Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis.

PubMed

Rosenbaek, Lena L; Kortenoeven, Marleen L A; Aroankins, Takwa S; Fenton, Robert A

2014-05-09

The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT). The transport activity of NCC can be regulated by phosphorylation, but knowledge of modulation of NCC trafficking by phosphorylation is limited. In this study, we generated novel tetracycline-inducible Madin-Darby canine kidney type I (MDCKI) cell lines expressing NCC to examine the role of NCC phosphorylation and ubiquitylation on NCC endocytosis. In MDCKI-NCC cells, NCC was highly glycosylated at molecular weights consistent with NCC monomers and dimers. NCC constitutively cycles to the apical plasma membrane of MDCKI-NCC cells, with 20-30% of the membrane pool of NCC internalized within 30 min. The use of dynasore, PitStop2, methyl-β-cyclodextrin, nystatin, and filipin (specific inhibitors of either clathrin-dependent or -independent endocytosis) demonstrated that NCC is internalized via a clathrin-mediated pathway. Reduction of endocytosis resulted in greater levels of NCC in the plasma membrane. Immunogold electron microscopy confirmed the association of NCC with the clathrin-mediated internalization pathway in rat DCT cells. Compared with controls, inducing phosphorylation of NCC via low chloride treatment or mimicking phosphorylation by replacing Thr-53, Thr-58, and Ser-71 residues with Asp resulted in increased membrane abundance and reduced rates of NCC internalization. NCC ubiquitylation was lowest in the conditions with greatest NCC phosphorylation, thus providing a mechanism for the reduced endocytosis. In conclusion, our data support a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT.

Phosphorylation Decreases Ubiquitylation of the Thiazide-sensitive Cotransporter NCC and Subsequent Clathrin-mediated Endocytosis*

PubMed Central

Rosenbaek, Lena L.; Kortenoeven, Marleen L. A.; Aroankins, Takwa S.; Fenton, Robert A.

2014-01-01

The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT). The transport activity of NCC can be regulated by phosphorylation, but knowledge of modulation of NCC trafficking by phosphorylation is limited. In this study, we generated novel tetracycline-inducible Madin-Darby canine kidney type I (MDCKI) cell lines expressing NCC to examine the role of NCC phosphorylation and ubiquitylation on NCC endocytosis. In MDCKI-NCC cells, NCC was highly glycosylated at molecular weights consistent with NCC monomers and dimers. NCC constitutively cycles to the apical plasma membrane of MDCKI-NCC cells, with 20–30% of the membrane pool of NCC internalized within 30 min. The use of dynasore, PitStop2, methyl-β-cyclodextrin, nystatin, and filipin (specific inhibitors of either clathrin-dependent or -independent endocytosis) demonstrated that NCC is internalized via a clathrin-mediated pathway. Reduction of endocytosis resulted in greater levels of NCC in the plasma membrane. Immunogold electron microscopy confirmed the association of NCC with the clathrin-mediated internalization pathway in rat DCT cells. Compared with controls, inducing phosphorylation of NCC via low chloride treatment or mimicking phosphorylation by replacing Thr-53, Thr-58, and Ser-71 residues with Asp resulted in increased membrane abundance and reduced rates of NCC internalization. NCC ubiquitylation was lowest in the conditions with greatest NCC phosphorylation, thus providing a mechanism for the reduced endocytosis. In conclusion, our data support a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT. PMID:24668812

Differential roles of WNK4 in regulation of NCC in vivo.

PubMed

Yang, Yih-Sheng; Xie, Jian; Yang, Sung-Sen; Lin, Shih-Hua; Huang, Chou-Long

2018-05-01

The Na + -Cl - cotransporter (NCC) in distal convoluted tubule (DCT) plays important roles in renal NaCl reabsorption. The current hypothesis for the mechanism of regulation of NCC focuses on WNK4 and intracellular Cl - concentration ([Cl - ] i ). WNK kinases bind Cl - , and Cl - binding decreases the catalytic activity. It is believed that hypokalemia under low K + intake decreases [Cl - ] i to activate WNK4, which thereby phosphorylates and stimulates NCC through activation of SPAK. However, increased NCC activity and apical NaCl entry would mitigate the fall in [Cl - ] i. Whether [Cl - ] i in DCT under low-K + diet is sufficiently low to activate WNK4 is unknown. Furthermore, increased luminal NaCl delivery also stimulates NCC and causes upregulation of the transporter. Unlike low K + intake, increased luminal NaCl delivery would tend to increase [Cl - ] i . Thus we investigated the role of WNK4 and [Cl - ] i in regulating NCC. We generated Wnk4-knockout mice and examined regulation of NCC by low K + intake and by increased luminal NaCl delivery in knockout (KO) and wild-type mice. Wnk4-KO mice have marked reduction in the abundance, phosphorylation, and functional activity of NCC vs. wild type. Low K + intake increases NCC phosphorylation and functional activity in wild-type mice, but not in Wnk4-KO mice. Increased luminal NaCl delivery similarly upregulates NCC, which, contrary to low K + intake, is not abolished in Wnk4-KO mice. The results reveal that modulation of WNK4 activity by [Cl - ] i is not the sole mechanism for regulating NCC. Increased luminal NaCl delivery upregulates NCC via yet unknown mechanism(s) that may override inhibition of WNK4 by high [Cl - ] i .

Characterization of a novel phosphorylation site in the sodium-chloride cotransporter, NCC.

PubMed

Rosenbaek, L L; Assentoft, M; Pedersen, N B; MacAulay, N; Fenton, R A

2012-12-01

The sodium-chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho-specific antibodies targeting pS124-NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy with kidney tubule segment-specific markers localized pS124-NCC to all distal convoluted tubule cells. Double immunogold electron microscopy demonstrated that pS124-NCC co-localized with total NCC in the apical plasma membrane of distal convoluted tubule cells and intracellular vesicles. Acute treatment of Munich-Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2 receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin-angiotensin-aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1-related proline-alanine-rich kinase and oxidative stress-response kinases (SPAK and OSR1) were not able to phosphorylate NCC at S124. Protein kinase arrays identified multiple kinases that were able to bind to the region surrounding S124. Four of these kinases (IRAK2, CDK6/Cyclin D1, NLK and mTOR/FRAP) showed weak but significant phosphorylation activity at S124. In oocytes, (36)Cl uptake studies combined with biochemical analysis showed decreased activity of plasma membrane-associated NCC when replacing S124 with alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell lines, S124A and S124D mutants were able to traffic to the plasma membrane similarly to wildtype NCC.

Characterization of a novel phosphorylation site in the sodium–chloride cotransporter, NCC

PubMed Central

Rosenbaek, L L; Assentoft, M; Pedersen, N B; MacAulay, N; Fenton, R A

2012-01-01

The sodium–chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho-specific antibodies targeting pS124-NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy with kidney tubule segment-specific markers localized pS124-NCC to all distal convoluted tubule cells. Double immunogold electron microscopy demonstrated that pS124-NCC co-localized with total NCC in the apical plasma membrane of distal convoluted tubule cells and intracellular vesicles. Acute treatment of Munich–Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2 receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin–angiotensin–aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1-related proline–alanine-rich kinase and oxidative stress-response kinases (SPAK and OSR1) were not able to phosphorylate NCC at S124. Protein kinase arrays identified multiple kinases that were able to bind to the region surrounding S124. Four of these kinases (IRAK2, CDK6/Cyclin D1, NLK and mTOR/FRAP) showed weak but significant phosphorylation activity at S124. In oocytes, 36Cl uptake studies combined with biochemical analysis showed decreased activity of plasma membrane-associated NCC when replacing S124 with alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell lines, S124A and S124D mutants were able to traffic to the plasma membrane similarly to wildtype NCC. PMID:22966159

SPAK-mediated NCC regulation in response to low-K+ diet.

PubMed

Wade, James B; Liu, Jie; Coleman, Richard; Grimm, P Richard; Delpire, Eric; Welling, Paul A

2015-04-15

The NaCl cotransporter (NCC) of the renal distal convoluted tubule is stimulated by low-K(+) diet by an unknown mechanism. Since recent work has shown that the STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) can function to stimulate NCC by phosphorylation of specific N-terminal sites, we investigated whether the NCC response to low-K(+) diet is mediated by SPAK. Using phospho-specific antibodies in Western blot and immunolocalization studies of wild-type and SPAK knockout (SPAK(-/-)) mice fed a low-K(+) or control diet for 4 days, we found that low-K(+) diet strongly increased total NCC expression and phosphorylation of NCC. This was associated with an increase in total SPAK expression in cortical homogenates and an increase in phosphorylation of SPAK at the S383 activation site. The increased pNCC in response to low-K(+) diet was blunted but not completely inhibited in SPAK(-/-) mice. These findings reveal that SPAK is an important mediator of the increased NCC activation by phosphorylation that occurs in the distal convoluted tubule in response to a low-K(+) diet, but other low-potassium-activated kinases are likely to be involved. Copyright © 2015 the American Physiological Society.

Aldosterone Modulates the Association between NCC and ENaC.

PubMed

Wynne, Brandi M; Mistry, Abinash C; Al-Khalili, Otor; Mallick, Rickta; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

2017-06-23

Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2). Given their co-localization within the DCT2, we hypothesized that NCC and ENaC interactions might be modulated by aldosterone (Aldo). Aldo treatment increased NCC and αENaC colocalization (electron microscopy) and interaction (coimmunoprecipitation). Finally, with co-expression of the Aldo-induced protein serum- and glucocorticoid-inducible kinase 1 (SGK1), NCC and αENaC interactions were increased. These data demonstrate that Aldo promotes increased interaction of NCC and ENaC, within the DCT2 revealing a novel method of regulation for distal sodium reabsorption.

WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway.

PubMed

Zhou, Bo; Zhuang, Jieqiu; Gu, Dingying; Wang, Hua; Cebotaru, Liudmila; Guggino, William B; Cai, Hui

2010-01-01

WNK kinase is a serine/threonine kinase that plays an important role in electrolyte homeostasis. WNK4 significantly inhibits the surface expression of the sodium chloride co-transporter (NCC) by enhancing the degradation of NCC through a lysosomal pathway, but the mechanisms underlying this trafficking are unknown. Here, we investigated the effect of the lysosomal targeting receptor sortilin on NCC expression and degradation. In Cos-7 cells, we observed that the presence of WNK4 reduced the steady-state amount of NCC by approximately half. Co-transfection with truncated sortilin (a dominant negative mutant) prevented this WNK4-induced reduction in NCC. NCC immunoprecipitated with both wild-type sortilin and, to a lesser extent, truncated sortilin. Immunostaining revealed that WNK4 increased the co-localization of NCC with the lysosomal marker cathepsin D, and NCC co-localized with wild-type sortilin, truncated sortilin, and WNK4 in the perinuclear region. These findings suggest that WNK4 promotes NCC targeting to the lysosome for degradation via a mechanism involving sortilin.

The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation.

PubMed

Rosenbaek, Lena L; Rizzo, Federica; Wu, Qi; Rojas-Vega, Lorena; Gamba, Gerardo; MacAulay, Nanna; Staub, Olivier; Fenton, Robert A

2017-10-11

The renal sodium chloride cotransporter, NCC, in the distal convoluted tubule is important for maintaining body Na + and K + homeostasis. Endogenous NCC is highly ubiquitylated, but the role of individual ubiquitylation sites is not established. Here, we assessed the role of 10 ubiquitylation sites for NCC function. Transient transfections of HEK293 cells with human wildtype (WT) NCC or various K to R mutants identified greater membrane abundance for K706R, K828R and K909R mutants. Relative to WT-NCC, stable tetracycline inducible MDCKI cell lines expressing K706R, K828R and K909R mutants had significantly higher total and phosphorylated NCC levels at the apical plasma membrane under basal conditions. Low chloride stimulation increased membrane abundance of all mutants to similar or greater levels than WT-NCC. Under basal conditions K828R and K909R mutants had less ubiquitylated NCC in the plasma membrane, and all mutants displayed reduced NCC ubiquitylation following low chloride stimulation. Thiazide-sensitive sodium-22 uptakes were elevated in the mutants and internalization from the plasma membrane was significantly less than WT-NCC. K909R had increased half-life, whereas chloroquine or MG132 treatment indicated that K706 and K909 play roles in lysosomal and proteasomal NCC degradation, respectively. In conclusion, site-specific ubiquitylation of NCC plays alternative roles for NCC function.

Embedding the Ni-SOD mimetic Ni-NCC within a polypeptide sequence alters the specificity of the reaction pathway.

PubMed

Krause, Mary E; Glass, Amanda M; Jackson, Timothy A; Laurence, Jennifer S

2013-01-07

The unique metal abstracting peptide asparagine-cysteine-cysteine (NCC) binds nickel in a square planar 2N:2S geometry and acts as a mimic of the enzyme nickel superoxide dismutase (Ni-SOD). The Ni-NCC tripeptide complex undergoes rapid, site-specific chiral inversion to dld-NCC in the presence of oxygen. Superoxide scavenging activity increases proportionally with the degree of chiral inversion. Characterization of the NCC sequence within longer peptides with absorption, circular dichroism (CD), and magnetic CD (MCD) spectroscopies and mass spectrometry (MS) shows that the geometry of metal coordination is maintained, though the electronic properties of the complex are varied to a small extent because of bis-amide, rather than amine/amide, coordination. In addition, both Ni-tripeptide and Ni-pentapeptide complexes have charges of -2. This study demonstrates that the chiral inversion chemistry does not occur when NCC is embedded in a longer polypeptide sequence. Nonetheless, the superoxide scavenging reactivity of the embedded Ni-NCC module is similar to that of the chirally inverted tripeptide complex, which is consistent with a minor change in the reduction potential for the Ni-pentapeptide complex. Together, this suggests that the charge of the complex could affect the SOD activity as much as a change in the primary coordination sphere. In Ni-NCC and other Ni-SOD mimics, changes in chirality, superoxide scavenging activity, and oxidation of the peptide itself all depend on the presence of dioxygen or its reduced derivatives (e.g., superoxide), and the extent to which each of these distinct reactions occurs is ruled by electronic and steric effects that emenate from the organization of ligands around the metal center.

Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC).

PubMed

Dimke, Henrik

2011-12-01

The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular explanation for pseudohypoaldosteronism type II (PHAII). Studies suggest that WNK4 regulates NCC via two distinct pathways, depending on its state of activation. Furthermore, an intact STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response 1 kinase (OSR1) pathway was found to be necessary for a WNK4 PHAII mutation to increase NCC phosphorylation and blood pressure in mice. The mouse protein 25α is a novel regulator of the SPAK/OSR1 kinase family, which greatly increases their activity. The phosphorylation status of NCC and the WNK is regulated by the serum- and glucocorticoid-inducible kinase 1, suggesting novel mechanisms whereby aldosterone modulates NCC activity. Dephosphorylation of NCC by protein phosphatase 4 strongly influences the activity of the cotransporter, confirming an important role for NCC phosphorylation. Finally, γ-adducin increases NCC activity. This stimulatory effect is dependent on the phosphorylation status of the cotransporter. γ-Adducin only binds the dephosphorylated cotransporter, suggesting that phosphorylation of NCC causes the dissociation of γ-adducin. Since γ-adducin is not a kinase, it is tempting to speculate that the protein exerts its function by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC transport activity and ultimately blood pressure.

Functional assessment of sodium chloride cotransporter NCC mutants in polarized mammalian epithelial cells.

PubMed

Rosenbaek, Lena L; Rizzo, Federica; MacAulay, Nanna; Staub, Olivier; Fenton, Robert A

2017-08-01

The thiazide-sensitive sodium chloride cotransporter NCC is important for maintaining serum sodium (Na + ) and, indirectly, serum potassium (K + ) levels. Functional studies on NCC have used cell lines with native NCC expression, transiently transfected nonpolarized cell lines, or Xenopus laevis oocytes. Here, we developed the use of polarized Madin-Darby canine kidney type I (MDCKI) mammalian epithelial cell lines with tetracycline-inducible human NCC expression to study NCC activity and membrane abundance in the same system. In radiotracer assays, induced cells grown on filters had robust thiazide-sensitive and chloride dependent sodium-22 ( 22 Na) uptake from the apical side. To minimize cost and maximize throughput, assays were modified to use cells grown on plastic. On plastic, cells had similar thiazide-sensitive 22 Na uptakes that increased following preincubation of cells in chloride-free solutions. NCC was detected in the plasma membrane, and both membrane abundance and phosphorylation of NCC were increased by incubation in chloride-free solutions. Furthermore, in cells exposed for 15 min to low or high extracellular K + , the levels of phosphorylated NCC increased and decreased, respectively. To demonstrate that the system allows rapid and systematic assessment of mutated NCC, three phosphorylation sites in NCC were mutated, and NCC activity was examined. 22 Na fluxes in phosphorylation-deficient mutants were reduced to baseline levels, whereas phosphorylation-mimicking mutants were constitutively active, even without chloride-free stimulation. In conclusion, this system allows the activity, cellular localization, and abundance of wild-type or mutant NCC to be examined in the same polarized mammalian expression system in a rapid, easy, and low-cost fashion. Copyright © 2017 the American Physiological Society.

Mechanisms of angiotensin II stimulation of NCC are time-dependent in mDCT15 cells.

PubMed

Ko, Benjamin; Mistry, Abinash; Hanson, Lauren; Mallick, Rickta; Hoover, Robert S

2015-04-01

Angiotensin II (ANG II) increases thiazide-sensitive sodium-chloride cotransporter (NCC) activity both acutely and chronically. ANG II has been implicated as a switch that turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4. Chronically, ANG II stimulation of NCC results in an increase in total and phosphorylated NCC, but the role of NCC phosphorylation in acute ANG II actions is unclear. Here, using a mammalian cell model with robust native NCC activity, we corroborate the role that ANG II plays in WNK4 regulation and clarify the role of Ste20-related proline alanine-rich kinase (SPAK)-induced NCC phosphorylation in ANG II action. ANG II was noted to have a biphasic effect on NCC, with a peak increase in NCC activity in the physiologic range of 10(-11) M ANG II. This effect was apparent as early as 15 min and remained sustained through 120 min. These changes correlated with significant increases in NCC surface protein expression. Knockdown of WNK4 expression sharply attenuated the effect of ANG II. SPAK knockdown did not affect ANG II action at early time points (15 and 30 min), but it did attenuate the response at 60 min. Correspondingly, NCC phosphorylation did not increase at 15 or 30 min, but increased significantly at 60 min. We therefore conclude that within minutes of an increase in ANG II, NCC is rapidly trafficked to the cell surface in a phosphorylation-independent but WNK4-dependent manner. Then, after 60 min, ANG II induces SPAK-dependent phosphorylation of NCC.

Mechanisms of angiotensin II stimulation of NCC are time-dependent in mDCT15 cells

PubMed Central

Mistry, Abinash; Hanson, Lauren; Mallick, Rickta; Hoover, Robert S.

2015-01-01

Angiotensin II (ANG II) increases thiazide-sensitive sodium-chloride cotransporter (NCC) activity both acutely and chronically. ANG II has been implicated as a switch that turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4. Chronically, ANG II stimulation of NCC results in an increase in total and phosphorylated NCC, but the role of NCC phosphorylation in acute ANG II actions is unclear. Here, using a mammalian cell model with robust native NCC activity, we corroborate the role that ANG II plays in WNK4 regulation and clarify the role of Ste20-related proline alanine-rich kinase (SPAK)-induced NCC phosphorylation in ANG II action. ANG II was noted to have a biphasic effect on NCC, with a peak increase in NCC activity in the physiologic range of 10−11 M ANG II. This effect was apparent as early as 15 min and remained sustained through 120 min. These changes correlated with significant increases in NCC surface protein expression. Knockdown of WNK4 expression sharply attenuated the effect of ANG II. SPAK knockdown did not affect ANG II action at early time points (15 and 30 min), but it did attenuate the response at 60 min. Correspondingly, NCC phosphorylation did not increase at 15 or 30 min, but increased significantly at 60 min. We therefore conclude that within minutes of an increase in ANG II, NCC is rapidly trafficked to the cell surface in a phosphorylation-independent but WNK4-dependent manner. Then, after 60 min, ANG II induces SPAK-dependent phosphorylation of NCC. PMID:25651566

WNK4 is the major WNK positively regulating NCC in the mouse kidney.

PubMed

Takahashi, Daiei; Mori, Takayasu; Nomura, Naohiro; Khan, Muhammad Zakir Hossain; Araki, Yuya; Zeniya, Moko; Sohara, Eisei; Rai, Tatemitsu; Sasaki, Sei; Uchida, Shinichi

2014-05-09

By analysing the pathogenesis of a hereditary hypertensive disease, PHAII (pseudohypoaldosteronism type II), we previously discovered that WNK (with-no-lysine kinase)-OSR1/SPAK (oxidative stress-responsive 1/Ste20-like proline/alanine-rich kinase) cascade regulates NCC (Na-Cl co-transporter) in the DCT (distal convoluted tubules) of the kidney. However, the role of WNK4 in the regulation of NCC remains controversial. To address this, we generated and analysed WNK4-/- mice. Although a moderate decrease in SPAK phosphorylation and a marked increase in WNK1 expression were evident in the kidneys of WNK4-/- mice, the amount of phosphorylated and total NCC decreased to almost undetectable levels, indicating that WNK4 is the major WNK positively regulating NCC, and that WNK1 cannot compensate for WNK4 deficiency in the DCT. Insulin- and low-potassium diet-induced NCC phosphorylation were abolished in WNK4-/- mice, establishing that both signals to NCC were mediated by WNK4. As shown previously, a high-salt diet decreases phosphorylated and total NCC in WNK4+/+ mice via AngII (angiotensin II) and aldosterone suppression. This was not ameliorated by WNK4 knock out, excluding the negative regulation of WNK4 on NCC postulated to be active in the absence of AngII stimulation. Thus, WNK4 is the major positive regulator of NCC in the kidneys.

WNK4 is the major WNK positively regulating NCC in the mouse kidney

PubMed Central

Takahashi, Daiei; Mori, Takayasu; Nomura, Naohiro; Khan, Muhammad Zakir Hossain; Araki, Yuya; Zeniya, Moko; Sohara, Eisei; Rai, Tatemitsu; Sasaki, Sei; Uchida, Shinichi

2014-01-01

By analysing the pathogenesis of a hereditary hypertensive disease, PHAII (pseudohypoaldosteronism type II), we previously discovered that WNK (with-no-lysine kinase)–OSR1/SPAK (oxidative stress-responsive 1/Ste20-like proline/alanine-rich kinase) cascade regulates NCC (Na–Cl co-transporter) in the DCT (distal convoluted tubules) of the kidney. However, the role of WNK4 in the regulation of NCC remains controversial. To address this, we generated and analysed WNK4−/− mice. Although a moderate decrease in SPAK phosphorylation and a marked increase in WNK1 expression were evident in the kidneys of WNK4−/− mice, the amount of phosphorylated and total NCC decreased to almost undetectable levels, indicating that WNK4 is the major WNK positively regulating NCC, and that WNK1 cannot compensate for WNK4 deficiency in the DCT. Insulin- and low-potassium diet-induced NCC phosphorylation were abolished in WNK4−/− mice, establishing that both signals to NCC were mediated by WNK4. As shown previously, a high-salt diet decreases phosphorylated and total NCC in WNK4+/+ mice via AngII (angiotensin II) and aldosterone suppression. This was not ameliorated by WNK4 knock out, excluding the negative regulation of WNK4 on NCC postulated to be active in the absence of AngII stimulation. Thus, WNK4 is the major positive regulator of NCC in the kidneys. PMID:24655003

Functionomics of NCC mutations in Gitelman syndrome using a novel mammalian cell-based activity assay.

PubMed

Valdez-Flores, Marco A; Vargas-Poussou, Rosa; Verkaart, Sjoerd; Tutakhel, Omar A Z; Valdez-Ortiz, Angel; Blanchard, Anne; Treard, Cyrielle; Hoenderop, Joost G J; Bindels, René J M; Jeleń, Sabina

2016-12-01

Gitelman syndrome (GS) is an autosomal recessive salt-wasting tubular disorder resulting from loss-of-function mutations in the thiazide-sensitive NaCl cotransporter (NCC). Functional analysis of these mutations has been limited to the use of Xenopus laevis oocytes. The aim of the present study was, therefore, to analyze the functional consequences of NCC mutations in a mammalian cell-based assay, followed by analysis of mutated NCC protein expression as well as glycosylation and phosphorylation profiles using human embryonic kidney (HEK) 293 cells. NCC activity was assessed with a novel assay based on thiazide-sensitive iodide uptake in HEK293 cells expressing wild-type or mutant NCC (N59I, R83W, I360T, C421Y, G463R, G731R, L859P, or R861C). All mutations caused a significantly lower NCC activity. Immunoblot analysis of the HEK293 cells revealed that 1) all NCC mutants have decreased NCC protein expression; 2) mutant N59I, R83W, I360T, C421Y, G463R, and L859P have decreased NCC abundance at the plasma membrane; 3) mutants C421Y and L859P display impaired NCC glycosylation; and 4) mutants N59I, R83W, C421Y, C731R, and L859P show affected NCC phosphorylation. In conclusion, we developed a mammalian cell-based assay in which NCC activity assessment together with a profiling of mutated protein processing aid our understanding of the pathogenic mechanism of the NCC mutations. Copyright © 2016 the American Physiological Society.

NCC: A Physics-Based Design and Analysis Tool for Combustion Systems

NASA Technical Reports Server (NTRS)

Liu, Nan-Suey; Quealy, Angela

2000-01-01

The National Combustion Code (NCC) is an integrated system of computer codes for physics-based design and analysis of combustion systems. It uses unstructured meshes and runs on parallel computing platforms. The NCC is composed of a set of distinct yet closely related modules. They are: (1) a gaseous flow module solving 3-D Navier-Stokes equations; (2) a turbulence module containing the non-linear k-epsilon models; (3) a chemistry module using either the conventional reduced kinetics approach of solving species equations or the Intrinsic Low Dimensional Manifold (ILDM) kinetics approach of table looking up in conjunction with solving the equations of the progressive variables; (4) a turbulence-chemistry interaction module including the option of solving the joint probability density function (PDF) for species and enthalpy; and (5) a spray module for solving the liquid phase equations. In early 1995, an industry-government team was formed to develop the NCC. In July 1998, the baseline beta version was completed and presented in two NCC sessions at the 34th AIAA/ASME/SAE/ASEE Joint Propulsion Conference & Exhibit, July 1998. An overview of this baseline beta version was presented at the NASA HPCCP/CAS Workshop 98, August 1998. Since then, the effort has been focused on the streamlining, validation, and enhancement of the th baseline beta version. The progress is presented in two NCC sessions at the AIAA 38 Aerospace Sciences Meeting & Exhibit, January 2000. At this NASA HPCCP/CAS Workshop 2000, an overview of the NCC papers presented at the AIAA 38 th Aerospace Sciences Meeting & Exhibit is presented, with emphasis on the reduction of analysis time of simulating the (gaseous) reacting flows in full combustors. In addition, results of NCC simulation of a modern turbofan combustor will also be reported.

Results from the Ncc/nicmos Spare-Detector June 2000 Emi Test

NASA Astrophysics Data System (ADS)

Schneider, Glenn

2000-08-01

Analysis of power spectra and images obtained with a NICMOS-3 flight spare detector, operated in conjunction with the NICMOS Cryo-Cooler (NCC) and mated with flight-like ground connections, indicate the total absence of any NCC induced electromagnetic interference in any of the more than 3000 NICMOS science data readouts (64K pixel) images examined. As a differential experiment, making use of the independently measured time-correlated samples provided by each of the four detector quadrants, the system sensitivities to detect EMI induced periodic and quasi-periodic signals in the frequency range from 5 Hz to 50 Khz closely reached, or exceeded, the per-pixel sensitivities of the NICMOS flight detectors in the flight instrument. A similar experiment performed in May, 1998, before the NCC test on the HOST mission, revealed the presence of complex broad-band signals impressed in the NICMOS science data readouts manifesting themselves as temporally varying "herringbone" patterns in the images with strong power components in the ~ 5-9 Khz region. The June 2000 test was conducted over a period of two days with NICMOS data collected with the NCC in an "off" state, and while being operated at a variety of compressor speeds from 5000 to 7200 rps. While significant non-NCC induced 60/180Hz contamination at the 10 DN (50 electron) peak-to-peak level was prevalent, and much smaller amplitude monochromatic signals were seen at higher frequencies, these were both unquestionably due to other sources. Frames taken with the NCC on and off were indistinguishable. It is apparent that changes in the NCC design and their implementation since its pre-HOST incarnation have succeeded in producing a unit which produces no measurable levels of induced signals in NICMOS science data readouts and is fully compatible with the use of NICMOS detectors onorbit thereby alleviating previous EMI concerns.

Spherical nanocrystalline cellulose (NCC) from oil palm empty fruit bunch pulp via ultrasound assisted hydrolysis.

PubMed

Zianor Azrina, Z A; Beg, M Dalour H; Rosli, M Y; Ramli, Ridzuan; Junadi, Norhafzan; Alam, A K M Moshiul

2017-04-15

Nanocrystalline cellulose (NCC) was isolated from oil palm empty fruit bunch pulp (EFBP) using ultrasound assisted acid hydrolysis. The obtained NCC was analysed using FESEM, XRD, FTIR, and TGA, and compared with raw empty fruit bunch fibre (REFB), empty fruit bunch pulp (EFBP), and treated empty fruit bunch pulp (TEFBP). Based on FESEM analysis, it was found that NCC has a spherical shaped after acid hydrolysis with the assistance of ultrasound. This situation was different compared to previous studies that obtained rod-like shaped of NCC. Furthermore, the crystallinity of NCC is higher compared to REFB and EFBP. According to thermal stability, the NCC obtained shows remarkable sign of high thermal stability compared to REFB and EFBP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

PubMed

Nicolet-Barousse, Laurence; Blanchard, Anne; Roux, Christian; Pietri, Laurence; Bloch-Faure, May; Kolta, Sami; Chappard, Christine; Geoffroy, Valérie; Morieux, Caroline; Jeunemaitre, Xavier; Shull, Gary E; Meneton, Pierre; Paillard, Michel; Houillier, Pascal; De Vernejoul, Marie-Christine

2005-05-01

Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion. Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD. To understand the underlying mechanisms, Ca and bone metabolism were studied in two models of genetic inactivation of the thiazide-sensitive NaCl cotransporter (NCC): patients with Gitelman syndrome (GS) and Ncc knockout (Ncc(-/-)) mice. Ca metabolism was analyzed in GS patients and Ncc(-/-) mice under conditions of low dietary Ca. BMD was measured by DXA in patients and mice, and bone histomorphometry was analyzed in mice. GS patients had low plasma Mg. They exhibited reduced UVCa, but similar serum Ca and GFR as control subjects, suggesting increased renal Ca reabsorption. Blood PTH was lower despite lower serum ionized Ca, and Mg repletion almost corrected both relative hypoparathyroidism and low UVCa. BMD was significantly increased in GS patients at both lumbar (+7%) and femoral (+16%) sites, and osteocalcin was reduced. In Ncc(-/-) mice, serum Ca and GFR were unchanged, but UVCa was reduced and PTH was elevated; Mg repletion largely corrected both abnormalities. Trabecular and cortical BMD were higher than in Ncc(+/+) mice (+4% and +5%, respectively), and despite elevated PTH, were associated with higher cortical thickness and lower endosteal osteoclastic surface. Higher BMD is observed in GS patients and Ncc(-/-) mice. Relative hypoparathyroidism (human) and bone resistance to PTH (mice), mainly caused by Mg depletion, can explain the low bone remodeling and normal/low serum Ca despite increased renal Ca reabsorption.

Cortisol regulates sodium homeostasis by stimulating the transcription of sodium-chloride transporter (NCC) in zebrafish (Danio rerio).

PubMed

Lin, Chia-Hao; Hu, Huei-Jyun; Hwang, Pung-Pung

2016-02-15

In mammals, sodium/hydrogen exchanger (NHE) and sodium-chloride cotransporter (NCC) are expressed in renal tubules, and exhibit functional redundancy and mutual compensation in Na(+) uptake. In teleosts, the gills of the adult and skin of the embryonic stage function as external kidneys, and ionocytes are responsible for ionoregulation in these tissues. NHE- and NCC-expressing ionocytes mutually cooperate to adjust Na(+) uptake, which is analogous to the activity of the mammalian kidney. Cortisol is a hormone that controls Na(+) uptake through regulating NCC expression and activity in mammals; however, cortisol-mediated control of NCC expression is little understood in non-mammalian vertebrates, such as teleosts. It is essential for our understanding of the evolution of such regulation to determine whether cortisol has a conserved effect on NCC in vertebrates. In the present study, we treated zebrafish embryos with low Na(+) medium (LNa, 0.04 mM Na(+)) for 3 d to stimulate the mRNA expression of nhe3b, ncc, and cyp11b1 (a cortisol-synthesis enzyme) and whole body cortisol level. Exogenous cortisol treatment (20 mg/l, 3 d) resulted in an elevation of whole-body Na(+) content, ncc expression, and the density of ncc-expressing cells in zebrafish larvae. In loss-of-function experiments, microinjection of glucocorticoid receptor (gr) morpholino (MO) suppressed sodium content, ncc expression, and the density of ncc-expressing cells, but injection of mr MO had no such effects. In addition, exogenous cortisol treatment and gr MO injection also altered ncc expression and the density of ncc-expressing cells in gcm2 morphant larvae. Taken together, cortisol and GR appear to regulate Na(+) absorption through stimulating ncc expression and the differentiation of ncc-expressing ionocytes, providing new insights into the actions of cortisol on Na(+) uptake. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Using CLIPS in a distributed system: The Network Control Center (NCC) expert system

NASA Technical Reports Server (NTRS)

Wannemacher, Tom

1990-01-01

This paper describes an intelligent troubleshooting system for the Help Desk domain. It was developed on an IBM-compatible 80286 PC using Microsoft C and CLIPS and an AT&T 3B2 minicomputer using the UNIFY database and a combination of shell script, C programs and SQL queries. The two computers are linked by a lan. The functions of this system are to help non-technical NCC personnel handle trouble calls, to keep a log of problem calls with complete, concise information, and to keep a historical database of problems. The database helps identify hardware and software problem areas and provides a source of new rules for the troubleshooting knowledge base.

WNK4 inhibits NCC protein expression through MAPK ERK1/2 signaling pathway.

PubMed

Zhou, Bo; Wang, Dexuan; Feng, Xiuyan; Zhang, Yiqian; Wang, Yanhui; Zhuang, Jieqiu; Zhang, Xuemei; Chen, Guangping; Delpire, Eric; Gu, Dingying; Cai, Hui

2012-03-01

WNK [with no lysine (K)] kinase is a subfamily of serine/threonine kinases. Mutations in two members of this family (WNK1 and WNK4) cause pseudohypoaldosteronism type II featuring hypertension, hyperkalemia, and metabolic acidosis. WNK1 and WNK4 were shown to regulate sodium chloride cotransporter (NCC) activity through phosphorylating SPAK and OSR1. Previous studies including ours have also shown that WNK4 inhibits NCC function and its protein expression. A recent study reported that a phorbol ester inhibits NCC function via activation of extracellular signal-regulated kinase (ERK) 1/2 kinase. In the current study, we investigated whether WNK4 affects NCC via the MAPK ERK1/2 signaling pathway. We found that WNK4 increased ERK1/2 phosphorylation in a dose-dependent manner in mouse distal convoluted tubule (mDCT) cells, whereas WNK4 mutants with the PHA II mutations (E562K and R1185C) lost the ability to increase the ERK1/2 phosphorylation. Hypertonicity significantly increased ERK1/2 phosphorylation in mDCT cells. Knock-down of WNK4 expression by siRNA resulted in a decrease of ERK1/2 phosphorylation. We further showed that WNK4 knock-down significantly increases the cell surface and total NCC protein expressions and ERK1/2 knock-down also significantly increases cell surface and total NCC expression. These data suggest that WNK4 inhibits NCC through activating the MAPK ERK1/2 signaling pathway.

NCC and Computers in Education.

ERIC Educational Resources Information Center

Brown, Ron L.

1982-01-01

This introduction to the work of the National Computing Centre (NCC), looks at industry/education links, the development of case studies, the use of computers in training, work in the Department of Industry - Micros in Schools Scheme, and at the Department of Education and Science-Micro-Electronics in Education Programme. (MP)

Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles.

PubMed

Lee, Donna H; Riquier, Anne D M; Yang, Li E; Leong, Patrick K K; Maunsbach, Arvid B; McDonough, Alicia A

2009-04-01

When blood pressure (BP) is elevated above baseline, a pressure natriuresis-diuresis response ensues, critical to volume and BP homeostasis. Distal convoluted tubule Na(+)-Cl(-) cotransporter (NCC) is regulated by trafficking between the apical plasma membrane (APM) and subapical cytoplasmic vesicles (SCV). We aimed to determine whether NCC trafficking contributes to pressure diuresis by decreasing APM NCC or compensates for increased volume flow to the DCT by increasing APM NCC. BP was raised 50 mmHg (high BP) in rats by arterial constriction for 5 or 20-30 min, provoking a 10-fold diuresis at both times. Kidneys were excised, and NCC subcellular distribution was analyzed by 1) sorbitol density gradient fractionation and immunoblotting and 2) immunoelectron microscopy (immuno-EM). NCC distribution did not change after 5-min high BP. After 20-30 min of high BP, 20% of NCC redistributed from low-density, APM-enriched fractions to higher density, endosome-enriched fractions, and, by quantitative immuno-EM, pool size of APM NCC decreased 14% and SCV pool size increased. Because of the time lag of the response, we tested the hypothesis that internalization of NCC was secondary to the decrease in ANG II that accompanies high BP. Clamping ANG II at a nonpressor level by coinfusion of captopril (12 microg/min) and ANG II (20 ng.kg(-1).min(-1)) during 30-min high BP reduced diuresis to eightfold and prevented redistribution of NCC from APM- to SCV-enriched fractions. We conclude that DCT NCC may participate in pressure natriuresis-diuresis by retraction out of apical plasma membranes and that the retraction is, at least in part, driven by the fall in ANG II that accompanies acute hypertension.

Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC).

PubMed

Pathare, Ganesh; Anderegg, Manuel; Albano, Giuseppe; Lang, Florian; Fuster, Daniel G

2018-02-26

Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH) 2 D 3 . It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect further in a model of mild hypovolemia, we studied mice lacking the thiazide sensitive NaCl cotransporter (NCC). Our data indicate that NCC knockout mice (KO) have significantly higher FGF23, PTH and aldosterone concentrations than corresponding wild type (WT) mice. However, 1,25(OH) 2 D 3 , fractional phosphate excretion and renal brush border expression of the sodium/phosphate co-transporter 2a were not different between the two genotypes. In addition, renal expression of FGF23 receptor FGFR1 and the co-receptor Klotho were unaltered in NCC KO mice. FGF23 transcript was increased in the bone of NCC KO mice compared to WT mice, but treatment of primary murine osteoblasts with the NCC inhibitor hydrochlorothiazide did not elicit an increase of FGF23 transcription. In contrast, the mineralocorticoid receptor blocker eplerenone reversed excess FGF23 levels in KO mice but not in WT mice, indicating that FGF23 upregulation in NCC KO mice is primarily aldosterone-mediated. Together, our data reveal that lack of renal NCC causes an aldosterone-mediated upregulation of circulating FGF23.

Liquid crystal behavior induced assembling fabrication of conductive chiral MWCNTs@NCC nanopaper

NASA Astrophysics Data System (ADS)

Ren, Yumei; Wang, Tianjiao; Chen, Zhimin; Li, Jing; Tian, Qiuge; Yang, Hongxia; Xu, Qun

2016-11-01

The conductive chiral MWCNTs@NCC nanopapers obtained by the assembly of nanocrystalline cellulose liquid crystals (NCC LCs) host matrix along with one-dimensional (1-D) multi-walled carbon nanotubes (MWCNTs) have been studied in this work. Circular dichroism (CD) studies show strong signals stemming from the chiral nematic structure. Notably, the introduction of the MWCNTs has a pronounced effect on the chiral structure of the as-prepared nanopaper. Our experimental results indicate the multiple weak molecular interactions existing between MWCNTs and NCC are responsible for the effective dispersion and stabilization of MWCNTs. Moreover it also confirms the resulting nanopaper has an increased conductivity of 4.2 S/m at 1.96 wt% MWCNTs. So the co-assembly of the nanocomposite herein opens a gateway for preparing functional materials combining the photonic properties of the NCC LCs matrix with other building blocks that can supply other advantageous functions.

Construction of nanometer cisplatin core-ferritin (NCC-F) and proteomic analysis of gastric cancer cell apoptosis induced with cisplatin released from the NCC-F.

PubMed

Ji, Xue-Tao; Huang, Lin; Huang, He-Qing

2012-06-18

Both transmission electron microscopy (TEM) and fluorescence spectrometry were used to reveal the characteristics of both subunit disassociation and recombination in apo-pig pancreas ferritin (apoPPF) in an alkaline medium ranging reversibly from pH 7.0 to 13.0. The experimental results indicated that apoPPF could be completely disassociated into 24 free subunits at pH 13.0, and then these subunits could be quickly reassembled into the original apoPPF once the pH of the reactive medium was returned to pH7.0. This novel and simple method could be used to effectively construct a novel nanometer cisplatin core-PPF (NCC-PPF). The major characteristics of NCC-PPF were investigated using various analytical methods such as ultraviolet-spectrometry, circular dichroism spectrometry and TEM, which indicated that its molecular structure was still similar to that of the original apoPPF. Results from the inductively coupled plasma mass spectrometer (ICP-MS) method showed that 11.26 cisplatin (CDDP) molecules were successfully packaged within the NCC-PPF shell, indicating that each molecule of apoPPF had the ability to enwrap 11.26 CDDP molecules for constructing the NCC-PPF. Flow cytometry showed that NCC-PPF also had the ability to release CDDP for inducing the apoptosis of gastric cancer cells BGC823 (GCC), but this phenomenon could scarcely be observed using apoPPF. A differential proteomic technique using two-dimensional electrophoresis (2-DE) gels selected and identified the differential proteins from cell apoptosis in order to reveal the molecular pathway of GCC apoptosis by both NCC-PPF and free CDDP, giving 13 differential expression proteins. These differential proteins could be further classified into six groups, which were described as being involved in the regulation of apoptosis, RNA transcription, oxidative stress response, signal transduction, cell metabolism, and cytoskeleton changes. In addition, a real-time PCR method was used to prove the expression level of

Endohedral metallofullerene Sc3NC@C84: a theoretical prediction.

PubMed

Wang, Dong-Lai; Xu, Hong-Liang; Su, Zhong-Min; Xin, Guang

2012-11-21

Very recently, two novel Sc(3)NC-based cluster fullerenes Sc(3)NC@C(80) (Wang et. al. J. Am. Chem. Soc. 2010, 132, 16362) and Sc(3)NC@C(78) (Wu et. al. J. Phys. Chem. C 2011, 115, 23755) were prepared and characterized, respectively. Inspired by these findings, the possibility of encapsulating Sc(3)NC cluster in the C(84) fullerene is performed using density functional theory (DFT). Firstly, the isolated pentagon rule (IPR) D(2d) (23) C(84) fullerene is employed to encase the Sc(3)NC cluster: four possible endohedral metallofullerene isomers a-d are designed. The large binding energies (ranging from 163.7 to 210.0 kcal mol(-1)) indicate that the planar quinary cluster Sc(3)NC can be stably encapsulated in the C(84) (isomer 23) cage. Further, we consider the incorporation of Sc(3)NC into the non-IPR C(s) (51365) C(84) cage leading to isomer e and show the high stability of isomer e, which has a larger binding energy, larger HOMO-LUMO gap, higher adiabatic (vertical) ionization potential, and lower adiabatic (vertical) electron affinity than the former four Sc(3)NC@C(84) (isomer 23). Significantly, the predicted binding energy (294.2 kcal mol(-1)) of isomer e is even larger than that (289.2 and 277.7 kcal mol(-1), respectively) of the synthesized Sc(3)NC@C(80) and Sc(3)NC@C(78,) suggesting a considerable possibility for experimental realization. The (13)C NMR chemical shifts and Raman spectra of this a new endofullerene have been explored to assist future experimental characterization.

Towards Accurate Prediction of Turbulent, Three-Dimensional, Recirculating Flows with the NCC

NASA Technical Reports Server (NTRS)

Iannetti, A.; Tacina, R.; Jeng, S.-M.; Cai, J.

2001-01-01

The National Combustion Code (NCC) was used to calculate the steady state, nonreacting flow field of a prototype Lean Direct Injection (LDI) swirler. This configuration used nine groups of eight holes drilled at a thirty-five degree angle to induce swirl. These nine groups created swirl in the same direction, or a corotating pattern. The static pressure drop across the holes was fixed at approximately four percent. Computations were performed on one quarter of the geometry, because the geometry is considered rotationally periodic every ninety degrees. The final computational grid used was approximately 2.26 million tetrahedral cells, and a cubic nonlinear k - epsilon model was used to model turbulence. The NCC results were then compared to time averaged Laser Doppler Velocimetry (LDV) data. The LDV measurements were performed on the full geometry, but four ninths of the geometry was measured. One-, two-, and three-dimensional representations of both flow fields are presented. The NCC computations compare both qualitatively and quantitatively well to the LDV data, but differences exist downstream. The comparison is encouraging, and shows that NCC can be used for future injector design studies. To improve the flow prediction accuracy of turbulent, three-dimensional, recirculating flow fields with the NCC, recommendations are given.

2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular carcinoma: HCC diagnostic algorithm.

PubMed

Lee, Jeong Min; Park, Joong-Won; Choi, Byung Ihn

2014-01-01

Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer in Korea and typically has a poor prognosis with a 5-year survival rate of only 28.6%. Therefore, it is of paramount importance to achieve the earliest possible diagnosis of HCC and to recommend the most up-to-date optimal treatment strategy in order to increase the survival rate of patients who develop this disease. After the establishment of the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC), Korea jointly produced for the first time the Clinical Practice Guidelines for HCC in 2003, revised them in 2009, and published the newest revision of the guidelines in 2014, including changes in the diagnostic criteria of HCC and incorporating the most recent medical advances over the past 5 years. In this review, we will address the noninvasive diagnostic criteria and diagnostic algorithm of HCC included in the newly established KLCSG-NCC guidelines in 2014, and review the differences in the criteria for a diagnosis of HCC between the KLCSG-NCC guidelines and the most recent imaging guidelines endorsed by the European Organisation for Research and Treatment of Cancer (EORTC), the Liver Imaging Reporting and Data System (LI-RADS), the Organ Procurement and Transplantation Network (OPTN) system, the Asian Pacific Association for the Study of the Liver (APASL) and the Japan Society of Hepatology (JSH).

Modulation of NCC activity by low and high K+ intake: insights into the signaling pathways involved

PubMed Central

Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika

2014-01-01

Modulation of Na+-Cl− cotransporter (NCC) activity is essential to adjust K+ excretion in the face of changes in dietary K+ intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K+ diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K+-citrate diets for 4 days. The low-K+ diet decreased and high-K+ diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr44/Thr48/Thr53) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser383/Ser325). The effect of the low-K+ diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K+ diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K+ diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K+-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K+ increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K+ diet. PMID:24761002

Redistribution of distal tubule Na+-Cl- cotransporter (NCC) in response to a high-salt diet.

PubMed

Sandberg, Monica B; Maunsbach, Arvid B; McDonough, Alicia A

2006-08-01

The distal convoluted tubule (DCT) apical Na(+)-Cl(-) cotransporter (NCC) is responsible for the reabsorption of 5-10% of filtered NaCl and is the target for thiazide diuretics. NCC abundance is increased during dietary NaCl restriction and by aldosterone and decreased during a high-salt (HS) diet and mineralocorticoid blockade. This study tested the hypothesis that subcellular distribution of NCC is also regulated in response to changes in dietary salt. Six-week-old Sprague-Dawley rats were fed a normal-salt diet (NS; 0.4% NaCl) for 3 wk, then switched to a HS diet (4% NaCl) for 3 wk or a low-salt diet (LS; 0.07% NaCl) for 1 wk. Under anesthesia, kidneys were excised, renal cortex was dissected, and NCC was analyzed with specific antibodies after either 1) density gradient centrifugation followed by immunoblotting or 2) fixation followed by immunoelectron microscopy. The HS diet decreased NCC abundance to 0.50 +/- 0.10 of levels in LS diet (1.00 +/- 0.23). The HS diet also caused a redistribution of NCC from low to higher density membranes. Immunoelectron microscopy revealed that NCC resides predominantly in the apical membrane in rats fed the LS diet and increases in subapical vesicles in rats fed the HS diet. In conclusion, a HS diet provokes a rapid and persistent redistribution of NCC from apical to subapical membranes, a mechanism that would facilitate a homeostatic decrease in NaCl reabsorption in the DCT to compensate for increased dietary salt.

Comparing Spray Characteristics from Reynolds Averaged Navier-Stokes (RANS) National Combustion Code (NCC) Calculations Against Experimental Data for a Turbulent Reacting Flow

NASA Technical Reports Server (NTRS)

Iannetti, Anthony C.; Moder, Jeffery P.

2010-01-01

Developing physics-based tools to aid in reducing harmful combustion emissions, like Nitrogen Oxides (NOx), Carbon Monoxide (CO), Unburnt Hydrocarbons (UHC s), and Sulfur Dioxides (SOx), is an important goal of aeronautics research at NASA. As part of that effort, NASA Glenn Research Center is performing a detailed assessment and validation of an in-house combustion CFD code known as the National Combustion Code (NCC) for turbulent reacting flows. To assess the current capabilities of NCC for simulating turbulent reacting flows with liquid jet fuel injection, a set of Single Swirler Lean Direct Injection (LDI) experiments performed at the University of Cincinnati was chosen as an initial validation data set. This Jet-A/air combustion experiment operates at a lean equivalence ratio of 0.75 at atmospheric pressure and has a 4 percent static pressure drop across the swirler. Detailed comparisons of NCC predictions for gas temperature and gaseous emissions (CO and NOx) against this experiment are considered in a previous work. The current paper is focused on detailed comparisons of the spray characteristics (radial profiles of drop size distribution and at several radial rakes) from NCC simulations against the experimental data. Comparisons against experimental data show that the use of the correlation for primary spray break-up implemented by Raju in the NCC produces most realistic results, but this result needs to be improved. Given the single or ten step chemical kinetics models, use of a spray size correlation gives similar, acceptable results

Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules.

PubMed

Grimm, P Richard; Coleman, Richard; Delpire, Eric; Welling, Paul A

2017-09-01

Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrent with the restoration of urinary potassium excretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt. Copyright © 2017 by the American Society of Nephrology.

CERA: Clerkships Need National Curricula on Care Delivery, Awareness of Their NCC Gaps.

PubMed

Cochella, Susan; Liaw, Winston; Binienda, Juliann; Hustedde, Carol

2016-06-01

The Society of Teachers of Family Medicine's (STFM) National Clerkship Curriculum (NCC) was created to standardize and improve teaching of a minimum core curriculum in family medicine clerkships, promoting the Triple Aim of better care and population health at lower cost. It includes competencies all clerkships should teach and tools to support clerkship directors (CDs). This 2014 CERA survey of clerkship directors is one of several needs assessments that guide STFM's NCC Editorial Board in targeting improvements and peer-review processes. CERA's 2014 survey of CDs was sent to all 137 CDs at US and Canadian allopathic medical schools. Primary aims included: (1) Identify curricular topics of greatest need, (2) Inventory the percent of family medicine clerkships teaching each NCC topic, and (3) Determine if longitudinal or blended clerkship have unique needs. This survey also assessed use of NCC to advocate for teaching resources and collaborate with colleagues at other institutions. Ninety-one percent of CDs completed the survey. Sixty-four percent reported their clerkship covers all of the NCC minimum core, but on detailed analysis, only 1% teach all topics. CDs need curricula on care delivery topics (cost-effective approach to acute care, role of family medicine in the health care system, quality/safety, and comorbid substance abuse). Single-question assessments overestimate the percentage of clerkships teaching all of the NCC minimum core. Clerkships need national curricula on care delivery topics and tools to help them find their curricular gaps.

WNK-OSR1/SPAK-NCC signal cascade has circadian rhythm dependent on aldosterone.

PubMed

Susa, Koichiro; Sohara, Eisei; Isobe, Kiyoshi; Chiga, Motoko; Rai, Tatemitsu; Sasaki, Sei; Uchida, Shinichi

2012-11-02

Blood pressure and renal salt excretion show circadian rhythms. Recently, it has been clarified that clock genes regulate circadian rhythms of renal transporter expression in the kidney. Since we discovered the WNK-OSR1/SPAK-NaCl cotransporter (NCC) signal cascade, which is important for regulating salt balance and blood pressure, we have sought to determine whether NCC protein expression or phosphorylation shows diurnal rhythms in the mouse kidneys. Male C57BL/6J mice were sacrificed every 4h (at 20:00, 0:00, 4:00, 8:00, 12:00, and 16:00), and the expression and phosphorylation of WNK4, OSR1, SPAK, and NCC were determined by immunoblot. (Lights were turned on at 8:00, which was the start of the rest period, and turned off at 20:00, which was the start of the active period, since mice are nocturnal.) Although expression levels of each protein did not show diurnal rhythm, the phosphorylation levels of OSR1, SPAK, and NCC were increased around the start of the active period and decreased around the start of the rest period. Oral administration of eplerenone (10mg/day) attenuated the phosphorylation levels of these proteins and also diminished the diurnal rhythm of NCC phosphorylation. Thus, the activity of the WNK4-OSR1/SPAK-NCC cascade was shown to have a diurnal rhythm in the kidney that may be governed by aldosterone. Copyright © 2012 Elsevier Inc. All rights reserved.

Circadian exosomal expression of renal thiazide-sensitive NaCl cotransporter (NCC) and prostasin in healthy individuals.

PubMed

Castagna, Annalisa; Pizzolo, Francesca; Chiecchi, Laura; Morandini, Francesca; Channavajjhala, Sarath Kiran; Guarini, Patrizia; Salvagno, Gianluca; Olivieri, Oliviero

2015-06-01

A circadian timing system is involved in the maintenance of fluid and electrolyte balance and blood pressure control. Aldosterone and vasopressin modulate ion transporters and channels crucial in sodium (Na) and water reabsorption such as the epithelium Na channel and the renal thiazide-sensitive NaCl cotransporter (NCC). We analyzed in urinary exosomes the intraday variations of NCC and prostasin expression and the association with electrolytes and water balance parameters. Blood and urine samples were collected at five time points during the day from five healthy subjects. Blood renin, aldosterone, cortisol, ACTH, and plasmatic and urinary Na, potassium, creatinine, adiuretin (ADH), NCC, and prostasin were evaluated. ACTH and cortisol showed a circadian pattern, similarly to aldosterone, while exosomal NCC and prostasin pattern were similar to urinary ADH, decreased in the morning and subsequently increased in the afternoon and evening. In urinary exosomes, NCC and prostasin had a diurnal pattern parallel to ADH and aquaporin 2, confirming that, in healthy subjects, both prostasin and NCC relate to water balance. These results provide suggestions for a possible chronotherapeutic approach in patients treated with thiazides, diuretic drugs acting as specific inhibitors of NCC-mediated Na reabsorption. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oxygen relieves the CO2 and acetate dependency of Lactobacillus johnsonii NCC 533.

PubMed

Hertzberger, Rosanne Y; Pridmore, R David; Gysler, Christof; Kleerebezem, Michiel; Teixeira de Mattos, M Joost

2013-01-01

Oxygen relieves the CO2 and acetate dependency of Lactobacillus johnsonii NCC 533. The probiotic Lactobacillus johnsonii NCC 533 is relatively sensitive to oxidative stress; the presence of oxygen causes a lower biomass yield due to early growth stagnation. We show however that oxygen can also be beneficial to this organism as it relieves the requirement for acetate and CO2 during growth. Both on agar- and liquid-media, anaerobic growth of L. johnsonii NCC 533 requires CO2 supplementation of the gas phase. Switching off the CO2 supply induces growth arrest and cell death. The presence of molecular oxygen overcomes the CO2 dependency. Analogously, L. johnsonii NCC 533 strictly requires media with acetate to sustain anaerobic growth, although supplementation at a level that is 100-fold lower (120 microM) than the concentration in regular growth medium for lactobacilli already suffices for normal growth. Analogous to the CO2 requirement, oxygen supply relieves this acetate-dependency for growth. The L. johnsonii NCC 533 genome indicates that this organism lacks genes coding for pyruvate formate lyase (PFL) and pyruvate dehydrogenase (PDH), both CO2 and acetyl-CoA producing systems. Therefore, C1- and C2- compound production is predicted to largely depend on pyruvate oxidase activity (POX). This proposed role of POX in C2/C1-generation is corroborated by the observation that in a POX deficient mutant of L. johnsonii NCC 533, oxygen is not able to overcome acetate dependency nor does it relieve the CO2 dependency.

Oxygen Relieves the CO2 and Acetate Dependency of Lactobacillus johnsonii NCC 533

PubMed Central

Hertzberger, Rosanne Y.; Pridmore, R. David; Gysler, Christof; Kleerebezem, Michiel; Teixeira de Mattos, M. Joost

2013-01-01

Oxygen relieves the CO2 and acetate dependency of Lactobacillus johnsonii NCC 533. The probiotic Lactobacillus johnsonii NCC 533 is relatively sensitive to oxidative stress; the presence of oxygen causes a lower biomass yield due to early growth stagnation. We show however that oxygen can also be beneficial to this organism as it relieves the requirement for acetate and CO2 during growth. Both on agar- and liquid-media, anaerobic growth of L. johnsonii NCC 533 requires CO2 supplementation of the gas phase. Switching off the CO2 supply induces growth arrest and cell death. The presence of molecular oxygen overcomes the CO2 dependency. Analogously, L. johnsonii NCC 533 strictly requires media with acetate to sustain anaerobic growth, although supplementation at a level that is 100-fold lower (120 microM) than the concentration in regular growth medium for lactobacilli already suffices for normal growth. Analogous to the CO2 requirement, oxygen supply relieves this acetate-dependency for growth. The L. johnsonii NCC 533 genome indicates that this organism lacks genes coding for pyruvate formate lyase (PFL) and pyruvate dehydrogenase (PDH), both CO2 and acetyl-CoA producing systems. Therefore, C1- and C2- compound production is predicted to largely depend on pyruvate oxidase activity (POX). This proposed role of POX in C2/C1-generation is corroborated by the observation that in a POX deficient mutant of L. johnsonii NCC 533, oxygen is not able to overcome acetate dependency nor does it relieve the CO2 dependency. PMID:23468944

Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved.

PubMed

Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika; Gamba, Gerardo

2014-06-15

Modulation of Na(+)-Cl(-) cotransporter (NCC) activity is essential to adjust K(+) excretion in the face of changes in dietary K(+) intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K(+) diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K(+)-citrate diets for 4 days. The low-K(+) diet decreased and high-K(+) diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr(44)/Thr(48)/Thr(53)) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser(383)/Ser(325)). The effect of the low-K(+) diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K(+) diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K(+) diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K(+)-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K(+) increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K(+) diet. Copyright © 2014 the American Physiological Society.

The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

PubMed

Mistry, Abinash C; Wynne, Brandi M; Yu, Ling; Tomilin, Viktor; Yue, Qiang; Zhou, Yiqun; Al-Khalili, Otor; Mallick, Rickta; Cai, Hui; Alli, Abdel A; Ko, Benjamin; Mattheyses, Alexa; Bao, Hui-Fang; Pochynyuk, Oleh; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

2016-10-01

The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Aldosterone does not require angiotensin II to activate NCC through a WNK4-SPAK-dependent pathway.

PubMed

van der Lubbe, Nils; Lim, Christina H; Meima, Marcel E; van Veghel, Richard; Rosenbaek, Lena Lindtoft; Mutig, Kerim; Danser, Alexander H J; Fenton, Robert A; Zietse, Robert; Hoorn, Ewout J

2012-06-01

We and others have recently shown that angiotensin II can activate the sodium chloride cotransporter (NCC) through a WNK4-SPAK-dependent pathway. Because WNK4 was previously shown to be a negative regulator of NCC, it has been postulated that angiotensin II converts WNK4 to a positive regulator. Here, we ask whether aldosterone requires angiotensin II to activate NCC and if their effects are additive. To do so, we infused vehicle or aldosterone in adrenalectomized rats that also received the angiotensin receptor blocker losartan. In the presence of losartan, aldosterone was still capable of increasing total and phosphorylated NCC twofold to threefold. The kinases WNK4 and SPAK also increased with aldosterone and losartan. A dose-dependent relationship between aldosterone and NCC, SPAK, and WNK4 was identified, suggesting that these are aldosterone-sensitive proteins. As more functional evidence of increased NCC activity, we showed that rats receiving aldosterone and losartan had a significantly greater natriuretic response to hydrochlorothiazide than rats receiving losartan only. To study whether angiotensin II could have an additive effect, rats receiving aldosterone with losartan were compared with rats receiving aldosterone only. Rats receiving aldosterone only retained more sodium and had twofold to fourfold increase in phosphorylated NCC. Together, our results demonstrate that aldosterone does not require angiotensin II to activate NCC and that WNK4 appears to act as a positive regulator in this pathway. The additive effect of angiotensin II may favor electroneutral sodium reabsorption during hypovolemia and may contribute to hypertension in diseases with an activated renin-angiotensin-aldosterone system.

Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention

PubMed Central

McDonough, Alicia A.; Masilamani, Shyama M. E.; Verlander, Jill W.; Baylis, Chris

2015-01-01

Pregnancy is characterized by plasma volume expansion due to Na+ retention, driven by aldosterone. The aldosterone-responsive epithelial Na+ channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na+-Cl− cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na+ channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K+ intake or other undefined mechanisms. PMID:25925254

Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention.

PubMed

West, Crystal A; McDonough, Alicia A; Masilamani, Shyama M E; Verlander, Jill W; Baylis, Chris

2015-07-01

Pregnancy is characterized by plasma volume expansion due to Na(+) retention, driven by aldosterone. The aldosterone-responsive epithelial Na(+) channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na(+)-Cl(-) cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na(+) channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K(+) intake or other undefined mechanisms. Copyright © 2015 the American Physiological Society.

Performance of the PHENIX NCC Prototype

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

O'Brien, E.; Kistenev, E.; Li, Z.

2006-10-27

The first prototype of NCC Si-W electromagnetic calorimeter have been built and tested at U-70 accelerator (IHEP, Protvino). Tests have been performed for 10 GeV electrons and 70 GeV protons.This paper describes design and construction of the prototype and tests results. Final prototype energy resolution is about 11% at 90% CL.

Double knockout of carbonic anhydrase II (CAII) and Na(+)-Cl(-) cotransporter (NCC) causes salt wasting and volume depletion.

PubMed

Xu, Jie; Barone, Sharon; Brooks, Mary-Beth; Soleimani, Manoocher

2013-01-01

The thiazide-sensitive Na(+)-Cl(-) cotransporter NCC and the Cl(-)/HCO3(-)exchanger pendrin are expressed on apical membranes of distal cortical nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na(+) channel (ENaC) and the Na(+)-dependent chloride/bicarbonate exchanger (NDCBE), whereas NCC is working by itself. A recent study showed that NCC and pendrin compensate for loss of each other under basal conditions, therefore masking the role that each plays in salt reabsorption. Carbonic anhydrase II (CAII, CA2 or CAR2) plays an important role in acid-base transport and salt reabsorption in the proximal convoluted tubule and acid-base transport in the collecting duct. Animals with CAII deletion show remodeling of intercalated cells along with the downregulation of pendrin. NCC KO mice on the other hand show significant upregulation of pendrin and ENaC. Neither model shows any significant salt wasting under baseline conditions. We hypothesized that the up-regulation of pendrin is essential for the prevention of salt wasting in NCC KO mice. To test this hypothesis, we generated NCC/CAII double KO (dKO) mice by crossing mice with single deletion of NCC and CAII. The NCC/CAII dKO mice displayed significant downregulation of pendrin, along with polyuria and salt wasting. As a result, the dKO mice developed volume depletion, which was associated with the inability to concentrate urine. We conclude that the upregulation of pendrin is essential for the prevention of salt and water wasting in NCC deficient animals and its downregulation or inactivation will result in salt wasting, impaired water conservation and volume depletion in the setting of NCC inactivation or inhibition. © 2014 S. Karger AG, Basel.

Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure.

PubMed

Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Shull, Gary E; Siddiqui, Faraz; Zahedi, Kamyar; Amlal, Hassane

2012-08-14

The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema.

Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure

PubMed Central

Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Shull, Gary E.; Siddiqui, Faraz; Zahedi, Kamyar; Amlal, Hassane

2012-01-01

The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema. PMID:22847418

Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1.

PubMed

Vallon, Volker; Schroth, Jana; Lang, Florian; Kuhl, Dietmar; Uchida, Shinichi

2009-09-01

The Na-Cl cotransporter NCC is expressed in the distal convoluted tubule, activated by phosphorylation, and has been implicated in renal NaCl and K(+) homeostasis. The serum and glucocorticoid inducible kinase 1 (SGK1) contributes to renal NaCl retention and K(+) excretion, at least in part, by stimulating the epithelial Na(+) channel and Na(+)-K(+)-ATPase in the downstream segments of aldosterone-sensitive Na(+)/K(+) exchange. In this study we confirmed in wild-type mice (WT) that dietary NaCl restriction increases renal NCC expression and its phosphorylation at Thr(53), Thr(58), and Ser(71), respectively. This response, however, was attenuated in mice lacking SGK1 (Sgk1(-/-)), which may contribute to impaired NaCl retention in those mice. Total renal NCC expression and phosphorylation at Thr(53), Thr(58), and Ser(71) in WT were greater under low- compared with high-K(+) diet. This finding is consistent with a regulation of NCC to modulate Na(+) delivery to downstream segments of Na(+)/K(+) exchange, thereby modulating K(+) excretion. Dietary K(+)-dependent variation in renal expression of total NCC and phosphorylated NCC were not attenuated in Sgk1(-/-) mice. In fact, high-K(+) diet-induced NCC suppression was enhanced in Sgk1(-/-) mice. The hyperkalemia induced in Sgk1(-/-) mice by a high-K(+) diet may have augmented NCC suppression, thereby increasing Na(+) delivery and facilitating K(+) excretion in downstream segments of impaired Na(+)/K(+) exchange. In summary, changes in NaCl and K(+) intake altered NCC expression and phosphorylation, an observation consistent with a role of NCC in NaCl and K(+) homeostasis. The two maneuvers dissociated plasma aldosterone levels from NCC expression and phosphorylation, implicating additional regulators. Regulation of NCC expression and phosphorylation by dietary NaCl restriction appears to involve SGK1.

Neurocysticercosis (NCC) with Hydrocephalus, Optic Atrophy and Vision Loss: A Rare Presentation.

PubMed

Chaudhary, Nagendra; Mahato, Shyam Kumar; Khan, Salamat; Pathak, Santosh; Bhatia, B D

2015-02-01

Neurocysticercosis (NCC) is one of the most common parasitic infestations (Taenia solium) of central nervous system (CNS) in children. Seizures are the common presenting symptoms. Hydrocephalus and optic atrophy are rare complications which may require neurosurgical interventions. We report a case of NCC with hydrocephalus and bilateral optic atrophy associated with vision loss in a Nepalese patient who improved with anti-parasitic therapy followed by ventriculo-peritoneal (VP) shunting.

Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis.

PubMed

Rengarajan, Srinivas; Lee, Donna H; Oh, Young Taek; Delpire, Eric; Youn, Jang H; McDonough, Alicia A

2014-05-01

Dietary potassium loading results in rapid kaliuresis, natriuresis, and diuresis associated with reduced phosphorylation (p) of the distal tubule Na(+)-Cl(-) cotransporter (NCC). Decreased NCC-p inhibits NCC-mediated Na(+) reabsorption and shifts Na(+) downstream for reabsorption by epithelial Na(+) channels (ENaC), which can drive K(+) secretion. Whether the signal is initiated by ingesting potassium or a rise in plasma K(+) concentration ([K(+)]) is not understood. We tested the hypothesis, in male rats, that an increase in plasma [K(+)] is sufficient to reduce NCC-p and drive kaliuresis. After an overnight fast, a single 3-h 2% potassium (2%K) containing meal increased plasma [K(+)] from 4.0 ± 0.1 to 5.2 ± 0.2 mM; increased urinary K(+), Na(+), and volume excretion; decreased NCC-p by 60%; and marginally reduced cortical Na(+)-K(+)-2Cl(-) cotransporter (NKCC) phosphorylation 25% (P = 0.055). When plasma [K(+)] was increased by tail vein infusion of KCl to 5.5 ± 0.1 mM over 3 h, significant kaliuresis and natriuresis ensued, NCC-p decreased by 60%, and STE20/SPS1-related proline alanine-rich kinase (SPAK) phosphorylation was marginally reduced 35% (P = 0.052). The following were unchanged at 3 h by either the potassium-rich meal or KCl infusion: Na(+)/H(+) exchanger 3 (NHE3), NHE3-p, NKCC, ENaC subunits, and renal outer medullary K(+) channel. In summary, raising plasma [K(+)] by intravenous infusion to a level equivalent to that observed after a single potassium-rich meal triggers renal kaliuretic and natriuretic responses, independent of K(+) ingestion, likely driven by decreased NCC-p and activity sufficient to shift sodium reabsorption downstream to where Na(+) reabsorption and flow drive K(+) secretion.

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome.

PubMed

Glaudemans, Bob; Yntema, Helger G; San-Cristobal, Pedro; Schoots, Jeroen; Pfundt, Rolph; Kamsteeg, Erik-J; Bindels, René J; Knoers, Nine V A M; Hoenderop, Joost G; Hoefsloot, Lies H

2012-03-01

Gitelman syndrome (GS) is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis in conjunction with significant hypomagnesemia and hypocalciuria. The GS phenotype is caused by mutations in the solute carrier family 12, member 3 (SLC12A3) gene that encodes the thiazide-sensitive NaCl cotransporter (NCC). We analyzed DNA samples of 163 patients with a clinical suspicion of GS by direct sequencing of all 26 exons of the SLC12A3 gene. In total, 114 different mutations were identified, 31 of which have not been reported before. These novel variants include 3 deletions, 18 missense, 6 splice site and 4 nonsense mutations. We selected seven missense mutations to investigate their effect on NCC activity and plasma membrane localization by using the Xenopus laevis oocyte expression system. The Thr392Ile mutant did not display transport activity (probably class 2 mutation), while the Asn442Ser and Gln1030Arg NCC mutants showed decreased plasma membrane localization and consequently function, likely due to impaired trafficking (class 3 mutation). Even though the NaCl uptake was hampered for NCC mutants Glu121Asp, Pro751Leu, Ser475Cys and Tyr489His, the transporters reached the plasma membrane (class 4 mutation), suggesting an effect on NCC regulation or ion affinity. The present study shows the identification of 38 novel mutations in the SLC12A3 gene and provides insight into the mechanisms that regulate NCC.

Beneficial effect of Lactococcus lactis NCC 2287 in a murine model of eosinophilic esophagitis.

PubMed

Holvoet, S; Doucet-Ladevèze, R; Perrot, M; Barretto, C; Nutten, S; Blanchard, C

2016-12-01

Eosinophilic esophagitis (EoE) is a severe inflammatory disease of the esophagus which is characterized histologically by an eosinophilic infiltration into the esophageal tissue. The efficacy of probiotics in the context of atopic diseases has been well investigated but, to date, there has been no study which has evaluated probiotic effects on EoE inflammation. This study sought to identify a probiotic which improves esophageal inflammation in experimental EoE. Two candidate probiotics, Lactococcus lactis NCC 2287 and Bifidobacterium lactis NCC 2818, were tested in a murine model of EoE elicited by epicutaneous sensitization with Aspergillus fumigatus protein extract. Administration of bacterial strains in drinking water was used, respectively, as a preventive or treatment measure, or continuously throughout the study. Inflammatory parameters were assessed in the esophagus, skin, and lungs after allergen challenge. In this EoE model, supplementation with L. lactis NCC 2287 significantly decreased esophageal and bronchoalveolar eosinophilia but only when given as a therapeutic treatment. No significant effect on eosinophilia was observed when NCC 2287 was given as a preventive or a continuous intervention. NCC 2287 supplementation had no significant effect on immunoglobulin levels, skin symptom scores, or on transepidermal water loss. Supplementation with another probiotic, B. lactis NCC 2818, had no significant effect on esophageal eosinophilia. We identified a L. lactis strain, able to attenuate esophageal eosinophilic inflammation in a preclinical model of EoE. This effect is strain specific and depends on the timing and duration of bacterial supplementation. Confirmation of these observations in human clinical trials is warranted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PTH modulation of NCC activity regulates TRPV5 Ca2+ reabsorption.

PubMed

Hoover, Robert S; Tomilin, Viktor; Hanson, Lauren; Pochynyuk, Oleh; Ko, Benjamin

2016-01-15

Since parathyroid hormone (PTH) is known to increase transient receptor potential vanilloid (TRPV)5 activity and decrease Na(+)-Cl(-) cotransporter (NCC) activity, we hypothesized that decreased NCC-mediated Na(+) reabsorption contributes to the enhanced TRPV5 Ca(2+) reabsorption seen with PTH. To test this, we used mDCT15 cells expressing functional TRPV5 and ruthenium red-sensitive (45)Ca(2+) uptake. PTH increased (45)Ca(2+) uptake to 8.8 ± 0.7 nmol·mg(-1)·min(-1) (n = 4, P < 0.01) and decreased NCC activity from 75.4 ± 2.7 to 20.3 ± 1.3 nmol·mg(-1)·min(-1) (n = 4, P < 0.01). Knockdown of Ras guanyl-releasing protein (RasGRP)1 had no baseline effect on (45)Ca(2+) uptake but significantly attenuated the response to PTH from a 45% increase (6.0 ± 0.2 to 8.7 ± 0.4 nmol·mg(-1)·min(-1)) in control cells to only 20% in knockdown cells (6.1 ± 0.1 to 7.3 ± 0.2 nmol·mg(-1)·min(-1), n = 4, P < 0.01). Inhibition of PKC and PKA resulted in further attenuation of the PTH effect. RasGRP1 knockdown decreased the magnitude of the TRPV5 response to PTH (7.9 ± 0.1 nmol·mg(-1)·min(-1) for knockdown compared with 9.1 ± 0.1 nmol·mg(-1)·min(-1) in control), and the addition of thiazide eliminated this effect (a nearly identical 9.0 ± 0.1 nmol·mg(-1)·min(-1)). This indicates that functionally active NCC is required for RasGRP1 knockdown to impact the PTH effect on TRPV5 activity. Knockdown of with no lysine kinase (WNK)4 resulted in an attenuation of the increase in PTH-mediated TRPV5 activity. TRPV5 activity increased by 36% compared with 45% in control (n = 4, P < 0.01 between PTH-treated groups). PKC blockade further attenuated the PTH effect, whereas combined PKC and PKA blockade in WNK4KD cells abolished the effect. We conclude that modulation of NCC activity contributes to the response to PTH, implying a role for hormonal modulation of NCC activity in distal Ca(2+) handling.

Hydrogen peroxide production by Lactobacillus johnsonii NCC 533 and its role in anti-Salmonella activity.

PubMed

Pridmore, Raymond David; Pittet, Anne-Cécile; Praplan, Fabienne; Cavadini, Christoph

2008-06-01

The human intestinal isolate Lactobacillus johnsonii NCC 533 (La1) is a probiotic strain with well-documented antimicrobial properties. Previous research has identified the production of lactic acid and bacteriocins as important factors, but that other unidentified factors are also involved. We used the recently published genome sequence of L. johnsonii NCC 533 to search for novel antipathogen factors and identified three potential gene products that may catalyze the synthesis of the known antimicrobial factor hydrogen peroxide, H(2)O(2). In this work, we confirmed the ability of NCC 533 as well as eight different L. johnsonii strains and Lactobacillus gasseri to produce H(2)O(2) when resting cells were incubated in the presence of oxygen, and that culture supernatant containing NCC 533-produced H(2)O(2) was effective in killing the model pathogen Salmonella enterica serovar Typhimurium SL1344 in vitro.

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout.

PubMed

Boscardin, Emilie; Perrier, Romain; Sergi, Chloé; Maillard, Marc P; Loffing, Johannes; Loffing-Cueni, Dominique; Koesters, Robert; Rossier, Bernard C; Hummler, Edith

2018-03-01

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the α ENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of α ENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa + )/low potassium (LK + ) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γ ENaC subunit in the PHA-I phenotype. Nephron-specific γ ENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking α ENaC or β ΕΝaC, an HNa + /LK + diet did not normalize plasma potassium (K + ) concentration or increase NCC activation. However, when K + was eliminated from the diet at the time that γ ENaC was deleted, plasma K + concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced β ENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K + concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na + balance in γ ENaC-deficient mice. Copyright © 2018 by the American Society of Nephrology.

PI3K/Akt Signaling Pathway Activates the WNK-OSR1/SPAK-NCC Phosphorylation Cascade in Hyperinsulinemic db/db Mice

PubMed Central

Nishida, Hidenori; Sohara, Eisei; Nomura, Naohiro; Chiga, Motoko; Alessi, Dario R; Rai, Tatemitsu; Sasaki, Sei; Uchida, Shinichi

2013-01-01

Metabolic syndrome patients have insulin resistance, which causes hyperinsulinemia, which in turn causes aberrant increased renal sodium reabsorption. The precise mechanisms underlying this greater salt-sensitivity of hyperinsulinemic patients remain unclear. Abnormal activation of the recently-identified WNK kinase-OSR1/SPAK kinases-NCC transporter phosphorylation cascade results in the salt-sensitive hypertension of pseudohypoaldosteronism type II. Here, we report a study of renal WNK-OSR1/SPAK-NCC cascade activation in the db/db mouse model of hyperinsulinemic metabolic syndrome. Thiazide sensitivity was increased, suggesting greater activity of NCC in db/db mice. In fact, increased phosphorylation of OSR1/SPAK and NCC was observed. In both SpakT243A/+ and Osr1T185A/+ knock-in db/db mice, which carry mutations that disrupt the signal from WNK kinases, increased phosphorylation of NCC and elevated blood pressure were completely corrected, indicating that phosphorylation of SPAK and OSR1 by WNK kinases is required for the increased activation and phosphorylation of NCC in this model. Renal phosphorylated Akt was increased in db/db mice, suggesting that increased NCC phosphorylation is regulated by the PI3K/Akt signaling cascade in the kidney in response to hyperinsulinemia. A PI3K inhibitor (NVP-BEZ235) corrected the increased OSR1/SPAK-NCC phosphorylation. Another more specific PI3K inhibitor (GDC-0941) and an Akt inhibitor (MK-2206) also inhibited increased NCC phosphorylation. These results indicate that the PI3K/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in db/db mice. This mechanism may play a role in the pathogenesis of salt-sensitive hypertension in human hyperinsulinemic conditions such as the metabolic syndrome. PMID:22949526

Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice.

PubMed

Nishida, Hidenori; Sohara, Eisei; Nomura, Naohiro; Chiga, Motoko; Alessi, Dario R; Rai, Tatemitsu; Sasaki, Sei; Uchida, Shinichi

2012-10-01

Metabolic syndrome patients have insulin resistance, which causes hyperinsulinemia, which in turn causes aberrant increased renal sodium reabsorption. The precise mechanisms underlying this greater salt sensitivity of hyperinsulinemic patients remain unclear. Abnormal activation of the recently identified with-no-lysine kinase (WNK)-oxidative stress-responsive kinase 1 (OSR1)/STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NaCl cotransporter (NCC) phosphorylation cascade results in the salt-sensitive hypertension of pseudohypoaldosteronism type II. Here, we report a study of renal WNK-OSR1/SPAK-NCC cascade activation in the db/db mouse model of hyperinsulinemic metabolic syndrome. Thiazide sensitivity was increased, suggesting greater activity of NCC in db/db mice. In fact, increased phosphorylation of OSR1/SPAK and NCC was observed. In both SpakT243A/+ and Osr1T185A/+ knock-in db/db mice, which carry mutations that disrupt the signal from WNK kinases, increased phosphorylation of NCC and elevated blood pressure were completely corrected, indicating that phosphorylation of SPAK and OSR1 by WNK kinases is required for the increased activation and phosphorylation of NCC in this model. Renal phosphorylated Akt was increased in db/db mice, suggesting that increased NCC phosphorylation is regulated by the phosphatidylinositol 3-kinase/Akt signaling cascade in the kidney in response to hyperinsulinemia. A phosphatidylinositol 3-kinase inhibitor (NVP-BEZ235) corrected the increased OSR1/SPAK-NCC phosphorylation. Another more specific phosphatidylinositol 3-kinase inhibitor (GDC-0941) and an Akt inhibitor (MK-2206) also inhibited increased NCC phosphorylation. These results indicate that the phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in db/db mice. This mechanism may play a role in the pathogenesis of salt-sensitive hypertension in human hyperinsulinemic conditions, such as the metabolic syndrome.

Albuminuria enhances NHE3 and NCC via stimulation of mitochondrial oxidative stress/angiotensin II axis.

PubMed

Jia, Zhanjun; Zhuang, Yibo; Hu, Caiyu; Zhang, Xintong; Ding, Guixia; Zhang, Yue; Rohatgi, Rajeev; Hua, Hu; Huang, Songming; He, John Ci-Jiang; Zhang, Aihua

2016-07-26

Imbalance of salt and water is a frequent and challenging complication of kidney disease, whose pathogenic mechanisms remain elusive. Employing an albumin overload mouse model, we discovered that albuminuria enhanced the expression of NHE3 and NCC but not other transporters in murine kidney in line with the stimulation of angiotensinogen (AGT)/angiotensin converting enzyme (ACE)/angiotensin (Ang) II cascade. In primary cultures of renal tubular cells, albumin directly stimulated AGT/ACE/Ang II and upregulated NHE3 and NCC expression. Blocking Ang II production with an ACE inhibitor normalized the upregulation of NHE3 and NCC in cells. Interestingly, albumin overload significantly reduced mitochondrial superoxide dismutase (SOD2), and administration of a SOD2 mimic (MnTBAP) normalized the expression of NHE3, NCC, and the components of AGT/ACE pathway affected by albuminuria, indicating a key role of mitochondria-derived oxidative stress in modulating renin-angiotensin system (RAS) and renal sodium transporters. In addition, the functional data showing the reduced urinary excretion of Na and Cl and enhanced response to specific NCC inhibitor further supported the regulatory results of sodium transporters following albumin overload. More importantly, the upregulation of NHE3 and NCC and activation of ACE/Ang II signaling pathway were also observed in albuminuric patient kidneys, suggesting that our animal model accurately replicates the human condition. Taken together, these novel findings demonstrated that albuminuria is of importance in resetting renal salt handling via mitochondrial oxidative stress-initiated stimulation of ACE/Ang II cascade. This may also offer novel, effective therapeutic targets for dealing with salt and water imbalance in proteinuric renal diseases.

Synergistic effect of nano calcium carbonate (NCC)/carbon black (CB) on the cure characteristics and physico-mechanical properties of NR/SBR blends

NASA Astrophysics Data System (ADS)

Mamauod, Siti Nur Liyana; Romli, Ahmad Zafir; Rizuan, Mohd Ismail Rifdi

2017-09-01

This research was carried out as to develop hybrid filler reinforced into the blend of natural rubber (NR) and styrene butadiene rubber (SBR). The NR/SBR blend was reinforced using carbon black (CB) and nano calcium carbonate (NCC). The NCC content varied from 2-10 phr which was incorporated into the NR/SBR blend filled with fixed 50 phr of CB. The main aim of this project was to study the synergistic effect of NCC and CB reinforced NR/SBR blends towards the curing characteristics using cure rheometer, the viscosity of uncured NR/SBR compounds, physical and mechanical property blends. From the results obtained, the optimum ratio of blending was identified at 4 phr of NCC loading. Tensile strength, elongation at break, modulus and hardness increased progressively with increasing the NCC loading from 0 phr up to a maximum value at 4 phr. This increment occurs due to consolidation of the network structure of the polymer chains with the increasing NCC content. Up to the optimum amount of NCC, the tendency for NCC particles to form aggregate was very high and hence reduces the properties of rubber blends. It proved that NCC acts as a co-reinforcing agent for CB to improve the performance in the NR/SBR blends.

P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells.

PubMed

Gailly, P; Szutkowska, M; Olinger, E; Debaix, H; Seghers, F; Janas, S; Vallon, V; Devuyst, O

2014-11-01

Luminal nucleotide stimulation is known to reduce Na(+) transport in the distal nephron. Previous studies suggest that this mechanism may involve the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca(2+) transients and decreased the expression of NCC at both mRNA and protein levels. Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished ATP/UTP-induced Ca(2+) transients and significantly reduced ATP/UTP-induced decrease of NCC expression. To test whether local variations in the intracellular Ca(2+) concentration ([Ca(2+)]i) may control NCC transcription, we overexpressed the Ca(2+)-binding protein parvalbumin selectively in the cytosol or in the nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was abolished in cells overexpressing cytosolic PV but not in cells overexpressing either a nuclear-targeted PV or a mutated PV unable to bind Ca(2+). Using a firefly luciferase reporter gene strategy, we observed that the activity of NCC promoter region from -1 to -2,200 bp was not regulated by changes in [Ca(2+)]i. In contrast, high cytosolic calcium level induced instability of NCC mRNA. We conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular Ca(2+) signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of cytoplasmic Ca(2+) concentration down-regulates the expression of NCC; (3) the decrease of NCC expression occurs, at least in part, via destabilization of its mRNA.

WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4.

PubMed

Chávez-Canales, María; Zhang, Chong; Soukaseum, Christelle; Moreno, Erika; Pacheco-Alvarez, Diana; Vidal-Petiot, Emmanuelle; Castañeda-Bueno, María; Vázquez, Norma; Rojas-Vega, Lorena; Meermeier, Nicholas P; Rogers, Shaunessy; Jeunemaitre, Xavier; Yang, Chao-Ling; Ellison, David H; Gamba, Gerardo; Hadchouel, Juliette

2014-11-01

The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt), associated with an activation of the Na-Cl cotransporter (NCC). Although it is clear that WNK4 mutants activate NCC via Ste20 proline-alanine-rich kinase, the mechanisms responsible for WNK1-related FHHt and alterations in NCC activity are not as clear. We tested whether WNK1 modulates NCC through WNK4, as predicted by some models, by crossing our recently developed WNK1-FHHt mice (WNK1(+/FHHt)) with WNK4(-/-) mice. Surprisingly, the activated NCC, hypertension, and hyperkalemia of WNK1(+/FHHt) mice remain in the absence of WNK4. We demonstrate that WNK1 powerfully stimulates NCC in a WNK4-independent and Ste20 proline-alanine-rich kinase-dependent manner. Moreover, WNK4 decreases the WNK1 and WNK3-mediated activation of NCC. Finally, the formation of oligomers of WNK kinases through their C-terminal coiled-coil domain is essential for their activity toward NCC. In conclusion, WNK kinases form a network in which WNK4 associates with WNK1 and WNK3 to regulate NCC. © 2014 American Heart Association, Inc.

Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill

USGS Publications Warehouse

Breves, Jason P.; Serizier, Sandy B.; Goffin, Vincent; McCormick, Stephen D.; Karlstrom, Rolf O.

2013-01-01

Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na+/Cl− cotransporter (ncc; slc12a10.2), Na+/H+ exchanger (nhe3b; slc9a3.2), and epithelial Ca2+ channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl− uptake in zebrafish for the first time.

The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway.

PubMed

Bazúa-Valenti, Silvana; Rojas-Vega, Lorena; Castañeda-Bueno, María; Barrera-Chimal, Jonatan; Bautista, Rocío; Cervantes-Pérez, Luz G; Vázquez, Norma; Plata, Consuelo; Murillo-de-Ozores, Adrián R; González-Mariscal, Lorenza; Ellison, David H; Riccardi, Daniela; Bobadilla, Norma A; Gamba, Gerardo

2018-05-30

Background Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle's loop controls Ca 2+ excretion and NaCl reabsorption in response to extracellular Ca 2+ However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Results Thiazide-sensitive 22 Na + uptake assays in Xenopus laevis oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd 3+ In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Conclusions Activation of CaSR can increase NCC activity via the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca 2+ in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca 2+ reabsorption, further promoting hypercalciuria. Copyright © 2018 by the American Society of Nephrology.

Proteogenomic analysis of NCC-S1M, a gastric cancer stem cell-like cell line that responds to anti-PD-1.

PubMed

Park, Jun Won; Um, Hyejin; Yang, Hanna; Ko, Woori; Kim, Dae-Yong; Kim, Hark Kyun

2017-03-11

To elucidate signaling pathways that regulate gastric cancer stem cell (CSC) phenotypes and immune checkpoint, we performed a proteogenomic analysis of NCC-S1M, which is a gastric cancer cell line with CSC-like characteristics and is the only syngeneic gastric tumor cell line transplant model created in the scientific community. We found that the NCC-S1M allograft was responsive to anti-PD-1 treatment, and overexpressed Cd274 encoding PD-L1. PD-L1 was transcriptionally activated by loss of the TGF-β signaling. Il1rl1 protein was overexpressed in NCC-S1M cells compared with NCC-S1 cells that are less tumorigenic and less chemoresistant. Il1rl1 knockdown in NCC-S1M cells reduced tumorigenic potential and in vivo chemoresistance. Our proteogenomic analysis demonstrates a role of Smad4 loss in the PD-L1 immune evasion, as well as Il1rl1's role in CSC-like properties of NCC-S1M. Copyright © 2017 Elsevier Inc. All rights reserved.

NCC-AUC: an AUC optimization method to identify multi-biomarker panel for cancer prognosis from genomic and clinical data.

PubMed

Zou, Meng; Liu, Zhaoqi; Zhang, Xiang-Sun; Wang, Yong

2015-10-15

In prognosis and survival studies, an important goal is to identify multi-biomarker panels with predictive power using molecular characteristics or clinical observations. Such analysis is often challenged by censored, small-sample-size, but high-dimensional genomic profiles or clinical data. Therefore, sophisticated models and algorithms are in pressing need. In this study, we propose a novel Area Under Curve (AUC) optimization method for multi-biomarker panel identification named Nearest Centroid Classifier for AUC optimization (NCC-AUC). Our method is motived by the connection between AUC score for classification accuracy evaluation and Harrell's concordance index in survival analysis. This connection allows us to convert the survival time regression problem to a binary classification problem. Then an optimization model is formulated to directly maximize AUC and meanwhile minimize the number of selected features to construct a predictor in the nearest centroid classifier framework. NCC-AUC shows its great performance by validating both in genomic data of breast cancer and clinical data of stage IB Non-Small-Cell Lung Cancer (NSCLC). For the genomic data, NCC-AUC outperforms Support Vector Machine (SVM) and Support Vector Machine-based Recursive Feature Elimination (SVM-RFE) in classification accuracy. It tends to select a multi-biomarker panel with low average redundancy and enriched biological meanings. Also NCC-AUC is more significant in separation of low and high risk cohorts than widely used Cox model (Cox proportional-hazards regression model) and L1-Cox model (L1 penalized in Cox model). These performance gains of NCC-AUC are quite robust across 5 subtypes of breast cancer. Further in an independent clinical data, NCC-AUC outperforms SVM and SVM-RFE in predictive accuracy and is consistently better than Cox model and L1-Cox model in grouping patients into high and low risk categories. In summary, NCC-AUC provides a rigorous optimization framework to

Effect of angiotensin II on the WNK-OSR1/SPAK-NCC phosphorylation cascade in cultured mpkDCT cells and in vivo mouse kidney.

PubMed

Talati, Gulibaha; Ohta, Akihito; Rai, Tatemitsu; Sohara, Eisei; Naito, Shotaro; Vandewalle, Alain; Sasaki, Sei; Uchida, Shinichi

2010-03-19

In our recent study using Wnk4(D561A/+) knockin mice, we determined that the WNK-OSR1/SPAK-NaCl cotransporter (NCC) phosphorylation cascade is important for regulating NCC function in vivo. Phosphorylation of NCC was necessary for its plasma membrane localization. Previously, angiotensin II infusion was shown to increase apical membrane expression of NCC in rats. Therefore, we investigated whether angiotensin II was an upstream regulator for the WNK-OSR1/SPAK-NCC cascade in cultured cells and in vivo kidney. In mpkDCT cells, the phosphorylation of OSR1 and NCC was increased 30 min after the addition of angiotensin II (10(-9)-10(-7)M) but returned to baseline after 18 h. In mice, a 5-min infusion of angiotensin II (5 ng/g/min) increased NCC phosphorylation in the kidney at 30 min and 2h after the injection but returned to baseline 24h later. This increase was inhibited by angiotensin II receptor blocker (valsartan) but not by aldosterone receptor blocker (eplerenone). Ten-day infusions of angiotensin II (720 ng/day) also increased phosphorylation of OSR1 and NCC in the mouse kidney, and both valsartan and eplerenone inhibited the increased phosphorylation. Although angiotensin II is identified as an upstream regulator for the WNK-OSR1/SPAK-NCC cascade in vivo, aldosterone appears to be the major regulator of this signal cascade in the long-term regulation by angiotensin II. Copyright 2010 Elsevier Inc. All rights reserved.

The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion.

PubMed

Czogalla, Jan; Vohra, Twinkle; Penton, David; Kirschmann, Moritz; Craigie, Eilidh; Loffing, Johannes

2016-05-01

Aldosterone binds to the mineralocorticoid receptor (MR) and increases renal Na(+) reabsorption via up-regulation of the epithelial Na(+) channel (ENaC) and the Na(+)-K(+)-ATPase in the collecting system (CS) and possibly also via the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). However, whether aldosterone directly regulates NCC via MR or indirectly through systemic alterations remains controversial. We used mice with deletion of MR in ∼20 % of renal tubule cells (MR/X mice), in which MR-positive (MR(wt)) and -negative (MR(ko)) cells can be studied side-by-side in the same physiological context. Adult MR/X mice showed similar mRNA and protein levels of renal ion transport proteins to control mice. In MR/X mice, no differences in NCC abundance and phosphorylation was seen between MR(wt) and MR(ko) cells and dietary Na(+) restriction up-regulated NCC to similar extent in both groups of cells. In contrast, MR(ko) cells in the CS did not show any detectable alpha-ENaC abundance or apical targeting of ENaC neither on control diet nor in response to dietary Na(+) restriction. Furthermore, Na(+)-K(+)-ATPase expression was unaffected in MR(ko) cells of the DCT, while it was lost in MR(ko) cells of the CS. In conclusion, MR is crucial for ENaC and Na(+)-K(+)-ATPase regulation in the CS, but is dispensable for NCC and Na(+)-K(+)-ATPase regulation in the DCT.

East Spar development: NCC buoy--The vertical submarine

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

Boyle, E.C.

1998-02-01

The remote East Spar gas/condensate field has been developed using a subsea production system operated by an unmanned navigation, communication, and control (NCC) buoy. The use of this type of system allows control of the field from any convenient location, with the command-response time and the cost of the facility almost completely independent of the distance to the shore or host facility. Successes during the project (such as using model tests to prove the concept and using a tension-leg mooring system to reduce the motion response of the buoy) are discussed and compared to failures, like the weight and sizemore » growth of the structure, caused as the design requirements were finalized and external factors changed. The operation and layout of this facility is summarized, showing why it was described as a vertical submarine. Conclusions are drawn about the use of an NCC buoy to develop this field, showing that the main objectives have been achieved. The limited operating experience to date is also considered in the review of the design objectives. The paper concludes with the possibilities for the future of this type of concept.« less

Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill.

PubMed

Breves, Jason P; Serizier, Sandy B; Goffin, Vincent; McCormick, Stephen D; Karlstrom, Rolf O

2013-04-30

Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na(+)/Cl(-) cotransporter (ncc; slc12a10.2), Na(+)/H(+) exchanger (nhe3b; slc9a3.2), and epithelial Ca(2+) channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl(-) uptake in zebrafish for the first time. Copyright © 2013. Published by Elsevier Ireland Ltd.

Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis.

PubMed

Hunter, Robert W; Craigie, Eilidh; Homer, Natalie Z M; Mullins, John J; Bailey, Matthew A

2014-02-15

Na(+) reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K(+) excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K(+) balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na(+) channel (ENaC) downstream. This effect might be mediated by changes in distal Na(+) delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na(+) flux through ENaC, with a concomitant increase in renal K(+) excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K(+) excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na(+) reabsorption was not normally limited by Na(+) delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na(+) restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na(+) reabsorption through ENaC solely by increasing distal Na(+) delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments.

A qualitative examination of the effects of international counter-drug interdictions.

PubMed

Toth, Alexander G; Mitchell, Ojmarrh

2018-05-01

The purpose of this study is to utilize unique qualitative data to determine the effects of sporadic international drug interdictions on drug trafficking, and to assess whether the responses of drug traffickers align with rational choice theory. Qualitative data obtained from 23 high-level United States Drug Enforcement Administration (DEA) informants, who are embedded in international drug trafficking groups, are examined to identify common responses to drug interdiction operations. The findings indicate that sporadic counter-drug interdictions do not a have permanent deterrent effect on transnational drug smuggling operations. However, these types of law enforcement operations produce temporary alterations in drug trafficking, as traffickers adopted a variety of methods to thwart the efforts of law enforcement-often by relying on information acquired from corrupt local law enforcement. The results also indicate that while interdiction operations displaced trafficking activities (temporally, spatially, and methodological), there is little evidence that drug traffickers responded to such operations by moving into new areas (i.e., malign spatial displacement). Sporadic international drug interdiction programs do little to deter drug trafficking organizations (DTOs) from engaging in their illicit trade. Instead, DTOs adjust in a calculating manner to these operations to ensure that their illegal products reach consumer marketplaces, which is congruent with the rational choice theoretical perspective. Copyright © 2018 Elsevier B.V. All rights reserved.

Pituitary control of branchial NCC, NKCC and Na(+), K (+)-ATPase α-subunit gene expression in Nile tilapia, Oreochromis niloticus.

PubMed

Breves, Jason P; Seale, Andre P; Moorman, Benjamin P; Lerner, Darren T; Moriyama, Shunsuke; Hopkins, Kevin D; Grau, E Gordon

2014-05-01

This study investigated endocrine control of branchial ionoregulatory function in Nile tilapia (Oreochromis niloticus) by prolactin (Prl188 and Prl177), growth hormone (Gh) and cortisol. Branchial expression of Na(+)/Cl(-) cotransporter (ncc) and Na(+)/K(+)/2Cl(-) cotransporter (nkcc) genes were employed as specific markers for freshwater- and seawater-type ionocytes, respectively. We further investigated whether Prl, Gh and cortisol direct expression of two Na(+), K(+)-ATPase (nka)-α1 subunit genes, denoted nka-α1a and nka-α1b. Tilapia transferred to fresh water following hypophysectomy failed to adequately activate gill ncc expression; ncc expression was subsequently restored by Prl replacement. Prl188 and Prl177 stimulated ncc expression in cultured gill filaments in a concentration-related manner, suggesting that ncc is regulated by Prl in a gill-autonomous fashion. Tilapia transferred to brackish water (23 ‰) following hypophysectomy exhibited a reduced capacity to up-regulate nka-α1b expression. However, Gh and cortisol failed to affect nka-α1b expression in vivo. Similarly, we found no clear effects of Gh or cortisol on nkcc expression both in vivo and in vitro. When considered with patterns previously described in euryhaline Mozambique tilapia (O. mossambicus), the current study suggests that ncc is a conserved target of Prl in tilapiine cichlids. In addition, we revealed contrasting dependencies upon the pituitary to direct nka-α1b expression in hyperosmotic environments between Nile and Mozambique tilapia.

Improved engine performance via use of nickel ceramic composite coatings (NCC coat)

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

Funatani, K.; Kurosawa, K.; Fabiyi, P.A.

1994-09-01

In seeking to produce lightweight aluminum block based engines, a variety of metallurgical and surface modification techniques for cylinder bores, pistons and piston rings are available. This paper discusses these various alternative methods while placing particular emphasis on electroplated nickel ceramic composite coatings (NCC). NCC Coating properties are characterized by high hardness, high corrosion resistance, high temperature wear and scuff resistance and low frictional coefficients. The application of NCC Coatings in 2-stroke motorcycle and diesel engines has resulted in benefits in the following areas: elimination of cast iron liners; reduced cylinder wall temperature, engine weight and increased power; lowering ofmore » oil consumption; improved fuel economy; reduction in emissions; improved scuff and wear resistance on cylinder bores, pistons and piston rings; friction reduction; combating of piston ring groove microwelding and pound out; thermal barrier protection on diesel piston domes; reduction in carbon deposition on piston domes; reduced noise from piston slap; and ability to operate in corrosive environments. The sum of the above stated benefits holds much potential for contributing towards greater flexibility in materials selection for the design of lightweight, fuel efficient vehicles based upon the use of aluminum engines. 13 refs., 13 figs.« less

Lactococcus lactis NCC 2287 Alleviates Food Allergic Manifestations in Sensitized Mice by Reducing IL-13 Expression Specifically in the Ileum

PubMed Central

Zuercher, Adrian W.; Weiss, Marietta; Holvoet, Sébastien; Moser, Mireille; Moussu, Hélène; van Overtvelt, Laurence; Horiot, Stéphane; Moingeon, Philippe; Nutten, Sophie; Prioult, Guénolée; Singh, Anurag; Mercenier, Annick

2012-01-01

Objective. Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. Methods. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA) plus cholera toxin (CT) by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase) or after sensitization (management phase). Results. Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1) and CCL17 (TARC) in the ileum. No effect was observed in the jejunum. Conclusion/Significance. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms. PMID:21961022

Lactococcus lactis NCC 2287 alleviates food allergic manifestations in sensitized mice by reducing IL-13 expression specifically in the ileum.

PubMed

Zuercher, Adrian W; Weiss, Marietta; Holvoet, Sébastien; Moser, Mireille; Moussu, Hélène; van Overtvelt, Laurence; Horiot, Stéphane; Moingeon, Philippe; Nutten, Sophie; Prioult, Guénolée; Singh, Anurag; Mercenier, Annick

2012-01-01

Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA) plus cholera toxin (CT) by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase) or after sensitization (management phase). Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1) and CCL17 (TARC) in the ileum. No effect was observed in the jejunum. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms.

Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency.

PubMed

Chee, K N; Vorontsova, I; Lim, J C; Kistler, J; Donaldson, P J

2010-05-04

To characterize the expression patterns of the Na+-K+-Cl(-) cotransporter (NKCC) 1 and NKCC2, and the Na+-Cl(-) cotransporter (NCC) in the rat lens and to determine if they play a role in regulating lens volume and transparency. RT-PCR was performed on RNA extracted from fiber cells to identify sodium dependent cotransporters expressed in the rat lens. Western blotting and immunohistochemistry, using NKCC1, NKCC2, and NCC antibodies, were used to verify expression at the protein level and to localize transporter expression. Organ cultured rat lenses were incubated in Artificial Aqueous Humor (AAH) of varying osmolarities or isotonic AAH that contained either the NKCC specific inhibitor bumetanide, or the NCC specific inhibitor thiazide for up to 18 h. Lens transparency was monitored with dark field microscopy, while tissue morphology and antibody labeling patterns were recorded using a confocal microscope. Molecular experiments showed that NKCC1 and NCC were expressed in the lens at both the transcript and protein levels, but NKCC2 was not. Immunohistochemistry showed that both NKCC1 and NCC were expressed in the lens cortex, but NCC expression was also found in the lens core. In the lens cortex the majority of labeling for both transporters was cytoplasmic in nature, while in the lens core, NCC labeling was associated with the membrane. Exposure of lenses to either hypotonic or hypertonic AAH had no noticeable effects on the predominantly cytoplasmic location of either transporter in the lens cortex. Incubation of lenses in isotonic AAH plus the NKCC inhibitor bumetanide for 18 h induced a cortical opacity that was initiated by a shrinkage of peripheral fiber cells and the dilation of the extracellular space between fiber cells in a deeper zone located some approximately 150 microm in from the capsule. In contrast, lenses incubated in isotonic AAH and the NCC inhibitor thiazide maintained both their transparency and their regular fiber cell morphology. We have

Validation of the NCC Code for Staged Transverse Injection and Computations for a RBCC Combustor

NASA Technical Reports Server (NTRS)

Ajmani, Kumud; Liu, Nan-Suey

2005-01-01

The NCC code was validated for a case involving staged transverse injection into Mach 2 flow behind a rearward facing step. Comparisons with experimental data and with solutions from the FPVortex code was then used to perform computations to study fuel-air mixing for the combustor of a candidate rocket based combined cycle engine geometry. Comparisons with a one-dimensional analysis and a three-dimensional code (VULCAN) were performed to assess the qualitative and quantitative performance of the NCC solver.

Fabrication of (PPC/NCC)/PVA composites with inner-outer double constrained structure and improved glass transition temperature.

PubMed

Cui, Shaoying; Li, Li; Wang, Qi

2018-07-01

Improving glass transition temperature (T g ) and mechanical property of the environment-friendly poly(propylene carbonate) via intermacromolecular complexation through hydrogen bonding is attractive and of great importance. A novel and effective strategy to prepare (polypropylene carbonate/nanocrystalline cellulose)/polyvinyl alcohol ((PPC/NCC)/PVA) composites with inner-outer double constrained structure was reported in this work. Outside the PPC phase, PVA, as a strong skeleton at microscale, could constrain the movement of PPC molecular chains by forming hydrogen bonding with PPC at the interface of PPC and PVA phases; inside the PPC phase, the rod-like NCC could restrain the flexible molecular chains of PPC at nanoscale by forming multi-hydrogen bonding with PPC. Under the synergistic effect of this novel inner-outer double constrained structure, T g , mechanical properties and thermal stability of (PPC/NCC)/PVA composite were significantly increased, e.g. T g of the composite researched the maximum value of 49.6 °C, respectively 15.6 °C, 5.7 °C and 4.2 °C higher than that of PPC, PPC/NCC and PPC/PVA composite. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Goddard Earth Sciences and Technology Center (GEST Center)

NASA Technical Reports Server (NTRS)

2002-01-01

The following is a technical report of the progress made under Cooperative Agreement NCC5494, the Goddard Earth Sciences and Technology Center (GEST). The period covered by this report is October 1, 2001 through December 31, 2001. GEST is a consortium of scientists and engineers, led by the University of Maryland, Baltimore County (UMBC), to conduct scientific research in Earth and information sciences and related technologies in collaboration with the NASA Goddard Space Flight Center (GSFC). GEST was established through a cooperative agreement signed May 11, 2000, following a competitive procurement process initiated by GSFC.

Adenylyl cyclase 6 enhances NKCC2 expression and mediates vasopressin-induced phosphorylation of NKCC2 and NCC.

PubMed

Rieg, Timo; Tang, Tong; Uchida, Shinichi; Hammond, H Kirk; Fenton, Robert A; Vallon, Volker

2013-01-01

Arginine vasopressin (AVP) affects kidney function via vasopressin V2 receptors that are linked to activation of adenylyl cyclase (AC) and an increase in cyclic adenosine monophosphate formation. AVP/cyclic adenosine monophosphate enhance the phosphorylation of the Na-K-2Cl cotransporter (NKCC2) at serine residue 126 (pS126 NKCC2) and of the Na-Cl cotransporter (NCC) at threonine 58 (pT58 NCC). The isoform(s) of AC involved in these responses, however, were unknown. Phosphorylation of S126 NKCC2 and T58 NCC, induced by the V2 receptor agonist (1-desamino-8-D-arginine vasopressin) in wild-type mice, is lacking in knockout mice for AC isoform 6 (AC6). With regard to NKCC2 phosphorylation, the stimulatory effect of 1-desamino-8-D-AVP and the defect in AC6(-/-) mice seem to be restricted to the medullary portion of the thick ascending limb. AC6 is also a stimulator of total renal NKCC2 protein abundance in medullary and cortical thick ascending limb. Consequently, mice lacking AC6 have lower NKCC2 expression and a mild Bartter syndrome-like phenotype, including lower plasma concentrations of K+ and H+ and compensatory upregulation of NCC. Increased AC6-independent phosphorylation of NKCC2 at S126 might help to stabilize NKCC2 activity in the absence of AC6. Renal AC6 determines total NKCC2 expression and mediates vasopressin-induced NKCC2/NCC phosphorylation. These regulatory mechanisms, which are defective in AC knockout mice, are likely responsible for the observed mild Bartter syndrome. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Regulation of blood pressure and renal function by NCC and ENaC: lessons from genetically engineered mice.

PubMed

Verouti, Sophia N; Boscardin, Emilie; Hummler, Edith; Frateschi, Simona

2015-04-01

The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted tubule (DCT) of the nephron, while ENaC reabsorbs the filtered Na(+) in the late DCT and in the cortical collecting ducts (CCD) providing the final renal adjustment to Na(+) balance. Here, we aim to highlight the recent advances made using transgenic mouse models towards the understanding of the regulation of NCC and ENaC function relevant to the control of sodium balance and blood pressure. We thus like to pave the way for common mechanisms regulating these two sodium-transporting proteins and their potential implication in structural remodeling of the nephron segments and Na(+) and Cl(-) reabsorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nature Conservancy of Canada (NCC)--Manitoba Region's Environmental Education Program

ERIC Educational Resources Information Center

Shaluk, Cathy

2007-01-01

The Nature Conservancy of Canada (NCC) is excited and proud to offer its first ever in-class education programs on the Tall Grass Prairie Ecosystem. These curriculum-based programs are offered to students from Kindergarten through to Grade 12. This experience gives many students who may never have the opportunity to visit a real live prairie to…

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

PubMed

Liu, Yunmeng; Rafferty, Tonya M; Rhee, Sung W; Webber, Jessica S; Song, Li; Ko, Benjamin; Hoover, Robert S; He, Beixiang; Mu, Shengyu

2017-01-09

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8 + T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8 + T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8 + T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K + channel Kir4.1, and stimulation of the Cl - channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

PubMed Central

Liu, Yunmeng; Rafferty, Tonya M.; Rhee, Sung W.; Webber, Jessica S.; Song, Li; Ko, Benjamin; Hoover, Robert S.; He, Beixiang; Mu, Shengyu

2017-01-01

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl− channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension. PMID:28067240

Vibration extraction based on fast NCC algorithm and high-speed camera.

PubMed

Lei, Xiujun; Jin, Yi; Guo, Jie; Zhu, Chang'an

2015-09-20

In this study, a high-speed camera system is developed to complete the vibration measurement in real time and to overcome the mass introduced by conventional contact measurements. The proposed system consists of a notebook computer and a high-speed camera which can capture the images as many as 1000 frames per second. In order to process the captured images in the computer, the normalized cross-correlation (NCC) template tracking algorithm with subpixel accuracy is introduced. Additionally, a modified local search algorithm based on the NCC is proposed to reduce the computation time and to increase efficiency significantly. The modified algorithm can rapidly accomplish one displacement extraction 10 times faster than the traditional template matching without installing any target panel onto the structures. Two experiments were carried out under laboratory and outdoor conditions to validate the accuracy and efficiency of the system performance in practice. The results demonstrated the high accuracy and efficiency of the camera system in extracting vibrating signals.

Thiazide-sensitive Na+ -Cl- cotransporter (NCC) gene inactivation results in increased duodenal Ca2+ absorption, enhanced osteoblast differentiation and elevated bone mineral density.

PubMed

Hsu, Yu-Juei; Yang, Sung-Sen; Cheng, Chih-Jen; Liu, Shu-Ting; Huang, Shih-Ming; Chau, Tom; Chu, Pauling; Salter, Donald M; Lee, Herng-Sheng; Lin, Shih-Hua

2015-01-01

Inactivation of the thiazide-sensitive sodium chloride cotransporter (NCC) due to genetic mutations in Gitelman's syndrome (GS) or pharmacological inhibition with thiazide diuretics causes hypocalciuria and increased bone mineral density (BMD) with unclear extrarenal calcium (Ca(2+) ) regulation. We investigated intestinal Ca(2+) absorption and bone Ca(2+) metabolism in nonsense Ncc Ser707X (S707X) homozygous knockin mice (Ncc(S707X/S707X) mice). Compared to wild-type and heterozygous knockin littermates, Ncc(S707X/S707X) mice had increased intestinal absorption of (45) Ca(2+) and expression of the active Ca(2+) transport machinery (transient receptor potential vanilloid 6, calbindin-D9K , and plasma membrane Ca(2+) ATPase isoform 1b). Ncc(S707X/S707X) mice had also significantly increased Ca(2+) content accompanied by greater mineral apposition rate (MAR) in their femurs and higher trabecular bone volume, cortical bone thickness, and BMD determined by μCT. Their osteoblast differentiation markers, such as bone alkaline phosphatase, procollagen I, osteocalcin, and osterix, were also significantly increased while osteoclast activity was unaffected. Analysis of marrow-derived bone cells, either treated with thiazide or directly cultured from Ncc S707X knockin mice, showed that the differentiation of osteoblasts was associated with increased phosphorylation of mechanical stress-induced focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). In conclusion, NCC inhibition stimulates duodenal Ca(2+) absorption as well as osteoblast differentiation and bone Ca(2+) storage, possibly through a FAK/ERK dependent mechanism. © 2014 American Society for Bone and Mineral Research.

Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC.

PubMed

Argaiz, Eduardo R; Chavez-Canales, Maria; Ostrosky-Frid, Mauricio; Rodriguez-Gama, Alejandro; Vázquez, Norma; Gonzalez-Rodriguez, Xochiquetzal; Garcia-Valdés, Jesus; Hadchouel, Juliette; Ellison, David H; Gamba, Gerardo

2018-05-30

Familial Hyperkalemic Hypertension (FHHt) can be mainly attributed to increased activity of the renal Na+:Cl- cotransporter (NCC), which is caused by altered expression and regulation of the WNK1 and WNK4 kinases. The WNK1 gene gives rise to a kidney-specific isoform that lacks the kinase domain (KS-WNK1), the expression of which occurs primarily in the distal convoluted tubule. The role played by KS-WNK1 in the modulation of the WNK/SPAK/NCC pathway remains elusive. In the present study, we assessed the effect of human KS-WNK1 on NCC activity and on the WNK4-SPAK pathway. Microinjection of oocytes with human KS-WNK1 cRNA induces remarkable activation and phosphorylation of SPAK and NCC. The effect of KS-WNK1 was abrogated by eliminating a WNK-WNK interacting domain and by a specific WNK inhibitor, WNK463, indicating that the activation of SPAK/NCC by KS-WNK1 is due to interaction with another WNK kinase. Under control conditions in oocytes, the activating serine 335 of the WNK4 T loop is not phosphorylated. In contrast, this serine becomes phosphorylated when the intracellular chloride concentration ([Cl-]i) is reduced or when KS-WNK1 is co-expressed with WNK4. KS-WNK1-mediated activation of WNK4 is not due to a decrease of the [Cl-]i. Coimmunoprecipitation analysis revealed that KS-WNK1 and WNK4 interact with each other and that WNK4 becomes autophosphorylated at serine 335 when it is associated with KS-WNK1. Together, these observations suggest that WNK4 becomes active in the presence of KS-WNK1, despite a constant [Cl-]i.

The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation.

PubMed

Patel-Chamberlin, Mina; Varasteh Kia, Mujan; Xu, Jie; Barone, Sharon; Zahedi, Kamyar; Soleimani, Manoocher

2016-01-01

The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice. WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis. Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt excretion in both NCC KO and WT

Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models.

PubMed

Liu, Zhen; Xie, Jian; Wu, Tao; Truong, Thao; Auchus, Richard J; Huang, Chou-Long

2011-03-01

WNK1 (with-no-lysine[K]-1) is a protein kinase of which mutations cause a familial hypertension and hyperkalemia syndrome known as pseudohypoaldosteronism type 2 (PHA2). Kidney-specific (KS) WNK1 is an alternatively spliced form of WNK1 kinase missing most of the kinase domain. KS-WNK1 downregulates the Na(+)-Cl(-) cotransporter NCC by antagonizing the effect of full-length WNK1 when expressed in Xenopus oocytes. The physiological role of KS-WNK1 in the regulation of NCC and potentially other Na(+) transporters in vivo is unknown. Here, we report that mice overexpressing KS-WNK1 in the kidney exhibited renal Na(+) wasting, elevated plasma levels of angiotensin II and aldosterone yet lower blood pressure relative to wild-type littermates. Immunofluorescent staining revealed reduced surface expression of total and phosphorylated NCC and the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in the distal convoluted tubule and the thick ascending limb of Henle's loop, respectively. Conversely, mice with targeted deletion of exon 4A (the first exon for KS-WNK1) exhibited Na(+) retention, elevated blood pressure on a high-Na(+) diet and increased surface expression of total and phosphorylated NCC and NKCC2 in respective nephron segments. Thus, KS-WNK1 is a negative regulator of NCC and NKCC2 in vivo and plays an important role in the control of Na(+) homeostasis and blood pressure. These results have important implications to the pathogenesis of PHA2 with WNK1 mutations.

AT2R (Angiotensin II Type 2 Receptor)-Mediated Regulation of NCC (Na-Cl Cotransporter) and Renal K Excretion Depends on the K Channel, Kir4.1.

PubMed

Wu, Peng; Gao, Zhong-Xiuzi; Duan, Xin-Peng; Su, Xiao-Tong; Wang, Ming-Xiao; Lin, Dao-Hong; Gu, Ruimin; Wang, Wen-Hui

2018-04-01

AT2R (AngII [angiotensin II] type 2 receptor) is expressed in the distal nephrons. The aim of the present study is to examine whether AT2R regulates NCC (Na-Cl cotransporter) and Kir4.1 of the distal convoluted tubule. AngII inhibited the basolateral 40 pS K channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule treated with losartan but not with PD123319. AT2R agonist also inhibits the K channel, indicating that AT2R was involved in tonic regulation of Kir4.1. The infusion of PD123319 stimulated the expression of tNCC (total NCC) and pNCC (phosphorylated NCC; Thr 53 ) by a time-dependent way with the peak at 4 days. PD123319 treatment (4 days) stimulated the basolateral 40 pS K channel activity, augmented the basolateral K conductance, and increased the negativity of distal convoluted tubule membrane. The stimulation of Kir4.1 was essential for PD123319-induced increase in NCC because inhibiting AT2R increased the expression of tNCC and pNCC only in wild-type but not in the kidney-specific Kir4.1 knockout mice. Renal clearance study showed that thiazide-induced natriuretic effect was larger in PD123319-treated mice for 4 days than untreated mice. However, this effect was absent in kidney-specific Kir4.1 knockout mice which were also Na wasting under basal conditions. Finally, application of AT2R antagonist decreased the renal ability of K excretion and caused hyperkalemia in wild-type but not in kidney-specific Kir4.1 knockout mice. We conclude that AT2R-dependent regulation of NCC requires Kir4.1 in the distal convoluted tubule and that AT2R plays a role in stimulating K excretion by inhibiting Kir4.1 and NCC. © 2018 American Heart Association, Inc.

The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation

PubMed Central

Patel-Chamberlin, Mina; Varasteh Kia, Mujan; Xu, Jie; Barone, Sharon; Zahedi, Kamyar; Soleimani, Manoocher

2016-01-01

Background The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice. Methods WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis. Results Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt

TECHNICAL DESIGN REPORT FOR A NOSECONE CALORIMETER (NCC) FOR THE PHENIX EXPERIMENT.

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

PHENIX EXPERIMENT; OBRIEN,E.; BOOSE, S.

2007-08-01

A remarkable result has emerged from the first several years of data taking at RHIC--the high temperature and density phase of QCD matter created in heavy ion collisions at RHIC is best described as a near perfect fluid--the strongly interacting Quark-Gluon-Plasma (sQGP). This state is characterized by a small viscosity to entropy ratio, and a high density of color charges which induces huge energy losses of partons transversing the medium. The task for the future is to understand the characteristics of the sQGP, and perhaps more importantly--to gain some insight into how and why such a medium is created. Themore » PHENIX detector has been one of the primary experimental tools at RHIC; in particular the electromagnetic calorimeter has been a critical component of many of the measurements leading to this discovery. The coverage of the present PHENIX electromagnetic calorimeter is rather limited, covering half the azimuth and -0.35< {eta} <0.35 Further progress requires larger coverage of electromagnetic calorimetry, both to increase the rate for low cross section phenomena, and to cover a broader range of pseudorapidity to study the rapidity dependence of the medium. A pair of Nosecone Calorimeters (NCC) has been designed covering both positive and negative rapidity regions 1< |{eta}| <3 of the PHENIX detector. The NCC will make it possible to perform tomographic studies of the jet energy dependence of energy loss and medium response, by using direct photons as trigger particles over a large rapidity range. The technique of correlating trigger hadrons with low momentum hadrons has been powerfully exploited at RHIC to study the evolution of back to back jets [1, 2] and hence the response of the medium. The NCC will make it possible to do such studies using direct photons as the trigger particles. The direct photon in such ''photon-jet'' events tags the transverse momentum of outgoing parton which then fragments into lower energy particles. Together with the Forward

Oral administration of Lactobacillus paracasei NCC 2461 for the modulation of grass pollen allergic rhinitis: a randomized, placebo-controlled study during the pollen season.

PubMed

Nembrini, Chiara; Singh, Anurag; De Castro, Carlos Antonio; Mercenier, Annick; Nutten, Sophie

2015-01-01

The efficacy of Lactobacillus paracasei NCC 2461 in modulating allergic rhinitis was previously evaluated in two exploratory clinical studies. Oral administration with NCC 2461 reduced specific subjective symptoms following nasal provocation tests with controlled grass pollen allergen concentrations. Our aim was to confirm the anti-allergic effect of NCC 2461 in grass pollen allergic subjects exposed to natural doses of allergens during the pollen season. A double-blind, randomized, placebo-controlled, parallel study was conducted with 131 grass pollen allergic subjects from May to July 2012 in concomitance with the pollen season in Berlin. NCC 2461 or placebo was administered daily for an 8-week period to adult subjects with clinical history of allergic rhinitis to grass pollen, positive skin prick test and IgE to grass pollen. During the 8 weeks, symptoms and quality of life questionnaires were filled out, and plasma was collected for IgE analysis at screening and at the end of the intervention. All subjects were included within a 5-day interval, ensuring exposure to similar air pollen counts for each individual during the trial period. The results obtained show that symptoms increased with pollen loads, confirming a natural exposure to the allergen and presence of pollen-induced allergic rhinitis in the subjects. However, no significant differences were observed in allergic rhinitis symptoms scores, quality of life, or specific IgE levels between subjects receiving NCC 2461 as compared to placebo administration. In contrast to previous findings, oral administration of NCC 2461 did not show a beneficial effect on allergic rhinitis in a field trial. The influence of study design, allergen exposure and intervention window on the efficacy of NCC 2461 in modulating respiratory allergy should be further evaluated.

WNK3-SPAK interaction is required for the modulation of NCC and other members of the SLC12 family.

PubMed

Pacheco-Alvarez, Diana; Vázquez, Norma; Castañeda-Bueno, María; de-Los-Heros, Paola; Cortes-González, César; Moreno, Erika; Meade, Patricia; Bobadilla, Norma A; Gamba, Gerardo

2012-01-01

The serine/threonine with no lysine kinase 3 (WNK3) modulates the activity of the electroneutral cation-coupled chloride cotransporters (CCC) to promote Cl(-) influx and prevent Cl(-) efflux, thus fitting the profile for a putative "Cl(-)-sensing kinase". The Ste20-type kinases, SPAK/OSR1, become phosphorylated in response to reduction in intracellular chloride concentration and regulate the activity of NKCC1. Several studies have now shown that WNKs function upstream of SPAK/OSR1. This study was designed to analyze the role of WNK3-SPAK interaction in the regulation of CCCs with particular emphasis on NCC. In this study we used the functional expression system of Xenopus laevis oocytes to show that different SPAK binding sites in WNK3 ((241, 872, 1336)RFxV) are required for the kinase to have effects on CCCs. WNK3-F1337A no longer activated NKCC2, but the effects on NCC, NKCC1, and KCC4 were preserved. In contrast, the effects of WNK3 on these cotransporters were prevented in WNK3-F242A. The elimination of F873 had no consequence on WNK3 effects. WNK3 promoted NCC phosphorylation at threonine 58, even in the absence of the unique SPAK binding site of NCC, but this effect was abolished in the mutant WNK3-F242A. Thus, our data support the hypothesis that the effects of WNK3 upon NCC and other CCCs require the interaction and activation of the SPAK kinase. The effect is dependent on one of the three binding sites for SPAK that are present in WNK3, but not on the SPAK binding sites on the CCCs, which suggests that WNK3 is capable of binding both SPAK and CCCs to promote their phosphorylation. Copyright © 2012 S. Karger AG, Basel.

Simulation of HLNC and NCC measurements

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

Lu, Ming-Shih; Teichmann, T.; De Ridder, P.

1994-03-01

This report discusses an automatic method of simulating the results of High Level Neutron Coincidence Counting (HLNC) and Neutron Collar Coincidence Counting (NCC) measurements to facilitate the safeguards` inspectors understanding and use of these instruments under realistic conditions. This would otherwise be expensive, and time-consuming, except at sites designed to handle radioactive materials, and having the necessary variety of fuel elements and other samples. This simulation must thus include the behavior of the instruments for variably constituted and composed fuel elements (including poison rods and Gd loading), and must display the changes in the count rates as a function ofmore » these characteristics, as well as of various instrumental parameters. Such a simulation is an efficient way of accomplishing the required familiarization and training of the inspectors by providing a realistic reproduction of the results of such measurements.« less

Effect of filler loading of characteristic natural rubber latex (NRL) film filled with nanocrystal cellulose (NCC) and dipersion agent polyvinylpyrrolidone (PVP)

NASA Astrophysics Data System (ADS)

Harahap, Hamidah; Lubis, Yuni Aldriani; Taslim, Iriany, Nasution, Halimatuddahliana; Agustini, Hamda Eka

2018-04-01

A study has been conducted on the effect of filler loading on NRL films filled with NCC from corn cob waste. This study reviews on the filler loading of NRL film characteristics. The process begins with the production of NCC filler and then proceed with the production NRL film which is processed by coagulant dipping method. NRL is filled with NCC and PVP as dispersion agent of 2, 4, 3, 8 grams (filler loading) and 1% PVP by weight. The production of NRL film started with pre-vulcanization process at 70 °C and followed by vulcanization process at 110 °C for 20 minutes. The results showed that higher filler loading improved the higher crosslink density and mechanical properties of NRL film.

Establishment and characterization of the NCC-SS1-C1 synovial sarcoma cell line.

PubMed

Kito, Fusako; Oyama, Rieko; Takai, Yoko; Sakumoto, Marimu; Shiozawa, Kumiko; Qiao, Zhiwei; Uehara, Takenori; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

2018-04-01

Synovial sarcoma is an aggressive mesenchymal malignancy characterized by unique gene fusions. Tissue culture cells are essential tools for further understanding tumorigenesis and anti-cancer drug development; however, only a limited number of well-characterized synovial sarcoma cell lines exist. Thus, the objective of this study was to establish a patient-derived synovial sarcoma cell line. We established a synovial sarcoma cell line from tumor tissue isolated from a 72-year-old female patient. Prepared cells were analyzed for the presence of gene fusions by fluorescence in situ hybridization, RT-PCR, and karyotyping. In addition, the resulting cell line was characterized by viability, short tandem repeat, colony and spheroid formation, and invasion analyses. Differences in gene enrichment between the primary tumor and cell line were examined by mass spectrometric protein expression profiling and KEGG pathway analysis. Our analyses revealed that the primary tumor and NCC-SS1-C1 cell line harbored the SS18-SSX1 fusion gene typical of synovial sarcoma and similar proteomics profiles. In vitro analyses also confirmed that the established cell line harbored invasive, colony-forming, and spheroid-forming potentials. Moreover, drug screening with chemotherapeutic agents and tyrosine kinase inhibitors revealed that doxorubicin, a subset of tyrosine kinase inhibitors, and several molecular targeting drugs markedly decreased NCC-SS1-C1 cell viability. Results from the present study support that the NCC-SS1-C1 cell line will be an effective tool for sarcoma research.

Establishment and proteomic characterization of a novel cell line, NCC-UPS2-C1, derived from a patient with undifferentiated pleomorphic sarcoma.

PubMed

Oyama, Rieko; Kito, Fusako; Sakumoto, Marimu; Shiozawa, Kumiko; Toki, Shunichi; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

2018-03-01

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal malignancy requiring novel therapeutic approaches to improve clinical outcome. Patient-derived cancer cell lines are an essential tool for investigating molecular mechanisms underlying cancer initiation and development; however, there is a lack of patient-derived cell lines of UPS available for research. The objective of this study was to develop a patient-derived cell model of UPS. A cell line designated NCC-UPS2-C1 was established from the primary tumor tissue of an 84-yr-old female patient with UPS. The short tandem repeat pattern of NCC-UPS2-C1 cells was identical to that of the original tumor and distinct from that of any other cell lines deposited in public cell banks. NCC-UPS2-C1 cells were maintained as a monolayer culture for over 80 passages during 30 mo and exhibited spindle-like morphology, continuous growth, and ability for spheroid formation and invasion. Proteomic profiling using mass spectrometry and functional treemap analysis revealed that the original tumor and the derived NCC-UPS2-C1 cells had similar but distinct protein expression patterns. Our results indicate that a novel UPS cell line was successfully established and could be used to study UPS development and effects of anti-cancer drugs. However, the revealed difference between proteomes of the original tumor and NCC-UPS2-C1 cells should be further investigated to determine the appropriate applications of this cell line in UPS research.

Addition by subtraction in coupled-cluster theory: a reconsideration of the CC and CI interface and the nCC hierarchy.

PubMed

Bartlett, Rodney J; Musiał, Monika

2006-11-28

The nCC hierarchy of coupled-cluster approximations, where n guarantees exactness for n electrons and all products of n electrons are derived and applied to several illustrative problems. The condition of exactness for n=2 defines nCCSD=2CC, with nCCSDT=3CC and nCCSDTQ=4CC being exact for three and four electrons. To achieve this, the minimum number of diagrams is evaluated, which is less than in the corresponding CC model. For all practical purposes, nCC is also the proper definition of a size-extensive CI. 2CC is also an orbitally invariant coupled electron pair approximation. The numerical results of nCC are close to those for the full CC variant, and in some cases are closer to the full CI reference result. As 2CC is exact for separated electron pairs, it is the natural zeroth-order approximation for the correlation problem in molecules with other effects introduced as these units start to interact. The nCC hierarchy of approximations has all the attractive features of CC including its size extensivity, orbital invariance, and orbital insensitivity, but in a conceptually appealing form suited to bond breaking, while being computationally less demanding. Excited states from the equation of motion (EOM-2CC) are also reported, which show results frequently approaching those of EOM-CCSDT.

Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel.

PubMed

Wang, Ming-Xiao; Cuevas, Catherina A; Su, Xiao-Tong; Wu, Peng; Gao, Zhong-Xiuzi; Lin, Dao-Hong; McCormick, James A; Yang, Chao-Ling; Wang, Wen-Hui; Ellison, David H

2018-04-01

Kir4.1 in the distal convoluted tubule plays a key role in sensing plasma potassium and in modulating the thiazide-sensitive sodium-chloride cotransporter (NCC). Here we tested whether dietary potassium intake modulates Kir4.1 and whether this is essential for mediating the effect of potassium diet on NCC. High potassium intake inhibited the basolateral 40 pS potassium channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule, decreased basolateral potassium conductance, and depolarized the distal convoluted tubule membrane in Kcnj10flox/flox mice, herein referred to as control mice. In contrast, low potassium intake activated Kir4.1, increased potassium currents, and hyperpolarized the distal convoluted tubule membrane. These effects of dietary potassium intake on the basolateral potassium conductance and membrane potential in the distal convoluted tubule were completely absent in inducible kidney-specific Kir4.1 knockout mice. Furthermore, high potassium intake decreased, whereas low potassium intake increased the abundance of NCC expression only in the control but not in kidney-specific Kir4.1 knockout mice. Renal clearance studies demonstrated that low potassium augmented, while high potassium diminished, hydrochlorothiazide-induced natriuresis in control mice. Disruption of Kir4.1 significantly increased basal urinary sodium excretion but it abolished the natriuretic effect of hydrochlorothiazide. Finally, hypokalemia and metabolic alkalosis in kidney-specific Kir4.1 knockout mice were exacerbated by potassium restriction and only partially corrected by a high-potassium diet. Thus, Kir4.1 plays an essential role in mediating the effect of dietary potassium intake on NCC activity and potassium homeostasis. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Transmission electron microscopy of polyhydroxybutyrate-co-valerate (PHBV)/nanocrystalline cellulose (NCC) bio-nanocomposite prepared using cryo-ultramicrotomy

NASA Astrophysics Data System (ADS)

Ismarul, N. I.; Engku, A. H. E. U.; Siti, N. K.; Tay, K. Y.

2017-12-01

Environmental issues on disposal and end-of-life for product made from synthetic petroleum-derived polymers have gained increasing attention from materials scientist to search for new materials with similar physical and mechanical properties but environmental friendly in a way that they are renewable and biodegradable as well. This work is to study the effect of nanocrystalline cellulose in improving the thermal stability of polyhydroxybutyrate-co-valerate biopolymer for high temperature processing of packaging material. 10 % w/w PHBV-NCC bio-nanocomposite feedstock pellet prepared using RONDOL minilab compounder was used as the sample for the preparation of Transmission Electron Microscopy (TEM) sample. RMC Cryo-Ultramicrotomy equipment was used to prepare the ultra-thin slice of the bio-nanocomposite pellet under liquid nitrogen at - 60 °C. Diamond knife was used to slice off about 80-100 nm ultra-thin bio-nanocomposite films and was transferred into the lacey carbon film coated grid using cooled sugar solution. A few drops of phosphotungstic acid was used as negative stain to improve the contrast during the TEM analysis. HITACHI TEM systems was used to obtain the TEM micrograph of PHBV-NCC bio-nanocomposite using 80kV accelerating voltage. A well dispersed NCC in PHBV matrix, ranging from 5 to 25 nm in width was observed.

WNK4 inhibits plasma membrane targeting of NCC through regulation of syntaxin13 SNARE formation.

PubMed

Chung, Woo Young; Park, Hyun Woo; Han, Jung Woo; Lee, Min Goo; Kim, Joo Young

2013-12-01

WNK4, a serine/threonine kinase, plays a critical role in the expression of membrane proteins in the cell surface; however, the underlying mechanism of WNK4 is not clear. Here, we demonstrate that WNK4 inhibits the fusion of plasma membrane delivering vesicle with sorting/recycling endosome through disrupting SNARE formation of syntaxin13, an endosomal t-SNARE and VAMP2, the v-SNARE in plasma membrane delivering vesicle. Their interaction and co-localization were enhanced by hyperosmotic stimulation which is known for WNK4 activation. The kinase domain of WNK4 interacts with the transmembrane domain (TM) of syntaxin13 and this interaction was abolished when the TM was replaced with that of syntaxin16. Interestingly, cell fractionation using sucrose gradients revealed that WNK4 inhibited the formation of the syntaxin13/VAMP2 SNARE complex in the endosomal compartment, but not syntaxin16/VAMP2 or syntaxin13/VAMP7. Syntaxin13 was not phosphorylated by WNK4 and WNK4KI also showed the same binding strength and similar inhibitory regulation on SNARE formation of syntaxin13. Physiological relevance of this mechanism was proved with the expression of NCC (Na(+) C1(-) co-transporter) in the cell surface. The inhibiting activity of WNK4 on surface expression of NCC was abolished by syntaxin13 siRNA transfection. These results suggest that WNK4 attenuates PM targeting of NCC proteins through regulation of syntaxin13 SNARE complex formation with VAMP2 in recycling and sorting endosome. © 2013.

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment.

PubMed

Ledeganck, Kristien J; Boulet, Gaëlle A; Horvath, Caroline A; Vinckx, Marleen; Bogers, Johannes J; Van Den Bossche, Rita; Verpooten, Gert A; De Winter, Benedicte Y

2011-09-01

Renal magnesium (Mg(2+)) and sodium (Na(+)) loss are well-known side effects of cyclosporine (CsA) treatment in humans, but the underlying mechanisms still remain unclear. Recently, it was shown that epidermal growth factor (EGF) stimulates Mg(2+) reabsorption in the distal convoluted tubule (DCT) via TRPM6 (Thébault S, Alexander RT, Tiel Groenestege WM, Hoenderop JG, Bindels RJ. J Am Soc Nephrol 20: 78-85, 2009). In the DCT, the final adjustment of renal sodium excretion is regulated by the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which is activated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to gain more insight into the molecular mechanisms of CsA-induced hypomagnesemia and hyponatremia. Therefore, the renal expression of TRPM6, TRPM7, EGF, EGF receptor, claudin-16, claudin-19, and the NCC, and the effect of the RAAS on NCC expression, were analyzed in vivo in a rat model of CsA nephrotoxicity. Also, the effect of EGF administration on these parameters was studied. CsA significantly decreased the renal expression of TRPM6, TRPM7, NCC, and EGF, but not that of claudin-16 and claudin-19. Serum aldosterone was significantly lower in CsA-treated rats. In control rats treated with EGF, an increased renal expression of TRPM6 together with a decreased fractional excretion of Mg(2+) (FE Mg(2+)) was demonstrated. EGF did not show this beneficial effect on TRPM6 and FE Mg(2+) in CsA-treated rats. These data suggest that CsA treatment affects Mg(2+) homeostasis via the downregulation of TRPM6 in the DCT. Furthermore, CsA downregulates the NCC in the DCT, associated with an inactivation of the RAAS, resulting in renal sodium loss.

ENaC activity in collecting ducts modulates NCC in cirrhotic mice.

PubMed

Mordasini, David; Loffing-Cueni, Dominique; Loffing, Johannes; Beatrice, Rohrbach; Maillard, Marc P; Hummler, Edith; Burnier, Michel; Escher, Geneviève; Vogt, Bruno

2015-12-01

Cirrhosis is a frequent and severe disease, complicated by renal sodium retention leading to ascites and oedema. A better understanding of the complex mechanisms responsible for renal sodium handling could improve clinical management of sodium retention. Our aim was to determine the importance of the amiloride-sensitive epithelial sodium channel (ENaC) in collecting ducts in compensate and decompensate cirrhosis. Bile duct ligation was performed in control mice (CTL) and collecting duct-specific αENaC knockout (KO) mice, and ascites development, aldosterone plasma concentration, urinary sodium/potassium ratio and sodium transporter expression were compared. Disruption of ENaC in collecting ducts (CDs) did not alter ascites development, urinary sodium/potassium ratio, plasma aldosterone concentrations or Na,K-ATPase abundance in CCDs. Total αENaC abundance in whole kidney increased in cirrhotic mice of both genotypes and cleaved forms of α and γ ENaC increased only in ascitic mice of both genotypes. The sodium chloride cotransporter (NCC) abundance was lower in non-ascitic KO, compared to non-ascitic CTL, and increased when ascites appeared. In ascitic mice, the lack of αENaC in CDs induced an upregulation of total ENaC and NCC and correlated with the cleavage of ENaC subunits. This revealed compensatory mechanisms which could also take place when treating the patients with diuretics. These compensatory mechanisms should be considered for future development of therapeutic strategies.

A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo.

PubMed

Oi, Katsuyuki; Sohara, Eisei; Rai, Tatemitsu; Misawa, Moko; Chiga, Motoko; Alessi, Dario R; Sasaki, Sei; Uchida, Shinichi

2012-02-15

Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII). We previously discovered that WNK kinases phosphorylate and activate OSR1/SPAK kinases that regulate renal SLC12A family transporters such as NKCC2 and NCC, and clarified that the constitutive activation of this cascade causes PHAII. WNK3, another member of the WNK kinase family, was reported to be a strong activator of NCC/NKCC2 when assayed in Xenopus oocytes, suggesting that WNK3 also plays a major role in regulating blood pressure and sodium reabsorption in the kidney. However, it remains to be determined whether WNK3 is in fact involved in the regulation of these transporters in vivo. To clarify this issue, we generated and analyzed WNK3 knockout mice. Surprisingly, phosphorylation and expression of OSR1, SPAK, NKCC2 and NCC did not decrease in knockout mouse kidney under normal and low-salt diets. Similarly, expression of epithelial Na channel and Na/H exchanger 3 were not affected in knockout mice. Na(+) and K(+) excretion in urine in WNK3 knockout mice was not affected under different salt diets. Blood pressure in WNK3 knockout mice was not lower under normal diet. However, lower blood pressure was observed in WNK3 knockout mice fed low-salt diet. WNK4 and WNK1 expression was slightly elevated in the knockout mice under low-salt diet, suggesting compensation for WNK3 knockout by these WNKs. Thus, WNK3 may have some role in the WNK-OSR1/SPAK-NCC/NKCC2 signal cascade in the kidney, but its contribution to total WNK kinase activity may be minimal.

Paradoxical activation of the sodium chloride cotransporter (NCC) without hypertension in kidney deficient in a regulatory subunit of Na,K-ATPase, FXYD2.

PubMed

Arystarkhova, Elena; Ralph, Donna L; Liu, Yi Bessie; Bouley, Richard; McDonough, Alicia A; Sweadner, Kathleen J

2014-12-01

Na,K-ATPase generates the driving force for sodium reabsorption in the kidney. Na,K-ATPase functional properties are regulated by small proteins belonging to the FXYD family. In kidney FXYD2 is the most abundant: it is an inhibitory subunit expressed in almost every nephron segment. Its absence should increase sodium pump activity and promote Na(+) retention, however, no obvious renal phenotype was detected in mice with global deletion of FXYD2 (Arystarkhova et al. 2013). Here, increased total cortical Na,K-ATPase activity was documented in the Fxyd2(-/-) mouse, without increased α1β1 subunit expression. We tested the hypothesis that adaptations occur in distal convoluted tubule (DCT), a major site of sodium adjustments. Na,K-ATPase immunoreactivity in DCT was unchanged, and there was no DCT hypoplasia. There was a marked activation of thiazide-sensitive sodium chloride cotransporter (NCC; Slc12a3) in DCT, predicted to increase Na(+) reabsorption in this segment. Specifically, NCC total increased 30% and NCC phosphorylated at T53 and S71, associated with activation, increased 4-6 fold. The phosphorylation of the closely related thick ascending limb (TAL) apical NKCC2 (Slc12a1) increased at least twofold. Abundance of the total and cleaved (activated) forms of ENaC α-subunit was not different between genotypes. Nonetheless, no elevation of blood pressure was evident despite the fact that NCC and NKCC2 are in states permissive for Na(+) retention. Activation of NCC and NKCC2 may reflect an intracellular linkage to elevated Na,K-ATPase activity or a compensatory response to Na(+) loss proximal to the TAL and DCT. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Establishment and proteomic characterization of a novel synovial sarcoma cell line, NCC-SS2-C1.

PubMed

Oyama, Rieko; Kito, Fusako; Sakumoto, Marimu; Shiozawa, Kumiko; Toki, Shunichi; Endo, Makoto; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

2018-05-01

Synovial sarcoma is an aggressive mesenchymal tumor, characterized by the presence of unique transfusion gene, SS18-SSX. Cell lines enable researchers to investigate the molecular backgrounds of disease and the significance of SS18-SSX in relevant cellular contexts. We report the establishment and proteomic characterization of a novel synovial sarcoma cell line. Primary tissue culture was performed using tumor tissue of synovial sarcoma. The established cell line was authenticated by assessing its DNA microsatellite short tandem repeat analysis and characterized by in vitro assay. Proteomic study was achieved by mass spectrometry, and the results were analyzed by treemap. The cell line NCC-SS2-C1 was established from a primary tumor tissue of a synovial sarcoma patient. The cell line has grown well for 11 mo and has been subcultured more than 15 times. The established cells were authenticated by assessing their short tandem repeat pattern comparing with that of original tumor tissue. The cells showed polygonal in shape and formed spheroid when seeded on the low-attachment dish. Proteomic analysis revealed the molecular pathways which are unique to the original tumor tissue or the established cell line. In conclusion, a novel synovial sarcoma cell line NCC-SS2-C1 was successfully established from the primary tumor tissue. The cell line has characteristic transfusion SS18-SSX and poses aggressive in vitro growth and capability of spheroid formation. Thus, NCC-SS2-C1 cell line will be a useful tool for investigation of the mechanisms of disease and the biological role of fusion gene.

Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome.

PubMed

Yang, Sung-Sen; Lo, Yi-Fen; Yu, I-Shing; Lin, Shu-Wha; Chang, Tai-Hsiang; Hsu, Yu-Juei; Chao, Tai-Kuang; Sytwu, Huey-Kang; Uchida, Shinichi; Sasaki, Sei; Lin, Shih-Hua

2010-12-01

Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypomagnesemia, hypokalemic metabolic alkalosis, and hypocalciuria. To better model human GS caused by a specific mutation in the thiazide-sensitive Na(+) -Cl(-) cotransporter (NCC) gene SLC12A3, we generated a nonsense Ncc Ser707X knockin mouse corresponding to human p.Ser710X (c.2135C>A), a recurrent mutation with severe phenotypes in Chinese GS patients. Compared with wild-type or heterozygous littermates, homozygous (Hom) knockin mice fully recapitulated the phenotype of human GS. The markedly reduced Ncc mRNA and virtually absent Ncc protein expression in kidneys of Hom mice was primarily due to nonsense-mediated mRNA decay (NMD) surveillance mechanisms. Expression of epithelial Na(+) channel (Enac), Ca(2+) channels (Trpv5 and Trpv6), and K(+) channels (Romk1 and maxi-K) were significantly increased. Late distal convoluted tubules (DCT) volume was increased and DCT cell ultrastructure appeared intact. High K(+) intake could not correct hypokalemia but caused a further increase in maxi-K but not Romk1 expression. Renal tissue from a patient with GS also showed the enhanced TRPV5 and ROMK1 expression in distal tubules. We suggest that the upregulation of TRPV5/6 and of ROMK1 and Maxi-K may contribute to hypocalciuria and hypokalemia in Ncc Ser707X knockin mice and human GS, respectively. © 2010 Wiley-Liss, Inc.

Catalytic conversion of carbohydrates to 5-hydroxymethylfurfural from the waste liquid of acid hydrolysis NCC.

PubMed

Sun, Yonghui; Liu, Pengtao; Liu, Zhong

2016-05-20

The principal goal of this work was to reuse the carbohydrates and recycle sulfuric acid in the waste liquid of acid hydrolysis nanocrystalline cellulose (NCC). Therefore, in this work, the optimizations of further hydrolysis of waste liquid of acid hydrolysis NCC and catalytic conversion of L4 to 5-hydroxymethylfurfural (5-HMF) were studied. Sulfuric acid was separated by spiral wound diffusion dialysis (SWDD). The results revealed that cellulose can be hydrolyze to glucose absolutely under the condition of temperature 35 °C, 3 h, and sulfuric acid's concentration 62 wt%. And 78.3% sulfuric acid was recovered by SWDD. The yield of 5-HMF was highest in aqueous solution under the optimal condition was as follows, temperature 160 °C, 3 h, and sulfuric acid's concentration 12 wt%. Then the effect of biphasic solvent systems catalytic conversion and inorganic salt as additives were still examined. The results showed that both of them contributed to prepare 5-HMF. The yield and selectivity of 5-HMF was up to 21.0% and 31.4%, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of Turbulence-Chemistry Interaction Models in the National Combustion Code (NCC) - Part I

NASA Technical Reports Server (NTRS)

Wey, Thomas Changju; Liu, Nan-suey

2011-01-01

This paper describes the implementations of the linear-eddy model (LEM) and an Eulerian FDF/PDF model in the National Combustion Code (NCC) for the simulation of turbulent combustion. The impacts of these two models, along with the so called laminar chemistry model, are then illustrated via the preliminary results from two combustion systems: a nine-element gas fueled combustor and a single-element liquid fueled combustor.

X-33 Flight Operations Center

NASA Technical Reports Server (NTRS)

1999-01-01

In response to Clause 17 of the Cooperative Agreement NCC8-115, Lockheed Martin Skunk Works has compiled an Annual Performance Report of the X-33/RLV Program. This report consists of individual reports from all industry team members, as well as NASA team centers. Contract award was announced on July 2, 1996 and the first milestone was hand delivered to NASA MSFC on July 17, 1996. With the dedication of the launch site, and continuing excellence in technological achievement, the third year of the Cooperative Agreement has been one of outstanding accomplishment and excitement.

A role for the circadian clock protein Per1 in the regulation of the NaCl co-transporter (NCC) and the with-no-lysine kinase (WNK) cascade in mouse distal convoluted tubule cells.

PubMed

Richards, Jacob; Ko, Benjamin; All, Sean; Cheng, Kit-Yan; Hoover, Robert S; Gumz, Michelle L

2014-04-25

It has been well established that blood pressure and renal function undergo circadian fluctuations. We have demonstrated that the circadian protein Per1 regulates multiple genes involved in sodium transport in the collecting duct of the kidney. However, the role of Per1 in other parts of the nephron has not been investigated. The distal convoluted tubule (DCT) plays a critical role in renal sodium reabsorption. Sodium is reabsorbed in this segment through the actions of the NaCl co-transporter (NCC), which is regulated by the with-no-lysine kinases (WNKs). The goal of this study was to test if Per1 regulates sodium transport in the DCT through modulation of NCC and the WNK kinases, WNK1 and WNK4. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of NCC and WNK1 but increased expression of WNK4 in the renal cortex of mice. These findings were confirmed by using Per1 siRNA and pharmacological blockade of Per1 nuclear entry in mDCT15 cells, a model of the mouse distal convoluted tubule. Transcriptional regulation was demonstrated by changes in short lived heterogeneous nuclear RNA. Chromatin immunoprecipitation experiments demonstrated interaction of Per1 and CLOCK with the promoters of NCC, WNK1, and WNK4. This interaction was modulated by blockade of Per1 nuclear entry. Importantly, NCC protein expression and NCC activity, as measured by thiazide-sensitive, chloride-dependent (22)Na uptake, were decreased upon pharmacological inhibition of Per1 nuclear entry. Taken together, these data demonstrate a role for Per1 in the transcriptional regulation of NCC, WNK1, and WNK4.

Enhancement of the Open National Combustion Code (OpenNCC) and Initial Simulation of Energy Efficient Engine Combustor

NASA Technical Reports Server (NTRS)

Miki, Kenji; Moder, Jeff; Liou, Meng-Sing

2016-01-01

In this paper, we present the recent enhancement of the Open National Combustion Code (OpenNCC) and apply the OpenNCC to model a realistic combustor configuration (Energy Efficient Engine (E3)). First, we perform a series of validation tests for the newly-implemented advection upstream splitting method (AUSM) and the extended version of the AUSM-family schemes (AUSM+-up). Compared with the analytical/experimental data of the validation tests, we achieved good agreement. In the steady-state E3 cold flow results using the Reynolds-averaged Navier-Stokes(RANS), we find a noticeable difference in the flow fields calculated by the two different numerical schemes, the standard Jameson- Schmidt-Turkel (JST) scheme and the AUSM scheme. The main differences are that the AUSM scheme is less numerical dissipative and it predicts much stronger reverse flow in the recirculation zone. This study indicates that two schemes could show different flame-holding predictions and overall flame structures.

The Assessment Supplement: A Faculty-Designed Addition to NCC's Manual, "Concepts & Procedures for Academic Assessment." First Edition.

ERIC Educational Resources Information Center

Nassau Community Coll., Garden City, NY.

This document is the first in a series of annual, faculty-designed supplements to Nassau Community College's (NCC's) (New York) manual, "Concepts & Procedures for Academic Assessment." The supplements are intended to provide faculty a forum through which they can communicate assessment designs and the impacts of those designs on…

Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

PubMed

Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

2013-02-01

The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

Assessment of Microphysical Models in the National Combustion Code (NCC) for Aircraft Particulate Emissions: Particle Loss in Sampling Lines

NASA Technical Reports Server (NTRS)

Wey, Thomas; Liu, Nan-Suey

2008-01-01

This paper at first describes the fluid network approach recently implemented into the National Combustion Code (NCC) for the simulation of transport of aerosols (volatile particles and soot) in the particulate sampling systems. This network-based approach complements the other two approaches already in the NCC, namely, the lower-order temporal approach and the CFD-based approach. The accuracy and the computational costs of these three approaches are then investigated in terms of their application to the prediction of particle losses through sample transmission and distribution lines. Their predictive capabilities are assessed by comparing the computed results with the experimental data. The present work will help establish standard methodologies for measuring the size and concentration of particles in high-temperature, high-velocity jet engine exhaust. Furthermore, the present work also represents the first step of a long term effort of validating physics-based tools for the prediction of aircraft particulate emissions.

KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the early distal convoluted tubule (DCT1).

PubMed

Zhang, Chengbiao; Wang, Lijun; Zhang, Junhui; Su, Xiao-Tong; Lin, Dao-Hong; Scholl, Ute I; Giebisch, Gerhard; Lifton, Richard P; Wang, Wen-Hui

2014-08-12

The renal phenotype induced by loss-of-function mutations of inwardly rectifying potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia, metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.4.1 mutations cause the tubulopathy is not completely understood. Here we demonstrate that Kcnj10 is a main contributor to the basolateral K conductance in the early distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl cotransporter (NCC) in the DCT. Immunostaining demonstrated Kcnj10 and Kcnj16 were expressed in the basolateral membrane of DCT, and patch-clamp studies detected a 40-pS K channel in the basolateral membrane of the DCT1 of p8/p10 wild-type Kcnj10(+/+) mice (WT). This 40-pS K channel is absent in homozygous Kcnj10(-/-) (knockout) mice. The disruption of Kcnj10 almost completely eliminated the basolateral K conductance and decreased the negativity of the cell membrane potential in DCT1. Moreover, the lack of Kcnj10 decreased the basolateral Cl conductance, inhibited the expression of Ste20-related proline-alanine-rich kinase and diminished the apical NCC expression in DCT. We conclude that Kcnj10 plays a dominant role in determining the basolateral K conductance and membrane potential of DCT1 and that the basolateral K channel activity in the DCT determines the apical NCC expression possibly through a Ste20-related proline-alanine-rich kinase-dependent mechanism.

Identification of genes associated with the long-gut-persistence phenotype of the probiotic Lactobacillus johnsonii strain NCC533 using a combination of genomics and transcriptome analysis.

PubMed

Denou, Emmanuel; Pridmore, Raymond David; Berger, Bernard; Panoff, Jean-Michel; Arigoni, Fabrizio; Brüssow, Harald

2008-05-01

Lactobacillus johnsonii strains NCC533 and ATCC 33200 (the type strain of this species) differed significantly in gut residence time (12 versus 5 days) after oral feeding to mice. Genes affecting the long gut residence time of the probiotic strain NCC533 were targeted for analysis. We hypothesized that genes specific for this strain, which are expressed during passage of the bacterium through the gut, affect the phenotype. When the DNA of the type strain was hybridized against a microarray of the sequenced NCC533 strain, we identified 233 genes that were specific for the long-gut-persistence isolate. Whole-genome transcription analysis of the NCC533 strain using the microarray format identified 174 genes that were strongly and consistently expressed in the jejunum of mice monocolonized with this strain. Fusion of the two microarray data sets identified three gene loci that were both expressed in vivo and specific to the long-gut-persistence isolate. The identified genes included LJ1027 and LJ1028, two glycosyltransferase genes in the exopolysaccharide synthesis operon; LJ1654 to LJ1656, encoding a sugar phosphotransferase system (PTS) transporter annotated as mannose PTS; and LJ1680, whose product shares 30% amino acid identity with immunoglobulin A proteases from pathogenic bacteria. Knockout mutants were tested in vivo. The experiments revealed that deletion of LJ1654 to LJ1656 and LJ1680 decreased the gut residence time, while a mutant with a deleted exopolysaccharide biosynthesis cluster had a slightly increased residence time.

Current Status of Superheat Spray Modeling With NCC

NASA Technical Reports Server (NTRS)

Raju, M. S.; Bulzan, Dan L.

2012-01-01

An understanding of liquid fuel behavior at superheat conditions is identified to be a topic of importance in the design of modern supersonic engines. As a part of the NASA's supersonics project office initiative on high altitude emissions, we have undertaken an effort to assess the accuracy of various existing CFD models used in the modeling of superheated sprays. As a part of this investigation, we have completed the implementation of a modeling approach into the national combustion code (NCC), and then applied it to investigate the following three cases: (1) the validation of a flashing jet generated by the sudden release of pressurized R134A from a cylindrical nozzle, (2) the differences between two superheat vaporization models were studied based on both hot and cold flow calculations of a Parker-Hannifin pressure swirl atomizer, (3) the spray characteristics generated by a single-element LDI (Lean Direct Injector) experiment were studied to investigate the differences between superheat and non-superheat conditions. Further details can be found in the paper.

Mutual Cross-Feeding Interactions between Bifidobacterium longum subsp. longum NCC2705 and Eubacterium rectale ATCC 33656 Explain the Bifidogenic and Butyrogenic Effects of Arabinoxylan Oligosaccharides

PubMed Central

Rivière, Audrey; Gagnon, Mérilie; Weckx, Stefan; Roy, Denis

2015-01-01

Arabinoxylan oligosaccharides (AXOS) are a promising class of prebiotics that have the potential to stimulate the growth of bifidobacteria and the production of butyrate in the human colon, known as the bifidogenic and butyrogenic effects, respectively. Although these dual effects of AXOS are considered beneficial for human health, their underlying mechanisms are still far from being understood. Therefore, this study investigated the metabolic interactions between Bifidobacterium longum subsp. longum NCC2705 (B. longum NCC2705), an acetate producer and arabinose substituent degrader of AXOS, and Eubacterium rectale ATCC 33656, an acetate-converting butyrate producer. Both strains belong to prevalent species of the human colon microbiota. The strains were grown on AXOS during mono- and coculture fermentations, and their growth, AXOS consumption, metabolite production, and expression of key genes were monitored. The results showed that the growth of both strains and gene expression in both strains were affected by cocultivation and that these effects could be linked to changes in carbohydrate consumption and concomitant metabolite production. The consumption of the arabinose substituents of AXOS by B. longum NCC2705 with the concomitant production of acetate allowed E. rectale ATCC 33656 to produce butyrate (by means of a butyryl coenzyme A [CoA]:acetate CoA-transferase), explaining the butyrogenic effect of AXOS. Eubacterium rectale ATCC 33656 released xylose from the AXOS substrate, which favored the B. longum NCC2705 production of acetate, explaining the bifidogenic effect of AXOS. Hence, those interactions represent mutual cross-feeding mechanisms that favor the coexistence of bifidobacterial strains and butyrate producers in the same ecological niche. In conclusion, this study provides new insights into the bifidogenic and butyrogenic effects of AXOS. PMID:26319874

A Validation Summary of the NCC Turbulent Reacting/non-reacting Spray Computations

NASA Technical Reports Server (NTRS)

Raju, M. S.; Liu, N.-S. (Technical Monitor)

2000-01-01

This pper provides a validation summary of the spray computations performed as a part of the NCC (National Combustion Code) development activity. NCC is being developed with the aim of advancing the current prediction tools used in the design of advanced technology combustors based on the multidimensional computational methods. The solution procedure combines the novelty of the application of the scalar Monte Carlo PDF (Probability Density Function) method to the modeling of turbulent spray flames with the ability to perform the computations on unstructured grids with parallel computing. The calculation procedure was applied to predict the flow properties of three different spray cases. One is a nonswirling unconfined reacting spray, the second is a nonswirling unconfined nonreacting spray, and the third is a confined swirl-stabilized spray flame. The comparisons involving both gas-phase and droplet velocities, droplet size distributions, and gas-phase temperatures show reasonable agreement with the available experimental data. The comparisons involve both the results obtained from the use of the Monte Carlo PDF method as well as those obtained from the conventional computational fluid dynamics (CFD) solution. Detailed comparisons in the case of a reacting nonswirling spray clearly highlight the importance of chemistry/turbulence interactions in the modeling of reacting sprays. The results from the PDF and non-PDF methods were found to be markedly different and the PDF solution is closer to the reported experimental data. The PDF computations predict that most of the combustion occurs in a predominantly diffusion-flame environment. However, the non-PDF solution predicts incorrectly that the combustion occurs in a predominantly vaporization-controlled regime. The Monte Carlo temperature distribution shows that the functional form of the PDF for the temperature fluctuations varies substantially from point to point. The results also bring to the fore some of the

NCC-RANSAC: a fast plane extraction method for 3-D range data segmentation.

PubMed

Qian, Xiangfei; Ye, Cang

2014-12-01

This paper presents a new plane extraction (PE) method based on the random sample consensus (RANSAC) approach. The generic RANSAC-based PE algorithm may over-extract a plane, and it may fail in case of a multistep scene where the RANSAC procedure results in multiple inlier patches that form a slant plane straddling the steps. The CC-RANSAC PE algorithm successfully overcomes the latter limitation if the inlier patches are separate. However, it fails if the inlier patches are connected. A typical scenario is a stairway with a stair wall where the RANSAC plane-fitting procedure results in inliers patches in the tread, riser, and stair wall planes. They connect together and form a plane. The proposed method, called normal-coherence CC-RANSAC (NCC-RANSAC), performs a normal coherence check to all data points of the inlier patches and removes the data points whose normal directions are contradictory to that of the fitted plane. This process results in separate inlier patches, each of which is treated as a candidate plane. A recursive plane clustering process is then executed to grow each of the candidate planes until all planes are extracted in their entireties. The RANSAC plane-fitting and the recursive plane clustering processes are repeated until no more planes are found. A probabilistic model is introduced to predict the success probability of the NCC-RANSAC algorithm and validated with real data of a 3-D time-of-flight camera-SwissRanger SR4000. Experimental results demonstrate that the proposed method extracts more accurate planes with less computational time than the existing RANSAC-based methods.

NCC-RANSAC: A Fast Plane Extraction Method for 3-D Range Data Segmentation

PubMed Central

Qian, Xiangfei; Ye, Cang

2015-01-01

This paper presents a new plane extraction (PE) method based on the random sample consensus (RANSAC) approach. The generic RANSAC-based PE algorithm may over-extract a plane, and it may fail in case of a multistep scene where the RANSAC procedure results in multiple inlier patches that form a slant plane straddling the steps. The CC-RANSAC PE algorithm successfully overcomes the latter limitation if the inlier patches are separate. However, it fails if the inlier patches are connected. A typical scenario is a stairway with a stair wall where the RANSAC plane-fitting procedure results in inliers patches in the tread, riser, and stair wall planes. They connect together and form a plane. The proposed method, called normal-coherence CC-RANSAC (NCC-RANSAC), performs a normal coherence check to all data points of the inlier patches and removes the data points whose normal directions are contradictory to that of the fitted plane. This process results in separate inlier patches, each of which is treated as a candidate plane. A recursive plane clustering process is then executed to grow each of the candidate planes until all planes are extracted in their entireties. The RANSAC plane-fitting and the recursive plane clustering processes are repeated until no more planes are found. A probabilistic model is introduced to predict the success probability of the NCC-RANSAC algorithm and validated with real data of a 3-D time-of-flight camera–SwissRanger SR4000. Experimental results demonstrate that the proposed method extracts more accurate planes with less computational time than the existing RANSAC-based methods. PMID:24771605

Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension.

PubMed

Hadchouel, Juliette; Soukaseum, Christelle; Büsst, Cara; Zhou, Xiao-ou; Baudrie, Véronique; Zürrer, Tany; Cambillau, Michelle; Elghozi, Jean-Luc; Lifton, Richard P; Loffing, Johannes; Jeunemaitre, Xavier

2010-10-19

Mutations in WNK1 and WNK4 lead to familial hyperkalemic hypertension (FHHt). Because FHHt associates net positive Na(+) balance together with K(+) and H(+) renal retention, the identification of WNK1 and WNK4 led to a new paradigm to explain how aldosterone can promote either Na(+) reabsorption or K(+) secretion in a hypovolemic or hyperkalemic state, respectively. WNK1 gives rise to L-WNK1, an ubiquitous kinase, and KS-WNK1, a kinase-defective isoform expressed in the distal convoluted tubule. By inactivating KS-WNK1 in mice, we show here that this isoform is an important regulator of sodium transport. KS-WNK1(-/-) mice display an increased activity of the Na-Cl cotransporter NCC, expressed specifically in the distal convoluted tubule, where it participates in the fine tuning of sodium reabsorption. Moreover, the expression of the ROMK and BKCa potassium channels was modified in KS-WNK1(-/-) mice, indicating that KS-WNK1 is also a regulator of potassium transport in the distal nephron. Finally, we provide an alternative model for FHHt. Previous studies suggested that the activation of NCC plays a central role in the development of hypertension and hyperkalemia. Even though the increase in NCC activity in KS-WNK1(-/-) mice was less pronounced than in mice overexpressing a mutant form of WNK4, our study suggests that the activation of Na-Cl cotransporter is not sufficient by itself to induce a hyperkalemic hypertension and that the deregulation of other channels, such as the Epithelial Na(+) channel (ENaC), is probably required.

Outcomes of neonatal patent ductus arteriosus ligation in Canadian neonatal units with and without pediatric cardiac surgery programs.

PubMed

Wong, Charles; Mak, Michael; Shivananda, Sandesh; Yang, Junmin; Shah, Prakeshkumar S; Seidlitz, Wendy; Pemberton, Julia; Fitzgerald, Peter G; Cameron, Brian H

2013-05-01

Preterm infants needing patent ductus arteriosus (PDA) ligation are transferred to a pediatric cardiac center (CC) unless the operation can be done locally by a pediatric surgeon at a non-cardiac center (NCC). We compared infant outcomes after PDA ligation at CC and NCC. We analyzed 990 preterm infants who had PDA ligation between 2005 and 2009 using the Canadian Neonatal Network database. In-hospital mortality and major morbidities were compared between CC (n=18) and NCC (n=9). SNAP-II-adjusted mortality rates were similar (CC=8.7% vs NCC=10.7%, P=.32). Significant cranial ultrasound abnormalities (CC=24.1% vs NCC=32.1%, P<.01) and culture-proven sepsis (CC=39.7% vs NCC=54.8%, P<.01) were more frequent in infants treated at NCC. Infants transferred to CC had higher rates of cranial ultrasound abnormalities (transferred 31.6% vs non-transferred 20.4%, P<.01). NSAIDs prior to PDA ligation were used more often at NCC (CC 36.6% vs NCC 75.6%, P<.001). Mortality rates after PDA ligation were similar at CC and NCC, but cranial ultrasound abnormalities and sepsis rates were higher at NCC. Higher morbidity may be associated with different PDA management strategies, including NSAID use or infant transfer. Further studies are needed to investigate the reasons for these differences in morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

Counter - Drug: Mandate for the Army.

DTIC Science & Technology

1991-03-01

this comprehensive review will provide a basis for responding to new missions assigned...observations for determining the short-, mid-, and long-term direction of Army support to the national counter-drug effort. Also, this comprehensive review will provide...and long-term direction of Army support to the national counter-drug effort. Also, this comprehensive review will provide a basis for responding

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.

Improving the Flow

NASA Technical Reports Server (NTRS)

2004-01-01

In early 1995, NASA s Glenn Research Center (then Lewis Research Center) formed an industry-government team with several jet engine companies to develop the National Combustion Code (NCC), which would help aerospace engineers solve complex aerodynamics and combustion problems in gas turbine, rocket, and hypersonic engines. The original development team consisted of Allison Engine Company (now Rolls-Royce Allison), CFD Research Corporation, GE Aircraft Engines, Pratt and Whitney, and NASA. After the baseline beta version was established in July 1998, the team focused its efforts on consolidation, streamlining, and integration, as well as enhancement, evaluation, validation, and application. These activities, mainly conducted at NASA Glenn, led to the completion of NCC version 1.0 in October 2000. NCC version 1.0 features high-fidelity representation of complex geometry, advanced models for two-phase turbulent combustion, and massively parallel computing. Researchers and engineers at Glenn have been using NCC to provide analysis and design support for various aerospace propulsion technology development projects. NASA transfers NCC technology to external customers using non- exclusive Space Act Agreements. Glenn researchers also communicate research and development results derived from NCC's further development through publications and special sessions at technical conferences.

14 CFR § 1274.212 - Document format and numbering.

Code of Federal Regulations, 2014 CFR

2014-01-01

... implemented, cooperative agreement numbering shall conform to NFS 1804.7102, except that a NCC prefix will be used in lieu of the NAS prefix. Along with the prefix NCC, a one or two digit Center Identification...

14 CFR 1274.212 - Document format and numbering.

Code of Federal Regulations, 2012 CFR

2012-01-01

... implemented, cooperative agreement numbering shall conform to NFS 1804.7102, except that a NCC prefix will be used in lieu of the NAS prefix. Along with the prefix NCC, a one or two digit Center Identification...

14 CFR 1274.212 - Document format and numbering.

Code of Federal Regulations, 2011 CFR

2011-01-01

... implemented, cooperative agreement numbering shall conform to NFS 1804.7102, except that a NCC prefix will be used in lieu of the NAS prefix. Along with the prefix NCC, a one or two digit Center Identification...

14 CFR 1274.212 - Document format and numbering.

Code of Federal Regulations, 2013 CFR

2013-01-01

... implemented, cooperative agreement numbering shall conform to NFS 1804.7102, except that a NCC prefix will be used in lieu of the NAS prefix. Along with the prefix NCC, a one or two digit Center Identification...

14 CFR 1274.212 - Document format and numbering.

Code of Federal Regulations, 2010 CFR

2010-01-01

... implemented, cooperative agreement numbering shall conform to NFS 1804.7102, except that a NCC prefix will be used in lieu of the NAS prefix. Along with the prefix NCC, a one or two digit Center Identification...

Lithium fluxes indicate presence of Na-Cl cotransport (NCC) in human lens epithelial cells.

PubMed

Lauf, Peter K; Chimote, Ameet A; Adragna, Norma C

2008-01-01

During regulatory volume decrease (RVD) of human lens epithelial cells (hLECs) by clotrimazole (CTZ)-sensitive K fluxes, Na-K-2Cl cotransport (NKCC) remains active and K-Cl cotransport (KCC) inactive. To determine whether such an abnormal behavior was caused by RVD-induced cell shrinkage, NKCC was measured in the presence of either CTZ or in high K media to prevent RVD. NKCC transports RbCl + NaCl, and LiCl + KCl; thus ouabain-insensitive, bumetanide-sensitive (BS) or Cl-dependent (ClD) Rb and Li fluxes were determined in hyposmotic high NaCl media with CTZ, or in high KCl media alone, or with sulfamate (Sf) or nitrate as Cl replacement at varying Rb, Li or Cl mol fractions (MF). Unexpectedly, NKCC was inhibited by 80% with CTZ (IC(50) = 31 microM). In isosmotic (300 mOsM) K, Li influx was approximately 1/3 of Rb influx in Na, 50% lower in Sf, and bumetanide-insensitive (BI). In hypotonic (200 mOsM) K, only the ClD but not BS Li fluxes were detected. At Li MFs from 0.1-1, Li fluxes fitted a bell-shaped curve maxing at approximately 0.6 Li MF, with the BS fluxes equaling approximately 1/4 of the ClD-Li influx. The difference, i.e. the BI/ClD Li influx, saturated with increasing Li and Cl MFs, with K(ms) for Li of 11 with, and 7 mM without K, and of approximately 46 mM for Cl. Inhibition of this K-independent Li influx by thiazides was weak whilst furosemide (<100 microM) was ineffective. Reverse transcription polymerase chain reaction and Western blots verified presence of both NKCC1 and Na-Cl cotransport (NCC). In conclusion, in hyposmotic high K media, which prevents CTZ-sensitive K flux-mediated RVD in hLECs, NKCC1, though molecularly expressed, was functionally silent. However, a K-independent and moderately thiazide-sensitive ClD-Li flux, i.e. LiCC, likely occurring through NCC was detected operationally and molecularly. (c) 2008 S. Karger AG, Basel.

Effect of heterozygous deletion of WNK1 on the WNK-OSR1/ SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels.

PubMed

Susa, Koichiro; Kita, Satomi; Iwamoto, Takahiro; Yang, Sung-Sen; Lin, Shih-Hua; Ohta, Akihito; Sohara, Eisei; Rai, Tatemitsu; Sasaki, Sei; Alessi, Dario R; Uchida, Shinichi

2012-08-01

We found that a mechanism of hypertension in pseudohypoaldosteronism type II (PHAII) caused by a WNK4 missense mutation (D561A) was activation of the WNK-OSR1/SPAK-NCC signal cascade. However, the pathogenic effect of intronic deletions in WNK1 genes also observed in PHAII patients remains unclear. To understand the pathophysiological roles of WNK1 in vivo, WNK1(+/-)mice have been analyzed, because homozygous WNK1 knockout is embryonic lethal. Although WNK1(+/-) mice have been reported to have hypotension, detailed analyses of the WNK signal cascade in the kidney and other organs of WNK1(+/-) mice have not been performed. We assess the effect of heterozygous deletion of WNK1 on the WNK-OSR1/SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels. Contrary to the previous report, the blood pressure of WNK1(+/-) mice was not decreased, even under a low-salt diet. Under a WNK4(D561A/+) background, the heterozygous deletion of the WNK1 gene did not reduce the high blood pressure either. We then evaluated the phosphorylation status of OSR1, SPAK, NCC, NKCC1, and NKCC2 in the kidney, but no significant decrease in the phosphorylation was observed in WNK1(+/-) mice or WNK1(+/-)WNK4(D561A/+) mice. In contrast, a significant decrease in NKCC1 phosphorylation in the aorta and a decreased pressure-induced myogenic response in the mesenteric arteries were observed in WNK1(+/-) mice. The contribution of WNK1 to total WNK kinase activity in the kidney may be small, but that WNK1 may play a substantial role in the regulation of blood pressure in the arteries.

CFD Simulation on the J-2X Engine Exhaust in the Center-Body Diffuser and Spray Chamber at the B-2 Facility

NASA Technical Reports Server (NTRS)

Wang, Xiao-Yen; Wey, Thomas; Buehrle, Robert

2009-01-01

A computational fluid dynamic (CFD) code is used to simulate the J-2X engine exhaust in the center-body diffuser and spray chamber at the Spacecraft Propulsion Facility (B-2). The CFD code is named as the space-time conservation element and solution element (CESE) Euler solver and is very robust at shock capturing. The CESE results are compared with independent analysis results obtained by using the National Combustion Code (NCC) and show excellent agreement.

Biotransformation of caffeoyl quinic acids from green coffee extracts by Lactobacillus johnsonii NCC 533.

PubMed

Bel-Rhlid, Rachid; Thapa, Dinesh; Kraehenbuehl, Karin; Hansen, Carl Erik; Fischer, Lutz

2013-01-01

The potential of Lactobacillus johnsonii NCC 533 to metabolize chlorogenic acids from green coffee extract was investigated. Two enzymes, an esterase and a hydroxycinnamate decarboxylase (HCD), were involved in this biotransformation. The complete hydrolysis of 5-caffeoylquinic acid (5-CQA) into caffeic acid (CA) by L. johnsonii esterase occurred during the first 16 h of reaction time. No dihydrocaffeic acid was identified in the reaction mixture. The decarboxylation of CA into 4-vinylcatechol (4-VC) started only when the maximum concentration of CA was reached (10 μmol/ml). CA was completely transformed into 4-VC after 48 h of incubation. No 4-vinylphenol or other derivatives could be identified in the reaction media. In this study we demonstrate the capability of L. johnsonii to transform chlorogenic acids from green coffee extract into 4-VC in two steps one pot reaction. Thus, the enzymatic potential of certain lactobacilli might be explored to generate flavor compounds from plant polyphenols.

Establishment and proteomic characterization of NCC-LMS1-C1, a novel cell line of primary leiomyosarcoma of the bone.

PubMed

Sakumoto, Marimu; Takahashi, Mami; Oyama, Rieko; Takai, Yoko; Kito, Fusako; Shiozawa, Kumiko; Qiao, Zhiwei; Yoshida, Akihiko; Endo, Makoto; Kawai, Akira; Kondo, Tadashi

2017-10-01

Leiomyosarcoma (LMS) is one of most aggressive mesenchymal malignancies that differentiate towards smooth muscle. The clinical outcome of LMS patients is poor; as such, there is an urgent need for novel therapeutic approaches. Experimental models such as patient-derived cell lines are invaluable tools for pre-clinical studies. In the present study, we established a stable cell line from the tumor tissue of a patient with a primary LMS of the bone. Despite the urgent need for novel therapeutic strategies in LMS, there are only a few LMS cell lines available in public cell banks, none of which are primary to the bone. Bone primary LMS tumor tissues were sampled to establish cell lines. Morphological and proteomic analyses were performed and sensitivity to pazopanib was evaluated. NCC-LMS1-C1 cells were maintained for over 100 passages. The cells exhibited a spindle shape and aggressive growth; they also expressed smooth muscle actin, reflecting the original LMS tissue (i.e. smooth muscle cells). The cells also showed tumor characteristics such as colony formation on soft agar and sensitivity to pazopanib, doxorubicin and cisplatin, with half-maximal inhibitory concentrations of 4.5, 0.11 and 20 μM, respectively. Proteomic analyses by mass spectrometry and antibody array revealed some differences in the protein expression profiles of these cells as compared to the original tumor tissue. Our results indicate that the NCC-LMS1-C1 cell lines will be useful for LMS research. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Engineering technology for networks

NASA Technical Reports Server (NTRS)

Paul, Arthur S.; Benjamin, Norman

1991-01-01

Space Network (SN) modeling and evaluation are presented. The following tasks are included: Network Modeling (developing measures and metrics for SN, modeling of the Network Control Center (NCC), using knowledge acquired from the NCC to model the SNC, and modeling the SN); and Space Network Resource scheduling.

Nunez Community College, Exploring America's Communities. Progress Report.

ERIC Educational Resources Information Center

Nunez Community Coll., Chalmette, LA.

In 1996, Louisiana's Nunez Community College (NCC) participated in the Exploring America's Communities project sponsored by the American Association of Community Colleges. The project works to strengthen the teaching and learning of American history, literature, and culture at U.S. community colleges. NCC's primary goal was centered on providing…

Northampton Community College Adult Learner Competencies Implementation. Final Report, 1998-1999 [and] Adult Learner Competencies Implementation Manual for Workshops #1 and #2 and NCC Competencies-Based Lesson Plan "Mini-Bank".

ERIC Educational Resources Information Center

Sullivan, Judy

A project provided training and guidance to Northampton Community College (NCC) staff in implementing the "new" adult learner skill competencies. Two workshops were held to serve 29 staff in Monroe, Wayne, and Pike counties in Pennsylvania. Among the topics covered were defining and introducing portfolios to adult learners, individualizing…

Implementation of Neurocritical Care Is Associated With Improved Outcomes in Traumatic Brain Injury.

PubMed

Sekhon, Mypinder S; Gooderham, Peter; Toyota, Brian; Kherzi, Navid; Hu, Vivien; Dhingra, Vinay K; Hameed, Morad S; Chittock, Dean R; Griesdale, Donald E

2017-07-01

Background Traditionally, the delivery of dedicated neurocritical care (NCC) occurs in distinct NCC units and is associated with improved outcomes. Institution-specific logistical challenges pose barriers to the development of distinct NCC units; therefore, we developed a consultancy NCC service coupled with the implementation of invasive multimodal neuromonitoring, within a medical-surgical intensive care unit. Our objective was to evaluate the effect of a consultancy NCC program on neurologic outcomes in severe traumatic brain injury patients. We conducted a single-center quasi-experimental uncontrolled pre- and post-NCC study in severe traumatic brain injury patients (Glasgow Coma Scale ≤8). The NCC program includes consultation with a neurointensivist and neurosurgeon and multimodal neuromonitoring. Demographic, injury severity metrics, neurophysiologic data, and therapeutic interventions were collected. Glasgow Outcome Scale (GOS) at 6 months was the primary outcome. Multivariable ordinal logistic regression was used to model the association between NCC implementation and GOS at 6 months. A total of 113 patients were identified: 76 pre-NCC and 37 post-NCC. Mean age was 39 years (standard deviation [SD], 2) and 87 of 113 (77%) patients were male. Median admission motor score was 3 (interquartile ratio, 1-4). Daily mean arterial pressure was higher (95 mmHg [SD, 10]) versus (88 mmHg [SD, 10], p<0.001) and daily mean core body temperature was lower (36.6°C [SD, 0.90]) versus (37.2°C [SD, 1.0], p=0.001) post-NCC compared with pre-NCC, respectively. Multivariable regression modelling revealed the NCC program was associated with a 2.5 increased odds (odds ratios, 2.5; 95% confidence interval, 1.1-5.3; p=0.022) of improved 6-month GOS. Implementation of a NCC program is associated with improved 6 month GOS in severe TBI patients.

Perinatal maternal administration of Lactobacillus paracasei NCC 2461 prevents allergic inflammation in a mouse model of birch pollen allergy.

PubMed

Schabussova, Irma; Hufnagl, Karin; Tang, Mimi L K; Hoflehner, Elisabeth; Wagner, Angelika; Loupal, Gerhard; Nutten, Sophie; Zuercher, Adrian; Mercenier, Annick; Wiedermann, Ursula

2012-01-01

The hygiene hypothesis implies that microbial agents including probiotic bacteria may modulate foetal/neonatal immune programming and hence offer effective strategies for primary allergy prevention; however their mechanisms of action are poorly understood. We investigated whether oral administration of Lactobacillus paracasei NCC 2461 to mothers during gestation/lactation can protect against airway inflammation in offspring in a mouse model of birch pollen allergy, and examined the immune mechanisms involved. BALB/c mice were treated daily with L. paracasei in drinking water or drinking water alone in the last week of gestation and during lactation. Their offspring were sensitized with recombinant Bet v 1, followed by aerosol challenge with birch pollen extract. Maternal exposure to L. paracasei prevented the development of airway inflammation in offspring, as demonstrated by attenuation of eosinophil influx in the lungs; reduction of IL-5 levels in bronchoalveolar lavage, and in lung and mediastinal lymph node cell cultures; and reduced peribronchial inflammatory infiltrate and mucus hypersecretion. While allergen-specific IgE and IgG antibody levels remained unchanged by the treatment, IL-4 and IL-5 production in spleen cell cultures were significantly reduced upon allergen stimulation in offspring of L. paracasei treated mice. Offspring of L. paracasei supplemented mothers had significantly reduced Bet v 1-specific as well as Concanavalin A-induced responses in spleen and mesenteric lymph node cell cultures, suggesting the modulation of both antigen-specific and mitogen-induced immune responses in offspring. These effects were associated with increased Foxp3 mRNA expression in the lungs and increased TGF-beta in serum. Our data show that in a mouse model of birch pollen allergy, perinatal administration of L. paracasei NCC 2461 to pregnant/lactating mothers protects against the development of airway inflammation in offspring by activating regulatory pathways

Perinatal Maternal Administration of Lactobacillus paracasei NCC 2461 Prevents Allergic Inflammation in a Mouse Model of Birch Pollen Allergy

PubMed Central

Schabussova, Irma; Hufnagl, Karin; Tang, Mimi L. K.; Hoflehner, Elisabeth; Wagner, Angelika; Loupal, Gerhard; Nutten, Sophie; Zuercher, Adrian; Mercenier, Annick; Wiedermann, Ursula

2012-01-01

Background The hygiene hypothesis implies that microbial agents including probiotic bacteria may modulate foetal/neonatal immune programming and hence offer effective strategies for primary allergy prevention; however their mechanisms of action are poorly understood. We investigated whether oral administration of Lactobacillus paracasei NCC 2461 to mothers during gestation/lactation can protect against airway inflammation in offspring in a mouse model of birch pollen allergy, and examined the immune mechanisms involved. Methods BALB/c mice were treated daily with L. paracasei in drinking water or drinking water alone in the last week of gestation and during lactation. Their offspring were sensitized with recombinant Bet v 1, followed by aerosol challenge with birch pollen extract. Results Maternal exposure to L. paracasei prevented the development of airway inflammation in offspring, as demonstrated by attenuation of eosinophil influx in the lungs; reduction of IL-5 levels in bronchoalveolar lavage, and in lung and mediastinal lymph node cell cultures; and reduced peribronchial inflammatory infiltrate and mucus hypersecretion. While allergen-specific IgE and IgG antibody levels remained unchanged by the treatment, IL-4 and IL-5 production in spleen cell cultures were significantly reduced upon allergen stimulation in offspring of L. paracasei treated mice. Offspring of L. paracasei supplemented mothers had significantly reduced Bet v 1-specific as well as Concanavalin A-induced responses in spleen and mesenteric lymph node cell cultures, suggesting the modulation of both antigen-specific and mitogen-induced immune responses in offspring. These effects were associated with increased Foxp3 mRNA expression in the lungs and increased TGF-beta in serum. Conclusion Our data show that in a mouse model of birch pollen allergy, perinatal administration of L. paracasei NCC 2461 to pregnant/lactating mothers protects against the development of airway inflammation in offspring

15 CFR 950.3 - National Climatic Center (NCC).

Code of Federal Regulations, 2014 CFR

2014-01-01

...; develops analytical and descriptive products to meet user requirements; and provides facilities for the... Meteorological Experiment meteorological data, Global Atmospheric Research Program basic data set, solar...

15 CFR 950.3 - National Climatic Center (NCC).

Code of Federal Regulations, 2012 CFR

2012-01-01

...; develops analytical and descriptive products to meet user requirements; and provides facilities for the... Meteorological Experiment meteorological data, Global Atmospheric Research Program basic data set, solar...

15 CFR 950.3 - National Climatic Center (NCC).

Code of Federal Regulations, 2010 CFR

2010-01-01

...; develops analytical and descriptive products to meet user requirements; and provides facilities for the... Meteorological Experiment meteorological data, Global Atmospheric Research Program basic data set, solar...

15 CFR 950.3 - National Climatic Center (NCC).

Code of Federal Regulations, 2013 CFR

2013-01-01

...; develops analytical and descriptive products to meet user requirements; and provides facilities for the... Meteorological Experiment meteorological data, Global Atmospheric Research Program basic data set, solar...

15 CFR 950.3 - National Climatic Center (NCC).

Code of Federal Regulations, 2011 CFR

2011-01-01

...; develops analytical and descriptive products to meet user requirements; and provides facilities for the... Meteorological Experiment meteorological data, Global Atmospheric Research Program basic data set, solar...

Hubble Space Telescope Pointing Performance Due to Micro-Dynamic Disturbances from the NICMOS Cryogenic Cooler

NASA Technical Reports Server (NTRS)

Clapp, Brian R.; Sills, Joel W., Jr.; Voorhees, Carl R.; Griffin, Thomas J. (Technical Monitor)

2002-01-01

The Vibration Admittance Test (VET) was performed to measure the emitted disturbances of the Near Infrared Camera and Multi-Object Spectrometer (NICMOS) Cryogenic Cooler (NCC) in preparation for NCC installation onboard the Hubble Space Telescope (HST) during Servicing Mission 3B (SM3B). Details of the VET ground-test are described, including facility characteristics, sensor complement and configuration, NCC suspension, and background noise measurements. Kinematic equations used to compute NCC mass center displacements and accelerations from raw measurements are presented, and dynamic equations of motion for the NCC VET system are developed and verified using modal test data. A MIMO linear frequency-domain analysis method is used to compute NCC-induced loads and HST boresight jitter from VET measurements. These results are verified by a nonlinear time-domain analysis approach using a high-fidelity structural dynamics and pointing control simulation for HST. NCC emitted acceleration levels not exceeding 35 micro-g rms were measured in the VET and analysis methods herein predict 3.1 milli-areseconds rms jitter for HST on-orbit. Because the NCC is predicted to become the predominant disturbance source for HST, VET results indicate that HST will continue to meet the 7 milli-arcsecond pointing stability mission requirement in the post-SM3B era.

Integrated compensatory network is activated in the absence of NCC phosphorylation.

PubMed

Grimm, P Richard; Lazo-Fernandez, Yoskaly; Delpire, Eric; Wall, Susan M; Dorsey, Susan G; Weinman, Edward J; Coleman, Richard; Wade, James B; Welling, Paul A

2015-05-01

Thiazide diuretics are used to treat hypertension; however, compensatory processes in the kidney can limit antihypertensive responses to this class of drugs. Here, we evaluated compensatory pathways in SPAK kinase-deficient mice, which are unable to activate the thiazide-sensitive sodium chloride cotransporter NCC (encoded by Slc12a3). Global transcriptional profiling, combined with biochemical, cell biological, and physiological phenotyping, identified the gene expression signature of the response and revealed how it establishes an adaptive physiology. Salt reabsorption pathways were created by the coordinate induction of a multigene transport system, involving solute carriers (encoded by Slc26a4, Slc4a8, and Slc4a9), carbonic anhydrase isoforms, and V-type H⁺-ATPase subunits in pendrin-positive intercalated cells (PP-ICs) and ENaC subunits in principal cells (PCs). A distal nephron remodeling process and induction of jagged 1/NOTCH signaling, which expands the cortical connecting tubule with PCs and replaces acid-secreting α-ICs with PP-ICs, were partly responsible for the compensation. Salt reabsorption was also activated by induction of an α-ketoglutarate (α-KG) paracrine signaling system. Coordinate regulation of a multigene α-KG synthesis and transport pathway resulted in α-KG secretion into pro-urine, as the α-KG-activated GPCR (Oxgr1) increased on the PP-IC apical surface, allowing paracrine delivery of α-KG to stimulate salt transport. Identification of the integrated compensatory NaCl reabsorption mechanisms provides insight into thiazide diuretic efficacy.

Integrated compensatory network is activated in the absence of NCC phosphorylation

PubMed Central

Grimm, P. Richard; Lazo-Fernandez, Yoskaly; Delpire, Eric; Wall, Susan M.; Dorsey, Susan G.; Weinman, Edward J.; Coleman, Richard; Wade, James B.; Welling, Paul A.

2015-01-01

Thiazide diuretics are used to treat hypertension; however, compensatory processes in the kidney can limit antihypertensive responses to this class of drugs. Here, we evaluated compensatory pathways in SPAK kinase–deficient mice, which are unable to activate the thiazide-sensitive sodium chloride cotransporter NCC (encoded by Slc12a3). Global transcriptional profiling, combined with biochemical, cell biological, and physiological phenotyping, identified the gene expression signature of the response and revealed how it establishes an adaptive physiology. Salt reabsorption pathways were created by the coordinate induction of a multigene transport system, involving solute carriers (encoded by Slc26a4, Slc4a8, and Slc4a9), carbonic anhydrase isoforms, and V-type H+-ATPase subunits in pendrin-positive intercalated cells (PP-ICs) and ENaC subunits in principal cells (PCs). A distal nephron remodeling process and induction of jagged 1/NOTCH signaling, which expands the cortical connecting tubule with PCs and replaces acid-secreting α-ICs with PP-ICs, were partly responsible for the compensation. Salt reabsorption was also activated by induction of an α-ketoglutarate (α-KG) paracrine signaling system. Coordinate regulation of a multigene α-KG synthesis and transport pathway resulted in α-KG secretion into pro-urine, as the α-KG–activated GPCR (Oxgr1) increased on the PP-IC apical surface, allowing paracrine delivery of α-KG to stimulate salt transport. Identification of the integrated compensatory NaCl reabsorption mechanisms provides insight into thiazide diuretic efficacy. PMID:25893600

Gene expression of commensal Lactobacillus johnsonii strain NCC533 during in vitro growth and in the murine gut.

PubMed

Denou, Emmanuel; Berger, Bernard; Barretto, Caroline; Panoff, Jean-Michel; Arigoni, Fabrizio; Brüssow, Harald

2007-11-01

Work with pathogens like Vibrio cholerae has shown major differences between genes expressed in bacteria grown in vitro and in vivo. To explore this subject for commensals, we investigated the transcription of the Lactobacillus johnsonii NCC533 genome during in vitro and in vivo growth using the microarray technology. During broth growth, 537, 626, and 277 of the 1,756 tested genes were expressed during exponential phase, "adaptation" (early stationary phase), and stationary phase, respectively. One hundred one, 150, and 33 genes, respectively, were specifically transcribed in these three phases. To explore the in vivo transcription program, we fed L. johnsonii containing a resistance plasmid to antibiotic-treated mice. After a 2-day washout phase, we determined the viable-cell counts of lactobacilli that were in the lumina and associated with the mucosae of different gut segments. While the cell counts showed a rather uniform distribution along the gut, we observed marked differences with respect to the expression of the Lactobacillus genome. The largest number of transcribed genes was in the stomach (n = 786); the next-largest numbers occurred in the cecum (n = 391) and the jejunum (n = 296), while only 26 Lactobacillus genes were transcribed in the colon. In vitro and in vivo transcription programs overlapped only partially. One hundred ninety-one of the transcripts from the lactobacilli in the stomach were not detected during in vitro growth; 202 and 213 genes, respectively, were transcribed under all in vitro and in vivo conditions; but the core transcriptome for all growth conditions comprised only 103 genes. Forty-four percent of the NCC533 genes were not detectably transcribed under any of the investigated conditions. Nontranscribed genes were clustered on the genome and enriched in the variable-genome part. Our data revealed not only major differences between in vitro- and in vivo-expressed genes in a Lactobacillus gut commensal organism but also marked

ENEL power generation and transmission control (PGTC) system

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

Galli, F.; Schiavi

1986-08-01

The ENEL (Italian State Power Board) PGTC System has a multi-level architecture which consists of a National Control Center (NCC), eight Area Control Centers (ACC), and Remote Terminal Units (RTU). Remote Control Centers (RCC), representing the third hierarchical level of the control system, will be integrated into the system beginning in 1987. This paper describes the structure of the PGTC system from the remote stations up to the NCC and the main control functions. The method of implementation, the organizational and managerial problems that were faced in the development of the project are also described.

Assessment of the Partially Resolved Numerical Simulation (PRNS) Approach in the National Combustion Code (NCC) for Turbulent Nonreacting and Reacting Flows

NASA Technical Reports Server (NTRS)

Shih, Tsan-Hsing; Liu, Nan-Suey

2008-01-01

This paper describes an approach which aims at bridging the gap between the traditional Reynolds-averaged Navier-Stokes (RANS) approach and the traditional large eddy simulation (LES) approach. It has the characteristics of the very large eddy simulation (VLES) and we call this approach the partially-resolved numerical simulation (PRNS). Systematic simulations using the National Combustion Code (NCC) have been carried out for fully developed turbulent pipe flows at different Reynolds numbers to evaluate the PRNS approach. Also presented are the sample results of two demonstration cases: nonreacting flow in a single injector flame tube and reacting flow in a Lean Direct Injection (LDI) hydrogen combustor.

Intraventricular Neurocysticercosis: Experience and Long-Term Outcome from a Tertiary Referral Center in the United States.

PubMed

Nash, Theodore E; Ware, JeanAnne M; Mahanty, Siddhartha

2018-04-23

Ventricular involvement in neurocysticercosis (NCC), a common serious manifestation of NCC, has distinct clinical presentations, complications, and treatments primarily because of partial or complete obstruction of the cerebrospinal fluid (CSF) flow by Taenia solium cysts. We review the clinical course, treatments, and long-term outcomes in 23 of 121 (19.0%) total NCC patients with ventricular cysts referred to the National Institutes of Health from 1985 to the October 2017. Patients had a median age of 31.8 (range: 22.4-52.6 years), were 60.9% male, diagnosed a median of 6.5 years (range: 0.17-16 years) after immigration, and were followed for a median of 3.6 years (range: 0.1-30.5 years). Other forms and manifestations of NCC were present in 73.9% (17/23). The fourth ventricle was involved in a majority (15/23, 65.2%) resulting in hydrocephalus (73.9%), ventriculitis, and periventricular edema (7/23, 30.4%). Cystectomy was accomplished in 60.9%, usually by removal of a fourth ventricular cyst through a suboccipital craniotomy. Nonresectable cysts were treated medically. Ventriculoperitoneal shunts were inserted in 43.5% (10/23) and failed in four, three from infection. Other complications included surgically induced injuries (4/23, 17.4%) and entrapment of a lateral ventricle (2/23, 8.7%). Despite a common severe early course, 90.9% (20/22) stabilized without recurrence, 15% (3/20) complained of mild-to-moderate neurological complaints, and 15% (3/20) were significantly disabled. Four patients who underwent removal of ventricular cysts without significant other NCC and who received with no cysticidal treatment became CSF cestode antigen negative without recurrence indicating that after successful extraction of cysts, additional cysticidal treatment may not be needed.

Modification of the technical properties of Lactobacillus johnsonii NCC 533 by supplementing the growth medium with unsaturated fatty acids.

PubMed

Muller, J A; Ross, R P; Sybesma, W F H; Fitzgerald, G F; Stanton, C

2011-10-01

The aim of this study was to investigate the influence of supplementing growth medium with unsaturated fatty acids on the technical properties of the probiotic strain Lactobacillus johnsonii NCC 533, such as heat and acid tolerance, and inhibition of Salmonella enterica serovar Typhimurium infection. Our results showed that the membrane composition and morphology of L. johnsonii NCC 533 were significantly changed by supplementing a minimal Lactobacillus medium with oleic, linoleic, and linolenic acids. The ratio of saturated to unsaturated plus cyclic fatty acids in the bacterial membrane decreased by almost 2-fold when minimal medium was supplemented with unsaturated fatty acids (10 μg/ml). The subsequent acid and heat tolerance of L. johnsonii decreased by 6- and 20-fold when the strain was grown in the presence of linoleic and linolenic acids, respectively, compared with growth in oleic acid (all at 10 μg/ml). Following acid exposure, significantly higher (P < 0.05) oleic acid content was detected in the membrane when growth medium was supplemented with linoleic or linolenic acid, indicating that saturation of the membrane fatty acids occurred during acid stress. Cell integrity was determined in real time during stressed conditions using a fluorescent viability kit in combination with flow cytometric analysis. Following heat shock (at 62.5°C for 5 min), L. johnsonii was unable to form colonies; however, 60% of the bacteria showed no cell integrity loss, which could indicate that the elevated heat inactivated vital processes within the cell, rendering it incapable of replication. Furthermore, L. johnsonii grown in fatty acid-enriched minimal medium had different adhesion properties and caused a 2-fold decrease in S. enterica serovar Typhimurium UK1-lux invasion of HT-29 epithelial cells compared with bacteria grown in minimal medium alone. This could be related to changes in the hydrophobicity and fluidity of the membrane. Our study shows that technical

Molecular insights from dysregulation of the thiazide-sensitive WNK/SPAK/NCC pathway in the kidney: Gordon syndrome and thiazide-induced hyponatraemia.

PubMed

Glover, Mark; O'Shaughnessy, Kevin M

2013-12-01

Human blood pressure is dependent on balancing dietary salt intake with its excretion by the kidney. Mendelian syndromes of altered blood pressure demonstrate the importance of the distal nephron in this process and of the thiazide-sensitive pathway in particular. Gordon syndrome (GS), the phenotypic inverse of the salt-wasting Gitelman syndrome, is a condition of hyperkalaemic hypertension that is reversed by low-dose thiazide diuretics or a low-salt diet. Variants within at least four genes [i.e. with-no-lysine(K) kinase 1 (WNK1), WNK4, kelch-like family member 3 (KLHL3) and cullin 3 (CUL3)] can cause the phenotype of GS. Details are still emerging for some of these genes, but it is likely that they all cause a gain-of-function in the thiazide-sensitive Na(+) -Cl(-) cotransporter (NCC) and hence salt retention. Herein, we discuss the key role of STE20/sporulation-specific protein 1 (SPS1)-related proline/alanine-rich kinase (SPAK), which functions as an intermediary between the WNKs and NCC and for which a loss-of-function mutation produces a Gitelman-type phenotype in a mouse model. In addition to Mendelian blood pressure syndromes, the study of patients who develop thiazide-induced-hyponatraemia (TIH) may give further molecular insights into the role of the thiazide-sensitive pathway for salt reabsorption. In the present paper we discuss the key features of TIH, including its high degree of reproducibility on rechallenge, possible genetic predisposition and mechanisms involving excessive saliuresis and water retention. Together, studies of Gordon syndrome and TIH may increase our understanding of the molecular regulation of sodium trafficking via the thiazide-sensitive pathway and have important implications for hypertensive patients, both in the identification of new antihypertensive drug targets and avoidance of hyponatraemic side-effects. © 2013 Wiley Publishing Asia Pty Ltd.

Numerical Simulations of Two-Phase Reacting Flow in a Single-Element Lean Direct Injection (LDI) Combustor Using NCC

NASA Technical Reports Server (NTRS)

Liu, Nan-Suey; Shih, Tsan-Hsing; Wey, C. Thomas

2011-01-01

A series of numerical simulations of Jet-A spray reacting flow in a single-element lean direct injection (LDI) combustor have been conducted by using the National Combustion Code (NCC). The simulations have been carried out using the time filtered Navier-Stokes (TFNS) approach ranging from the steady Reynolds-averaged Navier-Stokes (RANS), unsteady RANS (URANS), to the dynamic flow structure simulation (DFS). The sub-grid model employed for turbulent mixing and combustion includes the well-mixed model, the linear eddy mixing (LEM) model, and the filtered mass density function (FDF/PDF) model. The starting condition of the injected liquid spray is specified via empirical droplet size correlation, and a five-species single-step global reduced mechanism is employed for fuel chemistry. All the calculations use the same grid whose resolution is of the RANS type. Comparisons of results from various models are presented.

Modification of the Technical Properties of Lactobacillus johnsonii NCC 533 by Supplementing the Growth Medium with Unsaturated Fatty Acids ▿

PubMed Central

Muller, J. A.; Ross, R. P.; Sybesma, W. F. H.; Fitzgerald, G. F.; Stanton, C.

2011-01-01

The aim of this study was to investigate the influence of supplementing growth medium with unsaturated fatty acids on the technical properties of the probiotic strain Lactobacillus johnsonii NCC 533, such as heat and acid tolerance, and inhibition of Salmonella enterica serovar Typhimurium infection. Our results showed that the membrane composition and morphology of L. johnsonii NCC 533 were significantly changed by supplementing a minimal Lactobacillus medium with oleic, linoleic, and linolenic acids. The ratio of saturated to unsaturated plus cyclic fatty acids in the bacterial membrane decreased by almost 2-fold when minimal medium was supplemented with unsaturated fatty acids (10 μg/ml). The subsequent acid and heat tolerance of L. johnsonii decreased by 6- and 20-fold when the strain was grown in the presence of linoleic and linolenic acids, respectively, compared with growth in oleic acid (all at 10 μg/ml). Following acid exposure, significantly higher (P < 0.05) oleic acid content was detected in the membrane when growth medium was supplemented with linoleic or linolenic acid, indicating that saturation of the membrane fatty acids occurred during acid stress. Cell integrity was determined in real time during stressed conditions using a fluorescent viability kit in combination with flow cytometric analysis. Following heat shock (at 62.5°C for 5 min), L. johnsonii was unable to form colonies; however, 60% of the bacteria showed no cell integrity loss, which could indicate that the elevated heat inactivated vital processes within the cell, rendering it incapable of replication. Furthermore, L. johnsonii grown in fatty acid-enriched minimal medium had different adhesion properties and caused a 2-fold decrease in S. enterica serovar Typhimurium UK1-lux invasion of HT-29 epithelial cells compared with bacteria grown in minimal medium alone. This could be related to changes in the hydrophobicity and fluidity of the membrane. Our study shows that technical

Evaluating a medical error taxonomy.

PubMed

Brixey, Juliana; Johnson, Todd R; Zhang, Jiajie

2002-01-01

Healthcare has been slow in using human factors principles to reduce medical errors. The Center for Devices and Radiological Health (CDRH) recognizes that a lack of attention to human factors during product development may lead to errors that have the potential for patient injury, or even death. In response to the need for reducing medication errors, the National Coordinating Council for Medication Errors Reporting and Prevention (NCC MERP) released the NCC MERP taxonomy that provides a standard language for reporting medication errors. This project maps the NCC MERP taxonomy of medication error to MedWatch medical errors involving infusion pumps. Of particular interest are human factors associated with medical device errors. The NCC MERP taxonomy of medication errors is limited in mapping information from MEDWATCH because of the focus on the medical device and the format of reporting.

Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung’s Disease

PubMed Central

Gosain, Ankush; Barlow-Anacker, Amanda J.; Erickson, Chris S.; Pierre, Joseph F.; Heneghan, Aaron F.; Epstein, Miles L.; Kudsk, Kenneth A.

2015-01-01

Hirschsprung’s disease (HSCR) is characterized by aganglionosis from failure of neural crest cell (NCC) migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung’s-associated enterocolitis (HAEC), with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI) mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrB NCC-/-) resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P) 21–24, prior to histological signs of enterocolitis. We found that EdnrB NCC-/- display lymphopenia of their Peyer’s Patches, the major inductive site of GI mucosal immunity. EdnrB NCC-/- Peyer’s Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature) B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrB NCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrB NCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrB NCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrB NCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not

ITC field test memorandum for Independence National Historical Park.

DOT National Transportation Integrated Search

2000-12-01

This memorandum documents a field test conducted on October 26, 2000 in Philadelphia, PA for the proposed Independence Transportation Center (ITC). The ITC is a bus depot to support visitation to the National Constitution Center (NCC) and the Nationa...

The Role of Army National Guard Special Forces Domestically And in Special Operations Command - North

DTIC Science & Technology

2014-12-01

Domestic Cannabis Suppression Operations Support ...................20 4. Counterdrug-Related Training and Training LEA/Military Personnel...Forces Qualification Course. 3. Domestic Cannabis Suppression Operations Support The assistance provided to a law enforcement agency through aerial

32 CFR 298.2 - Organization.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONUS), Alaska, Hawaii, and Puerto Rico; the Defense Industrial Security Clearance Office (DISCO), Columbus, Ohio; the Personnel Investigations Center (PIC) and National Computer Center (NCC) in Baltimore, Maryland; Office of Industrial Security International Europe (OISI-E), located in Brussels, Belgium with a...

32 CFR 298.2 - Organization.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONUS), Alaska, Hawaii, and Puerto Rico; the Defense Industrial Security Clearance Office (DISCO), Columbus, Ohio; the Personnel Investigations Center (PIC) and National Computer Center (NCC) in Baltimore, Maryland; Office of Industrial Security International Europe (OISI-E), located in Brussels, Belgium with a...

32 CFR 298.2 - Organization.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONUS), Alaska, Hawaii, and Puerto Rico; the Defense Industrial Security Clearance Office (DISCO), Columbus, Ohio; the Personnel Investigations Center (PIC) and National Computer Center (NCC) in Baltimore, Maryland; Office of Industrial Security International Europe (OISI-E), located in Brussels, Belgium with a...

32 CFR 298.2 - Organization.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONUS), Alaska, Hawaii, and Puerto Rico; the Defense Industrial Security Clearance Office (DISCO), Columbus, Ohio; the Personnel Investigations Center (PIC) and National Computer Center (NCC) in Baltimore, Maryland; Office of Industrial Security International Europe (OISI-E), located in Brussels, Belgium with a...

32 CFR 298.2 - Organization.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONUS), Alaska, Hawaii, and Puerto Rico; the Defense Industrial Security Clearance Office (DISCO), Columbus, Ohio; the Personnel Investigations Center (PIC) and National Computer Center (NCC) in Baltimore, Maryland; Office of Industrial Security International Europe (OISI-E), located in Brussels, Belgium with a...

Developing a space network interface simulator: The NTS approach

NASA Technical Reports Server (NTRS)

Hendrzak, Gary E.

1993-01-01

This paper describes the approach used to redevelop the Network Control Center (NCC) Test System (NTS), a hardware and software facility designed to make testing of the NCC Data System (NCCDS) software efficient, effective, and as rigorous as possible prior to operational use. The NTS transmits and receives network message traffic in real-time. Data transfer rates and message content are strictly controlled and are identical to that of the operational systems. NTS minimizes the need for costly and time-consuming testing with the actual external entities (e.g., the Hubble Space Telescope (HST) Payload Operations Control Center (POCC) and the White Sands Ground Terminal). Discussed are activities associated with the development of the NTS, lessons learned throughout the project's lifecycle, and resulting productivity and quality increases.

NCI and the Chinese National Cancer Center pursue new collaborations in cancer research

Cancer.gov

CGH Director, Dr. Ted Trimble, and East Asia Program Director, Dr. Ann Chao, traveled to Beijing with Mr. Matthew Brown from the Department of Health and Human Services Office of Global Affairs to attend the Joint Meeting of the NCC and the U.S. NCI.

Current Status of Post-combustor Trace Chemistry Modeling and Simulation at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Wey, Thomas; Liu, Nan-Suey

2003-01-01

The overall objective of the current effort at NASA GRC is to evaluate, develop, and apply methodologies suitable for modeling intra-engine trace chemical changes over post combustor flow path relevant to the pollutant emissions from aircraft engines. At the present time, the focus is the high pressure turbine environment. At first, the trace chemistry model of CNEWT were implemented into GLENN-HT as well as NCC. Then, CNEWT, CGLENN-HT, and NCC were applied to the trace species evolution in a cascade of Cambridge University's No. 2 rotor and in a turbine vane passage. In general, the results from these different codes provide similar features. However, the details of some of the quantities of interest can be sensitive to the differences of these codes. This report summaries the implementation effort and presents the comparison of the No. 2 rotor results obtained from these different codes. The comparison of the turbine vane passage results is reported elsewhere. In addition to the implementation of trace chemistry model into existing CFD codes, several pre/post-processing tools that can handle the manipulations of the geometry, the unstructured and structured grids as well as the CFD solutions also have been enhanced and seamlessly tied with NCC, CGLENN-HT, and CNEWT. Thus, a complete CFD package consisting of pre/post-processing tools and flow solvers suitable for post-combustor intra-engine trace chemistry study is assembled.

Joint Counterdrug Operations

DTIC Science & Technology

1998-02-17

II-8 • Marijuana (Cannabis) Industry ................................................................................ II-9...High Intensity Drug Trafficking Areas ................................................................ III-26 • Organized Crime Drug Enforcement...IV-4 • Legal or Regulatory Considerations ....................................................................... IV-5 • Major

The Drug war: Diplomatic and Security Implications for Mexico and the United States

DTIC Science & Technology

2011-06-10

The PRI electoral gains will make it impossible for President Calderon to push significant reforms through without serious concessions to the PRI-if...August 2002), 5. 83 GLOSSARY Commission Nacional de Derechos Humanos (CNDH). Mexico’s National Commission on Human Rights. Counter-drug

The ambient noise and earthquake surface wave tomography of the North China Craton

NASA Astrophysics Data System (ADS)

Pan, J.; Obrebski, M. J.; Wu, Q.; Li, Y.

2010-12-01

The North China Craton (NCC) is unique for its unusual Phanerozoic tectonic activity. The NCC was internally tectonically stable until Jurassic when its southern margin collided with the Yangzte Craton. Subsequently, the eastern and central part of the NCC underwent distinctive evolutions during the Late Mesozoic and Cenozoic. In contrast to the Erdos block located in the western part of NCC and that seems to have preserved the typical features of a stable craton, the eastern NCC has experienced significant lithospheric thinning as evidenced by widespread magmatism activity and normal faulting, among other manifestations. The eastern part of the NCC is also one of the most seismically active intracontinental regions in the world. Here we focus on the region that comprises the North China Basin and the Yanshan-Taihang Mountains, two major tectonic units located to the east and in the center of the NCC, respectively. We combine ambient noise data and ballistic surface wave data recorded by the dense temporary seismic array deployed in the North China to obtain phase velocity maps at periods ranging from 5s to 60s. 1587 and 3667 ray paths were obtained from earthquake surface waves and ambient noise correlations, respectively. The phase velocity distribution was reconstructed with grid size 0.25x0.25 degrees and 0.5x0.5 degrees from ambient noise tomography and earthquake surface wave tomography. For periods shorter than 15s, the phase velocity variations are well correlated with the principal geological units in the NCC, with low-speed anomalies corresponding to the major sedimentary basins and high-speed anomalies coinciding with the main mountain ranges. Within the period range from 20s to 30s, the phase velocity variations seem to be related to the local variations of the crustal thickness. For the periods above 30s, the strength of the phase velocity variations decreases with increasing periods, which may imply that the uppermost mantle is much more homogeneous

HF Over-the-Horizon Radar System Performance Analysis

DTIC Science & Technology

2007-09-01

system. Figure 37. The AN/TPS-71 ROTHR Transmission Array (From [42]). 42 A project named “terrain mapping” ( TMAP ) was initiated to improve...application of these ROTHRs is to support counterdrug (CD) aircraft surveillance and interdiction. The immediate operational application of the TMAP

Department of Defense counterdrug technology development of non-intrusive inspection systems

NASA Astrophysics Data System (ADS)

Pennella, John J.

1997-02-01

The Naval Surface Warfare Center Dahlgren Division serves as the executive agent for the DoD's Contraband Detection and Cargo Container Inspection Technology Development Program. The goal of the DoD non-intrusive inspection (NII) program is to develop prototype equipment that can be used to inspect containers and vehicles, quickly and in large numbers without unnecessary delays in the movement of legitimate cargo. This paper summaries the past accomplishments of the program, current status, and future plans.

Is the US Investing Wisely in Latin America? Let Us Take a Closer Look at Ecuador

DTIC Science & Technology

2009-04-01

approximately $90 million to programs like the Andean Counterdrug Program, Child Survival and Health, Development Assistance, Economic Support Fund...Delamer, Goldstein, and Porn , p. 95. See also “Russia Warily Finesses China Ties,” Stratfor.com, www.cdi.org/russia/216­ 10.cfm, July 24, 2002

The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.

PubMed

Bercik, P; Park, A J; Sinclair, D; Khoshdel, A; Lu, J; Huang, X; Deng, Y; Blennerhassett, P A; Fahnestock, M; Moine, D; Berger, B; Huizinga, J D; Kunze, W; McLean, P G; Bergonzelli, G E; Collins, S M; Verdu, E F

2011-12-01

The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Methods  Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system. © 2011 Blackwell Publishing Ltd.

The Iranian National Geodata Revision Strategy and Realization Based on Geodatabase

NASA Astrophysics Data System (ADS)

Haeri, M.; Fasihi, A.; Ayazi, S. M.

2012-07-01

In recent years, using of spatial database for storing and managing spatial data has become a hot topic in the field of GIS. Accordingly National Cartographic Center of Iran (NCC) produces - from time to time - some spatial data which is usually included in some databases. One of the NCC major projects was designing National Topographic Database (NTDB). NCC decided to create National Topographic Database of the entire country-based on 1:25000 coverage maps. The standard of NTDB was published in 1994 and its database was created at the same time. In NTDB geometric data was stored in MicroStation design format (DGN) which each feature has a link to its attribute data (stored in Microsoft Access file). Also NTDB file was produced in a sheet-wise mode and then stored in a file-based style. Besides map compilation, revision of existing maps has already been started. Key problems of NCC are revision strategy, NTDB file-based style storage and operator challenges (NCC operators are almost preferred to edit and revise geometry data in CAD environments). A GeoDatabase solution for national Geodata, based on NTDB map files and operators' revision preferences, is introduced and released herein. The proposed solution extends the traditional methods to have a seamless spatial database which it can be revised in CAD and GIS environment, simultaneously. The proposed system is the common data framework to create a central data repository for spatial data storage and management.

Generating trunk neural crest from human pluripotent stem cells

PubMed Central

Huang, Miller; Miller, Matthew L.; McHenry, Lauren K.; Zheng, Tina; Zhen, Qiqi; Ilkhanizadeh, Shirin; Conklin, Bruce R.; Bronner, Marianne E.; Weiss, William A.

2016-01-01

Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior “cranial” NCC form craniofacial bone, whereas solely posterior “trunk” NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages. PMID:26812940

REMOVING COOL CORES AND CENTRAL METALLICITY PEAKS IN GALAXY CLUSTERS WITH POWERFUL ACTIVE GALACTIC NUCLEUS OUTBURSTS

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

Guo Fulai; Mathews, William G., E-mail: fulai@ucolick.or

2010-07-10

Recent X-ray observations of galaxy clusters suggest that cluster populations are bimodally distributed according to central gas entropy and are separated into two distinct classes: cool core (CC) and non-cool core (NCC) clusters. While it is widely accepted that active galactic nucleus (AGN) feedback plays a key role in offsetting radiative losses and maintaining many clusters in the CC state, the origin of NCC clusters is much less clear. At the same time, a handful of extremely powerful AGN outbursts have recently been detected in clusters, with a total energy {approx}10{sup 61}-10{sup 62} erg. Using two-dimensional hydrodynamic simulations, we showmore » that if a large fraction of this energy is deposited near the centers of CC clusters, which is likely common due to dense cores, these AGN outbursts can completely remove CCs, transforming them to NCC clusters. Our model also has interesting implications for cluster abundance profiles, which usually show a central peak in CC systems. Our calculations indicate that during the CC to NCC transformation, AGN outbursts efficiently mix metals in cluster central regions and may even remove central abundance peaks if they are not broad enough. For CC clusters with broad central abundance peaks, AGN outbursts decrease peak abundances, but cannot effectively destroy the peaks. Our model may simultaneously explain the contradictory (possibly bimodal) results of abundance profiles in NCC clusters, some of which are nearly flat, while others have strong central peaks similar to those in CC clusters. A statistical analysis of the sizes of central abundance peaks and their redshift evolution may shed interesting insights on the origin of both types of NCC clusters and the evolution history of thermodynamics and AGN activity in clusters.« less

Efficacy of Bifidobacterium breve NCC2950 against DSS-induced colitis is dependent on bacterial preparation and timing of administration.

PubMed

Hayes, C L; Natividad, J M M; Jury, J; Martin, R; Langella, P; Verdu, E F

2014-03-01

Probiotics have been proposed as a therapy for inflammatory bowel disease, but variations in strains, formulations, and protocols used in clinical trials have hindered the creation of guidelines for their use. Thus, preclinical insight into the mechanisms of specific probiotic strains and mode of administration would be useful to guide future clinical trial design. In this study, live, heat inactivated (HI), and spent culture medium preparations of the probiotic Bifidobacterium breve NCC2950 were administered to specific pathogen free C57BL/6 mice before or during colitis, as well as before colitis reactivation. Five days of 3.5% dextran sulphate sodium in drinking water was used to induce colitis. Pretreatment with live B. breve reduced disease severity, myeloperoxidase activity, microscopic damage, cytokine production, interleukin (IL)-12/IL-10 ratio, and lymphocyte infiltration in the colon. B. breve did not attenuate on-going colitis. After acute colitis, disease symptoms were normalised sooner with live and HI B. breve treatment; however, reactivation of colitis was not prevented. These findings indicate that the efficacy of a probiotic to modulate intestinal inflammation is dependent on the formulation as well as state of inflammation when administered. Overall, live B. breve was most efficacious in preventing acute colitis. Live and HI B. breve also promoted recovery from diarrhoea and colon bleeding after a bout of acute colitis.

Multimedia case management system implemented in Java

NASA Astrophysics Data System (ADS)

Stewart, Howard D.; Davis, Midge L.; Handy, Dale L.; Kvarfordt, Kent B.; Ford, Glenn

1999-01-01

Managing the timely access of information is a major challenge facing law enforcement agencies. One of the areas of greatest need is that of the case management process. During the course of FY98, the Office of National Drug Control Policy (ONDCP), the Counterdrug Technology Assessment Center (CTAC), the Idaho National Engineering and Environmental Laboratory (INEEL), and the Criminal Investigative Bureau (CIB) of the state of Idaho, created a Northwest testbed to develop and integrate a multimedia case management system. A system was developed to assist investigators in tracking and maintaining investigative cases and improving access to internal and external data resources. In this paper, we discuss the results of our case management system development and the ability to present state and federal information incorporating object oriented and multimedia techniques. We then outline our plans for future research and development.

76 FR 57981 - National Coal Council

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... DEPARTMENT OF ENERGY National Coal Council AGENCY: Department of Energy. ACTION: Notice of open meeting. SUMMARY: This notice announces a meeting of the National Coal Council (NCC). The Federal Advisory.... Presentation by Phil Ren on the Northeast Asia Coal Exchange Center. Presentation by Barry Worthington...

National Space Biomedical Research Institute

NASA Technical Reports Server (NTRS)

2001-01-01

This report outlines National Space Biomedical Research Institute (NSBRI) activities during FY 2001, the fourth year of the NSBRI's programs. It is prepared in accordance with Cooperative Agreement NCC 9-58 between NASA's Lyndon B. Johnson Space Center and Baylor College of Medicine (NSBRI).

GWAS for detecting QTL associated with Columnaris Disease in two rainbow trout breeding populations

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to prospect genomic regions that explain large portion of the additive genetic variance for resistance against Columnaris disease (CD) in rainbow trout. Two important aquaculture populations were investigated. The National Center for Cool and Cold Water Aquaculture (NCC...

National Guard Counterdrug Programs

DTIC Science & Technology

2001-02-14

comparisons to locate indoor Marijuana grows, outdoor infrastructure - Monitor activity at known sites - Meth labs, stash houses, marijuana grows - Real...Identifies key signatures of structures for indoor growth of cannabis - Vehiclelvessel surveillance * Video capabilities for evidence e Global Positioning...System Navigational Equipment - Identify marijuana locations for ground recovery Contact Information Voice (703) 607-5665 DSN Voice 327-5665 FAX (703

National Space Biomedical Research Institute

NASA Technical Reports Server (NTRS)

2004-01-01

This report outlines the National Space Biomedical Research Institute's (NSBRI) activities during FY 2004, the Institute's seventh year. It is prepared in accordance with Cooperative Agreement NCC 9-58 between NASA's Lyndon B. Johnson Space Center (JSC) and the Institute's lead institution, Baylor College of Medicine.

The Effect of Spray Initial Conditions on Heat Release and Emissions in LDI CFD Calculations (Preprint)

DTIC Science & Technology

2008-06-01

Shih, T.-H., Povinelli , L. A., Liu, N.-S and Chen, K.-H., (2000), “Generalized Wall Function for...J. Marek, T. D. Smith, N.-S. Liu, and L. A. Povinelli (NASA, Glenn Research Center, Cleveland, OH, “A Study of Hydrogen/Air Combustor Using NCC

A new model of the distal convoluted tubule

PubMed Central

Ko, Benjamin; Mistry, Abinash C.; Hanson, Lauren; Mallick, Rickta; Cooke, Leslie L.; Hack, Bradley K.; Cunningham, Patrick

2012-01-01

The Na+-Cl− cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney is a key determinant of Na+ balance. Disturbances in NCC function are characterized by disordered volume and blood pressure regulation. However, many details concerning the mechanisms of NCC regulation remain controversial or undefined. This is partially due to the lack of a mammalian cell model of the DCT that is amenable to functional assessment of NCC activity. Previously reported investigations of NCC regulation in mammalian cells have either not attempted measurements of NCC function or have required perturbation of the critical without a lysine kinase (WNK)/STE20/SPS-1-related proline/alanine-rich kinase regulatory pathway before functional assessment. Here, we present a new mammalian model of the DCT, the mouse DCT15 (mDCT15) cell line. These cells display native NCC function as measured by thiazide-sensitive, Cl−-dependent 22Na+ uptake and allow for the separate assessment of NCC surface expression and activity. Knockdown by short interfering RNA confirmed that this function was dependent on NCC protein. Similar to the mammalian DCT, these cells express many of the known regulators of NCC and display significant baseline activity and dimerization of NCC. As described in previous models, NCC activity is inhibited by appropriate concentrations of thiazides, and phorbol esters strongly suppress function. Importantly, they display release of WNK4 inhibition of NCC by small hairpin RNA knockdown. We feel that this new model represents a critical tool for the study of NCC physiology. The work that can be accomplished in such a system represents a significant step forward toward unraveling the complex regulation of NCC. PMID:22718890

Acute Insulin Stimulation Induces Phosphorylation of the Na-Cl Cotransporter in Cultured Distal mpkDCT Cells and Mouse Kidney

PubMed Central

Sohara, Eisei; Rai, Tatemitsu; Yang, Sung-Sen; Ohta, Akihito; Naito, Shotaro; Chiga, Motoko; Nomura, Naohiro; Lin, Shih-Hua; Vandewalle, Alain; Ohta, Eriko; Sasaki, Sei; Uchida, Shinichi

2011-01-01

The NaCl cotransporter (NCC) is essential for sodium reabsorption at the distal convoluted tubules (DCT), and its phosphorylation increases its transport activity and apical membrane localization. Although insulin has been reported to increase sodium reabsorption in the kidney, the linkage between insulin and NCC phosphorylation has not yet been investigated. This study examined whether insulin regulates NCC phosphorylation. In cultured mpkDCT cells, insulin increased phosphorylation of STE20/SPS1-related proline-alanine-rich kinase (SPAK) and NCC in a dose-dependent manner. This insulin-induced phosphorylation of NCC was suppressed in WNK4 and SPAK knockdown cells. In addition, Ly294002, a PI3K inhibitor, decreased the insulin effect on SPAK and NCC phosphorylation, indicating that insulin induces phosphorylation of SPAK and NCC through PI3K and WNK4 in mpkDCT cells. Moreover, acute insulin administration to mice increased phosphorylation of oxidative stress-responsive kinase-1 (OSR1), SPAK and NCC in the kidney. Time-course experiments in mpkDCT cells and mice suggested that SPAK is upstream of NCC in this insulin-induced NCC phosphorylation mechanism, which was confirmed by the lack of insulin-induced NCC phosphorylation in SPAK knockout mice. Moreover, insulin administration to WNK4 hypomorphic mice did not increase phosphorylation of OSR1, SPAK and NCC in the kidney, suggesting that WNK4 is also involved in the insulin-induced OSR1, SPAK and NCC phosphorylation mechanism in vivo. The present results demonstrated that insulin is a potent regulator of NCC phosphorylation in the kidney, and that WNK4 and SPAK are involved in this mechanism of NCC phosphorylation by insulin. PMID:21909387

The Thiazide-sensitive NaCl Cotransporter Is Targeted for Chaperone-dependent Endoplasmic Reticulum-associated Degradation*

PubMed Central

Needham, Patrick G.; Mikoluk, Kasia; Dhakarwal, Pradeep; Khadem, Shaheen; Snyder, Avin C.; Subramanya, Arohan R.; Brodsky, Jeffrey L.

2011-01-01

The thiazide-sensitive NaCl cotransporter (NCC, SLC12A3) mediates salt reabsorption in the distal nephron of the kidney and is the target of thiazide diuretics, which are commonly prescribed to treat hypertension. Mutations in NCC also give rise to Gitelman syndrome, a hereditary salt-wasting disorder thought in most cases to arise from impaired NCC biogenesis through enhanced endoplasmic reticulum-associated degradation (ERAD). Because the machinery that mediates NCC quality control is completely undefined, we employed yeast as a model heterologous expression system to identify factors involved in NCC degradation. We confirmed that NCC was a bona fide ERAD substrate in yeast, as the majority of NCC polypeptide was integrated into ER membranes, and its turnover rate was sensitive to proteasome inhibition. NCC degradation was primarily dependent on the ER membrane-associated E3 ubiquitin ligase Hrd1. Whereas several ER luminal chaperones were dispensable for NCC ERAD, NCC ubiquitination and degradation required the activity of Ssa1, a cytoplasmic Hsp70 chaperone. Compatible findings were observed when NCC was expressed in mammalian kidney cells, as the cotransporter was polyubiquitinated and degraded by the proteasome, and mammalian cytoplasmic Hsp70 (Hsp72) coexpression stimulated the degradation of newly synthesized NCC. Hsp70 also preferentially associated with the ER-localized NCC glycosylated species, indicating that cytoplasmic Hsp70 plays a critical role in selecting immature forms of NCC for ERAD. Together, these results provide the first survey of components involved in the ERAD of a mammalian SLC12 cation chloride cotransporter and provide a framework for future studies on NCC ER quality control. PMID:22027832

An Overview of Spray Modeling With OpenNCC and its Application to Emissions Predictions of a LDI Combustor at High Pressure

NASA Technical Reports Server (NTRS)

Raju, M. S.

2016-01-01

The open national combustion code (Open- NCC) is developed with the aim of advancing the current multi-dimensional computational tools used in the design of advanced technology combustors. In this paper we provide an overview of the spray module, LSPRAY-V, developed as a part of this effort. The spray solver is mainly designed to predict the flow, thermal, and transport properties of a rapidly evaporating multi-component liquid spray. The modeling approach is applicable over a wide-range of evaporating conditions (normal, superheat, and supercritical). The modeling approach is based on several well-established atomization, vaporization, and wall/droplet impingement models. It facilitates large-scale combustor computations through the use of massively parallel computers with the ability to perform the computations on either structured & unstructured grids. The spray module has a multi-liquid and multi-injector capability, and can be used in the calculation of both steady and unsteady computations. We conclude the paper by providing the results for a reacting spray generated by a single injector element with 600 axially swept swirler vanes. It is a configuration based on the next-generation lean-direct injection (LDI) combustor concept. The results include comparisons for both combustor exit temperature and EINOX at three different fuel/air ratios.

Coexistence of diploid, triploid and tetraploid crucian carp (Carassius auratus) in natural waters

PubMed Central

2011-01-01

Background Crucian carp (abbreviated CC) belongs to the genus of Carassius within the family of Cyprinidae. It has been one of the most important freshwater species for Chinese aquaculture and is especially abundant in the Dongting water system of Hunan province. CC used to be considered as all diploid forms. However, coexistence of diploid (abbreviated 2nCC), triploid (abbreviated 3nCC) and tetraploid crucian carp (abbreviated 4nCC) population of the Dongting water system was first found by our recently researches. Results We examined the ploidy level and compared biological characteristics in different ploidy CC. In reproductive mode, 2nCC was bisexual generative and 4nCC generated all-female offspring by gynogenesis. However, 3nCC generated progenies in two different ways. 3nCC produced bisexual triploid offspring fertilized with 3nCC spermatozoa, while it produced all-female triploid offspring by gynogenesis when its ova were activated by heterogenous spermatozoa. The complete mitochondrial DNA of three different ploidy fishes was sequenced and analyzed, suggesting no significant differences. Interestingly, microchromosomes were found only in 3nCC, which were concluded to be the result of hybridization. Allogenetic DNA fragments of Sox genes were obtained in 3nCC and 4nCC, which were absent in 2nCC. Phylogenetics analysis based on Sox4 gene indicated 3nCC and 4nCC formed a separate group from 2nCC. Conclusions In summary, this is the first report of the co-existence of three types of different ploidy crucian carps in natural waters in China. It was proved that the coexistence of different ploidy CC was reproductively maintained. We further hypothesized that 3nCC and 4nCC were allopolyploids that resulted from hybridization. The different ploidy CC population we obtained in this study possesses great significance for the study of polyploidization and the evolution of vertebrates. PMID:21276259

Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway.

PubMed

Feng, Xiuyan; Zhang, Yiqian; Shao, Ningjun; Wang, Yanhui; Zhuang, Zhizhi; Wu, Ping; Lee, Matthew J; Liu, Yingli; Wang, Xiaonan; Zhuang, Jieqiu; Delpire, Eric; Gu, Dingying; Cai, Hui

2015-05-15

Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in maintaining blood pressure. Aldosterone is known to modulate NCC abundance. Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To exclude the influence of SPAK signaling pathway on the role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we investigated the effects of dietary salt changes and aldosterone on NCC abundance in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet significantly increased total NCC abundance while reducing ERK1/2 phosphorylation, whereas high-salt diet decreased total NCC while increasing ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression, an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and reversed the aldosterone-mediated increments of NCC partly by increasing NCC ubiquitination. Therefore, these data suggest that aldosterone modulates NCC abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal pathway in SPAK KO mice and part of the effects of dietary salt changes may be mediated by aldosterone in the DCTs.

Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway

PubMed Central

Feng, Xiuyan; Zhang, Yiqian; Shao, Ningjun; Wang, Yanhui; Zhuang, Zhizhi; Wu, Ping; Lee, Matthew J.; Liu, Yingli; Wang, Xiaonan; Zhuang, Jieqiu; Delpire, Eric; Gu, Dingying

2015-01-01

Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in maintaining blood pressure. Aldosterone is known to modulate NCC abundance. Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To exclude the influence of SPAK signaling pathway on the role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we investigated the effects of dietary salt changes and aldosterone on NCC abundance in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet significantly increased total NCC abundance while reducing ERK1/2 phosphorylation, whereas high-salt diet decreased total NCC while increasing ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression, an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and reversed the aldosterone-mediated increments of NCC partly by increasing NCC ubiquitination. Therefore, these data suggest that aldosterone modulates NCC abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal pathway in SPAK KO mice and part of the effects of dietary salt changes may be mediated by aldosterone in the DCTs. PMID:25761881

Systems engineering technology for networks

NASA Technical Reports Server (NTRS)

1994-01-01

The report summarizes research pursued within the Systems Engineering Design Laboratory at Virginia Polytechnic Institute and State University between May 16, 1993 and January 31, 1994. The project was proposed in cooperation with the Computational Science and Engineering Research Center at Howard University. Its purpose was to investigate emerging systems engineering tools and their applicability in analyzing the NASA Network Control Center (NCC) on the basis of metrics and measures.

The receptor tyrosine kinase RET regulates hindgut colonization by sacral neural crest cells.

PubMed

Delalande, Jean-Marie; Barlow, Amanda J; Thomas, Aaron J; Wallace, Adam S; Thapar, Nikhil; Erickson, Carol A; Burns, Alan J

2008-01-01

The enteric nervous system (ENS) is formed from vagal and sacral neural crest cells (NCC). Vagal NCC give rise to most of the ENS along the entire gut, whereas the contribution of sacral NCC is mainly limited to the hindgut. This, and data from heterotopic quail-chick grafting studies, suggests that vagal and sacral NCC have intrinsic differences in their ability to colonize the gut, and/or to respond to signalling cues within the gut environment. To better understand the molecular basis of these differences, we studied the expression of genes known to be essential for ENS formation, in sacral NCC within the chick hindgut. Our results demonstrate that, as in vagal NCC, Sox10, EdnrB, and Ret are expressed in sacral NCC within the gut. Since we did not detect a qualitative difference in expression of these ENS genes we performed DNA microarray analysis of vagal and sacral NCC. Of 11 key ENS genes examined from the total data set, Ret was the only gene identified as being highly differentially expressed, with a fourfold increase in expression in vagal versus sacral NCC. We also found that over-expression of RET in sacral NCC increased their ENS developmental potential such that larger numbers of cells entered the gut earlier in development, thus promoting the fate of sacral NCC towards that of vagal NCC.

Hsp70 and Hsp90 Multichaperone Complexes Sequentially Regulate Thiazide-sensitive Cotransporter Endoplasmic Reticulum-associated Degradation and Biogenesis*

PubMed Central

Donnelly, Bridget F.; Needham, Patrick G.; Snyder, Avin C.; Roy, Ankita; Khadem, Shaheen; Brodsky, Jeffrey L.; Subramanya, Arohan R.

2013-01-01

The thiazide-sensitive NaCl cotransporter (NCC) is the primary mediator of salt reabsorption in the distal convoluted tubule and is a key determinant of the blood pressure set point. Given its complex topology, NCC is inefficiently processed and prone to endoplasmic reticulum (ER)-associated degradation (ERAD), although the mechanisms governing this process remain obscure. Here, we identify factors that impact the ER quality control of NCC. Analyses of NCC immunoprecipitates revealed that the cotransporter formed complexes with the core chaperones Hsp90, Hsp70, and Hsp40. Disruption of Hsp90 function accelerated NCC degradation, suggesting that Hsp90 promotes NCC folding. In addition, two cochaperones, the C terminus of Hsp70-interacting protein (CHIP) and the Hsp70/Hsp90 organizer protein, were associated with NCC. Although CHIP, an E3 ubiquitin ligase, promoted NCC ubiquitination and ERAD, the Hsp70/Hsp90 organizer protein stabilized NCC turnover, indicating that these two proteins differentially remodel the core chaperone systems to favor cotransporter degradation and biogenesis, respectively. Adjusting the folding environment in mammalian cells via reduced temperature enhanced NCC biosynthetic trafficking, increased Hsp90-NCC interaction, and diminished binding to Hsp70. In contrast, cotransporters harboring disease-causing mutations that impair NCC biogenesis failed to escape ERAD as efficiently as the wild type protein when cells were incubated at a lower temperature. Instead, these mutants interacted more strongly with Hsp70, Hsp40, and CHIP, consistent with a role for the Hsp70/Hsp40 system in selecting misfolded NCC for ERAD. Collectively, these observations indicate that Hsp70 and Hsp90 comprise two functionally distinct ER quality control checkpoints that sequentially monitor NCC biogenesis. PMID:23482560

Numerical Study of Outlet Boundary Conditions for Unsteady Turbulent Internal Flows Using the NCC

NASA Technical Reports Server (NTRS)

Liu, Nan-Suey; Shih, Tsan-Hsing

2009-01-01

This paper presents the results of studies on the outlet boundary conditions for turbulent internal flow simulations. Several outlet boundary conditions have been investigated by applying the National Combustion Code (NCC) to the configuration of a LM6000 single injector flame tube. First of all, very large eddy simulations (VLES) have been performed using the partially resolved numerical simulation (PRNS) approach, in which both the nonlinear and linear dynamic subscale models were employed. Secondly, unsteady Reynolds averaged Navier- Stokes (URANS) simulations have also been performed for the same configuration to investigate the effects of different outlet boundary conditions in the context of URANS. Thirdly, the possible role of the initial condition is inspected by using three different initial flow fields for both the PRNS/VLES simulation and the URANS simulation. The same grid is used for all the simulations and the number of mesh element is about 0.5 million. The main purpose of this study is to examine the long-time behavior of the solution as determined by the imposed outlet boundary conditions. For a particular simulation to be considered as successful under the given initial and boundary conditions, the solution must be sustainable in a physically meaningful manner over a sufficiently long period of time. The commonly used outlet boundary condition for steady Reynolds averaged Navier-Stokes (RANS) simulation is a fixed pressure at the outlet with all the other dependent variables being extrapolated from the interior. The results of the present study suggest that this is also workable for the URANS simulation of the LM6000 injector flame tube. However, it does not work for the PRNS/VLES simulation due to the unphysical reflections of the pressure disturbances at the outlet boundary. This undesirable situation can be practically alleviated by applying a simple unsteady convection equation for the pressure disturbances at the outlet boundary. The

A technique for production of nanocrystalline cellulose with a narrow size distribution

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

Bai, Wen; Holbery, James D.; Li, Kaichang

2009-02-01

Nanocrystalline cellulose (NCC) was prepared by sulfuric acid hydrolysis of microcrystalline cellulose. A differential centrifugation technique was studied to obtain NCC whiskers with a narrow size distribution. It was shown that the volume of NCC in different fractions had an inverse relationship with relative centrifugal force (RCF). The length of NCC whiskers was also fractionized by differential RCF. The aspect ratio of NCC in different fractions had a relatively narrow range. This technique provides an easy way of producing NCC whiskers with a narrow size distribution.

Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India.

PubMed

Prabhakaran, Vasudevan; Drevets, Douglas A; Ramajayam, Govindan; Manoj, Josephine J; Anderson, Michael P; Hanas, Jay S; Rajshekhar, Vedantam; Oommen, Anna; Carabin, Hélène

2017-06-01

Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches. Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients' samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications. Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to

A systematic review of the frequency of neurocyticercosis with a focus on people with epilepsy.

PubMed

Ndimubanzi, Patrick C; Carabin, Hélène; Budke, Christine M; Nguyen, Hai; Qian, Ying-Jun; Rainwater, Elizabeth; Dickey, Mary; Reynolds, Stephanie; Stoner, Julie A

2010-11-02

The objective of this study is to conduct a systematic review of studies reporting the frequency of neurocysticercosis (NCC) worldwide. PubMed, Commonwealth Agricultural Bureau (CAB) abstracts and 23 international databases were systematically searched for articles published from January 1, 1990 to June 1, 2008. Articles were evaluated for inclusion by at least two researchers focusing on study design and methods. Data were extracted independently using standardized forms. A random-effects binomial model was used to estimate the proportion of NCC among people with epilepsy (PWE). Overall, 565 articles were retrieved and 290 (51%) selected for further analysis. After a second analytic phase, only 4.5% of articles, all of which used neuroimaging for the diagnosis of NCC, were reviewed. Only two studies, both from the US, estimated an incidence rate of NCC using hospital discharge data. The prevalence of NCC in a random sample of village residents was reported from one study where 9.1% of the population harboured brain lesions of NCC. The proportion of NCC among different study populations varied widely. However, the proportion of NCC in PWE was a lot more consistent. The pooled estimate for this population was 29.0% (95%CI: 22.9%-35.5%). These results were not sensitive to the inclusion or exclusion of any particular study. Only one study has estimated the prevalence of NCC in a random sample of all residents. Hence, the prevalence of NCC worldwide remains unknown. However, the pooled estimate for the proportion of NCC among PWE was very robust and could be used, in conjunction with estimates of the prevalence and incidence of epilepsy, to estimate this component of the burden of NCC in endemic areas. The previously recommended guidelines for the diagnostic process and for declaring NCC an international reportable disease would improve the knowledge on the global frequency of NCC.

Thermal Stability of Oil Palm Empty Fruit Bunch (OPEFB) Nanocrystalline Cellulose: Effects of post-treatment of oven drying and solvent exchange techniques

NASA Astrophysics Data System (ADS)

Indarti, E.; Marwan; Wanrosli, W. D.

2015-06-01

Nanocrystallinecellulose (NCC) from biomass is a promising material with huge potentials in various applications. A big challenge in its utilization is the agglomeration of the NCC's during processing due to hydrogen bonding among the cellulose chains when in close proximity to each other. Obtaining NCC's in a non-agglomerated and non-aqueous condition is challenging. In the present work NCC's was isolated from oil palm empty fruit bunch (OPEFB) using TEMPO-oxidation reaction method. To obtain non-agglomerated and non-aqueous products, the NCC's underwent post-treatment using oven drying (OD) and solvent exchanged (SE) techniques. The thermal stability of all samples was determined from TGA and DTG profiles whilst FTIR was used to analyzethe chemical modifications that occurred under these conditions. NCC-SE has better thermal stability than the NCC-OD and its on-set degradation temperature and residue are also higher. FTIR analysis shows that NCC-SE has a slightly different chemical composition whereby the absorption band at 1300 cm-1 (due to C-O symmetric stretching) is absent as compared to NCC-OD indicating that in NCC-SE the carboxylate group is in acid form which contribute to its thermal stability

National Space Biomedical Research Institute

NASA Technical Reports Server (NTRS)

2003-01-01

This report outlines the activities of the National Space Biomedical Research Institute (NSBRI) during FY 2003, the sixth year of the NSBRI's programs. It is prepared in accordance with Cooperative Agreement NCC 9-58 between NASA's Lyndon B. Johnson Space Center (JSC) and the Institute's lead institution, Baylor College of Medicine.

National Combustion Code: Parallel Performance

NASA Technical Reports Server (NTRS)

Babrauckas, Theresa

2001-01-01

This report discusses the National Combustion Code (NCC). The NCC is an integrated system of codes for the design and analysis of combustion systems. The advanced features of the NCC meet designers' requirements for model accuracy and turn-around time. The fundamental features at the inception of the NCC were parallel processing and unstructured mesh. The design and performance of the NCC are discussed.

Use of Conventional U.S. Naval Forces to Conduct FID in Colombia

DTIC Science & Technology

2009-06-01

Estrategia Naval Contra el Narcoterrorismo, (Colombia, June 2007). http://www.armada.mil.co (accessed September 13, 2008), 3. 15...counter-drug and counter- terrorism operations. The Estrategia Naval Contra el Narcoterrorismo fills in the gaps left by these forces...Colombia’s Estrategia Naval Contra el Narcoterrorismo (Navy Strategy Against Narcoterrorism) of June 2007 outlines the navy’s plan to deny narco- terrorists

Clinical presentation of neurocysticercosis-related epilepsy.

PubMed

Duque, Kevin R; Burneo, Jorge G

2017-11-01

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and a major risk factor for seizures and epilepsy. Seizure types in NCC vary largely across studies and seizure semiology is poorly understood. We discuss here the studies regarding seizure types and seizure semiology in NCC, and examine the clinical presentation in patients with NCC and drug-resistant epilepsy. We also provide evidence of the role of MRI and EEG in the diagnosis of NCC-related epilepsy. Focal seizures are reported in 60-90% of patients with NCC-related epilepsy, and around 90% of all seizures registered prospectively are focal not evolving to bilateral tonic-clonic seizures. A great number of cases suggest that seizure semiology is topographically related to NCC lesions. Patients with hippocampal sclerosis and NCC have different clinical and neurophysiological characteristics than those with hippocampal sclerosis alone. Different MRI protocols have allowed to better differentiate NCC from other etiologies. Lesions' stages might account on the chances of finding an interictal epileptiform discharge. Studies pursuing the seizure onset in patients with NCC are lacking and they are specially needed to determine both whether the reported events of individual cases are seizures, and whether they are related to the NCC lesion or lesions. This article is part of a Special Issue entitled "Neurocysticercosis and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

Functional materials based on nanocrystalline cellulose

NASA Astrophysics Data System (ADS)

Surov, O. V.; Voronova, M. I.; Zakharov, A. G.

2017-10-01

The data on the synthesis of functional materials based on nanocrystalline cellulose (NCC) published over the past 10 years are analyzed. The liquid-crystal properties of NCC suspensions, methods of investigation of NCC suspensions and films, conditions for preserving chiral nematic structure in the NCC films after removal of the solvent and features of templated sol-gel synthesis of functional materials based on NCC are considered. The bibliography includes 106 references.

Analysis of Power Laws, Shape Collapses, and Neural Complexity: New Techniques and MATLAB Support via the NCC Toolbox

PubMed Central

Marshall, Najja; Timme, Nicholas M.; Bennett, Nicholas; Ripp, Monica; Lautzenhiser, Edward; Beggs, John M.

2016-01-01

Neural systems include interactions that occur across many scales. Two divergent methods for characterizing such interactions have drawn on the physical analysis of critical phenomena and the mathematical study of information. Inferring criticality in neural systems has traditionally rested on fitting power laws to the property distributions of “neural avalanches” (contiguous bursts of activity), but the fractal nature of avalanche shapes has recently emerged as another signature of criticality. On the other hand, neural complexity, an information theoretic measure, has been used to capture the interplay between the functional localization of brain regions and their integration for higher cognitive functions. Unfortunately, treatments of all three methods—power-law fitting, avalanche shape collapse, and neural complexity—have suffered from shortcomings. Empirical data often contain biases that introduce deviations from true power law in the tail and head of the distribution, but deviations in the tail have often been unconsidered; avalanche shape collapse has required manual parameter tuning; and the estimation of neural complexity has relied on small data sets or statistical assumptions for the sake of computational efficiency. In this paper we present technical advancements in the analysis of criticality and complexity in neural systems. We use maximum-likelihood estimation to automatically fit power laws with left and right cutoffs, present the first automated shape collapse algorithm, and describe new techniques to account for large numbers of neural variables and small data sets in the calculation of neural complexity. In order to facilitate future research in criticality and complexity, we have made the software utilized in this analysis freely available online in the MATLAB NCC (Neural Complexity and Criticality) Toolbox. PMID:27445842

Analysis of Power Laws, Shape Collapses, and Neural Complexity: New Techniques and MATLAB Support via the NCC Toolbox.

PubMed

Marshall, Najja; Timme, Nicholas M; Bennett, Nicholas; Ripp, Monica; Lautzenhiser, Edward; Beggs, John M

2016-01-01

Neural systems include interactions that occur across many scales. Two divergent methods for characterizing such interactions have drawn on the physical analysis of critical phenomena and the mathematical study of information. Inferring criticality in neural systems has traditionally rested on fitting power laws to the property distributions of "neural avalanches" (contiguous bursts of activity), but the fractal nature of avalanche shapes has recently emerged as another signature of criticality. On the other hand, neural complexity, an information theoretic measure, has been used to capture the interplay between the functional localization of brain regions and their integration for higher cognitive functions. Unfortunately, treatments of all three methods-power-law fitting, avalanche shape collapse, and neural complexity-have suffered from shortcomings. Empirical data often contain biases that introduce deviations from true power law in the tail and head of the distribution, but deviations in the tail have often been unconsidered; avalanche shape collapse has required manual parameter tuning; and the estimation of neural complexity has relied on small data sets or statistical assumptions for the sake of computational efficiency. In this paper we present technical advancements in the analysis of criticality and complexity in neural systems. We use maximum-likelihood estimation to automatically fit power laws with left and right cutoffs, present the first automated shape collapse algorithm, and describe new techniques to account for large numbers of neural variables and small data sets in the calculation of neural complexity. In order to facilitate future research in criticality and complexity, we have made the software utilized in this analysis freely available online in the MATLAB NCC (Neural Complexity and Criticality) Toolbox.

The probiotic Lactobacillus johnsonii NCC 533 produces high-molecular-mass inulin from sucrose by using an inulosucrase enzyme.

PubMed

Anwar, Munir A; Kralj, Slavko; van der Maarel, Marc J E C; Dijkhuizen, Lubbert

2008-06-01

Fructansucrase enzymes polymerize the fructose moiety of sucrose into levan or inulin fructans, with beta(2-6) and beta(2-1) linkages, respectively. The probiotic bacterium Lactobacillus johnsonii strain NCC 533 possesses a single fructansucrase gene (open reading frame AAS08734) annotated as a putative levansucrase precursor. However, (13)C nuclear magnetic resonance (NMR) analysis of the fructan product synthesized in situ revealed that this is of the inulin type. The ftf gene of L. johnsonii was cloned and expressed to elucidate its exact identity. The purified L. johnsonii protein was characterized as an inulosucrase enzyme, producing inulin from sucrose, as identified by (13)C NMR analysis. Thin-layer chromatographic analysis of the reaction products showed that InuJ synthesized, besides the inulin polymer, a broad range of fructose oligosaccharides. Maximum InuJ enzyme activity was observed in a pH range of 4.5 to 7.0, decreasing sharply at pH 7.5. InuJ exhibited the highest enzyme activity at 55 degrees C, with a drastic decrease at 60 degrees C. Calcium ions were found to have an important effect on enzyme activity and stability. Kinetic analysis showed that the transfructosylation reaction of the InuJ enzyme does not obey Michaelis-Menten kinetics. The non-Michaelian behavior of InuJ may be attributed to the oligosaccharides that were initially formed in the reaction and which may act as better acceptors than the growing polymer chain. This is only the second example of the isolation and characterization of an inulosucrase enzyme and its inulin (oligosaccharide) product from a Lactobacillus strain. Furthermore, this is the first Lactobacillus strain shown to produce inulin polymer in situ.

γ-Adducin Stimulates the Thiazide-sensitive NaCl Cotransporter

PubMed Central

Dimke, Henrik; San-Cristobal, Pedro; de Graaf, Mark; Lenders, Jacques W.; Deinum, Jaap; Hoenderop, Joost G.J.

2011-01-01

The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found that γ-adducin interacts with the NCC transporter. γ-Adducin colocalized with NCC to the distal convoluted tubule. 22Na+ uptake experiments in the Xenopus laevis oocyte showed that γ-adducin stimulated NCC activity in a dose-dependent manner, an effect that occurred upstream from With No Lysine (WNK) 4 kinase. The binding site of γ-adducin mapped to the N terminus of NCC and encompassed three previously reported phosphorylation sites. Supporting this site of interaction, competition with the N-terminal domain of NCC abolished the stimulatory effect of γ-adducin on the transporter. γ-Adducin failed to increase NCC activity when these phosphorylation sites were constitutively inactive or active. In addition, γ-adducin bound only to the dephosphorylated N terminus of NCC. Taken together, our observations suggest that γ-adducin dynamically regulates NCC, likely by amending the phosphorylation state, and consequently the activity, of the transporter. These data suggest that γ-adducin may influence BP homeostasis by modulating renal NaCl transport. PMID:21164023

Effective components of nurse-coordinated care to prevent recurrent coronary events: a systematic review and meta-analysis.

PubMed

Snaterse, Marjolein; Dobber, Jos; Jepma, Patricia; Peters, Ron J G; Ter Riet, Gerben; Boekholdt, S Matthijs; Buurman, Bianca M; Scholte op Reimer, Wilma J M

2016-01-01

Current guidelines on secondary prevention of cardiovascular disease recommend nurse-coordinated care (NCC) as an effective intervention. However, NCC programmes differ widely and the efficacy of NCC components has not been studied. To investigate the efficacy of NCC and its components in secondary prevention of coronary heart disease by means of a systematic review and meta-analysis of randomised controlled trials. 18 randomised trials (11 195 patients in total) using 15 components of NCC met the predefined inclusion criteria. These components were placed into three main intervention strategies: (1) risk factor management (13 studies); (2) multidisciplinary consultation (11 studies) and (3) shared decision making (10 studies). Six trials combined NCC components from all three strategies. In total, 30 outcomes were observed. We summarised observed outcomes in four outcome categories: (1) risk factor levels (16 studies); (2) clinical events (7 studies); (3) patient-perceived health (7 studies) and (4) guideline adherence (3 studies). Compared with usual care, NCC lowered systolic blood pressure (weighted mean difference (WMD) 2.96 mm Hg; 95% CI 1.53 to 4.40 mm Hg) and low-density lipoprotein cholesterol (WMD 0.23 mmol/L; 95% CI 0.10 to 0.36 mmol/L). NCC also improved smoking cessation rates by 25% (risk ratio 1.25; 95% CI 1.08 to 1.43). NCC demonstrated to have an effect on a small number of outcomes. NCC that incorporated blood pressure monitoring, cholesterol control and smoking cessation has an impact on the improvement of secondary prevention. Additionally, NCC is a heterogeneous concept. A shared definition of NCC may facilitate better comparisons of NCC content and outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The effect of nanocrystalline cellulose on flow properties of fiber crop aqueous suspension.

PubMed

Gharehkhani, Samira; Seyed Shirazi, Seyed Farid; Yarmand, Hooman; Montazer, Elham; Kazi, Salim Newaz; Ibrahim, Rushdan; Ashjaei, Mehdi; Zulkifli, Nurin Wahidah Binti Mohd; Rahmati, Sadegh

2018-03-15

Nanocrystalline cellulose (NCC) a nature-based material, has gained significant attentions for its unique properties. The present study aims to investigate the flow behavior of cellulosic suspension containing non-wood pulp fibers and NCC, by means of rheological and pressure drop measurements. The NCC sample was prepared by sulfuric acid hydrolysis from Acacia mangium fibers. The rheological properties of kenaf/NCC suspensions were studied using viscosity and yield stress measurements. The pressure drop properties of the suspension flow were studied with respect to variation in flow velocity (0.4 m/s-3.6 m/s) and the NCC concentration (70 mg/l and 150 mg/l). The pressure drop results showed that the pulp suspension containing 150 mg/l NCC had higher drag reduction than kenaf suspension alone. The present insights into the flow of pulp/NCC suspension provide a new data and promote the application of NCC in industries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway

PubMed Central

Fang, Yu-Wei; Yang, Sung-Sen; Cheng, Chih-Jen; Tseng, Min-Hua; Hsu, Hui-Min; Lin, Shih-Hua

2016-01-01

The mechanism by which chronic metabolic acidosis (CMA) regulates sodium (Na+)-chloride (Cl−) cotransporter (NCC) in the renal distal convoluted tubules remains unexplored. We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA. CMA was induced by NH4Cl in wild type mice (WTA mice), SPAK, and WNK4 knockout mice. The quantities of Ncc mRNA, expression of total NCC, phosphorylated (p)-NCC, SPAK and WNK4 in the kidneys as well as NCC inhibition with hydrochlorothiazide and Na+ balance were evaluated. Relative to WT mice, WTA mice had similar levels of Ncc mRNA, but increased expression of total and p-NCC, SPAK, and WNK4 and an exaggerated response to hydrochlorothiazide which could not be observed in SPAK or WNK4 knockout mice with CMA. In WTA mice, increased plasma renin activity, aldosterone and angiotensin II concentrations accompanied by a significantly negative Na+ balance. High Na+ diet abolished the enhanced NCC expression in WTA mice. Furthermore, an angiotensin II type 1 receptor blocker rather than a mineralocorticoid receptor antagonist exerted a marked inhibition on Na+ reabsorption and NCC phosphorylation in WTA mice. CMA increases WNK4-SPAK-dependent NCC phosphorylation and appears to be secondary to previous natriuresis with volume-dependent angiotensin II activation. PMID:26728390

A Systematic Review of the Frequency of Neurocyticercosis with a Focus on People with Epilepsy

PubMed Central

Ndimubanzi, Patrick C.; Carabin, Hélène; Budke, Christine M.; Nguyen, Hai; Qian, Ying-Jun; Rainwater, Elizabeth; Dickey, Mary; Reynolds, Stephanie; Stoner, Julie A.

2010-01-01

Background The objective of this study is to conduct a systematic review of studies reporting the frequency of neurocysticercosis (NCC) worldwide. Methods/Principal Findings PubMed, Commonwealth Agricultural Bureau (CAB) abstracts and 23 international databases were systematically searched for articles published from January 1, 1990 to June 1, 2008. Articles were evaluated for inclusion by at least two researchers focusing on study design and methods. Data were extracted independently using standardized forms. A random-effects binomial model was used to estimate the proportion of NCC among people with epilepsy (PWE). Overall, 565 articles were retrieved and 290 (51%) selected for further analysis. After a second analytic phase, only 4.5% of articles, all of which used neuroimaging for the diagnosis of NCC, were reviewed. Only two studies, both from the US, estimated an incidence rate of NCC using hospital discharge data. The prevalence of NCC in a random sample of village residents was reported from one study where 9.1% of the population harboured brain lesions of NCC. The proportion of NCC among different study populations varied widely. However, the proportion of NCC in PWE was a lot more consistent. The pooled estimate for this population was 29.0% (95%CI: 22.9%–35.5%). These results were not sensitive to the inclusion or exclusion of any particular study. Conclusion/Significance Only one study has estimated the prevalence of NCC in a random sample of all residents. Hence, the prevalence of NCC worldwide remains unknown. However, the pooled estimate for the proportion of NCC among PWE was very robust and could be used, in conjunction with estimates of the prevalence and incidence of epilepsy, to estimate this component of the burden of NCC in endemic areas. The previously recommended guidelines for the diagnostic process and for declaring NCC an international reportable disease would improve the knowledge on the global frequency of NCC. PMID:21072231

Face Recognition Vendor Test 2000: Evaluation Report

DTIC Science & Technology

2001-02-16

The biggest change in the facial recognition community since the completion of the FERET program has been the introduction of facial recognition products...program and significantly lowered system costs. Today there are dozens of facial recognition systems available that have the potential to meet...inquiries from numerous government agencies on the current state of facial recognition technology prompted the DoD Counterdrug Technology Development Program

Need for Cognitive Closure Modulates How Perceptual Decisions Are Affected by Task Difficulty and Outcome Relevance.

PubMed

Viola, Vanda; Tosoni, Annalisa; Brizi, Ambra; Salvato, Ilaria; Kruglanski, Arie W; Galati, Gaspare; Mannetti, Lucia

2015-01-01

The aim of this study was to assess the extent to which Need for Cognitive Closure (NCC), an individual-level epistemic motivation, can explain inter-individual variability in the cognitive effort invested on a perceptual decision making task (the random motion task). High levels of NCC are manifested in a preference for clarity, order and structure and a desire for firm and stable knowledge. The study evaluated how NCC moderates the impact of two variables known to increase the amount of cognitive effort invested on a task, namely task ambiguity (i.e., the difficulty of the perceptual discrimination) and outcome relevance (i.e., the monetary gain associated with a correct discrimination). Based on previous work and current design, we assumed that reaction times (RTs) on our motion discrimination task represent a valid index of effort investment. Task ambiguity was associated with increased cognitive effort in participants with low or medium NCC but, interestingly, it did not affect the RTs of participants with high NCC. A different pattern of association was observed for outcome relevance; high outcome relevance increased cognitive effort in participants with moderate or high NCC, but did not affect the performance of low NCC participants. In summary, the performance of individuals with low NCC was affected by task difficulty but not by outcome relevance, whereas individuals with high NCC were influenced by outcome relevance but not by task difficulty; only participants with medium NCC were affected by both task difficulty and outcome relevance. These results suggest that perceptual decision making is influenced by the interaction between context and NCC.

Evaluation and analysis of non-intrusive techniques for detecting illicit substances

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

Micklich, B.J.; Roche, C.T.; Fink, C.L.

1995-12-31

Argonne National Laboratory (ANL) and the Houston Advanced Research Center (HARC) have been tasked by the Counterdrug Technology Assessment Center of the Office of National Drug Control Policy to conduct evaluations and analyses of technologies for the non-intrusive inspection of containers for illicit substances. These technologies span the range of nuclear, X-ray, and chemical techniques used in nondestructive sample analysis. ANL has performed assessments of nuclear and X-ray inspection concepts and undertaken site visits with developers to understand the capabilities and the range of applicability of candidate systems. ANL and HARC have provided support to law enforcement agencies (LEAs), includingmore » participation in numerous field studies. Both labs have provided staff to assist in the Narcotics Detection Technology Assessment (NDTA) program for evaluating drug detection systems. Also, the two labs are performing studies of drug contamination of currency. HARC has directed technical evaluations of automated ballistics imaging and identification systems under consideration by law enforcement agencies. ANL and HARC have sponsored workshops and a symposium, and are participating in a Non-Intrusive Inspection Study being led by Dynamics Technology, Incorporated.« less

Long-term aldosterone administration increases renal Na+-Cl- cotransporter abundance in late distal convoluted tubule.

PubMed

Poulsen, Søren Brandt; Christensen, Birgitte Mønster

2017-09-01

Renal Na + -Cl - cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2). NCC activity can be stimulated by aldosterone administration, and the mechanism is assumed to depend on the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids that would otherwise occupy aldosterone receptors. Because 11β-HSD2 in rat may only be abundantly expressed in DCT2 cells and not in DCT1 cells, it has been speculated that aldosterone specifically stimulates NCC activity in DCT2 cells. In mice, however, it is debated if 11β-HSD2 is expressed in DCT2 cells. The present study examined whether aldosterone administration in mice stimulates NCC abundance and phosphorylation in DCT2 cells but not in DCT1 cells. B6/C57 male mice were administered 100 µg aldosterone·kg body weight -1 ·24 h -1 for 6 days and euthanized during isoflurane inhalation. Western blotting of whole kidney homogenate showed that aldosterone administration stimulated NCC and pT58-NCC abundances ( P < 0.001). In DCT1 cells, confocal microscopy detected no effect of the aldosterone administration on NCC and pT58-NCC abundances. By contrast, NCC and pT58-NCC abundances were stimulated by aldosterone administration in the middle of DCT2 ( P < 0.001 and <0.01, respectively) and at the junction between DCT2 and CNT ( P < 0.001 and <0.05, respectively). In contrast to rat, immunohistochemistry in mouse showed no/very weak 11β-HSD2 expression in DCT2 cells. Collectively, long-term aldosterone administration stimulates mouse NCC and pT58-NCC abundances in DCT2 cells and presumably not in DCT1 cells. Copyright © 2017 the American Physiological Society.

Estimating the Non-Monetary Burden of Neurocysticercosis in Mexico

PubMed Central

Bhattarai, Rachana; Budke, Christine M.; Carabin, Hélène; Proaño, Jefferson V.; Flores-Rivera, Jose; Corona, Teresa; Ivanek, Renata; Snowden, Karen F.; Flisser, Ana

2012-01-01

Background Neurocysticercosis (NCC) is a major public health problem in many developing countries where health education, sanitation, and meat inspection infrastructure are insufficient. The condition occurs when humans ingest eggs of the pork tapeworm Taenia solium, which then develop into larvae in the central nervous system. Although NCC is endemic in many areas of the world and is associated with considerable socio-economic losses, the burden of NCC remains largely unknown. This study provides the first estimate of disability adjusted life years (DALYs) associated with NCC in Mexico. Methods DALYs lost for symptomatic cases of NCC in Mexico were estimated by incorporating morbidity and mortality due to NCC-associated epilepsy, and morbidity due to NCC-associated severe chronic headaches. Latin hypercube sampling methods were employed to sample the distributions of uncertain parameters and to estimate 95% credible regions (95% CRs). Findings In Mexico, 144,433 and 98,520 individuals are estimated to suffer from NCC-associated epilepsy and NCC-associated severe chronic headaches, respectively. A total of 25,341 (95% CR: 12,569–46,640) DALYs were estimated to be lost due to these clinical manifestations, with 0.25 (95% CR: 0.12–0.46) DALY lost per 1,000 person-years of which 90% was due to NCC-associated epilepsy. Conclusion This is the first estimate of DALYs associated with NCC in Mexico. However, this value is likely to be underestimated since only the clinical manifestations of epilepsy and severe chronic headaches were included. In addition, due to limited country specific data, some parameters used in the analysis were based on systematic reviews of the literature or primary research from other geographic locations. Even with these limitations, our estimates suggest that healthy years of life are being lost due to NCC in Mexico. PMID:22363827

Mid-lithospheric discontinuity and its roles in the dynamic evolution of the craton-example from the North China Craton

NASA Astrophysics Data System (ADS)

Chen, Ling; Wei, Zigen; Jiang, Mingming; Ling, Yuan

2016-04-01

Mid-lithospheric discontinuity and its roles in the dynamic evolution of the craton - example from the North China Craton Ling Chen1,2, Zigen Wei3, Mingming Jiang1, Yuan Ling1 1. State Key Laboratory of Lithospheric Evolution, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029, China 2. CAS Center for Excellence in Tibetan Plateau Earth Sciences, Beijing100101, China 3. State Key Laboratory of Geodesy and Earth's Dynamics, Institute of Geodesy and Geophysics, Chinese Academy of Sciences, Wuhan 430077, China Detailed knowledge of lithospheric structure is essential for understanding the long-term evolution and dynamics of continents. We present an integrated lithospheric structural image along an E-W profile across the North China Craton (NCC) derived from the teleseismic data recorded at two dense seismic arrays in combination with other geophysical and geological observations. Our S- and P-receiver function images show substantial undulations of the lithosphere-asthenosphere boundary (LAB), from 60-100 km in the eastern NCC to ~160-200 km in the central-western NCC, and <150-km in the Qilian orogenic belt further to the west, accompanying marked lithospheric structural variations. This agrees with previous studies that suggest the occurrence of fundamental destruction in the eastern NCC but localized lithospheric thinning and modifications in the central-western NCC. A negative velocity discontinuity is identified at the depth of ~80-100 km within the thick lithosphere of the central-western NCC, spatially coincident with the top interface of a relatively low velocity layer in the overall high velocity mantle root imaged by surface wave tomography. Detailed data analyses show that this mid- or intra-lithospheric discontinuity has considerably larger S-to-P and P-to-S conversion amplitudes than the LAB below, which provides observational constraints to further decipher the origin of the discontinuity. Our imaging results corroborate

Reliability of Diagnostic Criteria for Neurocysticercosis for Patients with Ventricular Cystic Lesions or Granulomas: A systematic review.

PubMed

Bustos, Javier A; García, Hector H; Del Brutto, Oscar H

2017-09-01

Intraventricular neurocysticercosis (NCC) is a severe form of NCC requiring prompt diagnosis and treatment. We aimed to assess the reliability of the most recent version of diagnostic criteria for this form of NCC. Two systematic literature reviews were performed; one included case reports of patients with intraventricular cysticercosis and the other included case reports of patients with intraventricular cystic lesions or granulomas caused by infections other than NCC. All assessed cases were categorized according to the last revision of the long-standing Del Brutto's set of diagnostic criteria to determine its sensitivity, specificity, and predictive value for this form of NCC. The search disclosed 128 patients with intraventricular NCC and 41 with other infections. The set of diagnostic criteria classified as definitive NCC 93 cases with intraventricular NCC (sensitivity 72.7%, 95% CI, 63.9-79.9%), as well as four cases with other infections (specificity 90.2%, 95% CI, 75.9-96.8%). The positive and negative predictive values of the criteria were 0.96 (95% CI, 0.89-0.99) and 0.51 (95% CI, 0.39-0.63), respectively. The revised Del Brutto's set of diagnostic criteria for NCC is acceptably sensitive and highly specific for diagnosing patients with the ventricular form of the disease.

Cochleovestibular nerve development is integrated with migratory neural crest cells

PubMed Central

Sandell, Lisa L.; Butler Tjaden, Naomi E.; Barlow, Amanda J.; Trainor, Paul A.

2015-01-01

The cochleovestibular (CV) nerve, which connects the inner ear to the brain, is the nerve that enables the senses of hearing and balance. The aim of this study was to document the morphological development of the mouse CV nerve with respect to the two embryonic cells types that produce it, specifically, the otic vesicle-derived progenitors that give rise to neurons, and the neural crest cell (NCC) progenitors that give rise to glia. Otic tissues of mouse embryos carrying NCC lineage reporter transgenes were whole mount immunostained to identify neurons and NCC. Serial optical sections were collected by confocal microscopy and were compiled to render the three dimensional (3D) structure of the developing CV nerve. Spatial organization of the NCC and developing neurons suggest that neuronal and glial populations of the CV nerve develop in tandem from early stages of nerve formation. NCC form a sheath surrounding the CV ganglia and central axons. NCC are also closely associated with neurites projecting peripherally during formation of the vestibular and cochlear nerves. Physical ablation of NCC in chick embryos demonstrates that survival or regeneration of even a few individual NCC from ectopic positions in the hindbrain results in central projection of axons precisely following ectopic pathways made by regenerating NCC. PMID:24252775

Regulation of the renal Na+-Cl− cotransporter by phosphorylation and ubiquitylation

PubMed Central

2012-01-01

The activity of the renal thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubule plays a key role in defining arterial blood pressure levels. Increased or decreased activity of the NCC is associated with arterial hypertension or hypotension, respectively. Thus it is of major interest to understand the activity of NCC using in vivo models. Phosphorylation of certain residues of the amino-terminal domain of NCC has been shown to be associated with its activation. The development of phospho-specific antibodies against these sites provides a powerful tool that is helping to increase our understanding of the molecular physiology of NCC. Additionally, NCC expression in the plasma membrane is modulated by ubiquitylation, which represents another major mechanism for regulating protein activity. This work presents a review of our current knowledge of the regulation of NCC activity by phosphorylation and ubiquitylation. PMID:23034942

Neurocysticercosis as an infectious acquired epilepsy worldwide.

PubMed

Reddy, Doodipala Samba; Volkmer, Randy

2017-11-01

Aside from brain injury and genetic causes, there is emerging information on brain infection and inflammation as a common cause of epilepsy. Neurocysticercosis (NCC), the most common cause of epilepsy worldwide, is caused by brain cysts from the Taenia solium tapeworm. In this article, we provide a critical analysis of current and emerging information on the relationship between NCC infection and epilepsy occurrence. We searched PubMed and other databases for reports on the prevalence of NCC and incidence of epilepsy in certain regions worldwide. NCC is caused by brain cysts from the T. solium and related tapeworms. Many people with NCC infection may develop epilepsy but the rates are highly variable. MRI imaging shows many changes including localization of cysts as well as the host response to treatment. Epilepsy, in a subset of NCC patients, appears to be due to hippocampal sclerosis. Serologic and brain imaging profiles are likely diagnostic biomarkers of NCC infection and are also used to monitor the course of treatments. Limited access to these tools is a key limitation to identify and treat NCC-related epilepsy in places with high prevalence of this parasite infestation. Overall, NCC is a common infection in many patients with epilepsy worldwide. Additional clinical and animal studies could confirm common pathology of NCC as a postinfectious epilepsy that is curable. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Box-Behnken design for extraction optimization of crude polysaccharides from Tunisian Phormidium versicolor cyanobacteria (NCC 466): Partial characterization, in vitro antioxidant and antimicrobial activities.

PubMed

Belhaj, Dalel; Frikha, Donyez; Athmouni, Khaled; Jerbi, Bouthaina; Ahmed, Mohammad Boshir; Bouallagui, Zouhaier; Kallel, Monem; Maalej, Sami; Zhou, John; Ayadi, Habib

2017-12-01

In this study, response surface methodology (RSM) based on Box-Behnken design (BBD) was employed to optimize the aqueous extraction of crude polysaccharides from Tunisian cyanobacteria Phormidium versicolor (NCC 466). The optimal extraction conditions with an extraction yield of 21.56±0.92% were as follows: extraction temperature at 81.05°C, extraction time of 3.99h, and water to raw material ratio of 21.52mLg -1 . Crude Phormidium versicolor polysaccharides (CPv-PS) are found to be a hetero-sulfated-anionic polysaccharides that contained carbohydrate (79.37±1.58%), protein (0.45±0.11%), uronic acids (4.37±0.19%) and sulfate (6.83±0.28%). The carbohydrate fraction was composed of arabinose, xylose, ribose, rhamnose, N-acetyl glucosamine, galactose, glucose, mannose, glucuronic acid and saccharose with corresponding mole percentages of 2.41, 14.58, 2.18, 6.23, 7.04, 28.21, 26.04, 3.02, 0.86 and 5.07, respectively. Evaluation of the antioxidant activity in vitro suggested that CPv-PS strongly scavenged radicals, prevented bleaching of β-carotene and reduced activity. Furthermore, the CPv-PS exhibited effective antimicrobial properties. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Improving first-time donor attendance rates through the use of enhanced donor preparation materials.

PubMed

Masser, Barbara; France, Christopher R; Foot, Jayne; Rozsa, Amy; Hayman, Jane; Waller, Daniel; Hunder, Everard

2016-06-01

Many nondonors are positive about blood donation and this motivates booking an appointment to donate. However, as their appointment approaches barriers to donating-such as anxiety-may become salient and deter attendance. Building on research of France and colleagues demonstrating the positive effect of enhanced preparation materials on donor recruitment, this study sought to determine whether these materials could effectively boost first donation appointment attendance. A field study comprising a 3 (brochure: none, e-mail, hard copy) × 2 (national call center [NCC] contact: none, call) between-subjects design was conducted with 3646 nondonors who had scheduled their first appointment. Participants in the brochure conditions received either a hard copy or an e-mailed link to electronic materials modeled on the donor preparation research of France and colleagues. Participants in the NCC call condition also received a call scripted in line with these preparation materials. The key outcome was new donor attendance rate. Although first-appointment attendance rates were high in the control (no additional contact) condition at 85.07% of those not canceling in advance, dual exposure to the preparation materials through a NCC call and an electronic brochure boosted attendance. The relative risk of attending in the NCC call and electronic brochure condition was 1.0836 (95% confidence interval, 1.0352-1.1343; p = 0.0006), with attendance 8.36% higher than in the control. This gain in attendance came at a relative increase in recruitment costs of 2%. The use of tailored communication to address new donors' concerns and prepare them for donating bolsters attendance rates. © 2016 AABB.

The Relationship of Community-based Nurse Care Coordination to Costs in the Medicare and Medicaid Programs

PubMed Central

Marek, Karen Dorman; Adams, Scott J.; Stetzer, Frank; Popejoy, Lori; Rantz, Marilyn

2011-01-01

The purpose of this evaluation was to study the relationship of nurse care coordination (NCC) to the costs of Medicare and Medicaid in a community-based care program called Missouri Care Options (MCO). A retrospective cohort design was used comparing 57 MCO clients with NCC to 80 MCO clients without NCC. Total cost was measured using Medicare and Medicaid claims databases. Fixed effects analysis was used to estimate the relationship of the NCC intervention to costs. Controlling for high resource use on admission, monthly Medicare costs were lower ($686) in the 12 months of NCC intervention (p =.04) while Medicaid costs were higher ($203; p=.03) for the NCC group when compared to the costs of MCO group. PMID:20499393

Hydrophobic kenaf nanocrystalline cellulose for the binding of curcumin.

PubMed

Zainuddin, Norhidayu; Ahmad, Ishak; Kargarzadeh, Hanieh; Ramli, Suria

2017-05-01

Nanocrystalline cellulose (NCC) extracted from lignocellulosic materials has been actively investigated as a drug delivery excipients due to its large surface area, high aspect ratio, and biodegradability. In this study, the hydrophobically modified NCC was used as a drug delivery excipient of hydrophobic drug curcumin. The modification of NCC with a cationic surfactant, cetyl trimethylammonium bromide (CTAB) was used to modulate the loading of hydrophobic drugs that would not normally bind to NCC. The FTIR, Elemental analysis, XRD, TGA, and TEM were used to confirm the modification of NCC with CTAB. The effect of concentration of CTAB on the binding efficiency of hydrophobic drug curcumin was investigated. The amounts of curcumin bound onto the CTAB-NCC nanoparticles were analyzed by UV-vis Spectrophotometric. The result showed that the modified CTAB-NCC bound a significant amount of curcumin, in a range from 80% to 96% curcumin added. Nevertheless, at higher concentration of CTAB resulted in lower binding efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Attacking Transnational Organized Criminal Networks: Applying Principles of Irregular Warfare to an Emerging Salient Threat

DTIC Science & Technology

2014-12-04

of anonymity. 6 The environmental frame of this monograph expands on the Title 10 and NDAA authorities that frame DoD counterdrug support to...36 United Nations Office on Drugs and Crime, The Globalization of Crime, 131. Smuggling of environmental resources constitutes a growing illicit...initial context for an examination of the DoD CD mission. In 1986, in response to increased trafficking of Colombian cocaine into the United States

Other Than War: The American Military Experience and Operations in the Post-Cold War Decade

DTIC Science & Technology

2013-01-01

drugs" did not seem to legitimize the en - terprise within the military services that viewed counter-drug operations as outside the normal scope of their... immigration generated considerable work for United States Southern Command was head- quartered first in Panama and by the end of the decade in...1994-1995 immigrant interdiction (Cubans) Sustain Liberty 1994-1997 defense/security During the decade, other Caribbean countries, particularly Cuba

Protein Phosphatase 1 Inhibitor-1 Deficiency Reduces Phosphorylation of Renal NaCl Cotransporter and Causes Arterial Hypotension

PubMed Central

Picard, Nicolas; Trompf, Katja; Yang, Chao-Ling; Miller, R. Lance; Carrel, Monique; Loffing-Cueni, Dominique; Fenton, Robert A.; Ellison, David H.

2014-01-01

The thiazide-sensitive NaCl cotransporter (NCC) of the renal distal convoluted tubule (DCT) controls ion homeostasis and arterial BP. Loss-of-function mutations of NCC cause renal salt wasting with arterial hypotension (Gitelman syndrome). Conversely, mutations in the NCC-regulating WNK kinases or kelch-like 3 protein cause familial hyperkalemic hypertension. Here, we performed automated sorting of mouse DCTs and microarray analysis for comprehensive identification of novel DCT-enriched gene products, which may potentially regulate DCT and NCC function. This approach identified protein phosphatase 1 inhibitor-1 (I-1) as a DCT-enriched transcript, and immunohistochemistry revealed I-1 expression in mouse and human DCTs and thick ascending limbs. In heterologous expression systems, coexpression of NCC with I-1 increased thiazide-dependent Na+ uptake, whereas RNAi-mediated knockdown of endogenous I-1 reduced NCC phosphorylation. Likewise, levels of phosphorylated NCC decreased by approximately 50% in I-1 (I-1−/−) knockout mice without changes in total NCC expression. The abundance and phosphorylation of other renal sodium-transporting proteins, including NaPi-IIa, NKCC2, and ENaC, did not change, although the abundance of pendrin increased in these mice. The abundance, phosphorylation, and subcellular localization of SPAK were similar in wild-type (WT) and I-1−/− mice. Compared with WT mice, I-1−/− mice exhibited significantly lower arterial BP but did not display other metabolic features of NCC dysregulation. Thus, I-1 is a DCT-enriched gene product that controls arterial BP, possibly through regulation of NCC activity. PMID:24231659

Nedd4-2 Modulates Renal Na+-Cl− Cotransporter via the Aldosterone-SGK1-Nedd4-2 Pathway

PubMed Central

Arroyo, Juan Pablo; Lagnaz, Dagmara; Ronzaud, Caroline; Vázquez, Norma; Ko, Benjamin S.; Moddes, Lauren; Ruffieux-Daidié, Dorothée; Hausel, Pierrette; Koesters, Robert; Yang, Baoli; Stokes, John B.; Hoover, Robert S.

2011-01-01

Regulation of renal Na+ transport is essential for controlling blood pressure, as well as Na+ and K+ homeostasis. Aldosterone stimulates Na+ reabsorption by the Na+-Cl− cotransporter (NCC) in the distal convoluted tubule (DCT) and by the epithelial Na+ channel (ENaC) in the late DCT, connecting tubule, and collecting duct. Aldosterone increases ENaC expression by inhibiting the channel's ubiquitylation and degradation; aldosterone promotes serum-glucocorticoid-regulated kinase SGK1-mediated phosphorylation of the ubiquitin-protein ligase Nedd4-2 on serine 328, which prevents the Nedd4-2/ENaC interaction. It is important to note that aldosterone increases NCC protein expression by an unknown post-translational mechanism. Here, we present evidence that Nedd4-2 coimmunoprecipitated with NCC and stimulated NCC ubiquitylation at the surface of transfected HEK293 cells. In Xenopus laevis oocytes, coexpression of NCC with wild-type Nedd4-2, but not its catalytically inactive mutant, strongly decreased NCC activity and surface expression. SGK1 prevented this inhibition in a kinase-dependent manner. Furthermore, deficiency of Nedd4-2 in the renal tubules of mice and in cultured mDCT15 cells upregulated NCC. In contrast to ENaC, Nedd4-2-mediated inhibition of NCC did not require the PY-like motif of NCC. Moreover, the mutation of Nedd4-2 at either serine 328 or 222 did not affect SGK1 action, and mutation at both sites enhanced Nedd4-2 activity and abolished SGK1-dependent inhibition. Taken together, these results suggest that aldosterone modulates NCC protein expression via a pathway involving SGK1 and Nedd4-2 and provides an explanation for the well-known aldosterone-induced increase in NCC protein expression. PMID:21852580

Three-Dimensional Rheological Structure of North China Craton Determined by Integration of Multiple observations: Controlling Role for Lithospheric Rifting

NASA Astrophysics Data System (ADS)

Xiong, X.; Shan, B.; Li, Y.

2017-12-01

The North China Craton (NCC) has undergone significant lithospheric rejuvenation in late Mesozoic and Cenozoic, one feature of which is the widespread extension and rifting. The extension is distinct between the two parts of NCC: widespread rifting in the eastern NCC and localized narrow rifting in the west. The mechanism being responsible for this difference is uncertain and highly debated. Since lithospheric deformation can be regarded as the response of lithosphere to various dynamic actions, the rheological properties of lithosphere must have a fundamental influence on its tectonics and deformation behavior. In this study, we investigated the 3D thermal and rheological structure of NCC by developing a model integrating several geophysical observables (such as surface heatflow, regional elevation, gravity and geoid anomalies, and seismic tomography models). The results exhibit obvious lateral variation in rheological structure between the eastern and western NCC. The overall lithospheric strength is higher in the western NCC than in the east. Despite of such difference in rheology, both parts of NCC are characterized by mantle dominated strength regime, which facilitates the development of narrow rifting. Using ancient heatflow derived from mantle xenoliths studies, and taking the subduction-related dehydration reactions during Mesozoic into account, we constructed the thermal and rheological structure of NCC in Ordovician, early Cretaceous and early Cenozoic. Combining the evidence from numerical simulations, we proposed an evolution path of the rifting in NCC. The lithosphere of NCC in Ordovician was characterized by a normal craton features: low geotherm, high strength and mantle dominated regime. During Jurassic and Cretaceous, the mantle lithosphere in the eastern NCC was hydrated by fluid released by the suduction of the Pacific plate, resulting in weakening of the lithosphere and a transition from mantle dominated to crust dominated regime, which

Synthesis and Development of Porous Polymeric Column Packing and Microchip Detectors for GC Analysis of Extraterrestrial Atmospheres

NASA Technical Reports Server (NTRS)

Shen, Thomas C.

1999-01-01

This report summarizes the last nine years research accomplishments under Cooperative Agreement NCC2-650 between NASA, Ames Research Center and SETI Institute. Four Major research tasks are conducted: 1. Gas chromatography column development. 2. Pyrosensor development. 3. Micro-machining gas chromatography instrument development. 4. Amino acid analysis and high molecular weight polyamino acid synthesis under prebiotic conditions. The following describes these results.

Magnetic fabrics and rock magnetism of the Xiong'er volcanic rocks and their implications for tectonic correlation of the North China Craton with other crustal blocks in the Nuna/Columbia supercontinent

NASA Astrophysics Data System (ADS)

Xu, Huiru; Yang, Zhenyu; Peng, Peng; Ge, Kunpeng; Jin, Zhenmin; Zhu, Rixiang

2017-08-01

The tectonic background of the Paleoproterozoic Xiong'er volcanic rocks (XVR) is important for understanding the tectonic evolution of the North China Craton (NCC), as well as its paleogeographic position during the assembly of the Nuna/Columbia supercontinent. Here we report the results of the first anisotropy of magnetic susceptibility (AMS) study of the XVR, and use the interpreted flow directions to constrain the emplacement mechanism and to assess its geological significance for the reconstruction of the Nuna/Columbia supercontinent. Thirty lavas were sampled from three sections in western Henan Province. Detailed rock magnetic analyses, including measurements of hysteresis loops, magnetization versus temperature curves and first order reverse curves, were performed to identify the main magnetic phases and grain sizes. The inferred directions from the AMS results reveal a radial flow pattern with an eruption center probably located near Xiong'er Mountain. Our data suggest that the XVR may have been emplaced in a triple-conjugated continental rift on the south margin of the NCC, probably initiated from a paleoplume. Based on this interpretation, a comparison of geological and paleomagnetic results among the proposed crustal blocks in the Nuna/Columbia supercontinent suggests a close linkage of the NCC with São Francisco-Congo, Rio de la Plate and Siberia.

Human neural crest cells display molecular and phenotypic hallmarks of stem cells

PubMed Central

Thomas, Sophie; Thomas, Marie; Wincker, Patrick; Babarit, Candice; Xu, Puting; Speer, Marcy C.; Munnich, Arnold; Lyonnet, Stanislas; Vekemans, Michel; Etchevers, Heather C.

2008-01-01

The fields of both developmental and stem cell biology explore how functionally distinct cell types arise from a self-renewing founder population. Multipotent, proliferative human neural crest cells (hNCC) develop toward the end of the first month of pregnancy. It is assumed that most differentiate after migrating throughout the organism, although in animal models neural crest stem cells reportedly persist in postnatal tissues. Molecular pathways leading over time from an invasive mesenchyme to differentiated progeny such as the dorsal root ganglion, the maxillary bone or the adrenal medulla are altered in many congenital diseases. To identify additional components of such pathways, we derived and maintained self-renewing hNCC lines from pharyngulas. We show that, unlike their animal counterparts, hNCC are able to self-renew ex vivo under feeder-free conditions. While cross species comparisons showed extensive overlap between human, mouse and avian NCC transcriptomes, some molecular cascades are only active in the human cells, correlating with phenotypic differences. Furthermore, we found that the global hNCC molecular profile is highly similar to that of pluripotent embryonic stem cells when compared with other stem cell populations or hNCC derivatives. The pluripotency markers NANOG, POU5F1 and SOX2 are also expressed by hNCC, and a small subset of transcripts can unambiguously identify hNCC among other cell types. The hNCC molecular profile is thus both unique and globally characteristic of uncommitted stem cells. PMID:18689800

Stereo- and Regioselective Phyllobilane Oxidation in Leaf Homogenates of the Peace Lily (Spathiphyllum wallisii): Hypothetical Endogenous Path to Yellow Chlorophyll Catabolites

PubMed Central

Vergeiner, Clemens; Ulrich, Markus; Li, Chengjie; Liu, Xiujun; Müller, Thomas; Kräutler, Bernhard

2015-01-01

In senescent leaves, chlorophyll typically is broken down to colorless and essentially photo-inactive phyllobilanes, which are linear tetrapyrroles classified as “nonfluorescent” chlorophyll catabolites (NCCs) and dioxobilane-type NCCs (DNCCs). In homogenates of senescent leaves of the tropical evergreen Spathiphyllum wallisii, when left at room temperature and extracted with methanol, the major endogenous, naturally formed NCC was regio- and stereoselectively oxidized (in part) to a mixture of its 15-hydroxy and 15-methoxy derivative. In the absence of methanol in the extract, only the 15-OH-NCC was observed. The endogenous oxidation process depended upon molecular oxygen. It was inhibited by carbon monoxide, as well as by keeping the leaf homogenate and extract at low temperatures. The remarkable “oxidative activity” was inactivated by heating the homogenate for 10 min at 70 °C. Upon addition of a natural epimeric NCC (epiNCC) to the homogenate of senescent or green Sp. wallisii leaves at room temperature, the exogenous epiNCC was oxidized regio- and stereoselectively to 15-OH-epiNCC and 15-OMe-epiNCC. The identical two oxidized epiNCCs were also obtained as products of the oxidation of epiNCC with dicyanodichlorobenzoquinone (DDQ). Water elimination from 15-OH-epiNCC occurred readily and gave a known “yellow” chlorophyll catabolite (YCC). The endogenous oxidation process, described here, may represent the elusive natural path from the colorless NCCs to yellow and pink coloured phyllobilins, which were found in (extracts of) some senescent leaves. PMID:25382809

STFM's National Clerkship Curriculum: CERA reveals impact, clerkship director needs.

PubMed

Cochella, Susan; Steiner, Beat D; Clinch, C Randall; WinklerPrins, Vince

2014-06-01

Consistency is needed in family medicine clerkships nationwide. The Society of Teachers of Family Medicine's (STFM) National Clerkship Curriculum (NCC) and supporting NCC website have been developed to address this need. A survey was used to measure these tools' effect and guide future improvements. The Council of Academic Family Medicine's (CAFM) Educational Research Alliance (CERA) 2012 survey of clerkship directors (CD) was used to answer two research questions: (1) To what extent are clerkships teaching the minimum core curriculum? and (2) What resources do clerkship directors identify as important in their role? The survey response rate was 66% (88/134). Ninety-two percent of these CDs are aware of the NCC, 74% report having visited the NCC website, and 71% plan to visit it more than once per year in the future. A total of 21.6% strongly agree that their clerkship content matches the NCC. CDs rate the quality of materials on the website as high and place greatest value on materials that can be downloaded and adapted to their clerkships. STFM's NCC website and materials are familiar to CDs although only one in five state their clerkship curriculum matches the NCC minimum core curriculum. The NCC editorial board needs to better understand why so few teach curriculum that closely matches the minimum core. Continued outreach to CDs can answer this question and improve our ability to support CDs as they incorporate the NCC into family medicine clerkships.

Isolation and characterization of nanocrystalline cellulose from roselle-derived microcrystalline cellulose.

PubMed

Kian, Lau Kia; Jawaid, Mohammad; Ariffin, Hidayah; Karim, Zoheb

2018-07-15

Roselle fiber is a renewable and sustainable agricultural waste enriched with cellulose polysaccharides. The isolation of Nanocrystalline cellulose (NCC) from roselle-derived microcrystalline cellulose (MCC) is an alternative approach to recover the agricultural roselle plant residue. In the present study, acid hydrolysis with different reaction time was carried out to degrade the roselle-derived MCC to form NCC. The characterizations of isolated NCC were conducted through Fourier Transform Infrared Ray (FTIR), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS), Energy Dispersive Spectroscopy (EDS), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). As evaluated from the performed morphological investigations, the needle-like shape NCC nanostructures were observed under TEM and AFM microscopy studies, while irregular rod-like shape of NCC was observed under FESEM analysis. With 60min hydrolysis time, XRD analysis demonstrated the highest NCC crystallinity degree with 79.5%. In thermal analysis by TGA and DSC, the shorter hydrolysis time tended to produce NCC with higher thermal stability. Thus, the isolated NCC from roselle-derived MCC has high potential to be used in application of pharmaceutical and biomedical fields for nanocomposite fabrication. Copyright © 2018 Elsevier B.V. All rights reserved.

Cell Biology of Thiazide Bone Effects

NASA Astrophysics Data System (ADS)

Gamba, Gerardo; Riccardi, Daniela

2008-09-01

The thiazide-sensitive Na+:Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian kidney. The activity of NCC is not only related to salt metabolism, but also to calcium and magnesium homeostasis due to the inverse relationship between NCC activity and calcium reabsorption. Hence, the thiazide-type diuretics that specifically block NCC have been used for years, not only for treatment of hypertension and edematous disease, but also for the management of renal stone disease. Epidemiological studies have shown that chronic thiazide treatment is associated with higher bone mineral density and reduced risk of bone fractures, which can only partly be explained in terms of their effects on the kidney. In this regard, we have recently shown that NCC is expressed in bone cells and that inhibition of NCC in bone, either by thiazides or by reduction of NCC protein with specific siRNA, is associated with increased mineralization in vitro. These observations open a field of study to begin to understand the cell biology of the beneficial effects of thiazides in bone.

The practice of pediatric neurocritical care by the child neurologist.

PubMed

Riviello, James J; Chang, Cherylee

2014-12-01

Pediatric neurocritical care (NCC) has emerged as a defined subspecialty in child neurology and requires a collaborative effort among child neurologists, pediatric critical care medicine specialists, and pediatric neurosurgeons. Pediatric NCC has evolved differently in children than in adults, and its delivery depends on the local resources available for pediatric care. This article reviews the current practice of pediatric NCC by child neurologists: where it is practiced, how it is practiced, the disorders encountered (that differ from adult NCC), the training required to care for these disorders, and what is needed for the future of pediatric NCC. Copyright © 2014 Elsevier Inc. All rights reserved.

A simplified parsimonious higher order multivariate Markov chain model with new convergence condition

NASA Astrophysics Data System (ADS)

Wang, Chao; Yang, Chuan-sheng

2017-09-01

In this paper, we present a simplified parsimonious higher-order multivariate Markov chain model with new convergence condition. (TPHOMMCM-NCC). Moreover, estimation method of the parameters in TPHOMMCM-NCC is give. Numerical experiments illustrate the effectiveness of TPHOMMCM-NCC.

National Composite Center-A new roof for composite industries in Malaysia

NASA Astrophysics Data System (ADS)

Abdullah, Abu; Yuhazri, M. Y.; Sulaiman, Mohd Yusoff

2016-03-01

Today's Malaysia has more than 70 companies that are actively involved in composite activities. The activities are ranging from various business sectors, using different technology and material. Composites has been used in a wide range of applications in Malaysia and contributes to growth in a diverse range of industry value chains from utilities through to boat building, manufacturing and industrial applications, aerospace, consumer products and construction products. Thus, a key part of this strategy is the establishment of the National Composites Centre (NCC), which will bring together dynamic companies and enterprising academics to develop new technologies for the design and rapid manufacture of high-quality composite products.

Lithospheric thermal evolution and dynamic mechanism of destruction of the North China Craton

NASA Astrophysics Data System (ADS)

Li, Zian; Zhang, Lu; Lin, Ge; Zhao, Chongbin; Liang, Yingjie

2018-06-01

The dynamic mechanism for destruction of the North China Craton (NCC) has been extensively discussed. Numerical simulation is used in this paper to discuss the effect of mantle upward throughflow (MUT) on the lithospheric heat flux of the NCC. Our results yield a three-stage destruction of the NCC lithosphere as a consequence of MUT variation. (1) In Late Paleozoic, the elevation of MUT, which was probably caused by southward and northward subduction of the paleo-Asian and paleo-Tethyan oceans, respectively, became a prelude to the NCC destruction. The geological consequences include a limited decrease of the lithospheric thickness, an increase of heat flux, and a gradual enhancement of the crustal activity. But the tectonic attribute of the NCC maintained a stable craton. (2) During Late Jurassic-Early Cretaceous, the initial velocity of the MUT became much faster probably in response to subduction of the Pacific Ocean; the conductive heat flux at the base of the NCC lithosphere gradually increased from west to east; and the lithospheric thickness was significantly decreased. During this stage, the heat flux distribution was characterized by zonation and partition, with nearly horizontal layering in the lithosphere and vertical layering in the underlying asthenosphere. Continuous destruction of the NCC lithosphere was associated with the intense tectono-magmatic activity. (3) From Late Cretaceous to Paleogene, the velocity of MUT became slower due to the retreat of the subducting Pacific slab; the conductive heat flux at the base of lithosphere was increased from west to east; the distribution of heat flux was no longer layered. The crust of the western NCC is relatively hotter than the mantle, so-called as a `hot crust but cold mantle' structure. At the eastern NCC, the crust and the mantle characterized by a `cold crust but hot mantle.' The western NCC (e.g., the Ordos Basin) had a tectonically stable crust with low thermal gradients in the lithosphere; whereas

Lithospheric thermal evolution and dynamic mechanism of destruction of the North China Craton

NASA Astrophysics Data System (ADS)

Li, Zian; Zhang, Lu; Lin, Ge; Zhao, Chongbin; Liang, Yingjie

2017-09-01

The dynamic mechanism for destruction of the North China Craton (NCC) has been extensively discussed. Numerical simulation is used in this paper to discuss the effect of mantle upward throughflow (MUT) on the lithospheric heat flux of the NCC. Our results yield a three-stage destruction of the NCC lithosphere as a consequence of MUT variation. (1) In Late Paleozoic, the elevation of MUT, which was probably caused by southward and northward subduction of the paleo-Asian and paleo-Tethyan oceans, respectively, became a prelude to the NCC destruction. The geological consequences include a limited decrease of the lithospheric thickness, an increase of heat flux, and a gradual enhancement of the crustal activity. But the tectonic attribute of the NCC maintained a stable craton. (2) During Late Jurassic-Early Cretaceous, the initial velocity of the MUT became much faster probably in response to subduction of the Pacific Ocean; the conductive heat flux at the base of the NCC lithosphere gradually increased from west to east; and the lithospheric thickness was significantly decreased. During this stage, the heat flux distribution was characterized by zonation and partition, with nearly horizontal layering in the lithosphere and vertical layering in the underlying asthenosphere. Continuous destruction of the NCC lithosphere was associated with the intense tectono-magmatic activity. (3) From Late Cretaceous to Paleogene, the velocity of MUT became slower due to the retreat of the subducting Pacific slab; the conductive heat flux at the base of lithosphere was increased from west to east; the distribution of heat flux was no longer layered. The crust of the western NCC is relatively hotter than the mantle, so-called as a `hot crust but cold mantle' structure. At the eastern NCC, the crust and the mantle characterized by a `cold crust but hot mantle.' The western NCC (e.g., the Ordos Basin) had a tectonically stable crust with low thermal gradients in the lithosphere; whereas

Extraparenchymal neurocysticercosis: Demographic, clinicoradiological, and inflammatory features

PubMed Central

Marcin Sierra, Mariana; Arroyo, Mariana; Cadena Torres, May; Ramírez Cruz, Nancy; García Hernández, Fernando; Taboada, Diana; Galicia Martínez, Ángeles; Govezensky, Tzipe; Sciutto, Edda; Toledo, Andrea

2017-01-01

Background Extraparenchymal neurocysticercosis (ExPNCC), an infection caused by Taenia solium cysticerci that mainly occurs in the ventricular compartment (Ve) or the basal subarachnoid space (SAb), is more severe but less frequent and much less studied than parenchymal neurocysticercosis (ParNCC). Demographic, clinical, radiological, and lumbar cerebrospinal fluid features of patients affected by ExPNCC are herein described and compared with those of ParNCC patients. Methodology and principal findings 429 patients with a confirmed diagnosis of neurocysticercosis, attending the Instituto Nacional de Neurología y Neurocirugía, a tertiary reference center in Mexico City, from 2000 through 2014, were included. Demographic information, signs and symptoms, radiological patterns, and lumbar cerebrospinal fluid (CSF) laboratory values were retrieved from medical records for all patients. Data were statistically analyzed to assess potential differences depending on cyst location and to determine the effects of age and sex on the disease presentation. In total, 238 ExPNCC and 191 ParNCC patients were included. With respect to parenchymal cysts, extraparenchymal parasites were diagnosed at an older age (P = 0.002), chiefly caused intracranial hypertension (P < 0.0001), were more frequently multiple and vesicular (P < 0.0001), and CSF from these patients showed higher protein concentration and cell count (P < 0.0001). SAb patients were diagnosed at an older age than Ve patients, and showed more frequently seizures, vesicular cysticerci, and higher CSF cellularity. Gender and age modulated some traits of the disease. Conclusions This study evidenced clear clinical, radiological, and inflammatory differences between ExPNCC and ParNCC, and between SAb and Ve patients, and demonstrated that parasite location determines different pathological entities. PMID:28599004

Quality of Life in Patients with Neurocysticercosis in Mexico

PubMed Central

Bhattarai, Rachana; Budke, Christine M.; Carabin, Hélène; Proaño, Jefferson V.; Flores-Rivera, Jose; Corona, Teresa; Cowan, Linda D.; Ivanek, Renata; Snowden, Karen F.; Flisser, Ana

2011-01-01

The objective of this study was to compare quality of life measures in patients with neurocysticercosis (NCC) to those of a matched control group. The NCC outpatients and their controls were recruited from two neurology referral hospitals in Mexico City, Mexico during 2007–2008. The quality of life of 224 NCC patients was compared with 224 age-sex-hospital-day matched controls using the short form 12 v2 (SF-12 v2) quality of life survey. Medical chart reviews were also conducted for the NCC outpatients to evaluate presenting clinical manifestations. Compared with the controls, NCC patients had a significantly lower score for each of the eight domains of health evaluated and significantly lower Physical and Mental Component Summary scores. Chart reviews indicated that hydrocephalus (48%), severe headaches (47%), and epilepsy (31%) were the most common clinical manifestations in these NCC outpatients. PMID:21540389

Surface grafting of reduced graphene oxide using nanocrystalline cellulose via click reaction

NASA Astrophysics Data System (ADS)

Kabiri, Roya; Namazi, Hassan

2014-07-01

Reduced graphene oxide (RGO) sheet was functionalized with nanocrystalline cellulose (NCC) via click coupling between azide-functionalized graphene oxide (GO-N3) and terminal propargyl-functionalized nanocrystalline cellulose (PG-NCC). First, the reactive azide groups were introduced on the surface of GO with azidation of 2-chloroethyl isocyanate-treated graphene oxide (GO-Cl). Then, the resulted compounds were reacted with PG-NCC utilizing copper-catalyzed azide-alkyne cycloaddition. During the click reaction, GO was simultaneously reduced to graphene. The coupling was confirmed by Fourier transform infrared, Raman, DEPT135, and 13C NMR spectroscopy, and the complete exfoliation of graphene in the NCC matrix was confirmed with X-ray diffraction measurement. The degree of functionalization from the gradual mass loss of RGO-NCC suggests that around 23 mass % has been functionalized covalently. The size of both NCC and GO was found to be in nanometric range, which decreased after click reaction.

The influence of negative current collector size on a liquid metal positive electrode

NASA Astrophysics Data System (ADS)

Mohammad, Ibrahim; Ashour, Rakan; Kelley, Douglas

2017-11-01

Fluid mixing in the positive electrode of a liquid metal battery (LMB) governs some performance-related factors such as the rate of charge and discharge of the battery. The negative current collector (NCC) of a LMB is always smaller than the positive current collector, implying that current is convergent at the NCC. Also, different NCC sizes introduce different thermal, electromagnetic, and flow boundary conditions. In this talk, I will show how our lab studies the influence of NCC diameter on the flow in a liquid metal positive electrode driven by electrical current. I will present measurements of the flow velocity taken via Ultrasonic Doppler Velocimetry (UDV) over a range of different currents, at different NCC diameters.

Endosulfan decreases cytotoxic activity of nonspecific cytotoxic cells and expression of granzyme gene in Oreochromis niloticus.

PubMed

Téllez-Bañuelos, Martha Cecilia; Ortiz-Lazareno, Pablo Cesar; Jave-Suárez, Luis Felipe; Siordia-Sánchez, Victor Hugo; Bravo-Cuellar, Alejandro; Santerre, Anne; Zaitseva, Galina P

2014-05-01

The effect of the organochlorinated insecticide endosulfan, on the cytotoxic activity of Nile tilapia nonspecific cytotoxic cells (NCC) was assessed. Juvenile Nile tilapia were exposed to endosulfan (7 ppb) for 96 h and splenic NCC were isolated. Flow cytometric phenotyping of NCC was based on the detection of the NCC specific membrane signaling protein NCCRP-1 by using the monoclonal antibody Mab 5C6; granzyme expression was evaluated by quantitative RT-PCR. The cytotoxic activity of sorted NCC on HL-60 tumoral cells was assessed using propidium iodide (PI) staining of DNA in HL-60 nuclei, indicating dead cells. Nile tilapia splenic NCC had the ability to kill HL-60 tumoral cells, however, the exposure to endosulfan significantly reduced, by a 65%, their cytotoxic activity when using the effector:target ratio of 40:1. Additionally, the exposure to endosulfan tended to increase the expression of NCCRP-1, which is involved in NCC antigen recognition and signaling. Moreover, it decreased the expression of the granzyme gene in exposed group as compared with non-exposed group; however significant differences between groups were not detected. In summary, the acute exposure of Nile tilapia to sublethal concentration of endosulfan induces alteration in function of NCC: significant decrease of cytotoxic activity and a tendency to lower granzyme expression, severe enough to compromise the immunity of this species. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel proton exchange membranes based on structure-optimized poly(ether ether ketone ketone)s and nanocrystalline cellulose

NASA Astrophysics Data System (ADS)

Ni, Chuangjiang; Wei, Yingcong; Zhao, Qi; Liu, Baijun; Sun, Zhaoyan; Gu, Yan; Zhang, Mingyao; Hu, Wei

2018-03-01

Two sulfonated fluorenyl-containing poly(ether ether ketone ketone)s (SFPEEKKs) were synthesized as the matrix of composite proton exchange membranes by directly sulfonating copolymer precursors comprising non-sulfonatable fluorinated segments and sulfonatable fluorenyl-containing segments. Surface-modified nanocrystalline cellulose (NCC) was produced as the "performance-enhancing" filler by treating the microcrystalline cellulose with acid. Two families of SFPEEKK/NCC nanocomposite membranes with various NCC contents were prepared via a solution-casting procedure. Results revealed that the insertion of NCC at a suitable ratio could greatly enhance the proton conductivity of the pristine membranes. For example, the proton conductivity of SFPEEKK-60/NCC-4 (SFPEEKK with 60% fluorenyl segments in the repeating unit, and inserted with 4% NCC) composite membrane was as high as 0.245 S cm-1 at 90 °C, which was 61.2% higher than that of the corresponding pure SFPEEKK-60 membrane. This effect could be attributed to the formation of hydrogen bond networks and proton conduction paths through the interaction between -SO3H/-OH groups on the surface of NCC particles and -SO3H groups on the SFPEEKK backbones. Furthermore, the chemically modified NCC filler and the optimized chemical structure of the SFPEEKK matrix also provided good dimensional stability and mechanical properties of the obtained nanocomposites. In conclusion, these novel nanocomposites can be promising proton exchange membranes for fuel cells at moderate temperatures.

Enhanced networks operations using the X Window System

NASA Technical Reports Server (NTRS)

Linares, Irving

1993-01-01

We propose an X Window Graphical User Interface (GUI) which is tailored to the operations of NASA GSFC's Network Control Center (NCC), the NASA Ground Terminal (NGT), the White Sands Ground Terminal (WSGT), and the Second Tracking and Data Relay Satellite System (TDRSS) Ground Terminal (STGT). The proposed GUI can also be easily extended to other Ground Network (GN) Tracking Stations due to its standardized nature.

Discrimination between active and inactive neurocysticercosis by metacestode excretory/secretory antigens of Taenia solium in an enzyme-linked immunosorbent assay.

PubMed

Molinari, José L; García-Mendoza, Esperanza; de la Garza, Yazmin; Ramírez, José A; Sotelo, Julio; Tato, Patricia

2002-06-01

To detect IgG antibodies to Taenia solium, a controlled double-blind study was conducted using 91 coded cerebrospinal fluid samples from patients with neurocysticercosis (NCC) and other neurologic disorders. Samples were tested in an enzyme-linked immunosorbent assay (ELISA) using metacestode excretion/secretion antigens. The results were correlated with data from medical records on the diagnosis of NCC (based on computed tomography and magnetic resonance imaging criteria) and other neurologic disorders. The ELISA results were positive in 22 of the 24 cases with active NCC. In contrast, six cases with calcified cysts (inactive NCC), as well as one case in a transitional stage, were negative. One case with a calcified granuloma and another with a granuloma plus calcifications (classified as inactive NCC) had positive results. The remaining negative results corresponded to other neurologic disorders (58 cases). The results of the ELISA showed a significant difference between active and inactive NCC (P = 0.0034).

Potential of nanocrystalline cellulose-fibrin nanocomposites for artificial vascular graft applications

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

Brown, Elvie; Hu, Dehong; Abu-Lail, Nehal

2013-02-19

Nanocrystalline cellulose, a new bio-nanomaterial is utilized as a reinforcing material for biocompatible fibrin matrix to form into a nanocomposite for small-diameter replacement vascular graft application (SDRVG). The periodate oxidation of NCC, which provided it with a reactive carbonyl group, allowed molecular interaction between NCC and fibrin. Such interaction resulted into an effective mechanical reinforcement indicated by the improvement of max. force, elongation at break and modulus when oxidized NCC (ONCC) was incorporated into fibrin. The nanocomposite’s mechanical properties can be manipulated to conform to the native blood vessel by varying the ONCC to fibrin ratio and/or by controlling themore » degree of oxidation of NCC. Using atomic force microscopy had provided fundamental information on the effects of molecular interactions to the nanolevel mechanical properties of NCC/fibrin nanocomposites. This fundamental information established the positive feasibility and commenced continuing investigation for the practical SDRVG application of NCC/fibrin nanocomposite.« less

A Configurable Internet Telemetry Server / Remote Client System

NASA Astrophysics Data System (ADS)

Boyd, W. T.; Hopkins, A.; Abbott, M. J.; Girouard, F. R.

2000-05-01

We have created a general, object-oriented software framework in Java for remote viewing of telemetry over the Internet. The general system consists of a data server and a remote client that can be extended by any project that uses telemetry to implement a remote telemetry viewer. We have implemented a system that serves live telemetry from NASA's Extreme Ultraviolet Explorer satellite and a client that can display the telemetry at a remote location. An authenticated user may run a standalone graphical or text-based client, or an applet on a web page, to view EUVE telemetry. In the case of the GUI client, a user can build displays to his/her own specifications using a GUI view-building tool. This work was supported by grants NCC2-947 and NCC2-966 from NASA Ames Research Center and grant JPL-960684 from NASA Jet Propulsion Laboratory.

A two-fold reduction in measurement time for neutron assay: Initial tests of a prototype dual-gated shift register

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

Stewart, J.E.; Bourret, S.C.; Krick, M.S.

1996-09-01

Neutron coincidence counting (NCC) is used routinely around the world for nondestructive mass assay of uranium and plutonium in many forms, including waste. Compared with other methods, NCC is generally the most flexible, economic, and rapid. Many applications of NCC would benefit from a reduction in counting time required for a fixed random error. We have developed and tested the first prototype of a dual- gated, shift-register-based electronics unit that offers the potential of decreased measurement time for all passive and active NCC applications.

A two-fold reduction in measurement time for neutron assay: Initial tests of a prototype dual-gated shift register

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

Stewart, J.E.; Bourret, S.C.; Krick, M.S.

1996-12-31

Neutron coincidence counting (NCC) is used routinely around the world for nondestructive mass assay of uranium and plutonium in many forms, including waste. Compared with other methods, NCC is generally the most flexible, economic, and rapid. Many applications of NCC would benefit from a reduction in counting time required for a fixed random error. The authors have developed and tested the first prototype of a dual-gated, shift-register-based electronics unit that offers the potential of decreased measurement time for all passive and active NCC applications.

The Facts, Faces, and Figures of Nassau Community College, 2000-2001.

ERIC Educational Resources Information Center

Nassau Community Coll., Garden City, NY.

This fact book for Nassau Community College (NCC), New York, for 2000-2001 offers information about NCC's mission, publications, organizations, resources, services, and faculty and students. NCC is the largest community college in the state of New York, as well as one of the largest single-campus community colleges in the country. Report…

Probing inhibitory effects of nanocrystalline cellulose: inhibition versus surface charge

NASA Astrophysics Data System (ADS)

Male, Keith B.; Leung, Alfred C. W.; Montes, Johnny; Kamen, Amine; Luong, John H. T.

2012-02-01

NCC derived from different biomass sources was probed for its plausible cytotoxicity by electric cell-substrate impedance sensing (ECIS). Two different cell lines, Spodoptera frugiperda Sf9 insect cells and Chinese hamster lung fibroblast V79, were exposed to NCC and their spreading and viability were monitored and quantified by ECIS. Based on the 50%-inhibition concentration (ECIS50), none of the NCC produced was judged to have any significant cytotoxicity on these two cell lines. However, NCC derived from flax exhibited the most pronounced inhibition on Sf9 compared to hemp and cellulose powder. NCCs from flax and hemp pre-treated with pectate lyase were also less inhibitory than NCCs prepared from untreated flax and hemp. Results also suggested a correlation between the inhibitory effect and the carboxylic acid contents on the NCC.

The causal relationship between neurocysticercosis infection and the development of epilepsy - a systematic review.

PubMed

Gripper, Lucy B; Welburn, Susan C

2017-04-05

Neurocysticercosis (NCC) is a parasitic infection of the human central nervous system, the most common form of which involves infection of the brain parenchyma with the larval form of the Taenia solium tapeworm. A causal relationship between such an NCC infection and the development of epilepsy in infected individuals is acknowledged, in part supported by high levels of comorbidity in endemic countries worldwide. This study undertook a systematic review and critical analysis of the NCC-epilepsy relationship with the primary objective of quantifying the risk of developing epilepsy following NCC infection. A secondary aim was to analyse the proportions of NCC-associated epilepsy within different populations. Significant emphasis was placed on the importance of neuroimaging (CT or MRI) availability and use of clear guidelines for epilepsy diagnosis, in order to avoid overestimations of prevalence rates of either condition; a limitation identified in several previous studies. A common odds ratio of 2.76 was identified from meta-analysis of case-control studies, indicating that an individual infected with NCC has almost a three times higher risk of developing epilepsy than an uninfected individual. Furthermore, meta-analysis of studies identified a common proportion of 31.54% of epilepsy cases associated with NCC infection which suggests that amongst epileptic populations in at risk countries, approximately one-third may be associated with NCC infection. A significant finding was the lack of good clinical data to enable accurate determination of a causal relationship. Even studies that were included had noticeable limitations, including a general lack of consistency in diagnostics, and lack of accurate epidemiological data. This review highlights a need for consistency in research in this field. In the absence of reliable estimates of its global burden, NCC will remain of low priority in the eyes of funding agencies - a truly neglected disease.

Epilepsy and neurocysticercosis in Latin America: a systematic review and meta-analysis.

PubMed

Bruno, Elisa; Bartoloni, Alessandro; Zammarchi, Lorenzo; Strohmeyer, Marianne; Bartalesi, Filippo; Bustos, Javier A; Santivañez, Saul; García, Héctor H; Nicoletti, Alessandra

2013-01-01

The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors, including the distribution of infectious diseases with neurologic sequels. To define the burden of epilepsy in Latin American Countries (LAC) and to investigate the strength of association with neurocysticercosis (NCC), considered one of the leading causes of epilepsy, we performed a systematic review and meta-analysis of the literature. Studies published until 2012 were selected applying predefined inclusion criteria. Lifetime epilepsy (LTE) prevalence, active epilepsy (AE) prevalence, incidence, mortality, treatment gap (TG) and NCC proportion among people with epilepsy (PWE) were extracted. Median values were obtained for each estimate using random effects meta-analysis. The impact of NCC prevalence on epilepsy estimates was determined using meta-regression models. To assess the association between NCC and epilepsy, a further meta-analysis was performed on case-control studies. The median LTE prevalence was 15.8/1,000 (95% CI 13.5-18.3), the median AE prevalence was 10.7/1,000 (95% CI 8.4-13.2), the median incidence was 138.2/100,000 (95% CI 83.6-206.4), the overall standardized mortality ratio was 1.4 (95% CI 0.01-6.1) and the overall estimated TG was 60.6% (95% CI 45.3-74.9). The median NCC proportion among PWE was 32.3% (95% CI 26.0-39.0). Higher TG and NCC estimates were associated with higher epilepsy prevalence. The association between NCC and epilepsy was significant (p<0.001) with a common odds ratio of 2.8 (95% CI 1.9-4.0). A high burden of epilepsy and of NCC in LAC and a consistent association between these two diseases were pointed out. Furthermore, NCC prevalence and TG were identified as important factors influencing epilepsy prevalence to be considered in prevention and intervention strategies.

Preparation and application of nanocrystalline cellulose derived from sugarcane waste as filler modified alkanolamide on crosslink of natural rubber latex film

NASA Astrophysics Data System (ADS)

Harahap, Hamidah; Hayat, Nuim; Lubis, Marfuah

2017-07-01

Sugarcane waste is abundant sources of cellulose and it has potential to reutilize. Cellulose from sugarcane waste can be derived into nanocystalline cellulose (NCC) from crystalline region. The NCC as a filler has capability to reinforce natural rubber latex product. The crosslink in vulcanized natural rubber latex film influences several properties of product. In this work, we extracted NCC from sugarcane waste then added into natural rubber latex as filler modified alkanolamide (ALK) and also studied the crosslink of natural rubber latex films. NCC were produced from sugarcane waste by hydrolysis process with sulfuric acid 45%. The obtained NCC was characterized by using x-ray diffraction (XRD), transmission electron microscopy (TEM), and fourier transform infra red (FTIR). NCC was modified by alkanolamide and dispersed in water with filler concentration of 10%. Then the dispersion were added into latex system followed by pre-vulcanization at 70 °C. The films were prepared by coagulant dipping method and dried at 100 °C and 120 °C for 20 minutes. Characterization of NCC from sugarcane waste by using FTIR was done, it clearly showed the functional groups of cellulose. TEM showed the obtained NCC were rod-shaped with about 40-160 nm in diameter and several hundred nm in length, and XRD showed that the degree of crystalinity of NCC from sugarcane waste is 92.33%. The crosslink of natural rubber films were studied by measure the crosslink density for different filler loading by using swelling measurement with toluene solution. The result show that the crosslink density increased in line with amount of filler which added into the system, and also the crosslink density that obtained from vulcanization at 120 °C were higher than 100 °C.

The Effect of WNK4 on the Na+-Cl- Cotransporter Is Modulated by Intracellular Chloride.

PubMed

Bazúa-Valenti, Silvana; Chávez-Canales, María; Rojas-Vega, Lorena; González-Rodríguez, Xochiquetzal; Vázquez, Norma; Rodríguez-Gama, Alejandro; Argaiz, Eduardo R; Melo, Zesergio; Plata, Consuelo; Ellison, David H; García-Valdés, Jesús; Hadchouel, Juliette; Gamba, Gerardo

2015-08-01

It is widely recognized that the phenotype of familial hyperkalemic hypertension is mainly a consequence of increased activity of the renal Na(+)-Cl(-) cotransporter (NCC) because of altered regulation by with no-lysine-kinase 1 (WNK1) or WNK4. The effect of WNK4 on NCC, however, has been controversial because both inhibition and activation have been reported. It has been recently shown that the long isoform of WNK1 (L-WNK1) is a chloride-sensitive kinase activated by a low Cl(-) concentration. Therefore, we hypothesized that WNK4 effects on NCC could be modulated by intracellular chloride concentration ([Cl(-)]i), and we tested this hypothesis in oocytes injected with NCC cRNA with or without WNK4 cRNA. At baseline in oocytes, [Cl(-)]i was near 50 mM, autophosphorylation of WNK4 was undetectable, and NCC activity was either decreased or unaffected by WNK4. A reduction of [Cl(-)]i, either by low chloride hypotonic stress or coinjection of oocytes with the solute carrier family 26 (anion exchanger)-member 9 (SLC26A9) cRNA, promoted WNK4 autophosphorylation and increased NCC-dependent Na(+) transport in a WNK4-dependent manner. Substitution of the leucine with phenylalanine at residue 322 of WNK4, homologous to the chloride-binding pocket in L-WNK1, converted WNK4 into a constitutively autophosphorylated kinase that activated NCC, even without chloride depletion. Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC. These observations suggest that WNK4 can exert differential effects on NCC, depending on the intracellular chloride concentration. Copyright © 2015 by the American Society of Nephrology.

Navajo Community College--The President's Report, 1979-80.

ERIC Educational Resources Information Center

Jackson, Dean C.

An overview of the Navajo Community College (NCC) is presented with a message from the president and facts pertaining to both the Tsaile and Shiprock campuses. NCC President Jackson states that the uniqueness of NCC lies primarily in the instructional area which promotes the use of educational concepts contained in the Navajo culture to reinforce…

[Clinical and epidemiological aspects of neurocysticercosis in Brazil: a critical approach].

PubMed

Agapejev, Svetlana

2003-09-01

With the objective to show the characteristics of neurocysticercosis (NCC) in Brazil, was performed a critical analysis of national literature which showed a frequency of 1.5% in autopsies and 3.0% in clinical studies, corresponding to 0.3% of all admissions in general hospitals. In seroepidemiological studies the positivity of specific reactions was 2.3%. Brazilian patient with NCC presents a general clinical-epidemilogical profile (31-50 years old man, rural origin, complex partial epileptic crisis, increased protein levels or normal CSF, CT showing calcifications, constituting the inactive form of NCC), and a profile of severity (21-40 years old woman, urban origin, vascular headache and intracranial hypertension, typical CSF syndrome of NCC or alteration of two or more CSF parameters, CT showing vesicles and/or calcifications, constituting the active form of NCC). Although two localities from the state of S o Paulo have 72:100000 and 96:100000/habitants as prevalence coefficients, regional and national prevalences are very underestimated. Some aspects related to underestimation of NCC prevalence in Brazil are discussed.

Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake.

PubMed

Baek, Jong-Suep; Cho, Cheong-Weon

2017-08-01

Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2

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

Naruse, Kuniko; Nomiyama, Hisayuki; Miura, Retsu

1996-06-01

CC chemokines are cytokines that attract and activate leukocytes. The human genes for the CC chemokines are clustered on chromosome 17. To elucidate the genomic organization of the CC chemokine genes, we constructed a YAC contig comprising 34 clones. The contig was shown to contain all 10 CC chemokine genes reported so far, except for one gene whose nucleotide sequence is not available. The contig also contains 4 CC chemokine-like genes, which were deposited in GenBank as ESTs and are here referred to as NCC-1, NCC-2, NCC-3, and NCC-4. Within the contig, the CC chemokine genes were localized in twomore » regions. In addition, the CC chemokine genes were localized in two regions. In addition, the CC chemokine genes were more precisely mapped on chromosome 17q11.2 using a somatic cell hybrid cell DNA panel containing various portions of human chromosome 17. Interestingly, a reciprocal translocation t(Y;17) breakpoint, contained in the hybrid cell line Y1741, lay between the two chromosome 17 chemokine gene regions covered by our YAC contig. From these results, the order and the orientation of CC chemokine genes on chromosome 17 were determined as follows: centromere-neurofibromatosis 1-(MCP-3, MCP-1, NCC-1, I-309)-Y1741 breakpoint-RANTES-(LD78{gamma}, AT744.2, LD78{beta})-(NCC-3, NCC-2, AT744.1, LD78{alpha})-NCC-4-retinoic acid receptor {alpha}-telomere. 22 refs., 1 fig., 2 tabs.« less

Compensatory regulation of Na+ absorption by Na+/H+ exchanger and Na+-Cl- cotransporter in zebrafish (Danio rerio)

PubMed Central

2013-01-01

Introduction In mammals, internal Na+ homeostasis is maintained through Na+ reabsorption via a variety of Na+ transport proteins with mutually compensating functions, which are expressed in different segments of the nephrons. In zebrafish, Na+ homeostasis is achieved mainly through the skin/gill ionocytes, namely Na+/H+ exchanger (NHE3b)-expressing H+-ATPase rich (HR) cells and Na+-Cl- cotransporter (NCC)-expressing NCC cells, which are functionally homologous to mammalian proximal and distal convoluted tubular cells, respectively. The present study aimed to investigate whether or not the functions of HR and NCC ionocytes are differentially regulated to compensate for disruptions of internal Na+ homeostasis and if the cell differentiation of the ionocytes is involved in this regulation pathway. Results Translational knockdown of ncc caused an increase in HR cell number and a resulting augmentation of Na+ uptake in zebrafish larvae, while NHE3b loss-of-function caused an increase in NCC cell number with a concomitant recovery of Na+ absorption. Environmental acid stress suppressed nhe3b expression in HR cells and decreased Na+ content, which was followed by up-regulation of NCC cells accompanied by recovery of Na+ content. Moreover, knockdown of ncc resulted in a significant decrease of Na+ content in acid-acclimated zebrafish. Conclusions These results provide evidence that HR and NCC cells exhibit functional redundancy in Na+ absorption, similar to the regulatory mechanisms in mammalian kidney, and suggest this functional redundancy is a critical strategy used by zebrafish to survive in a harsh environment that disturbs body fluid Na+ homeostasis. PMID:23924428

Effect of a lotion containing the heat-treated probiotic strain Lactobacillus johnsonii NCC 533 on Staphylococcus aureus colonization in atopic dermatitis.

PubMed

Blanchet-Réthoré, Sandrine; Bourdès, Valérie; Mercenier, Annick; Haddar, Cyrille H; Verhoeven, Paul O; Andres, Philippe

2017-01-01

Staphylococcus aureus dominates the skin microbiota in patients with atopic dermatitis (AD), with bacterial loads correlating with disease severity. The aim of this exploratory study was to investigate the effect of a cosmetic lotion containing heat-treated Lactobacillus johnsonii NCC 533 (HT La1) on S. aureus colonization in AD patients. This open-label, multicenter study was performed in AD patients in Germany. First, detection of S. aureus was performed in all patients using the swab or scrub-wash method of sampling, followed by quantitative culture or quantitative polymerase chain reaction. Repeatability and reproducibility of all method combinations were evaluated to select the best combination of sampling and quantification. Second, a lotion containing HT La1 was applied to lesional skin twice daily for 3 weeks. Scoring using local objective SCORing Atopic Dermatitis (SCORAD), measurement of S. aureus load, and lesional microbiome analysis were performed before and after the 3-week treatment period. Thirty-one patients with AD were included in the study. All sampling and quantification methods were found to be robust, reproducible, and repeatable for assessing S. aureus load. For simplicity, a combination of swab and quantitative polymerase chain reaction was chosen to assess the efficacy of HT La1. Following application of a lotion containing HT La1 to AD lesions for 3 weeks, a reduction in S. aureus load was observed in patients, which correlated with a decrease in local objective SCORAD. Interestingly, high baseline skin concentrations of S. aureus were associated with good responses to the lotion. This study demonstrated that the application of a lotion containing HT La1 to the lesional skin of patients with AD for 3 weeks controlled S. aureus colonization and was associated with local clinical improvement (SCORAD). These findings support further development of topical treatments containing heat-treated nonreplicating beneficial bacteria for patients with

Brittle Deformation in the Ordos Basin in response to the Mesozoic destruction of the North China Craton

NASA Astrophysics Data System (ADS)

Wang, Q.; Jiang, L.

2012-12-01

Craton is continental block that has been tectonically stable since at least Proterozoic. Some cratons, however, become unstable for some geodynamic reasons. The North China Craton (NCC) is an example. Structure geological, geochemical, and geophysical works have revealed that the NCC was destructed in Cretaceous and that lithosphere thickness beneath the eastern NCC were thinned by 120 km. The present study will focus on deformation of the western NCC, and to understand the effect of the Mesozoic destruction of the North China Craton (NCC). Structural partitioning of the Ordos Basin, which is located in the western NCC, from the eastern NCC occurred during the Mesozoic. Unlike the eastern NCC where many Cretaceous metamorphic core complexes developed, sedimentary cover of the NCC remains nearly horizontal and deformation is manifested by joint. We visited 216 sites of outcrops and got 1928 joints measurements, among which 270 from Jurassic sandstones, 1378 from the Upper Triassic sandstones, 124 from the Middle and Lower Triassic sandstones, and 156 from Paleozoic sandstones. In the interior of the Ordos Basin, joints developed quite well in the Triassic strata, while joints in the Jurassic stata developed weakly and no joint in the Cretaceous strata. The Mesozoic stratigraphic thickness are: 1000 meters for the Lower Triassic, the Middle Triassic sandstone with thickness of 800 meters, 3000 meters for the Upper Triassic, 4000 meters for the Jurassic, and 1100 meters for the Lower Cretaceous. The vertical difference in joint development might be related to the burying depth of the strata: the higher the strata, the smaller the lithostatic stress, and then the weaker the joint. Joints in all stratigraphic levels showed a similar strain direction with the sigma 1 (the maximum pressure stress) vertical and the sigma 3 (the minimum pressure stress) horizontal and running N-S. The unconformity below the Cretaceous further indicates that joints in Jurassic and Triassic

Ethics of energy production and use: debate within the National Council of Churches

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

Harnik, P.

1979-02-01

An Energy Policy Statement emanating from a panel for the National Council of Churches (NCC) in the United States was presented in May 1978 to the governing board of the NCC. The proposed Energy Policy Statement is composed of four sections: Opinions and Perspectives, Theological Dimensions of the Energy Situation, Ecological Justice and Human choice, and A Challenge to the Churches. Controversy concerning the proposed plan was great. The controversy on nuclear energy is specifically described. While the NCC was anti-nuclear, the World Council of Churches was tilting toward nuclear power. The NCC focused on ethics of energy and themore » WCC is not focusing on ethics; its nuclear statement does not constitute policy; and another WCC committee is aggressively promoting conservation and appropriate technology. The lessons drawn from the NCC debate are summarized. (MCW)« less

Clinical Manifestations Associated with Neurocysticercosis: A Systematic Review

PubMed Central

Carabin, Hélène; Ndimubanzi, Patrick Cyaga; Budke, Christine M.; Nguyen, Hai; Qian, Yingjun; Cowan, Linda Demetry; Stoner, Julie Ann; Rainwater, Elizabeth; Dickey, Mary

2011-01-01

Background The clinical manifestations of neurocysticercosis (NCC) are poorly understood. This systematic review aims to estimate the frequencies of different manifestations, complications and disabilities associated with NCC. Methods A systematic search of the literature published from January 1, 1990, to June 1, 2008, in 24 different electronic databases and 8 languages was conducted. Meta-analyses were conducted when appropriate. Results A total of 1569 documents were identified, and 21 included in the analysis. Among patients seen in neurology clinics, seizures/epilepsy were the most common manifestations (78.8%, 95%CI: 65.1%–89.7%) followed by headaches (37.9%, 95%CI: 23.3%–53.7%), focal deficits (16.0%, 95%CI: 9.7%–23.6%) and signs of increased intracranial pressure (11.7%, 95%CI: 6.0%–18.9%). All other manifestations occurred in less than 10% of symptomatic NCC patients. Only four studies reported on the mortality rate of NCC. Conclusions NCC is a pleomorphic disease linked to a range of manifestations. Although definitions of manifestations were very rarely provided, and varied from study to study, the proportion of NCC cases with seizures/epilepsy and the proportion of headaches were consistent across studies. These estimates are only applicable to patients who are ill enough to seek care in neurology clinics and likely over estimate the frequency of manifestations among all NCC cases. PMID:21629722

Clinical manifestations associated with neurocysticercosis: a systematic review.

PubMed

Carabin, Hélène; Ndimubanzi, Patrick Cyaga; Budke, Christine M; Nguyen, Hai; Qian, Yingjun; Cowan, Linda Demetry; Stoner, Julie Ann; Rainwater, Elizabeth; Dickey, Mary

2011-05-01

The clinical manifestations of neurocysticercosis (NCC) are poorly understood. This systematic review aims to estimate the frequencies of different manifestations, complications and disabilities associated with NCC. A systematic search of the literature published from January 1, 1990, to June 1, 2008, in 24 different electronic databases and 8 languages was conducted. Meta-analyses were conducted when appropriate. A total of 1569 documents were identified, and 21 included in the analysis. Among patients seen in neurology clinics, seizures/epilepsy were the most common manifestations (78.8%, 95%CI: 65.1%-89.7%) followed by headaches (37.9%, 95%CI: 23.3%-53.7%), focal deficits (16.0%, 95%CI: 9.7%-23.6%) and signs of increased intracranial pressure (11.7%, 95%CI: 6.0%-18.9%). All other manifestations occurred in less than 10% of symptomatic NCC patients. Only four studies reported on the mortality rate of NCC. NCC is a pleomorphic disease linked to a range of manifestations. Although definitions of manifestations were very rarely provided, and varied from study to study, the proportion of NCC cases with seizures/epilepsy and the proportion of headaches were consistent across studies. These estimates are only applicable to patients who are ill enough to seek care in neurology clinics and likely over estimate the frequency of manifestations among all NCC cases.

Interleukin 18 function requires both interleukin 18 receptor and Na-Cl co-transporter

PubMed Central

Wang, Jing; Sun, Chongxiu; Gerdes, Norbert; Liu, Conglin; Liao, Mengyang; Liu, Jian; Shi, Michael A.; He, Aina; Zhou, Yi; Sukhova, Galina K.; Chen, Huimei; Cheng, Xianwu; Kuzuya, Masafumi; Murohara, Toyoaki; Zhang, Jie; Cheng, Xiang; Jiang, Mengmeng; Shull, Gary E.; Rogers, Shaunessy; Yang, Chao-Ling; Ke, Qiang; Jelen, Sabina; Bindels, René; Ellison, David H.; Jarolim, Petr; Libby, Peter; Shi, Guo-Ping

2015-01-01

Interleukin-18 (IL18) participates in atherogenesis through several putative mechanisms1,2. Interruption of IL18 action reduces atherosclerosis in mice3,4. This study shows that the absence of IL18 receptor (IL18r) does not affect atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice, nor does it affect IL18 cell surface binding or signaling. IL18 antibody-mediated immunoprecipitation identified an interaction between IL18 and Na-Cl co-transporter (NCC), a 12-transmembrane-domain ion transporter protein preferentially expressed in the kidney5. Yet, we find NCC expression and colocalization with IL18r in atherosclerotic lesions and both molecules form a complex. IL18 also binds to the cell surface and induces cell signaling and down-stream cytokine expression in NCC-transfected COS-7 cells that do not express IL18r. In Apoe−/− mice, combined deficiency of IL18r and NCC, but not single deficiency, protects mice from atherosclerosis. Peritoneal macrophages from Apoe−/− mice or those lacking IL18r or NCC respond to IL18 binding or IL18 induction of cell signaling and cytokine and chemokine production, but those with combined deficiency of IL18r and NCC do not. This study identifies NCC as an IL18-binding protein that coordinates with IL18r in cell signaling, inflammatory molecule expression, and experimental atherogenesis. PMID:26099046

Distribution and Potential Indicators of Hospitalized Cases of Neurocysticercosis and Epilepsy in Ecuador from 1996 to 2008.

PubMed

Ron-Garrido, Lenin; Coral-Almeida, Marco; Gabriël, Sarah; Benitez-Ortiz, Washington; Saegerman, Claude; Dorny, Pierre; Berkvens, Dirk; Abatih, Emmanuel Nji

2015-11-01

Epilepsy is one of the most common signs of Neurocysticercosis (NCC). In this study, spatial and temporal variations in the incidence of hospitalized cases (IHC) of epilepsy and NCC in Ecuadorian municipalities were analyzed. Additionally, potential socio-economic and landscape indicators were evaluated in order to understand in part the macro-epidemiology of the Taenia solium taeniasis/cysticercosis complex. Data on the number of hospitalized epilepsy and NCC cases by municipality of residence were obtained from morbidity-hospital systems in Ecuador. SatScan software was used to determine whether variations in the IHC of epilepsy and NCC in space and time. In addition, several socio-economic and landscape variables at municipality level were used to study factors intervening in the macro-epidemiology of these diseases. Negative Binomial regression models through stepwise selection and Bayesian Model Averaging (BMA) were used to explain the variations in the IHC of epilepsy and NCC. Different clusters were identified through space and time. Traditional endemic zones for NCC and epilepsy, recognized in other studies were confirmed in our study. However, for both disorders more recent clusters were identified. Among municipalities, an increasing tendency for IHC of epilepsy, and a decreasing tendency for the IHC of NCC were observed over time. In contrast, within municipalities a positive linear relationship between both disorders was found. An increase in the implementation of systems for eliminating excrements would help to reduce the IHC of epilepsy by 1.00% (IC95%; 0.2%-1.8%) and by 5.12% (IC95%; 3.63%-6.59%) for the IHC of NCC. The presence of pig production was related to IHC of NCC. Both disorders were related to the lack of an efficient system for eliminating excrements. Given the appearance of recent epilepsy clusters, these locations should be studied in depth to discriminate epilepsies due to NCC from epilepsies due to other causes. Field studies are

Distribution and Potential Indicators of Hospitalized Cases of Neurocysticercosis and Epilepsy in Ecuador from 1996 to 2008

PubMed Central

Gabriël, Sarah; Benitez-Ortiz, Washington; Saegerman, Claude; Dorny, Pierre; Berkvens, Dirk; Abatih, Emmanuel Nji

2015-01-01

Background Epilepsy is one of the most common signs of Neurocysticercosis (NCC). In this study, spatial and temporal variations in the incidence of hospitalized cases (IHC) of epilepsy and NCC in Ecuadorian municipalities were analyzed. Additionally, potential socio-economic and landscape indicators were evaluated in order to understand in part the macro-epidemiology of the Taenia solium taeniasis/cysticercosis complex. Methodology Data on the number of hospitalized epilepsy and NCC cases by municipality of residence were obtained from morbidity-hospital systems in Ecuador. SatScan software was used to determine whether variations in the IHC of epilepsy and NCC in space and time. In addition, several socio-economic and landscape variables at municipality level were used to study factors intervening in the macro-epidemiology of these diseases. Negative Binomial regression models through stepwise selection and Bayesian Model Averaging (BMA) were used to explain the variations in the IHC of epilepsy and NCC. Principal findings Different clusters were identified through space and time. Traditional endemic zones for NCC and epilepsy, recognized in other studies were confirmed in our study. However, for both disorders more recent clusters were identified. Among municipalities, an increasing tendency for IHC of epilepsy, and a decreasing tendency for the IHC of NCC were observed over time. In contrast, within municipalities a positive linear relationship between both disorders was found. An increase in the implementation of systems for eliminating excrements would help to reduce the IHC of epilepsy by 1.00% (IC95%; 0.2%–1.8%) and by 5.12% (IC95%; 3.63%-6.59%) for the IHC of NCC. The presence of pig production was related to IHC of NCC. Conclusion/Significance Both disorders were related to the lack of an efficient system for eliminating excrements. Given the appearance of recent epilepsy clusters, these locations should be studied in depth to discriminate epilepsies due

Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl−‐dependent and independent mechanisms

PubMed Central

Penton, David; Czogalla, Jan; Wengi, Agnieszka; Himmerkus, Nina; Loffing‐Cueni, Dominique; Carrel, Monique; Rajaram, Renuga Devi; Staub, Olivier; Bleich, Markus; Schweda, Frank

2016-01-01

Key points High dietary potassium (K+) intake dephosphorylates and inactivates the NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT).Using several ex vivo models, we show that physiological changes in extracellular K+, similar to those occurring after a K+ rich diet, are sufficient to promote a very rapid dephosphorylation of NCC in native DCT cells.Although the increase of NCC phosphorylation upon decreased extracellular K+ appears to depend on cellular Cl− fluxes, the rapid NCC dephosphorylation in response to increased extracellular K+ is not Cl−‐dependent.The Cl−‐dependent pathway involves the SPAK/OSR1 kinases, whereas the Cl− independent pathway may include additional signalling cascades. Abstract A high dietary potassium (K+) intake causes a rapid dephosphorylation, and hence inactivation, of the thiazide‐sensitive NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Based on experiments in heterologous expression systems, it was proposed that changes in extracellular K+ concentration ([K+]ex) modulate NCC phosphorylation via a Cl−‐dependent modulation of the with no lysine (K) kinases (WNK)‐STE20/SPS‐1‐44 related proline‐alanine‐rich protein kinase (SPAK)/oxidative stress‐related kinase (OSR1) kinase pathway. We used the isolated perfused mouse kidney technique and ex vivo preparations of mouse kidney slices to test the physiological relevance of this model on native DCT. We demonstrate that NCC phosphorylation inversely correlates with [K+]ex, with the most prominent effects occurring around physiological plasma [K+]. Cellular Cl− conductances and the kinases SPAK/OSR1 are involved in the phosphorylation of NCC under low [K+]ex. However, NCC dephosphorylation triggered by high [K+]ex is neither blocked by removing extracellular Cl−, nor by the Cl− channel blocker 4,4′‐diisothiocyano‐2,2′‐stilbenedisulphonic acid. The response to [K+]ex on a low extracellular chloride

National Combustion Code, a Multidisciplinary Combustor Design System, Will Be Transferred to the Commercial Sector

NASA Technical Reports Server (NTRS)

Steele, Gynelle C.

1999-01-01

The NASA Lewis Research Center and Flow Parametrics will enter into an agreement to commercialize the National Combustion Code (NCC). This multidisciplinary combustor design system utilizes computer-aided design (CAD) tools for geometry creation, advanced mesh generators for creating solid model representations, a common framework for fluid flow and structural analyses, modern postprocessing tools, and parallel processing. This integrated system can facilitate and enhance various phases of the design and analysis process.

An intermediate significant bit (ISB) watermarking technique using neural networks.

PubMed

Zeki, Akram; Abubakar, Adamu; Chiroma, Haruna

2016-01-01

Prior research studies have shown that the peak signal to noise ratio (PSNR) is the most frequent watermarked image quality metric that is used for determining the levels of strength and weakness of watermarking algorithms. Conversely, normalised cross correlation (NCC) is the most common metric used after attacks were applied to a watermarked image to verify the strength of the algorithm used. Many researchers have used these approaches to evaluate their algorithms. These strategies have been used for a long time, however, which unfortunately limits the value of PSNR and NCC in reflecting the strength and weakness of the watermarking algorithms. This paper considers this issue to determine the threshold values of these two parameters in reflecting the amount of strength and weakness of the watermarking algorithms. We used our novel watermarking technique for embedding four watermarks in intermediate significant bits (ISB) of six image files one-by-one through replacing the image pixels with new pixels and, at the same time, keeping the new pixels very close to the original pixels. This approach gains an improved robustness based on the PSNR and NCC values that were gathered. A neural network model was built that uses the image quality metrics (PSNR and NCC) values obtained from the watermarking of six grey-scale images that use ISB as the desired output and that are trained for each watermarked image's PSNR and NCC. The neural network predicts the watermarked image's PSNR together with NCC after the attacks when a portion of the output of the same or different types of image quality metrics (PSNR and NCC) are obtained. The results indicate that the NCC metric fluctuates before the PSNR values deteriorate.

Adsorption and desorption of methylene blue on porous carbon monoliths and nanocrystalline cellulose.

PubMed

He, Xiaoyun; Male, Keith B; Nesterenko, Pavel N; Brabazon, Dermot; Paull, Brett; Luong, John H T

2013-09-11

The dynamic batch adsorption of methylene blue (MB), a widely used and toxic dye, onto nanocrystalline cellulose (NCC) and crushed powder of carbon monolith (CM) was investigated using the pseudo-first- and -second-order kinetics. CM outperformed NCC with a maximum capacity of 127 mg/g compared to 101 mg/g for NCC. The Langmuir isotherm model was applicable for describing the binding data for MB on CM and NCC, indicating the homogeneous surface of these two materials. The Gibbs free energy of -15.22 kJ/mol estimated for CM unravelled the spontaneous nature of this adsorbent for MB, appreciably faster than the use of NCC (-4.47 kJ/mol). Both pH and temperature exhibited only a modest effect on the adsorption of MB onto CM. The desorption of MB from CM using acetonitrile was very effective with more than 94 % of MB desorbed from CM within 10 min to allow the reusability of this porous carbon material. In contrast, acetonitrile was less effective than ethanol in desorbing MB from NCC. The two solvents were incapable of completely desorbing MB on commercial granular coal-derived activated carbon.

Environmental and ecological controls of coral community metabolism on Palmyra Atoll

NASA Astrophysics Data System (ADS)

Koweek, David; Dunbar, Robert B.; Rogers, Justin S.; Williams, Gareth J.; Price, Nichole; Mucciarone, David; Teneva, Lida

2015-03-01

Accurate predictions of how coral reefs may respond to global climate change hinge on understanding the natural variability to which these ecosystems are exposed and to which they contribute. We present high-resolution estimates of net community calcification (NCC) and net community production (NCP) from Palmyra Atoll, an uninhabited, near-pristine coral reef ecosystem in the central Pacific. In August-October 2012, we employed a combination of Lagrangian and Eulerian frameworks to establish high spatial (~2.5 km2) and temporal (hourly) resolution coral community metabolic estimates. Lagrangian drifts, all conducted during daylight hours, resulted in NCC estimates of -51 to 116 mmol C m-2 h-1, although most NCC estimates were in the range of 0-40 mmol C m-2 h-1. Lagrangian drift NCP estimates ranged from -7 to 67 mmol C m-2 h-1. In the Eulerian setup, we present carbonate system parameters (dissolved inorganic carbon, total alkalinity, pH, and pCO2) at sub-hourly resolution through several day-night cycles and provide hourly NCC and NCP rate estimates. We compared diel cycles of all four carbonate system parameters to the offshore surface water (0-50 m depth) and show large departures from offshore surface water chemistry. Hourly Eulerian estimates of NCC aggregated over the entire study ranged from 14 to 53 mmol C m-2 h-1, showed substantial variability during daylight hours, and exhibited a diel cycle with elevated NCC in the afternoons and depressed, but positive, NCC at night. The Eulerian NCP range was very high (-55 to 177 mmol C m-2 h-1) and exhibited strong variability during daylight hours. Principal components analysis revealed that NCC and NCP were most closely aligned with diel cycle forcing, whereas the NCC/NCP ratio was most closely aligned with reef community composition. Our analysis demonstrates that ecological community composition is the primary determinant of coral reef biogeochemistry on a near-pristine reef and that reef biogeochemistry is

Epilepsy and Neurocysticercosis in Latin America: A Systematic Review and Meta-analysis

PubMed Central

Bruno, Elisa; Bartoloni, Alessandro; Zammarchi, Lorenzo; Strohmeyer, Marianne; Bartalesi, Filippo; Bustos, Javier A.; Santivañez, Saul; García, Héctor H.; Nicoletti, Alessandra

2013-01-01

Background The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors, including the distribution of infectious diseases with neurologic sequels. To define the burden of epilepsy in Latin American Countries (LAC) and to investigate the strength of association with neurocysticercosis (NCC), considered one of the leading causes of epilepsy, we performed a systematic review and meta-analysis of the literature. Methodology Studies published until 2012 were selected applying predefined inclusion criteria. Lifetime epilepsy (LTE) prevalence, active epilepsy (AE) prevalence, incidence, mortality, treatment gap (TG) and NCC proportion among people with epilepsy (PWE) were extracted. Median values were obtained for each estimate using random effects meta-analysis. The impact of NCC prevalence on epilepsy estimates was determined using meta-regression models. To assess the association between NCC and epilepsy, a further meta-analysis was performed on case-control studies. Principal findings The median LTE prevalence was 15.8/1,000 (95% CI 13.5–18.3), the median AE prevalence was 10.7/1,000 (95% CI 8.4–13.2), the median incidence was 138.2/100,000 (95% CI 83.6–206.4), the overall standardized mortality ratio was 1.4 (95% CI 0.01–6.1) and the overall estimated TG was 60.6% (95% CI 45.3–74.9). The median NCC proportion among PWE was 32.3% (95% CI 26.0–39.0). Higher TG and NCC estimates were associated with higher epilepsy prevalence. The association between NCC and epilepsy was significant (p<0.001) with a common odds ratio of 2.8 (95% CI 1.9–4.0). Significance A high burden of epilepsy and of NCC in LAC and a consistent association between these two diseases were pointed out. Furthermore, NCC prevalence and TG were identified as important factors influencing epilepsy prevalence to be considered in prevention and intervention strategies. PMID:24205415

The effect of Lactobacillus johnsonii Ncc533 (La1) on the balance of Th1/Th2 cells in BALB/c mice.

PubMed

Yang, Junli; Li, Wen; Sun, Ruopeng; Li, Baomin

2011-08-01

To determine the effect of Lactobacillus johnsonii Ncc533 (La1) on Th1/Th2 balance, the production of IL-4 and IFN-γ by splenocytes was evaluated following its administration to mice from newborn to adult. Changes in IL-4 and IFN-γ expression and serum levels of OVA-specific-IgE were then investigated in an asthma model. Using flow cytometry (FCM) and ELISA, the percentage of IL-4 and IFN-γ expressing splenocytes and serum levels of OVA-specific-IgE were measured in different groups of mice. The percentages of IL-4 and IFN-γ expressing splenocytes in the offspring and in the adults of the La1-treated group were not significantly different when compared with the water-treated group. In the asthma model, the percentages of IL-4 expressing cells and the serum levels of OVA-specific-IgE in the La1-treated and water-treated group were significantly increased compared with those in the control group. The percentage of IFN-γ expressing cells was significantly lower in the La1-treated and water-treated groups. The percentage of IL-4 expressing cells and the serum levels of OVA-specific-IgE in the La1-treated group were significantly lower compared with those in the water-treated group, whereas the percentage of IFN-γ expressing cells was significantly higher. Administration of La1 had no effect on the immune system from the neonate to the adult in the normal mice. It did, however, significantly alter the percentages of IL-4 or IFN-γ expressing CD4+ T lymphocytes in the asthma model, suggesting that administration of La1 might regulate the immune response.

Calcineurin inhibitors block sodium-chloride cotransporter dephosphorylation in response to high potassium intake.

PubMed

Shoda, Wakana; Nomura, Naohiro; Ando, Fumiaki; Mori, Yutaro; Mori, Takayasu; Sohara, Eisei; Rai, Tatemitsu; Uchida, Shinichi

2017-02-01

Dietary potassium intake is inversely related to blood pressure and mortality. Moreover, the sodium-chloride cotransporter (NCC) plays an important role in blood pressure regulation and urinary potassium excretion in response to potassium intake. Previously, it was shown that NCC is activated by the WNK4-SPAK cascade and dephosphorylated by protein phosphatase. However, the mechanism of NCC regulation with acute potassium intake is still unclear. To identify the molecular mechanism of NCC regulation in response to potassium intake, we used adult C57BL/6 mice fed a 1.7% potassium solution by oral gavage. We confirmed that acute potassium load rapidly dephosphorylated NCC, which was not dependent on the accompanying anions. Mice were treated with tacrolimus (calcineurin inhibitor) and W7 (calmodulin inhibitor) before the oral potassium loads. Dephosphorylation of NCC induced by potassium was significantly inhibited by both tacrolimus and W7 treatment. There was no significant difference in WNK4, OSR1, and SPAK expression after high potassium intake, even after tacrolimus and W7 treatment. Another phosphatase, protein phosphatase 1, and its endogenous inhibitor I-1 did not show a significant change after potassium intake. Hyperkaliuria, induced by high potassium intake, was significantly suppressed by tacrolimus treatment. Thus, calcineurin is activated by an acute potassium load, which rapidly dephosphorylates NCC, leading to increased urinary potassium excretion. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

An Investigation Into The Viability Of Nanocrystalline Cellulose As A Packaging Material

NASA Astrophysics Data System (ADS)

Glass, John

The focus of this proposal is to identify unexplored areas of research in the field of packaging science, specifically related to the incorporation of Nanocrystalline Cellulose (NCC) as a functional material in fiber based packaging, as well as to highlight some of potential risks and unknowns in the product lifecycle. This research hypothesizes that incorporating NCC into wood fiber-based c-flute corrugated packaging medium will show a sufficient performance improvement to justify additional research. Nanomaterials, as a whole, are still being understood, including those using naturally occurring bases such as NCC. Further incremental testing with NCC will help provide a performance and safety baseline for the necessary future research prior to mass production. NCC holds great promise for the future: a commonly available, naturally occurring material that's easily recyclable and biodegradable, yet has the strength of steel. Due diligence is required for this material to come to market in a safe and sustainable manner.

A Mechanical Cryogenic Cooler for the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Jedrich, Nicholas; Zimbelman, Darell; Swift, Walter; Dolan, Francis; Brumfield, Mark (Technical Monitor)

2002-01-01

This paper presents a description of the Hubble Space Telescope (HST) Near-Infrared Camera and Multi-Object Spectrometer (NICMOS) Cryo Cooler (NCC), the cutting edge technology involved, its evolution, performance, and future space applications. The NCC is the primary hardware component of the NICMOS Cooling System comprised of the NCC, an Electronics Support Module, a Capillary Pumped Loop/Radiator, and associated interface harnessing. The system will be installed during extravehicular activities on HST during Servicing Mission 3B scheduled for launch in February 2002. The NCC will be used to revive the NICMOS instrument, which experienced a reduced operational lifetime due to an internal thermal short in its dewar structure, and restore HST scientific infrared capability to operational status. The NCC is a state-of-the-art reverse Turbo-Brayton cycle cooler employing gas bearing micro turbo machinery, driven by advanced power conversion electronics, operating at speeds up to 7300 revolutions per second (rps) to remove heat from the NICMOS instrument.

Nanocrystalline cellulose as an eco-friendly reinforcing additive to polyurethane coating for augmented anticorrosive behavior.

PubMed

Abd El-Fattah, M; Hasan, Abdulraheim M A; Keshawy, Mohamed; El Saeed, Ashraf M; Aboelenien, Ossama M

2018-03-01

Nanocrystalline cellulose (NCC) and micro-powdered cellulose (MPC) were extracted from rice straw by mechanical and alkali treatment methods, then characterized via infrared spectroscopy and dynamic light scattering. A series of polyurethane nanocrystalline cellulose composite (PNCCC) and polyurethane micro-powdered cellulose composite (PMPCC) coatings were prepared with various loading levels of NCC and MPC from 0.5 to 2.0 wt.%, and the coatings were applied onto the pretreated mild steel substrate at room temperature. The results showed that the NCC and MPC influenced positively the studied properties of the polyurethane coating; furthermore the most pronounced anticorrosive properties were obtained at 1 wt.% NCC and MPC, as confirmed by open circuit potential (OCP) study, electrochemical impedance spectroscopy (EIS) study and salt spray test. However, the optimum enhancement of mechanical properties was found at 1.5 wt.% loading level, after which further loading of NCC and MPC led to the reduction in the mechanical properties. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cranial neural crest recycle surface integrins in a substratum-dependent manner to promote rapid motility.

PubMed

Strachan, Lauren R; Condic, Maureen L

2004-11-08

Cell migration is essential for proper development of numerous structures derived from embryonic neural crest cells (NCCs). Although the migratory pathways of NCCs have been determined, the molecular mechanisms regulating NCC motility remain unclear. NCC migration is integrin dependent, and recent work has shown that surface expression levels of particular integrin alpha subunits are important determinants of NCC motility in vitro. Here, we provide evidence that rapid cranial NCC motility on laminin requires integrin recycling. NCCs showed both ligand- and receptor-specific integrin regulation in vitro. On laminin, NCCs accumulated internalized laminin but not fibronectin receptors over 20 min, whereas on fibronectin neither type of receptor accumulated internally beyond 2 min. Internalized laminin receptors colocalized with receptor recycling vesicles and were subsequently recycled back to the cell surface. Blocking receptor recycling with bafilomycin A inhibited NCC motility on laminin, indicating that substratum-dependent integrin recycling is essential for rapid cranial neural crest migration.

Severe hyperkalemia is rescued by low-potassium diet in renal βENaC-deficient mice.

PubMed

Boscardin, Emilie; Perrier, Romain; Sergi, Chloé; Maillard, Marc; Loffing, Johannes; Loffing-Cueni, Dominique; Koesters, Robert; Rossier, Bernard Claude; Hummler, Edith

2017-10-01

In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium (HNa + /LK + ) diet. In the present study, we addressed whether renal βENaC expression is required for sodium and potassium balance or can be compensated by remaining (α and γ) ENaC subunits using adult nephron-specific knockout (Scnn1b Pax8/LC1 ) mice. Upon induction, these mice present a severe PHA-1 phenotype with weight loss, hyperkalemia, and dehydration, but unlike the Scnn1a Pax8/LC1 mice without persistent salt wasting. This is followed by a marked downregulation of STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) and Na + /Cl - co-transporter (NCC) protein expression and activity. Most of the experimental Scnn1b Pax8/LC1 mice survived with a HNa + /LK + diet that partly normalized NCC phosphorylation, but not total NCC expression. Since salt loss was minor, we applied a standard-sodium/LK + diet that efficiently rescued these mice resulting in normokalemia and normalization of NCC phosphorylation, but not total NCC expression. A further switch to LNa + /standard-K + diet induced again a severe PHA-1-like phenotype, but with only transient salt wasting indicating that low-K + intake is critical to decrease hyperkalemia in a NCC-dependent manner. In conclusion, while the βENaC subunit plays only a minor role in sodium balance, severe hyperkalemia results in downregulation of NCC expression and activity. Our data demonstrate the importance to primarily correct the hyperkalemia with a low-potassium diet that normalizes NCC activity.

Reactive sulfur species: kinetics and mechanism of the oxidation of cystine by hypochlorous acid to give N,N'-dichlorocystine.

PubMed

Nagy, Péter; Ashby, Michael T

2005-06-01

Cystine and HOCl (a neutrophil-derived oxidant) react to form an intermediate that has a half-life of ca. 5 min at pH 7.5. The intermediate subsequently decomposes to eventually yield a mixture of cystine, higher oxides of Cys, and other uncharacterized species. Spectral titrations, transitory (1)H NMR and UV-vis spectra, and the reaction properties of the intermediate are consistent with a formulation of N,N'-dichlorocystine {NDC = [-SCH(2)CH(NHCl)(CO(2)H)](2)}. The reaction of equimolar amounts of HOCl with cystine at pH 11.3 does not yield N-chlorocystine [NCC = (-O2C)(H3N+)CHCH(2)SSCH(2)CH(NHCl)(CO(2)H)] but rather a 1:1 mixture of NDC and cystine. This result could be explained by two mechanisms: rapid disproportionation of NCC to produce NDC and cystine or a faster reaction of the second equivalent of HOCl with NCC than the first equivalent of HOCl reacts with cystine. The latter mechanism is favored because of our observation by NMR spectroscopy that NDC decomposes via a species that we have assigned as NCC. Thus, disproportionation of NCC is apparently a relatively slow process. The rates of reaction of cystine(0) = [-SCH(2)CH(NH(3)(+))(CO(2)(-))](2) degrees , cystine(1-) = [((-)O(2)C)(H(2)N)CHCH(2)SSCH(2)CH(NH(3)(+))(CO(2)(-))](-), and cystine(2-) = [-SCH(2)CH(NH2)(CO2)(-))]2(2-) have been investigated, and it is clear that cystine(0) is unreactive, whereas cystine(2-) is about four times more reactive than cystine(1-). Accordingly, the following mechanism is proposed (constants for 5 degrees C): HOCl = H+ + OCl-, pK1 = 7.47; cystine(0) = cystine(1-) + H+, pK2 = 8.15; cystine(1-) = cystine(2-) + H+, pK3 = 9.00; cystine(1-) + HOCl --> NCC(1-) + H2O, k4 = 4.3(2) x 10(6) M(-1) s(-1); cystine(2-) + HOCl --> NCC(2)(-) + H2O, k5 = 1.6(2) x 10(7) M(-1) s(-1); NCC(1-) --> NCC(2-) + H+, k6 = fast; NCC(2-) + HOCl --> NDC(2-) + H2O, k7 = fast. At physiologic pH, the k4 pathway dominates. The generation of long-lived chloramine derivatives of cystine may have

Primary administration of Lactobacillus johnsonii NCC533 in weaning period suppresses the elevation of proinflammatory cytokines and CD86 gene expressions in skin lesions in NC/Nga mice.

PubMed

Inoue, Ryo; Otsuka, Mai; Nishio, Ayako; Ushida, Kazunari

2007-06-01

The administration of probiotic lactic acid bacteria (LAB) has been studied for its potential to prevent atopic dermatitis (AD). The objective of this study was to assess the inhibitory mechanism of a skin lesion by LAB using an experimental model that we previously demonstrated in NC/Nga mice. Lactobacillus johnsonii NCC533 (La1) was administered orally to the La1 group from 20 to 22 days after birth, while phosphate-buffered saline was given to the control group. After the induction of skin lesions in 6-week-old mice, the expression of genes supposedly involved in AD was evaluated. Gene expression of the proinflammatory cytokines [interleukin-8 (IL-8), IL-12 and IL-23] was significantly enhanced in the lesional skin of the control group by the induction of the lesion, whereas gene expression of those in the La1 group was not elevated. Interestingly, expression of the costimulatory molecule CD86 showed a pattern similar to the expression of the cytokines in the lesional skin. Moreover, the La1 group showed a significantly lower gene expression of CD86 in Peyer's patches and mesenteric lymph nodes than the control group. The suppression of proinflammatory cytokines and CD86 by primary administration of La1 may significantly contribute to the inhibitory effect on the skin lesion.

Individual Differences in Information Processing in Networked Decision Making

DTIC Science & Technology

2015-03-31

conclu- sion. On the other hand, need-for-cognitive-closure ( NCC ) [Webster and Kruglanski, 1994] indicates the desire to arrive at a decision quickly to...avoid discomfort caused by ambiguity or uncertainty. It has been shown that the individual differences in NC and NCC play a significant role in...and NCC scales on accuracy and timeliness of decision making has not been studied deeply in the literature. In this paper, we introduce an agent-based

Nurse-coordinated care improves the achievement of LDL cholesterol targets through more intensive medication titration.

PubMed

Snaterse, Marjolein; Jorstad, Harald T; Heiligenberg, Marlies; Ter Riet, Gerben; Boekholdt, S Matthijs; Scholte Op Reimer, Wilma; Peters, Ron J

2017-01-01

Nurse-coordinated care (NCC) improves the achievement of low-density lipoprotein-cholesterol (LDL-C) targets after an acute coronary syndrome (ACS). We hypothesised that NCC improves achievement of LDL-C targets through more intensive medication titration. We used data from Randomised Evaluation of Secondary Prevention by Outpatient Nurse Specialists (RESPONSE), a multicentre randomised trial on the efficacy of NCC in 754 ACS patients. Follow-up data were collected at 6 and 12 months. To enable comparison between the various types and dosages of statins, we used the average lipid-lowering potency (ALLP, % LDL-C lowering) as an indicator of lipid-lowering medication intensity. Most patients in NCC intervention and usual care groups (96%) had started lipid-lowering therapy during the index hospitalisation. At 6 months, titration activities (up or down) were applied in 45% of NCC patients compared with 24% of patients receiving usual care (p<0.001), and a difference was also seen at 12 months follow-up (52% vs 34%, p<0.001). In patients not on LDL-C target at baseline, titration activities at 6 months were recorded in 63% and 30% of NCC and usual care patients respectively (p<0.001), with increased titration activities in both groups at 12 months (69% vs 43%, p<0.001). NCC is associated with more frequent and intense lipid-lowering medication titration to reach LDL-C targets as compared with usual care alone. Further, merely starting the guideline-recommended dose is insufficient to reach the guideline-recommended LDL-C target level. TC1290 (Netherlands).

77 FR 28606 - Agency Information Collection Activities: Proposed Collection: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-15

... of both competitive programs will need to complete non-competing continuation (NCC) progress reports...-year project periods. Development Grant recipients will be required to complete one NCC to secure the...

Center Size and Center Performance.

ERIC Educational Resources Information Center

Helburn, Suzanne; Morris, John

1996-01-01

Examined the impact of child care center size on cost, quality, and profits per child. Examined centers ranging from 40 to 80 children and found total cost and revenue per child were similar for small, medium, and large centers. Found profits per child were highest in large centers and that there was no relationship between center quality and…

Gauge Theories on Noncommutative Spacetime Treated by the Seiberg-Witten Method*

NASA Astrophysics Data System (ADS)

Wess, J.

The idea of noncommutative coordinates (NCC) is almost as old as quantum field theory (QFT) itself. It was W.Heisenberg who proposed NCC in 1930 in a letter to Peierls [1]. He expressed the hope that uncertainty relations of the coordinates, derived from NCC, might provide a natural cut-off for divergent integrals in QFT. This idea propagated via W.Pauli, R.Oppenheimer and Oppenheimer's student H.S.Snyder [2]. He then published the first analysis of a quantum thoery on NCC. Paul [3] called this work mathematically ingenious but rejected it for reasons of physics, arguing that an effective cut-off would act like a universal length and thus lead to strange consequences for large momenta of order h/l0.

Performance management system enhancement and maintenance

NASA Technical Reports Server (NTRS)

Cleaver, T. G.; Ahour, R.; Johnson, B. R.

1984-01-01

The research described in this report concludes a two-year effort to develop a Performance Management System (PMS) for the NCC computers. PMS provides semi-automated monthly reports to NASA and contractor management on the status and performance of the NCC computers in the TDRSS program. Throughout 1984, PMS was tested, debugged, extended, and enhanced. Regular PMS monthly reports were produced and distributed. PMS continues to operate at the NCC under control of Bendix Corp. personnel.

Towards a Holistic Model for the Tectonic Evolution of the North China Craton

NASA Astrophysics Data System (ADS)

Kusky, T. M.; Polat, A.; Windley, B. F.; Wang, J.; Deng, H.

2016-12-01

The North China Craton (NCC) consists of distinctly different tectonic elements assembled during the late Archean - early Proterozoic. We propose a new tectonic evolution of the NCC. The Eastern Block (EB) consists of small microblocks that resemble a collage of accreted arc-rocks from a sutured archipelago similar to the SW Pacific, accreted between 2.6 and 2.7 Ga. An Atlantic-type margin developed on the western side of the EB by 2.5 Ga, and a >1,300 km long arc/accretionary prism collided with this passive margin at 2.5 Ga, obducting ophiolites and ophiolitic mélanges, and forming a foreland basin. This was followed by arc-polarity reversal, and injection of mantle wedge-derived melts. By 2.43 Ga, the ocean behind the accreted arc closed through the collision of an oceanic plateau. Rifting of the amalgamated craton followed at 2.4-2.35 Ga, with a failed rift arm preserved in the center of the craton, and two that successfully made an ocean along the northern margin. By 2.3 Ga an arc built on older cratonic material collided with this passive margin which soon converted to an Andean-type margin. Andean margin tectonics affected much of the craton from 2.3-1.9 Ga, forming a broad E-W swath of continental margin magmas, and retro-arc sedimentary basins including a superimposed basin over the passive margin on the northern margin. From 1.88-1.79 Ga the craton experienced a craton-wide granulite facies metamorphism and basement reactivation event with high-pressure granulites and eclogites in the north, and medium-pressure granulites across the craton. Early Proterozoic granulites and anatectic melts were generated by high-grade metamorphism and partial melting at mid-crustal levels beneath a collisionally-thickened plateau. This collision of the NCC on its northern margin was with the Columbia (Nuna) Continent. The NCC broke out in the period 1753-1673 Ma, as indicated by the formation of a suite of anorthosite, mangerite, charnockite, and alkali-feldspar granites

Preparation and characterization of nanocrystalline cellulose/Eucommia ulmoides gum nanocomposite film.

PubMed

Sun, Qianqian; Zhao, Xinkun; Wang, Dongmei; Dong, Juane; She, Diao; Peng, Pai

2018-02-01

The nanocomposite films were prepared using Eucommia ulmoides gum (EUG) matrix reinforced with nanocrystalline cellulose (NCC) at different concentrations. Subsequently, the obtained films were characterized by Raman spectra, AFM, XRD, TGA, and DSC. Meanwhile, the wettability, mechanical, and water vapor barrier properties of these films were analyzed. AFM noticed that the average sizes of NCC were 81.95×50.17×13.06nm, while the size of molecular chain for EUG was 2530×57.33×1.28nm. In comparison with control film, a certain amount of NCC obviously improved elongation at break and enhanced their crystallinity and ΔH m . More importantly, NCC/EUG nanocomposite films presented lower thermal stability, glass transition temperature (T g ), melting temperature (T m ), and water vapor permeability (WVP) values, especially the WVP values of 4% NCC film were the lowest as 0.28×10 -9 , 0.30×10 -9 , and 0.58×10 -9 g/m/h/Pa at RH 34%, 55%, and 76%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Overview of High-Fidelity Modeling Activities in the Numerical Propulsion System Simulations (NPSS) Project

NASA Technical Reports Server (NTRS)

Veres, Joseph P.

2002-01-01

A high-fidelity simulation of a commercial turbofan engine has been created as part of the Numerical Propulsion System Simulation Project. The high-fidelity computer simulation utilizes computer models that were developed at NASA Glenn Research Center in cooperation with turbofan engine manufacturers. The average-passage (APNASA) Navier-Stokes based viscous flow computer code is used to simulate the 3D flow in the compressors and turbines of the advanced commercial turbofan engine. The 3D National Combustion Code (NCC) is used to simulate the flow and chemistry in the advanced aircraft combustor. The APNASA turbomachinery code and the NCC combustor code exchange boundary conditions at the interface planes at the combustor inlet and exit. This computer simulation technique can evaluate engine performance at steady operating conditions. The 3D flow models provide detailed knowledge of the airflow within the fan and compressor, the high and low pressure turbines, and the flow and chemistry within the combustor. The models simulate the performance of the engine at operating conditions that include sea level takeoff and the altitude cruise condition.

Testing the Large-scale Environments of Cool-core and Non-cool-core Clusters with Clustering Bias

NASA Astrophysics Data System (ADS)

Medezinski, Elinor; Battaglia, Nicholas; Coupon, Jean; Cen, Renyue; Gaspari, Massimo; Strauss, Michael A.; Spergel, David N.

2017-02-01

There are well-observed differences between cool-core (CC) and non-cool-core (NCC) clusters, but the origin of this distinction is still largely unknown. Competing theories can be divided into internal (inside-out), in which internal physical processes transform or maintain the NCC phase, and external (outside-in), in which the cluster type is determined by its initial conditions, which in turn leads to different formation histories (I.e., assembly bias). We propose a new method that uses the relative assembly bias of CC to NCC clusters, as determined via the two-point cluster-galaxy cross-correlation function (CCF), to test whether formation history plays a role in determining their nature. We apply our method to 48 ACCEPT clusters, which have well resolved central entropies, and cross-correlate with the SDSS-III/BOSS LOWZ galaxy catalog. We find that the relative bias of NCC over CC clusters is b = 1.42 ± 0.35 (1.6σ different from unity). Our measurement is limited by the small number of clusters with core entropy information within the BOSS footprint, 14 CC and 34 NCC clusters. Future compilations of X-ray cluster samples, combined with deep all-sky redshift surveys, will be able to better constrain the relative assembly bias of CC and NCC clusters and determine the origin of the bimodality.

Mechanically Enhanced Liquid Interfaces at Human Body Temperature Using Thermosensitive Methylated Nanocrystalline Cellulose.

PubMed

Scheuble, N; Geue, T; Kuster, S; Adamcik, J; Mezzenga, R; Windhab, E J; Fischer, P

2016-02-09

The mechanical performance of materials at oil/water interfaces after consumption is a key factor affecting hydrophobic drug release. In this study, we methylated the surface of nanocrystalline cellulose (NCC) by mercerization and dimethyl sulfate exposure to produce thermosensitive biopolymers. These methylated NCC (metNCC) were used to investigate interfacial thermogelation at air/water and medium-chain triglyceride (MCT)/water interfaces at body temperature. In contrast to bulk fluid dynamics, elastic layers were formed at room temperature, and elasticity increased significantly at body temperature, which was measured by interfacial shear and dilatational rheology in situ. This unique phenomenon depends on solvent quality, temperature, and polymer concentration at interfaces. Thus, by adjusting the degree of hydrophobicity of metNCC, the interfacial elasticity and thermogelation of the interfaces could be varied. In general, these new materials (metNCC) formed more brittle interfacial layers compared to commercial methylcellulose (MC A15). Thermogelation of methylcellulose promotes attractive intermolecular forces, which were reflected in a change in self-assembly of metNCC at the interface. As a consequence, layer thickness and density increased as a function of temperature. These effects were measured by atomic force microscopy (AFM) images of the displaced interface and confirmed by neutron reflection. The substantial structural and mechanical change of methylcellulose interfaces at body temperature represents a controllable encapsulation parameter allowing optimization of lipid-based drug formulations.

Blocking Gastric Lipase Adsorption and Displacement Processes with Viscoelastic Biopolymer Adsorption Layers.

PubMed

Scheuble, Nathalie; Lussi, Micha; Geue, Thomas; Carrière, Frédéric; Fischer, Peter

2016-10-10

Delayed fat digestion might help to fight obesity. Fat digestion begins in the stomach by adsorption of gastric lipases to oil/water interfaces. In this study we show how biopolymer covered interfaces can act as a physical barrier for recombinant dog gastric lipase (rDGL) adsorption and thus gastric lipolysis. We used β-lactoglobulin (β-lg) and thermosensitive methylated nanocrystalline cellulose (metNCC) as model biopolymers to investigate the role of interfacial fluid dynamics and morphology for interfacial displacement processes by rDGL and polysorbate 20 (P20) under gastric conditions. Moreover, the influence of the combination of the flexible β-lg and the elastic metNCC was studied. The interfaces were investigated combining interfacial techniques, such as pendant drop, interfacial shear and dilatational rheology, and neutron reflectometry. Displacement of biopolymer layers depended mainly on the fluid dynamics and thickness of the layers, both of which were drastically increased by the thermal induced gelation of metNCC at body temperature. Soft, thin β-lg interfaces were almost fully displaced from the interface, whereas the composite β-lg-metNCC layer thermogelled to a thick interfacial layer incorporating β-lg as filler material and therefore resisted higher shear forces than a pure metNCC layer. Hence, with metNCC alone lipolysis by rDGL was inhibited, whereas the layer performance could be increased by the combination with β-lg.

High-quality AlN film grown on a nanosized concave-convex surface sapphire substrate by metalorganic vapor phase epitaxy

NASA Astrophysics Data System (ADS)

Yoshikawa, Akira; Nagatomi, Takaharu; Morishita, Tomohiro; Iwaya, Motoaki; Takeuchi, Tetsuya; Kamiyama, Satoshi; Akasaki, Isamu

2017-10-01

We developed a method for fabricating high-crystal-quality AlN films by combining a randomly distributed nanosized concavo-convex sapphire substrate (NCC-SS) and a three-step growth method optimized for NCC-SS, i.e., a 3-nm-thick nucleation layer (870 °C), a 150-nm-thick high-temperature layer (1250 °C), and a 3.2-μm-thick medium-temperature layer (1110 °C). The NCC-SS is easily fabricated using a conventional metalorganic vapor phase epitaxy reactor equipped with a showerhead plate. The resultant AlN film has a crack-free and single-step surface with a root-mean-square roughness of 0.5 nm. The full-widths at half-maxima of the X-ray rocking curve were 50/250 arcsec for the (0002)/(10-12) planes, revealing that the NCC surface is critical for achieving such a high-quality film. Hexagonal-pyramid-shaped voids at the AlN/NCC-SS interface and confinement of dislocations within the 150-nm-thick high-temperature layer were confirmed. The NCC surface feature and resultant faceted voids play an important role in the growth of high-crystal-quality AlN films, likely via localized and/or disordered growth of AlN at the initial stage, contributing to the alignment of high-crystal-quality nuclei and dislocations.

Net current control device. Final report

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

Fugate, D.; Cooper, J.H.

1998-11-01

Net currents generally result in elevated magnetic fields because the alternate paths are distant from the circuit conductors. Investigations have shown that one of the primary sources of power frequency magnetic fields in residential buildings is currents that return to their source via paths other than the neutral conductors. As part of EPRI`s Magnetic Field Shielding Project, ferromagnetic devices, called net current control (NCC) devices, were developed and tested for use in reducing net currents on electric power cables and the resulting magnetic fields. Applied to a residential service drop, an NCC device reduces net current by forcing current offmore » local non-utility ground paths, and back onto the neutral conductor. Circuit models and basic design equations for the NCC concept were developed, and proof-of-principles tests were carried out on an actual residence with cooperation from the local utility. After proving the basic concepts, three prototype NCC devices were built and tested on a simulated neighborhood power system. Additional prototypes were built for testing by interested EPRI utility members. Results have shown that the NCC prototypes installed on residential service drops reduce net currents to milliampere levels with compromising the safety of the ground system. Although the focus was on application to residential service cables, the NCC concept is applicable to single-phase and three-phase distribution systems as well.« less

Testing the Large-scale Environments of Cool-core and Non-cool-core Clusters with Clustering Bias

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

Medezinski, Elinor; Battaglia, Nicholas; Cen, Renyue

2017-02-10

There are well-observed differences between cool-core (CC) and non-cool-core (NCC) clusters, but the origin of this distinction is still largely unknown. Competing theories can be divided into internal (inside-out), in which internal physical processes transform or maintain the NCC phase, and external (outside-in), in which the cluster type is determined by its initial conditions, which in turn leads to different formation histories (i.e., assembly bias). We propose a new method that uses the relative assembly bias of CC to NCC clusters, as determined via the two-point cluster-galaxy cross-correlation function (CCF), to test whether formation history plays a role in determiningmore » their nature. We apply our method to 48 ACCEPT clusters, which have well resolved central entropies, and cross-correlate with the SDSS-III/BOSS LOWZ galaxy catalog. We find that the relative bias of NCC over CC clusters is b = 1.42 ± 0.35 (1.6 σ different from unity). Our measurement is limited by the small number of clusters with core entropy information within the BOSS footprint, 14 CC and 34 NCC clusters. Future compilations of X-ray cluster samples, combined with deep all-sky redshift surveys, will be able to better constrain the relative assembly bias of CC and NCC clusters and determine the origin of the bimodality.« less

Nurse-coordinated care improves the achievement of LDL cholesterol targets through more intensive medication titration

PubMed Central

Snaterse, Marjolein; Jorstad, Harald T; Heiligenberg, Marlies; ter Riet, Gerben; Boekholdt, S Matthijs; Scholte op Reimer, Wilma; Peters, Ron J

2017-01-01

Background Nurse-coordinated care (NCC) improves the achievement of low-density lipoprotein-cholesterol (LDL-C) targets after an acute coronary syndrome (ACS). We hypothesised that NCC improves achievement of LDL-C targets through more intensive medication titration. Methods We used data from Randomised Evaluation of Secondary Prevention by Outpatient Nurse Specialists (RESPONSE), a multicentre randomised trial on the efficacy of NCC in 754 ACS patients. Follow-up data were collected at 6 and 12 months. To enable comparison between the various types and dosages of statins, we used the average lipid-lowering potency (ALLP, % LDL-C lowering) as an indicator of lipid-lowering medication intensity. Results Most patients in NCC intervention and usual care groups (96%) had started lipid-lowering therapy during the index hospitalisation. At 6 months, titration activities (up or down) were applied in 45% of NCC patients compared with 24% of patients receiving usual care (p<0.001), and a difference was also seen at 12 months follow-up (52% vs 34%, p<0.001). In patients not on LDL-C target at baseline, titration activities at 6 months were recorded in 63% and 30% of NCC and usual care patients respectively (p<0.001), with increased titration activities in both groups at 12 months (69% vs 43%, p<0.001). Conclusion NCC is associated with more frequent and intense lipid-lowering medication titration to reach LDL-C targets as compared with usual care alone. Further, merely starting the guideline-recommended dose is insufficient to reach the guideline-recommended LDL-C target level. Trial Registration number TC1290 (Netherlands). PMID:28761680

Antigenic fractions from Taenia crassiceps metacestodes obtained by hydrophobicity for the immunodiagnosis of active and inactive forms of neurocysticercosis in human cerebrospinal fluid samples.

PubMed

da Silva, Gabriela B; Nunes, Daniela S; de Sousa, José Eduardo N; Gonçalves-Pires, Maria do R F; Levenhagen, Marcelo A; Costa-Cruz, Julia M

2017-04-01

This study aimed to evaluate the total extract of Taenia crassiceps metacestodes (TC) and its antigenic fractions obtained by Triton X-114 fractionation techniques, such as detergent (DC) and aqueous (AC), in the immunodiagnosis of human neurocysticercosis (NCC). Cerebrospinal fluid samples were divided into two groups: Group 1 (n=40), which was further divided into active (n=20) and inactive (n=20) NCC, and Group 2 (control group), which comprised 39 CSF samples from patients who had another neurological disorder, were suffering from other infectious diseases of the brain or had other parasitic infections. The total extracts and antigenic fractions were tested by enzyme-linked immunosorbent assay (ELISA) to detect human IgG anti-Taenia solium. T. crassiceps fractions (DC and AC) showed the same value of sensitivity (Se), 100%, for active and inactive NCC and a specificity (Sp) of 97.4%. The DS fraction obtained from T. solium showed 100% Se for active NCC, 95% Se for inactive NCC and a 92.3% Sp. The AS fraction obtained from T. solium showed 100% Se for both active and inactive NCC and a 94.9% Sp. There was a positive correlation between the total saline extract of T. crassiceps (TC) and T. solium (TS) and their fractions (DC, AC, DS and AS). Positive predictive value, negative predictive value, diagnostic efficiency and Youden index were calculated. In conclusion, these results demonstrated that detergent and aqueous fractions obtained from T. crassiceps metacestodes are important sources of specific antigens and are efficient for immunodiagnosis of active and inactive NCC. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

The non-diuretic hypotensive effects of thiazides are enhanced during volume depletion states

PubMed Central

Alshahrani, Saeed; Rapoport, Robert M.; Zahedi, Kamyar; Jiang, Min; Nieman, Michelle; Barone, Sharon; Meredith, Andrea L.; Lorenz, John N.; Rubinstein, Jack

2017-01-01

Thiazide derivatives including Hydrochlorothiazide (HCTZ) represent the most common treatment of mild to moderate hypertension. Thiazides initially enhance diuresis via inhibition of the kidney Na+-Cl- Cotransporter (NCC). However, chronic volume depletion and diuresis are minimal while lowered blood pressure (BP) is maintained on thiazides. Thus, a vasodilator action of thiazides is proposed, likely via Ca2+-activated K+ (BK) channels in vascular smooth muscles. This study ascertains the role of volume depletion induced by salt restriction or salt wasting in NCC KO mice on the non-diuretic hypotensive action of HCTZ. HCTZ (20mg/kg s.c.) lowered BP in 1) NCC KO on a salt restricted diet but not with normal diet; 2) in volume depleted but not in volume resuscitated pendrin/NCC dKO mice; the BP reduction occurs without any enhancement in salt excretion or reduction in cardiac output. HCTZ still lowered BP following treatment of NCC KO on salt restricted diet with paxilline (8 mg/kg, i.p.), a BK channel blocker, and in BK KO and BK/NCC dKO mice on salt restricted diet. In aortic rings from NCC KO mice on normal and low salt diet, HCTZ did not alter and minimally decreased maximal phenylephrine contraction, respectively, while contractile sensitivity remained unchanged. These results demonstrate 1) the non-diuretic hypotensive effects of thiazides are augmented with volume depletion and 2) that the BP reduction is likely the result of HCTZ inhibition of vasoconstriction through a pathway dependent on factors present in vivo, is unrelated to BK channel activation, and involves processes associated with intravascular volume depletion. PMID:28719636

Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting

PubMed Central

Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X.; Smith, Roger D.; Zahedi, Kamyar

2016-01-01

Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

Layer-by-layer assembled thin films and microcapsules of nanocrystalline cellulose for hydrophobic drug delivery.

PubMed

Mohanta, Vaishakhi; Madras, Giridhar; Patil, Satish

2014-11-26

A layer-by-layer (LbL) approach has been employed for the fabrication of multilayer thin films and microcapsules having nanofibrous morphology using nanocrystalline cellulose (NCC) as one of the components of the assembly. The applicability of these nanoassemblies as drug delivery carriers has been explored by the loading of an anticancer drug, doxorubicin hydrochloride, and a water-insoluble drug, curcumin. Doxorubicin hydrochloride, having a good water solubility, is postloaded in the assembly. In the case of curcumin, which is very hydrophobic and has limited solubility in water, a stable dispersion is prepared via noncovalent interaction with NCC prior to incorporation in the LbL assembly. The interaction of various other lipophilic drugs with NCC was analyzed theoretically by molecular docking in consideration of NCC as a general carrier for hydrophobic drugs.

Center for Adaptive Optics | Center

Science.gov Websites

Center for Adaptive Optics A University of California Science and Technology Center home Contact Us Director: Claire Max Office: Room 205, Center for Adaptive Optics Phone: (831) 459-2049 Fax: (831 ) 459-5717 Email: max@ucolick.org Associate Director: Donald Gavel Office: Room 209, Center for Adaptive

Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and γ-ENaC abundance in rat kidney.

PubMed

Zachar, Rikke; Al-Mashhadi, Ammar; Dimke, Henrik; Svenningsen, Per; Jensen, Boye L; Carlström, Mattias

2018-05-16

Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na+ transporters; and iii) the injured UPJO kidney allows aberrant filtration of plasminogen leading to proteolytic activation of the epithelial sodium channel gamma subunit (γ-ENaC). Hydronephrosis due to UPJO in pediatric patients and rats was associated with increased urinary plasminogen/creatinine ratio. In pediatric patients, plasma renin, angiotensin II, urine and plasma aldosterone and urine soluble pro-renin receptor did not differ significantly before and after surgery, or compared with controls. Increased plasmin/plasminogen ratio was seen in UPJO rats. Intact γ-ENaC abundance was not changed in UPJO kidney while low-molecular cleavage product abundance increased. The Na-Cl cotransporter (NCC) displayed significantly lower abundance in the UPJO kidney compared to the non-obstructed contralateral kidney. The Na-K-ATPase alpha-subunit was unaltered. Treatment with an angiotensin-converting enzyme inhibitor (8 days, captopril) significantly lowered blood pressure in UPJO rats. It is concluded that the RAAS contributes to hypertension following partial obstruction of urine flow at the pelvo-ureteric junction with potential contribution from proteolytic activation of ENaC.

The Reluctant Hegemon Counterdrug Efforts in Colombia

DTIC Science & Technology

2000-04-01

officers, General Fernando Perez and General Rito Alejo .22 On 2 May 99, government talks with the FARC resumed, and Pastrana and Marulanda met again...those who want war and those who want peace… It is a fight between generations.”24 FARC leaders are willing to negotiate, according to Alejo

2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma.

PubMed

2015-05-23

The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.

SPAK and OSR1 play essential roles in potassium homeostasis through actions on the distal convoluted tubule

PubMed Central

Ferdaus, Mohammed Z.; Barber, Karl W.; López‐Cayuqueo, Karen I.; Terker, Andrew S.; Argaiz, Eduardo R.; Gassaway, Brandon M.; Chambrey, Régine; Gamba, Gerardo; Rinehart, Jesse

2016-01-01

Key points STE20 (Sterile 20)/SPS‐1 related proline/alanine‐rich kinase (SPAK) and oxidative stress‐response kinase‐1 (OSR1) phosphorylate and activate the renal Na+–K+–2Cl− cotransporter 2 (NKCC2) and Na+Cl− cotransporter (NCC).Mouse models suggest that OSR1 mainly activates NKCC2‐mediated sodium transport along the thick ascending limb, while SPAK mainly activates NCC along the distal convoluted tubule, but the kinases may compensate for each other. We hypothesized that disruption of both kinases would lead to polyuria and severe salt‐wasting, and generated SPAK/OSR1 double knockout mice to test this.Despite a lack of SPAK and OSR1, phosphorylated NKCC2 abundance was still high, suggesting the existence of an alternative activating kinase.Compensatory changes in SPAK/OSR1‐independent phosphorylation sites on both NKCC2 and NCC and changes in sodium transport along the collecting duct were also observed.Potassium restriction revealed that SPAK and OSR1 play essential roles in the emerging model that NCC activation is central to sensing changes in plasma [K+]. Abstract STE20 (Sterile 20)/SPS‐1 related proline/alanine‐rich kinase (SPAK) and oxidative stress‐response kinase‐1 (OSR1) activate the renal cation cotransporters Na+–K+–2Cl− cotransporter (NKCC2) and Na+–Cl− cotransporter (NCC) via phosphorylation. Knockout mouse models suggest that OSR1 mainly activates NKCC2, while SPAK mainly activates NCC, with possible cross‐compensation. We tested the hypothesis that disrupting both kinases causes severe polyuria and salt‐wasting by generating SPAK/OSR1 double knockout (DKO) mice. DKO mice displayed lower systolic blood pressure compared with SPAK knockout (SPAK‐KO) mice, but displayed no severe phenotype even after dietary salt restriction. Phosphorylation of NKCC2 at SPAK/OSR1‐dependent sites was lower than in SPAK‐KO mice, but still significantly greater than in wild type mice. In the renal medulla, there was

Cost Analysis of a Home-Based Nurse Care Coordination Program

PubMed Central

Marek, Karen Dorman; Stetzer, Frank; Adams, Scott J; Bub, Linda Denison; Schlidt, Andrea; Colorafi, Karen Jiggins

2014-01-01

Objectives To determine whether a home-based care coordination program focused on medication self-management would affect the cost of care to the Medicare program and whether the addition of technology, a medication-dispensing machine, would further reduce cost. Design Randomized, controlled, three-arm longitudinal study. Setting Participant homes in a large Midwestern urban area. Participants Older adults identified as having difficulty managing their medications at discharge from Medicare Home Health Care (N = 414). Intervention A team consisting of advanced practice nurses (APNs) and registered nurses (RNs) coordinated care for two groups: home-based nurse care coordination (NCC) plus a pill organizer group and NCC plus a medication-dispensing machine group. Measurements To measure cost, participant claims data from 2005 to 2011 were retrieved from Medicare Part A and B Standard Analytical Files. Results Ordinary least squares regression with covariate adjustment was used to estimate monthly dollar savings. Total Medicare costs were $447 per month lower in the NCC plus pill organizer group (P = .11) than in a control group that received usual care. For participants in the study at least 3 months, total Medicare costs were $491 lower per month in the NCC plus pill organizer group (P = .06) than in the control group. The cost of the NCC plus pill organizer intervention was $151 per month, yielding a net savings of $296 per month or $3,552 per year. The cost of the NCC plus medication-dispensing machine intervention was $251 per month, and total Medicare costs were $409 higher per month than in the NCC plus pill organizer group. Conclusion Nurse care coordination plus a pill organizer is a cost-effective intervention for frail elderly Medicare beneficiaries. The addition of the medication machine did not enhance the cost effectiveness of the intervention. PMID:25482242

Epilepsy surgery in context of neurocysticercosis

PubMed Central

Singh, Gagandeep; Chowdhary, Ashwani Kumar

2014-01-01

The association between neurocysticercosis (NCC) and epilepsy is well known and NCC is an important risk factor for epileptic seizures in many Taenia solium-endemic regions of the world. However, while the relationship between NCC and epilepsy is well known, the association between NCC and medically refractory (or surgically remediable epilepsy) has received little attention in the past. Our experience and review of the sparse literature available suggests that NCC is causally related to surgically remediable epilepsy albeit uncommonly so and that association derives its underpinnings from several different scenarios: (1) Medically refractory lesional epilepsy, in which seizures arise from the vicinity of the calcified neurocysticercus lesion (CNL), (2) Medically refractory epilepsy with dual pathology type of relationship between the hippocampal sclerosis (HS) and CNL in which both have been unequivocally demonstrated to give rise to independent seizures and (3) Mesial temporal lobe epilepsy due to HS with a distantly-located CNL, which is in itself not epileptogenic. A major point of controversy revolves around whether or not there exists a causal association between the CNL and HS. We believe that an association exists between NCC and HS and the most important factor influencing this association is the location of the CNL. Furthermore, NCC is a risk factor for medically-refractory epilepsy and that this might account for a considerable proportion of the intractable epilepsy population in endemic regions; the association has been largely ignored owing to the lack of availability of presurgical work-up facilities in these regions. Finally, from a clinical standpoint of presurgical evaluation, patients with CNL and HS should be evaluated on a case by case basis owing to disparate settings underlying the association. PMID:24791092

Cost analysis of a home-based nurse care coordination program.

PubMed

Marek, Karen Dorman; Stetzer, Frank; Adams, Scott J; Bub, Linda Denison; Schlidt, Andrea; Colorafi, Karen Jiggins

2014-12-01

To determine whether a home-based care coordination program focused on medication self-management would affect the cost of care to the Medicare program and whether the addition of technology, a medication-dispensing machine, would further reduce cost. Randomized, controlled, three-arm longitudinal study. Participant homes in a large Midwestern urban area. Older adults identified as having difficulty managing their medications at discharge from Medicare Home Health Care (N = 414). A team consisting of advanced practice nurses (APNs) and registered nurses (RNs) coordinated care for two groups: home-based nurse care coordination (NCC) plus a pill organizer group and NCC plus a medication-dispensing machine group. To measure cost, participant claims data from 2005 to 2011 were retrieved from Medicare Part A and B Standard Analytical Files. Ordinary least squares regression with covariate adjustment was used to estimate monthly dollar savings. Total Medicare costs were $447 per month lower in the NCC plus pill organizer group (P = .11) than in a control group that received usual care. For participants in the study at least 3 months, total Medicare costs were $491 lower per month in the NCC plus pill organizer group (P = .06) than in the control group. The cost of the NCC plus pill organizer intervention was $151 per month, yielding a net savings of $296 per month or $3,552 per year. The cost of the NCC plus medication-dispensing machine intervention was $251 per month, and total Medicare costs were $409 higher per month than in the NCC plus pill organizer group. Nurse care coordination plus a pill organizer is a cost-effective intervention for frail elderly Medicare beneficiaries. The addition of the medication machine did not enhance the cost effectiveness of the intervention. © 2014 The Authors.The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

Petrochronology of Granitoids in the Langshan Reveals Carboniferous Plutonism along the Northeast Edge of the Alxa Block (NW China)

NASA Astrophysics Data System (ADS)

Rea-Downing, G.; Lippert, P. C.; Stearns, M.

2017-12-01

The Alxa block is positioned between the western North China Craton (NCC) to the east and the Tarim Craton to the west. Several first-order characteristics of the Alxa region remain largely unresolved due to the limited outcrop exposure and remote nature of the region. For example, the crustal affinity and thermo-tectonic history of the Alxa block throughout Central Asian terrane accretion may have pre-conditioned the Cenozoic and Recent strain. Recent paleomagnetic and detrital zircon studies within the Alxa block indicate that its basement geology and apparent polar wander path are substantially different from the NCC. These data suggest that Alxa was not initially part of the NCC. Identification of a suture between Alxa and the NCC, timing of the incorporation of the Alxa block with the NCC, and the correlation of well-studied tectono-thermal events occurring in the NCC to the comparatively understudied Alxa block to the west are poorly constrained. Preliminary petrochronologic data from granitoid bodies within the Langshan range address these limitations by characterizing the bedrock age and affinity along the NE edge of the Alxa block. LA-Q-ICP-MS analysis of zircons including U-Pb dates, major and minor trace elemental data, and rare earth element compositions are combined with bulk rock geochemistry to place early-mid Carboniferous ( 350 Ma) Langshan plutons in a regional context. The relative rarity of plutons of this age in a region replete with Permo-Triassic plutonism indicates that the Langshan includes a record of relatively understudied magmatism along the periphery of the NCC. The approach utilized here allows for 1) direct age and compositional comparisons to other Carboniferous-Permian plutons in central Asia and 2) a robust provenance data point for future detrital zircon studies of the Paleozoic paleogeography in the heart of Central Asia.

High-risk human papillomavirus among HIV-infected women with normal cervical cytology: a pilot study in Jos, Nigeria.

PubMed

Musa, Jonah; Taiwo, Babafemi; Achenbach, Chad; Olugbenga, Silas; Berzins, Baiba; Sagay, Atiene S; Idoko, John A; Kanki, Phyllis J; Murphy, Robert L

2013-12-01

Cervical cancer is strongly linked to high-risk human papillomavirus (HR-HPV) and is typically preceded by cytological abnormalities. Less is known in patients with normal cervical cytology (NCC). We investigated the epidemiology of HR-HPV among HIV-infected women with NCC. We conducted a cross-sectional study between January and June 2011 among HIV-infected women with NCC at an adult HIV clinic in Jos, Nigeria. Cervical sampling and analysis for HR-HPV by hybrid capture (HC2) with signal amplification was done to determine presence of one or more of the following HR-HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68. Epidemiologic factors associated with HR-HPV were determined using bivariate statistics and multivariate logistic regression. We evaluated 103 HIV-infected women with Pap cytology. The median age of the women was 32 years (range 21-49). Ninety-seven (94.2%) had NCC. Cervical samples for HR-HPV DNA testing were available from 89/97 (91.8%) of the HIV-infected women with NCC. Of the 89 women with cervical samples for HR-HPV DNA testing, 40 (44.9%) had detectable HR-HPV by HC2 giving a HR-HPV prevalence of 44.9% (95% CI 33.9-55.5%). Age < 30 years was associated with HR-HPV (OR 2.69 [95% CI 1.05-6.91, p = 0.039]) while history of previous abortion showed an inverse association with HR-HPV (OR 0.33[95% CI 0.15-0.94, p = 0.039]). The prevalence of HR-HPV is seemingly high among HIV-infected women with NCC in our clinical setting. These data provide support for further investigation of the clinical implications of positive HR-HPV among HIV-infected women with NCC report in cervical cancer prevention programs in Nigeria.

Controlling the Chiral Inversion Reaction of the Metallopeptide Ni-Asparagine-Cysteine-Cysteine with Dioxygen

PubMed Central

Glass, Amanda M.; Krause, Mary E.; Laurence, Jennifer S.; Jackson, Timothy A.

2014-01-01

Synthetically generated metallopeptides have the potential to serve a variety of roles in biotechnology applications, but the use of such systems is often hampered by the inability to control secondary reactions. We have previously reported that the NiII complex of the tripeptide LLL-asparagine-cysteine-cysteine, LLL-NiII-NCC, undergoes metal-facilitated chiral inversion to DLD-NiII-NCC, which increases the observed superoxide scavenging activity. However, the mechanism for this process remained unexplored. Electronic absorption and circular dichroism studies of the chiral inversion reaction of NiII-NCC reveal a unique dependence on dioxygen. Specifically, in the absence of dioxygen, the chiral inversion is not observed, even at elevated pH, whereas the addition of O2 initiates this reactivity and concomitantly generates superoxide. Scavenging experiments using acetaldehyde are indicative of the formation of carbanion intermediates, demonstrating that inversion takes place by deprotonation of the alpha carbons of Asn1 and Cys3. Together, these data are consistent with the chiral inversion being dependent on the formation of a NiIII-NCC intermediate from NiII-NCC and O2. The data further suggest that the anionic thiolate and amide ligands in NiII-NCC inhibit Cα–H deprotonation for the NiII oxidation state, leading to a stable complex in the absence of O2. Together, these results offer insights into the factors controlling reactivity in synthetic metallopeptides. PMID:22928993

Low sensitivity and frequent cross-reactions in commercially available antibody detection ELISA assays for Taenia solium cysticercosis.

PubMed

Garcia, Hector H; Castillo, Yesenia; Gonzales, Isidro; Bustos, Javier A; Saavedra, Herbert; Jacob, Louis; Del Brutto, Oscar H; Wilkins, Patricia P; Gonzalez, Armando E; Gilman, Robert H

2018-01-01

To evaluate the diagnostic performance of two commercially available ELISA kits, Novalisa ® and Ridascreen ® , for the detection of antibodies to Taenia solium, compared to serological diagnosis of neurocysticercosis (NCC) by LLGP-EITB (electro-immunotransfer blot assay using lentil-lectin purified glycoprotein antigens). Archive serum samples from patients with viable NCC (n = 45) or resolved, calcified NCC (n = 45), as well as sera from patients with other cestode parasites (hymenolepiasis, n = 45 and cystic hydatid disease, n = 45), were evaluated for cysticercosis antibody detection using two ELISA kits, Novalisa ® and Ridascreen ® . All NCC samples had previously tested positive, and all samples from heterologous infections were negative on LLGP-EITB for cysticercosis. Positive rates were calculated by kit and sample group and compared between the two kits. Compared to LLGP-EITB, the sensitivity of both ELISA assays to detect specific antibodies in patients with viable NCC was low (44.4% and 22.2%), and for calcified NCC, it was only 6.7% and 4.5%. Sera from patients with cystic hydatid disease were highly cross-reactive in both ELISA assays (38/45, 84.4%; and 25/45, 55.6%). Sera from patients with hymenolepiasis cross-reacted in five cases in one of the assays (11.1%) and in only one sample with the second assay (2.2%). The performance of Novalisa ® and Ridascreen ® was poor. Antibody ELISA detection cannot be recommended for the diagnosis of neurocysticercosis. © 2017 John Wiley & Sons Ltd.

Estimates for Pu-239 loadings in burial ground culverts based on fast/slow neutron measurements

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

Winn, W.G.; Hochel, R.C.; Hofstetter, K.J.

1989-08-15

This report provides guideline estimates for Pu-239 mass loadings in selected burial ground culverts. The relatively high recorded Pu-239 contents of these culverts have been appraised as suspect relative to criticality concerns, because they were assayed only with the solid waste monitor (SWM) per gamma-ray counting. After 1985, subsequent waste was also assayed with the neutron coincidence counter (NCC), and a comparison of the assay methods showed that the NCC generally yielded higher assays than the SWM. These higher NCC readings signaled a need to conduct non-destructive/non-intrusive nuclear interrogations of these culverts, and a technical team conducted scoping measurements tomore » illustrate potential assay methods based on neutron and/or gamma counting. A fast/slow neutron method has been developed to estimate the Pu-239 in the culverts. In addition, loading records include the SWM assays of all Pu-239 cuts of some of the culvert drums and these data are useful in estimating the corresponding NCC drum assays from NCC vs SWM data. Together, these methods yield predictions based on direct measurements and statistical inference.« less

Revisiting the NaCl cotransporter regulation by with-no-lysine kinases

PubMed Central

Bazúa-Valenti, Silvana

2015-01-01

The renal thiazide-sensitive Na+-Cl− cotransporter (NCC) is the salt transporter in the distal convoluted tubule. Its activity is fundamental for defining blood pressure levels. Decreased NCC activity is associated with salt-remediable arterial hypotension with hypokalemia (Gitelman disease), while increased activity results in salt-sensitive arterial hypertension with hyperkalemia (pseudohypoaldosteronism type II; PHAII). The discovery of four different genes causing PHAII revealed a complex multiprotein system that regulates the activity of NCC. Two genes encode for with-no-lysine (K) kinases WNK1 and WNK4, while two encode for kelch-like 3 (KLHL3) and cullin 3 (CUL3) proteins that form a RING type E3 ubiquitin ligase complex. Extensive research has shown that WNK1 and WNK4 are the targets for the KLHL3-CUL3 complex and that WNKs modulate the activity of NCC by means of intermediary Ste20-type kinases known as SPAK or OSR1. The understanding of the effect of WNKs on NCC is a complex issue, but recent evidence discussed in this review suggests that we could be reaching the end of the dark ages regarding this matter. PMID:25788573

Neurocysticercosis: Diagnostic problems & current therapeutic strategies

PubMed Central

Rajshekhar, Vedantam

2016-01-01

Neurocysticercosis (NCC) is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis) can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug) may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues. PMID:28139530

Authority defied: need for cognitive closure influences regulatory control when resisting authority.

PubMed

Damen, Tom G E; van Leeuwen, Matthijs L; Dijksterhuis, Ap; van Baaren, Rick B

2014-08-01

The present studies examined whether differences in need for cognitive closure (NCC) were related to differences in regulatory control when confronted with authority. In two studies, levels of regulatory control were measured when participants resisted (Study 1; N = 46) or prepared to resist the influence attempt of an authority figure (Study 2; N = 50). Results showed that resisting the influence attempt from a high-authority figure was more depleting for participants higher in NCC compared to individuals lower in NCC. However, when they were given instructions and time to prepare the act of resistance, individuals high in NCC actually showed an increase in regulatory control. Authority is usually viewed as a general principle of influence; however, the present studies suggest that there are individual differences that influence how people may experience interactions with authorities. © 2013 Wiley Periodicals, Inc.

The Carbonaceous - Non-Carbonaceous Chondrite Reservoir Dichotomy and the Challenge of Ureilites

NASA Astrophysics Data System (ADS)

Goodrich, C. A.

2017-08-01

Solar system materials are strongly divided into CC (carbonaceous chondrite) and NCC (non-CC) groups in terms of nucleosynthetic isotope anomalies. Ureilites are in the NCC group but seem to have had volatile-rich precursors. How could this be?

2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma

PubMed Central

2015-01-01

The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC. PMID:25918260

Report: EPA Could Improve Physical Access and Service Continuity/Contingency Controls for Financial and Mixed-Financial Systems Located at its Research Triangle Park Campus

EPA Pesticide Factsheets

Report #2006-P-00005, December 14, 2005. Controls needed to be improved in areas such as visitor access to facilities, use of contractor access badges, and general physical access to the NCC, computer rooms outside the NCC, and media storage rooms.

Evidence for an apical Na-Cl cotransporter involved in ion uptake in a teleost fish

USGS Publications Warehouse

Hiroi, J.; Yasumasu, S.; McCormick, S.D.; Hwang, P.-P.; Kaneko, T.

2008-01-01

Cation-chloride cotransporters, such as the Na+/K +/2Cl- cotransporter (NKCC) and Na+/Cl - cotransporter (NCC), are localized to the apical or basolateral plasma membranes of epithelial cells and are involved in active ion absorption or secretion. The objectives of this study were to clone and identify 'freshwater-type' and 'seawater-type' cation-chloride cotransporters of euryhaline Mozambique tilapia (Oreochromis mossambicus) and to determine their intracellular localization patterns within mitochondria-rich cells (MRCs). From tilapia gills, we cloned four full-length cDNAs homologous to human cation-chloride cotransporters and designated them as tilapia NKCC1a, NKCC1b, NKCC2 and NCC. Out of the four candidates, the mRNA encoding NKCC1a was highly expressed in the yolk-sac membrane and gills (sites of the MRC localization) of seawater-acclimatized fish, whereas the mRNA encoding NCC was exclusively expressed in the yolk-sac membrane and gills of freshwater-acclimatized fish. We then generated antibodies specific for tilapia NKCC1a and NCC and conducted whole-mount immunofluorescence staining for NKCC1a and NCC, together with Na+/K+-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR) and Na+/H+ exchanger 3 (NHE3), on the yolk-sac membrane of tilapia embryos acclimatized to freshwater or seawater. The simultaneous quintuple-color immunofluorescence staining allowed us to classify MRCs clearly into four types: types I, II, III and IV. The NKCC1a immunoreactivity was localized to the basolateral membrane of seawater-specific type-IV MRCs, whereas the NCC immunoreactivity was restricted to the apical membrane of freshwater-specific type-II MRCs. Taking account of these data at the level of both mRNA and protein, we deduce that NKCC1a is the seawater-type cotransporter involved in ion secretion by type-IV MRCs and that NCC is the freshwater-type cotransporter involved in ion absorption by type-II MRCs. We propose a novel ion-uptake model by MRCs in

Critical role of the SPAK protein kinase CCT domain in controlling blood pressure

PubMed Central

Zhang, Jinwei; Siew, Keith; Macartney, Thomas; O'Shaughnessy, Kevin M.; Alessi, Dario R.

2015-01-01

The STE20/SPS1-related proline/alanine-rich kinase (SPAK) controls blood pressure (BP) by phosphorylating and stimulating the Na-Cl (NCC) and Na-K-2Cl (NKCC2) co-transporters, which regulate salt reabsorption in the kidney. SPAK possesses a conserved carboxy-terminal (CCT) domain, which recognises RFXV/I motifs present in its upstream activator [isoforms of the With-No-lysine (K) kinases (WNKs)] as well as its substrates (NCC and NKCC2). To define the physiological importance of the CCT domain, we generated knock-in mice in which the critical CCT domain Leu502 residue required for high affinity recognition of the RFXI/V motif was mutated to Alanine. The SPAK CCT domain defective knock-in animals are viable, and the Leu502Ala mutation abolished co-immunoprecipitation of SPAK with WNK1, NCC and NKCC2. The CCT domain defective animals displayed markedly reduced SPAK activity and phosphorylation of NCC and NKCC2 co-transporters at the residues phosphorylated by SPAK. This was also accompanied by a reduction in the expression of NCC and NKCC2 protein without changes in mRNA levels. The SPAK CCT domain knock-in mice showed typical features of Gitelman Syndrome with mild hypokalaemia, hypomagnesaemia, hypocalciuria and displayed salt wasting on switching to a low-Na diet. These observations establish that the CCT domain plays a crucial role in controlling SPAK activity and BP. Our results indicate that CCT domain inhibitors would be effective at reducing BP by lowering phosphorylation as well as expression of NCC and NKCC2. PMID:25994507

The Association Between Neurocysticercosis and Hippocampal Atrophy is Related to Age

PubMed Central

Del Brutto, Oscar H.; Issa, Naoum P.; Salgado, Perla; Del Brutto, Victor J.; Zambrano, Mauricio; Lama, Julio; García, Héctor H.

2017-01-01

Neurocysticercosis (NCC) has been associated with hippocampal atrophy, but the prevalence and pathogenic mechanisms implicated in this relationship are unknown. Using a population-based, case–control study design, residents in a rural village (Atahualpa) aged ≥ 40 years with calcified NCC were identified as cases and paired to NCC-free individuals (control subjects) matched by age, sex, and level of education. Cases and control subjects underwent magnetic resonance imaging for hippocampal rating according to the Scheltens' scale for medial temporal atrophy and were interviewed to identify those with a clinical seizure disorder. The prevalence of hippocampal atrophy was compared between cases and control subjects by the use of the McNemar's test for correlated proportions. Seventy-five individuals with calcified NCC and their matched control subjects were included in the analysis. Hippocampal atrophy was noted in 26 (34.7%) cases and nine (12%) control subjects (odds ratio: 4.4; 95% confidence interval: 1.6–14.9, P < 0.0021). Stratification of pairs according to tertiles of age revealed an age-related trend in this association, which became significant only in those aged ≥ 68 years (P = 0.027). Only five cases and one control had recurrent seizures (P = 0.221); three of these five cases had hippocampal atrophy, and the single control subject had normal hippocampi. This study confirms an association between NCC and hippocampal atrophy, and shows that this association is stronger in older age groups. This suggests that NCC-related hippocampal atrophy takes a long time to develop. PMID:28077750

Meeting the Needs of Rural Students Through Distance Advising: The Role of Transfer Guides in Three Measures of Student Success.

ERIC Educational Resources Information Center

Dawson, Erica Cantrell; Dell, Cindy Ann

1997-01-01

Describes course information and supportive advising provided in articulation guides for students transferring from Northwest Community College (Montana) (NCC) to Montana State University. Comparison of post-transfer grade declines, grade recovery, and persistence of NCC transfer students with other community college transfers indicates that…

Mini-review: regulation of the renal NaCl cotransporter by hormones.

PubMed

Rojas-Vega, Lorena; Gamba, Gerardo

2016-01-01

The renal thiazide-sensitive NaCl cotransporter, NCC, is the major pathway for salt reabsorption in the distal convoluted tubule. The activity of this cotransporter is critical for regulation of several physiological variables such as blood pressure, serum potassium, acid base metabolism, and urinary calcium excretion. Therefore, it is not surprising that numerous hormone-signaling pathways regulate NCC activity to maintain homeostasis. In this review, we will provide an overview of the most recent evidence on NCC modulation by aldosterone, angiotensin II, vasopressin, glucocorticoids, insulin, norepinephrine, estradiol, progesterone, prolactin, and parathyroid hormone. Copyright © 2016 the American Physiological Society.

Finite-SNR analysis for partial relaying cooperation with channel coding and opportunistic relay selection

NASA Astrophysics Data System (ADS)

Vu, Thang X.; Duhamel, Pierre; Chatzinotas, Symeon; Ottersten, Bjorn

2017-12-01

This work studies the performance of a cooperative network which consists of two channel-coded sources, multiple relays, and one destination. To achieve high spectral efficiency, we assume that a single time slot is dedicated to relaying. Conventional network-coded-based cooperation (NCC) selects the best relay which uses network coding to serve the two sources simultaneously. The bit error rate (BER) performance of NCC with channel coding, however, is still unknown. In this paper, we firstly study the BER of NCC via a closed-form expression and analytically show that NCC only achieves diversity of order two regardless of the number of available relays and the channel code. Secondly, we propose a novel partial relaying-based cooperation (PARC) scheme to improve the system diversity in the finite signal-to-noise ratio (SNR) regime. In particular, closed-form expressions for the system BER and diversity order of PARC are derived as a function of the operating SNR value and the minimum distance of the channel code. We analytically show that the proposed PARC achieves full (instantaneous) diversity order in the finite SNR regime, given that an appropriate channel code is used. Finally, numerical results verify our analysis and demonstrate a large SNR gain of PARC over NCC in the SNR region of interest.

A Deeper Look at the "Neural Correlate of Consciousness".

PubMed

Fink, Sascha Benjamin

2016-01-01

A main goal of the neuroscience of consciousness is: find the neural correlate to conscious experiences (NCC). When have we achieved this goal? The answer depends on our operationalization of "NCC." Chalmers (2000) shaped the widely accepted operationalization according to which an NCC is a neural system with a state which is minimally sufficient (but not necessary) for an experience. A deeper look at this operationalization reveals why it might be unsatisfactory: (i) it is not an operationalization of a correlate for occurring experiences, but of the capacity to experience; (ii) it is unhelpful for certain cases which are used to motivate a search for neural correlates of consciousness; (iii) it does not mirror the usage of "NCC" by scientists who seek for unique correlates; (iv) it hardly allows for a form of comparative testing of hypotheses, namely experimenta crucis. Because of these problems (i-iv), we ought to amend or improve on Chalmers's operationalization. Here, I present an alternative which avoids these problems. This "NCC2.0" also retains some benefits of Chalmers's operationalization, namely being compatible with contributions from extended, embedded, enacted, or embodied accounts (4E-accounts) and allowing for the possibility of non-biological or artificial experiencers.

Properties and function of nephrocalcin: mechanism of kidney stone inhibition or promotion.

PubMed

Nakagawa, Y

1997-03-01

Nephrocalcin (NC), an acidic glycoprotein with molecular weight 14,000, is present in urine and prevents kidney stone formation. Histoimmunochemical staining shows that NC is localized in the proximal tubles in kidneys. Isolated NC from mammalian urine, revealed at least 4 isoforms of NC (we call these isoforms NC-A, NC-B, NC-C, and NC-D in the order of elution) during DEAE cellulose column chromatography with a linear gradient of NaCl elution step. Non-stone forming people excrete more NC-A and NC-B isoforms in urine; however, more NC-C and NC-D isoforms were found in stone formers' urine. When the organic matrix was extracted from surgically removed calcium oxalate kidney stones, we found greater quantities of NC-C and NC-D isoforms than those of NC-A and NC-B isoforms. Amino acid compositions and carbohydrate contents of these 4 isoforms were similar with the exception of the gamma-carboxyglutamic acid (GLA) residues. Only the NC-A and NC-B isoforms contained residues of GLA. There were more phosphate residues present in NC-C and NC-D than in NC-A and NC-B. Upon removal of phosphate residues by alkaline phosphatase, NC-C eluted at the same salt concentrations as NC-A eluted. This indicates that the backbone protein could be similar, but the NC-C isoform is modified by excess phosphate residues. Surface tension measurements using a Lauda film balance indicated that NC-A and -B were strongly amphiphilic while NC-C and -D were less amphiphilic. NC-A has an elongated shape, and occupies a smaller area per molecule; whereas NC-C is a bulky molecule. Using NC-A as a model of a "good" inhibitor and NC-C as a model of a "poor" inhibitor, both bound with 4 atoms of Ca2+ per molecule as investigated by equilibrium dialysis method, 31P-NMR, and electron spin resonance spectrometry. Isoforms A and B changed their conformation upon Ca2+ binding, but C and D did not change their conformation. All these observations suggest that isoforms A and B are strong inhibitors of

FIESTA: An operational decision aid for space network fault isolation

NASA Technical Reports Server (NTRS)

Lowe, Dawn; Quillin, Bob; Matteson, Nadine; Wilkinson, Bill; Miksell, Steve

1987-01-01

The Fault Tolerance Expert System for Tracking and Data Relay Satellite System (TDRSS) Applications (FIESTA) is a fault detection and fault diagnosis expert system being developed as a decision aid to support operations in the Network Control Center (NCC) for NASA's Space Network. The operational objectives which influenced FIESTA development are presented and an overview of the architecture used to achieve these goals are provided. The approach to the knowledge engineering effort and the methodology employed are also presented and illustrated with examples drawn from the FIESTA domain.

Information sharing guidebook for transportation management centers, emergency operations centers, and fusion centers.

DOT National Transportation Integrated Search

2010-06-01

This guidebook provides an overview of the mission and functions of transportation management centers, emergency operations centers, and fusion centers. The guidebook focuses on the types of information these centers produce and manage and how the sh...

Information sharing guidebook for transportation management centers, emergency operations centers, and fusion centers

DOT National Transportation Integrated Search

2010-06-01

This guidebook provides an overview of the mission and functions of transportation management centers, emergency operations centers, and fusion centers. The guidebook focuses on the types of information these centers produce and manage and how the sh...

OCULUS SeaTM: integrated maritime surveillance platform

NASA Astrophysics Data System (ADS)

Kanellopoulos, Sotirios A.; Katsoulis, Stavros; Motos, Dionysis; Lampropoulos, Vassilis; Margonis, Chris; Dimitros, Kostantinos; Thomopoulos, Stelios C. A.

2015-05-01

OCULUS Sea™ is a C2 platform for Integrated Maritime Surveillance. The platform consists of "loosely coupled" National/ Regional and Local C2 Centers which are "centrally governed". "Loosely coupled" as C2 Centers are located separately, share their Situational Pictures via a Message Oriented Middleware but preserve their administrational and operational autonomy. "Centrally governed" as there exists a central governance mechanism at the NCC that registers, authenticates and authorizes Regional and Local C2 centers into the OCULUS Sea network. From operational point of view, OCULUS Sea has been tested under realistic conditions during the PERSEUS [3] Eastern Campaign and has been positively evaluated by Coast Guard officers from Spain and Greece. From Research and Development point of view, OCULUS Sea can act as a test bed for validating any technology development is this domain in the near future.

A Space Science Summer Program for Minority Students in Middle School

NASA Astrophysics Data System (ADS)

Baker, A. M.; Patterson, L. A., III; Walter, D. K.

2003-05-01

South Carolina State University's (SCSU) Center for NASA Research and Technology started the Space Science Academy in 1998 for underrepresented minority students and teachers in grades 7-9. It has been offered every summer since then and has expanded from five half-days in 1998 to its current format as a full, two-week, residential program for the students with an additional three days of training for the teachers. Nearly 120 students and twenty teachers have participated over the years. The three day workshop for in-service and preservice teachers is based on the national and state science standards and includes hands-on, inquiry-based activities. The students live in the dorms on the campus at SCSU during the two weeks of the Space Science Academy. Sample activities include construction of model rockets and the planet Saturn, an in-depth study of the Sun and accessing astrophysical and NASA websites. We wish to acknowledge generous funding from the NASA MU-SPIN project through NCC 5-116 and NCC 5-534 as well as an IDEAS grant HST-ED-90242.01-A through the Space Telescope Science Institute.

78 FR 7424 - National Coal Council

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-01

... DEPARTMENT OF ENERGY National Coal Council AGENCY: Department of Energy. ACTION: Notice of open meeting. SUMMARY: This notice announces a meeting of the National Coal Council (NCC). The Federal Advisory... 2013 meeting of the National Coal Council. Agenda: 1. Opening Remarks by NCC Chairman John Eaves 2...

Educational Revolution on the Reservation: A Working Model.

ERIC Educational Resources Information Center

Murphy, Pete

1993-01-01

Since 1986, Navajo Community College (NCC) and Lawrence Livermore National Laboratory (LLNL) have collaborated to improve science and technical education on the Navajo Reservation through equipment loans, faculty exchanges, summer student work at LLNL, scholarships for NCC students, summer workshops for elementary science teachers, and classroom…

Assessment of Reduced-Kinetics Mechanisms for Combustion of Jet Fuel in CFD Applications

NASA Technical Reports Server (NTRS)

Ajmani, Kumud; Kundu, Krihna P.; Yungster, Shaye J.

2014-01-01

A computational effort was undertaken to analyze the details of fluid flow in Lean-Direct Injection (LDI) combustors for next-generation LDI design. The National Combustor Code (NCC) was used to perform reacting flow computations on single-element LDI injector configurations. The feasibility of using a reduced chemical-kinetics approach, which optimizes the reaction rates and species to model the emissions characteristics typical of lean-burning gas-turbine combustors, was assessed. The assessments were performed with Reynolds- Averaged Navier-Stokes (RANS) and Time-Filtered Navier Stokes (TFNS) time-integration, with a Lagrangian spray model with the NCC code. The NCC predictions for EINOx and combustor exit temperature were compared with experimental data for two different single-element LDI injector configurations, with 60deg and 45deg axially swept swirler vanes. The effects of turbulence-chemistry interaction on the predicted flow in a typical LDI combustor were studied with detailed comparisons of NCC TFNS with experimental data.

Beta Testing of CFD Code for the Analysis of Combustion Systems

NASA Technical Reports Server (NTRS)

Yee, Emma; Wey, Thomas

2015-01-01

A preliminary version of OpenNCC was tested to assess its accuracy in generating steady-state temperature fields for combustion systems at atmospheric conditions using three-dimensional tetrahedral meshes. Meshes were generated from a CAD model of a single-element lean-direct injection combustor, and the latest version of OpenNCC was used to calculate combustor temperature fields. OpenNCC was shown to be capable of generating sustainable reacting flames using a tetrahedral mesh, and the subsequent results were compared to experimental results. While nonreacting flow results closely matched experimental results, a significant discrepancy was present between the code's reacting flow results and experimental results. When wide air circulation regions with high velocities were present in the model, this appeared to create inaccurately high temperature fields. Conversely, low recirculation velocities caused low temperature profiles. These observations will aid in future modification of OpenNCC reacting flow input parameters to improve the accuracy of calculated temperature fields.

Enhanced structural stability of nanoporous zirconia under irradiation of He

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

Yang, Tengfei; Huang, Xuejun; Wang, Chenxu

2012-01-01

This work reports a greatly enhanced tolerance for He irradiation-induced swelling in nanocrystalline zirconia film with interconnected nanoporous structure (hereinafter referred as to NC-C). Compared to bulk yttria-stabilized zirconia (YSZ) and another nanocrystalline zirconia film only with discrete nano voids (hereinafter referred as to NC-V), the NC-C film reveals good tolerance for irradiation of high-fluence He. No appreciable surface blistering can be found even at the highest fluence of 6 1017 cm2 in NCC film. From TEM analysis of as-irradiated samples, the enhanced tolerance for volume swelling in NCC film is attributed to the enhanced diffusion mechanism of deposited Hemore » via widely distributed nano channels. Furthermore, the growth of grain size is quite small for both nanocrystalline zirconia films after irradiation, which is ascribed to the decreasing of area of grain boundary due to loose structure and low energy of primary knock-on atoms for He ions.« less

Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride.

PubMed

Terker, Andrew S; Zhang, Chong; McCormick, James A; Lazelle, Rebecca A; Zhang, Chengbiao; Meermeier, Nicholas P; Siler, Dominic A; Park, Hae J; Fu, Yi; Cohen, David M; Weinstein, Alan M; Wang, Wen-Hui; Yang, Chao-Ling; Ellison, David H

2015-01-06

Dietary potassium deficiency, common in modern diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure. The effect is dependent on plasma potassium, which modulates DCT cell membrane voltage and, in turn, intracellular chloride. Low intracellular chloride stimulates WNK kinases to activate NCC, limiting potassium losses, even at the expense of increased blood pressure. These data show that DCT cells, like adrenal cells, sense potassium via membrane voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride

PubMed Central

Terker, Andrew S.; Zhang, Chong; McCormick, James A.; Lazelle, Rebecca A.; Zhang, Chengbiao; Meermeier, Nicholas P.; Siler, Dominic A.; Park, Hae J.; Fu, Yi; Cohen, David M.; Weinstein, Alan M.; Wang, Wen-Hui; Yang, Chao-Ling; Ellison, David H.

2015-01-01

SUMMARY Dietary potassium deficiency, common in Western diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure. The effect is dependent on plasma potassium, which modulates DCT cell membrane voltage and, in turn, intracellular chloride. Low intracellular chloride stimulates WNK kinases to activate NCC, limiting potassium losses, even at the expense of increased blood pressure. These data show that DCT cells, like adrenal cells, sense potassium via membrane voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis. PMID:25565204

National Combustion Code: Parallel Implementation and Performance

NASA Technical Reports Server (NTRS)

Quealy, A.; Ryder, R.; Norris, A.; Liu, N.-S.

2000-01-01

The National Combustion Code (NCC) is being developed by an industry-government team for the design and analysis of combustion systems. CORSAIR-CCD is the current baseline reacting flow solver for NCC. This is a parallel, unstructured grid code which uses a distributed memory, message passing model for its parallel implementation. The focus of the present effort has been to improve the performance of the NCC flow solver to meet combustor designer requirements for model accuracy and analysis turnaround time. Improving the performance of this code contributes significantly to the overall reduction in time and cost of the combustor design cycle. This paper describes the parallel implementation of the NCC flow solver and summarizes its current parallel performance on an SGI Origin 2000. Earlier parallel performance results on an IBM SP-2 are also included. The performance improvements which have enabled a turnaround of less than 15 hours for a 1.3 million element fully reacting combustion simulation are described.

On the relationship between calcified neurocysticercosis and epilepsy in an endemic village: A large-scale, computed tomography-based population study in rural Ecuador.

PubMed

Del Brutto, Oscar H; Arroyo, Gianfranco; Del Brutto, Victor J; Zambrano, Mauricio; García, Héctor H

2017-11-01

Using a large-scale population-based study, we aimed to assess prevalence and patterns of presentation of neurocysticercosis (NCC) and its relationship with epilepsy in community-dwellers aged ≥20 years living in Atahualpa (rural Ecuador). In a three-phase epidemiological study, individuals with suspected seizures were identified during a door-to-door survey and an interview (phase I). Then, neurologists evaluated suspected cases and randomly selected negative persons to estimate epilepsy prevalence (phase II). In phase III, all participants were offered noncontrast computed tomography (CT) for identifying NCC cases. The independent association between NCC (exposure) and epilepsy (outcome) was assessed by the use of multivariate logistic regression models adjusted for age, sex, level of education, and alcohol intake. CT findings were subsequently compared to archived brain magnetic resonance imaging in a sizable subgroup of participants. Of 1,604 villagers aged ≥20 years, 1,462 (91%) were enrolled. Forty-one persons with epilepsy (PWE) were identified, for a crude prevalence of epilepsy of 28 per 1,000 population (95% confidence interval [CI] = 20.7-38.2). A head CT was performed in 1,228 (84%) of 1,462 participants, including 39 of 41 PWE. CT showed lesions consistent with calcified parenchymal brain cysticerci in 118 (9.6%) cases (95% CI = 8.1-11.4%). No patient had other forms of NCC. Nine of 39 PWE, as opposed to 109 of 1,189 participants without epilepsy, had NCC (23.1% vs. 9.2%, p = 0.004). This difference persisted in the adjusted logistic regression model (odds ratio = 3.04, 95% CI = 1.35-6.81, p = 0.007). This large CT-based study demonstrates that PWE had three times the odds of having NCC than those without epilepsy, providing robust epidemiological evidence favoring the relationship between NCC and epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Reciprocal contribution of clinical studies and the HP10 antigen ELISA for the diagnosis of extraparenchymal neurocysticercosis.

PubMed

Parkhouse, R Michael E; Carpio, Arturo; Campoverde, Alfredo; Sastre, Patricia; Rojas, Glenda; Cortez, María Milagros

2018-02-01

To evaluate diagnosis of active neurocysticercosis, paired cerebral spinal fluid (CSF) and serum samples from 24 neurocysticercosis (NCC) patients and 17 control neurological patients were assayed in the HP10 Taenia antigen (Ag) ELISA. The CSF samples were also tested with an HP10 Lateral Flow Assay (LFA). The HP10 Ag was detected by ELISA in the CSF of 5/5 patients with Definitive extraparenchymal NCC, and in 4/5 of the corresponding sera. In the Definitive parenchymal group, on the other hand, the HP10 Ag was absent in 2/3 CSF (with a very low value in the one positive sample) and all the corresponding serum samples. Samples of CSF from 4/7 patients in the Probable parenchymal group, were also significantly HP10 Ag positive, suggesting the presence of extraparenchymal cysts not identified by the imaging studies. With the possible exception of one patient, the corresponding serum samples of the Probable parenchymal NCC group, were all HP10 Ag negative. Samples of CSF from 9 NCC patients diagnosed with Mixed parenchymal and extraparenchymal NCC were all significantly HP10 Ag positive, confirming the presence of extraparenchymal cysts, with only 7/9 of the corresponding serum samples being HP10 positive. Thus detection of the HP10 Ag indicates extraparenchymal and not parenchymal cyst localization and is more sensitive with CSF than serum. Three neurological patients clinically diagnosed as subarachnoid cyst, hydrocephalus and tuberculoma, respectively, were clearly positive for HP10 Ag. Of these, two were confirmed as NCC by subsequent imaging; the third died prior to further examination. Thus, a total of 8 patients had their clinical diagnosis questioned. Finally, there was good agreement between the HP10 Ag ELISA and LFA with CSF samples giving an optical density ≥0.4 in the ELISA assay. In conclusion, the HP10 Ag assay should provide a valuable and reciprocal tool in the clinical diagnosis and follow up of extraparenchymal NCC. Copyright © 2017 Elsevier B

Association between Taenia solium infection and HIV/AIDS in northern Tanzania: a matched cross sectional-study.

PubMed

Schmidt, Veronika; Kositz, Christian; Herbinger, Karl-Heinz; Carabin, Hélène; Ngowi, Bernard; Naman, Ezra; Wilkins, Patricia P; Noh, John; Matuja, William; Winkler, Andrea Sylvia

2016-12-01

The frequency of Taenia solium, a zoonotic helminth, is increasing in many countries of sub-Saharan Africa, where the prevalence of the human immunodeficiency virus (HIV) is also high. However, little is known about how these two infections interact. The aim of this study was to compare the proportion of HIV positive (+) and negative (-) individuals who are infected with Taenia solium (TSOL) and who present with clinical and neurological manifestations of cysticercosis (CC). In northern Tanzania, 170 HIV+ individuals and 170 HIV- controls matched for gender, age and village of origin were recruited. HIV staging and serological tests for TSOL antibodies (Ab) and antigen (Ag) were performed. Neurocysticercosis (NCC) was determined by computed tomography (CT) using standard diagnostic criteria. Neurological manifestations were confirmed by a standard neurological examination. In addition, demographic, clinical and neuroimaging data were collected. Further, CD4 + cell counts as well as information on highly active antiretroviral treatment (HAART) were noted. No significant differences between HIV+ and HIV- individuals regarding the sero-prevalence of taeniosis-Ab (0.6% vs 1.2%), CC-Ab (2.4% vs 2.4%) and CC-Ag (0.6% vs 0.0%) were detected. A total of six NCC cases (3 HIV+ and 3 HIV-) were detected in the group of matched participants. Two individuals (1 HIV+ and 1 HIV-) presented with headaches as the main symptom for NCC, and four with asymptomatic NCC. Among the HIV+ group, TSOL was not associated with CD4 + cell counts, HAART duration or HIV stage. This study found lower prevalence of taeniosis, CC and NCC than had been reported in the region to date. This low level of infection may have resulted in an inability to find cross-sectional associations between HIV status and TSOL infection or NCC. Larger sample sizes will be required in future studies conducted in that area to conclude if HIV influences the way NCC manifests itself.

Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

PubMed

Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

2016-01-15

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. Copyright © 2016 the American Physiological Society.

Space Life Sciences Research and Education Program

NASA Technical Reports Server (NTRS)

Coats, Alfred C.

2001-01-01

Since 1969, the Universities Space Research Association (USRA), a private, nonprofit corporation, has worked closely with the National Aeronautics and Space Administration (NASA) to advance space science and technology and to promote education in those areas. USRA's Division of Space Life Sciences (DSLS) has been NASA's life sciences research partner for the past 18 years. For the last six years, our Cooperative Agreement NCC9-41 for the 'Space Life Sciences Research and Education Program' has stimulated and assisted life sciences research and education at NASA's Johnson Space Center (JSC) - both at the Center and in collaboration with outside academic institutions. To accomplish our objectives, the DSLS has facilitated extramural research, developed and managed educational programs, recruited and employed visiting and staff scientists, and managed scientific meetings.

User-Centered Design through Learner-Centered Instruction

ERIC Educational Resources Information Center

Altay, Burçak

2014-01-01

This article initially demonstrates the parallels between the learner-centered approach in education and the user-centered approach in design disciplines. Afterward, a course on human factors that applies learner-centered methods to teach user-centered design is introduced. The focus is on three tasks to identify the application of theoretical and…

A Comprehensive Program for Handicapped Students at the Two-Year College.

ERIC Educational Resources Information Center

Hanson, Karen M.

A summary is presented of the objectives and activities of a grant-supported project conducted at Normandale Community College (NCC) to expand programming for handicapped and learning disabled students. Introductory material provides a background to NCC's efforts in aiding students with special needs. Next, the populations receiving assistance…

Academic Performance of Community College Transferees.

ERIC Educational Resources Information Center

Fernandez, Thomas V.; And Others

A study was conducted at Nassau Community College (NCC) to determine how transfer students' performance at NCC compared with their performance at baccalaureate institutions; to compare the academic performance of graduate transfers with non-graduate transfers; and to determine what percentage of the transfers graduated from the baccalaureate…

Academic Planning through Program Review: Can It Work?

ERIC Educational Resources Information Center

Fernandez, Thomas V.; Raab, Marjorie K.

Nassau Community College (NCC) is currently working with a program evaluation model in which faculty from one department serve as peer evaluation consultants to direct the self-evaluations of other departments. The four functional objectives initially motivating the development of NCC's plan directed that: real decisions about academic programs…

Development of an integrated, unattended assay system for LWR-MOX fuel pellet trays

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

Stewart, J.E.; Hatcher, C.R.; Pollat, L.L.

1994-08-01

Four identical unattended plutonium assay systems have been developed for use at the new light-water-reactor mixed oxide (LWR-MOX) fuel fabrication facility at Hanau, Germany. The systems provide quantitative plutonium verification for all MOX pellet trays entering or leaving a large, intermediate store. Pellet-tray transport and storage systems are highly automated. Data from the ``I-Point`` (information point) assay systems will be shared by the Euratom and International Atomic Energy Agency (IAEA) Inspectorates. The I-Point system integrates, for the first time, passive neutron coincidence counting (NCC) with electro-mechanical sensing (EMS) in unattended mode. Also, provisions have been made for adding high-resolution gammamore » spectroscopy. The system accumulates data for every tray entering or leaving the store between inspector visits. During an inspection, data are analyzed and compared with operator declarations for the previous inspection period, nominally one month. Specification of the I-point system resulted from a collaboration between the IAEA, Euratom, Siemens, and Los Alamos. Hardware was developed by Siemens and Los Alamos through a bilateral agreement between the German Federal Ministry of Research and Technology (BMFT) and the US DOE. Siemens also provided the EMS subsystem, including software. Through the USSupport Program to the IAEA, Los Alamos developed the NCC software (NCC COLLECT) and also the software for merging and reviewing the EMS and NCC data (MERGE/REVIEW). This paper describes the overall I-Point system, but emphasizes the NCC subsystem, along with the NCC COLLECT and MERGE/REVIEW codes. We also summarize comprehensive testing results that define the quality of assay performance.« less

Effects of ACE inhibition and ANG II stimulation on renal Na-Cl cotransporter distribution, phosphorylation, and membrane complex properties

PubMed Central

Lee, Donna H.; Maunsbach, Arvid B.; Riquier-Brison, Anne D.; Nguyen, Mien T. X.; Fenton, Robert A.; Bachmann, Sebastian; Yu, Alan S.

2013-01-01

The renal distal tubule Na-Cl cotransporter (NCC) reabsorbs <10% of the filtered Na+ but is a key control point for blood pressure regulation by angiotensin II (ANG II), angiotensin-converting enzyme inhibitors (ACEI), and thiazide diuretics. This study aimed to determine whether NCC phosphorylation (NCCp) was regulated by acute (20–30 min) treatment with the ACEI captopril (12 μg/min × 20 min) or by a sub-pressor dose of ANG II (20 ng·kg−1·min−1) in Inactin-anesthetized rats. By immuno-EM, NCCp was detected exclusively in or adjacent to apical plama membranes (APM) in controls and after ACEI or ANG II treatment, while NCC total was detected in both APM and subapical cytoplasmic vesicles (SCV) in all conditions. In renal homogenates, neither ACEI nor ANG II treatment altered NCCp abundance, assayed by immunoblot. However, by density gradient fractionation we identified a pool of low-density APM in which NCCp decreased 50% in response to captopril and was restored during ANG II infusion, and another pool of higher-density APM that responded reciprocally, indicative of regulated redistribution between two APM pools. In both pools, NCCp was preferentially localized to Triton-soluble membranes. Blue Native gel electrophoresis established that APM NCCp localized to ∼700 kDa complexes (containing γ-adducin) while unphosphorylated NCC in intracellular membranes primarily localized to ∼400 kDa complexes: there was no evidence for native monomeric or dimeric NCC or NCCp. In summary, this study demonstrates that phosphorylated NCC, localized to multimeric complexes in the APM, redistributes in a regulated manner within the APM in response to ACEI and ANG II. PMID:23114965

Microtubule-dependent changes in morphology and localization of chloride transport proteins in gill mitochondria-rich cells of the tilapia, Oreochromis mossambicus.

PubMed

Yang, Wen-Kai; Wu, Yu-Ching; Tang, Cheng-Hao; Lee, Tsung-Han

2016-08-01

The tilapia (Oreochromis mossambicus) is a euryhaline fish exhibiting adaptive changes in cell size, phenotype, and ionoregulatory functions upon salinity challenge. Na(+) /Cl(-) cotransporter (NCC) and Na(+) /K(+) /2Cl(-) cotransporter (NKCC) are localized in the apical and basolateral membranes of mitochondria-rich (MR) cells of the gills. These cells are responsible for chloride absorption (NCC) and secretion (NKCC), respectively, thus, the switch of gill NCC and NKCC expression is a crucial regulatory mechanism for salinity adaptation in tilapia. However, little is known about the interaction of cytoskeleton and these adaptive changes. In this study, we examined the time-course of changes in the localization of NKCC/NCC in the gills of tilapia transferred from fresh water (FW) to brackish water (20‰) and from seawater (SW; 35‰) to FW. The results showed that basolateral NKCC disappeared and NCC was expressed in the apical membrane of MR cells. To further clarify the process of these adaptive changes, colchicine, a specific inhibitor of microtubule-dependent cellular regulating processes was used. SW-acclimated tilapia were transferred to SW, FW, and FW with colchicine (colchicine-FW) for 96 h. Compared with the FW-treatment group, in the MR cells of colchicine-FW-treatment group, (1) the average size was significantly larger, (2) only wavy-convex-subtype apical surfaces were found, and (3) the basolateral (cytoplasmic) NKCC signals were still exhibited. Taken together, our results suggest that changes in size, phenotype, as well as the expression of NCC and NKCC cotransporters of MR cells in the tilapia are microtubule-dependent. J. Morphol. 277:1113-1122, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Drainage water management combined with cover crop enhances reduction of soil phosphorus loss.

PubMed

Zhang, T Q; Tan, C S; Zheng, Z M; Welacky, T; Wang, Y T

2017-05-15

Integrating multiple practices for mitigation of phosphorus (P) loss from soils may enhance the reduction efficiency, but this has not been studied as much as individual ones. A four-year study was conducted to determine the effects of cover crop (CC) (CC vs. no CC, NCC) and drainage water management (DWM) (controlled drainage with sub-irrigation, CDS, vs. regular free tile drainage, RFD) and their interaction on P loss through both surface runoff (SR) and tile drainage (TD) water in a clay loam soil of the Lake Erie region. Cover crop reduced SR flow volume by 32% relative to NCC, regardless of DWM treatment. In contrast, CC increased TD flow volume by 57 and 9.4% with CDS and RFD, respectively, compared to the corresponding DWM treatment with NCC. The total (SR+TD) field water discharge volumes were comparable amongst all the treatments. Cover crop reduced flow-weighted mean (FWM) concentrations of particulate P (PP) by 26% and total P (TP) by 12% in SR, while it didn't affect the FWM dissolved reactive P (DRP) concentration, regardless of DWM treatments. Compared with RFD, CDS reduced FWM DRP concentration in TD water by 19%, while CC reduced FWM PP and TP concentrations in TD by 21 and 17%, respectively. Total (SR+TD) soil TP loss was the least with CDS-CC followed by RFD-CC, CDS-NCC, and RFD-NCC. Compared with RFD-NCC, currently popular practice in the region, total TP loss was reduced by 23% with CDS-CC. The CDS-CC system can be an effective practice to ultimately mitigate soil P loading to water resource. Copyright © 2017 Elsevier B.V. All rights reserved.

SUPERMODEL ANALYSIS OF GALAXY CLUSTERS

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

Fusco-Femiano, R.; Cavaliere, A.; Lapi, A.

2009-11-01

We present the analysis of the X-ray brightness and temperature profiles for six clusters belonging to both the Cool Core (CC) and Non Cool Core (NCC) classes, in terms of the Supermodel (SM) developed by Cavaliere et al. Based on the gravitational wells set by the dark matter (DM) halos, the SM straightforwardly expresses the equilibrium of the intracluster plasma (ICP) modulated by the entropy deposited at the boundary by standing shocks from gravitational accretion, and injected at the center by outgoing blast waves from mergers or from outbursts of active galactic nuclei. The cluster set analyzed here highlights notmore » only how simply the SM represents the main dichotomy CC versus NCC clusters in terms of a few ICP parameters governing the radial entropy run, but also how accurately it fits even complex brightness and temperature profiles. For CC clusters like A2199 and A2597, the SM with a low level of central entropy straightforwardly yields the characteristic peaked profile of the temperature marked by a decline toward the center, without requiring currently strong radiative cooling and high mass deposition rates. NCC clusters like A1656 require instead a central entropy floor of a substantial level, and some like A2256 and even more A644 feature structured temperature profiles that also call for a definite floor extension; in such conditions the SM accurately fits the observations, and suggests that in these clusters the ICP has been just remolded by a merger event, in the way of a remnant cool core. The SM also predicts that DM halos with high concentration should correlate with flatter entropy profiles and steeper brightness in the outskirts; this is indeed the case with A1689, for which from X-rays we find concentration values c approx 10, the hallmark of an early halo formation. Thus, we show the SM to constitute a fast tool not only to provide wide libraries of accurate fits to X-ray temperature and density profiles, but also to retrieve from the

The Petri Project Pipeline for Education, Training Resources, and Innovation

ERIC Educational Resources Information Center

Adams, Cindy; Bortz, Carolyn

2010-01-01

Northampton Community College (NCC) responded to an industry identified need within the regional biotechnology community for entry-level production workers in biomanufacturing. In an effort to meet this need and create a transitional program of study for dislocated and incumbent workers, NCC partnered with the local Workforce Investment Boards,…

The "No Crossing Constraint" in Autosegmental Phonology.

ERIC Educational Resources Information Center

Coleman, John; Local, John

A discussion of autosegmental phonology (AP), a theory of phonological representation that uses graphs rather than strings as the central data structure, considers its principal constraint, the "No Crossing Constraint" (NCC). The NCC is the statement that in a well-formed autosegmental diagram, lines of association may not cross. After…

Nature-Computer Camp. Final Evaluation Report 1984-1985. E.C.I.A. Chapter 2.

ERIC Educational Resources Information Center

District of Columbia Public Schools, Washington, DC. Div. of Quality Assurance.

This report presents a description and evaluation of the Nature-Computer Camp (NCC), a science- and technology-oriented program for sixth-grade students from the District of Columbia Public Schools. The NCC experience is designed to offer students opportunities in such environmentally-related areas as woodland ecology, stream ecology, geology, as…

Assessment of Student Academic Achievement.

ERIC Educational Resources Information Center

Neosho County Community Coll., Chanute, KS.

Neosho Community College (NCC) in Kansas developed an assessment program to measure changes in student learning and progress in courses and programs. The specific objectives of student assessment at NCC are to determine readiness for regular college courses; to determine proper placement; to assist students in meeting personal objectives; and to…

Comparative Academic Performance at the Baccalaureate Level Between Graduate Transferees at Nassau Community College and Native Students at Selected Public/Private Institutions.

ERIC Educational Resources Information Center

Fernandez, Thomas V., Jr.; And Others

The academic performance of 1973 graduate transferees from Nassau Community College (NCC) was compared at the baccalaureate level with 1975 native student graduates from 12 four-year public and private colleges and universities. These senior institutions were selected on the basis of the large number of NCC transferees they received. The…

Tracing fresh assimilates through Larix decidua exposed to elevated CO₂ and soil warming at the alpine treeline using compound-specific stable isotope analysis.

PubMed

Streit, Kathrin; Rinne, Katja T; Hagedorn, Frank; Dawes, Melissa A; Saurer, Matthias; Hoch, Günter; Werner, Roland A; Buchmann, Nina; Siegwolf, Rolf T W

2013-02-01

How will carbon source-sink relations of 35-yr-old larch trees (Larix decidua) at the alpine treeline respond to changes in atmospheric CO(2) and climate? We evaluated the effects of previously elevated CO(2) concentrations (9 yr, 580 ppm, ended the previous season) and ongoing soil warming (4 yr, + 4°C). Larch branches were pulse labeled (50 at% (13)CO(2)) in July 2010 to trace fresh assimilates through tissues (buds, needles, bark and wood) and non-structural carbon compounds (NCC; starch, lipids, individual sugars) using compound-specific isotope analysis. Nine years of elevated CO(2) did not lead to increased NCC concentrations, nor did soil warming increase NCC transfer velocities. By contrast, we found slower transfer velocities and higher NCC concentrations than reported in the literature for lowland larch. As a result of low dilution with older carbon, sucrose and glucose showed the highest maximum (13)C labels, whereas labels were lower for starch, lipids and pinitol. Label residence times in needles were shorter for sucrose and starch (c. 2 d) than for glucose (c. 6 d). Although our treatments showed no persistent effect on larch carbon relations, low temperature at high altitudes clearly induced a limitation of sink activities (growth, respiration, root exudation), expressed in slower carbon transfer and higher NCC concentrations. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

The European Eel NCCβ Gene Encodes a Thiazide-resistant Na-Cl Cotransporter*

PubMed Central

Moreno, Erika; Plata, Consuelo; Rodríguez-Gama, Alejandro; Argaiz, Eduardo R.; Vázquez, Norma; Leyva-Ríos, Karla; Islas, León; Cutler, Christopher; Pacheco-Alvarez, Diana; Mercado, Adriana; Cariño-Cortés, Raquel; Castañeda-Bueno, María; Gamba, Gerardo

2016-01-01

The thiazide-sensitive Na-Cl cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule. NCC plays a key role in the regulation of blood pressure. Its inhibition with thiazides constitutes the primary baseline therapy for arterial hypertension. However, the thiazide-binding site in NCC is unknown. Mammals have only one gene encoding for NCC. The eel, however, contains a duplicate gene. NCCα is an ortholog of mammalian NCC and is expressed in the kidney. NCCβ is present in the apical membrane of the rectum. Here we cloned and functionally characterized NCCβ from the European eel. The cRNA encodes a 1043-amino acid membrane protein that, when expressed in Xenopus oocytes, functions as an Na-Cl cotransporter with two major characteristics, making it different from other known NCCs. First, eel NCCβ is resistant to thiazides. Single-point mutagenesis supports that the absence of thiazide inhibition is, at least in part, due to the substitution of a conserved serine for a cysteine at position 379. Second, NCCβ is not activated by low-chloride hypotonic stress, although the unique Ste20-related proline alanine-rich kinase (SPAK) binding site in the amino-terminal domain is conserved. Thus, NCCβ exhibits significant functional differences from NCCs that could be helpful in defining several aspects of the structure-function relationship of this important cotransporter. PMID:27587391

Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.

PubMed

Pinto-Sanchez, Maria Ines; Hall, Geoffrey B; Ghajar, Kathy; Nardelli, Andrea; Bolino, Carolina; Lau, Jennifer T; Martin, Francois-Pierre; Cominetti, Ornella; Welsh, Christopher; Rieder, Amber; Traynor, Jenna; Gregory, Caitlin; De Palma, Giada; Pigrau, Marc; Ford, Alexander C; Macri, Joseph; Berger, Bernard; Bergonzelli, Gabriela; Surette, Michael G; Collins, Stephen M; Moayyedi, Paul; Bercik, Premysl

2017-08-01

Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and

Performance assessment of small-package-class nonintrusive inspection systems

NASA Astrophysics Data System (ADS)

Spradling, Michael L.; Hyatt, Roger

1997-02-01

The DoD Counterdrug Technology Development Program has addressed the development and demonstration of technology to enhance nonintrusive inspection of small packages such as passenger baggage, commercially delivered parcels, and breakbulk cargo items. Within the past year they have supported several small package-class nonintrusive inspection system performance assessment activities. All performance assessment programs involved the use of a red/blue team concept and were conducted in accordance with approved assessment protocols. This paper presents a discussion related to the systematic performance assessment of small package-class nonintrusive inspection technologies, including transmission, backscatter and computed tomography x-ray imaging, and protocol-related considerations for the assessment of these systems.

Comparative Study on Inclusive and Special Education Curricula in Hungary

ERIC Educational Resources Information Center

Gita, Szilvia; Bognar, Jozsef; Kalbli, Katalin; Dorogi, Laszlo

2008-01-01

Study aim: To compare the National Core Curriculum (NCC) and the special education curriculum regarding how much they are suitable for children with disabilities in the field of physical education and sports. Material and methods: Content analysis of Hungarian NCC and of 5 special schools curricula was employed to obtain information on specific…

An Overview of the NCC Spray/Monte-Carlo-PDF Computations

NASA Technical Reports Server (NTRS)

Raju, M. S.; Liu, Nan-Suey (Technical Monitor)

2000-01-01

This paper advances the state-of-the-art in spray computations with some of our recent contributions involving scalar Monte Carlo PDF (Probability Density Function), unstructured grids and parallel computing. It provides a complete overview of the scalar Monte Carlo PDF and Lagrangian spray computer codes developed for application with unstructured grids and parallel computing. Detailed comparisons for the case of a reacting non-swirling spray clearly highlight the important role that chemistry/turbulence interactions play in the modeling of reacting sprays. The results from the PDF and non-PDF methods were found to be markedly different and the PDF solution is closer to the reported experimental data. The PDF computations predict that some of the combustion occurs in a predominantly premixed-flame environment and the rest in a predominantly diffusion-flame environment. However, the non-PDF solution predicts wrongly for the combustion to occur in a vaporization-controlled regime. Near the premixed flame, the Monte Carlo particle temperature distribution shows two distinct peaks: one centered around the flame temperature and the other around the surrounding-gas temperature. Near the diffusion flame, the Monte Carlo particle temperature distribution shows a single peak. In both cases, the computed PDF's shape and strength are found to vary substantially depending upon the proximity to the flame surface. The results bring to the fore some of the deficiencies associated with the use of assumed-shape PDF methods in spray computations. Finally, we end the paper by demonstrating the computational viability of the present solution procedure for its use in 3D combustor calculations by summarizing the results of a 3D test case with periodic boundary conditions. For the 3D case, the parallel performance of all the three solvers (CFD, PDF, and spray) has been found to be good when the computations were performed on a 24-processor SGI Origin work-station.

A topical treatment containing heat-treated Lactobacillus johnsonii NCC 533 reduces Staphylococcus aureus adhesion and induces antimicrobial peptide expression in an in vitro reconstructed human epidermis model.

PubMed

Rosignoli, Carine; Thibaut de Ménonville, Séverine; Orfila, Danielle; Béal, Méline; Bertino, Béatrice; Aubert, Jérôme; Mercenier, Annick; Piwnica, David

2018-04-01

Staphylococcus aureus colonization is thought to contribute to the pathophysiology of atopic dermatitis (AD). AD patients exhibit reduced levels of cutaneous antimicrobial peptides (AMPs), which may explain their increased susceptibility to infections. Using an in vitro reconstructed human epidermis (RHE) model, we sought to determine whether topical application of a non-replicating probiotic, heat-treated Lactobacillus johnsonii NCC 533 (HT La1), could inhibit S. aureus adhesion to skin and boost cutaneous innate immunity. We found that application of HT La1 suspension to RHE samples reduced the binding of radiolabelled S. aureus by up to 74%. To investigate a potential effect of HT La1 on innate immunity, we analysed the expression of nine AMP genes, including those encoding beta defensins and S100 proteins, following topical application of HT La1 in suspension or in a daily moisturizer lotion. Analysed genes were induced by up to fourfold in a dose-dependent manner by HT La1 in suspension and by up to 2.4-fold by HT La1 in the moisturizer lotion. Finally, using ELISA and immunohistochemical detection, we evaluated the expression and secretion of the AMPs hBD-2 and psoriasin and determined that both proteins were induced by topical HT La1, particularly in the stratum corneum of the RHE. These findings demonstrate that a topically applied, non-replicating probiotic can modulate endogenous AMP expression and inhibit binding of S. aureus to an RHE model in vitro. Moreover, they suggest that a topical formulation containing HT La1 could benefit atopic skin by enhancing cutaneous innate immunity and reducing S. aureus colonization. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Insanity: Four Decades of U.S. Counterdrug Strategy

DTIC Science & Technology

2012-04-01

270 And, even if we could, domestically-produced marijuana , methamphetamine, and a host of illicit synthetic drugs would still be available to meet... marijuana .63 The Nixon Drug Spending Record  FY 1970 represented a 50% increase in the overall drug budget from FY 1969  Spending on demand...reduction spending  Spending between demand- reduction and supply- reduction reached parity 9 marijuana . Drug abuse was no longer ―public enemy

Reassessment of US Counter-Drug Strategy and Policy

DTIC Science & Technology

2007-03-30

imposed on society. Illegal drugs indiscriminately destroy old and young, men and women, from all racial and ethnic groups and every walk of life.3...curtail funding. Legalization is not recommended. History has shown that legalization increases drug use.84 Decriminalization , however, is a way to...and resolve. It is unlikely that 23 legislators or an administration will pursue decriminalization unless public pressure results in a mandate

An Empirical Examination of Counterdrug Interdiction Program Effectiveness.

DTIC Science & Technology

1997-01-01

inversely correlated with the street price index. Chapter IV examines the time dependence of the street price index and argues that interdiction activities...essentially asymptotic behavior in which the cumulative distribution function, for large values of the independent variable, converges to an inverse power-law...log(S) /log(M). Such an inverse power-law relation between unit purchase price and purchase volume is indeed observed within the STRIDE data

Are Special Operations Imperatives Applicable to Counterdrug Operations?

DTIC Science & Technology

1992-06-04

especially our neighbors to the south. In Peru the farmers have few other ways of making a profitable living. Peruvian leaders fear that their economic...was the inclusion of such local facilities as the courthouse, high school football field, railroad bridge trestle, sandbags provided by the local fire

Federal Lands Counterdrug Strategy and Enforcement Enhancement Act

THOMAS, 111th Congress

Rep. Nunes, Devin [R-CA-21

2010-06-30

House - 11/16/2010 Referred to the Subcommittee on Department Operations, Oversight, Nutrition and Forestry. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Diagnostic criteria for neurocysticercosis, revisited

PubMed Central

Del Brutto, Oscar H

2012-01-01

Diagnosis of neurocysticercosis (NCC) can be a challenge. Clinical manifestations are non-specific, most neuroimaging findings are non-pathognomonic, and some serologic tests have low sensitivity or specificity. A set of diagnostic criteria was proposed in 2001 to avoid the over diagnosis of NCC that occurs in epidemiologic surveys, and to help clinicians evaluating patients with suspected NCC. The set included four stratified categories of criteria, including: (1) absolute: histological demonstration of cysticerci, cystic lesions showing the scolex on neuroimaging studies, and direct visualization of subretinal parasites by fundoscopic examination; (2) major: lesions highly suggestive of NCC on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot (EITB) for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after cysticidal drug therapy, and spontaneous resolution of single enhancing lesions; (3) minor: lesions compatible with NCC on neuroimaging studies, suggestive clinical manifestations, positive cerebrospinal fluid (CSF) ELISA for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the nervous system; and (4) epidemiological: evidence of a household contact with Taenia solium infection, individuals coming from or living in cysticercosis endemic areas, and history of travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: (1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiological criteria; and (2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiological criteria, and in those who have three minor plus one epidemiological criteria. After 10 years of usage, this set has been proved useful in both, field studies, and hospital settings. Recent

Navajo Studies at Navajo Community College.

ERIC Educational Resources Information Center

Hatathli, Ned

The document covers the Navajo Studies Program (NSP) at Navajo Community College (NCC). The Navajo Studies Program differs from other Indian Studies Programs in 7 ways, e.g.: (1) it is located on the Navajo Reservation and controlled by the tribe; (2) NCC incorporates Indian studies into every individual program and area of concentration--English…

Family Planning Attitudes of Traditional and Acculturated Navajo Indians.

ERIC Educational Resources Information Center

Ackerman, Alan; And Others

To determine whether various indices of "acculturation" would predict attitudes towards family planning was the major purpose of a survey conducted among a highly educated group of Navajo people at Navajo Community College (NCC). Owned and operated by the Navajo Tribe, NCC served as a target survey model due to its 90% population of…

Diameter-height and crown relationships for loblolly pine from North Carolina and Oklahoma-Arkansas seed sources near the western edge of the natural range

Treesearch

Thomas B. Lynch; Rodney E. Will; Thomas C. Hennessey; Robert Heinemann; Randal Holeman; Dennis Wilson; Keith Anderson; Gregory Campbell

2013-01-01

In southeastern Oklahoma, loblolly pine (Pinus taeda L.) has been planted extensively outside the western boundary of its natural range. Furthermore, many plantings have been based on seed sources such as North Carolina Coastal (NCC) rather than Oklahoma-Arkansas (OA). NCC plantings are also frequent in nearby areas of Oklahoma and Arkansas which are...

Posterior Fossa Craniotomy for Adherent Fourth Ventricle Neurocysticercosis.

PubMed

Franko, Lynze R; Pandian, Balaji; Gupta, Avneesh; Savastano, Luis E; Chen, Kevin S; Riddell, James; Orringer, Daniel A

2018-06-14

Neurocysticercosis (NCC) is an infectious helminthic disease often presenting in patients who have immigration or travel history from areas where NCC is endemic. Fourth ventricle cysts from NCC pose a unique treatment challenge, as there is little consensus on the best treatment. This case study describes the treatment of a patient with fourth ventricle neurocysticercosis (FVNCC), examines the therapeutic decision-making, and provides a video of a posterior fossa craniotomy (PFC) resection of a degenerative cyst. The patient presented with headache, dizziness, nausea, and memory difficulties. A fourth ventricle cyst consistent with NCC was found on magnetic resonance imaging, and serum enzyme-linked immunosorbent assay (ELISA) confirmed the diagnosis. The cyst was removed utilizing an open PFC followed by antihelminthic therapy and corticosteroids. There was resolution of symptoms at 9 mo postoperatively. Several treatment modalities have been proposed for isolated cysts in the fourth ventricle, including medication, ventriculoperitoneal shunt, endoscopic removal, and PFC. The treatment decision is complex, and there is little guidance on the best treatment choices. In this article, we describe treatment via PFC for an adherent FVNCC cyst.

Paleoproterozoic high-pressure metamorphism in the northern North China Craton and implications for the Nuna supercontinent

PubMed Central

Wan, Bo; Windley, Brian F.; Xiao, Wenjiao; Feng, Jianyun; Zhang, Ji'en

2015-01-01

The connection between the North China Craton (NCC) and contiguous cratons is important for the configuration of the Nuna supercontinent. Here we document a new Paleoproterozoic high-pressure (HP) complex dominated by garnet websterite on the northern margin of the NCC. The peak metamorphism of the garnet websterite was after ∼1.90 Ga when it was subducted to eclogite facies at ∼2.4 GPa, then exhumed back to granulite facies at ∼0.9 GPa before ∼1.82 Ga. The rock associations with their structural relationships and geochemical affinities are comparable to those of supra-subduction zone ophiolites, and supported by subduction-related signatures of gabbros and basalts. We propose that a ∼1.90 Ga oceanic fragment was subducted and exhumed into an accretionary complex along the northern margin of the NCC. Presence of the coeval Sharyzhalgai complex with comparable HP garnet websterites in the southern Siberian active margin favours juxtaposition against the NCC in the Paleoproterozoic. PMID:26388458

Medical management of neurocysticercosis.

PubMed

Takayanagui, Osvaldo Massaiti; Odashima, Newton Satoru; Bonato, Pierina S; Lima, Jose Eduardo; Lanchote, Vera Lucia

2011-12-01

Neurocysticercosis (NCC) is considered to be the most common cause of acquired epilepsy worldwide. Formerly restricted to palliative measures, therapy for NCC has advanced with the advent of two drugs that are considered to be effective: praziquantel (PZQ) and albendazole (ALB). All available articles regarding research related to the treatment of NCC were searched. Relevant articles were then reviewed and used as sources of information for this review. Anticysticercal therapy has been marked by intense controversy. Recent descriptions of spontaneous resolution of parenchymal cysticercosis with benign evolution, risks of complications and reports of no long-term benefits have reinforced the debate over the usefulness and safety of anticysticercal therapy. High interindividual variability and complex pharmacological interactions will require the close monitoring of plasma concentrations of ALB and PZQ metabolites in future trials. Given the relative scarcity of clinical trials, more comparative interventional studies - especially randomized controlled trials in long-term clinical evolution - are required to clarify the controversy over the validity of parasitic therapy in patients with NCC.

Taeniasis/cysticercosis in Bali, Indonesia.

PubMed

Wandra, Toni; Sudewi, A A Raka; Swastika, I Kadek; Sutisna, Putu; Dharmawan, Nyoman S; Yulfi, Hemma; Darlan, Dewi Masyithah; Kapti, I Nengah; Samaan, Gina; Sato, Marcello Otake; Okamoto, Munehiro; Sako, Yasuhito; Ito, Akira

2011-07-01

Taenia solium and Taenia saginata are found in humans in Bali, Indonesia. During a field survey of 660 people in Bali from 2002-2009 of taeniasis/cysticercosis cases using mitochondrial DNA confirmation of the species, we detected 80 cases of T. saginata taeniasis, 2 dual T. saginata/T. solium infections with T. solium metacestodes in the brain and 12 neurocysticercosis (NCC) cases at Sanglah Hospital, Denpasar. Although the prevalence of NCC in Bali is low, sporadic cases are still present. There is no Taenia asiatica in Bali. We summarize here the field survey findings of taeniasis, including 1 dual infection with taeniasis and cysticercosis in 2007, and the reason why there are no T. asiatica cases and we describe 3 NCC cases admitted to Sanglah Hospital, Denpasar, Bali in 2004. Diagnosis was based on anamnesis, clinical examination, including CT Scan, histopathological, serological and mitochondrial DNA examinations. In order to prevent unexpected symptomatic NCC after treatment with praziquantel, we recommend introducing a rapid test to confirm taeniasis carriers and cysticercosis cases as a tool for real time diagnosis.

Alternative Fuels Data Center: Johnson Space Center Explores Alternative

Science.gov Websites

Fuel Vehicles Johnson Space Center Explores Alternative Fuel Vehicles to someone by E-mail Share Alternative Fuels Data Center: Johnson Space Center Explores Alternative Fuel Vehicles on Facebook Tweet about Alternative Fuels Data Center: Johnson Space Center Explores Alternative Fuel Vehicles on

Preschoolers' Perceptions of Performance and Satisfaction under Competitive and Non-Competitive Conditions

ERIC Educational Resources Information Center

Tsiakara, Angeliki A.; Digelidis, Nikolaos M.

2015-01-01

The aim of this study was to explore preschool children's perceptions of their performance under competitive and non-competitive conditions (NCC) and their satisfaction. Eighty preschool children (40 boys, 40 girls) aged 4-6 years (M age?=?5.48, SD?=?0.57) took part in this study. Preschool children built a tower under competitive and NCC and…

An Evaluation of the Implementation of National Core Curricula in Australia. Summary Report.

ERIC Educational Resources Information Center

Parkinson, Kevin J.; Broderick, John S.

As part of a study of the development and implementation of the National Core Curricula (NCC) in Australia, a historical background was prepared from a number of data sources and views on NCC were sought from senior Technical and Further Education (TAFE) officers in Australia. More specific information was sought in three case studies, the project…

Let your fingers do the walking: The projects most invaluable tool

NASA Technical Reports Server (NTRS)

Zirk, Deborah A.

1993-01-01

The barrage of information pertaining to the software being developed for a project can be overwhelming. Current status information, as well as the statistics and history of software releases, should be 'at the fingertips' of project management and key technical personnel. This paper discusses the development, configuration, capabilities, and operation of a relational database, the System Engineering Database (SEDB) which was designed to assist management in monitoring of the tasks performed by the Network Control Center (NCC) Project. This database has proven to be an invaluable project tool and is utilized daily to support all project personnel.

Improving Conceptual Design for Launch Vehicles. The Bimese Concept: A Study of Mission and Economic Options

NASA Technical Reports Server (NTRS)

Olds, John R.; Tooley, Jeffrey

1999-01-01

This report summarizes key activities conducted in the third and final year of the cooperative agreement NCC1-229 entitled "Improving Conceptual Design for Launch Vehicles." This project has been funded by the Vehicle Analysis Branch at NASA's Langley Research Center in Hampton, VA. Work has been performed by the Space Systems Design Lab (SSDL) at the Georgia Institute of Technology, Atlanta, GA. Accomplishments during the first and second years of this project have been previously reported in annual progress reports. This report will focus on the third and final year of the three year activity.

Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis.

PubMed

Terker, Andrew S; Zhang, Chong; Erspamer, Kayla J; Gamba, Gerardo; Yang, Chao-Ling; Ellison, David H

2016-01-01

Dietary potassium deficiency activates thiazide-sensitive sodium chloride cotransport along the distal nephron. This may explain, in part, the hypertension and cardiovascular mortality observed in individuals who consume a low-potassium diet. Recent data suggest that plasma potassium affects the distal nephron directly by influencing intracellular chloride, an inhibitor of the with-no-lysine kinase (WNK)-Ste20p-related proline- and alanine-rich kinase (SPAK) pathway. As previous studies used extreme dietary manipulations, we sought to determine whether the relationship between potassium and NaCl cotransporter (NCC) is physiologically relevant and clarify the mechanisms involved. We report that modest changes in both dietary and plasma potassium affect NCC in vivo. Kinase assay studies showed that chloride inhibits WNK4 kinase activity at lower concentrations than it inhibits activity of WNK1 or WNK3. Also, chloride inhibited WNK4 within the range of distal cell chloride concentration. Mutation of a previously identified WNK chloride-binding motif converted WNK4 effects on SPAK from inhibitory to stimulatory in mammalian cells. Disruption of this motif in WNKs 1, 3, and 4 had different effects on NCC, consistent with the three WNKs having different chloride sensitivities. Thus, potassium effects on NCC are graded within the physiological range, which explains how unique chloride-sensing properties of WNK4 enable it to mediate effects of potassium on NCC in vivo. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Assessment of Reference Height Models on Quality of Tandem-X dem

NASA Astrophysics Data System (ADS)

Mirzaee, S.; Motagh, M.; Arefi, H.

2015-12-01

The aim of this study is to investigate the effect of various Global Digital Elevation Models (GDEMs) in producing high-resolution topography model using TanDEM-X (TDX) Coregistered Single Look Slant Range Complex (CoSSC) images. We selected an image acquired on Jun 12th, 2012 over Doroud region in Lorestan, west of Iran and used 4 external digital elevation models in our processing including DLR/ASI X-SAR DEM (SRTM-X, 30m resolution), ASTER GDEM Version 2 (ASTER-GDEMV2, 30m resolution), NASA SRTM Version 4 (SRTM-V4, 90m resolution), and a local photogrammetry-based DEM prepared by National Cartographic Center (NCC DEM, 10m resolution) of Iran. InSAR procedure for DEM generation was repeated four times with each of the four external height references. The quality of each external DEM was initially assessed using ICESat filtered points. Then, the quality of, each TDX-based DEM was assessed using the more precise external DEM selected in the previous step. Results showed that both local (NCC) DEM and SRTM X-band performed the best (RMSE< 9m) for TDX-DEM generation. In contrast, ASTER GDEM v2 and SRTM C-band v4 showed poorer quality.

When teacher-centered instructors are assigned to student-centered classrooms

NASA Astrophysics Data System (ADS)

Lasry, Nathaniel; Charles, Elizabeth; Whittaker, Chris

2014-06-01

Technology-rich student-centered classrooms such as SCALE-UP and TEAL are designed to actively engage students. We examine what happens when the design of the classroom (conventional or teacher-centered versus student-centered classroom spaces) is consistent or inconsistent with the teacher's epistemic beliefs about learning and teaching (traditional or teacher-centered versus student-centered pedagogies). We compare two types of pedagogical approaches and two types of classroom settings through a quasiexperimental 2×2 factorial design. We collected data from 214 students registered in eight sections of an introductory calculus-based mechanics course given at a Canadian publicly funded two-year college. All students were given the Force Concept Inventory at the beginning and at the end of the 15-week-long course. We then focused on six teachers assigned to teach in the student-centered classroom spaces. We used qualitative observations and the Approaches to Teaching Inventory (ATI), a self-reported questionnaire, to determine the teachers' epistemic beliefs (teacher-centered or student-centered) and how these beliefs affected their use of the space and their students' conceptual learning. We report four main findings. First, the student-centered classroom spaces are most effective when used with student-centered pedagogies. Second, student-centered classrooms are ineffective when used with teacher-centered pedagogies and may have negative effects for students with low prior knowledge. Third, we find a strong correlation between six instructors' self-reported epistemic beliefs of student centeredness and their classes' average normalized gain (r =0.91; p =0.012). Last, we find that some instructors are more willing to adopt student-centered teaching practices after using student-centered classroom spaces. These data suggest that student-centered classrooms are effective only when instructors' epistemic framework of teaching and learning is consistent with a student-centered

Urban forest assessment in northern Delaware

Treesearch

David J. Nowak; Robert E. Hoehn; Jun Wang; Andy Lee; Vikram Krishnamurthy; Gary Schwetz

2009-01-01

Presents results of an analysis of the urban forest of the Wilmington, Delaware, the metropolitan corridor in New Castle County (NCC), and Rattlesnake Run sewershed in the city of Wilmington using the Urban Forest Effects (UFORE) model. This analysis reveals that there are about 882,700 trees (19.3 percent tree cover) in the NCC metro corridor and about 136,000 trees (...

National Combustion Code Parallel Performance Enhancements

NASA Technical Reports Server (NTRS)

Quealy, Angela; Benyo, Theresa (Technical Monitor)

2002-01-01

The National Combustion Code (NCC) is being developed by an industry-government team for the design and analysis of combustion systems. The unstructured grid, reacting flow code uses a distributed memory, message passing model for its parallel implementation. The focus of the present effort has been to improve the performance of the NCC code to meet combustor designer requirements for model accuracy and analysis turnaround time. Improving the performance of this code contributes significantly to the overall reduction in time and cost of the combustor design cycle. This report describes recent parallel processing modifications to NCC that have improved the parallel scalability of the code, enabling a two hour turnaround for a 1.3 million element fully reacting combustion simulation on an SGI Origin 2000.

Spray and High-Pressure Flow Computations in the National Combustion Code (NCC) Improved

NASA Technical Reports Server (NTRS)

Raju, Manthena S.

2002-01-01

Sprays occur in a wide variety of industrial and power applications and in materials processing. A liquid spray is a two-phase flow with a gas as the continuous phase and a liquid as the dispersed phase in the form of droplets or ligaments. The interactions between the two phases--which are coupled through exchanges of mass, momentum, and energy--can occur in different ways at disparate time and length scales involving various thermal, mass, and fluid dynamic factors. An understanding of the flow, combustion, and thermal properties of a rapidly vaporizing spray requires careful modeling of the ratecontrolling processes associated with turbulent transport, mixing, chemical kinetics, evaporation, and spreading rates of the spray, among many other factors. With the aim of developing an efficient solution procedure for use in multidimensional combustor modeling, researchers at the NASA Glenn Research Center have advanced the state-of-the-art in spray computations in several important ways.

13. SAC command center, weather center, underground structure, building 501, ...

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

13. SAC command center, weather center, underground structure, building 501, undated - Offutt Air Force Base, Strategic Air Command Headquarters & Command Center, Command Center, 901 SAC Boulevard, Bellevue, Sarpy County, NE

5. Command center doors at command center entry, building 501, ...

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

5. Command center doors at command center entry, building 501, looking north - Offutt Air Force Base, Strategic Air Command Headquarters & Command Center, Command Center, 901 SAC Boulevard, Bellevue, Sarpy County, NE

Chlorophyll Catabolites in Senescent Leaves of the Plum Tree (Prunus domestica).

PubMed

Erhart, Theresia; Mittelberger, Cecilia; Vergeiner, Clemens; Scherzer, Gerhard; Holzner, Barbara; Robatscher, Peter; Oberhuber, Michael; Kräutler, Bernhard

2016-11-01

In cold extracts of senescent leaves of the plum tree (Prunus domestica ssp. domestica), six colorless non-fluorescent chlorophyll catabolites (NCCs) were characterized, named Pd-NCCs. In addition, several minor NCC fractions were tentatively classified. The structure of the most polar one of the NCCs, named Pd-NCC-32, featured an unprecedented twofold glycosidation pattern. Three of the NCCs are also functionalized at their 3 2 -position by a glucopyranosyl group. In addition, two of these glycosidated NCCs carry a dihydroxyethyl group at their 18-position. In the polar Pd-NCC-32, the latter group is further glycosidated at the terminal 18 2 -position. Four other major Pd-NCCs and one minor Pd-NCC were identified with five NCCs from higher plants known to belong to the 'epi'-series. In addition, tentative structures were derived for two minor fractions, classified as yellow chlorophyll catabolites, which represented (formal) oxidation products of two of the observed Pd-NCCs. The chlorophyll catabolites in leaves of plum feature the same basic structural pattern as those found in leaves of apple and pear trees. © 2016 The Authors. Chemistry & Biodiversity Published by Wiley-VHCA AG, Zurich, Switzerland.

Alternative Fuels Data Center: About the Alternative Fuels Data Center

Science.gov Websites

About Printable Version Share this resource Send a link to Alternative Fuels Data Center: About the Alternative Fuels Data Center to someone by E-mail Share Alternative Fuels Data Center: About the Alternative Fuels Data Center on Facebook Tweet about Alternative Fuels Data Center: About the Alternative Fuels

Introduction to special section: Science and technology of over-the-horizon radar

NASA Astrophysics Data System (ADS)

Berkey, F. Tom

1998-07-01

The rationale for the development of over-the-horizon (OTH) radar systems operating at frequencies in the HF band arose out of a perceived need for an early-warning defense network. That need changed with the end of the Cold War; however, today OTH radars play a major role in the CounterDrug Program for the interdiction of drug-smuggling aircraft. This special section of Radio Science is devoted to a review of OTH radar technology, with emphasis on contemporary developments in this field. The collection of papers presented here has evolved largely from research and development efforts directed to improving the performance of OTH radar systems deployed both in the United States and in Australia.

Tcof1 acts as a modifier of Pax3 during enteric nervous system development and in the pathogenesis of colonic aganglionosis

PubMed Central

Barlow, Amanda J.; Dixon, Jill; Dixon, Michael; Trainor, Paul A.

2013-01-01

Hirschsprung disease (HSCR) is a human congenital disorder, defined by the absence of ganglia from variable lengths of the colon. These ganglia comprise the enteric nervous system (ENS) and are derived from migratory neural crest cells (NCCs). The inheritance of HSCR is complex, often non-Mendelian and characterized by variable penetrance. Although extensive research has identified many key players in the pathogenesis of Hirschsprung disease, a large number of cases remain genetically undefined. Therefore, additional unidentified genes or modifiers must contribute to the etiology and pathogenesis of Hirschsprung disease. We have discovered that Tcof1 may be one such modifier. Haploinsufficiency of Tcof1 in mice results in a reduction of vagal NCCs and their delayed migration along the length of the gut during early development. This alone, however, is not sufficient to cause colonic aganglionosis as alterations in the balance of NCC proliferation and differentiation ensures NCC colonize the entire length of the gut of Tcof1+/− mice by E18.5. In contrast, Tcof1 haploinsufficiency is able to sensitize Pax3+/− mice to colonic aganglionosis. Although, Pax3 heterozygous mice do not show ENS defects, compound Pax3;Tcof1 heterozygous mice exhibit cumulative apoptosis which severely reduces the NCC population that migrates into the foregut. In addition, the proliferative capacity of these NCC is also diminished. Taken together with the opposing effects of Pax3 and Tcof1 on NCC differentiation, the synergistic haploinsufficiency of Tcof1 and Pax3 results in colonic aganglionosis in mice and may contribute to the pathogenesis of Hirschsprung disease. PMID:23283078

Tcof1 acts as a modifier of Pax3 during enteric nervous system development and in the pathogenesis of colonic aganglionosis.

PubMed

Barlow, Amanda J; Dixon, Jill; Dixon, Michael; Trainor, Paul A

2013-03-15

Hirschsprung disease (HSCR) is a human congenital disorder, defined by the absence of ganglia from variable lengths of the colon. These ganglia comprise the enteric nervous system (ENS) and are derived from migratory neural crest cells (NCCs). The inheritance of HSCR is complex, often non-Mendelian and characterized by variable penetrance. Although extensive research has identified many key players in the pathogenesis of Hirschsprung disease, a large number of cases remain genetically undefined. Therefore, additional unidentified genes or modifiers must contribute to the etiology and pathogenesis of Hirschsprung disease. We have discovered that Tcof1 may be one such modifier. Haploinsufficiency of Tcof1 in mice results in a reduction of vagal NCCs and their delayed migration along the length of the gut during early development. This alone, however, is not sufficient to cause colonic aganglionosis as alterations in the balance of NCC proliferation and differentiation ensures NCC colonize the entire length of the gut of Tcof1(+/-) mice by E18.5. In contrast, Tcof1 haploinsufficiency is able to sensitize Pax3(+/-) mice to colonic aganglionosis. Although, Pax3 heterozygous mice do not show ENS defects, compound Pax3;Tcof1 heterozygous mice exhibit cumulative apoptosis which severely reduces the NCC population that migrates into the foregut. In addition, the proliferative capacity of these NCC is also diminished. Taken together with the opposing effects of Pax3 and Tcof1 on NCC differentiation, the synergistic haploinsufficiency of Tcof1 and Pax3 results in colonic aganglionosis in mice and may contribute to the pathogenesis of Hirschsprung disease.

Norway's New Culture Policy and the Arts: Values in Conflict.

ERIC Educational Resources Information Center

Klausen, Arne Martin

The basis for the New Norwegian Culture policy (NCC) is discussed in terms of the political attempt to extend the fundamental values of equality and social security into art and cultural life. The NCC is a result of a series of reports presented in the early 1970s which reflected a desire to see a broader welfare policy in Norway. The old form of…

Severe seizures in pigs naturally infected with Taenia solium in Tanzania.

PubMed

Trevisan, Chiara; Mkupasi, Ernatus M; Ngowi, Helena A; Forkman, Björn; Johansen, Maria V

2016-04-15

Neurocysticercosis (NCC) caused by Taenia solium is a serious neurological disease. In humans neurological symptoms have been thoroughly studied and documented, however, there is limited information on clinical signs in pigs infected with T. solium cysticerci. Among the scientific community, it is in fact believed that pigs with NCC rarely show neurological signs. The aim of this study was to describe clinical manifestations associated with NCC in pigs and correlate the manifestations to the number and distribution of cysticerci in brains of naturally infected pigs in Tanzania. Sixteen infected and 15 non-infected control pigs were observed for 14 days during daylight hours, and subsequently videotaped for another 14 consecutive days using close circuit television cameras. All occurrences of abnormal behaviour (trembling, twitching, mouth and ear paralysis, ataxia, dribbling, salivating, eye blinking, walking in circles) were recorded. At the end of the recording period, pigs were slaughtered and their brains dissected, cysticerci counted and locations noted. During the recording period, two infected pigs were observed having seizures. Some of the observed autonomic signs during a seizure were chewing motions with foamy salivation and ear stiffening. Motor signs included tonic muscle contractions followed by a sudden diminution in all muscle function leading to collapse of the animal. Stereotypic walking in circles was observed on several occasions. At dissection, both pigs had a high number of brain cysticerci (241 and 247 cysticerci). The two pigs with seizures were also older (36 months) compared to the others (18.3 months, ± 8.2 standard deviation). Results of this study have shown that pigs with NCC can develop clinical signs and suffer from seizures like humans with symptomatic NCC. Results of this study could potentially open up a new experimental pathway to explore the aetiology of neurological symptoms in humans with NCC associated epilepsy. Copyright �

Fertile lithospheric mantle beneath the northwestern North China and its implication for the subduction of the Paleo-Asian Ocean

NASA Astrophysics Data System (ADS)

Dai, H. K.; Zheng, J.; Su, Y. P.; Xiong, Q.; Pan, S. K.

2017-12-01

The nature of the sub-continental lithospheric mantle (SCLM) beneath the western North China Craton (NCC) is poorly known, which hinders understanding the cratonic response to the southward subduction of the Paleo-Asian Ocean. Mineral chemical data of spinel lherzolite xenoliths from newly discovered Cenozoic Langshan basalts in the northwestern part of the craton have been integrated with data from other localities across the western NCC, to put constrains on the SCLM nature and to explore the reworking processes involved. Compositions of mineral cores (i.e., Mg# in olivine = 88 91) and P-T estimates ( 1.2 GPa, 950 oC) suggest the Langshan xenoliths/xenocrysts represent fragments of the uppermost SCLM and experienced <15% melt extraction. These characteristics are similar to those of mantle xenoliths from other locaties (Siziwangqi and Hannuoba) along the northern margin of the western NCC. Disequilibrium characteristics are observed in xenoliths/xenocrysts in this study, including pyroxene spongy coronae and compositionally zoned olivine. They are interpreted to be induced by partial melting and by ironic diffusion with silicate melts in the mantle respectively, shortly before the eruption of host basalt. Metasomatism is recorded in clinopyroxene cores by concomitant enrichments in light rare earth elements and high field strength elements and was likely related to the migration of silicate melts derived from a mantle modified by slab melts during the Paleozoic time. The SCLM along the northern margin of the western NCC is fertile in nature constrained by mantle xenoliths from several localities (Langshan in this study, Siziwangqi and Hannuoba in references). Considering 1) the coexistence of fertile lithospheric mantle (similar to the Phanerozoic SCLM of the eastern NCC) and the overlying ancient continental crust, and 2) the sharp decrease in lithospheric thickness from the inner part to the northern margin of the western NCC, the SCLM beneath the northwestern

Radiocarbon determination of fossil and contemporary carbon contribution to aerosol in the Pacific Islands.

PubMed

Isley, C F; Nelson, P F; Taylor, M P; Williams, A A; Jacobsen, G E

2018-06-21

Combustion emissions are of growing concern across all Pacific Island Countries, which account for >10,000 km 2 of the earth's surface area; as for many other small island states globally. Apportioning emissions inputs for Suva, the largest Pacific Island city, will aid in development of emission reduction strategies. Total suspended particulate (TSP) and fine particulate (PM 2.5 ) samples were collected for Suva City, a residential area (Kinoya, TSP) and a mainly ocean-influenced site (Suva Point, TSP) from 2014 to 2015. Percentages of contemporary and fossil carbon were determined by radiocarbon analysis (accelerator mass spectrometry); for non‑carbonate carbon (NCC), elemental carbon (EC) and organic carbon (OC). Source contributions to particulate matter were identified and the accuracy of previous emissions inventory and source apportionment studies was evaluated. Suva Point NCC concentrations (2.7 ± 0.4 μg/m 3 ) were four times lower than for City (13 ± 2 μg/m 3 in TSP) and Kinoya (13 ± 1 μg/m 3 in TSP); demonstrating the contribution of land-based emissions activities in city and residential areas. In Suva City, total NCC in air was 81% (79%-83%) fossil carbon, from vehicles, shipping, power generation and industry; whilst in the residential area, 48% (46%-50%) of total NCC was contemporary carbon; reflecting the higher incidence of biomass and waste burning and of cooking activities. Secondary organic fossil carbon sources contributed >36% of NCC mass at the city and >29% at Kinoya; with biogenic carbon being Kinoya's most significant source (approx. 30% of NCC mass). These results support the previous source apportionment studies for the city area; yet show that, in line with emissions inventory studies, biomass combustion contributes more PM 2.5 mass in residential areas. Hence air quality management strategies need to target open burning activities as well as fossil fuel combustion. Copyright © 2018 Elsevier B.V. All rights

Syntectonic emplacement of the Triassic biotite-syenogranite intrusions in the Taili area, western Liaoning, NE China: Insights from petrogenesis, rheology and geochronology

NASA Astrophysics Data System (ADS)

Li, Weimin; Liu, Yongjiang; Jin, Wei; Neubauer, Franz; Zhao, Yingli; Liang, Chenyue; Wen, Quanbo; Feng, Zhiqiang; Li, Jing; Liu, Qing

2017-05-01

deduce much higher strain rates in the center (1.26 × 10-11-2.24 × 10-9 s-1) than at the margin (9.07 × 10-12-1.31 × 10-9 s-1) of the pluton. These observations are interpreted by the rheological behavior of magma during the magmatic ;pipe; flow. The adakitic source melts ascended through the conduits along weak NE-trending sinistral shear zones, and emplaced at the shallower depth of ∼16 km before Early Jurassic (∼190 Ma). The biotite-syenogranites were still in a semisolid state, when garnet-bearing granitic aplites injected at ∼220 Ma. This stage records elongate (constrictional) strain under the sinistral shear stresses, particularly in quartz grains occurring in the margin of intrusions. In combination with previous studies, an exhumation rate of the NCC's Archean basement (from ∼25 km to ∼11 km in depth) is calculated as initial low exhumation rate of ∼4.0 mm/kyr from Neoarchean to Late Triassic, and subsequent a rapid exhumation process of ∼63 mm/kyr between Late Triassic to Early Cretaceous. All the results presented here allow us to consider the geodynamic evolution of the eastern NCC and constrain the onset of lithospheric thinning and cratonic destruction of the NCC as early as Middle Triassic (∼240 Ma) triggered by the amalgamation of adjacent blocks. It developed prosperously since Late Triassic, due to the oblique subduction of the Paleo-Pacific Plate.

Vertebral growth modulation by hemicircumferential electrocoagulation: an experimental study in pigs.

PubMed

Caballero, Alberto; Barrios, Carlos; Burgos, Jesús; Hevia, Eduardo; Correa, Carlos

2011-08-01

This experimental study in pigs was aimed at evaluating spinal growth disorders after partial arrest of the vertebral epiphyseal plates (EP) and neurocentral cartilages (NCC). Unilateral and multisegmental single or combined lesions of the physeal structures were performed by electrocoagulation throughout a video-assisted thoracoscopical approach. Thirty 4-week-old domestic pigs (mean weight 16 kg) were included in the experiments. The superior and inferior epiphyseal plates of T5 to T9 vertebra were damaged in ten animals by hemicircumferential electrocoagulation (group I). In other ten pigs (group II), right NCC at the same T5-T9 levels were damaged. Ten other animals underwent combined lesions of the ipsilateral hemiepiphyseal plates and NCC at the T5-T9 levels. A total of 26 animals could be evaluated after 12 weeks of follow-up using conventional X-rays, CT scans and histology. The pigs with hemicircumferential EP damage developed very slight concave non-structured scoliotic deformities without vertebral rotation.(mean 12° Cobb; range10-16°). Some of the damaged vertebra showed a marked wedgening with unilateral development alteration of the vertebral body, including the adjacent discs The animals with damage of the NCC developed mild scoliotic curves (mean 19° Cobb; range 16-24°) with convexity opposite to the damaged side and loss of physiological kyphosis. The injured segments showed an asymmetric growth with hypoplasia of the pedicle and costovertebral joints at the damaged side. The pigs undergoing combined EP and NCC lesions developed minimal non-structured curves, ranging from 10 to 12° Cobb. In these animals there was a lack of growth of a vertebral hemibody and disc hypoplasia at the damaged segments. Both damage of the NCC and the EP affect the height of the vertebral body. No spinal stenosis was found in any case. In most cases, the adjacent superior and inferior vertebral EP to damaged segments had a compensatory growth that maintained the

[New perspective on the role of WNK1 and WNK4 in the regulation of NaCl reabsorption and K(+) secretion by the distal nephron].

PubMed

Rafael, Chloé; Chavez-Canales, Maria; Hadchouel, Juliette

2016-03-01

The study of Familial Hyperkalemic Hypertension (FHHt), a rare monogenic disease, allowed remarkable advances in the understanding of the mechanisms of regulation of NaCl reabsorption by the distal nephron. FHHt results from mutations in the genes encoding WNK1 and WNK4, two serine-threonine kinases of the WNK (With No lysine [K]) family. The clinical manifestations of FHHt are due, among others, to an increased activity of the Na(+)-Cl(-) cotransporter NCC. Several groups therefore tried to understand how WNK1 and WNK4 could regulate NCC. However, the data were often contradictory. Two of our recent studies allowed to partially explain these controversies and to propose a new model for the regulation of NCC by the WNKs. © 2016 médecine/sciences – Inserm.

Nanocrystalline cellulose-dispersed AKD emulsion for enhancing the mechanical and multiple barrier properties of surface-sized paper.

PubMed

Yang, Luming; Lu, Sheng; Li, Juanjuan; Zhang, Fengshan; Cha, Ruitao

2016-01-20

In this study, we employed nanocrystalline cellulose (NCC) as an efficient dispersant to perpare alkyl ketene dimer (AKD) emulsion. The particle size and zeta potential of AKD/NCC emulsion were measured, which were approximately 5 μm and -50 mV, respectively. The surface-sized paper possessed multiple barriers properties. The air permeability of surface-sized paper was 0.29 μm/Pas and the sizing degree reached 42 s when the amount of sizing was 12.58 g/m(2) with a 96.83% decrease and a 40.00%, increase, respectively. Furthermore, the mechanical properties were optimal when the amount of sizing was about 8 g/m(2). AKD/NCC emulsion acted as a good reinforcing agent in surface-sized paper. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of a reengineered electronic error-reporting system on medication event reporting and care process improvements at an urban medical center.

PubMed

McKaig, Donald; Collins, Christine; Elsaid, Khaled A

2014-09-01

A study was conducted to evaluate the impact of a reengineered approach to electronic error reporting at a 719-bed multidisciplinary urban medical center. The main outcome of interest was the monthly reported medication errors during the preimplementation (20 months) and postimplementation (26 months) phases. An interrupted time series analysis was used to describe baseline errors, immediate change following implementation of the current electronic error-reporting system (e-ERS), and trend of error reporting during postimplementation. Errors were categorized according to severity using the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Medication Error Index classifications. Reported errors were further analyzed by reporter and error site. During preimplementation, the monthly reported errors mean was 40.0 (95% confidence interval [CI]: 36.3-43.7). Immediately following e-ERS implementation, monthly reported errors significantly increased by 19.4 errors (95% CI: 8.4-30.5). The change in slope of reported errors trend was estimated at 0.76 (95% CI: 0.07-1.22). Near misses and no-patient-harm errors accounted for 90% of all errors, while errors that caused increased patient monitoring or temporary harm accounted for 9% and 1%, respectively. Nurses were the most frequent reporters, while physicians were more likely to report high-severity errors. Medical care units accounted for approximately half of all reported errors. Following the intervention, there was a significant increase in reporting of prevented errors and errors that reached the patient with no resultant harm. This improvement in reporting was sustained for 26 months and has contributed to designing and implementing quality improvement initiatives to enhance the safety of the medication use process.

Galaxy Clusters: A Novel Look at Diffuse Baryons Withstanding Dark Matter Gravity

NASA Astrophysics Data System (ADS)

Cavaliere, A.; Lapi, A.; Fusco-Femiano, R.

2009-06-01

In galaxy clusters, the equilibria of the intracluster plasma (ICP) and of the gravitationally dominant dark matter (DM) are governed by the hydrostatic equation and by the Jeans equation, respectively; in either case gravity is withstood by the corresponding, entropy-modulated pressure. Jeans, with the DM "entropy" set to K vprop r α and α ≈ 1.25-1.3 applying from groups to rich clusters, yields our radial α-profiles these, compared to the empirical Navarro-Frenk-White distribution, are flatter at the center and steeper in the outskirts as required by recent gravitational lensing data. In the ICP, on the other hand, the entropy run k(r) is mainly shaped by shocks, as steadily set by supersonic accretion of gas at the cluster boundary, and intermittently driven from the center by merging events or by active galactic nuclei (AGNs); the resulting equilibrium is described by the exact yet simple formalism constituting our ICP Supermodel. With two parameters, this accurately represents the runs of density n(r) and temperature T(r) as required by up-to-date X-ray data on surface brightness and spectroscopy for both cool core (CC) and non-cool core (NCC) clusters; the former are marked by a middle temperature peak, whose location is predicted from rich clusters to groups. The Supermodel inversely links the inner runs of n(r) and T(r), and highlights their central scaling with entropy nc vprop k -1 c and Tc vprop k 0.35 c , to yield radiative cooling times tc ≈ 0.3(kc /15 keV cm2)1.2 Gyr. We discuss the stability of the central values so focused: against radiative erosion of kc in the cool dense conditions of CC clusters, that triggers recurrent AGN activities resetting it back; or against energy inputs from AGNs and mergers whose effects are saturated by the hot central conditions of NCC clusters. From the Supermodel, we also derive as limiting cases the classic polytropic β-models, and the "mirror" model with T(r) vprop σ2(r) suitable for NCC and CC clusters

The Precarious Question of Black Cultural Centers Versus Multicultural Centers.

ERIC Educational Resources Information Center

Princes, Carolyn D. W.

This paper discusses the role of black cultural centers on university campuses, focusing on whether black cultural centers or multicultural centers best meet the needs of an increasingly diverse student body and society. It examines the historical role of black cultural centers as vehicles to promote educational opportunity, student retention, and…

X-33 Phase 2

NASA Technical Reports Server (NTRS)

1997-01-01

In response to Clause 17 of the Cooperative Agreement NCC8-115, Lockheed Martin Skunk Works has compiled an Annual Performance Report of the X-33/RLV Program. This report consists of individual reports from all industry team members, as well as NASA team centers. Contract award was announced on July 2, 1996 and the first milestone was hand delivered to NASA MSFC on July 17, 1996. The first year has been one of growth and progress as all team members staffed up and embarked on the technical adventure of the 20th century... the ultimate goal . . a Single Stage to Orbit (SSTO) Reuseable Launch Vehicle (RLV).

National Space Biomedical Research Institute

NASA Technical Reports Server (NTRS)

1999-01-01

This report summarizes the activities of the National Space Biomedical Research Institute (NSBRI) during FY 1999, the second full year of existence of the NSBRI's research program, and is prepared in accordance with Cooperative Agreement NCC9-58 between NASA's Lyndon B. Johnson Space Center and Baylor College of Medicine (NSBRI). The report consists of progress reports on projects related to the effects of microgravity and space on physiology. The research is broken up in nine areas: (1) Bone loss, (2) Cardiovascular alterations, (3) human performance, (3) immunology, infection and hematology, (4) muscle alterations and atrophy,(5) Neurovestibular adaptation, radiation effects, (6) technology development, and (7) synergy projects.

Renewable Energy Opportunity Assessment

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

Hancock, Ed; Mas, Carl

1998-11-13

Presently, the US EPA is constructing a new complex at Research Triangle Park, North Carolina to consolidate its research operations in the Raleigh-Durham area. The National Computer Center (NCC) is currently in the design process and is planned for construction as part of this complex. Implementation of the new technologies can be planned as part of the normal construction process, and full credit for elimination of the conventional technologies can be taken. Several renewable technologies are specified in the current plans for the buildings. The objective of this study is to identify measures that are likely to be both technicallymore » and economically feasible.« less

Aerial view of the Kennedy Space Center Visitor Center

NASA Technical Reports Server (NTRS)

1998-01-01

This Shuttle/Gantry mockup and Post Show Dome anchor the northeast corner of the Kennedy Space Center Visitor Complex. The Astronaut Memorial is located just above. Sprawling across 70 acres on Florida's Space Coast, the complex is located off State Road 405, NASA Parkway, six miles inside the Space Center entrance. The building at the upper left is the Theater Complex. Other exhibits and buildings on the site are the Center for Space Education, Cafeteria, Space Flight Exhibit Building, Souvenir Sales Building, Spaceport Central, Ticket Pavilion and Center for Space Education.

Disease behaviours of sows naturally infected with Taenia solium in Tanzania.

PubMed

Trevisan, Chiara; Johansen, Maria Vang; Mkupasi, Ernatus Martin; Ngowi, Helena Aminel; Forkman, Björn

2017-02-15

Neurocysticercosis (NCC) is a disease caused by the zoonotic parasite Taenia solium lodging in the central nervous system. Both humans and pigs can get NCC. The impact of the disease in pigs has so far been little explored. The aim of this study was to describe the effect of NCC on social and feeding behaviours as well as the pattern of activity as indicators of reduced welfare in naturally infected sows. In total 13 T. solium naturally infected and 15 non-infected control sows were videotaped for 2 consecutive weeks using close circuit television cameras at research facilities at Sokoine University of Agriculture, Morogoro, Tanzania. Videos were analysed at the beginning, in the middle and at the end of the 2 week recording period. For each time point, videos were analysed during feeding, while the enrichment was provided, and by recording every half an hour the sows' behaviours performed over the course of a whole day. Sows with NCC spent significantly less time at the feeding trough, especially during the second half of the feeding period. Infected sows were also more passive e.g. lying and standing still significantly more during a whole day period and showed social isolation compared to non-infected control sows by performing behaviours more distant to their nearest neighbour. Results of this study indicated that NCC changed the behaviour of infected sows. The behavioural changes are indicative of decreased welfare. Efforts to reinforce the animal welfare aspect are needed as this has so far been neglected. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

A Deeper Look at the “Neural Correlate of Consciousness”

PubMed Central

Fink, Sascha Benjamin

2016-01-01

A main goal of the neuroscience of consciousness is: find the neural correlate to conscious experiences (NCC). When have we achieved this goal? The answer depends on our operationalization of “NCC.” Chalmers (2000) shaped the widely accepted operationalization according to which an NCC is a neural system with a state which is minimally sufficient (but not necessary) for an experience. A deeper look at this operationalization reveals why it might be unsatisfactory: (i) it is not an operationalization of a correlate for occurring experiences, but of the capacity to experience; (ii) it is unhelpful for certain cases which are used to motivate a search for neural correlates of consciousness; (iii) it does not mirror the usage of “NCC” by scientists who seek for unique correlates; (iv) it hardly allows for a form of comparative testing of hypotheses, namely experimenta crucis. Because of these problems (i–iv), we ought to amend or improve on Chalmers's operationalization. Here, I present an alternative which avoids these problems. This “NCC2.0” also retains some benefits of Chalmers's operationalization, namely being compatible with contributions from extended, embedded, enacted, or embodied accounts (4E-accounts) and allowing for the possibility of non-biological or artificial experiencers. PMID:27507950

FGF23 regulates renal sodium handling and blood pressure

PubMed Central

Andrukhova, Olena; Slavic, Svetlana; Smorodchenko, Alina; Zeitz, Ute; Shalhoub, Victoria; Lanske, Beate; Pohl, Elena E; Erben, Reinhold G

2014-01-01

Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. Here, we show that FGF23 directly regulates the membrane abundance of the Na+:Cl− co-transporter NCC in distal renal tubules by a signaling mechanism involving the FGF receptor/αKlotho complex, extracellular signal-regulated kinase 1/2 (ERK1/2), serum/glucocorticoid-regulated kinase 1 (SGK1), and with-no lysine kinase-4 (WNK4). Renal sodium (Na+) reabsorption and distal tubular membrane expression of NCC are reduced in mouse models of Fgf23 and αKlotho deficiency. Conversely, gain of FGF23 function by injection of wild-type mice with recombinant FGF23 or by elevated circulating levels of endogenous Fgf23 in Hyp mice increases distal tubular Na+ uptake and membrane abundance of NCC, leading to volume expansion, hypertension, and heart hypertrophy in a αKlotho and dietary Na+-dependent fashion. The NCC inhibitor chlorothiazide abrogates FGF23-induced volume expansion and heart hypertrophy. Our findings suggest that FGF23 is a key regulator of renal Na+ reabsorption and plasma volume, and may explain the association of FGF23 with cardiovascular risk in chronic kidney disease patients. PMID:24797667

White spotting phenotype induced by targeted REST disruption during neural crest specification to a melanocyte cell lineage.

PubMed

Aoki, Hitomi; Hara, Akira; Kunisada, Takahiro

2015-05-01

Neural crest cells (NCCs) emerge from the dorsal region of the neural tube of vertebrate embryos and have the pluripotency to differentiate into both neuronal and non-neuronal lineages including melanocytes. Rest, also known as NRSF (neuro-restrictive silencer factor), is a regulator of neuronal development and function and suggested to be involved in the lineage specification of NCCs. However, further investigations of Rest gene functions in vivo have been hampered by the fact that Rest null mice show early embryonic lethality. To investigate the function of Rest in NCC development, we recently established NCC-specific Rest conditional knockout (CKO) mice and observed their neonatal death. Here, we have established viable heterozygous NCC-specific Rest CKO mice to analyze the function of Rest in an NCC-derived melanocyte cell lineage and found that the white spotting phenotype was associated with the reduction in the number of melanoblasts in the embryonic skin. The Rest deletion induced after the specification to melanocytes did not reduce the number of melanoblasts; therefore, the expression of REST during the early neural crest specification stage was necessary for the normal development of melanoblasts to cover all of the skin. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Economic burden of neurocysticercosis: results from Peru.

PubMed

Rajkotia, Yogesh; Lescano, Andres G; Gilman, Robert H; Cornejo, Christian; Garcia, Hector H

2007-08-01

Neurocysticercosis (NCC) is a major cause of neurological morbidity in the developing world. This study aimed to assess the treatment costs and productivity losses associated with NCC in Peru. NCC patients were identified through retrospective chart analysis. Patients meeting inclusion criteria were interviewed in order to obtain data on symptom history, treatment costs, productivity losses and health service utilisation patterns. These data were modelled to determine average treatment costs and productivity losses over 2 years. Our findings show that treatment costs and productivity losses consume 54% of an annual minimum wage salary during the first year of treatment and 16% during the second year. Diagnosis (36%) and drug therapy (27%) represent the most expensive healthcare-related costs. These costs are prohibitive for some-8% of our study sample had no diagnostic tests during their first 6 months of disease, and two-thirds of those who delayed treatment reportedly did so due to their inability to pay. Two-thirds of wage-earners lost their jobs owing to NCC and only 61% were able to re-engage in wage-earning activities. This study highlights the need to expand financial coverage to ensure the poor have access to health services and do not become further impoverished.

Low temperature synthesis of diamond-based nano-carbon composite materials with high electron field emission properties

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

Saravanan, A.; Huang, B. R.; Yeh, C. J.

2015-06-08

A diamond-based nano-carbon composite (d/NCC) material, which contains needle-like diamond grains encased with the nano-graphite layers, was synthesized at low substrate temperature via a bias enhanced growth process using CH{sub 4}/N{sub 2} plasma. Such a unique granular structure renders the d/NCC material very conductive (σ = 714.8 S/cm), along with superior electron field emission (EFE) properties (E{sub 0} = 4.06 V/μm and J{sub e} = 3.18 mA/cm{sup 2}) and long lifetime (τ = 842 min at 2.41 mA/cm{sup 2}). Moreover, the electrical conductivity and EFE behavior of d/NCC material can be tuned in a wide range that is especially useful for different kind of applications.

Intracavity optically controlled crystal modulators for a CO/sub 2/ laser

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

Chizhevskii, V.N.; Churakov, V.V.

1986-06-01

This paper presents the results of studies of intracavity amplitude modulation of CW CO/sub 2/ laser radiation by its optically controlled absorption on nonequilibrium charge carriers (NCC) in KRS-5, KRS-6, and ZnSe crystals. The fundamental variables which determine the efficiency of such a modulation method are discussed. The radiation from a ruby laser with a 35-nsec pulse width was used to produce the nonequilibrium charge carriers. The variation of the modulation percentage of the intensity vs. excitation level at lambda = 0.6943 ..mu..m is shown for different powers of the CO/sub 2/ laser. The studies attest to the relatively highmore » efficiency of intracavity modulation based on IR radiation absorption by NCC in crystals, where the NCC are generated under the influence of external excitation.« less

Surface grafting of cellulose nanocrystals with poly(ethylene oxide) in aqueous media.

PubMed

Kloser, Elisabeth; Gray, Derek G

2010-08-17

Aqueous suspensions of poly(ethylene oxide)-grafted nanocrystalline cellulose (PEO-grafted NCC) were prepared in order to achieve steric instead of electrostatic stabilization. A two-step process was employed: in the first step NCC suspensions prepared by sulfuric acid hydrolysis were desulfated with sodium hydroxide, and in the second step the surfaces of the crystals were functionalized with epoxy-terminated poly(ethylene oxide) (PEO epoxide) under alkaline conditions. The PEO-grafted samples were analyzed by conductometric titration, ATR-IR, solid-state NMR, MALDI-TOF MS, SEC MALLS, and AFM. The covalent nature of the linkage was confirmed by weight increase and MALDI-TOF analysis. The PEO-grafted cellulose nanocrystals (CNCs) formed a stable colloidal suspension that remained well dispersed, while the desulfated nanoparticles aggregated and precipitated. Upon concentration of the PEO-grafted aqueous NCC suspension, a chiral nematic phase was observed.

U.S. Army Aviation Participation in the Counterdrug Effort

DTIC Science & Technology

1993-03-29

SCHEDULE is unlimited. 4. PERFORMING ORGANIZATION REPORT NUMBERS) S. MONITORING ORGANIZATION REPORT NUMBER(S) 6a. NAME OF PERFORMING ORGANIZATION 6b...American society in health, law * enforcement, imprisonment, absenteeism , crime, and corruption. Only through a genuine national effort that...Unclassified Illicit drugs account for tremendous losses to American society in health, law enforcement, imprisonment, absenteeism , crime, and corruption

The Brazilian Military: Its Role in Counter-Drug Activities

DTIC Science & Technology

1992-06-01

34Police Uncover ’New’ Medellin Cartel Drug Route," Brasilia Radio Nacional de Amazonia , in Portuguese, 29 November 1989, translated in FBIS, 30...42 "Destruction of Clandestine Airstrips to Begin," Brasi Radio Nacional de Amazonia Network, in Portuguese, 2 May 1990, translated in FBIS, 3 May... de Ciencia Politica e Relacoes Internacionais (REL) Universidade de Brasilia 70.910 Brasilia, D.F. BRAZIL 107

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

Hannum, David W.; Shannon, Gary W.

This report describes the collaboration between the South Texas Specialized Crimes and Narcotics Task Force (STSCNTF) and Sandia National Laboratories (SNL) in a field test that provided prototype hand-held trace detection technology for use in counter-drug operations. The National Institute of Justice (NIJ)/National Law Enforcement and Corrections Technology Center (NLECTC)/Border Research and Technology Center (BRTC) was contacted by STSCNTF for assistance in obtaining cutting-edge technology. The BRTC created a pilot project for Sandia National Laboratories (SNL) and the STSCNTF for the use of SNL’s Hound, a hand-held sample collection and preconcentration system that, when combined with a commercial chemical detector,more » can be used for the trace detection of illicit drugs and explosives. The STSCNTF operates in an area of high narcotics trafficking where methods of concealment make the detection of narcotics challenging. Sandia National Laboratories’ (SNL) Contraband Detection Department personnel provided the Hound system hardware and operational training. The Hound system combines the GE VaporTracer2, a hand-held commercial chemical detector, with an SNL-developed sample collection and preconcentration system. The South Texas Task force reported a variety of successes, including identification of a major shipment of methamphetamines, the discovery of hidden compartments in vehicles that contained illegal drugs and currency used in drug deals, and the identification of a suspect in a nightclub shooting. The main advantage of the hand-held trace detection unit is its ability to quickly identify the type of chemical (drugs or explosives) without a long lag time for laboratory analysis, which is the most common analysis method for current law enforcement procedures.« less

Trace Contraband Detection Field-Test by the South Texas Specialized Crimes and Narcotics Task Force

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

Hannum, David W.; Shannon, Gary W.

This report describes the collaboration between the South Texas Specialized Crimes and Narcotics Task Force (STSCNTF) and Sandia National Laboratories (SNL) in a field test that provided prototype hand-held trace detection technology for use in counter-drug operations. The National Institute of Justice (NIJ)/National Law Enforcement and Corrections Technology Center (NLECTC)/Border Research and Technology Center (BRTC) was contacted by STSCNTF for assistance in obtaining cutting-edge technology. The BRTC created a pilot project for Sandia National Laboratories (SNL) and the STSCNTF for the use of SNL’s Hound, a hand-held sample collection and preconcentration system that, when combined with a commercial chemical detector,more » can be used for the trace detection of illicit drugs and explosives. The STSCNTF operates in an area of high narcotics trafficking where methods of concealment make the detection of narcotics challenging. Sandia National Laboratories’ (SNL) Contraband Detection Department personnel provided the Hound system hardware and operational training. The Hound system combines the GE VaporTracer2, a hand-held commercial chemical detector, with an SNL-developed sample collection and preconcentration system. The South Texas Task force reported a variety of successes, including identification of a major shipment of methamphetamines, the discovery of hidden compartments in vehicles that contained illegal drugs and currency used in drug deals, and the identification of a suspect in a nightclub shooting. The main advantage of the hand-held trace detection unit is its ability to quickly identify the type of chemical (drugs or explosives) without a long lag time for laboratory analysis, which is the most common analysis method for current law enforcement procedures.« less

Histological and molecular biology diagnosis of neurocysticercosis in a patient without history of travel to endemic areas: case report.

PubMed

L'Ollivier, C; González, L M; Gárate, T; Martin, L; Martha, B; Duong, M; Huerre, M; Cuisenier, B; Harrison, L J S; Dalle, F; Bonnin, A

2012-11-01

in endemic areas, neurocysticercosis appears mainly as a single, large, spherical and non-enhancing intracranial cyst. an atypical case of neurocysticercosis (NCC) in a French Caucasian, without history of travel to endemic areas, was confirmed by histology and molecular speciation. Imaging was atypical, showing several hook-bearing scolices visible in the cyst, while the serology employed was non-contributary. NCC should be considered when multiple taeniid scolices are observed within the same cystic lesion.

Cognitive Limitations at Work Among Employed Breast Cancer Survivors in China.

PubMed

Zeng, Yingchun; Cheng, Andy S K; Feuerstein, Michael

This study aimed to determine whether levels of distress (anxiety and depression) and cognitive symptoms at work are related to work productivity and quality of life (QOL) in Chinese breast cancer survivors (BCS), compared to a group of Chinese women without cancer but with different musculoskeletal pain related to work. This study used a cross-sectional study design. Working BCS were recruited in a tumor hospital's outpatient department, and women with no history of cancer (noncancer comparison [NCC] group) were recruited from a rehabilitation center. A total of 412 participants were included. Multiple regression analyses indicated that higher anxiety was associated with work limitations (B = .005, p = .014) and QOL (B = 2.417, p = .004) in the BCS group only. Cognitive limitations at work were associated with work limitations (B = .002, p = .001) and QOL (B = 1.022, p = .003) in the BCS group only. Depressive symptoms (B = .028, p = .017) were significantly associated with work limitations in the NCC group. Breast cancer survivors reported higher levels of cognitive limitations at work and anxiety, lower levels of work productivity, and QOL. When remaining at work is a viable option for the cancer survivor with cognitive limitations at work, the rehabilitation nurse should consider approaches to best accommodate the specific cognitive limitations and work tasks, as well as help the patient manage associated anxiety when present.

3. CONNECTING TUNNEL AT BOTTOM CENTER TO CENTER, CONTROL BUILDING ...

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

3. CONNECTING TUNNEL AT BOTTOM CENTER TO CENTER, CONTROL BUILDING B AT CENTER, WATER TANK TO UPPER LEFT, VIEW TOWARDS WEST. - Glenn L. Martin Company, Titan Missile Test Facilities, Control Building B, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

NASA(Field Center Based) Technology Commercialization Centers

NASA Technical Reports Server (NTRS)

1995-01-01

Under the direction of the IC(sup 2) Institute, the Johnson Technology Commercialization Center has met or exceeded all planned milestones and metrics during the first two and a half years of the NTCC program. The Center has established itself as an agent for technology transfer and economic development in- the Clear Lake community, and is positioned to continue as a stand-alone operation. This report presents data on the experimental JTCC program, including all objective measures tracked over its duration. While the metrics are all positive, the data indicates a shortage of NASA technologies with strong commercial potential, barriers to the identification and transfer of technologies which may have potential, and small financial return to NASA via royalty-bearing licenses. The Center has not yet reached the goal of self-sufficiency based on rental income, and remains dependent on NASA funding. The most important issues raised by the report are the need for broader and deeper community participation in the Center, technology sourcing beyond JSC, and the form of future funding which will be appropriate.

National Health Information Center

MedlinePlus

... About ODPHP National Health Information Center National Health Information Center The National Health Information Center (NHIC) is ... of interest View the NHO calendar . Federal Health Information Centers and Clearinghouses Federal Health Information Centers and ...

Children's cancer centers

MedlinePlus

Pediatric cancer center; Pediatric oncology center; Comprehensive cancer center ... Treating childhood cancer is not the same as treating adult cancer. The cancers are different. So are the treatments and the ...

Trauma center staffing, infrastructure, and patient characteristics that influence trauma center need.

PubMed

Faul, Mark; Sasser, Scott M; Lairet, Julio; Mould-Millman, Nee-Kofi; Sugerman, David

2015-01-01

The most effective use of trauma center resources helps reduce morbidity and mortality, while saving costs. Identifying critical infrastructure characteristics, patient characteristics and staffing components of a trauma center associated with the proportion of patients needing major trauma care will help planners create better systems for patient care. We used the 2009 National Trauma Data Bank-Research Dataset to determine the proportion of critically injured patients requiring the resources of a trauma center within each Level I-IV trauma center (n=443). The outcome variable was defined as the portion of treated patients who were critically injured. We defined the need for critical trauma resources and interventions ("trauma center need") as death prior to hospital discharge, admission to the intensive care unit, or admission to the operating room from the emergency department as a result of acute traumatic injury. Generalized Linear Modeling (GLM) was used to determine how hospital infrastructure, staffing Levels, and patient characteristics contributed to trauma center need. Nonprofit Level I and II trauma centers were significantly associated with higher levels of trauma center need. Trauma centers that had a higher percentage of transferred patients or a lower percentage of insured patients were associated with a higher proportion of trauma center need. Hospital infrastructure characteristics, such as bed capacity and intensive care unit capacity, were not associated with trauma center need. A GLM for Level III and IV trauma centers showed that the number of trauma surgeons on staff was associated with trauma center need. Because the proportion of trauma center need is predominantly influenced by hospital type, transfer frequency, and insurance status, it is important for administrators to consider patient population characteristics of the catchment area when planning the construction of new trauma centers or when coordinating care within state or regional

Stephenson Cancer Center

Cancer.gov

Stephenson Cancer Center at the University of Oklahoma in Oklahoma City is an NCI-designated cancer center at the forefront of NCI-supported cancer research. Learn more about the Stephenson Cancer Center's mission.

Methodologic considerations in the design and analysis of nested case-control studies: association between cytokines and postoperative delirium.

PubMed

Ngo, Long H; Inouye, Sharon K; Jones, Richard N; Travison, Thomas G; Libermann, Towia A; Dillon, Simon T; Kuchel, George A; Vasunilashorn, Sarinnapha M; Alsop, David C; Marcantonio, Edward R

2017-06-06

The nested case-control study (NCC) design within a prospective cohort study is used when outcome data are available for all subjects, but the exposure of interest has not been collected, and is difficult or prohibitively expensive to obtain for all subjects. A NCC analysis with good matching procedures yields estimates that are as efficient and unbiased as estimates from the full cohort study. We present methodological considerations in a matched NCC design and analysis, which include the choice of match algorithms, analysis methods to evaluate the association of exposures of interest with outcomes, and consideration of overmatching. Matched, NCC design within a longitudinal observational prospective cohort study in the setting of two academic hospitals. Study participants are patients aged over 70 years who underwent scheduled major non-cardiac surgery. The primary outcome was postoperative delirium from in-hospital interviews and medical record review. The main exposure was IL-6 concentration (pg/ml) from blood sampled at three time points before delirium occurred. We used nonparametric signed ranked test to test for the median of the paired differences. We used conditional logistic regression to model the risk of IL-6 on delirium incidence. Simulation was used to generate a sample of cohort data on which unconditional multivariable logistic regression was used, and the results were compared to those of the conditional logistic regression. Partial R-square was used to assess the level of overmatching. We found that the optimal match algorithm yielded more matched pairs than the greedy algorithm. The choice of analytic strategy-whether to consider measured cytokine levels as the predictor or outcome-- yielded inferences that have different clinical interpretations but similar levels of statistical significance. Estimation results from NCC design using conditional logistic regression, and from simulated cohort design using unconditional logistic regression, were

Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis.

PubMed

Mishra, Pramod K; Li, Qun; Munoz, Luis E; Mares, Chris A; Morris, Elizabeth G; Teale, Judy M; Cardona, Astrid E

2016-06-01

Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to

Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis

PubMed Central

Mishra, Pramod K.; Li, Qun; Munoz, Luis E.; Mares, Chris A.; Morris, Elizabeth G.; Teale, Judy M.; Cardona, Astrid E.

2016-01-01

Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to

When Teacher-Centered Instructors Are Assigned to Student-Centered Classrooms

ERIC Educational Resources Information Center

Lasry, Nathaniel; Charles, Elizabeth; Whittaker, Chris

2014-01-01

Technology-rich student-centered classrooms such as SCALE-UP and TEAL are designed to actively engage students. We examine what happens when the design of the classroom (conventional or teacher-centered versus student-centered classroom spaces) is consistent or inconsistent with the teacher's epistemic beliefs about learning and teaching…

[Advanced Composites Technology Initiatives

NASA Technical Reports Server (NTRS)

Julian, Mark R.

2002-01-01

This final report closes out the W02 NASA Grant #NCC5-646. The FY02 grant for advanced technology initiatives through the Advanced Composites Technology Institute in Bridgeport, WV, at the Robert C. Byrd Institute (RCBI) Bridgeport Manufacturing Technology Center, is complete; all funding has been expended. RCBI continued to expand access to technology; develop and implement a workforce-training curriculum; improve material development; and provide prototyping and demonstrations of new and advanced composites technologies for West Virginia composites firms. The FY 02 efforts supported workforce development, technical training and the HST development effort of a super-lightweight composite carrier prototype and expanded the existing technical capabilities of the growing aerospace industry across West Virginia to provide additional support for NASA missions. Additionally, the Composites Technology and Training Center was awarded IS0 9001 - 2000 certification and Cleanroom Class 1000 certification during this report period.

Double Knockout of the Na+-Driven Cl-/HCO3- Exchanger and Na+/Cl- Cotransporter Induces Hypokalemia and Volume Depletion.

PubMed

Sinning, Anne; Radionov, Nikita; Trepiccione, Francesco; López-Cayuqueo, Karen I; Jayat, Maximilien; Baron, Stéphanie; Cornière, Nicolas; Alexander, R Todd; Hadchouel, Juliette; Eladari, Dominique; Hübner, Christian A; Chambrey, Régine

2017-01-01

We recently described a novel thiazide-sensitive electroneutral NaCl transport mechanism resulting from the parallel operation of the Cl - /HCO 3 - exchanger pendrin and the Na + -driven Cl - /2HCO 3 - exchanger (NDCBE) in β-intercalated cells of the collecting duct. Although a role for pendrin in maintaining Na + balance, intravascular volume, and BP is well supported, there is no in vivo evidence for the role of NDCBE in maintaining Na + balance. Here, we show that deletion of NDCBE in mice caused only subtle perturbations of Na + homeostasis and provide evidence that the Na + /Cl - cotransporter (NCC) compensated for the inactivation of NDCBE. To unmask the role of NDCBE, we generated Ndcbe/Ncc double-knockout (dKO) mice. On a normal salt diet, dKO and single-knockout mice exhibited similar activation of the renin-angiotensin-aldosterone system, whereas only dKO mice displayed a lower blood K + concentration. Furthermore, dKO mice displayed upregulation of the epithelial sodium channel (ENaC) and the Ca 2+ -activated K + channel BKCa. During NaCl depletion, only dKO mice developed marked intravascular volume contraction, despite dramatically increased renin activity. Notably, the increase in aldosterone levels expected on NaCl depletion was attenuated in dKO mice, and single-knockout and dKO mice had similar blood K + concentrations under this condition. In conclusion, NDCBE is necessary for maintaining sodium balance and intravascular volume during salt depletion or NCC inactivation in mice. Furthermore, NDCBE has an important role in the prevention of hypokalemia. Because NCC and NDCBE are both thiazide targets, the combined inhibition of NCC and the NDCBE/pendrin system may explain thiazide-induced hypokalemia in some patients. Copyright © 2016 by the American Society of Nephrology.

Environmental controls on daytime net community calcification on a Red Sea reef flat

NASA Astrophysics Data System (ADS)

Bernstein, W. N.; Hughen, K. A.; Langdon, C.; McCorkle, D. C.; Lentz, S. J.

2016-06-01

Coral growth and carbonate accumulation form the foundation of the coral reef ecosystem. Changes in environmental conditions due to coastal development, climate change, and ocean acidification may pose a threat to net carbonate production in the near future. Controlled laboratory studies demonstrate that calcification by corals and coralline algae is sensitive to changes in aragonite saturation state (Ωa), as well as temperature, light, and nutrition. Studies also show that the dissolution rate of carbonate substrates is impacted by changes in carbonate chemistry. The sensitivity of coral reefs to these parameters must be confirmed and quantified in the natural environment in order to predict how coral reefs will respond to local and global changes, particularly ocean acidification. We estimated the daytime hourly net community metabolic rates, both net community calcification (NCC) and net community productivity (NCP), at Sheltered Reef, an offshore platform reef in the central Red Sea. Average NCC was 8 ± 3 mmol m-2 h-1 in December 2010 and 11 ± 1 mmol m-2 h-1 in May 2011, and NCP was 21 ± 7 mmol m-2 h-1 in December 2010 and 44 ± 4 mmol m-2 h-1 in May 2011. We also monitored a suite of physical and chemical properties to help relate the rates at Sheltered Reef to published rates from other sites. While previous research shows that short-term field studies investigating the NCC-Ωa relationship have differing results due to confounding factors, it is important to continue estimating NCC in different places, seasons, and years, in order to monitor changes in NCC versus Ω in space and time, and to ultimately resolve a broader understanding of this relationship.

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation during Angiotensin II Hypertension

PubMed Central

Veiras, Luciana C.; Han, Jiyang; Ralph, Donna L.; McDonough, Alicia A.

2016-01-01