Polymorphism in endothelin-related genes limits exercise-induced decreases in arterial stiffness in older subjects.

PubMed

Iemitsu, Motoyuki; Maeda, Seiji; Otsuki, Takeshi; Sugawara, Jun; Tanabe, Takumi; Jesmin, Subrina; Kuno, Shinya; Ajisaka, Ryuichi; Miyauchi, Takashi; Matsuda, Mitsuo

2006-05-01

Increase in arterial stiffness is associated with aging, which is improved by regular exercise. Endothelin (ET) system has crucial roles in regulating vascular tone and in the progression of atherosclerosis. We hypothesized that molecular variations (ie, gene polymorphisms) in ET-related gene might affect exercise-induced improvement in arterial stiffness with age in human subjects. The present study provides a cross-sectional investigation of 191 healthy middle-aged and older (65+/-1 years) human subjects to clarify the relationship between the regular exercise-induced improvement of arterial stiffness and the gene polymorphisms of ET converting enzyme (ECE)-1, ECE-2, ET-A receptor (ET-A), and ET-B receptor (ET-B). The study subjects were divided into active and inactive groups based on the median value (186 kcal/d) of energy expenditure. Brachial-ankle arterial pulse wave velocity (baPWV) was used to evaluate arterial stiffness. All individuals were genotyped for 4 different polymorphisms of the ET system: 2013(+289)A/G in intron 17 of ECE-1, 669(+17)T/C in intron 5 of ECE-2, 958A/G in exon 6 of ET-A, and 831A/G in exon 4 of ET-B. The baseline baPWV was significantly lower in the active group without any change in blood pressure. Polymorphisms in ECE-1 influenced basal blood pressure. Polymorphisms in ECE-1 and ECE-2 had no effect on baPWV between active and inactive groups. However, polymorphisms in both ET-A and ET-B affected baPWV in the 2 groups. The present results suggest that differences in ET-A and ET-B polymorphisms may influence the response of the vascular wall to exercise whereas ECE-1 polymorphisms may affect basal blood pressure.

Abeta-degrading enzymes in Alzheimer's disease.

PubMed

Miners, James Scott; Baig, Shabnam; Palmer, Jennifer; Palmer, Laura E; Kehoe, Patrick G; Love, Seth

2008-04-01

In Alzheimer's disease (AD) Abeta accumulates because of imbalance between the production of Abeta and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Abeta is partly, if not in some cases solely, because of defects in its removal--mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Abeta. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Abeta-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Abetain vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEepsilon4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to Abeta plaque load. Up-regulation of some Abeta-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Abeta-clearance pathways, reductions in the activity of particular Abeta-degrading enzymes may become critical, leading to the development of AD and CAA.

Nitric oxide inhibits the production of soluble endothelin converting enzyme-1.

PubMed

Kuruppu, Sanjaya; Rajapakse, Niwanthi W; Dunstan, Rhys A; Smith, A Ian

2014-11-01

This study examined the effect of nitric oxide on the production of soluble ECE-1. Activity of ECE-1 in media was measured using a quenched fluorescent substrate assay, and expressed as a percentage of control. Endothelial cells were incubated with the nitric oxide donor Diethylenetriamine NONOate (DETA; 250-800 µM), NOS substrate L-Arg (200-1,000 µM), a L-Arg transport inhibitor (L-Lys; 10 µM) and NOS inhibitors (L-Gln and N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester, monohydrochloride (L-NAME); 10-100 µM). The effect of L-Arg (1,000 µM) was also tested in the presence of L-Lys (10 µM), L-Gln (100 µM) and L-NAME (10-100 µM). Ultracentrifugation (100,000×g, 4 °C, 1 h) completely removed ECE-1 activity from the supernatant. In addition, fractionation of concentrated media on a sucrose density gradient indicated that ECE-1 activity was localised to the mid portion of the gradient, thus suggesting the possible role of exosomes in ECE-1 release. Production of soluble ECE-1 by Ea.hy926 cells was inhibited significantly (P < 0.05, unpaired t test, n = 4) in the presence of DETA (75.31 ± 3.59; 800 µM) and L-Arg (60.97 ± 9.22; 1,000 µM). L-Arg-mediated reduction in the release of soluble ECE-1 was blocked by the inhibition of NOS using L-NAME (100 µM; 99.19 ± 0.58) and L-Gln (100 µM; 104.41 ± 0.65). In addition, the presence of L-Lys (10 µM) significantly blocked the L-Arg (1,000 µM)-induced reduction in soluble ECE-1 levels (122.38 ± 13.16). These treatments had no effect on the expression of ECE-1 on the cell surface. Our data provide evidence that NO can inhibit the production of soluble ECE-1 by endothelial cells.

Agonist-biased trafficking of somatostatin receptor 2A in enteric neurons.

PubMed

Zhao, Peishen; Canals, Meritxell; Murphy, Jane E; Klingler, Diana; Eriksson, Emily M; Pelayo, Juan-Carlos; Hardt, Markus; Bunnett, Nigel W; Poole, Daniel P

2013-09-06

Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions.

Agonist-biased Trafficking of Somatostatin Receptor 2A in Enteric Neurons*

PubMed Central

Zhao, Peishen; Canals, Meritxell; Murphy, Jane E.; Klingler, Diana; Eriksson, Emily M.; Pelayo, Juan-Carlos; Hardt, Markus; Bunnett, Nigel W.; Poole, Daniel P.

2013-01-01

Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions. PMID:23913690

Role of endothelin-converting enzyme, chymase and neutral endopeptidase in the processing of big ET-1, ET-1(1-21) and ET-1(1-31) in the trachea of allergic mice.

PubMed

De Campo, Benjamin A; Goldie, Roy G; Jeng, Arco Y; Henry, Peter J

2002-08-01

The present study examined the roles of endothelin-converting enzyme (ECE), neutral endopeptidase (NEP) and mast cell chymase as processors of the endothelin (ET) analogues ET-1(1-21), ET-1(1-31) and big ET-1 in the trachea of allergic mice. Male CBA/CaH mice were sensitized with ovalbumin (10 microg) delivered intraperitoneal on days 1 and 14, and exposed to aerosolized ovalbumin on days 14, 25, 26 and 27 (OVA mice). Mice were killed and the trachea excised for histological analysis and contraction studies on day 28. Tracheae from OVA mice had 40% more mast cells than vehicle-sensitized mice (sham mice). Ovalbumin (10 microg/ml) induced transient contractions (15+/-3% of the C(max)) in tracheae from OVA mice. The ECE inhibitor CGS35066 (10 microM) inhibited contractions induced by big ET-1 (4.8-fold rightward shift of dose-response curve; P<0.05), but not those induced by either ET-1(1-21) or ET-1(1-31). The chymase inhibitors chymostatin (10 microM) and Bowman-Birk inhibitor (10 microM) had no effect on contractions induced by any of the ET analogues used. The NEP inhibitor CGS24592 (10 microM) inhibited contractions induced by ET-1(1-31) (6.2-fold rightward shift; P<0.05) but not ET-1(1-21) or big ET-1. These data suggest that big ET-1 is processed predominantly by a CGS35066-sensitive ECE within allergic airways rather than by mast cell-derived proteases such as chymase. If endogenous ET-1(1-31) is formed within allergic airways, it is likely to undergo further conversion by NEP to more active products.

GPER mediates the age-dependent upregulation of the myocardial endothelin system

PubMed Central

Meyer, Matthias R.; Fredette, Natalie C.; Sharma, Geetanjali; Barton, Matthias; Prossnitz, Eric R.

2016-01-01

Aims Cardiac aging is associated with progressive structural changes and functional impairment, such as left ventricular hypertrophy, fibrosis and diastolic dysfunction. Aging also increases myocardial activity of endothelin-1 (ET-1), a multifunctional peptide with growth-promoting and pro-fibrotic activity. Because the G protein-coupled estrogen receptor (GPER) regulates vascular responsiveness to ET-1, we investigated whether GPER also plays a role in the regulation of the cardiac endothelin system with aging. Main methods Young (4 month-old) and aged (24 month-old) wild-type and Gper-deficient (Gper-/-) mice were studied. Gene expression levels of prepro-ET-1, endothelin converting enzymes ECE-1 and ECE-2, and endothelin ETA and ETB receptors were determined by qPCR in left ventricular myocardium. Key findings Aging markedly increased steady-state mRNA expression levels of ECE-1, ECE-2, ETA and ETB receptors (each p<0.001 vs. young mice). Deletion of Gper inhibited the age-dependent increase in ECE-2 and ETB receptor mRNA levels (57% and 40% reduction, respectively, each p<0.01 vs. wild-type mice), whereas gene expression of prepro-ET-1, ECE-1, or the ETA receptor was unaffected in Gper-/- mice. Significance We identified a novel regulatory mechanism through which the endogenous Gper facilitates the age-dependent increase in myocardial expression of ECE-2 and the ETB receptor, which is compatible with an activating role of GPER for the cardiac endothelin system with aging. Targeting GPER signaling by selective antagonists may therefore be considered a new therapeutic approach to reduce age-dependent increased ET-1 activity and the associated development of left ventricular hypertrophy, fibrosis and heart failure. PMID:26880534

GPER is required for the age-dependent upregulation of the myocardial endothelin system.

PubMed

Meyer, Matthias R; Fredette, Natalie C; Sharma, Geetanjali; Barton, Matthias; Prossnitz, Eric R

2016-08-15

Cardiac aging is associated with progressive structural changes and functional impairment, such as left ventricular hypertrophy, fibrosis and diastolic dysfunction. Aging also increases myocardial activity of endothelin-1 (ET-1), a multifunctional peptide with growth-promoting and pro-fibrotic activity. Because the G protein-coupled estrogen receptor (GPER) regulates vascular responsiveness to ET-1, we investigated whether GPER also plays a role in the regulation of the myocardial endothelin system with aging. Young (4month-old) and aged (24month-old) wild-type and Gper-deficient (Gper(-/-)) mice were studied. Gene expression levels of prepro-ET-1, endothelin converting enzymes ECE-1 and ECE-2, and endothelin ETA and ETB receptors were determined by qPCR in left ventricular myocardium. Aging markedly increased steady-state mRNA expression levels of ECE-1, ECE-2, ETA and ETB receptors (each p<0.001 vs. young mice). Deletion of Gper inhibited the age-dependent increase in ECE-2 and ETB receptor mRNA levels (57% and 40% reduction, respectively, each p<0.01 vs. wild-type mice), whereas gene expression of prepro-ET-1, ECE-1, and the ETA receptor was unaffected in Gper(-/-) mice. We identified a novel regulatory mechanism through which the endogenous Gper facilitates the age-dependent increase in myocardial expression of ECE-2 and the ETB receptor, which is compatible with an activating role of GPER for the local endothelin system with aging. Targeting GPER signaling by selective antagonists may therefore be considered a new therapeutic approach to reduce age-dependent increased ET-1 activity and the associated development of left ventricular hypertrophy, fibrosis and heart failure. Copyright © 2016 Elsevier Inc. All rights reserved.

[Inhibition of antisense-endothelin converting enzyme RNA on interleukin-5 released from dust mite-challenged peripheral blood mononuclear cells in patients with allergic asthma].

PubMed

Li, Li; Xu, Ju; Zhong, Nan-shan

2003-09-01

To investigate the effect of antisense endothelin converting enzyme (ECE) RNA on levels of cytokines released from CD(4)(+) lymphocytes in patients with allergic diseases responsive to house dust mites. Peripheral blood mononuclear cells (PBMCs) were separated from 21 patients who were sensitive to dust mites. PBMCs from those patients were divided into two groups. No stimulation group (A group) induded A(1) group (anti-ECE epithelial cells + PBMCs) and A(2) group (control cells + PBMCs). Stimulation group (B group) included B(1) group (anti-ECE epithelial cells + PBMCs + dust mites extract) and B(2) group (control cells + PBMCs + dust mites extract). House dust mite extract (20 microg/ml) was added to the culture of stimulation group as described above. After 72 hours, supernatants from both groups were collected and the levels of IL-5 and IFN-ggr; released into the supernatants were detected by enzyme-linked immunoabsorbent assay. IL-5 levels were increased significantly after treatment with dust mite in twelve of 21 cases. No significant differences of IL-5 were found between the groups of A(1)[(6.0 +/- 1.3) x 10(-9) g/L] and A(2) [(7.5 +/- 1.1) x 10(-9) g/L] before house dust mite stimulation in the 12 cases (P > 0.05), and no significant differences in IFN-ggr; were found between the groups of A(1) [(63 +/- 26) x 10(-9) g/L] and A(2) [(70 +/- 52) x 10(-9) g/L] before house dust mite stimulation (P > 0.05). IL-5 level was increased in both groups after stimulation but it was significantly lower in the B(1) group [(8.2 +/- 1.6) x 10(-9) g/L] than that in the B(2) [(12.0 +/- 1.8) x 10(-9) g/L] (P = 0.047). It seemed that increased IFN-ggr; level after stimulation was higher in B(2) [(153 +/- 71) x 10(-9) g/L] than that in the B(1) group (100 +/- 41) x 10(-9) g/L], but there was no statistic significance (P > 0.05). In addition, our results also showed that the release of IL-5 was significantly increased in those cases with asthma, or asthma plus allergic rhinitis after dust mites stimulation [(44 +/- 15)%] compared with that in those with urticaria [(7 +/- 4)%] (P = 0.047). Antisense-ECE downregulated the IL-5 secretion from Th2 lymphocytes in patients with allergic asthma after being challenged with dust mites. It is indicated that ET-1 is an important cytokine involved with allergic airway inflammation. Antisense-ECE RNA management in airways may be of value in treating allergic asthma.

Endothelin-converting Enzyme 1 and β-Arrestins Exert Spatiotemporal Control of Substance P-induced Inflammatory Signals*

PubMed Central

Jensen, Dane D.; Halls, Michelle L.; Murphy, Jane E.; Canals, Meritxell; Cattaruzza, Fiore; Poole, Daniel P.; Lieu, TinaMarie; Koon, Hon-Wai; Pothoulakis, Charalabos; Bunnett, Nigel W.

2014-01-01

Although the intracellular trafficking of G protein-coupled receptors controls specific signaling events, it is unclear how the spatiotemporal control of signaling contributes to complex pathophysiological processes such as inflammation. By using bioluminescence resonance energy transfer and superresolution microscopy, we found that substance P (SP) induces the association of the neurokinin 1 receptor (NK1R) with two classes of proteins that regulate SP signaling from plasma and endosomal membranes: the scaffolding proteins β-arrestin (βARRs) 1 and 2 and the transmembrane metallopeptidases ECE-1c and ECE-1d. In HEK293 cells and non-transformed human colonocytes, we observed that G protein-coupled receptor kinase 2 and βARR1/2 terminate plasma membrane Ca2+ signaling and initiate receptor trafficking to endosomes that is necessary for sustained activation of ERKs in the nucleus. βARRs deliver the SP-NK1R endosomes, where ECE-1 associates with the complex, degrades SP, and allows the NK1R, freed from βARRs, to recycle. Thus, both ECE-1 and βARRs mediate the resensitization of NK1R Ca2+ signaling at the plasma membrane. Sustained exposure of colonocytes to SP activates NF-κB and stimulates IL-8 secretion. This proinflammatory signaling is unaffected by inhibition of the endosomal ERK pathway but is suppressed by ECE-1 inhibition or βARR2 knockdown. Inhibition of protein phosphatase 2A, which also contributes to sustained NK1R signaling at the plasma membrane, similarly attenuates IL-8 secretion. Thus, the primary function of βARRs and ECE-1 in SP-dependent inflammatory signaling is to promote resensitization, which allows the sustained NK1R signaling from the plasma membrane that drives inflammation. PMID:24898255

Effects of phosphoramidon on endothelin-1 and big endothelin-1 production in human aortic endothelial cells.

PubMed

Matsumura, Y; Tsukahara, Y; Kojima, T; Murata, S; Murakami, A; Takada, K; Takaoka, M; Morimoto, S

1995-03-01

Using cultured human aortic endothelial cells, we examined the effects of phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, on the release of endogenous endothelin-1 (ET-1) and big endothelin-1 (big ET-1), and on the generation of ET-1 from exogenously applied big ET-1. Phosphoramidon, at concentrations of 10(-6) to 2 x 10(-4) M, caused a biphasic alteration of the ET-1 release, i.e., at lower concentrations of the drug, there were slight but unexpected increases of the release, whereas higher concentrations led to a decrease which is due to the drug-induced inhibition of ECE. The former effect appears to be based on the inhibition of ET-1 degradation by neutral endopeptidase 24.11 (NEP), since kelatorphan, a specific NEP inhibitor, produced a similar increasing effect on ET-1 release. Phosphoramidon enhanced the big ET-1 release from the cells in a concentration-dependent manner. When high concentrations of phosphoramidon were added, there was a dramatic increase in the release of big ET-1, which cannot be explained only by the drug-induced inhibition of ECE. This increase in big ET-1 release appeared to be partly due to a transient stimulation of the expression of prepro ET-1 mRNA. The amount of ET-1 generated from exogenously applied big ET-1 was markedly decreased by phosphoramidon in a concentration-dependent manner. In a similar fashion, phosphoramidon markedly inhibited ECE activity of the membrane fraction of cultured cells. Thus, ET-1 generation from exogenously applied big ET-1 reflects the functional phosphoramidon-sensitive ECE activities in human aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein phosphatase 2A mediates resensitization of the neurokinin 1 receptor

PubMed Central

Murphy, Jane E.; Roosterman, Dirk; Cottrell, Graeme S.; Padilla, Benjamin E.; Feld, Micha; Brand, Eva; Cedron, Wendy J.; Steinhoff, Martin

2011-01-01

Activated G protein-coupled receptors (GPCRs) are phosphorylated and interact with β-arrestins, which mediate desensitization and endocytosis. Endothelin-converting enzyme-1 (ECE-1) degrades neuropeptides in endosomes and can promote recycling. Although endocytosis, dephosphorylation, and recycling are accepted mechanisms of receptor resensitization, a large proportion of desensitized receptors can remain at the cell surface. We investigated whether reactivation of noninternalized, desensitized (phosphorylated) receptors mediates resensitization of the substance P (SP) neurokinin 1 receptor (NK1R). Herein, we report a novel mechanism of resensitization by which protein phosphatase 2A (PP2A) is recruited to dephosphorylate noninternalized NK1R. A desensitizing concentration of SP reduced cell-surface SP binding sites by only 25%, and SP-induced Ca2+ signals were fully resensitized before cell-surface binding sites started to recover, suggesting resensitization of cell-surface-retained NK1R. SP induced association of β-arrestin1 and PP2A with noninternalized NK1R. β-Arrestin1 small interfering RNA knockdown prevented SP-induced association of cell-surface NK1R with PP2A, indicating that β-arrestin1 mediates this interaction. ECE-1 inhibition, by trapping β-arrestin1 in endosomes, also impeded SP-induced association of cell-surface NK1R with PP2A. Resensitization of NK1R signaling required both PP2A and ECE-1 activity. Thus, after stimulation with SP, PP2A interacts with noninternalized NK1R and mediates resensitization. PP2A interaction with NK1R requires β-arrestin1. ECE-1 promotes this process by releasing β-arrestin1 from NK1R in endosomes. These findings represent a novel mechanism of PP2A- and ECE-1-dependent resensitization of GPCRs. PMID:21795521

Endothelin-converting enzyme 1 and β-arrestins exert spatiotemporal control of substance P-induced inflammatory signals.

PubMed

Jensen, Dane D; Halls, Michelle L; Murphy, Jane E; Canals, Meritxell; Cattaruzza, Fiore; Poole, Daniel P; Lieu, TinaMarie; Koon, Hon-Wai; Pothoulakis, Charalabos; Bunnett, Nigel W

2014-07-18

Although the intracellular trafficking of G protein-coupled receptors controls specific signaling events, it is unclear how the spatiotemporal control of signaling contributes to complex pathophysiological processes such as inflammation. By using bioluminescence resonance energy transfer and superresolution microscopy, we found that substance P (SP) induces the association of the neurokinin 1 receptor (NK1R) with two classes of proteins that regulate SP signaling from plasma and endosomal membranes: the scaffolding proteins β-arrestin (βARRs) 1 and 2 and the transmembrane metallopeptidases ECE-1c and ECE-1d. In HEK293 cells and non-transformed human colonocytes, we observed that G protein-coupled receptor kinase 2 and βARR1/2 terminate plasma membrane Ca(2+) signaling and initiate receptor trafficking to endosomes that is necessary for sustained activation of ERKs in the nucleus. βARRs deliver the SP-NK1R endosomes, where ECE-1 associates with the complex, degrades SP, and allows the NK1R, freed from βARRs, to recycle. Thus, both ECE-1 and βARRs mediate the resensitization of NK1R Ca(2+) signaling at the plasma membrane. Sustained exposure of colonocytes to SP activates NF-κB and stimulates IL-8 secretion. This proinflammatory signaling is unaffected by inhibition of the endosomal ERK pathway but is suppressed by ECE-1 inhibition or βARR2 knockdown. Inhibition of protein phosphatase 2A, which also contributes to sustained NK1R signaling at the plasma membrane, similarly attenuates IL-8 secretion. Thus, the primary function of βARRs and ECE-1 in SP-dependent inflammatory signaling is to promote resensitization, which allows the sustained NK1R signaling from the plasma membrane that drives inflammation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of small hairpin RNA targeting endothelin-converting enzyme-1 in monocrotaline-induced pulmonary hypertensive rats.

PubMed

Son, Jae Sung; Kim, Kwan Chang; Kim, Bo Kyung; Cho, Min-Sun; Hong, Young Mi

2012-12-01

The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ET(A)) were significantly decreased in the shRNA group in week 4. The protein levels of ET(A) were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-α and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension.

Renoprotective effects of combined endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage.

PubMed

Sharkovska, Yuliya; Kalk, Philipp; von Websky, Karoline; Relle, Katharina; Pfab, Thiemo; Alter, Markus; Fischer, Yvan; Hocher, Berthold

2011-01-01

Acute kidney injury (AKI) as well as chronic renal failure are associated with a huge mortality/morbidity. However, so far no drugs have been approved for the treatment of acute kidney failure and only a few for the treatment of chronic kidney disease (CKD). We analysed the effect of SLV338, a neutral endopeptidase (NEP)/endothelin converting enzyme (ECE)-inhibitor in animal models of acute kidney failure as well as chronic renal failure. Acute renal failure was induced in male Wistar rats by uninephrectomy and clamping of the remaining kidney for 55 minutes. SLV338 (total dose: 4.9 mg/kg) or vehicle was continuously infused for 2 hours (starting 20 minutes prior to clamping). Sham operated animals served as controls. Plasma creatinine was measured at baseline and day 2 and 8 after renal ischemia-reperfusion. Hypertensive renal damage was induced in male Sprague Dawley rats by nitric oxide deficiency using L-NAME (50 mg/kg per day, added to drinking water for 4 weeks). One group was treated over the same time period with SLV338 (30 mg/kg per day, mixed with food). Systolic blood pressure was monitored weekly. At study end, urine and blood samples were collected and kidneys were harvested. Acute renal ischemia-reperfusion caused a 5-fold plasma creatinine elevation (day 2), which was significantly attenuated by more than 50% in animals treated with SLV338 (p < 0.05). Renal failure was accompanied by a 67% mortality in vehicle-treated rats, but only 20% after SLV338 treatment (p = 0.03 compared to sham controls). Chronic L-NAME administration caused hypertension, urinary albumin excretion, glomerulosclerosis, renal arterial remodelling, and renal interstitial fibrosis. Treatment with SLV338 did not significantly affect blood pressure, but abolished renal tissue damage (interstitial fibrosis, glomerulosclerosis, renal arterial remodelling (p < 0.05 versus L-NAME group in each case). The dual ECE/NEP inhibitor SLV338 preserves kidney function and reduces mortality in severe acute ischemic renal failure. Moreover, combined ECE/NEP inhibition prevents hypertensive renal tissue damage in a blood pressure independent manner in L-NAME-treated rats.

The effect of big endothelin-1 in the proximal tubule of the rat kidney

PubMed Central

Beara-Lasić, Lada; Knotek, Mladen; Čejvan, Kenan; Jakšić, Ozren; Lasić, Zoran; Skorić, Boško; Brkljačić, Vera; Banfić, Hrvoje

1997-01-01

An obligatory step in the biosynthesis of endothelin-1 (ET-1) is the conversion of its inactive precursor, big ET-1, into the mature form by the action of specific, phosphoramidon-sensitive, endothelin converting enzyme(s) (ECE). Disparate effects of big ET-1 and ET-1 on renal tubule function suggest that big ET-1 might directly influence renal tubule function. Therefore, the role of the enzymatic conversion of big ET-1 into ET-1 in eliciting the functional response (generation of 1,2-diacylglycerol) to big ET-1 was studied in the rat proximal tubules.In renal cortical slices incubated with big ET-1, pretreatment with phosphoramidon (an ECE inhibitor) reduced tissue immunoreactive ET-1 to a level similar to that of cortical tissue not exposed to big ET-1. This confirms the presence and effectiveness of ECE inhibition by phosphoramidon.In freshly isolated proximal tubule cells, big ET-1 stimulated the generation of 1,2-diacylglycerol (DAG) in a time- and dose-dependent manner. Neither phosphoramidon nor chymostatin, a chymase inhibitor, influenced the generation of DAG evoked by big ET-1.Big ET-1-dependent synthesis of DAG was found in the brush-border membrane. It was unaffected by BQ123, an ETA receptor antagonist, but was blocked by bosentan, an ETA,B-nonselective endothelin receptor antagonist.These results suggest that the proximal tubule is a site for the direct effect of big ET-1 in the rat kidney. The effect of big ET-1 is confined to the brush-border membrane of the proximal tubule, which may be the site of big ET-1-sensitive receptors. PMID:9051300

Investigating the Et-1/SphK/S1P Pathway as a Novel Approach for the Prevention of Inflammation-Induced Preterm Birth.

PubMed

Giusto, Kiersten; Ashby, Charles R

2018-01-30

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, occurs in up to 18 percent of births worldwide and accounts for the majority of perinatal morbidity and mortality. While the single most common cause of PTB has been identified as inflammation, safe and effective pharmacotherapy to prevent PTB has yet to be developed. Our group has used an in vivo model of inflammation driven PTB, biochemical methods, pharmacological approaches, a novel endothelin receptor antagonist that we synthesized and RNA knockdown to help establish the role of endothelin-1 (ET-1) in inflammation-associated PTB. Further, we have used our in vivo model to test whether sphingosine kinase, which acts downstream of ET-1, plays a role in PTB. We have shown that levels of endothelin converting enzyme-1 (ECE-1) and ET-1 are increased when PTB is induced in timed pregnant mice with lipopolysaccharide (LPS) and that blocking ET-1 action, pharmacologically or using ECE-1 RNA silencing, rescues LPS-induced mice from PTB. ET-1 activates the sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) pathway. S1P, in turn, is an important signaling molecule in the pro-inflammatory response. Interestingly, we have shown that SphK inhibition also prevents LPS-induced PTB in timed pregnant mice. Further, we showed that SphK inhibition suppresses the ECE-1/ET-1 axis, implicating positive feedback regulation of the SphK/S1P/ECE-1/ET-1 axis. The ET-1/SphK/SIP pathway is a potential pharmacotherapeutic target for the prevention of PTB. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Impact of angiotensin and endothelin converting enzymes and related bradykinin on renal functions in L-NAME hypertensive rats

NASA Astrophysics Data System (ADS)

Omar, Ali Zainal; Maulood, Ismail M.

2017-09-01

The renin-angiotensin system (RAS), one of the most important hormonal systems, controls the kidney functions by regulating fluid volume, and electrolyte balance. The current study included the effects of kinin-kallikrein system (KKS) and its interaction with both angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE) on some of kidney function test parameters. In the present experiment, rats were divided into six groups, the first group was infused with normal saline, the second group was L-NG-Nitroarginine methyl ester (L-NAME) treated rats, third group was bradykinin (BK), forth group was captopril (ACEi), fifth group was phosphoramidon (ECEi), sixth group was a combination of BK with phosphoramidon. L-NAME was intravenously infused for one hour to develop systematic hypertension in male rats. After one hour of infusion, the results showed that L-NAME significantly increased serum creatinine. While, it decreased glomerular filtration rate (GFR), and K+ excretion rate. Moreover, BK increased packed cell volume PCV%, serum creatinine and K+ ion concentration. While, it reduced GFR, serum Ca+2 ion concentration, K+ and Na+ excretion rates. On the other hand, captopril infusion showed its effect by reduction in GFR, serum Ca+2 ion and electrolyte excretion rates. Phosphoramidon an ECEi dramatically reduced serum Ca+2 ion, but it increased pH, GFR and Ca+2 excretion rate. The results suggested that BK and Captopril each alone severely reduces GFR value. Interestingly, inhibition of ET-1 production via phosphoramidon could markedly elevate GFR values.

Effects of the ECE/NEP inhibitor CGS 34225 on the big ET-1-induced pressor response and plasma atrial natriuretic peptide concentration in conscious rats.

PubMed

Trapani, Angelo J; Beil, Michael E; Bruseo, Charles W; Fink, Cynthia A; Hoyer, Denton; Savage, Paula; Jeng, Arco Y

2002-08-01

CGS 34226 is a thiol-containing, potent dual inhibitor of endothelin converting enzyme-1 (ECE-1) and neutral endopeptidase 24.11 (NEP) with IC(50) values of 11 and 5 nM respectively. The purpose of the present study was to characterize the inhibitory effects of CGS 34225, an orally active prodrug of CGS 34226, on ECE-1 and NEP in vivo. The effects on ECE-1 and NEP were assessed by determining the inhibition of big endothelin-1 (big ET-1)-induced increases in mean arterial pressure (MAP) and increases in plasma atrial natriuretic peptide (ANP) concentrations respectively, in conscious rats. Thirty and 120 min after the administration of vehicle, big ET-1 (0.3 nmol/kg, intravenously; i.v.) produced pressor responses of approximately 800 mmHg.min (area under the curve for change in MAPxtime). Treatment with CGS 34225 at 1 mgEq/kg, per os (p.o.), decreased the pressor effect of big ET-1 by 39 and 53% at 30 and 120 min respectively (P<0.05, both times). Increasing the dose of CGS 34255 to 30 mgEq/kg, p.o., resulted in greater inhibition, 84 and 92% (P<0.05) at 30 and 120 min respectively. Furthermore, at this higher dose, the inhibitory effect on ECE-1 was long-lasting, averaging 86, 75 and 30% (P<0.05, all times) at 4, 8 and 24 h respectively. In rats treated with vehicle, the infusion of ANP at 450 ng/kg per min i.v. resulted in plasma ANP concentrations of 3.9-4.8 ng/ml that remained relatively constant for 4 h. Treatment with CGS 34225 at 10 mgEq/kg, p.o., increased the ANP level to 7.7+/-1.0 and 10.6+/-1.8 ng/ml at 1 and 4 h after dosing (P<0.05, both times). These data demonstrate that CGS 34225 is a potent, orally active and long-acting inhibitor of ECE-1 and NEP in vivo. It is anticipated that compounds with this dual function may be useful in the treatment of cardiovascular diseases where the ET system plays a pathogenic role and the potentiation of ANP elicits therapeutic benefits.

Bioinformatic analysis of the neprilysin (M13) family of peptidases reveals complex evolutionary and functional relationships.

PubMed

Bland, Nicholas D; Pinney, John W; Thomas, Josie E; Turner, Anthony J; Isaac, R Elwyn

2008-01-23

The neprilysin (M13) family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2), which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates and thus allows M13 peptidases to fulfil a broad range of physiological roles. The M13 family of peptidases have diversified extensively in all species examined, indicating wide ranging roles in numerous physiological processes. It is predicted that differences in the S2' subsite are fundamental to determining the substrate specificities that facilitate this functional diversity.

Estrogen and progesterone regulate expression of the endothelins in the rhesus macaque endometrium

PubMed Central

Keator, Christopher S.; Mah, Kuni; Ohm, Lindsay; Slayden, Ov D.

2011-01-01

BACKGROUND Endothelins (EDNs) are thought to modulate endometrial blood flow during menses, stromal healing and endometrial growth during the proliferative phase. Our goal was to assess the effects of estrogen and progesterone on the EDN paracrine system in the endometrium of rhesus macaques. METHODS In this study, archived samples were used. These samples were collected from oophorectomized rhesus macaques that were treated sequentially with estradiol (E2) and then E2 plus progesterone to create artificial menstrual cycles. Endometrium from animals in the menstrual, proliferative and secretory phases of the artificial cycle were analyzed by real-time PCR, in situ hybridization and immunocytochemistry to detect changes in EDN peptides (EDN1, EDN2, EDN3), EDN receptors (EDNRA, EDNRB), EDN-converting enzyme 1 (ECE1) and membrane metalloendopeptidase (MME)—an enzyme that degrades the EDNs. RESULTS Compared with the late secretory phase, progesterone withdrawal at the end of the artificial menstrual cycle triggered an increase (P< 0.05) in EDN1, EDNRB and ECE1 in the upper functionalis zone during menses of the next cycle. Treatment with E2 alone in the proliferative phase increased (P< 0.05) EDNRA transcript, which was confined predominantly to the stromal cells. E2 plus progesterone in the artificial secretory phase suppressed (P< 0.05) the expression of EDN3 in the functionalis zone stroma and epithelia, tended (P= 0.08) to attenuate levels of epithelial EDN2 and markedly up-regulated (P< 0.05) the stromal expression of MME. CONCLUSIONS Our results indicate that estrogen and progesterone regulate the EDN family during the menstrual cycle. The changes in the EDN paracrine system during the mid-secretory phase may indicate a role for EDN during embryo implantation. PMID:21505040

Enhanced electrochemical sensitivity of enzyme precipitate coating (EPC)-based glucose oxidase biosensors with increased free CNT loadings.

PubMed

Kim, Jae Hyun; Jun, Sun-Ae; Kwon, Yongchai; Ha, Su; Sang, Byong-In; Kim, Jungbae

2015-02-01

Enzymatic electrodes were fabricated by using three different immobilizations of glucose oxidase (GOx): covalent enzyme attachment (CA), enzyme coating (EC), and enzyme precipitate coating (EPC), here referred to as CA-E, EC-E, and EPC-E, respectively. When additional carbon nanotubes (CNTs) were introduced from 0 to 75wt% for the EPC-E design, its initial biosensor sensitivity was improved from 2.40×10(-3) to 16.26×10(-3) A∙M(-1)∙cm(-2), while its electron charge transfer rate constant was increased from 0.33 to 1.47s(-1). When a fixed ratio of CNTs was added for three different electrode systems, EPC-E showed the best glucose sensitivity and long-term thermal stability. For example, when 75wt% of additional CNTs was added, the initial sensitivity of EPC-E was 16.26×10(-3) A∙M(-1)∙cm(-2), while those of EC-E and CA-E were only 6.42×10(-3) and 1.18×10(-3) A∙M(-1)∙cm(-2), respectively. Furthermore, EPC-E retained 63% of its initial sensitivity after thermal treatment at 40°C over 41days, while EC-E and CA-E showed only 12% and 1% of initial sensitivities, respectively. Consequently, the EPC approach with additional CNTs achieved both high sensitivity and long-term stability, which are required for continuous and accurate glucose monitoring. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of mechanical deformation on energy conversion efficiency of piezoelectric nanogenerators.

PubMed

Yoo, Jinho; Cho, Seunghyeon; Kim, Wook; Kwon, Jang-Yeon; Kim, Hojoong; Kim, Seunghyun; Chang, Yoon-Suk; Kim, Chang-Wan; Choi, Dukhyun

2015-07-10

Piezoelectric nanogenerators (PNGs) are capable of converting energy from various mechanical sources into electric energy and have many attractive features such as continuous operation, replenishment and low cost. However, many researchers still have studied novel material synthesis and interfacial controls to improve the power production from PNGs. In this study, we report the energy conversion efficiency (ECE) of PNGs dependent on mechanical deformations such as bending and twisting. Since the output power of PNGs is caused by the mechanical strain of the piezoelectric material, the power production and their ECE is critically dependent on the types of external mechanical deformations. Thus, we examine the output power from PNGs according to bending and twisting. In order to clearly understand the ECE of PNGs in the presence of those external mechanical deformations, we determine the ECE of PNGs by the ratio of output electrical energy and input mechanical energy, where we suggest that the input energy is based only on the strain energy of the piezoelectric layer. We calculate the strain energy of the piezoelectric layer using numerical simulation of bending and twisting of the PNG. Finally, we demonstrate that the ECE of the PNG caused by twisting is much higher than that caused by bending due to the multiple effects of normal and lateral piezoelectric coefficients. Our results thus provide a design direction for PNG systems as high-performance power generators.

Mechanisms Underlying Endothelin-1 Level Elevations Caused by Excessive Fluoride Exposure.

PubMed

Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Xiaona; Li, Bingyun; Cui, Xiaohui; Sun, Dianjun

2016-01-01

To explore the mechanisms underlying endothelin-1 (ET-1) elevations induced by excessive fluoride exposure. We measured serum and bone fluoride ion content and plasma ET-1 levels and compared these parameters among different groups in an animal model. We also observed morphological changes in the aorta and endothelium of rabbits. In cell experiments, human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of NaF for 24h, with or without 10 µM U0126 pretreatment for 1 h. ET-1 levels in culture fluid and intracellular reactive oxygen species (ROS) levels, as well as ET1 gene, endothelin-converting enzyme-1 (ECE-1), extracellular signal-regulating kinase 1/2 (ERK1/2), pERK1/2 expression levels and RAS activation were measured and compared among the groups. Plasma ET-1 levels of rabbits increased significantly in fluorinated groups compared with those in the control group. The rabbit thoracic aortas became slightly hardened in fluorinated groups compared with those in the control group, and some vacuoles were present in the endothelial cell cytoplasm of the rabbits in fluorinated groups. In our cell experiments, ET1 gene and ECE-1 expression levels in HUVECs and ET-1 expression levels in the cell culture supernatants increased significantly in some experimental groups compared with those in the control group. These trends paralleled the changes in intracellular ROS levels, RAS activation, and the pERK1/2-to-ERK1/2 ratio. After U0126 was added, ECE-1 expression and ET-1 levels decreased significantly. Excessive fluoride exposure leads to characteristic endothelial damage (vacuoles), thoracic aorta hardening, and plasma ET-1 level elevations in rabbits. In addition, the ROS-RAS-MEK1/2-pERK1/2/ERK1/2 pathway plays a crucial-and at least partial-role in ET-1 over-expression, which is promoted by excessive fluoride exposure. © 2016 The Author(s) Published by S. Karger AG, Basel.

Inflammation-induced abnormalities in the subcellular localization and trafficking of the neurokinin 1 receptor in the enteric nervous system

PubMed Central

Lieu, TinaMarie; Pelayo, Juan Carlos; Eriksson, Emily M.; Veldhuis, Nicholas A.; Bunnett, Nigel W.

2015-01-01

Activated G protein-coupled receptors traffic to endosomes and are sorted to recycling or degradative pathways. Endosomes are also a site of receptor signaling of sustained and pathophysiologically important processes, including inflammation. However, the mechanisms of endosomal sorting of receptors and the impact of disease on trafficking have not been fully defined. We examined the effects of inflammation on the subcellular distribution and trafficking of the substance P (SP) neurokinin 1 receptor (NK1R) in enteric neurons. We studied NK1R trafficking in enteric neurons of the mouse colon using immunofluorescence and confocal microscopy. The impact of inflammation was studied in IL10−/−-piroxicam and trinitrobenzenesulfonic acid colitis models. NK1R was localized to the plasma membrane of myenteric and submucosal neurons of the uninflamed colon. SP evoked NK1R endocytosis and recycling. Deletion of β-arrestin2, which associates with the activated NK1R, accelerated recycling. Inhibition of endothelin-converting enzyme-1 (ECE-1), which degrades endosomal SP, prevented recycling. Inflammation was associated with NK1R endocytosis in myenteric but not submucosal neurons. Whereas the NK1R in uninflamed neurons recycled within 60 min, NK1R recycling in inflamed neurons was delayed for >120 min, suggesting defective recycling machinery. Inflammation was associated with β-arrestin2 upregulation and ECE-1 downregulation, which may contribute to the defective NK1R recycling. We conclude that inflammation evokes redistribution of NK1R from the plasma membrane to endosomes of myenteric neurons through enhanced SP release and defective NK1R recycling. Defective recycling may be secondary to upregulation of β-arrestin2 and downregulation of ECE-1. Internalized NK1R may generate sustained proinflammatory signals that disrupt normal neuronal functions. PMID:26138465

Bioinformatic analysis of the neprilysin (M13) family of peptidases reveals complex evolutionary and functional relationships

PubMed Central

2008-01-01

Background The neprilysin (M13) family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2), which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. Results The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates and thus allows M13 peptidases to fulfil a broad range of physiological roles. Conclusion The M13 family of peptidases have diversified extensively in all species examined, indicating wide ranging roles in numerous physiological processes. It is predicted that differences in the S2' subsite are fundamental to determining the substrate specificities that facilitate this functional diversity. PMID:18215274

Ontogeny of Big endothelin-1 effects in newborn piglet pulmonary vasculature.

PubMed

Liben, S; Stewart, D J; De Marte, J; Perreault, T

1993-07-01

Endothelin-1 (ET-1), a 21-amino acid peptide produced by endothelial cells, results from the cleavage of preproendothelin, generating Big ET-1, which is then cleaved by the ET-converting enzyme (ECE) to form ET-1. Big ET-1, like ET-1, is released by endothelial cells. Big ET-1 is equipotent to ET-1 in vivo, whereas its vasoactive effects are less in vitro. It has been suggested that the effects of Big ET-1 depend on its conversion to ET-1. ET-1 has potent vasoactive effects in the newborn pig pulmonary circulation, however, the effects of Big ET-1 remain unknown. Therefore, we studied the effects of Big ET-1 in isolated perfused lungs from 1- and 7-day-old piglets using the ECE inhibitor, phosphoramidon, and the ETA receptor antagonist, BQ-123Na. The rate of conversion of Big ET-1 to ET-1 was measured using radioimmunoassay. ET-1 (10(-13) to 10(-8) M) produced an initial vasodilation, followed by a dose-dependent potent vasoconstriction (P < 0.001), which was equal at both ages. Big ET-1 (10(-11) to 10(-8) M) also produced a dose-dependent vasoconstriction (P < 0.001). The constrictor effects of Big ET-1 and ET-1 were similar in the 1-day-old, whereas in the 7-day-old, the constrictor effect of Big ET-1 was less than that of ET-1 (P < 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of leptin in modulation of Porphyromonas gingivalis lipopolysaccharide-induced up-regulation of endothelin-1 in salivary gland acinar cells.

PubMed

Slomiany, Bronislaw L; Slomiany, Amalia

2005-08-01

Leptin, a pleiotropic cytokine that regulates food intake and metabolic and endocrine responses, has emerged recently as an important regulator of mucosal inflammatory responses to bacterial infection. In this study, we report that in sublingual salivary gland acinar cells leptin plays a role in the suppression of up-regulation in endothelin-1 (ET-1), induced by the LPS of a periodontopathic bacterium P. gingivalis. We show that P. gingivalisLPS detrimental effect on salivary mucin synthesis, associated with up-regulation (3.9-fold) in ET-1 generation and the enhancement (3.2-fold) in endothelin-converting enzyme-1 (ECE-1) activity, was subject to a dose-dependent suppression by leptin. The impedance by leptin of the LPS inhibitory effect on mucin synthesis was blocked by wortmannin, an inhibitor of PI3K, as well as by ERK inhibitor, PD98059. However, while the blockade of ERK led also to amplification in the impedance by leptin of the LPS-induced expression of ECE-1 and ET-1, the effect was not observed in the presence of wortmannin. The findings are the first to demonstrate that leptin counters the pathological consequences of P. gingivalisinfection on the synthesis of salivary mucin through the involvement in signaling events of PI3K and ERK pathways. We also show that the ERK cascade represents a critical signaling target for leptin in the LPS-induced up-regulation in ET-1.

Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease

PubMed Central

Nalivaeva, Natalia N.; Belyaev, Nikolai D.; Kerridge, Caroline; Turner, Anthony J.

2014-01-01

Abnormal elevation of amyloid β-peptide (Aβ) levels in the brain is the primary trigger for neuronal cell death specific to Alzheimer’s disease (AD). It is now evident that Aβ levels in the brain are manipulable due to a dynamic equilibrium between its production from the amyloid precursor protein (APP) and removal by amyloid clearance proteins. Clearance can be either enzymic or non-enzymic (binding/transport proteins). Intriguingly several of the main amyloid-degrading enzymes (ADEs) are members of the M13 peptidase family (neprilysin (NEP), NEP2 and the endothelin converting enzymes (ECE-1 and -2)). A distinct metallopeptidase, insulin-degrading enzyme (IDE), also contributes to Aβ degradation in the brain. The ADE family currently embraces more than 20 members, both membrane-bound and soluble, and of differing cellular locations. NEP plays an important role in brain function terminating neuropeptide signals. Its decrease in specific brain areas with age or after hypoxia, ischaemia or stroke contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP (and other genes) by the APP intracellular domain (AICD) and its dependence on the cell type and APP isoform expression suggest possibilities for selective manipulation of NEP gene expression in neuronal cells. We have also observed that another amyloid-clearing protein, namely transthyretin (TTR), is also regulated in the neuronal cell by a mechanism similar to NEP. Dependence of amyloid clearance proteins on histone deacetylases and the ability of HDAC inhibitors to up-regulate their expression in the brain opens new avenues for developing preventive strategies in AD. PMID:25278875

Hyphae-specific genes HGC1, ALS3, HWP1, and ECE1 and relevant signaling pathways in Candida albicans.

PubMed

Fan, Yan; He, Hong; Dong, Yan; Pan, Hengbiao

2013-12-01

Fungal virulence mechanisms include adhesion to epithelia, morphogenesis, production of secretory hydrolytic enzymes, and phenotype switching, all of which contribute to the process of pathogenesis. A striking feature of the biology of Candida albicans is its ability to grow in yeast, pseudohyphal, and hyphal forms. The hyphal form plays an important role in causing disease, by invading epithelial cells and causing tissue damage. In this review, we illustrate some of the main hyphae-specific genes, namely HGC1, UME6, ALS3, HWP1, and ECE1, and their relevant and reversed signal transduction pathways in reactions stimulated by environmental factors, including pH, CO2, and serum.

Big endothelin changes the cellular miRNA environment in TMOb osteoblasts and increases mineralization.

PubMed

Johnson, Michael G; Kristianto, Jasmin; Yuan, Baozhi; Konicke, Kathryn; Blank, Robert

2014-08-01

Endothelin (ET1) promotes the growth of osteoblastic breast and prostate cancer metastases. Conversion of big ET1 to mature ET1, catalyzed primarily by endothelin converting enzyme 1 (ECE1), is necessary for ET1's biological activity. We previously identified the Ece1, locus as a positional candidate gene for a pleiotropic quantitative trait locus affecting femoral size, shape, mineralization, and biomechanical performance. We exposed TMOb osteoblasts continuously to 25 ng/ml big ET1. Cells were grown for 6 days in growth medium and then switched to mineralization medium for an additional 15 days with or without big ET1, by which time the TMOb cells form mineralized nodules. We quantified mineralization by alizarin red staining and analyzed levels of miRNAs known to affect osteogenesis. Micro RNA 126-3p was identified by search as a potential regulator of sclerostin (SOST) translation. TMOb cells exposed to big ET1 showed greater mineralization than control cells. Big ET1 repressed miRNAs targeting transcripts of osteogenic proteins. Big ET1 increased expression of miRNAs that target transcripts of proteins that inhibit osteogenesis. Big ET1 increased expression of 126-3p 121-fold versus control. To begin to assess the effect of big ET1 on SOST production we analyzed both SOST transcription and protein production with and without the presence of big ET1 demonstrating that transcription and translation were uncoupled. Our data show that big ET1 signaling promotes mineralization. Moreover, the results suggest that big ET1's osteogenic effects are potentially mediated through changes in miRNA expression, a previously unrecognized big ET1 osteogenic mechanism.

Large Electrocaloric Effect in Relaxor Ferroelectric and Antiferroelectric Lanthanum Doped Lead Zirconate Titanate Ceramics

PubMed Central

Lu, Biao; Li, Peilian; Tang, Zhenhua; Yao, Yingbang; Gao, Xingsen; Kleemann, Wolfgang; Lu, Sheng-Guo

2017-01-01

Both relaxor ferroelectric and antiferroelectric materials can individually demonstrate large electrocaloric effects (ECE). However, in order to further enhance the ECE it is crucial to find a material system, which can exhibit simultaneously both relaxor ferroelectric and antiferroelectric properties, or easily convert from one into another in terms of the compositional tailoring. Here we report on a system, in which the structure can readily change from antiferroelectric into relaxor ferroelectric and vice versa. To this end relaxor ferroelectric Pb0.89La0.11(Zr0.7Ti0.3)0.9725O3 and antiferroelectric Pb0.93La0.07(Zr0.82Ti0.18)0.9825O3 ceramics were designed near the antiferroelectric-ferroelectric phase boundary line in the La2O3-PbZrO3-PbTiO3 phase diagram. Conventional solid state reaction processing was used to prepare the two compositions. The ECE properties were deduced from Maxwell relations and Landau-Ginzburg-Devonshire (LGD) phenomenological theory, respectively, and also directly controlled by a computer and measured by thermometry. Large electrocaloric efficiencies were obtained and comparable with the results calculated via the phenomenological theory. Results show great potential in achieving large cooling power as refrigerants. PMID:28345655

Accuracy of Computed Tomography for Predicting Pathologic Nodal Extracapsular Extension in Patients With Head-and-Neck Cancer Undergoing Initial Surgical Resection

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

Prabhu, Roshan S., E-mail: roshansprabhu@gmail.com; Winship Cancer Institute, Emory University, Atlanta, Georgia; Magliocca, Kelly R.

2014-01-01

Purpose: Nodal extracapsular extension (ECE) in patients with head-and-neck cancer increases the loco-regional failure risk and is an indication for adjuvant chemoradiation therapy (CRT). To reduce the risk of requiring trimodality therapy, patients with head-and-neck cancer who are surgical candidates are often treated with definitive CRT when preoperative computed tomographic imaging suggests radiographic ECE. The purpose of this study was to assess the accuracy of preoperative CT imaging for predicting pathologic nodal ECE (pECE). Methods and Materials: The study population consisted of 432 consecutive patients with oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent preoperative CT imaging before initialmore » surgical resection and neck dissection. Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. Results: Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in 87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%, respectively. The sensitivity of radiographic ECE increased from 18.8% for grade 1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE criteria of adjacent structure invasion was a better predictor than irregular borders/fat stranding for pECE. Conclusions: Radiographic ECE has poor sensitivity, but excellent specificity for pECE in patients who undergo initial surgical resection. PPV and NPV are reasonable for clinical decision making. The performance of preoperative CT imaging increased as pECE grade increased. Patients with resectable head-and-neck cancer with radiographic ECE based on adjacent structure invasion are at high risk for high-grade pECE requiring adjuvant CRT when treated with initial surgery; definitive CRT as an alternative should be considered where appropriate.« less

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

C. BARNES

Electron cyclotron emission (ECE) has been employed as a standard electron temperature profile diagnostic on many tokamaks and stellarators, but most magnetically confined plasma devices cannot take advantage of standard ECE diagnostics to measure temperature. They are either overdense, operating at high density relative to the magnetic field (e.g. {omega}{sub pe} >> {Omega}{sub ce} in a spherical torus) or they have insufficient density and temperature to reach the blackbody condition ({tau} > 2). Electron Bernstein waves (EBWs) are electrostatic waves which can propagate in overdense plasmas and have a high optical thickness at the electron cyclotron resonance layers, as amore » result of their large K{sub i}. This talk reports on measurements of EBW emission on the CDX-U spherical torus, where B{sub 0} {approx} 2 kG, {approx} 10{sup 13} cm{sup -3} and T{sub e} {approx} 10 - 200 eV. Results will be presented for both direct detection of EBWs and for mode-converted EBW emission. The EBW emission was absolutely calibrated and compared to the electron temperature profile measured by a multi-point Thomson scattering diagnostic. Depending on the plasma conditions, the mode-converted EBW radiation temperature was found to be {le} T{sub e} and the emission source was determined to be radially localized at the electron cyclotron resonance layer. A Langmuir triple probe was employed to measure changes in edge density profile in the vicinity of the upper hybrid resonance where the mode conversion of the EBWs is expected to occur. Changes in the mode conversion efficiency may explain the observation of mode-converted EBW radiation temperatures below T{sub e}. Initial results suggest EBW emission and EBW heating are viable concepts for plasmas where {omega}{sub pe} >> {Omega}{sub ce}.« less

High endothelin-converting enzyme-1 expression independently predicts poor survival of patients with esophageal squamous cell carcinoma.

PubMed

Wu, Ching-Fang; Lee, Ching-Tai; Kuo, Yao-Hung; Chen, Tzu-Haw; Chang, Chi-Yang; Chang, I-Wei; Wang, Wen-Lun

2017-09-01

Patients with esophageal squamous cell carcinoma have poor survival and high recurrence rate, thus an effective prognostic biomarker is needed. Endothelin-converting enzyme-1 is responsible for biosynthesis of endothelin-1, which promotes growth and invasion of human cancers. The role of endothelin-converting enzyme-1 in esophageal squamous cell carcinoma is still unknown. Therefore, this study investigated the significance of endothelin-converting enzyme-1 expression in esophageal squamous cell carcinoma clinically. We enrolled patients with esophageal squamous cell carcinoma who provided pretreated tumor tissues. Tumor endothelin-converting enzyme-1 expression was evaluated by immunohistochemistry and was defined as either low or high expression. Then we evaluated whether tumor endothelin-converting enzyme-1 expression had any association with clinicopathological findings or predicted survival of patients with esophageal squamous cell carcinoma. Overall, 54 of 99 patients with esophageal squamous cell carcinoma had high tumor endothelin-converting enzyme-1 expression, which was significantly associated with lymph node metastasis ( p = 0.04). In addition, tumor endothelin-converting enzyme-1 expression independently predicted survival of patients with esophageal squamous cell carcinoma, and the 5-year survival was poorer in patients with high tumor endothelin-converting enzyme-1 expression ( p = 0.016). Among patients with locally advanced and potentially resectable esophageal squamous cell carcinoma (stage II and III), 5-year survival was poorer with high tumor endothelin-converting enzyme-1 expression ( p = 0.003). High tumor endothelin-converting enzyme-1 expression also significantly predicted poorer survival of patients in this population. In patients with esophageal squamous cell carcinoma, high tumor endothelin-converting enzyme-1 expression might indicate high tumor invasive property. Therefore, tumor endothelin-converting enzyme-1 expression could be a good biomarker to identify patients with worse survival and higher risks of recurrence, who might benefit from the treatment by endothelin-converting enzyme-1 inhibitor.

Role of the neutral endopeptidase 24.11 in the conversion of big endothelins in guinea-pig lung parenchyma.

PubMed Central

Lebel, N.; D'Orléans-Juste, P.; Fournier, A.; Sirois, P.

1996-01-01

1. We have studied the conversion of big endothelin-1 (big ET-1), big endothelin-2 (big ET-2) and big endothelin-3 (big ET-3) and characterized the enzyme involved in the conversion of the three peptides in guinea-pig lung parenchyma (GPLP). 2. Endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3) (10 nM to 100 nM) caused similar concentration-dependent contractions of strips of GPLP. 3. Big ET-1 and big ET-2 also elicited concentration-dependent contractions of GPLP strips. In contrast, big ET-3, up to a concentration of 100 nM, failed to induce a contraction of the GPLP. 4. Incubation of strips of GPLP with the dual endothelin converting enzyme (ECE) and neutral endopeptidase (NEP) inhibitor, phosphoramidon (10 microM), as well as two other NEP inhibitors thiorphan (10 microM) or SQ 28,603 (10 microM) decreased by 43% (P < 0.05), 42% (P < 0.05) and 40% (P < 0.05) the contractions induced by 30 nM of big ET-1 respectively. Captopril (10 microM), an angiotensin-converting enzyme inhibitor, had no effect on the contractions induced by big ET-1. 5. The incubation of strips of GPLP with phosphoramidon (10 microM), thiorphan (10 microM) or SQ 28,603 (10 microM) also decreased by 74% (P < 0.05), 34% and 50% (P < 0.05) the contractions induced by 30 nM big ET-2 respectively. As for the contractions induced by big ET-1, captopril (10 microM) had no effect on the concentration-dependent contractions induced by big ET-2. 6. Phosphoramidon (10 microM), thiorphan (10 microM) and SQ 28,603 (10 microM) significantly potentiated the contractions of strips of GPLP induced by both ET-1 (30 nM) and ET-3 (30 nM). However, the enzymatic inhibitors did not significantly affect the contractions induced by ET-2 (30 nM) in this tissue. 7. These results suggest that the effects of big ET-1 and big ET-2 result from the conversion to ET-1 and ET-2 by at least one enzyme sensitive to phosphoramidon, thiorphan and SQ 28,603. This enzyme corresponds possibly to EC 3.4.24.11 (NEP 24.11) and could also be responsible for the degradation of ETs in the GPLP. Images Figure 4 PMID:8825361

Summary of ECE presentations at EC-18

DOE PAGES

Taylor, G.

2015-03-12

There were nine ECE and one EBE presentation at EC-18. Four of the presentations were on various aspects of ECE on ITER. The ITER ECE diagnostic has entered an important detailed preliminary design phase and faces several design challenges in the next 2-3 years. Most of the other ECE presentations at the workshop were focused on applications of ECE diagnostics to plasma measurements, rather than improvements in technology, although it was apparent that heterodyne receiver technology continues to improve. CECE, ECE imaging and EBE imaging are increasingly providing valuable insights into plasma behavior that is important to understand if futuremore » burning plasma devices, such as ITER, FNSF and DEMO, are to be successful.« less

The effects of ECE on the benefits of PMRT for breast cancer patients with positive axillary nodes.

PubMed

Geng, Wenwen; Zhang, Bin; Li, Danhua; Liang, Xinrui; Cao, Xunchen

2013-07-01

The purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1-3, 4-9 and ≥10 positive axillary nodes). A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as 'Radio + /ECE + ', 'Radio-/ECE + ', 'Radio + /ECE-' or 'Radio-/ECE-' according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1-3 (P = 0.5720), ≥10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4-9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). In our study, regardless of the ECE status, PMRT didn't significantly improve the LRFFS for patients with 1-3 or ≥10 positive axillary nodes. However, for patients with 4-9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.

Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema.

PubMed

Byrd, James Brian; Touzin, Karine; Sile, Saba; Gainer, James V; Yu, Chang; Nadeau, John; Adam, Albert; Brown, Nancy J

2008-01-01

Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor-associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor-associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor-associated angioedema and 176 angiotensin-converting enzyme inhibitor-exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg(9)-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6+/-7.8 versus 29.6+/-7.3 nmol/mL per minute; P=0.026) and antigen (465.8+/-260.8 versus 563.1+/-208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor-associated angioedema compared with angiotensin-converting enzyme inhibitor-exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5+/-4.9 versus 29.8+/-6.7 nmol/mL per minute; P=0.001) and antigen (354.4+/-124.7 versus 559.8+/-163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema.

Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema

PubMed Central

Byrd, James Brian; Touzin, Karine; Sile, Saba; Gainer, James V.; Yu, Chang; Nadeau, John; Adam, Albert; Brown, Nancy J.

2009-01-01

Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor–associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor–associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor–associated angioedema and 176 angiotensin-converting enzyme inhibitor–exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg9-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6±7.8 versus 29.6±7.3 nmol/mL per minute; P=0.026) and antigen (465.8±260.8 versus 563.1±208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor–associated angioedema compared with angiotensin-converting enzyme inhibitor–exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5±4.9 versus 29.8±6.7 nmol/mL per minute; P=0.001) and antigen (354.4±124.7 versus 559.8±163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema. PMID:18025295

Material System Engineering for Advanced Electrocaloric Cooling Technology

NASA Astrophysics Data System (ADS)

Qian, Xiaoshi

Electrocaloric effect refers to the entropy change and/or temperature change in dielectrics caused by the electric field induced polarization change. Recent discovery of giant ECE provides an opportunity to realize highly efficient cooling devices for a broad range of applications ranging from household appliances to industrial applications, from large-scale building thermal management to micro-scale cooling devices. The advances of electrocaloric (EC) based cooling device prototypes suggest that highly efficient cooling devices with compact size are achievable, which could lead to revolution in next generation refrigeration technology. This dissertation focuses on both EC based materials and cooling devices with their recent advances that address practical issues. Based on better understandings in designing an EC device, several EC material systems are studied and improved to promote the performances of EC based cooling devices. In principle, applying an electric field to a dielectric would cause change of dipolar ordering states and thus a change of dipolar entropy. Giant ECE observed in ferroelectrics near ferroelectric-paraelectric (FE-PE) transition temperature is owing to the large dipolar orientation change, between random-oriented dipolar states in paraelectric phase and spontaneous-ordered dipolar states in ferroelectric phases, which is induced by external electric fields. Besides pursuing large ECE, studies on EC cooling devices indicated that EC materials are required to possess wide operational temperature window, in which large ECE can be maintained for efficient operations. Although giant ECE was first predicted in ferroelectric polymers, where the large effect exhibits near FEPE phase transition, the narrow operation temperature window poses obstacles for these normal ferroelectrics to be conveniently perform in wide range of applications. In this dissertation, we demonstrated that the normal ferroelectric polymers can be converted to relaxor ferroelectric polymers which possess both giant ECE (27 Kelvin temperature drop) and much wider operating temperature window (over 50 kelvin covering RT) by proper defect modification which delicately tailors ferroelectrics in meso-, micro- and molecular scales. In addition, in order to be practical, EC device requires EC material can be driven at low electric fields upon achieve the large ECE. It is demonstrated in this dissertation that by facially modifying materials structure in meso-, micro- and molecular scale, lowfield ECE can be greatly improved. Large ECE, induced by low electric fields and existing in wide temperature window, is a major improvement in EC materials for practical applications. Besides EC polymers, this thesis also investigated EC ceramics. Due to several unique opportunities offered by the EC ceramics, Ba(ZrxTi 1-x)O3 (BZT), that is studied. (i) This class of EC ceramics offers a possibility to explore the invariant critical point (ICP), which maximizes the number of coexistent phase and provides a nearly vanishing energy barrier for switching among different phases. As demonstrated in this thesis, the BZT bulk ceramics at x˜ 0.2 exhibits a large adiabatic temperature drop DeltaTc=4.5 K, a large isothermal entropy change DeltaS = 8 Jkg-1K-1, a large EC coefficient (|DeltaT c/DeltaE| = 0.52x10-6 KmV-1 and DeltaS/DeltaE=0.93x10 -6 Jmkg-1K-1V-1) over a wide operating temperature range Tspan>30K. (ii) The thermal conductivity of EC ceramics is in general, much higher than that of EC polymers, and consequently they will allow EC cooling configurations which are not accessible by the EC polymers. Moreover, in the same device configuration, the high thermal conductivity of EC ceramics (kappa> 5 W/mK, compared with EC polymer, ˜ 0.25 W/mK) allows higher operation frequency and therefore a higher cooling power. (iii) Well-established fabrication processes of multilayer ceramic capacitor (MLCC) provide a foundation for the EC ceramic toward mass production. In this thesis, BZT thick film double layers have been fabricated and large ECE has been directly measured. EC induced temperature drop (DeltaT) around 6.3 °C and entropy change (DeltaS) of 11.0 Jkg-1K -1 are observed under an electric field of DeltaE=14.6 MV/m at 40 °C was observed in BZT thick film double layers. The result encourages further investigations on ECE in MLCC for practical applications. (Abstract shortened by ProQuest.).

Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis

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

Nosal, A.; Schleissner, L.A.; Mishkin, F.S.

1979-03-01

Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. Itmore » was concluded that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis.« less

Tackling extremes: challenges for ecological and evolutionary research on extreme climatic events.

PubMed

Bailey, Liam D; van de Pol, Martijn

2016-01-01

Extreme climatic events (ECEs) are predicted to become more frequent as the climate changes. A rapidly increasing number of studies - though few on animals - suggest that the biological consequences of ECEs can be severe. However, ecological research on the impacts of ECEs has been limited by a lack of cohesiveness and structure. ECEs are often poorly defined and have often been confusingly equated with climatic variability, making comparison between studies difficult. In addition, a focus on short-term studies has provided us with little information on the long-term implications of ECEs, and the descriptive and anecdotal nature of many studies has meant it is still unclear what the key research questions are. Synthesizing the current state of work is essential to identify ways to make progress. We conduct a synthesis of the literature and discuss conceptual and practical challenges faced by research on ECEs. We consider three steps to advance research. First, we discuss the importance of choosing an ECE definition and identify the pros and cons of 'climatological' and 'biological' definitions of ECEs. Secondly, we advocate research beyond short-term descriptive studies to address questions concerning the long-term implications of ECEs, focussing on selective pressures and phenotypically plastic responses and how they might differ from responses to a changing climatic mean. Finally, we encourage a greater focus on multi-event studies that help us understand the implications of changing patterns of ECEs, through the combined use of modelling, experimental and observational field studies. This study aims to open a discussion on the definitions, questions and methods currently used to study ECEs, which will lead to a more cohesive approach to future ECE research. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Early Childhood Leadership through the Lens of Distributed Leadership

ERIC Educational Resources Information Center

Heikka, Johanna; Hujala, Eeva

2013-01-01

This study aims to investigate distribution of responsibilities for leadership in early childhood education (ECE) context. It focuses on the enactments of leadership by investigating how ECE stakeholders, e.g. teachers, ECE centre directors and administrative ECE leaders in municipalities perceive the leadership responsibilities. Using focus…

Inclusion in Early Childhood Education: A Zimbabwean Perspective

ERIC Educational Resources Information Center

Majoko, Tawanda

2017-01-01

The current study examined Early Childhood Education (ECE) teachers' understanding, attitudes and demographic influences regarding inclusion in ECE. Embedded within inclusive pedagogical philosophy, the present descriptive study draws on a sample of 21 ECE teachers purposively selected from ECE settings in Mashonaland West educational province of…

21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Angiotensin converting enzyme (A.C.E.) test system... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of angiotensin...

Predictors of Public Early Care and Education Use among Children of Low-Income Immigrants

PubMed Central

Johnson, Anna D.; Padilla, Christina; Votruba-Drzal, Elizabeth

2017-01-01

Little is known about predictors of publicly funded early care and education (ECE) use among low-income children of immigrants. Without this knowledge, it is difficult to effectively increase participation in these public programs, which promote school readiness but are underused by children of immigrants. Using nationally representative data from the Early Childhood Longitudinal Study -Birth Cohort (ECLS-B), this study attempts to identify pertinent family, child, maternal ECE preference, broader contextual, and immigrant specific characteristics predictive of ECE use among 4-year old children in a sample of low-income children of immigrants (N ≈ 1,050). Specifically, we estimate multinomial logistic regression models predicting type of ECE (Head Start, public pre-k, subsidized ECE, unsubsidized ECE, parental care) from these characteristics. Findings suggest that even in a low-income sample, correlates of disadvantage such as low maternal education and prior receipt of public benefits are important predictors of public ECE use, as are maternal preferences for certain features of care and supply-side factors such as ECE availability. Immigrant-specific factors such as English proficiency, citizenship status, availability of non-English speaking caregivers, and generosity of state policies toward immigrants emerged as particularly salient for explaining the public ECE selection patterns of low-income immigrants. Results point to future research areas and potential policy solutions aimed at increasing public ECE use for children who may stand to benefit the most. PMID:28966423

Dynamic linear modeling of monthly electricity demand in Japan: Time variation of electricity conservation effect

PubMed Central

Shiraki, Hiroto; Ashina, Shuichi

2018-01-01

After the severe nuclear disaster in Fukushima, which was triggered by the Great East Japan earthquake in March 2011, nuclear power plants in Japan were temporarily shut down for mandatory inspections. To prevent large-scale blackouts, the Japanese government requested companies and households to reduce electricity consumption in summer and winter. It is reported that the domestic electricity demand had a structural decrease because of the electricity conservation effect (ECE). However, quantitative analysis of the ECE is not sufficient, and especially time variation of the ECE remains unclear. Understanding the ECE is important because Japan’s NDC (nationally determined contribution) assumes the reduction of CO2 emissions through aggressive energy conservation. In this study, we develop a time series model of monthly electricity demand in Japan and estimate time variation of the ECE. Moreover, we evaluate the impact of electricity conservation on CO2 emissions from power plants. The dynamic linear model is used to separate the ECE from the effects of other irrelevant factors (e.g. air temperature, economic production, and electricity price). Our result clearly shows that consumers’ electricity conservation behavior after the earthquake was not temporary but became established as a habit. Between March 2011 and March 2016, the ECE on industrial electricity demand ranged from 3.9% to 5.4%, and the ECE on residential electricity demand ranged from 1.6% to 7.6%. The ECE on the total electricity demand was estimated at 3.2%–6.0%. We found a seasonal pattern that the residential ECE in summer is higher than that in winter. The emissions increase from the shutdown of nuclear power plants was mitigated by electricity conservation. The emissions reduction effect was estimated at 0.82 MtCO2–2.26 MtCO2 (−4.5% on average compared to the zero-ECE case). The time-varying ECE is necessary for predicting Japan’s electricity demand and CO2 emissions after the earthquake. PMID:29708988

Dynamic linear modeling of monthly electricity demand in Japan: Time variation of electricity conservation effect.

PubMed

Honjo, Keita; Shiraki, Hiroto; Ashina, Shuichi

2018-01-01

After the severe nuclear disaster in Fukushima, which was triggered by the Great East Japan earthquake in March 2011, nuclear power plants in Japan were temporarily shut down for mandatory inspections. To prevent large-scale blackouts, the Japanese government requested companies and households to reduce electricity consumption in summer and winter. It is reported that the domestic electricity demand had a structural decrease because of the electricity conservation effect (ECE). However, quantitative analysis of the ECE is not sufficient, and especially time variation of the ECE remains unclear. Understanding the ECE is important because Japan's NDC (nationally determined contribution) assumes the reduction of CO2 emissions through aggressive energy conservation. In this study, we develop a time series model of monthly electricity demand in Japan and estimate time variation of the ECE. Moreover, we evaluate the impact of electricity conservation on CO2 emissions from power plants. The dynamic linear model is used to separate the ECE from the effects of other irrelevant factors (e.g. air temperature, economic production, and electricity price). Our result clearly shows that consumers' electricity conservation behavior after the earthquake was not temporary but became established as a habit. Between March 2011 and March 2016, the ECE on industrial electricity demand ranged from 3.9% to 5.4%, and the ECE on residential electricity demand ranged from 1.6% to 7.6%. The ECE on the total electricity demand was estimated at 3.2%-6.0%. We found a seasonal pattern that the residential ECE in summer is higher than that in winter. The emissions increase from the shutdown of nuclear power plants was mitigated by electricity conservation. The emissions reduction effect was estimated at 0.82 MtCO2-2.26 MtCO2 (-4.5% on average compared to the zero-ECE case). The time-varying ECE is necessary for predicting Japan's electricity demand and CO2 emissions after the earthquake.

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor.

PubMed

Charbonneau, Hélène; Buléon, Marie; Minville, Vincent; Faguer, Stanislas; Girolami, Jean-Pierre; Bascands, Jean-Loup; Tack, Ivan; Mayeur, Nicolas

2016-09-01

Angiotensin-converting enzyme inhibitors are associated with deleterious hypotension during anesthesia and shock. Because the pharmacologic effects of angiotensin-converting enzyme inhibitors are partly mediated by increased bradykinin B2 receptor activation, this study aimed to determine the impact of acute B2 receptor blockade during hemorrhagic shock in angiotensin-converting enzyme inhibitor-treated mice. In vivo study. University research unit. C57/Bl6 mice. The hemodynamic effect of B2 receptor blockade using icatibant (B2 receptor antagonist) was studied using a pressure-targeted hemorrhagic shock and a volume-targeted hemorrhagic shock. Animals were anesthetized with ketamine and xylazine (250 mg/kg and 10 mg/kg, respectively), intubated using intratracheal cannula, and ventilated (9 mL/kg, 150 min). Five groups were studied: 1) sham-operated animals, 2) control shocked mice, 3) shocked mice treated with ramipril for 7 days (angiotensin-converting enzyme inhibitors) before hemorrhagic shock, 4) shocked mice treated with angiotensin-converting enzyme inhibitors and a single bolus of icatibant (HOE-140) immediately before anesthesia (angiotensin-converting enzyme inhibitors + icatibant), and 5) shocked mice treated with a single bolus of icatibant. One hour after volume-targeted hemorrhagic shock, blood lactate was measured to evaluate organ failure. During pressure-targeted hemorrhagic shock, the mean blood volume withdrawn was significantly lower in the angiotensin-converting enzyme inhibitor group than in the other groups (p < 0.001). During volume-targeted hemorrhagic shock, icatibant prevented blood pressure lowering in the angiotensin-converting enzyme inhibitor group (p < 0.001). Blood lactate was significantly higher in the angiotensin-converting enzyme inhibitor group than in the other groups, particularly the HOE groups. During hemorrhagic shock, acute B2 receptor blockade significantly attenuates the deleterious hemodynamic effect of angiotensin-converting enzyme inhibitor treatment in mice. This beneficial effect of B2 receptor blockade is rapidly reached and sustained with a single bolus of icatibant. This benefit could be of interest in angiotensin-converting enzyme inhibitor-treated patients during both emergency anesthesia and resuscitation.

Behavioural, ecological and evolutionary responses to extreme climatic events: challenges and directions.

PubMed

van de Pol, Martijn; Jenouvrier, Stéphanie; Cornelissen, Johannes H C; Visser, Marcel E

2017-06-19

More extreme climatic events (ECEs) are among the most prominent consequences of climate change. Despite a long-standing recognition of the importance of ECEs by paleo-ecologists and macro-evolutionary biologists, ECEs have only recently received a strong interest in the wider ecological and evolutionary community. However, as with many rapidly expanding fields, it lacks structure and cohesiveness, which strongly limits scientific progress. Furthermore, due to the descriptive and anecdotal nature of many ECE studies it is still unclear what the most relevant questions and long-term consequences are of ECEs. To improve synthesis, we first discuss ways to define ECEs that facilitate comparison among studies. We then argue that biologists should adhere to more rigorous attribution and mechanistic methods to assess ECE impacts. Subsequently, we discuss conceptual and methodological links with climatology and disturbance-, tipping point- and paleo-ecology. These research fields have close linkages with ECE research, but differ in the identity and/or the relative severity of environmental factors. By summarizing the contributions to this theme issue we draw parallels between behavioural, ecological and evolutionary ECE studies, and suggest that an overarching challenge is that most empirical and theoretical evidence points towards responses being highly idiosyncratic, and thus predictability being low. Finally, we suggest a roadmap based on the proposition that an increased focus on the mechanisms behind the biological response function will be crucial for increased understanding and predictability of the impacts of ECE.This article is part of the themed issue 'Behavioural, ecological and evolutionary responses to extreme climatic events'. © 2017 The Author(s).

Effectiveness of the Lunch is in the Bag program on communication between the parent, child and child-care provider around fruits, vegetables and whole grain foods: a group-randomized controlled trial

PubMed Central

Rashid, Tasnuva; Ranjit, Nalini; Byrd-Williams, Courtney; Chuang, Ru-Jye; Roberts-Gray, Cindy; Briley, Margaret; Sweitzer, Sara; Hoelscher, Deanna M.

2015-01-01

Objective To evaluate the effectiveness of the parent- and early care education (ECE) center-based Lunch is in the Bag program on communication between parent, child, and their ECE center providers around fruits, vegetables and whole grain foods (FVWG). Method A total of n=30 ECE center; 577 parent-child dyads participated in this group-randomized controlled trial conducted from 2011–2013 in Texas (n=15 ECE center, 327 dyads intervention group; n=15 ECE center, 250 dyads comparison group). Parent-child and parent-ECE center provider communication was measured using a parent-reported survey administered at baseline and end of the five-week intervention period. Multilevel linear regression analysis was used to compare the pre-to-post intervention changes in the parent-child and parent-ECE center provider communication scales. Significance was set at p<0.05. Results At baseline, parent-child and parent-ECE center provider communication scores were low. There was a significant increase post-intervention in the parent-ECE center provider communication around vegetables (Adjusted β = 0.78, 95%CI: 0.13, 1.43, p=0.002), and around fruit (Adjusted β = 0.62, 95%CI: 0.04, 0.20, p=0.04) among the parents in the intervention group as compared to those in the comparison group. There were no significant intervention effects on parent-child communication. Conclusion Lunch is in the Bag had significant positive effects on improving communication between the parents and ECE center providers around FVWG. PMID:26190371

Behavioural, ecological and evolutionary responses to extreme climatic events: challenges and directions

PubMed Central

2017-01-01

More extreme climatic events (ECEs) are among the most prominent consequences of climate change. Despite a long-standing recognition of the importance of ECEs by paleo-ecologists and macro-evolutionary biologists, ECEs have only recently received a strong interest in the wider ecological and evolutionary community. However, as with many rapidly expanding fields, it lacks structure and cohesiveness, which strongly limits scientific progress. Furthermore, due to the descriptive and anecdotal nature of many ECE studies it is still unclear what the most relevant questions and long-term consequences are of ECEs. To improve synthesis, we first discuss ways to define ECEs that facilitate comparison among studies. We then argue that biologists should adhere to more rigorous attribution and mechanistic methods to assess ECE impacts. Subsequently, we discuss conceptual and methodological links with climatology and disturbance-, tipping point- and paleo-ecology. These research fields have close linkages with ECE research, but differ in the identity and/or the relative severity of environmental factors. By summarizing the contributions to this theme issue we draw parallels between behavioural, ecological and evolutionary ECE studies, and suggest that an overarching challenge is that most empirical and theoretical evidence points towards responses being highly idiosyncratic, and thus predictability being low. Finally, we suggest a roadmap based on the proposition that an increased focus on the mechanisms behind the biological response function will be crucial for increased understanding and predictability of the impacts of ECE. This article is part of the themed issue ‘Behavioural, ecological and evolutionary responses to extreme climatic events’. PMID:28483865

Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: implications for radiation target volume design.

PubMed

Olszyna-Serementa, Marta; Socha, Joanna; Wierzchowski, Marek; Kępka, Lucyna

2013-05-01

Overall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (-) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design. Eighty R1-resected (37 ECE+ and 43 ECE-) patients received PORT (60Gy, 2Gy daily) between 2002 and 2011. Patients with N2 disease received limited elective nodal irradiation (ENI); for pN0-1 disease the use of ENI was optional. Among ECE- (extranodal-R1) patients there were 35 pN0-1 and eight pN2 cases; in pN0-1 patients, patterns of failure and outcomes were analyzed with respect to the use of ENI. Loco-regional failure (LRF) was defined as in-field relapse; isolated nodal failure (INF) was defined as out-of-field regional nodal recurrence occurring without LRF, irrespective of distant metastases. The actuarial 3-year OS rate was 36.3% (median: 30 months). Three-year OS rates in the ECE- and ECE+ group were 40.4% and 31.4%, with median OS of 31 and 24 months, respectively (p=0.43). In multivariate analysis, the presence of ECE was correlated with OS (HR=3.02; 95% CI: 1.00-9.16; p=0.05). Three-year cumulative incidence of LRF (CILRF) was 14.5% and 15.5% in the ECE- and ECE+ groups, respectively (p=0.98). Three-year cumulative incidence of INF (CIINF) was 14.1% in the ECE- group and 11.1% in the ECE+ group (p=0.76). For pN0-1 patients treated with and without ENI (13 and 22 patients) 3-year CILRF rates were 7.7% and 20.8%, respectively (p=0.20); 3-year CIINF rates were 9.1% and 16.3%, respectively (p=0.65). PORT resulted in a relatively good survival of R1-resected NSCLC patients. Relatively high incidence of INF was found in both ECE+ and ECE- patients. For ECE+ patients, treated with limited ENI, distant failure remains a major concern, so the design of ENI fields seems of lesser importance. Omission of ENI in pN0-1 (extranodal-R1) patients resulted in an unacceptably high incidence of INF. We postulate the use of some form of ENI in this setting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Elsholtzia ciliata (Thunb.) Hylander attenuates renal inflammation and interstitial fibrosis via regulation of TGF-ß and Smad3 expression on unilateral ureteral obstruction rat model.

PubMed

Kim, Tae-Won; Kim, Young-Jung; Seo, Chang-Seob; Kim, Hyun-Tae; Park, Se-Ra; Lee, Mee-Young; Jung, Ju-Young

2016-04-15

Renal interstitial fibrosis is characterized by excessive accumulation of extracellular matrix, which leads to end-stage renal failure. The aim of this study was to explore the effect of Elsholtzia ciliata (Thunb.) Hylander ethanol extract (ECE) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). After quantitative analysis of ECE using the high performance liquid chromatography-photodiode array (HPLC-PDA) method, an in vitro study was performed to assess the anti-inflammatory and anti-fibrotic effects of ECE, using lipopolysaccharide (LPS) and transforming growth factor-ß (TGF-ß), respectively. For in vivo study, all male Sprague Dawley (SD) rats (n=10/group), except for those in the control group, underwent UUO. The rats were orally treated with water (control), captopril (positive control, 200 mg/kg), and ECE (300 and 500 mg/kg) for 14 days. In ECE, luteolin and rosmarinic acid were relatively abundant among the other flavonoids and phenolic acids. ECE treatment ameliorated LPS-induced overexpression of nuclear factor-κB, tumor necrosis factor (TNF-α), and interleukin-6 and improved oxidative stress in RAW 264.7 cells. Furthermore, ECE treatment suppressed TGF-ß-induced α-smooth muscle actin and matrix metalloproteinase 9 expression in human renal mesangial cells. In the UUO model, 14 consecutive days of ECE treatment improved UUO-induced renal damage and attenuated histopathological alterations and interstitial fibrosis. Moreover, the renal expression of TNF-α, TGF-ß, and Smad 3 were inhibited by ECE treatment. Taken together, the effects of ECE may be mediated by blocking the activation of TGF-ß and inflammatory cytokines, leading subsequently to degradation of the ECM accumulation pathway. Based on these findings, ECE might serve as an improved treatment strategy for renal fibrotic disease. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effectiveness of the Lunch is in the Bag program on communication between the parent, child and child-care provider around fruits, vegetables and whole grain foods: A group-randomized controlled trial.

PubMed

Sharma, Shreela V; Rashid, Tasnuva; Ranjit, Nalini; Byrd-Williams, Courtney; Chuang, Ru-Jye; Roberts-Gray, Cynthia; Briley, Margaret; Sweitzer, Sara; Hoelscher, Deanna M

2015-12-01

To evaluate the effectiveness of the parent- and early care education (ECE) center-based Lunch is in the Bag program on communication between parent, child, and their ECE center providers around fruits, vegetables and whole grain foods (FVWG). A total of n=30 ECE center; 577 parent-child dyads participated in this group-randomized controlled trial conducted from 2011 to 2013 in Texas (n=15 ECE center, 327 dyads intervention group; n=15 ECE center, 250 dyads comparison group). Parent-child and parent-ECE center provider communication was measured using a parent-reported survey administered at baseline and end of the five-week intervention period. Multilevel linear regression analysis was used to compare the pre-to-post intervention changes in the parent-child and parent-ECE center provider communication scales. Significance was set at p<0.05. At baseline, parent-child and parent-ECE center provider communication scores were low. There was a significant increase post-intervention in the parent-ECE center provider communication around vegetables (Adjusted β=0.78, 95%CI: 0.13, 1.43, p=0.002), and around fruit (Adjusted β=0.62, 95%CI: 0.04, 0.20, p=0.04) among the parents in the intervention group as compared to those in the comparison group. There were no significant intervention effects on parent-child communication. Lunch is in the Bag had significant positive effects on improving communication between the parents and ECE center providers around FVWG. Copyright © 2015 Elsevier Inc. All rights reserved.

Upgrades and Real Time Ntm Control Application of the Ece Radiometer on Asdex Upgrade

NASA Astrophysics Data System (ADS)

Hicks, N. K.; Suttrop, W.; Behler, K.; Giannone, L.; Manini, A.; Maraschek, M.; Raupp, G.; Reich, M.; Sips, A. C. C.; Stober, J.; Treutterer, W.; ASDEX Upgrade Team; Cirant, S.

2009-04-01

The 60-channel electron cyclotron emission (ECE) radiometer diagnostic on the ASDEX Upgrade tokamak is presently being upgraded to include a 1 MHz sampling rate data acquisition system. This expanded capability allows electron temperature measurements up to 500 kHz (anti-aliasing filter cut-off) with spatial resolution ~1 cm, and will thus provide measurement of plasma phenomena on the MHD timescale, such as neoclassical tearing modes (NTMs). The upgraded and existing systems may be run in parallel for comparison, and some of the first plasma measurements using the two systems together are presented. A particular planned application of the upgraded radiometer is integration into a real-time NTM stabilization loop using targeted deposition of electron cyclotron resonance heating (ECRH). For this loop, it is necessary to determine the locations of the NTM and ECRH deposition using ECE measurements. As the magnetic island of the NTM repeatedly rotates through the ECE line of sight, electron temperature fluctuations at the NTM frequency are observed. The magnetic perturbation caused by the NTM is independently measured using Mirnov coils, and a correlation profile between these magnetic measurements and the ECE data is constructed. The phase difference between ECE oscillations on opposite sides of the island manifests as a zero-crossing of the correlation profile, which determines the NTM location in ECE channel space. To determine the location of ECRH power deposition, the power from a given gyrotron may be modulated at a particular frequency. Correlation analysis of this modulated signal and the ECE data identifies a particular ECE channel associated with the deposition of that gyrotron. Real time equilibrium reconstruction allows the ECE channels to be translated into flux surface and spatial coordinates for use in the feedback loop.

Update on the status of the ITER ECE diagnostic design

NASA Astrophysics Data System (ADS)

Taylor, G.; Austin, M. E.; Basile, A.; Beno, J. H.; Danani, S.; Feder, R.; Houshmandyar, S.; Hubbard, A. E.; Johnson, D. W.; Khodak, A.; Kumar, R.; Kumar, S.; Ouroua, A.; Padasalagi, S. B.; Pandya, H. K. B.; Phillips, P. E.; Rowan, W. L.; Stillerman, J.; Thomas, S.; Udintsev, V. S.; Vayakis, G.; Walsh, M.; Weeks, D.

2017-07-01

Considerable progress has been made on the design of the ITER electron cyclotron emission (ECE) diagnostic over the past two years. Radial and oblique views are still included in the design in order to measure distortions in the electron momentum distribution, but the oblique view has been redirected to reduce stray millimeter radiation from the electron cyclotron heating system. A major challenge has been designing the 1000 K calibration sources and remotely activated mirrors located in the ECE diagnostic shield module (DSM) in the equatorial port plug #09. These critical systems are being modeled and prototypes are being developed. Providing adequate neutron shielding in the DSM while allowing sufficient space for optical components is also a significant challenge. Four 45-meter long low-loss transmission lines transport the 70-1000 GHz ECE from the DSM to the ECE instrumentation room. Prototype transmission lines are being tested, as are the polarization splitter modules that separate O-mode and X-mode polarized ECE. A highly integrated prototype 200-300 GHz radiometer is being tested on the DIII-D tokamak in the USA. Design activities also include integration of ECE signals into the ITER plasma control system and determining the hardware and software architecture needed to control and calibrate the ECE instruments.

Patterns of care and outcomes of adjuvant therapy for high-risk head and neck cancer after surgery.

PubMed

Osborn, Virginia Wedell; Givi, Babak; Rineer, Justin; Roden, Dylan; Sheth, Niki; Lederman, Ariel; Katsoulakis, Evangelia; Hu, Kenneth; Schreiber, David

2018-06-01

Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE). The National Cancer Data Base (NCDB) was queried to identify patients with squamous cell carcinoma of the head and neck with stages III to IVB disease or with positive margins and/or ECE diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using univariable and multivariable logistic and Cox regression, we assessed for predictors of CRT use and covariables impacting overall survival (OS), including in a propensity-matched subset. Of 12 224 patients, 67.1% with positive margins and/or ECE received CRT as well as 54.0% without positive margins and/or ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity-matched cohort, OS benefit persisted with CRT, including in a subset with positive margins and/or ECE but not without. Postoperative CRT seems underutilized with positive margins and/or ECE and overutilized without positive margins and/or ECE. The CRT was associated with improved OS but the benefit persisted only in the subset with positive margins and/or ECE. © 2018 Wiley Periodicals, Inc.

154 GHz collective Thomson scattering in LHD

NASA Astrophysics Data System (ADS)

Tanaka, K.; Nishiura, M.; Kubo, S.; Shimozuma, T.; Saito, T.; Moseev, D.; Abramovic, I.

2018-01-01

Collective Thomson scattering (CTS) was developed by using a 154 GHz gyrotron, and the first data has been obtained. Already, 77 GHz CTS has worked successfully. However, in order to access higher density region, 154 GHz option enhances the usability that reduces the refraction effect, which deteriorates in the local measurements. The system in the down converted frequency was almost identical to the system for 77 GHz. Probing beam, a notch filter, a mixer, and a local oscillator in the receiver system for 77 GHz option were replaced to those for the 154 GHz option. 154 GHz gyrotron was originally prepared for the second harmonic electron cyclotron heating (ECRH) at 2.75 T. However, scattering signal was masked by the second harmonic electron cyclotron emission (ECE) at 2.75 T. Therefore, 154 GHz CTS was operated at 1.375 T with fourth harmonic ECE, and an acceptable signal to noise ratio was obtained. There is a signature of fast ion components with neutral beam (NB) injection. In addition, the CTS spectrum became broader in hydrogen discharge than in deuterium discharge, as the theoretical CTS spectrum expects. This observation indicates a possibility to identify ion species ratio by the 154 GHz CTS diagnostic.

Intermediate frequency band digitized high dynamic range radiometer system for plasma diagnostics and real-time Tokamak control

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

Bongers, W. A.; Beveren, V. van; Westerhof, E.

2011-06-15

An intermediate frequency (IF) band digitizing radiometer system in the 100-200 GHz frequency range has been developed for Tokamak diagnostics and control, and other fields of research which require a high flexibility in frequency resolution combined with a large bandwidth and the retrieval of the full wave information of the mm-wave signals under investigation. The system is based on directly digitizing the IF band after down conversion. The enabling technology consists of a fast multi-giga sample analog to digital converter that has recently become available. Field programmable gate arrays (FPGA) are implemented to accomplish versatile real-time data analysis. A prototypemore » system has been developed and tested and its performance has been compared with conventional electron cyclotron emission (ECE) spectrometer systems. On the TEXTOR Tokamak a proof of principle shows that ECE, together with high power injected and scattered radiation, becomes amenable to measurement by this device. In particular, its capability to measure the phase of coherent signals in the spectrum offers important advantages in diagnostics and control. One case developed in detail employs the FPGA in real-time fast Fourier transform (FFT) and additional signal processing. The major benefit of such a FFT-based system is the real-time trade-off that can be made between frequency and time resolution. For ECE diagnostics this corresponds to a flexible spatial resolution in the plasma, with potential application in smart sensing of plasma instabilities such as the neoclassical tearing mode (NTM) and sawtooth instabilities. The flexible resolution would allow for the measurement of the full mode content of plasma instabilities contained within the system bandwidth.« less

Human uterine cervical epithelial cells grown on permeable support--a new model for the study of differentiation.

PubMed

Gorodeski, G I; Romero, M F; Hopfer, U; Rorke, E; Utian, W H; Eckert, R L

1994-04-01

The purpose of the present study was to establish culture conditions for human uterine cervical epithelial cells on permeable support and to determine how it affects cervical cell differentiation. Human ectocervical epithelial cells (hECE), HPV-16 immortalized hECE cells (ECE16-1) and Caski cells were grown on collagen-coated filters. Culture conditions, density of cells in culture and expression of epithelial and cervical-cell phenotypic markers were determined and compared in cells grown on filter and on solid support. Compared with the latter, cultures on filter had a higher cell density, hECE cells stratified to 5-12 cell layers compared to 1-3 on solid support, and cells of all three types expressed intercellular tight junctions. The cytokeratin profiles revealed differences between the three cell types as well as differences within the same cell species when grown on filter, compared to solid support. Of particular importance was the finding of a higher expression of K-13 in hECE grown on filter compared to solid support; K-13 is a marker of ectocervical cell differentiation. The cytokeratin profiles of the cultured hECE, ECE16-1 and Caski cells resembled those of ectocervical, squamous metaplastic and endocervical epithelia, respectively. hECE and ECE16-1 expressed involucrin protein, the level of which in both was higher in cells grown on filter compared to solid support. Polarization of the cultures was determined by morphology (stratification of hECE cells, expression of pseudomicrovilli in the apical cell membrane), selective apical vs. basolateral secretion of [35S]methionine- and [35S]cysteine-, [3H]fucose- and [14C]glucosamine-labeled molecules, and positive short-circuit current (Isc) under voltage-clamp conditions. Confluency of the cultures was determined by measuring transepithelial unidirectional fluxes of inert molecules with different molecular weights (MWs) through the paracellular pathway, and by measuring transepithelial conductance. The results indicated transepithelial permeability of 7-22.10(-6) cm.sec-1, which was 5-100 fold smaller compared to blank inserts, with a cut-off MW of 40-70 kDa for hECE and Caski cells. Transepithelial conductance ranged 18.5 to 51.5 mS.cm-2, indicating a leaky but confluent epithelia. Collectively the results indicate the epithelial nature of the cells and their improved differentiation when grown on filter support; hECE is a model for ectocervical epithelium while ECE16-1 and Caski express phenotypic characteristics of squamous metaplastic cervical epithelium and endocervical epithelium respectively.

Pre-school nutrition-related behaviours at home and early childhood education services: findings from the Growing Up in New Zealand longitudinal study.

PubMed

Gerritsen, Sarah; Anderson, Sarah E; Morton, Susan Mb; Wall, Clare R

2018-05-01

Pre-school nutrition-related behaviours influence diet and development of lifelong eating habits. We examined the prevalence and congruence of recommended nutrition-related behaviours (RNB) in home and early childhood education (ECE) services, exploring differences by child and ECE characteristics. Telephone interviews with mothers. Online survey of ECE managers/head teachers. New Zealand. Children (n 1181) aged 45 months in the Growing Up in New Zealand longitudinal study. A mean 5·3 of 8 RNB were followed at home, with statistical differences by gender and ethnic group, but not socio-economic position. ECE services followed a mean 4·8 of 8 RNB, with differences by type of service and health-promotion programme participation. No congruence between adherence at home and in ECE services was found; half of children with high adherence at home attended a service with low adherence. A greater proportion of children in deprived communities attended a service with high adherence, compared with children living in the least deprived communities (20 and 12 %, respectively). Children, across all socio-economic positions, may not experience RNB at home. ECE settings provide an opportunity to improve or support behaviours learned at home. Targeting of health-promotion programmes in high-deprivation areas has resulted in higher adherence to RNB at these ECE services. The lack of congruence between home and ECE behaviours suggests health-promotion messages may not be effectively communicated to parents/family. Greater support is required across the ECE sector to adhere to RNB and promote wider change that can reach into homes.

A potent feed preservative candidate produced by Calcarisporium sp., an endophyte residing in stargrass (Cynodon dactylon).

PubMed

Ji, L L; Song, Y C; Tan, R X

2004-01-01

The cultures of an endophytic fungus Calcarisporium sp. were screened for inhibitors on the growth of feed-associated moulds and on the aflatoxin biosynthesis to find a safe and effective feed preservative. Eight test fungi were isolated from the spoiled poultry feed. The endophytic fungus Calcarisporium sp. was separated from the Chinese coastal grass Cynodon dactylon. The antifungal action concerning the endophytic culture extract (ECE) was performed with propionic acid (PPA) as the corresponding reference. The ECE had a similar antifungal efficacy to PPA in a concentration-dependent manner. The susceptibility order of the ECE to the test fungi was found to be Fusarium sp. > Aspergillus spp. > Penicillium spp. Furthermore, the application of the ECE in pelleted-layer duck feed as a preservative was carried out at a humidity of 10, 15 and 20%. It has been discerned that mould growth and aflatoxin biosynthesis could be co-inhibited almost completely by ECE at concentrations higher than 1.0% (w/w). The LD50 of the ECE on mice was shown to be higher than 28 g kg-1. The ECE can be selected as an inhibitor to preserve poultry feed on inhibiting the growth of mould and aflatoxin biosynthesis during feed storage. The ECE may be an effective and biosafe antifungal ingredient for poultry feed and holds a potential market prospect in feed industry.

Does aggregate school-wide achievement mediate fifth grade outcomes for former early childhood education participants?

PubMed

Curenton, Stephanie M; Dong, Nianbo; Shen, Xiangjin

2015-07-01

This study used a multilevel mediation model to test the theory that former early childhood education (ECE) attendees' 5th grade achievement is mediated by the aggregate school-wide achievement of their elementary school. Aggregate school-wide achievement was defined as the percentage of 5th graders in a school who were at/above academic proficiency in reading or math. Research questions were: (a) Do ECE program participants have better achievement at 5th grade compared with their matched peers who did not participate in an ECE program?; and (b) Is the association between ECE attendance and 5th grade academic performance mediated by school-wide achievement? Results indicated that children who attended prekindergarten (pre-K) and child care outperformed their matched peers who had not attended ECE programs; conversely, those children who did not attend ECE actually outperformed their Head Start counterparts. Mediation analyses indicated that aggregate school-wide achievement at 5th grade partially mediated the association between former ECE attendance and 5th grade performance; however, these mediated effects were small. Overall, the size of the total effects of ECE and the 5th grade academic outcomes were consistent with prior studies. This research confirms the long-term effects of pre-K and child care until 5th grade. (c) 2015 APA, all rights reserved).

Dihydroquercetin Does Not Affect Age-Dependent Increase in Blood Pressure and Angiotensin-Converting Enzyme Activity in the Aorta of Hypertensive Rats.

PubMed

Slashcheva, G A; Rykov, V A; Lobanov, A V; Murashev, A N; Kim, Yu A; Arutyunyan, T V; Korystova, A F; Kublik, L N; Levitman, M Kh; Shaposhnikona, V V; Korystov, Yu N

2016-09-01

We analyzed changes in angiotensin-converting enzyme activity in the aorta of hypertensive SHR rats against the background of age-related BP increase (from week 7 to 14) and the effect of dihydroquercetin on BP rise and angiotensin-converting enzyme activity. Normotensive WKY rats of the same age were used as the control. BP and activity of angiotensin-converting enzyme in the aorta of SHR rats increased with age. Dihydroquercetin in doses of 100 and 300 μg/kg per day had no effect on the increase of these parameters; dihydroquercetin administered to 14-week-old WKY rats in a dose of 300 μg/kg reduced activity of the angiotensin-converting enzyme. Thus, the early (7-14 weeks) increase in BP and angiotensin-converting enzyme activity in the aorta of SHR rats was not modified by flavonoids (dihydroquercetin) in contrast to other rat strains and humans, which is indicative of specificity of hypertension mechanism in SHR rats.

Identification of BACE2 as an avid ß-amyloid-degrading protease

PubMed Central

2012-01-01

Background Proteases that degrade the amyloid ß-protein (Aß) have emerged as key players in the etiology and potential treatment of Alzheimer’s disease (AD), but it is unlikely that all such proteases have been identified. To discover new Aß-degrading proteases (AßDPs), we conducted an unbiased, genome-scale, functional cDNA screen designed to identify proteases capable of lowering net Aß levels produced by cells, which were subsequently characterized for Aß-degrading activity using an array of downstream assays. Results The top hit emerging from the screen was ß-site amyloid precursor protein-cleaving enzyme 2 (BACE2), a rather unexpected finding given the well-established role of its close homolog, BACE1, in the production of Aß. BACE2 is known to be capable of lowering Aß levels via non-amyloidogenic processing of APP. However, in vitro, BACE2 was also found to be a particularly avid AßDP, with a catalytic efficiency exceeding all known AßDPs except insulin-degrading enzyme (IDE). BACE1 was also found to degrade Aß, albeit ~150-fold less efficiently than BACE2. Aß is cleaved by BACE2 at three peptide bonds—Phe19-Phe20, Phe20-Ala21, and Leu34-Met35—with the latter cleavage site being the initial and principal one. BACE2 overexpression in cultured cells was found to lower net Aß levels to a greater extent than multiple, well-established AßDPs, including neprilysin (NEP) and endothelin-converting enzyme-1 (ECE1), while showing comparable effectiveness to IDE. Conclusions This study identifies a new functional role for BACE2 as a potent AßDP. Based on its high catalytic efficiency, its ability to degrade Aß intracellularly, and other characteristics, BACE2 represents a particulary strong therapeutic candidate for the treatment or prevention of AD. PMID:22986058

Initial Data of Digital Correlation ECE with a Giga Hertz Sampling Digitizer

NASA Astrophysics Data System (ADS)

Tsuchiya, Hayato; Inagaki, Shigeru; Tokuzawa, Tokihiko; Nagayama, Yoshio

2015-03-01

The proposed Digital Correlation ECE (DCECE) technique is applied in Large Helical Device. DCECE is realized by the use of the Giga Hertz Sampling Digitizer. The waveform of intermediate frequency band of ECE, whose frequency is several giga hertz, can be discretized and saved directly. The discretized IF data can be used for the analysis of correlation ECE with arbitrary parameter of spatial resolution and temporal resolution. In this paper, the characteristic of DCECE and initial Data in LHD is introduced.

Combining Phylogenetic and Syntenic Analyses for Understanding the Evolution of TCP ECE Genes in Eudicots

PubMed Central

Citerne, Hélène L.; Le Guilloux, Martine; Sannier, Julie; Nadot, Sophie; Damerval, Catherine

2013-01-01

TCP ECE genes encode transcription factors which have received much attention for their repeated recruitment in the control of floral symmetry in core eudicots, and more recently in monocots. Major duplications of TCP ECE genes have been described in core eudicots, but the evolutionary history of this gene family is unknown in basal eudicots. Reconstructing the phylogeny of ECE genes in basal eudicots will help set a framework for understanding the functional evolution of these genes. TCP ECE genes were sequenced in all major lineages of basal eudicots and Gunnera which belongs to the sister clade to all other core eudicots. We show that in these lineages they have a complex evolutionary history with repeated duplications. We estimate the timing of the two major duplications already identified in the core eudicots within a timeframe before the divergence of Gunnera and after the divergence of Proteales. We also use a synteny-based approach to examine the extent to which the expansion of TCP ECE genes in diverse eudicot lineages may be due to genome-wide duplications. The three major core-eudicot specific clades share a number of collinear genes, and their common evolutionary history may have originated at the γ event. Genomic comparisons in Arabidopsis thaliana and Solanum lycopersicum highlight their separate polyploid origin, with syntenic fragments with and without TCP ECE genes showing differential gene loss and genomic rearrangements. Comparison between recently available genomes from two basal eudicots Aquilegia coerulea and Nelumbo nucifera suggests that the two TCP ECE paralogs in these species are also derived from large-scale duplications. TCP ECE loci from basal eudicots share many features with the three main core eudicot loci, and allow us to infer the makeup of the ancestral eudicot locus. PMID:24019982

Do early care and education services improve language development for maltreated children? Evidence from a national child welfare sample.

PubMed

Merritt, Darcey H; Klein, Sacha

2015-01-01

Young children under 6 years old are over-represented in the U.S. child welfare system (CWS). Due to their exposure to early deprivation and trauma, they are also highly vulnerable to developmental problems, including language delays. High quality early care and education (ECE) programs (e.g. preschool, Head Start) can improve children's development and so policymakers have begun calling for increased enrollment of CWS-supervised children in these programs. However, it is not a given that ECE will benefit all children who experience maltreatment. Some types of maltreatment may result in trauma-related learning and behavior challenges or developmental deficits that cause children to respond to ECE settings differently. The current study uses data from a nationally representative survey of children in the U.S. child welfare system, the National Survey of Child and Adolescent Well-Being II, to assess whether young CWS-supervised children (N=1,652) who were enrolled in ECE had better language development outcomes 18 months later than those not enrolled in ECE. We also explore whether the type of maltreatment that brought children to the CWS' attention moderates the relationship between ECE and children's language development. After controlling for children's initial scores on the Preschool Language Scale (PLS-3), type(s) of maltreatment experienced, and child and caregiver demographics, we found that ECE participation predicted better PLS-3 scores at follow-up, with a positive interaction between ECE participation and supervisory neglect. ECE seems to be beneficial for CWS-involved children's early language development, especially for children referred to the CWS because they lack appropriate parent supervision at home. Copyright © 2014 Elsevier Ltd. All rights reserved.

Endothelin-2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer

PubMed Central

Ling, Lowell; Maguire, Janet J; Davenport, Anthony P

2013-01-01

Endothelin-2 [ET-2; also known as vasoactive intestinal contractor (VIC), in rodents] differs from endothelin-1 (ET-1) by only two amino acids, and unlike the third isoform, endothelin-3 (ET-3), it has the same affinity as ET-1 for both ETA and ETB receptors. It is often assumed that ET-2 would mimic the actions of the more abundant ET-1 and current pharmacological interventions used to inhibit the ET system would also block the actions of ET-2. These assumptions have focused research on ET-1 with ET-2 studied in much less detail. Recent research suggests that our understanding of the ET family requires re-evaluation. Although ET-2 is very similar in structure as well as pharmacology to ET-1, and may co-exist in the same tissue compartments, there is converging evidence for an important and distinct ET-2 pathway. Specifically is has been demonstrated that ET-2 has a key role in ovarian physiology, with ET-2-mediated contraction proposed as a final signal facilitating ovulation. Furthermore, ET-2 may also have a pathophysiological role in heart failure, immunology and cancer. Comparison of ET-2 versus ET-1 mRNA expression suggests this may be accomplished at the level of gene expression but differences may also exist in peptide synthesis by enzymes such as endothelin converting enzymes (ECEs) and chymase, which may allow the two pathways to be distinguished pharmacologically and become separate drug targets. LINKED ARTICLES This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168.issue-1 PMID:22118774

Gas-permeable ethylene bags for the small scale cultivation of highly pathogenic avian influenza H5N1 and other viruses in embryonated chicken eggs.

PubMed

Hamilton, Sara B; Daniels, Deirdre E; Sosna, William A; Jeppesen, Eric R; Owells, Julie M; Halpern, Micah D; McCurdy, Kimberly S; Rayner, Jonathan O; Lednicky, John A

2010-01-28

Embryonated chicken eggs (ECE) are sometimes used for the primary isolation or passage of influenza viruses, other viruses, and certain bacteria. For small-scale experiments with pathogens that must be studied in biosafety level three (BSL3) facilities, inoculated ECE are sometimes manipulated and maintained in small egg incubators within a biosafety cabinet (BSC). To simplify the clean up and decontamination of an egg incubator in case of egg breakage, we explored whether ethylene breather bags could be used to encase ECE inoculated with pathogens. This concept was tested by determining embryo survival and examining virus yields in bagged ECE. Virus yields acceptable for many applications were attained when influenza-, alpha-, flavi-, canine distemper-, and mousepox viruses were propagated in ECE sealed within ethylene breather bags. For many small-scale applications, ethylene breather bags can be used to encase ECE inoculated with various viruses.

Preface: Impacts of extreme climate events and disturbances on carbon dynamics

USGS Publications Warehouse

Xiao, Jingfeng; Liu, Shuguang; Stoy, Paul C.

2016-01-01

The impacts of extreme climate events and disturbances (ECE&D) on the carbon cycle have received growing attention in recent years. This special issue showcases a collection of recent advances in understanding the impacts of ECE&D on carbon cycling. Notable advances include quantifying how harvesting activities impact forest structure, carbon pool dynamics, and recovery processes; observed drastic increases of the concentrations of dissolved organic carbon and dissolved methane in thermokarst lakes in western Siberia during a summer warming event; disentangling the roles of herbivores and fire on forest carbon dioxide flux; direct and indirect impacts of fire on the global carbon balance; and improved atmospheric inversion of regional carbon sources and sinks by incorporating disturbances. Combined, studies herein indicate several major research needs. First, disturbances and extreme events can interact with one another, and it is important to understand their overall impacts and also disentangle their effects on the carbon cycle. Second, current ecosystem models are not skillful enough to correctly simulate the underlying processes and impacts of ECE&D (e.g., tree mortality and carbon consequences). Third, benchmark data characterizing the timing, location, type, and magnitude of disturbances must be systematically created to improve our ability to quantify carbon dynamics over large areas. Finally, improving the representation of ECE&D in regional climate/earth system models and accounting for the resulting feedbacks to climate are essential for understanding the interactions between climate and ecosystem dynamics.

Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort.

PubMed

Roshanov, Pavel S; Rochwerg, Bram; Patel, Ameen; Salehian, Omid; Duceppe, Emmanuelle; Belley-Côté, Emilie P; Guyatt, Gordon H; Sessler, Daniel I; Le Manach, Yannick; Borges, Flavia K; Tandon, Vikas; Worster, Andrew; Thompson, Alexandra; Koshy, Mithin; Devereaux, Breagh; Spencer, Frederick A; Sanders, Robert D; Sloan, Erin N; Morley, Erin E; Paul, James; Raymer, Karen E; Punthakee, Zubin; Devereaux, P J

2017-01-01

The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown. In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes. Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery. Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.

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

Velletri, P.A.; Aquilano, D.R.; Bruckwick, E.

Hypophysectomy of prepubescent (3-week-old) rats prevented the pubertal development of testicular, but not pulmonary, angiotensin-converting enzyme (EC 3.4.15.1). Additionally, hypophysectomy resulted in a loss of testicular converting enzyme activity in 10-week-old rats that had achieved puberty and had developed enzyme activity. Hormone regimens consisting of FSH/LH (7.5 U/rat X day), hCG (10 U/rat X day), or testosterone (1 mg/rat X day) were employed to ascertain their ability to maintain activity in hypophysectomized rats. All three of the above hormone regimens, if initiated on the first day after hypophysectomy of 10-week-old rats, were capable of maintaining testicular converting enzyme activity. Centrifugalmore » elutriation of dispersed testicular cells indicated that the majority of enzyme activity in mature rats was associated with the germinal cells, a result consistent with the data accumulated from the hormonal studies. Lastly, (/sup 3/H)captopril bound specifically to cellular fractions enriched in germinal cells. The above studies suggest that the pituitary gland is required for the development and maintenance of testicular angiotensin-converting enzyme in the rat by stimulating steroidogenesis in the testes. Furthermore, the sensitivity of converting enzyme activity to androgen coupled with the centrifugal elutriation and (/sup 3/H) captopril binding studies strongly support the notion that testicular converting enzyme is associated with germinal cells.« less

Perceptions of Early Childhood Education Professionals on Teacher Leadership in Finland

ERIC Educational Resources Information Center

Heikka, Johanna; Halttunen, Leena; Waniganayake, Manjula

2018-01-01

This study investigated perceptions of early childhood education (ECE) professionals employed at three ECE centres on teacher leadership enactment in Finland. These professionals comprised childcare nurses, teachers and ECE centre directors. Theoretically, the study was anchored on an analysis of teacher leadership and distributed leadership…

Occurrence of equine coital exanthema (ECE) in stallions in Japan and effectiveness of treatment with valacyclovir for ECE

PubMed Central

TOISHI, Yuko; TSUNODA, Nobuo; KIRISAWA, Rikio

2017-01-01

Equine coital exanthema (ECE) has been reported in many countries, but equine herpesvirus 3 (EHV-3) has been isolated only once in Japan. In 2015, symptoms of ECE were found, and EHV-3 was isolated in two stallions. Valacyclovir, an anti-herpesvirus agent, was administered orally. The stallions rested from mating for more than two weeks, causing enormous financial losses because of their high fees. This is the first study in which valacyclovir was administered for ECE. Though valacyclovir treatment did not shorten the duration of healing, the affected area did not expand after administration of valacyclovir. Valacyclovir therefore seems to be effective for suppression of EHV-3 infection. Further investigation about the administration protocol might be required. PMID:28123140

Water and nitrogen availability co-control ecosystem CO2 exchange in a semiarid temperate steppe.

PubMed

Zhang, Xiaolin; Tan, Yulian; Li, Ang; Ren, Tingting; Chen, Shiping; Wang, Lixin; Huang, Jianhui

2015-10-23

Both water and nitrogen (N) availability have significant effects on ecosystem CO2 exchange (ECE), which includes net ecosystem productivity (NEP), ecosystem respiration (ER) and gross ecosystem photosynthesis (GEP). How water and N availability influence ECE in arid and semiarid grasslands is still uncertain. A manipulative experiment with additions of rainfall, snow and N was conducted to test their effects on ECE in a semiarid temperate steppe of northern China for three consecutive years with contrasting natural precipitation. ECE increased with annual precipitation but approached peak values at different precipitation amount. Water addition, especially summer water addition, had significantly positive effects on ECE in years when the natural precipitation was normal or below normal, but showed trivial effect on GEP when the natural precipitation was above normal as effects on ER and NEP offset one another. Nitrogen addition exerted non-significant or negative effects on ECE when precipitation was low but switched to a positive effect when precipitation was high, indicating N effect triggered by water availability. Our results indicate that both water and N availability control ECE and the effects of future precipitation changes and increasing N deposition will depend on how they can change collaboratively in this semiarid steppe ecosystem.

Creating an Agile ECE Learning Environment through Engineering Clinics

ERIC Educational Resources Information Center

Jansson, P. M.; Ramachandran, R. P.; Schmalzel, J. L.; Mandayam, S. A.

2010-01-01

To keep up with rapidly advancing technology, numerous innovations to the electrical and computer engineering (ECE) curriculum, learning methods and pedagogy have been envisioned, tested, and implemented. It is safe to say that no single approach will work for all of the diverse ECE technologies and every type of learner. However, a few key…

A Universal Early Childhood Education System

ERIC Educational Resources Information Center

Brown, Christopher P.

2006-01-01

In this article, the author demonstrates how the current emphasis on viewing early childhood education (ECE) as an investment keeps ECE at the margins of U.S. political debates as well as in other discussions around the world. Historically, the field of ECE in the United States has struggled, and continues to struggle, for political positioning.…

An initial reliability and validity study of the Interaction, Communication, and Literacy Skills Audit.

PubMed

El-Choueifati, Nisrine; Purcell, Alison; McCabe, Patricia; Heard, Robert; Munro, Natalie

2014-06-01

Early childhood educators (ECEs) have an important role in promoting positive outcomes for children's language and literacy development. This paper reports the development of a new tool, The Interaction Communication and Literacy (ICL) Skills Audit, and pilots its reliability and validity. Intra- and inter-rater reliability was examined by three speech-language pathologists (SLPs). Five skill areas relating to ECE language and literacy practice were rated. The face and content validity of the ICL Skills Audit was examined by expert SLPs (n = 8) and expert ECEs (n = 4) via questionnaire. The overall intra-rater reliability for the ICL Skills Audit was excellent with percentage close agreement (PCA) of 91-94. Inter-rater agreement was PCA 68-80. Expert SLPs and ECEs agreed that the content was comprehensive and practical. Based on this preliminary study, the ICL Skills Audit appears to be a promising tool that can be used by SLPs and ECEs in collaboration to measure the skills of ECEs in the areas of language and literacy support. Future psychometric and outcome research on the revised ICL Skills Audit is warranted.

Development and internal validation of a side-specific, multiparametric magnetic resonance imaging-based nomogram for the prediction of extracapsular extension of prostate cancer.

PubMed

Martini, Alberto; Gupta, Akriti; Lewis, Sara C; Cumarasamy, Shivaram; Haines, Kenneth G; Briganti, Alberto; Montorsi, Francesco; Tewari, Ashutosh K

2018-04-19

To develop a nomogram for predicting side-specific extracapsular extension (ECE) for planning nerve-sparing radical prostatectomy. We retrospectively analysed data from 561 patients who underwent robot-assisted radical prostatectomy between February 2014 and October 2015. To develop a side-specific predictive model, we considered the prostatic lobes separately. Four variables were included: prostate-specific antigen; highest ipsilateral biopsy Gleason grade; highest ipsilateral percentage core involvement; and ECE on multiparametric magnetic resonance imaging (mpMRI). A multivariable logistic regression analysis was fitted to predict side-specific ECE. A nomogram was built based on the coefficients of the logit function. Internal validation was performed using 'leave-one-out' cross-validation. Calibration was graphically investigated. The decision curve analysis was used to evaluate the net clinical benefit. The study population consisted of 829 side-specific cases, after excluding negative biopsy observations (n = 293). ECE was reported on mpMRI and final pathology in 115 (14%) and 142 (17.1%) cases, respectively. Among these, mpMRI was able to predict ECE correctly in 57 (40.1%) cases. All variables in the model except highest percentage core involvement were predictors of ECE (all P ≤ 0.006). All variables were considered for inclusion in the nomogram. After internal validation, the area under the curve was 82.11%. The model demonstrated excellent calibration and improved clinical risk prediction, especially when compared with relying on mpMRI prediction of ECE alone. When retrospectively applying the nomogram-derived probability, using a 20% threshold for performing nerve-sparing, nine out of 14 positive surgical margins (PSMs) at the site of ECE resulted above the threshold. We developed an easy-to-use model for the prediction of side-specific ECE, and hope it serves as a tool for planning nerve-sparing radical prostatectomy and in the reduction of PSM in future series. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

E.C.E. Connection: A Newsletter for Early Childhood Education (E.C.E.), 1994-1998.

ERIC Educational Resources Information Center

E.C.E. Connection, 1998

1998-01-01

This document consists of the first 39 consecutive issues of the newsletter, "E.C.E. Connection," published monthly (except August) to offer information and support to early childhood practitioners. Articles from the 1994 issues include: "Some 'Affordable' Ideas To Brighten Your Classroom"; "A Notice Board: A Way To Keep…

Global Vision, Local Reality: Transforming Pre-Primary Teacher Training in Tanzania

ERIC Educational Resources Information Center

Wilinski, Bethany; Nguyen, Cuong Huy; Landgraf, Jessica M.

2016-01-01

Global attention to early childhood education (ECE) has led to an increased focus on ECE teacher training as a critical component of providing young children with access to high-quality ECE programs. In this paper, we ask how Tanzanian stakeholders at different levels of implementation experienced and responded to efforts to build capacity in…

Getting Early Childhood Educators Up and Running: Creating Strong Technology Curators, Facilitators, Guides, and Users. Policy Brief

ERIC Educational Resources Information Center

Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

2014-01-01

Providers of early childhood education (ECE) are well positioned to help ensure that technology is used effectively in ECE settings. Indeed, the successful integration of technology into ECE depends on providers who have the ability to curate the most appropriate devices and content, "facilitate" effective patterns of use, guide families…

A Design of an Appropriate Early Childhood Education Funding System in China

ERIC Educational Resources Information Center

Xiaodong, Zeng

2008-01-01

This study analyzes the structural reform of local governments funding for early childhood education (ECE) as the general public still casts doubts about the fairness of ECE system in China. A particular case in point is the Shenzhen Municipal Government's reform on their ECE funding system. Because the reform efforts are more about restructuring…

Diversity in New Zealand Early Childhood Education: Challenges and Opportunities

ERIC Educational Resources Information Center

Shuker, Mary Jane; Cherrington, Sue

2016-01-01

The early childhood education (ECE) sector in New Zealand has long been recognised for the diversity of service types and range of organisations involved in delivering ECE. However, less attention has been paid to diversity within individual ECE services. This article draws on a national survey carried out as part of a larger project, "The…

Music Education from Birth to Five: An Examination of Early Childhood Educators' Music Teaching Practices

ERIC Educational Resources Information Center

Bolduc, Jonathan; Evrard, Melanie

2017-01-01

Children from birth to five are generally enthusiastic about music. However, because many early-childhood educators (ECEs) feel that they have insufficient knowledge to foster musical development, music education practices are not equivalent across ECEs. This study aimed to identify and determine the frequency of music activities used by ECEs. In…

Giant Electrocaloric Effect in Ferroelectrics with Tailored Polaw-Nanostructures

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

Zhang, Qiming

2015-06-24

Electrocaloric effect (ECE) is the temperature and/or entropy change in a dielectric material caused by an electric field induced polarization change. Although ECE has been studied since 1930s, the very small ECE observed in earlier studies in bulk materials before 2007 makes it not attractive for practical cooling applications. The objectives of this DOE program are to carry out a systematical scientific research on the entropy change and ECE in polar-dielectrics, especially ferroelectrics based on several fundamental hypotheses and to search for answers on a few scientific questions. Especially, this research program developed a series of polar-dielectric materials with controlledmore » nano- and meso-structures and carried out studies on how these structures affect the polar-ordering, correlations, energy landscapes, and consequently the entropy states at different phases and ECE. The key hypotheses of the program include: (i) Whether a large ECE can be obtained near the ferroelectric-paraelectric (FE-PE) transition in properly designed ferroelectrics which possess large polarization P and large ß (the coefficient in the thermodynamic Landau theory where the Gibbs free energy G = G = G 0+ ½ a P 2 +1/4 b P 4 + 1/6 c P 6 – EP, and a = ß (T-T c), where b,c,ß and Tc are constants)? (ii) What determines/determine ß? Whether a ferroelectric material with built-in disorders, which disrupt the polar-correlations and enabling a large number of local polar-states, such as a properly designed ferroelectric relaxor, can achieve a large ECE? (iii) How to design a ferroelectric material which has flat energy landscape so that the energy barriers for switching among different phases are vanishingly small? What are the necessary conditions to maximize the number of coexisting phases? (iv) How to design ferroelectric materials with a large tunable dielectric response? That is, at zero electric field, the material possesses very low polar-correlation and hence a very small dielectric constant, under the application of electric field, the material develops long range polar-correlation and hence a high dielectric response. Studying and developing these materials will deepen our understanding on the polarization responses in strongly coupled materials and the roles of molecular and nano, meso-, and micro-scale defects and structures on the polarization responses. On the application front, besides ECE, these dielectrics will also have great impact on micro-electronics and communications. (v) The multi-field effect, besides the electric, elastic and even magnetic effects, could be made use of to tune the energy landscape of polar-materials and hence enhance the ECE. Hence the question is what are the suitable material systems to develop and maximize the multi-field effects? (vi) Besides solid dielectric, liquid dielectrics with properly designed molecular structures and dipolar coupling can also exhibit a large ECE near the dipolar order-disorder transition. The study of order-disorder transition and their influence on entropy change and ECE will provide additional avenue to study dielectrics and understand relationship between the polar-ordering and dipolar entropy in dielectrics. (vii) Besides the regular ECE in which applying an electric field will induce dipolar ordering, there are dielectric material systems which can exhibit negative ECE in which the applied field will reduce the dipolar ordering and anomalous ECE in which applying an electric field pulse will generate cooling only. The question is how to control and balance the nano- and meso-scale polar coupling in dielectrics to achieve such effects? ECE in dielectrics provides an interesting and effective avenue to probe the polar-correlation in dielectrics. Thus the study of ECE in polar-dielectrics, besides the application values, will also deepen our understanding of strongly coupled materials systems, phase transitions, and materials systems with nano- and meso-scale disorders. Through the efforts of this DoE program, we have developed understandings for many questions and materials approaches for many hypotheses listed above. The major accomplishments include: (i) The first one to show that a giant ECE can be obtained in bulk materials of ferroelectric P(VDF-TrFE) copolymer, which has a large ß coefficient and high polarization, near FE-PE transition.[1,3,12] (ii) The first who developed the theoretical analyses on the upper bound of dipolar entropy change in polar-materials and the general approach to maximize the coexisting phases with vanishingly small switching fields among the coexisting phases[10,23] Experimental results confirm these theoretical predictions.[24] (iii) The first to show that the relaxor ferroelectrics, due to built-in defects structures at nano- and meso scale, exhibit a giant ECE over a broad temperature range.[1,3,7,14] (iv) The first to show that a large ECE can be obtained near order-disorder transition in dielectric fluids such as liquid crystals with large dielectric anisotropy. Also the study developed a general approach for developing dielectric fluids to achieve a large electric field induced entropy change.[26] (v) We are starting to explore the multi-field effect (multiferroic effect) in nanocomposites in which there exist large dielectric contrasts between the matrix and nanofilelrs and showed that a significantly enhanced ECE compared with polymer matrix.[36] (vi) By facially tuning the nano- and meso-scale dipolar coupling, we are the first to show that an anomalous ECE can be obtained in a relaxor/normal ferroelectric blend.[39] (vii) Introduced and demonstrated that the internal bias field approach can be effective in enhancing the EC response at low electric field. The result is significant since for practical applications, a low applied field is highly desired. (viii) A high sensitivity ECE characterization system has been developed. This program has made major contributions to the advancement of the EC materials and understandings of EC phenomena. To reflect the advancement in the EC materials development and scientific understandings on ECE through in this time period (from Sept. 1, 2007 to May 2015), this final report is written based on the reports complied each year through the program. Some early works on the ECE which were obtained using the indirect method are not included in this report.« less

Professional Development of the Early Childhood Education Teaching Workforce in the United States: An Overview

ERIC Educational Resources Information Center

Gomez, Rebecca E.; Kagan, Sharon Lynn; Fox, Emily A.

2015-01-01

Resulting from a fragmented landscape of policies for and uneven investments in the early childhood education (ECE) field in the United States, the qualifications of the ECE teaching workforce are typically quite low. This article first reviews the history and status of the ECE teaching workforce in the United States, focusing on the evolution of…

When Business Gets Involved: A Case Study of Business Community Involvement In Illinois' Early Childhood Education Policy

ERIC Educational Resources Information Center

Kovach, Melissa

2009-01-01

As the first state to offer universal preschool to three-year-olds, Illinois' experience with early childhood education (ECE) policy reform efforts offers lessons about how such change takes shape. This report details Illinois' ECE activities from 1992 to the present, with a particular focus on the business role in ECE policy. Lessons learned…

Shared Services: A Powerful Strategy to Support Sustainability of ECE Businesses

ERIC Educational Resources Information Center

Stoney, Louise

2009-01-01

As Co-Founder of the Alliance for Early Childhood Finance, it is the author's job to think about how they pay for early care and education (ECE) services in the United States. Generating the operating revenue needed to establish and sustain a high-quality ECE program has never been easy--and in a recession economy it is becoming even more…

Effect of Male and Female Early Childhood Education Teacher's Educational Practices on Children's Social Adaptation

ERIC Educational Resources Information Center

Besnard, Thérèse; Letarte, Marie-Josée

2017-01-01

It is believed children stand to benefit from a greater male teacher presence in early childhood education (ECE) where, internationally, the vast majority of ECE teachers are female. This study (N = 180) examines the relationship between children's social adaptation and the educational practices of 53 ECE teachers, 23 (44%) of which were male.…

Impacts of an In-Service Education Program on Promoting Language Development in Young Children: A Pilot Study with Early Childhood Educators

ERIC Educational Resources Information Center

Scarinci, Nerina; Rose, Tanya; Pee, Jerrine; Webb, Kylie

2015-01-01

Early childhood educators (ECEs) play an important role in fostering language development in young children. In-service education, led by speech-language pathologists (SLPs), has a potential role in educating ECEs about language development. In this pilot study, 42 ECEs attended an in-service education program and completed pre- and…

"Old, Borrowed, and Renewed": A Review of Early Childhood Education Policy in Post-Reform Indonesia

ERIC Educational Resources Information Center

Octarra, Harla Sara; Hendriati, Agustina

2018-01-01

Early childhood education (ECE) is not new in Indonesia. However, in the past decade, it has received more attention, as shown by the growing number of ECE centres in both urban and rural areas. This growth is accompanied by policy development that corresponds to the global agenda of ECE. Policy development is inevitably linked with the support of…

The ECE Pre-Service Teachers' Perception on Factors Affecting the Integration of Educational Computer Games in Two Conditions: Selecting versus Redesigning

ERIC Educational Resources Information Center

Sancar Tokmak, Hatice; Ozgelen, Sinan

2013-01-01

This case study aimed to examine early childhood education (ECE) pre-service teachers' perception on the factors affecting integration of educational computer games to their instruction in two areas: selecting and redesigning. Twenty-six ECE pre-service teachers participated in the study. The data was collected through open-ended questionnaires,…

Monocyte Tumor Necrosis Factor-α–Converting Enzyme Catalytic Activity and Substrate Shedding in Sepsis and Noninfectious Systemic Inflammation*

PubMed Central

O’Callaghan, David J. P.; O’Dea, Kieran P.; Scott, Alasdair J.; Takata, Masao

2015-01-01

Objectives: To determine the effect of severe sepsis on monocyte tumor necrosis factor-α–converting enzyme baseline and inducible activity profiles. Design: Observational clinical study. Setting: Mixed surgical/medical teaching hospital ICU. Patients: Sixteen patients with severe sepsis, 15 healthy volunteers, and eight critically ill patients with noninfectious systemic inflammatory response syndrome. Interventions: None. Measurements and Main Results: Monocyte expression of human leukocyte antigen-D-related peptide, sol-tumor necrosis factor production, tumor necrosis factor-α–converting enzyme expression and catalytic activity, tumor necrosis factor receptor 1 and 2 expression, and shedding at 48-hour intervals from day 0 to day 4, as well as p38-mitogen activated protein kinase expression. Compared with healthy volunteers, both sepsis and systemic inflammatory response syndrome patients’ monocytes expressed reduced levels of human leukocyte antigen-D-related peptide and released less sol-tumor necrosis factor on in vitro lipopolysaccharide stimulation, consistent with the term monocyte deactivation. However, patients with sepsis had substantially elevated levels of basal tumor necrosis factor-α–converting enzyme activity that were refractory to lipopolysaccharide stimulation and this was accompanied by similar changes in p38-mitogen activated protein kinase signaling. In patients with systemic inflammatory response syndrome, monocyte basal tumor necrosis factor-α–converting enzyme, and its induction by lipopolysaccharide, appeared similar to healthy controls. Changes in basal tumor necrosis factor-α–converting enzyme activity at day 0 for sepsis patients correlated with Acute Physiology and Chronic Health Evaluation II score and the attenuated tumor necrosis factor-α–converting enzyme response to lipopolysaccharide was associated with increased mortality. Similar changes in monocyte tumor necrosis factor-α–converting enzyme activity could be induced in healthy volunteer monocytes using an in vitro two-hit inflammation model. Patients with sepsis also displayed reduced shedding of monocyte tumor necrosis factor receptors upon stimulation with lipopolysaccharide. Conclusions: Monocyte tumor necrosis factor-α–converting enzyme catalytic activity appeared altered by sepsis and may result in reduced shedding of tumor necrosis factor receptors. Changes seemed specific to sepsis and correlated with illness severity. A better understanding of how tumor necrosis factor-α–converting enzyme function is altered during sepsis will enhance our understanding of sepsis pathophysiology, which will help in the assessment of patient inflammatory status and ultimately may provide new strategies to treat sepsis. PMID:25867908

27 CFR 24.246 - Materials authorized for the treatment of wine and juice.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (alpha-Amylase): To convert starches to fermentable carbohydrates The amylase enzyme activity shall be... 184.1027. Carbohydrase (beta-Amylase): To convert starches to fermentable carbohydrates The amylase... (Glucoamylase, Amylogluco-sidase): To convert starches to fermentable carbohydrates The amylase enzyme activity...

27 CFR 24.246 - Materials authorized for the treatment of wine and juice.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (alpha-Amylase): To convert starches to fermentable carbohydrates The amylase enzyme activity shall be... 184.1027. Carbohydrase (beta-Amylase): To convert starches to fermentable carbohydrates The amylase... (Glucoamylase, Amylogluco-sidase): To convert starches to fermentable carbohydrates The amylase enzyme activity...

27 CFR 24.246 - Materials authorized for the treatment of wine and juice.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (alpha-Amylase): To convert starches to fermentable carbohydrates The amylase enzyme activity shall be... 184.1027. Carbohydrase (beta-Amylase): To convert starches to fermentable carbohydrates The amylase... (Glucoamylase, Amylogluco-sidase): To convert starches to fermentable carbohydrates The amylase enzyme activity...

27 CFR 24.246 - Materials authorized for the treatment of wine and juice.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (alpha-Amylase): To convert starches to fermentable carbohydrates The amylase enzyme activity shall be... 184.1027. Carbohydrase (beta-Amylase): To convert starches to fermentable carbohydrates The amylase... (Glucoamylase, Amylogluco-sidase): To convert starches to fermentable carbohydrates The amylase enzyme activity...

The build-up of energetic electrons triggering electron cyclotron emission bursts due to a magnetohydrodynamic mode at the edge of tokamaks

DOE PAGES

Li, Erzhong; Austin, Max E.; White, R. B.; ...

2017-08-21

Intense bursts of electron cyclotron emission (ECE) triggered by magnetohydrodynamic (MHD) instabilities such as edge localized modes (ELMs) have been observed on many tokamaks. On the DIII-D tokamak, it is found that an MHD mode is observed to trigger the ECE bursts in the low collisionality regime at the plasma edge. ORBIT-code simulations have shown that energetic electrons build up due to an interaction between barely trapped electrons with an MHD mode (f = 50 kHz for current case). The energetic tail of the electron distribution function develops a bump within several microseconds for this collisionless case. This behavior dependsmore » on the competition between the perturbing MHD mode and slowing down and pitch angle scattering due to collisions. As a result, for typical DIII-D parameters, the calculated ECE radiation transport predicted by ORBIT is in excellent agreement with ECE measurements, clarifying the electron dynamics of the ECE bursts for the first time.« less

Exploring the Relationship between Early Childhood and Elementary Grade-Level Overlap and Early Childhood Teacher Output

ERIC Educational Resources Information Center

Fowler, R. Clarke

2017-01-01

This study explores the relationship between grade-level overlap between elementary education (ELED) and early childhood education (ECED) licenses and ECED teacher output. Analysis of Title 2 data indicates that ECED/ELED overlap is extensive, as evidenced by the number of states with grade-level overlaps of 5 (n = 2), 4 (n = 24), 3 (n = 10), and…

A Noble Bet in Early Care and Education: Lessons from One Community’s Experience

DTIC Science & Technology

2002-01-01

Finally, the RAND study team explored existing empirical literature on ECE. Although ECI led to the establishment of new , high-quality ECE ser...objectives and articulates the breadth of the initiative’s ambition to create a comprehensive new system for delivering ECE to low-income chil- dren in...70 Incentives to Neighborhood Agencies .............. 71 Who Would Provide ECI Services? . . . . . . . . . . . . . . . . . . 73 New Providers and

Status of the design of the ITER ECE diagnostic

DOE PAGES

Taylor, G.; Austin, M. E.; Beno, J. H.; ...

2015-03-12

In this study, the baseline design for the ITER electron cyclotron emission (ECE) diagnostic has entered the detailed preliminary design phase. Two plasma views are planned, a radial view and an oblique view that is sensitive to distortions in the electron momentum distribution near the average thermal momentum. Both views provide high spatial resolution electron temperature profiles when the momentum distribution remains Maxwellian. The ECE diagnostic system consists of the front-end optics, including two 1000 K calibration sources, in equatorial port plug EP9, the 70-1000 GHz transmission system from the front-end to the diagnostics hall, and the ECE instrumentation inmore » the diagnostics hall. The baseline ECE instrumentation will include two Michelson interferometers that can simultaneously measure ordinary and extraordinary mode ECE from 70 to 1000 GHz, and two heterodyne radiometer systems, covering 122-230 GHz and 244-355 GHz. Significant design challenges include 1) developing highly-reliable 1000 K calibration sources and the associated shutters/mirrors, 2) providing compliant couplings between the front-end optics and the polarization splitter box that accommodate displacements of the vacuum vessel during plasma operations and bake out, 3) protecting components from damage due to stray ECH radiation and other intense millimeter wave emission and 4) providing the low-loss broadband transmission system.« less

Repeatability and validity of a field kit for estimation of cholinesterase in whole blood.

PubMed Central

London, L; Thompson, M L; Sacks, S; Fuller, B; Bachmann, O M; Myers, J E

1995-01-01

OBJECTIVES--To evaluate a spectrophotometric field kit (Test-Mate-OP) for repeatability and validity in comparison with reference laboratory methods and to model its anticipated sensitivity and specificity based on these findings. METHODS--76 farm workers between the age of 20 and 55, of whom 30 were pesticide applicators exposed to a range of organophosphates in the preceding 10 days, had blood taken for plasma cholinesterase (PCE) and erythrocyte cholinesterase (ECE) measurement by field kit or laboratory methods. Paired blinded duplicate samples were taken from subgroups in the sample to assess repeatability of laboratory and field kit methods. Field kits were also used to test venous blood in one subgroup. The variance obtained for the field kit tests was then applied to two hypothetical scenarios that used published action guidelines to model the kit's sensitivity and specificity. RESULTS--Repeatability for PCE was much poorer and for ECE slightly poorer than that of laboratory measures. A substantial upward bias for field kit ECE relative to laboratory measurements was found. Sensitivity of the kit to a 40% drop in PCE was 67%, whereas that for ECE was 89%. Specificity of the kit with no change in mean of the population was 100% for ECE and 91% for PCE. CONCLUSION--Field kit ECE estimation seems to be sufficiently repeatable for surveillance activities, whereas PCE does not. Repeatability of both tests seems to be too low for use in epidemiological dose-response investigations. Further research is indicated to characterise the upward bias in ECE estimation on the kit. PMID:7697143

Changes of Serum Angiotensin-Converting Enzyme Activity During Treatment of Patients with Graves’ Disease*

PubMed Central

Lee, Dong Soo; Chung, June-Key; Cho, Bo Youn; Koh, Chang-Soon; Lee, Munho

1986-01-01

Serum angiotensin-converting enzyme activity was measured spectrophotometrically, and serum thyrotropin-binding-inhibitory immunoglobulin (TBII) activity was measured by radioreceptor assay in normal subjects and in patients with Graves’ disease serially before and during treatment, and these activities were compared with each other and with thyroid hormone levels in various thyroid functional status. Correlation between serum angiotensin-converting enzyme activity and serum thyroid hormone level was pursued with relation to the changes of thyroid functional status in patients with Graves’ disease during treatment. Serum angiotensin-converting enzyme activity was significantly elevated in patients with hyperthyroid Graves’ disease before the start of treatment (35 ± 13 nmol/min/ml, n=50), and not in patients with Graves’ disease, euthyroid state during treatment with antithyroid drugs or radioactive iodine (23 ± 9 nmol/min/ml, n=12), but decreased significantly in patients with Graves’ disease, hypothyroid state transiently during treatment (15 ± 4 nmol/min/ml, n=12), respectively in comparison with normal control subjects. Serum angiotensin-converting enzyme activity was positively correlated with the log value of serum T3 concentration (r=0.62, p<0.001, n=95), and with the log value of free thyroxine index (r=0.66, p<0.001, n=91) but not statistically significantly with serum TBII activity. Serum angiotensin-converting enzyme activity was followed in 11 patients with initially increased activity and the activity decreased in proportion to serum thyroid hormone level during treatment, irrespective of treatment modality. It is suggested that thyroid hormones play a role in the increase and decrease of serum angiotensin-converting enzyme activity directly or indirectly influencing the peripheral tissues (probably reticuloendothelial cells or peripheral endothelial cells) in patients with Graves’ disease. PMID:15759385

Perindopril

MedlinePlus

... in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It makes blood flow more smoothly ... if you are allergic to perindopril, angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), ...

Does Gender Make a Difference? Results from the German "Tandem Study" on the Pedagogical Activity of Female and Male ECE Workers

ERIC Educational Resources Information Center

Brandes, Holger; Andrä, Markus; Röseler, Wenke; Schneider-Andrich, Petra

2015-01-01

Based on an everyday quasi-experimental situation with multiple materials, the behavior of male and female early childhood education (ECE) workers is recorded and compared. The research is based on a sample of 41 female and 41 male ECE workers, who in each case work together in tandem in a kindergarten class, as well as a control group of 12…

Temperature gradient scale length measurement: A high accuracy application of electron cyclotron emission without calibration

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

Houshmandyar, S., E-mail: houshmandyar@austin.utexas.edu; Phillips, P. E.; Rowan, W. L.

2016-11-15

Calibration is a crucial procedure in electron temperature (T{sub e}) inference from a typical electron cyclotron emission (ECE) diagnostic on tokamaks. Although the calibration provides an important multiplying factor for an individual ECE channel, the parameter ΔT{sub e}/T{sub e} is independent of any calibration. Since an ECE channel measures the cyclotron emission for a particular flux surface, a non-perturbing change in toroidal magnetic field changes the view of that channel. Hence the calibration-free parameter is a measure of T{sub e} gradient. B{sub T}-jog technique is presented here which employs the parameter and the raw ECE signals for direct measurement ofmore » electron temperature gradient scale length.« less

Transcriptional alterations of ET-1 axis and DNA damage in lung tissue of a rat obesity model.

PubMed

Del Ry, Silvia; Cabiati, Manuela; Salvadori, Costanza; Guiducci, Letizia; Caselli, Chiara; Prescimone, Tommaso; Facioni, Maria Sole; Azzarà, Alessia; Chiaramonte, Anna; Mazzoni, Stefano; Bruschi, Fabrizio; Giannessi, Daniela; Scarpato, Roberto

2015-03-01

Obesity has been implicated in the development of many cancers. This can lead to genome damage, especially in the form of double-strand break, the presence of which is now easily detected through nuclear phosphorylation of histone H2AX (γ-H2AX) focus assay. Recently, the endothelin (ET) axis has also been shown to have a role in the growth and progression of several tumors, including lung cancer. The aim of this study was to evaluate the ET-1 system transcriptional alterations and γ-H2AX in lung tissue of Zucker rats subdivided into obese (O, n=22) and controls (CO, n=18) rats: under either fasting conditions (CO(fc)-O(fc)) or acute hyperglycemia (CO(AH)-O(AH)). Significantly higher prepro-ET-1 (p=0.05) and ET-converting enzyme (ECE)-2 mRNA expression was observed in O with respect to CO. A significant positive association was observed between prepro-ET-1 and ET-A in the whole rat population (p=0.009) or in the obese group alone (p=0.007). The levels of γ-H2AX in O and in O(AH) rats were significantly higher (p=0.019) than in the corresponding CO and CO(AH) rats (p=0.038). The study shows an inappropriate secretion of ET-1 in O animals with a parallel DNA damage in their lungs, providing novel mechanisms by which ET receptor antagonist may exert organ protection.

Benazepril and Hydrochlorothiazide

MedlinePlus

... in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals ... benazepril (Lotensin); hydrochlorothiazide (HCTZ, Microzide, Oretic); angiotensin-converting enzyme (ACE) inhibitors such as captopril (Capoten), enalapril (Vasotec, ...

Lisinopril and Hydrochlorothiazide

MedlinePlus

... in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals ... to lisinopril; hydrochlorothiazide (HCTZ, Microzide, Oretic); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), ...

Enalapril and Hydrochlorothiazide

MedlinePlus

... in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals ... in Vaseretic); hydrochlorothiazide (HCTZ, Microzide, Oretic); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), ...

Effect of angiotensin-converting enzyme inhibitors on vascular endothelial function in hypertensive patients after intensive periodontal treatment.

PubMed

Rubio, María C; Lewin, Pablo G; De la Cruz, Griselda; Sarudiansky, Andrea N; Nieto, Mauricio; Costa, Osvaldo R; Nicolosi, Liliana N

2016-04-01

There is a relation between vascular endothelial function, atherosclerotic disease, and inflammation. Deterioration of endothelial function has been observed twenty-four hours after intensive periodontal treatment. This effect may be counteracted by the action of angiotensin-converting enzyme inhibitors, which improve endothelial function. The aim of the present study was to evaluate vascular endothelial function after intensive periodontal treatment, in hypertensive patients treated with angiotensinconverting enzyme inhibitors. A prospective, longitudinal, comparative study involving repeated measurements was conducted. Fifty-two consecutive patients with severe periodontal disease were divided into two groups, one comprising hypertensive patients treated with converting enzyme inhibitors and the other comprising patients with no clinical signs of pathology and not receiving angiotensin-converting enzyme inhibitors. Endothelial function was assessed by measuring postischemic dilation of the humeral artery (baseline echocardiography Doppler), and intensive periodontal treatment was performed 24h later. Endothelial function was re-assessed 24h and 15 days after periodontal treatment. Results were analyzed using the SPSS 20 statistical software package. Student's t test and MANOVA were calculated and linear regression analysis with 95% confidence intervals and α<0.05 was performed. Arterial dilation at 24 hours was lower compared to baseline in both groups; values corresponding to the groups receiving angiotensin-converting enzyme inhibitors were 11.89 ± 4.87 vs. 7.30 ± 2.90% (p<0.01) and those corresponding to the group not receiving ACE inhibitors were 12.72 ± 4.62 vs. 3.56 ± 2.39 (p<0.001). The differences between groups were statistically significant (p<0.001). The increase in endothelial dysfunction after intensive periodontal treatment was significantly lower in hypertensive patients treated with angiotensin-converting enzyme inhibitors. Endothelial function improved 15 days after periodontal treatment, reaching baseline values. These results support the protective effect of angiotensin converting enzyme inhibitors on the endothelial function after intensive periodontal treatment. Sociedad Argentina de Investigación Odontológica.

Meals for Good: An innovative community project to provide healthy meals to children in early care and education programs through food bank catering.

PubMed

Carpenter, Leah R; Smith, Teresa M; Stern, Katherine; Boyd, Lisa Weissenburger-Moser; Rasmussen, Cristy Geno; Schaffer, Kelly; Shuell, Julie; Broussard, Karen; Yaroch, Amy L

2017-12-01

Innovative approaches to childhood obesity prevention are warranted in early care and education (ECE) settings, since intervening early among youth is recommended to promote and maintain healthy behaviors. The objective of the Meals for Good pilot was to explore feasibility of implementing a food bank-based catering model to ECE programs to provide more nutritious meals, compared to meals brought from home (a parent-prepared model). In 2014-2015, a 12-month project was implemented by a food bank in central Florida in four privately-owned ECE programs. An explanatory sequential design of a mixed-methods evaluation approach was utilized, including a pre-post menu analysis comparing parent-prepared meals to the catered meals, and stakeholder interviews to determine benefits and barriers. The menu analysis of lunches showed daily reductions in calories, fat, and saturated fat, but an increase in sodium in catered meals when compared to parent-prepared meals. Interviews with ECE directors, teachers, parents, and food bank project staff, identified several benefits of the catered meals, including healthfulness of meals, convenience to parents, and the ECE program's ability to market this meal service. Barriers of the catered meals included the increased cost to parents, transportation and delivery logistics, and change from a 5 to a 2-week menu cycle during summer food service. This pilot demonstrated potential feasibility of a food bank-ECE program partnership, by capitalizing on the food bank's existing facilities and culinary programming, and interest in implementing strategies focused on younger children. The food bank has since leveraged lessons learned and expanded to additional ECE programs.

Archaeal Extrachromosomal Genetic Elements

PubMed Central

Wang, Haina; Peng, Nan; Shah, Shiraz A.

2015-01-01

SUMMARY Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes, such as spindles, rods, filaments, spheres, head-tails, bottles, and droplets, and some of these new viruses have been classified into one order, 10 families, and 16 genera. Investigation of model archaeal viruses has yielded important insights into mechanisms underlining various steps in the viral life cycle, including infection, DNA replication and transcription, and virion egression. Many of these mechanisms are unprecedented for any known bacterial or eukaryal viruses. Studies of plasmids isolated from different archaeal hosts have also revealed a striking diversity in gene content and innovation in replication strategies. Highly divergent replication proteins are identified in both viral and plasmid genomes. Genomic studies of archaeal ECEs have revealed a modular sequence structure in which modules of DNA sequence are exchangeable within, as well as among, plasmid families and probably also between viruses and plasmids. In particular, it has been suggested that ECE-host interactions have shaped the coevolution of ECEs and their archaeal hosts. Furthermore, archaeal hosts have developed defense systems, including the innate restriction-modification (R-M) system and the adaptive CRISPR (clustered regularly interspaced short palindromic repeats) system, to restrict invasive plasmids and viruses. Together, these interactions permit a delicate balance between ECEs and their hosts, which is vitally important for maintaining an innovative gene reservoir carried by ECEs. In conclusion, while research on archaeal ECEs has just started to unravel the molecular biology of these genetic entities and their interactions with archaeal hosts, it is expected to accelerate in the next decade. PMID:25694123

Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling

PubMed Central

de Albuquerque, Felipe Neves; Brandão, Andréa Araujo; da Silva, Dayse Aparecida; Mourilhe-Rocha, Ricardo; Duque, Gustavo Salgado; Gondar, Alyne Freitas Pereira; Neves, Luiza Maceira de Almeida; Bittencourt, Marcelo Imbroinise; Pozzan, Roberto; de Albuquerque, Denilson Campos

2014-01-01

Background The role of angiotensin-converting enzyme genetic polymorphisms as a predictor of echocardiographic outcomes on heart failure is yet to be established. The local profile should be identified so that the impact of those genotypes on the Brazilian population could be identified. This is the first study on exclusively non-ischemic heart failure over a follow-up longer than 5 years. Objective To determine the distribution of angiotensin-converting enzyme genetic polymorphism variants and their relation with echocardiographic outcome of patients with non-ischemic heart failure. Methods Secondary analysis of the medical records of 111 patients and identification of the angiotensin-converting enzyme genetic polymorphism variants, classified as DD (Deletion/Deletion), DI (Deletion/Insertion) or II (Insertion/Insertion). Results The cohort means were as follows: follow-up, 64.9 months; age, 59.5 years; male sex, 60.4%; white skin color, 51.4%; use of beta-blockers, 98.2%; and use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker, 89.2%. The angiotensin-converting enzyme genetic polymorphism distribution was as follows: DD, 51.4%; DI, 44.1%; and II, 4.5%. No difference regarding the clinical characteristics or treatment was observed between the groups. The final left ventricular systolic diameter was the only isolated echocardiographic variable that significantly differed between the angiotensin-converting enzyme genetic polymorphisms: 59.2 ± 1.8 for DD versus 52.3 ± 1.9 for DI versus 59.2 ± 5.2 for II (p = 0.029). Considering the evolutionary behavior, all echocardiographic variables (difference between the left ventricular ejection fraction at the last and first consultation; difference between the left ventricular systolic diameter at the last and first consultation; and difference between the left ventricular diastolic diameter at the last and first consultation) differed between the genotypes (p = 0.024; p = 0.002; and p = 0.021, respectively). Conclusion The distribution of the angiotensin-converting enzyme genetic polymorphisms differed from that of other studies with a very small number of II. The DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile (increased left ventricular ejection fraction and decreased left ventricular diameters). PMID:24270863

Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling.

PubMed

Albuquerque, Felipe Neves de; Brandão, Andréa Araujo; Silva, Dayse Aparecida da; Mourilhe-Rocha, Ricardo; Duque, Gustavo Salgado; Gondar, Alyne Freitas Pereira; Neves, Luiza Maceira de Almeida; Bittencourt, Marcelo Imbroinise; Pozzan, Roberto; Albuquerque, Denilson Campos de

2014-01-01

The role of angiotensin-converting enzyme genetic polymorphisms as a predictor of echocardiographic outcomes on heart failure is yet to be established. The local profile should be identified so that the impact of those genotypes on the Brazilian population could be identified. This is the first study on exclusively non-ischemic heart failure over a follow-up longer than 5 years. To determine the distribution of angiotensin-converting enzyme genetic polymorphism variants and their relation with echocardiographic outcome of patients with non-ischemic heart failure. Secondary analysis of the medical records of 111 patients and identification of the angiotensin-converting enzyme genetic polymorphism variants, classified as DD (Deletion/Deletion), DI (Deletion/Insertion) or II (Insertion/Insertion). The cohort means were as follows: follow-up, 64.9 months; age, 59.5 years; male sex, 60.4%; white skin color, 51.4%; use of beta-blockers, 98.2%; and use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker, 89.2%. The angiotensin-converting enzyme genetic polymorphism distribution was as follows: DD, 51.4%; DI, 44.1%; and II, 4.5%. No difference regarding the clinical characteristics or treatment was observed between the groups. The final left ventricular systolic diameter was the only isolated echocardiographic variable that significantly differed between the angiotensin-converting enzyme genetic polymorphisms: 59.2 ± 1.8 for DD versus 52.3 ± 1.9 for DI versus 59.2 ± 5.2 for II (p = 0.029). Considering the evolutionary behavior, all echocardiographic variables (difference between the left ventricular ejection fraction at the last and first consultation; difference between the left ventricular systolic diameter at the last and first consultation; and difference between the left ventricular diastolic diameter at the last and first consultation) differed between the genotypes (p = 0.024; p = 0.002; and p = 0.021, respectively). The distribution of the angiotensin-converting enzyme genetic polymorphisms differed from that of other studies with a very small number of II. The DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile (increased left ventricular ejection fraction and decreased left ventricular diameters).

No phenotypic plasticity in nest-site selection in response to extreme flooding events.

PubMed

Bailey, Liam D; Ens, Bruno J; Both, Christiaan; Heg, Dik; Oosterbeek, Kees; van de Pol, Martijn

2017-06-19

Phenotypic plasticity is a crucial mechanism for responding to changes in climatic means, yet we know little about its role in responding to extreme climatic events (ECEs). ECEs may lack the reliable cues necessary for phenotypic plasticity to evolve; however, this has not been empirically tested. We investigated whether behavioural plasticity in nest-site selection allows a long-lived shorebird ( Haematopus ostralegus ) to respond to flooding. We collected longitudinal nest elevation data on individuals over two decades, during which time flooding events have become increasingly frequent. We found no evidence that individuals learn from flooding experiences, showing nest elevation change consistent with random nest-site selection. There was also no evidence of phenotypic plasticity in response to potential environmental cues (lunar nodal cycle and water height). A small number of individuals, those nesting near an artificial sea wall, did show an increase in nest elevation over time; however, there is no conclusive evidence this occurred in response to ECEs. Our study population showed no behavioural plasticity in response to changing ECE patterns. More research is needed to determine whether this pattern is consistent across species and types of ECEs. If so, ECEs may pose a major challenge to the resilience of wild populations.This article is part of the themed issue 'Behavioural, ecological and evolutionary responses to extreme climatic events'. © 2017 The Author(s).

Elevated CO2 maintains grassland net carbon uptake under a future heat and drought extreme

PubMed Central

Roy, Jacques; Picon-Cochard, Catherine; Augusti, Angela; Benot, Marie-Lise; Thiery, Lionel; Darsonville, Olivier; Landais, Damien; Piel, Clément; Defossez, Marc; Devidal, Sébastien; Escape, Christophe; Ravel, Olivier; Fromin, Nathalie; Volaire, Florence; Milcu, Alexandru; Bahn, Michael; Soussana, Jean-François

2016-01-01

Extreme climatic events (ECEs) such as droughts and heat waves are predicted to increase in intensity and frequency and impact the terrestrial carbon balance. However, we lack direct experimental evidence of how the net carbon uptake of ecosystems is affected by ECEs under future elevated atmospheric CO2 concentrations (eCO2). Taking advantage of an advanced controlled environment facility for ecosystem research (Ecotron), we simulated eCO2 and extreme cooccurring heat and drought events as projected for the 2050s and analyzed their effects on the ecosystem-level carbon and water fluxes in a C3 grassland. Our results indicate that eCO2 not only slows down the decline of ecosystem carbon uptake during the ECE but also enhances its recovery after the ECE, as mediated by increases of root growth and plant nitrogen uptake induced by the ECE. These findings indicate that, in the predicted near future climate, eCO2 could mitigate the effects of extreme droughts and heat waves on ecosystem net carbon uptake. PMID:27185934

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

Simonetto, A.; Sozzi, C.; Garavaglia, S.

A Martin Puplett interferometer for electron cyclotron emission (ECE) measurements from JET tokamak plasmas was extended to multichannel operation for simultaneous radial and oblique ECE measurements. This paper describes the new optics and the instrument's performance.

Design and first plasma measurements of the ITER-ECE prototype radiometer.

PubMed

Austin, M E; Brookman, M W; Rowan, W L; Danani, S; Bryerton, E W; Dougherty, P

2016-11-01

On ITER, second harmonic optically thick electron cyclotron emission (ECE) in the range of 220-340 GHz will supply the electron temperature (T e ). To investigate the requirements and capabilities prescribed for the ITER system, a prototype radiometer covering this frequency range has been developed by Virginia Diodes, Inc. The first plasma measurements with this instrument have been carried out on the DIII-D tokamak, with lab bench tests and measurements of third through fifth harmonic ECE from high T e plasmas. At DIII-D the instrument shares the transmission line of the Michelson interferometer and can simultaneously acquire data. Comparison of the ECE radiation temperature from the absolutely calibrated Michelson and the prototype receiver shows that the ITER radiometer provides accurate measurements of the millimeter radiation across the instrument band.

The evolution of renin-angiotensin blockade: angiotensin-converting enzyme inhibitors as the starting point.

PubMed

Sica, Domenic A

2010-04-01

The renin-angiotensin system has been a target in the treatment of hypertension for close to three decades. Several medication classes that block specific aspects of this system have emerged as useful therapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and, most recently, direct renin inhibitors. There has been a natural history to the development of each of these three drug classes, starting with their use as antihypertensive agents; thereafter, in each case they have been employed as end-organ protective agents. To date, there has been scant evidence to favor angiotensin receptor blockers or direct renin inhibitors over angiotensin-converting enzyme inhibitors in treating hypertension or in affording end-organ protection; thus, angiotensin-converting enzyme inhibitors remain the standard of care when renin-angiotensin system blockade is warranted.

Substance P increases Sympathetic Activity during Combined Angiotensin Converting Enzyme and Dipeptidyl Peptidase-4 Inhibition

PubMed Central

Devin, Jessica K.; Pretorius, Mias; Nian, Hui; Yu, Chang; Billings, Frederic T.; Brown, Nancy J.

2014-01-01

Dipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce post-prandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme. During angiotensin-converting enzyme inhibition, substance P is inactivated primarily by dipeptidyl peptidase-4, while bradykinin is first inactivated by aminopeptidase P. This study tested the hypothesis that dipeptidyl peptidase-4 inhibition potentiates vasodilator and fibrinolytic responses to substance P when angiotensin-converting enzyme is inhibited. Twelve healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received sitagliptin 200 mg p.o. or placebo. Substance P and bradykinin were infused via brachial artery before and during intra-arterial enalaprilat. Sitagliptin and enalaprilat each reduced forearm vascular resistance and increased forearm blood flow without affecting mean arterial pressure, but there was no interactive effect of the inhibitors. Enalaprilat increased bradykinin-stimulated vasodilation and tissue plasminogen activator release; sitagliptin did not affect these responses to bradykinin. The vasodilator response to substance P was unaffected by sitagliptin and enalaprilat, however, substance P increased heart rate and vascular release of norepinephrine during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition. In women, sitagliptin diminished tissue plasminogen activator release in response to substance P both alone and during enalaprilat. Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition. PMID:24516103

Localization and characterization of angiotensin II receptor binding and angiotensin converting enzyme in the human medulla oblongata.

PubMed

Allen, A M; Chai, S Y; Clevers, J; McKinley, M J; Paxinos, G; Mendelsohn, F A

1988-03-08

Angiotensin II receptor and angiotensin converting enzyme distributions in the human medulla oblongata were localised by quantitative in vitro autoradiography. Angiotensin II receptors were labelled with the antagonist analogue 125I-[Sar1, Ile8] AII while angiotensin converting enzyme was labelled with 125I-351A, a derivative of the specific converting enzyme inhibitor, lisinopril. Angiotensin II receptor binding and angiotensin converting enzyme are present in high concentrations in the nucleus of the solitary tract, the dorsal motor nucleus of vagus, the rostral and caudal ventrolateral reticular nucleus, and in a band connecting the dorsal and ventral regions. In the rostral and caudal ventrolateral reticular nucleus, angiotensin II receptors are distributed in a punctate pattern that registers with neuronal cell bodies. The distribution and density of these cell bodies closely resemble those of catecholamine-containing neurones mapped by others. In view of the known interactions of angiotensin II with both central and peripheral catecholamine-containing neurons of laboratory animals, the current anatomical findings suggest similar interactions between these neuroactive compounds in the human central nervous system. The presence of angiotensin II receptors and angiotensin converting enzyme in the nucleus of the solitary tract, dorsal motor nucleus of vagus, and rostral and caudal ventrolateral reticular nucleus demonstrates sites for central angiotensin II to exert its known actions on vasopressin release and autonomic functions including blood pressure control. These data also suggest a possible interaction between angiotensin II and central catecholeminergic systems.

Exploitation of Unintentional Ethernet Cable Emissions Using Constellation Based-Distinct Native Attribute (CB-DNA) Fingerprints to Enhance Network Security

DTIC Science & Technology

2015-09-17

Exploitation of Unintentional Information Leakage from Inte- grated Circuits”. Ph.D. dissertation, ECE, AFIT, Wright- Patt AFB, OH, 2011. 16. Cobb, W. E...Ph.D. dissertation, ECE, AFIT, Wright- Patt AFB, OH, 2014. 48. Ramsey, B. W., Temple, M. A., and Mullins, B. E. PHY Foundation for Multi-Factor...dissertation, ECE, AFIT, Wright- Patt AFB, OH, 2012. 132 51. Reising, D. R., Temple, M. A., and Oxley, M. E. Gabor-Based RF-DNA Fingerprinting for

Cadence Feedback With ECE PEDO to Monitor Physical Activity Intensity: A Pilot Study.

PubMed

Ardic, Fusun; Göcer, Esra

2016-03-01

The purpose of this study was to examine the monitoring capabilities of the equipment for clever exercise pedometer (ECE PEDO) that provides audible feedback when the person exceeds the upper and lower limits of the target step numbers per minute and to compare step counts with Yamax SW-200 (YX200) as the criterion pedometer.A total of 30 adult volunteers (15 males and 15 females) were classified as normal weight (n = 10), overweight (n = 10), and obese (n = 10). After the submaximal exercise test on a treadmill, the moderate intensity for walking was determined by using YX200 pedometer and then the number of steps taken in a minute was measured. Lower and upper limits of steps per minute (cadence) were recorded in ECE PEDO providing audible feedback when the person's walking speed gets out of the limits. Volunteers walked for 30 minutes in the individual step count range by attaching the ECE PEDO and YX200 pedometer on both sides of the waist belt in the same session. Step counts of the volunteers were recorded. Wilcoxon, Spearman correlation, and Bland-Altman analyses were performed to show the relationship and agreement between the results of 2 devices.Subjects took an average of 3511 ± 426 and 3493 ± 399 steps during 30 minutes with ECE PEDO and criterion pedometer, respectively. About 3500 steps taken by ECE PEDO reflected that this pedometer has capability of identifying steps per minute to meet moderate intensity of physical activity. There was a strong correlation between step counts of both devices (P < 0.001, r = 0.96). Correlations across all three BMI categories and both sex remained consistently high ranging from 0.92 to 0.95. There was a high level of agreement between the ECE PEDO and YX200 pedometer in the Bland-Altman analysis.Although both devices showed a strong similarity in counting steps, the ECE PEDO provides monitoring of intensity such that a person can walk in a specified time with a desired speed.

Cadence Feedback With ECE PEDO to Monitor Physical Activity Intensity

PubMed Central

Ardic, Fusun; Göcer, Esra

2016-01-01

Abstract The purpose of this study was to examine the monitoring capabilities of the equipment for clever exercise pedometer (ECE PEDO) that provides audible feedback when the person exceeds the upper and lower limits of the target step numbers per minute and to compare step counts with Yamax SW-200 (YX200) as the criterion pedometer. A total of 30 adult volunteers (15 males and 15 females) were classified as normal weight (n = 10), overweight (n = 10), and obese (n = 10). After the submaximal exercise test on a treadmill, the moderate intensity for walking was determined by using YX200 pedometer and then the number of steps taken in a minute was measured. Lower and upper limits of steps per minute (cadence) were recorded in ECE PEDO providing audible feedback when the person's walking speed gets out of the limits. Volunteers walked for 30 minutes in the individual step count range by attaching the ECE PEDO and YX200 pedometer on both sides of the waist belt in the same session. Step counts of the volunteers were recorded. Wilcoxon, Spearman correlation, and Bland–Altman analyses were performed to show the relationship and agreement between the results of 2 devices. Subjects took an average of 3511 ± 426 and 3493 ± 399 steps during 30 minutes with ECE PEDO and criterion pedometer, respectively. About 3500 steps taken by ECE PEDO reflected that this pedometer has capability of identifying steps per minute to meet moderate intensity of physical activity. There was a strong correlation between step counts of both devices (P < 0.001, r = 0.96). Correlations across all three BMI categories and both sex remained consistently high ranging from 0.92 to 0.95. There was a high level of agreement between the ECE PEDO and YX200 pedometer in the Bland–Altman analysis. Although both devices showed a strong similarity in counting steps, the ECE PEDO provides monitoring of intensity such that a person can walk in a specified time with a desired speed. PMID:26962822

Attitude of medical students towards Early Clinical Exposure in learning endocrine physiology

PubMed Central

Sathishkumar, Solomon; Thomas, Nihal; Tharion, Elizabeth; Neelakantan, Nithya; Vyas, Rashmi

2007-01-01

Background Different teaching-learning methods have been used in teaching endocrine physiology for the medical students, so as to increase their interest and enhance their learning. This paper describes the pros and cons of the various approaches used to reinforce didactic instruction in endocrine physiology and goes on to describe the value of adding an Early Clinical Exposure program (ECE) to didactic instruction in endocrine physiology, as well as student reactions to it as an alternative approach. Discussion Various methods have been used to reinforce didactic instruction in endocrine physiology such as case-stimulated learning, problem-based learning, patient-centred learning and multiple-format sessions. We devised a teaching-learning intervention in endocrine physiology, which comprised of traditional didactic lectures, supplemented with an ECE program consisting of case based lectures and a hospital visit to see patients. A focus group discussion was conducted with the medical students and, based on the themes that emerged from it, a questionnaire was developed and administered to further enquire into the attitude of all the students towards ECE in learning endocrine physiology. The students in their feedback commented that ECE increased their interest for the subject and motivated them to read more. They also felt that ECE enhanced their understanding of endocrine physiology, enabled them to remember the subject better, contributed to their knowledge of the subject and also helped them to integrate their knowledge. Many students said that ECE increased their sensitivity toward patient problems and needs. They expressed a desire and a need for ECE to be continued in teaching endocrine physiology for future groups of students and also be extended for teaching other systems as well. The majority of the students (96.4%) in their feedback gave an overall rating of the program as good to excellent on a 5 point Likert scale. Summary The ECE program was introduced as an alternative approach to reinforce didactic instruction in endocrine physiology for the first year medical students. The study demonstrated that students clearly enjoyed the experience and perceived that it was valuable. This method could potentially be used for other basic science topics as well. PMID:17784967

Expression and regulation of estrogen-converting enzymes in ectopic human endometrial tissue.

PubMed

Fechner, Sabine; Husen, Bettina; Thole, Hubert; Schmidt, Markus; Gashaw, Isabella; Kimmig, Rainer; Winterhager, Elke; Grümmer, Ruth

2007-10-01

To investigate the regulation of estrogen-converting enzymes in human ectopic endometrial tissue. Animal study. Academic medical center. Sixty female nude mice with implanted human endometrial tissue. Twenty-two premenopausal women undergoing endometrial biopsy or hysterectomy. Human endometrial tissue was implanted into the peritoneal cavity of nude mice, and the effect of therapeutic drugs on transcription of steroid receptors and estrogen-converting enzymes was analyzed. Transcript levels of steroid hormone receptors, 17beta-hydroxysteroid dehydrogenase type 1 and 2, aromatase, and steroid sulfatase as well as proliferation rate were analyzed in the human ectopic endometrial tissue. Steroid receptors and estrogen-converting enzymes were expressed in the ectopic human endometrial fragments. Application of medroxyprogesterone acetate, dydrogesterone, danazol, and the aromatase inhibitor finrozole significantly inhibited aromatase transcription. In addition, danazol caused a significant decrease in transcription of steroid sulfatase, and finrozole, of 17beta-hydroxysteroid dehydrogenase type 1 in parallel to a decrease in proliferation rate in the ectopic human endometrial tissue. Pharmacological regulation of transcription of estrogen-converting enzymes in human endometrium cultured in nude mice may help to develop new therapeutic concepts based on local regulation of estrogen metabolism in endometriosis.

Multiparametric magnetic resonance imaging for the assessment of extracapsular invasion and other staging parameters in patients with prostate cancer candidates for radical prostatectomy.

PubMed

Lista, F; Gimbernat, H; Cáceres, F; Rodríguez-Barbero, J M; Castillo, E; Angulo, J C

2014-06-01

the proper evaluation of the extracapsular extension (ECE), the invasion of seminal vesicles and regional lymph nodes are necessary to plan the treatment of localized prostate cancer. A model that assesses the risk of ECE in the specimen considering the clinical, histological and imaging findings is defined. prospective study in 85 patients with prostate cancer treated with radical prostatectomy. Prostate biopsy was performed 4 weeks before multiparametric study (mpMRI). mpMRI included T2-weighted endorectal magnetic resonance imaging (T2W-MRI), diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The apparent diffusion coefficient (ADC) was also measured. A study of consistency (k) was assessed comparing receiver operating characteristic (ROC) curve and area under the curve (AUC), which were obtained in each case (Z). Finally, a regression model was performed to predict ECE. the mean age was 63.7 ± 6.9 years and the mean value of PSA 12.6 ± 13.8. In 31.7% of cases, digital rectal examination was suspicious for malignancy. Prostatectomy specimen showed pT2a in 12 cases (14%), pT2b in 3 (3%), pT2c in 37 (43%), pT3a in 19(22%) and pT3b 14 cases (17%). ECE was evidenced in 33 (39%) of the specimens, seminal vesicle invasion in 14 (16.5%) and pelvic node involvement in 5 patients (6%). The consistency in the evaluation of ECE (image and pathological studies) was .35 for MRI (sensitivity .33, specificity .96) and .62 for mpMRI (sensitivity .58, specificity .98). Mean value of ADC was .76 ± .2 in patients with ECE. This value was not associated with Gleason score (P = .2) or with PSA value (P = .6). AUC value as predictor of ECE was of 65% for MRI, 78% for mpMRI and 50% ADC (Z = .008). Univariate analysis demonstrated that ECE probability increases with each Gleason score point, whilst this probability increases 1.06 times with each PSA point, and decreases .3 times with each point of ADC. Multivariate analysis confirmed that ADC value is a slight protective factor against ECE (OR = .01; CI 95% .002-.14). The consistency in the evaluation of seminal vesicles was .43 for MRI and .67 for mpMRI. AUC was 69% and 82% respectively (Z = .02). The consistency in the evaluation of positive lymph nodes was .4 for MRI and .7 for mpMRI. AUC was 68% and 88% respectively (Z = .36). multiparametric study allows to carry out a more proper preoperative evaluation of ECE than convectional MRI. The most reliable predictors of ECE are DW-MRI combined with DCE-MRI, ADC coefficient and Gleason score. The superiority of mpMRI is also demonstrated for detection of seminal vesicles invasion, but not for the evaluation of lymph nodes invasion. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Design and first plasma measurements of the ITER-ECE prototype radiometer

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

Austin, M. E.; Brookman, M. W.; Rowan, W. L.

2016-11-15

On ITER, second harmonic optically thick electron cyclotron emission (ECE) in the range of 220-340 GHz will supply the electron temperature (T{sub e}). To investigate the requirements and capabilities prescribed for the ITER system, a prototype radiometer covering this frequency range has been developed by Virginia Diodes, Inc. The first plasma measurements with this instrument have been carried out on the DIII-D tokamak, with lab bench tests and measurements of third through fifth harmonic ECE from high T{sub e} plasmas. At DIII-D the instrument shares the transmission line of the Michelson interferometer and can simultaneously acquire data. Comparison of themore » ECE radiation temperature from the absolutely calibrated Michelson and the prototype receiver shows that the ITER radiometer provides accurate measurements of the millimeter radiation across the instrument band.« less

High-frequency intrinsic dynamics of the electrocaloric effect from direct atomistic simulations

NASA Astrophysics Data System (ADS)

Lisenkov, S.; Ponomareva, I.

2018-05-01

We propose a computational methodology capable of harvesting isothermal heat and entropy change in molecular dynamics simulations. The methodology is applied to study high-frequency dynamics of the electrocaloric effect (ECE) in ferroelectric PbTiO3. ECE is associated with a reversible change in temperature under adiabatic application of electric field or with a reversible change in entropy under isothermal application of the electric field. Accurate assessment of electrocaloric performance requires the knowledge of three quantities: isothermal heat, isothermal entropy change, and adiabatic temperature change. Our methodology allows computations of all these quantities directly, that is, without restoring to the reversible thermodynamical models. Consequently, it captures both reversible and irreversible effects, which is critical for ECE simulations. The approach is well suited to address the dynamics of the ECE, which so far remains underexplored. We report the following basic features of the intrinsic dynamics of ECE: (i) the ECE is independent of the electric field frequency, rate of application, or field profile; (ii) the effect persists up to the frequencies associated with the onset of dielectric losses and deteriorates from there due to the creation of irreversible entropy; and (iii) in the vicinity of the phase transition and in the paraelectric phase the onset of irreversible dynamics occurs at lower frequency as compared to the ferroelectric phase. The latter is attributed to lower intrinsic soft-mode frequencies and and larger losses in the paraelectric phase.

Is substance P released from slices of the rat spinal cord inactivated by peptidase(s) distinct from both 'enkephalinase' and 'angiotensin-converting enzyme'?

PubMed

Mauborgne, A; Bourgoin, S; Benoliel, J J; Hamon, M; Cesselin, F

1991-02-25

Studies on the effects of peptidase inhibitors on substance P-like immunoreactive material (SPLI) released by K(+)-induced depolarization from slices of the rat spinal cord showed that bacitracin was the most potent agent to protect SPLI from degradation. Captopril and thiorphan which inhibit, respectively, angiotensin I converting enzyme and endopeptidase-24.11 also protected SPLI from degradation. However other inhibitors of these two enzymes, kelatorphan for endopeptidase-24.11 and enalaprilat for angiotensin I converting enzyme were essentially inactive, indicating that both enzymes are probably not involved in the degradation of endogenous substance P. Instead, the non-additive protecting effect of bacitracin, captopril and thiorphan might be due to the blockade of some 'bacitracin-sensitive enzyme' playing a key role in the catabolism of SP within the rat spinal cord.

Quasi-adiabatic calorimeter for direct electrocaloric measurements

NASA Astrophysics Data System (ADS)

Sanlialp, Mehmet; Shvartsman, Vladimir V.; Faye, Romain; Karabasov, Maksim O.; Molin, Christian; Gebhardt, Sylvia; Defay, Emmanuel; Lupascu, Doru C.

2018-03-01

The electrocaloric effect (ECE) in ferroelectric materials is a promising candidate for small, effective, low cost, and environmentally friendly solid state cooling applications. Instead of the commonly used indirect estimates based on Maxwell's relations, direct measurements of the ECE are required to obtain reliable values. In this work, we report on a custom-made quasi-adiabatic calorimeter for direct ECE measurements. The ECE is measured for two promising lead-free materials: Ba(Zr0.12Ti0.88)O3 and Ba(Zr0.2Ti0.8)O3 bulk ceramics. Adiabatic temperature changes of ΔTEC = 0.5 K at 355 K and ΔTEC = 0.3 K at 314 K were achieved under the application of an electric field of 2 kV/mm for the Ba(Zr0.12Ti0.88)O3 and Ba(Zr0.2Ti0.8)O3 samples, respectively. The quasi-adiabatic ECE measurements reliably match other direct EC measurements using a differential scanning calorimeter or an infrared camera. The data are compared to indirect EC estimations based on Maxwell's relations and show that the indirect measurements typically underestimate the effect to a certain degree.

Location priority for non-formal early childhood education school based on promethee method and map visualization

NASA Astrophysics Data System (ADS)

Ayu Nurul Handayani, Hemas; Waspada, Indra

2018-05-01

Non-formal Early Childhood Education (non-formal ECE) is an education that is held for children under 4 years old. The implementation in District of Banyumas, Non-formal ECE is monitored by The District Government of Banyumas and helped by Sanggar Kegiatan Belajar (SKB) Purwokerto as one of the organizer of Non-formal Education. The government itself has a program for distributing ECE to all villages in Indonesia. However, The location to construct the ECE school in several years ahead is not arranged yet. Therefore, for supporting that program, a decision support system is made to give some recommendation villages for constructing The ECE building. The data are projected based on Brown’s Double Exponential Smoothing Method and utilizing Preference Ranking Organization Method for Enrichment Evaluation (Promethee) to generate priority order. As the recommendations system, it generates map visualization which is colored according to the priority level of sub-district and village area. The system was tested with black box testing, Promethee testing, and usability testing. The results showed that the system functionality and Promethee algorithm were working properly, and the user was satisfied.

Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

PubMed

Bahia, Malkeet S; Silakari, Om

2010-05-01

Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

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

Nally, J.V. Jr.; Clarke, H.S. Jr.; Grecos, G.P.

In an effort to improve on the noninvasive detection of renal artery stenosis, we investigated the effect of angiotensin converting enzyme inhibition on computer-assisted /sup 99m/Tc-diethylenetriaminepentaacetic acid (DTPA) renal flow studies in a canine model of two-kidney, one clip hypertension and compared these findings with clearances of inulin and p-aminohippuric acid in the stenotic and contralateral kidney before and after converting enzyme inhibition. The /sup 99m/Tc-DTPA renal flow study with the converting enzyme inhibitor captopril (1.5 mg/kg bolus with 1.5 mg/min infusion) showed an increased sensitivity in the detection of unilateral renal artery stenosis over the use of the /supmore » 99m/Tc-DTPA study alone. Captopril induced striking alterations that were most evident in the 15-minute /sup 99m/Tc-DTPA renal flow study, in which all nine curves exhibited severely blunted uptake and excretion of the radionuclide. These changes were reversed during a recovery study without converting enzyme inhibition and were not seen when blood pressure was lowered with nitroprusside to a level similar to that observed during converting enzyme inhibition. The changes shown by the /sup 99m/Tc-DTPA study during converting enzyme inhibition correlated with a decrease in the glomerular filtration rate of the stenotic kidney. Captopril infusion significantly decreased the glomerular filtration rate of the stenotic kidney (16.0 +/- 3.1 vs 11.0 +/- 2.5 mg/min, p less than 0.03) but not of the contralateral kidney (32.4 +/- 2.6 vs 28.4 +/- 2.8 mg/min).« less

Commissioning of inline ECE system within waveguide based ECRH transmission systems on ASDEX upgrade

NASA Astrophysics Data System (ADS)

Bongers, W. A.; Kasparek, W.; Doelman, N.; van den Braber, R.; van den Brand, H.; Meo, F.; de Baar, M. R.; Amerongen, F. J.; Donné, A. J. H.; Elzendoorn, B. S. Q.; Erckmann, V.; Goede, A. P. H.; Giannone, L.; Grünwald, G.; Hollman, F.; Kaas, G.; Krijger, B.; Michel, G.; Lubyako, L.; Monaco, F.; Noke, F.; Petelin, M.; Plaum, B.; Purps, F.; ten Pierik, J. G. W.; Schüller, C.; Slob, J. W.; Stober, J. K.; Schütz, H.; Wagner, D.; Westerhof, E.; Ronden, D. M. S.

2012-09-01

A CW capable inline electron cyclotron emission (ECE) separation system for feedback control, featuring oversized corrugated waveguides, is commissioned on ASDEX upgrade (AUG). The system is based on a combination of a polarization independent, non-resonant, Mach-Zehnder diplexer equipped with dielectric plate beam splitters [2, 3] employed as corrugated oversized waveguide filter, and a resonant Fast Directional Switch, FADIS [4, 5, 6, 7] as ECE/ECCD separation system. This paper presents an overview of the system, the low power characterisation tests and first high power commissioning on AUG.

An exploration of Early Childhood Education students’ knowledge and preparation to facilitate physical activity for preschoolers: a cross-sectional study

PubMed Central

2014-01-01

Background Early childhood educators play an important role in influencing preschoolers’ physical activity levels. The current study sought to explore Early Childhood Education (ECE) students’ physical activity-related knowledge and educational experience during their formal training in Ontario. Methods A total of 1,113 ECE students from 20 Ontario Colleges completed the study survey (online or on paper), which examined students’ physical activity course content; awareness of physical activity guidelines; understanding of health-related benefits of physical activity; self-efficacy to facilitate physical activity for preschoolers; self-reported physical activity levels; as well as physical activity-related resource needs. Descriptive statistics and independent samples t-tests were used to analyze the quantitative findings. Results Survey results identified that 72.1% of ECE students had not completed any physical activity/physical education specific courses, while only 28.7% were familiar with, and 2.0% accurately reported, the Canadian Physical Activity Guidelines for the Early Years. Only 10.5% of ECE students reported personal physical activity behaviors consistent with national recommendations for adults (150 minutes/week). ECE students’ mean overall task self-efficacy to facilitate physical activity was 7.37 (SD = 1.64). Self-efficacy was significantly higher (p < .05) when students had taken one or more courses devoted to physical activity/physical education, as well as when students engaged in sufficient physical activity to meet the national guidelines for adults (p < .05). Conclusions The results indicate that the current ECE college curriculum represents an excellent opportunity to provide future childcare providers with enriched physical activity-related training and support, such as physical activity guidelines, workshops, and new ideas for activities. Emphasizing the health benefits of physical activity for adults might be important in light of ECE students’ low self-reported physical activity levels. PMID:25034415

UNAVCO's Education and Community Engagement Program: Evaluating Five years of Geoscience Education and Community Outreach

NASA Astrophysics Data System (ADS)

Charlevoix, D. J.; Dutilly, E.

2017-12-01

In 2013, UNAVCO, a facility co-sponsored by the NSF and NASA, received a five-year award from the NSF: Geodesy Advancing Geosciences and EarthScope (GAGE). Under GAGE, UNAVCO's Education and Community Engagement (ECE) program conducts outreach and education activities, in essence broader impacts for the scientific community and public. One major challenge of this evaluation was the breadth and depth of the dozens of projects conducted by the ECE program under the GAGE award. To efficiently solve this problem of a large-scale program evaluation, we adopted a deliberative democratic (DD) approach that afforded UNAVCO ECE staff a prominent voice in the process. The evaluator directed staff members to chose the projects they wished to highlight as case studies of their finest broader impacts work. The DD approach prizes inclusion, dialogue, and deliberation. The evaluator invited ECE staff to articulate qualities of great programs and develop a case study of their most valuable broader impacts work. To anchor the staff's opinion in more objectivity than opinion, the evaluator asked each staff member to articulate exemplary qualities of their chosen project, discuss how these qualities fit their case study, and helped staff to develop data collection systems that lead to an evidence-based argument in support of their project's unique value. The results of this evaluation show that the individual ECE work areas specialized in certain kinds of projects. However, when viewed at the aggregate level, ECE projects spanned almost the entire gamut of NSF broader impacts categories. Longitudinal analyses show that since the beginning of the GAGE award, many projects grew in impact from year 1 to year 5. While roughly half of the ECE projects were prior work projects, by year five at least 33% of projects were newly developed under GAGE. All selected case studies exemplified how education and outreach work can be productively tied to UNAVCO's core mission of promoting geodesy.

Role of LA Shape in Predicting Embolic Cerebrovascular Events in Mitral Stenosis

PubMed Central

Nunes, Maria Carmo P.; Handschumacher, Mark D.; Levine, Robert A.; Barbosa, Marcia M.; Carvalho, Vinicius T.; Esteves, William A.; Zeng, Xin; Guerrero, J. Luis; Zheng, Hui; Tan, Timothy C.; Hung, Judy

2015-01-01

OBJECTIVES This study was designed to assess the role of left atrial (LA) shape in predicting embolic cerebrovascular events (ECE) in patients with mitral stenosis (MS). BACKGROUND Patients with rheumatic MS are at increased risk for ECE. LA remodeling in response to MS involves not only chamber dilation but also changes in the shape. We hypothesized that a more spherical LA shape may be associated with increased embolic events due to predisposition to thrombus formation or to atrial arrhythmias compared with an elliptical-shaped LA of comparable volume. METHODS A total of 212 patients with MS and 20 control subjects were enrolled. LA volume, LA emptying fraction, and cross-sectional area were measured by 3-dimensional (3D) transthoracic echocardiography. LA shape was expressed as the ratio of measured LA end-systolic volume to hypothetical sphere volume ([4/3π r3] where r was obtained from 3D cross-sectional area). The lower the LA shape index, the more spherical the shape. RESULTS A total of 41 patients presented with ECE at the time of enrollment or during follow-up. On multivariate analysis, LA 3D emptying fraction (adjusted odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.92 to 0.99; p = 0.028) and LA shape index (OR: 0.73; 95% CI: 0.61 to 0.87; p < 0.001) emerged as important factors associated with ECE, after adjustment for age and anticoagulation therapy. In patients in sinus rhythm, LA shape index remained associated with ECE (OR: 0.79; 95% CI: 0.67 to 0.94; p = 0.007), independent of age and LA function. An in vitro phantom atrial model demonstrated more stagnant flow profiles in spherical compared with ellipsoidal chamber. CONCLUSIONS In rheumatic MS patients, differential LA remodeling affects ECE risk. A more spherical LA shape was independently associated with an increased risk for ECE, adding incremental value in predicting events beyond that provided by age and LA function. PMID:24831206

Tuning the electrocaloric enhancement near the morphotropic phase boundary in lead-free ceramics

NASA Astrophysics Data System (ADS)

Le Goupil, Florian; McKinnon, Ruth; Koval, Vladimir; Viola, Giuseppe; Dunn, Steve; Berenov, Andrey; Yan, Haixue; Alford, Neil Mcn.

2016-06-01

The need for more energy-efficient and environmentally-friendly alternatives in the refrigeration industry to meet global emission targets has driven efforts towards materials with a potential for solid state cooling. Adiabatic depolarisation cooling, based on the electrocaloric effect (ECE), is a significant contender for efficient new solid state refrigeration techniques. Some of the highest ECE performances reported are found in compounds close to the morphotropic phase boundary (MPB). This relationship between performance and the MPB makes the ability to tune the position of the MPB an important challenge in electrocaloric research. Here, we report direct ECE measurements performed on MPB tuned NBT-06BT bulk ceramics with a combination of A-site substitutions. We successfully shift the MPB of these lead-free ceramics closer to room temperature, as required for solid state refrigeration, without loss of the criticality of the system and the associated ECE enhancement.

Tuning the electrocaloric enhancement near the morphotropic phase boundary in lead-free ceramics

PubMed Central

Le Goupil, Florian; McKinnon, Ruth; Koval, Vladimir; Viola, Giuseppe; Dunn, Steve; Berenov, Andrey; Yan, Haixue; Alford, Neil McN.

2016-01-01

The need for more energy-efficient and environmentally-friendly alternatives in the refrigeration industry to meet global emission targets has driven efforts towards materials with a potential for solid state cooling. Adiabatic depolarisation cooling, based on the electrocaloric effect (ECE), is a significant contender for efficient new solid state refrigeration techniques. Some of the highest ECE performances reported are found in compounds close to the morphotropic phase boundary (MPB). This relationship between performance and the MPB makes the ability to tune the position of the MPB an important challenge in electrocaloric research. Here, we report direct ECE measurements performed on MPB tuned NBT-06BT bulk ceramics with a combination of A-site substitutions. We successfully shift the MPB of these lead-free ceramics closer to room temperature, as required for solid state refrigeration, without loss of the criticality of the system and the associated ECE enhancement. PMID:27312287

Design and first plasma measurements of the ITER-ECE prototype radiometer

DOE PAGES

Austin, M. E.; Brookman, M. W.; Rowan, W. L.; ...

2016-08-09

On ITER, second harmonic optically thick electron cyclotron emission (ECE) in the range of 220-340 GHz will supply the electron temperature (T e). In order to investigate the requirements and capabilities prescribed for the ITER system, a prototype radiometer covering this frequency range has been developed by Virginia Diodes, Inc. The first plasma measurements with this instrument have been carried out on the DIII-D tokamak, with lab bench tests and measurements of third through fifth harmonic ECE from high T e plasmas. At DIII-D the instrument shares the transmission line of the Michelson interferometer and can simultaneously acquire data. Inmore » our comparison of the ECE radiation temperature from the absolutely calibrated Michelson and the prototype receiver we show that the ITER radiometer provides accurate measurements of the millimeter radiation across the instrument band.« less

Tuning the electrocaloric enhancement near the morphotropic phase boundary in lead-free ceramics.

PubMed

Le Goupil, Florian; McKinnon, Ruth; Koval, Vladimir; Viola, Giuseppe; Dunn, Steve; Berenov, Andrey; Yan, Haixue; Alford, Neil McN

2016-06-17

The need for more energy-efficient and environmentally-friendly alternatives in the refrigeration industry to meet global emission targets has driven efforts towards materials with a potential for solid state cooling. Adiabatic depolarisation cooling, based on the electrocaloric effect (ECE), is a significant contender for efficient new solid state refrigeration techniques. Some of the highest ECE performances reported are found in compounds close to the morphotropic phase boundary (MPB). This relationship between performance and the MPB makes the ability to tune the position of the MPB an important challenge in electrocaloric research. Here, we report direct ECE measurements performed on MPB tuned NBT-06BT bulk ceramics with a combination of A-site substitutions. We successfully shift the MPB of these lead-free ceramics closer to room temperature, as required for solid state refrigeration, without loss of the criticality of the system and the associated ECE enhancement.

Assay for Angiotensin-Converting Enzyme.

ERIC Educational Resources Information Center

Russo, Salvatore F.

1983-01-01

Describes a three-hour experiment designed to introduce students to chemistry of the angiotensis-converting enzyme, illustrate design of a quenched fluorescence substrate, and examine considerations necessary in designing a clinical assay. Includes background information on the biochemistry of hypertension, reagents/materials needed, procedures…

Lignocellulose-converting enzyme activity profiles correlate with molecular systematics and phylogeny grouping in the incoherent genus Phlebia (Polyporales, Basidiomycota).

PubMed

Kuuskeri, Jaana; Mäkelä, Miia R; Isotalo, Jarkko; Oksanen, Ilona; Lundell, Taina

2015-10-19

The fungal genus Phlebia consists of a number of species that are significant in wood decay. Biotechnological potential of a few species for enzyme production and degradation of lignin and pollutants has been previously studied, when most of the species of this genus are unknown. Therefore, we carried out a wider study on biochemistry and systematics of Phlebia species. Isolates belonging to the genus Phlebia were subjected to four-gene sequence analysis in order to clarify their phylogenetic placement at species level and evolutionary relationships of the genus among phlebioid Polyporales. rRNA-encoding (5.8S, partial LSU) and two protein-encoding gene (gapdh, rpb2) sequences were adopted for the evolutionary analysis, and ITS sequences (ITS1+5.8S+ITS2) were aligned for in-depth species-level phylogeny. The 49 fungal isolates were cultivated on semi-solid milled spruce wood medium for 21 days in order to follow their production of extracellular lignocellulose-converting oxidoreductases and carbohydrate active enzymes. Four-gene phylogenetic analysis confirmed the polyphyletic nature of the genus Phlebia. Ten species-level subgroups were formed, and their lignocellulose-converting enzyme activity profiles coincided with the phylogenetic grouping. The highest enzyme activities for lignin modification (manganese peroxidase activity) were obtained for Phlebia radiata group, which supports our previous studies on the enzymology and gene expression of this species on lignocellulosic substrates. Our study implies that there is a species-level connection of molecular systematics (genotype) to the efficiency in production of both lignocellulose-converting carbohydrate active enzymes and oxidoreductases (enzyme phenotype) on spruce wood. Thus, we may propose a similar phylogrouping approach for prediction of lignocellulose-converting enzyme phenotypes in new fungal species or genetically and biochemically less-studied isolates of the wood-decay Polyporales.

External validation of a nomogram for prediction of side-specific extracapsular extension at robotic radical prostatectomy.

PubMed

Zorn, Kevin C; Gallina, Andrea; Hutterer, Georg C; Walz, Jochen; Shalhav, Arieh L; Zagaja, Gregory P; Valiquette, Luc; Gofrit, Ofer N; Orvieto, Marcelo A; Taxy, Jerome B; Karakiewicz, Pierre I

2007-11-01

Several staging tools have been developed for open radical prostatectomy (ORP) patients. However, the validity of these tools has never been formally tested in patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). We tested the accuracy of an ORP-derived nomogram in predicting the rate of extracapsular extension (ECE) in a large RALP cohort. Serum prostate specific antigen (PSA) and side-specific clinical stage and biopsy Gleason sum information were used in a previously validated nomogram predicting side-specific ECE. The nomogram-derived predictions were compared with the observed rate of ECE, and the accuracy of the predictions was quantified. Each prostate lobe was analyzed independently. As complete data were available for 576 patients, the analyses targeted 1152 prostate lobes. Median age and serum PSA concentration at radical prostatectomy were 60 years and 5.4 ng/mL, respectively. The majority of side-specific clinical stages were T(1c) (993; 86.2%). Most side-specific biopsy Gleason sums were 6 (572; 49.7%). The median side-specific percentages of positive cores and of cancer were, respectively, 20.0% and 5.0%. At final pathologic review, 107 patients (18.6%) had ECE, and side-specific ECE was present in 117 patients (20.3%). The nomogram was 89% accurate in the RALP cohort v 84% in the previously reported ORP validation. The ORP side-specific ECE nomogram is highly accurate in the RALP population, suggesting that predictive and possibly prognostic tools developed in ORP patients may be equally accurate in their RALP counterparts.

Push or Pull? Proton Responsive Ligand Effects in Rhenium Tricarbonyl CO 2 Reduction Catalysts

DOE PAGES

Manbeck, Gerald F.; Muckerman, James T.; Szalda, David J.; ...

2015-02-19

Proton responsive ligands offer control of catalytic reactions through modulation of pH-dependent properties, second coordination sphere stabilization of transition states, or by providing a local proton source for multi-proton, multi-electron reactions. Two fac-[ReI(α-diimine)(CO)₃Cl] complexes with α-diimine = 4,4'- (or 6,6'-) dihydroxy-2,2'-bipyridine (4DHBP and 6DHBP) have been prepared and analyzed as electrocatalysts for reduction of carbon dioxide. Consecutive electrochemical reduction of these complexes yields species identical to those obtained by chemical deprotonation. An energetically feasible mechanism for reductive deprotonation is proposed in which the bpy anion is protonated followed by loss of H₂ and 2H⁺. Cyclic voltammetry reveals a two-electron, three-wavemore » system owing to competing EEC and ECE pathways. The chemical step of the ECE pathway might be attributed to the reductive deprotonation. but cannot be distinguished from chloride dissociation. The rate obtained by digital simulation is approximately 8 s⁻¹. Under CO₂, these competing reactions generate a two-slope catalytic waveform with onset potential of –1.65 V vs Ag/AgCl. Reduction of CO₂ to CO by the [ReI (4DHBP–2H⁺)(CO)₃]⁻ suggests the interaction of CO₂ with the deprotonated species or a third reduction followed by catalysis. Conversely, the reduced form of [Re(6DHBP)(CO)₃Cl] converts CO₂ to CO with a single turnover.« less

Early Clinical Exposure as a Learning Tool to Teach Neuroanatomy for First Year MBBS Students.

PubMed

Kar, Maitreyee; Kar, Chinmaya; Roy, Hironmoy; Goyal, Parmod

2017-12-01

Early clinical exposure (ECE) is one of the important tools to teach basic science to the MBBS students. It is one form of vertical integration between basic science and clinical subjects. This study is an effort at exploring the use of ECE as a motivational tool toward better learning in neuroanatomy for first year MBBS students. This study aims to make the students interested and motivated to study neuroanatomy by using ECE as learning tool in neuroanatomy and to make the students enable to retain the knowledge of neuroanatomy more efficiently and correlate the knowledge of neuroanatomy with neuromedicine. This study was conducted in collaboration with the Departments of Anatomy, General Medicine and Medical Education Unit in the year 2016. This was cross-sectional study. One hundred and fifty students of 1 st Professional MBBS were subdivided into two groups. After preliminary classes on brain, brainstem, and spinal cord for both groups, conventional lecture classes were taken for Group A only on upper motor neuron (UMN) and lower motor neuron (LMN) paralysis, and only Group B visited General Medicine ward where HOD, General Medicine showed and examined patients of UMN paralysis and LMN paralysis, elicited different symptoms, and discussed different investigation. It was followed by assessment of all by problem-based multiple choice questions (MCQ) and short answer questions. Then, Group B attended lecture class on different cranial nerve palsy whereas Group A visited medicine ward. It was followed by assessment of both groups by problem-based MCQ and short answer questions. The performance was compared. Then, the feedback of the students on ECE was collected by means of reflection writing followed by administration of questionnaire. Then, the perception of teachers regarding ECE was recorded by focused group discussion. Student's t -test was used to compare the performance of both batches. Reflection writing and focus group discussion were analyzed qualitatively. There was a significant difference in Group A ( P = 0.019) but no significant difference in Group B ( P = 0.679). All the teachers opined that ECE was an efficient method but more time and interdepartmental collaboration were necessary. Group A improved performance due to ECE but Group B maintained the motivational effect of it. Therefore, ECE can be used as an effective learning tool.

The Impact of Magnetic Resonance Imaging on Prediction of Extraprostatic Extension and Prostatectomy Outcome in Patients with Low-, Intermediate- and High-Risk Prostate Cancer: Try to Find a Standard.

PubMed

Radtke, Jan Philipp; Hadaschik, Boris A; Wolf, Maya B; Freitag, Martin T; Schwab, Constantin; Alt, Celine; Roth, Wilfried; Duensing, Stefan; Pahernik, Sascha A; Roethke, Matthias C; Schlemmer, Heinz-Peter; Hohenfellner, Markus; Teber, Dogu

2015-12-01

To investigate the value of multiparametric magnetic resonance imaging (mpMRI) and to predict extracapsular extension (ECE), seminal vesicle (SV) infiltration, and a negative surgical margin (SM) status at radical prostatectomy (RP) for different prostate cancer (PC) risk groups. In the study, 805 men underwent 3 tesla mpMRI without endorectal coil before MRI/transrectal ultrasonography-fusion guided prostate biopsy. MRIs were analyzed using the prostate imaging reporting and data system. The cohort was classified into risk groups according to National Comprehensive Cancer Network (NCCN) criteria. Of 132 men who subsequently underwent RP, pathologic stage and SM status at RP were used as reference. Retrospectively, we investigated a European Society of Urogenital Radiology (ESUR) score for ECE and SV-infiltration. Statistical analyses included regression analyses, receiver operating characteristics (ROC), and Youden Index to assess an ESUR-score cutoff. Area under the curve in ROC curve analyses was 0.82 for ESUR-ECE score to detect pT(3a)-disease and 0.77 for ESUR-SV score for pT(3b). Using a cutoff of 4 for ECE and of 2 for SV, the positive predictive value of the ECE-score for harboring pT(3) was 50.0%, 90.0%, and 88.8% for the low-, intermediate- and high-risk cohort. Retrospectively, the use of the ESUR-ECE score preoperatively would have changed the initial surgical plan, according to NCCN criteria, in 31.1% of patients. In the high-risk subgroup, 9/35 (25.7%) patients were correctly assessed as not harboring pT(3) by imaging (ECE score <4), and would have allowed secure robot-assisted radical prostatectomy and nerve-sparing surgery (NSS). When T3 suspicion on preoperative MRI would be taken into account, intraoperative frozen-sections (IFS) might avoid positive SM in 12/18 high-risk patients and an oncologic secure NSS in 8/20 intermediate-risk patients. Prediction of pT(3) disease is crucial to plan NSS and to achieve negative SM in RP. Standardized ECE scoring on mpMRI is an independent predictor of pT(3) and may help to plan RP with oncologic security, even in high-risk patients. In addition, it allows more accurate selection of a subgroup of patients for systematic and MRI-guided IFS.

Angiotensin-converting enzyme: I. New strategies for assay

PubMed Central

Ryan, James W.; Chung, Alfred; Ryan, Una S.

1980-01-01

The disposition of converting enzyme (kininase II) on the luminal surface of pulmonary endothelial cells is well established. Further, it is known that there is a net conversion of angiotensin I into angiotensin II as blood passes through the lungs. However, little is known about modulations of converting enzyme activity that may arise through, e.g., changes in the quality of inhalants, blood flow, or blood oxygenation. There are few data on the effects of lung disease. A major barrier to studies to examine for pathophysiologic modulations of converting enzyme is that of assay. The enzyme can be measured in terms of the rate of formation of angiotensin II from a known quantity of angiotensin I. However, both peptides are biologically active, and lungs contain other enzymes capable of degrading them. We have developed a series of radiolabeled, acylated tripeptides to improve our ability to examine for changes in the net converting enzyme of intact lungs. The enzyme, a dipeptidyl carboxypeptidase, is capable of removing C-terminal dipeptides from a variety of oligopeptides. We have prepared benzoyl-Gly-Gly-Gly (I), benzoyl-Pro-Phe-Arg (II), benzoyl-Gly-His-Leu (III), benzoyl-Phe-Ala-Pro (IV), and benzoyl-Phe-His-Leu (V), each containing a 3H-atom in the para position of the benzoyl moiety. Substrates I and III have been used previously in photometric assays of low sensitivity. II is the acylated C-terminal tripeptide of bradykinin, IV is an acylated tripeptide analog of BPP5a (

[Association between visual improvement after photocoagulation and the use of angiotensin converting enzyme inhibitors in diabetic macular oedema].

PubMed

Somilleda-Ventura, Selma Alin; García-Rubio, Yatzul Zuhaila; Razo Blanco-Hernández, Dulce Milagros; Lima-Gómez, Virgilio

2016-01-01

Angiotensin converting enzyme inhibitors are effective in delaying the progression of diabetic retinopathy. It is unknown if their use is associated with a better visual outcome in patients with diabetic macular oedema. A non-experimental, comparative, longitudinal and retrospective study was performed on patients with diabetic macular oedema treated by focal photocoagulation, and with systemic arterial hypertension treated with angiotensin converting enzyme inhibitors (Group 1), and without hypertension (Group 2). The dependent variable was the proportion with visual improvement, operatively defined as the gain of one or more lines of vision three weeks after photocoagulation. The independent variable was the use of angiotensin converting enzyme inhibitors. The proportion of eyes with visual improvement after treatment was compared between groups using the Chi squared (χ(2)) test. A total of 33 eyes (51.6%) were assigned to group 1, and 31 (48.2%), to group 2. The mean of visual acuity improved after three weeks, compared with baseline (p=0.002). The proportion of eyes with visual improvement did not differ between patients treated with angiotensin converting enzyme inhibitors (45.5%) and those that did not use them (51.6%, p=0.4). There was no statistical difference in the proportion of eyes with visual improvement between patients treated with angiotensin converting enzyme inhibitors and in those where they were not used. There is no support for the inhibition of angiotensin II in addition to photocoagulation for improving the outcome in patients with diabetic macular oedema. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Discovery of piperonal-converting oxidase involved in the metabolism of a botanical aromatic aldehyde

PubMed Central

Doi, Shiori; Hashimoto, Yoshiteru; Tomita, Chiaki; Kumano, Takuto; Kobayashi, Michihiko

2016-01-01

Piperonal-catabolizing microorganisms were isolated from soil, the one (strain CT39-3) exhibiting the highest activity being identified as Burkholderia sp. The piperonal-converting enzyme involved in the initial step of piperonal metabolism was purified from strain CT39-3. Gene cloning of the enzyme and a homology search revealed that the enzyme belongs to the xanthine oxidase family, which comprises molybdoenzymes containing a molybdopterin cytosine dinucleotide cofactor. We found that the piperonal-converting enzyme acts on piperonal in the presence of O2, leading to formation of piperonylic acid and H2O2. The growth of strain CT39-3 was inhibited by higher concentrations of piperonal in the culture medium. Together with this finding, the broad substrate specificity of this enzyme for various aldehydes suggests that it would play an important role in the defense mechanism against antimicrobial compounds derived from plant species. PMID:27905507

What's Happening with Computer Technology in Early Childhood Education Settings?

ERIC Educational Resources Information Center

Wood, Eileen; Willoughby, Teena; Specht, Jacqueline

1998-01-01

This in-depth survey of 75 early-childhood-education directors examined the current status of computer use in early childhood education (ECE). Results suggest that training may be necessary to facilitate the introduction of computers in ECE environments. (Author/LRW)

Factors that influence the efficiency of electrochemical chloride extraction during corrosion mitigation in reinforced concrete structures.

DOT National Transportation Integrated Search

2006-01-01

Electrochemical chloride extraction (ECE) is an electrochemical bridge restoration method for mitigating corrosion in reinforced concrete structures. ECE does this by moving chlorides away from the reinforcement and out of the concrete while simultan...

Identification of interleukin-8 converting enzyme as cathepsin L.

PubMed

Ohashi, Kensaku; Naruto, Masanobu; Nakaki, Toshio; Sano, Emiko

2003-06-26

IL-8 is produced by various cells, and the NH(2)-terminal amino acid sequence of IL-8 displays heterogeneity among cell types. The mature form of IL-8 has 72 amino acids (72IL-8), while a precursor form (77IL-8) of IL-8 has five additional amino acids to the 72IL-8 NH(2)-terminal. However, it has been unclear how IL-8 is processed to yield the mature form. In this study, converting enzyme was purified as a single 31-kDa band on silver-stained polyacrylamide gel from 160 l of cultured fibroblast supernatant by sequential chromatography. NH(2)-terminal amino acid sequence analysis revealed a sequence, EAPRSVDWRE, which was identified as a partial sequence of cathepsin L. Polyclonal antibodies raised against cathepsin L recognized the purified converting enzyme on Western blot. Moreover, human hepatic cathepsin L cleaved 77IL-8 between Arg(5) and Ser(6), which is the same cleavage site as the putative converting enzyme, resulting in 72IL-8 formation. These data indicate that the converting enzyme of the partially purified fraction of the human fibroblast culture supernatant was cathepsin L. Furthermore, 72IL-8 was sevenfold more potent than 77IL-8 in a neutrophil chemotaxis assay. These results show that cathepsin L is secreted from human fibroblasts in response to external stimuli and plays an important role in IL-8 processing in inflammatory sites.

New Developments

ERIC Educational Resources Information Center

Lohmander, Maelis Karlson; Vandenbroeck, Michel; Pirard, Florence; Peeters, Jan; Alvestad, Marit

2009-01-01

New developments and challenges regarding early childhood education (ECE) policy and practice in Norway and in the Flemish and French communities in Belgium are presented in this issue. There are clear differences between the countries when comparing systems they have chosen for ECE. In Belgium, supervision and responsibilities for education,…

Engineering aspects of design and integration of ECE diagnostic in ITER

DOE PAGES

Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; ...

2015-03-12

ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnosticsmore » with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.« less

Temperature induced phase transformations and negative electrocaloric effect in (Pb,La)(Zr,Sn,Ti)O3 antiferroelectric single crystal

NASA Astrophysics Data System (ADS)

Zhuo, Fangping; Li, Qiang; Yan, Qingfeng; Zhang, Yiling; Wu, Hong-Hui; Xi, Xiaoqing; Chu, Xiangcheng; Cao, Wenwu

2017-10-01

Temperature induced phase transitions and electrocaloric effect (ECE) of (Pb,La)(Zr,Sn,Ti)O3 (PLZST) single crystals have been comprehensively studied. Based on the in situ evolution of domain structures and dielectric properties of the PLZST crystals, the phase transitions during heating are in the sequence of orthorhombic antiferroelectric → rhombohedral ferroelectric → cubic paraelectric. Coexistence of the negative and positive ECEs has been achieved in the PLZST single crystals. A negative ECE value of -1.26 °C and enhanced electrocaloric strength of -0.21 K mm/kV near the Curie temperature have been obtained. A modified Landau model gives a satisfactory description of the experimentally observed unusual ECE. Moreover, a temperature-electric field phase diagram is also established based on theoretical analysis. Our results will help people understand better the electrocaloric family, particularly on the negative and/or positive effect in antiferroelectrics and ferroelectrics.

Pre-Service Teachers' Perceptions on Tpack Development after Designing Educational Games

ERIC Educational Resources Information Center

Sancar Tokmak, Hatice

2015-01-01

This qualitative case study aimed to investigate Early Childhood Education (ECE) pre-service teachers' perception of development in their technological, pedagogical, content knowledge (TPACK) after designing educational computer games for young children. Participants included 21 ECE pre-service teachers enrolled in the course Instructional…

Colossal Room-Temperature Electrocaloric Effect in Ferroelectric Polymer Nanocomposites Using Nanostructured Barium Strontium Titanates.

PubMed

Zhang, Guangzu; Zhang, Xiaoshan; Yang, Tiannan; Li, Qi; Chen, Long-Qing; Jiang, Shenglin; Wang, Qing

2015-07-28

The electrocaloric effect (ECE) refers to conversion of thermal to electrical energy of polarizable materials and could form the basis for the next-generation refrigeration and power technologies that are highly efficient and environmentally friendly. Ferroelectric materials such as ceramic and polymer films exhibit large ECEs, but each of these monolithic materials has its own limitations for practical cooling applications. In this work, nanosized barium strontium titanates with systematically varied morphologies have been prepared to form polymer nanocomposites with the ferroelectric polymer matrix. The solution-processed polymer nanocomposites exhibit an extraordinary room-temperature ECE via the synergistic combination of the high breakdown strength of a ferroelectric polymer matrix and the large change of polarization with temperature of ceramic nanofillers. It is found that a sizable ECE can be generated under both modest and high electric fields, and further enhanced greatly by tailoring the morphology of the ferroelectric nanofillers such as increasing the aspect ratio of the nanoinclusions. The effect of the geometry of the nanofillers on the dielectric permittivity, polarization, breakdown strength, ECE and crystallinity of the ferroelectric polymer has been systematically investigated. Simulations based on the phase-field model have been carried out to substantiate the experimental results. With the remarkable cooling energy density and refrigerant capacity, the polymer nanocomposites are promising for solid-state cooling applications.

Detecting non-maxwellian electron velocity distributions at JET by high resolution Thomson scattering.

PubMed

Beausang, K V; Prunty, S L; Scannell, R; Beurskens, M N; Walsh, M J; de la Luna, E

2011-03-01

The present work is motivated by a long standing discrepancy between the electron temperature measurements of Thomson scattering (TS) and electron cyclotron emission (ECE) diagnostics for plasmas with strong auxiliary heating observed at both JET and TFTR above 6–7 keV, where in some cases the ECE electron temperature measurements can be 15%–20% higher than the TS measurements. Recent analysis based on ECE results at JET has shown evidence of distortions to the Maxwellian electron velocity distribution and a correlation with the TS and ECE discrepancies has been suggested. In this paper, a technique to determine the presence of non-Maxwellian behavior using TS diagnostics is outlined. The difficulties and limitations of modern TS system designs to determine the electron velocity distribution are also discussed. It is demonstrated that small deviations such as those suggested by previous ECE analysis could be potentially detected, depending on the spectral layout of the TS polychromators. The spectral layout of the JET high resolution Thomson scattering system is such that it could be used to determine these deviations between 1 and 6 keV, and the results presented here indicate that no evidence of non-Maxwellian behavior is observed in this range. In this paper, a modification to the current polychromator design is proposed, allowing non-Maxwellian distortions to be detected up to at least 10 keV.

Active Early: one-year policy intervention to increase physical activity among early care and education programs in Wisconsin.

PubMed

LaRowe, Tara L; Tomayko, Emily J; Meinen, Amy M; Hoiting, Jill; Saxler, Courtney; Cullen, Bridget

2016-07-20

Early childcare and education (ECE) is a prime setting for obesity prevention and the establishment of healthy behaviors. The objective of this quasi-experimental study was to examine the efficacy of the Active Early guide, which includes evidenced-based approaches, provider resources, and training, to improve physical activity opportunities through structured (i.e. teacher-led) activity and environmental changes thereby increasing physical activity among children, ages 2-5 years, in the ECE setting. Twenty ECE programs in Wisconsin, 7 family and 13 group, were included. An 80-page guide, Active Early, was developed by experts and statewide partners in the fields of ECE, public health, and physical activity and was revised by ECE providers prior to implementation. Over 12 months, ECE programs received on-site training and technical assistance to implement the strategies and resources provided in the Active Early guide. Main outcome measures included observed minutes of teacher-led physical activity, physical activity environment measured by the Environment and Policy Assessment and Observation (EPAO) instrument, and child physical activity levels via accelerometry. All measures were collected at baseline, 6 months, and 12 months and were analyzed for changes over time. Observed teacher-led physical activity significantly increased from 30.9 ± 22.7 min at baseline to 82.3 ± 41.3 min at 12 months. The change in percent time children spent in sedentary activity decreased significantly after 12 months (-4.4 ± 14.2 % time, -29.2 ± 2.6 min, p < 0.02). Additionally, as teacher led-activity increased, percent time children were sedentary decreased (r = -0.37, p < 0.05) and percent time spent in light physical activity increased (r = 0.35, p < 0.05). Among all ECE programs, the physical activity environment improved significantly as indicated by multiple sub-scales of the EPAO; scores showing the greatest increases were the Training and Education (14.5 ± 6.5 at 12-months vs. 2.4 ± 3.8 at baseline, p < 0.01) and Physical Activity Policy (18.6 ± 4.6 at 12-months vs. 2.0 ± 4.1 at baseline, p < 0.01). Active Early promoted improvements in providing structured (i.e. teacher-led) physical activity beyond the recommended 60 daily minutes using low- to no-cost strategies along with training and environmental changes. Furthermore, it was observed that Active Early positively impacted child physical activity levels by the end of the intervention. However, resources, training, and technical assistance may be necessary for ECE programs to be successful beyond the use of the Active Early guide. Implementing local-level physical activity policies combined with support from local and statewide partners has the potential to influence higher standards for regulated ECE programs.

Application of liquid chromatography-electrospray ionization mass spectrometry for study of steroid-converting enzymes.

PubMed

Miksík, Ivan; Mikulíková, Katerina; Pácha, Jirí; Kucka, Marek; Deyl, Zdenek

2004-02-05

A high-performance liquid chromatography-atmospheric pressure ionization-electrospray ionization mass spectrometry (HPLC-API-ESI-MS) method was developed for the analysis of steroids in a study of steroid-converting enzymes. Separations ware done on a Zorbax Eclipse XDB-C18 column (eluted with a linear methanol-water-acetic acid gradient) and identification of the steroids involved was done by API-ESI-MS using positive ion mode and extracted ion analysis. The applicability of the present method for studying steroid metabolism was proven in assaying two steroid-converting enzymes (20beta-hydroxysteroid dehydrogenase and 11beta-hydroxysteroid dehydrogenase) in various biological samples (rat and chicken intestine, chicken oviduct).

Playing the Assessment Game: An English Early Childhood Education Perspective

ERIC Educational Resources Information Center

Basford, Jo; Bath, Caroline

2014-01-01

Assessment and the documentation of learning is an international issue in early childhood education (ECE) and has increasingly become a way for governments to exercise direct control over the practitioners working with young children. This paper details recent statutory guidance about assessment and documentation for English ECE settings and…

Building Capacity through an Early Education Leadership Academy

ERIC Educational Resources Information Center

Goffin, Stacie G.

2013-01-01

In 2013, the early childhood education (ECE) field is paying limited attention to leadership development (Goffin & Janke, 2013; Goffin & Means, 2009). A recent survey of ECE leadership development programs suggests that the field does not fully recognize the potential of leadership to serve as a change catalyst, although there is evidence…

Language Arts: Exceptional Child Education Curriculum K-12.

ERIC Educational Resources Information Center

Curran, Teresa; And Others

The Exceptional Child Education (ECE) program of Jefferson County Public Schools in Louisville, Kentucky, presents this language arts curriculum for use with K-12 students who have learning problems. The ECE program uses the curriculum and materials of the general education program whenever appropriate, but has access to special instructional…

Constructing Relational Space in Early Childhood Education

ERIC Educational Resources Information Center

Vuorisalo, Mari; Rutanen, Niina; Raittila, Raija

2015-01-01

This paper examines early childhood education (ECE) by applying and developing relational-spatial perspectives on everyday life in educational institutions for young children. The aim is to investigate the dynamic process of construction of space and to illustrate with selected empirical episodes how this process occurs in ECE. Drawing on authors…

21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

Biological production of organic compounds

DOEpatents

Yu, Jianping; Wang, Bo; Paddock, Troy; Carrieri, Damian; Maness, Pin-Ching; Seibert, Michael

2018-03-13

Methods of producing ethylene oxide and ethylene glycol are disclosed herein. Ethylene produced by cyanobacteria engineered to express ethylene-forming enzymes may be converted to ethylene oxide by bacteria engineered to express a monooxygenase enzyme. Ethylene oxide may be converted to ethylene glycol by exposure to an acidic solution. The methods may be performed in a bioreactor.

Possible identity of IL-8 converting enzyme in human fibroblasts as a cysteine protease.

PubMed

Ohashi, Kensaku; Sano, Emiko; Nakaki, Toshio; Naruto, Masanobu

2003-04-01

A converting activity was characterized in human diploid fibroblasts, which secrete 72IL-8 and 77IL-8 in treatment with IFN-beta and poly I: poly C. 77IL-8 was significantly converted to 72IL-8 by a partially purified fraction of the culture supernatant of human diploid fibroblasts. The converting activity, which was temperature-dependent and optimal at pH 6, was completely inhibited by cysteine protease inhibitors, antipain dihydrochloride and E-64, but not by other types of protease inhibitors. These data clearly show that human diploid fibroblasts are capable of processing IL-8 to produce a mature IL-8 and that the putative converting enzyme appears to be a cysteine protease.

[Prospective observational study of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with chronic renal failure].

PubMed

Ben Mahmoud, Lobna; Ghozzi, Hanene; Kammoun, Khawla; Hakim, Ahmed; Kharrat, Mahmoud; Ben Hmida, Mohamed; Jarraya, Faical; Sahnoun, Zouheir; Zeghal, Khaled; Hachicha, Jamil

2013-04-01

To study the incidence and risk factors of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with hypertension and preexisting chronic renal failure. Two-months prospective observational study was used including all hospitalized patients older than 18 years with a history of hypertension, non-dialyzed chronic renal failure and who had angiotensin converting enzyme prescription at the time of the admission. Hyperkalemia greater than or equal to 5 mmol/L was detected in these patients. The studied variables were demographic, clinical, biological and therapeutic. Eight patients, among 27 included, had a hyperkalemia (2963%). They were 73±15 years old. Factors that predispose to hyperkalemia were present in all patients. Hyperkalemia was associated in six cases with decompensation of renal function. The age was associated with hyperkalaemia in patients treated with angiotensin converting enzyme inhibitors (RC=1.21; IC95 1,11-1,46; P=0,021). Diabetes is a possible risk factor (OR=59 021 et, 95 0.93 to 2410, P=0.053). Compared with patients who did not develop hyperkalemia, the occurrence of hyperkalemia in patients included was associated with a longer duration of hospitalization (OR=130, 95 112 to 160, P=0. 022). The prescription of angiotensin converting enzyme inhibitors in the elderly with chronic renal failure and diabetes requires careful monitoring of serum potassium. Copyright © 2012 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Antihypertensive effect of Carica papaya via a reduction in ACE activity and improved baroreflex.

PubMed

Brasil, Girlandia Alexandre; Ronchi, Silas Nascimento; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Romão, Wanderson; da Costa, Helber Barcellos; Scherer, Rodrigo; Ventura, José Aires; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

2014-11-01

The aims of this study were to evaluate the antihypertensive effects of the standardised methanolic extract of Carica papaya, its angiotensin converting enzyme inhibitory effects in vivo, its effect on the baroreflex and serum angiotensin converting enzyme activity, and its chemical composition. The chemical composition of the methanolic extract of C. papaya was evaluated by liquid chromatography-mass/mass and mass/mass spectrometry. The angiotensin converting enzyme inhibitory effect was evaluated in vivo by Ang I administration. The antihypertensive assay was performed in spontaneously hypertensive rats and Wistar rats that were treated with enalapril (10 mg/kg), the methanolic extract of C. papaya (100 mg/kg; twice a day), or vehicle for 30 days. The baroreflex was evaluated through the use of sodium nitroprusside and phenylephrine. Angiotensin converting enzyme activity was measured by ELISA, and cardiac hypertrophy was evaluated by morphometric analysis. The methanolic extract of C. papaya was standardised in ferulic acid (203.41 ± 0.02 µg/g), caffeic acid (172.60 ± 0.02 µg/g), gallic acid (145.70 ± 0.02 µg/g), and quercetin (47.11 ± 0.03 µg/g). The flavonoids quercetin, rutin, nicotiflorin, clitorin, and manghaslin were identified in a fraction of the extract. The methanolic extract of C. papaya elicited angiotensin converting enzyme inhibitory activity. The antihypertensive effects elicited by the methanolic extract of C. papaya were similar to those of enalapril, and the baroreflex sensitivity was normalised in treated spontaneously hypertensive rats. Plasma angiotensin converting enzyme activity and cardiac hypertrophy were also reduced to levels comparable to the enalapril-treated group. These results may be associated with the chemical composition of the methanolic extract of C. papaya, and are the first step into the development of a new phytotherapic product which could be used in the treatment of hypertension. Georg Thieme Verlag KG Stuttgart · New York.

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

PubMed

Danchin, Nicolas; Cucherat, Michel; Thuillez, Christian; Durand, Eric; Kadri, Zena; Steg, Philippe G

2006-04-10

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases.

PubMed

Reilly, C F; Tewksbury, D A; Schechter, N M; Travis, J

1982-08-10

Human neutrophil cathepsin G and human skin mast cell chymase rapidly convert angiotensin I to angiotensin II with only minor cleavage elsewhere in the molecule. The rate of cleavage is consistent with a potential role for either or both of these enzymes in an alternate pathway for angiotensin II synthesis. Since neither enzyme in inhibited by captopril, an angiotensin converting enzyme inactivator, it is possible that leukocyte and mast cell enzymes may play a significant role in the development of abnormally high local concentrations of angiotensin II, associated with various inflammatory processes.

Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

PubMed

Blute, Michael L; Rushmer, Timothy J; Shi, Fangfang; Fuller, Benjamin J; Abel, E Jason; Jarrard, David F; Downs, Tracy M

2015-11-01

Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04). Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Combined enzyme mediated fermentation of cellulous and xylose to ethanol by Schizosaccharoyces pombe, cellulase, .beta.-glucosidase, and xylose isomerase

DOEpatents

Lastick, Stanley M.; Mohagheghi, Ali; Tucker, Melvin P.; Grohmann, Karel

1994-01-01

A process for producing ethanol from mixed sugar streams from pretreated biomass comprising xylose and cellulose using enzymes to convert these substrates to fermentable sugars; selecting and isolating a yeast Schizosaccharomyces pombe ATCC No. 2476, having the ability to ferment these sugars as they are being formed to produce ethanol; loading the substrates with the fermentation mix composed of yeast, enzymes and substrates; fermenting the loaded substrates and enzymes under anaerobic conditions at a pH range of between about 5.0 to about 6.0 and at a temperature range of between about 35.degree. C. to about 40.degree. C. until the fermentation is completed, the xylose being isomerized to xylulose, the cellulose being converted to glucose, and these sugars being concurrently converted to ethanol by yeast through means of the anaerobic fermentation; and recovering the ethanol.

Combined enzyme mediated fermentation of cellulose and xylose to ethanol by Schizosaccharomyces pombe, cellulase, [beta]-glucosidase, and xylose isomerase

DOEpatents

Lastick, S.M.; Mohagheghi, A.; Tucker, M.P.; Grohmann, K.

1994-12-13

A process for producing ethanol from mixed sugar streams from pretreated biomass comprising xylose and cellulose using enzymes to convert these substrates to fermentable sugars; selecting and isolating a yeast Schizosaccharomyces pombe ATCC No. 2476, having the ability to ferment these sugars as they are being formed to produce ethanol; loading the substrates with the fermentation mix composed of yeast, enzymes and substrates; fermenting the loaded substrates and enzymes under anaerobic conditions at a pH range of between about 5.0 to about 6.0 and at a temperature range of between about 35 C to about 40 C until the fermentation is completed, the xylose being isomerized to xylulose, the cellulose being converted to glucose, and these sugars being concurrently converted to ethanol by yeast through means of the anaerobic fermentation; and recovering the ethanol. 2 figures.

Dipeptidyl peptidase-4 inhibitor induced angioedema - an overlooked and potentially lethal adverse drug reaction?

PubMed

Scott, Susanne Irene; Andersen, Michelle Fog; Aagaard, Lise; Buchwald, Christian Von; Rasmussen, Eva Rye

2017-02-14

Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. Dipeptidyl peptidase-4 inhibitors are anti-diabetic drugs used to improve glycaemic control. They, as a class effect, inadvertently affect the degradation of the vasoactive kinins bradykinin and substance P, both of which can cause angioedema due to vasodilatation and increase in vascular permeability in the capillaries. Objective To assess the risk and pathomechanism of angioedema due to inhibition of dipeptidyl peptidase-4 inhibitors when used as monotherapy and in combination with angiotensin converting enzyme-inhibitors. Method PubMed, Embase, the Cochrane Library, PubMed Central, Web of Science, Google Scholar and clinicaltrials.gov were searched using different combinations of keywords "angioedema", "dipeptidyl peptidase 4", "dipeptidyl peptidase 4 inhibitors", "gliptins", "bradykinin", "substance P" and "angiotensin converting enzyme-inhibitors". Original research papers were preferably used as references and their bibliographies were used to further the search for original research results. Results Both angiotensin converting enzyme and dipeptidyl peptidase-4 are major enzymes in the degradation pathway of bradykinin and substance P, and when inhibited pharmacologically - especially at the same time - the theoretical risk of angioedema is increased due to accumulation of vasoactive kinins. Conclusion Treatment with dipeptidyl peptidase-4 inhibitors must be carefully considered and monitored especially during concurrent treatment with angiotensin converting enzyme-inhibitors or when treating patients with a known predisposition to angioedema. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Early Childhood Educators' Understanding of Early Communication: Application to Their Work with Young Children

ERIC Educational Resources Information Center

Brebner, Chris; Jovanovic, Jessie; Lawless, Angela; Young, Jessica

2016-01-01

Young children need rich learning experiences to maximize their potential. Early childhood educators (ECEs) working in childcare have knowledge of individual children as well as skills and professional knowledge that afford opportunities to provide language-rich environments for learning. To successfully work in partnership with ECEs,…

Canadian Early-Childhood Educators' Perceptions of Children's Gendered Shy, Aggressive, and Prosocial Behaviors

ERIC Educational Resources Information Center

Woods, Heather; Bosacki, Sandra; Coplan, Robert J.

2016-01-01

Early childhood educators' (ECE) perceptions of gender roles may contribute to the development of children's own gender-role identities. This qualitative study examined 40 Canadian female ECEs' perceptions of gender and children's shy, aggressive, and prosocial behaviors. Content analysis of extensive interviews revealed three themes: (1) shyness…

The Influence of Gender Bias on Children in Childcare Settings

ERIC Educational Resources Information Center

Ikram, R

2011-01-01

To date, Early Childhood Education (ECE) courses and curriculum are primarily focused on a being gender neutral and teaching non-traditional gender practices in childcare settings. Further, many child care providers, specifically ECE teachers, are women. This paper describes how many teachers in childcare settings are teaching boys and girls to…

Brokering to Support Participation of Disadvantaged Families in Early Childhood Education

ERIC Educational Resources Information Center

Mitchell, Linda; Meagher-Lundberg, Patricia

2017-01-01

This paper discusses findings from an evaluation of the New Zealand Ministry of Education's Early Childhood Education (ECE) Participation Programme that targeted local areas where there are high numbers of children starting school who have not participated in ECE. The aim of the programme is to increase participation of these low-income…

Praxis in Early Childhood Research with Infants and Educators

ERIC Educational Resources Information Center

Salamon, Andi

2017-01-01

As emerging literature reflects, "praxis" is an important and useful concept for thinking about the many aspects of early childhood education (ECE) and early childhood research. In this article, I seek to contribute to discussions about praxis in ECE as a valuable concept for meeting the ethical challenges that arise in participatory…

Examining Quality in Two Preschool Settings: Publicly Funded Early Childhood Education and Inclusive Early Childhood Education Classrooms

ERIC Educational Resources Information Center

Pelatti, Christina Yeager; Dynia, Jaclyn M.; Logan, Jessica A.; Justice, Laura M.; Kaderavek, Joan

2016-01-01

Background: Although classroom quality is an important consideration, few recent research studies have examined the process and structural quality in publicly funded early childhood education (ECE) and inclusive ECE classrooms. This study provides an important contribution to the literature by comparing two conceptualizations of quality in…

The Eros of Counter Education

ERIC Educational Resources Information Center

Luzon, Pinhas

2016-01-01

Erotic Counter Education (ECE) is the educational position of the late Ilan Gur-Ze'ev. In ECE Gur-Ze'ev combines two opposing positions in the philosophy of education, one teleological and anti-utopian, the other teleological and utopian. In light of this unique combination, I ask what mediates between these two poles and suggest that the answer…

Homophobia, Sexism, and Early Childhood Education: A Review of the Literature

ERIC Educational Resources Information Center

Duke, Thomas Scott; McCarthy, Kathrin W.

2009-01-01

We reviewed 31 articles that explored issues related to gender and sexuality in early childhood education (ECE) settings. This body of literature suggests that ECE programs and elementary schools often reinforce the homophobia, heterosexism, and sexism that characterize contemporary U.S. society. A number of the articles described strategies that…

Electronic Continuing Education in the Health Professions: An Update on Evidence from RCTs

ERIC Educational Resources Information Center

Lam-Antoniades, Margarita; Ratnapalan, Savithiri; Tait, Gordon

2009-01-01

Introduction: Demonstrating the effectiveness of the rapidly expanding field of electronic continuing education (e-CE) has important implications for CE in the health professions. This study provides an update on evidence from randomized controlled trials (RCTs) assessing the effectiveness of e-CE in the health professions. Methods: A literature…

Early Childhood Education in Eighteen Countries in the Middle East and North Africa.

ERIC Educational Resources Information Center

Khattab, Mohammad S.

1996-01-01

Examined the status of early childhood education (ECE) in 18 middle eastern and north African countries, incorporating country profiles, ECE institutions, teachers, and children. Identified the critical issues needing priority attention, and a set of indicators that could be used by educational planners and policymakers for monitoring and…

Disarming Contankerous People: Coping with Difficult Personalities in ECE Work Settings

ERIC Educational Resources Information Center

Hernandez, Luis; Smith, Connie Jo

2009-01-01

Difficult personalities come in a variety of roles in just about every setting. While types have been identified in the typical corporate and business culture, difficult work personalities also inhabit the world of early childhood education (ECE) workplaces. Because difficult people have an impact on workplace morale and productivity, the topic…

Shared-Reading Volume in Early Childhood Special Education Classrooms

ERIC Educational Resources Information Center

Dynia, Jaclyn M.; Justice, Laura M.

2015-01-01

This study describes book reading practices occurring in early childhood special education (ECSE) classrooms in comparison to early childhood education (ECE) classrooms. Reading logs submitted by 19 ECSE teachers and 13 ECE teachers over one academic year included all books read in whole class settings; these logs were analyzed to assess the…

Experienced Early Childhood Teachers as Graduate Students: A Process of Change

ERIC Educational Resources Information Center

Mevorach, Miriam; Miron, Mordechai

2011-01-01

This paper explores perceptions of professional identity among experienced early childhood educators (ECEs) who are novice students in a new master's degree program in ECE. We sought to examine the changes experienced by these educators. The study used qualitative content analysis, which included an open-ended questionnaire that was administered…

Financing the Early Childhood Education System: NAEYC Policy Brief.

ERIC Educational Resources Information Center

Young Children, 2001

2001-01-01

Discusses the view of the National Association for the Education of Young Children (NAEYC) regarding financing a system of early childhood education (ECE) in every state and community. Considers how to create a system, why financing is so important, the need to finance ECE programs and infrastructure, and various financing mechanisms. Concludes…

Challenges in Implementation of Early Childhood Education in Nigeria: The Way Forward

ERIC Educational Resources Information Center

Akinrotimi, Adenike A.; Olowe, Peter K.

2016-01-01

Early Childhood Education (ECE) comprises essential programmes and activities which are critical to holistic development, academic success and future achievements of children. ECE is recognised by the federal government of Nigeria as a foundational and essential programme that Nigerian children must experience. This is why the government has given…

Ways of dealing with science learning: a study based on Swedish early childhood education practice

NASA Astrophysics Data System (ADS)

Gustavsson, Laila; Jonsson, Agneta; Ljung-Djärf, Agneta; Thulin, Susanne

2016-07-01

The Swedish school system offers curriculum-based early childhood education (ECE) organised as preschool (for 0-5-year-olds) and preschool class (for 6-year-olds). The intention to create a playful and educational environment based on children's perspectives, interests, and questions is strongly based on historical and cultural traditions. This article develops knowledge of ECE teachers' approaches to science-learning situations. The study applies a phenomenographic approach. The analysis is based on approximately 9.5 hours of video documentation of teacher-led and child-initiated Swedish ECE science activities. We identified two descriptive categories and four subcategories dealing with science-learning situations: (A) making anything visible, containing the three subcategories (Aa) addressing everyone, (Ab) addressing everything, and (Ac) addressing play and fantasy; and (B) creating a shared space for learning (Ba) addressing common content. These categories are related to how efforts to take advantage of children's perspectives are interpreted and addressed in educational practice. The article discusses and exemplifies the use of various categories and their potential implications for ECE learning practice.

Ideal kink and neoclassical tearing mode identification in DIII-D with ECE

NASA Astrophysics Data System (ADS)

Zhao, Hailin; Austin, Max; Brookman, Michale; Rowan, William; La Haye, R. J.

2017-10-01

Detection of neoclassical tearing modes (NTMs), which can degrade plasma confinement or cause disruptions, is important in tokamaks. We have developed a code to cross-correlate ECE/magnetics data to get the amplitude and phase profiles of the electron temperature (Te) oscillation caused by the rotating magnetic island and/or a kink. It has been observed that the ΔTe amplitude on the two sides of the island center can be very different in some discharges. Also, a discrepancy often exists between the location of the rational q surface according to MSE-constrained EFIT and the location of island center according to ECE; this can be an issue for ECCD suppression of NTMs. We explore the possible causes of these two phenomena in terms of ECE location and calibration accuracy. By analyzing the Te fluctuation phase evolution after a large sawtooth crash which triggers an NTM, the presence of a kink-like mode before the onset of NTM can be discerned. Work supported by the US DOE under DE-FG02-97ER54415 and DE-FC02-04ER54698.

Enhanced electrocaloric effect in displacive-type organic ferroelectrics

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

Ding, L. J., E-mail: dinglinjie82@126.com; Zhong, Y.; Fan, S. W.

2015-08-07

We explore the intrinsic feature of electrocaloric effect (ECE) accompanied by ferroelectric (FE)-paraelectric (PE) transition for displacive-type organic ferroelectrics using Green's function theory. It is demonstrated that decreasing elastic constant K or increasing spin-lattice coupling λ can enhance the ECE, as well as polarization P and transition temperature T{sub C}. Indeed, one expects that the optimal operating temperature for solid-state refrigeration is around room temperature, at which the ECE achieves its maximum. As T{sub C} is tuned to ∼310 K, it presents larger ECE response and remanent polarization with lower coercive field for smaller K value, suggesting that well flexible displacive-typemore » organic ferroelectrics are excellent candidates both for electric cooling and data storage in the design of nonvolatile FE random-access memories. Furthermore, in an electric field, it provides a bridge between a Widom line that denotes FE-PE crossover above T{sub C} and a metaelectric transition line below T{sub C} that demonstrates an FE switching behavior with an antiparallel field.« less

Screening the ToxCast Phase 1, 2, and e1k Chemical Libraries for Inhibition of Deiodinase Type 1, 2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent on multiple proteins for TH synthesis, transport, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting THs between active and inactive forms by converting the pro-hormone thyroxine (T4) to...

Angiotensin converting enzyme inhibitors and aortic arch obstructive malformations.

PubMed

Maliheh, Kadivar; Abdorrazagh, Kiani; Armen, Kocharian; Reza, Shabanian

2006-10-01

We describe two newborn infants with aortic arch obstructive malformations who became anuric after initiation of captopril. Since angiotensin converting enzyme inhibitors can alter renal blood flow by reduction in angiotensin II and blocking autoregulation phenomenon, it is important to use them with great caution in neonates with aortic arch obstructive malformations, while monitoring their renal function closely.

Giant electrocaloric effect in a cracked ferroelectrics

NASA Astrophysics Data System (ADS)

Huang, Cheng; Yang, Hai-Bing; Gao, Cun-Fa

2018-04-01

The electrocaloric effect (ECE) is the temperature change in a material induced by electrical field variation under adiabatic condition. Considering an external electric load applied on a cracked ferroelectric solid, a non-uniform electric field would be induced at the crack tip, and thus, incompatible strain field and local stress concentration would be generated around it. Furthermore, the enormous strain energy and the electrostatic energy would affect the polarization switching of the ferroelectric solid, important for the electrocaloric response. In this paper, the large negative and positive ECEs in a ferroelectric sheet with a conducting crack are investigated by the phase field method with the consideration of time-dependent Ginzburg-Landau equation. The numerical calculations indicated that the polarization field generates a sharp rise during the domain transition from polydomain to monodomain under a certain electric load. Large negative ECEs, about -10.21 K and -7.55 K, are obtained at 135 °C and 85 °C, respectively. The domain transition temperature is much lower than the Curie temperature, which enlarges the existence scope of the large ECE in ferroelectrics. The results also imply that the domain transition from a multi-domain state to a single domain takes place with the minimization of total free energy, which involves the courses of the electric field, stress field, temperature, and polarization interaction. Therefore, the non-uniform distributions of the stress-electric fields induced by the crack play an important role in ECE.

Novel single-cell mega-size chambers for electrochemical etching of panorama position-sensitive polycarbonate ion image detectors

NASA Astrophysics Data System (ADS)

Sohrabi, Mehdi

2017-11-01

A novel development is made here by inventing panorama single-cell mega-size electrochemical etching (MS-ECE) chamber systems for processing panorama position-sensitive mega-size polycarbonate ion image detectors (MS-PCIDs) of potential for many neutron and ion detection applications in particular hydrogen ions or proton tracks and images detected for the first time in polycarbonates in this study. The MS-PCID is simply a large polycarbonate sheet of a desired size. The single-cell MS-ECE invented consists of two large equally sized transparent Plexiglas sheets as chamber walls holding a MS-PCID and the ECE chamber components tightly together. One wall has a large flat stainless steel electrode (dry cell) attached to it which is directly in contact with the MS-PCID and the other wall has a rod electrode with two holes to facilitate feeding and draining out the etching solution from the wet cell. A silicon rubber washer plays the role of the wet cell to hold the etchant and the electrical insulator to isolate the dry cell from the wet cell. A simple 50 Hz-HV home-made generator provides an adequate field strength through the two electrodes across the MS-ECE chamber. Two panorama single-cell MS-ECE chamber systems (circular and rectangular shapes) constructed were efficiently applied to processing the MS-PCIDs for 4π ion emission image detection of different gases in particular hydrogen ions or protons in a 3.5 kJ plasma focus device (PFD as uniquely observed by the unaided eyes). The panorama MS-PCID/MS-ECE image detection systems invented are novel with high potential for many applications in particular as applied to 4π panorama ion emission angular distribution image detection studies in PFD space, some results of which are presented and discussed.

Novel single-cell mega-size chambers for electrochemical etching of panorama position-sensitive polycarbonate ion image detectors.

PubMed

Sohrabi, Mehdi

2017-11-01

A novel development is made here by inventing panorama single-cell mega-size electrochemical etching (MS-ECE) chamber systems for processing panorama position-sensitive mega-size polycarbonate ion image detectors (MS-PCIDs) of potential for many neutron and ion detection applications in particular hydrogen ions or proton tracks and images detected for the first time in polycarbonates in this study. The MS-PCID is simply a large polycarbonate sheet of a desired size. The single-cell MS-ECE invented consists of two large equally sized transparent Plexiglas sheets as chamber walls holding a MS-PCID and the ECE chamber components tightly together. One wall has a large flat stainless steel electrode (dry cell) attached to it which is directly in contact with the MS-PCID and the other wall has a rod electrode with two holes to facilitate feeding and draining out the etching solution from the wet cell. A silicon rubber washer plays the role of the wet cell to hold the etchant and the electrical insulator to isolate the dry cell from the wet cell. A simple 50 Hz-HV home-made generator provides an adequate field strength through the two electrodes across the MS-ECE chamber. Two panorama single-cell MS-ECE chamber systems (circular and rectangular shapes) constructed were efficiently applied to processing the MS-PCIDs for 4π ion emission image detection of different gases in particular hydrogen ions or protons in a 3.5 kJ plasma focus device (PFD as uniquely observed by the unaided eyes). The panorama MS-PCID/MS-ECE image detection systems invented are novel with high potential for many applications in particular as applied to 4π panorama ion emission angular distribution image detection studies in PFD space, some results of which are presented and discussed.

Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats

PubMed Central

Jaarin, Kamsiah; Foong, Wai Dic; Yeoh, Min Hui; Kamarul, Zaman Yusoff Nik; Qodriyah, Haji Mohd Saad; Azman, Abdullah; Zuhair, Japar Sidik Fadhlullah; Juliana, Abdul Hamid; Kamisah, Yusof

2015-01-01

OBJECTIVES This study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers. METHODS: Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration. RESULTS Nigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO. CONCLUSION: The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension. PMID:26602523

Tying Early Childhood Education More Closely to Schooling: Promise, Perils and Practical Problems

ERIC Educational Resources Information Center

Halpern, Robert

2013-01-01

Background: Over the past decade or so, the idea of joining early childhood education (ECE) and schooling has gained currency in the educational reform arena. Numerous education reform proposals and plans include ECE as a component. Scores of school districts around the country have added preschool classrooms to at least some of their elementary…

Teaming and Teaching in ECE: Neoliberal Reforms, Teacher Metaphors, and Identity in Head Start

ERIC Educational Resources Information Center

Bullough, Robert V., Jr.

2015-01-01

Noting that surprisingly little researcher attention has been directed toward teaming in early childhood education (ECE), the author conducted parallel case studies of two Head Start teacher teams in a single center. Drawing on interviews, extensive observational notes taken over the course of a school year, and teacher-generated metaphors, the…

Do Learning Stories Tell the Whole Story of Children's Learning? A Phenomenographic Enquiry

ERIC Educational Resources Information Center

Zhang, Qilong

2017-01-01

This study compares the stances of practitioners, parents and the quality assurance authority on the assessment of learning in New Zealand (NZ) early childhood education (ECE). The phenomenographic interview participants include practitioners (24) and parents (11) from 11 ECE settings. The reports issued by the Education Review Office (ERO) on all…

Impacts of Early Childhood Education on Medium- and Long-Term Educational Outcomes

ERIC Educational Resources Information Center

McCoy, Dana Charles; Yoshikawa, Hirokazu; Ziol-Guest, Kathleen M.; Duncan, Greg J.; Schindler, Holly S.; Magnuson, Katherine; Yang, Rui; Koepp, Andrew; Shonkoff, Jack P.

2017-01-01

Despite calls to expand early childhood education (ECE) in the United States, questions remain regarding its medium- and long-term impacts on educational outcomes. We use meta-analysis of 22 high-quality experimental and quasi-experimental studies conducted between 1960 and 2016 to find that on average, participation in ECE leads to statistically…

Early Childhood Teachers at the Center: A Qualitative Case Study of Professional Development in an Urban District

ERIC Educational Resources Information Center

Baker, Megina

2018-01-01

Professional development for early childhood educators (ECE PD) is an essential component of supporting a professional early childhood workforce. Yet research on ECE PD frequently centers on narrow fidelity data, while teachers' individual voices and teaching contexts are only rarely considered in order to understand teacher experiences with PD…

Moving up the Ladder: How Do States Deliver Quality Improvement Supports within Their Quality Rating and Improvement Systems? Brief

ERIC Educational Resources Information Center

Holod, Aleksandra; Faria, Ann-Marie; Weinberg, Emily; Howard, Eboni

2015-01-01

As national attention has increasingly focused on the potential for high-quality early childhood education (ECE) to improve children's school readiness, states have developed quality rating and improvement systems (QRISs) to document the quality of ECE programs, support systematic quality improvement, and provide clear information to families…

Choice of the Medium of Instruction in Kenyan Preschools: Averting Xenocentrism

ERIC Educational Resources Information Center

Waithaka, Esther N.

2017-01-01

This qualitative study sought to prompt a critical and reflective discourse on the dismal use of mother tongue in Kenyan early childhood education (ECE) institutions in an attempt to detect existence of xenocentrism. Although the Kenyan ECE policy framework sanctions use of the language of the catchment area when teaching and communicating with…

The World Bank's Position on Early Child Education in Brazil: A Critical Assessment of Contributions and Shortcomings

ERIC Educational Resources Information Center

Fernandes, Sabrina

2014-01-01

In 2010, the World Bank published a policy study on early child education (ECE) developments in Brazil, entitled "Early Child Education: Making Programs Work for Brazil's Most Important Generation. Development." This paper analyses the report's assessment of ECE policy in Brazil as well as the recommendations it provides. A critical…

Early Care and Education: Policy Considerations for Ensuring High-Quality Pre-K Programs

ERIC Educational Resources Information Center

Best, Jane; Cohen, Courtney

2013-01-01

Interest in early care and education (ECE), also referred to as an early childhood education, has escalated in recent years. The interest is bipartisan, as evidenced by the multiple ECE-related bills already introduced by the 113th Congress. Further, 39 states have implemented prekindergarten (pre-K) programs. In 2013, 27 governors mentioned ECE…

Chutes or Ladders? Creating Support Services to Help Early Childhood Students Succeed in Higher Education

ERIC Educational Resources Information Center

Dukakis, Kara; Bellm, Dan; Seer, Natalie; Lee, Yuna

2007-01-01

This report explores efforts in California to generally support nontraditional students, and early care and education (ECE) nontraditional students in particular. It is recommended that institutions of higher education and local planners work together to assess the needs of nontraditional students in their ECE programs, the adequacy of existing…

Early Care and Education as Educational Panacea: What Do We Really Know about Its Effectiveness?

ERIC Educational Resources Information Center

Lowenstein, Amy E.

2011-01-01

Most young children in the United States regularly spend time in early care and education (ECE) settings. Institutionalized messages surrounding ECE claim that it has the potential to promote children's life-long success, especially among low-income children. I examine the legitimacy of these claims by reviewing empirical evidence that bears on…

Early Childhood Educators' Perspectives and Practices about Inclusion of Children with Special Needs in Botswana

ERIC Educational Resources Information Center

Chhabra, Simmi; Bose, Kabita; Chadha, Neerja

2018-01-01

The purpose of this study was to investigate perspectives of Early Childhood Educators (ECEds) about inclusion of Children With Special Needs (CWSN) by examining their attitudes, training needs, and inclusive practices used in the inclusive classroom. One hundred twenty-eight ECEds completed a questionnaire that included the Scale of Teachers'…

The Current State of Early Childhood Education Programs: How Early Childhood Center Directors Manage Their Human Resources

ERIC Educational Resources Information Center

Arend, Lauren E.

2010-01-01

Purpose: Research in the field of early childhood education (ECE) demonstrated the association between skilled directors and high quality programs. Still, most state licensing requirements do not delineate the requisite knowledge or experience necessary to be an effective director. Many ECE directors advance to their position directly from the…

Four Good Reasons Why ECE Is Not Just Important, but Essential

ERIC Educational Resources Information Center

Mitchell, Anne W.

2009-01-01

As an advocate for young children and families and an advocate for early childhood education, the author has long argued for improving quality and for investing more public dollars in ECE. To make her case, the author used several different arguments, including: moral; workforce productivity; brain research; and return on investment. The author…

Overview of Integrated Child Development Services Programme in India: Some Policy Implications for Nepal.

ERIC Educational Resources Information Center

Shrestha, Kishor

This paper presents an overview of the Integrated Child Development Services (ICDS) program in India, discusses the context of Early Childhood Education (ECE) in Nepal, analyzes the best practices of the ICDS, and draws some policy implications for improving ECE in Nepal. The ICDS program is an integrated child development program with the…

Early Childhood Education in Pakistan--Progress and Challenges

ERIC Educational Resources Information Center

Shami, Pervez A.

2009-01-01

This paper is on Early Childhood Education (ECE)--a goal of Education For All (EFA), assesses the progress of Pakistan's efforts and strategies mainly during post Dakar period 2001-02 to 2005-06 and the major challenges being encountered. The information includes analysis of National Educational Data on ECE in the light of policies and plans, EFA…

Tensions between Discourses of Development, Religion, and Human Capital in Early Childhood Education Policy Texts: The Case of Indonesia

ERIC Educational Resources Information Center

Formen, Ali; Nuttall, Joce

2014-01-01

In this paper we consider how particular discourses have come to dominate early childhood education (ECE) policy in Indonesia. We briefly explain the governance of Indonesian ECE and then our approach to policy analysis using critical discourse analysis. Three prevalent discourses are identified and discussed: "developmentalism",…

The Impact of Every Classroom, Every Day on High School Student Achievement: Results from a School-Randomized Trial

ERIC Educational Resources Information Center

Early, Diane M.; Berg, Juliette K.; Alicea, Stacey; Si, Yajuan; Aber, J. Lawrence; Ryan, Richard M.; Deci, Edward L.

2016-01-01

Every Classroom, Every Day (ECED) is a set of instructional improvement interventions designed to increase student achievement in math and English/language arts (ELA). ECED includes three primary components: (a) systematic classroom observations by school leaders, (b) intensive professional development and support for math teachers and…

Funding Early Childhood Education: The President's Plan for the Future and States' Current Actions

ERIC Educational Resources Information Center

Best, Jane; Cohen, Courtney

2013-01-01

Increased attention to proposed federal early childhood education (ECE) legislation has sparked a debate on what the future holds for state-funded ECE systems. This brief explores how the goal of universal preschool is being shaped by the federal agenda and examines state programs in various stages of development. President Obama's Preschool for…

Improving Latino Children's Early Language and Literacy Development: Key Features of Early Childhood Education within Family Literacy Programmes

ERIC Educational Resources Information Center

Jung, Youngok; Zuniga, Stephen; Howes, Carollee; Jeon, Hyun-Joo; Parrish, Deborah; Quick, Heather; Manship, Karen; Hauser, Alison

2016-01-01

Noting the lack of research on how early childhood education (ECE) programmes within family literacy programmes influence Latino children's early language and literacy development, this study examined key features of ECE programmes, specifically teacher-child interactions and child engagement in language and literacy activities and how these…

A Novel Conceptual Model of Environmental Communal Education: Content Analysis Based on Distance Education Approach

ERIC Educational Resources Information Center

Hafezi, Soheila; Shobeiri, Seyed Mohammad; Sarmadi, Mohammad Reza; Ebadi, Abbas

2013-01-01

Environmental education as a learning process increases people's knowledge and awareness about the environment. Although in some countries, the Environmental Communal Education (ECE) is the core of the environmental education by formal and informal organizations and groups, but, it has not clarified the meaning of the ECE's concept. Therefore the…

ECE-imaging of the H-mode pedestal (invited).

PubMed

Tobias, B J; Austin, M E; Boom, J E; Burrell, K H; Classen, I G J; Domier, C W; Luhmann, N C; Nazikian, R; Snyder, P B

2012-10-01

A synthetic diagnostic has been developed that reproduces the highly structured electron cyclotron emission (ECE) spectrum radiated from the edge region of H-mode discharges. The modeled dependence on local perturbations of the equilibrium plasma pressure allows for interpretation of ECE data for diagnosis of local quantities. Forward modeling of the diagnostic response in this region allows for improved mapping of the observed fluctuations to flux surfaces within the plasma, allowing for the poloidal mode number of coherent structures to be resolved. In addition, other spectral features that are dependent on both T(e) and n(e) contain information about pedestal structure and the electron energy distribution of localized phenomena, such as edge filaments arising during edge-localized mode (ELM) activity.

Inhibition of the renin-angiotensin-aldosterone system: is there room for dual blockade in the cardiorenal continuum?

PubMed

Volpe, Massimo; Danser, A H Jan; Menard, Joël; Waeber, Bernard; Mueller, Dominik N; Maggioni, Aldo P; Ruilope, Luis M

2012-04-01

Antagonism of renin-angiotensin-aldosterone system is exerted through angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, renin inhibitors and mineralocorticoid receptor antagonists. These drugs have been successfully tested in numerous trials and in different clinical settings. The original indications of renin-angiotensin-aldosterone system blockers have progressively expanded from the advanced stages to the earlier stages of cardiorenal continuum. To optimize the degree of blockade of renin-angiotensin-aldosterone system, dose uptitrations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists or the use of a dual blockade, initially identified with the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, have been proposed. The data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study do not support this specific dual blockade approach. However, the dual blockade of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists with direct renin inhibitors is currently under investigation while that based on an aldosterone blocker with any of the previous three drugs requires more evidence beyond heart failure. In this review, we revisited potential advantages of dual blockade of renin-angiotensin-aldosterone system in arterial hypertension and diabetes.

Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression.

PubMed

Thomson, Errol M; Kumarathasan, Prem; Calderón-Garcidueñas, Lilian; Vincent, Renaud

2007-10-01

Recent work suggests that air pollution is a risk factor for cerebrovascular and neurodegenerative disease. Effects of inhaled pollutants on the production of vasoactive factors such as endothelin (ET) and nitric oxide (NO) in the brain may be relevant to disease pathogenesis. Inhaled pollutants increase circulating levels of ET-1 and ET-3, and the pituitary is a potential source of plasma ET, but the effects of pollutants on the expression of ET and NO synthase genes in the brain and pituitary are not known. In the present study, Fischer-344 rats were exposed by nose-only inhalation to particles (0, 5, 50mg/m3 EHC-93), ozone (0, 0.4, 0.8 ppm), or combinations of particles and ozone for 4 h. Real-time reverse transcription polymerase chain reaction was used to measure mRNA levels in the cerebral hemisphere and pituitary 0 and 24 h post-exposure. Ozone inhalation significantly increased preproET-1 but decreased preproET-3 mRNAs in the cerebral hemisphere, while increasing mRNA levels of preproET-1, preproET-3, and the ET-converting enzyme (ECE)-1 in the pituitary. Inducible NO synthase (iNOS) was initially decreased in the cerebral hemisphere after ozone inhalation, but increased 24 h post-exposure. Particles decreased tumour necrosis factor (TNF)-alpha mRNA in the cerebral hemisphere, and both particles and ozone decreased TNF-alpha mRNA in the pituitary. Our results show that ozone and particulate matter rapidly modulate the expression of genes involved in key vasoregulatory pathways in the brain and pituitary, substantiating the notion that inhaled pollutants induce cerebrovascular effects.

Sensitivity of UK butterflies to local climatic extremes: which life stages are most at risk?

PubMed

McDermott Long, Osgur; Warren, Rachel; Price, Jeff; Brereton, Tom M; Botham, Marc S; Franco, Aldina M A

2017-01-01

There is growing recognition as to the importance of extreme climatic events (ECEs) in determining changes in species populations. In fact, it is often the extent of climate variability that determines a population's ability to persist at a given site. This study examined the impact of ECEs on the resident UK butterfly species (n = 41) over a 37-year period. The study investigated the sensitivity of butterflies to four extremes (drought, extreme precipitation, extreme heat and extreme cold), identified at the site level, across each species' life stages. Variations in the vulnerability of butterflies at the site level were also compared based on three life-history traits (voltinism, habitat requirement and range). This is the first study to examine the effects of ECEs at the site level across all life stages of a butterfly, identifying sensitive life stages and unravelling the role life-history traits play in species sensitivity to ECEs. Butterfly population changes were found to be primarily driven by temperature extremes. Extreme heat was detrimental during overwintering periods and beneficial during adult periods and extreme cold had opposite impacts on both of these life stages. Previously undocumented detrimental effects were identified for extreme precipitation during the pupal life stage for univoltine species. Generalists were found to have significantly more negative associations with ECEs than specialists. With future projections of warmer, wetter winters and more severe weather events, UK butterflies could come under severe pressure given the findings of this study. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Energy efficiency and its relationship with milk, body, and intake traits and energy status among primiparous Nordic Red dairy cattle.

PubMed

Mäntysaari, P; Liinamo, A-E; Mäntysaari, E A

2012-06-01

Existing variation in energy efficiency and its relationship with milk yield and milk composition, body weight and body condition, feed intake, and energy status was studied in primiparous Nordic Red dairy cattle with data including 3,752 weekly records from 145 cows. Energy efficiency was defined as energy conversion efficiency (ECE) and as residual energy intake (REI) estimated based on Finnish feeding standards (REI₁) or from the current data (REI₂). The results indicated true phenotypic variation in energy efficiency of the cows. The proportion of total variance due to the animal was 0.35 for REI₁, 0.30 for REI₂, and 0.50 for ECE. The high efficiency based on ECE was associated with increased mobilization of body reserves (r = -0.50) and decreased dry matter intake (r = -0.51). With REI as an energy efficiency measure, the increased efficiency was associated with a large decrease in feed intake (REI₁: r = 0.60; REI2: r = 0.74) without any effect on body weight change (REI₁: r = 0.13; REI2: r = 0.00). Increased efficiency based on ECE and REI₁ was associated with increased milk yield (ECE: r = 0.58; REI₁: r = -0.41). A clear effect of stage of lactation on REI was found, which could be caused by true differences in utilization of metabolizable energy during lactation. However, it might also be related, in part, to the lack of knowledge of the composition of body weight change in the beginning of lactation. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Investigating Business Schools' Intentions about Offering E-Commerce Education Using an Extended Theory of Planned Behavior

ERIC Educational Resources Information Center

Dodor, Jean Baptiste K.; Rana, Dharam S.

2009-01-01

This study investigates business schools' intentions about offering e-commerce education (ECE) using an extended theory of planned behavior (ETPB). The need for an adequate match between future supply and demand of e-commerce skills constitutes the main motivation for the study. The results show that most business schools consider ECE important…

Korean Early Childhood Educators' Multi-Dimensional Teacher Self-Efficacy and ECE Center Climate and Depression Severity in Teachers as Contributing Factors

ERIC Educational Resources Information Center

Kim, Yeon Ha; Kim, Yang Eun

2010-01-01

This study investigated profiles of South Korean early childhood educators' teacher self-efficacy and contributing factors to teacher self-efficacy. The contributing factors were examined with a focus on early childhood education (ECE) center climate and depression severity in teachers as well as teacher and classroom characteristics. The results…

Learning Together: A Study of Six B.A. Completion Cohort Programs in Early Care and Education--Year 4

ERIC Educational Resources Information Center

Kipnis, F.; Whitebook, M.; Almaraz, M.; Sakai, L.; Austin, L. J. E.

2012-01-01

The Learning Together longitudinal study focuses on four counties' efforts to expand bachelor's degree opportunities in early care and education (ECE) for adults currently working in the field. The "student cohort" model--in which small groups of ECE students with similar interests and characteristics pursue a bachelor's degree together,…

Shifting Views: Exploring the Potential for Technology Integration in Early Childhood Education Programs

ERIC Educational Resources Information Center

Dietze, Beverlie; Kashin, Diane

2013-01-01

Using technology with children in play-based early learning programs creates questions for some within the Early Childhood Education (ECE) community. This paper presents how two faculty who teach in ECE-related degree programs integrated educational technology into their teaching pedagogy as a way to model to their students how it can be used to…

Getting on the Same Page: Identifying Goals for Technology Use in Early Childhood Education. Policy Brief

ERIC Educational Resources Information Center

Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

2014-01-01

Technology use among young children is increasingly a fact of life, and establishing a clear set of goals that are broadly accepted by stakeholders is critical to planning for the successful integration of technology into early childhood education (ECE). However, debates about the role of technology in ECE settings are ongoing, with some…

An Exploratory Study of Young Students' Core Virtues of e-Character Education: The Taiwanese Teachers' Perspective

ERIC Educational Resources Information Center

Chang, Chih-Ming; Chou, Chien

2015-01-01

The e-character education (e-CE) approach refers to systems of ethics education that pertain specifically to cyberspace. This exploratory study used a survey to collect 2495 teachers' responses regarding virtues important to e-CE. Furthermore, in order to identify the teaching concerns associated with these most important virtues, this study used…

Development and Evaluation of an Integrated Pest Management Toolkit for Child Care Providers

ERIC Educational Resources Information Center

Alkon, Abbey; Kalmar, Evie; Leonard, Victoria; Flint, Mary Louise; Kuo, Devina; Davidson, Nita; Bradman, Asa

2012-01-01

Young children and early care and education (ECE) staff are exposed to pesticides used to manage pests in ECE facilities in the United States and elsewhere. The objective of this pilot study was to encourage child care programs to reduce pesticide use and child exposures by developing and evaluating an Integrated Pest Management (IPM) Toolkit for…

A Comprehensive Review of the Status of Early Childhood Development in the Middle East and North Africa.

ERIC Educational Resources Information Center

Khattab, Mohammad Salih

This report reviews the status of early childhood education (ECE) programs in UNICEF's Middle East and North Africa region. The report compiles information about ECE programs in 18 countries based on a questionnaire sent to UNICEF country offices and other sources. The introduction sets out the economic and social rationales for investing in early…

Pre-Kindergarten and Kindergarten Classroom Quality and Children's Social and Academic Skills in Early Elementary Grades

ERIC Educational Resources Information Center

Mokrova, Irina; Broekhuizen, Martine; Burchinal, Margaret

2015-01-01

A growing body of research has shown that high quality early care and education (ECE) is positively related to the development of children's social and academic skills (e.g., Barnett, 2011; Lamb & Ahnert, 2006; NICHD ECCRN, 2006). There is evidence that high quality ECE experiences can improve children's levels of social adjustment (Bierman et…

How Much and What Kind? Identifying an Adequate Technology Infrastructure for Early Childhood Education. Policy Brief

ERIC Educational Resources Information Center

Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

2014-01-01

To realize the potential benefits of technology use in early childhood education (ECE), and to ensure that technology can help to address the digital divide, providers, families of young children, and young children themselves must have access to an adequate technology infrastructure. The goals for technology use in ECE that a technology…

Increasing State Investments in Early Care and Education: Lessons Learned from Advocates and Best Practices, Spring 2008

ERIC Educational Resources Information Center

Voices for America's Children, 2008

2008-01-01

This report showcases advocacy efforts of 11 member organizations in 10 states that recently passed an early care and education (ECE) legislative initiative. The aim of the report is to provide advocates with proven strategies for advancing progress in securing access to ECE and expanding the opportunity for all children to start school prepared…

Building Community Systems for Young Children: Early Childhood Education. Building State Early Childhood Comprehensive Systems Series, Number 11

ERIC Educational Resources Information Center

Bassok, Daphna; Stipek, Deborah; Inkelas, Moira; Kuo, Alice

2005-01-01

This report examines the importance and funding sources of early child care and education (ECE), and the ways in which the State Early Childhood Comprehensive Systems (SECCS) Initiative improves early childhood outcomes. Section I presents what is known about the importance of ECE, quality and access. Section II describes the current funding…

ITER ECE Diagnostic: Design Progress of IN-DA and the diagnostic role for Physics

NASA Astrophysics Data System (ADS)

Pandya, H. K. B.; Kumar, Ravinder; Danani, S.; Shrishail, P.; Thomas, Sajal; Kumar, Vinay; Taylor, G.; Khodak, A.; Rowan, W. L.; Houshmandyar, S.; Udintsev, V. S.; Casal, N.; Walsh, M. J.

2017-04-01

The ECE Diagnostic system in ITER will be used for measuring the electron temperature profile evolution, electron temperature fluctuations, the runaway electron spectrum, and the radiated power in the electron cyclotron frequency range (70-1000 GHz), These measurements will be used for advanced real time plasma control (e.g. steering the electron cyclotron heating beams), and physics studies. The scope of the Indian Domestic Agency (IN-DA) is to design and develop the polarizer splitter units; the broadband (70 to 1000 GHz) transmission lines; a high temperature calibration source in the Diagnostics Hall; two Michelson Interferometers (70 to 1000 GHz) and a 122-230 GHz radiometer. The remainder of the ITER ECE diagnostic system is the responsibility of the US domestic agency and the ITER Organization (IO). The design needs to conform to the ITER Organization’s strict requirements for reliability, availability, maintainability and inspect-ability. Progress in the design and development of various subsystems and components considering various engineering challenges and solutions will be discussed in this paper. This paper will also highlight how various ECE measurements can enhance understanding of plasma physics in ITER.

Functional Activities and Immunohistochemical Distribution of Superoxide Dismutase in Normal, Dysplastic and Squamous Cell Carcinoma Oral Tissues

DTIC Science & Technology

2001-07-26

antioxidant enzymes: SOD, catalase ( CAT ), and glutathione peroxidase (GPO).2 ° SOD converts superoxide radical into hydrogen peroxide, while CAT and GPO convert...in endometriosis and adenomyosis. Fertility and Sterility 1999; 1:129-134. 45. Muse KE, Oberley TD, Sempf JM, Oberley LW. Immunolocalization of antioxidant enzymes in adult hamster kidney. Histochem J 1994;9:734-753. 43

Utilization of peptide carrier system to improve intestinal absorption: targeting prolidase as a prodrug-converting enzyme

NASA Technical Reports Server (NTRS)

Bai, J. P.; Hu, M.; Subramanian, P.; Mosberg, H. I.; Amidon, G. L.

1992-01-01

The feasibility of targeting prolidase as a peptide prodrug-converting enzyme has been examined. The enzymatic hydrolysis by prolidase of substrates for the peptide transporter L-alpha-methyldopa-pro and several dipeptide analogues without an N-terminal alpha-amino group (phenylpropionylproline, phenylacetylproline, N-benzoylproline, and N-acetylproline) was investigated. The Michaelis-Menten parameters Km and Vmax for L-alpha-methyldopa-pro are 0.09 +/- 0.02 mM and 3.98 +/- 0.25 mumol/min/mg protein, respectively. However, no hydrolysis of the dipeptide analogues without an N-terminal alpha-amino group is observed, suggesting that an N-terminal alpha-amino group is required for prolidase activity. These results demonstrate that prolidase may serve as a prodrug-converting enzyme for the dipeptide-type prodrugs, utilizing the peptide carrier for transport of prodrugs into the mucosal cells and prolidase, a cytosolic enzyme, to release the drug. However, a free alpha-amino group appears to be necessary for prolidase hydrolysis.

Molecular diversity of tuliposide B-converting enzyme in tulip (Tulipa gesneriana): identification of the third isozyme with a distinct expression profile.

PubMed

Nomura, Taiji; Kuchida, Ryo; Kitaoka, Naoki; Kato, Yasuo

2018-02-23

6-Tuliposide B (PosB), a major secondary metabolite that accumulates in tulip (Tulipa gesneriana), is converted to the antibacterial lactone, tulipalin B (PaB), by PosB-converting enzyme (TCEB). TgTCEB1 and TgTCEB-R, which encode TCEB, are specifically expressed in tulip pollen and roots, respectively, but are hardly expressed in other tissues (e.g. leaves) despite the presence of substantial PosB-converting activity, suggesting the existence of another TCEB isozyme. Here, we describe the identification of TgTCEB-L ("L" for leaf), a paralog of TgTCEB1 and TgTCEB-R, from leaves via native enzyme purification. The enzymatic characters of TgTCEB-L, including catalytic activity and subcellular localization, were substantially the same as those of TgTCEB1 and TgTCEB-R. However, TgTCEB-L did not exhibit tissue-specific expression. Identification of TgTCEB-L explains the PosB-converting activity detected in tissues where TgTCEB1 and TgTCEB-R transcripts could not be detected, indicating that tulip subtilizes the three TgTCEB isozymes depending on the tissue.

Genetic vulnerability interacts with parenting and early care education to predict increasing externalizing behavior.

PubMed

Lipscomb, Shannon T; Laurent, Heidemarie; Neiderhiser, Jenae M; Shaw, Daniel S; Natsuaki, Misaki N; Reiss, David; Leve, Leslie D

2014-01-01

The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children.

Genetic vulnerability interacts with parenting and early care education to predict increasing externalizing behavior

PubMed Central

Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.

2014-01-01

The current study examined interactions among genetic influences and children’s early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children. PMID:25067867

Angiotensin-converting enzyme 2 activation improves endothelial function.

PubMed

Fraga-Silva, Rodrigo A; Costa-Fraga, Fabiana P; Murça, Tatiane M; Moraes, Patrícia L; Martins Lima, Augusto; Lautner, Roberto Q; Castro, Carlos H; Soares, Célia Maria A; Borges, Clayton L; Nadu, Ana Paula; Oliveira, Marilene L; Shenoy, Vinayak; Katovich, Michael J; Santos, Robson A S; Raizada, Mohan K; Ferreira, Anderson J

2013-06-01

Diminished release and function of endothelium-derived nitric oxide coupled with increases in reactive oxygen species production is critical in endothelial dysfunction. Recent evidences have shown that activation of the protective axis of the renin-angiotensin system composed by angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor promotes many beneficial vascular effects. This has led us to postulate that activation of intrinsic angiotensin-converting enzyme 2 would improve endothelial function by decreasing the reactive oxygen species production. In the present study, we tested 1-[[2-(dimetilamino)etil]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT), a small molecule angiotensin-converting enzyme 2 activator, on endothelial function to validate this hypothesis. In vivo treatment with XNT (1 mg/kg per day for 4 weeks) improved the endothelial function of spontaneously hypertensive rats and of streptozotocin-induced diabetic rats when evaluated through the vasorelaxant responses to acetylcholine/sodium nitroprusside. Acute in vitro incubation with XNT caused endothelial-dependent vasorelaxation in aortic rings of rats. This vasorelaxation effect was attenuated by the Mas antagonist D-pro7-Ang-(1-7), and it was reduced in Mas knockout mice. These effects were associated with reduction in reactive oxygen species production. In addition, Ang II-induced reactive oxygen species production in human aortic endothelial cells was attenuated by preincubation with XNT. These results showed that chronic XNT administration improves the endothelial function of hypertensive and diabetic rat vessels by attenuation of the oxidative stress. Moreover, XNT elicits an endothelial-dependent vasorelaxation response, which was mediated by Mas. Thus, this study indicated that angiotensin-converting enzyme 2 activation promotes beneficial effects on the endothelial function and it is a potential target for treating cardiovascular disease.

In Vitro Studies on the Antioxidant Property and Inhibition of α-Amylase, α-Glucosidase, and Angiotensin I-Converting Enzyme by Polyphenol-Rich Extracts from Cocoa (Theobroma cacao) Bean

PubMed Central

Ademosun, Ayokunle O.; Ademiluyi, Adedayo O.; Omojokun, Olasunkanmi S.; Nwanna, Esther E.; Longe, Kuburat O.

2014-01-01

Background. This study sought to investigate the antidiabetic and antihypertensive mechanisms of cocoa (Theobroma cacao) bean through inhibition of α-amylase, α-glucosidase, angiotensin-1 converting enzyme, and oxidative stress. Methodology. The total phenol and flavonoid contents of the water extractable phytochemicals from the powdered cocoa bean were determined and the effects of the extract on α-amylase, α-glucosidase, and angiotensin-1 converting enzyme activities were investigated in vitro. Furthermore, the radicals [1,1-diphenyl-2 picrylhydrazyl (DPPH), 2,2..-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), hydroxyl (OH), and nitric oxide (NO)] scavenging ability and ferric reducing antioxidant property of the extract were assessed. Results. The results revealed that the extract inhibited α-amylase (1.81 ± 0.22 mg/mL), α-glucosidase (1.84 ± 0.17 mg/mL), and angiotensin-1 converting enzyme (0.674 ± 0.06 mg/mL [lungs], 1.006 ± 0.08 mg/mL [heart]) activities in a dose-dependent manner and also showed dose-dependent radicals [DPPH (16.94 ± 1.34 mg/mL), NO (6.98 ± 0.886 mg/mL), OH (3.72 ± 0.26 mg/mL), and ABTS (15.7 ± 1.06 mmol/TEAC·g] scavenging ability. Conclusion. The inhibition of α-amylase, α-glucosidase, and angiotensin-1 converting enzyme activities by the cocoa bean extract could be part of the possible mechanism by which the extract could manage and/or prevent type-2 diabetes and hypertension. PMID:25295218

Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers: results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.

PubMed

Cesari, Matteo; Kritchevsky, Stephen B; Atkinson, Hal H; Penninx, Brenda W; Di Bari, Mauro; Tracy, Russell P; Pahor, Marco

2009-02-01

Beneficial effects of angiotensin-converting enzyme (ACE) inhibitors seem to be mediated by mechanisms that are partly independent of blood pressure lowering. The present study evaluates effects of an ACE inhibitor (ie, fosinopril) intervention on novel cardiovascular risk factors. Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial enrolling subjects > or =55 years old with high cardiovascular disease risk profile. Biomarkers of hemostasis (ie, plasminogen activator inhibitor 1, D-dimer), inflammation (ie, C-reactive protein, interleukin-6), and endothelial function (ie, endothelin 1, vascular cell adhesion molecule 1) were measured at the baseline, at the midterm, and at end of follow-up (after 1 year) clinic visits. Paired t test analyses (after Sidak's adjustment, P < .009) were performed to compare biomarkers modifications after fosinopril/placebo interventions. Mean age of the sample (n = 290, women 43.4%) was 66.0 years old. No significant differences were reported for C-reactive protein, interleukin 6, plasminogen activator inhibitor 1, vascular cell adhesion molecule 1, and endothelin 1 levels in the comparisons between fosinopril and placebo interventions. D-dimer was the only biomarker showing a significant difference between fosinopril intervention (median 0.32 microg/mL, interquartile range 0.22-0.52 microg/mL) and placebo (median 0.29 microg/mL, interquartile range 0.20-0.47 microg/mL, P = .007) when analyses were restricted to participants with higher compliance to treatment and receiving the maximum ACE inhibitor dosage. Angiotensin-converting enzyme inhibition does not significantly modify major biomarkers of inflammation, hemostasis, and endothelial function. Further studies should confirm the possible effect of ACE inhibitors on the fibrinolysis pathway.

In Vitro Studies on the Antioxidant Property and Inhibition of α-Amylase, α-Glucosidase, and Angiotensin I-Converting Enzyme by Polyphenol-Rich Extracts from Cocoa (Theobroma cacao) Bean.

PubMed

Oboh, Ganiyu; Ademosun, Ayokunle O; Ademiluyi, Adedayo O; Omojokun, Olasunkanmi S; Nwanna, Esther E; Longe, Kuburat O

2014-01-01

Background. This study sought to investigate the antidiabetic and antihypertensive mechanisms of cocoa (Theobroma cacao) bean through inhibition of α-amylase, α-glucosidase, angiotensin-1 converting enzyme, and oxidative stress. Methodology. The total phenol and flavonoid contents of the water extractable phytochemicals from the powdered cocoa bean were determined and the effects of the extract on α-amylase, α-glucosidase, and angiotensin-1 converting enzyme activities were investigated in vitro. Furthermore, the radicals [1,1-diphenyl-2 picrylhydrazyl (DPPH), 2,2..-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), hydroxyl (OH), and nitric oxide (NO)] scavenging ability and ferric reducing antioxidant property of the extract were assessed. Results. The results revealed that the extract inhibited α-amylase (1.81 ± 0.22 mg/mL), α-glucosidase (1.84 ± 0.17 mg/mL), and angiotensin-1 converting enzyme (0.674 ± 0.06 mg/mL [lungs], 1.006 ± 0.08 mg/mL [heart]) activities in a dose-dependent manner and also showed dose-dependent radicals [DPPH (16.94 ± 1.34 mg/mL), NO (6.98 ± 0.886 mg/mL), OH (3.72 ± 0.26 mg/mL), and ABTS (15.7 ± 1.06 mmol/TEAC·g] scavenging ability. Conclusion. The inhibition of α-amylase, α-glucosidase, and angiotensin-1 converting enzyme activities by the cocoa bean extract could be part of the possible mechanism by which the extract could manage and/or prevent type-2 diabetes and hypertension.

Addition of vitamin D reverses the decline in GFR following treatment with ACE inhibitors/angiotensin receptor blockers in patients with chronic kidney disease.

PubMed

Soares, Abel Esteves; Maes, Michael; Godeny, Paula; Matsumoto, Andressa Keiko; Barbosa, Décio Sabbatini; da Silva, Taysa Antonia F; Souza, Flávio Henrique M O; Delfino, Vinicius Daher Alvares

2017-12-15

Vitamin D has anti-inflammatory, anti-fibrotic effect, and may block the intrarenal renin-angiotensin system. Adequate vitamin D levels in conjunction with the use of Angiotensin-converting Enzyme Inhibitors/Angiotensin Receptor Blockers may help to slow down chronic kidney disease progression. To study a possible beneficial effect of vitamin D supplementation in chronic kidney disease patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on chronic kidney disease progression we performed a clinical study involving vitamin D supplementation in patients with deficiency of this vitamin. This study was conducted in two chronic kidney disease clinics in the city of Londrina, Brazil, from October 2010 to December 2012. It was involved stage 3 and 4 chronic kidney disease (estimated glomerular filtration rate between 60 and 15mL/min/1.73m 2 ) patients with and without vitamin D deficiency. The patients ingested six-month cholecalciferol 50,000IU oral supplementation to chronic kidney disease patients with vitamin D deficiency. We hypothesize changes in estimated glomerular filtration rate over study period. Our data demonstrate reservation of estimated glomerular filtration with cholecalciferol supplementation to chronic kidney disease patients taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. The combination treatment of angiotensin converting enzyme inhibitors/angiotensin receptor blockers with cholecalciferol prevents the decline in estimated glomerular filtration in patients with chronic kidney disease following treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and may represent a valid approach to reduce renal disease progression in chronic kidney disease patients with vitamin D deficiency. This result needs confirmation in prospective controlled clinical trials. Copyright © 2017. Published by Elsevier Inc.

Digital Mapping of Soil Salinity and Crop Yield across a Coastal Agricultural Landscape Using Repeated Electromagnetic Induction (EMI) Surveys

PubMed Central

Yao, Rongjiang; Yang, Jingsong; Wu, Danhua; Xie, Wenping; Gao, Peng; Jin, Wenhui

2016-01-01

Reliable and real-time information on soil and crop properties is important for the development of management practices in accordance with the requirements of a specific soil and crop within individual field units. This is particularly the case in salt-affected agricultural landscape where managing the spatial variability of soil salinity is essential to minimize salinization and maximize crop output. The primary objectives were to use linear mixed-effects model for soil salinity and crop yield calibration with horizontal and vertical electromagnetic induction (EMI) measurements as ancillary data, to characterize the spatial distribution of soil salinity and crop yield and to verify the accuracy of spatial estimation. Horizontal and vertical EMI (type EM38) measurements at 252 locations were made during each survey, and root zone soil samples and crop samples at 64 sampling sites were collected. This work was periodically conducted on eight dates from June 2012 to May 2013 in a coastal salt-affected mud farmland. Multiple linear regression (MLR) and restricted maximum likelihood (REML) were applied to calibrate root zone soil salinity (ECe) and crop annual output (CAO) using ancillary data, and spatial distribution of soil ECe and CAO was generated using digital soil mapping (DSM) and the precision of spatial estimation was examined using the collected meteorological and groundwater data. Results indicated that a reduced model with EMh as a predictor was satisfactory for root zone ECe calibration, whereas a full model with both EMh and EMv as predictors met the requirement of CAO calibration. The obtained distribution maps of ECe showed consistency with those of EMI measurements at the corresponding time, and the spatial distribution of CAO generated from ancillary data showed agreement with that derived from raw crop data. Statistics of jackknifing procedure confirmed that the spatial estimation of ECe and CAO exhibited reliability and high accuracy. A general increasing trend of ECe was observed and moderately saline and very saline soils were predominant during the survey period. The temporal dynamics of root zone ECe coincided with those of daily rainfall, water table and groundwater data. Long-range EMI surveys and data collection are needed to capture the spatial and temporal variability of soil and crop parameters. Such results allowed us to conclude that, cost-effective and efficient EMI surveys, as one part of multi-source data for DSM, could be successfully used to characterize the spatial variability of soil salinity, to monitor the spatial and temporal dynamics of soil salinity, and to spatially estimate potential crop yield. PMID:27203697

Digital Mapping of Soil Salinity and Crop Yield across a Coastal Agricultural Landscape Using Repeated Electromagnetic Induction (EMI) Surveys.

PubMed

Yao, Rongjiang; Yang, Jingsong; Wu, Danhua; Xie, Wenping; Gao, Peng; Jin, Wenhui

2016-01-01

Reliable and real-time information on soil and crop properties is important for the development of management practices in accordance with the requirements of a specific soil and crop within individual field units. This is particularly the case in salt-affected agricultural landscape where managing the spatial variability of soil salinity is essential to minimize salinization and maximize crop output. The primary objectives were to use linear mixed-effects model for soil salinity and crop yield calibration with horizontal and vertical electromagnetic induction (EMI) measurements as ancillary data, to characterize the spatial distribution of soil salinity and crop yield and to verify the accuracy of spatial estimation. Horizontal and vertical EMI (type EM38) measurements at 252 locations were made during each survey, and root zone soil samples and crop samples at 64 sampling sites were collected. This work was periodically conducted on eight dates from June 2012 to May 2013 in a coastal salt-affected mud farmland. Multiple linear regression (MLR) and restricted maximum likelihood (REML) were applied to calibrate root zone soil salinity (ECe) and crop annual output (CAO) using ancillary data, and spatial distribution of soil ECe and CAO was generated using digital soil mapping (DSM) and the precision of spatial estimation was examined using the collected meteorological and groundwater data. Results indicated that a reduced model with EMh as a predictor was satisfactory for root zone ECe calibration, whereas a full model with both EMh and EMv as predictors met the requirement of CAO calibration. The obtained distribution maps of ECe showed consistency with those of EMI measurements at the corresponding time, and the spatial distribution of CAO generated from ancillary data showed agreement with that derived from raw crop data. Statistics of jackknifing procedure confirmed that the spatial estimation of ECe and CAO exhibited reliability and high accuracy. A general increasing trend of ECe was observed and moderately saline and very saline soils were predominant during the survey period. The temporal dynamics of root zone ECe coincided with those of daily rainfall, water table and groundwater data. Long-range EMI surveys and data collection are needed to capture the spatial and temporal variability of soil and crop parameters. Such results allowed us to conclude that, cost-effective and efficient EMI surveys, as one part of multi-source data for DSM, could be successfully used to characterize the spatial variability of soil salinity, to monitor the spatial and temporal dynamics of soil salinity, and to spatially estimate potential crop yield.

A novel lactone-forming carboxylesterase: molecular identification of a tuliposide A-converting enzyme in tulip.

PubMed

Nomura, Taiji; Ogita, Shinjiro; Kato, Yasuo

2012-06-01

Tuliposides, the glucose esters of 4-hydroxy-2-methylenebutanoate and 3,4-dihydroxy-2-methylenebutanoate, are major secondary metabolites in tulip (Tulipa gesneriana). Their lactonized aglycons, tulipalins, function as defensive chemicals due to their biological activities. We recently found that tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins, but the possibility of the presence of several TCE isozymes was raised: TCE in tissues other than bulbs is different from bulb TCE. Here, to prove this hypothesis, TCE was purified from petals, which have the second highest TCE activity after bulbs. The purified enzyme, like the bulb enzyme, preferentially accepted tuliposides as substrates, with 6-tuliposide A the best substrate, which allowed naming the enzyme tuliposide A-converting enzyme (TCEA), but specific activity and molecular mass differed between the petal and bulb enzymes. After peptide sequencing, a novel cDNA (TgTCEA) encoding petal TCEA was isolated, and the functional characterization of the recombinant enzyme verified that TgTCEA catalyzes the conversion of 6-tuliposide A to tulipalin A. TgTCEA was transcribed in all tulip tissues but not in bulbs, indicating the presence of a bulb-specific TgTCEA, as suggested by the distinct enzymatic characters between the petal and bulb enzymes. Plastidial localization of TgTCEA enzyme was revealed, which allowed proposing a cytological mechanism of TgTCE-mediated tulipalin formation in the tulip defensive strategy. Site-directed mutagenesis of TgTCEA suggested that the oxyanion hole and catalytic triad characteristic of typical carboxylesterases are essential for the catalytic process of TgTCEA enzyme. To our knowledge, TgTCEA is the first identified member of the lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification.

A Novel Lactone-Forming Carboxylesterase: Molecular Identification of a Tuliposide A-Converting Enzyme in Tulip1[W

PubMed Central

Nomura, Taiji; Ogita, Shinjiro; Kato, Yasuo

2012-01-01

Tuliposides, the glucose esters of 4-hydroxy-2-methylenebutanoate and 3,4-dihydroxy-2-methylenebutanoate, are major secondary metabolites in tulip (Tulipa gesneriana). Their lactonized aglycons, tulipalins, function as defensive chemicals due to their biological activities. We recently found that tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins, but the possibility of the presence of several TCE isozymes was raised: TCE in tissues other than bulbs is different from bulb TCE. Here, to prove this hypothesis, TCE was purified from petals, which have the second highest TCE activity after bulbs. The purified enzyme, like the bulb enzyme, preferentially accepted tuliposides as substrates, with 6-tuliposide A the best substrate, which allowed naming the enzyme tuliposide A-converting enzyme (TCEA), but specific activity and molecular mass differed between the petal and bulb enzymes. After peptide sequencing, a novel cDNA (TgTCEA) encoding petal TCEA was isolated, and the functional characterization of the recombinant enzyme verified that TgTCEA catalyzes the conversion of 6-tuliposide A to tulipalin A. TgTCEA was transcribed in all tulip tissues but not in bulbs, indicating the presence of a bulb-specific TgTCEA, as suggested by the distinct enzymatic characters between the petal and bulb enzymes. Plastidial localization of TgTCEA enzyme was revealed, which allowed proposing a cytological mechanism of TgTCE-mediated tulipalin formation in the tulip defensive strategy. Site-directed mutagenesis of TgTCEA suggested that the oxyanion hole and catalytic triad characteristic of typical carboxylesterases are essential for the catalytic process of TgTCEA enzyme. To our knowledge, TgTCEA is the first identified member of the lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification. PMID:22474185

Reframing the Debate about the Relationship between Learning and Development: An Effort to Resolve Dilemmas and Reestablish Dialogue in a Fractured Field

ERIC Educational Resources Information Center

Fowler, R. Clarke

2017-01-01

The field of early childhood education (ECE) is currently unable to reach consensus on the extent to which ECE should be based on child development. One manifestation of this situation is the dilemma that early educators purportedly face between teaching the whole child and the curriculum, between developmentally appropriate practice (DAP) and…

Preparing Teachers of Young Children: The Current State of Knowledge, and a Blueprint for the Future. Executive Summary. Policy Report

ERIC Educational Resources Information Center

Whitebook, Marcy; Gomby, Deanna; Bellm, Dan; Sakai, Laura; Kipnis, Fran

2009-01-01

Across the political spectrum, high-quality early care and education (ECE) is viewed as essential to educational reform. No ECE program can succeed without teachers who can establish warm and caring relationships with children, light the fires of children's curiosity and love of learning, and foster their development and readiness for school.…

The Effect of Expertise-Based Training on the Quality of Digital Stories Created to Teach Mathematics to Young Children

ERIC Educational Resources Information Center

Sancar-Tokmak, Hatice; Incikabi, Lutfi

2013-01-01

This study investigated the effect of expertise-based training (XBT) on the quality of digital stories created by early childhood education (ECE) pre-service teachers. The participants of the study were 69 pre-service teachers from the ECE Department. The study was experimental, utilizing a static-group pre-test/post-test design, supported with…

Bodies Displayed on Walls: Are Children's Bodies Represented in an Inclusive Way in the Pictures on the Walls in Their Early Childhood Educational Environments?

ERIC Educational Resources Information Center

Martínez-Bello, Vladimir E.; Martínez-Bello, Judith T.

2017-01-01

The messages conveyed by visual representations in the early childhood education (ECE) environment are critical to ensuring the success of inclusive practices. Given that anti-bias education permeates and affects everything which takes place in ECE institutions, the challenge for early childhood educators is to think creatively about how classroom…

The Tension between Teacher Control and Children's Freedom in a Child-Centered Classroom: Resolving the Practical Dilemma through a Closer Look at the Related Theories

ERIC Educational Resources Information Center

Tzuo, Pei Wen

2007-01-01

This article explores the meaning of child-centeredness in Early Childhood Education (ECE), by shedding light on the nuanced tensions between teacher control and children's freedom. While ECE professionals advocate the importance of children's individual interests and needs in education, they diverge somewhat in their perspectives about the…

A One-Credit Hands-On Introductory Course in Electrical and Computer Engineering Using a Variety of Topic Modules

ERIC Educational Resources Information Center

Pierre, J. W.; Tuffner, F. K.; Anderson, J. R.; Whitman, D. L.; Ula, A. H. M. S.; Kubichek, R. F.; Wright, C. H. G.; Barrett, S. F.; Cupal, J. J.; Hamann, J. C.

2009-01-01

This paper describes a one-credit laboratory course for freshmen majoring in electrical and computer engineering (ECE). The course is motivational in nature and exposes the students to a wide range of areas of electrical and computer engineering. The authors believe it is important to give freshmen a broad perspective of what ECE is all about, and…

Respecting but Not Sustaining Play: Early Childhood Educators' and Home Childcare Providers' Practices That Support Children's Play

ERIC Educational Resources Information Center

Lemay, Lise; Bigras, Nathalie; Bouchard, Caroline

2016-01-01

This study examined and compared the extent to which early childhood educators' (ECEs) and home childcare providers' (HCPs) practices supported children's play. The sample included 50 ECEs and 20 HCPs in settings that care for 70 children at 18, 24, and 36 months old. At each time point, the childcare process quality was observed using the…

Contrasting Effects of Extreme Drought and Snowmelt Patterns on Mountain Plants along an Elevation Gradient.

PubMed

Rosbakh, Sergey; Leingärtner, Annette; Hoiss, Bernhard; Krauss, Jochen; Steffan-Dewenter, Ingolf; Poschlod, Peter

2017-01-01

Despite the evidence that increased frequency and magnitude of extreme climate events (ECE) considerably affect plant performance, there is still a lack of knowledge about how these events affect mountain plant biodiversity and mountain ecosystem functioning. Here, we assessed the short-term (one vegetation period) effects of simulated ECEs [extreme drought (DR), advanced and delayed snowmelt (AD and DE), respectively] on the performance of 42 plant species occurring in the Bavarian Alps (Germany) along an elevational gradient of 600-2000 m a.s.l. in terms of vegetative growth and reproduction performance. We demonstrate that plant vegetative and generative traits respond differently to the simulated ECEs, but the nature and magnitude treatment effects strongly depend on study site location along the elevational gradient, species' altitudinal origin and plant functional type (PFT) of the target species. For example, the negative effect of DR treatment on growth (e.g., lower growth rates and lower leaf nitrogen content) and reproduction (e.g., lower seed mass) was much stronger in upland sites, as compared to lowlands. Species' response to the treatments also differed according to their altitudinal origin. Specifically, upland species responded negatively to extreme DR (e.g., lower growth rates and lower leaf carbon concentrations, smaller seed set), whereas performance of lowland species remained unaffected (e.g., stable seed set and seed size) or even positively responded (e.g., higher growth rates) to that treatment. Furthermore, we were able to detect some consistent differences in responses to the ECEs among three PFTs (forbs, graminoids, and legumes). For instance, vegetative growth and sexual reproduction of highly adaptable opportunistic graminoids positively responded to nearly all ECEs, likely on the costs of other, more conservative, forbs and legumes. Our results suggest that ECEs can significantly modify the performance of specific plant groups and therefore lead to changes in plant community structure and composition under ongoing climate change. Our study therefore underlines the need for more experimental studies on the effects of extreme climate events to understand the potential consequences of climate change for the alpine ecosystem.

Reducing Enzyme Costs Increases Market Potential of Biofuels; The Spectrum of Clean Energy Innovation (Fact Sheet)

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

Not Available

Fact sheet describing NREL's work with enzyme producers Novozymes and Genencor to engineer new cellulase enzymes to breakdown cellulosic ethanol into fermentable sugars that can be converted into biofuels.

Pharmacologic modulation of ACE2 expression.

PubMed

Soler, María José; Barrios, Clara; Oliva, Raymond; Batlle, Daniel

2008-10-01

Angiotensin-converting enzyme 2 (ACE2) is an enzymatically active homologue of angiotensin-converting enzyme that degrades angiotensin I, angiotensin II, and other peptides. Recent studies have shown that under pathologic conditions, ACE2 expression in the kidney is altered. In this review, we briefly summarize recent studies dealing with pharmacologic interventions that modulate ACE2 expression. ACE2 amplification may have a potential therapeutic role for kidney disease and hypertension.

Rediscovering ACE: Novel insights into the many roles of the angiotensin-converting enzyme

PubMed Central

Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Bernstein, Ellen A.; Janjulia, Tea; Taylor, Brian; Giani, Jorge F.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Shi, Peng D.; Fuchs, Sebastien; Bernstein, Kenneth E.

2013-01-01

Angiotensin converting enzyme (ACE) is best known for the catalytic conversion of angiotensin I to angiotensin II. However, the use of gene-targeting techniques has led to mouse models highlighting many other biochemical properties and actions of this enzyme. This review discusses recent studies examining the functional significance of ACE tissue-specific expression and the presence in ACE of two independent catalytic sites with distinct substrates and biological effects. It is these features which explain why ACE makes important contributions to many different physiological processes including renal development, blood pressure control, inflammation and immunity. PMID:23686164

Prostate weight: an independent predictor for positive surgical margins during robotic-assisted laparoscopic radical prostatectomy.

PubMed

Msezane, Lambda P; Gofrit, Ofer N; Lin, Shang; Shalhav, Arieh L; Zagaja, Gregory P; Zorn, Kevin C

2007-10-01

Pre-operative prediction of pathological stage represents the cornerstone of prostate cancer management. Patient counseling is routinely based on pre-operative PSA, Gleason score and clinical stage. In this study, we evaluated whether prostate weight (PW) is an independent predictor of extracapsular extension (ECE) and positive surgical margin (PSM). Between February 2003 and November 2006, 709 men underwent robotic-assisted laparoscopic radical prostatectomy (RLRP). Pre-operative parameters (patient age, pre-operative PSA, biopsy Gleason score, clinical stage) as well as pathological data (prostate weight, pathological stage) were prospectively gathered after internal-review board (IRB) approval. Evaluation of the influence of these variables on ECE and PSM outcomes were assessed using both univariate and multivariate logistic regression analysis. Mean overall patient age, pre-operative PSA and PW were 59.6 years, 6.5 ng/ml and 52.9 g (range 5.5 g-198.7 g), respectively. Of the 393, 209 and 107 men with PW < 50 g, 50 g-< 70 g and < 70 g, ECE was observed in 20.1%, 15.3% and 9.3%, respectively (p = 0.015). In the same patient cohorts, PSM was observed in 25.4%, 14.4% and 7.5%, respectively (p < 0.001). In a multivariate logistic regression analysis, PW, in addition to pre-operative PSA, biopsy Gleason score and clinical stage, was an independent risk factor for ECE (p < 0.001). Similarly, in multi-variate analysis, PW was observed to be a risk factor for PSM (p < 0.001). PW is an independent predictor of both ECE and PSM, with an inverse relationship having been demonstrated between both variables. PW should be considered when counseling patients with prostate cancer treatment.

Extreme weather and climate events with ecological relevance: a review

PubMed Central

Meehl, Gerald A.

2017-01-01

Robust evidence exists that certain extreme weather and climate events, especially daily temperature and precipitation extremes, have changed in regard to intensity and frequency over recent decades. These changes have been linked to human-induced climate change, while the degree to which climate change impacts an individual extreme climate event (ECE) is more difficult to quantify. Rapid progress in event attribution has recently been made through improved understanding of observed and simulated climate variability, methods for event attribution and advances in numerical modelling. Attribution for extreme temperature events is stronger compared with other event types, notably those related to the hydrological cycle. Recent advances in the understanding of ECEs, both in observations and their representation in state-of-the-art climate models, open new opportunities for assessing their effect on human and natural systems. Improved spatial resolution in global climate models and advances in statistical and dynamical downscaling now provide climatic information at appropriate spatial and temporal scales. Together with the continued development of Earth System Models that simulate biogeochemical cycles and interactions with the biosphere at increasing complexity, these make it possible to develop a mechanistic understanding of how ECEs affect biological processes, ecosystem functioning and adaptation capabilities. Limitations in the observational network, both for physical climate system parameters and even more so for long-term ecological monitoring, have hampered progress in understanding bio-physical interactions across a range of scales. New opportunities for assessing how ECEs modulate ecosystem structure and functioning arise from better scientific understanding of ECEs coupled with technological advances in observing systems and instrumentation. This article is part of the themed issue ‘Behavioural, ecological and evolutionary responses to extreme climatic events’. PMID:28483866

Should reporting of peri-neural invasion and extra prostatic extension be mandatory in prostate cancer biopsies? correlation with outcome in biopsy cases treated conservatively

PubMed Central

Ahmad, Amar S.; Parameshwaran, Vishnu; Beltran, Luis; Fisher, Gabrielle; North, Bernard V.; Greenberg, David; Soosay, Geraldine; Møller, Henrik; Scardino, Peter; Cuzick, Jack; Berney, Daniel M.

2018-01-01

The identification of perineural invasion (PNI) and extraprostatic extension (ECE) in prostate cancer (PC) biopsies is time consuming and can be difficult. Although this is required information in many datasets, there is little evidence on their effect on outcome in patients treated conservatively. Cases of PC were identified from three cancer registries in the UK from men with clinically localized prostate cancer diagnosed by needle biopsy from 1990–2003. The endpoint was prostate cancer death (DOD). Patients treated radically within 6 months, those with objective evidence of metastases or who had prior hormone therapy were excluded. Follow-up was through cancer registries up until 2012. Deaths were divided into those from PC and those from other causes, according to WHO criteria. 988 biopsy cases (6522 biopsy cores) were centrally reviewed by three uropathologists and assigned a Gleason score and Grade Group (GG). The presence of both PNI and ECE was recorded. Of 988 patients, PNI was present in 288 (DOD = 75) and ECE in 23 (DOD = 5). On univariable analysis PNI was highly significantly associated with DOD (hazard ratio [HR] 2.28, 95% CI: 1.68, 3.1, log-rank test p-value = 4.8 × 10–8), but ECE was not (log-rank test p-value = 0.334). On multivariable analysis with GG, serum PSA (per 10%), clinical stage and extent of disease (per 10%), PNI lost significance (HR 1.16, 95% CI: 0.83, 1.63, likelihood ratio test p-value = 0.371). The utility of routinely examining prostate biopsies for ECE and PNI is doubtful as it is not independently associated with higher grade, stage or prognosis. PMID:29755671

Should reporting of peri-neural invasion and extra prostatic extension be mandatory in prostate cancer biopsies? correlation with outcome in biopsy cases treated conservatively.

PubMed

Ahmad, Amar S; Parameshwaran, Vishnu; Beltran, Luis; Fisher, Gabrielle; North, Bernard V; Greenberg, David; Soosay, Geraldine; Møller, Henrik; Scardino, Peter; Cuzick, Jack; Berney, Daniel M

2018-04-17

The identification of perineural invasion (PNI) and extraprostatic extension (ECE) in prostate cancer (PC) biopsies is time consuming and can be difficult. Although this is required information in many datasets, there is little evidence on their effect on outcome in patients treated conservatively. Cases of PC were identified from three cancer registries in the UK from men with clinically localized prostate cancer diagnosed by needle biopsy from 1990-2003. The endpoint was prostate cancer death (DOD). Patients treated radically within 6 months, those with objective evidence of metastases or who had prior hormone therapy were excluded. Follow-up was through cancer registries up until 2012. Deaths were divided into those from PC and those from other causes, according to WHO criteria. 988 biopsy cases (6522 biopsy cores) were centrally reviewed by three uropathologists and assigned a Gleason score and Grade Group (GG). The presence of both PNI and ECE was recorded. Of 988 patients, PNI was present in 288 (DOD = 75) and ECE in 23 (DOD = 5). On univariable analysis PNI was highly significantly associated with DOD (hazard ratio [HR] 2.28, 95% CI: 1.68, 3.1, log-rank test p -value = 4.8 × 10 -8 ), but ECE was not (log-rank test p -value = 0.334). On multivariable analysis with GG, serum PSA (per 10%), clinical stage and extent of disease (per 10%), PNI lost significance (HR 1.16, 95% CI: 0.83, 1.63, likelihood ratio test p -value = 0.371). The utility of routinely examining prostate biopsies for ECE and PNI is doubtful as it is not independently associated with higher grade, stage or prognosis.

Extreme weather and climate events with ecological relevance: a review.

PubMed

Ummenhofer, Caroline C; Meehl, Gerald A

2017-06-19

Robust evidence exists that certain extreme weather and climate events, especially daily temperature and precipitation extremes, have changed in regard to intensity and frequency over recent decades. These changes have been linked to human-induced climate change, while the degree to which climate change impacts an individual extreme climate event (ECE) is more difficult to quantify. Rapid progress in event attribution has recently been made through improved understanding of observed and simulated climate variability, methods for event attribution and advances in numerical modelling. Attribution for extreme temperature events is stronger compared with other event types, notably those related to the hydrological cycle. Recent advances in the understanding of ECEs, both in observations and their representation in state-of-the-art climate models, open new opportunities for assessing their effect on human and natural systems. Improved spatial resolution in global climate models and advances in statistical and dynamical downscaling now provide climatic information at appropriate spatial and temporal scales. Together with the continued development of Earth System Models that simulate biogeochemical cycles and interactions with the biosphere at increasing complexity, these make it possible to develop a mechanistic understanding of how ECEs affect biological processes, ecosystem functioning and adaptation capabilities. Limitations in the observational network, both for physical climate system parameters and even more so for long-term ecological monitoring, have hampered progress in understanding bio-physical interactions across a range of scales. New opportunities for assessing how ECEs modulate ecosystem structure and functioning arise from better scientific understanding of ECEs coupled with technological advances in observing systems and instrumentation.This article is part of the themed issue 'Behavioural, ecological and evolutionary responses to extreme climatic events'. © 2017 The Author(s).

The Role of Access to Head Start and Quality Ratings for Spanish-Speaking Dual Language Learners’ (DLLs) Participation in Early Childhood Education

PubMed Central

2014-01-01

Data from the Head Start Impact Study (N = 4,442) were used to test for differences between Spanish-speaking Dual Language Learners (DLLs) and monolingual English-speaking children in: (1) Head Start attendance rates when randomly assigned admission; and (2) quality ratings of other early childhood education (ECE) programs attended when not randomly assigned admission to Head Start. Logistic regressions showed that Spanish-speaking DLL children randomly assigned a spot in Head Start were more likely than monolingual-English learners to attend. Further, Spanish-speaking DLLs not randomly assigned a spot in Head Start were more likely to attend higher-quality ECE centers than non-DLL children. Policy implications are discussed, suggesting that, if given access, Spanish-speaking DLL families will take advantage of quality ECE programs. PMID:25018585

Using State Early Care and Education Workforce Registry Data to Inform Training-Related Questions: Issues to Consider. Research Report. ETS RR-16-31

ERIC Educational Resources Information Center

Ackerman, Debra J.

2016-01-01

The current early care and education (ECE) policy context is bringing increased attention to the training completed by the child care workforce and to the use of registries to track such training. Although ECE workforce registries are designed to record individuals' data, aggregate registry data have the potential to shed light on the workforce's…

The ECE Culminating Design Experience: Analysis of ABET 2000 Compliance at Leading Academic Institutions

DTIC Science & Technology

2006-05-01

a significant design project that requires development of a large scale software project . A distinct shortcoming of Purdue ECE...18-540: Rapid Prototyping of Computer Systems This is a project -oriented course which will deal with all four aspects of project development ; the...instructors, will develop specifications for a mobile computer to assist in inspection and maintenance. The application will be partitioned

Towards Resilient Information-Aware Communication Networks

DTIC Science & Technology

2013-02-01

kPa) kilo pascal (kPa) kilogram (kg) kilogram-meter 2 (kg-m2) kilogram-meter 3 (kg/m 3 ) **Gray (Gy) coulomb /kilogram (C/kg) second (s...Dept. of ECE). Iowa State University Collaborated with Prof. Lei Ying (Dep. of ECE). Massachusetts Institute of Technology Collaborated with Prof...courses on De - sign and Analysis of Communication Networks and also supervised students in a Smart Phone labo- ratory during this period. Both the

Health and safety needs in early care and education programs: what do directors, child health records, and national standards tell us?

PubMed

Alkon, Abbey; To, Kim; Mackie, Joanna F; Wolff, Mimi; Bernzweig, Jane

2010-01-01

To identify the overlapping and unique health and safety needs and concerns identified by early care and education (ECE) directors, health records, and observed compliance with national health and safety (NHS) standards. Cross-sectional study. 127 ECE programs from 5 California counties participated in the study, including 118 directors and 2,498 children's health records. Qualitative data were collected using standardized ECE directors' interviews to identify their health and safety concerns; and objective, quantitative data were collected using child health record reviews to assess regular health care, immunizations, health insurance, special health care needs, and screening tests and an observation Checklist of 66 key NHS standards collected by research assistants. The overlapping health and safety needs and concerns identified by the directors and through observations were hygiene and handwashing, sanitation and disinfection, supervision, and the safety of indoor and outdoor equipment. Some of the health and safety needs identified by only one assessment method were health and safety staff training, medical plans for children with special health care needs and follow-up on positive screening tests. Comprehensive, multimethod assessments are useful to identify health and safety needs and develop public health nursing interventions for ECE programs.

Embedded Cohesive Elements (ECE) Approach to the Simulation of Spall Fracture Experiment

NASA Astrophysics Data System (ADS)

Bonora, Nicola; Esposito, Luca; Ruggiero, Andrew

2007-06-01

Discrepancies between the calculated and observed velocity vs time plot, relatively to the spall signal portion in terms of both signal amplitude and frequency, in numerical simulations of flyer plate impact test are usually shown. These are often ascribed either to material model or the numerical scheme used. Bonora et al. (2003 )[Bonora N., Ruggiero A. and Milella P.P., 2003, Fracture energy effect on spall signal, Proc. of 13^th APS SCCM03, Portland, USA] showed that, for ductile metals, these differences can be the imputed to the dissipation process during fracturing due to the viscous separation of spall fracture plane surfaces. In this work that concept has been further developed implementing an embedded cohesive elements (ECE) technology into FEM. The ECE method consists in embedding cohesive elements (normal and shear forces only) into standard isoparametric 2D or 3D FEM continuum elements. The cohesive elements remain silent and inactive until the continuum element fails. At failure, the continuum element is removed while the ECE becomes active until the separation energy is dissipated. Here, the methodology is presented and applied to simulate soft spall in ductile metals such as OHFC copper. Results of parametric study on mesh size and cohesive law shape effect are presented.

Depressive effects on the central nervous system and underlying mechanism of the enzymatic extract and its phlorotannin-rich fraction from Ecklonia cava edible brown seaweed.

PubMed

Cho, Suengmok; Han, Daeseok; Kim, Seon-Bong; Yoon, Minseok; Yang, Hyejin; Jin, Young-Ho; Jo, Jinho; Yong, Hyeim; Lee, Sang-Hoon; Jeon, You-Jin; Shimizu, Makoto

2012-01-01

Marine plants have been reported to possess various pharmacological properties; however, there have been few reports on their neuropharmacological effects. Terrestrial plants have depressive effects on the central nervous system (CNS) because of their polyphenols which make them effective as anticonvulsants and sleep inducers. We investigated in this study the depressive effects of the polyphenol-rich brown seaweed, Ecklonia cava (EC), on CNS. An EC enzymatic extract (ECEE) showed significant anticonvulsive (>500 mg/kg) and sleep-inducing (>500 mg/kg) effects on the respective mice seizure induced by picrotoxin and on the mice sleep induced by pentobarbital. The phlorotannin-rich fraction (PTRF) from ECEE significantly potentiated the pentobarbital-induced sleep at >50 mg/kg. PTRF had binding activity to the gamma aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. The sleep-inducing effects of diazepam (DZP, a well-known GABA(A)-BZD agonist), ECEE, and PTRF were completely blocked by flumazenil, a well-known antagonist of GABA(A)-BZD receptors. These results imply that ECEE produced depressive effects on CNS by positive allosteric modulation of its phlorotannins on GABA(A)-BZD receptors like DZP. Our study proposes EC as a candidate for the effective treatment of neuropsychiatric disorders such as anxiety and insomnia.

Preclinical students’ experiences in early clerkships after skills training partly offered in primary health care centers: a qualitative study from Indonesia

PubMed Central

2012-01-01

Background Students may encounter difficulties when they have to apply clinical skills trained in their pre-clinical studies in clerkships. Early clinical exposure in the pre-clinical phase has been recommended to reduce these transition problems. The aim of this study is to explore differences in students' experiences during the first clerkships between students exclusively trained in a skills laboratory and peers for whom part of their skills training was substituted by early clinical experiences (ECE). Methods Thirty pre-clinical students trained clinical skills exclusively in a skills laboratory; 30 peers received part of their skills training in PHC centers. Within half a year after commencing their clerkships all 60 students shared their experiences in focus group discussions (FGDs). Verbatim transcripts of FGDs were analyzed using Atlas-Ti software. Results Clerkship students who had participated in ECE in PHC centers felt better prepared to perform their clinical skills during the first clerkships than peers who had only practiced in a skills laboratory. ECE in PHC centers impacted positively in particular on students’ confidence, clinical reasoning, and interpersonal communication. Conclusion In the Indonesian setting ECE in PHC centers reduce difficulties commonly encountered by medical students in the first clerkships. PMID:22640419

Glutamic acid is an active site residue of angiotensin I-converting enzyme. Use of the Lossen rearrangement for identification of dicarboxylic acid residues.

PubMed

Harris, R B; Wilson, I B

1983-01-25

A set of chemical reactions was used to show that one glutamic acid residue at the active site of bovine lung angiotensin I-converting enzyme is esterified with the alkylating agent p-[N,N-bis(chloroethyl)amino] phenylbutyryl-L-Pro (chlorambucyl-L-Pro), an affinity label for this enzyme (Harris, R. B., and Wilson, I. B. (1982) J. Biol. Chem. 257, 811-815). The same procedure was used to confirm that a glutamic acid residue of carboxypeptidase A alpha is esterified by reaction with bromoacetyl-N-methyl-L-phenylalanine (Haas, G. M., and Neurath, H. (1971) Biochemistry 10, 3535-3546). In the procedure described in this paper, the esterified residue at the active site is converted to the hydroxamic acid by reaction with hydroxylamine and the hydroxamic acid is subject to the Lossen rearrangement. If a glutamic acid residue was esterified, 1 eq of 2,4-diaminobutyric acid will be formed. Aspartyl esters will give 2,3-diaminopropionic acid. The diamino acids can be quantitatively measured using the short column of an amino acid analyzer if the amount of lysine and histidine is largely decreased by modification with suitable side chain protecting groups. With carboxypeptidase A, the reactions were done on the whole undigested enzyme. With the converting enzyme, we first cleaved the esterified enzyme with cyanogen bromide. Twenty-nine cleavage peptides were separated on high performance liquid chromatography and one of these contained all of the bound radioactive inhibitor. This active site peptide was then subjected to the derivatization and Lossen procedures, and 1 eq of 2,4-diaminobutyric acid was obtained.

Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors.

PubMed

Bukhari, S N A; Butt, A M; Amjad, M W B; Ahmad, W; Shah, V H; Trivedi, A R

2013-11-01

Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.

Enzymatic conversion of sucrose to glucose and its anomerization by quantitative NMR spectroscopy: Application of a simple consecutive reaction rates approach

NASA Astrophysics Data System (ADS)

Singh, Jaideep; Her, Cheenou; Krishnan, V. V.

2018-02-01

The anomerization of carbohydrates is an essential process that determines the relative stabilization of stereoisomers in an aqueous solution. In a typical real-time enzyme kinetics experiment, the substrate (sucrose) is converted to glucose and fructose by the enzyme invertase. The product (α-D-glucose) starts to convert to β-D-glucose immediately by hydrolysis. Though the anomerization process is independent of the enzyme catalysis, the progress curve describing the production of β-D-glucose from α-D-glucose is directly affected by the kinetics of consecutive reactions. When α-D-glucose is continually converted to β-D-glucose, by the enzymatic action, the time course of both α- and β-D-glucose is influenced by the enzyme kinetics. Thus, a reversible first-order rate equation is not adequate to model the reaction mechanism, leading to erroneous results on the rates of formation of the glucose anomers. In this manuscript, we incorporate an approximate method to address consecutive general reactions involving enzyme kinetics and first-order reaction processes. The utility of the approach is demonstrated in the real-time NMR measurement of the anomerization process of α-D-glucose (enzymatically produced from sucrose) to β-D-glucose, as a function of invertase enzyme concentration. Variable temperature experiments were used to estimate the thermodynamic parameters of the anomerization process and are consistent with literature values.

Pathway for biodegradation of p-nitrophenol in a Moraxella sp

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

Spain, J.C.; Gibson, D.T.

1991-03-01

A Moraxella strain grew on p-nitrophenol with stoichiometric release of nitrite. During induction of the enzymes for growth on p-nitrophenol, traces of hydroquinone accumulated in the medium. In the presence of 2,2{prime}-dipyidyl, p-nitrophenol, was converted stoichiometrically to hydroquinone. Particulate enzymes catalyzed the conversion of p-nitrophenol to hydroquinone in the presence of NADPH and oxygen. Soluble enzymes catalyzed the conversion of hydroquinone to {gamma}-hydroxymuconic semialdehyde, which was identified by high-performance liquid chromatography (HPLC)-mass spectroscopy. Upon addition of catalytic amounts of NAD{sup +}, {gamma}-hydroxymuconic semialdehyde was converted to {beta}-ketoadipic acid. In the presence of pyruvate and lactic dehydrogenase, substrate amounts of NADmore » were required and {gamma}-hydroxymuconic semialdehyde was converted to maleylacetic acid, which was identified by HPLC-mass spectroscopy. Similar results were obtained when the reaction was carried out in the presence of potassium ferricyanide. Extracts prepared from p-nitrophenol-grown cells also contained an enzyme that catalyzed the oxidation of 1,2,4-benzenetriol to maleylacetic acid. The enzyme responsible for the oxidation of 1,2,4-benzenetriol was separated from the enzyme responsible for hydroquinone oxidation by DEAE-cellulose chromatography. The results indicate that the pathway for biodegradation of p-nitrophenol involves the initial removal of the nitro group as nitrite and formation of hydroquinone.« less

Which Early Care and Education Centers Participate in Head Start or Public Pre-Kindergarten? National Survey of Early Care & Education. Technical Report. OPRE Report 2015-92a

ERIC Educational Resources Information Center

Administration for Children & Families, 2015

2015-01-01

This report draws on newly available data from the National Survey of Early Care and Education (NSECE) to describe early care and education (ECE) centers that participate in two prominent publicly-funded ECE initiatives: Head Start and publicly-funded pre-kindergarten. Although a great deal is known about Head Start programs, and there are sources…

Early Education and Care: Overlap Indicates Need To Assess Crosscutting Programs. Report to the Chairman, Subcommittee on Oversight of Government Management, Restructuring and the District of Columbia, U.S. Senate.

ERIC Educational Resources Information Center

Shaul, Marnie S.

In response to Congressional requests reflecting the nationwide attention on early childhood education (ECE) and care, the General Accounting Office assessed the federally funded programs that provide or support ECE and care for children under 5 years. Information was obtained by means of an electronic search of the June 1999 Catalog of Federal…

A Guide to Nuclear Weapons Phenomena and Effects Literature

DTIC Science & Technology

1984-10-31

and Disarmament Agency. An article entitled "Limited Nuclear War" in Scientific American (Reference ECE-14) is also of interest because of its rela... Sistems and the Aemosphere’-BCj=9. 43 Personne l; .-EP)- / 47 Civilian .S’ector and the .Environment, (ECE) 50 5 SPECIAL REFERENCE MATERIALS (R) ’<ൾ...approximations. DNA has sponsored the development of software for scientific and military applications of nuclear weapon phenomena and effects information

Investigation of factors influencing chloride extraction efficiency during electrochemical chloride extraction from reinforcing concrete

NASA Astrophysics Data System (ADS)

Sharp, Stephen R.

2005-11-01

Electrochemical chloride extraction (ECE) is an accelerated bridge restoration method similar to cathodic protection, but operates at higher current densities and utilizes a temporary installation. Both techniques prolong the life of a bridge by reducing the corrosion rate of the reinforcing bar when properly applied. ECE achieves this by moving chlorides away from the reinforcement and out of the concrete while simultaneously increasing the alkalinity of the electrolyte near the reinforcing steel. Despite the proven success, significant use of ECE has not resulted in part due to an incomplete understanding in the following areas: (1) An estimation of the additional service life that can be expected following treatment when the treated member is again subjected to chlorides; (2) The cause of the decrease in current flow and, therefore, chloride removal rate during treatment; (3) Influence of water-to-cement (w/c) ratio and cover depth on the time required for treatment. This dissertation covers the research that is connected to the last two areas listed above. To begin examining these issues, plain carbon steel reinforcing bars (rebar) were embedded in portland cement concrete slabs of varying water-to-cement (w/c) ratios and cover depths, and then exposed to chlorides. A fraction of these slabs had sodium chloride added as an admixture, with all of the slabs subjected to cyclical ponding with a saturated solution of sodium chloride. ECE was then used to remove the chlorides from these slabs while making electrical measurements in the different layers between the rebar (cathode) and the titanium mat (anode) to follow the progress of the ECE process. During this study, it was revealed that the resistance of the outer concrete surface layer increases during ECE, inevitably restricting current flow, while the resistance of the underlying concrete decreases or remains constant. During ECE treatment, a white residue formed on the surface of the concrete. Analyses of the residue revealed that it contains calcium carbonate, calcium chloride, and other yet unidentified minor components when calcium hydroxide was used as the electrolyte. The surface film can be completely removed mechanically or to some extent inhibited chemically, with both of these processes resulting in an increase in the efficiency of the electrochemical chloride extraction process. In addition, an obvious relationship between the cover depth, water-to-cement ratio, and chloride extraction efficiency does not exist, however, cover depth does influence the current density. The final phase of this study will be presented in a VTRC/FHWA final report. This report will include the results that are presented in this dissertation, in addition to the results from the ongoing research. It will also include an estimation of the additional service life that can be expected following treatment.

Central nervous system considerations in the use of beta-blockers, angiotensin-converting enzyme inhibitors, and thiazide diuretics in managing essential hypertension.

PubMed

Gengo, F M; Gabos, C

1988-07-01

The most common mild side effects occurring with use of beta-blockers, thiazide diuretics, and angiotensin-converting enzyme inhibitors for blood pressure control are central nervous system symptoms, specifically lethargy, sedation, and fatigue. These symptoms affect 5% to 10% of patients taking these drugs. The mechanism by which beta-blockers may induce central nervous system effects is uncertain. Relative lipophilicity as a factor affecting penetrance of the blood-brain barrier has not proved to be a reliable predictor of whether the drug will cause such disturbances. Comparisons of atenolol (hydrophilic) and metoprolol (lipophilic) have shown no differences between these drugs with respect to side effects of the central nervous system. The incidence of central nervous system effects with angiotensin-converting enzyme inhibitors is similar to that for most beta-blockers. The precise role of the angiotensin-converting enzyme in the central nervous system is not well defined. Most thiazide diuretics are not associated with major complications of the central nervous system, although electrolyte imbalance may occasionally lead to complaints of neurologic symptoms. Because the incidence of central nervous system effects with these three classes of drugs is so low, concern for the side effects of the central nervous system is not a prime consideration in the choice of an initial antihypertensive agent.

[Risk for hyperkalemia during long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetics in relation to the glomerular filtration rate].

PubMed

Raml, A; Schmekal, B; Grafinger, P; Biesenbach, G

2001-11-23

The risk for hyperkalaemia during therapy with angiotensin-converting enzyme inhibitors is especially increased in the elderly diabetic because of a decrease in glomerular filtration rate (GFR), as well as the occurrence of hyporeninaemic hypoaldosteronism. We evaluated the risk for hyperkalaemia under long-term angiotensin-converting enyzme inhibition in 86 insulin-dependent type 2 diabetic patients in relation to their GFR. We compared the influence of a 3 to 6 months long treatment with angiotensin-converting enzyme inhibitors on the serum potassium levels, the creatinine clearance and the urinary albumin excretion in insulin-dependent type 2 diabetic patients with an initial creatinine clearance < 50 ml/min/1.73m(2) (n = 15, age 66 +/- 6 years) and >/= 50 ml/min/1.73m(2) respectively (n = 71, age 61 +/- 10 years). In addition, we also investigated the influence on the metabolic control and the blood pressure values in both groups of patients. In the patients with creatinine clearance >/= 50 ml/min/1,73m(2) the mean potassium level increased from 4.3 +/- 0.2 to 4.6 +/- 0.4 mmol/l (P < 0,01), while the incidence of a potassium level > 5 mmol/l was 17 %. In the group with a creatinine clearance < 50 ml/min/1.73m(2) the potassium level rose from 4.5 +/- 0.2 to 5.0 +/- 0.4 mmol/l (P < 0.01). The incidence of potassium levels > 5 mmol/l was 66 % (P < 0,01). In both patient groups the creatinine clearances did not change significantly during angiotensin-converting enzyme inhibition, and the urinary albumin excretion as well as the HbA(1c) values and blood pressure showed only a tendency towards a decrease. Long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetic patients leads to a significant increase in serum potassium. The incidence of hyperkalaemia with potassium levels > 5 mmol/l is significantly higher in the patients with initial creatinine clearance < 50 ml/min/1.73m(2). Severe hyperkalaemia with potassium levels > 6 mmol/l was not observed.

Impact of Postmastectomy Radiation on Locoregional Recurrence in Breast Cancer Patients With 1-3 Positive Lymph Nodes Treated With Modern Systemic Therapy

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

Tendulkar, Rahul D., E-mail: tendulr@ccf.org; Rehman, Sana; Shukla, Monica E.

2012-08-01

Purpose: Postmastectomy radiation therapy (PMRT) remains controversial for patients with 1-3 positive lymph nodes (LN+). Methods and Materials: We conducted a retrospective review of all 369 breast cancer patients with 1-3 LN+ who underwent mastectomy without neoadjuvant systemic therapy between 2000 and 2007 at Cleveland Clinic. Results: We identified 271 patients with 1-3 LN+ who did not receive PMRT and 98 who did receive PMRT. The median follow-up time was 5.2 years, and the median number of LN dissected was 11. Of those not treated with PMRT, 79% received adjuvant chemotherapy (of whom 70% received a taxane), 79% received hormonalmore » therapy, and 5% had no systemic therapy. Of the Her2/neu amplified tumors, 42% received trastuzumab. The 5-year rate of locoregional recurrence (LRR) was 8.9% without PMRT vs 0% with PMRT (P=.004). For patients who did not receive PMRT, univariate analysis showed 6 risk factors significantly (P<.05) correlated with LRR: estrogen receptor/progesterone receptor negative (hazard ratio [HR] 2.6), lymphovascular invasion (HR 2.4), 2-3 LN+ (HR 2.6), nodal ratio >25% (HR 2.7), extracapsular extension (ECE) (HR 3.7), and Bloom-Richardson grade III (HR 3.1). The 5-year LRR rate was 3.4% (95% confidence interval [CI], 0.1%-6.8%] for patients with 0-1 risk factor vs 14.6% [95% CI, 8.4%-20.9%] for patients with {>=}2 risk factors (P=.0006), respectively. On multivariate analysis, ECE (HR 4.3, P=.0006) and grade III (HR 3.6, P=.004) remained significant risk factors for LRR. The 5-year LRR was 4.1% in patients with neither grade III nor ECE, 8.1% with either grade III or ECE, and 50.4% in patients with both grade III and ECE (P<.0001); the corresponding 5-year distant metastasis-free survival rates were 91.8%, 85.4%, and 59.1% (P=.0004), respectively. Conclusions: PMRT offers excellent control for patients with 1-3 LN+, with no locoregional failures to date. Patients with 1-3 LN+ who have grade III disease and/or ECE should be strongly considered for PMRT.« less

Molecular identification of tuliposide B-converting enzyme: a lactone-forming carboxylesterase from the pollen of tulip.

PubMed

Nomura, Taiji; Murase, Tatsunori; Ogita, Shinjiro; Kato, Yasuo

2015-07-01

6-Tuliposides A (PosA) and B (PosB), which are the major secondary metabolites in tulip (Tulipa gesneriana), are enzymatically converted to the antimicrobial lactonized aglycons, tulipalins A (PaA) and B (PaB), respectively. We recently identified a PosA-converting enzyme (TCEA) as the first reported member of the lactone-forming carboxylesterases. Herein, we describe the identification of another lactone-forming carboxylesterase, PosB-converting enzyme (TCEB), which preferentially reacts with PosB to give PaB. This enzyme was isolated from tulip pollen, which showed high PosB-converting activity. Purified TCEB exhibited greater activity towards PosB than PosA, which was contrary to that of the TCEA. Novel cDNA (TgTCEB1) encoding the TCEB was isolated from tulip pollen. TgTCEB1 belonged to the carboxylesterase family and was approximately 50% identical to the TgTCEA polypeptides. Functional characterization of the recombinant enzyme verified that TgTCEB1 catalyzed the conversion of PosB to PaB with an activity comparable with the native TCEB. RT-qPCR analysis of each part of plant revealed that TgTCEB1 transcripts were limited almost exclusively to the pollen. Furthermore, the immunostaining of the anther cross-section using anti-TgTCEB1 polyclonal antibody verified that TgTCEB1 was specifically expressed in the pollen grains, but not in the anther cells. N-terminal transit peptide of TgTCEB1 was shown to function as plastid-targeted signal. Taken together, these results indicate that mature TgTCEB1 is specifically localized in plastids of pollen grains. Interestingly, PosB, the substrate of TgTCEB1, accumulated on the pollen surface, but not in the intracellular spaces of pollen grains. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

An Image Morphing Technique Based on Optimal Mass Preserving Mapping

DTIC Science & Technology

2007-06-01

Yan Yang, Steven Haker , and Allen Tannenbaum Abstract—Image morphing, or image interpolation in the time domain, deals with the metamorphosis of one...of Technology, Atlanta, GA 30332 USA (e-mail: zlzl@ece.gatech.edu; zhulei1976@hotmail.com; yan.yang@gatech.edu; tannenba@ece.gatech.edu). S. Haker is...with the Surgical Planning Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115 USA (e-mail: haker @bwh.harvard.edu

A Prospective Multi-center Trial of Escherichia coli Extract for the Prophylactic Treatment of Patients with Chronically Recurrent Cystitis

PubMed Central

Kim, Kun Suk; Kim, Ji-Yoon; Jeong, In Gab; Paick, Jae-Seung; Son, Hwancheol; Lim, Dae Jung; Shim, Hong Bang; Park, Won Hee; Jung, Hee Chang

2010-01-01

We have assessed the efficacy and safety of Escherichia coli extract (ECE; Uro-Vaxom®) which contains active immunostimulating fractions, in the prophylactic treatment of chronically recurrent cystitis. Forty-two patients with more than 2 episodes of cystitis in the proceeding 6 months were treated for 3 months with one capsule daily of ECE and observed for a further 6 months. The primary efficacy criterion was the number of episodes of recurrent cystitis during the 6 months after treatment compared to those during the 6 months before treatment. At the end of the 9-month trial, 34 patients (all women) were eligible for statistical analysis. Their mean age was 56.4 yr (range, 34-75 yr), and they had experienced recurrent urinary tract infections for 7.2±5.2 yr. The number of recurrences was significantly lower during the 6-month follow-up period than during the 6 months preceding the trial (0.35 vs. 4.26, P<0.001). During the follow-up, 28 (82.4%) patients had no recurrences and 4 (11.8%) had 1 each. In patients who relapsed, ECE alleviated cystitis symptoms, including painful voiding, frequency and urgency. There were no serious adverse events related to the study drug. Our study demonstrates the efficacy and safety of ECE in the prophylactic treatment of chronically recurrent cystitis. PMID:20191044

External Validation of the Updated Partin Tables in a Cohort of French and Italian Men

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

Bhojani, Naeem; Department of Urology, University of Montreal, Montreal, PQ; Salomon, Laurent

2009-02-01

Purpose: To test the discrimination and calibration properties of the newly developed 2007 Partin Tables in two European cohorts with localized prostate cancer. Methods: Data on clinical and pathologic characteristics were obtained for 1,064 men treated with radical prostatectomy at the Creteil University Health Center in France (n = 839) and at the Milan University Vita-Salute in Italy (n = 225). Overall discrimination was assessed with receiver operating characteristic curve analysis, which quantified the accuracy of stage predictions for each center. Calibration plots graphically explored the relationship between predicted and observed rates of extracapsular extension (ECE), seminal vesicle invasion (SVI)more » and lymph node invasion (LNI). Results: The rates of ECE, SVI, and LNI were 28%, 14%, and 2% in the Creteil cohort vs. 11%, 5%, and 5% in the Milan cohort. In the Creteil cohort, the accuracy of ECE, SVI, and LNI prediction was 61%, 71%, and 82% vs. 66%, 92% and 75% for the Milan cohort. Important departures were recorded between Partin Tables' predicted and observed rates of ECE, SVI, and LNI within both cohorts. Conclusions: The 2007 Partin Tables demonstrated worse performance in European men than they originally did in North American men. This indicates that predictive models need to be externally validated before their implementation into clinical practice.« less

Detection of bluetongue virus in the blood of inoculated calves: comparison of virus isolation, PCR assay, and in vitro feeding of Culicoides variipennis.

PubMed

MacLachlan, N J; Nunamaker, R A; Katz, J B; Sawyer, M M; Akita, G Y; Osburn, B I; Tabachnick, W J

1994-01-01

The interval after infection when bluetongue virus (BTV) was present in the blood of calves inoculated with BTV serotype 10 (BTV 10) was evaluated by virus isolation (VI) in embryonated chicken eggs (ECE), BTV-specific polymerase chain reaction (PCR), and in vitro blood feeding of vector Culicoides variipennis (C.v.) sonorensis. BTV nucleic acid was detected by PCR in blood cells for 16 to 20 weeks after infection whereas infectious virus was detected by VI in ECE for 2 to 8 weeks. BTV was detected in calf blood by in vitro feeding of C.v. sonorensis for only 0 to 2 weeks after inoculation of calves with BTV 10. Selected bloods which were positive by PCR analysis but not by VI in ECE were not infectious for sheep. The data are consistent with the hypothesis that prolonged viremia in BTV-infected cattle results from association of the virus with blood cells, especially erythrocytes. The fact that calf blood that contained viral nucleic acid as determined by PCR analysis, but not infectious virus as determined by VI in ECE, was not infectious for either the insect vector or sheep suggests that cattle whose blood contains BTV nucleic acid but not infectious virus are unimportant to the epidemiology of BTV infection.

Electroclinic effect in the chiral lamellar α phase of a lyotropic liquid crystal

NASA Astrophysics Data System (ADS)

Harjung, Marc D.; Giesselmann, Frank

2018-03-01

In thermotropic chiral Sm -A* phases, an electric field along the smectic layers breaks the D∞ symmetry of the Sm -A* phase and induces a tilt of the liquid crystal director. This so-called electroclinic effect (ECE) was first reported by Garoff and Meyer in 1977 and attracted substantial scientific and technological interest due to its linear and submicrosecond electro-optic response [S. Garoff and R. B. Meyer, Phys. Rev. A 19, 338 (1979), 10.1103/PhysRevA.19.338]. We now report the observation of an ECE in the pretransitional regime from a lyotropic chiral lamellar Lα* phase into a lyo-Sm -C* phase, the lyotropic analog to the thermotropic Sm -C* phase which was recently discovered by Bruckner et al. [Angew. Chem. Int. Ed. 52, 8934 (2013), 10.1002/anie.201303344]. We further show that the observed ECE has all signatures of its thermotropic counterpart, namely (i) the effect is chiral in nature and vanishes in the racemic Lα phase, (ii) the effect is essentially linear in the sign and magnitude of the electric field, and (iii) the magnitude of the effect diverges hyperbolically as the temperature approaches the critical temperature of the second order tilting transition. Specific deviations between the ECEs in chiral lamellar and chiral smectic phases are related to the internal field screening effect of electric double layers formed by inevitable ionic impurities in lyotropic phases.

Detailed Performance Assessment for the ITER ECE Diagnostic

NASA Astrophysics Data System (ADS)

Rowan, W.; Austin, M.; Houshmandyar, S.; Phillips, P.; Beno, J.; Bryant, A.; Ouroua, A.; Weeks, D.; Hubbard, A.; Taylor, G.

2017-10-01

One of the primary diagnostics for electron temperature (Te) measurement on ITER is based on the detection of electron cyclotron emission (ECE) Here we describe the predicted performance of the newly completed ECE diagnostic design by quantitatively following the emission from the plasma to the instruments and including the calibration method to assess accuracy. Operation of the diagnostic at 5.3 T is the main interest here but critical features of the emission spectra for 2.65 T and 1.8 T will be described. ECE will be collected by two very similar optical systems: one a radial view, the other an oblique view. Both measurements are used for Te while the oblique view also allows detection of non-thermal distortion in the electron distribution. An in-vacuum calibration source is included in the front end of each view to calibrate out the effect of any degradation of in-vessel optics. Following collection, the emission is split into orthogonal polarizations and transmitted to the detection instruments via waveguides filled with dry nitrogen, a choice that simplifies construction and analysis. Near the instruments, a switchyard is used to select which polarization and view is detected by each instrument. The design for the radiometer used for 5.3 T will be described in detail. Supported by PPPL/US-DA via subcontract S013464-H to UT Austin.

Transfer of Timing Information from RGC to LGN Spike Trains

NASA Astrophysics Data System (ADS)

Teich, Malvin C.; Lowen, Steven B.; Saleh, Bahaa E. A.; Kaplan, Ehud

1998-03-01

We have studied the firing patterns of retinal ganglion cells (RGCs) and their target lateral geniculate nucleus (LGN) cells. We find that clusters of spikes in the RGC neural firing pattern appear at the LGN output essentially unchanged, while isolated RGC firing events are more likely to be eliminated; thus the LGN action-potential sequence is therefore not merely a randomly deleted version of the RGC spike train. Employing information-theoretic techniques we developed for point processes,(B. E. A. Saleh and M. C. Teich, Phys. Rev. Lett.) 58, 2656--2659 (1987). we are able to estimate the information efficiency of the LGN neuronal output --- the proportion of the variation in the LGN firing pattern that carries information about its associated RGC input. A suitably modified integrate-and-fire neural model reproduces both the enhanced clustering in the LGN data (which accounts for the increased coefficient of variation) and the measured value of information efficiency, as well as mimicking the results of other observed statistical measures. Reliable information transmission therefore coexists with fractal fluctuations, which appear in RGC and LGN firing patterns.(M. C. Teich, C. Heneghan, S. B. Lowen, T. Ozaki, and E. Kaplan, J. Opt. Soc. Am. A) 14, 529--546 (1997).

EI-2128-1, a novel interleukin-1beta converting enzyme inhibitor produced by Penicillium sp. E-2128.

PubMed

Koizumi, Fumito; Agatsuma, Tsutomu; Ando, Katsuhiko; Kondo, Hidemasa; Saitoh, Yutaka; Matsuda, Yuzuru; Nakanishi, Satoshi

2003-11-01

EI-2128-1, a novel interleukin-1beta converting enzyme (ICE) inhibitor, was isolated from the culture broths of Penicillium sp. E-2128. EI-2128-1 selectively inhibited human recombinant ICE activity with IC50 value of 0.59 microM, without inhibiting elastase and cathepsin B. EI-2128-1 also inhibited mature interleukin-1beta secretion from THP-1 cells induced by LPS with IC50 value of 0.28 microM.

21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) This enzyme preparation is derived from the nonpathogenic, nontoxicogenic yeast Kluyveromyces lactis... 683), which converts lactose to glucose and galactose. It is prepared from yeast that has been grown...

Use of the Environment and Policy Evaluation and Observation as a Self-Report Instrument (EPAO-SR) to measure nutrition and physical activity environments in child care settings: validity and reliability evidence.

PubMed

Ward, Dianne S; Mazzucca, Stephanie; McWilliams, Christina; Hales, Derek

2015-09-26

Early care and education (ECE) centers are important settings influencing young children's diet and physical activity (PA) behaviors. To better understand their impact on diet and PA behaviors as well as to evaluate public health programs aimed at ECE settings, we developed and tested the Environment and Policy Assessment and Observation - Self-Report (EPAO-SR), a self-administered version of the previously validated, researcher-administered EPAO. Development of the EPAO-SR instrument included modification of items from the EPAO, community advisory group and expert review, and cognitive interviews with center directors and classroom teachers. Reliability and validity data were collected across 4 days in 3-5 year old classrooms in 50 ECE centers in North Carolina. Center teachers and directors completed relevant portions of the EPAO-SR on multiple days according to a standardized protocol, and trained data collectors completed the EPAO for 4 days in the centers. Reliability and validity statistics calculated included percent agreement, kappa, correlation coefficients, coefficients of variation, deviations, mean differences, and intraclass correlation coefficients (ICC), depending on the response option of the item. Data demonstrated a range of reliability and validity evidence for the EPAO-SR instrument. Reporting from directors and classroom teachers was consistent and similar to the observational data. Items that produced strongest reliability and validity estimates included beverages served, outside time, and physical activity equipment, while items such as whole grains served and amount of teacher-led PA had lower reliability (observation and self-report) and validity estimates. To overcome lower reliability and validity estimates, some items need administration on multiple days. This study demonstrated appropriate reliability and validity evidence for use of the EPAO-SR in the field. The self-administered EPAO-SR is an advancement of the measurement of ECE settings and can be used by researchers and practitioners to assess the nutrition and physical activity environments of ECE settings.

Can animal habitat use patterns influence their vulnerability to extreme climate events? An estuarine sportfish case study.

PubMed

Boucek, Ross E; Heithaus, Michael R; Santos, Rolando; Stevens, Philip; Rehage, Jennifer S

2017-10-01

Global climate forecasts predict changes in the frequency and intensity of extreme climate events (ECEs). The capacity for specific habitat patches within a landscape to modulate stressors from extreme climate events, and animal distribution throughout habitat matrices during events, could influence the degree of population level effects following the passage of ECEs. Here, we ask (i) does the intensity of stressors of an ECE vary across a landscape? And (ii) Do habitat use patterns of a mobile species influence their vulnerability to ECEs? Specifically, we measured how extreme cold spells might interact with temporal variability in habitat use to affect populations of a tropical, estuarine-dependent large-bodied fish Common Snook, within Everglades National Park estuaries (FL US). We examined temperature variation across the estuary during cold disturbances with different degrees of severity, including an extreme cold spell. Second, we quantified Snook distribution patterns when the passage of ECEs is most likely to occur from 2012 to 2016 using passive acoustic tracking. Our results revealed spatial heterogeneity in the intensity of temperature declines during cold disturbances, with some habitats being consistently 3-5°C colder than others. Surprisingly, Snook distributions during periods of greatest risk to experience an extreme cold event varied among years. During the winters of 2013-2014 and 2014-2015 a greater proportion of Snook occurred in the colder habitats, while the winters of 2012-2013 and 2015-2016 featured more Snook observed in the warmest habitats. This study shows that Snook habitat use patterns could influence vulnerability to extreme cold events, however, whether Snook habitat use increases or decreases their vulnerability to disturbance depends on the year, creating temporally dynamic vulnerability. Faunal global change research should address the spatially explicit nature of extreme climate events and animal habitat use patterns to identify potential mechanisms that may influence population effects following these disturbances. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Enzymes: A Workshop for Secondary School Students.

ERIC Educational Resources Information Center

Bering, C. Larry

1994-01-01

Describes the weekend science workshop on enzymes and includes several projects that involve students directly, parts of which can be incorporated into a traditional chemistry, biology, or physical science course at the secondary level. Subjects include catalysts and catalytic converters in cars, enzymes as consumer products and in industrial…

More Nuts and Bolts of Michaelis-Menten Enzyme Kinetics

ERIC Educational Resources Information Center

Lechner, Joseph H.

2011-01-01

Several additions to a classroom activity are proposed in which an "enzyme" (the student) converts "substrates" (nut-bolt assemblies) into "products" (separated nuts and bolts) by unscrewing them. (Contains 1 table.)

Investigation into the Mechanism of Homo- and Heterodimerization of Angiotensin-Converting Enzyme.

PubMed

Abrie, J Albert; Moolman, Wessel J A; Cozier, Gyles E; Schwager, Sylva L; Acharya, K Ravi; Sturrock, Edward D

2018-04-01

Angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system (RAS), which is primarily responsible for blood pressure homeostasis. Studies have shown that ACE inhibitors yield cardiovascular benefits that cannot be entirely attributed to the inhibition of ACE catalytic activity. It is possible that these benefits are due to interactions between ACE and RAS receptors that mediate the protective arm of the RAS, such as angiotensin II receptor type 2 (AT 2 R) and the receptor MAS. Therefore, in this study, we investigated the molecular interactions of ACE, including ACE homodimerization and heterodimerization with AT 2 R and MAS, respectively. Molecular interactions were assessed by fluorescence resonance energy transfer and bimolecular fluorescence complementation in human embryonic kidney 293 cells and Chinese hamster ovary-K1 cells transfected with vectors encoding fluorophore-tagged proteins. The specificity of dimerization was verified by competition experiments using untagged proteins. These techniques were used to study several potential requirements for the germinal isoform of angiotensin-converting enzyme expressed in the testes (tACE) dimerization as well as the effect of ACE inhibitors on both somatic isoforms of angiotensin-converting enzyme expressed in the testes (sACE) and tACE dimerization. We demonstrated constitutive homodimerization of sACE and of both of its domains separately, as well as heterodimerization of both sACE and tACE with AT 2 R, but not MAS. In addition, we investigated both soluble sACE and the sACE N domain using size-exclusion chromatography-coupled small-angle X-ray scattering and we observed dimers in solution for both forms of the enzyme. Our results suggest that ACE homo- and heterodimerization does occur under physiologic conditions. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Channel microband electrode arrays for mechanistic electrochemistry. Two-dimensional voltammetry:  transport-limited currents.

PubMed

Alden, J A; Feldman, M A; Hill, E; Prieto, F; Oyama, M; Coles, B A; Compton, R G; Dobson, P J; Leigh, P A

1998-05-01

A channel electrode array, with electrodes ranging in size from the millimeter to the submicrometer scale, is used for the amperometric interrogation of mechanistically complex electrode processes. In this way, the transport-limited current, measured as a function of both electrode size and electrolyte flow rate (convection), is shown to provide a highly sensitive probe of mechanism and kinetics. The application of "two-dimensional voltammetry" to diverse electrode processes, including E, ECE, ECEE, EC', and DISP2 reactions, is reported.

Stepping Up Together: Financing Early Care and Education in the 21st Century. Volume 2. Proceedings for "Making It Economically Viable: Financing Early Care and Education." A Working Meeting (Santa Cruz, California, March 3-5, 1999).

ERIC Educational Resources Information Center

National Association of Child Advocates, Washington, DC.

The need for an adequate financial base for the future of quality early care and education (ECE) for young children is being increasingly recognized. This document presents the proceedings for a 1999 working meeting of individuals from diverse fields to identify and explore possible actions related to financing ECE for children birth through 5…

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

PubMed Central

Gilbert, Cameron; Wald, Ron; Bell, Chaim; Perl, Jeff; Juurlink, David; Beyene, Joseph; Shah, Prakesh S

2012-01-01

Objective To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011. Study selection Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes. Results 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89). Conclusion Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels. PMID:22232539

EFFECT OF SYSTEMIC BETA-BLOCKERS, ACE INHIBITORS, AND ANGIOTENSIN RECEPTOR BLOCKERS ON DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION.

PubMed

Thomas, Akshay S; Redd, Travis; Hwang, Thomas

2015-10-01

Recent studies have suggested that the use of systemic beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models. The purpose of this study is to evaluate if these agents have a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration. In this single-center retrospective case-control study, the charts of 250 patients with neovascular age-related macular degeneration were compared with those of 250 controls with dry age-related macular degeneration. Charts were reviewed for current and past use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Frequency tables were generated, and associations were examined using chi-square tests, t-tests, and multivariate logistic regression. There was no statistically significant difference between rates of beta-blocker use (P = 0.57), angiotensin-converting enzyme inhibitors use (P = 0.20), or angiotensin receptor blockers use (P = 0.61) between the 2 groups. Additionally, there was no statistically significant difference between rates of use of combinations of the above drugs between the two groups. Although there is growing evidence that beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models, these medications do not seem to confer a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration.

Degradation of neurotensin by rat brain synaptic membranes: involvement of a thermolysin-like metalloendopeptidase (enkephalinase), angiotensin-converting enzyme, and other unidentified peptidases.

PubMed

Checler, F; Vincent, J P; Kitabgi, P

1983-08-01

Neurotensin was inactivated by membrane-bound and soluble degrading activities present in purified preparations of rat brain synaptic membranes. Degradation products were identified by HPLC and amino acid analysis. The major points of cleavage of neurotensin were the Arg8-Arg9, Pro10-Tyr11, and Tyr11-Ile12 peptide bonds with the membrane-bound activity and the Arg8-Arg9 and Pro10-Tyr11 bonds with the soluble activity. Several lines of evidence indicated that the cleavage of the Arg8-Arg9 bond by the membrane-bound activity resulted mainly from the conversion of neurotensin1-10 to neurotensin1-8 by a dipeptidyl carboxypeptidase. In particular, captopril inhibited this cleavage with an IC50 (5.7 nM) close to its K1 (7 nM) for angiotensin-converting enzyme. Thiorphan inhibited the cleavage at the Tyr11-Ile12 bond by the membrane-bound activity with an IC50 (17 nM) similar to its K1 (4.7 nM) for enkephalinase. Both cleavages were inhibited by 1,10-phenanthroline. These and other data suggested that angiotensin-converting enzyme and a thermolysin-like metalloendopeptidase (enkephalinase) were the membrane-bound peptidases responsible for cleavages at the Arg8-Arg9 and Tyr11-Ile12 bonds, respectively. In contrast, captopril had no effect on the cleavage at the Arg8-Arg9 bond by the soluble activity, indicating that the enzyme responsible for this cleavage was different from angiotensin-converting enzyme. The cleavage at the Pro10-Tyr11 bond by both the membrane-bound and the soluble activities appeared to be catalyzed by an endopeptidase different from known brain proline endopeptidases. The possibility is discussed that the enzymes described here participate in physiological mechanisms of neurotensin inactivation at the synaptic level.

21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., nontoxicogenic yeast C. pseudotropicalis. It contains the enzyme lactase (β-D-galactoside galactohydrolase, EC 3.2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been...

21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., nontoxicogenic yeast C. pseudotropicalis. It contains the enzyme lactase (β-D-galactoside galactohydrolase, EC 3.2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been...

Genetics Home Reference: Crigler-Najjar syndrome

MedlinePlus

... from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form ... the body. The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers ...

Understanding the bursty electron cyclotron emission during a sawtooth crash in the HT-7 tokamak

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

Li, Erzhong, E-mail: rzhonglee@ipp.ac.cn; Hu, Liqun; Chen, Kaiyun

2014-01-15

Bursts in electron cyclotron emission (ECE) were observed during sawtooth crashes in HT-7 in discharges with ion cyclotron resonance heating injected near the q = 1 rational surface (q is the safety factor). The local ECE measurement indicated that the bursty radiation is only observed on channels near but a little away outward from the q = 1 magnetic surface. In conjunction with the soft x-ray tomography analysis, it was determined that, for the first time, only a compression process survives in the later stage of fast magnetic reconnection but before prompt heat transport. The compression enhanced the electron radiation temperature, the increased amplitudemore » of which agreed well with the estimation according to a kinetic compression theory model [R. J. Hastie and T. C. Hender, Nucl. Fusion 28, 585 (1988)]. This paper presents the experimental evidence that there indeed exists a transient compression phase which results in the bursty ECE radiation during a sawtooth crash.« less

Effect of ultrasound on electrochemical chloride extraction from mortar

NASA Astrophysics Data System (ADS)

Chen, Yiqun; Yao, Wu; Zuo, Junqing

2018-03-01

In this paper, the effect of auxiliary ultrasound on electrochemical chloride extraction (ECE) was studied. The chloride removal efficiency was investigated by examining the chloride content with ultrasound-assisted ECE and changing the introducing time of ultrasound. The experimental results showed that removal of chloride ions was noted to be more effective in ECE treatment assisted with ultrasound treatment (UT). In addition, the lower w/c ratio led to more distinct effect of ultrasonic cavitation on chloride removal. Electrochemical behaviors measured with different treatment revealed that UT treatment was effective on moderating the corrosion condition. Microstructural analyses revealed a significant alteration in composition and morphology of cementitious phases with UT treatment. Pull-out tests indicated that ultrasound had a certain negative impact on the bond strength. Although the effect of introducing ultrasound in the first 2 weeks or the last 2 weeks on the extraction efficiency was not obvious, intermittent ultrasound could not only ensure the chloride extraction efficiency, but also reduce the adverse effect of ultrasound on the bond strength.

In silico prediction of potential chemical reactions mediated by human enzymes.

PubMed

Yu, Myeong-Sang; Lee, Hyang-Mi; Park, Aaron; Park, Chungoo; Ceong, Hyithaek; Rhee, Ki-Hyeong; Na, Dokyun

2018-06-13

Administered drugs are often converted into an ineffective or activated form by enzymes in our body. Conventional in silico prediction approaches focused on therapeutically important enzymes such as CYP450. However, there are more than thousands of different cellular enzymes that potentially convert administered drug into other forms. We developed an in silico model to predict which of human enzymes including metabolic enzymes as well as CYP450 family can catalyze a given chemical compound. The prediction is based on the chemical and physical similarity between known enzyme substrates and a query chemical compound. Our in silico model was developed using multiple linear regression and the model showed high performance (AUC = 0.896) despite of the large number of enzymes. When evaluated on a test dataset, it also showed significantly high performance (AUC = 0.746). Interestingly, evaluation with literature data showed that our model can be used to predict not only enzymatic reactions but also drug conversion and enzyme inhibition. Our model was able to predict enzymatic reactions of a query molecule with a high accuracy. This may foster to discover new metabolic routes and to accelerate the computational development of drug candidates by enabling the prediction of the potential conversion of administered drugs into active or inactive forms.

Targeted enzyme prodrug therapies.

PubMed

Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

2010-09-01

The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

Biosynthesis of the enzymes of the cellulase system by T. Reesei QM 9414 in the presence of sophorose

NASA Astrophysics Data System (ADS)

Gritzali, M.

1982-12-01

As conventional, nonrenewable energy sources are rapidly depleted and it was necessary to search for alternative sources of energy. It was increasingly apparent that biomass and waste are alternatives well worth exploring. The sources of biomass and wastes that considered for conversion to useful products are quite diverse, but the most abundant constituent of almost every type is cellulose. Cellulose is cleanly converted to soluble fermentable sugars enzymatically, and cellulose enzymes were isolated from a number of microbial sources. It is generally agreed that the most effective system of enzymes for the conversion of cellulose to glucose is produced by species of the imperfect fungus Trichoderma. The mutant organism Trichoderma reesei QM 9414 is among the best producers of high levels of enzymes; these are extracellular and have carbonhydrate covalently bound to the peptide. Trichoderma produces three types of enzymes which, in a sequential and cooperative manner, convert cellulose to soluble oligosaccharides and glucose.

Potential utility of natural products as regulators of breast cancer-assoicated aromatase promoters

USDA-ARS?s Scientific Manuscript database

Aromatase, the key enzyme in estrogen biosynthesis, converts androstenedione to estrone and testosterone to estradiol. The enzyme is expressed in various tissues such as ovary, placenta, bone, brain, skin, and adipose tissue. Aromatase enzyme is encoded by a single gene CYP 19A1 and its expression i...

The Nuts and Bolts of Michaelis-Menten Enzyme Kinetics: Suggestions and Clarifications

ERIC Educational Resources Information Center

Silverstein, Todd

2011-01-01

Matthew Junker's recent article describes a useful and effective enzyme kinetics application and analogy in which students simulate enzyme activity by unscrewing nut-bolt "substrate molecules", thus, converting them into separate nuts and bolts "products". A number of suggestions and corrections are presented that improve the clarity and accuracy…

Efficient conversion of mannitol derived from brown seaweed to fructose for fermentation with a thraustochytrid.

PubMed

Tajima, Takahisa; Tomita, Kousuke; Miyahara, Hiroyuki; Watanabe, Kenshi; Aki, Tsunehiro; Okamura, Yoshiko; Matsumura, Yukihiko; Nakashimada, Yutaka; Kato, Junichi

2018-02-01

Macroalgae are a promising biomass feedstock for energy and valuable chemicals. Mannitol and alginate are the major carbohydrates found in the microalga Laminaria japonica (Konbu). To convert mannitol to fructose for its utilization as a carbon source in mannitol non-assimilating bacteria, a psychrophile-based simple biocatalyst (PSCat) was constructed using a psychrophile as a host by expressing mesophilic enzymes, including mannitol 2-dehydrogenase for mannitol oxidation, and NADH oxidase and alkyl hydroxyperoxide reductase for NAD + regeneration. PSCat was treated at 40 °C to inactivate the psychrophilic enzymes responsible for byproduct formation and to increase the membrane permeability of the substrate. PSCat efficiently converted mannitol to fructose with high conversion yield without additional input of NAD + . Konbu extract containing mannitol was converted to fructose with hydroperoxide scavenging, inhibiting the mannitol dehydrogenase activity. Auranthiochytrium sp. could grow well in the presence of fructose converted by PSCat. Thus, PSCat is a potential carbohydrate converter for mannitol non-assimilating microorganism. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Elastic Cherenkov effects in transversely isotropic soft materials-I: Theoretical analysis, simulations and inverse method

NASA Astrophysics Data System (ADS)

Li, Guo-Yang; Zheng, Yang; Liu, Yanlin; Destrade, Michel; Cao, Yanping

2016-11-01

A body force concentrated at a point and moving at a high speed can induce shear-wave Mach cones in dusty-plasma crystals or soft materials, as observed experimentally and named the elastic Cherenkov effect (ECE). The ECE in soft materials forms the basis of the supersonic shear imaging (SSI) technique, an ultrasound-based dynamic elastography method applied in clinics in recent years. Previous studies on the ECE in soft materials have focused on isotropic material models. In this paper, we investigate the existence and key features of the ECE in anisotropic soft media, by using both theoretical analysis and finite element (FE) simulations, and we apply the results to the non-invasive and non-destructive characterization of biological soft tissues. We also theoretically study the characteristics of the shear waves induced in a deformed hyperelastic anisotropic soft material by a source moving with high speed, considering that contact between the ultrasound probe and the soft tissue may lead to finite deformation. On the basis of our theoretical analysis and numerical simulations, we propose an inverse approach to infer both the anisotropic and hyperelastic parameters of incompressible transversely isotropic (TI) soft materials. Finally, we investigate the properties of the solutions to the inverse problem by deriving the condition numbers in analytical form and performing numerical experiments. In Part II of the paper, both ex vivo and in vivo experiments are conducted to demonstrate the applicability of the inverse method in practical use.

Edible gardens in early childhood education settings in Aotearoa, New Zealand.

PubMed

Dawson, A; Richards, R; Collins, C; Reeder, A I; Gray, A

2013-12-01

This paper aims to explore the presence and role of edible gardens in Aotearoa/New Zealand Early Childhood Education Services (ECES). Participant ECES providers were identified from the Ministry of Education database of Early Childhood Education Services (March 2009). These include Education and Care and Casual Education and Care, Kindergarten, Home-based Education and Care services, Playcentres, Te Kōhanga Reo. A structured, self-administered questionnaire was sent to the Principal or Head Teacher of the service. Of the 211 ECES that responded (55% response rate), 71% had edible gardens, incorporating vegetables, berry fruit, tree fruit, edible flowers and nut trees. Garden activities were linked with teaching across all strands of the New Zealand early childhood curriculum. In addition, 34% provided guidance on using garden produce and 30% linked the garden with messages on fruit and vegetable consumption. Most gardens were established recently (past 2 years) and relied on financial and non-financial support from parents, teachers and community organisations. Barriers included a lack of funding, space, time and staff support. Study findings suggest that gardens are already being used as a versatile teaching tool in many ECES settings. Most gardens are new, with a need to support the sustainability and workforce development among teachers and parents in order to be able to maintain these resources for future generations. SO WHAT?: Given the inherent links between gardening and healthy food and exercise, there seem to be extensive opportunities for health promotion aligned with the edible garden movement.

Endovascular coil embolization of aneurysm neck for the treatment of ruptured intracranial aneurysm with bleb formation

PubMed Central

Wan, Jun; Gu, Weijin; Zhang, Xiaolong; Geng, Daoying; Lu, Gang; Huang, Lei; Zhang, Lei; Ge, Liang; Ji, Lihua

2014-01-01

Background Ruptured intracranial aneurysm (ICA) with bleb formation (RICABF) is a special type of ruptured ICA. However, the exact role and effectiveness of endovascular coil embolization (ECE) in RICABF is unknown. We aimed to investigate the effectiveness and safety of ECE of aneurysm neck for RICABF treatment. Material/Methods We retrospectively assessed consecutive patients who were hospitalized in our endovascular intervention center between October 2004 and May 2012. Overall, 86 patients underwent ECE of aneurysm neck for 86 RICABF. Treatments outcomes included secondary rupture/bleeding rate, aneurysm neck embolization rate, residual/recurrent aneurysm, intraoperative incidents, and post-embolization complications, as well as improvements in the Glasgow outcome scale (extended) (GOS-E). Results Complete occlusion was achieved in 72 aneurysms (72/86, 83.7%), while 12 aneurysms (12/86, 14.0%) had a residual neck, and 2 aneurysms (2/86, 2.3%) had a residual aneurysm. The postoperative GOS-E was 3 in 3 patients (3.5%), 4 in 10 patients (11.6%), and 5 in 73 patients (84.9%). Follow-up angiography was performed in all patients (mean 9.0 months, interquartile range of 9.0). Recurrence was found in 3 patients (3/86, 3.5%). No aneurysm rupture or bleeding was reported. Conclusions Our mid-term follow-up study showed that ECE of aneurysm neck was an effective and safe treatment modality for RICABF. The long-term effectiveness and safety of this interventional radiology technique need to be investigated in prospective and comparative studies. PMID:24986761

Primary Systemic Amyloidosis and High Levels of Angiotensin-Converting Enzyme: Two Case Reports

PubMed Central

Praena-Segovia, J.; Sanchez-Gastaldo, A.; Bernabeu-Wittel, M.; Ocete-Pérez, R.; Ávila-Polo, R.; Martino, M. L.

2013-01-01

Infiltrative heart diseases are caused by a heterogeneous group of disorders; amyloidosis and sarcoidosis are two frequent causes of myocardial infiltration, which differ in clinical and biological outcome and treatment issues. The presence of high levels of angiotensin-converting enzyme (ACE) in a patient with infiltrative heart disease may increase suspicion of sarcoidosis. Nevertheless, no mention about increased ACE levels in extracerebral primary systemic amyloidosis is available. We present two cases of primary systemic amyloidosis, which are cardiac involvement and elevated ACE levels. PMID:24826302

Bronchoalveolar lavage, serum angiotensin-converting enzyme, and /sup 67/Ga scanning in extrathoracic sarcoidosis

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

Wallaert, B.; Ramon, P.; Fournier, E.

1982-11-01

Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis.

Improvement on sugar cane bagasse hydrolysis using enzymatic mixture designed cocktail.

PubMed

Bussamra, Bianca Consorti; Freitas, Sindelia; Costa, Aline Carvalho da

2015-01-01

The aim of this work was to study cocktail supplementation for sugar cane bagasse hydrolysis, where the enzymes were provided from both commercial source and microorganism cultivation (Trichoderma reesei and genetically modified Escherichia coli), followed by purification. Experimental simplex lattice mixture design was performed to optimize the enzymatic proportion. The response was evaluated through hydrolysis microassays validated here. The optimized enzyme mixture, comprised of T. reesei fraction (80%), endoglucanase (10%) and β-glucosidase (10%), converted, theoretically, 72% of cellulose present in hydrothermally pretreated bagasse, whereas commercial Celluclast 1.5L converts 49.11%±0.49. Thus, a rational enzyme mixture designed by using synergism concept and statistical analysis was capable of improving biomass saccharification. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigating a Bio-Engineered Enzyme.

ERIC Educational Resources Information Center

Bullerwell, Lornie; And Others

1994-01-01

Describes science experiments with the enzyme lactose, which is available commercially as Lactaid and Dairy Ease. Experiments show how the rate of reaction of lactose converted to glucose and galactose is influenced by temperature, pH, and substrate concentration. (PR)

Enzymatic activity and partial purification of solanapyrone synthase: first enzyme catalyzing Diels-Alder reaction.

PubMed

Katayama, K; Kobayashi, T; Oikawa, H; Honma, M; Ichihara, A

1998-05-19

In cell-free extracts of Alternaria solani, an enzymatic activity converting prosolanapyrone II to solanapyrones A and D via oxidation and subsequent Diels-Alder reaction has been found. Chromatography with DEAE-Sepharose provided two active fractions, pools 1 and 2. The former fraction converted prosolanapyrone II to solanapyrones A and D in a ratio of 2.2:1 with optical purities of 99% and 45% ee, respectively. The latter fraction did so in a ratio of 7.6:1 with 99% and nearly 0% ee, respectively. The enzyme partially purified from pool 2 native molecular weight of 40-62 kD and a pl of 4.25. The high reactivity of prosolanapyrone III in aqueous solution and the chromatographic behavior of the enzyme in pool 2 suggest that a single enzyme catalyzes both the oxidation and Diels-Alder reaction.

A re-evaluation of the final step of vanillin biosynthesis in the orchid Vanilla planifolia.

PubMed

Yang, Hailian; Barros-Rios, Jaime; Kourteva, Galina; Rao, Xiaolan; Chen, Fang; Shen, Hui; Liu, Chenggang; Podstolski, Andrzej; Belanger, Faith; Havkin-Frenkel, Daphna; Dixon, Richard A

2017-07-01

A recent publication describes an enzyme from the vanilla orchid Vanilla planifolia with the ability to convert ferulic acid directly to vanillin. The authors propose that this represents the final step in the biosynthesis of vanillin, which is then converted to its storage form, glucovanillin, by glycosylation. The existence of such a "vanillin synthase" could enable biotechnological production of vanillin from ferulic acid using a "natural" vanilla enzyme. The proposed vanillin synthase exhibits high identity to cysteine proteases, and is identical at the protein sequence level to a protein identified in 2003 as being associated with the conversion of 4-coumaric acid to 4-hydroxybenzaldehyde. We here demonstrate that the recombinant cysteine protease-like protein, whether expressed in an in vitro transcription-translation system, E. coli, yeast, or plants, is unable to convert ferulic acid to vanillin. Rather, the protein is a component of an enzyme complex that preferentially converts 4-coumaric acid to 4-hydroxybenzaldehyde, as demonstrated by the purification of this complex and peptide sequencing. Furthermore, RNA sequencing provides evidence that this protein is expressed in many tissues of V. planifolia irrespective of whether or not they produce vanillin. On the basis of our results, V. planifolia does not appear to contain a cysteine protease-like "vanillin synthase" that can, by itself, directly convert ferulic acid to vanillin. The pathway to vanillin in V. planifolia is yet to be conclusively determined. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biocatalysis for the production of industrial products and functional foods from rice and other agricultural produce.

PubMed

Akoh, Casimir C; Chang, Shu-Wei; Lee, Guan-Chiun; Shaw, Jei-Fu

2008-11-26

Many industrial products and functional foods can be obtained from cheap and renewable raw agricultural materials. For example, starch can be converted to bioethanol as biofuel to reduce the current demand for petroleum or fossil fuel energy. On the other hand, starch can also be converted to useful functional ingredients, such as high fructose and high maltose syrups, wine, glucose, and trehalose. The conversion process involves fermentation by microorganisms and use of biocatalysts such as hydrolases of the amylase superfamily. Amylases catalyze the process of liquefaction and saccharification of starch. It is possible to perform complete hydrolysis of starch by using the fusion product of both linear and debranching thermostable enzymes. This will result in saving energy otherwise needed for cooling before the next enzyme can act on the substrate, if a sequential process is utilized. Recombinant enzyme technology, protein engineering, and enzyme immobilization are powerful tools available to enhance the activity of enzymes, lower the cost of enzyme through large scale production in a heterologous host, increase their thermostability, improve pH stability, enhance their productivity, and hence making it competitive with the chemical processes involved in starch hydrolysis and conversions. This review emphasizes the potential of using biocatalysis for the production of useful industrial products and functional foods from cheap agricultural produce and transgenic plants. Rice was selected as a typical example to illustrate many applications of biocatalysis in converting low-value agricultural produce to high-value commercial food and industrial products. The greatest advantages of using enzymes for food processing and for industrial production of biobased products are their environmental friendliness and consumer acceptance as being a natural process.

A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization.

PubMed

Wintroub, B U; Kaempfer, C E; Schechter, N M; Proud, D

1986-01-01

We have used a high performance liquid chromatography assay, which detects chymotryptic cleavage of the phe8-his9 bond of angiotensin I to yield angiotensin II, in order to examine human lung mast cells for the presence of chymotryptic activity. Mast cells, purified from human lung by enzymatic dispersion, countercurrent elutriation, and Percoll gradient centrifugation, were lysed or challenged with goat anti-human IgE. In multiple experiments angiotensin II-converting activity was detected in lysates of 10-99% pure mast cell preparations. Regression analysis of net percent release values of histamine and the angiotensin I-converting activity from dose-response experiments demonstrated a correlation between the two parameters, indicating that the chymotrypsin-like enzyme is a constituent of the mast cell secretory granule. The chymotryptic activity was completely inhibited by 10(-3) M phenylmethylsulfonylfluoride but not by 10(-3) M Captopril, and the pH optimum of activity was 7.5-9.5. Gel filtration of released material separated the activity from tryptase and demonstrated an approximate molecular weight of 30-35,000. The mast cell enzyme, like a human skin chymotrypsin-like proteinase, can be distinguished from leukocyte cathepsin G by lack of susceptibility to inhibition by bovine pancreatic trypsin inhibitor. Thus, an enzyme with limited chymotryptic specificity is present in human lung mast cells. The Michaelis constant of the enzyme for angiotensin I of 6.0 X 10(-5) M is similar to that of endothelial cell angiotensin-converting enzyme and is consistent with a reaction of physiologic importance.

Aedes aegypti juvenile hormone acid methyl transferase, the ultimate enzyme in the biosynthetic pathway of juvenile hormone III, exhibits substrate control

USDA-ARS?s Scientific Manuscript database

We report on the cloning, sequencing, characterization, 3D modeling and docking of Aedes aegypti juvenile hormone acid methyl transferase (AeaJHAMT), the enzyme that converts juvenile hormone acid (JHA) into juvenile hormone (JH). Purified recombinant AeaJHAMT was extensively characterized for enzym...

Arginine production in the neonate

USDA-ARS?s Scientific Manuscript database

Endogenous arginine synthesis in adults is a complex multiorgan process, in which citrulline is synthesized in the gut, enters the general circulation, and is converted into arginine in the kidney, by what is known as the intestinal-renal axis. In neonates, the enzymes required to convert citrulline...

Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats.

PubMed

Laughlin, M Harold; Padilla, Jaume; Jenkins, Nathan T; Thorne, Pamela K; Martin, Jeffrey S; Rector, R Scott; Akter, Sadia; Davis, J Wade

2015-09-15

Using next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of Otsuka Long Evans Tokushima Fatty (OLETF) rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). We hypothesized that the greatest effects of exercise would be in the gastrocnemius arterioles. Results show that EX caused the largest number of changes in gene expression in the soleus and white gastrocnemius 2a arterioles with little to no changes in the feed arteries. In contrast, SPRINT caused substantial changes in gene expression in the feed arteries. IPA canonical pathway analysis revealed 18 pathways with significant changes in gene expression when analyzed across vessels and revealed that EX induces increased expression of the following genes in all arterioles examined: Shc1, desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein binding protein, alpha (Gnat1), and Bcl2l1 and decreased expression of ubiquitin D (Ubd) and cAMP response element modulator (Crem). EX increased expression of endothelin converting enzyme (Ece1), Hsp90b, Fkbp5, and Cdcl4b in four of five arterioles. SPRINT had effects on expression of Crem, Dhh, Bcl2l1, and Ubd that were similar to EX. SPRINT also increased expression of Nfkbia, Hspa5, Tubb 2a and Tubb 2b, and Fkbp5 in all five arterioles and increased expression of Gnat1 in all but the soleus second-order arterioles. Many contractile and/or structural protein genes were increased by SPRINT in the gastrocnemius feed artery, but the same genes exhibited decreased expression in red gastrocnemius arterioles. We conclude that training-induced changes in arteriolar gene expression patterns differ by muscle fiber type composition and along the arteriolar tree.

The effect of angiotensin-converting enzyme inhibition throughout a superovulation protocol in ewes.

PubMed

Pereira, Alécio Matos; de Souza Júnior, Antônio; Machado, Fernanda Brandão; Gonçalves, Gleisy Kelly Neves; Feitosa, Lauro César Soares; Reis, Adelina Martha; Santos, Robson Augusto Souza; Honorato-Sampaio, Kinulpe; Costa, Amilton Raposo

2015-12-01

Many studies identified new components of the renin–angiotensin system (RAS), such as Angiotensin-(1-7) [Ang-(1–7)] and Angiotensin-converting enzyme type 2 (ACE2), in mammalian ovaries.We previously showed Angiotensin-Converting Enzyme (ACE) inhibition, which increases the level of Ang-(1–7), stimulated ovarian estradiol output in ewe after estrous synchronization. Considering that Ang-(1–7) stimulates ovarian function and elevated estradiol before ovulation is associated with increased chance of achieving pregnancy, the present study investigated whether ACE inhibition throughout a superovulation protocol in ewe might improve ovulation outcome. At first, immunohistochemistry in ovaries of nonpregnant ewes revealed localization of Angiotensin II (Ang II), Ang-(1–7) and ACE2 in theca cells of antral follicles and in corpus luteum. Ang II and Ang-(1–7)were also detected in follicular fluid (FF) by Radioimmunoassay (RIA). Enalapril treatment throughout the superovulation protocol decreased 17β-estradiol (E2) output and raised progesterone:estradiol (P4:E2) ratio without a direct influence on ovulation and quality of embryos.

Budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme upon high-altitude exposure.

PubMed

Li, Hui-Jie; Zheng, Cheng-Rong; Chen, Guo-Zhu; Qin, Jun; Zhang, Ji-Hang; Yu, Jie; Zhang, En-Hao; Huang, Lan

2016-01-01

Inhaled budesonide is a novel approach to prevent acute mountain sickness (AMS). However, its mechanism is not completely understood. We aimed to investigate the effects of budesonide and dexamethasone on renin-angiotensin-aldosterone system in AMS prevention. Data were obtained from a randomised controlled trial including 138 participants. The participants were randomly assigned to receive budesonide, dexamethasone or placebo as prophylaxis before they travelled to 3450 m altitude from 400 m by car. Their plasma concentrations of renin, angiotensin-converting enzyme (ACE) and aldosterone were measured at both altitudes. All parameters were comparable among the three groups at 400 m. After high-altitude exposure of 3450, renin in all groups increased significantly; the ACE, aldosterone concentrations, as well as the aldosterone/renin ratio, rose markedly in the dexamethasone and placebo groups but not in the budesonide group. Moreover, the aldosterone/renin ratio correlated closely with ACE concentration. Upon acute high-altitude exposure, budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme. © The Author(s) 2016.

Measurement of crude-cell-extract glycerol dehydratase activity in recombinant Escherichia coli using coupled-enzyme reactions.

PubMed

Sankaranarayanan, Mugesh; Seol, Eunhee; Kim, Yeonhee; Chauhan, Ashish Singh; Park, Sunghoon

2017-03-01

Glycerol dehydratase (GDHt), which converts glycerol to 3-hydroxypropionaldehyde, is essential to the production of 1,3-propanediol (1,3-PDO) or 3-hydroxypropionic acid (3-HP). A reliable GDHt activity assay in crude-cell extract was developed. In the assay, GDHt converted 1,2-propanediol (1,2-PDO) to propionaldehyde, which was further converted to 1-propionic acid by aldehyde dehydrogenase (KGSADH) or to 1-propanol by yeast-alcohol dehydrogenase (yADH), while the NADH concentration change was monitored spectrophotometrically. Cells should be disintegrated by Bead Beater/French Press, not by chemical methods (BugBuster ® /B-PER™), because the reagents significantly inactivated GDHt and coupling enzymes. Furthermore, in the assay mixture, a much higher activity of KGSADH (>200-fold) or yADH (>400-fold) than that of GDHt should have been maintained. Under optimal conditions, both KGSADH and yADH showed practically the same activity. The coupled-enzyme assay method established here should prove to be applicable to recombinant strains developed for the production of 3-HP and/or 1,3-PDO from glycerol.

Angiotensin-converting enzyme inhibition and angiotensin AT1 receptor blockade downregulate angiotensin-converting enzyme expression and attenuate renal injury in streptozotocin-induced diabetic rats.

PubMed

Motawi, Tarek K; El-Maraghy, Shohda A; Senousy, Mahmoud A

2013-07-01

Angiotensin-converting enzyme (ACE) is upregulated in the diabetic kidney and contributes to renal injury. This study investigates the possible beneficial effects of the ACE inhibitor (ACEI), enalapril and the AT1 receptor blocker (ARB), valsartan, on renal ACE expression, renal structure, and function in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were allocated into four groups: control, STZ-diabetic rats, and STZ-diabetic rats treated with either enalapril (10 mg/kg/day) or valsartan (50 mg/kg/day) for 8 weeks. Enalapril and valsartan reduced renal ACE mRNA and protein expression, Na(+) /K(+) -ATPase activity, oxidative stress, and serum transforming growth factor-β1 levels compared to the diabetic group. Both treatments normalized renal nitrate/nitrite levels and ameliorated the observed histopathological changes. In conclusion, ACE downregulation by ACEI and ARB indicates that angiotensin II upregulates ACE through AT1 receptor. Prevention of diabetes-induced changes in ACE expression and Na(+) /K(+) -ATPase activity could be a new explanation of the renoprotective effects of ACEIs and ARBs. © 2013 Wiley Periodicals, Inc.

Analysis and Evaluation of the Inhibitory Mechanism of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide Derived from Casein Hydrolysate.

PubMed

Tu, Maolin; Liu, Hanxiong; Zhang, Ruyi; Chen, Hui; Mao, Fengjiao; Cheng, Shuzhen; Lu, Weihong; Du, Ming

2018-04-25

Casein hydrolysates exert various biological activities, and the responsible functional peptides are being identified from them continuously. In this study, the tryptic casein hydrolysate was fractionated by an ultrafiltration membrane (3 kDa), and the peptides were identified by capillary electrophoresis-quadrupole-time-of-flight-tandem mass spectrometry. Meanwhile, in silico methods were used to analyze the toxicity, solubility, stability, and affinity between the peptides and angiotensin-I-converting enzyme (ACE). Finally, a new angiotensin-I-converting enzyme inhibitory (ACEI) peptide, EKVNELSK, derived from α s1 -casein (fragment 35-42) was screened. The half maximal inhibitory concentration value of the peptide is 5.998 mM, which was determined by a high-performance liquid chromatography method. The Lineweaver-Burk plot indicated that this peptide is a mixed-type inhibitor against ACE. Moreover, Discovery Studio 2017 R2 software was adopted to perform molecular docking to propose the potential mechanisms underlying the ACEI activity of the peptide. These results indicated that EKVNELSK is a new ACEI peptide identified from casein hydrolysate.

Ontogenetic role of angiontensin-converting enzyme in rats: thirst and sodium appetite evaluation.

PubMed

Mecawi, André S; Araujo, Iracema G; Rocha, Fábio F; Coimbra, Terezila M; Antunes-Rodrigues, José; Reis, Luís C

2010-01-12

We investigated the influence of captopril (an angiotensin converting enzyme inhibitor) treatment during pregnancy and lactation period on hydromineral balance of the male adult offspring, particularly, concerning thirst and sodium appetite. We did not observe significant alterations in basal hydromineral (water intake, 0.3M NaCl intake, volume and sodium urinary concentration) or cardiovascular parameters in adult male rats perinatally treated with captopril compared to controls. However, male offspring rats that perinatally exposed to captopril showed a significant attenuation in water intake induced by osmotic stimulation, extracellular dehydration and beta-adrenergic stimulation. Moreover, captopril treatment during perinatal period decreased the salt appetite induced by sodium depletion. This treatment also attenuated thirst and sodium appetite aroused during inhibition of peripheral angiotensin II generation raised by low concentration of captopril in the adult offspring. Interestingly, perinatal exposure to captopril did not alter water or salt intake induced by i.c.v. administration of angiotensin I or angiotensin II. These results showed that chronic inhibition of angiotensin converting enzyme during pregnancy and lactation modifies the regulation of induced thirst and sodium appetite in adulthood.

Budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme upon high-altitude exposure

PubMed Central

Li, Hui-Jie; Zheng, Cheng-Rong; Chen, Guo-Zhu; Qin, Jun; Zhang, Ji-Hang; Yu, Jie; Zhang, En-Hao; Huang, Lan

2016-01-01

Introduction: Inhaled budesonide is a novel approach to prevent acute mountain sickness (AMS). However, its mechanism is not completely understood. We aimed to investigate the effects of budesonide and dexamethasone on renin–angiotensin–aldosterone system in AMS prevention. Materials and methods: Data were obtained from a randomised controlled trial including 138 participants. The participants were randomly assigned to receive budesonide, dexamethasone or placebo as prophylaxis before they travelled to 3450 m altitude from 400 m by car. Their plasma concentrations of renin, angiotensin-converting enzyme (ACE) and aldosterone were measured at both altitudes. Results: All parameters were comparable among the three groups at 400 m. After high-altitude exposure of 3450, renin in all groups increased significantly; the ACE, aldosterone concentrations, as well as the aldosterone/renin ratio, rose markedly in the dexamethasone and placebo groups but not in the budesonide group. Moreover, the aldosterone/renin ratio correlated closely with ACE concentration. Conclusions: Upon acute high-altitude exposure, budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme. PMID:27317302

Effect of SQ29,852, a new angiotensin converting enzyme (ACE) inhibitor with a phosphonic acid group, on the activity of angiotensin converting enzyme from human kidney.

PubMed

Hiwada, K; Inoue, Y; Kokubu, T

1990-01-01

1. An in vitro experiment was carried out to compare the inhibitory effect of SQ29,852 on human renal angiotensin converting enzyme (ACE) with those of captopril, enalapril and enalaprilat. 2. SQ29,852 strongly inhibited human renal ACE; its IC50 value was 1.5 x 10(-8) M. In terms of the IC50, SQ29,852's efficacy was about 1/10 of that of captopril and 1/28 of that of enalaprilat, but it was about 14 times more potent than enalapril. 3. SQ29,852 showed no inhibitory effects on cathepsin D, urinary kallikrein, renal renin, pepsin, trypsin and chymotrypsin. Its ACE-specificity was higher than that of captopril. 4. ACE inhibition by SQ29,852 was shown to be competitive, as revealed by Lineweaver-Burk plots. The affinity of SQ29,852 to ACE was shown to be high by a Ki value of 1.2 x 10(-8) M.

Genetics Home Reference: Bietti crystalline dystrophy

MedlinePlus

... broken down and converted into energy, but the enzyme's specific function is not well understood. CYP4V2 gene mutations that cause Bietti crystalline dystrophy impair or eliminate the function of this enzyme and are believed to affect lipid breakdown. However, ...

Mapping soil salinity and a fresh-water intrusion in three-dimensions using a quasi-3d joint-inversion of DUALEM-421S and EM34 data

NASA Astrophysics Data System (ADS)

Zare, Ehsan; Huang, Jingyi; Koganti, Triven; Triantafilis, John

2017-04-01

In order to understand the drivers of topsoil salinization, the distribution and movement of salt in accordance with groundwater need mapping. In this study, we described a method to map the distribution of soil salinity, as measured by the electrical conductivity of a saturated soil-paste extract (ECe), and in 3-dimensions around a water storage reservoir in an irrigated field near Bourke, New South Wales, Australia. A quasi-3d electromagnetic conductivity image (EMCI) or model of the true electrical conductivity (sigma) was developed using 133 apparent electrical conductivity (ECa) measurements collected on a 50 m grid and using various coil arrays of DUALEM-421S and EM34 instruments. For the DUALEM-421S we considered ECa in horizontal coplanar (i.e., 1 mPcon, 2 mPcon and 4 mPcon) and vertical coplanar (i.e., 1 mHcon, 2 mHcon and 4 mHcon) arrays. For the EM34, three measurements in the horizontal mode (i.e., EM34-10H, EM34-20H and EM34-40H) were considered. We estimated σ using a quasi-3d joint-inversion algorithm (EM4Soil). The best correlation (R2 = 0.92) between σ and measured soil ECe was identified when a forward modelling (FS), inversion algorithm (S2) and damping factor (lambda = 0.2) were used and using both DUALEM-421 and EM34 data; but not including the 4 m coil arrays of the DUALEM-421S. A linear regression calibration model was used to predict ECe in 3-dimensions beneath the study field. The predicted ECe was consistent with previous studies and revealed the distribution of ECe and helped to infer a freshwater intrusion from a water storage reservoir at depth and as a function of its proximity to near-surface prior stream channels and buried paleochannels. It was concluded that this method can be applied elsewhere to map the soil salinity and water movement and provide guidance for improved land management.|

Health and Safety Checklist for Early Care and Education Programs to Assess Key National Health and Safety Standards.

PubMed

Alkon, Abbey; Rose, Roberta; Wolff, Mimi; Kotch, Jonathan B; Aronson, Susan S

2016-01-01

The project aims were to (1) develop an observational Health and Safety Checklist to assess health and safety practices and conditions in early care and education (ECE) programs using Stepping Stones To Caring For Our Children, 3rd Edition national standards, (2) pilot test the Checklist, completed by nurse child care health consultants, to assess feasibility, ease of completion, objectivity, validity, and reliability, and (3) revise the Checklist based on the qualitative and quantitative results of the pilot study. The observable national health and safety standards were identified and then rated by health, safety, and child care experts using a Delphi technique to validate the standards as essential to prevent harm and promote health. Then, child care health consultants recruited ECE centers and pilot tested the 124-item Checklist. The pilot study was conducted in Arizona, California and North Carolina. The psychometric properties of the Checklist were assessed. The 37 participating ECE centers had 2627 children from ethnically-diverse backgrounds and primarily low-income families. The child care health consultants found the Checklist easy to complete, objective, and useful for planning health and safety interventions. The Checklist had content and face validity, inter-rater reliability, internal consistency, and concurrent validity. Based on the child care health consultant feedback and psychometric properties of the Checklist, the Checklist was revised and re-written at an 8th grade literacy level. The Health and Safety Checklist provides a standardized instrument of observable, selected national standards to assess the quality of health and safety in ECE centers.

Liquid crystal polymer substrate MMIC receiver modules for the ECE Imaging system on the DIII-D

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

Zhu, Y.; Ye, Y.; Yu, J-H

A new generation of millimeter-wave heterodyne imaging receiver arrays has been developed and demonstrated on the DIII-D ECEI system. Improved circuit integration, allowing for absolute calibration, improved noise performance, and shielding from out-of-band emission, is made possible by using advanced liquid crystal polymer (LCP) substrates and MMIC (Monolithic Microwave Integrated Circuit) receiver chips. This array exhibits ~ 15 dB additional gain and > 30x reduction in noise temperature compared to the previous generation and provide ECEI capability for absolute 2-D electron temperature profile measurements. Each LCP horn-waveguide module houses a 3x3 mm GaAs MMIC receiver chip, which consists of amore » low noise amplifier (LNA), balanced mixer, local oscillator multiplier chain driven by ~12 GHz input via an RF cable to the enclosure box, and IF amplifier. A proof-of-principle instrument with 5 poloidal channels was installed on DIII-D in 2017. The full proof-of-principle system installation (20 poloidal x 8 radial channels) was commissioned early in 2018. The LCP ECEI system is used for pedestal region measurements, especially focusing on temperature evolution during ELM bursting. The DIII-D ECE Imaging signal has been significantly improved with extremely effective shielding of out-of-band microwave noise which plagued previous ECE Imaging studies on DIII-D. In H-mode ELM bursting, the radial propagation of electron heat flow has been detected on DIII-D. The LCP ECE Imaging is expected to be a valuable diagnostic tool for ELM physics investigations.« less

The role of early childhood education programmes in the promotion of child and adolescent mental health in low- and middle-income countries.

PubMed

Baker-Henningham, Helen

2014-04-01

There is growing evidence that early childhood education (ECE) interventions can reduce the loss of developmental potential of disadvantaged children in low- and middle-income countries (LAMIC). Less attention has been paid to the potential of these programmes to prevent child mental health problems and promote child well-being. Peer-reviewed journal articles describing controlled evaluations of ECE interventions in LAMIC were reviewed to identify studies with child mental health outcomes. Studies with proximal outcomes for child mental health including caregiver practices and caregiver mental health were also reviewed. Of 63 studies identified, 21 (33.33%) included child mental health outcomes; 12 of 16 studies with short-term measures showed benefits; 6 studies included a longer-term follow-up and all found benefits; 25 studies included caregiver outcomes: consistent benefits were found for caregiver practices (21 studies) and 6 of 9 studies that measured caregiver mental health reported benefits. Gains to child mental health may be most likely when ECE interventions include three main elements: (i) activities to increase child skills including cognition, language, self-regulation and social-emotional competence; (ii) training caregivers in the skills required to provide a cognitively stimulating and emotionally supportive environment; and (iii) attention to the caregivers' mental health, motivation and self-efficacy. Recommendations for the design and implementation of programmes are provided. ECE interventions are an important component of mental health prevention and promotion in LAMIC, and promoting child and caregiver well-being is a fundamental aspect of interventions to improve child development.

Runaway electron generation as possible trigger for enhancement of magnetohydrodynamic plasma activity and fast changes in runaway beam behavior

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

Pankratov, I. M., E-mail: pankratov@kipt.kharkov.ua, E-mail: rjzhou@ipp.ac.cn; Zhou, R. J., E-mail: pankratov@kipt.kharkov.ua, E-mail: rjzhou@ipp.ac.cn; Hu, L. Q.

2015-07-15

Peculiar phenomena were observed during experiments with runaway electrons: rapid changes in the synchrotron spot and its intensity that coincided with stepwise increases in the electron cyclotron emission (ECE) signal (cyclotron radiation of suprathermal electrons). These phenomena were initially observed in TEXTOR (Tokamak Experiment for Technology Oriented Research), where these events only occurred in the current decay phase or in discharges with thin stable runaway beams at a q = 1 drift surface. These rapid changes in the synchrotron spot were interpreted by the TEXTOR team as a fast pitch angle scattering event. Recently, similar rapid changes in the synchrotron spot andmore » its intensity that coincided with stepwise increases in the non-thermal ECE signal were observed in the EAST (Experimental Advanced Superconducting Tokamak) runaway discharge. Runaway electrons were located around the q = 2 rational magnetic surface (ring-like runaway electron beam). During the EAST runaway discharge, stepwise ECE signal increases coincided with enhanced magnetohydrodynamic (MHD) activity. This behavior was peculiar to this shot. In this paper, we show that these non-thermal ECE step-like jumps were related to the abrupt growth of suprathermal electrons induced by bursting electric fields at reconnection events during this MHD plasma activity. Enhancement of the secondary runaway electron generation also occurred simultaneously. Local changes in the current-density gradient appeared because of local enhancement of the runaway electron generation process. These current-density gradient changes are considered to be a possible trigger for enhancement of the MHD plasma activity and the rapid changes in runaway beam behavior.« less

[Multiparametric 3T MRI in the routine staging of prostate cancer].

PubMed

Largeron, J P; Galonnier, F; Védrine, N; Alfidja, A; Boyer, L; Pereira, B; Boiteux, J P; Kemeny, J L; Guy, L

2014-03-01

To analyse the detection ability of a multiparametric 3T MRI with phased-array coil in comparison with the pathological data provided by the prostatectomy specimens. Prospective study of 30 months, including 74 patients for whom a diagnosis of prostate cancer had been made on randomized prostate biopsies, and all eligible to a radical prostatectomy. They all underwent multiparametric 3T MRI with pelvic phased-array coil including T2-weighted imaging (T2W), dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) with an ADC mapping. Each gland was divided in octants. Three specific criteria have been sought (detection ability, capsular contact [CC] and extracapsular extension [ECE]), in comparison with the pathological data provided by the prostatectomy specimens. Five hundred and ninety-two octants were considered with 124 significant tumors (volume ≥ 0.1cm(3)). The general ability of tumor detection had a sensitivity, specificity, PPV and NPV respectively to 72.3%, 87.4%, 83.2% and 78.5%. The estimate of the CC and ECE had a high negative predictive power with specificities and VPN respectively to 96.4% and 95.4% for CC, and 97.5 and 97.7% for ECE. Multiparametric 3T MRI with pelvic phased-array coil appeared to be a reliable imaging technique in clinical and routine practice for the detection of localized prostate cancer. Estimation of the CC and millimeter ECE remains to be clarified, even if the negative predictive power for these parameters seems encouraging. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Runaway electron generation as possible trigger for enhancement of magnetohydrodynamic plasma activity and fast changes in runaway beam behavior

NASA Astrophysics Data System (ADS)

Pankratov, I. M.; Zhou, R. J.; Hu, L. Q.

2015-07-01

Peculiar phenomena were observed during experiments with runaway electrons: rapid changes in the synchrotron spot and its intensity that coincided with stepwise increases in the electron cyclotron emission (ECE) signal (cyclotron radiation of suprathermal electrons). These phenomena were initially observed in TEXTOR (Tokamak Experiment for Technology Oriented Research), where these events only occurred in the current decay phase or in discharges with thin stable runaway beams at a q = 1 drift surface. These rapid changes in the synchrotron spot were interpreted by the TEXTOR team as a fast pitch angle scattering event. Recently, similar rapid changes in the synchrotron spot and its intensity that coincided with stepwise increases in the non-thermal ECE signal were observed in the EAST (Experimental Advanced Superconducting Tokamak) runaway discharge. Runaway electrons were located around the q = 2 rational magnetic surface (ring-like runaway electron beam). During the EAST runaway discharge, stepwise ECE signal increases coincided with enhanced magnetohydrodynamic (MHD) activity. This behavior was peculiar to this shot. In this paper, we show that these non-thermal ECE step-like jumps were related to the abrupt growth of suprathermal electrons induced by bursting electric fields at reconnection events during this MHD plasma activity. Enhancement of the secondary runaway electron generation also occurred simultaneously. Local changes in the current-density gradient appeared because of local enhancement of the runaway electron generation process. These current-density gradient changes are considered to be a possible trigger for enhancement of the MHD plasma activity and the rapid changes in runaway beam behavior.

Analysis of serum angiotensin-converting enzyme.

PubMed

Muller, B R

2002-09-01

Serum angiotensin-converting enzyme (SACE) levels are influenced by genetic polymorphism. Interpretation of serum levels with the appropriate genotypic reference range improves the diagnostic sensitivity of the assay for sarcoidosis. SACE assays are performed by a large number of routine clinical laboratories. However, there is no external quality assessment (EQA) for SACE other than an informal regional scheme. This showed analytical performance of SACE assays to be poor, with a diversity of reference ranges, leading to widely disparate clinical classification of EQA samples. Genetic polymorphism combined with poor analytical performance suggest that perhaps SACE assays should revert to being the province of specialized laboratories.

Orientation dependent cyclic stability of the elastocaloric effect in textured Ni-Mn-Ga alloys

NASA Astrophysics Data System (ADS)

Wei, Longsha; Zhang, Xuexi; Liu, Jian; Geng, Lin

2018-05-01

High-performance elastocaloric materials require a large reversible elastocaloric effect and long life cyclic stability. Here, we fabricated textured polycrystalline Ni50.4Mn27.3Ga22.3 alloys by cost-effective casting method to create a <001> texture. A strong correlation between the cyclic stability and the crystal orientation was demonstrated. A large reversible adiabatic temperature change ΔT ˜6 K was obtained when the external stress was applied parallel to <001> direction. However, the ΔT decreased rapidly after 50 cycles, showing an unstable elastocaloric effect (eCE). On the other hand, when the external stress was applied perpendicular to <001>, the adiabatic ΔT was smaller ˜4 K, but was stable over 100 cycles. This significantly enhanced eCE stability was related to the high yield strength, low transformation strain and much higher crack initiation-propagation resistances perpendicular to <001> direction. This study provides a feasible strategy for optimizing the eCE property by creation of the texture structure in polycrystalline Ni-Mn-Ga and Ni-Mn-X (X= In, Sn, Sb) alloys.

Personal glucose meters for detection and quantification of a broad range of analytes

DOEpatents

Lu, Yi; Xiang, Yu

2015-02-03

A general methodology for the development of highly sensitive and selective sensors that can achieve portable, low-cost and quantitative detection of a broad range of targets using only a personal glucose meter (PGM) is disclosed. The method uses recognition molecules that are specific for a target agent, enzymes that can convert an enzyme substrate into glucose, and PGM. Also provided are sensors, which can include a solid support to which is attached a recognition molecule that permits detection of a target agent, wherein the recognition molecule specifically binds to the target agent in the presence of the target agent but not significantly to other agents as well as an enzyme that can catalyze the conversion of a substance into glucose, wherein the enzyme is attached directly or indirectly to the recognition molecule, and wherein in the presence of the target agent the enzyme can convert the substance into glucose. The disclosed sensors can be part of a lateral flow device. Methods of using such sensors for detecting target agents are also provided.

Pie waste - A component of food waste and a renewable substrate for producing ethanol.

PubMed

Magyar, Margaret; da Costa Sousa, Leonardo; Jayanthi, Singaram; Balan, Venkatesh

2017-04-01

Sugar-rich food waste is a sustainable feedstock that can be converted into ethanol without an expensive thermochemical pretreatment that is commonly used in first and second generation processes. In this manuscript we have outlined the pie waste conversion to ethanol through a two-step process, namely, enzyme hydrolysis using commercial enzyme products mixtures and microbial fermentation using yeast. Optimized enzyme cocktail was found to be 45% alpha amylase, 45% gamma amylase, and 10% pectinase at 2.5mg enzyme protein/g glucan produced a hydrolysate with high glucose concentration. All three solid loadings (20%, 30%, and 40%) produced sugar-rich hydrolysates and ethanol with little to no enzyme or yeast inhibition. Enzymatic hydrolysis and fermentation process mass balance was carried out using pie waste on a 1000g dry weight basis that produced 329g ethanol at 20% solids loading. This process clearly demonstrate how food waste could be efficiently converted to ethanol that could be used for making biodiesel by reacting with waste cooking oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative study on the conventional and non thermal simultaneous saccharification and fermentation of Manihot glaziovii root starch

NASA Astrophysics Data System (ADS)

Hargono, Kumoro, Andri Cahyo; Jos, Bakti

2015-12-01

Inconventional ethanol production process, starch is converted into dextrins via liquefaction using α-amylase enzyme at high temperature (90-120°C). Then, dextrins are saccharified by glucoamylase to obtain to monomeric sugars (glucose). Recently, a granular starch hydrolyzing enzymes (GSHE), Stargen 002, was developed to convert starch into dextrins at low temperature (< 32°C) and hydrolyzes dextrins into glucose. The subject of this research was to compare ethanol production using a granular starch hydrolyzing enzymes and conventional enzymatic liquefaction and saccharification in cassava starch processing. Starch slurry concentrations were 20% w/v, and dosage of enzymes 0.50, 1.0 and 2%, respectively, were studied. After 48 hr process the final ethanol concentration for the respective enzyme concentration for conventional process were 34.90, 36.16 and 42.10 g/L, whereas for the non-thermal treatment, final ethanol concentration were 46.4, 57.62 and 59.65 g/L, respectively. By implementation of this non thermal process, the use of energy can be saved by carrying out saccharification step at lower temperature (30°C) could be realized.

Angiotensin II-producing enzyme III from acidified serum of nephrectomized dogs.

PubMed

Haas, E; Lewis, L; Koshy, T J; Varde, A U; Renerts, L; Bagai, R C

1989-09-01

A highly active angiotensin-producing enzyme (enzyme III) was obtained from the serum of bilaterally nephrectomized dogs by acid treatment and ammonium sulfate fractionation. An inactive precursor (proenzyme III) was converted to enzyme III during prolonged storage (or by treatment with acid or with cathepsin G or by incubation at 38 degrees C as described in the following paper). Enzyme III reacted maximally at pH 7.7 and it produced up to 400 ng of angiotensin II/mL serum/h (i.e., amounts 4000 times higher than that generated by the endogenous renin present in serum after bilateral nephrectomy). Enzyme III produced angiotensin II at identical rates when either dog angiotensinogen or angiotensin I was used as substrate, but the rate was 710 times higher with synthetic tetradecapeptide renin substrate. Enzyme III is not identical to renin, cathepsin G, tonin, enzyme I, enzyme II, the calcium-dependent angiotensin I-converting enzyme, or the calcium-independent carboxy peptidase, which acts by sequential cleavage of angiotensin I. Enzyme III was inhibited by alpha-1-antitrypsin, diisopropyl fluorophosphate, and lima bean trypsin inhibitor (hence it is a serine proteinase). It was not inhibited by Captopril, Teprotide, or Enalapril. It had been reported previously that cathepsin G released from neutrophil granulocytes, by producing high local concentrations of angiotensin II, may provide a mobile means for modulating blood flow in tissue microvasculature during the inflammatory response. The present study offers a new, additional pathway, by enzyme III, for a similar rapid formation of angiotensin II from serum protein substrate or angiotensin I.

Monkey search algorithm for ECE components partitioning

NASA Astrophysics Data System (ADS)

Kuliev, Elmar; Kureichik, Vladimir; Kureichik, Vladimir, Jr.

2018-05-01

The paper considers one of the important design problems – a partitioning of electronic computer equipment (ECE) components (blocks). It belongs to the NP-hard class of problems and has a combinatorial and logic nature. In the paper, a partitioning problem formulation can be found as a partition of graph into parts. To solve the given problem, the authors suggest using a bioinspired approach based on a monkey search algorithm. Based on the developed software, computational experiments were carried out that show the algorithm efficiency, as well as its recommended settings for obtaining more effective solutions in comparison with a genetic algorithm.

Acute kidney injury post-major orthopaedic surgery: A single-Centre case-control study.

PubMed

Ying, Tracey; Chan, Samantha; Lane, Stephen; Somerville, Christine

2018-02-01

To identify risk factors for acute kidney injury following major orthopaedic surgery. We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. We reviewed the patients' history of cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus along with presence of sepsis and obesity. Associations of hypothetical risk factors were estimated using conditional logistic regression. We identified 164 cases of AKI in an elderly cohort (median age = 73 years). Controlling for baseline comorbidities, both diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were found to be associated with a twofold risk of acute kidney injury (diuretic - OR 2.06 95% CI:1.30-3.26, P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use OR 2.09 95% CI:1.31-3.32, P < 0.005). A dose-effect model accounting for perioperative nonsteroidal anti-inflammatory drug administration demonstrated a linear relationship between the number of times these drugs were given and postoperative acute kidney injury risk (OR 1.35 95% CI:1.05-1.73, P = 0.02). We identified perioperative diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to be significantly associated with postoperative AKI. Further prospective studies are required to confirm this. © 2016 Asian Pacific Society of Nephrology.

Peptidases in dog-ileum circular and longitudinal smooth-muscle plasma membranes. Their relative contribution to the metabolism of neurotensin.

PubMed

Checler, F; Ahmad, S; Kostka, P; Barelli, H; Kitabgi, P; Fox, J A; Kwan, C Y; Daniel, E E; Vincent, J P

1987-07-15

We established the content in neuropeptide-metabolizing peptidases present in highly purified plasma membranes prepared from the circular and longitudinal muscles of dog ileum. Activities were measured by the use of fluorigenic substrates and the identities of enzymes were confirmed by the use of specific peptidase inhibitors. Endopeptidase 24.11, angiotensin-converting enzyme, post-proline dipeptidyl aminopeptidase and aminopeptidases were found in both membrane preparations. Proline endopeptidase was only detected in circular smooth muscle plasma membranes while pyroglutamyl-peptide hydrolase was not observed in either tissue. The relative contribution of these peptidases to the inactivation of neurotensin was assessed. The enzymes involved in the primary inactivating cleavages occurring on the neurotensin molecule were as follows. In both membrane preparations, endopeptidase 24.11 was responsible for the formation of neurotensin-(1-11) and contributed to the formation of neurotensin-(1-10); a recently purified neurotensin-degrading neutral metallopeptidase was also involved in the formation of neurotensin-(1-10). A carboxypeptidase-like activity hydrolysed neurotensin at the Ile12-Leu13 peptide bond, leading to the formation of neurotensin-(1-12). Proline endopeptidase and endopeptidase 24.15 only occurred in circular muscle plasma membranes, yielding neurotensin-(1-7) and neurotensin-(1-8), respectively. In addition, the secondary processing of neurotensin degradation products was catalyzed by the following peptidases. In circular and longitudinal muscle membranes, angiotensin-converting enzyme converted neurotensin-(1-10) into neurotensin-(1-8) and tyrosine resulted from the rapid hydrolysis of neurotensin-(11-13) by bestatin-sensitive aminopeptidases. A post-proline dipeptidyl aminopeptidase activity converted neurotensin-(9-13) into neurotensin-(11-13) in circular muscle plasma membranes. The mechanism of neurotensin inactivation occurring in these membranes will be compared to that previously established for membranes from central origin.

Purification and characterization of a tuliposide-converting enzyme from bulbs of Tulipa gesneriana.

PubMed

Kato, Yasuo; Shoji, Kazuaki; Ubukata, Makoto; Shigetomi, Kengo; Sato, Yukio; Nakajima, Noriyuki; Ogita, Shinjiro

2009-08-01

An enzyme that catalyzes the stoichiometric conversion of 6-tuliposide into tulipalin was purified and characterized from bulbs of Tulipa gesneriana. The enzyme appeared to be a dimer, the relative molecular mass (Mr) of each subunit being 34,900; it had maximum activity and stability at neutral pH and moderate temperature. The enzyme preferentially acted on such glucose esters as 6-tuliposides, and to a lesser extent on p-nitrophenylacetate.

Genetics Home Reference: combined malonic and methylmalonic aciduria

MedlinePlus

... acids are building blocks used to make fats (lipids). The ACSF3 enzyme performs a chemical reaction that converts malonic acid to malonyl-CoA, which is the first step of fatty acid synthesis in cellular structures called mitochondria . Based on this activity, the enzyme ...

Efficient, environmentally-friendly and specific valorization of lignin: promising role of non-radical lignolytic enzymes.

PubMed

Wang, Wenya; Zhang, Chao; Sun, Xinxiao; Su, Sisi; Li, Qiang; Linhardt, Robert J

2017-06-01

Lignin is the second most abundant bio-resource in nature. It is increasingly important to convert lignin into high value-added chemicals to accelerate the development of the lignocellulose biorefinery. Over the past several decades, physical and chemical methods have been widely explored to degrade lignin and convert it into valuable chemicals. Unfortunately, these developments have lagged because of several difficulties, of which high energy consumption and non-specific cleavage of chemical bonds in lignin remain the greatest challenges. A large number of enzymes have been discovered for lignin degradation and these are classified as radical lignolytic enzymes and non-radical lignolytic enzymes. Radical lignolytic enzymes, including laccases, lignin peroxidases, manganese peroxidases and versatile peroxidases, are radical-based bio-catalysts, which degrade lignins through non-specific cleavage of chemical bonds but can also catalyze the radical-based re-polymerization of lignin fragments. In contrast, non-radical lignolytic enzymes selectively cleave chemical bonds in lignin and lignin model compounds and, thus, show promise for use in the preparation of high value-added chemicals. In this mini-review, recent developments on non-radical lignolytic enzymes are discussed. These include recently discovered non-radical lignolytic enzymes, their metabolic pathways for lignin conversion, their recent application in the lignin biorefinery, and the combination of bio-catalysts with physical/chemical methods for industrial development of the lignin refinery.

Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence.

PubMed

Masuyer, Geoffrey; Yates, Christopher J; Sturrock, Edward D; Acharya, K Ravi

2014-10-01

Somatic angiotensin-I converting enzyme (sACE) has an essential role in the regulation of blood pressure and electrolyte fluid homeostasis. It is a zinc protease that cleaves angiotensin-I (AngI), bradykinin, and a broad range of other signalling peptides. The enzyme activity is provided by two homologous domains (N- and C-), which display clear differences in substrate specificities and chloride activation. The presence of chloride ions in sACE and its unusual role in activity was identified early on in the characterisation of the enzyme. The molecular mechanisms of chloride activation have been investigated thoroughly through mutagenesis studies and shown to be substrate-dependent. Recent results from X-ray crystallography structural analysis have provided the basis for the intricate interactions between ACE, its substrate and chloride ions. Here we describe the role of chloride ions in human ACE and its physiological consequences. Insights into the chloride activation of the N- and C-domains could impact the design of improved domain-specific ACE inhibitors.

Molecular diversity of tuliposide B-converting enzyme in tulip (Tulipa gesneriana): identification of the root-specific isozyme.

PubMed

Nomura, Taiji; Ueno, Ayaka; Ogita, Shinjiro; Kato, Yasuo

2017-06-01

6-Tuliposide B (PosB) is a glucose ester accumulated in tulip (Tulipa gesneriana) as a major secondary metabolite. PosB serves as the precursor of the antimicrobial lactone tulipalin B (PaB), which is formed by PosB-converting enzyme (TCEB). The gene TgTCEB1, encoding a TCEB, is transcribed in tulip pollen but scarcely transcribed in other tissues (e.g. roots) even though those tissues show high TCEB activity. This led to the prediction of the presence of a TCEB isozyme with distinct tissue specificity. Herein, we describe the identification of the TgTCEB-R gene from roots via native enzyme purification; this gene is a paralog of TgTCEB1. Recombinant enzyme characterization verified that TgTCEB-R encodes a TCEB. Moreover, TgTCEB-R was localized in tulip plastids, as found for pollen TgTCEB1. TgTCEB-R is transcribed almost exclusively in roots, indicating a tissue preference for the transcription of TCEB isozyme genes.

Redirection of pyruvate flux toward desired metabolic pathways through substrate channeling between pyruvate kinase and pyruvate-converting enzymes in Saccharomyces cerevisiae.

PubMed

Kim, Sujin; Bae, Sang-Jeong; Hahn, Ji-Sook

2016-04-07

Spatial organization of metabolic enzymes allows substrate channeling, which accelerates processing of intermediates. Here, we investigated the effect of substrate channeling on the flux partitioning at a metabolic branch point, focusing on pyruvate metabolism in Saccharomyces cerevisiae. As a platform strain for the channeling of pyruvate flux, PYK1-Coh-Myc strain was constructed in which PYK1 gene encoding pyruvate kinase is tagged with cohesin domain. By using high-affinity cohesin-dockerin interaction, the pyruvate-forming enzyme Pyk1 was tethered to heterologous pyruvate-converting enzymes, lactate dehydrogenase and α-acetolactate synthase, to produce lactic acid and 2,3-butanediol, respectively. Pyruvate flux was successfully redirected toward desired pathways, with a concomitant decrease in ethanol production even without genetic attenuation of the ethanol-producing pathway. This pyruvate channeling strategy led to an improvement of 2,3-butanediol production by 38%, while showing a limitation in improving lactic acid production due to a reduced activity of lactate dehydrogenase by dockerin tagging.

Angiotensin-converting enzyme in epithelial and neuroepithelial cells.

PubMed

Defendini, R; Zimmerman, E A; Weare, J A; Alhenc-Gelas, F; Erdös, E G

1983-07-01

Angiotensin-converting enzyme (CE) occurs in three types of cell: endothelial, epithelial, and neuroepithelial. In all three, it appears to be bound to plasma membrane. With antisera to the human enzyme, CE is demonstrated in paraffin sections on the apical surface of epithelial cells in the proximal tubule of the kidney, the mucosa of the small intestine, the syncytial trophoblast of the placenta, and the choroid plexus. Epithelial CE is characteristically found on microvillous surfaces in contact with an effluent, well placed to act on substrate in flux. In the brain, CE occurs in nerve fibers and terminals, mainly mesiobasally and in basal ganglia. Mesiobasal CE coincides with other components of the renin-angiotensin system (RAS) in the choroid/ventricular fluid, the subfornical organ, and the magnocellular neurosecretory system of the hypothalamus. Extrapyramidal CE, however, may not be related to the RAS. In the substantia nigra and the globus pallidus, the enzyme has the same cellular distribution as two putative neuromodulators, substance P and enkephalin, the latter a known substrate of CE.

An in vitro synthetic biology platform for the industrial biomanufacturing of myo-inositol from starch.

PubMed

You, Chun; Shi, Ting; Li, Yunjie; Han, Pingping; Zhou, Xigui; Zhang, Yi-Heng Percival

2017-08-01

Myo-Inositol (vitamin B8) is widely used in the drug, cosmetic, and food & feed industries. Here, we present an in vitro non-fermentative enzymatic pathway that converts starch to inositol in one vessel. This in vitro pathway is comprised of four enzymes that operate without ATP or NAD + supplementation. All enzyme BioBricks are carefully selected from hyperthermophilic microorganisms, that is, alpha-glucan phosphorylase from Thermotoga maritima, phosphoglucomutase from Thermococcus kodakarensis, inositol 1-phosphate synthase from Archaeoglobus fulgidus, and inositol monophosphatase from T. maritima. They were expressed efficiently in high-density fermentation of Escherichia coli BL21(DE3) and easily purified by heat treatment. The four-enzyme pathway supplemented with two other hyperthermophilic enzymes (i.e., 4-α-glucanotransferase from Thermococcus litoralis and isoamylase from Sulfolobus tokodaii) converts branched or linear starch to inositol, accomplishing a very high product yield of 98.9 ± 1.8% wt./wt. This in vitro (aeration-free) biomanufacturing has been successfully operated on 20,000-L reactors. Less costly inositol would be widely added in heath food, low-end soft drink, and animal feed, and may be converted to other value-added biochemicals (e.g., glucarate). This biochemical is the first product manufactured by the in vitro synthetic biology platform on an industrial scale. Biotechnol. Bioeng. 2017;114: 1855-1864. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

[Angiotensin converting enzyme 2 and its emerging role in the regulation of the renin angiotensin system].

PubMed

Soler, María José; Lloveras, Josep; Batlle, Daniel

2008-07-12

The renin-angiotensin system (RAS) plays a key role in the regulation of cardiovascular and renal function. Thus, RAS blockade with an angiotensin-converting enzyme (ACE) and/or angiotensin receptor blocker decreases blood pressure, cardiovascular events, and delays the progression of kidney disease. The discovery of ACE2, a homologue of ACE, capable of degrading angiotensin II to angiotensin 1-7, may offer new insights into the RAS. In this review we discuss the possible protective role of ACE2 in different organs, namely heart, lungs and kidneys. The role of this enzyme is inferred from recent studies performed using genetically manipulated mice that lack the ACE2 gene and also mice treated with pharmacological ACE2 inhibitors. These results suggest that ACE2 might be a new therapeutic target within the RAS.

Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules

PubMed Central

1992-01-01

T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin- 1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design. PMID:1316930

21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

Code of Federal Regulations, 2011 CFR

2011-04-01

...-galactoside galactohydrase (CAS Reg. No. CBS 683), which converts lactose to glucose and galactose. It is... in § 170.3(o)(9) of this chapter to convert lactose to glucose and galactose. (2) The ingredient is... practice is to use this ingredient in milk to produce lactase-treated milk, which contains less lactose...

21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-galactoside galactohydrase (CAS Reg. No. CBS 683), which converts lactose to glucose and galactose. It is... in § 170.3(o)(9) of this chapter to convert lactose to glucose and galactose. (2) The ingredient is... practice is to use this ingredient in milk to produce lactase-treated milk, which contains less lactose...

Augmented Reality Robot-assisted Radical Prostatectomy: Preliminary Experience.

PubMed

Porpiglia, Francesco; Fiori, Cristian; Checcucci, Enrico; Amparore, Daniele; Bertolo, Riccardo

2018-05-01

To present our preliminary experience with augmented reality robot-assisted radical prostatectomy (AR-RARP). From June to August 2017, patients candidate to RARP were enrolled and underwent high-resolution multi-parametric magnetic resonance imaging (1-mm slices) according to dedicated protocol. The obtained three-dimensional (3D) reconstruction was integrated in the robotic console to perform AR-RARP. According to the staging at magnetic resonance imaging or reconstruction, in case of cT2 prostate cancer, intrafascial nerve sparing (NS) was performed: a mark was placed on the prostate capsule to indicate the virtual underlying intraprostatic lesion; in case of cT3, standard NS AR-RARP was scheduled with AR-guided biopsy at the level of suspected extracapsular extension (ECE). Prostate specimens were scanned to assess the 3D model concordance. Sixteen patients underwent intrafascial NS technique (cT2), whereas 14 underwent standard NS+ selective biopsy of suspected ECE (cT3). Final pathology confirmed clinical staging. Positive surgical margins' rate was 30% (no positive surgical margins in pT2). In patients whose intraprostatic lesions were marked, final pathology confirmed lesion location. In patients with suspected ECE, AR-guided selective biopsies confirmed the ECE location, with 11 of 14 biopsies (78%) positive for prostate cancer. Prostate specimens were scanned with finding of a good overlap. The mismatch between 3D reconstruction and scanning ranged from 1 to 5 mm. In 85% of the entire surface, the mismatch was <3 mm. In our preliminary experience, AR-RARP seems to be safe and effective. The accuracy of 3D reconstruction seemed to be promising. This technology has still limitations: the virtual models are manually oriented and rigid. Future collaborations with bioengineers will allow overcoming these limitations. Copyright © 2018 Elsevier Inc. All rights reserved.

Strength of obesity prevention interventions in early care and education settings: A systematic review.

PubMed

Ward, Dianne S; Welker, Emily; Choate, Ashley; Henderson, Kathryn E; Lott, Megan; Tovar, Alison; Wilson, Amanda; Sallis, James F

2017-02-01

2010-2015; INTERNATIONAL: Given the high levels of obesity in young children, numbers of children in out-of-home care, and data suggesting a link between early care and education (ECE) participation and overweight/obesity, obesity prevention in ECE settings is critical. As the field has progressed, a number of interventions have been reviewed yet there is a need to summarize the data using more sophisticated analyses to answer questions on the effectiveness of interventions. We conducted a systematic review of obesity prevention interventions in center-based ECE settings published between 2010 and 2015. Our goal was to identify promising intervention characteristics associated with successful behavioral and anthropometric outcomes. A rigorous search strategy resulted in 43 interventions that met inclusion criteria. We developed a coding strategy to assess intervention strength, used a validated study quality assessment tool, and presented detailed descriptive information about interventions (e.g., target behaviors, intervention strategies, and mode of delivery). Intervention strength was positively correlated with reporting of positive anthropometric outcomes for physical activity, diet, and combined interventions, and parent engagement components increased the strength of these relationships. Study quality was modestly related to percent successful healthy eating outcomes. Relationships between intervention strength and behavioral outcomes demonstrated negative relationships for all behavioral outcomes. Specific components of intervention strength (number of intervention strategies, potential impact of strategies, frequency of use, and duration of intervention) were correlated with some of the anthropometric and parent engagement outcomes. The review provided tentative evidence that multi-component, multi-level ECE interventions with parental engagement are most likely to be effective with anthropometric outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials.

PubMed

Lodise, Thomas P; Redell, Mark; Armstrong, Shannon O; Sulham, Katherine A; Corey, G Ralph

2017-01-01

The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7-10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Renin-angiotensin-aldosterone system inhibition: overview of the therapeutic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors.

PubMed

Mercier, Kelly; Smith, Holly; Biederman, Jason

2014-12-01

Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy in hypertensive diabetic patients with macroalbuminuria, microalbuminuria, or normoalbuminuria has been repeatedly shown to improve cardiovascular mortality and reduce the decline in glomerular filtration rate. Renin-angiotensin-aldosterone system (RAAS) blockade in normotensive diabetic patients with normoalbuminuria or microalbuminuria cannot be advocated at present. Dual RAAS inhibition with ACE inhibitors plus ARBs or ACE inhibitors plus direct renin inhibitors has failed to improve cardiovascular or renal outcomes but has predisposed patients to serious adverse events. Copyright © 2014 Elsevier Inc. All rights reserved.

Angiotensin converting enzyme over expression in myelocytes enhances the immune response

PubMed Central

Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.; Giani, Jorge F.; Shah, Kandarp; Bernstein, Ellen; Janjulia, Tea; Koronyo, Yosef; Shi, Peng D.; Koronyo-Hamaoui, Maya; Fuchs, Sebastien; Shen, Xiao Z.

2015-01-01

Angiotensin converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis and several aspects of the immune response. ACE 10/10 mice over express ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization towards a proinflammatory phenotype. As a result, ACE 10/10 mice have a highly effective immune response following challenge with either melanoma, bacterial infection or Alzheimer’s disease. The ACE 10/10 mice suggest that enhanced monocytic function greatly contributes to the ability of the immune response to defend against a wide variety of antigenic and non-antigenic challenges. PMID:24633750

Reduction of dopaminergic degeneration and oxidative stress by inhibition of angiotensin converting enzyme in a MPTP model of parkinsonism.

PubMed

Muñoz, Ana; Rey, Pablo; Guerra, Maria J; Mendez-Alvarez, Estefania; Soto-Otero, Ramon; Labandeira-Garcia, Jose L

2006-07-01

There is growing evidence indicating that oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. The brain, and particularly the basal ganglia, possesses a local rennin-angiotensin system. Angiotensin activates NAD(P)H-dependent oxidases, which are a major intracellular source of superoxide, and angiotensin converting enzyme inhibitors (ACEIs) have shown antioxidant properties. We treated mice with MPTP and the ACEI captopril to study the possible neuroprotective and antioxidant effects of the latter on the dopaminergic system. Pre-treatment with captopril induced a significant reduction in the MPTP-induced loss of dopaminergic neurons in the substantia nigra and a significant reduction in the loss of dopaminergic terminals in the striatum. Furthermore, captopril reduced the MPTP-induced increase in the levels of major oxidative stress indicators (i.e. lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum. Captopril did not reduce striatal MPP(+) levels, MAO-B activity or dopamine transporter activity, which may reduce MPTP neurotoxicity. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease, and that further investigation should focus on the neuroprotective capacity of these compounds.

Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates

PubMed Central

Ghanbari, Raheleh; Zarei, Mohammad; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

2015-01-01

In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions. PMID:26690117

Necessity of angiotensin-converting enzyme-related gene for cardiac functions and longevity of Drosophila melanogaster assessed by optical coherence tomography

NASA Astrophysics Data System (ADS)

Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan

2014-01-01

Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.

Production of angiotensin I converting enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in reducing hypertension.

PubMed

Rai, Amit Kumar; Sanjukta, Samurailatpam; Jeyaram, Kumaraswamy

2017-09-02

Fermented milk is a potential source of various biologically active peptides with specific health benefits. Angiotensin converting enzyme inhibitory (ACE-I) peptides are one of the most studied bioactive peptides produced during milk fermentation. The presence of these peptides is reported in various fermented milk products such as, yoghurt, cheese, sour milk, etc., which are also available as commercial products. Many of the ACE-I peptides formed during milk fermentation are resistant to gastrointestinal digestion and inhibit angiotensin converting enzyme (ACE) in the rennin angiotension system (RAS). There are various factors, which affect the formation ACE-I peptides and their ability to reach the target tissue in active form, which includes type of starters (lactic acid bacteria (LAB), yeast, etc.), substrate composition (casein type, whey protein, etc.), composition of ACE-I peptide, pre and post-fermentation treatments, and its stability during gastrointestinal digestion. The antihypertensive effect of fermented milk products has also been proved by various in vitro and in vivo (animal and human trials) experiments. This paper reviews the literature on fermented milk products as a source of ACE-I peptides and various factors affecting the production and activity of ACE-I peptides.

The Effects of Including Piezoelectric Film as Part of a Wing Surface

NASA Astrophysics Data System (ADS)

Sappo, Charlotte

2014-11-01

Micro air vehicles (MAVs) are size- and weight-restricted, unmanned, flying vehicles that often exploit biology for inspiration. Membrane wings, one commonly employed biological adaptation, improves aerodynamic efficiency. These efficiency gains are due to the passive deformations and vibrations of the membrane. Piezoelectric films have the potential to further utilize these vibrations through the conversion of this motion into measureable electrical energy. In this investigation, an amplifier circuit was designed to measure the charge generated by a flexible polyvinylidene fluoride (PVDF) film adhered to a rectangular wing frame (aspect ratio of 2). The trailing edge was unattached and free to vibrate. The circuit consisted of two charge amplifiers, to convert the high impedance charge of the piezoelectric film into an output voltage, and an instrumentation amplifier, to reject common-mode noise. Amplifying and filtering the output signal appropriately, through the use of the feedback capacitance and resistance, was discovered to be of the utmost importance for this endeavor. Results from shaker and wind tunnels tests are presented. NSF ECE Grant 1358991 supported the first author as a REU student.

A biological/chemical process for reduced waste and energy consumption: caprolactam production. Final report

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

NONE

1996-05-01

A biological/chemical process for converting cyclohexane into caprolactam was investigated: microorganisms in a bioreactor would be used to convert cyclohexane into caprolactone followed by chemical synthesis of caprolactam using ammonia. Four microorganisms were isolated from natural soil and water, that can utilize cyclohexane as a sole source of C and energy for growth. They were shown to have the correct metabolic intermediates and enzymes to convert cyclohexane into cyclohexanol, cyclohexanone, and caprolactone. Genetic techniques to create and select for caprolactone hydrolase negative-mutants were developed; those are used to convert cyclohexane into caprolactone but, because of the block, are unable tomore » metabolize the caprolactone further. Because of a new nylon carpet reycle process and the long time frame for a totally new bioprocess, a limited study was done to evaluate whether a simplified bioprocess to convert cyclohexanol into cyclohexanone or caprolactone was feasible; growth rates and key enzyme levels were measured in a collection of microorganisms that metabolize cyclohexanol to determine if the bioactivity is high enough to support an economical cyclohexanol bioprocess. Although these microorganisms had sufficient bioactivity, they could tolerate only low levels (<1%) of cyclohexanol and thus are not suitable for developing a cost effective bioprocess because of the high cost of dilute product recovery.« less

Service quality of Early Childhood Education web portals in Finnish municipalities

NASA Astrophysics Data System (ADS)

Koskivaara, Eija; Pihlaja, Päivi

Increasing number of governmental organizations have transformed material on their web sites as a way of providing users with information about their products and services. In this paper, we apply Yang et al (2005) instrument for analyzing municipal early childhood education (ECE) web sites in Finland. The objective of the study was to find out the quality of ECE web portals as well as to give hints to improve their value from users' point of view. In general the five dimensions, usability, usefulness of content, adequacy of information, accessibility, and interaction, of the Yang et al model seems to be applicable also in the early childhood education environment.

Understanding the Scientific Basis of Electrocaloric Effect in Defects Modified Ferroelectric Polymers

DTIC Science & Technology

2014-12-19

0.2), but is higher than that of BZT(x=0.25). The directly recorded ECE signal from BZT(x=0.2) (at 35 oC under a E = 9.5 MVm -1) is presented in Fig...the sample as the field is removed are presented in Fig. 7(b) for the BZT(x=0.2) at 35 oC under different E. The data reveals that at E = 14 MVm -1...samples in the ECE study, the highest field that can be applied was 14 MVm -1. To make a comparison with the results on BT thick films, we extrapolate the

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

The ECE application forecasts annual costs of preventive and corrective maintenance for budgeting purposes. Features within the application enable the user to change the specifications of the model to customize your forecast to best fit their needs and support “what if” analysis. Based on the user's selections, the ECE model forecasts annual maintenance costs. Preventive maintenance costs include the cost of labor to perform preventive maintenance activities at the specific frequency and labor rate. Corrective maintenance costs include the cost of labor and the cost of replacement parts. The application presents forecasted maintenance costs for the next five years inmore » two tables: costs by year and costs by site.« less

The excess choice effect: The role of outcome valence and counterfactual thinking.

PubMed

Hafner, Rebecca J; White, Mathew P; Handley, Simon J

2016-02-01

Contrary to economic theory, psychological research has demonstrated increased choice can undermine satisfaction. When and why this 'excess choice effect' (ECE) occurs remains unclear. Building on theories of counterfactual thinking we argue the ECE is more likely to occur when people experience counterfactual thought or emotion and that a key trigger is a negative versus positive task outcome. Participants either selected a drink (Experiment 1) or chocolate (Experiment 2) from a limited (6) versus extensive (24) selection (Experiment 1) or were given no choice versus extensive (24) choice (Experiment 2). In both experiments, however, the choice was illusory: Half the participants tasted a 'good' flavour, half a 'bad' flavour. As predicted, extensive choice was only detrimental to satisfaction when participants tasted the 'bad' drink or chocolate, and this was mediated by the experience of counterfactual thought (Experiment 1) or emotion (Experiment 2). When outcomes were positive, participants were similarly satisfied with limited versus extensive and no choice versus extensive choice. Implications for our theoretical understanding of the ECE and for the construction of choice architectures aimed at promoting individual satisfaction and well-being are discussed. © 2015 The British Psychological Society.

Understanding the Thermodynamic Properties of the Elastocaloric Effect Through Experimentation and Modelling

NASA Astrophysics Data System (ADS)

Tušek, Jaka; Engelbrecht, Kurt; Mañosa, Lluis; Vives, Eduard; Pryds, Nini

2016-12-01

This paper presents direct and indirect methods for studying the elastocaloric effect (eCE) in shape memory materials and its comparison. The eCE can be characterized by the adiabatic temperature change or the isothermal entropy change (both as a function of applied stress/strain). To get these quantities, the evaluation of the eCE can be done using either direct methods, where one measures (adiabatic) temperature changes or indirect methods where one can measure the stress-strain-temperature characteristics of the materials and from these deduce the adiabatic temperature and isothermal entropy changes. The former can be done using the basic thermodynamic relations, i.e. Maxwell relation and Clausius-Clapeyron equation. This paper further presents basic thermodynamic properties of shape memory materials, such as the adiabatic temperature change, isothermal entropy change and total entropy-temperature diagrams (all as a function of temperature and applied stress/strain) of two groups of materials (Ni-Ti and Cu-Zn-Al alloys) obtained using indirect methods through phenomenological modelling and Maxwell relation. In the last part of the paper, the basic definition of the efficiency of the elastocaloric thermodynamic cycle (coefficient of performance) is defined and discussed.

Comparison of Inboard-Outboard Pedestal Temperature Measurements in JET Using ECE Diagnostics

NASA Astrophysics Data System (ADS)

Barrera, L.; de la Luna, E.; Figini, L.

2008-03-01

Despite considerable effort, both theoretically and experimentally, a complete physical model to describe the particle and energy losses during ELMs is far from complete. On the experimental front, improved description of the spatial structure (poloidal asymmetry, radial distribution) and the dynamics of the ELM crash is a key requirement to answer some of the basic outstanding questions concerning the physics of ELMs. A significant number of diagnostics is now capable of fast measurements of the pedestal profile during an ELM, however, there is a lack of data from the inboard midplane, so assumptions of poloidal symmetry on the flux surfaces have often to be made. The aim of this work is to explore the capabilities of the electron cyclotron emission (ECE) diagnostics to provide simultaneous measurements of the edge temperature for both inboard and outboard plasma midplane. Access to the inboard region of the plasma is achieved in JET by using 1 harmonic/O-mode polarization, as it is not affected by harmonic overlap with the 2nd harmonic. This paper focuses on the validation of the inboard ECE data and the identification of the limitations of the measurements and the data analysis.

Electrochemical etching technique of platinum-iridium tips for scanning tunneling microscopy

NASA Astrophysics Data System (ADS)

Herrera, Oscar

The scanning tunneling microscope (STM) allows researchers to investigate atomic and molecular structures and properties of nanomaterials. Through the quantum tunneling effect a charge is transferred between the surface of the material and a Platinum-Iridium (Pt-Ir) tip. The production of Pt-Ir tips by electrochemical etching (ECE) has been developed as an alternative technique, to achieve enhanced scanned images of samples, in contrast to the standard mechanical method (SMM). The sharpness apex structure is an essential feature during scanning in order to provide reliable data. We generated a control group of tips by the SMM technique and another group by the ECE technique to investigate the resolution effectiveness in scanning of graphite. The etching of the tips was produced using an auto-variable transformer running a 30 V AC in a 1.5 and 4.0 M CaCl2 solution. The scanning of the graphite surface was conducted at 7x7 nm image width, 0.2 seconds time/line, 256 points/line and 0.05 V for tip voltage. ECE etched tips displayed consistent image resolution, and the sharpness of the tip apex was generally uniform.

Characterization of gossypol biosynthetic pathway

PubMed Central

Tian, Xiu; Ruan, Ju-Xin; Huang, Jin-Quan; Fang, Xin; Chen, Zhi-Wen; Hong, Hui; Wang, Ling-Jian; Mao, Ying-Bo; Lu, Shan; Zhang, Tian-Zhen; Chen, Xiao-Ya

2018-01-01

Gossypol and related sesquiterpene aldehydes in cotton function as defense compounds but are antinutritional in cottonseed products. By transcriptome comparison and coexpression analyses, we identified 146 candidates linked to gossypol biosynthesis. Analysis of metabolites accumulated in plants subjected to virus-induced gene silencing (VIGS) led to the identification of four enzymes and their supposed substrates. In vitro enzymatic assay and reconstitution in tobacco leaves elucidated a series of oxidative reactions of the gossypol biosynthesis pathway. The four functionally characterized enzymes, together with (+)-δ-cadinene synthase and the P450 involved in 7-hydroxy-(+)-δ-cadinene formation, convert farnesyl diphosphate (FPP) to hemigossypol, with two gaps left that each involves aromatization. Of six intermediates identified from the VIGS-treated leaves, 8-hydroxy-7-keto-δ-cadinene exerted a deleterious effect in dampening plant disease resistance if accumulated. Notably, CYP71BE79, the enzyme responsible for converting this phytotoxic intermediate, exhibited the highest catalytic activity among the five enzymes of the pathway assayed. In addition, despite their dispersed distribution in the cotton genome, all of the enzyme genes identified show a tight correlation of expression. Our data suggest that the enzymatic steps in the gossypol pathway are highly coordinated to ensure efficient substrate conversion. PMID:29784821

Quantifying the Spatial and Seasonal Hydrodynamics of Subsurface Soil Salinity and Selenium Mobilization in the Pariette Watershed, Uintah Basin, UT

NASA Astrophysics Data System (ADS)

Amakor, X. N.; Jacobson, A. R.; Cardon, G. E.; Grossl, P. R.

2011-12-01

A recent water quality report recognized concentrations of salts and selenium above total maximum daily loads (TMDLs) in the Pariette Wetlands located in the Uintah Basin, Utah. Since the wetlands are located in the Pacific Migratory Flyway and frequented by numerous water fowl, the elevated levels of total dissolved solids and Se are of concern. To determine whether it possible to manage the mobilization of salts and associated contaminants through the watershed soils into the Pariette Wetlands, knowledge of the spatio-temporal dynamics and distribution of these contaminants is required. Thus, the objective of this study is to characterize the spatio-temporal mobilization of salts and total selenium in the Pariette Draw watershed. Intensive soil information is being collected along the streams feeding the wetlands from fields representing the dominant land-uses in the watershed (irrigated agricultural fields, fallow salt-crusted fields, oil and natural gas extraction fields) using both the noninvasive electromagnetic induction (EMI) sensing technique (EM38DD) and the invasive time-domain reflectometry (TDR). At each site, ground truth samples were collected from optimally determined points generated using the ESAP-RSSD program based on the bulk soil electrical conductivity survey information. Stable soil properties affecting the measurement of salinity (e.g., clay content, organic matter content, cation exchange capacity, bulk density) were also characterized at these points. Parameters affected by fluctuations in soil moisture content (e.g., pH, electrical conductivity of saturation paste extract (ECe), dissolved organic carbon (DOC), and total selenium in the dissolved saturation extract) are being measured repeatedly over a minimum of 1 year. Based on regression models of collocated EMI, TDR and ECe measurements, the dense survey data are transformed into ECe. Geostatistical kriging methods are applied to the transformed ECe and volumetric water content to reveal the complex spatio-temporal patterns of salinity, water content, and total selenium (based on the association between ECe and total Se) across portions of the watershed. Temporal changes are being compared using the paired t-test. Here we present the spatio-temporal correlations among the properties and over the sampling times for the 2011 summer and fall seasons with an initial evaluation of the underlying processes contributing to the elevated contaminant loads at the wetlands. Additional measurements will be made in 2012 to capture the effects of early spring snowmelt and runoff.

Porcine pulmonary angiotensin I-converting enzyme--biochemical characterization and spatial arrangement of the N- and C-domains by three-dimensional electron microscopic reconstruction.

PubMed

Chen, Hui-Ling; Lünsdorf, Heinrich; Hecht, Hans-Jürgen; Tsai, Hsin

2010-08-01

The somatic angiotensin I-converting enzyme (sACE; peptidyl-dipeptidase A; EC 3.4.15.1) was isolated from pig lung and purified to homogeneity. The purified enzyme has a molecular mass of about 180 kDa. Upon proteolytic cleavage, two approximately 90 kDa fragments were obtained and identified by amino-terminal sequence analysis as the N- and C-domains of sACE. Both purified domains were shown to be catalytically active. A 2.3 nm resolution model of sACE was obtained by three-dimensional electron microscopic reconstruction of negatively stained sACE particles, based on atomic X-ray data fitting. Our model shows for the first time the relative orientation of the sACE catalytically active domains and their spatial distance. (c) 2010 Elsevier Ltd. All rights reserved.

An Enzyme-Catalyzed Multistep DNA Refolding Mechanism in Hairpin Telomere Formation

PubMed Central

Shi, Ke; Huang, Wai Mun; Aihara, Hideki

2013-01-01

Hairpin telomeres of bacterial linear chromosomes are generated by a DNA cutting–rejoining enzyme protelomerase. Protelomerase resolves a concatenated dimer of chromosomes as the last step of chromosome replication, converting a palindromic DNA sequence at the junctions between chromosomes into covalently closed hairpins. The mechanism by which protelomerase transforms a duplex DNA substrate into the hairpin telomeres remains largely unknown. We report here a series of crystal structures of the protelomerase TelA bound to DNA that represent distinct stages along the reaction pathway. The structures suggest that TelA converts a linear duplex substrate into hairpin turns via a transient strand-refolding intermediate that involves DNA-base flipping and wobble base-pairs. The extremely compact di-nucleotide hairpin structure of the product is fully stabilized by TelA prior to strand ligation, which drives the reaction to completion. The enzyme-catalyzed, multistep strand refolding is a novel mechanism in DNA rearrangement reactions. PMID:23382649

21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

Code of Federal Regulations, 2010 CFR

2010-04-01

....2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been... defined in § 170.3(o)(9) of this chapter, to convert lactose to glucose and galactose. (2) The ingredient... manufacturing practice is limited to use of this ingredient to reduce the lactose content in milk and milk...

21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

Code of Federal Regulations, 2011 CFR

2011-04-01

....2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been... defined in § 170.3(o)(9) of this chapter, to convert lactose to glucose and galactose. (2) The ingredient... manufacturing practice is limited to use of this ingredient to reduce the lactose content in milk and milk...

Sacubitril/Valsartan: The Newest Addition to the Toolbox for Guideline-Directed Medical Therapy of Heart Failure.

PubMed

Rodgers, Jo E

2017-06-01

Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril. The rate of all-cause mortality was also significantly reduced. Subsequently, the American College of Cardiology/American Heart Association/Heart Failure Society of America recently updated guideline recommendations for Stage C patients with heart failure with reduced ejection fraction to recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril/valsartan in conjunction with other evidence-based therapies to reduce morbidity and mortality. Several analyses have suggested the cost-effectiveness of this new therapy. To ensure tolerability, initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients. A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan. Similarly, sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema. Copyright © 2017 Elsevier Inc. All rights reserved.

Mining novel starch-converting Glycoside Hydrolase 70 enzymes from the Nestlé Culture Collection genome database: The Lactobacillus reuteri NCC 2613 GtfB.

PubMed

Gangoiti, Joana; van Leeuwen, Sander S; Meng, Xiangfeng; Duboux, Stéphane; Vafiadi, Christina; Pijning, Tjaard; Dijkhuizen, Lubbert

2017-08-30

The Glycoside hydrolase (GH) family 70 originally was established for glucansucrases of lactic acid bacteria (LAB) converting sucrose into α-glucan polymers. In recent years we have identified 3 subfamilies of GH70 enzymes (designated GtfB, GtfC and GtfD) as 4,6-α-glucanotransferases, cleaving (α1 → 4)-linkages in maltodextrins/starch and synthesizing new (α1 → 6)-linkages. In this work, 106 putative GtfBs were identified in the Nestlé Culture Collection genome database with ~2700 genomes, and the L. reuteri NCC 2613 one was selected for further characterization based on variations in its conserved motifs. Using amylose the L. reuteri NCC 2613 GtfB synthesizes a low-molecular-mass reuteran-like polymer consisting of linear (α1 → 4) sequences interspersed with (α1 → 6) linkages, and (α1 → 4,6) branching points. This product specificity is novel within the GtfB subfamily, mostly comprising 4,6-α-glucanotransferases synthesizing consecutive (α1 → 6)-linkages. Instead, its activity resembles that of the GtfD 4,6-α-glucanotransferases identified in non-LAB strains. This study demonstrates the potential of large-scale genome sequence data for the discovery of enzymes of interest for the food industry. The L. reuteri NCC 2613 GtfB is a valuable addition to the starch-converting GH70 enzyme toolbox. It represents a new evolutionary intermediate between families GH13 and GH70, and provides further insights into the structure-function relationships of the GtfB subfamily enzymes.

Production of 2-deoxyribose 5-phosphate from fructose to demonstrate a potential of artificial bio-synthetic pathway using thermophilic enzymes.

PubMed

Honda, Kohsuke; Maya, Shohei; Omasa, Takeshi; Hirota, Ryuichi; Kuroda, Akio; Ohtake, Hisao

2010-08-02

Six thermophilic enzymes from Thermus thermophilus were used to construct an 'artificial bio-synthetic pathway' for the production of 2-deoxyribose 5-phosphate from fructose. By a simple operation using six recombinant Escherichia coli strains producing the thermophilic enzymes, respectively, fructose was converted to 2-deoxyribose 5-phosphate with a molar yield of 55%. Copyright 2010 Elsevier B.V. All rights reserved.

Cloning and Characterization of the Glycoside Hydrolases That Remove Xylosyl Groups from 7-β-xylosyl-10-deacetyltaxol and Its Analogues*

PubMed Central

Cheng, Hai-Li; Zhao, Rui-Yu; Chen, Tian-Jiao; Yu, Wen-Bo; Wang, Fen; Cheng, Ke-Di; Zhu, Ping

2013-01-01

Paclitaxel, a natural antitumor compound, is produced by yew trees at very low concentrations, causing a worldwide shortage of this important anticancer medicine. These plants also produce significant amounts of 7-β-xylosyl-10-deacetyltaxol, which can be bio-converted into 10-deacetyltaxol for the semi-synthesis of paclitaxel. Some microorganisms can convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol, but the bioconversion yield needs to be drastically improved for industrial applications. In addition, the related β-xylosidases of these organisms have not yet been defined. We set out to discover an efficient enzyme for 10-deacetyltaxol production. By combining the de novo sequencing of β-xylosidase isolated from Lentinula edodes with RT-PCR and the rapid amplification of cDNA ends, we cloned two cDNA variants, Lxyl-p1–1 and Lxyl-p1–2, which were previously unknown at the gene and protein levels. Both variants encode a specific bifunctional β-d-xylosidase/β-d-glucosidase with an identical ORF length of 2412 bp (97% identity). The enzymes were characterized, and their 3.6-kb genomic DNAs (G-Lxyl-p1–1, G-Lxyl-p1–2), each harboring 18 introns, were also obtained. Putative substrate binding motifs, the catalytic nucleophile, the catalytic acid/base, and potential N-glycosylation sites of the enzymes were predicted. Kinetic analysis of both enzymes showed kcat/Km of up to 1.07 s−1mm−1 against 7-β-xylosyl-10-deacetyltaxol. Importantly, at substrate concentrations of up to 10 mg/ml (oversaturated), the engineered yeast could still robustly convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol with a conversion rate of over 85% and a highest yield of 8.42 mg/ml within 24 h, which is much higher than those reported previously. Therefore, our discovery might lead to significant progress in the development of new 7-β-xylosyl-10-deacetyltaxol-converting enzymes for more efficient use of 7-β-xylosyltaxanes to semi-synthesize paclitaxel and its analogues. This work also might lead to further studies on how these enzymes act on 7-β-xylosyltaxanes and contribute to the growing database of glycoside hydrolases. PMID:23665501

Screening the ToxCast Phase I, II, and e1K Chemical Libraries for Inhibition of Deiodinase Type 1,2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) signaling and homeostasis is dependent upon coordination of multiple key events including thyroidal iodide uptake and hormone synthesis, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting the pro-hormone thyroxi...

Characterization of Enzymes Catalyzing Transformations of Cysteine S-Conjugated Intermediates in the Lincosamide Biosynthetic Pathway.

PubMed

Ushimaru, Richiro; Lin, Chia-I; Sasaki, Eita; Liu, Hung-Wen

2016-09-02

Lincosamides such as lincomycin A, celesticetin, and Bu-2545, constitute an important group of antibiotics. These natural products are characterized by a thiooctose linked to a l-proline residue, but they differ with regards to modifications of the thioacetal moiety, the pyrrolidine ring, and the octose core. Here we report that the pyridoxal 5'-phosphate-dependent enzyme CcbF (celesticetin biosynthetic pathway) is a decarboxylating deaminase that converts a cysteine S-conjugated intermediate into an aldehyde. In contrast, the homologous enzyme LmbF (lincomycin biosynthetic pathway) catalyzes C-S bond cleavage of the same intermediate to afford a thioglycoside. We show that Ccb4 and LmbG (downstream methyltransferases) convert the aldehyde and thiol intermediates into a variety of methylated lincosamide compounds including Bu-2545. The substrates used in these studies are the β-anomers of the natural substrates. The findings not only provide insight into how the biosynthetic pathway of lincosamide antibiotics can bifurcate to generate different lincosamides, but also reveal the promiscuity of the enzymes involved. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immobilized enzymes to convert N-sulfo, N-acetyl heparosan to a critical intermediate in the production of bioengineered heparin.

PubMed

Xiong, Jian; Bhaskar, Ujjwal; Li, Guoyun; Fu, Li; Li, Lingyun; Zhang, Fuming; Dordick, Jonathan S; Linhardt, Robert J

2013-09-10

Heparin is a critically important anticoagulant drug that is prepared from pig intestine. In 2007-2008, there was a crisis in the heparin market when the raw material was adulterated with the toxic polysaccharide, oversulfated chondroitin sulfate, which was associated with 100 deaths in the U.S. alone. As the result of this crisis, our laboratory and others have been actively pursuing alternative sources for this critical drug, including synthetic heparins and bioengineered heparin. In assessing the bioengineering processing costs it has become clear that the use of both enzyme-catalyzed cofactor recycling and enzyme immobilization will be needed for commercialization. In the current study, we examine the use of immobilization of C₅-epimerase and 2-O-sulfotransferase involved in the first enzymatic step in the bioengineered heparin process, as well as arylsulfotransferase-IV involved in cofactor recycling in all three enzymatic steps. We report the successful immobilization of all three enzymes and their use in converting N-sulfo, N-acetyl heparosan into N-sulfo, N-acetyl 2-O-sulfo heparin. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis.

PubMed

Lin, Kai; Zhang, Lanwei; Han, Xue; Meng, Zhaoxu; Zhang, Jianming; Wu, Yifan; Cheng, Dayou

2018-03-28

In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (<3 kDa) derived from combinations of thermolysin + alcalase and thermolysin + proteinase K demonstrated high ACE inhibitory activities. Peptide sequences in hydrolysates derived from these two combinations were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). On the basis of the QSAR modeling prediction, a total of 16 peptides were selected for molecular docking analysis. The docking study revealed that four of the peptides (KFPQY, MPFPKYP, MFPPQ, and QWQVL) bound the active site of ACE. These four novel peptides were chemically synthesized, and their IC 50 was determined. Among these peptides, KFPQY showed the highest ACE inhibitory activity (IC 50 = 12.37 ± 0.43 μM). Our study indicated that Qula casein presents an excellent source to produce ACE inhibitory peptides.

Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food.

PubMed

Murakami, Keiko; Yamanaka, Naoki; Ohnishi, Katsunori; Fukayama, Minoru; Yoshino, Masataka

2012-06-01

Angiotensin I converting enzyme (ACE) was inhibited by the culture medium of Bacillus subtilis subsp. natto, which ferments boiled soy beans to natto, a Japanese traditional food. Subtilisin NAT (nattokinase) produced by B. subtilis also inhibited ACE, and the inhibition was markedly stimulated by heat treatment of subtilisin at 120 °C for 15 min. Inhibition of ACE by subtilisin was of a mixed type: the decrease in V(max) and the increase in K(m) value. SDS-polyacrylamide gel electrophoresis showed that heat treatment of subtilisin caused inactivation with fragmentation of the enzyme protein into small peptides. The inhibitory action of subtilisin was not due to an enzymatic action of protease, but may be ascribed to the potent ACE-inhibitory peptides such as LY and FY, amino acid sequences in subtilisin. HPLC-MS analysis of heat-inactivated subtilisin confirmed that LY and FY were liberated by fragmentation of the enzyme. Inhibition of ACE by subtilisin and its degradation peptides such as LY and FY may participate in the suppression of blood pressure by ingestion of natto.

Conversion of 2-chloro-cis,cis-muconate and its metabolites 2-chloro- and 5-chloromuconolactone by chloromuconate cycloisomerases of pJP4 and pAC27.

PubMed Central

Vollmer, M D; Schlömann, M

1995-01-01

2-Chloro-cis,cis-muconate, the product of ortho-cleavage of 3-chlorocatechol, was converted by purified preparations of the pJP4- and pAC27-encoded chloromuconate cycloisomerases (EC 5.5.1.7) to trans-dienelactone (trans-4-carboxymethylenebut-2-en-4-olide). The same compound was also formed when (+)-2-chloro- and (+)-5-chloromuconolactone were substrates of these enzyme preparations. Thus, the pJP4- and pAC27-encoded chloromuconate cycloisomerases are able to catalyze chloride elimination from (+)-5-chloromuconolactone. The ability to convert (+)-2-chloromuconolactone differentiates these enzymes from other groups of cycloisomerases. PMID:7751312

The linkage disequilibrium pattern of the angiotensin converting enzyme gene in Arabic and Asian population groups.

PubMed

Kharrat, Najla; Abdelmouleh, Wafa; Abdelhedi, Rania; Alfadhli, Suad; Rebai, Ahmed

2012-01-01

DNA variations within the Angiotensin-Converting Enzyme (ACE) gene have been shown to be involved in the aetiology of several common diseases and the therapeutic response. This study reports a comparison of haplotype analysis of five SNPs in the ACE gene region using a sample of 100 healthy subjects derived from five different populations (Tunisian, Iranian, Kuwaiti, Bahraini and Indian). Strong linkage disequilibrium was found among all SNPs studied for all populations. Two SNPs (rs1800764 and rs4340) were identified as key SNPs for all populations. These SNPs will be valuable for future effective association studies of the ACE gene polymorphisms in Arab and Asian populations.

Screening the Brazilian flora for antihypertensive plant species for in vitro angiotensin-I-converting enzyme inhibiting activity.

PubMed

Castro Braga, F; Wagner, H; Lombardi, J A; de Oliveira, A B

2000-06-01

The evaluation of several antihypertensive activity of Brazilian plant species was performed using in vitro inhibition of the angiotensin I-converting enzyme (ACE). Nineteen species belonging to 13 families were investigated. Plants were selected based on their use as diuretics and on a chemosystematic consideration. Extracts of the following species presented the highest ACE inhibition rate, at concentrations of 0.33 mg/ml: Ouratea semiserrata (Mart. & Nees) Engl. stems (68%), Cuphea cartagenesis (Jacq.) Macbride leaves (50%) and Mansoa hirsuta DC. leaves (54%). Some hypotheses about the nature of the compounds that may be responsible for the activity of these species are discussed in the paper.

LECITHINASE AND LYSOLECITHINASE ACTIVITY OF RAT INTESTINAL MUCOSA AFTER WHOLE-BODY X-IRRADIATION

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

Ottolenghi, A.; Bernheim, F.

1961-11-01

Twenty-four hours after whole-body x irradiation the lecithinase activity of rat intestinal mucosa has markedly decreased and the lysolecithinase activity has decreasecp to a lesser extent. Addition of normal mucosa or chyi'otrypsin to the irradiated mucosa restores the activity of both enzymes. This indicates that irradiation eithei produces an inhibitor or inactivates a mechanism necessarly to convert pro-enzymes into active enzymes. Since chymo trypsin can increase to some extent the activity of the enzymes in normal mucosa, the second possibility seems more probable. (auth)

HPLC-DAD Analysis and In-Vitro Property of Polyphenols Extracts from (Solanum Aethiopium) Fruits on α -Amylase, α -Glucosidase and Angiotensin - 1- Converting Enzyme Activities

PubMed Central

Nwanna, E. E; Ibukun, E. O; Oboh, G.; Ademosun, A. O.; Boligon, A. A.; Athayde, M.

2014-01-01

AIM: Garden egg (Solanum aethiopium) is an edible fruits vegetable with  different species.This study investigated characterisation and the effect of the phenolics extracts from S. aethiopium species with enzymes linked with type -2-diabetes (α-amylase and α-glucosidase) and hypertension [Angiotensin-1-converting enzyme (ACE)]. METHODS: Fresh samples of the 5 species of the garden egg namely, [Solanum gilo (PW), Solanum torvum (TWS), Solanum kumba (PGR), Solanum incanum (GSB), and Solanum indicum (WSB)] were oven-dried at 50°C and milled into flour. The aqueous extracts were prepared (1:50 w/v). The phenolic contents (total phenol and total flavonoid), vitamin C and 1,1-diphenyl–2-picrylhydrazyl (DPPH), the antioxidant activities of the extracts were evaluated. The ability of the extracts to inhibit diabetes enzymes in rat pancreas as well as the inhibition of angiotensin-1-converting (ACE) enzyme in lungs homogenates in vitro were investigated. Furthermore, the fruits polyphenols were identified and quantified using HPLC-DAD. RESULTS: The phenolic contents ranged from 2.70-3.76 mgGAE/g, while there were no significant (P>0.05) differences in their flavonoid content and ability to reduce Fe3+ to Fe2+. The vitamin C contents of the species ranged from 4.01-6.52 mg/ml. The extracts scavenged DPPH in a dose dependent manner with the IC50 values ranging from 3.23-4.20 mg/ml. Furthermore, the extracts showed strong inhibition of α-glucosidase, mild inhibition of α-amylase and strong inhibition of ACE activities. CONCLUSION: This study showed that the inhibition of the key enzymes relevant to type-2 diabetes and hypertension could be part of the mechanisms by which garden egg manage/prevent the degenerative conditions. PMID:25598760

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

PubMed Central

Ong, Frank S.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Giani, Jorge F.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien

2013-01-01

Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of ACE is that it is composed of two homologous and independently catalytic domains, the result of an ancient gene duplication, and ACE-like genes are widely distributed in nature. The two ACE catalytic domains contribute to the wide substrate diversity of ACE and, by extension, the physiologic impact of the enzyme. Several studies suggest that the two catalytic domains have different biologic functions. Recently, the X-ray crystal structure of ACE has elucidated some of the structural differences between the two ACE domains. This is important now that ACE domain-specific inhibitors have been synthesized and characterized. Once widely available, these reagents will undoubtedly be powerful tools for probing the physiologic actions of each ACE domain. In turn, this knowledge should allow clinicians to envision new therapies for diseases not currently treated with ACE inhibitors. PMID:23257181

The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism

PubMed Central

Sonsalla, Patricia K.; Coleman, Christal; Wong, Lai-Yoong; Harris, Suzan L.; Richardson, Jason R.; Gadad, Bharathi S.; Li, Wenhao; German, Dwight C.

2013-01-01

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin converting enzyme inhibitor captopril protects the striatum from acutely administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP), and that chronic captopril protects the nigral DA cell bodies from degeneration in a progressive rat model of parkinsonism created by the chronic intracerebral infusion of 1-methyl-4-phenylpyridinium (MPP+). The accompanying activation of microglia in the substantia nigra of MPP+-treated rats was reduced by the chronic captopril treatment. These findings indicate that captopril is neuroprotective for nigrostriatal DA neurons in both acute and chronic rodent PD models. Targeting the brain AngII pathway may be a feasible approach to slowing neurodegeneration in PD. PMID:24184050

Production of high concentration of L-lactic acid from cellobiose by thermophilic Bacillus coagulans WCP10-4.

PubMed

Ong, Shufen Angeline; Ng, Zhi Jian; Wu, Jin Chuan

2016-07-01

Thermophilic Bacillus coagulans WCP10-4 is found to be able to convert cellobiose to optically pure L-lactic acid. Its β-glucosidase activity is detected in whole cells (7.3 U/g dry cells) but not in culture medium, indicating the intracellular location of the enzyme. Its β-glucosidase activity is observed only when cultured using cellobiose as the sole carbon source, indicating that the expression of this enzyme is tightly regulated in cells. The enzyme is most active at 50 °C and pH 7.0. The supplement of external β-glucosidase during fermentation of cellobiose (106 g/l) by B. coagulans WCP10-4 increased the fermentation time from 21 to 23 h and decreased the lactic acid yield from 96.1 to 92.9 % compared to the control without β-glucosidase supplementation. B. coagulans WCP10-4 converted 200 g/l of cellobiose to 196.3 g/l of L-lactic acid at a yield of 97.8 % and a productivity of 7.01 g/l/h. This result shows that B. coagulans WCP10-4 is a highly efficient strain for converting cellobiose to L-lactic acid without the need of supplementing external β-glucosidases.

Discovery and structural characterisation of new fold type IV-transaminases exemplify the diversity of this enzyme fold

PubMed Central

Pavkov-Keller, Tea; Strohmeier, Gernot A.; Diepold, Matthias; Peeters, Wilco; Smeets, Natascha; Schürmann, Martin; Gruber, Karl; Schwab, Helmut; Steiner, Kerstin

2016-01-01

Transaminases are useful biocatalysts for the production of amino acids and chiral amines as intermediates for a broad range of drugs and fine chemicals. Here, we describe the discovery and characterisation of new transaminases from microorganisms which were enriched in selective media containing (R)-amines as sole nitrogen source. While most of the candidate proteins were clearly assigned to known subgroups of the fold IV family of PLP-dependent enzymes by sequence analysis and characterisation of their substrate specificity, some of them did not fit to any of these groups. The structure of one of these enzymes from Curtobacterium pusillum, which can convert d-amino acids and various (R)-amines with high enantioselectivity, was solved at a resolution of 2.4 Å. It shows significant differences especially in the active site compared to other transaminases of the fold IV family and thus indicates the existence of a new subgroup within this family. Although the discovered transaminases were not able to convert ketones in a reasonable time frame, overall, the enrichment-based approach was successful, as we identified two amine transaminases, which convert (R)-amines with high enantioselectivity, and can be used for a kinetic resolution of 1-phenylethylamine and analogues to obtain the (S)-amines with e.e.s >99%. PMID:27905516

Purification and characterization of a bacterial nitrophenol oxygenase which converts ortho-nitrophenol to catechol and nitrite.

PubMed Central

Zeyer, J; Kocher, H P

1988-01-01

A nitrophenol oxygenase which stoichiometrically converted ortho-nitrophenol (ONP) to catechol and nitrite was isolated from Pseudomonas putida B2 and purified. The substrate specificity of the enzyme was broad and included several halogen- and alkyl-substituted ONPs. The oxygenase consisted of a single polypeptide chain with a molecular weight of 58,000 (determined by gel filtration) or 65,000 (determined on a sodium dodecyl sulfate-polyacrylamide gel). The enzymatic reaction was NADPH dependent, and one molecule of oxygen was consumed per molecule of ONP converted. Enzymatic activity was stimulated by magnesium or manganese ions, whereas the addition of flavin adenine dinucleotide, flavin mononucleotide, or reducing agents had no effect. The apparent Kms for ONP and NADPH were 8 and 140 microM, respectively. 2,4-Dinitrophenol competitively (Ki = 0.5 microM) inhibited ONP turnover. The optimal pH for enzyme stability and activity was in the range of 7.5 to 8.0. At 40 degrees C, the enzyme was totally inactivated within 2 min; however, in the presence of 1 mM ONP, 40% of the activity was recovered, even after 10 min. Enzymatic activity was best preserved at -20 degrees C in the presence of 50% glycerol. Images PMID:3350791

Enhanced electrocaloric effect in La-based PZT antiferroelectric ceramics

NASA Astrophysics Data System (ADS)

Mendez-González, Y.; Peláiz-Barranco, A.; Yang, Tongqing; Guerra, J. D. S.

2018-03-01

The electrocaloric effect (ECE) has been investigated in (Pb0.98La0.02)(Zr0.95Ti0.05)0.995O3 antiferroelectric ceramics obtained via the solid-state reaction method. The results from indirect measurements across the temperature range considered reveal a large electrocaloric temperature change (ΔT) of approximately 5 K at 373 K. The enhanced ECE, which is significantly higher than those reported for some lead-free and lead-based electro-ceramics, was obtained by applying an electric field of 60 kV/cm lower than what has been reported for commonly studied ceramic systems. This result suggests that this system is a potential candidate for practical electrocaloric device applications.

Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials.

PubMed

Brownstein, Daniel J; Salagre, Estela; Köhler, Cristiano; Stubbs, Brendon; Vian, João; Pereira, Ciria; Chavarria, Victor; Karmakar, Chandan; Turner, Alyna; Quevedo, João; Carvalho, André F; Berk, Michael; Fernandes, Brisa S

2018-01-01

It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life. Meta-analysis of published literature. PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017. Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration. Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p < 0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15). Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.

Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype: evidence for gene-environment interaction in healthy volunteers.

PubMed

Lely, A Titia; Heerspink, Hiddo J Lambers; Zuurman, Mike; Visser, Folkert W; Kocks, Menno J A; Boomsma, Frans; Navis, Gerjan

2010-12-01

Renin-angiotensin-aldosterone system blockade is a cornerstone in cardiovascular protection. Angiotensin-converting enzyme (ACE)-DD genotype has been associated with resistance to angiotensin-converting enzyme inhibition (ACEi), but data are conflicting. As sodium intake modifies the effect of ACEi as well as the genotype-phenotype relationship, we hypothesize gene-environment interaction between sodium-status, the response to ACEi, and ACE genotype. Thirty-five male volunteers (26 ± 9 years; II n = 6, ID n = 18, DD n = 11) were studied during placebo and ACEi (double blind, enalapril 20 mg/day) on low [7 days 50 mmol Na/day (low salt)] and high [7 days 200 mmol Na/day (high salt)] sodium, with a washout of 6 weeks in-between. After each period mean arterial pressure (MAP) was measured before and during graded infusion of angiotensin II (Ang II). During high salt, ACEi reduced MAP in II and ID, but not in DD [II: 88 (78-94) versus 76 (72-88); ID: 87 (84-91) versus 83 (79-87); both P < 0.05 and DD: 86 (82-96) versus 88 (80-90); ns, P < 0.05 between genotypes]. However, during low salt, ACEi reduced MAP in all genotype groups [II: 83 (78-89) versus 77 (72-83); ID: 88 (84-91) versus 82 (78-86); DD: 84 (80-91) versus 81 (75-85); all P < 0.05]. During high salt + ACEi, the Ang II response was blunted in DD, with an 18% rise in MAP during the highest dose versus 22 and 31% in ID and II (P < 0.05). Low salt annihilated these differences. In healthy participants, the MAP response to ACEi is selectively blunted in DD genotype during high salt, accompanied by blunted sensitivity to Ang II. Low salt corrects both abnormalities. Further analysis of this gene-environment interaction in patients may contribute to strategies for improvement of individual treatment efficacy.

Impact of Empagliflozin on Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension by Background Antihypertensive Medication.

PubMed

Mancia, Giuseppe; Cannon, Christopher P; Tikkanen, Ilkka; Zeller, Cordula; Ley, Ludwin; Woerle, Hans J; Broedl, Uli C; Johansen, Odd Erik

2016-12-01

In the EMPA-REG BP trial, empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin, blood pressure (BP), and weight versus placebo in patients with type 2 diabetes mellitus and hypertension. Patients received placebo (n=271), empagliflozin 10 mg (n=276), or empagliflozin 25 mg (n=276) for 12 weeks (n=full analysis set). This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP (SBP) and diastolic BP (DBP) in patients receiving 0, 1, or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Compared with placebo, empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 (10 mg: -3.89/-2.58 mm Hg; 25 mg: -3.77/-2.45 mm Hg), 1 (10 mg: -4.74/-1.97 mm Hg; 25 mg: -4.27/-1.81 mm Hg), or ≥2 (10 mg: -2.36/-0.68 mm Hg; 25 mg: -4.17/-1.54 mm Hg) antihypertensives. The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP (interaction P value 0.448) or DBP (interaction P value 0.498). Empagliflozin reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, with no significant difference between subgroups by use/no use of diuretics (interaction P values 0.380 [systolic]; 0.240 [diastolic]) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (interaction P values 0.900 [systolic]; 0.359 [diastolic]). In conclusion, in patients with type 2 diabetes mellitus and hypertension, empagliflozin for 12 weeks reduced SBP and DBP versus placebo, irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. URL: https://clinicaltrials.gov. Unique identifier: NCT01370005. © 2016 American Heart Association, Inc.

Discovery of novel hydroxamates as highly potent tumor necrosis factor-[alpha] converting enzyme inhibitors. Part II: Optimization of the S3′ pocket

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

Mazzola Jr., Robert D.; Zhu, Zhaoning; Sinning, Lisa

2010-10-01

A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1{prime}-S3{prime} pocket.

Focus on increased serum angiotensin-converting enzyme level: From granulomatous diseases to genetic mutations.

PubMed

Lopez-Sublet, Marilucy; di Lanzacco, Lorenzo Caratti; Jan Danser, A H; Lambert, Michel; Elourimi, Ghassan; Persu, Alexandre

2018-06-18

Angiotensin I-converting enzyme (ACE) is a well-known zinc-metallopeptidase that converts angiotensin I to the potent vasoconstrictor angiotensin II and degrades bradykinin, a powerful vasodilator, and as such plays a key role in the regulation of vascular tone and cardiac function. Increased circulating ACE (cACE) activity has been reported in multiple diseases, including but not limited to granulomatous disorders. Since 2001, genetic mutations leading to cACE elevation have also been described. This review takes advantage of the identification of a novel ACE mutation (25-IVS25 + 1G > A) in two Belgian pedigrees to summarize current knowledge about the differential diagnosis of cACE elevation, based on literature review and the experience of our centre. Furthermore, we propose a practical approach for the evaluation and management of patients with elevated cACE and discuss in which cases search for genetic mutations should be considered. Copyright © 2018. Published by Elsevier Inc.

Angiotensin converting enzyme immobilized on magnetic beads as a tool for ligand fishing.

PubMed

de Almeida, Fernando G; Vanzolini, Kenia L; Cass, Quezia B

2017-01-05

Angiotensin converting enzyme (ACE) presents an important role in blood pressure regulation, since that converts angiotensin I to the vasoconstrictor angiotensin II. Some commercially available ACE inhibitors are captopril, lisinopril and enalapril; due to their side effects, naturally occurring inhibitors have been prospected. In order to endorse this research field we have developed a new tool for ACE ligand screening. To this end, ACE was extracted from bovine lung, purified and chemically immobilized in modified ferrite magnetic beads (ACE-MBs). The ACE-MBs have shown a Michaelian kinetic behavior towards hippuryl-histidyl-leucine. Moreover, as proof of concept, the ACE-MBs was inhibited by lisinopril with a half maximal inhibitory concentration (IC 50 ) of 10nM. At the fishing assay, ACE-MBs were able not only to fish out the reference inhibitor, but also one peptide from a pool of tryptic digested BSA. In conclusion, ACE-MBs emerge as new straightforward tool for ACE kinetics determination, inhibition and binder screening. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of progenin III from total steroidal saponins of Dioscorea nipponica Makino using a crude enzyme from Aspergillus oryzae strain.

PubMed

Liu, Tingqiang; Yu, Hongshan; Liu, Chunying; Bao, Yongming; Hu, Xiangchun; Wang, Yuanhao; Liu, Bing; Fu, Yaoyao; Tang, Sihui; Jin, Fengxie

2013-05-01

Progenin III, one of the most active spirostanol saponins, is a potential candidate for anti-cancer therapy due to its strong antitumor activity and low hemolytic activity. However, the concentration of progenin III is extremely low in natural Dioscorea plants. In this paper, the progenin III production from total steroidal saponins of Dioscorea nipponica Makino was studied using the crude enzyme from Aspergillus oryzae DLFCC-38. The crude enzyme converting total steroidal saponins into progenin III was obtained from the A. oryzae DLFCC-38 culture. For enzyme production, the strain was cultured for 72 h at 30 °C with shaking at 150 rpm in 5 % (w/v) malt extract medium containing 2 % (v/v) extract of D. nipponica as the enzyme inducer. The crude enzyme converted total steroidal saponins into major progenin III with a high yield when the reaction was carried out for 9 h at 50 °C and pH 5.0 with the 20 mg/ml of substrate. In the preparation of progenin III, 117 g of crude progenin III was obtained from 160 g of substrate, and the crude product was purified with silica gel column to obtain 60.3 g progenin III of 93.4 % purity.

Screening the ToxCast Phase 1, 2, and e1k chemical libraries for inhibition of Deiodinase Types 1, 2 and 3 enzyme activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent on multiple proteins for TH synthesis, transport, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting THs between active and inactive forms by deiodinating the pro-hormone thyroxine (T4) ...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... isomerase enzyme preparations are used in the production of high fructose corn syrup described in § 184.1866... defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good manufacturing practice. [48 FR 5720, Feb...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

Serine proteases as candidates for proteolytic processing of angiotensin-I converting enzyme.

PubMed

Aragão, Danielle S; de Andrade, Maria Claudina C; Ebihara, Fabiana; Watanabe, Ingrid K M; Magalhães, Dayane C B P; Juliano, Maria Aparecida; Hirata, Izaura Yoshico; Casarini, Dulce Elena

2015-01-01

Somatic angiotensin-I converting enzyme (sACE) is a broadly distributed peptidase which plays a role in blood pressure and electrolyte homeostasis by the conversion of angiotensin I into angiotensin II. N-domain isoforms (nACE) with 65 and 90 kDa have been described in body fluids, tissues and mesangial cells (MC), and a 90 kDa nACE has been described only in spontaneously hypertensive rats. The aim of this study was to investigate the existence of proteolytic enzymes that may act in the hydrolysis of sACE generating nACEs in MC. After the confirmation of the presence of ACE sheddases in Immortalized MC (IMC), we purified and characterized these enzymes using fluorogenic substrates specifically designed for ACE sheddases. Purified enzyme identified as a serine protease by N-terminal sequence was able to generate nACE. In the present study, we described for the first time the presence of ACE sheddases in IMC, identified as serine proteases able to hydrolyze sACE in vitro. Further investigations are necessary to elucidate the mechanisms responsible for the expression and regulation of ACE sheddases in MC and their roles in the generation of nACEs, especially the 90 kDa form possibly related to hypertension. Copyright © 2014 Elsevier B.V. All rights reserved.

Back-reactions, short-circuits, leaks and other energy wasteful reactions in biological electron transfer: redox tuning to survive life in O(2).

PubMed

Rutherford, A William; Osyczka, Artur; Rappaport, Fabrice

2012-03-09

The energy-converting redox enzymes perform productive reactions efficiently despite the involvement of high energy intermediates in their catalytic cycles. This is achieved by kinetic control: with forward reactions being faster than competing, energy-wasteful reactions. This requires appropriate cofactor spacing, driving forces and reorganizational energies. These features evolved in ancestral enzymes in a low O(2) environment. When O(2) appeared, energy-converting enzymes had to deal with its troublesome chemistry. Various protective mechanisms duly evolved that are not directly related to the enzymes' principal redox roles. These protective mechanisms involve fine-tuning of reduction potentials, switching of pathways and the use of short circuits, back-reactions and side-paths, all of which compromise efficiency. This energetic loss is worth it since it minimises damage from reactive derivatives of O(2) and thus gives the organism a better chance of survival. We examine photosynthetic reaction centres, bc(1) and b(6)f complexes from this view point. In particular, the evolution of the heterodimeric PSI from its homodimeric ancestors is explained as providing a protective back-reaction pathway. This "sacrifice-of-efficiency-for-protection" concept should be generally applicable to bioenergetic enzymes in aerobic environments. Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers.

PubMed

Onoyovwe, Akpevwe; Hagel, Jillian M; Chen, Xue; Khan, Morgan F; Schriemer, David C; Facchini, Peter J

2013-10-01

Immunofluorescence labeling and shotgun proteomics were used to establish the cell type-specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy.

Capsule endoscopy in pediatrics: a 10-years journey.

PubMed

Oliva, Salvatore; Cohen, Stanley A; Di Nardo, Giovanni; Gualdi, Gianfranco; Cucchiara, Salvatore; Casciani, Emanuele

2014-11-28

Video capsule endoscopy (CE) for evaluation the esophagus (ECE), small bowel (SBCE) and the colon (CCE) is particularly useful in pediatrics, because this imaging modality does not require ionizing radiation, deep sedation or general anesthesia. The risk of capsule retention appears to be dependent on indication rather than age and parallels the adult experience by indication, making SBCE a relatively safe procedure with a significant diagnostic yield. The newest indication, assessment of mucosal change, greatly enhances and expands its potential benefit. The diagnostic role of CE extends beyond the SB. The use of ECE also may enhance our knowledge of esophageal disease and assist patient care. Colon CCE is a novel minimally invasive and painless endoscopic technique allowing exploration of the colon without need for sedation, rectal intubation and gas insufflation. The limited data on ECE and CCE in pediatrics does not yet allow the same conclusions regarding efficacy; however, both appear to provide safe methods to assess and monitor mucosal change in their respective areas with little discomfort. Moreover, although experience has been limited, the patency capsule may help lessen the potential of capsule retention; and newly researched protocols for bowel cleaning may further enhance CE's diagnostic yield. However, further research is needed to optimize the use of the various CE procedures in pediatric populations.

Traveling magnetopause distortion related to a large-scale magnetosheath plasma jet: THEMIS and ground-based observations

NASA Astrophysics Data System (ADS)

Dmitriev, A. V.; Suvorova, A. V.

2012-08-01

Here, we present a case study of THEMIS and ground-based observations of the perturbed dayside magnetopause and the geomagnetic field in relation to the interaction of an interplanetary directional discontinuity (DD) with the magnetosphere on 16 June 2007. The interaction resulted in a large-scale local magnetopause distortion of an "expansion - compression - expansion" (ECE) sequence that lasted for ˜15 min. The compression was caused by a very dense, cold, and fast high-βmagnetosheath plasma flow, a so-called plasma jet, whose kinetic energy was approximately three times higher than the energy of the incident solar wind. The plasma jet resulted in the effective penetration of magnetosheath plasma inside the magnetosphere. A strong distortion of the Chapman-Ferraro current in the ECE sequence generated a tripolar magnetic pulse "decrease - peak- decrease" (DPD) that was observed at low and middle latitudes by some ground-based magnetometers of the INTERMAGNET network. The characteristics of the ECE sequence and the spatial-temporal dynamics of the DPD pulse were found to be very different from any reported patterns of DD interactions with the magnetosphere. The observed features only partially resembled structures such as FTE, hot flow anomalies, and transient density events. Thus, it is difficult to explain them in the context of existing models.

Managing the risk of extreme climate events in Australian major wheat production systems

NASA Astrophysics Data System (ADS)

Luo, Qunying; Trethowan, Richard; Tan, Daniel K. Y.

2018-06-01

Extreme climate events (ECEs) such as drought, frost risk and heat stress cause significant economic losses in Australia. The risk posed by ECEs in the wheat production systems of Australia could be better managed through the identification of safe flowering (SFW) and optimal time of sowing (TOS) windows. To address this issue, three locations (Narrabri, Roseworthy and Merredin), three cultivars (Suntop and Gregory for Narrabri, Mace for both Roseworthy and Merredin) and 20 TOS at 1-week intervals between 1 April and 12 August for the period from 1957 to 2007 were evaluated using the Agricultural Production System sIMulator (APSIM)-Wheat model. Simulation results show that (1) the average frequency of frost events decreased with TOS from 8 to 0 days (d) across the four cases (the combination of locations and cultivars), (2) the average frequency of heat stress events increased with TOS across all cases from 0 to 10 d, (3) soil moisture stress (SMS) increased with earlier TOS before reaching a plateau and then slightly decreasing for Suntop and Gregory at Narrabri and Mace at Roseworthy while SMS increased with TOS for Mace at Merredin from 0.1 to 0.8, (4) Mace at Merredin had the earliest and widest SFW (216-260) while Mace at Roseworthy had latest SFW (257-280), (5) frost risk and heat stress determine SFW at wetter sites (i.e. Narrabri and Roseworthy) while frost risk and SMS determine SFW at drier site (i.e. Merredin) and (6) the optimal TOS (window) to maximise wheat yield are 6-20 May, 13-27 May and 15 April at Narrabri, Roseworthy and Merredin, respectively. These findings provide important and specific information for wheat growers about the management of ECE risk on farm. Furthermore, the coupling of the APSIM crop models with state-of-the-art seasonal and intra-seasonal climate forecast information provides an important tool for improved management of the risk of ECEs in economically important cropping industries in the foreseeable future.

Telemedicine for gastrointestinal endoscopy: The Endoscopic Club E-conference in the Asia Pacific Region

PubMed Central

Ho, Shiaw-Hooi; Rerknimitr, Rungsun; Kudo, Kuriko; Tomimatsu, Shunta; Ahmad, Mohamad Zahir; Aso, Akira; Seo, Dong Wan; Goh, Khean-Lee; Shimizu, Shuji

2017-01-01

Background and study aims An Endoscopic Club E-conference (ECE) was set up in May 2014 to cater to increased demand for gastrointestinal endoscopy-related teleconferences in the Asia-Pacific region which were traditionally organized by the medical working group (MWG) of Asia-Pacific Advanced Network. This study describes how the ECE meeting was run, examines the group dynamics, outlines feedback and analyzes factors affecting the enthusiasm of participants. It is hoped that the findings here can serve as guidance for future development of other teleconference groups. Methods The preparation, running of and feedback on the ECE teleconference were evaluated and described. The country’s economic situation, time zone differences, connectivity with a research and education network (REN) and engineering cooperation of each member were recorded and analyzed with regard to their association with participant enthusiasm, which was taken as participation in at least 50 % of the meetings since joining. Associations were calculated using 2-way table with chi-square test to generate odds ratio and P value. Results To date, ECE members have increased from 7 to 29 (increment of 314 %). Feedback received indicated a high level of satisfaction with program content, audiovisual transmission and ease of technical preparation. Upper gastrointestinal luminal endoscopy-related topics were the most favored program content. Those topics were presented mainly via case studies with a focus on management challenges. Time zone differences of more than 6 hours and poor engineering cooperation were independently associated with inactive participation (P values of 0.04 and 0.001 respectively). Conclusions Good program content and high-quality audiovisual transmission are keys to the success of an endoscopic medical teleconference. In our analysis, poor engineering cooperation and discordant time zones contributed to inactive participation while connectivity with REN and a country’s economic situation were not significantly associated with participant enthusiasm. PMID:28382322

Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

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

Riaz, Nadeem; Afaq, Asim; Akin, Oguz

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes.more » The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.« less

Telemedicine for gastrointestinal endoscopy: The Endoscopic Club E-conference in the Asia Pacific Region.

PubMed

Ho, Shiaw-Hooi; Rerknimitr, Rungsun; Kudo, Kuriko; Tomimatsu, Shunta; Ahmad, Mohamad Zahir; Aso, Akira; Seo, Dong Wan; Goh, Khean-Lee; Shimizu, Shuji

2017-04-01

Background and study aims  An Endoscopic Club E-conference (ECE) was set up in May 2014 to cater to increased demand for gastrointestinal endoscopy-related teleconferences in the Asia-Pacific region which were traditionally organized by the medical working group (MWG) of Asia-Pacific Advanced Network. This study describes how the ECE meeting was run, examines the group dynamics, outlines feedback and analyzes factors affecting the enthusiasm of participants. It is hoped that the findings here can serve as guidance for future development of other teleconference groups. Methods  The preparation, running of and feedback on the ECE teleconference were evaluated and described. The country's economic situation, time zone differences, connectivity with a research and education network (REN) and engineering cooperation of each member were recorded and analyzed with regard to their association with participant enthusiasm, which was taken as participation in at least 50 % of the meetings since joining. Associations were calculated using 2-way table with chi-square test to generate odds ratio and P value. Results  To date, ECE members have increased from 7 to 29 (increment of 314 %). Feedback received indicated a high level of satisfaction with program content, audiovisual transmission and ease of technical preparation. Upper gastrointestinal luminal endoscopy-related topics were the most favored program content. Those topics were presented mainly via case studies with a focus on management challenges. Time zone differences of more than 6 hours and poor engineering cooperation were independently associated with inactive participation ( P values of 0.04 and 0.001 respectively). Conclusions  Good program content and high-quality audiovisual transmission are keys to the success of an endoscopic medical teleconference. In our analysis, poor engineering cooperation and discordant time zones contributed to inactive participation while connectivity with REN and a country's economic situation were not significantly associated with participant enthusiasm.

Field Testing of High Current Electrokinetic Nanoparticle Treatment for Corrosion Mitigation in Reinforced Concrete

NASA Technical Reports Server (NTRS)

Cardenas, Henry; Alexander, Joshua; Kupwade-Patil, Kunal; Calle, Luz marina

2010-01-01

Electrokinetic Nanoparticle (EN) treatment was used as a rapid repair measure to mitigate chloride induced corrosion of reinforced concrete in the field. EN treatment uses an electric field to transport positively charged nanoparticles to the reinforcement through the concrete capillary pores. Cylindrical reinforced concrete specimens were batched with 4.5 wt % salt content (based on cement mass). Three distinct electrokinetic treatments were conducted using high current density (up to 5 A/m2) to form a chloride penetration barrier that was established in 5 days, as opposed to the traditional 6-8 weeks, generally required for electrochemical chloride extraction (ECE). These treatments included basic EN treatment, EN with additional calcium treatment, and basic ECE treatment. Field exposures were conducted at the NASA Beachside Corrosion Test Site, Kennedy Space Center, Florida, USA. The specimens were subjected to sea water immersion at the test site as a posttreatment exposure. Following a 30-day post-treatment exposure period, the specimens were subjected to indirect tensile testing to evaluate treatment impact. The EN treated specimens exhibited 60% and 30% increases in tensile strength as compared to the untreated controls and ECE treated specimens respectively. The surfaces of the reinforcement bars of the control specimens were 67% covered by corrosion products. In contrast, the EN treated specimens exhibited corrosion coverage of only 4%. Scanning electron microscopy (SEM) revealed a dense concrete microstructure adjacent to the bars of the treated specimens as compared to the control and ECE specimens. Energy dispersive spectroscopic (EDS) analysis of the polished EN treated specimens showed a reduction in chloride content by a factor of 20 adjacent to the bars. This study demonstrated that EN treatment was successful in forming a chloride penetration barrier rapidly. This work also showed that the chloride barrier was effective when samples were exposed to field conditions at one of the most severely corrosive environments in North America.

Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-alpha converting enzyme (TACE): discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1' substituents.

PubMed

Lu, Zhonghui; Ott, Gregory R; Anand, Rajan; Liu, Rui-Qin; Covington, Maryanne B; Vaddi, Krishna; Qian, Mingxin; Newton, Robert C; Christ, David D; Trzaskos, James; Duan, James J-W

2008-03-15

Potent and selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC(50) value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F%>90%) in rat n-in-1 PK studies.

Enzymes involved in branched-chain amino acid metabolism in humans.

PubMed

Adeva-Andany, María M; López-Maside, Laura; Donapetry-García, Cristóbal; Fernández-Fernández, Carlos; Sixto-Leal, Cristina

2017-06-01

Branched-chain amino acids (leucine, isoleucine and valine) are structurally related to branched-chain fatty acids. Leucine is 2-amino-4-methyl-pentanoic acid, isoleucine is 2-amino-3-methyl-pentanoic acid, and valine is 2-amino-3-methyl-butanoic acid. Similar to fatty acid oxidation, leucine and isoleucine produce acetyl-coA. Additionally, leucine generates acetoacetate and isoleucine yields propionyl-coA. Valine oxidation produces propionyl-coA, which is converted into methylmalonyl-coA and succinyl-coA. Branched-chain aminotransferase catalyzes the first reaction in the catabolic pathway of branched-chain amino acids, a reversible transamination that converts branched-chain amino acids into branched-chain ketoacids. Simultaneously, glutamate is converted in 2-ketoglutarate. The branched-chain ketoacid dehydrogenase complex catalyzes the irreversible oxidative decarboxylation of branched-chain ketoacids to produce branched-chain acyl-coA intermediates, which then follow separate catabolic pathways. Human tissue distribution and function of most of the enzymes involved in branched-chain amino acid catabolism is unknown. Congenital deficiencies of the enzymes involved in branched-chain amino acid metabolism are generally rare disorders. Some of them are associated with reduced pyruvate dehydrogenase complex activity and respiratory chain dysfunction that may contribute to their clinical phenotype. The biochemical phenotype is characterized by accumulation of the substrate to the deficient enzyme and its carnitine and/or glycine derivatives. It was established at the beginning of the twentieth century that the plasma level of the branched-chain amino acids is increased in conditions associated with insulin resistance such as obesity and diabetes mellitus. However, the potential clinical relevance of this elevation is uncertain.

Fructose 1,6-diphosphatase in striated muscle

PubMed Central

Krebs, H. A.; Woodford, Muriel

1965-01-01

1. The occurrence of fructose diphosphatase in muscle tissue was investigated with reference to the question whether lactate can be converted into glycogen in muscle, as postulated by Meyerhof (1930), fructose diphosphatase being one of the enzymes required for this conversion. 2. Fructose diphosphatase was found in skeletal muscle of man, dog, cat, rat, mouse, rabbit, guinea pig, cattle, sheep, pigeon, fowl and frog. Under the test conditions between 5 and 60 μmoles of substrate were split/g. fresh wt./hr. at 22°. 3. Like liver fructose diphosphatase, the muscle enzyme is inhibited by substrate concentrations above 0·1 mm, by AMP and by trace quantities of Zn2+, Fe2+ and Fe3+; it is `activated' by EDTA. Inhibitions by the above agents may account for the failure of previous authors to detect the enzyme. 4. Heart muscle of several vertebrate species and the smooth muscle of pigeon and fowl gizzard had no measurable activity. 5. The presence of fructose diphosphatase and the virtual absence of the enzyme systems converting pyruvate into phosphopyruvate means that lactate and pyruvate cannot be converted into glycogen in muscle, whereas the phosphorylated C3 compounds can. The reconversion into carbohydrate of lactate (which readily diffuses out of muscle) occurs in liver and kidney only. The reconversion of phosphorylated C3 intermediates (which cannot diffuse out of the tissue) can occur only within the muscle. 6. α-Glycerophosphate is probably the main intermediate requiring conversion into glycogen. The possible role of α-glycerophosphate formation in vertebrate muscle, already well established in insect muscle, is discussed. PMID:14346089

Efficacy of the Lunch is in the Bag intervention to increase parents' packing of healthy bag lunches for young children: a cluster-randomized trial in early care and education centers.

PubMed

Roberts-Gray, Cindy; Briley, Margaret E; Ranjit, Nalini; Byrd-Williams, Courtney E; Sweitzer, Sara J; Sharma, Shreela V; Palafox, Maria Romo; Hoelscher, Deanna M

2016-01-08

Lunches that parents pack for their young children to eat at school or the Early Care and Education (ECE) center fall short of recommended standards. Lunch is in the Bag is a multi-level behavioral nutrition intervention to increase parents' packing of fruit, vegetables, and whole grains in their children's lunches. Designed for implementation in ECE centers, the five-week long intervention is followed three months later with a one-week booster. Efficacy of Lunch is in the Bag was tested in cluster randomized trial. Participants were 633 families from 30 ECE centers (15 intervention, 15 control) across Austin, San Antonio, and Houston, Texas, USA. Primary outcomes were servings of fruit, vegetables, and whole grains observed in the children's parent-packed bag lunches. Servings of refined grains, meats/beans/eggs/nuts, dairy, chips, and sweets also were observed. Data were collected at baseline, post-intervention (6-week follow-up), pre-booster (22-weeks follow-up), and post-booster (28-week follow-up). Time-by-treatment interactions were analyzed separately for each of the food groups using multi-level models to compare changes from baseline. Analyses were adjusted for relevant demographic variables and clustering within centers and parents. The intervention effected increases from baseline to 6-week follow-up in vegetables (0.17 servings, SE = 0.04, P < 0.001) and whole grains (0.30 servings, SE = 0.13, P = 0.018). The increase in whole grains was maintained through the 28-week follow-up (0.34 servings, SE = 0.13, P = 0.009). Fruit averaged more than 1.40 servings with no differences between groups or across time. The intervention prevented increase in sweets (-0.43 servings, SE = 0.11, P < .001, at the 22-week follow-up). Parents persisted, however, in packing small amounts of vegetables (averages of 0.41 to 0.52 servings) and large amounts of sweets and chips (averages of 1.75 to 1.99 servings). The need for and positive effects of the Lunch is in the Bag intervention at ECE centers where parents send bag lunch for their preschool-aged children was confirmed. An important direction for future research is discovery of more options for leveraging the partnership of ECE centers and families to help young children learn to eat and enjoy vegetables and other healthy foods in preference to less healthy choices such as chips and sweets. The Clinical Trials Number is NCT01292434 .

The chemical mechanism of sheep liver 6-phosphogluconate dehydrogenase. A Schiff-base intermediate is not involved.

PubMed Central

Topham, C M; Dalziel, K

1986-01-01

[2-18O]Ribulose 5-phosphate was prepared and shown to be converted enzymically by 6-phosphogluconate dehydrogenase from sheep liver into 6-phosphogluconate with complete retention of the heavy isotope. This finding unequivocally excludes the possibility of a Schiff-base mechanism for the enzyme. The involvement of metal ions has already been excluded, and other possible mechanisms are discussed. The enzyme was purified by an improved large-scale procedure, which is briefly described. PMID:3718491

The 46 kDa dimeric protein from Variovorax paradoxus shows faster methotrexate degrading activity in its nanoform compare to the native enzyme.

PubMed

Bayineni, Venkata Krishna; Venkatesh, Krishna; Sahu, Chandan Kumar; Kadeppagari, Ravi-Kumar

2016-04-01

Methotrexate degrading enzymes are required to overcome the toxicity of the methotrexate while treating the cancer. The enzyme from Variovorax paradoxus converts the methotrexate in to non toxic products. Methotrexate degrading enzyme from V. paradoxus is a dimeric protein with a molecular mass of 46 kDa and it acts on casein and gelatin. This enzyme is optimally active at pH 7.5 and 40°C and nanoparticles of this enzyme were prepared by desolvation-crosslinking method. Enzyme nanoparticles could degrade methotrexate faster than the native enzyme and they show lower Km compare to the native enzyme. Enzyme nanoparticles show better thermostability and they were stable for much longer time in the serum compare to the native enzyme. Enzyme nanoparticles show better functionality than the native enzyme while clearing the methotrexate added to the serum suggesting their advantage over the native enzyme for the therapeutic and biotechnological applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Joseph Rudinger memorial lecture: Unexpected functions of angiotensin converting enzyme, beyond its enzymatic activity.

PubMed

Martinez, Jean

2017-10-01

Angiotensin converting enzyme (ACE) is a well-known enzyme, largely studied for its action on hypertension, as it produces angiotensin II from angiotensin I. This paper describes two original behaviours of ACE. We showed that ACE could hydrolyse gastrin, a neuropeptide from the gastrointestinal tract, releasing the C-terminal amidated dipeptide H-Asp-Phe-NH 2 . This dipeptide is believed to be involved in the gastrin-induced acid secretion in the stomach. This hypothetic mechanism of action of gastrin resulted in a strategy to rationally design gastrin receptor antagonists. Beyond, we showed that the brain renin angiotensin system (RAS) could be activated by a new characterized peptide named acein, resulting in stimulation of dopamine release within the striatum. This new and original 'receptor-like' activity for brain membrane-bound ACE is quite significant taking into account the role of dopamine in the brain, particularly in neurodegenerative diseases. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Active peptides from skate (Okamejei kenojei) skin gelatin diminish angiotensin-I converting enzyme activity and intracellular free radical-mediated oxidation.

PubMed

Ngo, Dai-Hung; Ryu, BoMi; Kim, Se-Kwon

2014-01-15

Skin gelatin of skate (Okamejei kenojei) was hydrolyzed using Alcalase, flavourzyme, Neutrase and protamex. It was found that the Alcalase hydrolysate exhibited the highest angiotensin-I converting enzyme (ACE) inhibitory activity. Then, Alcalase hydrolysate was further hydrolyzed with protease and separated by an ultrafiltration membrane system. Finally, two peptides responsible for ACE inhibitory activity were identified to be MVGSAPGVL (829Da) and LGPLGHQ (720Da), with IC50 values of 3.09 and 4.22μM, respectively. Moreover, the free radical-scavenging activity of the purified peptides was determined in human endothelial cells. In addition, the antioxidative mechanism of the purified peptides was evaluated by protein and gene expression levels of antioxidant enzymes. The current study demonstrated that the peptides derived from skate skin gelatin could be used in the food industry as functional ingredients with potent antihypertensive and antioxidant benefits. Copyright © 2013 Elsevier Ltd. All rights reserved.

A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea.

PubMed

Berg, Ivan A; Kockelkorn, Daniel; Buckel, Wolfgang; Fuchs, Georg

2007-12-14

The assimilation of carbon dioxide (CO2) into organic material is quantitatively the most important biosynthetic process. We discovered that an autotrophic member of the archaeal order Sulfolobales, Metallosphaera sedula, fixed CO2 with acetyl-coenzyme A (acetyl-CoA)/propionyl-CoA carboxylase as the key carboxylating enzyme. In this system, one acetyl-CoA and two bicarbonate molecules were reductively converted via 3-hydroxypropionate to succinyl-CoA. This intermediate was reduced to 4-hydroxybutyrate and converted into two acetyl-CoA molecules via 4-hydroxybutyryl-CoA dehydratase. The key genes of this pathway were found not only in Metallosphaera but also in Sulfolobus, Archaeoglobus, and Cenarchaeum species. Moreover, the Global Ocean Sampling database contains half as many 4-hydroxybutyryl-CoA dehydratase sequences as compared with those found for another key photosynthetic CO2-fixing enzyme, ribulose-1,5-bisphosphate carboxylase-oxygenase. This indicates the importance of this enzyme in global carbon cycling.

Europe Report, Science and Technology.

DTIC Science & Technology

1986-06-18

amylase, heat stable alpha-amylase and glucoamylase for processing starch as a substrate for 71 glucose and its isomerization to fructose using an...continuous column process under laboratory conditions. We have demonstrated that these preparations isomerize glucose syrups up to 42 percent, converting...food industry is the leading consumer of microbial enzymes devouring about 80 percent of the world production of enzymes -- glucose isomerase, alpha

Cholecystokinin-converting enzymes in brain.

PubMed Central

Malesci, A; Straus, E; Yalow, R S

1980-01-01

Crude extracts of porcine cerebral cortical tissue convert cholecystokinin (CCK) to its COOH-terminal fragments, the dodecapeptide (CCK-12) and the octapeptide (CCK-8). The Sephadex G-75 void volume eluate of the crude extract cleaves the arginine-isoleucine bond and effects conversion only to CCK-12; the Sephadex G-50 void volume eluate of the same extract cleaves the arginine-aspartate bond as well, so that both CCK-12 and CCK-8 are end products. Thus, there are at least two enzymes; the one involved in the conversion to CCK-12 is of larger molecular radius than the other. The Km for the cleavage of CCK at the arginine-isoleucine bond by the Sephadex G-75 void volume eluate enzyme is 1.1 X 10(-6) M; the Km for trypsin cleavage of the same bond is 4.7 x 10(-6) M. The lower Vmax for the brain enzyme (1.5 x 10(-11) mol/min per g of extract) compared with trypsin (66 x 10(-11) mol/min per g of trypsin) simply reflects the lesser degree of purify of the brain extract than of the highly purified trypsin. Images PMID:6987659

Epilactose production by 2 cellobiose 2-epimerases in natural milk.

PubMed

Krewinkel, Manuel; Gosch, Maria; Rentschler, Eva; Fischer, Lutz

2014-01-01

It was reported recently that cellobiose 2-epimerases (CE) from various aerobic microorganisms convert lactose to epilactose in defined buffer systems. In this study, we showed that CE from 2 mesophilic microorganisms, Flavobacterium johnsoniae and Pedobacter heparinus, were capable of converting lactose to prebiotic epilactose not only in buffer but also in a complex milk system. First, the 2 enzymes were separately cloned, recombinantly expressed in Escherichia coli, and purified by column chromatography. The production of F. johnsoniae CE was carried out in a stirred-tank reactor, indicating that future upscaling is possible. The bioconversions of milk lactose were carried out at an industrially relevant low temperature of 8°C to avoid undesired microbial contaminations or chemical side reactions. Both enzymes were reasonably active at this low temperature, because of their origin from mesophilic organisms. The enzymes showed different operational stabilities over a 24-h time-course. A conversion yield of about 30 to 33% epilactose was achieved with both enzymes. No side products were detected other than epilactose. Therefore, CE may introduce an added value for particular dairy products by in situ production of the prebiotic sugar epilactose. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Child Care Enrollment Decisions Among Dual Language Learner Families: The Role of Spanish Language Instruction in the Child Care Setting

PubMed Central

Miller, Elizabeth B.

2016-01-01

Data from the Head Start Impact Study (N = 1,141) and the Head Start Family and Child Experiences Survey, 2009 Cohort (N = 825) were used to describe child care enrollment decisions among Spanish-speaking Dual Language Learner (DLL) families. In particular, logistic regression models tested which child, family, and institutional characteristics predicted enrollment in early care and education (ECE) settings that used Spanish for instruction versus enrollment in settings that did not use Spanish. Results showed that whether the child’s first language was exclusively Spanish and whether other DLL families previously attended the ECE arrangement strongly predicted whether that child enrolled. Policy implications for Head Start-eligible Spanish-speaking DLLs are discussed. PMID:26900255

Starch Biorefinery Enzymes.

PubMed

Läufer, Albrecht

2017-03-07

Nature uses enzymes to build and convert biomass; mankind uses the same enzymes and produces them on a large scale to make optimum use of biomass in biorefineries. Bacterial α-amylases and fungal glucoamylases have been the workhorses of starch biorefineries for many decades. Pullulanases were introduced in the 1980s. Proteases, cellulases, hemicellulases, and phytases have been on the market for a few years as process aids, improving yields, performance, and costs. Detailed studies of the complex chemical structures of biomass and of the physicochemical limitations of industrial biorefineries have led enzyme developers to produce novel tailor-made solutions for improving yield and profitability in the industry. This chapter reviews the development of enzyme applications in the major starch biorefining processes.

Soybean phenolic-rich extracts inhibit key-enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) and hypertension (angiotensin I converting enzyme) in vitro.

PubMed

Ademiluyi, Adedayo O; Oboh, Ganiyu

2013-03-01

This study sought to assess the inhibitory activities of phenolic-rich extracts from soybean on α-amylase, α-glucosidase and angiotensin I converting enzyme (ACE) activities in vitro. The free phenolic extract of the soybean was obtained by extraction with 80% acetone, while that of the bound phenolic extract was done by extracting the alkaline and acid hydrolyzed residue with ethyl acetate. The inhibitory action of these extracts on the enzymes activity as well as their antioxidant properties was assessed. Both phenolic-rich extracts inhibited α-amylase, α-glucosidase and ACE enzyme activities in a dose dependent pattern. However, the bound phenolic extract exhibited significantly (P < 0.05) higher α-amylase and ACE inhibition while the free phenolic extract had significantly (P < 0.05) higher α-glucosidase inhibitory activity. Nevertheless, the free phenolic extract had higher α-glucosidase inhibitory activity when compared to that of α-amylase; this property confer an advantage on soybean phenolic-rich extracts over commercial antidiabetic drugs with little or no side effect. And inhibition of ACE suggests the antihypertension potential of soybean phenolic-rich extracts. Furthermore, the enzyme inhibitory activities of the phenolic-rich extracts were not associated with their phenolic content. Therefore, phenolic-rich extracts of soybean could inhibit key-enzyme linked to type 2 diabetes (α-amylase and α-glucosidase) and hypertension (ACE) and thus could explain in part the mechanism by which soybean renders these health promoting effect. Copyright © 2011 Elsevier GmbH. All rights reserved.

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines.

PubMed

Boboia, Anamaria; Grigorescu, Marius Rareş; Turcu-Ştiolică, Adina

2017-01-01

The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans.

In vitro angiotensin I converting enzyme inhibition by a peptide isolated from Chiropsalmus quadrigatus Haeckel (box jellyfish) venom hydrolysate.

PubMed

So, Pamela Berilyn T; Rubio, Peter; Lirio, Stephen; Macabeo, Allan Patrick; Huang, Hsi-Ya; Corpuz, Mary Jho-Anne T; Villaflores, Oliver B

2016-09-01

The anti-angiotensin I converting enzyme activity of box jellyfish, Chiropsalmus quadrigatus Haeckel venom hydrolysate was studied. The venom extract was obtained by centrifugation and ultrasonication. Protein concentration of 12.99 μg/mL was determined using Bradford assay. The pepsin and papain hydrolysate was tested for its toxicity by Limit test following the OECD Guideline 425 using 5 female Sprague-Dawley rats. Results showed that the hydrolysate is nontoxic with an LD50 above 2000 mg/kg. In vitro angiotensin I converting enzyme (ACE) inhibitory activity was determined using ACE kit-WST. Isolation of ACE inhibitory peptides using column chromatography with SP-Sephadex G-25 yielded 8 pooled fractions with fraction 3 (86.5%) exhibiting the highest activity. This was followed by reverse phase - high performance liquid chromatography (RP-HPLC) with an octadecyl silica column (Inertsil ODS-3) using methanol:water 15:85 at a flow rate of 1.0 mL/min. Among the 13 fractions separated with the RP-HPLC, fraction 3.5 exhibited the highest ACE inhibitory activity (84.1%). The peptide sequence ACPGPNPGRP (IC50 2.03 μM) from fraction 3.5 was identified using Matrix-assisted laser desorption/ionization with time-of-flight tandem mass spectroscopy analysis (MALDI-TOF/MS). Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of Two Late-Stage Enzymes Involved in Fosfomycin Biosynthesis in Pseudomonads.

PubMed

Olivares, Philip; Ulrich, Emily C; Chekan, Jonathan R; van der Donk, Wilfred A; Nair, Satish K

2017-02-17

The broad-spectrum phosphonate antibiotic fosfomycin is currently in use for clinical treatment of infections caused by both Gram-positive and Gram-negative uropathogens. The antibiotic is biosynthesized by various streptomycetes, as well as by pseudomonads. Notably, the biosynthetic strategies used by the two genera share only two steps: the first step in which primary metabolite phosphoenolpyruvate (PEP) is converted to phosphonopyruvate (PnPy) and the terminal step in which 2-hydroxypropylphosphonate (2-HPP) is converted to fosfomycin. Otherwise, distinct enzymatic paths are employed. Here, we biochemically confirm the last two steps in the fosfomycin biosynthetic pathway of Pseudomonas syringae PB-5123, showing that Psf3 performs the reduction of 2-oxopropylphosphonate (2-OPP) to (S)-2-HPP, followed by the Psf4-catalyzed epoxidation of (S)-2-HPP to fosfomycin. Psf4 can also accept (R)-2-HPP as a substrate but instead performs an oxidation to make 2-OPP. We show that the combined activities of Psf3 and Psf4 can be used to convert racemic 2-HPP to fosfomycin in an enantioconvergent process. X-ray structures of each enzyme with bound substrates provide insights into the stereospecificity of each conversion. These studies shed light on the reaction mechanisms of the two terminal enzymes in a distinct pathway employed by pseudomonads for the production of a potent antimicrobial agent.

Injections of angiotensin-converting enzyme2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats

PubMed Central

Diz, Debra I.; Garcia-Espinosa, Maria A.; Gegick, Stephen; Tommasi, Ellen N.; Ferrario, Carlos M.; Tallant, E. Ann; Chappell, Mark C.; Gallagher, Patricia E.

2009-01-01

Injections of the angiotensin(1–7) [Ang(1–7)] antagonist [d-Ala7]-Ang(1–7) into the nucleus of the solitary tract (NTS) of Sprague–Dawley rats reduce baroreceptor reflex sensitivity (BRS) for control of heart rate by ~40%, whereas injections of the angiotensin II (Ang II) type 1 receptor antagonist candesartan increase BRS by 40% when reflex bradycardia is assessed. The enzyme angiotensin-converting enzyme 2 (ACE2) is known to convert Ang II to Ang(1–7). We report that ACE2 activity, as well as ACE and neprilysin activities, are present in plasma membrane fractions of the dorsomedial medulla of Sprague–Dawley rats. Moreover, we show that BRS for reflex bradycardia is attenuated (1.16±0.29 ms mmHg−1 before versus 0.33±0.11 ms mmHg−1 after; P < 0.05; n = 8) 30–60 min following injection of the selective ACE2 inhibitor MLN4760 (12 pmol in 120 nl) into the NTS. These findings support the concept that within the NTS, local synthesis of Ang(1–7) from Ang II is required for normal sensitivity for the baroreflex control of heart rate in response to increases in arterial pressure. PMID:18356558

Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

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

Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko

Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recoverymore » of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.« less

Effect of protease inhibitors on angiotensin-converting enzyme activity in human T-lymphocytes.

PubMed

Petrov, V; Fagard, R; Lijnen, P

2000-05-01

The purpose of these investigations was to determine whether the aminopeptidase B and leucine aminopeptidase inhibitor bestatin, the chymase inhibitor chymostatin, the calpain inhibitor E-64, and the neutral serine protease inhibitor leupeptin affect the angiotensin converting enzyme (ACE) activity in T-lymphocytes. ACE activity in homogenates of T-lymphocytes or in intact T-lymphocytes in suspension was measured by determining fluorimetrically histidyl-leucine, formed from the conversion of hippuryl-histidyl-leucine, coupled with ophtaldialdehyde. The effect of various concentrations (10(-9) to 10(-3) mol/L) of the angiotensin-converting enzyme inhibitors lisinopril and captopril and of the various protease inhibitors on ACE activity was studied. Lisinopril and captopril reduced the ACE activity in homogenates of T-lymphocytes in a concentration-dependent manner. Lisinopril exhibited a more pronounced inhibition of ACE in T-lymphocytes than did captopril. Chymostatin and E-64 had no effect on the ACE activity in T-lymphocytes, whereas leupeptin inhibited its activity in a dose-dependent fashion. Bestatin, on the contrary, increased the ACE activity in homogenates of T-lymphocytes as well as in intact T-lymphocytes in proportion to the concentration. Our data showed that the ACE activity in T-lymphocytes was stimulated by bestatin and inhibited by leupeptin, whereas chymostatin and E-64 did not affect the ACE activity in T-lymphocytes.

Predictors of heart failure in patients with stable coronary artery disease: a PEACE study.

PubMed

Lewis, Eldrin F; Solomon, Scott D; Jablonski, Kathleen A; Rice, Madeline Murguia; Clemenza, Francesco; Hsia, Judith; Maggioni, Aldo P; Zabalgoitia, Miguel; Huynh, Thao; Cuddy, Thomas E; Gersh, Bernard J; Rouleau, Jean; Braunwald, Eugene; Pfeffer, Marc A

2009-05-01

Heart failure (HF) is a disease commonly associated with coronary artery disease. Most risk models for HF development have focused on patients with acute myocardial infarction. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition population enabled the development of a risk model to predict HF in patients with stable coronary artery disease and preserved ejection fraction. In the 8290, Prevention of Events with Angiotensin-Converting Enzyme Inhibition patients without preexisting HF, new-onset HF hospitalizations, and fatal HF were assessed over a median follow-up of 4.8 years. Covariates were evaluated and maintained in the Cox regression multivariable model using backward selection if P<0.05. A risk score was developed and converted to an integer-based scoring system. Among the Prevention of Events with Angiotensin-Converting Enzyme Inhibition population (age, 64+/-8; female, 18%; prior myocardial infarction, 55%), there were 268 cases of fatal and nonfatal HF. Twelve characteristics were associated with increased risk of HF along with several baseline medications, including older age, history of hypertension, and diabetes. Randomization to trandolapril independently reduced the risk of HF. There was no interaction between trandolapril treatment and other risk factors for HF. The risk score (range, 0 to 21) demonstrated excellent discriminatory power (c-statistic 0.80). Risk of HF ranged from 1.75% in patients with a risk score of 0% to 33% in patients with risk score >or=16. Among patients with stable coronary artery disease and preserved ejection fraction, traditional and newer factors were independently associated with increased risk of HF. Trandolopril decreased the risk of HF in these patients with preserved ejection fraction.

Effects of synchronicity of carbohydrate and protein degradation on rumen fermentation characteristics and microbial protein synthesis.

PubMed

Seo, J K; Kim, M H; Yang, J Y; Kim, H J; Lee, C H; Kim, K H; Ha, Jong K

2013-03-01

A series of in vitro studies were carried out to determine i) the effects of enzyme and formaldehyde treatment on the degradation characteristics of carbohydrate and protein sources and on the synchronicity of these processes, and ii) the effects of synchronizing carbohydrate and protein supply on rumen fermentation and microbial protein synthesis (MPS) in in vitro experiments. Untreated corn (C) and enzyme-treated corn (EC) were combined with soy bean meal with (ES) and without (S) enzyme treatment or formaldehyde treatment (FS). Six experimental feeds (CS, CES, CFS, ECS, ECES and ECFS) with different synchrony indices were prepared. Highly synchronous diets had the greatest dry matter (DM) digestibility when untreated corn was used. However, the degree of synchronicity did not influence DM digestibility when EC was mixed with various soybean meals. At time points of 12 h and 24 h of incubation, EC-containing diets showed lower ammonia-N concentrations than those of C-containing diets, irrespective of the degree of synchronicity, indicating that more efficient utilization of ammonia-N for MPS was achieved by ruminal microorganisms when EC was offered as a carbohydrate source. Within C-containing treatments, the purine base concentration increased as the diets were more synchronized. This effect was not observed when EC was offered. There were significant effects on VFA concentration of both C and S treatments and their interactions. Similar to purine concentrations, total VFA production and individual VFA concentration in the groups containing EC as an energy source was higher than those of other groups (CS, CES and CFS). The results of the present study suggested that the availability of energy or the protein source are the most limiting factors for rumen fermentation and MPS, rather than the degree of synchronicity.

Heterologous Expression of a Bioactive β-Hexosyltransferase, an Enzyme Producer of Prebiotics, from Sporobolomyces singularis

PubMed Central

Dagher, Suzanne F.; Azcarate-Peril, M. Andrea

2013-01-01

Galacto-oligosaccharides (GOS) are indigestible dietary fibers that are able to reach the lower gastrointestinal tract to be selectively fermented by health-promoting bacteria. In this report, we describe the heterologous expression of an optimized synthetically produced version of the β-hexosyltransferase gene (Bht) from Sporobolomyces singularis. The Bht gene encodes a glycosyl hydrolase (EC 3.2.1.21) that acts as galactosyltransferase, able to catalyze a one-step conversion of lactose to GOS. Expression of the enzyme in Escherichia coli yielded an inactive insoluble protein, while the methylotrophic yeast Pichia pastoris GS115 produced a bioactive β-hexosyltransferase (rBHT). The enzyme exhibited faster kinetics at pHs between 3.5 and 6 and at temperatures between 40 and 50°C. Enzyme stability improved at temperatures lower than 40°C, and glucose was found to be a competitive inhibitor of enzymatic activity. P. pastoris secreted a fraction of the bioactive rBHT into the fermentation broth, while the majority of the enzyme remained associated with the outer membrane. Both the secreted and the membrane-associated forms were able to efficiently convert lactose to GOS. Additionally, resting cells with membrane-bound enzyme converted 90% of the initial lactose into GOS at 68% yield (g/g) (the maximum theoretical is 75%) with no secondary residual (glucose or galactose) products. This is the first report of a bioactive BHT from S. singularis that has been heterologously expressed. PMID:23241974

Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

PubMed

Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

2008-12-01

Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

Angiotensin converting enzyme inhibition and the kidney

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.

1988-01-01

Angiotensin II (Ang II) induces a marked reduction in renal blood flow at doses well below those required to induce a pressor response, and as blood flow falls there is a decline in glomerular filtration rate and sodium excretion. This striking sensitivity of the renal blood supply led many workers to consider the possibility that angiotensin functions as a local renal hormone. As angiotensin converting enzyme (ACE) was found in particular abundance in the lung, it seemed reasonable to suspect that most of the conversion occurred there, and that the function of Ang II would be primarily systemic, rather than intrarenal. In this review, I will explore the evidence that has accumulated on these two possibilities, since they have important implications for our current understanding of normal kidney function and derangements of kidney function in disease.

Angiotensin converting enzyme insertion/deletion polymorphism: association with ethnic origin.

PubMed

Barley, J; Blackwood, A; Carter, N D; Crews, D E; Cruickshank, J K; Jeffery, S; Ogunlesi, A O; Sagnella, G A

1994-08-01

To determine the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in several ethnic groups: Caucasian Europeans, Black Nigerians, Samoan Polynesians and Yanomami Indians. The ratio of the frequencies of the II, ID and DD genotypes were 1:2:1 in the Europeans, but there was a tendency towards a higher frequency of the D allele in the Nigerians. In contrast, the Samoans and the Yanomami Indians displayed a much higher frequency of the I allele than of the D allele. The relationship between ACE genotype and disease in these latter groups is still not known, but the present results clearly suggest that ethnic origin should be carefully considered in the increasing number of studies on the association between I/D ACE genotype and disease aetiology.

Synthesis and evaluation of novel triazoles and mannich bases functionalized 1,4-dihydropyridine as angiotensin converting enzyme (ACE) inhibitors.

PubMed

Kumbhare, Ravindra M; Kosurkar, Umesh B; Bagul, Pankaj K; Kanwal, Abhinav; Appalanaidu, K; Dadmal, Tulshiram L; Banerjee, Sanjay Kumar

2014-11-01

A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.713 μM, 0.409 μM and 0.653 μM, respectively. Among mannich bases series compounds, only 7c resulted as most active ACE inhibitor with IC50 value of 0.928 μM. Copyright © 2014. Published by Elsevier Ltd.

Purification of angiotensin I-converting enzyme (ACE) inhibitory peptides from casein hydrolysate by IMAC-Ni2.

PubMed

Wu, Shanguang; Feng, Xuezhen; Lu, Yuan; Lu, Yuting; Liu, Saisai; Tian, Yuhong

2017-10-01

Casein proteins were hydrolyzed by papain to identify inhibitory peptides of angiotensin I-converting enzyme (ACE). The hydrolysate was fractionized by immobilized metal affinity chromatography (IMAC-Ni 2+ ). The fraction with high ACE inhibitory activity was enriched and further chromatographed on a reverse-phase column to yield four fractions. Among the fractions, the L4 fraction exhibited the highest ACE inhibitory activity and was identified by sequence analysis as Trp-Tyr-Leu-His-Tyr-Ala (WYLHYA), with IC 50 value of 16.22 ± 0.83 µM in vitro. This peptide was expected to be applied as an ingredient for preventing hypertension and IMAC-Ni 2+ may provide a simple method for purification of ACE inhibitory peptides.

Analysis of nucleotide diphosphate sugar dehydrogenases reveals family and group-specific relationships.

PubMed

Freas, Nicholas; Newton, Peter; Perozich, John

2016-01-01

UDP-glucose dehydrogenase (UDPGDH), UDP-N-acetyl-mannosamine dehydrogenase (UDPNAMDH) and GDP-mannose dehydrogenase (GDPMDH) belong to a family of NAD (+)-linked 4-electron-transfering oxidoreductases called nucleotide diphosphate sugar dehydrogenases (NDP-SDHs). UDPGDH is an enzyme responsible for converting UDP-d-glucose to UDP-d-glucuronic acid, a product that has different roles depending on the organism in which it is found. UDPNAMDH and GDPMDH convert UDP-N-acetyl-mannosamine to UDP-N-acetyl-mannosaminuronic acid and GDP-mannose to GDP-mannuronic acid, respectively, by a similar mechanism to UDPGDH. Their products are used as essential building blocks for the exopolysaccharides found in organisms like Pseudomonas aeruginosa and Staphylococcus aureus. Few studies have investigated the relationships between these enzymes. This study reveals the relationships between the three enzymes by analysing 229 amino acid sequences. Eighteen invariant and several other highly conserved residues were identified, each serving critical roles in maintaining enzyme structure, coenzyme binding or catalytic function. Also, 10 conserved motifs that included most of the conserved residues were identified and their roles proposed. A phylogenetic tree demonstrated relationships between each group and verified group assignment. Finally, group entropy analysis identified novel conservations unique to each NDP-SDH group, including residue positions critical to NDP-sugar substrate interaction, enzyme structure and intersubunit contact. These positions may serve as targets for future research. UDP-glucose dehydrogenase (UDPGDH, EC 1.1.1.22).

Integrated Optic Chemical-Biological Sensors

DTIC Science & Technology

1999-02-26

response. In this process, an enzyme ( urease ) acts as a catalyst, converting a specific substrate (urea) to a specific product (ammonia). Implementing...a sandwich assay, a urease labeled antibody is introduced to a surface bound antigen. This complex is exposed to urea, generating ammonia. Using a...containing suspected agents. After agent binding to the antibody-coated beads, an appropriate enzyme labeled antibody (an antibody with a urease label

Differential processing of substance P and neurokinin A by plasma dipeptidyl(amino)peptidase IV, aminopeptidase M and angiotensin converting enzyme.

PubMed

Wang, L H; Ahmad, S; Benter, I F; Chow, A; Mizutani, S; Ward, P E

1991-01-01

In addition to plasma metabolism of substance P (SP) by angiotensin converting enzyme (ACE; EC 3.4.15.1) (less than 1.0 nmol/min/ml), the majority of SP hydrolysis by rat and human plasma was due to dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) (3.15-5.91 nmol/min/ml), which sequentially converted SP to SP(3-11) and SP(5-11). In turn, the SP(5-11) metabolite was rapidly hydrolyzed by rat and human plasma aminopeptidase M (AmM; EC 3.4.11.2) (24.2-25.5 nmol/min/ml). The Km values of SP for DAP IV and of SP(5-11) for AmM ranged from 32.7 to 123 microM. In contrast, neurokinin A (NKA) was resistant to both ACE and DAP IV but was subject to N-terminal hydrolysis by AmM (3.76-10.8 nmol/min/ml; Km = 90.7 microM). These data demonstrate differential processing of SP and NKA by specific peptidases in rat and human plasma.

Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides from a cholecystokinin/gastrin and a LH-RH peptide extended at the C-terminus with gly-Arg/Lys-arg, but not from diarginyl insulin.

PubMed

Isaac, R E; Michaud, A; Keen, J N; Williams, T A; Coates, D; Wetsel, W C; Corvol, P

1999-06-01

Endoproteolytic cleavage of protein prohormones often generates intermediates extended at the C-terminus by Arg-Arg or Lys-Arg, the removal of which by a carboxypeptidase (CPE) is normally an important step in the maturation of many peptide hormones. Recent studies in mice that lack CP activity indicate the existence of alternative tissue or plasma enzymes capable of removing C-terminal basic residues from prohormone intermediates. Using inhibitors of angiotensin I-converting enzyme (ACE) and CP, we show that both these enzymes in mouse serum can remove the basic amino acids from the C-terminus of CCK5-GRR and LH-RH-GKR, but only CP is responsible for converting diarginyl insulin to insulin. ACE activity removes C-terminal dipeptides to generate the Gly-extended peptides, whereas CP hydrolysis gives rise to CCK5-GR and LH-RH-GK, both of which are susceptible to the dipeptidyl carboxypeptidase activity of ACE. Somatic ACE has two similar protein domains (the N-domain and the C-domain), each with an active site that can display different substrate specificities. CCK5-GRR is a high-affinity substrate for both the N-domain and C-domain active sites of human sACE (Km of 9.4 microm and 9.0 microm, respectively) with the N-domain showing greater efficiency (kcat : Km ratio of 2.6 in favour of the N-domain). We conclude that somatic forms of ACE should be considered as alternatives to CPs for the removal of basic residues from some Arg/Lys-extended peptides.

Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich syndrome.

PubMed

Gulácsy, Vera; Freiberger, Tomas; Shcherbina, Anna; Pac, Malgorzata; Chernyshova, Liudmyla; Avcin, Tadej; Kondratenko, Irina; Kostyuchenko, Larysa; Prokofjeva, Tatjana; Pasic, Srdjan; Bernatowska, Ewa; Kutukculer, Necil; Rascon, Jelena; Iagaru, Nicolae; Mazza, Cinzia; Tóth, Beáta; Erdos, Melinda; van der Burg, Mirjam; Maródi, László

2011-02-01

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. WAS is caused by mutations in the WASP gene which encodes WASP, a 502-amino acid protein. WASP plays a critical role in actin cytoskeleton organization and signalling, and functions of immune cells. We present here the results of genetic analysis of patients with WAS from eleven Eastern and Central European (ECE) countries and Turkey. Clinical and haematological information of 87 affected males and 48 carrier females from 77 WAS families were collected. The WASP gene was sequenced from genomic DNA of patients with WAS, as well as their family members to identify carriers. In this large cohort, we identified 62 unique mutations including 17 novel sequence variants. The mutations were scattered throughout the WASP gene and included single base pair changes (17 missense and 11 nonsense mutations), 7 small insertions, 18 deletions, and 9 splice site defects. Genetic counselling and prenatal diagnosis were applied in four affected families. This study was part of the J Project aimed at identifying genetic basis of primary immunodeficiency disease in ECE countries. This report provides the first comprehensive overview of the molecular genetic and demographic features of WAS in ECE. Copyright © 2010 Elsevier Ltd. All rights reserved.