open-circuit performance curves to interpret performances in terms of reductions in concentration overpotentials. The use of a 40 kHz sonicator bath can consistently increase the voltage of the battery and reduce overpotential losses up to 30%. This work demonstrates and quantifies battery enhancement due to enhanced diffusion made possible with ultrasonic energy.

  15. Platelets enhance neutrophil transendothelial migration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Platelets are increasingly recognized as important mediators of inflammation in addition to thrombosis. While platelets have been shown to promote neutrophil (PMN) adhesion to endothelium in various inflammatory models, it is unclear whether platelets enhance neutrophil transmigration across inflame...

  16. IN SITU ENHANCED SOURCE REMOVAL

    EPA Science Inventory

    This html report describes and compares the performance of in situ technologies designed to accelerate the removal of organic contaminants from unconsolidated soils and aquifers. The research was conducted through the Enhanced Source Removal (ESR) Program within the Subsurface Pr...

  17. Moderate eugenics and human enhancement.

    PubMed

    Selgelid, Michael J

    2014-02-01

    Though the reputation of eugenics has been tarnished by history, eugenics per se is not necessarily a bad thing. Many advocate a liberal new eugenics--where individuals are free to choose whether or not to employ genetic technologies for reproductive purposes. Though genetic interventions aimed at the prevention of severe genetic disorders may be morally and socially acceptable, reproductive liberty in the context of enhancement may conflict with equality. Enhancement could also have adverse effects on utility. The enhancement debate requires a shift in focus. What the equality and/or utility costs of enhancement will be is an empirical question. Rather than philosophical speculation, more social science research is needed to address it. Philosophers, meanwhile, should address head-on the question of how to strike a balance between liberty, equality, and utility in cases of conflict (in the context of genetics).

  18. Cognitive enhancers for anxiety disorders.

    PubMed

    Hofmann, Stefan G; Smits, Jasper A J; Asnaani, Anu; Gutner, Cassidy A; Otto, Michael W

    2011-08-01

    Cognitive-behavioral therapy is an effective intervention for anxiety disorders. However, a significant number of people do not respond or only show partial response even after an adequate course of the treatment. Recent research has shown that the efficacy of the intervention can be improved by the use of cognitive enhancers that augment the core learning processes of cognitive-behavior therapy. This manuscript provides a review of the current state of cognitive enhancers for the treatment of anxiety disorders.

  19. Chemically enhanced in situ recovery

    SciTech Connect

    Sale, T.; Pitts, M.; Wyatt, K.

    1996-08-01

    Chemically enhanced recovery is a promising alternative to current technologies for management of subsurface releases of organic liquids. Through the inclusion of surfactants, solvents, polymers, and/or alkaline agents to a waterflood, the transport of targeted organic compounds can be increased and rates of recovery enhanced. By far, the vast majority of work done in the field of chemically enhanced recovery has been at a laboratory scale. The following text focuses on chemically enhanced recovery from a field application perspective with emphasis given to chlorinated solvents in a low permeability setting. While chlorinated solvents are emphasized, issues discussed are also relevant to organic liquids less dense than water such as petroleum products. Topics reviewed include: (1) Description of technology; (2) General technology considerations; (3) Low permeability media considerations; (4) Cost and reliability considerations; (5) Commercial availability; and (6) Case histories. Through this paper an appreciation is developed of both the potential and limitations of chemically enhanced recovery. Excluded from the scope of this paper is the in situ destruction of organic compounds through processes such as chemical or biological oxidation, chemically enhanced recovery of inorganic compounds, and ex situ soil treatment processes. 11 refs., 2 figs., 1 tab.

  20. [STUDY RELATIVE EXPRESSION OF GENES THAT CONTROL GLUCOSE METABOLISM IN THE LIVER IN MICE WITH DEVELOPMENT OF MELANOCORTIN OBESITY].

    PubMed

    Baklanov, A V; Bazhan, N M

    2015-06-01

    The relative gene expressions of glucose-6-phosphatase (G6P), phosphoenolpyruvate carbo- xykinase (PEPCK)--markers of gluconeogenesis, glucokinase (GK)--a marker of glycolysis, glucose transporter type 2 (GLUT2)--a marker of input and output of glucose in the liver were measured during the development of melanocortin (MC) obesity in male mice of C57BL/6J strain with mutation yellow in the Agouti locus (Ay/a mice). The mutation decreases MC receptor activity and induces hyperphagia and MC obesity. The males of the same line with mutation nonagouti were used as control. Tissue samples were taken at age 10 (before obesity), 15 (moderate obesity) and 30 (developed obesity) weeks. It has been shown that Ay/a mice had decreased glucose tolerance since 10-week age. There were age-related changes in mRNA levels in the liver of Ay/a mice, unlike a/a mice. In Ay/a mice the mRNA GLUT2 levels at the age of 10 weeks, mRNA GK levels at the age of 15 weeks, and mRNA G6P levels at the age of 3O weeks were higher than those in Ada mice of other ages. InAYfa mice the mRNA GK levels at the age of 15 weeks and mRNA G6F levels at the age of 30 weeks were increased relatively to those in a/a mice. Thus, Ay/a mice before the development of MK obesity had changes in the mRNA levels genes of proteins that regulate hepatic glucose metabolism, which may contribute to the compensation of glucose metabolism disorders caused by a hereditary decrease of MK system activity

  1. Moral enhancement requires multiple virtues.

    PubMed

    Hughes, James J

    2015-01-01

    Some of the debates around the concept of moral enhancement have focused on whether the improvement of a single trait, such as empathy or intelligence, would be a good in general, or in all circumstances. All virtue theories, however, both secular and religious, have articulated multiple virtues that temper and inform one another in the development of a mature moral character. The project of moral enhancement requires a reengagement with virtue ethics and contemporary moral psychology to develop an empirically grounded model of the virtues and a fuller model of character development. Each of these virtues may be manipulable with electronic, psychopharmaceutical, and genetic interventions. A set of interdependent virtues is proposed, along with some of the research pointing to ways such virtues could be enhanced.

  2. Sexual dimorphism and human enhancement.

    PubMed

    Casal, Paula

    2013-12-01

    Robert Sparrow argues that because of women's longer life expectancy philosophers who advocate the genetic modification of human beings to enhance welfare rather than merely supply therapy are committed to favouring the selection of only female embryos, an implication he deems sufficiently implausible to discredit their position. If Sparrow's argument succeeds, then philosophers who advocate biomedical moral enhancement also seem vulnerable to a similar charge because of men's greater propensity for various forms of harmful wrongdoing. This paper argues there are various flaws in Sparrow's argument that render it unsuccessful. The paper also examines whether dimorphism reduction is a more desirable outcome than male elimination, thereby further illustrating the difficulties besetting the distinction between therapy and enhancement.

  3. Moral enhancement requires multiple virtues.

    PubMed

    Hughes, James J

    2015-01-01

    Some of the debates around the concept of moral enhancement have focused on whether the improvement of a single trait, such as empathy or intelligence, would be a good in general, or in all circumstances. All virtue theories, however, both secular and religious, have articulated multiple virtues that temper and inform one another in the development of a mature moral character. The project of moral enhancement requires a reengagement with virtue ethics and contemporary moral psychology to develop an empirically grounded model of the virtues and a fuller model of character development. Each of these virtues may be manipulable with electronic, psychopharmaceutical, and genetic interventions. A set of interdependent virtues is proposed, along with some of the research pointing to ways such virtues could be enhanced. PMID:25473861

  4. Piezoelectric enhancement under negative pressure

    PubMed Central

    Kvasov, Alexander; McGilly, Leo J.; Wang, Jin; Shi, Zhiyong; Sandu, Cosmin S.; Sluka, Tomas; Tagantsev, Alexander K.; Setter, Nava

    2016-01-01

    Enhancement of ferroelectric properties, both spontaneous polarization and Curie temperature under negative pressure had been predicted in the past from first principles and recently confirmed experimentally. In contrast, piezoelectric properties are expected to increase by positive pressure, through polarization rotation. Here we investigate the piezoelectric response of the classical PbTiO3, Pb(Zr,Ti)O3 and BaTiO3 perovskite ferroelectrics under negative pressure from first principles and find significant enhancement. Piezoelectric response is then tested experimentally on free-standing PbTiO3 and Pb(Zr,Ti)O3 nanowires under self-sustained negative pressure, confirming the theoretical prediction. Numerical simulations verify that negative pressure in nanowires is the origin of the enhanced electromechanical properties. The results may be useful in the development of highly performing piezoelectrics, including lead-free ones. PMID:27396411

  5. Piezoelectric enhancement under negative pressure.

    PubMed

    Kvasov, Alexander; McGilly, Leo J; Wang, Jin; Shi, Zhiyong; Sandu, Cosmin S; Sluka, Tomas; Tagantsev, Alexander K; Setter, Nava

    2016-01-01

    Enhancement of ferroelectric properties, both spontaneous polarization and Curie temperature under negative pressure had been predicted in the past from first principles and recently confirmed experimentally. In contrast, piezoelectric properties are expected to increase by positive pressure, through polarization rotation. Here we investigate the piezoelectric response of the classical PbTiO3, Pb(Zr,Ti)O3 and BaTiO3 perovskite ferroelectrics under negative pressure from first principles and find significant enhancement. Piezoelectric response is then tested experimentally on free-standing PbTiO3 and Pb(Zr,Ti)O3 nanowires under self-sustained negative pressure, confirming the theoretical prediction. Numerical simulations verify that negative pressure in nanowires is the origin of the enhanced electromechanical properties. The results may be useful in the development of highly performing piezoelectrics, including lead-free ones. PMID:27396411

  6. Piezoelectric enhancement under negative pressure.

    PubMed

    Kvasov, Alexander; McGilly, Leo J; Wang, Jin; Shi, Zhiyong; Sandu, Cosmin S; Sluka, Tomas; Tagantsev, Alexander K; Setter, Nava

    2016-07-11

    Enhancement of ferroelectric properties, both spontaneous polarization and Curie temperature under negative pressure had been predicted in the past from first principles and recently confirmed experimentally. In contrast, piezoelectric properties are expected to increase by positive pressure, through polarization rotation. Here we investigate the piezoelectric response of the classical PbTiO3, Pb(Zr,Ti)O3 and BaTiO3 perovskite ferroelectrics under negative pressure from first principles and find significant enhancement. Piezoelectric response is then tested experimentally on free-standing PbTiO3 and Pb(Zr,Ti)O3 nanowires under self-sustained negative pressure, confirming the theoretical prediction. Numerical simulations verify that negative pressure in nanowires is the origin of the enhanced electromechanical properties. The results may be useful in the development of highly performing piezoelectrics, including lead-free ones.

  7. Human enhancement: The new eugenics.

    PubMed

    Vizcarrondo, Felipe E

    2014-08-01

    Supporters of human enhancement through genetic and other reproductive technologies claim that the new liberal eugenics, based on science and individual consent differs from the old eugenics which was unscientific and coercive. Supporters claim it is the parent's moral obligation to produce the best children possible. At this time, a defective gene that is identified in an unborn child cannot be repaired. To prevent the manifestation of the undesirable trait the unborn child is destroyed. The arguments in support of human enhancement are based on an ethic of consequence that could allow for nearly any means as long as the desired end is reached. Medical enhancement may affect the parent-child family unit; the parents' love for the child may be conditioned on the expected results. The new eugenics, although based on science, continues to pursue the same goal as the old eugenics, the development of a superior individual and the elimination of those considered inferior.

  8. Piezoelectric enhancement under negative pressure

    NASA Astrophysics Data System (ADS)

    Kvasov, Alexander; McGilly, Leo J.; Wang, Jin; Shi, Zhiyong; Sandu, Cosmin S.; Sluka, Tomas; Tagantsev, Alexander K.; Setter, Nava

    2016-07-01

    Enhancement of ferroelectric properties, both spontaneous polarization and Curie temperature under negative pressure had been predicted in the past from first principles and recently confirmed experimentally. In contrast, piezoelectric properties are expected to increase by positive pressure, through polarization rotation. Here we investigate the piezoelectric response of the classical PbTiO3, Pb(Zr,Ti)O3 and BaTiO3 perovskite ferroelectrics under negative pressure from first principles and find significant enhancement. Piezoelectric response is then tested experimentally on free-standing PbTiO3 and Pb(Zr,Ti)O3 nanowires under self-sustained negative pressure, confirming the theoretical prediction. Numerical simulations verify that negative pressure in nanowires is the origin of the enhanced electromechanical properties. The results may be useful in the development of highly performing piezoelectrics, including lead-free ones.

  9. Human enhancement: The new eugenics

    PubMed Central

    Vizcarrondo, Felipe E.

    2014-01-01

    Supporters of human enhancement through genetic and other reproductive technologies claim that the new liberal eugenics, based on science and individual consent differs from the old eugenics which was unscientific and coercive. Supporters claim it is the parent's moral obligation to produce the best children possible. At this time, a defective gene that is identified in an unborn child cannot be repaired. To prevent the manifestation of the undesirable trait the unborn child is destroyed. The arguments in support of human enhancement are based on an ethic of consequence that could allow for nearly any means as long as the desired end is reached. Medical enhancement may affect the parent–child family unit; the parents’ love for the child may be conditioned on the expected results. The new eugenics, although based on science, continues to pursue the same goal as the old eugenics, the development of a superior individual and the elimination of those considered inferior. PMID:25249705

  10. Directionally enhanced probe for side-illumination Tip enhanced spectroscopy

    NASA Astrophysics Data System (ADS)

    Shen, Hongming; Lu, Guowei; Cao, Zhengmin; He, Yingbo; Cheng, Yuqing; Li, Jiafang; Li, Zhi-Yuan; Gong, Qihuang

    2016-10-01

    We demonstrate a high-performance apertureless near-field probe made of a tapered metal tip with a set of periodic shallow grooves near the apex. The spontaneous emission from a single emitter near the tip is investigated systematically for the side-illumination tip enhanced spectroscopy (TES). In contrast with the bare tapered metal tip in conventional side-illumination TES, the corrugated probe not only enhances strongly local excitation field but also concentrates the emission directivity, which leads to high collection efficiency and signal-to-noise ratio. In particular, we propose an asymmetric TES tip based on two coupling nanorods with different length at the apex to realize unidirectional enhanced emission rate from a single emitter. Interestingly, we find that the radiation pattern is sensitive to the emission wavelength and the emitter positions respective to the apex, which can result in an increase of signal-to-noise ratio by suppressing undesired signal. The proposed asymmetrical corrugated probe opens up a broad range of practical applications, e.g. increasing the detection efficiency of tip enhanced spectroscopy at the single-molecule level.

  11. Plasmon enhancement of luminescence upconversion.

    PubMed

    Park, Wounjhang; Lu, Dawei; Ahn, Sungmo

    2015-05-21

    Frequency conversion has always been an important topic in optics. Nonlinear optics has traditionally focused on frequency conversion based on nonlinear susceptibility but with the recent development of upconversion nanomaterials, luminescence upconversion has begun to receive renewed attention. While upconversion nanomaterials open doors to a wide range of new opportunities, they remain too inefficient for most applications. Incorporating plasmonic nanostructures provides a promising pathway to highly efficient upconversion. Naturally, a plethora of theoretical and experimental studies have been published in recent years, reporting enhancements up to several hundred. It is however difficult to make meaningful comparisons since the plasmonic fields are highly sensitive to the local geometry and excitation condition. Also, many luminescence upconversion processes involve multiple steps via different physical mechanisms and the overall output is often determined by a delicate interplay among them. This review is aimed at offering a comprehensive framework for plasmon enhanced luminescence upconversion. We first present quantum electrodynamics descriptions for all the processes involved in luminescence upconversion, which include absorption, emission, energy transfer and nonradiative transitions. We then present a bird's eye view of published works on plasmon enhanced upconversion, followed by more detailed discussion on comparable classes of nanostructures, the effects of spacer layers and local heating, and the dynamics of the plasmon enhanced upconversion process. Plasmon enhanced upconversion is a challenging and exciting field from the fundamental scientific perspective and also from technological standpoints. It offers an excellent system to study how optical processes are affected by the local photonic environment. This type of research is particularly timely as the plasmonics is placing heavier emphasis on nonlinearity. At the same time, efficient upconversion

  12. Biological enhancement of hydrocarbon extraction

    DOEpatents

    Brigmon, Robin L.; Berry, Christopher J.

    2009-01-06

    A method of microbial enhanced oil recovery for recovering oil from an oil-bearing rock formation is provided. The methodology uses a consortium of bacteria including a mixture of surfactant producing bacteria and non-surfactant enzyme producing bacteria which may release hydrocarbons from bitumen containing sands. The described bioprocess can work with existing petroleum recovery protocols. The consortium microorganisms are also useful for treatment of above oil sands, ground waste tailings, subsurface oil recovery, and similar materials to enhance remediation and/or recovery of additional hydrocarbons from the materials.

  13. Power enhanced frequency conversion system

    NASA Technical Reports Server (NTRS)

    Sanders, Steven (Inventor); Lang, Robert J. (Inventor); Waarts, Robert G. (Inventor)

    2001-01-01

    A frequency conversion system includes at least one source providing a first near-IR wavelength output including a gain medium for providing high power amplification, such as double clad fiber amplifier, a double clad fiber laser or a semiconductor tapered amplifier to enhance the power output level of the near-IR wavelength output. The NFM device may be a difference frequency mixing (DFM) device or an optical parametric oscillation (OPO) device. Pump powers are gain enhanced by the addition of a rare earth amplifier or oscillator, or a Ra-man/Brillouin amplifier or oscillator between the high power source and the NFM device.

  14. Enhanced coagulation for arsenic removal

    SciTech Connect

    Cheng, R.C.; Liang, S.; Wang, H.C.; Beuhler, M.D. )

    1994-09-01

    The possible use of enhanced coagulation for arsenic removal was examined at the facilities of a California utility in 1992 and 1993. The tests were conducted at bench, pilot, and demonstration scales, with two source waters. Alum and ferric chloride, with cationic polymer, were investigated at various influence arsenic concentrations. The investigators concluded that for the source waters tested, enhanced coagulation could be effective for arsenic removal and that less ferric chloride than alum, on a weight basis, is needed to achieve the same removal.

  15. Plasmon-enhanced UV photocatalysis

    SciTech Connect

    Honda, Mitsuhiro; Saito, Yuika Kawata, Satoshi; Kumamoto, Yasuaki; Taguchi, Atsushi

    2014-02-10

    We report plasmonic nanoparticle enhanced photocatalysis on titanium dioxide (TiO{sub 2}) in the deep-UV range. Aluminum (Al) nanoparticles fabricated on TiO{sub 2} film increases the reaction rate of photocatalysis by factors as high as 14 under UV irradiation in the range of 260–340 nm. The reaction efficiency has been determined by measuring the decolorization rate of methylene blue applied on the TiO{sub 2} substrate. The enhancement of photocatalysis shows particle size and excitation wavelength dependence, which can be explained by the surface plasmon resonance of Al nanoparticles.

  16. Sorption enhanced CO2 methanation.

    PubMed

    Borgschulte, Andreas; Gallandat, Noris; Probst, Benjamin; Suter, Riccardo; Callini, Elsa; Ferri, Davide; Arroyo, Yadira; Erni, Rolf; Geerlings, Hans; Züttel, Andreas

    2013-06-28

    The transformation from the fatuous consumption of fossil energy towards a sustainable energy circle is most easily marketable by not changing the underlying energy carrier but generating it from renewable energy. Hydrocarbons can be principally produced from renewable hydrogen and carbon dioxide collected by biomass. However, research is needed to increase the energetic and economic efficiency of the process. We demonstrate the enhancement of CO2 methanation by sorption enhanced catalysis. The preparation and catalytic activity of sorption catalysts based on Ni particles in zeolites is reported. The functioning of the sorption catalysis is discussed together with the determination of the reaction mechanism, providing implications for new ways in catalysis. PMID:23673365

  17. Enhanced image capture through fusion

    NASA Technical Reports Server (NTRS)

    Burt, Peter J.; Hanna, Keith; Kolczynski, Raymond J.

    1993-01-01

    Image fusion may be used to combine images from different sensors, such as IR and visible cameras, to obtain a single composite with extended information content. Fusion may also be used to combine multiple images from a given sensor to form a composite image in which information of interest is enhanced. We present a general method for performing image fusion and show that this method is effective for diverse fusion applications. We suggest that fusion may provide a powerful tool for enhanced image capture with broad utility in image processing and computer vision.

  18. Temporal resolution enhancement from motion

    NASA Astrophysics Data System (ADS)

    Rollason, M. P.; Watson, G. H.; Strens, M. J. A.

    2009-09-01

    We describe progress in the third year of the EMRS DTC TEP theme project entitled "Temporal Resolution Enhancement from Motion". The aim is to develop algorithms that combine evidence over time from a sequence of images in order to improve spatial resolution and reduce unwanted artefacts. Years one and two of this project developed and demonstrated an efficient algorithm that provided good resolution enhancement of a scene viewed in the far field (approximately flat) [1]. This paper reports a new algorithm which is applicable to a three dimensional scene where substantial depth variation causes parallax within the imagery. The new algorithm is demonstrated using airborne infra-red imagery.

  19. Lift enhancement in flying snakes

    NASA Astrophysics Data System (ADS)

    Krishnan, Anush; Socha, John; Vlachos, Pavlos; Barba, Lorena

    2013-11-01

    Flying snakes use a unique method of aerial locomotion: they jump from tree branches, flatten their bodies and undulate through the air to produce a glide. The shape of their body cross-section during the glide plays an important role in generating lift. We present a computational investigation of the aerodynamics of the cross-sectional shape. We performed two-dimensional simulations of incompressible flow past the anatomically correct cross-section of the species Chrysopelea paradisi, which show that a significant enhancement in lift appears at an angle of attack of 35 degrees, for Reynolds numbers 2000 and above. Previous experiments on physical models also demonstrated an increased lift and at the same angle of attack. The simulations point to the lift enhancement arising from the early separation of the boundary layer on the dorsal surface of the snake profile, without stall. The separated shear layer rolls up and interacts with secondary vorticity in the near-wake, inducing the primary vortex to remain closer to the body and thus cause enhanced suction, resulting in higher lift. In physical experiments, the flow is inherently 3-D due to fluid instabilities, and it is intriguing that the enhanced lift also appears in the two-dimensional simulations.

  20. Communication Enhancement: Principles and Practices.

    ERIC Educational Resources Information Center

    Shane, Howard

    1988-01-01

    A physician discusses the work of the Communications Enhancement Clinic at Children's Hospital-Boston in providing assistance to children with severe speech problems. He describes the process of evaluating and matching a child's strengths and weaknesses to available technology, including educational software, speech or print output devices, and…

  1. Managing to enhance soil health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Healthy soils are critical for meeting current and future societal demands. Management strategies that protect the soil against erosion, build soil organic matter and promote nutrient cycling are ways to enhance soil health. Keeping soils covered and judicious use of agrochemicals are akin to us “hu...

  2. Engage, Enhance, and Extend Learning!

    ERIC Educational Resources Information Center

    Keren-Kolb, Liz

    2013-01-01

    Educators often say that technology is more than a gimmick or add-on, and that it should engage, enhance, or extend learning in ways that traditional tools do not. Yet they seldom stop to define these terms, and they can be confusing, especially for teachers and preservice teachers. Recently, while collaborating on an English language arts and…

  3. 10 Suggestions for Enhancing Lecturing

    ERIC Educational Resources Information Center

    Heitzmann, Ray

    2010-01-01

    Criticism of the lecture method remains a staple of discussion and writing in academia--and most of the time it's deserved! Those interested in improving this aspect of their teaching might wish to consider some or all of the following suggestions for enhancing lectures. These include: (1) Lectures must start with a "grabber"; (2) Lectures must be…

  4. Enhancing hydrogen spillover and storage

    DOEpatents

    Yang, Ralph T.; Li, Yingwel; Lachawiec, Jr., Anthony J.

    2011-05-31

    Methods for enhancing hydrogen spillover and storage are disclosed. One embodiment of the method includes doping a hydrogen receptor with metal particles, and exposing the hydrogen receptor to ultrasonification as doping occurs. Another embodiment of the method includes doping a hydrogen receptor with metal particles, and exposing the doped hydrogen receptor to a plasma treatment.

  5. Enhancing hydrogen spillover and storage

    DOEpatents

    Yang, Ralph T; Li, Yingwei; Lachawiec, Jr., Anthony J

    2013-02-12

    Methods for enhancing hydrogen spillover and storage are disclosed. One embodiment of the method includes doping a hydrogen receptor with metal particles, and exposing the hydrogen receptor to ultrasonication as doping occurs. Another embodiment of the method includes doping a hydrogen receptor with metal particles, and exposing the doped hydrogen receptor to a plasma treatment.

  6. Centers for Enhancement of Education.

    ERIC Educational Resources Information Center

    Biggerstaff, Ed

    The Center for Enhancement of Education organizes seven specialized centers within the School of Education and Human Services to provide faculty and students with the opportunity for research, development, and public service activities that complement and supplement classroom teaching. Each of the seven centers stresses one of the following…

  7. Alumina-Enhanced Thermal Barrier

    NASA Technical Reports Server (NTRS)

    Smith, Marnell; Leiser, Dan; Goldstein, Howard

    1989-01-01

    Rigid, fibrous ceramic tile material called "alumina-enhanced thermal barrier" (AETB) extends temperature capability of insulating materials. Material has obvious potential for terrestrial use in kilns, furnaces, heat engines, and other applications in which light weight and high operating temperature are specified. Three kinds of ceramic fibers are blended, molded, and sintered to make refractory tiles.

  8. Key Issue: Enhancing Teacher Leadership

    ERIC Educational Resources Information Center

    National Comprehensive Center for Teacher Quality, 2007

    2007-01-01

    "Teachers are leaders when they function in professional communities to affect student learning; contribute to school improvement; inspire excellence in practice; and empower stakeholders to participate in educational improvement" (Childs-Bowen, Moller, & Scrivner, 2000, p. 28). Enhancing teacher leadership can help schools and districts reach the…

  9. Germplasm enhancement for RWA resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our contribution to this annual newsletter is a summary of research accomplishments in the past year in germplasm enhancement for RWA resistance in barley at the USDA-ARS, Wheat, Peanut and Other Field Crops Research Unit, Stillwater, OK. RWA is a serious pest of barley in the intermountain regions...

  10. Germplasm enhancement for RWA resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our contribution to this annual newsletter is a summary of research accomplishments in the past year in germplasm enhancement for RWA resistance in barley at the USDA-ARS Wheat, Peanut and Other Field Crops Research Unit, Stillwater, OK. Russian wheat aphid (RWA) is a serious pest of barley in the ...

  11. Enhancing What Students Can Do

    ERIC Educational Resources Information Center

    Poel, Elissa Wolfe

    2007-01-01

    The Human Function Model, as described in the University of Kentucky Assistive Technology Project, places assistive technology in its proper perspective, as an external support that can enhance an individual's ability to function within the environment. The National Assistive Technology Research Institute groups assistive technology and related…

  12. Enhancing Instruction through Software Infusion.

    ERIC Educational Resources Information Center

    Sia, Archie P.

    The presence of the computer in the classroom is no longer considered an oddity; it has become an ordinary resource for teachers to use for the enhancement of instruction. This paper presents an examination of software infusion, i.e., the use of computer software to enrich instruction in an academic curriculum. The process occurs when a chosen…

  13. Forensics: Enhancing Civic Literacy & Democracy

    ERIC Educational Resources Information Center

    Briscoe, Shawn F.

    2009-01-01

    Forensics--interpretation, speech, and debate--can and should be a meaningful part of every school's curriculum. To put it simply, the course of study, alongside cocurricular competition, promotes civic education and enhances the standard curriculum by helping students explore myriad topics from multiple angles and find the truth in each,…

  14. Innovative Solution to Video Enhancement

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Through a licensing agreement, Intergraph Government Solutions adapted a technology originally developed at NASA's Marshall Space Flight Center for enhanced video imaging by developing its Video Analyst(TM) System. Marshall's scientists developed the Video Image Stabilization and Registration (VISAR) technology to help FBI agents analyze video footage of the deadly 1996 Olympic Summer Games bombing in Atlanta, Georgia. VISAR technology enhanced nighttime videotapes made with hand-held camcorders, revealing important details about the explosion. Intergraph's Video Analyst System is a simple, effective, and affordable tool for video enhancement and analysis. The benefits associated with the Video Analyst System include support of full-resolution digital video, frame-by-frame analysis, and the ability to store analog video in digital format. Up to 12 hours of digital video can be stored and maintained for reliable footage analysis. The system also includes state-of-the-art features such as stabilization, image enhancement, and convolution to help improve the visibility of subjects in the video without altering underlying footage. Adaptable to many uses, Intergraph#s Video Analyst System meets the stringent demands of the law enforcement industry in the areas of surveillance, crime scene footage, sting operations, and dash-mounted video cameras.

  15. CPS Science Laboratory Enhancement Project

    SciTech Connect

    James, Chandra

    2011-11-30

    The lab enhancement initiative was designed to support early implementation efforts of new policy to promote safe learning environments and school labs called the Chemical Safety and Hygiene Plan (CSHP). These efforts included comprehensive inventories and chemical removals at all Chicago Public High Schools, conducted by environmental health and safety consultants, and the development of professional development resources for teachers.

  16. Biosurfactant and enhanced oil recovery

    DOEpatents

    McInerney, Michael J.; Jenneman, Gary E.; Knapp, Roy M.; Menzie, Donald E.

    1985-06-11

    A pure culture of Bacillus licheniformis strain JF-2 (ATCC No. 39307) and a process for using said culture and the surfactant lichenysin produced thereby for the enhancement of oil recovery from subterranean formations. Lichenysin is an effective surfactant over a wide range of temperatures, pH's, salt and calcium concentrations.

  17. Enhancements to PVM's BEOLIN architecture

    NASA Technical Reports Server (NTRS)

    Springer, Paul L.

    2005-01-01

    .4.3 of PVM had previously been enhanced by the addition of a new architecture, BEOLIN, which allowed a PVM user to abstract a Beowulf class computer with a private network to appear as a single system, visible to the outside world, which could spawn tasks on different internal nodes.

  18. Enhancing Author's Voice through Scripting

    ERIC Educational Resources Information Center

    Young, Chase J.; Rasinski, Timothy V.

    2011-01-01

    The authors suggest using scripting as a strategy to mentor and enhance author's voice in writing. Through gradual release, students use authentic literature as a model for writing with voice. The authors also propose possible extensions for independent practice, integration across content areas, and tips for evaluation.

  19. Who Benefits from Pension Enhancements?

    ERIC Educational Resources Information Center

    Koedel, Cory; Ni, Shawn; Podgursky, Michael

    2014-01-01

    During the late 1990s public pension funds across the United States accrued large actuarial surpluses. The seemingly flush conditions of the pension funds led legislators in most states to substantially improve retirement benefits for public workers, including teachers. In this study we examine the benefit enhancements to the teacher pension…

  20. Effectiveness of Enhanced Safety Management

    SciTech Connect

    Waterfall, K.W. )

    1988-01-01

    This paper discusses the development of an Enhanced Safety Management (ESM) campaign to improve safety and reduce risk in oil and gas exploration. The essentials of ESM are summarized by the author. The paper addresses the method developed to implement ESM and how the control of process designs to control operations minimizes the risk of a major accident.

  1. Discovery and Structure-Guided Optimization of Diarylmethanesulfonamide Disrupters of Glucokinase-Glucokinase Regulatory Protein (GK-GKRP) Binding: Strategic Use of a N → S (nN → σ*S-X) Interaction for Conformational Constraint.

    PubMed

    Pennington, Lewis D; Bartberger, Michael D; Croghan, Michael D; Andrews, Kristin L; Ashton, Kate S; Bourbeau, Matthew P; Chen, Jie; Chmait, Samer; Cupples, Rod; Fotsch, Christopher; Helmering, Joan; Hong, Fang-Tsao; Hungate, Randall W; Jordan, Steven R; Kong, Ke; Liu, Longbin; Michelsen, Klaus; Moyer, Carolyn; Nishimura, Nobuko; Norman, Mark H; Reichelt, Andreas; Siegmund, Aaron C; Sivits, Glenn; Tadesse, Seifu; Tegley, Christopher M; Van, Gwyneth; Yang, Kevin C; Yao, Guomin; Zhang, Jiandong; Lloyd, David J; Hale, Clarence; St Jean, David J

    2015-12-24

    The HTS-based discovery and structure-guided optimization of a novel series of GKRP-selective GK-GKRP disrupters are revealed. Diarylmethanesulfonamide hit 6 (hGK-hGKRP IC50 = 1.2 μM) was optimized to lead compound 32 (AMG-0696; hGK-hGKRP IC50 = 0.0038 μM). A stabilizing interaction between a nitrogen atom lone pair and an aromatic sulfur system (nN → σ*S-X) in 32 was exploited to conformationally constrain a biaryl linkage and allow contact with key residues in GKRP. Lead compound 32 was shown to induce GK translocation from the nucleus to the cytoplasm in rats (IHC score = 0; 10 mg/kg po, 6 h) and blood glucose reduction in mice (POC = -45%; 100 mg/kg po, 3 h). X-ray analyses of 32 and several precursors bound to GKRP were also obtained. This novel disrupter of GK-GKRP binding enables further exploration of GKRP as a potential therapeutic target for type II diabetes and highlights the value of exploiting unconventional nonbonded interactions in drug design.

  2. Image enhancement method for fingerprint recognition system.

    PubMed

    Li, Shunshan; Wei, Min; Tang, Haiying; Zhuang, Tiange; Buonocore, Michael

    2005-01-01

    Image enhancement plays an important role in Fingerprint Recognition System. In this paper fingerprint image enhancement method, a refined Gabor filter, is presented. This enhancement method can connect the ridge breaks, ensures the maximal gray values located at the ridge center and has the ability to compensate for the nonlinear deformations. The result shows it can improve the performance of image enhancement.

  3. Blob-enhanced reconstruction technique

    NASA Astrophysics Data System (ADS)

    Castrillo, Giusy; Cafiero, Gioacchino; Discetti, Stefano; Astarita, Tommaso

    2016-09-01

    A method to enhance the quality of the tomographic reconstruction and, consequently, the 3D velocity measurement accuracy, is presented. The technique is based on integrating information on the objects to be reconstructed within the algebraic reconstruction process. A first guess intensity distribution is produced with a standard algebraic method, then the distribution is rebuilt as a sum of Gaussian blobs, based on location, intensity and size of agglomerates of light intensity surrounding local maxima. The blobs substitution regularizes the particle shape allowing a reduction of the particles discretization errors and of their elongation in the depth direction. The performances of the blob-enhanced reconstruction technique (BERT) are assessed with a 3D synthetic experiment. The results have been compared with those obtained by applying the standard camera simultaneous multiplicative reconstruction technique (CSMART) to the same volume. Several blob-enhanced reconstruction processes, both substituting the blobs at the end of the CSMART algorithm and during the iterations (i.e. using the blob-enhanced reconstruction as predictor for the following iterations), have been tested. The results confirm the enhancement in the velocity measurements accuracy, demonstrating a reduction of the bias error due to the ghost particles. The improvement is more remarkable at the largest tested seeding densities. Additionally, using the blobs distributions as a predictor enables further improvement of the convergence of the reconstruction algorithm, with the improvement being more considerable when substituting the blobs more than once during the process. The BERT process is also applied to multi resolution (MR) CSMART reconstructions, permitting simultaneously to achieve remarkable improvements in the flow field measurements and to benefit from the reduction in computational time due to the MR approach. Finally, BERT is also tested on experimental data, obtaining an increase of the

  4. Enhancing who? Enhancing what? Ethics, bioethics, and transhumanism.

    PubMed

    Koch, Tom

    2010-12-01

    Transhumanists advance a "posthuman" condition in which technological and genetic enhancements will transform humankind. They are joined in this goal by bioethicists arguing for genetic selection as a means of "enhancing evolution," improving if not also the species then at least the potential lives of future individuals. The argument of both, this paper argues, is a new riff on the old eugenics tune. As ever, it is done in the name of science and its presumed knowledge base. As ever, the result is destructive rather than instructive, bad faith promoted as high ideal. The paper concludes with the argument that species advancement is possible but in a manner thoroughly distinct from that advanced by either of these groups.

  5. In vitro evidence supports the presence of glucokinase-independent glucosensing mechanisms in hypothalamus and hindbrain of rainbow trout.

    PubMed

    Otero-Rodiño, Cristina; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2016-06-01

    We previously obtained evidence in rainbow trout for the presence and response to changes in circulating levels of glucose (induced by intraperitoneal hypoglycaemic and hyperglycaemic treatments) of glucosensing mechanisms based on liver X receptor (LXR), mitochondrial production of reactive oxygen species (ROS) leading to increased expression of uncoupling protein 2 (UCP2), and sweet taste receptor in the hypothalamus, and on sodium/glucose co-transporter 1 (SGLT-1) in hindbrain. However, these effects of glucose might be indirect. Therefore, we evaluated the response of parameters related to these glucosensing mechanisms in a first experiment using pooled sections of hypothalamus and hindbrain incubated for 6 h at 15°C in modified Hanks' medium containing 2, 4 or 8 mmol l(-1) d-glucose. The responses observed in some cases were consistent with glucosensing capacity. In a second experiment, pooled sections of hypothalamus and hindbrain were incubated for 6 h at 15°C in modified Hanks' medium with 8 mmol l(-1) d-glucose alone (control) or containing 1 mmol l(-1) phloridzin (SGLT-1 antagonist), 20 µmol l(-1) genipin (UCP2 inhibitor), 1 µmol l(-1) trolox (ROS scavenger), 100 µmol l(-1) bezafibrate (T1R3 inhibitor) and 50 µmol l(-1) geranyl-geranyl pyrophosphate (LXR inhibitor). The response observed in the presence of these specific inhibitors/antagonists further supports the proposal that critical components of the different glucosensing mechanisms are functioning in rainbow trout hypothalamus and hindbrain.

  6. In vitro evidence supports the presence of glucokinase-independent glucosensing mechanisms in hypothalamus and hindbrain of rainbow trout.

    PubMed

    Otero-Rodiño, Cristina; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2016-06-01

    We previously obtained evidence in rainbow trout for the presence and response to changes in circulating levels of glucose (induced by intraperitoneal hypoglycaemic and hyperglycaemic treatments) of glucosensing mechanisms based on liver X receptor (LXR), mitochondrial production of reactive oxygen species (ROS) leading to increased expression of uncoupling protein 2 (UCP2), and sweet taste receptor in the hypothalamus, and on sodium/glucose co-transporter 1 (SGLT-1) in hindbrain. However, these effects of glucose might be indirect. Therefore, we evaluated the response of parameters related to these glucosensing mechanisms in a first experiment using pooled sections of hypothalamus and hindbrain incubated for 6 h at 15°C in modified Hanks' medium containing 2, 4 or 8 mmol l(-1) d-glucose. The responses observed in some cases were consistent with glucosensing capacity. In a second experiment, pooled sections of hypothalamus and hindbrain were incubated for 6 h at 15°C in modified Hanks' medium with 8 mmol l(-1) d-glucose alone (control) or containing 1 mmol l(-1) phloridzin (SGLT-1 antagonist), 20 µmol l(-1) genipin (UCP2 inhibitor), 1 µmol l(-1) trolox (ROS scavenger), 100 µmol l(-1) bezafibrate (T1R3 inhibitor) and 50 µmol l(-1) geranyl-geranyl pyrophosphate (LXR inhibitor). The response observed in the presence of these specific inhibitors/antagonists further supports the proposal that critical components of the different glucosensing mechanisms are functioning in rainbow trout hypothalamus and hindbrain. PMID:27026717

  7. Fertility-enhancing hysteroscopic surgery.

    PubMed

    Cela, Vito; Litta, Pietro; Franchini, Mario; Sergiampietri, Claudia; Simi, Giovanna; Freschi, Letizia; Artini, Paolo G; Papini, Francesca

    2016-04-01

    Anatomical uterine element and functional components play a fundamental role in the enhancing of fertility are the major actors. Uterine pathologies, including congenital or acquired lesions, have been reported in 21 to 47% of patients undergoing in vitro fertilization cycles. Hysteroscopy is an important procedure in the study of one of the most important element of fertility: the uterus, even if its use in the world of infertility is discussed. There are many studies on safety and feasibility of the procedure and on patient compliance, but there is no consensus on its systemic use. This study, thanks to the wide literature about the use of hysteroscopic surgery to enhance fertility in most of the congenital and acquired problems affecting women in fertility age, allows defining that diagnostic and operative hysteroscopy is a rapid and safety technology to improve fertility. PMID:26928416

  8. Nonhereditary enhancement of progeny growth

    NASA Technical Reports Server (NTRS)

    Khan, Amir S.; Fiorotto, Marta L.; Hill, Leigh-Anne; Malone, P. Brandon; Cummings, Kathleen K.; Parghi, Deena; Schwartz, Robert J.; Smith, Roy G.; Draghia-Akli, Ruxandra

    2002-01-01

    The im electroporated injection of a protease-resistant GH-releasing hormone cDNA into rat dams at 16 d gestation resulted in enhanced long-term growth of the F(1) offspring. The offspring were significantly heavier by 2 wk of age, and the difference was sustained to 10 wk of age. Consistent with their augmented growth, the plasma IGF-I concentration of the F(1) progeny was increased significantly. The pituitary gland of the offspring was significantly heavier and contained an increased number of somatotrophs and PRL-secreting cells, which is indicative of modification of cell lineage differentiation. These unique findings demonstrate that enhanced GH-releasing hormone expression in pregnant dams can result in intergenerational growth promotion by altering development of the pituitary gland in the offspring.

  9. Enhancing Research Papers in Astronomy

    NASA Astrophysics Data System (ADS)

    Kroffe, Kerry; McCann, G.

    2013-01-01

    XML-based production of journal articles, combined with real-time transformations, now make it possible to develop new enhancements to the reading experience and to the content of the article itself. Papers from AAS journals are now available in ‘Article Evolution’ HTML format, providing both familiar and new functionality that improves the reading experience. This poster will outline the roadmap for the development of ‘Article Evolution’ functionality and ask for input to help shape future enhancements that meet the needs of the astronomy community. Two of the ongoing developments described are ’semantic enrichment’ of articles and adoption of ORCID (Open Researcher and Contributor ID). Both of these have exciting possibilities at an article level within ‘Article Evolution’ but will also impact widely on third party services, such as linking and discovery of research papers.

  10. Biosurfactant-enhanced soil bioremediation

    SciTech Connect

    Kosaric, N.; Lu, G.; Velikonja, J.

    1995-12-01

    Bioremediation of soil contaminated with organic chemicals is a viable alternative method for clean-up and remedy of hazardous waste sites. The final objective in this approach is to convert the parent toxicant into a readily biodegradable product which is harmless to human health and/or the environment. Biodegradation of hydrocarbons in soil can also efficiently be enhanced by addition or in-situ production of biosufactants. It was generally observed that the degradation time was shortened and particularly the adaptation time for the microbes. More data from our laboratories showed that chlorinated aromatic compounds, such as 2,4-dichlorophenol, a herbicide Metolachlor, as well as naphthalene are degraded faster and more completely when selected biosurfactants are added to the soil. More recent data demonstrated an enhanced biodegradation of heavy hydrocarbons in petrochemical sludges, and in contaminated oil when biosurfactants were present or were added prior to the biodegradation process.

  11. Ras enhances Myc protein stability.

    PubMed

    Sears, R; Leone, G; DeGregori, J; Nevins, J R

    1999-02-01

    Various experiments have demonstrated a collaborative action of Myc and Ras, both in normal cell growth control as well as during oncogenesis. We now show that Ras enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas Myc has a very short half-life when produced in the absence of mitogenic signals, due to degradation by the 26S proteasome, the half-life of Myc increases markedly in growth-stimulated cells. This stabilization is dependent on the Ras/Raf/MAPK pathway and is not augmented by proteasome inhibition, suggesting that Ras inhibits the proteasome-dependent degradation of Myc. We propose that one aspect of Myc-Ras collaboration is an ability of Ras to enhance the accumulation of transcriptionally active Myc protein.

  12. Mixing enhancement using axial flow

    NASA Technical Reports Server (NTRS)

    Papamoschou, Dimitri (Inventor)

    2003-01-01

    A method and an apparatus for enhancing fluid mixing. The method comprises the following: (a) configuring a duct to have an effective outer wall, an effective inner wall, a cross-sectional shape, a first cross-sectional area and an exit area, the first cross-sectional area and the exit area being different in size; (b) generating a first flow at the first cross-sectional area, the first flow having a total pressure and a speed equal to or greater than a local speed of sound; and (c) generating a positive streamwise pressure gradient in a second flow in proximity of the exit area. The second flow results from the first flow. Fluid mixing is enhanced downstream from the duct exit area.

  13. Resolution enhanced sound detecting apparatus

    NASA Technical Reports Server (NTRS)

    Kendall, J. M. (Inventor)

    1979-01-01

    An apparatus is described for enhancing the resolution of a sound detector of the type which includes an acoustic mirror for focusing sound from an object onto a microphone to enable the determination of the location from which the sound arises. The enhancement apparatus includes an enclosure which surrounds the space between the mirror and microphone, and contains a gas heavier than air, such as Freon, through which sound moves slower and therefore with a shorter wavelength than in air, so that a mirror of given size has greater resolving power. An acoustically transparent front wall of the enclosure which lies forward of the mirror, can include a pair of thin sheets with pressured air between them, to form an end of the region of heavy gas into a concave shape.

  14. Three Fresh Exposures, Enhanced Color

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This enhanced-color panoramic camera image from the Mars Exploration Rover Opportunity features three holes created by the rock abrasion tool between sols 143 and 148 (June 18 and June 23, 2004) inside 'Endurance Crater.' The enhanced image makes the red colors a little redder and blue colors a little bluer, allowing viewers to see differences too subtle to be seen without the exaggeration. When compared with an approximately true color image, the tailings from the rock abrasion tool and the interior of the abraded holes are more prominent in this view. Being able to discriminate color variations helps scientists determine rocks' compositional differences and texture variations. This image was created using the 753-, 535- and 432-nanometer filters.

  15. Method for enhanced oil recovery

    DOEpatents

    Comberiati, Joseph R.; Locke, Charles D.; Kamath, Krishna I.

    1980-01-01

    The present invention is directed to an improved method for enhanced recovery of oil from relatively "cold" reservoirs by carbon dioxide flooding. In oil reservoirs at a temperature less than the critical temperature of 87.7.degree. F. and at a pore pressure greater than the saturation pressure of carbon dioxide at the temperature of the reservoir, the carbon dioxide remains in the liquid state which does not satisfactorily mix with the oil. However, applicants have found that carbon dioxide can be vaporized in situ in the reservoir by selectively reducing the pore pressure in the reservoir to a value less than the particular saturated vapor pressure so as to greatly enhance the mixing of the carbon dioxide with the oil.

  16. Quantum-Enhanced Machine Learning

    NASA Astrophysics Data System (ADS)

    Dunjko, Vedran; Taylor, Jacob M.; Briegel, Hans J.

    2016-09-01

    The emerging field of quantum machine learning has the potential to substantially aid in the problems and scope of artificial intelligence. This is only enhanced by recent successes in the field of classical machine learning. In this work we propose an approach for the systematic treatment of machine learning, from the perspective of quantum information. Our approach is general and covers all three main branches of machine learning: supervised, unsupervised, and reinforcement learning. While quantum improvements in supervised and unsupervised learning have been reported, reinforcement learning has received much less attention. Within our approach, we tackle the problem of quantum enhancements in reinforcement learning as well, and propose a systematic scheme for providing improvements. As an example, we show that quadratic improvements in learning efficiency, and exponential improvements in performance over limited time periods, can be obtained for a broad class of learning problems.

  17. Effect of High Sugar Intake on Glucose Transporter and Weight Regulating Hormones in Mice and Humans

    PubMed Central

    Ritze, Yvonne; Bárdos, Gyöngyi; D’Haese, Jan G.; Ernst, Barbara; Thurnheer, Martin; Schultes, Bernd; Bischoff, Stephan C.

    2014-01-01

    Objective Sugar consumption has increased dramatically over the last decades in Western societies. Especially the intake of sugar-sweetened beverages seems to be a major risk for the development of obesity. Thus, we compared liquid versus solid high-sugar diets with regard to dietary intake, intestinal uptake and metabolic parameters in mice and partly in humans. Methods Five iso-caloric diets, enriched with liquid (in water 30% vol/vol) or solid (in diet 65% g/g) fructose or sucrose or a control diet were fed for eight weeks to C57bl/6 mice. Sugar, liquid and caloric intake, small intestinal sugar transporters (GLUT2/5) and weight regulating hormone mRNA expression, as well as hepatic fat accumulation were measured. In obese versus lean humans that underwent either bariatric surgery or small bowel resection, we analyzed small intestinal GLUT2, GLUT5, and cholecystokinin expression. Results In mice, the liquid high-sucrose diet caused an enhancement of total caloric intake compared to the solid high-sucrose diet and the control diet. In addition, the liquid high-sucrose diet increased expression of GLUT2, GLUT5, and cholecystokinin expression in the ileum (P<0.001). Enhanced liver triglyceride accumulation was observed in mice being fed the liquid high-sucrose or -fructose, and the solid high-sucrose diet compared to controls. In obese, GLUT2 and GLUT5 mRNA expression was enhanced in comparison to lean individuals. Conclusions We show that the form of sugar intake (liquid versus solid) is presumably more important than the type of sugar, with regard to feeding behavior, intestinal sugar uptake and liver fat accumulation in mice. Interestingly, in obese individuals, an intestinal sugar transporter modulation also occurred when compared to lean individuals. PMID:25010715

  18. Enhancing Soundtracks From Old Movies

    NASA Technical Reports Server (NTRS)

    Frazer, Robert E.

    1992-01-01

    Proposed system enhances soundtracks of old movies. Signal on optical soundtrack of film digitized and processed to reduce noise and improve quality; timing signals added, and signal recorded on compact disk. Digital comparator and voltage-controlled oscillator synchronizes speed of film-drive motor and compact disk motor. Frame-coded detector reads binary frame-identifying marks on film. Digital comparator generates error signal if marks on film do not match those on compact disk.

  19. Preactivated thiomers: permeation enhancing properties.

    PubMed

    Wang, Xueqing; Iqbal, Javed; Rahmat, Deni; Bernkop-Schnürch, Andreas

    2012-11-15

    The study was aimed to prepare a series of poly(acrylic acid)-cysteine-2-mercaptonicotinic acid conjugates (preactivated thiomers) and to evaluate the influence of molecular mass or degree of preactivation with 2-mercaptonicotinic acid (2MNA) on their permeation enhancing properties. Preactivated thiomers with different molecular mass and different degree of preactivation were synthesized and categorized on the basis of their molecular mass and degree of preactivation as PAA(100)-Cys-2MNA (h), PAA(250)-Cys-2MNA (h), PAA(450)-Cys-2MNA (h), PAA(450)-Cys-2MNA (m) and PAA(450)-Cys-2MNA (l). In vitro permeation studies, the permeation enhancement ability for preactivated thiomers was ranked as PAA(450)-Cys-2MNA (h)>PAA(250)-Cys-2MNA (h)>PAA(100)-Cys-2MNA (h) on both Caco-2 cell monolayers and rat intestinal mucosa. Comparing the influence of degree of preactivation with 2MNA on permeation enhancement, the following order PAA(450)-Cys-2MNA (h)>PAA(450)-Cys-2MNA (m)≈PAA(450)-Cys-2MNA (l) on Caco-2 cell monolayers and PAA(450)-Cys-2MNA (m)>PAA(450)-Cys-2MNA (h)>PAA(450)-Cys-2MNA (l) on intestinal mucosa was observed. The P(app) of sodium fluorescein was 5.08-fold improved on Caco-2 cell monolayers for PAA(450)-Cys-2MNA (h) and 2.46-fold improved on intestinal mucosa for PAA(450)-Cys-2MNA (m), respectively, in comparison to sodium fluorescein in buffer only. These results indicated that preactivated thiomers could be considered as a promising macromolecular permeation enhancing polymer for non-invasive drug administration.

  20. Closing thoughts for cognitive enhancement.

    PubMed

    Kantak, Kathleen M; Wettstein, Joseph G

    2015-01-01

    The wide-ranging field of cognition enhancing research along with its ethics as it stands today is summarized. In the forefront are potentially novel drugs and non-pharmacological treatments for cognitive impairment across many different psychiatric and neurologic indications. Today's research will bring new drugs to patients tomorrow, and tomorrow's research will bring new molecular targets to clinical development that should be cognitive domain-specific. There is the likelihood that special populations may be better treated and that personalized medicine for cognitive impairment could become a reality. It is conceivable that with the current research effort, cognition enhancing drugs will become available to wide-ranging populations of people with neuropsychiatric illness and to those that are healthy. In some cultures, there is a push in society to be more intelligent or have more cognitive prowess. Thus, the ethical use of cognitive enhancing drugs should be an area of debate and communication. Neuroethics is a growing field and it intends to bring together key contributors such as physicians, disease experts, regulatory officials, and policy makers to discuss how such medicines can or should be made available. Together with this, one has to consider the possibility that no single medicine or technology will have a great impact on cognition and, therefore, combination therapy of drugs plus other approaches like exercise or transcranial direct-current stimulation may be the path forward. This is another area of scientific inquiry and debate, and the results should be fruitful and helpful to patients. The science of cognition is advancing at a rapid rate, and communication of its progress along with the development of rational and ethical policies for use of cognitive enhancers will be beneficial.

  1. CARE 3, Version 4 enhancements

    NASA Technical Reports Server (NTRS)

    Bryant, L. A.; Stiffler, J. J.

    1985-01-01

    The enhancements and error corrections to CARE III Version 4 are listed. All changes to Version 4 with the exception of the internal redundancy model were implemented in Version 5. Version 4 is the first public release version for execution on the CDC Cyber 170 series computers. Version 5 is the second release version and it is written in ANSI standard FORTRAN 77 for execution on the DEC VAX 11/700 series computers and many others.

  2. Technology Education Professional Enhancement Project

    NASA Technical Reports Server (NTRS)

    Hughes, Thomas A., Jr.

    1996-01-01

    The two goals of this project are: the use of integrative field of aerospace technology to enhance the content and instruction delivered by math, science, and technology teachers through the development of a new publication entitled NASA Technology Today, and to develop a rationale and structure for the study of technology, which establishes the foundation for developing technology education standards and programs of the future.

  3. Enhancing Centrifugal Separation With Electrophoresis

    NASA Technical Reports Server (NTRS)

    Herrmann, F. T.

    1986-01-01

    Separation of biological cells by coil-planet centrifuge enhanced by electrophoresis. By itself, coil-planet centrifuge offers relatively gentle method of separating cells under low centrifugal force in physiological medium that keeps cells alive. With addition of voltage gradient to separation column of centrifuge, separation still gentle but faster and more complete. Since separation apparatus contains no rotary seal, probability of leakage, contamination, corrosion, and short circuits reduced.

  4. Enhanced heat transfer using nanofluids

    DOEpatents

    Choi, Stephen U. S.; Eastman, Jeffrey A.

    2001-01-01

    This invention is directed to a method of and apparatus for enhancing heat transfer in fluids such as deionized water. ethylene glycol, or oil by dispersing nanocrystalline particles of substances such as copper, copper oxide, aluminum oxide, or the like in the fluids. Nanocrystalline particles are produced and dispersed in the fluid by heating the substance to be dispersed in a vacuum while passing a thin film of the fluid near the heated substance. The fluid is cooled to control its vapor pressure.

  5. Photodetector with enhanced light absorption

    DOEpatents

    Kane, James

    1985-01-01

    A photodetector including a light transmissive electrically conducting layer having a textured surface with a semiconductor body thereon. This layer traps incident light thereby enhancing the absorption of light by the semiconductor body. A photodetector comprising a textured light transmissive electrically conducting layer of SnO.sub.2 and a body of hydrogenated amorphous silicon has a conversion efficiency about fifty percent greater than that of comparative cells. The invention also includes a method of fabricating the photodetector of the invention.

  6. Chemical enhancement of surface deposition

    DOEpatents

    Patch, Keith D.; Morgan, Dean T.

    1997-07-29

    A method and apparatus for increasing the deposition of ions onto a surface, such as the adsorption of uranium ions on the detecting surface of a radionuclide detector. The method includes the step of exposing the surface to a complexing agent, such as a phosphate ion solution, which has an affinity for the dissolved species to be deposited on the surface. This provides, for example, enhanced sensitivity of the radionuclide detector.

  7. Chemical enhancement of surface deposition

    DOEpatents

    Patch, K.D.; Morgan, D.T.

    1997-07-29

    A method and apparatus are disclosed for increasing the deposition of ions onto a surface, such as the adsorption of uranium ions on the detecting surface of a radionuclide detector. The method includes the step of exposing the surface to a complexing agent, such as a phosphate ion solution, which has an affinity for the dissolved species to be deposited on the surface. This provides, for example, enhanced sensitivity of the radionuclide detector. 16 figs.

  8. The Likelihood of Cognitive Enhancement

    PubMed Central

    Lynch, Gary; Palmer, Linda C.; Gall, Christine M.

    2011-01-01

    Whether drugs that enhance cognition in healthy individuals will appear in the near future has become a topic of considerable interest. We address this possibility using a three variable system (psychological effect, neurobiological mechanism, efficiency vs. capabilities) for classifying candidates. Ritalin and modafinil, two currently available compounds, operate on primary psychological states that in turn affect cognitive operations (attention, memory), but there is little evidence that these effects translate into improvements in complex cognitive processing. A second category of potential enhancers includes agents that improve memory encoding, generally without large changes in primary psychological states. Unfortunately, there is little information on how these compounds affect cognitive performance in standard psychological tests. Recent experiments have identified a number of sites at which memory drugs could, in principle, manipulate the cell biological systems underlying the learning-related long-term potentiation (LTP) effect; this may explain the remarkable diversity of memory promoting compounds. Indeed, many of these agents are known to have positive effects on LTP. A possible third category of enhancement drugs directed specifically at integrated cognitive operations is nearly empty. From a neurobiological perspective, two plausible candidate classes have emerged that both target the fast excitatory transmission responsible for communication within cortical networks. One acts on nicotinic receptors (alpha7, alpha4) that regulate release of the neurotransmitter glutamate while the other (‘ampakines’) allosterically modulates the glutamate receptors mediating the post-synaptic response (EPSCs). Brain imaging in primates has shown that ampakines expand cortical networks engaged by a complex task; coupled with behavioral data, these findings provide evidence for the possibility of generating new cognitive capabilities. Finally, we suggest that

  9. How rotational vortices enhance transfers

    NASA Astrophysics Data System (ADS)

    Griffani, D.; Rognon, P.; Metzger, B.; Einav, I.

    2013-09-01

    Inspired by recent observations of granular flow, we examine how rotational vortices contribute to heat or mass transfer enhancement in a fluid. We use a tracer method to simulate both diffusion and advection in systems of differing intrinsic diffusivities D0, vortex sizes R, vortex rotation frequencies f, and vortex lifetimes ℓ. The results reveal that these systems exhibit an effective diffusive behavior, characterized by an effective diffusivity Deff. A striking finding is the existence of two regimes, dichotomised by the Péclet number Pe = R2f/D0. When the Péclet number is less than one, there is no transfer enhancement, Deff = D0. For higher values, vortices produce some transfer enhancement with a corresponding power law Deff/D0 ≈ Pen. The power n ranges from a lower bound of 0.5 for stationary vortices of lifetime infinity, to an upper bound of 1 for vortices of lifetimes shorter than half a rotation. This difference is attributed to two different internal mechanisms involving the coupling of diffusion and advection. These results could provide new insights on the transfer properties of fluid systems comprising rotational vortices, such as granular materials, suspensions, foams, and emulsions, as well as low Reynolds number stirred flows.

  10. Enhancement classification of galaxy images

    NASA Astrophysics Data System (ADS)

    Jenkinson, John

    With the advent of astronomical imaging technology developments, and the increased capacity of digital storage, the production of photographic atlases of the night sky have begun to generate volumes of data which need to be processed autonomously. As part of the Tonantzintla Digital Sky Survey construction, the present work involves software development for the digital image processing of astronomical images, in particular operations that preface feature extraction and classification. Recognition of galaxies in these images is the primary objective of the present work. Many galaxy images have poor resolution or contain faint galaxy features, resulting in the misclassification of galaxies. An enhancement of these images by the method of the Heap transform is proposed, and experimental results are provided which demonstrate the image enhancement to improve the presence of faint galaxy features thereby improving classification accuracy. The feature extraction was performed using morphological features that have been widely used in previous automated galaxy investigations. Principal component analysis was applied to the original and enhanced data sets for a performance comparison between the original and reduced features spaces. Classification was performed by the Support Vector Machine learning algorithm.

  11. Dispersion-Enhanced Laser Gyroscope

    NASA Technical Reports Server (NTRS)

    Smith, David D.; Chang, Hongrok; Arissian, L.; Diels, J. C.

    2008-01-01

    We analyze the effect of a highly dispersive element placed inside a modulated optical cavity on the frequency and amplitude of the output modulation to determine the conditions for enhanced gyroscopic sensitivities. The element is treated as both a phase and amplitude filter, and the time-dependence of the cavity field is considered. Both atomic gases (two-level and multi-level) and optical resonators (single and coupled) are considered and compared as dispersive elements. We find that it is possible to simultaneously enhance the gyro scale factor sensitivity and suppress the dead band by using an element with anomalous dispersion that has greater loss at the carrier frequency than at the side-band frequencies, i.e., an element that simultaneously pushes and intensifies the perturbed cavity modes, e.g. a two-level absorber or an under-coupled optical resonator. The sensitivity enhancement is inversely proportional to the effective group index, becoming infinite at a group index of zero. However, the number of round trips required to reach a steady-state also becomes infinite when the group index is zero (or two). For even larger dispersions a steady-state cannot be achieved, and nonlinear dynamic effects such as bistability and periodic oscillations are predicted in the gyro response.

  12. [Lower is better: ENHANCE affair].

    PubMed

    Scardi, Sabino; Umari, Paolo; D'Agata, Bianca Maria

    2008-06-01

    Ezetimibe lowers the intestinal absorption of cholesterol, being complementary to the effects of statin. To check its efficacy in lowering the carotid intima-media thickness, in 2002 a multicenter international trial called ENHANCE was started, in order to assess by ultrasound the regression of atherosclerotic plaques. The protocol tested the use of simvastatin 80 mg + placebo versus simvastatin 80 mg + ezetimibe 10 mg in 720 randomized patients. Both drugs were well tolerated. Combination therapy was associated with a larger reduction in LDL cholesterol, but there were no differences in the intima-media thickness measured at three sites in the carotid arteries, nor differences in cardiovascular events between the two groups in the trial. These results provoked disappointment of sponsors (Merck, Schering Plough) who, although the results of the trial were available since march 2007, delayed official communication of about 18 months. This led to speculations and rumors among media, American Government, cardiologic scientific associations, and consequences in the Ezetimibe market and at Wall Street. In particular, the American College of Cardiology didn't accept the communication of ENHANCE results to the Late Breaking Trial Session of the Chicago congress, diverting it to another secondary forum. In conclusion, the experience of the ENHANCE trial suggests to pharmaceutical companies, researchers, clinicians, scientific companies and media a deep meditation in order to avoid in the future similar problems in the management of results of medical research.

  13. Cyclosporine A enhances platelet aggregation.

    PubMed

    Grace, A A; Barradas, M A; Mikhailidis, D P; Jeremy, J Y; Moorhead, J F; Sweny, P; Dandona, P

    1987-12-01

    In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.

  14. Threshold enhancement of diphoton resonances

    NASA Astrophysics Data System (ADS)

    Bharucha, Aoife; Djouadi, Abdelhak; Goudelis, Andreas

    2016-10-01

    We revisit a mechanism to enhance the decay width of (pseudo-)scalar resonances to photon pairs when the process is mediated by loops of charged fermions produced near threshold. Motivated by the recent LHC data, indicating the presence of an excess in the diphoton spectrum at approximately 750 GeV, we illustrate this threshold enhancement mechanism in the case of a 750 GeV pseudoscalar boson A with a two-photon decay mediated by a charged and uncolored fermion having a mass at the 1/2MA threshold and a small decay width, < 1 MeV. The implications of such a threshold enhancement are discussed in two explicit scenarios: i) the Minimal Supersymmetric Standard Model in which the A state is produced via the top quark mediated gluon fusion process and decays into photons predominantly through loops of charginos with masses close to 1/2MA and ii) a two Higgs doublet model in which A is again produced by gluon fusion but decays into photons through loops of vector-like charged heavy leptons. In both these scenarios, while the mass of the charged fermion has to be adjusted to be extremely close to half of the A resonance mass, the small total widths are naturally obtained if only suppressed three-body decay channels occur. Finally, the implications of some of these scenarios for dark matter are discussed.

  15. Enhanced vision meets pilot assistance

    NASA Astrophysics Data System (ADS)

    Hecker, Peter; Doehler, Hans-Ullrich; Suikat, Reiner

    1999-07-01

    As presented in previous contributions within SPIE's Enhanced and Synthetic Vision Conferences, DLR's Institute of Flight Guidance is involved in the design, development and testing of enhanced vision systems for flight guidance applications. The combination of forward looking imaging sensors (such as DaimlerChrysler's HiVision millimeter wave radar), terrain data stored in on-board databases plus information transmitted from ground or on-board other aircraft via data link is used to give the air crew an improved situational awareness. This helps pilots to handle critical tasks, such as landing approaches and taxiing especially under adverse weather conditions. The research and development of this system was mostly funded by a national research program from mid of 1996 to mid of 1999. On one hand this paper will give a general overview about the project and the lessons learned. Results of flight tests carried out recently will be shown as well as brief looks into evaluation tests on-board an Airbus A-340 full flight simulator performed mid of 1998 at the Flight Simulation Center Berlin. On the other hand an outlook will be presented, which shows enhanced vision systems as a major player in the theater of pilot assistance systems as they are under development at DLR's Institute of Flight Guidance in close cooperation with the University of the Federal Armed Forces in Munich, Germany.

  16. Polyphosphate enhances fibrin clot structure

    PubMed Central

    Smith, Stephanie A.

    2008-01-01

    Polyphosphate, a linear polymer of inorganic phosphate, is present in platelet dense granules and is secreted on platelet activation. We recently reported that polyphosphate is a potent hemostatic regulator, serving to activate the contact pathway of blood clotting and accelerate factor V activation. Because polyphosphate did not alter thrombin clotting times, it appeared to exert all its procoagulant actions upstream of thrombin. We now report that polyphosphate enhances fibrin clot structure in a calcium-dependent manner. Fibrin clots formed in the presence of polyphosphate had up to 3-fold higher turbidity, had higher mass-length ratios, and exhibited thicker fibers in scanning electron micrographs. The ability of polyphosphate to enhance fibrin clot turbidity was independent of factor XIIIa activity. When plasmin or a combination of plasminogen and tissue plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of polyphosphate exhibited prolonged clot lysis times. Release of polyphosphate from activated platelets or infectious microorganisms may play an important role in modulating fibrin clot structure and increasing its resistance to fibrinolysis. Polyphosphate may also be useful in enhancing the structure of surgical fibrin sealants. PMID:18544683

  17. Enhanced Jumping-Droplet Departure.

    PubMed

    Kim, Moon-Kyung; Cha, Hyeongyun; Birbarah, Patrick; Chavan, Shreyas; Zhong, Chen; Xu, Yuehan; Miljkovic, Nenad

    2015-12-15

    Water vapor condensation on superhydrophobic surfaces has received much attention in recent years because of its ability to shed water droplets at length scales 3 decades smaller than the capillary length (∼1 mm) via coalescence-induced droplet jumping. Jumping-droplet condensation has been demonstrated to enhance heat transfer, anti-icing, and self-cleaning efficiency and is governed by the theoretical inertial-capillary scaled jumping speed (U). When two droplets coalesce, the experimentally measured jumping speed (Uexp) is fundamentally limited by the internal fluid dynamics during the coalescence process (Uexp < 0.23U). Here, we theoretically and experimentally demonstrate multidroplet (>2) coalescence as an avenue to break the two-droplet speed limit. Using side-view and top-view high-speed imaging to study more than 1000 jumping events on a copper oxide nanostructured superhydrophobic surface, we verify that droplet jumping occurs as a result of three fundamentally different mechanisms: (1) coalescence between two droplets, (2) coalescence among more than two droplets (multidroplet), and (3) coalescence between one or more droplets on the surface and a returning droplet that has already departed (multihop). We measured droplet-jumping speeds for a wide range of droplet radii (5-50 μm) and demonstrated that while the two-droplet capillary-to-inertial energy conversion mechanism is not identical to that of multidroplet jumping, speeds above the theoretical two-droplet limit (>0.23U) can be achieved. However, we discovered that multihop coalescence resulted in drastically reduced jumping speeds (≪0.23U) due to adverse momentum contributions from returning droplets. To quantify the impact of enhanced jumping speed on heat-transfer performance, we developed a condensation critical heat flux model to show that modest jumping speed enhancements of 50% using multidroplet jumping can enhance performance by up to 40%. Our results provide a starting point for the

  18. Integrating diverse datasets improves developmental enhancer prediction.

    PubMed

    Erwin, Genevieve D; Oksenberg, Nir; Truty, Rebecca M; Kostka, Dennis; Murphy, Karl K; Ahituv, Nadav; Pollard, Katherine S; Capra, John A

    2014-06-01

    Gene-regulatory enhancers have been identified using various approaches, including evolutionary conservation, regulatory protein binding, chromatin modifications, and DNA sequence motifs. To integrate these different approaches, we developed EnhancerFinder, a two-step method for distinguishing developmental enhancers from the genomic background and then predicting their tissue specificity. EnhancerFinder uses a multiple kernel learning approach to integrate DNA sequence motifs, evolutionary patterns, and diverse functional genomics datasets from a variety of cell types. In contrast with prediction approaches that define enhancers based on histone marks or p300 sites from a single cell line, we trained EnhancerFinder on hundreds of experimentally verified human developmental enhancers from the VISTA Enhancer Browser. We comprehensively evaluated EnhancerFinder using cross validation and found that our integrative method improves the identification of enhancers over approaches that consider a single type of data, such as sequence motifs, evolutionary conservation, or the binding of enhancer-associated proteins. We find that VISTA enhancers active in embryonic heart are easier to identify than enhancers active in several other embryonic tissues, likely due to their uniquely high GC content. We applied EnhancerFinder to the entire human genome and predicted 84,301 developmental enhancers and their tissue specificity. These predictions provide specific functional annotations for large amounts of human non-coding DNA, and are significantly enriched near genes with annotated roles in their predicted tissues and lead SNPs from genome-wide association studies. We demonstrate the utility of EnhancerFinder predictions through in vivo validation of novel embryonic gene regulatory enhancers from three developmental transcription factor loci. Our genome-wide developmental enhancer predictions are freely available as a UCSC Genome Browser track, which we hope will enable

  19. Freshwater aspects of anadromous salmonid enhancement

    USGS Publications Warehouse

    Gould, Rowan W.

    1982-01-01

    Freshwater enhancement of anadromous salmonid populations has been practiced in the United States and Canada since the late 1800's. Reduction of natural spawning habitat and increasing fishing pressure make artificial enhancement a possible alternative to declining populations. Enhancement of anadromous salmonids involved improvement of the natural environment and reducing natural mortality. Methods of enhancement include fishways, spawning and rearing channels, stream rehabilitation, lake fertilization, environmental management, and artificial propagation techniques. Five Pacific salmon species and steelhead trout are commonly enhanced, primarily in watershed entering the Pacific Ocean and Great Lakes. Enhancement efforts contribute heavily to a commercial and sport industry realizing over $1.5 billion.

  20. Polycarboxylates Enhance Beetle Antifreeze Protein Activity

    PubMed Central

    Amornwittawat, Natapol; Wang, Sen; Duman, John G.; Wen, Xin

    2008-01-01

    Summary Antifreeze proteins (AFPs) lower the noncolligative freezing point of water in the presence of ice below the ice melting point. The temperature difference between the melting point and the noncolligative freezing point is termed thermal hysteresis (TH). The magnitude of the TH depends on the specific activity and the concentration of AFP, and the concentration of enhancers in the solution. Known enhancers are certain low molecular mass molecules and proteins. Here, we investigated a series of polycarboxylates that enhance the TH activity of an AFP from the beetle Dendroides canadensis (DAFP) using differential scanning calorimetry (DSC). Triethylenetetramine-N,N,N′,N″,N‴,N‴-hexaacetate, the most efficient enhancer identified in this work, can increase the TH of DAFP by nearly 1.5 fold over than that of the published best enhancer, citrate. The Zn2+ coordinated carboxylate results in loss of the enhancement ability of the carboxylate on antifreeze activity. There is not an additional increase in TH when a weaker enhancer is added to a stronger enhancer solution. These observations suggest that the more carboxylate groups per enhancer molecule the better the efficiency of the enhancer and that the freedom of motion of these molecules is necessary for them to serve as enhancers for AFP. The hydroxyl groups in the enhancer molecules can also positively affect their TH enhancement efficiency, though not as strongly as carboxylate groups. Mechanisms are discussed. PMID:18620083

  1. Gasdynamic enhancement of nonpremixed combustion

    SciTech Connect

    Marble, F.E.

    1994-12-31

    To promote efficient performance of very high speed air-breathing propulsion systems, the combustor Mach number must be of the order of six for a flight Mach number of 18. Because of this high gas speed through the combustor, mixing rates of hydrogen fuel with air must be very rapid in order to allow a combustor of reasonable length. It is proposed to enhance the rate of mixing and combustion of hydrogen and air, and thereby reduce combustor length, through the introduction of streamwise vorticity generated by the interaction of a weak oblique shock wave with the density gradient between air and a cylindrical jet of hydrogen. Because of the high Mach number flow in the combustor, the oblique shock traverses the jet at a small angle with respect to the free stream direction, and the principle of slender body theory allows one conceptually to replace the three-dimensional steady flow with a two-dimensional unsteady flow. As a consequence, two-dimensional time-dependent computational studies and an extensive experimental shock tube investigation were employed to assess mixing rates for the steady flow in the combustor. The results indicated that under realistic conditions, adequate mixing could be accomplished within 1 ms, a rate that was technologically interesting. Encouraged by these experiments, a ``practical`` injector, utilizing shock-enhanced mixing, was designed for a combustor having a free stream Mach number of 6.0. A detailed aerodynamic and mixing investigation was carried out in the Mach 6 High Reynolds Number Tunnel at the NASA-Langley Research Center. The results confirmed both the details and the overall effectiveness of the shock-enhanced mixing concept.

  2. Permeability enhancement by shock cooling

    NASA Astrophysics Data System (ADS)

    Griffiths, Luke; Heap, Michael; Reuschlé, Thierry; Baud, Patrick; Schmittbuhl, Jean

    2015-04-01

    The permeability of an efficient reservoir, e.g. a geothermal reservoir, should be sufficient to permit the circulation of fluids. Generally speaking, permeability decreases over the life cycle of the geothermal system. As a result, is usually necessary to artificially maintain and enhance the natural permeability of these systems. One of the methods of enhancement -- studied here -- is thermal stimulation (injecting cold water at low pressure). This goal of this method is to encourage new thermal cracks within the reservoir host rocks, thereby increasing reservoir permeability. To investigate the development of thermal microcracking in the laboratory we selected two granites: a fine-grained (Garibaldi Grey granite, grain size = 0.5 mm) and a course-grained granite (Lanhelin granite, grain size = 2 mm). Both granites have an initial porosity of about 1%. Our samples were heated to a range of temperatures (100-1000 °C) and were either cooled slowly (1 °C/min) or shock cooled (100 °C/s). A systematic microstructural (2D crack area density, using standard stereological techniques, and 3D BET specific surface area measurements) and rock physical property (porosity, P-wave velocity, uniaxial compressive strength, and permeability) analysis was undertaken to understand the influence of slow and shock cooling on our reservoir granites. Microstructurally, we observe that the 2D crack surface area per unit volume and the specific surface area increase as a result of thermal stressing, and, for the same maximum temperature, crack surface area is higher in the shock cooled samples. This observation is echoed by our rock physical property measurements: we see greater changes for the shock cooled samples. We can conclude that shock cooling is an extremely efficient method of generating thermal microcracks and modifying rock physical properties. Our study highlights that thermal treatments are likely to be an efficient method for the "matrix" permeability enhancement of

  3. Enhanced radiation resistant fiber optics

    DOEpatents

    Lyons, Peter B.; Looney, Larry D.

    1993-01-01

    A process for producing an optical fiber having enhanced radiation resitance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation.

  4. Enhanced radiation resistant fiber optics

    DOEpatents

    Lyons, P.B.; Looney, L.D.

    1993-11-30

    A process for producing an optical fiber having enhanced radiation resistance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation. 4 figures.

  5. Enhancement of polyisoprene latex production

    NASA Technical Reports Server (NTRS)

    Bauman, Albert J. (Inventor)

    1979-01-01

    Production of high molecular weight polyisoprene latex is enhanced by administering to plants, particularly Guayule Plants, an amine containing at least one two-carbon chain substituent and preferably substituted trialkylamine of the general structure: ##STR1## where R.sub.4, R.sub.5 and R.sub.6 are alkyl, preferably ethyl and at least one of R.sub.4, R.sub.5 and R.sub.6 is preferably an electron withdrawing group substituted aryloxy or arylthio ethyl group.

  6. Privacy-enhanced electronic mail

    NASA Astrophysics Data System (ADS)

    Bishop, Matt

    1990-06-01

    The security of electronic mail sent through the Internet may be described in exactly three words: there is none. The Privacy and Security Research Group has recommended implementing mechanisms designed to provide security enhancements. The first set of mechanisms provides a protocol to provide privacy, integrity, and authentication for electronic mail; the second provides a certificate-based key management infrastructure to support key distribution throughout the internet, to support the first set of mechanisms. These mechanisms are described, as well as the reasons behind their selection and how these mechanisms can be used to provide some measure of security in the exchange of electronic mail.

  7. Intralymphatic immunization enhances DNA vaccination

    NASA Astrophysics Data System (ADS)

    Maloy, Kevin J.; Erdmann, Iris; Basch, Veronique; Sierro, Sophie; Kramps, Thomas A.; Zinkernagel, Rolf M.; Oehen, Stefan; Kündig, Thomas M.

    2001-03-01

    Although DNA vaccines have been shown to elicit potent immune responses in animal models, initial clinical trials in humans have been disappointing, highlighting a need to optimize their immunogenicity. Naked DNA vaccines are usually administered either i.m. or intradermally. The current study shows that immunization with naked DNA by direct injection into a peripheral lymph node enhances immunogenicity by 100- to 1,000-fold, inducing strong and biologically relevant CD8+ cytotoxic T lymphocyte responses. Because injection directly into a lymph node is a rapid and easy procedure in humans, these results have important clinical implications for DNA vaccination.

  8. Nutritional Supplements to Enhance Recovery

    NASA Astrophysics Data System (ADS)

    Ziegenfuss, Tim N.; Landis, Jamie; Greenwood, Mike

    The ability to recover from intense exercise often separates good athletes from great ones. In the past, "recovery" often simply included rest, physical modalities (e.g., massage, hydration therapy) and meeting basic nutritional needs for fluid and energy intake. Today, athletes have a number of additional options to help them recover from high intensity training, one of which includes the judicious use of dietary supplements. This chapter briefly reviews nutritional strategies that have a strong theoretical background for enhancing rehydration/electrolyte balance, replenishing energy reserves, minimizing oxidative damage, and stimulating muscle repair.

  9. Enhanced Master Controller Unit Tester

    NASA Technical Reports Server (NTRS)

    Benson, Patricia; Johnson, Yvette; Johnson, Brian; Williams, Philip; Burton, Geoffrey; McCoy, Anthony

    2007-01-01

    The Enhanced Master Controller Unit Tester (EMUT) software is a tool for development and testing of software for a master controller (MC) flight computer. The primary function of the EMUT software is to simulate interfaces between the MC computer and external analog and digital circuitry (including other computers) in a rack of equipment to be used in scientific experiments. The simulations span the range of nominal, off-nominal, and erroneous operational conditions, enabling the testing of MC software before all the equipment becomes available.

  10. Enhancing professionalism at GPU Nuclear

    SciTech Connect

    Coe, R.P. )

    1992-01-01

    Late in 1988, GPU Nuclear embarked on a major program aimed at enhancing professionalism at its Oyster Creek and Three Mile Island nuclear generating stations. The program was also to include its corporate headquarters in Parsippany, New Jersey. The overall program was to take several directions, including on-site degree programs, a sabbatical leave-type program for personnel to finish college degrees, advanced technical training for licensed staff, career progression for senior reactor operators, and expanded teamwork and leadership training for control room crew. The largest portion of this initiative was the development and delivery of professionalism training to the nearly 2,000 people at both nuclear generating sites.

  11. Computer Program Helps Enhance Images

    NASA Technical Reports Server (NTRS)

    Stanfill, Daniel F., IV

    1994-01-01

    Pixel Pusher is Macintosh application program for viewing and performing minor enhancements on imagery. Works with color images digitized to 8 bits. Reads image files in JPL's two primary image formats VICAR and PDS as well as in Macintosh PICT format. VICAR (NPO-18076) handles array of image-processing capabilities used for variety of applications, including processing of biomedical images, cartography, imaging of Earth resources, and geological exploration. Pixel Pusher also imports color lookup tables in VICAR format for viewing images in pseudocolor (256 colors). Written in Symantec's Think C.

  12. Feedback enhanced plasma spray tool

    DOEpatents

    Gevelber, Michael Alan; Wroblewski, Donald Edward; Fincke, James Russell; Swank, William David; Haggard, Delon C.; Bewley, Randy Lee

    2005-11-22

    An improved automatic feedback control scheme enhances plasma spraying of powdered material through reduction of process variability and providing better ability to engineer coating structure. The present inventors discovered that controlling centroid position of the spatial distribution along with other output parameters, such as particle temperature, particle velocity, and molten mass flux rate, vastly increases control over the sprayed coating structure, including vertical and horizontal cracks, voids, and porosity. It also allows improved control over graded layers or compositionally varying layers of material, reduces variations, including variation in coating thickness, and allows increasing deposition rate. Various measurement and system control schemes are provided.

  13. Elastic mismatch enhances cell motility

    NASA Astrophysics Data System (ADS)

    Bresler, Yony; Palmieri, Benoit; Grant, Martin

    In recent years, the study of physics phenomena in cancer has drawn considerable attention. In cancer metastasis, a soft cancer cell leaves the tumor, and must pass through the endothelium before reaching the bloodstream. Using a phase-field model we have shown that the elasticity mismatch between cells alone is sufficient to enhance the motility of thesofter cancer cell by means of bursty migration, in agreement with experiment. We will present further characterization of these behaviour, as well as new possible applications for this model.

  14. Enhancing the crisis management briefing.

    PubMed

    Clark, Daniel W; Volkmann, Peter

    2005-01-01

    The Crisis Management Briefing (CMB) is a powerful and versatile crisis intervention tool, effective within a wide variety of populations, settings, and critical incidents. Initially proposed by Everly (2000), the CMB uniquely fills the factual information void following a critical incident. Additionally, a CMB provides essential information on effective coping strategies and available helping resources, tailored to the specific incident(s). The authors expand on the original CMB construct using their combined field experience, offering recommendations on team composition, strategic planning factors, using CISDs vs. CMBs, and specific enhancements for the four phases. They conclude with examples of specific interventions across a variety of events to illustrate their recommendations.

  15. Enhanced thermopower of gated silicene

    NASA Astrophysics Data System (ADS)

    Yan, Yonghong; Wu, Haifei; Jiang, Feng; Zhao, Hui

    2013-11-01

    We theoretically investigate the thermopower of silicene systems in an external electric field perpendicular to the silicene sheet. In the absence of the field, we estimate that the thermopower of pure silicene is of order ˜80 μV/K. When a finite field is applied, a comparatively big band gap is opened and the thermopower is thus enhanced by several times as compared with the case without the field. The effect of disorder is also studied, and we find only minimal difference.

  16. Helium and Enhanced Image of the Sun

    NASA Video Gallery

    This video blinks between an image in Helium and an enhanced image. The original image is from AIA on SDO and the enhanced image was created at the LM Solar and Astrophysics Laboratory (LMSAL) by D...

  17. ATAMM enhancement and multiprocessor performance evaluation

    NASA Technical Reports Server (NTRS)

    Stoughton, John W.; Mielke, Roland R.; Som, Sukhamoy; Obando, Rodrigo; Malekpour, Mahyar R.; Jones, Robert L., III; Mandala, Brij Mohan V.

    1991-01-01

    ATAMM (Algorithm To Architecture Mapping Model) enhancement and multiprocessor performance evaluation is discussed. The following topics are included: the ATAMM model; ATAMM enhancement; ADM (Advanced Development Model) implementation of ATAMM; and ATAMM support tools.

  18. DENdb: database of integrated human enhancers.

    PubMed

    Ashoor, Haitham; Kleftogiannis, Dimitrios; Radovanovic, Aleksandar; Bajic, Vladimir B

    2015-01-01

    Enhancers are cis-acting DNA regulatory regions that play a key role in distal control of transcriptional activities. Identification of enhancers, coupled with a comprehensive functional analysis of their properties, could improve our understanding of complex gene transcription mechanisms and gene regulation processes in general. We developed DENdb, a centralized on-line repository of predicted enhancers derived from multiple human cell-lines. DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines. DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes. DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information. Database URL: http://www.cbrc.kaust.edu.sa/dendb/. PMID:26342387

  19. Textual Enhancement of Input: Issues and Possibilities

    ERIC Educational Resources Information Center

    Han, ZhaoHong; Park, Eun Sung; Combs, Charles

    2008-01-01

    The input enhancement hypothesis proposed by Sharwood Smith (1991, 1993) has stimulated considerable research over the last 15 years. This article reviews the research on textual enhancement of input (TE), an area where the majority of input enhancement studies have aggregated. Methodological idiosyncrasies are the norm of this body of research.…

  20. Transcriptional enhancer from milk protein genes

    DOEpatents

    Casperson, Gerald F.; Schmidhauser, Christian T.; Bissell, Mina J.

    1999-01-01

    The invention relates to novel enhancer nucleotide sequences which stimulate transcription of heterologous DNA in cells in culture. The enhancers are derived from major milk protein genes by the process of deletion mapping and functional analysis. The invention also relates to expression vectors containing the novel enhancers.

  1. Real-time digital image enhancement

    NASA Technical Reports Server (NTRS)

    Woods, R. E.; Gonzalez, R. C.

    1981-01-01

    A programmable system for enhancing monocular and stereographic images at video rates is presented. The system provides both automatic and interactive enhancement modes based on histogram modification and intensity mapping techniques. Experimental results which illustrate enhancement capabilities under a variety of scene types and conditions are described.

  2. RTU Comparison Calculator Enhancement Plan

    SciTech Connect

    Miller, James D.; Wang, Weimin; Katipamula, Srinivas

    2015-07-01

    Over the past two years, Department of Energy’s Building Technologies Office (BTO) has been investigating ways to increase the operating efficiency of the packaged rooftop units (RTUs) in the field. First, by issuing a challenge to the RTU manufactures to increase the integrated energy efficiency ratio (IEER) by 60% over the existing ASHRAE 90.1-2010 standard. Second, by evaluating the performance of an advanced RTU controller that reduces the energy consumption by over 40%. BTO has previously also funded development of a RTU comparison calculator (RTUCC). RTUCC is a web-based tool that provides the user a way to compare energy and cost savings for two units with different efficiencies. However, the RTUCC currently cannot compare savings associated with either the RTU Challenge unit or the advanced RTU controls retrofit. Therefore, BTO has asked PNNL to enhance the tool so building owners can compare energy and savings associated with this new class of products. This document provides the details of the enhancements that are required to support estimating energy savings from use of RTU challenge units or advanced controls on existing RTUs.

  3. Chromophore-enhanced bacterial photothermolysis

    NASA Astrophysics Data System (ADS)

    Huckleby, Jana K.; Morton, Rebecca J.; Bartels, Kenneth E.

    1999-06-01

    The use of chromophore dyes to enhance the bactericidal effect of laser energy was studied as a means to optimize laser treatment for the decontamination of wound. Using an in vitro study, various concentrations of indocyanine green (ICG), carbon black, and fluorescein were mixed with a suspension of bacteria and plated on tryptic soy agar. Plates were exposed to a laser beam of 10-15 watts for times ranging from 0 to 180 seconds, incubated overnight, and colony counts were performed. Bacteria not mixed with chromophore were used as controls. Six bacterial strains encompassing a range of bacterial types were used: Staphylococcus aureau, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus spore suspensions, and Clostridium perfringens. Laser treatment alone had no effect on any of the bacteria. Significant killing of gram-positive bacteria, including spores of Bacillus cereus, was observed only with the use of ICG and diode laser energy. No effect was observed using any of the chromophores on the gram-negative bacteria. The results of this study indicate that successful killing of gram-positive bacteria can be achieved using ICG combined with appropriate laser energy and wavelength. Efforts to enhance the susceptibility of gram-negative bacteria to photothermolysis by laser energy were unsuccessful.

  4. Thermal Enhanced Vapor Extraction System

    SciTech Connect

    Phelan, J.M.

    1992-01-01

    At some landfills, hazardous wastes were placed into disposal pits with other waste oils. Volatile organic wastes, such as cleaning solvents, when combined with oil are much more difficult to remove from the soils because the oil makes the volatile organic chemical evaporate much slower. The typical vacuum extraction remediation method could become a lengthy campaign. Since all chemicals evaporate faster when they are heated, if the contaminated soil could be heated, the chemicals would be easier to remove from the soil. By using heating techniques developed by the Oil and Gas Industry to enhance the removal of oil and gas resources from the soil, the problem of removing contamination from the soils could be solved. The Thermal Enhanced Vapor Extraction System (TEVES) demonstration will combine vacuum vapor extraction technology with powerline frequency soil heating and radiofrequency soil heating to accelerate the soil decontamination process. The premise that soil heating technology can actually reduce the costs of soil decontamination is complicated by the high capital costs of the soil heating equipment and the cost of electrode installation. By performing this field demonstration, Sandia will be able to collect the information needed to see if this new technology will improve the decontamination of soils.

  5. Thermal Enhanced Vapor Extraction System

    SciTech Connect

    Phelan, J.M.

    1992-12-31

    At some landfills, hazardous wastes were placed into disposal pits with other waste oils. Volatile organic wastes, such as cleaning solvents, when combined with oil are much more difficult to remove from the soils because the oil makes the volatile organic chemical evaporate much slower. The typical vacuum extraction remediation method could become a lengthy campaign. Since all chemicals evaporate faster when they are heated, if the contaminated soil could be heated, the chemicals would be easier to remove from the soil. By using heating techniques developed by the Oil and Gas Industry to enhance the removal of oil and gas resources from the soil, the problem of removing contamination from the soils could be solved. The Thermal Enhanced Vapor Extraction System (TEVES) demonstration will combine vacuum vapor extraction technology with powerline frequency soil heating and radiofrequency soil heating to accelerate the soil decontamination process. The premise that soil heating technology can actually reduce the costs of soil decontamination is complicated by the high capital costs of the soil heating equipment and the cost of electrode installation. By performing this field demonstration, Sandia will be able to collect the information needed to see if this new technology will improve the decontamination of soils.

  6. Electrokinetic Microstrirring to Enhance Immunoassays

    NASA Astrophysics Data System (ADS)

    Feldman, Hope; Sigurdson, Marin; Meinhart, Carl

    2006-11-01

    Electrokinetic microstirring is used to improve the sensitivity of microfluidic heterogeneous immuno-sensors by enhancing the transport in diffusion-limited reactions. The AC electrokinetic force, Electrothermal Flow, is exploited to create a circular stirring fluid motion, thereby providing more binding opportunities between suspended and wall-immobilized molecules. This process can significantly reduce test times, important for both field-portable biosensors and for lab-based assays. A 2-D numerical simulation model is used to predict the effect of electrothermal flow on a heterogeneous immunoassay resulting from an AC potential applied to two parallel electrodes. The binding is increased by a factor of 7 for an applied voltage of 10 Vrms. The effect was investigated experimentally using a high affinity biotin-streptavidin reaction. Microstirred reaction rates were compared with passive reactions. The measurements show on average an order of magnitude increase in binding between immobilized biotin and fluorescently-labeled streptavidin after 5 minutes. Therefore, this technique shows significant promise for reducing incubation time and enhancing the sensitivity of immunoassays.

  7. Defense mutualisms enhance plant diversification.

    PubMed

    Weber, Marjorie G; Agrawal, Anurag A

    2014-11-18

    The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity.

  8. Potential MCNP enhancements for NCT

    SciTech Connect

    Estes, G.P.; Taylor, W.M.

    1992-12-01

    MCNP a Monte Carlo radiation transport code, is currently widely used in the medical community for a variety of purposes including treatment planning, diagnostics, beam design, tomographic studies, and radiation protection. This is particularly true in the Neutron Capture Therapy (NCT) community. The current widespread medical use of MCNP after its general public distribution in about 1980 attests to the code`s general versatility and usefulness, particularly since its development to date has not been influenced by medical applications. This paper discusses enhancements to MCNP that could be implemented at Los Alamos for the benefit of the NCT community. These enhancements generally fall into two categories, namely those that have already been developed to some extent but are not yet publicly available, and those that seem both needed based on our current understanding of NCT goals, and achievable based on our working knowledge of the MCNP code. MCNP is a general, coupled neutron/photon/electron Monte Carlo code developed and maintained by the Radiation Transport Group at Los Alamos. It has been used extensively for radiation shielding studies, reactor analysis, detector design, physics experiment interpretation, oil and gas well logging, radiation protection studies, accelerator design, etc. over the years. MCNP is a three-dimensional geometry, continuous energy physics code capable of modeling complex geometries, specifying material regions such as organs by the intersections of analytical surfaces.

  9. Enhanced modeling features within TREETOPS

    NASA Technical Reports Server (NTRS)

    Vandervoort, R. J.; Kumar, Manoj N.

    1989-01-01

    The original motivation for TREETOPS was to build a generic multi-body simulation and remove the burden of writing multi-body equations from the engineers. The motivation of the enhancement was twofold: (1) to extend the menu of built-in features (sensors, actuators, constraints, etc.) that did not require user code; and (2) to extend the control system design capabilities by linking with other government funded software (NASTRAN and MATLAB). These enhancements also serve to bridge the gap between structures and control groups. It is common on large space programs for the structures groups to build hi-fidelity models of the structure using NASTRAN and for the controls group to build lower order models because they lack the tools to incorporate the former into their analysis. Now the controls engineers can accept the hi-fidelity NASTRAN models into TREETOPS, add sensors and actuators, perform model reduction and couple the result directly into MATLAB to perform their design. The controller can then be imported directly into TREETOPS for non-linear, time-history simulation.

  10. RTU Comparison Calculator Enhancement Plan

    SciTech Connect

    Miller, James D.; Wang, Weimin; Katipamula, Srinivas

    2014-03-31

    Over the past two years, Department of Energy’s Building Technologies Office (BTO) has been investigating ways to increase the operating efficiency of the packaged rooftop units (RTUs) in the field. First, by issuing a challenge to the RTU manufactures to increase the integrated energy efficiency ratio (IEER) by 60% over the existing ASHRAE 90.1-2010 standard. Second, by evaluating the performance of an advanced RTU controller that reduces the energy consumption by over 40%. BTO has previously also funded development of a RTU comparison calculator (RTUCC). RTUCC is a web-based tool that provides the user a way to compare energy and cost savings for two units with different efficiencies. However, the RTUCC currently cannot compare savings associated with either the RTU Challenge unit or the advanced RTU controls retrofit. Therefore, BTO has asked PNNL to enhance the tool so building owners can compare energy and savings associated with this new class of products. This document provides the details of the enhancements that are required to support estimating energy savings from use of RTU challenge units or advanced controls on existing RTUs.

  11. Psychopharmacological enhancement: a conceptual framework

    PubMed Central

    2012-01-01

    The availability of a range of new psychotropic agents raises the possibility that these will be used for enhancement purposes (smart pills, happy pills, and pep pills). The enhancement debate soon raises questions in philosophy of medicine and psychiatry (eg, what is a disorder?), and this debate in turn raises fundament questions in philosophy of language, science, and ethics. In this paper, a naturalistic conceptual framework is proposed for addressing these issues. This framework begins by contrasting classical and critical concepts of categories, and then puts forward an integrative position that is based on cognitive-affective research. This position can in turn be used to consider the debate between pharmacological Calvinism (which may adopt a moral metaphor of disorder) and psychotropic utopianism (which may emphasize a medical metaphor of disorder). I argue that psychiatric treatment of serious psychiatric disorders is justified, and that psychotropics are an acceptable kind of intervention. The use of psychotropics for sub-threshold phenomena requires a judicious weighing of the relevant facts (which are often sparse) and values. PMID:22244084

  12. Defense mutualisms enhance plant diversification

    PubMed Central

    Weber, Marjorie G.; Agrawal, Anurag A.

    2014-01-01

    The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity. PMID:25349406

  13. Resolution-enhanced Mapping Spectrometer

    NASA Technical Reports Server (NTRS)

    Kumer, J. B.; Aubrun, J. N.; Rosenberg, W. J.; Roche, A. E.

    1993-01-01

    A familiar mapping spectrometer implementation utilizes two dimensional detector arrays with spectral dispersion along one direction and spatial along the other. Spectral images are formed by spatially scanning across the scene (i.e., push-broom scanning). For imaging grating and prism spectrometers, the slit is perpendicular to the spatial scan direction. For spectrometers utilizing linearly variable focal-plane-mounted filters the spatial scan direction is perpendicular to the direction of spectral variation. These spectrometers share the common limitation that the number of spectral resolution elements is given by the number of pixels along the spectral (or dispersive) direction. Resolution enhancement by first passing the light input to the spectrometer through a scanned etalon or Michelson is discussed. Thus, while a detector element is scanned through a spatial resolution element of the scene, it is also temporally sampled. The analysis for all the pixels in the dispersive direction is addressed. Several specific examples are discussed. The alternate use of a Michelson for the same enhancement purpose is also discussed. Suitable for weight constrained deep space missions, hardware systems were developed including actuators, sensor, and electronics such that low-resolution etalons with performance required for implementation would weigh less than one pound.

  14. Cavity-Enhanced Ultrafast Spectroscopy

    NASA Astrophysics Data System (ADS)

    Allison, Thomas

    2016-05-01

    Ultrafast optical spectroscopy methods, such as transient absorption spectroscopy and 2D-spectroscopy, are widely used across many disciplines. However, these techniques are typically restricted to optically thick samples, such as solids and liquid solutions. Using a frequency comb laser and optical cavities, we present a new technique for performing ultrafast optical spectroscopy with high sensitivity, enabling work in dilute gas-phase molecular beams. Resonantly enhancing the probe pulses, we demonstrate transient absorption measurements with a detection limit of ΔOD = 2 ×10-10 (1 ×10-9 /√{Hz}). Resonantly enhancing the pump pulses allows us to produce a high excitation fraction at high repetition-rate, so that signals can be recorded from samples with optical densities as low as OD 10-8 , or column densities < 1010 molecules/ cm2. To our knowledge, this represents a 5,000-fold improvement of the state-of-the-art. This work was supported by the National Science Foundation under Grant Number 1404296.

  15. Transcriptional enhancers in ascidian development.

    PubMed

    Wang, Wei; Christiaen, Lionel

    2012-01-01

    The study of cis-regulatory DNAs that control developmental gene expression is integral to the modeling of comprehensive genomic regulatory networks for embryogenesis. Ascidian embryos provide a unique opportunity for the analysis of cis-regulatory DNAs with cellular resolution in the context of a simple but typical chordate body plan. Here, we review landmark studies that have laid the foundations for the study of transcriptional enhancers, among other cis-regulatory DNAs, and their roles in ascidian development. The studies using ascidians of the Ciona genus have capitalized on a unique electroporation technique that permits the simultaneous transfection of hundreds of fertilized eggs, which develop rapidly and express transgenes with little mosaicism. Current studies using the ascidian embryo benefit from extensively annotated genomic resources to characterize transcript models in silico. The search for functional noncoding sequences can be guided by bioinformatic analyses combining evolutionary conservation, gene coexpression, and combinations of overrepresented short-sequence motifs. The power of the transient transfection assays has allowed thorough dissection of numerous cis-regulatory modules, which provided insights into the functional constraints that shape enhancer architecture and diversification. Future studies will benefit from pioneering stable transgenic lines and the analysis of chromatin states. Whole genome expression, functional and DNA binding data are being integrated into comprehensive genomic regulatory network models of early ascidian cell specification with a single-cell resolution that is unique among chordate model systems.

  16. Enhanced flue gas conditioning study

    SciTech Connect

    Miller, S.J.; Laudal, D.L.

    1991-11-01

    Many electrostatic precipitators (ESPS) do not achieve acceptable particulate removal efficiencies because of high-resistivity ash. One method to improve ESP performance is to employ chemical conditioning agents to reduce fly ash resistivity. Widely used agents include sulfur trioxide (SO[sub 3]) and ammonia, which are sometimes used simultaneously. For some fly ashes, that have a low affinity for SO[sub 3], conditioning with SO[sub 3] alone is not adequate to reduce resistivity without excessive amounts of SO[sub 3] exiting the stack. In such cases, the use of ammonia in addition to SO[sub 3] may reduce the amount of required SO[sub 3] and prevent the emission of excess SO[sub 3] out of the stack. The general objective of the work was to test enhanced flue gas conditioning methods to improve the performance of ESPS. Specific objectives were to (1) verify the relationship between the required SO[sub 3] injection rates to maintain the desired fly ash resistivity and temperature for four coals, (2) verify that dual conditioning with both ammonia and SO[sub 3] promotes SO[sub 3] utilization and allows for resistivity modification with moderate SO[sub 3] injection rates, and (3) verify the effectiveness and practicality of an enhanced flue gas conditioning (EFGC) method. The EFGC method is a proprietary development of Wahlco, Inc.

  17. Enhancement of confinement in tokamaks

    SciTech Connect

    Furth, H.P.

    1986-05-01

    A plausible interpretation of the experimental evidence is that energy confinement in tokamaks is governed by two separate considerations: (1) the need for resistive MHD kink-stability, which limits the permissible range of current profiles - and therefore normally also the range of temperature profiles; and (2) the presence of strongly anomalous microscopic energy transport near the plasma edge, which calibrates the amplitude of the global temperature profile, thus determining the energy confinement time tau/sub E/. Correspondingly, there are two main paths towards the enhancement of tokamak confinement: (1) Configurational optimization, to increase the MHD-stable energy content of the plasma core, can evidently be pursued by varying the cross-sectional shape of the plasma and/or finding stable radial profiles with central q-values substantially below unity - but crossing from ''first'' to ''second'' stability within the peak-pressure region would have the greatest ultimate potential. (2) Suppression of edge turbulence, so as to improve the heat insulation in the outer plasma shell, can be pursued by various local stabilizing techniques, such as use of a poloidal divertor. The present confinement model and initial TFTR pellet-injection results suggest that the introduction of a super-high-density region within the plasma core should be particularly valuable for enhancing ntau/subE/. In D-T operation, a centrally peaked plasma pressure profile could possibly lend itself to alpha-particle-driven entry into the second-stability regime.

  18. Enhanced Video-Oculography System

    NASA Technical Reports Server (NTRS)

    Moore, Steven T.; MacDougall, Hamish G.

    2009-01-01

    A previously developed video-oculography system has been enhanced for use in measuring vestibulo-ocular reflexes of a human subject in a centrifuge, motor vehicle, or other setting. The system as previously developed included a lightweight digital video camera mounted on goggles. The left eye was illuminated by an infrared light-emitting diode via a dichroic mirror, and the camera captured images of the left eye in infrared light. To extract eye-movement data, the digitized video images were processed by software running in a laptop computer. Eye movements were calibrated by having the subject view a target pattern, fixed with respect to the subject s head, generated by a goggle-mounted laser with a diffraction grating. The system as enhanced includes a second camera for imaging the scene from the subject s perspective, and two inertial measurement units (IMUs) for measuring linear accelerations and rates of rotation for computing head movements. One IMU is mounted on the goggles, the other on the centrifuge or vehicle frame. All eye-movement and head-motion data are time-stamped. In addition, the subject s point of regard is superimposed on each scene image to enable analysis of patterns of gaze in real time.

  19. Optical antenna enhanced spontaneous emission

    PubMed Central

    Eggleston, Michael S.; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C.

    2015-01-01

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼200 THz optical frequency show a spontaneous emission intensity enhancement of 35× corresponding to a spontaneous emission rate speedup ∼115×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼2,500× spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d2. Unfortunately, at d < 10 nm, antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, Io = qω|xo|/d, feeding the antenna-enhanced spontaneous emission, where q|xo| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency. PMID:25624503

  20. Plasmonic enhancement of ultraviolet fluorescence

    NASA Astrophysics Data System (ADS)

    Jiao, Xiaojin

    Plasmonics relates to the interaction between electromagnetic radiation and conduction electrons at metallic interfaces or in metallic nanostructures. Surface plasmons are collective electron oscillations at a metal surface, which can be manipulated by shape, texture and material composition. Plasmonic applications cover a broad spectrum from visible to near infrared, including biosensing, nanolithography, spectroscopy, optoelectronics, photovoltaics and so on. However, there remains a gap in this activity in the ultraviolet (UV, < 400 nm), where significant opportunity exists for both fundamental and application research. Motivating factors in the study of UV Plasmonics are the direct access to biomolecular resonances and native fluorescence, resonant Raman scattering interactions, and the potential for exerting control over photochemical reactions. This dissertation aims to fill in the gap of Plasmonics in the UV with efforts of design, fabrication and characterization of aluminium (Al) and magnesium (Mg) nanostructures for the application of label-free bimolecular detection via native UV fluorescence. The first contribution of this dissertation addresses the design of Al nanostructures in the context of UV fluorescence enhancement. A design method that combines analytical analysis with numerical simulation has been developed. Performance of three canonical plasmonic structures---the dipole antenna, bullseye nanoaperture and nanoaperture array---has been compared. The optimal geometrical parameters have been determined. A novel design of a compound bullseye structure has been proposed and numerically analyzed for the purpose of compensating for the large Stokes shift typical of UV fluorescence. Second, UV lifetime modification of diffusing molecules by Al nanoapertures has been experimentally demonstrated for the first time. Lifetime reductions of ~3.5x have been observed for the high quantum yield (QY) laser dye p-terphenyl in a 60 nm diameter aperture with 50

  1. Glucose and lipid metabolism in the pancreas of rainbow trout is regulated at the molecular level by nutritional status and carbohydrate intake.

    PubMed

    Polakof, Sergio; Skiba-Cassy, Sandrine; Kaushik, Sadasivam; Seiliez, Iban; Soengas, Jose Luis; Panserat, Stephane

    2012-05-01

    Glucose and lipid metabolism in pancreatic islet organs is poorly characterized. In the present study, using as a model the carnivorous rainbow trout, a glucose-intolerant fish, we assessed mRNA expression levels of several genes involved in glucose and lipid metabolism (including ATP-citrate lyase; carnitine palmitoyltransferase-1 isoforms, CPT; the mitochondrial isoform of the phosphoenolpyrutave carboxykinase, mPEPCK and pyruvate kinase, PK) and glucosensing (glucose transporter type 2, Glut2; glucokinase, GK and the potassium channel, K(ATP)) in Brockmann bodies. We evaluated the response of these parameters to changes in feeding status (food deprived vs. fed fish) as well as to changes in the amount of carbohydrate (dextrin) in the diet. A general inhibition of the glycolytic (including the glucosensing marker GK) and β-oxidation pathways was found when comparing fed versus food-deprived fish. When comparing fish feeding on either low- or high-carbohydrate diets, we found that some genes related to lipid metabolism were more controlled by the feeding status than by the carbohydrate content (fatty acid synthase, CPTs). Findings are discussed in the context of pancreatic regulation of glucose and lipid metabolism in fish, and show that while trout pancreatic metabolism can partially adapt to a high-carbohydrate diet, some of the molecular actors studied seem to be poorly regulated (K(ATP)) and may contribute to the glucose intolerance observed in this species when fed high-carbohydrate diets.

  2. A Model of Insulin Resistance in Mice, Born to Diabetic Pregnancy, Is Associated with Alterations of Transcription-Related Genes in Pancreas and Epididymal Adipose Tissue

    PubMed Central

    Yessoufou, Akadiri; Moutairou, Kabirou; Khan, Naim Akhtar

    2011-01-01

    Objective. This study is conducted on a model of insulin-resistant (IR) mice born to dams which were rendered diabetic by the administration of streptozotocin. Methods. Adult IR and control offspring were selected and we determined the mRNA expression of transcription factors known to modulate pancreatic and adipose tissue activities and inflammation. Results. We observed that serum insulin increased, and the mRNA of insulin gene transcription factors, Pdx-1, Nkx6.1 and Maf-A, were upregulated in IR mice pancreas. Besides, their pancreatic functional capacity seemed to be exhausted as evidenced by low expression of pancreatic Glut2 and glucokinase mRNA. Though IR offspring exhibited reduced epididymal adipose tissue, their adipocytes seemed to be differentiated into macrophage-like cells, as they exhibited upregulated CD14 and CD68 antigens, generally expressed by macrophages. However, there was no peripheral macrophages infiltration into epididymal adipose tissue, as the expression of F4/80, a true macrophage marker, was undetectable. Furthermore, the expression of IL-6, TNF-α and TLR-2, key players of insulin resistance, was upregulated in the adipose tissue of IR offspring. Conclusion. Insulin resistant state in mice, born to diabetic pregnancy, alters the expression of function-related genes in pancreas and epididymal adipose tissue and these offspring are prone to develop metabolic syndrome. PMID:20936114

  3. PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function.

    PubMed

    Kaneto, Hideaki; Miyatsuka, Takeshi; Kawamori, Dan; Yamamoto, Kaoru; Kato, Ken; Shiraiwa, Toshihiko; Katakami, Naoto; Yamasaki, Yoshimitsu; Matsuhisa, Munehide; Matsuoka, Taka-Aki

    2008-05-01

    Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintenance of mature beta-cell function. PDX-1 expression is maintained in pancreatic precursor cells during pancreas development but becomes restricted to beta-cells in mature pancreas. In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. Furthermore, these transcription factors play an important role in induction of insulin-producing cells in various non-beta-cells and thus could be therapeutic targets for diabetes. On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in beta-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. It is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for beta-cell glucose toxicity found in diabetes.

  4. Crucial role of PDX-1 in pancreas development, beta-cell differentiation, and induction of surrogate beta-cells.

    PubMed

    Kaneto, Hideaki; Miyatsuka, Takeshi; Shiraiwa, Toshihiko; Yamamoto, Kaoru; Kato, Ken; Fujitani, Yoshio; Matsuoka, Taka-aki

    2007-01-01

    Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintaining mature beta-cell function. At an early stage of embryonic development, PDX-1 is initially expressed in the gut region when the foregut endoderm becomes committed to common pancreatic precursor cells. During pancreas development, PDX-1 expression is maintained in precursor cells, and later it becomes restricted to beta-cells. In mature beta-cells, PDX-1 transactivates the insulin gene and other genes involved in glucose sensing and metabolism, such as GLUT2 and glucokinase. MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulin-producing cell production. Furthermore, these transcription factors play a crucial role in inducing surrogate beta-cells from non-beta-cells and thus could be therapeutic targets for diabetes.

  5. Approach to intensely enhancing neck nodes

    PubMed Central

    Karandikar, Amit; Gummalla, Krishna Mohan; Loke, Siu Cheng; Goh, Julian; Tan, Tiong Yong

    2016-01-01

    Cervical node evaluation is one of the most common problems encountered by a radiologist. Here, we present a pictorial review of intensely enhancing neck nodes. While enhancement in a cervical node is a common radiologic finding on contrast-enhanced computed tomography scan, only few conditions cause intense enhancement in cervical nodes. We discuss the common causes of intensely enhancing neck nodes along with pertinent radiologic features and key differentiating points that aid radiologists in reaching a diagnosis. In addition, we discuss certain potential non-nodal mimics, which need to be excluded. PMID:26782154

  6. NORMAL HUMAN VARIATION: REFOCUSSING THE ENHANCEMENT DEBATE

    PubMed Central

    Kahane, Guy; Savulescu, Julian

    2015-01-01

    This article draws attention to several common mistakes in thinking about biomedical enhancement, mistakes that are made even by some supporters of enhancement. We illustrate these mistakes by examining objections that John Harris has recently raised against the use of pharmacological interventions to directly modulate moral decision-making. We then apply these lessons to other influential figures in the debate about enhancement. One upshot of our argument is that many considerations presented as powerful objections to enhancement are really strong considerations in favour of biomedical enhancement, just in a different direction. Another upshot is that it is unfortunate that much of the current debate focuses on interventions that will radically transform normal human capacities. Such interventions are unlikely to be available in the near future, and may not even be feasible. But our argument shows that the enhancement project can still have a radical impact on human life even if biomedical enhancement operated entirely within the normal human range. PMID:23906367

  7. Hydrodynamic enhanced dielectrophoretic particle trapping

    DOEpatents

    Miles, Robin R.

    2003-12-09

    Hydrodynamic enhanced dielectrophoretic particle trapping carried out by introducing a side stream into the main stream to squeeze the fluid containing particles close to the electrodes producing the dielelectrophoretic forces. The region of most effective or the strongest forces in the manipulating fields of the electrodes producing the dielectrophoretic forces is close to the electrodes, within 100 .mu.m from the electrodes. The particle trapping arrangement uses a series of electrodes with an AC field placed between pairs of electrodes, which causes trapping of particles along the edges of the electrodes. By forcing an incoming flow stream containing cells and DNA, for example, close to the electrodes using another flow stream improves the efficiency of the DNA trapping.

  8. Quantum-enhanced absorption refrigerators

    NASA Astrophysics Data System (ADS)

    Correa, Luis A.; Palao, José P.; Alonso, Daniel; Adesso, Gerardo

    2014-02-01

    Thermodynamics is a branch of science blessed by an unparalleled combination of generality of scope and formal simplicity. Based on few natural assumptions together with the four laws, it sets the boundaries between possible and impossible in macroscopic aggregates of matter. This triggered groundbreaking achievements in physics, chemistry and engineering over the last two centuries. Close analogues of those fundamental laws are now being established at the level of individual quantum systems, thus placing limits on the operation of quantum-mechanical devices. Here we study quantum absorption refrigerators, which are driven by heat rather than external work. We establish thermodynamic performance bounds for these machines and investigate their quantum origin. We also show how those bounds may be pushed beyond what is classically achievable, by suitably tailoring the environmental fluctuations via quantum reservoir engineering techniques. Such superefficient quantum-enhanced cooling realises a promising step towards the technological exploitation of autonomous quantum refrigerators.

  9. Enhanced High Resolution RBS System

    NASA Astrophysics Data System (ADS)

    Pollock, Thomas J.; Hass, James A.; Klody, George M.

    2011-06-01

    Improvements in full spectrum resolution with the second NEC high resolution RBS system are summarized. Results for 50 Å TiN/HfO films on Si yielding energy resolution on the order of 1 keV are also presented. Detector enhancements include improved pulse processing electronics, upgraded shielding for the MCP/RAE detector, and reduced noise generated from pumping. Energy resolution measurements on spectra front edge coupled with calculations using 0.4mStr solid angle show that beam energy spread at 400 KeV from the Pelletron® accelerator is less than 100 eV. To improve user throughput, magnet control has been added to the automatic data collection. Depth profiles derived from experimental data are discussed. For the thin films profiled, depth resolutions were on the Angstrom level with the non-linear energy/channel conversions ranging from 100 to 200 eV.

  10. Enhanced NIF neutron activation diagnostics

    SciTech Connect

    Yeamans, C. B.; Bleuel, D. L.; Bernstein, L. A.

    2012-10-15

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the {sup 89}Zr/{sup 89m}Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  11. Enhancing the US Power Infrastructure

    SciTech Connect

    Charles Alexander

    2010-05-31

    The primary motivation for this set of research activities was to develop a foundation in several aspects of power in order to position Cleveland State University to lead a multiuniversity effort to secure funding for enhanced power system projects and to be able to eventually secure a NASA Space Power Systems Center status through the competitive bidding process. This was accomplished by focusing on these major project areas, (1) the design of the next generation nuclear-electric power generation system, (2) the design of a distributed, fault-tolerant, and modular power system, and (3) the development of the dynamics and control of active magnetic bearings for flywheel energy storage without using conventional sensors.

  12. Feature enhancement and phonological acquisition.

    PubMed

    Yavas, M

    1997-01-01

    Distinctive features have been part of clinical work in phonological assessment and therapy. In almost all studies the set of features used was the Chomsky and Halle system. Stevens and Keyser (1989) offer a new look at distinctive features from the dimension of perceptual saliency, and account for the markedness relationship between segments. This paper explores to what extent it is possible to account for the substitution patterns in child phonologies based on the concepts of feature hierarchy, enhancement, and perceptual saliency as proposed by Stevens and Keyser. Concentrating on the consonantal substitutions in normal and disordered child speech, an attempt is made to distinguish between normal and unusual/idiosyncratic processes. Implications for assessment are discussed. PMID:21271756

  13. Enhanced NIF neutron activation diagnostics.

    PubMed

    Yeamans, C B; Bleuel, D L; Bernstein, L A

    2012-10-01

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  14. Quantum-enhanced absorption refrigerators.

    PubMed

    Correa, Luis A; Palao, José P; Alonso, Daniel; Adesso, Gerardo

    2014-01-01

    Thermodynamics is a branch of science blessed by an unparalleled combination of generality of scope and formal simplicity. Based on few natural assumptions together with the four laws, it sets the boundaries between possible and impossible in macroscopic aggregates of matter. This triggered groundbreaking achievements in physics, chemistry and engineering over the last two centuries. Close analogues of those fundamental laws are now being established at the level of individual quantum systems, thus placing limits on the operation of quantum-mechanical devices. Here we study quantum absorption refrigerators, which are driven by heat rather than external work. We establish thermodynamic performance bounds for these machines and investigate their quantum origin. We also show how those bounds may be pushed beyond what is classically achievable, by suitably tailoring the environmental fluctuations via quantum reservoir engineering techniques. Such superefficient quantum-enhanced cooling realises a promising step towards the technological exploitation of autonomous quantum refrigerators. PMID:24492860

  15. Shale Oil Value Enhancement Research

    SciTech Connect

    James W. Bunger

    2006-11-30

    Raw kerogen oil is rich in heteroatom-containing compounds. Heteroatoms, N, S & O, are undesirable as components of a refinery feedstock, but are the basis for product value in agrochemicals, pharmaceuticals, surfactants, solvents, polymers, and a host of industrial materials. An economically viable, technologically feasible process scheme was developed in this research that promises to enhance the economics of oil shale development, both in the US and elsewhere in the world, in particular Estonia. Products will compete in existing markets for products now manufactured by costly synthesis routes. A premium petroleum refinery feedstock is also produced. The technology is now ready for pilot plant engineering studies and is likely to play an important role in developing a US oil shale industry.

  16. Atomic force microscope: Enhanced sensitivity

    SciTech Connect

    Davis, D.T.

    1995-06-01

    Atomic force microscopes (AFMs) are a recent development representing the state of the art in measuring ultrafine surface features. Applications are found in such fields of research as biology, microfabrication, material studies, and surface chemistry. Fiber-optic interferometer techniques developed at LLNL offer the potential of improving the vertical resolution of these instruments by up to 2 orders of magnitude. We are attempting to replace the current AFM measurement scheme, which consists of an optical beam deflection approach, with our fiber-optic interferometer scheme, a much more sensitive displacement measurement technique. In performing this research, we hope to accomplish two important goals; (1) to enhance the sensitivity of the AFM, and (2) to achieve important improvements in our fiber-optic interferometer technology.

  17. Unrequited: neurochemical enhancement of love.

    PubMed

    Bamford, Rebecca

    2015-07-01

    I raise several concerns with Earp and colleagues' analysis of enhancement through neurochemical modulation of love as a key issue in contemporary neuroethics. These include: (i) strengthening their deflation of medicalization concerns by showing how the objection that love should be left outside of the scope of medicine would directly undermine the goal of medicine; (ii) developing stronger analysis of the social and political concerns relevant to neurochemical modulation of love, by exploring and suggesting possible counters to ways in which 'wellbeing' may be used as a tool of oppression; (iii) providing reasons to support a broad need for ecological investigation of, and indeed ecological education concerning, neurotechnology; (iv) suggesting ways in which philosophy, and the humanities more broadly, remain directly relevant to responding effectively to issues in contemporary neuroethics.

  18. Teacher Enhancement and Preparation Programs

    NASA Technical Reports Server (NTRS)

    1995-01-01

    These two programs provide opportunities for K-12 teachers of mathematics, science, and technology to spend two weeks at a NASA center learning about aeronautics and space. Participants are selected by peer review from a contracting agent that assists NASA in administering the program. Each teacher receives a stipend that covers the cost of travel, housing, meals, and graduate credit. NEWMAST provides for approximately 100 secondary teachers, and NEWTEST is a program designed to meet the needs of approximately 125 elementary teachers each summer. Teachers are provided with a wide variety of experiences including research laboratory observations, presentations, and 'shadowships'. Individual and team projects are used to enhance the participants knowledge of space and aeronautics and to motivate the teachers to incorporate the summer workshop activities into their classrooms.

  19. Image enhancement for pattern recognition

    NASA Astrophysics Data System (ADS)

    Huynh, Quyen Q.; Neretti, Nicola; Intrator, Nathan; Dobeck, Gerald J.

    1998-09-01

    We investigate various image enhancement techniques geared towards a specific detector. Our database consists of side- scan sonar images collected at the Naval Surface Warfare Center (NSWC), and the detector we use has proven to have excellent results on these data. We start by investigating various wavelet and wavelet packet denoising methods. Other methods we consider are based on more common filters (Gaussian and DOG filters). In wavelet based denoising we try different approaches, combining techniques that have been successfully used in signal and image denoising. We notice that the performance is mostly affected by the choice of the scale levels to which shrinkage is applied. We demonstrate that wavelet denoising can significantly improve detection performance while keeping low false alarm rates.

  20. Enhancing AFLOW Visualization using Jmol

    NASA Astrophysics Data System (ADS)

    Lanasa, Jacob; New, Elizabeth; Stefek, Patrik; Honaker, Brigette; Hanson, Robert; Aflow Collaboration

    The AFLOW library is a database of theoretical solid-state structures and calculated properties created using high-throughput ab initio calculations. Jmol is a Java-based program capable of visualizing and analyzing complex molecular structures and energy landscapes. In collaboration with the AFLOW consortium, our goal is the enhancement of the AFLOWLIB database through the extension of Jmol's capabilities in the area of materials science. Modifications made to Jmol include the ability to read and visualize AFLOW binary alloy data files, the ability to extract from these files information using Jmol scripting macros that can be utilized in the creation of interactive web-based convex hull graphs, the capability to identify and classify local atomic environments by symmetry, and the ability to search one or more related crystal structures for atomic environments using a novel extension of inorganic polyhedron-based SMILES strings

  1. Enhanced NIF neutron activation diagnosticsa)

    NASA Astrophysics Data System (ADS)

    Yeamans, C. B.; Bleuel, D. L.; Bernstein, L. A.

    2012-10-01

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the 89Zr/89mZr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  2. Simulator for enhanced ATAMM multiprocessing

    NASA Technical Reports Server (NTRS)

    Andrews, Asa M.; Jones, Robert L.; Hayes, Paul J.; Benz, Harry F.

    1991-01-01

    A simulator is introduced which follows the rules of the enhanced Algorithm to Architecture Mapping Model (ATAMM) multiprocessing strategy. ATAMM is a method for embedding an algorithm into a multiprocessing system in addition to providing system performance prediction capabilities. A discussion of the inner workings of the Architecture Design and Assessment System (ADAS) hosted simulator is introduced to illustrate how the simulator follows the ATAMM rule set. A sample 5-node algorithm graph is given as an example to illustrate: (1) entering of a graph into the simulator and how to run the graph using a graph entry tool; (2) how to analyze the data; and (3) a comparison of the simulation results with the predicted results from ATAMM.

  3. Does groundwater enhance evaporative cooling?

    NASA Astrophysics Data System (ADS)

    Rouholahnejad, E.

    2015-12-01

    Evaporation is a key process in land-climate interactions, not only because it directly regulates the hydrological cycle, but also because it contributes to the Earth's energy balance. Due to its feedbacks on large-scale water processes and its impact on the dynamics of the atmosphere, it has been considered as a driver of droughts and heatwaves1-3. While evaporation from ocean surfaces is likely to increase with rising temperatures, it is unclear whether evapotranspiration from land surfaces could similarly increase, due to possible limitations imposed by soil moisture and vegetation physiology4. Observations suggest that groundwater (hereafter GW) has an important role in hydrological budgets and soil moisture variability in many regions, supplying moisture for evapotranspiration during dry seasons5, 6. Although modeling studies suggest that GW is often close enough to the surface to interact with the atmosphere7, 8, the soil water storage is often underestimated by land surface models. This is most likely due to neglecting the lateral movement of water from topographically higher altitudes to valley bottoms and its convergence close to the land surface, as well as the upward movement of water in the capillary fringe.The focus of this study is to understand where and when GW may significantly enhance the availability of soil water for evapotranspiration. We also quantified the potential contribution of GW to evapotranspiration in the areas where GW is a major supply. We used the global network of eddy covariance observations9 (FLUXNET) along with global modeled GW depth10 and GLEAM ET model estimates11 to address the current gap in modelling ET due to neglecting GW supply. Having identified areas where GW is tightly coupled with the atmosphere through evaporation processes, the study provides the basis to examine the "air conditioning effect" of GW and test the idea if GW enhances evaporation to the extent that leads to a cooler temperatures and wetter climates.

  4. Enhanced Luminescence of Lanthanides: Determination of Europium by Enhanced Luminescence

    NASA Astrophysics Data System (ADS)

    Jenkins, Amanda L.; Murray, George M.

    1998-02-01

    An experiment has been developed to teach the principles of molecular luminescence spectroscopy. This laboratory experiment is designed for upper-level undergraduates as a less toxic alternative to current fluorescence experiments. It combines elements of physical and inorganic as well as analytical chemistry. The experiment can be performed on a variety of rudimentary fluorescence instrumentation and still give good analytical figures of merit. The object of the experiment is to measure the luminescent enhancement that is achieved when a lanthanide such as Eu(III) or Tb(III) is complexed with appropriate organic ligands, in this case 2,6 pyridinedicarboxylic acid. The importance of pH on metal ion coordination is also explored via luminescence intensity. This approach provides several advantages over current luminescence experiments. These advantages include limited toxicity and flammability of the chemicals involved, a large luminescence linear dynamic range, and low detection limits (parts per trillion). These low detection limits, achieved using modest equipment, allow the determination of the europium concentration in a variety of samples, such as tap water. The narrow lanthanide luminescent bands also permit incorporation of qualitative analysis of a mixture of lanthanides.

  5. Clay ingestion enhances intestinal triacylglycerol hydrolysis and non-esterified fatty acid absorption.

    PubMed

    Habold, Caroline; Reichardt, François; Le Maho, Yvon; Angel, Fabielle; Liewig, Nicole; Lignot, Jean-Hervé; Oudart, Hugues

    2009-07-01

    Consumption by animals and humans of earthy materials such as clay is often related to gut pathologies. Our aim was to determine the impact of kaolinite ingestion on glucose and NEFA transport through the intestinal mucosa. The expression of hexose transporters (Na/glucose co-transporter 1 (SGLT1), GLUT2, GLUT5) and of proteins involved in NEFA absorption (fatty acid transporter/cluster of differentiation 36 (FAT/CD36), fatty acid transport protein 4 (FATP4) and liver fatty acid binding protein (L-FABP)) was measured (1) in rats whose jejunum was perfused with a solution of kaolinite, and (2) in rats who ate spontaneously kaolinite pellets during 7 and 28 d. Also, we determined TAG and glucose absorption in the kaolinite-perfused group, and pancreatic lipase activity, gastric emptying and intestinal transit in rats orally administered with kaolinite. Glucose absorption was not affected by kaolinite perfusion or ingestion. However, kaolinite induced a significant increase in intestinal TAG hydrolysis and NEFA absorption. The cytoplasmic expression of L-FABP and FATP4 also increased due to kaolinite ingestion. NEFA may enter the enterocytes via endocytosis mainly since expression of NEFA transporters in the brush-border membrane was not affected by kaolinite. After uptake, rapid binding of NEFA by L-FABP and FATP4 could act as an intracellular NEFA buffer to prevent NEFA efflux. Increased TAG hydrolysis and NEFA absorption may be due to the adsorption properties of clay and also because kaolinite ingestion caused a slowing down of gastric emptying and intestinal transit.

  6. Diet effects on glucose absorption in the small intestine of neonatal calves: importance of intestinal mucosal growth, lactase activity, and glucose transporters.

    PubMed

    Steinhoff-Wagner, Julia; Zitnan, Rudolf; Schönhusen, Ulrike; Pfannkuche, Helga; Hudakova, Monika; Metges, Cornelia C; Hammon, Harald M

    2014-10-01

    Colostrum (C) feeding in neonatal calves improves glucose status and stimulates intestinal absorptive capacity, leading to greater glucose absorption when compared with milk-based formula feeding. In this study, diet effects on gut growth, lactase activity, and glucose transporters were investigated in several gut segments of the small intestine. Fourteen male German Holstein calves received either C of milkings 1, 3, and 5 (d 1, 2, and 3 in milk) or respective formulas (F) twice daily from d 1 to d 3 after birth. Nutrient content, and especially lactose content, of C and respective F were the same. On d 4, calves were fed C of milking 5 or respective F and calves were slaughtered 2h after feeding. Tissue samples from duodenum and proximal, mid-, and distal jejunum were taken to measure villus size and crypt depth, mucosa and brush border membrane vesicles (BBMV) were taken to determine protein content, and mRNA expression and activity of lactase and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter (GLUT2) were determined from mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and BBMV were determined, as well as immunochemically localized GLUT2 in the intestinal mucosa. Villus circumference, area, and height were greater, whereas crypt depth was smaller in C than in F. Lactase activity tended to be greater in C than in F. Protein expression of SGLT1 was greater in F than in C. Parameters of villus size, lactase activity, SGLT1 protein expression, as well as apical and basolateral GLUT2 localization in the enterocytes differed among gut segments. In conclusion, C feeding, when compared with F feeding, enhances glucose absorption in neonatal calves primarily by stimulating mucosal growth and increasing absorptive capacity in the small intestine, but not by stimulating abundance of intestinal glucose transporters.

  7. Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.

    PubMed

    Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

    2014-05-01

    Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis. PMID:24656388

  8. Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.

    PubMed

    Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

    2014-05-01

    Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis.

  9. Self-Enhancement: Food for Thought.

    PubMed

    Sedikides, Constantine; Gregg, Aiden P

    2008-03-01

    Self-enhancement denotes a class of psychological phenomena that involve taking a tendentiously positive view of oneself. We distinguish between four levels of self-enhancement-an observed effect, an ongoing process, a personality trait, and an underlying motive-and then use these distinctions to organize the wealth of relevant research. Furthermore, to render these distinctions intuitive, we draw an extended analogy between self-enhancement and the phenomenon of eating. Among the topics we address are (a) manifestations of self-enhancement, both obvious and subtle, and rival interpretations; (b) experimentally documented dynamics of affirming and threatening the ego; and (c) primacy of self-enhancement, considered alongside other intrapsychic phenomena, and across different cultures. Self-enhancement, like eating, is a fundamental part of human nature.

  10. Tip-Enhanced Raman Spectroscopy (TERS)

    NASA Astrophysics Data System (ADS)

    Pettinger, Bruno

    Tip-enhanced Raman spectroscopy is a vibrational spectroscopy with hitherto unprecedented sensitivity and spatial resolution. Since the enhancement is mainly provided by the near-field excited at the apex of a suitable tip, TERS appears to be a widely applicable spectroscopy and microscopy tool, in contrast to its parents, surface-enhanced Raman spectroscopy (SERS) and scanning near-field optical microscopy (SNOM). TER scattering has been observed for a number of molecules adsorbed at various substrates, including single-crystalline metal surfaces, showing thereby a more than million-fold enhancement of the Raman scattering. It is important to note that the field-enhancement provides, beyond TERS, promising avenues for applications to other optical techniques, such as tip-enhanced CARS, two-photon fluorescence and infrared scattering-type near-field microscopy.

  11. An evaluative conservative case for biomedical enhancement.

    PubMed

    Danaher, John

    2016-09-01

    It is widely believed that a conservative moral outlook is opposed to biomedical forms of human enhancement. In this paper, I argue that this widespread belief is incorrect. Using Cohen's evaluative conservatism as my starting point, I argue that there are strong conservative reasons to prioritise the development of biomedical enhancements. In particular, I suggest that biomedical enhancement may be essential if we are to maintain our current evaluative equilibrium (ie, the set of values that undergird and permeate our current political, economic and personal lives) against the threats to that equilibrium posed by external, non-biomedical forms of enhancement. I defend this view against modest conservatives who insist that biomedical enhancements pose a greater risk to our current evaluative equilibrium, and against those who see no principled distinction between the forms of human enhancement.

  12. An evaluative conservative case for biomedical enhancement.

    PubMed

    Danaher, John

    2016-09-01

    It is widely believed that a conservative moral outlook is opposed to biomedical forms of human enhancement. In this paper, I argue that this widespread belief is incorrect. Using Cohen's evaluative conservatism as my starting point, I argue that there are strong conservative reasons to prioritise the development of biomedical enhancements. In particular, I suggest that biomedical enhancement may be essential if we are to maintain our current evaluative equilibrium (ie, the set of values that undergird and permeate our current political, economic and personal lives) against the threats to that equilibrium posed by external, non-biomedical forms of enhancement. I defend this view against modest conservatives who insist that biomedical enhancements pose a greater risk to our current evaluative equilibrium, and against those who see no principled distinction between the forms of human enhancement. PMID:27354246

  13. A Thomistic appraisal of human enhancement technologies.

    PubMed

    Eberl, Jason T

    2014-08-01

    Debate concerning human enhancement often revolves around the question of whether there is a common "nature" that all human beings share and which is unwarrantedly violated by enhancing one's capabilities beyond the "species-typical" norm. I explicate Thomas Aquinas's influential theory of human nature, noting certain key traits commonly shared among human beings that define each as a "person" who possesses inviolable moral status. Understanding the specific qualities that define the nature of human persons, which includes self-conscious awareness, capacity for intellective thought, and volitional autonomy, informs the ethical assessment of various forms of enhancement. Some forms of cognitive and physical enhancement may be desirable from the perspective of what constitutes the "flourishing" of human persons in our fundamental nature; while other forms of enhancement, such as emotive or so-called "moral" enhancement, run the risk of detracting from human flourishing when evaluated from the virtue-theoretic perspective Aquinas promotes.

  14. Plasmon-enhanced optical sensors: a review.

    PubMed

    Li, Ming; Cushing, Scott K; Wu, Nianqiang

    2015-01-21

    Surface plasmon resonance (SPR) has found extensive applications in chemi-sensors and biosensors. Plasmons play different roles in different types of optical sensors. SPR transduces a signal in a colorimetric sensor through shifts in the spectral position and intensity in response to external stimuli. SPR can also concentrate the incident electromagnetic field in a nanostructure, modulating fluorescence emission and enabling plasmon-enhanced fluorescence to be used for ultrasensitive detection. Furthermore, plasmons have been extensively used for amplifying a Raman signal in a surface-enhanced Raman scattering sensor. This paper presents a review of recent research progress in plasmon-enhanced optical sensing, giving emphasis on the physical basis of plasmon-enhanced sensors and how these principles guide the design of sensors. In particular, this paper discusses the design strategies for nanomaterials and nanostructures to plasmonically enhance optical sensing signals, also highlighting the applications of plasmon-enhanced optical sensors in healthcare, homeland security, food safety and environmental monitoring.

  15. Enhanced potentiometry by metallic nanoparticles.

    PubMed

    Noyhouzer, T; Valdinger, I; Mandler, D

    2013-09-01

    Measuring the oxidation-reduction potential (Eh) requires an interface that is not selective toward specific species but exchanges electrons with all redox couples in the solution. Sluggish electron transfer (ET) kinetics with the species will not reflect the "true" Eh of the solution. Here, we present a novel approach by which adsorbed metal nanoparticles (NPs) are used for enhancing ET exchange rates between redox species and electrode surface and therefore affect significantly the measurement of the open circuit potential (OCP) and cyclic voltammetry (CV). The OCP and CV of various organic and inorganic species such as l-dopa, dopac, iron(II), and iodide are measured by bare stainless steel and by stainless steel modified by either Pt or Au NPs. We study the effect of the surface coverage of the stainless steel surface by NPs on the electrochemical response. Moreover, the stainless steel electrode was modified simultaneously by Au and Pt nanoparticles. This improved concurrently the stainless steel response (CV and potentiometry) toward two different species; l-dopa, which shows fast electron transfer on Pt, and catechol, which exhibits fast electron transfer on Au. We believe that this approach could be a first step toward developing a superior electrode for measuring the "true" Eh of complex aquatic systems.

  16. Holographic enhanced remote sensing system

    NASA Technical Reports Server (NTRS)

    Iavecchia, Helene P.; Gaynor, Edwin S.; Huff, Lloyd; Rhodes, William T.; Rothenheber, Edward H.

    1990-01-01

    The Holographic Enhanced Remote Sensing System (HERSS) consists of three primary subsystems: (1) an Image Acquisition System (IAS); (2) a Digital Image Processing System (DIPS); and (3) a Holographic Generation System (HGS) which multiply exposes a thermoplastic recording medium with sequential 2-D depth slices that are displayed on a Spatial Light Modulator (SLM). Full-parallax holograms were successfully generated by superimposing SLM images onto the thermoplastic and photopolymer. An improved HGS configuration utilizes the phase conjugate recording configuration, the 3-SLM-stacking technique, and the photopolymer. The holographic volume size is currently limited to the physical size of the SLM. A larger-format SLM is necessary to meet the desired 6 inch holographic volume. A photopolymer with an increased photospeed is required to ultimately meet a display update rate of less than 30 seconds. It is projected that the latter two technology developments will occur in the near future. While the IAS and DIPS subsystems were unable to meet NASA goals, an alternative technology is now available to perform the IAS/DIPS functions. Specifically, a laser range scanner can be utilized to build the HGS numerical database of the objects at the remote work site.

  17. Microbial enhanced oil recovery research

    SciTech Connect

    Sharma, M.M.; Georgiou, G.

    1990-01-01

    The objective of this work is to develop an engineering framework for the exploitation of microorganisms to enhance oil recovery. Specific goals include: (1) investigation of the mechanisms of microbially induced oil mobilization; (2) the production, isolation, chemical characterization and study of the physical properties of microbially produced surfactants; (3) model studies in sandstone cores for the characterization of the interactions between growing microbially cultures and oil reservoirs; (4) development of simulators for MEOR; and (5) design of operational strategies for the sequential injection of microorganisms and nutrient in reservoirs are: (1) systematic discussion of the mechanisms important in MEOR processes; (2) Measurement of the growth characteristics of Bacillus Licheniformis under various conditions of pH, temperature and salt concentration for both aerobic and anaerobic growth.; (3) measurement of interfacial tension reducing ability of the biosurfactant under different conditions of pH and salt concentration; (4) development of some preliminary methods to concentrate and characterize the biosurfactant; (5) development of a compositional numerical simulator for MEOR processes; and (6) Measurement of the lowest interfacial tension (IFT) value reported for biosurfactants to date. Demonstration of the fact that the low IFT values required for oil recovery can be attained with biosurfactants.

  18. Enhanced decision making through neuroscience

    NASA Astrophysics Data System (ADS)

    Szu, Harold; Jung, TP; Makeig, Scott

    2012-06-01

    We propose to enhance the decision making of pilot, co-pilot teams, over a range of vehicle platforms, with the aid of neuroscience. The goal is to optimize this collaborative decision making interplay in time-critical, stressful situations. We will research and measure human facial expressions, personality typing, and brainwave measurements to help answer questions related to optimum decision-making in group situations. Further, we propose to examine the nature of intuition in this decision making process. The brainwave measurements will be facilitated by a University of California, San Diego (UCSD) developed wireless Electroencephalography (EEG) sensing cap. We propose to measure brainwaves covering the whole head area with an electrode density of N=256, and yet keep within the limiting wireless bandwidth capability of m=32 readouts. This is possible because solving Independent Component Analysis (ICA) and finding the hidden brainwave sources allow us to concentrate selective measurements with an organized sparse source -->s sensing matrix [Φs], rather than the traditional purely random compressive sensing (CS) matrix[Φ].

  19. Enhanced Model for Fast Ignition

    SciTech Connect

    Mason, Rodney J.

    2010-10-12

    Laser Fusion is a prime candidate for alternate energy production, capable of serving a major portion of the nation's energy needs, once fusion fuel can be readily ignited. Fast Ignition may well speed achievement of this goal, by reducing net demands on laser pulse energy and timing precision. However, Fast Ignition has presented a major challenge to modeling. This project has enhanced the computer code ePLAS for the simulation of the many specialized phenomena, which arise with Fast Ignition. The improved code has helped researchers to understand better the consequences of laser absorption, energy transport, and laser target hydrodynamics. ePLAS uses efficient implicit methods to acquire solutions for the electromagnetic fields that govern the accelerations of electrons and ions in targets. In many cases, the code implements fluid modeling for these components. These combined features, "implicitness and fluid modeling," can greatly facilitate calculations, permitting the rapid scoping and evaluation of experiments. ePLAS can be used on PCs, Macs and Linux machines, providing researchers and students with rapid results. This project has improved the treatment of electromagnetics, hydrodynamics, and atomic physics in the code. It has simplified output graphics, and provided new input that avoids the need for source code access by users. The improved code can now aid university, business and national laboratory users in pursuit of an early path to success with Fast Ignition.

  20. Irradiation enhancement of biomass conversion

    NASA Astrophysics Data System (ADS)

    Smith, G. S.; Kiesling, H. E.; Galyean, M. L.; Bader, J. R.

    The vast supply of cellulosic agricultural residues and industrial by-products that is produced each year is a prospective resource of biomass suitable for conversion to useful products such as feedstock for the chemicals industry and feedstuffs for the livestock industry. Conversions of such biomass is poor at present, and utilization is inefficient, because of physio-chemical barriers to biological degradation and (or) anti-quality components such as toxicants that restrict biological usages. Improvements in biodegradability of ligno-cellulosic materials have been accomplished by gamma-ray and electron-beam irradiation at intermediate dosage (˜ 50 Mrad; .5 MGy); but applications of the technology have been hampered by questionable interpretations of results. Recent research with organic wastes such as sewage sludge and straw suggests opportunity for important applications of irradiation technology in enhancement of biomass conversion. Data from experiments using irradiated straw as feed for ruminants are presented and discussed in relation to research on prospective usage of sewage products as feed for ruminants. Findings are discussed in regard to prospective applications in industrial fermentation processes. Possible usage of irradiation technology for destruction of toxicants in exotic plants is considered in regard to prospective new feedstuffs.

  1. Ultrasound enhanced thrombolysis: Clinical evidence

    NASA Astrophysics Data System (ADS)

    Alexandrov, Andrei V.

    2005-04-01

    Phase II CLOTBUST randomized clinical trial (Houston, Barcelona, Edmonton, Calgary) evaluated patients with acute ischemic stroke due to intracranial occlusion and treated with intravenous tissue plasminogen activator (TPA) within 3 h of symptom onset. Randomization: monitoring with pulsed wave 2 MHz transcranial Doppler (TCD) (Target) or placebo monitoring (Control). Safety: symptomatic bleeding to the brain (sICH). Primary end-point: complete recanalization on TCD or dramatic clinical recovery by the total NIHSS score <3, or improvement by >10 NIHSS points within 2 hours after TPA bolus. All projected 126 patients were randomized 1:1 to target (median NIHSS 16) or control (NIHSS 17). sICH: 4.8% Target, 4.8% Controls. Primary end-point was achieved by 31 (49%, Target) versus 19 (30%, Control), p<0.03. At 3 months, 22 (42% Target) and 14 (29% Control) patients achieved favorable outcomes. Continuous TCD monitoring of intracranial occlusion safely augments TPA-induced arterial recanalization, and 2 MHz diagnostic ultrasound has a positive biological activity that aids systemic thrombolytic therapy. For the first time in clinical medicine, the CLOTBUST trial provides the evidence that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming intense multi-disciplinary experimental research conducted worldwide for the past 30 years.

  2. Facebook enhances antidepressant pharmacotherapy effects.

    PubMed

    Mota Pereira, Jorge

    2014-01-01

    Treatment-resistant major depressive disorder (TR-MDD) is a complex condition, with very low remission rates. In recent years some studies have been conducted on the implementation of cognitive behavioral therapy and psychodynamic psychotherapy interventions via the Internet to MDD patients, and results have been promising. However, there have been no studies in patients with TR-MDD nor with the use of Facebook with the psychiatrist as "friend." 60 TR-MDD patients were randomized to one of three groups: Facebook group with psychiatrist as "friend," Facebook group without psychiatrist as "friend," and control group (no Facebook use). Both Facebook groups spent at least 1 hour/day on Facebook, 7 days/week, during the 3 months. All patients maintained their usual pharmacotherapy. All participants were evaluated at baseline and at 1, 2, and 3 months for depressive symptoms using HAD17 and BDI-II. Results show that both Facebook groups had a decrease on HADM17 and BDI-II scores as well as higher remission and response rates than the control group, with better results if the psychiatrist was a "friend" on Facebook. Therefore, in TR-MDD, Facebook can be used as an effective enhancement therapy, adjuvant to pharmacological therapy with regular consultations, especially if the psychiatrist is the patient's online "friend."

  3. Enhanced safeguards via solution monitoring

    SciTech Connect

    Burr, T.; Wangen, L.

    1996-09-01

    Solution monitoring is defined as the essentially continuous monitoring of solution level, density, and temperature in all tanks in the process that contain, or could contain, safeguards-significant quantities of nuclear material. This report describes some of the enhancements that solution monitoring could make to international safeguards. The focus is on the quantifiable benefits of solution monitoring, but qualitatively, solution monitoring can be viewed as a form of surveillance. Quantitatively, solution monitoring can in some cases improve diversion detection probability. For example, the authors show that under certain assumptions, solution monitoring can be used to reduce the standard deviation of the annual material balance, {sigma}{sub MB}, from approximately 17 kg to approximately 4 kg. Such reduction in {sigma}{sub MB} will not always be possible, as they discuss. However, in all cases, solution monitoring would provide assurance that the measurement error models are adequate so that one has confidence in his estimate of {sigma}{sub MB}. Some of the results in this report were generated using data that were simulated with prototype solution monitoring software that they are developing. An accompanying document describes that software.

  4. Enhanced Eryptosis Following Gramicidin Exposure

    PubMed Central

    Malik, Abaid; Bissinger, Rosi; Liu, Guoxing; Liu, Guilai; Lang, Florian

    2015-01-01

    The peptide antibiotic and ionophore gramicidin has previously been shown to trigger apoptosis of nucleated cells. In analogy to apoptosis, the suicidal death of erythrocytes or eryptosis involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide. The present study explored, whether gramicidin triggers eryptosis. To this end phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, red blood cell distribution width (RDW) from electronic particle counting, reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, [Ca2+]i from Fluo3- and Fluo4 fluorescence, and ceramide abundance from binding of specific antibodies. As a result, a 24 h exposure of human erythrocytes to gramicidin significantly increased the percentage of annexin-V-binding cells (≥1 µg/mL), forward scatter (≥0.5 µg/mL) and hemolysis. Gramicidin enhanced ROS activity, [Ca2+]i and ceramide abundance at the erythrocyte surface. The stimulation of annexin-V-binding by gramicidin was significantly blunted but not abolished by removal of extracellular Ca2+. In conclusion, gramicidin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance. Despite increase of [Ca2+]i, gramicidin increases cell volume and slightly reduces RWD. PMID:25915718

  5. Facebook Enhances Antidepressant Pharmacotherapy Effects

    PubMed Central

    Mota Pereira, Jorge

    2014-01-01

    Treatment-resistant major depressive disorder (TR-MDD) is a complex condition, with very low remission rates. In recent years some studies have been conducted on the implementation of cognitive behavioral therapy and psychodynamic psychotherapy interventions via the Internet to MDD patients, and results have been promising. However, there have been no studies in patients with TR-MDD nor with the use of Facebook with the psychiatrist as “friend.” 60 TR-MDD patients were randomized to one of three groups: Facebook group with psychiatrist as “friend,” Facebook group without psychiatrist as “friend,” and control group (no Facebook use). Both Facebook groups spent at least 1 hour/day on Facebook, 7 days/week, during the 3 months. All patients maintained their usual pharmacotherapy. All participants were evaluated at baseline and at 1, 2, and 3 months for depressive symptoms using HAD17 and BDI-II. Results show that both Facebook groups had a decrease on HADM17 and BDI-II scores as well as higher remission and response rates than the control group, with better results if the psychiatrist was a “friend” on Facebook. Therefore, in TR-MDD, Facebook can be used as an effective enhancement therapy, adjuvant to pharmacological therapy with regular consultations, especially if the psychiatrist is the patient's online “friend.” PMID:24574930

  6. Advanced integrated enhanced vision systems

    NASA Astrophysics Data System (ADS)

    Kerr, J. R.; Luk, Chiu H.; Hammerstrom, Dan; Pavel, Misha

    2003-09-01

    In anticipation of its ultimate role in transport, business and rotary wing aircraft, we clarify the role of Enhanced Vision Systems (EVS): how the output data will be utilized, appropriate architecture for total avionics integration, pilot and control interfaces, and operational utilization. Ground-map (database) correlation is critical, and we suggest that "synthetic vision" is simply a subset of the monitor/guidance interface issue. The core of integrated EVS is its sensor processor. In order to approximate optimal, Bayesian multi-sensor fusion and ground correlation functionality in real time, we are developing a neural net approach utilizing human visual pathway and self-organizing, associative-engine processing. In addition to EVS/SVS imagery, outputs will include sensor-based navigation and attitude signals as well as hazard detection. A system architecture is described, encompassing an all-weather sensor suite; advanced processing technology; intertial, GPS and other avionics inputs; and pilot and machine interfaces. Issues of total-system accuracy and integrity are addressed, as well as flight operational aspects relating to both civil certification and military applications in IMC.

  7. Enhanced eryptosis following gramicidin exposure.

    PubMed

    Malik, Abaid; Bissinger, Rosi; Liu, Guoxing; Liu, Guilai; Lang, Florian

    2015-04-23

    The peptide antibiotic and ionophore gramicidin has previously been shown to trigger apoptosis of nucleated cells. In analogy to apoptosis, the suicidal death of erythrocytes or eryptosis involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide. The present study explored, whether gramicidin triggers eryptosis. To this end phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, red blood cell distribution width (RDW) from electronic particle counting, reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, [Ca2+]i from Fluo3- and Fluo4 fluorescence, and ceramide abundance from binding of specific antibodies. As a result, a 24 h exposure of human erythrocytes to gramicidin significantly increased the percentage of annexin-V-binding cells (≥1 µg/mL), forward scatter (≥0.5 µg/mL) and hemolysis. Gramicidin enhanced ROS activity, [Ca2+]i and ceramide abundance at the erythrocyte surface. The stimulation of annexin-V-binding by gramicidin was significantly blunted but not abolished by removal of extracellular Ca2+. In conclusion, gramicidin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance. Despite increase of [Ca2+]i, gramicidin increases cell volume and slightly reduces RWD.

  8. Facebook enhances antidepressant pharmacotherapy effects.

    PubMed

    Mota Pereira, Jorge

    2014-01-01

    Treatment-resistant major depressive disorder (TR-MDD) is a complex condition, with very low remission rates. In recent years some studies have been conducted on the implementation of cognitive behavioral therapy and psychodynamic psychotherapy interventions via the Internet to MDD patients, and results have been promising. However, there have been no studies in patients with TR-MDD nor with the use of Facebook with the psychiatrist as "friend." 60 TR-MDD patients were randomized to one of three groups: Facebook group with psychiatrist as "friend," Facebook group without psychiatrist as "friend," and control group (no Facebook use). Both Facebook groups spent at least 1 hour/day on Facebook, 7 days/week, during the 3 months. All patients maintained their usual pharmacotherapy. All participants were evaluated at baseline and at 1, 2, and 3 months for depressive symptoms using HAD17 and BDI-II. Results show that both Facebook groups had a decrease on HADM17 and BDI-II scores as well as higher remission and response rates than the control group, with better results if the psychiatrist was a "friend" on Facebook. Therefore, in TR-MDD, Facebook can be used as an effective enhancement therapy, adjuvant to pharmacological therapy with regular consultations, especially if the psychiatrist is the patient's online "friend." PMID:24574930

  9. Inhomogeneous thermal conductivity enhances thermoelectric cooling

    NASA Astrophysics Data System (ADS)

    Lu, Tingyu; Zhou, Jun; Li, Nianbei; Yang, Ronggui; Li, Baowen

    2014-12-01

    We theoretically investigate the enhancement of thermoelectric cooling performance in thermoelectric refrigerators made of materials with inhomogeneous thermal conductivity, beyond the usual practice of enhancing thermoelectric figure of merit (ZT) of materials. The dissipation of the Joule heat in such thermoelectric refrigerators is asymmetric which can give rise to better thermoelectric cooling performance. Although the thermoelectric figure of merit and the coefficient-of-performance are slightly enhanced, both the maximum cooling power and the maximum cooling temperature difference can be enhanced significantly. This finding can be used to increase the heat absorption at the cold end. We further find that the asymmetric dissipation of Joule heat leads to thermal rectification.

  10. Optical nanogap matrices for plasmonic enhancement applications

    NASA Astrophysics Data System (ADS)

    Bauman, Stephen J.; Debu, Desalegn T.; Hill, Avery M.; Novak, Eric C.; Natelson, Douglas; Herzog, Joseph B.

    2014-09-01

    Plasmonic structures can be used to enhance electromagnetic radiation, and nanoscale (<5 nm) gaps can increase this enhancement even further. Fabrication of these desired structures involves using a relatively new, previously developed self-aligned process to overcome typical electron beam lithography resolution limits. The resulting nanogap structures have been shown to exhibit enhanced optical emission. This technique enables the fabrication of a large-area two-dimensional matrix of such nanostructures which could prove useful for photovoltaics, plasmonically enhanced Raman spectroscopy, biosensing, and other optoelectronic applications. Computational electromagnetic simulations of the structures will prove useful for predicting behavior upon interaction with light and for experimental comparison.

  11. On the argument that enhancement is "cheating".

    PubMed

    Schermer, M

    2008-02-01

    One frequently used argument in the discussion on human enhancement is that enhancement is a form of cheating. This argument is well-known in relation to doping in sports, but recently it has also been used with regard to cognitive enhancement in the context of education and exams. This paper analyses the enhancement-is-cheating argument by comparing sports and education, and by evaluating how the argument can be interpreted in both contexts. If cheating is understood as breaking the rules in order to gain an unfair advantage over others, it can be argued that some enhancements are a form of cheating. This problem of cheating is, however, relatively easy to remedy by either changing the rules, or by instituting controls and sanctions. This does not, therefore, constitute a categorical objection to enhancement. A further analysis of the intuitions behind the enhancement-is-cheating argument, however, shows that if sports and education are understood as "practices", with their own internal goods and standards of excellence, some potential problems of enhancement can be articulated. These concern the internal goods and standards of excellence that are characteristic of specific practices. Seen from this perspective, the important question is how enhancement technologies might be embedded in specific practices--or how they might corrode them.

  12. Factors affecting enhanced video quality preferences

    PubMed Central

    Satgunam, PremNandhini; Woods, Russell L; Bronstad, P Matthew; Peli, Eli

    2013-01-01

    The development of video quality metrics requires methods for measuring perceived video quality. Most such metrics are designed and tested using databases of images degraded by compression and scored using opinion ratings. We studied video quality preferences for enhanced images of normally-sighted participants using the method of paired comparisons with a thorough statistical analysis. Participants (n=40) made pair-wise comparisons of high definition (HD) video clips enhanced at four different levels using a commercially available enhancement device. Perceptual scales were computed with binary logistic regression to estimate preferences for each level and to provide statistical inference of the differences among levels and the impact of other variables. While moderate preference for enhanced videos was found, two unexpected effects were also uncovered: (1) Participants could be broadly classified into two groups: those who preferred enhancement ("Sharp") and those who disliked enhancement ("Smooth"). (2) Enhancement preferences depended on video content, particularly for human faces to be enhanced less. The results suggest that algorithms to evaluate image quality (at least for enhancement) may need to be adjusted or applied differentially based on video content and viewer preferences. The possible impact of similar effects on image quality of compressed video needs to be evaluated. PMID:24107400

  13. Enhancing Ocean Research Data Access

    NASA Astrophysics Data System (ADS)

    Chandler, Cynthia; Groman, Robert; Shepherd, Adam; Allison, Molly; Arko, Robert; Chen, Yu; Fox, Peter; Glover, David; Hitzler, Pascal; Leadbetter, Adam; Narock, Thomas; West, Patrick; Wiebe, Peter

    2014-05-01

    The Biological and Chemical Oceanography Data Management Office (BCO-DMO) works in partnership with ocean science investigators to publish data from research projects funded by the Biological and Chemical Oceanography Sections and the Office of Polar Programs Antarctic Organisms & Ecosystems Program at the U.S. National Science Foundation. Since 2006, researchers have been contributing data to the BCO-DMO data system, and it has developed into a rich repository of data from ocean, coastal and Great Lakes research programs. While the ultimate goal of the BCO-DMO is to ensure preservation of NSF funded project data and to provide open access to those data, achievement of those goals is attained through a series of related phases that benefits from active collaboration and cooperation with a large community of research scientists as well as curators of data and information at complementary data repositories. The BCO-DMO is just one of many intermediate data management centers created to facilitate long-term preservation of data and improve access to ocean research data. Through partnerships with other data management professionals and active involvement in local and global initiatives, BCO-DMO staff members are working to enhance access to ocean research data available from the online BCO-DMO data system. Continuing efforts in use of controlled vocabulary terms, development of ontology design patterns and publication of content as Linked Open Data are contributing to improved discovery and availability of BCO-DMO curated data and increased interoperability of related content available from distributed repositories. We will demonstrate how Semantic Web technologies (e.g. RDF/XML, SKOS, OWL and SPARQL) have been integrated into BCO-DMO data access and delivery systems to better serve the ocean research community and to contribute to an expanding global knowledge network.

  14. Robotically enhanced rubber hand illusion.

    PubMed

    Arata, Jumpei; Hattori, Masashi; Ichikawa, Shohei; Sakaguchi, Masamichi

    2014-01-01

    The rubber hand illusion is a well-known multisensory illusion. In brief, watching a rubber hand being stroked by a paintbrush while one's own unseen hand is synchronously stroked causes the rubber hand to be attributed to one's own body and to "feel like it's my hand." The rubber hand illusion is thought to be triggered by the synchronized tactile stimulation of both the subject's hand and the fake hand. To extend the conventional rubber hand illusion, we introduce robotic technology in the form of a master-slave telemanipulator. The developed one degree-of-freedom master-slave system consists of an exoskeleton master equipped with an optical encoder that is worn on the subject's index finger and a motor-actuated index finger on the rubber hand, which allows the subject to perform unilateral telemanipulation. The moving rubber hand illusion has been studied by several researchers in the past with mechanically connected rigs between the subject's body and the fake limb. The robotic instruments let us investigate the moving rubber hand illusion with less constraints, thus behaving closer to the classic rubber hand illusion. In addition, the temporal delay between the body and the fake limb can be precisely manipulated. The experimental results revealed that the robotic instruments significantly enhance the rubber hand illusion. The time delay is significantly correlated with the effect of the multisensory illusion, and the effect significantly decreased at time delays over 100 ms. These findings can potentially contribute to the investigations of neural mechanisms in the field of neuroscience and of master-slave systems in the field of robotics.

  15. Enhanced absorption cycle computer model

    NASA Astrophysics Data System (ADS)

    Grossman, G.; Wilk, M.

    1993-09-01

    Absorption heat pumps have received renewed and increasing attention in the past two decades. The rising cost of electricity has made the particular features of this heat-powered cycle attractive for both residential and industrial applications. Solar-powered absorption chillers, gas-fired domestic heat pumps, and waste-heat-powered industrial temperature boosters are a few of the applications recently subjected to intensive research and development. The absorption heat pump research community has begun to search for both advanced cycles in various multistage configurations and new working fluid combinations with potential for enhanced performance and reliability. The development of working absorption systems has created a need for reliable and effective system simulations. A computer code has been developed for simulation of absorption systems at steady state in a flexible and modular form, making it possible to investigate various cycle configurations with different working fluids. The code is based on unit subroutines containing the governing equations for the system's components and property subroutines containing thermodynamic properties of the working fluids. The user conveys to the computer an image of his cycle by specifying the different subunits and their interconnections. Based on this information, the program calculates the temperature, flow rate, concentration, pressure, and vapor fraction at each state point in the system, and the heat duty at each unit, from which the coefficient of performance (COP) may be determined. This report describes the code and its operation, including improvements introduced into the present version. Simulation results are described for LiBr-H2O triple-effect cycles, LiCl-H2O solar-powered open absorption cycles, and NH3-H2O single-effect and generator-absorber heat exchange cycles. An appendix contains the user's manual.

  16. Electronic enhancement of tear secretion

    NASA Astrophysics Data System (ADS)

    Brinton, Mark; Lim Chung, Jae; Kossler, Andrea; Kook, Koung Hoon; Loudin, Jim; Franke, Manfred; Palanker, Daniel

    2016-02-01

    Objective. To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion. Approach. We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz). Main results. Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm-2 with 170-680 μs pulses) than the damage threshold (3.5 μC mm-2 with 1 ms pulses). Significance. Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and

  17. Unsuccessful Retrieval Attempts Enhance Subsequent Learning

    ERIC Educational Resources Information Center

    Kornell, Nate; Hays, Matthew Jensen; Bjork, Robert A.

    2009-01-01

    Taking tests enhances learning. But what happens when one cannot answer a test question--does an unsuccessful retrieval attempt impede future learning or enhance it? The authors examined this question using materials that ensured that retrieval attempts would be unsuccessful. In Experiments 1 and 2, participants were asked fictional…

  18. Sensor fusion method for machine performance enhancement

    SciTech Connect

    Mou, J.I.; King, C.; Hillaire, R.; Jones, S.; Furness, R.

    1998-03-01

    A sensor fusion methodology was developed to uniquely integrate pre-process, process-intermittent, and post-process measurement and analysis technology to cost-effectively enhance the accuracy and capability of computer-controlled manufacturing equipment. Empirical models and computational algorithms were also developed to model, assess, and then enhance the machine performance.

  19. Arousal-Enhanced Location Memory for Pictures

    ERIC Educational Resources Information Center

    Mather, Mara; Nesmith, Kathryn

    2008-01-01

    Four experiments revealed arousal-enhanced location memory for pictures. After an incidental encoding task, participants were more likely to remember the locations of positive and negative arousing pictures than the locations of non-arousing pictures, indicating better binding of location to picture. This arousal-enhanced binding effect did not…

  20. Nanoparticle Based Surface-Enhanced Raman Spectroscopy

    SciTech Connect

    Talley, C E; Huser, T R; Hollars, C W; Jusinski, L; Laurence, T; Lane, S M

    2005-01-03

    Surface-enhanced Raman scattering is a powerful tool for the investigation of biological samples. Following a brief introduction to Raman and surface-enhanced Raman scattering, several examples of biophotonic applications of SERS are discussed. The concept of nanoparticle based sensors using SERS is introduced and the development of these sensors is discussed.

  1. Enhancing Engineering Education through Engineering Management

    ERIC Educational Resources Information Center

    Pence, Kenneth R.; Rowe, Christopher J.

    2012-01-01

    Engineering Management courses are added to a traditional engineering curriculum to enhance the value of an undergraduate's engineering degree. A four-year engineering degree often leaves graduates lacking in business and management acumen. Engineering management education covers topics enhancing the value of new graduates by teaching management…

  2. Online Faculty Satisfaction and Quality Enhancement Initiatives

    ERIC Educational Resources Information Center

    Satterlee, Anita G.

    2010-01-01

    The purpose of this paper is to examine possible effects of an institution's quality enhancement initiatives on the job satisfaction of online faculty. Quality enhancement initiatives are a normal part of the accreditation process and faculty shoulder some of the responsibility for success of those initiatives. Therefore, it is imperative that…

  3. Surface-Enhanced Second-Harmonic Generation

    SciTech Connect

    Chen, C. K.; de Castro, A. R.B.; Shen, Y. R.

    1981-01-12

    Second harmonic generation at a silver-air interface was enhanced due to surface roughness by a factor of 10⁴. The local field enhancement is believed to be responsible for the effect. An unusually broad luminescence background extending far beyond the antiStokes side of the second harmonic was also observed.

  4. Enhancing critical current density of cuprate superconductors

    DOEpatents

    Chaudhari, Praveen

    2015-06-16

    The present invention concerns the enhancement of critical current densities in cuprate superconductors. Such enhancement of critical current densities include using wave function symmetry and restricting movement of Abrikosov (A) vortices, Josephson (J) vortices, or Abrikosov-Josephson (A-J) vortices by using the half integer vortices associated with d-wave symmetry present in the grain boundary.

  5. Animal Behaviour: Friendship Enhances Trust in Chimpanzees.

    PubMed

    Silk, Joan

    2016-01-25

    Individuals that participate in exchanges with delayed rewards can be exploited if their partners don't reciprocate. In humans, friendships are built on trust, and trust enhances cooperation. New evidence suggests that close social bonds also enhance trust in chimpanzees.

  6. Learning To Make Music Enhances Spatial Reasoning.

    ERIC Educational Resources Information Center

    Hetland, Lois

    2000-01-01

    Examines whether active instruction in music enhances preschool and elementary school student performance on spatial tasks. Reports that music enhances the spatial-temporal performance of children during and up to two years following the instruction and that the effect is moderate and consistent. Includes references. (CMK)

  7. Digital enhancement of flow field images

    NASA Technical Reports Server (NTRS)

    Kudlinski, Robert A.; Park, Stephen K.

    1988-01-01

    Most photographs of experimentally generated fluid flow fields have inherently poor photographic quality, specifically low contrast. Thus, there is a need to establish a process for quickly and accurately enhancing these photographs to provide improved versions for physical interpretation, analysis, and publication. A sequence of digital image processing techniques which have been demonstrated to effectively enhance such photographs is described.

  8. Conceptual and practical problems of moral enhancement.

    PubMed

    Beck, Birgit

    2015-05-01

    Recently, the debate on human enhancement has shifted from familiar topics like cognitive enhancement and mood enhancement to a new and - to no one's surprise - controversial subject, namely moral enhancement. Some proponents from the transhumanist camp allude to the 'urgent need' of improving the moral conduct of humankind in the face of ever growing technological progress and the substantial dangers entailed in this enterprise. Other thinkers express more sceptical views about this proposal. As the debate has revealed so far, there is no shared opinion among philosophers (or scientists) about the meaning, prospects, and ethical evaluation of moral enhancement. In this article I will address several conceptual and practical problems of this issue, in order to encourage discussion about the prospects of (thinking about) moral enhancement in the future. My assumption is that (i) for the short term, there is little chance of arriving at an agreement on the proper understanding of morality and the appropriateness of one single (meta-)ethical theory; (ii) apart from this, there are further philosophical puzzles loosely referred to in the debate which add to theoretical confusion; and (iii) even if these conceptual problems could be solved, there are still practical problems to be smoothed out if moral enhancement is ever to gain relevance apart from merely theoretical interest. My tentative conclusion, therefore, will be that moral enhancement is not very likely to be made sense of - let alone realized - in the medium-term future.

  9. Doping explosive materials for neutron radiographic enhancement.

    NASA Technical Reports Server (NTRS)

    Golliher, K. G.

    1971-01-01

    Discussion of studies relating to the selection of doping materials of high neutron absorption usable for enhancing the neutron radiographic imaging of explosive mixtures, without interfering with the proper chemical reaction of the explosives. The results of the studies show that gadolinium oxide is an excellent material for doping explosive mixtures to enhance the neutron radiographic image.

  10. Open Educational Practices for Curriculum Enhancement

    ERIC Educational Resources Information Center

    Armellini, Alejandro; Nie, Ming

    2013-01-01

    Open educational resources (OER) and open educational practices (OEP) are relatively new areas in educational research. How OER and OEP can help practitioners enhance curricula is one of a number of under-researched topics. This article aims to enable practitioners to identify and implement appropriate open practices to enhance higher education…

  11. Enhancing Vocabulary Development in Multiple Classroom Contexts.

    ERIC Educational Resources Information Center

    Harmon, Janis M.; Staton, Denise G.

    1999-01-01

    Describes ways teachers can enhance students' vocabulary development through multiple contexts available in typical middle school classroom settings. Addresses questions about vocabulary learning and offers suggestions for enhancing vocabulary with narrative and expository texts that involve multiple classroom contexts. Considers the Vocab-o-gram…

  12. Conceptual and practical problems of moral enhancement.

    PubMed

    Beck, Birgit

    2015-05-01

    Recently, the debate on human enhancement has shifted from familiar topics like cognitive enhancement and mood enhancement to a new and - to no one's surprise - controversial subject, namely moral enhancement. Some proponents from the transhumanist camp allude to the 'urgent need' of improving the moral conduct of humankind in the face of ever growing technological progress and the substantial dangers entailed in this enterprise. Other thinkers express more sceptical views about this proposal. As the debate has revealed so far, there is no shared opinion among philosophers (or scientists) about the meaning, prospects, and ethical evaluation of moral enhancement. In this article I will address several conceptual and practical problems of this issue, in order to encourage discussion about the prospects of (thinking about) moral enhancement in the future. My assumption is that (i) for the short term, there is little chance of arriving at an agreement on the proper understanding of morality and the appropriateness of one single (meta-)ethical theory; (ii) apart from this, there are further philosophical puzzles loosely referred to in the debate which add to theoretical confusion; and (iii) even if these conceptual problems could be solved, there are still practical problems to be smoothed out if moral enhancement is ever to gain relevance apart from merely theoretical interest. My tentative conclusion, therefore, will be that moral enhancement is not very likely to be made sense of - let alone realized - in the medium-term future. PMID:24654942

  13. College Enhancement Strategies and Socioeconomic Inequality

    ERIC Educational Resources Information Center

    Wolniak, Gregory C.; Wells, Ryan S.; Engberg, Mark E.; Manly, Catherine A.

    2016-01-01

    The study provides new information on the relationships between students' socioeconomic backgrounds, utilization of college enhancement strategies, and subsequent 4-year college enrollment. Enhancement strategies represent student behaviors used to bolster the competitiveness of a college application, such as Advanced Placement exams and a variety…

  14. Surfactant and process for enhanced oil recovery

    SciTech Connect

    Stapp, P. R.

    1985-03-12

    A novel surfactant is formed by reacting maleic anhydride with a polynuclear aromatic compound having a molecular weight of at least 155. A novel surfactant system useful in enhanced oil recovery containing the above surfactant is also provided. In addition, an improved process for the enhanced recovery of oil is provided utilizing the novel surfactant system.

  15. Bandwidth enhancement of dielectric resonator antennas

    NASA Technical Reports Server (NTRS)

    Lee, Richard Q.; Simons, Rainee N.

    1993-01-01

    An experimental investigation of bandwidth enhancement of dielectric resonator antennas (DRA) using parasitic elements is reported. Substantial bandwidth enhancement for the HE(sub 11delta) mode of the stacked geometry and for the HE(sub 13delta) mode of the coplanar collinear geometry was demonstrated. Excellent radiation patterns for the HE(sub 11delta) mode were also recorded.

  16. Molecular mechanism of the sweet taste enhancers

    PubMed Central

    Zhang, Feng; Klebansky, Boris; Fine, Richard M.; Liu, Haitian; Xu, Hong; Servant, Guy; Zoller, Mark; Tachdjian, Catherine; Li, Xiaodong

    2010-01-01

    Positive allosteric modulators of the human sweet taste receptor have been developed as a new way of reducing dietary sugar intake. Besides their potential health benefit, the sweet taste enhancers are also valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, we reveal how these sweet enhancers work at the molecular level. Our data argue that the sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor. PMID:20173095

  17. Molecular mechanism of the sweet taste enhancers.

    PubMed

    Zhang, Feng; Klebansky, Boris; Fine, Richard M; Liu, Haitian; Xu, Hong; Servant, Guy; Zoller, Mark; Tachdjian, Catherine; Li, Xiaodong

    2010-03-01

    Positive allosteric modulators of the human sweet taste receptor have been developed as a new way of reducing dietary sugar intake. Besides their potential health benefit, the sweet taste enhancers are also valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, we reveal how these sweet enhancers work at the molecular level. Our data argue that the sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.

  18. Enhancing nanoparticle electrodynamics with gold nanoplate mirrors.

    PubMed

    Yan, Zijie; Bao, Ying; Manna, Uttam; Shah, Raman A; Scherer, Norbert F

    2014-05-14

    Mirrors and optical cavities can modify and enhance matter-radiation interactions. Here we report that chemically synthesized Au nanoplates can serve as micrometer-size mirrors that enhance electrodynamic interactions. Because of their plasmonic properties, the Au nanoplates enhance the brightness of scattered light from Ag nanoparticles near the nanoplate surface in dark-field microscopy. More importantly, enhanced optical trapping and optical binding of Ag nanoparticles are demonstrated in interferometric optical traps created from a single laser beam and its reflection from individual Au nanoplates. The enhancement of the interparticle force constant is ≈20-fold more than expected from the increased intensity due to standing wave interference. We show that the additional stability for optical binding arises from the restricted axial thermal motion of the nanoparticles that couples to and reduces the fluctuations in the lateral plane. This new mechanism greatly advances the photonic synthesis of ultrastable nanoparticle arrays and investigation of their properties.

  19. Gabor filter based fingerprint image enhancement

    NASA Astrophysics Data System (ADS)

    Wang, Jin-Xiang

    2013-03-01

    Fingerprint recognition technology has become the most reliable biometric technology due to its uniqueness and invariance, which has been most convenient and most reliable technique for personal authentication. The development of Automated Fingerprint Identification System is an urgent need for modern information security. Meanwhile, fingerprint preprocessing algorithm of fingerprint recognition technology has played an important part in Automatic Fingerprint Identification System. This article introduces the general steps in the fingerprint recognition technology, namely the image input, preprocessing, feature recognition, and fingerprint image enhancement. As the key to fingerprint identification technology, fingerprint image enhancement affects the accuracy of the system. It focuses on the characteristics of the fingerprint image, Gabor filters algorithm for fingerprint image enhancement, the theoretical basis of Gabor filters, and demonstration of the filter. The enhancement algorithm for fingerprint image is in the windows XP platform with matlab.65 as a development tool for the demonstration. The result shows that the Gabor filter is effective in fingerprint image enhancement technology.

  20. Enhancing Dopant Solubility via Epitaxial Surfactant Growth

    SciTech Connect

    Zhang, L.; Yan, Y.; Wei, S.-H.

    2009-01-01

    A general concept for enhancing dopant solubility via epitaxial surfactant growth is proposed. The key of the concept is to find the appropriate surfactants that generate high (low) levels that can transfer electrons (holes) to dopant acceptor (donor) levels in p-type (n-type) doping, thus significantly lowering the formation energy of dopants. Using first-principles density-functional calculations, our concept explains excellently the recently discovered dual-surfactant effect of Sb and H on enhancing Zn doping in epitaxially grown GaP(100) thin film and suggests that sole surfactant Te can also induce enhancement of N solubility in ZnSe(100) film. We also proposed the surfactants for enhancing p-type doing of ZnO with epitaxial growth with (000{bar 1}) surface. General rules for selecting surfactants for enhancing both p-type and n-type dopings are provided.

  1. ELECTROSTATICALLY ENHANCED BARRIER FILTER COLLECTION

    SciTech Connect

    John Erjavec; Michael D. Mann; Ryan Z. Knutson; Michael L. Swanson; Michael E. Collings

    2003-06-01

    This work was performed through the University of North Dakota (UND) Chemical Engineering Department with assistance from UND's Energy & Environmental Research Center. This research was undertaken in response to the U.S. Department of Energy Federal Technology Center Program Solicitation No. DE-PS26-99FT40479, Support of Advanced Coal Research at U.S. Universities and Colleges. Specifically, this research was in support of the UCR Core Program and addressees Topic 1, Improved Hot-Gas Contaminant and Particulate Removal Techniques, introducing an advanced design for particulate removal. Integrated gasification combined cycle (IGCC) offers the potential for very high efficiency and clean electric generation. In IGCC, the product gas from the gasifier needs to be cleaned of particulate matter to avoid erosion and high-temperature corrosion difficulties arising with the turbine blades. Current methods involve cooling the gases to {approx}100 C to condense alkalis and remove sulfur and particulates using conventional scrubber technology. This ''cool'' gas is then directed to a turbine for electric generation. While IGCC has the potential to reach efficiencies of over 50%, the current need to cool the product gas for cleaning prior to firing it in a turbine is keeping IGCC from reaching its full potential. The objective of the current project was to develop a highly reliable particulate collector system that can meet the most stringent turbine requirements and emission standards, can operate at temperatures above 1500 F, is applicable for use with all U.S. coals, is compatible with various sorbent injection schemes for sulfur and alkali control, can be integrated into a variety of configurations for both pressurized gasification and combustion, increases allowable face velocity to reduce filter system capital cost, and is cost-competitive with existing technologies. The collector being developed is a new concept in particulate control called electrostatically enhanced

  2. Nutrient Composition of Enhanced and Non-enhanced Boneless Skinless Chicken Breast Fillets Purchased from Retail

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to compare nutritional composition of raw enhanced (E) and non-enhanced (NE), boneless, skinless chicken breast fillets (pectoralis major), obtained from U.S. retail supermarkets. Fillets were either enhanced with a salt, phosphate, and water solution, or were non-en...

  3. Experimental evaluation of the twofold electromagnetic enhancement theory of surface-enhanced resonance Raman scattering

    SciTech Connect

    Yoshida, Ken-ichi; Itoh, Tamitake; Biju, Vasudevanpillai; Ishikawa, Mitsuru; Ozaki, Yukihiro

    2009-02-15

    We examined an electromagnetic (EM) theory of surface-enhanced resonance Raman scattering (SERRS) using single Ag nanoaggregates. The SERRS-EM theory is characterized by twofold EM enhancement induced by the coupling of plasmon resonance with both excitation and emission of Raman scattering plus fluorescence. The total emission cross-section spectra of enhanced Raman scattering and enhanced fluorescence were calculated using the following parameters: the spectrum of enhancement factor induced by plasmon resonance, resonance Raman scattering overlapped with fluorescence, and excitation wavelengths. The calculations well agreed with experimental total emission cross-section spectra, thus providing strong indications that the SERRS-EM theory is quantitatively correct.

  4. Carbon dioxide efficiency of terrestrial enhanced weathering.

    PubMed

    Moosdorf, Nils; Renforth, Phil; Hartmann, Jens

    2014-05-01

    Terrestrial enhanced weathering, the spreading of ultramafic silicate rock flour to enhance natural weathering rates, has been suggested as part of a strategy to reduce global atmospheric CO2 levels. We budget potential CO2 sequestration against associated CO2 emissions to assess the net CO2 removal of terrestrial enhanced weathering. We combine global spatial data sets of potential source rocks, transport networks, and application areas with associated CO2 emissions in optimistic and pessimistic scenarios. The results show that the choice of source rocks and material comminution technique dominate the CO2 efficiency of enhanced weathering. CO2 emissions from transport amount to on average 0.5-3% of potentially sequestered CO2. The emissions of material mining and application are negligible. After accounting for all emissions, 0.5-1.0 t CO2 can be sequestered on average per tonne of rock, translating into a unit cost from 1.6 to 9.9 GJ per tonne CO2 sequestered by enhanced weathering. However, to control or reduce atmospheric CO2 concentrations substantially with enhanced weathering would require very large amounts of rock. Before enhanced weathering could be applied on large scales, more research is needed to assess weathering rates, potential side effects, social acceptability, and mechanisms of governance.

  5. Spectroscopic enhancement in nanoparticles embedded glasses

    NASA Astrophysics Data System (ADS)

    Sahar, M. R.; Ghoshal, S. K.

    2014-09-01

    This presentation provides an overview of the recent progress in the enhancement of the spectroscopic characteristics of the glass embedded with nanoparticles (NPs). Some of our research activities with few significantly new results are highlighted and facilely analyzed. The science and technology dealing with the manipulation of the physical properties of rare earth doped inorganic glasses by embedding metallic NPs or nanoclusters produce the so-called 'nanoglass'. Meanwhile, the spectroscopic enhancement relates the intensity of the luminescence measured at certain transition. The enhancement which expectedly due to the 'plasmonics wave' (referring to the coherent coupling of photons to free electron oscillations called plasmon) occurs at the interface between a conductor and a dielectric. Plasmonics being an emerging concept in advanced optical material of nanophotonics has given this material the ability to exploit the optical response at nanoscale and opened up a new avenue in metal-based glass optics. There is a vast array of plasmonic NPs concepts yet to be explored, with applications spanning solar cells, (bio) sensing, communications, lasers, solid-state lighting, waveguides, imaging, optical data transfer, display and even bio-medicine. Localized surface plasmon resonance (LSPR) can enhance the optical response of nanoglass by orders of magnitude as observed. The luminescence enhancement and surface enhanced Raman scattering (SERS) are new paradigm of research. The enhancement of luminescence due to the influence of metallic NPs is the recurring theme of this paper.

  6. Cardiac Imaging Techniques for Physicians: Late Enhancement

    PubMed Central

    Kellman, Peter; Arai, Andrew E.

    2012-01-01

    Late enhancement imaging is used to diagnose and characterize a wide range of ischemic and non-ischemic cardiomyopathies, and its use has become ubiquitous in the cardiac MR exam. As the use of late enhancement imaging has matured and the span of applications has widened, the demands on image quality have grown. The characterization of sub-endocardial MI now includes the accurate quantification of scar size, shape, and characterization of borders which have been shown to have prognostic significance. More diverse patterns of late enhancement including patchy, mid-wall, sub-epicardial, or diffuse enhancement are of interest in diagnosing non-ischemic cardiomyopathies. As clinicians are examining late enhancement images for more subtle indication of fibrosis, the demand for lower artifacts has increased. A range of new techniques have emerged to improve the speed and quality of late enhancement imaging including: methods for acquisition during free breathing, and fat water separated imaging for characterizing fibro-fatty infiltration and reduction of artifacts related to the presence of fat. Methods for quantification of T1 and extracellular volume fraction are emerging to tackle the issue of discriminating globally diffuse fibrosis from normal healthy tissue which is challenging using conventional late enhancement methods. The aim of this review will be to describe the current state of the art and to provide a guide to various clinical protocols that are commonly used. PMID:22903654

  7. Spectroscopic enhancement in nanoparticles embedded glasses

    SciTech Connect

    Sahar, M. R. Ghoshal, S. K.

    2014-09-25

    This presentation provides an overview of the recent progress in the enhancement of the spectroscopic characteristics of the glass embedded with nanoparticles (NPs). Some of our research activities with few significantly new results are highlighted and facilely analyzed. The science and technology dealing with the manipulation of the physical properties of rare earth doped inorganic glasses by embedding metallic NPs or nanoclusters produce the so-called 'nanoglass'. Meanwhile, the spectroscopic enhancement relates the intensity of the luminescence measured at certain transition. The enhancement which expectedly due to the 'plasmonics wave' (referring to the coherent coupling of photons to free electron oscillations called plasmon) occurs at the interface between a conductor and a dielectric. Plasmonics being an emerging concept in advanced optical material of nanophotonics has given this material the ability to exploit the optical response at nanoscale and opened up a new avenue in metal-based glass optics. There is a vast array of plasmonic NPs concepts yet to be explored, with applications spanning solar cells, (bio) sensing, communications, lasers, solid-state lighting, waveguides, imaging, optical data transfer, display and even bio-medicine. Localized surface plasmon resonance (LSPR) can enhance the optical response of nanoglass by orders of magnitude as observed. The luminescence enhancement and surface enhanced Raman scattering (SERS) are new paradigm of research. The enhancement of luminescence due to the influence of metallic NPs is the recurring theme of this paper.

  8. [Study on cine view of relative enhancement ratio map in O2-enhanced MRI].

    PubMed

    Fujii, Keita; Watanabe, Yasushi; Hanaoka, Shouhei; Motoyoshi, Kouichi; Goto, Masami; Amemiya, Shiori; Ino, Kenji; Akahane, Masaaki; Yano, Keiichi; Ohtomo, Kuni

    2014-11-01

    Magnetic resonance imaging (MRI) enables the evaluation of organ structure and function. Oxygen-enhanced MRI (O2-enhanced MRI) is a method for evaluating the pulmonary ventilation function using oxygen as a contrast agent. We created the Cine View of Relative Enhancement Ratio Map (Cine RER map) in O2-enhanced MRI to easily observe the contrast effect for clinical use. Relative enhancement ratio (RER) was determined as the pixel values of the Cine RER map. Moreover, six healthy volunteers underwent O2-enhanced MRI to determine the appropriate scale width of the Cine RER map. We calculated each RER and set 0 to 1.27 as the scale width of the Cine RER map based on the results. The Cine RER map made it possible to observe the contrast effect over time and thus is a convenient tool for evaluating the pulmonary ventilation function in O2-enhanced MRI.

  9. Detectivity enhancement in THz electrooptical sampling

    SciTech Connect

    Ahmed, Saima; Savolainen, Janne; Hamm, Peter

    2014-01-15

    We demonstrate and discuss a simple scheme that significantly enhances the detectivity of THz electro-optical sampling by introducing a sequence of Brewster windows that increases the ellipticity of the probe beam. By varying the window material or the number of Brewster windows, the enhancement factor can be adjusted; we demonstrate an enhancement factor of ≈20 with four ZnSe Brewster windows. The scheme is particularly useful when very small THz fields are to be measured in connection with low-repetition rate amplified Ti:S laser systems.

  10. Enhanced diffusion of phosphorus at grain boundaries

    NASA Technical Reports Server (NTRS)

    Cheng, L. J.; Shyu, C. M.; Stika, K. M.; Daud, T.; Crotty, G. T.

    1982-01-01

    Enhanced diffusion of phosphorus at grain boundaries in cast polycrystalline photovoltaic materials (Wacker, HEM, and Semix) was studied. It was found that the enhancements for the three materials were the same, indicating that the properties of boundaries are similar, even though they were grown by different techniques. In addition, it was observed that grain boundaries capable of enhancing the diffusion always have strong recombination activities. Both phenomena could be related to dangling bonds existing at the boundaries. The present study gives the first evidence that incoherent second order twins of 111/115-plane type are diffusion-active.

  11. Fingerprint image enhancement using CNN filtering techniques.

    PubMed

    Saatci, Ertugrul; Tavsanoglu, Vedat

    2003-12-01

    Due to noisy acquisition devices and variation in impression conditions, the ridgelines of fingerprint images are mostly corrupted by various kinds of noise causing cracks, scratches and bridges in the ridges as well as blurs. These cause matching errors in fingerprint recognition. For an effective recognition the correct ridge pattern is essential which requires the enhancement of fingerprint images. Segment by segment analysis of the fingerprint pattern yields various ridge direction and frequencies. By selecting a directional filter with correct filter parameters to match ridge features at each point, we can effectively enhance fingerprint ridges. This paper proposes a fingerprint image enhancement based on CNN Gabor-Type filters.

  12. The inevitability of genetic enhancement technologies.

    PubMed

    Baylis, Francoise; Robert, Jason Scott

    2004-01-01

    We outline a number of ethical objections to genetic technologies aimed at enhancing human capacities and traits. We then argue that, despite the persuasiveness of some of these objections, they are insufficient to stop the development and use of genetic enhancement technologies. We contend that the inevitability of the technologies results from a particular guiding worldview of humans as masters of the human evolutionary future, and conclude that recognising this worldview points to new directions for ethical thinking about genetic enhancement technologies. PMID:15168695

  13. Enhancing Rotational Diffusion Using Oscillatory Shear

    NASA Astrophysics Data System (ADS)

    Leahy, Brian D.; Cheng, Xiang; Ong, Desmond C.; Liddell-Watson, Chekesha; Cohen, Itai

    2013-05-01

    Taylor dispersion—shear-induced enhancement of translational diffusion—is an important phenomenon with applications ranging from pharmacology to geology. Through experiments and simulations, we show that rotational diffusion is also enhanced for anisotropic particles in oscillatory shear. This enhancement arises from variations in the particle’s rotation (Jeffery orbit) and depends on the strain amplitude, rate, and particle aspect ratio in a manner that is distinct from the translational diffusion. This separate tunability of translational and rotational diffusion opens the door to new techniques for controlling positions and orientations of suspended anisotropic colloids.

  14. Natural and enhanced attenuation of metals

    SciTech Connect

    Rouse, J.V.; Pyrih, R.Z.

    1996-12-31

    The ability of natural earthen materials to attenuate the movement of contamination can be quantified in relatively simple geochemical experiments. In addition, the ability of subsurface material to attenuate potential contaminants can be enhanced through modifications to geochemical parameters such as pH or redox conditions. Such enhanced geochemical attenuation has been demonstrated at a number of sites to be a cost-effective alternative to conventional pump and treat operations. This paper describes the natural attenuation reactions which occur in the subsurface, and the way to quantify such attenuation. It also introduces the concept of enhanced geochemical attenuation, wherein naturally-occurring geochemical reactions can be used to achieve in situ fixation. The paper presents examples where such natural and enhanced attenuation have been implemented as a part of an overall remedy.

  15. Surfactant and process for enhanced oil recovery

    SciTech Connect

    Stapp, P. R.

    1984-12-11

    A novel surfactant is formed by reacting maleic anhydride with either a petroleum sulfonate or an alkaryl sulfonate. A surfactant system containing the above surfactant useful in enhanced oil recovery processes is also provided.

  16. How emotion enhances the feeling of remembering.

    PubMed

    Sharot, Tali; Delgado, Mauricio R; Phelps, Elizabeth A

    2004-12-01

    Studies examining memories of arousing 'real-life' events show that emotion heightens the feeling of remembering, without necessarily enhancing the objective accuracy of the memories. We measured brain activity associated with the feeling of remembering emotional and neutral photos. Subjects indicated whether recognition was accompanied by a recollection of details about the study episode ('remember') or not ('know'). 'Remember' judgments were boosted for emotional photos, but accuracy did not differ. For neutral photos, 'remember' judgments were related to enhanced activity in the parahippocampal cortex, previously related to recognition of visual details, which one might expect to supply the retrieval clues for a 'remember' judgment. In contrast, 'remember' judgments for emotional photos were associated with enhanced activity in the amygdala, suggesting that subjects rely on arousal and perceptual fluency to evaluate these memories. For the first time, we identify the neural mechanisms underlying the enhanced feeling of remembering for emotional events.

  17. Development: facial makeup enhancing our looks.

    PubMed

    Rohner, Nicolas; Tschopp, Patrick; Tabin, Cliff

    2014-01-01

    A recent study in mice deciphers the complex genetic regulatory network underlying the morphogenesis of the face. The enhancer landscape underlying craniofacial development provides multiple entry points to understand what makes up the face, in natural variation or pathological conditions.

  18. An Evaluation of Enhanced Geothermal Systems Technology

    SciTech Connect

    Jelacic, Allan; Fortuna, Raymond; LaSala, Raymond; Nathwani, Jay; Nix, Gerald; Visser, Charles; Green, Bruce; Renner, Joel; Blankenship, Douglas; Kennedy, Mack; Bruton, Carol

    2008-04-01

    This 2008 document presents the results of an eight-month study by the Department of Energy (DOE) and its support staff at the national laboratories concerning the technological requirements to commercialize a new geothermal technology, Enhanced Geothermal Systems (EGS).

  19. Joint enhancement of multichannel SAR data

    NASA Astrophysics Data System (ADS)

    Ramakrishnan, Naveen; Ertin, Emre; Moses, Randolph L.

    2007-04-01

    In this paper we consider the problem of joint enhancement of multichannel Synthetic Aperture Radar (SAR) data. Previous work by Cetin and Karl introduced nonquadratic regularization methods for image enhancement using sparsity enforcing penalty terms. For multichannel data, independent enhancement of each channel is shown to degrade the relative phase information across channels that is useful for 3D reconstruction. We thus propose a method for joint enhancement of multichannel SAR data with joint sparsity constraints. We develop both a gradient-based and a Lagrange-Newton-based method for solving the joint reconstruction problem, and demonstrate the performance of the proposed methods on IFSAR height extraction problem from multi-elevation data.

  20. CLASSICAL CEPHEIDS REQUIRE ENHANCED MASS LOSS

    SciTech Connect

    Neilson, Hilding R.; Langer, Norbert; Izzard, Robert; Engle, Scott G.; Guinan, Ed

    2012-11-20

    Measurements of rates of period change of Classical Cepheids probe stellar physics and evolution. Additionally, better understanding of Cepheid structure and evolution provides greater insight into their use as standard candles and tools for measuring the Hubble constant. Our recent study of the period change of the nearest Cepheid, Polaris, suggested that it is undergoing enhanced mass loss when compared to canonical stellar evolution model predictions. In this work, we expand the analysis to rates of period change measured for about 200 Galactic Cepheids and compare them to population synthesis models of Cepheids including convective core overshooting and enhanced mass loss. Rates of period change predicted from stellar evolution models without mass loss do not agree with observed rates, whereas including enhanced mass loss yields predicted rates in better agreement with observations. This is the first evidence that enhanced mass loss as suggested previously for Polaris and {delta} Cephei must be a ubiquitous property of Classical Cepheids.

  1. Visualization of Enhancer-Derived Noncoding RNA.

    PubMed

    Shibayama, Youtaro; Fanucchi, Stephanie; Mhlanga, Musa M

    2017-01-01

    Enhancers are principal regulators that allow spatiotemporal tissue-specific control of gene expression. While mounting evidence suggests that enhancer-derived long noncoding RNAs (long ncRNAs), including enhancer RNAs (eRNAs), are an important component of enhancer function, their expression has not been broadly analyzed at a single cell level via imaging techniques. This protocol describes a method to image eRNA in single cells by in situ hybridization followed by tyramide signal amplification (TSA). The procedure can be multiplexed to simultaneously visualize both eRNA and protein-coding transcript at the site of transcriptional elongation, thereby permitting analysis of dynamics between the two transcript species in single cells. Our approach is not limited to eRNAs, but can be implemented on other transcripts.

  2. Fluorescence Enhancements on Silver Colloid Coated Surfaces

    PubMed Central

    Lukomska, Joanna; Malicka, Joanna; Gryczynski, Ignacy; Lakowicz, Joseph R.

    2009-01-01

    We observed a strong, more than 16-fold, enhancement of Texas Red-labeled BSA fluorescence emission when deposited on silver colloid coated surfaces (SCCS). The same labeled protein deposited on silver island films (SIFs) showed an approximate 8-fold fluorescence enhancement. The lifetimes of Texas Red-BSA fluorescence are significantly shorter on silvered surfaces than on uncoated quartz substrate indicating a strong change in radiative decay rate of the dyes. We also observed a 36-fold increased brightness of overlabeled fluorescein-HSA deposited on silver colloid coated surface. Stronger enhancement observed for overlabeled Fl-HSA protein indicates that presence of silver particles partially decreased self-quenching. Our results indicate that surfaces coated with silver colloids are valuable substrates for metal-enhanced fluorescence. PMID:15617384

  3. Non-pharmacological Approaches to Cognitive Enhancement.

    PubMed

    Kelly, Áine M

    2015-01-01

    Pharmaceuticals and medical devices hold the promise of enhancing brain function, not only of those suffering from neurodevelopmental, neuropsychiatric or neurodegenerative illnesses, but also of healthy individuals. However, a number of lifestyle interventions are proven cognitive enhancers, improving attention, problem solving, reasoning, learning and memory or even mood. Several of these interventions, such as physical exercise, cognitive, mental and social stimulation, may be described as environmental enrichments of varying types. Use of these non-pharmacological cognitive enhancers circumvents some of the ethical considerations associated with pharmaceutical or technological cognitive enhancement, being low in cost, available to the general population and presenting low risk to health and well-being. In this chapter, there will be particular focus on the effects of exercise and enrichment on learning and memory and the evidence supporting their efficacy in humans and in animal models will be described.

  4. Next generation enhanced vision system processing

    NASA Astrophysics Data System (ADS)

    Bernhardt, M.; Cowell, C.; Riley, T.

    2008-04-01

    The use of multiple, high sensitivity sensors can be usefully exploited within military airborne enhanced vision systems (EVS) to provide enhanced situational awareness. To realise such benefits, the imagery from the discrete sensors must be accurately combined and enhanced prior to image presentation to the aircrew. Furthermore, great care must be taken to not introduce artefacts or false information through the image processing routines. This paper outlines developments made to a specific system that uses three collocated low light level cameras. As well as seamlessly merging the individual images, sophisticated processing techniques are used to enhance image quality as well as to remove optical and sensor artefacts such as vignetting and CCD charge smear. The techniques have been designed and tested to be robust across a wide range of scenarios and lighting conditions, and the results presented here highlight the increased performance of the new algorithms over standard EVS image processing techniques.

  5. Behavioral Therapy, Incentives Enhance Addiction Treatment

    MedlinePlus

    ... Issue Past Issues Research News From NIH Behavioral Therapy, Incentives Enhance Addiction Treatment Past Issues / Summer 2006 Table of Contents For ... their addiction to marijuana can benefit from a treatment program that combines motivational incentives with cognitive-behavioral ...

  6. ENHANCED BIODEGRADATION THROUGH IN-SITU AERATION

    EPA Science Inventory

    This presentation provided an overview of enhanced aerobic bioremediation using in-situ aeration or venting. The following topics were covered: (1) Basic discussion on biodegradation and respiration testing; (2) Basic discussion on volatilization, rate-limited mass transport, an...

  7. Enhancement of radiation effects by acyclovir

    SciTech Connect

    Sougawa, M.; Akagi, K.; Murata, T.; Kawasaki, S.; Sawada, S.; Yoshii, G.; Tanaka, Y.

    1986-08-01

    Acyclovir (ACV), a new antiviral drug, was used to investigate its effect of radiosensitivity in tumors in vivo. In in vivo experiments with Sarcoma-180 transplanted into the ICR mouse and FM3A transplanted into the C/sub 3/H mouse, ACV enhanced the radiosensitivity of both tumors. In S-180, radiation effects were enhanced by treatment with 100 mg/kg of ACV from 30 min before to 60 min after irradiation. In S-180 treated by 400 mg/kg of ACV, the enhancement ratio was approximately 2.0, as evaluated by the growth delay method. In the FM3A tumor treated by 20 mg/kg of ACV, the enhancement ratio was approximately 1.3, as evaluated by tumor cure (TCD50 assay). ACV is already clinically used as an antiviral drug. Its ability to radiosensitize tumors could therefore have clinical potential when combined with radiotherapy.

  8. Visualization of Enhancer-Derived Noncoding RNA.

    PubMed

    Shibayama, Youtaro; Fanucchi, Stephanie; Mhlanga, Musa M

    2017-01-01

    Enhancers are principal regulators that allow spatiotemporal tissue-specific control of gene expression. While mounting evidence suggests that enhancer-derived long noncoding RNAs (long ncRNAs), including enhancer RNAs (eRNAs), are an important component of enhancer function, their expression has not been broadly analyzed at a single cell level via imaging techniques. This protocol describes a method to image eRNA in single cells by in situ hybridization followed by tyramide signal amplification (TSA). The procedure can be multiplexed to simultaneously visualize both eRNA and protein-coding transcript at the site of transcriptional elongation, thereby permitting analysis of dynamics between the two transcript species in single cells. Our approach is not limited to eRNAs, but can be implemented on other transcripts. PMID:27662867

  9. Salmon River Habitat Enhancement. 1990 Annual Report

    SciTech Connect

    Rowe, Mike

    1991-12-01

    The annual report contains three individual subproject sections detailing tribal fisheries work completed during the summer and fall of 1990. Subproject I contains summaries of evaluation/monitoring efforts associated with the Bear Valley Creek, Idaho enhancement project. Subproject II contains an evaluation of the Yankee Fork of the Salmon River habitat enhancement project. Subproject III concerns the East Fork of the Salmon River, Idaho.

  10. Recent Progress on Plasmon-Enhanced Fluorescence

    NASA Astrophysics Data System (ADS)

    Dong, Jun; Zhang, Zhenglong; Zheng, Hairong; Sun, Mentao

    2015-12-01

    The optically generated collective electron density waves on metal-dielectric boundaries known as surface plasmons have been of great scientific interest since their discovery. Being electromagnetic waves on gold or silver nanoparticle's surface, localised surface plasmons (LSP) can strongly enhance the electromagnetic field. These strong electromagnetic fields near the metal surfaces have been used in various applications like surface enhanced spectroscopy (SES), plasmonic lithography, plasmonic trapping of particles, and plasmonic catalysis. Resonant coupling of LSPs to fluorophore can strongly enhance the emission intensity, the angular distribution, and the polarisation of the emitted radiation and even the speed of radiative decay, which is so-called plasmon enhanced fluorescence (PEF). As a result, more and more reports on surface-enhanced fluorescence have appeared, such as SPASER-s, plasmon assisted lasing, single molecule fluorescence measurements, surface plasmoncoupled emission (SPCE) in biological sensing, optical orbit designs etc. In this review, we focus on recent advanced reports on plasmon-enhanced fluorescence (PEF). First, the mechanism of PEF and early results of enhanced fluorescence observed by metal nanostructure will be introduced. Then, the enhanced substrates, including periodical and nonperiodical nanostructure, will be discussed and the most important factor of the spacer between molecule and surface and wavelength dependence on PEF is demonstrated. Finally, the recent progress of tipenhanced fluorescence and PEF from the rare-earth doped up-conversion (UC) and down-conversion (DC) nanoparticles (NPs) are also commented upon. This review provides an introduction to fundamentals of PEF, illustrates the current progress in the design of metallic nanostructures for efficient fluorescence signal amplification that utilises propagating and localised surface plasmons.

  11. Biochemically enhanced oil recovery and oil treatment

    DOEpatents

    Premuzic, E.T.; Lin, M.

    1994-03-29

    This invention relates to the preparation of new, modified organisms, through challenge growth processes, that are viable in the extreme temperature, pressure and pH conditions and salt concentrations of an oil reservoir and that are suitable for use in microbial enhanced oil recovery. The modified microorganisms of the present invention are used to enhance oil recovery and remove sulfur compounds and metals from the crude oil. 62 figures.

  12. Tunable spectral enhancement of fiber supercontinuum

    NASA Astrophysics Data System (ADS)

    Yeom, Dong-Il; Bolger, Jeremy A.; Marshall, Graham D.; Austin, Dane R.; Kuhlmey, Boris T.; Withford, Michael J.; de Sterke, C. Martijn; Eggleton, Benjamin J.

    2007-06-01

    We demonstrate tunable spectral enhancement of the supercontinuum generated in a microstructured fiber with a fiber long-period grating. The long-period grating leads to phase distortion and loss that, with subsequent high-intensity propagation in uniform fiber, evolves into an enhancement around the grating's resonant wavelengths. Wavelength tunability is achieved by varying the temperature or the ambient refractive index, and the spectral peak can be extinguished by immersing the grating in index-matching oil.

  13. Tunable spectral enhancement of fiber supercontinuum.

    PubMed

    Yeom, Dong-Il; Bolger, Jeremy A; Marshall, Graham D; Austin, Dane R; Kuhlmey, Boris T; Withford, Michael J; Martijn de Sterke, C; Eggleton, Benjamin J

    2007-06-15

    We demonstrate tunable spectral enhancement of the supercontinuum generated in a microstructured fiber with a fiber long-period grating. The long-period grating leads to phase distortion and loss that, with subsequent high-intensity propagation in uniform fiber, evolves into an enhancement around the grating's resonant wavelengths. Wavelength tunability is achieved by varying the temperature or the ambient refractive index, and the spectral peak can be extinguished by immersing the grating in index-matching oil.

  14. The Geometry of Enhancement in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2011-01-01

    In linear multiple regression, "enhancement" is said to occur when R[superscript 2] = b[prime]r greater than r[prime]r, where b is a p x 1 vector of standardized regression coefficients and r is a p x 1 vector of correlations between a criterion y and a set of standardized regressors, x. When p = 1 then b [is congruent to] r and enhancement cannot…

  15. Cloned Hemoglobin Genes Enhance Growth Of Cells

    NASA Technical Reports Server (NTRS)

    Khosla, Chaitan; Bailey, James E.

    1991-01-01

    Experiments show that portable deoxyribonucleic acid (DNA) sequences incorporated into host cells make them produce hemoglobins - oxygen-binding proteins essential to function of red blood cells. Method useful in several biotechnological applications. One, enhancement of growth of cells at higher densities. Another, production of hemoglobin to enhance supplies of oxygen in cells, for use in chemical reactions requiring oxygen, as additive to serum to increase transport of oxygen, and for binding and separating oxygen from mixtures of gases.

  16. Ion acceleration enhanced by target ablation

    SciTech Connect

    Zhao, S.; Lin, C. Wang, H. Y.; Lu, H. Y.; He, X. T.; Yan, X. Q.; Chen, J. E.; Cowan, T. E.

    2015-07-15

    Laser proton acceleration can be enhanced by using target ablation, due to the energetic electrons generated in the ablation preplasma. When the ablation pulse matches main pulse, the enhancement gets optimized because the electrons' energy density is highest. A scaling law between the ablation pulse and main pulse is confirmed by the simulation, showing that for given CPA pulse and target, proton energy improvement can be achieved several times by adjusting the target ablation.

  17. Recent Enhancements to the National Transonic Facility

    NASA Technical Reports Server (NTRS)

    Kilgore, W. A.; Balakrishna, S.; Bobbitt, C. W.; Underwood, P.

    2003-01-01

    The National Transonic Facility continues to make enhancements to provide quality data in a safe, efficient and cost effective method for aerodynamic ground testing. Recent enhancements discussed in this paper include the restoration of reliability and improved performance of the heat exchanger systems resulting in the expansion of the NTF air operations envelope. Additionally, results are presented from a continued effort to reduce model dynamics through the use of a new stiffer balance and sting

  18. Recent Enhancements to the National Transonic Facility

    NASA Technical Reports Server (NTRS)

    Kilgore, W. A.; Balakrishna, S.; Bobbitt, C. W.; Underwood, P.

    2003-01-01

    The National Transonic Facility continues to make enhancements to provide quality data in a safe, efficient and cost effective method for aerodynamic ground testing. Recent enhancements discussed in this paper include the restoration of reliability and improved performance of the heat exchanger systems resulting in the expansion of the NTF air operations envelope. Additionally, results are presented from a continued effort to reduce model dynamics through the use of a new stiffer balance and sting.

  19. Biochemically enhanced oil recovery and oil treatment

    DOEpatents

    Premuzic, Eugene T.; Lin, Mow

    1994-01-01

    This invention relates to the preparation of new, modified organisms, through challenge growth processes, that are viable in the extreme temperature, pressure and pH conditions and salt concentrations of an oil reservoir and that are suitable for use in microbial enhanced oil recovery. The modified microorganisms of the present invention are used to enhance oil recovery and remove sulfur compounds and metals from the crude oil.

  20. Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation.

    PubMed

    Hsieh, Chen-Lin; Fei, Teng; Chen, Yiwen; Li, Tiantian; Gao, Yanfei; Wang, Xiaodong; Sun, Tong; Sweeney, Christopher J; Lee, Gwo-Shu Mary; Chen, Shaoyong; Balk, Steven P; Liu, Xiaole Shirley; Brown, Myles; Kantoff, Philip W

    2014-05-20

    The androgen receptor (AR) is a key factor that regulates the behavior and fate of prostate cancer cells. The AR-regulated network is activated when AR binds enhancer elements and modulates specific enhancer-promoter looping. Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e. Here, we demonstrate that KLK3e facilitates the spatial interaction of the KLK3 enhancer and the KLK2 promoter and enhances long-distance KLK2 transcriptional activation. KLK3e carries the core enhancer element derived from the androgen response element III (ARE III), which is required for the interaction of AR and Mediator 1 (Med1). Furthermore, we show that KLK3e processes RNA-dependent enhancer activity depending on the integrity of core enhancer elements. The transcription of KLK3e was detectable and its expression is significantly correlated with KLK3 (R(2) = 0.6213, P < 5 × 10(-11)) and KLK2 (R(2) = 0.5893, P < 5 × 10(-10)) in human prostate tissues. Interestingly, RNAi silencing of KLK3e resulted in a modest negative effect on prostate cancer cell proliferation. Accordingly, we report that an androgen-induced eRNA scaffolds the AR-associated protein complex that modulates chromosomal architecture and selectively enhances AR-dependent gene expression. PMID:24778216

  1. [Doping in sport and enhancement medicine].

    PubMed

    Missa, Jean-Noël

    2011-01-01

    The reason that gives doping in sport a deeper philosophical and ethical dimension is the emergence of a new medical paradigm: enhancement medicine. The question of enhancing performance in sport has become part of a broader societal debate on human enhancement. The gradual blurriness of the boarders between therapeutic medicine and enhancement medicine constitutes the most spectacular and the most troublesome form of these modifications. In the contemporary biomedicine, the new medicines and technologies can be used not only to cure the patients but also to enhance human capacities. This evolution represents a paradigmatic change in the medical practice: it is not the mere restoration of health which is expected anymore, nor the promotion of health. What is required is the improvement of performance and the perfectibility of the human being, including in the field of sport. Competitive sport could become the main laboratory of enhancement medicine. The intersection of science and sport raises fundamental philosophical, ethical and policy issues that cannot be answered easily. The prohibition and the war on doping is not the only solution. PMID:22238910

  2. Enhancement of Cellulose Degradation by Cattle Saliva

    PubMed Central

    Seki, Yasutaka; Kikuchi, Yukiko; Kimura, Yoshihiro; Yoshimoto, Ryo; Takahashi, Masatoshi; Aburai, Kenichi; Kanai, Yoshihiro; Ruike, Tatsushi; Iwabata, Kazuki; Sugawara, Fumio; Sakai, Hideki; Abe, Masahiko; Sakaguchi, Kengo

    2015-01-01

    Saccharification of cellulose is a promising technique for producing alternative source of energy. However, the efficiency of conversion of cellulose into soluble sugar using any currently available methodology is too low for industrial application. Many additives, such as surfactants, have been shown to enhance the efficiency of cellulose-to-sugar conversion. In this study, we have examined first whether cattle saliva, as an additive, would enhance the cellulase-catalyzed hydrolysis of cellulose, and subsequently elucidated the mechanism by which cattle saliva enhanced this conversion. Although cattle saliva, by itself, did not degrade cellulose, it enhanced the cellulase-catalyzed degradation of cellulose. Thus, the amount of reducing sugar produced increased approximately 2.9-fold by the addition of cattle saliva. We also found that non-enzymatic proteins, which were present in cattle saliva, were responsible for causing the enhancement effect. Third, the mechanism of cattle saliva mediated enhancement of cellulase activity was probably similar to that of the canonical surfactants. Cattle saliva is available in large amounts easily and cheaply, and it can be used without further purification. Thus, cattle saliva could be a promising additive for efficient saccharification of cellulose on an industrial scale. PMID:26402242

  3. Evolution of transcriptional enhancers and animal diversity

    PubMed Central

    Rubinstein, Marcelo; de Souza, Flávio S. J.

    2013-01-01

    Deciphering the genetic bases that drive animal diversity is one of the major challenges of modern biology. Although four decades ago it was proposed that animal evolution was mainly driven by changes in cis-regulatory DNA elements controlling gene expression rather than in protein-coding sequences, only now are powerful bioinformatics and experimental approaches available to accelerate studies into how the evolution of transcriptional enhancers contributes to novel forms and functions. In the introduction to this Theme Issue, we start by defining the general properties of transcriptional enhancers, such as modularity and the coexistence of tight sequence conservation with transcription factor-binding site shuffling as different mechanisms that maintain the enhancer grammar over evolutionary time. We discuss past and current methods used to identify cell-type-specific enhancers and provide examples of how enhancers originate de novo, change and are lost in particular lineages. We then focus in the central part of this Theme Issue on analysing examples of how the molecular evolution of enhancers may change form and function. Throughout this introduction, we present the main findings of the articles, reviews and perspectives contributed to this Theme Issue that together illustrate some of the great advances and current frontiers in the field. PMID:24218630

  4. Enhancement of Cellulose Degradation by Cattle Saliva.

    PubMed

    Seki, Yasutaka; Kikuchi, Yukiko; Kimura, Yoshihiro; Yoshimoto, Ryo; Takahashi, Masatoshi; Aburai, Kenichi; Kanai, Yoshihiro; Ruike, Tatsushi; Iwabata, Kazuki; Sugawara, Fumio; Sakai, Hideki; Abe, Masahiko; Sakaguchi, Kengo

    2015-01-01

    Saccharification of cellulose is a promising technique for producing alternative source of energy. However, the efficiency of conversion of cellulose into soluble sugar using any currently available methodology is too low for industrial application. Many additives, such as surfactants, have been shown to enhance the efficiency of cellulose-to-sugar conversion. In this study, we have examined first whether cattle saliva, as an additive, would enhance the cellulase-catalyzed hydrolysis of cellulose, and subsequently elucidated the mechanism by which cattle saliva enhanced this conversion. Although cattle saliva, by itself, did not degrade cellulose, it enhanced the cellulase-catalyzed degradation of cellulose. Thus, the amount of reducing sugar produced increased approximately 2.9-fold by the addition of cattle saliva. We also found that non-enzymatic proteins, which were present in cattle saliva, were responsible for causing the enhancement effect. Third, the mechanism of cattle saliva mediated enhancement of cellulase activity was probably similar to that of the canonical surfactants. Cattle saliva is available in large amounts easily and cheaply, and it can be used without further purification. Thus, cattle saliva could be a promising additive for efficient saccharification of cellulose on an industrial scale.

  5. [Doping in sport and enhancement medicine].

    PubMed

    Missa, Jean-Noël

    2011-01-01

    The reason that gives doping in sport a deeper philosophical and ethical dimension is the emergence of a new medical paradigm: enhancement medicine. The question of enhancing performance in sport has become part of a broader societal debate on human enhancement. The gradual blurriness of the boarders between therapeutic medicine and enhancement medicine constitutes the most spectacular and the most troublesome form of these modifications. In the contemporary biomedicine, the new medicines and technologies can be used not only to cure the patients but also to enhance human capacities. This evolution represents a paradigmatic change in the medical practice: it is not the mere restoration of health which is expected anymore, nor the promotion of health. What is required is the improvement of performance and the perfectibility of the human being, including in the field of sport. Competitive sport could become the main laboratory of enhancement medicine. The intersection of science and sport raises fundamental philosophical, ethical and policy issues that cannot be answered easily. The prohibition and the war on doping is not the only solution.

  6. Evolution of transcriptional enhancers and animal diversity.

    PubMed

    Rubinstein, Marcelo; de Souza, Flávio S J

    2013-12-19

    Deciphering the genetic bases that drive animal diversity is one of the major challenges of modern biology. Although four decades ago it was proposed that animal evolution was mainly driven by changes in cis-regulatory DNA elements controlling gene expression rather than in protein-coding sequences, only now are powerful bioinformatics and experimental approaches available to accelerate studies into how the evolution of transcriptional enhancers contributes to novel forms and functions. In the introduction to this Theme Issue, we start by defining the general properties of transcriptional enhancers, such as modularity and the coexistence of tight sequence conservation with transcription factor-binding site shuffling as different mechanisms that maintain the enhancer grammar over evolutionary time. We discuss past and current methods used to identify cell-type-specific enhancers and provide examples of how enhancers originate de novo, change and are lost in particular lineages. We then focus in the central part of this Theme Issue on analysing examples of how the molecular evolution of enhancers may change form and function. Throughout this introduction, we present the main findings of the articles, reviews and perspectives contributed to this Theme Issue that together illustrate some of the great advances and current frontiers in the field.

  7. Plasmon-Enhanced Optical Sensors: A Review

    PubMed Central

    Li, Ming; Cushing, Scott K

    2014-01-01

    Surface plasmon resonance (SPR) has found extensive applications in chemi-sensors and biosensors. Plasmons play different roles in different types of optical sensors. SPR transduces a signal in a colorimetric sensor through shifts in the spectral position and intensity in response to external stimuli. SPR can also concentrate the incident electromagnetic field in a nanostructure, modulating fluorescence emission and enabling plasmon-enhanced fluorescence to be used for ultrasensitive detection. Furthermore, plasmons have been extensively used for amplifying a Raman signal in a surface-enhanced Raman scattering sensor. This paper presents a review of recent research progress in plasmon-enhanced optical sensing, giving an emphasis on the physical basis of plasmon-enhanced sensors and how these principles guide the design of sensors. In particular, this paper discusses the design strategies for nanomaterials and nanostructures to plasmonically enhance optical sensing signals, also highlighting the applications of plasmon-enhanced optical sensors in health care, homeland security, food safety and environmental monitoring. PMID:25365823

  8. Does overfeeding enhance genotype effects on liver ability for lipogenesis and lipid secretion in ducks?

    PubMed

    Chartrin, Pascal; Bernadet, Marie-Dominique; Guy, Gérard; Mourot, Jacques; Hocquette, Jean-François; Rideau, Nicole; Duclos, Michel Jacques; Baéza, Elisabeth

    2006-11-01

    We evaluated the effects of genotype (Muscovy, Pekin and their crossbreed hinny and mule ducks) and feeding levels (overfeeding between 12 and 14 weeks of age vs ad libitum feeding) on liver ability for lipogenesis and lipid secretion in ducks. Samples of liver and blood were collected at 14 weeks of age from 8 birds per group. Plasma levels of insulin was considerably increased in overfed ducks (1.9-fold), stimulating the hepatic activity of the main enzymes involved in lipogenesis from glucose (glucokinase, GK, glucose-6-phosphate dehydrogenase, G6PDH, malic enzyme, ME, acetyl CoA carboxylase, ACX), while cytochrome-c oxidase (COX) activity, indicating overall oxidation ability of energy-yielding substrates, remained unchanged. Plasma levels of triglycerides, phospholipids and total cholesterol were therefore increased (1.9, 3.7, 1.6 and 1.6-fold, respectively). Glycaemia also significantly increased (+8%). Pekin ducks exhibited higher levels of GK and G6PDH activity in the liver than Muscovy ducks, suggesting a greater ability to use glucose consistent with their lower glycaemia. Muscovy ducks had greater ACX activity, suggesting greater ability to synthesise lipids. However, plasma lipid levels were much higher in Pekin ducks than in Muscovy ducks, suggesting a greater ability to export lipids from the liver. Values for the different criteria measured in this study were intermediate or similar in hinny and mule ducks to those of parental species. The high values for GK, G6PDH, ME and ACX activity in hybrid ducks enabled them to produce heavy fatty livers with the same chemical and lipid composition as Muscovy ducks and characterised by high amounts of triglycerides (around 96% of total lipids), and saturated and mono-unsaturated fatty acids.

  9. Metal enhanced fluorescence with gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Mattingly, Shaina LaRissa Strating

    A novel hybrid nanocomposite of Au nanoparticle-modified silicon nanowire was developed for surface enhanced fluorescence applications. The designed nanocomposite contained a silicon nanowire, gold nanoparticles and a silica layer doped with dye molecules. The hybrid nanomaterial was characterized using scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), fluorescence measurements, Fourier transform infrared (FT-IR) spectroscopy, and energy-dispersive X-ray spectroscopy (EDS). The results showed that the gold nanoparticles were uniformly adhered on the silicon nanowires and covered by a thin silica layer. The nanostructure exhibited strong capacity for surface enhanced fluorescence. Different enhancement factors were obtained by changing synthetic conditions. The second goal of the project was to determine if the shape of gold nanoparticles affects the extent of its fluorescence enhancement under constant external factors. Two shapes of gold nanoparticles were synthesized and characterized by SEM, STEM, zeta potential and absorbance measurements. Then they were coated with fluorescent dye-doped silica and the fluorescence intensity was measured and compared to the pure fluorescent dye. Gold nanorods enhanced fluorescence more than gold nanostars and that the fluorescent dye Alexafluor 700 showed a greater fluorescence intensity change in the presence of nanoparticles than methylene blue.

  10. A Framework for Reproducible Latent Fingerprint Enhancements

    PubMed Central

    Carasso, Alfred S.

    2014-01-01

    Photoshop processing1 of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology. PMID:26601028

  11. Videographic enhancement of GRASS imagery: Recent advances

    SciTech Connect

    Sullivan, R.G.

    1992-06-01

    The Geographic Resource Analysis Support System (GRASS), a geographic information system, has been fielded at approximately 50 US Army training installations as a land-management decision-making tool. Use of the GRASS geographic information system involves the production of numerous digital maps of environmental parameters, such as elevation, soils, hydrography, etc. A recently emerging technology called computer videographics can be used to graphically enhance GRASS images, thereby creating new ways to visualize GRASS analysis results. The project described in this report explored the enhancement of GRASS images through the use of videographic technology. General image quality of videographically enhanced GRASS images was improved through the use of high-resolution imagery and improved software. Several new types of geographic data visualizations were developed, including three-dimensional shaded-relief maps of GRASS data, overlay of GRASS images with satellite images, and integration of computer-aided-design imagery with GRASS images. GRASS images were successfully enhanced using Macintosh hardware and software, rather than the DOS-based equipment used previously. Images scanned with a document scanner were incorporated into GRASS imagery, and enhanced images were output in an S-VHS high-resolution video format.

  12. A Framework for Reproducible Latent Fingerprint Enhancements.

    PubMed

    Carasso, Alfred S

    2014-01-01

    Photoshop processing of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology.

  13. Enhancing cognitive function across the life span.

    PubMed

    Korol, Donna L

    2002-04-01

    Glucose administration regulates many neural and behavioral processes in rodents, including learning and memory. Given the important role of glucose in brain function and the safety of glucose as a treatment, we have investigated the effects of glucose administration in humans of different ages. In previous work, we examined the effects of early-morning glucose consumption on cognitive functions in elderly individuals. In this population, glucose enhanced performance on specific measures, particularly on those tasks where mild age-related deficits appear (e.g., verbal declarative memory). Interestingly, glucose failed to enhance cognitive functions in young adults. Our recent work has examined three issues related to glucose enhancement of cognition: First, is glucose effective only in reversing impairments or can it also facilitate performance in highly functioning individuals? Second, are glucose effects dependent either on time of day or on interactions with other meals? Third, are typical breakfast foods as effective as glucose in enhancing cognitive performance? Our findings suggest that glucose can improve memory in highly functioning populations as it does in populations with deficits. However, enhancement by glucose may require sufficient levels of task difficulty and of blood glucose. In addition, like glucose, early morning consumption of cereal can improve performance on some cognitive tests. These results have important implications for the nature of glucose facilitation of memory and for the role of dietary factors in performance of many daily activities. PMID:11976194

  14. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    PubMed

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

    2015-07-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied. PMID:26393186

  15. Nanodiamond nanofluids for enhanced thermal conductivity.

    PubMed

    Branson, Blake T; Beauchamp, Paul S; Beam, Jeremiah C; Lukehart, Charles M; Davidson, Jim L

    2013-04-23

    Deaggregation of oxidized ultradispersed diamond (UDD) in dimethylsulfoxide followed by reaction with glycidol monomer, purification via aqueous dialysis, and dispersion in ethylene glycol (EG) base fluid affords nanodiamond (ND)-poly(glycidol) polymer brush:EG nanofluids exhibiting 12% thermal conductivity enhancement at a ND loading of 0.9 vol %. Deaggregation of UDD in the presence of oleic acid/octane followed by dispersion in light mineral oil and evaporative removal of octane gives ND·oleic acid:mineral oil dispersions exhibiting 11% thermal conductivity enhancement at a ND loading of 1.9 vol %. Average particle sizes of ND additives, determined by dynamic light scattering, are, respectively, ca. 11 nm (in H2O) and 18 nm (in toluene). Observed thermal conductivity enhancements outperform enhancement effects calculated using Maxwell's effective medium approximation by 2- to 4-fold. Covalent ND surface modification gives 2-fold greater thermal conductivity enhancement than ND surface modification via hydrogen-bonding interactions at similar concentrations. Stable, static ND:mineral oil dispersions are reported for the first time. PMID:23488739

  16. Contrast Enhancement by Nonlinear Diffusion Filtering.

    PubMed

    Liang, Zhetong; Liu, Weijian; Yao, Ruohe

    2016-02-01

    To enhance the visual quality of an image that is degraded by uneven light, an effective method is to estimate the illumination component and compress it. Some previous methods have either defects of halo artifacts or contrast loss in the enhanced image due to incorrect estimation. In this paper, we discuss this problem and propose a novel method to estimate the illumination. The illumination is obtained by iteratively solving a nonlinear diffusion equation. During the diffusion process, surround suppression is embedded in the conductance function to specially enhance the diffusive strength in textural areas of the image. The proposed estimation method has the following two merits: 1) the boundary areas are preserved in the illumination, and thus halo artifacts are prevented and 2) the textural details are preserved in the reflectance to not suffer from illumination compression, which contributes to the contrast enhancement in the result. Experimental results show that the proposed algorithm achieves excellent performance in artifact removal and local contrast enhancement. PMID:26685234

  17. Enhancing skeletal features in digitally reconstructed radiographs

    NASA Astrophysics Data System (ADS)

    Fu, Dongshan; Kuduvalli, Gopinath

    2006-03-01

    Generation of digitally reconstructed radiographs (DRR) is a critical part of 2D-3D image registration that is utilized in patient position alignment for image-guided radiotherapy and radiosurgery. The DRRs are generated from a pre-operative CT scan and used as the references to match the X-ray images for determining the change of patient position. Skeletal structures are the primary image features to facilitate the registration between the DRR and X-ray images. In this paper, we present a method to enhance skeletal features of spinal regions in DRRs. The attenuation coefficient at each voxel is first calculated by applying an exponential transformation of the original attenuation coefficient in the CT scan. This is a preprocessing step that is performed prior to DRR generation. The DRR is then generated by integrating the newly calculated attenuation coefficients along the ray that connects the X-ray source and the pixel in the DRR. Finally, the DRR is further enhanced using a weighted top-hat filter. During the entire process, because there is no original CT information lost, even the small skeletal features contributed by low intensity part of CT data are preserved in the enhanced DRRs. Experiments on clinical data were conducted to compare the image quality of DRRs with and without enhancement. The results showed that the image contrast of skeletal features in the enhanced DRRs is significantly improved. This method has potential to be applied for more accurate and robust 2D-3D image registration.

  18. Non Pharmacological Cognitive Enhancers – Current Perspectives

    PubMed Central

    Kumar, Kuldip; Anand, Kuljeet Singh

    2015-01-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms ‘non pharmacological and cognitive’ in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied. PMID:26393186

  19. Real-time enhanced vision system

    NASA Astrophysics Data System (ADS)

    Hines, Glenn D.; Rahman, Zia-ur; Jobson, Daniel J.; Woodell, Glenn A.; Harrah, Steven D.

    2005-05-01

    Flying in poor visibility conditions, such as rain, snow, fog or haze, is inherently dangerous. However these conditions can occur at nearly any location, so inevitably pilots must successfully navigate through them. At NASA Langley Research Center (LaRC), under support of the Aviation Safety and Security Program Office and the Systems Engineering Directorate, we are developing an Enhanced Vision System (EVS) that combines image enhancement and synthetic vision elements to assist pilots flying through adverse weather conditions. This system uses a combination of forward-looking infrared and visible sensors for data acquisition. A core function of the system is to enhance and fuse the sensor data in order to increase the information content and quality of the captured imagery. These operations must be performed in real-time for the pilot to use while flying. For image enhancement, we are using the LaRC patented Retinex algorithm since it performs exceptionally well for improving low-contrast range imagery typically seen during poor visibility poor visibility conditions. In general, real-time operation of the Retinex requires specialized hardware. To date, we have successfully implemented a single-sensor real-time version of the Retinex on several different Digital Signal Processor (DSP) platforms. In this paper we give an overview of the EVS and its performance requirements for real-time enhancement and fusion and we discuss our current real-time Retinex implementations on DSPs.

  20. High fidelity nanohole enhanced Raman spectroscopy.

    SciTech Connect

    Bahns, J. T.; Guo, Q.; Gray, S. K.; Jaeger, H. M.; Chen, L.; Montgomery, J. M.; Univ. of Chicago

    2009-01-01

    Surface enhanced Raman spectroscopy (SERS) is a sensitive technique that can even detect single molecules. However, in many SERS applications, the strongly inhomogeneous distribution of intense local fields makes it very difficult for a quantitive assessment of the fidelity, or reproducibility of the signal, which limits the application of SERS. Herein, we report the development of exceptionally high-fidelity hole-enhanced Raman spectroscopy (HERS) from ordered, 2D hexagonal nanohole arrays. We take the fidelity f to be a measure of the percent deviation of the Raman peaks from measurement to measurement. Overall, area averaged fidelities for 12 gold array samples ranged from f {approx} 2-15% for HERS using aqueous R6G molecules. Furthermore, intensity modulations of the enhanced Raman spectra were measured for the first time as a function of polarization angle. The best of these measurements, which focus on static laser spots on the sample, could be consistent with even higher fidelities than the area-averaged results. Nanohole arrays in silver provided supporting polarization measurements and a more complete enhanced Raman fingerprint for phenylalanine molecules. We also carried out finite-difference time-domain calculations to assist in the interpretation of the experiments, identifying the polarization dependence as possibly arising from hole-hole interactions. Our results represent a step toward making quantitative and reproducible enhanced Raman measurements possible and also open new avenues for a large-scale source of highly uniform hot spots.