Sample records for factor xii fxii

  1. Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII

    PubMed Central

    Zakharova, Natalia V.; Artemenko, Elena O.; Podoplelova, Nadezhda A.; Sveshnikova, Anastasia N.; Demina, Irina A.; Ataullakhanov, Fazly I.; Panteleev, Mikhail A.

    2015-01-01

    Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP) accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey platelet syndrome did not activate fXII, which suggests that platelet-associated fXII-activating material might be released from α-granules. FXII was preferentially bound by phosphotidylserine-positive platelets and annexin V abrogated platelet-dependent fXII activation; however, artificial phosphotidylserine/phosphatidylcholine microvesicles did not support fXII activation under the conditions herein. Confocal microscopy using DAPI as a poly-phosphate marker did not reveal poly-phosphates associated with an activated platelet surface. Experimental data for fXII activation indicates an auto-inhibition mechanism (k i/k a = 180 molecules/platelet). Unlike surface-associated fXII activation, platelet secretion inhibited activated fXII (fXIIa), particularly due to a released C1-inhibitor. Platelet surface-associated fXIIa formation triggered contact pathway-dependent clotting in recalcified plasma. Computer modelling suggests that fXIIa inactivation was greatly decreased in thrombi under high blood flow due to inhibitor washout. Combined, the surface-associated fXII activation and its inhibition in solution herein may be regarded as a flow-sensitive regulator that can shift the balance between surface-associated clotting and plasma-dependent inhibition, which may explain the role of fXII at high shear and why fXII is important for thrombosis but negligible in haemostasis. PMID:25688860

  2. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding.

    PubMed

    Revenko, Alexey S; Gao, Dacao; Crosby, Jeff R; Bhattacharjee, Gourab; Zhao, Chenguang; May, Chris; Gailani, David; Monia, Brett P; MacLeod, A Robert

    2011-11-10

    Recent studies indicate that the plasma contact system plays an important role in thrombosis, despite being dispensable for hemostasis. For example, mice deficient in coagulation factor XII (fXII) are protected from arterial thrombosis and cerebral ischemia-reperfusion injury. We demonstrate that selective reduction of prekallikrein (PKK), another member of the contact system, using antisense oligonucleotide (ASO) technology results in an antithrombotic phenotype in mice. The effects of PKK deficiency were compared with those of fXII deficiency produced by specific ASO-mediated reduction of fXII. Mice with reduced PKK had ∼ 3-fold higher plasma levels of fXII, and reduced levels of fXIIa-serpin complexes, consistent with fXII being a substrate for activated PKK in vivo. PKK or fXII deficiency reduced thrombus formation in both arterial and venous thrombosis models, without an apparent effect on hemostasis. The amount of reduction of PKK and fXII required to produce an antithrombotic effect differed between venous and arterial models, suggesting that these factors may regulate thrombus formation by distinct mechanisms. Our results support the concept that fXII and PKK play important and perhaps nonredundant roles in pathogenic thrombus propagation, and highlight a novel, specific and safe pharmaceutical approach to target these contact system proteases.

  3. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding

    PubMed Central

    Revenko, Alexey S.; Gao, Dacao; Crosby, Jeff R.; Bhattacharjee, Gourab; Zhao, Chenguang; May, Chris; Gailani, David; Monia, Brett P.

    2011-01-01

    Recent studies indicate that the plasma contact system plays an important role in thrombosis, despite being dispensable for hemostasis. For example, mice deficient in coagulation factor XII (fXII) are protected from arterial thrombosis and cerebral ischemia-reperfusion injury. We demonstrate that selective reduction of prekallikrein (PKK), another member of the contact system, using antisense oligonucleotide (ASO) technology results in an antithrombotic phenotype in mice. The effects of PKK deficiency were compared with those of fXII deficiency produced by specific ASO-mediated reduction of fXII. Mice with reduced PKK had ∼ 3-fold higher plasma levels of fXII, and reduced levels of fXIIa-serpin complexes, consistent with fXII being a substrate for activated PKK in vivo. PKK or fXII deficiency reduced thrombus formation in both arterial and venous thrombosis models, without an apparent effect on hemostasis. The amount of reduction of PKK and fXII required to produce an antithrombotic effect differed between venous and arterial models, suggesting that these factors may regulate thrombus formation by distinct mechanisms. Our results support the concept that fXII and PKK play important and perhaps nonredundant roles in pathogenic thrombus propagation, and highlight a novel, specific and safe pharmaceutical approach to target these contact system proteases. PMID:21821705

  4. Evaluation of thromboelastography in two factor XII-deficient cats.

    PubMed

    Blois, Shauna L; Holowaychuk, Marie K; Wood, R Darren

    2015-01-01

    The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency.

  5. Evaluation of thromboelastography in two factor XII-deficient cats

    PubMed Central

    Holowaychuk, Marie K; Wood, R Darren

    2015-01-01

    Case summary The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. Relevance and novel information TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency. PMID:28491358

  6. Identification of Genetic Defects Underlying FXII Deficiency in Four Unrelated Chinese Patients.

    PubMed

    Yang, Lihong; Wang, Yingyu; Zhou, Jianpin; Cheng, Xiaoli; Hao, Xiuping; Xie, Haixiao; Jin, Yanhui; Wang, Mingshan

    2016-01-01

    Congenital factor XII (FXII) dexFB01;ciency is a rare autosomal recessive disorder, characterized by a great variability in its clinical manifestations. In this study, we screened for mutations in the F12 gene of 4 unrelated patients with FXII coagulant activity <10% of that of normal human plasma. To investigate the molecular defects in these FXII-deficient patients, we performed FXII mutation screening. By sequencing all coding exons as well as xFB02;anking intronic regions of the F12 gene, 6 different mutations, including 3 missense mutations (Gly341Arg, Glu502Lys and Gly542 Ser), 1 insertion (7142insertC) and 2 deletions (5741-5742 delCA and 6753-6755delACA), were identixFB01;ed on the F12 gene. Three of them (Gly341Arg, 5741-5742delCA and 6753-6755delACA) are reported here for the first time. Computer-based algorithms predicted these missense mutations to be deleterious. This study has increased our knowledge of the mutational spectrum underlying FXII deficiency. © 2016 S. Karger AG, Basel.

  7. Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

    PubMed Central

    Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

    2016-01-01

    Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

  8. Differential Roles for the Coagulation Factors XI and XII in Regulating the Physical Biology of Fibrin.

    PubMed

    Sylman, Joanna L; Daalkhaijav, Uranbileg; Zhang, Ying; Gray, Elliot M; Farhang, Parsa A; Chu, Tiffany T; Zilberman-Rudenko, Jevgenia; Puy, Cristina; Tucker, Erik I; Smith, Stephanie A; Morrissey, James H; Walker, Travis W; Nan, Xiaolin L; Gruber, András; McCarty, Owen J T

    2017-05-01

    In the contact activation pathway of the coagulation, zymogen factor XII (FXII) is converted to FXIIa, which triggers activation of FXI leading to the activation of FIX and subsequent thrombin generation and fibrin formation. Feedback activation of FXI by thrombin has been shown to promote thrombin generation in a FXII-independent manner and FXIIa can bypass FXI to directly activate FX and prothrombin in the presence of highly negatively charged molecules, such as long-chain polyphosphates (LC polyP). We sought to determine whether activation of FXII or FXI differentially regulate the physical biology of fibrin formation. Fibrin formation was initiated with tissue factor, ellagic acid (EA), or LC polyP in the presence of inhibitors of FXI and FXII. Our data demonstrated that inhibition of FXI decreased the rate of fibrin formation and fiber network density, and increased the fibrin network strength and rate of fibrinolysis when gelation was initiated via the contact activation pathway with EA. FXII inhibition decreased the fibrin formation and fibrin density, and increased the fibrinolysis rate only when fibrin formation was initiated via the contact activation pathway with LC polyP. Overall, we demonstrate that inhibition of FXI and FXII distinctly alter the biophysical properties of fibrin.

  9. Depletion of coagulation factor XII ameliorates brain pathology and cognitive impairment in Alzheimer disease mice.

    PubMed

    Chen, Zu-Lin; Revenko, Alexey S; Singh, Pradeep; MacLeod, A Robert; Norris, Erin H; Strickland, Sidney

    2017-05-04

    Vascular abnormalities and inflammation are found in many Alzheimer disease (AD) patients, but whether these changes play a causative role in AD is not clear. The factor XII (FXII) -initiated contact system can trigger both vascular pathology and inflammation and is activated in AD patients and AD mice. We have investigated the role of the contact system in AD pathogenesis. Cleavage of high-molecular-weight kininogen (HK), a marker for activation of the inflammatory arm of the contact system, is increased in a mouse model of AD, and this cleavage is temporally correlated with the onset of brain inflammation. Depletion of FXII in AD mice inhibited HK cleavage in plasma and reduced neuroinflammation, fibrinogen deposition, and neurodegeneration in the brain. Moreover, FXII-depleted AD mice showed better cognitive function than untreated AD mice. These results indicate that FXII-mediated contact system activation contributes to AD pathogenesis, and therefore this system may offer novel targets for AD treatment. © 2017 by The American Society of Hematology.

  10. A Comparison of Blood Factor XII Autoactivation in Buffer, Protein Cocktail, Serum, and Plasma Solutions

    PubMed Central

    Golas, Avantika; Yeh, Chyi-Huey Josh; Pitakjakpipop, Harit; Siedlecki, Christopher A.; Vogler, Erwin A.

    2012-01-01

    Activation of blood plasma coagulation in vitro by contact with material surfaces is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. The only plausible explanation consistent with current understanding of coagulation-cascade biochemistry is that procoagulant stimulus arising from the activation complex of the intrinsic pathway is dependent on activator surface area. And yet, it is herein shown that activation of the blood zymogen factor XII (Hageman factor, FXII) dissolved in buffer, protein cocktail, heat-denatured serum, and FXI deficient plasma does not exhibit activator surface-area dependence. Instead, a highly-variable burst of procoagulant-enzyme yield is measured that exhibits no measurable kinetics, sensitivity to mixing, or solution-temperature dependence. Thus, FXII activation in both buffer and protein-containing solutions does not exhibit characteristics of a biochemical reaction but rather appears to be a “mechanochemical” reaction induced by FXII molecule interactions with hydrophilic activator particles that do not formally adsorb blood proteins from solution. Results of this study strongly suggest that activator surface-area dependence observed in contact activation of plasma coagulation does not solely arise at the FXII activation step of the intrinsic pathway. PMID:23117212

  11. Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts.

    PubMed

    Jablonska, Ewa; Markart, Philipp; Zakrzewicz, Dariusz; Preissner, Klaus T; Wygrecka, Malgorzata

    2010-04-09

    Coagulation factor XII (FXII) is a liver-derived serine protease involved in fibrinolysis, coagulation, and inflammation. The regulation of FXII expression is largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that has been linked to several pathological processes, including tissue fibrosis by modulating procoagulant and fibrinolytic activities. This study investigated whether TGF-beta1 may regulate FXII expression in human lung fibroblasts. Treatment of human lung fibroblasts with TGF-beta1 resulted in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3. However, TGF-beta1-induced FXII expression was repressed only by the JNK inhibitor and JNK and Smad3 antisense oligonucleotides but not by MEK, p38, or phosphoinositide 3-kinase blockers. JNK inhibition had no effect on TGF-beta1-induced Smad3 phosphorylation, association with Smad4, and its translocation into the nucleus but strongly suppressed Smad3-DNA complex formation. FXII promoter analysis revealed that the -299/+1 region was sufficient for TGF-beta1 to induce FXII expression. Sequence analysis of this region detected a potential Smad-binding element at position -272/-269 (SBE-(-272/-269)). Chromatin immunoprecipitation and streptavidin pulldown assays demonstrated TGF-beta1-dependent Smad3 binding to SBE-(-272/-269). Mutation or deletion of SBE-(-272/-269) substantially reduced TGF-beta1-mediated activation of the FXII promoter. Clinical relevance was demonstrated by elevated FXII levels and its co-localization with fibroblasts in the lungs of patients with acute respiratory distress syndrome. Our results show that JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts and implicate its possible involvement in pathological conditions characterized by elevated TGF-beta1 levels.

  12. Ordered adsorption of coagulation factor XII on negatively charged polymer surfaces probed by sum frequency generation vibrational spectroscopy.

    PubMed

    Chen, Xiaoyun; Wang, Jie; Paszti, Zoltan; Wang, Fulin; Schrauben, Joel N; Tarabara, Volodymyr V; Schmaier, Alvin H; Chen, Zhan

    2007-05-01

    Electrostatic interactions between negatively charged polymer surfaces and factor XII (FXII), a blood coagulation factor, were investigated by sum frequency generation (SFG) vibrational spectroscopy, supplemented by several analytical techniques including attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), quartz crystal microbalance (QCM), zeta-potential measurement, and chromogenic assay. A series of sulfonated polystyrenes (sPS) with different sulfonation levels were synthesized as model surfaces with different surface charge densities. SFG spectra collected from FXII adsorbed onto PS and sPS surfaces with different surface charge densities showed remarkable differences in spectral features and especially in spectral intensity. Chromogenic assay experiments showed that highly charged sPS surfaces induced FXII autoactivation. ATR-FTIR and QCM results indicated that adsorption amounts on the PS and sPS surfaces were similar even though the surface charge densities were different. No significant conformational change was observed from FXII adsorbed onto surfaces studied. Using theoretical calculations, the possible contribution from the third-order nonlinear optical effect induced by the surface electric field was evaluated, and it was found to be unable to yield the SFG signal enhancement observed. Therefore it was concluded that the adsorbed FXII orientation and ordering were the main reasons for the remarkable SFG amide I signal increase on sPS surfaces. These investigations indicate that negatively charged surfaces facilitate or induce FXII autoactivation on the molecular level by imposing specific orientation and ordering on the adsorbed protein molecules.

  13. Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity.

    PubMed

    Mitchell, Joanne L; Lionikiene, Ausra S; Georgiev, Georgi; Klemmer, Anja; Brain, Chelsea; Kim, Paul Y; Mutch, Nicola J

    2016-12-15

    Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared with urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here, we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP 70 , of the chain length found in platelets (60-100 mer), and platelet-derived polyP significantly augment the plasminogen activation capacity of αFXIIa. PolyP 70 stimulated the autoactivation of FXII and subsequent plasminogen activation, indicating that once activated, αFXIIa remains bound to polyP 70 Indeed, complex formation between polyP 70 and αFXIIa provides protection against autodegradation. Plasminogen activation by βFXIIa was minimal and not enhanced by polyP 70 , highlighting the importance of the anion binding site. PolyP 70 did not modulate plasmin activity but stimulated activation of Glu and Lys forms of plasminogen by αFXIIa. Accordingly, polyP 70 was found to bind to FXII, αFXIIa, and plasminogen, but not βFXIIa. Fibrin and polyP 70 acted synergistically to enhance αFXIIa-mediated plasminogen activation. The plasminogen activator activity of the αFXIIa-polyP 70 complex was modulated by C1 inhibitor and histidine-rich glycoprotein, but not plasminogen activator inhibitors 1 and 2. Platelet polyP and FXII were found to colocalize on the activated platelet membrane in a fibrin-dependent manner and decorated fibrin strands extending from platelet aggregates. We show that in the presence of platelet polyP and the downstream substrate fibrin, αFXIIa is a highly efficient and favorable plasminogen activator. Our data are the first to document a profibrinolytic function of platelet polyP. © 2016 by The American Society of Hematology.

  14. Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity

    PubMed Central

    Lionikiene, Ausra S.; Georgiev, Georgi; Klemmer, Anja; Brain, Chelsea; Kim, Paul Y.

    2016-01-01

    Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared with urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here, we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP70, of the chain length found in platelets (60-100 mer), and platelet-derived polyP significantly augment the plasminogen activation capacity of αFXIIa. PolyP70 stimulated the autoactivation of FXII and subsequent plasminogen activation, indicating that once activated, αFXIIa remains bound to polyP70. Indeed, complex formation between polyP70 and αFXIIa provides protection against autodegradation. Plasminogen activation by βFXIIa was minimal and not enhanced by polyP70, highlighting the importance of the anion binding site. PolyP70 did not modulate plasmin activity but stimulated activation of Glu and Lys forms of plasminogen by αFXIIa. Accordingly, polyP70 was found to bind to FXII, αFXIIa, and plasminogen, but not βFXIIa. Fibrin and polyP70 acted synergistically to enhance αFXIIa-mediated plasminogen activation. The plasminogen activator activity of the αFXIIa-polyP70 complex was modulated by C1 inhibitor and histidine-rich glycoprotein, but not plasminogen activator inhibitors 1 and 2. Platelet polyP and FXII were found to colocalize on the activated platelet membrane in a fibrin-dependent manner and decorated fibrin strands extending from platelet aggregates. We show that in the presence of platelet polyP and the downstream substrate fibrin, αFXIIa is a highly efficient and favorable plasminogen activator. Our data are the first to document a profibrinolytic function of platelet polyP. PMID:27694320

  15. Contact Activation of Blood Plasma and Factor XII by Ion-exchange Resins

    PubMed Central

    Yeh, Chyi-Huey Josh; Dimachkie, Ziad O.; Golas, Avantika; Cheng, Alice; Parhi, Purnendu; Vogler, Erwin A.

    2011-01-01

    Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quarternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles ( FXII→surfaceactivatorFXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean-glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion-exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade. PMID

  16. Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding.

    PubMed

    Cai, Tian-Quan; Wu, Weizhen; Shin, Myung K; Xu, Yiming; Jochnowitz, Nina; Zhou, Yuchen; Hoos, Lizbeth; Bentley, Ross; Strapps, Walter; Thankappan, Anil; Metzger, Joseph M; Ogletree, Martin L; Tadin-Strapps, Marija; Seiffert, Dietmar A; Chen, Zhu

    2015-12-01

    This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ellagic acid-triggered thrombin generation assay (TGA) exhibited anticoagulant changes. In contrast, ex-vivo PT or high tissue factor-triggered TGA was indistinguishable from control. Rats receiving single doses (0, 0.01, 0.03, 0.1, 0.3, 1 mg/kg) of FXII siRNA exhibited dose-dependent knockdown in liver FXII mRNA and plasma FXII protein (95 and 99%, respectively, at 1 mg/kg) at day 7 post dosing. FXII knockdown was associated with dose-dependent thromboprotection (maximal efficacy achieved with 1 mg/kg in both models) and negligible change in cuticle bleeding times. Ex-vivo TGA triggered with low-level (0.5 μmol/l) ellagic acid tracked best with the knockdown levels and efficacy. Our findings confirm and extend literature reports of an attractive benefit-to-risk profile of targeting FXII for antithrombotic therapies. Titrating of FXII is instructive for its pharmacological inhibition. The knockout rat is valuable for evaluating both mechanism-based safety concerns and off-target effects of FXII(a) inhibitors. Detailed TGA analyses will inform on optimal trigger conditions in studying pharmacodynamic effects of FXII(a) inhibition.

  17. Endothelial Cell Permeability during Hantavirus Infection Involves Factor XII-Dependent Increased Activation of the Kallikrein-Kinin System

    PubMed Central

    Taylor, Shannon L.; Wahl-Jensen, Victoria; Copeland, Anna Maria; Jahrling, Peter B.; Schmaljohn, Connie S.

    2013-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC) display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF). To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS), we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation during

  18. The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

    PubMed Central

    Nickel, Katrin F.; Ronquist, Göran; Langer, Florian; Labberton, Linda; Fuchs, Tobias A.; Bokemeyer, Carsten; Sauter, Guido; Graefen, Markus; Mackman, Nigel; Stavrou, Evi X.; Ronquist, Gunnar

    2015-01-01

    Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies. PMID:26153520

  19. Factor XI and XII as antithrombotic targets.

    PubMed

    Müller, Felicitas; Gailani, David; Renné, Thomas

    2011-09-01

    Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.

  20. Reduction of factor XII in antiphospholipid antibody-positive patients with thrombotic events in the rheumatology clinic.

    PubMed

    Takeishi, M; Mimori, A; Nakajima, K; Mimura, T; Suzuki, T

    2003-02-01

    Although rheumatological diagnosis often includes an assessment of antiphospholipid (aPL) antibodies, the significance of other prothrombotic factors has not been established in thrombotic patients who are not afflicted with either arteriosclerosis or vasculitis syndrome. We have observed both the presence of antiphospholipid antibodies and a reduction of factor XII in such patients. Our results identified both lupus anticoagulant-positive (50%) and anticardiolipin antibody-positive (58%) patients. In addition, 83% of patients showed factor XII antigen level reduction. Furthermore, 70% of aPL-positive thrombotic patients showed factor XII antigen level reduction. Only two cases had antiphospholipid antibody alone, and 4/12 showed just factor XII antigen reduction. Recently, it has been reported that the presence of antiphospholipid antibodies induces factor XII reduction, and that anti-factor XII autoantibody can be detected in thrombotic patients. However, our results indicate that there are smaller factor XII reductions in non-thrombotic controls who are positive for antiphospholipid antibodies. Furthermore, anti-factor XII autoantibody was not detected in patients with decreased factor XII levels. Kindred research suggested that in two patients there was a genetic component to factor XII reduction. We concluded that the presence of both antiphospholipid antibodies and reduced serum factor XII was observed in most thrombotic patients from our rheumatology clinic. It is therefore possible to consider that the coexistence of these prothrombotic factors can contribute to the onset of thrombosis.

  1. Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.

    PubMed

    Li, Junhui; Li, Shan; Yan, Lufeng; Ding, Tian; Linhardt, Robert J; Yu, Yanlei; Liu, Xinyue; Liu, Donghong; Ye, Xingqian; Chen, Shiguo

    2017-10-20

    Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs. In vitro activities were measured by activated partial thromboplastin time (APTT), thrombin time (TT), thrombin and factor Xa inhibition, and activation of FXII. The results showed that free radicals preferentially acted on GlcA residues affording oligosaccharides that were purified from both fCSs. The inhibition of thrombin and factor X activities, mediated through antithrombin III and heparin cofactor II of fCSs oligosaccharides were affected by their molecular weight and fucose branches. Oligosaccharides with different sulfation patterns of the fucose branching had a similar ability to inhibit the FXa by the intrinsic factor Xase (factor IXa-VIIIa complex). Oligosaccharides with 2,4-O-sulfo fucose branches from fCS-Ib showed higher activities than ones with 3,4-O-disulfo branches obtained from fCS-Pg. Furthermore, a heptasaccharide is the minimum size oligosaccharide required for anticoagulation and FXII activation. This activity was absent for fCS oligosaccharides smaller than nonasaccharides. Molecular size and fucose branch sulfation are important for anticoagulant activity and reduction of size can reverse the activation of FXII caused by native fCSs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

    PubMed Central

    Wheeler, Allison P.; Gailani, David

    2016-01-01

    Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI and IX – the classical intrinsic pathway of coagulation. It is well recognized that this series of proteolytic reactions is not an accurate model for hemostasis in vivo, as factor XII deficiency does not cause abnormal bleeding, and fXI deficiency causes a relatively mild propensity to bleed excessively with injury. Despite their limited roles in hemostasis, there is mounting evidence that fXI and fXII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a relatively small effect on hemostasis. In this chapter the contributions of components of the intrinsic pathway to thrombosis in animal models and humans are discussed, and results of early clinical trials of drugs targeting factors IX, XI and XII are presented. PMID:27637310

  3. The activation of plasminogen by Hageman factor (Factor XII) and Hageman factor fragments.

    PubMed Central

    Goldsmith, G H; Saito, H; Ratnoff, O S

    1978-01-01

    Activation of plasminogen through surface-mediated reactions is well recognized. In the presence of kaolin, purified Hageman factor (Factor XII) changed plasminogen to plasmin, as assayed upon a synthetic amide substrate and by fibrinolysis. Kinetic studies suggested an enzymatic action of Hageman factor upon its substrate, plasminogen. Hageman factor fragments, at a protein concentration equivalent to whole Hageman factor, activated plasminogen to a lesser extent. These protein preparations were not contaminated with other agents implicated in surface-mediated fibrinolysis. Diisopropyl fluorophosphate treatment of plasminogen did not inhibit its activation by Hageman factor. These studies indicate that Hageman factor has a hitherto unsuspected function, the direct activation of plasminogen. PMID:659637

  4. Contact activation of blood-plasma coagulation

    NASA Astrophysics Data System (ADS)

    Golas, Avantika

    Surface engineering of biomaterials with improved hemocompatibility is an imperative, given the widespread global need for cardiovascular devices. Research summarized in this dissertation focuses on contact activation of FXII in buffer and blood plasma frequently referred to as autoactivation. The extant theory of contact activation imparts FXII autoactivation ability to negatively charged, hydrophilic surfaces. According to this theory, contact activation of plasma involves assembly of proteins comprising an "activation complex" on activating surfaces mediated by specific chemical interactions between complex proteins and the surface. This work has made key discoveries that significantly improve our core understanding of contact activation and unravel the existing paradigm of plasma coagulation. It is shown herein that contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension t°a=g° Iv costheta in dyne/cm, where g°Iv is water interfacial tension in dyne/cm and theta is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties --36 < t°a < 72 dyne/cm (O° ≤ theta < 120°), falling sharply through a broad minimum within the 20 < t°a < 40 dyne/cm (55° < theta < 75°). Furthermore, contact activation of FXII in buffer solution produces an ensemble of protein fragments exhibiting either procoagulant properties in plasma (proteolysis of blood factor XI or prekallikrein), amidolytic properties (cleavage of s-2302 chromogen), or the ability to suppress autoactivation through currently unknown biochemistry. The relative proportions of these fragments depend on activator surface chemistry/energy. We have also discovered that contact activation is moderated by adsorption of plasma proteins unrelated to coagulation through an

  5. Retinal venous thrombosis in a young patient with coagulation factor XII deficiency.

    PubMed

    Borrego-Sanz, L; Santos-Bueso, E; Sáenz-Francés, F; Martínez-de-la-Casa, J M; García-Feijoo, J; Gegúndez-Fernández, J A; García-Sánchez, J

    2014-08-01

    A 35-year-old woman, with no relevant medical history, was referred for sudden vision loss in the left eye. Ophthalmological examination showed best corrected visual acuity of 1.0 in the right eye and 0.3 in left eye, with normal anterior pole and intraocular pressure. Fundus examination of the left eye revealed a venous thrombosis in the superior temporal branch, with dilated and tortuous retinal veins. The patient was referred to the hematology unit for thrombophilia study, and was diagnosed with a coagulation XII or Hageman factor deficiency. The development of retinal vessel occlusions, in patients under 50 years of age, is frequently associated with thrombophilia or hypercoagulability disorders. Factor XII deficiency is a rare condition, and its presence could contribute to a higher risk of thromboembolic events. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis

    PubMed Central

    Guilarte, Mar; Sala-Cunill, Anna; Luengo, Olga; Labrador-Horrillo, Moisés; Cardona, Victoria

    2017-01-01

    Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems. Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis. Moreover, the severity of anaphylaxis is correlated with the increase in plasma heparin, BK formation and the intensity of contact system activation. FXII also activates plasminogen in the fibrinolysis system. Mast cell tryptase has been shown to participate in fibrinolysis through plasmin activation and by facilitating the degradation of fibrinogen. Some usual clinical manifestations in anaphylaxis, such as angioedema or hypotension, or other less common, such as metrorrhagia, may be explained by the direct effect of the activation of the coagulation and contact system driven by mast cell mediators. PMID:28798744

  7. Radioimmunoassay of human Hageman factor (factor XII). [/sup 125/I tracer technique

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

    Saito, H.; Ratnoff, O.D.; Pensky, J.

    A specific, sensitive, and reproducible radioimmunoassay for human Hageman factor (HF, factor XII) has been developed with purified human HF and monospecific rabbit antibody. Precise measurements of HF antigen were possible for concentrations as low as 0.1 percent of that in normal pooled plasma. A good correlation (correlation coefficient = 0.82) existed between the titers of HF measured by clot-promoting assays and radioimmunoassays among 42 normal adults. Confirming earlier studies, HF antigen was absent in Hageman trait plasma, but other congenital deficient plasmas, including those of individuals with Fletcher trait and Fitzgerald trait, contained normal amounts of HF antigen. HFmore » antigen was reduced in the plasmas of patients with disseminated intravascular coagulation or advanced liver cirrhosis, but it was normal in those of patients with chronic renal failure or patients under treatment with warfarin. HF antigen was detected by this assay in plasmas of primates, but not detectable in plasmas of 11 nonprimate mammalian and one avian species.« less

  8. Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke.

    PubMed

    Eggers, Arnold E

    2006-01-01

    A new hypothesis is presented on the function of factor XII, which is postulated to be a "missing link" between acute stress and transient hypercoagulability. The implications of this idea are developed to show how chronic stress, which involves activation of hypertension and migraine as well as hypercoagulability, can cause of cerebrovascular disease. "Acute stress" is defined as "the normal short-term physiological response to the perception of major threats or demands". "Chronic stress" is "the abnormal ongoing physiological response to the continuing perception of unresolvable major threats or demands". The factor XII hypothesis is as follows: Acute stress includes release of epinephrine by the adrenal medulla. Epinephrine activates platelets by binding to alpha-2A adrenergic receptors. Activated platelets convert pre-bound factor XII to its active form, which then initiates the intrinsic coagulation cascade. This can be called the "activated platelet initiation pathway" for coagulation. Neither tissue factor nor pre-formed thrombin is required. Thrombosis proceeds to completion, but only a minute amount of thrombin is formed, and the process normally stops at this point. In people who lapse into a state of chronic stress, essential hypertension, which is also a manifestation of stress, synergizes with hypercoagulability: there is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both. Upregulation of these two stress parameters is atherogenic: epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin II to cause, first, smooth muscle cell proliferation, which is a histological hallmark of atherosclerosis, and, lastly, a symptomatic thrombotic occlusion-the stroke. The migraine symptoms which often accompany this process are a marker of chronic stress and ongoing pathophysiologic damage. Therapeutic predictions are made regarding novel

  9. Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.

    PubMed

    Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido

    2008-04-01

    Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.

  10. The Effects of the Contact Activation System on Hemorrhage

    PubMed Central

    Simão, Fabrício; Feener, Edward P.

    2017-01-01

    The contact activation system (CAS) exerts effects on coagulation via multiple mechanisms, which modulate both the intrinsic and extrinsic coagulation cascades as well as fibrinolysis and platelet activation. While the effects of the CAS on blood coagulation measured as activated partial thromboplastin time shortening are well documented, genetic mutations that result in deficiencies in the expression of either plasma prekallikrein (PPK) or factor XII (FXII) are not associated with spontaneous bleeding or increased bleeding risk during surgery. Deficiencies in these proteins are often undiagnosed for decades and detected later in life during routine coagulation assays without an apparent clinical phenotype. Increased interest in the CAS as a potentially safe target for antithrombotic therapies has emerged, in large part, from studies on animal models with provoked thrombosis, which have shown that deficiencies in PPK or FXII can reduce thrombus formation without increasing bleeding. Gene targeting and pharmacological studies in healthy animals have confirmed that PPK and FXII blockade does not cause coagulopathies. These findings support the conclusion that CAS is not required for hemostasis. However, while deficiencies in FXII and PPK do not significantly affect bleeding associated with peripheral wounds, recent reports have demonstrated that these proteins can promote hemorrhage in the retina and brain. Intravitreal injection of plasma kallikrein (PKal) induces retinal hemorrhage and intracerebral injection of PKal increases intracranial bleeding. PPK deficiency and PKal inhibition ameliorates hematoma formation following cerebrovascular injury in diabetic animals. Moreover, both PPK and FXII deficiency are protective against intracerebral hemorrhage caused by tissue plasminogen activator-mediated thrombolytic therapy in mice with thrombotic middle cerebral artery occlusion. Thus, while the CAS is not required for hemostasis, its inhibition may provide an

  11. The Secondary Structure of Human Hageman Factor (Factor XII) and its Alteration by Activating Agents

    PubMed Central

    McMillin, Carl R.; Saito, Hidehiko; Ratnoff, Oscar D.; Walton, Alan G.

    1974-01-01

    Hageman factor (factor XII) is activated by exposure to surfaces such as glass or by solutions of certain compounds, notably ellagic acid. Changes in the structure of Hageman factor accompanying activation have been examined in this study by circular dichroism spectroscopy. The spectrum of unactivated Hageman factor in aqueous solutions suggests that its conformation is mainly aperiodic. Various perturbants altered the conformation of Hageman factor in differing ways, demonstrating the sensitivity of Hageman factor to its environment. After activation of Hageman factor with solutions of ellagic acid, a negative trough appeared in the region of the circular dichroism spectrum commonly assigned to tyrosine residues, along with other minor changes in the peptide spectral region. Some of these changes are similar to changes that occurred upon partial neutralization of the basic residues at alkali pH. Activation of Hageman factor by adsorption to quartz surfaces (in an aqueous environment) also produced changes similar to those in the ellagic acid-activated Hageman factor, including the negative ellipticity in the tyrosine region. These observations suggest that the activation process may be related to a change in status of some of the basic amino acid residues, coupled with a specific change in the environment of some tyrosine residues. The importance of these changes during the activation process remains to be determined. The sensitivity of Hageman factor to its environment is consistent with the view that the initiation of clotting by exposure of plasma to appropriate agents is brought about by alterations in the conformation of Hageman factor that occur in the apparent absence of Fletcher factor or other recognized clotting factors. Images PMID:4373492

  12. A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis.

    PubMed

    Yang, Aizhen; Zhou, Junsong; Wang, Bo; Dai, Jihong; Colman, Robert W; Song, Wenchao; Wu, Yi

    2017-12-01

    The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis. In a K/BxN serum transfer-induced arthritis (STIA) model, mice that lacked HK, pKal, or bradykinin receptors displayed protective phenotypes in joint swelling, histologic changes in inflammation, and cytokine production; however, FXII-deficient mice developed normal arthritis. Inhibition of Kal ameliorated arthritis severity and incidence at early stage STIA and reduced the levels of major cytokines in joints. In addition to releasing bradykinin from HK, Kal directly activated monocytes to produce proinflammatory cytokines, up-regulated their C5aR and FcRIII expression, and released C5a. Immune complex increased pKal activity, which led to HK cleavage. The absence of HK is associated with a decrease in joint vasopermeability. Thus, we identify a critical role for Kal in autoantibody-induced arthritis with pleiotropic effects, which suggests that it is a new target for the inhibition of arthritis.-Yang, A., Zhou, J., Wang, B., Dai, J., Colman, R. W., Song, W., Wu, Y. A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis. © FASEB.

  13. Human plasma kallikrein-kinin system: Physiological and biochemical parameters

    PubMed Central

    Bryant, J.W.; Shariat-Madar, z

    2016-01-01

    The plasma kallikrein-kinin system (KKS) plays a critical role in human physiology. The KKS encompasses coagulation factor XII (FXII), the complex of prekallikrein (PK) and high molecular weight kininogen (HK). The conversion of plasma to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin (BK) and activated HK (HKa, an antiangiogenic peptide). BK is a proinflammatory peptide, a pain mediator and potent vasodilator, leading to robust accumulation of fluid in the interstitium. Systemic production of BK, HKa with the interplay between BK bound-BK receptors and the soluble form of HKa are key to angiogenesis and hemodynamics. KKS has been implicated in the pathogenesis of inflammation, hypertension, endotoxemia, and coagulopathy. In all these cases increased BK levels is the hallmark. In some cases, the persistent production of BK due to the deficiency of the blood protein C1-inhibitor, which controls FXII, is detrimental to the survival of the patients with hereditary angioedema (HAE). In others, the inability of angiotensin converting enzyme (ACE) to degrade BK leads to elevated BK levels and edema in patients on ACE inhibitors. Thus, the mechanisms that interfere with BK liberation or degradation would lead to blood pressure dysfunction. In contrast, anti-kallikrein treatment could have adverse effects in hemodynamic changes induced by vasoconstrictor agents. Genetic models of kallikrein deficiency are needed to evaluate the quantitative role of kallikrein and to validate whether strategies designed to activate or inhibit kallikrein may be important for regulating whole-body BK sensitivity. PMID:19689262

  14. Pius XII and the Jews: A Bibliographical Review.

    ERIC Educational Resources Information Center

    Byers, Catherine

    1978-01-01

    Presents a brief biographical sketch of Pope Pius XII and samples literary treatment of Pius's actions with respect to Nazi atrocities against the Jewish people during World War II. Concludes that Pope Pius XII failed to show moral leadership. Materials reviewed include historical texts, studies of the Vatican, documents related to the war period,…

  15. Site Investigation Report. 161st Air Refueling Group, Arizona National Guard, Sky Harbor International Airport and Papago Military Reservation, Phoenix, Arizona. Volume 1. Report, Tables and Figures

    DTIC Science & Technology

    1992-11-01

    Tennessee 37831-7606 NTIS GP’A t managed by O-C T MARTIN MARIETTA ENERGY SYSTEMS, INC. for the U.S. DEPARTMENT OF ENERGY 1Y under contract DE -ACO5...conductivity ECD electron capture detector S K • , . , i F.xii S List of Acronyms (Continued) S EM electromagnetic induction Energy Systems Martin Marietta...Energy Sytems, Inc. EWA East Washington Area FID flame ionization detector 9 Fr/DAY feet per day FS feasibility scudy FSP field sampling plan GC gas

  16. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo.

    PubMed

    von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T; Wagner, Denisa D; Mackman, Nigel; Engelmann, Bernd; Massberg, Steffen

    2012-04-09

    Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features.

  17. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

    PubMed Central

    von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A.; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T.; Wagner, Denisa D.; Mackman, Nigel; Engelmann, Bernd

    2012-01-01

    Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features. PMID:22451716

  18. Arterial thrombosis is accelerated in mice deficient in histidine-rich glycoprotein.

    PubMed

    Vu, Trang T; Zhou, Ji; Leslie, Beverly A; Stafford, Alan R; Fredenburgh, James C; Ni, Ran; Qiao, Shengjun; Vaezzadeh, Nima; Jahnen-Dechent, Willi; Monia, Brett P; Gross, Peter L; Weitz, Jeffrey I

    2015-04-23

    Factor (F) XII, a key component of the contact system, triggers clotting via the intrinsic pathway, and is implicated in propagating thrombosis. Although nucleic acids are potent activators, it is unclear how the contact system is regulated to prevent uncontrolled clotting. Previously, we showed that histidine-rich glycoprotein (HRG) binds FXIIa and attenuates its capacity to trigger coagulation. To investigate the role of HRG as a regulator of the intrinsic pathway, we compared RNA- and DNA-induced thrombin generation in plasma from HRG-deficient and wild-type mice. Thrombin generation was enhanced in plasma from HRG-deficient mice, and accelerated clotting was restored to normal with HRG reconstitution. Although blood loss after tail tip amputation was similar in HRG-deficient and wild-type mice, carotid artery occlusion after FeCl3 injury was accelerated in HRG-deficient mice, and HRG administration abrogated this effect. To confirm that HRG modulates the contact system, we used DNase, RNase, and antisense oligonucleotides to characterize the FeCl3 model. Whereas DNase or FVII knockdown had no effect, carotid occlusion was abrogated with RNase or FXII knockdown, confirming that FeCl3-induced thrombosis is triggered by RNA in a FXII-dependent fashion. Therefore, in a nucleic acid-driven model, HRG inhibits thrombosis by modulating the intrinsic pathway of coagulation. © 2015 by The American Society of Hematology.

  19. Arterial thrombosis is accelerated in mice deficient in histidine-rich glycoprotein

    PubMed Central

    Vu, Trang T.; Zhou, Ji; Leslie, Beverly A.; Stafford, Alan R.; Fredenburgh, James C.; Ni, Ran; Qiao, Shengjun; Vaezzadeh, Nima; Jahnen-Dechent, Willi; Monia, Brett P.; Gross, Peter L.; Weitz, Jeffrey I.

    2015-01-01

    Factor (F) XII, a key component of the contact system, triggers clotting via the intrinsic pathway, and is implicated in propagating thrombosis. Although nucleic acids are potent activators, it is unclear how the contact system is regulated to prevent uncontrolled clotting. Previously, we showed that histidine-rich glycoprotein (HRG) binds FXIIa and attenuates its capacity to trigger coagulation. To investigate the role of HRG as a regulator of the intrinsic pathway, we compared RNA- and DNA-induced thrombin generation in plasma from HRG-deficient and wild-type mice. Thrombin generation was enhanced in plasma from HRG-deficient mice, and accelerated clotting was restored to normal with HRG reconstitution. Although blood loss after tail tip amputation was similar in HRG-deficient and wild-type mice, carotid artery occlusion after FeCl3 injury was accelerated in HRG-deficient mice, and HRG administration abrogated this effect. To confirm that HRG modulates the contact system, we used DNase, RNase, and antisense oligonucleotides to characterize the FeCl3 model. Whereas DNase or FVII knockdown had no effect, carotid occlusion was abrogated with RNase or FXII knockdown, confirming that FeCl3-induced thrombosis is triggered by RNA in a FXII-dependent fashion. Therefore, in a nucleic acid–driven model, HRG inhibits thrombosis by modulating the intrinsic pathway of coagulation. PMID:25691157

  20. REM Sleep–like Atonia of Hypoglossal (XII) Motoneurons Is Caused by Loss of Noradrenergic and Serotonergic Inputs

    PubMed Central

    Fenik, Victor B.; Davies, Richard O.; Kubin, Leszek

    2017-01-01

    Rationale Studies of hypoglossal (XII) motoneurons that innervate the genioglossus muscle, an upper airway dilator, suggested that the suppression of upper airway motor tone during REM sleep is caused by withdrawal of excitation mediated by norepinephrine and serotonin. Objectives Our objectives were to determine whether antagonism of aminergic receptors located in the XII nucleus region can abolish the REM sleep–like atonia of XII motoneurons, and whether both serotonergic and noradrenergic antagonists are required to achieve this effect. Methods REM sleep–like episodes were elicited in anesthetized rats by pontine carbachol injections before and at various times after microinjection of prazosin and methysergide combined, or of only one of the drugs, into the XII nucleus. Measurements and Main Results Spontaneous XII nerve activity was significantly reduced, by 35 to 81%, by each antagonist alone and in combination, indicating that XII motoneurons were under both noradrenergic and serotonergic endogenous excitatory drives. During the 32 to 81 min after microinjections of both antagonists, pontine carbachol caused no depression of XII nerve activity, whereas other characteristic effects (activation of the hippocampal and cortical EEG, and slowing of the respiratory rate) remained intact. A partial recovery of the depressant effect of carbachol then occurred parallel to the recovery of spontaneous XII nerve activity from the depressant effect of the antagonists. Microinjections of either antagonist alone did not eliminate the depressant effect of carbachol. Conclusions The REM sleep–like depression of XII motoneuronal activity induced by pontine carbachol can be fully accounted for by the combined withdrawal of noradrenergic and serotonergic effects on XII motoneurons. PMID:16100007

  1. Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.

    PubMed

    Syrjänen, Leo; Luukkaala, Tiina; Leppilampi, Mari; Kallioinen, Matti; Pastorekova, Silvia; Pastorek, Jaromir; Waheed, Abdul; Sly, William S; Parkkila, Seppo; Karttunen, Tuomo

    2014-09-01

    Purpose of the study was to evaluate the presence of hypoxia-inducible, tumour-associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  2. Zebrafish collagen XII is present in embryonic connective tissue sheaths (fascia) and basement membranes.

    PubMed

    Bader, Hannah L; Keene, Douglas R; Charvet, Benjamin; Veit, Guido; Driever, Wolfgang; Koch, Manuel; Ruggiero, Florence

    2009-01-01

    Connective tissues ensure the cohesion of the tissues of the body, but also form specialized structures such as tendon and bone. Collagen XII may enhance the stability of connective tissues by bridging collagen fibrils, but its function is still unclear. Here, we used the zebrafish model to visualize its expression pattern in the whole organism. The zebrafish col12a1 gene is homologous to the small isoform of the tetrapod col12a1 gene. In agreement with the biochemical data reported for the small isoform, the zebrafish collagen XII alpha1 chain was characterized as a collagenase sensitive band migrating at approximately 200 kDa. Using newly generated polyclonal antibodies and anti-sense probes, we performed a comprehensive analysis of its expression in developing zebrafish. Collagen XII exhibited a much broader expression pattern than previously thought: it was ubiquitously expressed in the connective tissue sheaths (fascia) that encase the tissues and organs of the body. For example, it was found in sclera, meninges, epimysia and horizontal and vertical myosepta. Collagen XII was also detected in head mesenchyme, pharyngeal arches and within the spinal cord, where it was first expressed within and then at the lateral borders of the floor plate and at the dorsal midline. Furthermore, double immunofluorescence staining with laminin and immunogold electron microscopy revealed that collagen XII is associated with basement membranes. These data suggest that collagen XII is implicated in tissue cohesion by stabilizing fascia and by linking fascia to basement membranes.

  3. 77 FR 13317 - Lock+ Hydro Friends Fund XII, BOST2, LLC, et al.; Notice Announcing Filing Priority for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-06

    ... al.] Lock+ Hydro Friends Fund XII, BOST2, LLC, et al.; Notice Announcing Filing Priority for Preliminary Permit Applications Project No. Lock+ Hydro Friends Fund XII 14260-000 BOST2, LLC 14264-000.... 2. BOST2, LLC: Project No. 14264-000. 3. Lock+ Hydro Friends Fund XII: Project No. 14260-000. 4...

  4. Computational investigation of the selectivity of salen and tetrahydrosalen compounds towards the tumor-associated hCA XII isozyme.

    PubMed

    Akdemir, Atilla; De Monte, Celeste; Carradori, Simone; Supuran, Claudiu T

    2015-02-01

    In previous work, 14 salen and tetrahydrosalen compounds have been synthesized and tested in enzyme inhibition assays against cytosolic human carbonic anhydrase isozymes I and II (hCA I and II) and tumor-associated isozymes IX and XII (hCA IX and XII). These compounds show selectivity against hCA XII over hCA I, II and IX. In this study, molecular modeling and docking studies were applied to understand this preference of the compounds for hCA XII. Most likely, the compounds can displace the zinc-bound water molecule of hCA XII to form a direct interaction with the Zn(2+) ion. In the other isozymes, the compounds might not be able to displace the water molecule nor are they expected to interact with the Zn(2+) ion.

  5. 77 FR 59669 - Comment Request for Information Collection; Unemployment Insurance (UI) Title XII Advances and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... Collection; Unemployment Insurance (UI) Title XII Advances and Voluntary Repayment Process; Extension Without... assessed. Currently, ETA is soliciting comments concerning the collection process for data on UI Title XII... request (ICR) can be obtained by contacting Mr. Gibbons. SUPPLEMENTARY INFORMATION: I. Background Title...

  6. 76 FR 75563 - Notice for Delay of Payment of Title XII Interest for Three States

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-02

    ... DEPARTMENT OF LABOR Employment and Training Administration Notice for Delay of Payment of Title.... SUMMARY: This notice announces the approval for delay of Title XII interest payment for three states... Title XII advances made during the last five months of the Federal fiscal year (FY) (May, June, July...

  7. Factor XII (Hageman factor) deficiency

    MedlinePlus

    ... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

  8. 40 CFR Appendix Xii to Part 86 - Tables for Production Compliance Auditing of Heavy-Duty Engines and Heavy-Duty Vehicles...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Tables for Production Compliance Auditing of Heavy-Duty Engines and Heavy-Duty Vehicles, Including Light-Duty Trucks XII Appendix XII to... Appendix XII to Part 86—Tables for Production Compliance Auditing of Heavy-Duty Engines and Heavy-Duty...

  9. Structure and function of transmembrane segment XII in osmosensor and osmoprotectant transporter ProP of Escherichia coli.

    PubMed

    Liu, Feng; Culham, Doreen E; Vernikovska, Yaroslava I; Keates, Robert A B; Boggs, Joan M; Wood, Janet M

    2007-05-15

    Escherichia coli transporter ProP acts as both an osmosensor and an osmoregulator. As medium osmolality rises, ProP is activated and mediates H+-coupled uptake of osmolytes like proline. A homology model of ProP with 12-transmembrane (TM) helices and cytoplasmic termini was created, and the protein's topology was substantiated experimentally. Residues 468-497, at the end of the C-terminal domain and linked to TM XII, form an intermolecular, homodimeric alpha-helical coiled-coil that tunes the transporter's response to osmolality. We aim to further define the structure and function of ProP residues Q415-E440, predicted to include TM XII. Each residue was replaced with cysteine (Cys) in a histidine-tagged, Cys-less ProP variant (ProP*). Cys at positions 415-418 and 438-440 were most reactive with Oregon Green Maleimide (OGM), suggesting that residues 419 through 437 are in the membrane. Except for V429-I433, reactivity of those Cys varied with helical periodicity. Cys predicted to face the interior of ProP were more reactive than Cys predicted to face the lipid. The former may be exposed to hydrated polar residues in the protein interior, particularly on the periplasmic side. Intermolecular cross-links formed when ProP* variants with Cys at positions 419, 420, 422, and 439 were treated with DTME. Thus TM XII can participate, along its entire length, in the dimer interface of ProP. Cys substitution E440C rendered ProP* inactive. All other variants retained more than 30% of the proline uptake activity of ProP* at high osmolality. Most variants with Cys substitutions in the periplasmic half of TM XII activated at lower osmolalities than ProP*. Variants with Cys substitutions on one face of the cytoplasmic half of TM XII required a higher osmolality to activate. They included elements of a GXXXG motif that are predicted to form the interface of TM XII with TM VII. These studies define the position of ProP TM XII within the membrane, further support the predicted

  10. Characterization of the interactions of type XII collagen with two small proteoglycans from fetal bovine tendon, decorin and fibromodulin.

    PubMed

    Font, B; Eichenberger, D; Rosenberg, L M; van der Rest, M

    1996-11-01

    In addition to the major collagens, such as type I or type II, connective tissues contain a number of less abundant collagens and proteoglycans, whose association contributes to the different properties of the tissues. Type XII and type XIV collagens have been described in soft connective tissues, and type XIV collagen has been shown to interact specifically with decorin through its glycosaminoglycan chain (Font et al., J. Biol. Chem. 268, 25015-25018, 1993). Interactions between these collagens and the small proteoglycans have been characterized further by studying the binding of type XII collagen to decorin by solid phase assays. Our results show a saturable binding of the proteoglycan through its glycosaminoglycan chain to type XII collagen, which does not seem to involve the large non-collagenous NC3 domain of the molecule. This interaction is strongly inhibited by heparin. Furthermore, we report that another small proteoglycan, fibromodulin, isolated from tendon under non-denaturing conditions, is able to bind to type XII collagen. This interaction has been characterized and, unlike that observed with decorin, type XII collagen-fibromodulin interaction seems to take place with the core protein of the proteoglycan. In addition, we report that type XII-type I collagen interactions are not necessarily mediated by decorin as previously suggested.

  11. Free factor XIII activation peptide (fAP-FXIII) is a regulator of factor XIII activity via factor XIII-B.

    PubMed

    Dodt, Johannes; Pasternack, Ralf; Seitz, Rainer; Volkers, Peter

    2016-02-01

    In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2 ) free FXIII activation peptide (fAP-FXII) prolonged the time to peak (TTP) but did not affect the area under the curve (AUC) or concentration at peak (CP). Addition of recombinant factorXIII-B2 (rFXIII-B2 ) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2 B2 ). FXIII-A2 B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2 B2 , indicating a role for FXIII-B in this observation. An effect of fAP-FXIII on thrombin, the proteolytic activator of FXIII, was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP-FXIII did not interfere with the FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2 ') also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2 'B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2 'B2 . In addition to its well-known role, FXIII-B also contributes to FXIII-A2 B2 stability or dissociation depending on fAP-FXIII and calcium concentrations. © 2015 John Wiley & Sons Ltd.

  12. 75 FR 37456 - Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of 2009

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-29

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5376-N-55] Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of 2009 AGENCY: Office of the Chief Information... Title of Proposal: Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of...

  13. [XII National Forum on Health Education].

    PubMed

    Ramiro-H, Manuel

    2015-01-01

    In Guadalajara, on August 19, 20 and 21 was held the XII Foro Nacional de Educación en Salud, in line with the interest that both, the Dirección General and the Dirección de Prestaciones Médicas of the IMSS, have in training and updating the human resources for the care of the beneficiaries. The Unidad de Educación, Investigación y Políticas de Salud organized a meeting in which the actors of these tasks, the institutional staff and authorities from various universities worked together with the IMSS.

  14. 77 FR 10741 - Lock+ Hydro Friends Fund XII, BOST2, LLC, Riverbank Hydro No. 21, LLC, FFP Project 96, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project Nos. 14260-000, 14264-000, 14267-000, 14273-000] Lock+ Hydro Friends Fund XII, BOST2, LLC, Riverbank Hydro No. 21, LLC, FFP Project... Greene and Hale counties, Alabama. The applications were filed by Lock+ Hydro Friends Fund XII for...

  15. Pyrazolylbenzo[d]imidazoles as new potent and selective inhibitors of carbonic anhydrase isoforms hCA IX and XII.

    PubMed

    Kumar, Satish; Ceruso, Mariangela; Tuccinardi, Tiziano; Supuran, Claudiu T; Sharma, Pawan K

    2016-07-01

    Novel pyrazolylbenzo[d]imidazole derivatives (2a-2f) were designed, synthesized and evaluated against four human carbonic anhydrase isoforms belonging to α family comprising of two cytosolic isoforms hCA I and II as well as two transmembrane tumor associated isoforms hCA IX and XII. Starting from these derivatives that showed high potency but low selectivity in favor of tumor associated isoforms hCA IX and XII, we investigated the impact of removing the sulfonamide group. Thus, analogs 3a-3f without sulfonamide moiety were synthesized and biological assay revealed a good activity as well as an excellent selectivity as inhibitors for tumor associated hCA IX and hCA XII and the same was analyzed by molecular docking studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.

    PubMed

    Lee, Melissa; Vecchio-Pagán, Briana; Sharma, Neeraj; Waheed, Abdul; Li, Xiaopeng; Raraigh, Karen S; Robbins, Sarah; Han, Sangwoo T; Franca, Arianna L; Pellicore, Matthew J; Evans, Taylor A; Arcara, Kristin M; Nguyen, Hien; Luan, Shan; Belchis, Deborah; Hertecant, Jozef; Zabner, Joseph; Sly, William S; Cutting, Garry R

    2016-05-15

    Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM #219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.908-1 G>A in a splice acceptor and a novel frameshift insertion c.859_860insACCT. In an unrelated consanguineous Omani family, two children with elevated sweat chloride, infantile FTT, and recurrent hyponatremia were homozygous for a novel missense variant (p.His121Gln). Deleterious CFTR variants were absent in both pedigrees. CA XII protein was localized apically in human bronchiolar epithelia and basolaterally in the reabsorptive duct of human sweat glands. Respiratory epithelial cell RNA from the adult proband revealed only aberrant CA12 transcripts and in vitro analysis showed greatly reduced CA XII protein. Studies of ion transport across respiratory epithelial cells in vivo and in culture revealed intact CFTR-mediated chloride transport in the adult proband. CA XII protein bearing either p.His121Gln or a previously identified p.Glu143Lys missense variant localized to the basolateral membranes of polarized Madin-Darby canine kidney (MDCK) cells, but enzyme activity was severely diminished when assayed at physiologic concentrations of extracellular chloride. Our findings indicate that loss of CA XII function should be considered in individuals without CFTR mutations who exhibit CF-like features in the sweat gland and lung. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Inhibition of carbonic anhydrase isoforms I, II, IX and XII with novel Schiff bases: identification of selective inhibitors for the tumor-associated isoforms over the cytosolic ones.

    PubMed

    Sarikaya, Busra; Ceruso, Mariangela; Carta, Fabrizio; Supuran, Claudiu T

    2014-11-01

    A series of new Schiff bases was obtained from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide and aromatic/heterocyclic aldehydes incorporating both hydrophobic and hydrophilic moieties. The obtained sulfonamides were investigated as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, as well as the transmembrane, tumor-associated CA IX and XII. Most derivatives were medium potency or weak hCA I/II inhibitors, but several of them showed nanomolar affinity for CA IX and/or XII, making them an interesting example of isoform-selective compounds. The nature of the aryl/hetaryl moiety present in the initial aldehyde was the main factor influencing potency and isoform selectivity. The best and most CA IX-selective compounds incorporated moieties such as 4-methylthiophenyl, 4-cyanophenyl-, 4-(2-pyridyl)-phenyl and the 4-aminoethylbenzenesulfonamide scaffold. The best hCA XII inhibitors, also showing selectivity for this isoform, incorporated 2-methoxy-4-nitrophenyl-, 2,3,5,6-tetrafluorophenyl and 4-(2-pyridyl)-phenyl functionalities and were also derivatives of 4-aminoethylbenzenesulfonamide. The sulfanilamide and 3-fluorosulfanilamide derived Schiff bases were less active compared to the corresponding 4-aminoethyl-benzenesulfonamide derivatives. As hCA IX/XII selective inhibition is attractive for obtaining antitumor agents/diagnostic tools with a new mechanism of action, compounds of the type described here may be considered interesting preclinical candidates. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Zinc induces exposure of hydrophobic sites in the C-terminal domain of gC1q-R/p33.

    PubMed

    Kumar, Rajeev; Peerschke, Ellinor I B; Ghebrehiwet, Berhane

    2002-09-01

    Endothelial cells and platelets are known to express gC1q-R on their surface. In addition to C1q, endothelial cell gC1q-R has been shown to bind high molecular weight kininogen (HK) and factor XII (FXII). However, unlike C1q, whose interaction with gC1q-R does not require divalent ions, the binding of HK to gC1q-R is absolutely dependent on the presence of zinc. However, the mechanism by which zinc modulates this interaction is not fully understood. To investigate the role of zinc, binding studies were done using the hydrophobic dye, bis-ANS. The fluorescence intensity of bis-ANS, greatly increases and the emission maximum is blue-shifted from 525 to 485nm upon binding to hydrophobic sites on proteins. In this report, we show that a blue-shift in emission maximum is also observed when bis-ANS binds to gC1q-R in the presence but not in the absence of zinc suggesting that zinc induces exposure of hydrophobic sites in the molecule. The binding of bis-ANS to gC1q-R is specific, dose-dependent, and reversible. In the presence of zinc, this binding is abrogated by monoclonal antibody 74.5.2 directed against gC1q-R residues 204-218. This segment of gC1q-R, which corresponds to the beta6 strand in the crystal structure, has been shown previously to be the binding site for HK. A similar trend in zinc-induced gC1q-R binding was also observed using the hydrophobic matrix octyl-Sepharose. Taken together, our data suggest that zinc can induce the exposure of hydrophobic sites in the C-terminal domain of gC1q-R involved in binding to HK/FXII.

  19. Coagulation factor XII genetic variation, ex vivo thrombin generation, and stroke risk in the elderly: results from the Cardiovascular Health Study.

    PubMed

    Olson, N C; Butenas, S; Lange, L A; Lange, E M; Cushman, M; Jenny, N S; Walston, J; Souto, J C; Soria, J M; Chauhan, G; Debette, S; Longstreth, W T; Seshadri, S; Reiner, A P; Tracy, R P

    2015-10-01

    The relationships of thrombin generation (TG) with cardiovascular disease risk are underevaluated in population-based cohorts. To evaluate the relationships of TG influenced by the contact and tissue factor coagulation pathways ex vivo with common single-nucleotide polymorphisms (SNPs) and incident cardiovascular disease and stroke. We measured peak TG (pTG) in baseline plasma samples of Cardiovascular Health Study participants (n = 5411), both with and without inhibitory anti-factor XIa antibody (pTG/FXIa(-) ). We evaluated their associations with ~ 50 000 SNPs by using the IBCv2 genotyping array, and with incident cardiovascular disease and stroke events over a median follow-up of 13.2 years. The minor allele for an SNP in the FXII gene (F12), rs1801020, was associated with lower pTG in European-Americans (β = - 34.2 ± 3.5 nm; P = 3.3 × 10(-22) ; minor allele frequency [MAF] = 0.23) and African-Americans (β = - 31.1 ± 7.9 nm; P = 9.0 × 10(-5) ; MAF = 0.42). Lower FXIa-independent pTG (pTG/FXIa(-) ) was associated with the F12 rs1801020 minor allele, and higher pTG/FXIa(-) was associated with the ABO SNP rs657152 minor allele (β = 16.3 nm; P = 4.3 × 10(-9) ; MAF = 0.37). The risk factor-adjusted ischemic stroke hazard ratios were 1.09 (95% confidence interval CI 1.01-1.17; P = 0.03) for pTG, 1.06 (95% CI 0.98-1.15; P = 0.17) for pTG/FXIa(-) , and 1.11 (95% CI 1.02-1.21; P = 0.02) for FXIa-dependent pTG (pTG/FXIa(+) ), per one standard deviation increment (n = 834 ischemic strokes). In a multicohort candidate gene analysis, rs1801020 was not associated with incident ischemic stroke (β = - 0.02; standard error = 0.08; P = 0.81). These results support the importance of contact activation pathway-dependent TG as a risk factor for ischemic stroke, and indicate the importance of F12 SNPs for TG ex vivo and in vivo. © 2015 International Society on Thrombosis and Haemostasis.

  20. Ramsay Hunt syndrome with unilateral polyneuropathy involving cranial nerves V, VII, VIII, and XII in a diabetic patient.

    PubMed

    Sun, Wei-Lian; Yan, Jian-Liang; Chen, Li-Li

    2011-01-01

    Ramsay Hunt syndrome is a rare complication of the varicella zoster virus, defined as a peripheral facial palsy that typically results from involvement of the facial and auditory nerves. Ramsay Hunt syndrome can be associated with cranial nerves V, VI, IX, and X but rarely with XII. We describe an atypical case of Ramsay Hunt syndrome with multiple cranial nerve involvement of nerves V, VII, VIII, and XII. Antiviral drugs, antibiotics, insulin, and traditional Chinese drugs were administered immediately after admission. After 3 months of combination therapy, the patient had recovered satisfactorily. Herpes zoster can cause severe infections in diabetic patients and should be treated as soon after detection as possible. Ramsay Hunt syndrome should be recognized as a polycranial neuritis characterized by damage to sensory and motor nerves. In addition to facial and vestibular nerve paralysis, Ramsay Hunt syndrome may also involve cranial nerves V and XII.

  1. OATYC Journal, Vol. XII, Nos. 1-2, Fall 1986-Spring 1987.

    ERIC Educational Resources Information Center

    Fullen, James, Ed.

    1987-01-01

    "OATYC Journal," published by the the Ohio Association of Two-Year Colleges, is designed as a forum for the exchange of concepts, methods, and findings relevant to the two-year college classroom. Along with commentaries and letters of reaction from the readership, the two issues of Volume XII present the following: (1) "Focus:…

  2. 76 FR 73614 - Lock Hydro Friends Fund XII; BOST2 LLC; Riverbank Hydro No. 21 LLC; FFP Project 96 LLC; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project Nos. 14260-000; 14264-000; 14267-000; 14273-000] Lock Hydro Friends Fund XII; BOST2 LLC; Riverbank Hydro No. 21 LLC; FFP Project 96..., Motions To Intervene, and Competing Applications On September 1, 2011, Lock Hydro Friends Fund XII (Lock...

  3. Natural history and clinical manifestations of hyponatremia and hyperchlorhidrosis due to carbonic anhydrase XII deficiency.

    PubMed

    Feinstein, Yael; Yerushalmi, Baruch; Loewenthal, Neta; Alkrinawi, Soliman; Birk, Ohad S; Parvari, Ruti; Hershkovitz, Eli

    2014-01-01

    We identified patients of Bedouin origin with a mutation in carbonic anhydrase XII (CA XII) leading to hyponatremia due to excessive salt loss via sweat. The medical records of patients were reviewed for clinical and laboratory data. A total of 11 subjects were identified; 7 symptomatic patients presented with hyponatremic dehydration in infancy. Screening of the entire kindred identified 4 asymptomatic individuals with elevated sweat chloride. All symptomatic patients had failure to thrive and moderate-severe hyponatremia (106-124 mmol·l(-1)); 6 had hypochloremia (79-94 mmol·l(-1)). All asymptomatic subjects had normal or near-normal serum sodium and chloride concentrations. Both symptomatic and asymptomatic subjects had normal renal functions and normal cortisol response on low-dose ACTH test. All symptomatic patients were treated by dietary salt, which prevents episodes of hyponatremic dehydration and promotes growth. At follow-up, the chief complaints remained heat intolerance, accumulation of salt precipitates on the face and hyperhidrosis. No evidence for chronic renal, respiratory, gastrointestinal or fertility abnormalities was found. Recognizing this newly described entity and differentiating it from cystic fibrosis and pseudohypoaldosteronism are important. Patients with CA XII mutations should be followed even after early childhood, especially in hot temperatures and intense physical activity. © 2014 S. Karger AG, Basel.

  4. Demonstration of resonant photopumping of Mo VII by Mo XII for a VUV laser near 600 {Angstrom}

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

    Ilcisin, K.J.; Aumayr, F.; Schwob, J.L.

    1993-09-01

    We present data of experiments on the resonant photopumping of Mo VII by Mo XII as a method of generating a coherent VUV source near 600 {angstrom}. The experiment is based on a scheme proposed by Feldman and Reader in which the 4p{sup 6} -- 4p{sup 5}6s transition in Mo VII in resonantly photopumped by the 5s {sup 2}S{sub 1/2} -- 4p {sup 2}P{sub 1/2} transition in Mo XII. Results of the laser produced plasma experiments show the successful enhancement of the population of the Mo VII 4p{sup 5}6s upper lasing level when pumped by an adjacent Mo VII plasma.more » No enhancement was seen in a control experiment where the Mo VII plasma was pumped by a Zr X plasma. Improvements of the intensity of the Mo XII pump source, achieved using an additional pump laser, lead to the generation of a population inversion for the VUV transition.« less

  5. Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII.

    PubMed

    Fiedler, L; Kellner, M; Gosewisch, A; Oos, R; Böning, G; Lindner, S; Albert, N; Bartenstein, P; Reulen, H-J; Zeidler, R; Gildehaus, F J

    2018-05-01

    Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177 Lu as an agent for RIT. 6A10 Fab fragment was modified and radiolabelled with 177 Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts. The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy. The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Colloidal Confinement of Polyphosphate on Gold Nanoparticles Robustly Activates the Contact Pathway of Blood Coagulation.

    PubMed

    Szymusiak, Magdalena; Donovan, Alexander J; Smith, Stephanie A; Ransom, Ross; Shen, Hao; Kalkowski, Joseph; Morrissey, James H; Liu, Ying

    2016-01-20

    Platelet-sized polyphosphate (polyP) was functionalized on the surface of gold nanoparticles (GNPs) via a facile conjugation scheme entailing EDAC (N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride)-catalyzed phosphoramidation of the terminal phosphate of polyP to cystamine. Subsequent reduction of the disulfide moiety allowed for anchoring to the colloidal surface. The ability of the synthesized polyP-GNPs to initiate the contact pathway of clotting in human pooled normal plasma (PNP) was then assayed by quantifying changes in viscous, mechanical, and optical properties upon coagulation. It is revealed that the polyP-GNPs are markedly superior contact activators compared to molecularly dissolved, platelet-sized polyP (of equivalent polymer chain length). Moreover, the particles' capacity to mobilize Factor XII (FXII) and its coactivating proteins appear to be identical to very-long-chain polyP typically found in bacteria. These data imply that nanolocalization of anionic procoagulants on colloidal surfaces, achieved through covalent anchoring, may yield a robust contact surface with the ability to sufficiently cluster active clotting factors together above their threshold concentrations to cease bleeding. The polyP-GNPs therefore serve as a promising foundation in the development of a nanoparticle hemostat to treat a range of hemorrhagic scenarios.

  7. Forces necessary for the disruption of the cisternal segments of cranial nerves II through XII.

    PubMed

    Tubbs, R Shane; Wellons, John C; Blount, Jeffrey P; Salter, E George; Oakes, W Jerry

    2007-04-01

    Manipulation of the cisternal segment of cranial nerves is often performed by the neurosurgeon. To date, attempts at quantifying the forces necessary to disrupt these nerves in situ, to our knowledge, has not been performed. The present study seeks to further elucidate the forces necessary to disrupt the cranial nerves while within the subarachnoid space. The cisternal segments of cranial nerves II through XII were exposed in six unfixed cadavers, all less than 6 hr postmortem. Forces to failure were then measured. Mean forces necessary to disrupt nerves for left sides in increasing order were found for cranial nerves IX, VII, IV, X, XII, III, VIII, XI, VI, V, and II, respectively. Mean forces for right-sided cranial nerves in increasing order were found for cranial nerves IX, VII, IV, X, XII, VIII, V, VI, XI, III, and II, respectively. Overall, cranial nerves requiring the least amount of force prior to failure included cranial nerves IV, VII, and IX. Those requiring the highest amount of force included cranial nerves II, V, VI, and XI. There was an approximately ten-fold difference between the least and greatest forces required to failure. Cranial nerve III was found to require significantly (P < 0.05) greater forces to failure for right versus left sides. To date, the neurosurgeon has had no experimentally derived data from humans for the in situ forces necessary to disrupt the cisternal segment of cranial nerves II through XII. We found that cranial nerve IX consistently took the least amount of force until its failure and cranial nerve II took the greatest. Other cranial nerves that took relatively small amount of force prior to failure included cranial nerves IV and VII. Although in vivo damage can occur prior to failure of a cranial nerve, our data may serve to provide a rough estimation for the maximal amount of tension that can be applied to a cranial nerve that is manipulated while within its cistern.

  8. Opisthorchiasis in infant remains from the medieval Zeleniy Yar burial ground of XII-XIII centuries AD

    PubMed Central

    Slepchenko, Sergey Mikhailovich; Gusev, Alexander Vasilevich; Ivanov, Sergey Nikolaevich; Svyatova, Evgenia Olegovna

    2015-01-01

    We present a paleoparasitological analysis of the medieval Zeleniy Yar burial ground of the XII-XII centuries AD located in the northern part of Western Siberia. Parasite eggs, identified as eggs of Opisthorchis felineus, were found in the samples from the pelvic area of a one year old infant buried at the site. Presence of these eggs in the soil samples from the infant’s abdomen suggests that he/she was infected with opisthorchiasis and imply consumption of undercooked fish. Ethnographic records collected among the population of the northern part of Western Siberia reveal numerous cases of feeding raw fish to their children. Zeleniy Yar case of opisthorchiasis suggests that this dietary custom has persisted from at least medieval times. PMID:26602874

  9. Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms.

    PubMed

    D'Ascenzio, Melissa; Guglielmi, Paolo; Carradori, Simone; Secci, Daniela; Florio, Rosalba; Mollica, Adriano; Ceruso, Mariangela; Akdemir, Atilla; Sobolev, Anatoly P; Supuran, Claudiu T

    2017-12-01

    A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (K i s > 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with K i s ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (K i s ranging between 4.3 and 432 nM). Since hCA IX and XII are the cancer-related isoforms recently validated as drug targets, these results represent an important goal in the development of new anticancer candidates. Finally, a computational approach has been performed to better correlate the biological data to the binding mode of these inhibitors.

  10. Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.

    PubMed

    Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

    2012-06-29

    The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone.

  11. Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure*

    PubMed Central

    Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R.; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

    2012-01-01

    The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone. PMID:22573329

  12. FOREWORD: The 12th International Workshop on Desorption Induced by Electronic Transitions (DIET XII) (Pine Mountain, Georgia, USA, 19-23 April 2009) The 12th International Workshop on Desorption Induced by Electronic Transitions (DIET XII) (Pine Mountain, Georgia, USA, 19-23 April 2009)

    NASA Astrophysics Data System (ADS)

    Orlando, Thomas M.; Diebold, Ulrike

    2010-03-01

    The 12th International Workshop on Desorption Induced by Electronic Transitions (DIET XII) took place from 19-23 April 2009 in Pine Mountain, Georgia, USA. This was the 12th conference in a strong and vibrant series, which dates back to the early 1980s. DIET XII continued the tradition of exceptional interdisciplinary science and focused on the study of desorption and dynamics induced by electronic excitations of surfaces and interfaces. The format involved invited lectures, contributed talks and a poster session on the most recent developments and advances in this area of surface physics. The Workshop International Steering Committee and attendees wish to dedicate DIET XII to the memory of the late Professor Theodore (Ted) Madey. Ted was one of the main pioneers of this field and was one of the primary individuals working to keep this area of science exciting and adventurous. His overall contributions to surface science were countless and his contributions to the DIET field and community were enormous. He is missed and remembered by many friends and colleagues throughout the world. The papers collected in this issue cover many of the highlights of DIET XII. Topics include ultrafast electron transfer at surfaces and interfaces, quantum and spatially resolved mapping of surface dynamics and desorption, photon-, electron- and ion-beam induced processes at complex interfaces, the role of non-thermal desorption in astrochemistry and astrophysics and laser-/ion-based methods of examining soft matter and biological media. Although the workshop attracted many scientists active in the general area of non-thermal surface processes, DIET XII also attracted many younger scientists (i.e., postdoctoral fellows, advanced graduate students, and a select number of advanced undergraduate students). This field has had an impact in a number of areas including nanoscience, device physics, astrophysics, and now biophysics. We believe that this special issue of Journal of Physics

  13. Future prospects for contact factors as therapeutic targets

    PubMed Central

    Gailani, David

    2015-01-01

    Anticoagulants currently used in clinical practice to treat or prevent thromboembolic disease are effective, but place patients at increased risk for serious bleeding because they interfere with plasma enzymes (thrombin and factor Xa) that are essential for hemostasis. In the past 10 years, work with genetically altered mice and studies in baboons and rabbits have demonstrated that the plasma contact proteases factor XI, factor XII, and prekallikrein contribute to the formation of occlusive thrombi despite having limited roles in hemostasis. In the case of factor XI, epidemiologic data from human populations indicate that elevated levels of this protein increase risk for stroke and venous thromboembolism and may also influence risk for myocardial infarction. These findings suggest that inhibiting contact activation may produce an antithrombotic effect without significantly compromising hemostasis. This chapter reviews strategies that are being developed for therapeutic targeting of factor XI and factor XII and their performances in preclinical and early human trials. PMID:25696834

  14. Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII.

    PubMed

    SitaRam; Celik, Gulsah; Khloya, Poonam; Vullo, Daniela; Supuran, Claudiu T; Sharma, Pawan K

    2014-03-15

    Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Implosion and heating experiments of fast ignition targets by Gekko-XII and LFEX lasers

    NASA Astrophysics Data System (ADS)

    Shiraga, H.; Fujioka, S.; Nakai, M.; Watari, T.; Nakamura, H.; Arikawa, Y.; Hosoda, H.; Nagai, T.; Koga, M.; Kikuchi, H.; Ishii, Y.; Sogo, T.; Shigemori, K.; Nishimura, H.; Zhang, Z.; Tanabe, M.; Ohira, S.; Fujii, Y.; Namimoto, T.; Sakawa, Y.; Maegawa, O.; Ozaki, T.; Tanaka, K. A.; Habara, H.; Iwawaki, T.; Shimada, K.; Key, M.; Norreys, P.; Pasley, J.; Nagatomo, H.; Johzaki, T.; Sunahara, A.; Murakami, M.; Sakagami, H.; Taguchi, T.; Norimatsu, T.; Homma, H.; Fujimoto, Y.; Iwamoto, A.; Miyanaga, N.; Kawanaka, J.; Kanabe, T.; Jitsuno, T.; Nakata, Y.; Tsubakimoto, K.; Sueda, K.; Kodama, R.; Kondo, K.; Morio, N.; Matsuo, S.; Kawasaki, T.; Sawai, K.; Tsuji, K.; Murakami, H.; Sarukura, N.; Shimizu, T.; Mima, K.; Azechi, H.

    2013-11-01

    The FIREX-1 project, the goal of which is to demonstrate fuel heating up to 5 keV by fast ignition scheme, has been carried out since 2003 including construction and tuning of LFEX laser and integrated experiments. Implosion and heating experiment of Fast Ignition targets have been performed since 2009 with Gekko-XII and LFEX lasers. A deuterated polystyrene shell target was imploded with the 0.53- μm Gekko-XII, and the 1.053- μm beam of the LFEX laser was injected through a gold cone attached to the shell to generate hot electrons to heat the imploded fuel plasma. Pulse contrast ratio of the LFEX beam was significantly improved. Also a variety of plasma diagnostic instruments were developed to be compatible with harsh environment of intense hard x-rays (γ rays) and electromagnetic pulses due to the intense LFEX beam on the target. Large background signals around the DD neutron signal in time-of-flight record of neutron detector were found to consist of neutrons via (γ,n) reactions and scattered gamma rays. Enhanced neutron yield was confirmed by carefully eliminating such backgrounds. Neutron enhancement up to 3.5 × 107 was observed. Heating efficiency was estimated to be 10-20% assuming a uniform temperature rise model.

  16. Optimization of Lyophilized Plasma for Use in Combat Casualties

    DTIC Science & Technology

    2013-01-21

    SD. (Fib: fibrinogen, FII: Factor II, FV: Factor V, FVII : Factor VII, FVIII: Factor VIII, FIX: Factor IX, FX: Factor X, FXI: Factor XI, FXII...coagulation factor activity. Twenty swine were anesthetized and subjected to a validated model of polytrauma and hemorrhagic shock. They were...to assess inflammatory markers. Major Findings: 50%LP had higher electrolyte concentrations, osmolarity, and increased coagulation factor activity

  17. Simulating Univariate and Multivariate Burr Type IIII and Type XII Distributions through the Method of L-Moments

    ERIC Educational Resources Information Center

    Pant, Mohan Dev

    2011-01-01

    The Burr families (Type III and Type XII) of distributions are traditionally used in the context of statistical modeling and for simulating non-normal distributions with moment-based parameters (e.g., Skew and Kurtosis). In educational and psychological studies, the Burr families of distributions can be used to simulate extremely asymmetrical and…

  18. Factor XII assay

    MedlinePlus

    ... your provider about the meaning of your specific test results. What Abnormal Results ... vary in size so it may be harder to take a blood sample from one person than another. Other slight risks from having ...

  19. Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

    PubMed

    Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

    2009-11-14

    To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (P<0.05) during the regeneration phase compared with D0. Among these 5 factors, factor IX and factor XI showed the most dramatic decline in their activities by about

  20. Pathotyping and Phylogenetic Characterization of Newcastle Disease Viruses Isolated in Peru: Defining Two Novel Subgenotypes Within Genotype XII.

    PubMed

    Chumbe, Ana; Izquierdo-Lara, Ray; Tataje, Luis; Gonzalez, Rosa; Cribillero, Giovana; González, Armando E; Fernández-Díaz, Manolo; Icochea, Eliana

    2017-03-01

    Infections of poultry with virulent strains of avian paramyxovirus 1 (APMV-1), also known as Newcastle disease viruses (NDVs), cause Newcastle disease (ND). This highly contagious disease affects poultry and many other species of birds worldwide. In countries where the disease is prevalent, constant monitoring and characterization of isolates causing outbreaks are necessary. In this study, we report the results of pathogenicity testing and phylogenetic analyses of seven NDVs isolated from several regions of Peru between 2004 and 2015. Six viruses had intracerebral pathogenicity indices (ICPIs) of between 1.75 and 1.88, corresponding to a velogenic pathotype. The remaining virus had an ICPI of 0.00, corresponding to a lentogenic pathotype. These results were consistent with amino acid sequences at the fusion protein (F) cleavage site. All velogenic isolates had the polybasic amino acid sequence 112 RRQKR↓F 117 at the F cleavage site. Phylogenetic analyses of complete F gene sequences showed that all isolates are classified in class II of APMV-1. The velogenic viruses are classified in genotype XII, while the lentogenic virus is classified in genotype II, closely related to the LaSota vaccine strain. Moreover, tree topology, bootstrap values, and genetic distances observed within genotype XII resulted in the identification of novel subgenotypes XIIa (in South America) and XIIb (in China) and possibly two clades within genotype XIIa. All velogenic Peruvian viruses belonged to subgenotype XIIa. Overall, our results confirm the presence of genotype XII in Peru and suggest that it is the prevalent genotype currently circulating in our country. The phylogenetic characterization of these isolates helps to characterize the evolution of NDV and may help with the development of vaccines specific to our regional necessities.

  1. Division XII: Commission 46: Education & Development of Astronomy

    NASA Astrophysics Data System (ADS)

    Ros, Rosa M.; Hearnshaw, John; Stavinschi, Magda; Garcia, Beatriz; Gerbaldi, Michele; de Greve, Jean-Pierre; Guinan, Edward; Haubold, Hans; Jones, Barrie; Marshall, Laurence A.; Pasachoff, Jay

    2015-08-01

    C46 is a Commission of the Executive Committee of the IAU under Division XII Union-Wide Activities. Aiming at improvement of astronomy education and research at all levels worldwide (through the various projects it initiates),maintains, develops, as well as through the dissemination of information. C46 has 332 members and it was managed by the Organizing Committee, formed by the Commission President (Rosa M. Ros, from Spain), the Vice-Presiden (John Hearnshaw, from New Zealand), the Retiring President (Magda Stavinschi, from Romania), the Vice-President of the IAU (George Miley, from Netherland) and the PG chairs: • Worldwide Development of Astronomy WWDA: John Hearnshaw • Teaching Astronomy for Development TAD: Edward Guinan and Laurence A. Marshall • International Schools for Young Astronomers ISYA; chair: Jean-Pierre de Greve • Network for Astronomy School Education NASE: Rosa M. Ros and Beatriz Garcia • Public Understanding at the times of Solar Eclipses and transit Phenomena PUTSE: Jay Pasachoff • National Liaison and Newsletter: Barrie Jones • Collaborative Programs: Hans Haubold

  2. Bayesian Estimation of Reliability Burr Type XII Under Al-Bayyatis’ Suggest Loss Function with Numerical Solution

    NASA Astrophysics Data System (ADS)

    Mohammed, Amal A.; Abraheem, Sudad K.; Fezaa Al-Obedy, Nadia J.

    2018-05-01

    In this paper is considered with Burr type XII distribution. The maximum likelihood, Bayes methods of estimation are used for estimating the unknown scale parameter (α). Al-Bayyatis’ loss function and suggest loss function are used to find the reliability with the least loss. So the reliability function is expanded in terms of a set of power function. For this performance, the Matlab (ver.9) is used in computations and some examples are given.

  3. Lyman-alpha observations of Comet Kohoutek 1973 XII with Copernicus

    NASA Technical Reports Server (NTRS)

    Drake, J. F.; Jenkins, E. B.; Bertaux, J. L.; Festou, M.; Keller, H. U.

    1976-01-01

    Comet Kohoutek 1973 XII was observed with a telescope-spectrometer on the Copernicus satellite on six occasions over a 1-month period starting on January 29, 1974. Positive detection of the cometary Ly-alpha emission profile was obtained on January 29 and February 2. Earlier observations of the geocoronal Ly-alpha emission profile allowed an instrumental intensity calibration and confirmation of the computed instrumental profile for an extended source at the Ly-alpha wavelength. After allowing for broadening by the instrument, a hydrogen-outflow velocity of about 10.6 km/s is derived from the width of the Ly-alpha emission on January 29. The intensity calibration combined with an appropriate cometary model led to cometary water-production rates for January 29 and February 2. Only upper limits were obtained for Ly-alpha on and after February 14. Searches for OH and D led to negative results.

  4. Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII).

    PubMed

    Scozzafava, Andrea; Passaponti, Maurizio; Supuran, Claudiu T; Gülçin, İlhami

    2015-01-01

    Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated for their inhibition of all the catalytically active mammalian isozymes of the Zn(2+)-containing CA (EC 4.2.1.1). All the phenolic compounds effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and XII), with Kis in the range of 2.20-515.98 μM. The various isozymes showed diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4-methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of the tumour-associated transmembrane isoforms (hCA IX and XII) in the submicromolar range, with high selectivity. The results obtained from this research may lead to the design of more effective carbonic anhydrase isoenzyme inhibitors (CAIs) based on such phenolic compound scaffolds.

  5. Surface-mediated molecular events in material-induced blood-plasma coagulation

    NASA Astrophysics Data System (ADS)

    Chatterjee, Kaushik

    Coagulation and thrombosis persist as major impediments associated with the use of blood-contacting medical devices. We are investigating the molecular mechanism underlying material-induced blood-plasma coagulation focusing on the role of the surface as a step towards prospective development of improved hemocompatible biomaterials. A classic observation in hematology is that blood/blood-plasma in contact with clean glass surface clots faster than when in contact with many plastic surfaces. The traditional biochemical theory explaining the underlying molecular mechanism suggests that hydrophilic surfaces, like that of glass, are specific activators of the coagulation cascade because of the negatively-charged groups on the surface. Hydrophobic surfaces are poor procoagulants or essentially "benign" because they lack anionic groups. Further, these negatively-charged surfaces are believed to not only activate blood factor XII (FXII), the key protein in contact activation, but also play a cofactor role in the amplification and propagation reactions that ultimately lead to clot formation. In sharp contrast to the traditional theory, our investigations indicate a need for a paradigm shift in the proposed sequence of contact activation events to incorporate the role of protein adsorption at the material surfaces. These studies have lead to the central hypothesis for this work proposing that protein adsorption to hydrophobic surfaces attenuates the contact activation reactions so that poorly-adsorbent hydrophilic surfaces appear to be stronger procoagulants relative to hydrophobic surfaces. Our preliminary studies measuring the plasma coagulation response of activated FXII (FXIIa) on different model surfaces suggested that the material did not play a cofactor role in the processing of this enzyme dose through the coagulation pathway. Therefore, we focused our efforts on studying the mechanism of initial production of enzyme at the procoagulant surface. Calculations for the

  6. Magnetic reconnection driven by Gekko XII lasers with a Helmholtz capacitor-coil target

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

    Pei, X. X.; University of Chinese Academy of Sciences, Beijing 100049; Zhong, J. Y., E-mail: jyzhong@bnu.edu.cn, E-mail: gzhao@bao.ac.cn

    2016-03-15

    We demonstrate a novel plasma device for magnetic reconnection, driven by Gekko XII lasers irradiating a double-turn Helmholtz capacitor-coil target. Optical probing revealed an accumulated plasma plume near the magnetic reconnection outflow. The background electron density and magnetic field were measured to be approximately 10{sup 18 }cm{sup −3} and 60 T by using Nomarski interferometry and the Faraday effect, respectively. In contrast with experiments on magnetic reconnection constructed by the Biermann battery effect, which produced high beta values, our beta value was much lower than one, which greatly extends the parameter regime of laser-driven magnetic reconnection and reveals its potential in astrophysicalmore » plasma applications.« less

  7. 4-Functionalized 1,3-diarylpyrazoles bearing 6-aminosulfonylbenzothiazole moiety as potent inhibitors of carbonic anhydrase isoforms hCA I, II, IX and XII.

    PubMed

    SitaRam; Ceruso, Mariangela; Khloya, Poonam; Supuran, Claudiu T; Sharma, Pawan K

    2014-12-15

    A series of 24 novel heterocyclic compounds-functionalized at position 4 with aldehyde (5a-5f), carboxylic acid (6a-6f), nitrile (7a-7f) and oxime (8a-8f) functional groups-bearing 6-aminosulfonybenzothiazole moiety at position 1 of pyrazole has been synthesized and investigated for the inhibition of four isoforms of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozyme hCA I, compounds 6a-6f showed medium-weak inhibitory potential with Ki values in the range of 157-690nM with 6a showing better potential than the standard drug acetazolamide (AZA). Against hCA II, all the compounds showed excellent to moderate inhibition with Ki values of compounds 5a, 5d, 5f, 6a-6f, 8d and 8f lower than 12nM (Ki of AZA). Against hCA IX, all the compounds showed moderate inhibition with the exception of 6e which showed nearly 9 fold a better profile compared to AZA, whereas against hCA XII, four compounds 6e, 7a, 7b and 7d showed Ki in the same order as that of AZA. Carboxylic acid 6e was found to be an excellent inhibitor of both hCA IX and XII, with Ki values of 2.8nM and 5.5nM, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Initial Resuscitation with Plasma and Other Blood Components Reduced Bleeding Compared to Hetastarch in Anesthetized Swine with Uncontrolled Splenic Hemorrhage

    DTIC Science & Technology

    2011-04-01

    products and Hextend. The fluid with the highest amount of coagulation factors , FFP resulted in the lowest blood loss. The FFP treatment had the highest...compared to humans and have higher concentrations of many of the clotting factors (FV, FVII , FVIII, F IX, and FXII).44 Although we have confirmed the higher...utilizing plasma early in treatment is to prevent dilution of remaining coagulation factors or reverse the coagulopathy that has been observed in

  9. Mast Cell Coupling to the Kallikrein–Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease

    PubMed Central

    Nascimento, Clarissa R.; Andrade, Daniele; Carvalho-Pinto, Carla Eponina; Serra, Rafaela Rangel; Vellasco, Lucas; Brasil, Guilherme; Ramos-Junior, Erivan Schnaider; da Mota, Julia Barbalho; Almeida, Larissa Nogueira; Andrade, Marcus V.; Correia Soeiro, Maria de Nazaré; Juliano, Luiz; Alvarenga, Patrícia Hessab; Oliveira, Ana Carolina; Sicuro, Fernando Lencastre; de Carvalho, Antônio C. Campos; Svensjö, Erik; Scharfstein, Julio

    2017-01-01

    During the course of Chagas disease, infectious forms of Trypanosoma cruzi are occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain) demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate sentinel cells via toll-like receptor 2 (TLR2). Upon plasma extravasation, proteolytically derived kinins and C5a stimulate immunoprotective Th1 responses via cross-talk between bradykinin B2 receptors (B2Rs) and C5aR. Awareness that TCTs invade cardiovascular cells in vitro via interdependent activation of B2R and endothelin receptors [endothelin A receptor (ETAR)/endothelin B receptor (ETBR)] led us to hypothesize that T. cruzi might reciprocally benefit from the formation of infection-associated edema via activation of kallikrein–kinin system (KKS). Using intravital microscopy, here we first examined the functional interplay between mast cells (MCs) and the KKS by topically exposing the hamster cheek pouch (HCP) tissues to dextran sulfate (DXS), a potent “contact” activator of the KKS. Surprisingly, although DXS was inert for at least 30 min, a subtle MC-driven leakage resulted in factor XII (FXII)-dependent activation of the KKS, which then amplified inflammation via generation of bradykinin (BK). Guided by this mechanistic insight, we next exposed TCTs to “leaky” HCP—forged by low dose histamine application—and found that the proinflammatory phenotype of TCTs was boosted by BK generated via the MC/KKS pathway. Measurements of footpad edema in MC-deficient mice linked TCT-evoked inflammation to MC degranulation (upstream) and FXII-mediated generation of BK (downstream). We then inoculated TCTs intracardiacally in mice and found a striking decrease of parasite DNA (quantitative polymerase chain reaction; 3 d.p.i.) in the heart of MC-deficient mutant mice. Moreover, the intracardiac parasite load was significantly reduced in WT mice

  10. [Effects of various adsorbants on coagulation factors (author's transl)].

    PubMed

    Soulier, J P; Prou-Wartelle, O

    1975-01-01

    Adsorption of clotting factors by various adsorbants is studied (tricalcium phosphate, baryum sulfate or carbonate or citrate, calcium oxalate, aluminium hydroxyde and several silicate such as: kaolin, celite, bentonite, attapulgite, beidellite, asbestos). The main properties of each adsorbant are listed as well as several applications such as: selective adsorption of fibrinogen, separation between fibrinogen and factor VIII, separation of factor II from the other components of the prothrombin complex. Activation of factors XII and XI by the various silicates, as well as the activation of factor V by attapulgite are studied. Finally, the action of such adsorbants on the fibrinolytic system is summarized.

  11. 77 FR 29633 - Alta Wind VII, LLC, Alta Wind IX, LLC, Alta Wind X, LLC, Alta Wind XI, LLC, Alta Wind XII, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-68-000] Alta Wind VII, LLC, Alta Wind IX, LLC, Alta Wind X, LLC, Alta Wind XI, LLC, Alta Wind XII, LLC, Alta Wind XIII, LLC, Alta Wind XIV, LLC, Alta Wind XV, LLC, Alta Windpower Development, LLC, TGP Development Company, LLC...

  12. Factor XI and Contact Activation as Targets for Antithrombotic Therapy

    PubMed Central

    Gailani, David; Bane, Charles E.; Gruber, Andras

    2015-01-01

    Summary The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa, or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and factor X. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that place them at unacceptable risk for hemorrhage. Studies in animals demonstrate that components of the plasma contact activation system contribute to experimentally-induced thrombosis, despite playing little or no role in hemostasis. Attention has focused on factor XII, the zymogen of a protease (factor XIIa) that initiates contact activation when blood is exposed to foreign surfaces; and factor XI, the zymogen of the protease factor XIa, which links contact activation to the thrombin generation mechanism. In the case of factor XI, epidemiologic data indicate this protein contributes to stroke and venous thromboembolism, and perhaps myocardial infarction, in humans. A phase 2 trial showing that reduction of factor XI may be more effective than low-molecular-weight heparin at preventing venous thrombosis during knee replacement surgery provides proof of concept for the premise that an antithrombotic effect can be uncoupled from an anticoagulant effect in humans by targeting components of contact activation. Here we review data on the role of factor XI and factor XII in thrombosis, and results of pre-clinical and human trials for therapies targeting these proteins. PMID:25976012

  13. Lyman-alpha observations of comet Kohoutek 1973 XII with Copernicus

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

    Drake, J.F.; Jenkins, E.B.; Bertaux, J.L.

    1976-10-01

    Comet Kohoutek 1973 XII was observed with the Princeton telescope-spectrometer on the Copernicus satellite on six occasions over a 1-month period starting on 1974 January 29. Positive detection of the cometary L..cap alpha.. emission profile was obtained on January 29 and February 2. Earlier observations of the geocoronal L..cap alpha.. emission profile allowed an instrumental intensity calibration and confirmation of the computed instrumental profile for an extended source at the L..cap alpha.. wavelength.After allowing for broadening by the instrument, we derived from the width of the L..cap alpha.. emission on January 29 a hydrogen-outflow velocity of 10.6 +- 1.8 kmmore » s/sup -1/. The intensity calibration combined with an appropriate cometary model led to cometary water-production rates with average values of 1.3 +- 0.4 x 10/sup 28/ molecules sr/sup -1/ s/sup -1/ for January 29 and 6.0 +- 2.5 x 10/sup 27/ molecules sr/sup -1/ s/sup -1/ for February 2. Only upper limits were obtained for L..cap alpha.. on and after February 14. Searches for OH and D led to negative results. (AIP)« less

  14. PREFACE: 12th Conference on Recent Developments in Gravity (NEB XII)

    NASA Astrophysics Data System (ADS)

    Christodoulakis, Theodosios; Vagenas, Elias C.

    2007-06-01

    Continuing the 24 year old tradition, one of the Greek relativistic groups, this time the Relativity Group of the Physics Department of the University of Athens, organized the 12th Conference of the series "Recent Developments in Gravity" (NEB XII). This time NEB took place at Nafplio, Greece, from Thursday 29 June to Sunday 2 July, 2006. The Conference was attended by more than 100 participants, more than 50% of whom were relativists from abroad (both Greek and other nationalities). This signifies a tendency of the last few Conferences to open up the Greek Relativity Conference to the international scientific community. Actually, many notable members of the relativistic community all over the globe showed particular interest in coming to Nafplio, and spend four relaxed days in a nice sunny and historical place, presenting the results of their more recent work and discussing it with colleagues and students from Greece. The NEB XII Conference covered various aspects of gravitational physics: Relativistic Astrophysics, Mathematical Relativity, Quantum Gravity, and Cosmology. Although the program was rather heavy and for the first time we had parallel sessions running in the afternoons, the wonderful weather (apart from the last afternoon when it rained heavily) and the beauty of Nafplio helped the organizers offer the participants a warm, pleasant, and creative time. According to most attendees, their impression was more than good, not only with respect to the hospitable environment, but with respect to the high level of talks as well. We hope the next Conference, which will be organized by the Relativity Group of the Aristotle University of Thessaloniki in the summer of 2008, will raise the standards of the Conference even higher, thus further establishing our Conference as a notable Conference in the Relativistic community all over the world. Finally, we would like to thank the Gravitational Physics Section of the European Physical Society (GPS/EPS), ILIAS

  15. The lower cranial nerves: IX, X, XI, XII.

    PubMed

    Sarrazin, J-L; Toulgoat, F; Benoudiba, F

    2013-10-01

    The lower cranial nerves innervate the pharynx and larynx by the glossopharyngeal (CN IX) and vagus (CN X) (mixed) nerves, and provide motor innervation of the muscles of the neck by the accessory nerve (CN XI) and the tongue by the hypoglossal nerve (CN XII). The symptomatology provoked by an anomaly is often discrete and rarely in the forefront. As with all cranial nerves, the context and clinical examinations, in case of suspicion of impairment of the lower cranial nerves, are determinant in guiding the imaging. In fact, the impairment may be located in the brain stem, in the peribulbar cisterns, in the foramens or even in the deep spaces of the face. The clinical localization of the probable seat of the lesion helps in choosing the adapted protocol in MRI and eventually completes it with a CT-scan. In the bulb, the intra-axial pathology is dominated by brain ischemia (in particular, with Wallenberg syndrome) and multiple sclerosis. Cisternal pathology is tumoral with two tumors, schwannoma and meningioma. The occurrence is much lower than in the cochleovestibular nerves as well as the leptomeningeal nerves (infectious, inflammatory or tumoral). Finally, foramen pathology is tumoral with, outside of the usual schwannomas and meningiomas, paragangliomas. For radiologists, fairly hesitant to explore these lower cranial pairs, it is necessary to be familiar with (or relearn) the anatomy, master the exploratory technique and be aware of the diagnostic possibilities. Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  16. Synthesis and Biological Evaluation of 4-Sulfamoylphenyl/Sulfocoumarin Carboxamides as Selective Inhibitors of Carbonic Anhydrase Isoforms hCA II, IX, and XII.

    PubMed

    Angapelly, Srinivas; Angeli, Andrea; Khan, Arbaj Jabbar; Sri Ramya, P V; Supuran, Claudiu T; Arifuddin, Mohammed

    2018-04-19

    With the aim to develop potent and selective human carbonic anhydrase inhibitors (hCAIs), we synthesized 4-sulfamoylphenyl/sulfocoumarin benzamides (series 5 a-r and series 7 a-q) and evaluated their inhibition profiles against five isoforms of the zinc-containing human carbonic anhydrase (hCA, EC 4.2.1.1): cytosolic hCA I and II, and the transmembrane isozymes hCA IV, IX, and XII. Compounds 5 a-r were found to selectively inhibit hCA II in the nanomolar range, while being less effective against the other hCA isoforms. As noted from the literature, sulfocoumarin (1,2-benzoxathiine 2,2-dioxide) acts as a "prodrug" inhibitor and is hydrolyzed by the esterase activity of hCA to form 2-hydroxyphenylvinylsulfonic acid, which thereafter binds to the enzyme in a manner similar to that of coumarins and sulfoxocoumarins. All these sulfocoumarins (compounds 7 a-q) were found to be very weak or ineffective as inhibitors of the housekeeping off-target hCA isoforms I and II, and effectively inhibited the transmembrane tumor-associated isoforms IX and XII in the high nanomolar to micromolar ranges. Further structural modifications of these molecules could be useful for the development of effective hCA inhibitors used for the treatment of glaucoma, epilepsy, and cancer. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Unmelted Meteoritic Debris Collected from Eltanin Ejecta in Polarstern Cores from Expedition ANT XII/4

    NASA Technical Reports Server (NTRS)

    Kyte, Frank T.

    2002-01-01

    A total of 1.7g of unmelted meteorite particles have been recovered from FS Polarstern piston cores collected on expedition ANT XII/4 that contain ejecta from the Eltanin impact event. Most of the mass (1.2 g) is a large, single specimen that is a polymict breccia, similar in mineralogy and chemistry to howardites or the silicate fraction of mesosiderites. Most of the remaining mass is in several large individual pieces (20-75mg each) that are polymict breccias, fragments dominated by pyroxene, and an igneous rock fragment. The latter has highly fractionated REE, similar to those reported in mafic clasts from mesosiderites. Other types of specimens identified include fragments dominated by maskelynite or olivine. These pieces of the projectile probably survived impact by being blown off the back surface of the Eltanin asteroid during its impact into the Bellingshausen Sea.

  18. Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

    PubMed

    Heinz, Stefan; Braspenning, Joris

    2015-01-01

    An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

  19. Energy Levels and Radiative Rates for Transitions in F-like Sc XIII and Ne-like Sc XII and Y XXX

    NASA Astrophysics Data System (ADS)

    Aggarwal, Kanti

    2018-05-01

    Energy levels, radiative rates and lifetimes are reported for F-like Sc~XIII and Ne-like Sc~XII and Y~XXX for which the general-purpose relativistic atomic structure package ({\\sc grasp}) has been adopted. For all three ions limited data exist in the literature but comparisons have been made wherever possible to assess the accuracy of the calculations. In the present work the lowest 102, 125 and 139 levels have been considered for the respective ions. Additionally, calculations have also been performed with the flexible atomic code ({\\sc fac}) to (particularly) confirm the accuracy of energy levels.

  20. Medicinal Flowers. XXXII. Structures of oleanane-type triterpene saponins, perennisosides VIII, IX, X, XI, and XII, from the flowers of Bellis perennis.

    PubMed

    Morikawa, Toshio; Li, Xuezheng; Nishida, Eriko; Nakamura, Seikou; Ninomiya, Kiyofumi; Matsuda, Hisashi; Hamao, Makoto; Muraoka, Osamu; Hayakawa, Takao; Yoshikawa, Masayuki

    2011-01-01

    Five new triterpene saponins perennisosides VIII (1), IX (2), X (3), XI (4), and XII (5) were isolated from the MeOH-eluated fraction of the methanolic extract from the flowers of Bellis perennis. The MeOH-eluted fraction of the methanolic extract from the flowers of B. perennis was found to inhibit gastric emptying in olive oil-loaded mice at a dose of 200 mg/kg, per os (p.o.). The stereostructures of 1-5 were elucidated on the basis of chemical and spectroscopic evidence.

  1. Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases.

    PubMed

    De Luca, Laura; Mancuso, Francesca; Ferro, Stefania; Buemi, Maria Rosa; Angeli, Andrea; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T; Gitto, Rosaria

    2018-01-01

    Coumarin derivatives are a peculiar class of inhibitors of the family of metalloenzymes carbonic anhydrases (CA, EC 4.2.1.1). Several coumarins display higher affinity and selectivity toward most relevant and druggable CA isoforms. By decorating the natural compound umbelliferone (1) we have identified a new series of coumarin-based compounds demonstrating high CA inhibitory effects with nanomolar affinity for hCA IX and hCA XII isoforms that were considered a target amenable to develop antitumor agents. The most active tested compounds proved to be potent inhibitors with K i values equal to that of the well-known inhibitor acetazolamide (AAZ), that lacks selectivity over ubiquitous hCA I and hCA II. As suggested by docking studies the coumarins, that are lacking of the canonical metal binding groups, do not interact with Zinc ion within the catalytic site as found for classical sulfonamide type inhibitors of CAs. Thus, the studied inhibitors might possess a non-classical inhibitory mode of action preventing the carbon dioxide to entry into catalytic cavity and its conversion into bicarbonate ion. Specifically, the most active inhibitor of hCA XII compound 18i (K i value of 5.5 nM) and its supposed hydrolytic products could establish a web of H-bond interactions within the enzymatic cavity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII.

    PubMed

    Feldshtein, Maya; Elkrinawi, Suliman; Yerushalmi, Baruch; Marcus, Barak; Vullo, Daniela; Romi, Hila; Ofir, Rivka; Landau, Daniel; Sivan, Sara; Supuran, Claudiu T; Birk, Ohad S

    2010-11-12

    Excessive chloride secretion in sweat (hyperchlorhidrosis), leading to a positive sweat test, is most commonly indicative of cystic fibrosis yet is found also in conjunction with various metabolic, endocrine, and dermatological disorders. There is conflicting evidence regarding the existence of autosomal-recessive hyperchlorhidrosis. We now describe a consanguineous Israeli Bedouin kindred with autosomal-recessive hyperchlohidrosis whose sole symptoms are visible salt precipitates after sweating, a preponderance to hyponatremic dehydration, and poor feeding and slow weight gain at infancy. Through genome-wide linkage analysis, we demonstrate that the phenotype is due to a homozygous mutation in CA12, encoding carbonic anhydrase XII. The mutant (c.427G>A [p.Glu143Lys]) protein showed 71% activity of the wild-type enzyme for catalyzing the CO₂ hydration to bicarbonate and H(+), and it bound the clinically used sulfonamide inhibitor acetazolamide with high affinity (K(I) of 10 nM). Unlike the wild-type enzyme, which is not inhibited by chloride, bromide, or iodide (K(I)s of 73-215 mM), the mutant is inhibited in the submicromolar range by these anions (K(I)s of 0.37-0.73 mM). Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase.

    PubMed

    Wu, Mingyi; Wen, Dandan; Gao, Na; Xiao, Chuang; Yang, Lian; Xu, Li; Lian, Wu; Peng, Wenlie; Jiang, Jianmin; Zhao, Jinhua

    2015-03-06

    Fucosylated chondroitin sulfate (FCS), a structurally unusual glycosaminoglycan, has distinct anticoagulant properties, and is an especially strong inhibitor of the intrinsic factor Xase (anti-Xase). To obtain a highly selective inhibitor of human Xase, we purified six native FCSs with various sulfation patterns, prepared a series of FCS derivatives, and then elucidated the relationship between the structures and the anticoagulant activities of FCSs. FCSs 1-3 containing higher Fuc2S4S exhibit stronger AT-dependent anti-IIa activities, whereas 4-6 containing more Fuc3S4S produce potent HCII-dependent anti-IIa activities. Saccharides containing a minimum of 6-8 trisaccharide units, free carboxyl groups, and full fucosylation of GlcA may be required for potent anti-Xase activity, and approximately six trisaccharide units and partial fucosylation of GlcA may contribute to potent HCII-dependent activity. Decreasing of the molecular weights markedly reduces their AT-dependent anti-IIa activities, and even eliminates human platelet and factor XII activation. Furthermore, in vitro and in vivo studies suggested that fractions of 6-12 kDa may be very promising compounds as putative selective intrinsic Xase inhibitors with antithrombotic action, but without the consequences of major bleeding and factor XII activation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Molecular size is important for the safety and selective inhibition of intrinsic factor Xase for fucosylated chondroitin sulfate.

    PubMed

    Yan, Lufeng; Li, Junhui; Wang, Danli; Ding, Tian; Hu, Yaqin; Ye, Xingqian; Linhardt, Robert J; Chen, Shiguo

    2017-12-15

    Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (FCS-Ib) showed potent anticoagulant activities without selectivity. The present study focused on developing safe FCS-Ib oligomers showing selective inhibition of intrinsic factor Xase (anti-FXase) prepared through partial N-deacetylation-deaminative cleavage. The N-deacetylation degree was regulated by reaction time, controlling the resulting oligomer distribution. Structure analysis confirmed the selectivity of degradation, and 12 high purity fractions with trisaccharide-repeating units were separated. In vitro anticoagulant assays indicated a decrease in molecular weight (Mw) dramatically reduced activated partial thromboplastin time (APTT), thrombin time (TT), AT-dependent anti-FIIa and anti-FXa activities, while the oligomers retained potent anti-FXase activity until they fell below 3kDa. Meanwhile, human FXII activation and platelet aggregation were markedly reduced with decreasing Mw and were moderate when under 12.0kDa. Thus, fragments of 3-12.0kDa should be safe and effective as selective inhibitors of intrinsic tenase complex for application as clinical anticoagulants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Protein corona changes mediated by surface modification of amorphous silica nanoparticles suppress acute toxicity and activation of intrinsic coagulation cascade in mice

    NASA Astrophysics Data System (ADS)

    Yoshida, Tokuyuki; Yoshioka, Yasuo; Morishita, Yuki; Aoyama, Michihiko; Tochigi, Saeko; Hirai, Toshiro; Tanaka, Kota; Nagano, Kazuya; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Higashisaka, Kazuma; Tsutsumi, Yasuo

    2015-06-01

    Recently, nanomaterial-mediated biological effects have been shown to be governed by the interaction of nanomaterials with some kinds of proteins in biological fluids, and the physical characteristics of the nanomaterials determine the extent and type of their interactions with proteins. Here, we examined the relationships between the surface properties of amorphous silica nanoparticles with diameters of 70 nm (nSP70), their interactions with some proteins in biological fluids, and their toxicity in mice after intravenous administration. The surface modification of nSP70 with amino groups (nSP70-N) prevented acute lethality and abnormal activation of the coagulation cascade found in the nSP70-treated group of mice. Since our previous study showed that coagulation factor XII played a role in the nSP70-mediated abnormal activation of the coagulation cascade, we examined the interaction of nSP70 and nSP70-N with coagulation factor XII. Coagulation factor XII bonded to the surface of nSP70 to a greater extent than that observed for nSP70-N, and consequently more activation of coagulation factor XII was observed for nSP70 than for nSP70-N. Collectively, our results suggest that controlling the interaction of nSP70 with blood coagulation factor XII by modifying the surface properties would help to inhibit the nSP70-mediated abnormal activation of the blood coagulation cascade.

  6. Complement, Kinins, and Hereditary Angioedema: Mechanisms of Plasma Instability when C1 Inhibitor is Absent.

    PubMed

    Kaplan, Allen P; Joseph, Kusumam

    2016-10-01

    Plasma of patients with types I and II hereditary angioedema is unstable if incubated in a plastic (i.e., inert) vessel at 37 °C manifested by progressively increasing formation of bradykinin. There is also a persistent low level of C4 in 95 % of patients even when they are symptomatic. These phenomena are due to the properties of the C1r subcomponent of C1, factor XII, and the bimolecular complex of prekallikrein with high molecular weight kininogen (HK). Purified C1r auto-activates in physiologic buffers, activates C1s, which in turn depletes C4. This occurs when C1 inhibitor is deficient. The complex of prekallikrein-HK acquires an inducible active site not present in prekallikrein which in Tris-type buffers cleaves HK stoichiometrically to release bradykinin, or in phosphate buffer auto-activates to generate kallikrein and bradykinin. Thus immunologic depletion of C1 inhibitor from factor XII-deficient plasma (phosphate is the natural buffer) auto-activates on incubation to release bradykinin. Normal C1 inhibitor prevents this from occurring. During attacks of angioedema, if factor XII auto-activates on surfaces, the initial factor XIIa formed converts prekallikrein to kallikrein, and kallikrein cleaves HK to release bradykinin. Kallikrein also rapidly activates most remaining factor XII to factor XIIa. Additional cleavages convert factor XIIa to factor XIIf and factor XIIf activates C1r enzymatically so that C4 levels approach zero, and C2 is depleted. There is also a possibility that kallikrein is generated first as a result of activation of the prekallikrein-HK complex by heat shock protein 90 released from endothelial cells, followed by kallikrein activation of factor XII.

  7. A Keck/DEIMOS spectroscopic survey of the faint M31 satellites AndIX, AndXI, AndXII and AndXIII†

    NASA Astrophysics Data System (ADS)

    Collins, M. L. M.; Chapman, S. C.; Irwin, M. J.; Martin, N. F.; Ibata, R. A.; Zucker, D. B.; Blain, A.; Ferguson, A. M. N.; Lewis, G. F.; McConnachie, A. W.; Peñarrubia, J.

    2010-10-01

    We present the first spectroscopic analysis of the faint M31 satellite galaxies, AndXI and AndXIII, as well as a re-analysis of existing spectroscopic data for two further faint companions, AndIX (correcting for an error in earlier geometric modelling that caused a misclassification of member stars in previous work) and AndXII. By combining data obtained using the Deep Imaging Multi-Object Spectrograph (DEIMOS) mounted on the Keck II telescope with deep photometry from the Suprime-Cam instrument on Subaru, we have identified the most probable members for each of the satellites based on their radial velocities (precise to several down to i ~ 22), distance from the centre of the dwarf spheroidal galaxies (dSphs) and their photometric [Fe/H]. Using both the photometric and spectroscopic data, we have also calculated global properties for the dwarfs, such as systemic velocities, metallicities and half-light radii. We find each dwarf to be very metal poor ([Fe/H] ~ -2 both photometrically and spectroscopically, from their stacked spectrum), and as such, they continue to follow the luminosity-metallicity relationship established with brighter dwarfs. We are unable to resolve dispersion for AndXI due to small sample size and low signal-to-noise ratio, but we set a 1σ upper limit of σv < 4.5kms-1. For AndIX, AndXII and AndXIII we resolve velocity dispersions of σv = 4.5+3.6-3.4, 2.6+5.1-2.6 and 9.7+8.9-4.5kms-1, though we note that the dispersion for AndXIII is based on just three stars. We derive masses within the half-light radii for these galaxies of 6.2+5.3-5.1 × 106, 2.4+6.5-2.4 × 106 and 1.1+1.4-0.7 × 107Msolar, respectively. We discuss each satellite in the context of the Mateo relations for dSphs, and in reference to the universal halo profiles established for Milky Way dwarfs. Both AndIX and AndXII fall below the universal halo profiles of Walker et al., indicating that they are less massive than would be expected for objects of their half-light radius. When

  8. Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII).

    PubMed

    Bialer, Meir; Johannessen, Svein I; Levy, René H; Perucca, Emilio; Tomson, Torbjörn; White, H Steve

    2015-03-01

    The Twelfth Eilat Conference on New Antiepileptic Drugs (AEDs) - EILAT XII, took place in Madrid, Spain from August 31st to September 3rd 2014. About 130 basic scientists, clinical pharmacologists and neurologists from 22 countries attended the conference, whose main themes included "Conquering pharmacoresistant epilepsy", "Innovative emergency treatments", "Progress report on second-generation treatment" and "New methods and formulations". Consistent with previous formats of this conference, a large part of the program was devoted to a review of AEDs in development, as well as updates on AEDs introduced since 2004. Like the EILAT X and EILAT XI reports, the current article focuses on the preclinical and clinical pharmacology of AEDs that are currently in development. These include adenosine-releasing silk, allopregnanolone (SAGE-547), AMP-X-0079, brivaracetam, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-glucose, everolimus, ganaxolone, huperzine A, imepitoin, minocycline, NAX 801-2, pitolisant, PRX 0023, SAGE-217, valnoctamide and its homologue sec-butyl-propylacetamide (SPD), and VLB-01. Since the previous Eilat conference, perampanel has been introduced into the market and twelve novel potential epilepsy treatments are presented for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Cytokine and estrogen stimulation of endothelial cells augments activation of the prekallikrein-high molecular weight kininogen complex: Implications for hereditary angioedema.

    PubMed

    Joseph, Kusumam; Tholanikunnel, Baby G; Kaplan, Allen P

    2017-07-01

    When the prekallikrein-high molecular weight kininogen complex is bound to endothelial cells, prekallikrein is stoichiometrically converted to kallikrein because of release of heat shock protein-90 (Hsp90). Although bradykinin formation is typically initiated by factor XII autoactivation, it is also possible to activate factor XII either by kallikrein, thus formed, or by plasmin. Because attacks of hereditary angioedema can be related to infection and/or exposure to estrogen, we questioned whether estrogen or cytokine stimulation of endothelial cells could augment release of Hsp90 and prekallikrein activation. We also tested release of profibrinolytic enzymes, urokinase, and tissue plasminogen activator (TPA) as a source for plasmin formation. Cells were stimulated with agonists, and secretion of Hsp90, urokinase, and TPA was measured in the culture supernatants by ELISA. Activation of the prekallikrein-HK complex was measured by using pro-phe-arg-p-nitroanilide reflecting kallikrein formation. Hsp90 release was stimulated with optimal doses of estradiol, IL-1, and TNF-α (10 ng/mL) from 15 minutes to 120 minutes. TPA release was not augmented by any of the agonists tested but urokinase was released by IL-1, TNF-α, and thrombin (positive control), but not estrogen. Augmented activation of the prekallikrein-HK complex to generate kallikrein was seen with each agonist that releases Hsp90. Addition of 0.1% factor XII relative to prekallikrein-HK leads to rapid formation of kallikrein; factor XII alone does not autoactivate. IL-1, TNF-α, and estrogen stimulate release of Hsp90 and augment activation of the prekallikrein-HK complex to generate kallikrein and bradykinin. IL-1 and TNF-α stimulate release of urokinase, which can convert plasminogen to plasmin and represents a possible source for plasmin generation in all types of hereditary angioedema, but particularly hereditary angioedema with normal C1 inhibitor with a factor XII mutation. Both kallikrein and

  10. Measurements of density dependent intensity ratios of extreme ultraviolet line emission from Fe X, XI, and XII

    NASA Astrophysics Data System (ADS)

    Shimizu, Erina; Ali, Safdar; Tsuda, Takashi; Sakaue, Hiroyuki A.; Kato, Daiji; Murakami, Izumi; Hara, Hirohisa; Watanabe, Tetsuya; Nakamura, Nobuyuki

    2017-05-01

    We report high-resolution density dependent intensity ratio measurements for middle charge states of iron in the extreme ultraviolet (EUV) spectral wavelength range of 160-200 Å. The measurements were performed at the Tokyo EBIT laboratory by employing a flat-field grazing incidence spectrometer installed on a low energy compact electron beam ion trap. The intensity ratios for several line pairs stemming from Fe X, Fe XI and Fe XII were extracted from spectra collected at the electron beam energies of 340 and 400 eV by varying the beam current between 7.5 and 12 mA at each energy. In addition, the effective electron densities were obtained experimentally by imaging the electron beam profile and ion cloud size with a pinhole camera and visible spectrometer, respectively. In this paper, the experimental results are compared with previous data from the literature and with the present calculations performed using a collisional-radiative model. Our experimental results show a rather good agreement with the calculations and previous reported results.

  11. Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes.

    PubMed

    Gul, Halise Inci; Yamali, Cem; Bulbuller, Merve; Kirmizibayrak, Petek Ballar; Gul, Mustafa; Angeli, Andrea; Bua, Silvia; Supuran, Claudiu T

    2018-08-01

    In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by 1 H NMR, 13 C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7-9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7-28.1 nM and 4.5-9.3 nM, respectively. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Expression of hypoxia-inducible carbonic anhydrases in brain tumors

    PubMed Central

    Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

    2005-01-01

    Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

  13. Autotransfusion from experimental hemothorax: levels of coagulation factors.

    PubMed

    Napoli, V M; Symbas, P J; Vroon, D H; Symbas, P N

    1987-03-01

    The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.

  14. New anticancer drug candidates sulfonamides as selective hCA IX or hCA XII inhibitors.

    PubMed

    Gul, Halise Inci; Yamali, Cem; Sakagami, Hiroshi; Angeli, Andrea; Leitans, Janis; Kazaks, Andris; Tars, Kaspars; Ozgun, Dilan Ozmen; Supuran, Claudiu T

    2018-04-01

    In this study, new 4-[3-(aryl)-5-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamides (19-36) were synthesized and evaluated their cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 34 (4-[5-(2,3,4-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl] benzensulfonamide, Potency-Selectivity Expression (PSE) = 141) and 36 (4-[5-(3,4,5-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide, PSE = 54.5) were found the leader anticancer compounds with the highest PSE values. In CA inhibitory studies, the compounds 36 and 24 (4-[5-(3,4,5-trimethoxyphenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide) were found the leader CA inhibitors depending on selectivity ratios. The compound 36 was a selective inhibitor of hCA XII isoenzyme (hCA I/hCA XII = 1250 and hCA II/hCA XII = 224) while the compound 24 was a selective inhibitor of hCA IX isoenzyme (hCA I/hCA IX = 161 and hCA II/hCA IX = 177). The compounds 24, 34, and 36 can be considered to develop new anticancer drug candidates. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. G Protein-Coupled Kinin Receptors and Immunity Against Pathogens.

    PubMed

    Scharfstein, Julio; Ramos, Pablo I P; Barral-Netto, Manoel

    2017-01-01

    For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes. Insight from mice models of thrombosis linked fibrin formation via the intrinsic pathway to the autoactivation of factor XII (FXII) by negatively charged "contact" substances, such as platelet-derived polyphosphates and DNA from neutrophil extracellular traps. Following cleavage by FXIIa, activated plasma kallikrein (PK) initiates inflammation by liberating the nonapeptide bradykinin (BK) from an internal domain of high molecular weight kininogen (HK). Acting as a paracrine mediator, BK induces vasodilation and increases microvascular permeability via activation of endothelial B2R, a constitutively expressed subtype of kinin receptor. During infection, neutrophil-driven extravasation of plasma fuels inflammation via extravascular activation of the kallikrein-kinin system (KKS). Whether liberated by plasma-borne PK, tissue kallikrein, and/or microbial-derived proteases, the short-lived kinins activate immature dendritic cells via B2R, thus linking the infection-associated innate immunity/inflammation to the adaptive arm of immunity. As inflammation persists, a GPI-linked carboxypeptidase M removes the C-terminal arginine from the primary kinin, converting the B2R agonist into a high-affinity ligand for B1R, a GPCR subtype that is transcriptionally upregulated in injured/inflamed tissues. As reviewed here, lessons taken

  16. Discovery of host-targeted covalent inhibitors of dengue virus

    PubMed Central

    de Wispelaere, Mélissanne; Carocci, Margot; Liang, Yanke; Liu, Qingsong; Sun, Eileen; Vetter, Michael L.; Wang, Jinhua; Gray, Nathanael S.; Yang, Priscilla L.

    2017-01-01

    We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of Flaviviruses and other viruses. We used two parallel cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active against dengue virus. We show that the compounds effectively block viral protein expression and that this inhibition is associated with repression of downstream processes of the infectious cycle, and thus significantly contributes to the potent antiviral activity of these compounds. We demonstrate that QL-XII-47’s antiviral activity requires selective, covalent modification of a host target by showing that the compound's antiviral activity is recapitulated when cells are preincubated with QL-XII-47 and then washed prior to viral infection and by showing that QL-XII-47R, a non-reactive analog, lacks antiviral activity at concentrations more than 20-fold higher than QL-XII-47's IC90. QL-XII-47’s inhibition of Zika virus, West Nile virus, hepatitis C virus, and poliovirus further suggests that it acts via a target mediating inhibition of these other medically relevant viruses. These results demonstrate the utility of screens targeting the host reactive cysteinome for rapid identification of compounds with potent antiviral activity. PMID:28034743

  17. Iridium Concentrations and Abundances of Meteoritic Ejecta from the Eltanin Impact in Sediment Cores from Polarstern Expedition ANT XII/4

    NASA Technical Reports Server (NTRS)

    Kyte, Frank T.

    2002-01-01

    The abundances of meteoritic ejecta from the Eltanin asteroid impact have been examined in several sediment cores recovered by the FS Polarstern during expedition ANT XII/4 using elemental concentrations of iridium and weights of coarse ejecta debris. Three cores with well-preserved impact deposits, PS204-1, PS2708-1, and PS2709-1, each contain Ir and ejecta fluences similar to those found in USNS Eltanin core E13-4. Small Ir anomalies and traces of ejecta were found in cores PS2706-1 and PS2710-1, but since these cores lack well-defined deposits, these are considered to be reworked and not representative of the fallout. No evidence of ejecta was found in cores PS2802-1 and PS2705-1. These results confirm earlier speculation that the Eltanin impact resulted in deposits of ejecta with up to 1 gram/sq centimeter of depris over a wide area of the ocean floor. However, there are sill large uncertainties over the actual regional or global extent of this unique sediment deposit.

  18. The impact of hydroquinone on acetylcholine esterase and certain human carbonic anhydrase isoenzymes (hCA I, II, IX, and XII).

    PubMed

    Scozzafava, Andrea; Kalın, Pınar; Supuran, Claudiu T; Gülçin, İlhami; Alwasel, Saleh H

    2015-12-01

    Carbonic anhydrases (CAs) are widespread and the most studied members of a great family of metalloenzymes in higher vertebrates including humans. CAs were investigated for their inhibition of all of the catalytically active mammalian isozymes of the Zn(2+)-containing CA, (CA, EC 4.2.1.1). On the other hand, acetylcholinesterase (AChE. EC 3.1.1.7), a serine protease, is responsible for ACh hydrolysis and plays a fundamental role in impulse transmission by terminating the action of the neurotransmitter ACh at the cholinergic synapses and neuromuscular junction. In the present study, the inhibition effect of the hydroquinone (benzene-1,4-diol) on AChE activity was evaluated and effectively inhibited AChE with Ki of 1.22 nM. Also, hydroquinone strongly inhibited some human cytosolic CA isoenzymes (hCA I and II) and tumour-associated transmembrane isoforms (hCA IX, and XII), with Kis in the range between micromolar (415.81 μM) and nanomolar (706.79 nM). The best inhibition was observed in cytosolic CA II.

  19. CALCULATIONS WITH SPECTROSCOPIC ACCURACY: ENERGIES AND TRANSITION RATES IN THE NITROGEN ISOELECTRONIC SEQUENCE FROM Ar XII TO Zn XXIV

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

    Wang, K.; Dang, W.; Si, R.

    2016-03-15

    Combined relativistic configuration interaction and many-body perturbation calculations are performed for the 359 fine-structure levels of the 2s{sup 2} 2p{sup 3}, 2 s2p{sup 4}, 2p{sup 5}, 2s{sup 2} 2p{sup 2} 3l, 2 s2p{sup 3} 3l, 2p{sup 4} 3l, and 2s{sup 2} 2p{sup 2} 4l configurations in N-like ions from Ar xii to Zn xxiv. Complete and consistent data sets of energies, wavelengths, radiative rates, oscillator strengths, and line strengths for all possible electric dipole, magnetic dipole, electric quadrupole, and magnetic quadrupole transitions among the 359 levels are given for each ion. The present work significantly increases the amount of accuratemore » data for ions in the nitrogen-like sequence, and the accuracy of the energy levels is high enough to enable the identification and interpretation of observed spectra involving the n = 3, 4 levels, for which experimental values are largely scarce. Meanwhile, the results should be of great help for modeling and diagnosing astrophysical and fusion plasmas.« less

  20. Characterisation of clotting factors, anticoagulant protein activities and viscoelastic analysis in healthy donkeys.

    PubMed

    Perez-Ecija, A; Mendoza, F J

    2017-11-01

    Studies have demonstrated differences in commonly measured haemostatic parameters between donkeys and horses. Whether clotting factors, anticoagulant protein activities and thromboelastography parameters also differ between species is still unknown. To characterise haemostatic parameters in healthy donkeys and to compare these with those in horses. Cross-sectional study. Clotting factors (V, VII, VIII, IX, X, XI and XII), and antithrombin III, Protein C and Protein S activities were measured in 80 healthy Andalusian and crossbred donkeys and 40 healthy Andalusian crossbred horses with assays based on human deficient plasmas. Thromboelastography was performed in 34 donkeys using a coagulation and platelet function analyser. Donkeys had shorter activated partial thromboplastin time (mean ± s.d. 33.4 ± 5.2 s vs. 38.8 ± 4.2 s; P<0.001) and higher Factor VII (1825 ± 206 vs. 1513 ± 174; P<0.001), IX (142 ± 41 vs. 114 ± 28; P<0.05) and XI (59.4 ± 14.0 vs. 27.2 ± 6.3; P<0.001) activities, whereas horses showed higher Factor X (130 ± 32 vs. 145 ± 23; P>0.05) and XII (96 ± 21 vs. 108 ± 15; P<0.001) activities. Antithrombin III (204 ± 26 vs. 174 ± 29; P<0.001), Protein C (33.16 ± 10.0 vs. 7.57 ± 1.70; P<0.001) and Protein S (median [interquartile range]: 7.8 [5.8-9.3] vs. 6.2 [5.2-7.0]; P<0.001) activities were higher in donkeys. Activated clot time (175 [159-189]), time to peak (6.5 [5.8-7.8]) and clot formation rate (26.9 [16.9-36.4]) in donkeys were shorter than reported values in horses. Haemostatic pathways could not be fully evaluated in donkeys because some tests are unavailable. Certain fibrinolytic parameters (plasmin, plasminogen, etc.) have not been characterised in donkeys and this may have affected our results. The haemostatic system in donkeys differs from that in horses and extrapolation of reference values between these species is not appropriate. © 2017 EVJ Ltd.

  1. Dirac R-matrix calculations of photoionization cross sections of Ni XII and atomic structure data of Ni XIII

    NASA Astrophysics Data System (ADS)

    Nazir, R. T.; Bari, M. A.; Bilal, M.; Sardar, S.; Nasim, M. H.; Salahuddin, M.

    2017-02-01

    We performed R-matrix calculations for photoionization cross sections of the two ground state configuration 3s23p5 (^2P^o3/2,1/2) levels and 12 excited states of Ni XII using relativistic Dirac Atomic R-matrix Codes (DARC) across the photon energy range between the ionizations thresholds of the corresponding states and well above the thresholds of the last level of the Ni XIII target ion. Generally, a good agreement is obtained between our results and the earlier theoretical photoionization cross sections. Moreover, we have used two independent fully relativistic GRASP and FAC codes to calculate fine-structure energy levels, wavelengths, oscillator strengths, transitions rates among the lowest 48 levels belonging to the configuration (3s23p4, 3s3p5, 3p6, 3s23p33d) in Ni XIII. Additionally, radiative lifetimes of all the excited states of Ni XIII are presented. Our results of the atomic structure of Ni XIII show good agreement with other theoretical and experimental results available in the literature. A good agreement is found between our calculated lifetimes and the experimental ones. Our present results are useful for plasma diagnostic of fusion and astrophysical plasmas.

  2. Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy.

    PubMed

    Hicks, Debbie; Farsani, Golara Torabi; Laval, Steven; Collins, James; Sarkozy, Anna; Martoni, Elena; Shah, Ashoke; Zou, Yaqun; Koch, Manuel; Bönnemann, Carsten G; Roberts, Mark; Lochmüller, Hanns; Bushby, Kate; Straub, Volker

    2014-05-01

    Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease characterized by contractures and proximal weakness, which can be caused by mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However, there may be additional causal genes to identify as in ∼50% of BM cases no mutations in the COL6 genes are identified. In a cohort of -24 patients with a BM-like phenotype, we first sequenced 12 candidate genes based on their function, including genes for known binding partners of collagen VI, and those enzymes involved in its correct post-translational modification, assembly and secretion. Proceeding to whole-exome sequencing (WES), we identified mutations in the COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with interrupted triple helices) in five individuals from two families. Both families showed dominant inheritance with a clinical phenotype resembling classical BM. Family 1 had a single-base substitution that led to the replacement of one glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating pattern, and Family 2 had a missense mutation, which created a mutant protein with an unpaired cysteine residue. Abnormality at the protein level was confirmed in both families by the intracellular retention of collagen XII in patient dermal fibroblasts. The mutation in Family 2 leads to the up-regulation of genes associated with the unfolded protein response (UPR) pathway and swollen, dysmorphic rough-ER. We conclude that the spectrum of causative genes in extracellular matrix (ECM)-related myopathies be extended to include COL12A1.

  3. [Pathogenic factors of vibrios with special emphasis on Vibrio vulnificus].

    PubMed

    Shinoda, Sumio

    2005-07-01

    Bacteria of the genus Vibrio are normal habitants of the aquatic environment and play roles for biocontrole of aquatic ecosystem, but some species are believed to be human pathogens. These species can be classified into two groups according to the types of diseases they cause: the gastrointestinal infections and the extraintestinal infections. The pathogenic species produce various pathogenic factors including enterotoxin, hemolysin, cytotoxin, protease, siderophore, adhesive factor, and hemagglutinin. We studied various pathogenic factors of vibrios with special emphasis on protease and hemolysin of V. vulnificus. V. vulnificus is now recognized as being among the most rapidly fatal of human pathogens, although the infection is appeared in patients having underlying disease(s) such as liver dysfunction, alcoholic cirrhosis or haemochromatosis. V. vulnificus protease (VVP) is thought to be a major toxic factor causing skin damage in the patients having septicemia. VVP is a metalloprotease and degrades a number of biologically important proteins including elastin, fibrinogen, and plasma proteinase inhibitors of complement components. VVP causes skin damages through activation of the Factor XII-plasma kallikrein-kinin cascade and/or exocytotic histamine release from mast cells, and a haemorrhagic lesion through digestion of the vascular basement membrane. Thus, the protease is the most probable candidate for tissue damage and bacterial invasion during an infection. Pathogenic roles and functional mechanism of other factors including hemolysins of V. vulnificus and V. mimicus are also shown in this review article.

  4. Anticoagulation beyond direct thrombin and factor Xa inhibitors: indications for targeting the intrinsic pathway?

    PubMed

    van Montfoort, Maurits L; Meijers, Joost C M

    2013-08-01

    Antithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. In terms of effectiveness, these drugs are comparable to the currently available anticoagulants; however, they are still associated with issues such as bleeding, reversal of the drug and complicated laboratory monitoring. Vitamin K antagonists, heparin, direct thrombin and factor Xa inhibitors have in common that they target key proteins of the haemostatic system. In an attempt to overcome these difficulties we investigated whether the intrinsic coagulation factors (VIII, IX, XI, XII, prekallikrein and high-molecular-weight kininogen) are superior targets for anticoagulation. We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.

  5. Preliminary report on AED deployment on the entire Air France commercial fleet: a joint venture with Paris XII University Training Programme.

    PubMed

    Bertrand, C; Rodriguez Redington, P; Lecarpentier, E; Bellaiche, G; Michel, D; Teiger, E; Morris, W; Le Bourgeois, J P; Barthout, M

    2004-11-01

    The positive effect of early defibrillation on survival from cardiac arrest has been demonstrated. We describe the use of AEDs over 1 year following the training of flight attendants. Air France and the University of Paris XII together designed a 1 year training programme for 14000 flight attendants. The university emergency departments (SAMU) provided 250 instructors. AEDs training and certification was conducted for crew members between November 2001 and November 2002. By January 2003, all aircraft were fully equipped with AEDs. All cases of cardiac arrest that occurred during the study were reviewed comprehensively. Comments from the crew were collected. Twelve cardiac arrests were reported between November 2002 and November 2003 out of 4194 cases of emergency care delivered to passengers. Shock treatment was advised initially in 5/12 cases. The survival rate after in-flight cardiac arrest was 3/12. The survival rate at discharge from hospital following in flight shock was 2/5. No complications arose from the use of AEDs. Training by professionals gave the flight attendants confidence and allowed for the survival of two young passengers. Our study highlights the ability of flight attendants to give better onboard care for the future. The next step is to consolidate the network between in-flight care and the medical dispatch centre in Paris.

  6. Quantitative analysis of substituted N,N-dimethyl-tryptamines in the presence of natural type XII alkaloids.

    PubMed

    Ivanova, Bojidarka; Spiteller, Michael

    2012-10-01

    This paper reports the qualitative and quantitative analysis (QA) of mixtures of hallucinogens, N,N-dimethyltryptamine (DMT) (1), 5-methoxy- (la) and 5-hydroxy-N,N-dimethyltryptamine (1b) in the presence of beta-carbolines (indole alkaloids of type XII) ((2), (3) and (5)}. The validated electronic absorption spectroscopic (EAs) protocol achieved a concentration limit of detection (LOD) of 7.2.10(-7) mol/L {concentration limit of quantification (LOQ) of 24.10(-7) mol/L) using bands (lambda max within 260+/-0.23-262+/-0.33 nm. Metrology, including accuracy, measurement repeatability, measurement precision, trueness of measurement, and reproducibility of the measurements are presented using N,N-dimethyltryptamine (DMA) as standard. The analytical quantities of mixtures of alkaloids 4, 6 and 7 are: lambda max 317+/-0.45, 338+/-0.69 and 430+/-0.09 for 4 (LOD, 8.6.10(-7) mol/L; LOQ, 28.66(6), mol/L), as well as 528+/-0.75 nm for 6 and 7 (LOD, 8.2.10(-7) mol/L; LOQ, 27.33(3), mol/L), respectively. The partially validated protocols by high performance liquid chromatography (HPLC), electrospray ionization (ESI), mass spectrometry (MS), both in single and tandem operation (MS/MS) mode, as well as matrix/assisted laser desorption/ionization (MALDI) MS are elaborated. The Raman spectroscopic (RS) protocol for analysis of psychoactive substances, characterized by strong fluorescence RS profile was developed, with the detection limits being discussed. The known synergistic effect leading to increase the psychoactive and hallucinogenic properties and the reported acute poisoning cases from 1-7, make the present study emergent, since as well the current lack of analytical data and the herein metrology obtained contributed to the elaboration of highly selective and precise analytical protocols, which would be of interest in the field of criminal forensic analysis.

  7. Novel Family of Insect Salivary Inhibitors Blocks Contact Pathway Activation by Binding to Polyphosphate, Heparin, and Dextran Sulfate

    PubMed Central

    Alvarenga, Patricia H.; Xu, Xueqing; Oliveira, Fabiano; Chagas, Andrezza C.; Nascimento, Clarissa R.; Francischetti, Ivo M.B.; Juliano, Maria A.; Juliano, Luiz; Scharfstein, Julio; Valenzuela, Jesus G.; Ribeiro, José M.C.; Andersen, John F.

    2014-01-01

    Objective Polyphosphate and heparin are anionic polymers released by activated mast cells and platelets that are known to stimulate the contact pathway of coagulation. These polymers promote both the autoactivation of factor XII and the assembly of complexes containing factor XI, prekallikrein, and high-molecular-weight kininogen. We are searching for salivary proteins from blood-feeding insects that counteract the effect of procoagulant and proinflammatory factors in the host, including elements of the contact pathway. Approach and Results Here, we evaluate the ability of the sand fly salivary proteins, PdSP15a and PdSP15b, to inhibit the contact pathway by disrupting binding of its components to anionic polymers. We attempt to demonstrate binding of the proteins to polyphosphate, heparin, and dextran sulfate. We also evaluate the effect of this binding on contact pathway reactions. We also set out to determine the x-ray crystal structure of PdSP15b and examine the determinants of relevant molecular interactions. Both proteins bind polyphosphate, heparin, and dextran sulfate with high affinity. Through this mechanism they inhibit the autoactivation of factor XII and factor XI, the reciprocal activation of factor XII and prekallikrein, the activation of factor XI by thrombin and factor XIIa, the cleavage of high-molecular-weight kininogen in plasma, and plasma extravasation induced by polyphosphate. The crystal structure of PdSP15b contains an amphipathic helix studded with basic side chains that forms the likely interaction surface. Conclusions The results of these studies indicate that the binding of anionic polymers by salivary proteins is used by blood feeders as an antihemostatic/anti-inflammatory mechanism. PMID:24092749

  8. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

    PubMed

    Bastian, H M; Roseman, J M; McGwin, G; Alarcón, G S; Friedman, A W; Fessler, B J; Baethge, B A; Reveille, J D

    2002-01-01

    The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95

  9. A probable case of gigantism/acromegaly in skeletal remains from the Jewish necropolis of "Ronda Sur" (Lucena, Córdoba, Spain; VIII-XII centuries CE).

    PubMed

    Viciano, Joan; De Luca, Stefano; López-Lázaro, Sandra; Botella, Daniel; Diéguez-Ramírez, Juan Pablo

    2015-01-01

    Pituitary gigantism is a rare endocrine disorder caused by hypersecretion of growth hormone during growing period. Individuals with this disorder have an enormous growth in height and associated degenerative changes. The continued hypersecretion of growth hormone during adulthood leads to acromegaly, a condition related to the disproportionate bone growth of the skull, hands and feet. The skeletal remains studied belong to a young adult male from the Jewish necropolis of "Ronda Sur" in Lucena (Córdoba, Spain, VIII-XII centuries CE). The individual shows a very large and thick neurocranium, pronounced supraorbital ridges, an extremely prominent occipital protuberance, and an extremely large and massive mandible. Additional pathologies include enlargement of the vertebral bodies with degenerative changes, thickened ribs, and a slight increased length of the diaphysis with an increased cortical bone thickness of lower limbs. Comparative metric analysis of the mandible with other individuals from the same population and a contemporary Mediterranean population shows a trend toward acromegalic morphology. This case is an important contribution in paleopathological literature because it is a rare condition that has not been widely documented in ancient skeletal remains.

  10. Crew Factors in Flight Operations XII: A Survey of Sleep Quantity and Quality in On-Board Crew Rest Facilities

    NASA Technical Reports Server (NTRS)

    Rosekind, Mark R.; Gregory, Kevin B.; Co, Elizabeth L.; Miller, Donna L.; Dinges, David F.

    2000-01-01

    Many aircraft operated on long-haul commercial airline flights are equipped with on-board crew rest facilities, or bunks, to allow crewmembers to rest during the flight. The primary objectives of this study were to gather data on how the bunks were used, the quantity and quality of sleep obtained by flight crewmembers in the facilities, and the factors that affected their sleep. A retrospective survey comprising 54 questions of varied format addressed demographics, home sleep habits, and bunk sleep habits. Crewmembers from three airlines with long-haul fleets carrying augmented crews consisting of B747-100/200, B747-400, and MD-11 aircraft equipped with bunks returned a total of 1404 completed surveys (a 37% response rate). Crewmembers from the three carriers were comparable demographically, although one carrier had older, more experienced flight crewmembers. Each group, on average, rated themselves as "good" or "very good" sleepers at home, and all groups obtained about the same average amount of sleep each night. Most were able to sleep in the bunks, and about two thirds indicated that these rest opportunities benefited their subsequent flight deck alertness and performance. Comfort, environment, and physiology (e.g., being ready for sleep) were identified as factors that most promoted sleep. Factors cited as interfering with sleep included random noise, thoughts, heat, and the need to use the bathroom. These factors, in turn, suggest potential improvements to bunk facilities and their use. Ratings of the three aircraft types suggested differences among facilities. Bunks in the MD-11 were rated significantly better than either of the B747 types, and the B747-400 bunks received better ratings than did the older, B747-100/200 facilities.

  11. Demonstration/Validation of the Snap Sampler Passive Ground Water Sampling Device for Sampling Inorganic Analytes at the Former Pease Air Force Base

    DTIC Science & Technology

    2009-07-01

    viii Unit Conversion Factors...sampler is also an economic alternative for sampling for inorganic analytes. ERDC/CRREL TR-09-12 xii Unit Conversion Factors Multiply By To Obtain...head- space and then covered with two layers of tightly fitting aluminum foil. To dissolve the analytes, the solutions were stirred for approximately

  12. Studies on a complex mechanism for the activation of plasminogen by kaolin and by chloroform: the participation of Hageman factor and additional cofactors

    PubMed Central

    Ogston, Derek; Ogston, C. Marie; Ratnoff, Oscar D.; Forbes, Charles D.

    1969-01-01

    As demonstrated by others, fibrinolytic activity was generated in diluted, acidified normal plasma exposed to kaolin, a process requiring Hageman factor (Factor XII). Generation was impaired by adsorbing plasma with glass or similar agents under conditions which did not deplete its content of Hageman factor or plasminogen. The defect could be repaired by addition of a noneuglobulin fraction of plasma or an agent or agents eluted from diatomaceous earth which had been exposed to normal plasma. The restorative agent, tentatively called Hageman factor-cofactor, was partially purified by chromatography and had an apparent molecular weight of approximately 165,000. It could be distinguished from plasma thromboplastin antecedent (Factor XI) and plasma kallikrein, other substrates of Hageman factor, and from the streptokinase-activated pro-activator of plasminogen. Evidence is presented that an additional component may be needed for the generation of fibrinolytic activity in mixtures containing Hageman factor, HF-cofactor, and plasminogen. The long-recognized generation of plasmin activity in chloroform-treated euglobulin fractions of plasma was found to be dependent upon the presence of Hageman factor. Whether chloroform activation of plasminogen requires Hageman factor-cofactor was not determined, but glass-adsorbed plasma, containing Hageman factor and plasminogen, did not generate appreciable fibrinolytic or caseinolytic activity. These studies emphasize the complex nature of the mechanisms which lead to the generation of plasmin in human plasma. PMID:4241814

  13. Normal Hemostatic Profiles and Coagulation Factors in Healthy Free-Living Florida Manatees ( Trichechus manatus latirostris).

    PubMed

    Barratclough, Ashley; Floyd, Ruth Francis; Conner, Bobbi; Reep, Roger; Ball, Ray; Stacy, Nicole

    2016-10-01

    Hemostatic disorders presumptively play an important role in the pathophysiology of several important disease conditions in the Florida manatee ( Trichechus manatus latirostris). Prior to pursuing such clinical implications, it is essential to establish normal hemostatic profiles in clinically healthy animals. During annual health assessments of free-living manatees organized by the US Geological Survey, blood samples were collected from 12 healthy animals from the Atlantic coast and 28 from the Gulf of Mexico coast of Florida, with body lengths of 210-324 cm. The following analyses were performed on citrated plasma: prothrombin (PT), partial thromboplastin time (PTT), and concentrations of fibrinogen, D-dimers, and coagulation factors VII, VIII, IX, X, XI, and XII. Compared to other mammalian species, manatees had short PT (9.2±1.5 s) and PTT (10.7±0.5 s), fibrinogen was 369±78.7 mg/dL, antithrombin III was 132±11%, and D-dimer was 142±122 ng/mL. Baseline concentrations for the listed coagulation factors were established. When comparing coagulation factors between locations, Atlantic coast manatees had significantly higher factors VIII, IX, and X than did Gulf Coast manatees. This finding may reflect differences in water salinity, diet, or genetics. There were no differences in coagulation factors when among sexes and sizes. These baselines for hemostatic profiles and coagulation factors in healthy free-living manatees lay the foundation for diagnosis and future research of hemostatic disorders and contribute to understanding their role in the pathophysiology of manatees affected by various diseases.

  14. Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro

    PubMed Central

    Yasuda, Kouichi; Robinson, Dean M; Selvaratnam, Subramaniam R; Walsh, Carmen W; McMorland, Angus J C; Funk, Gregory D

    2001-01-01

    The effects of substance P (SP), acting at NK1 receptors, on the excitability and inspiratory activity of hypoglossal (XII) motoneurons (MNs) were investigated using rhythmically active medullary-slice preparations from neonatal mice (postnatal day 0–3). Local application of the NK1 agonist [SAR9,Met (O2)11]-SP (SPNK1) produced a dose-dependent, spantide- (a non-specific NK receptor antagonist) and GR82334-(an NK1 antagonist) sensitive increase in inspiratory burst amplitude recorded from XII nerves. Under current clamp, SPNK1 significantly depolarized XII MNs, potentiated repetitive firing responses to injected currents and produced a leftward shift in the firing frequency-current relationships without affecting slope. Under voltage clamp, SPNK1 evoked an inward current and increased input resistance, but had no effect on inspiratory synaptic currents. SPNK1 currents persisted in the presence of TTX, were GR82334 sensitive, were reduced with hyperpolarization and reversed near the expected EK. Effects of the α1-noradrenergic receptor agonist phenylephrine (PE) on repetitive firing behaviour were virtually identical to those of SPNK1. Moreover, SPNK1 currents were completely occluded by PE, suggesting that common intracellular pathways mediate the actions of NK1 and α1-noradrenergic receptors. In spite of the similar actions of SPNK1 and PE on XII MN responses to somally injected current, α1-noradrenergic receptor activation potentiated inspiratory synaptic currents and was more than twice as effective in potentiating XII nerve inspiratory burst amplitude. GR82334 reduced XII nerve inspiratory burst amplitude and generated a small outward current in XII MNs. These observations, together with the first immunohistochemical evidence in the newborn for SP immunopositive terminals in the vicinity of SPNK1-sensitive inspiratory XII MNs, support the endogenous modulation of XII MN excitability by SP. In contrast to phrenic MNs (Ptak et al. 2000), blocking NMDA

  15. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population.

    PubMed

    Barillari, Giovanni; Fabbro, Elisabetta; Pasca, Samantha; Bigotto, Enrico

    2009-06-01

    Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P < 0.05) for tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein, factor VII and factor XI; conversely for factor VIII, factor IX, factor XII, antithrombin III and fibrinogen, the results gave a difference statistically significant (P < 0.01). In patients with DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically

  16. Risk factors for indications of intraoperative blood transfusion among patients undergoing surgical treatment for colorectal adenocarcinoma.

    PubMed

    Gonçalves, Iara; Linhares, Marcelo; Bordin, Jose; Matos, Delcio

    2009-01-01

    Identification of risk factors for requiring transfusions during surgery for colorectal cancer may lead to preventive actions or alternative measures, towards decreasing the use of blood components in these procedures, and also rationalization of resources use in hemotherapy services. This was a retrospective case-control study using data from 383 patients who were treated surgically for colorectal adenocarcinoma at 'Fundação Pio XII', in Barretos-SP, Brazil, between 1999 and 2003. To recognize significant risk factors for requiring intraoperative blood transfusion in colorectal cancer surgical procedures. Univariate analyses were performed using Fisher's exact test or the chi-squared test for dichotomous variables and Student's t test for continuous variables, followed by multivariate analysis using multiple logistic regression. In the univariate analyses, height (P = 0.06), glycemia (P = 0.05), previous abdominal or pelvic surgery (P = 0.031), abdominoperineal surgery (P<0.001), extended surgery (P<0.001) and intervention with radical intent (P<0.001) were considered significant. In the multivariate analysis using logistic regression, intervention with radical intent (OR = 10.249, P<0.001, 95% CI = 3.071-34.212) and abdominoperineal amputation (OR = 3.096, P = 0.04, 95% CI = 1.445-6.623) were considered to be independently significant. This investigation allows the conclusion that radical intervention and the abdominoperineal procedure in the surgical treatment of colorectal adenocarcinoma are risk factors for requiring intraoperative blood transfusion.

  17. Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure

    NASA Astrophysics Data System (ADS)

    Nabeshi, Hiromi; Yoshikawa, Tomoaki; Matsuyama, Keigo; Nakazato, Yasutaro; Arimori, Akihiro; Isobe, Masaaki; Tochigi, Saeko; Kondoh, Sayuri; Hirai, Toshiro; Akase, Takanori; Yamashita, Takuya; Yamashita, Kohei; Yoshida, Tokuyuki; Nagano, Kazuya; Abe, Yasuhiro; Yoshioka, Yasuo; Kamada, Haruhiko; Imazawa, Takayoshi; Itoh, Norio; Kondoh, Masuo; Yagi, Kiyohito; Mayumi, Tadanori; Tsunoda, Shin-ichi; Tsutsumi, Yasuo

    2012-02-01

    We previously reported that well-dispersed amorphous nanosilicas with particle size 70 nm (nSP70) penetrate skin and produce systemic exposure after topical application. These findings underscore the need to examine biological effects after systemic exposure to nanosilicas. The present study was designed to examine the biological effects. BALB/c mice were intravenously injected with amorphous nanosilicas of sizes 70, 100, 300, 1000 nm and then assessed for survival, blood biochemistry, and coagulation. As a result, injection of nSP70 caused fatal toxicity, liver damage, and platelet depletion, suggesting that nSP70 caused consumptive coagulopathy. Additionally, nSP70 exerts procoagulant activity in vitro associated with an increase in specific surface area, which increases as diameter reduces. In contrast, nSP70-mediated procoagulant activity was absent in factor XII-deficient plasma. Collectively, we revealed that interaction between nSP70 and intrinsic coagulation factors such as factor XII, were deeply related to nSP70-induced harmful effects. In other words, it is suggested that if interaction between nSP70 and coagulation factors can be suppressed, nSP70-induced harmful effects may be avoided. These results would provide useful information for ensuring the safety of nanomaterials (NMs) and open new frontiers in biological fields by the use of NMs.

  18. Impaired factor XIIa-dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications.

    PubMed

    Carmona, Francisco; Lázaro, Isabel; Reverter, Juan C; Tàssies, Dolors; Font, Josep; Cervera, Ricard; Balasch, Juan

    2006-02-01

    The objective of the study was to investigate the potential role of impaired factor XII-dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications. This was a prospective study in a third-level teaching hospital, including 75 patients: 25 pregnant patients having the antiphospholipid syndrome and carrying their pregnancies until 26 weeks' gestation or later (group 1); 25 pregnant patients having normal term pregnancies and delivery and no previous miscarriage (group 2); and 25 pregnant patients being diagnosed as having severe pre-eclampsia and/or intrauterine growth restriction but testing negative for antiphospholipid antibodies (group 3). Hemostatic evaluation was carried out from patients in groups 1 and 2 between 6 and 10 weeks, between 18 and 22 weeks, and between 28 and 32 weeks' gestation. Patients in group 3 were sampled between 28 and 32 weeks. An additional blood sample was obtained 4 to 6 months after delivery (baseline). The Mann-Whitney U test, the Friedman test, and the chi2 test were used. Patients in group 1 were characterized by increased factor VIIa levels, increased prothrombin fragment 1+2 levels, reduced factor XIIa levels, diminished functional urokinase-type plasminogen activator levels, and decreased levels of plasmin/alpha-2-plasmin inhibitor complexes. These abnormalities were more evident in patients in group 1 developing pre-eclampsia and/or intrauterine growth restriction. Impaired factor XIIa-dependent activation of fibrinolysis seems to be a key mechanism related to late-pregnancy complications in patients with the antiphospholipid syndrome.

  19. Essential role of carbonic anhydrase XII in secretory gland fluid and HCO3 (-) secretion revealed by disease causing human mutation.

    PubMed

    Hong, Jeong Hee; Muhammad, Emad; Zheng, Changyu; Hershkovitz, Eli; Alkrinawi, Soliman; Loewenthal, Neta; Parvari, Ruti; Muallem, Shmuel

    2015-12-15

    Fluid and HCO3 (-) secretion is essential for all epithelia; aberrant secretion is associated with several diseases. Carbonic anhydrase XII (CA12) is the key carbonic anhydrase in epithelial fluid and HCO3 (-) secretion and works by activating the ductal Cl(-) -HCO3 (-) exchanger AE2. Delivery of CA12 to salivary glands increases salivation in mice and of the human mutation CA12(E143K) markedly inhibits it. The human mutation CA12(E143K) causes disease due to aberrant CA12 glycosylation, and misfolding resulting in loss of AE2 activity. Aberrant epithelial fluid and HCO3 (-) secretion is associated with many diseases. The activity of HCO3 (-) transporters depends of HCO3 (-) availability that is determined by carbonic anhydrases (CAs). Which CAs are essential for epithelial function is unknown. CA12 stands out since the CA12(E143K) mutation causes salt wasting in sweat and dehydration in humans. Here, we report that expression of CA12 and of CA12(E143K) in mice salivary glands respectively increased and prominently inhibited ductal fluid secretion and salivation in vivo. CA12 markedly increases the activity and is the major HCO3 (-) supplier of ductal Cl(-) -HCO3 (-) exchanger AE2, but not of NBCe1-B. The E143K mutation alters CA12 glycosylation at N28 and N80, resulting in retention of the basolateral CA12 in the ER. Knockdown of AE2 and of CA12 inhibited pancreatic and salivary gland ductal AE2 activity and fluid secretion. Accordingly, patients homozygous for the CA12(E143K) mutation have a dry mouth, dry tongue phenotype. These findings reveal an unsuspected prominent role of CA12 in epithelial function, explain the disease and call for caution in the use of CA12 inhibitors in cancer treatment. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  20. 77 FR 72410 - Agency Information Collection Activities; Submission for OMB Review; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... for OMB Review; Comment Request; Unemployment Insurance Title XII Advances and Voluntary Repayment..., ``Unemployment Insurance Title XII Advances and Voluntary Repayment Process,'' to the Office of Management and... submission of responses. Agency: DOL-ETA. [[Page 72411

  1. Simultaneous Observation of High Temperature Plasma of Solar Corona By TESIS CORONAS-PHOTON and XRT Hinode.

    NASA Astrophysics Data System (ADS)

    Reva, A.; Kuzin, S.; Bogachev, S.; Shestov, S.

    2012-05-01

    The Mg XII spectroheliograph is a part of instrumentation complex TESIS (satellite CORONAS-PHOTON). This instrument builds monochromatic images of hot plasma of the solar corona (λ = 8.42 Å, T>5 MK). The Mg XII spectroheliograph observed hot plasma in the non-flaring active-region NOAA 11019 during nine days. We reconstructed DEM of this active region with the help of genetic algorithm (we used data of the Mg XII spectroheliograph, XRT and EIT). Emission measure of the hot component amounts 1 % of the emission measure of the cool component.

  2. Portraits - Apollo XII

    NASA Image and Video Library

    1969-07-03

    S69-38852 (22 Sept. 1969) --- These three astronauts have been named by the National Aeronautics and Space Administration (NASA) as the prime crew of the Apollo 12 lunar landing mission. Left to right are Charles Conrad Jr., Richard F. Gordon Jr., and Alan L. Bean.

  3. 'Candidatus phytoplasma solani’, a novel taxon associated with stolbur and bois noir related diseases of plants

    USDA-ARS?s Scientific Manuscript database

    Phytoplasmas classified in group 16SrXII infect a wide range of plants and are transmitted by polyphagous planthoppers of the family Cixiidae. Based on 16S rRNA gene sequence identity and biological properties, group 16SrXII encompasses several species, including ‘Candidatus Phytoplasma australiens...

  4. Synthesis of a new series of dithiocarbamates with effective human carbonic anhydrase inhibitory activity and antiglaucoma action.

    PubMed

    Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Akdemir, Atilla; Isik, Semra; Lanzi, Cecilia; Scozzafava, Andrea; Masini, Emanuela; Supuran, Claudiu T

    2015-05-15

    A new series of dithiocarbamates (DTCs) was prepared from primary/secondary amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, and carbon disulfide. The compounds were investigated for the inhibition of four mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, that is, the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient hCA I inhibitors (off-target isoform for both applications), efficiently inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering properties in an animal model of glaucoma, with a two times better efficiency compared to the clinically used sulfonamide dorzolamide. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. The plasma filling factor of coronal bright points. II. Combined EIS and TRACE results

    NASA Astrophysics Data System (ADS)

    Dere, K. P.

    2009-04-01

    Aims: In a previous paper, the volumetric plasma filling factor of coronal bright points was determined from spectra obtained with the Extreme ultraviolet Imaging Spectrometer (EIS). The analysis of these data showed that the median plasma filling factor was 0.015. One interpretation of this result was that the small filling factor was consistent with a single coronal loop with a width of 1-2´´, somewhat below the apparent width. In this paper, higher spatial resolution observations with the Transition Region and Corona Explorer (TRACE) are used to test this interpretation. Methods: Rastered spectra of regions of the quiet Sun were recorded by the EIS during operations with the Hinode satellite. Many of these regions were simultaneously observed with TRACE. Calibrated intensities of Fe xii lines were obtained and images of the quiet corona were constructed from the EIS measurements. Emission measures were determined from the EIS spectra and geometrical widths of coronal bright points were obtained from the TRACE images. Electron densities were determined from density-sensitive line ratios measured with EIS. A comparison of the emission measure and bright point widths with the electron densities yielded the plasma filling factor. Results: The median electron density of coronal bright points is 3 × 109 cm-3 at a temperature of 1.6 × 106 K. The volumetric plasma filling factor of coronal bright points was found to vary from 3 × 10-3 to 0.3 with a median value of 0.04. Conclusions: The current set of EIS and TRACE coronal bright-point observations indicate the median value of their plasma filling factor is 0.04. This can be interpreted as evidence of a considerable subresolution structure in coronal bright points or as the result of a single completely filled plasma loop with widths on the order of 0.2-1.5´´ that has not been spatially resolved in these measurements.

  6. Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993.

    PubMed

    Patel, Bella; Rai, Lena; Buck, Georgina; Richards, Sue M; Mortuza, Yeasmin; Mitchell, Wayne; Gerrard, Gareth; Moorman, Anthony V; Duke, Veronique; Hoffbrand, A Victor; Fielding, Adele K; Goldstone, Anthony H; Foroni, Letizia

    2010-01-01

    The predictive value of molecular minimal residual disease (MRD) monitoring using polymerase chain reaction amplification of clone-specific immunoglobulin or T-cell Receptor rearrangements was analysed in 161 patients with non T-lineage Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group (ECOG) 2993. MRD positivity (> or =10(-4)) in patients treated with chemotherapy alone was associated with significantly shorter relapse-free survival (RFS) at several time-points during the first year of therapy. MRD status best discriminated outcome after phase 2 induction, when the relative risk of relapse was 8.95 (2.85-28.09)-fold higher in MRD-positive (> or =10(-4)) patients and the 5-year RFS 15% [95% confidence interval (CI) 0-40%] compared to 71% (56-85%) in MRD-negative (<10(-4)) patients (P = 0.0002) When MRD was detected prior to autologous stem cell transplantation (SCT), a significantly higher rate of treatment failure was observed [5-year RFS 25% (CI 0-55%) vs. 77% (95% CI 54-100%) in MRD-negative/<10(-4), P = 0.01] whereas in recipients of allogeneic-SCT in first complete remission, MRD positivity pre-transplant did not adversely affect outcome. These data provide a rationale for introducing MRD-based risk stratification in future studies for the delineation of those at significant risk of treatment failure in whom intensification of therapy should be evaluated.

  7. Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

    PubMed

    Mourad, Waleed F; Young, Brett M; Young, Rebekah; Blakaj, Dukagjin M; Ohri, Nitin; Shourbaji, Rania A; Manolidis, Spiros; Gámez, Mauricio; Kumar, Mahesh; Khorsandi, Azita; Khan, Majid A; Shasha, Daniel; Blakaj, Adriana; Glanzman, Jonathan; Garg, Madhur K; Hu, Kenneth S; Kalnicki, Shalom; Harrison, Louis B

    2013-09-01

    Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. Published by Elsevier Ltd.

  8. 20 CFR 606.30 - Interest rates on advances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Interest rates on advances. 606.30 Section... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Interest on Advances § 606.30 Interest rates on advances. Advances made to States pursuant to title XII of the Social...

  9. 78 FR 76327 - Notice of Denial of Georgia's Application for a “Cap” of the 2013 Credit Reduction Under the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ... an outstanding balance of advances under Title XII of the Social Security Act at the beginning of... against the FUTA tax for the calendar year in which the most recent such January 1 occurs, if a balance of... Fund account having an outstanding balance of Title XII advances on January 1 of four consecutive years...

  10. 77 FR 38179 - Subtitle C, Regulations Relating to Education

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    .... XII, Part 1200 Subtitle C, Regulations Relating to Education CFR Correction In Title 34 of the Code of Federal Regulations, Part 680 to End, revised as of July 1, 2011, on page 395, the heading ``Subtitle C..., chapters XI and XII are designated under subtitle C. [FR Doc. 2012-15881 Filed 6-26-12; 8:45 am] BILLING...

  11. Large-Scale Coronal Heating from "Cool" Activity in the Solar Magnetic Network

    NASA Technical Reports Server (NTRS)

    Falconer, D. A.; Moore, R. L.; Porter, J. G.; Hathaway, D. H.

    1999-01-01

    In Fe XII images from SOHO/EIT, the quiet solar corona shows structure on scales ranging from sub-supergranular (i.e., bright points and coronal network) to multi-supergranular (large-scale corona). In Falconer et al 1998 (Ap.J., 501, 386) we suppressed the large-scale background and found that the network-scale features are predominantly rooted in the magnetic network lanes at the boundaries of the supergranules. Taken together, the coronal network emission and bright point emission are only about 5% of the entire quiet solar coronal Fe XII emission. Here we investigate the relationship between the large-scale corona and the network as seen in three different EIT filters (He II, Fe IX-X, and Fe XII). Using the median-brightness contour, we divide the large-scale Fe XII corona into dim and bright halves, and find that the bright-half/dim half brightness ratio is about 1.5. We also find that the bright half relative to the dim half has 10 times greater total bright point Fe XII emission, 3 times greater Fe XII network emission, 2 times greater Fe IX-X network emission, 1.3 times greater He II network emission, and has 1.5 times more magnetic flux. Also, the cooler network (He II) radiates an order of magnitude more energy than the hotter coronal network (Fe IX-X, and Fe XII). From these results we infer that: 1) The heating of the network and the heating of the large-scale corona each increase roughly linearly with the underlying magnetic flux. 2) The production of network coronal bright points and heating of the coronal network each increase nonlinearly with the magnetic flux. 3) The heating of the large-scale corona is driven by widespread cooler network activity rather than by the exceptional network activity that produces the network coronal bright points and the coronal network. 4) The large-scale corona is heated by a nonthermal process since the driver of its heating is cooler than it is. This work was funded by the Solar Physics Branch of NASA's office of

  12. Double-stabilized neurotensin analogues as potential radiopharmaceuticals for NTR-positive tumors.

    PubMed

    García-Garayoa, Elisa; Maes, Veronique; Bläuenstein, Peter; Blanc, Alain; Hohn, Alexander; Tourwé, Dirk; Schubiger, P August

    2006-05-01

    Overexpression of neurotensin (NT) receptors in exocrine pancreatic cancer and other neuroendocrine cancers make them interesting targets for tumor imaging and therapy. Modifications at the cleavage bonds 8-9 and 11-12 led to the synthesis of NT-XII, NT-XIII and NT-XVIII, three new stabilized analogues. (NalphaHis)Ac was coupled to the N-terminus for labeling with [(99m)Tc]-tricarbonyl. Stability was tested in vitro in human plasma and HT-29 cells. Binding to NT1 receptors and internalization/efflux were analyzed in intact HT-29 cells. Biodistribution studies were performed in nude mice bearing HT-29 xenografts. All analogues were very stable in human plasma, with half-lives of 20-21 days. Degradation in HT-29 cells was more rapid (t(1/2) of 6.5, 5 and 2.5 h for NT-XII, NT-XIII and NT-XVIII, respectively). They also showed high affinity and specificity for NT1 receptors. Bound activity was rapidly internalized at 37 degrees C. The pattern of externalization was different. NT-XII was released more slowly than NT-XIII and NT-XVIII (half of the activity still inside the cells after 24 h). Bigger differences were found in the biodistribution studies. NT-XII showed the highest tumor uptake as well as the best tumor to nontumor ratios. The modifications introduced in NT(8-13) increased plasma stability, maintaining unaffected the in vitro binding properties. The best biodistribution corresponded to NT-XII, which shows to be a good candidate for NT1 receptors overexpressing tumors. First clinical trials are ongoing.

  13. Suppression of nanoindentation-induced phase transformation in crystalline silicon implanted with hydrogen

    NASA Astrophysics Data System (ADS)

    Jelenković, Emil V.; To, Suet

    2017-09-01

    In this paper the effect of hydrogen implantation in silicon on nanoindentation-induced phase transformation is investigated. Hydrogen ions were implanted in silicon through 300 nm thick oxide with double energy implantation (75 and 40 keV). For both energies implantation dose was 4 × 1016 cm-2. Some samples were thermally annealed at 400 °C. The micro-Raman spectroscopy was applied on nanoindentation imprints and the obtained results were related to the pop out/elbow appearances in nanoindentatioin unloading-displacement curves. The Raman spectroscopy revealed a suppression of Si-XII and Si-III phases and formation of a-Si in the indents of hydrogen implanted Si. The high-resolution x-ray diffraction measurements were taken to support the analysis of silicon phase formation during nanoindentation. Implantation induced strain, high hydrogen concentration, and platelets generation were found to be the factors that control suppression of c-Si phases Si-XII and Si-III, as well as a-Si phase enhancement during nanoindentation. [Figure not available: see fulltext.

  14. Effects of surface wettability and contact time on protein adhesion to biomaterial surfaces

    PubMed Central

    Xu, Li-Chong; Siedlecki, Christopher A.

    2013-01-01

    Atomic force microscopy (AFM) was used to directly measure the adhesion forces between three test proteins and low density polyethylene (LDPE) surfaces treated by glow discharge plasma to yield various levels of water wettability. The adhesion of proteins to the LDPE substrates showed a step dependence on the wettability of surfaces as measured by the water contact angle (θ). For LDPE surfaces with θ > ∼60–65°, stronger adhesion forces were observed for bovine serum albumin, fibrinogen and human FXII than for the surfaces with θ < 60°. Smaller adhesion forces were observed for FXII than for the other two proteins on all surfaces although trends were identical. Increasing the contact time from 0 to 50 s for each protein–surface combination increased the adhesion force regardless of surface wettability. Time varying adhesion data was fit to an exponential model and free energies of protein unfolding were calculated. This data, viewed in light of previously published studies, suggests a 2-step model of protein denaturation, an early stage on the order of seconds to minutes where the outer surface of the protein interacts with the substrate and a second stage involving movement of hydrophobic amino acids from the protein core to the protein/surface interface. Impact statement The work described in this manuscript shows a stark transition between protein adherent and protein non-adherent materials in the range of water contact angles 60–65°, consistent with known changes in protein adsorption and activity. Time-dependent changes in adhesion force were used to calculate unfolding energies relating to protein–surface interactions. This analysis provides justification for a 2-step model of protein denaturation on surfaces. PMID:17466368

  15. XII Recontres De Blois

    NASA Technical Reports Server (NTRS)

    Kaluzienski, Louis (Technical Monitor); Forman, William

    2004-01-01

    In the initial awarding of the grant, we had difficulty phasing our proposed support of graduate students, postdoctoral fellows and young US scientists with the meeting schedule and the grant cycle. Initially, the grant arrived too late to support the meeting. The following year, a combination of the renewal process and the meeting announcement prevented us from announcing the support opportunity sufficiently in advance to allow us to make awards and provide support. As described in the initial proposal, the Moriond and Blois meetings are a unique opportunity for younger researchers to make oral presentations of their work at an international venue. As noted above, the phasing of meetings combined with the difficulty of arranging foreign travel for scientists at other institutions precluded the possibility of supporting the proposed meetings and providing young US scientists and post-doctoral fellows support to attend these meetings.

  16. Time-dependent Ionization in a Steady Flow in an MHD Model of the Solar Corona and Wind

    NASA Astrophysics Data System (ADS)

    Shen, Chengcai; Raymond, John C.; Mikić, Zoran; Linker, Jon A.; Reeves, Katharine K.; Murphy, Nicholas A.

    2017-11-01

    Time-dependent ionization is important for diagnostics of coronal streamers and pseudostreamers. We describe time-dependent ionization calculations for a three-dimensional magnetohydrodynamic (MHD) model of the solar corona and inner heliosphere. We analyze how non-equilibrium ionization (NEI) influences emission from a pseudostreamer during the Whole Sun Month interval (Carrington rotation CR1913, 1996 August 22 to September 18). We use a time-dependent code to calculate NEI states, based on the plasma temperature, density, velocity, and magnetic field in the MHD model, to obtain the synthetic emissivities and predict the intensities of the Lyα, O VI, Mg x, and Si xii emission lines observed by the SOHO/Ultraviolet Coronagraph Spectrometer (UVCS). At low coronal heights, the predicted intensity profiles of both Lyα and O VI lines match UVCS observations well, but the Mg x and Si xii emission are predicted to be too bright. At larger heights, the O VI and Mg x lines are predicted to be brighter for NEI than equilibrium ionization around this pseudostreamer, and Si xii is predicted to be fainter for NEI cases. The differences of predicted UVCS intensities between NEI and equilibrium ionization are around a factor of 2, but neither matches the observed intensity distributions along the full length of the UVCS slit. Variations in elemental abundances in closed field regions due to the gravitational settling and the FIP effect may significantly contribute to the predicted uncertainty. The assumption of Maxwellian electron distributions and errors in the magnetic field on the solar surface may also have notable effects on the mismatch between observations and model predictions.

  17. Single Crystal Diffractometry

    NASA Astrophysics Data System (ADS)

    Arndt, U. W.; Willis, B. T. M.

    2009-06-01

    Preface; Acknowledgements; Part I. Introduction; Part II. Diffraction Geometry; Part III. The Design of Diffractometers; Part IV. Detectors; Part V. Electronic Circuits; Part VI. The Production of the Primary Beam (X-rays); Part VII. The Production of the Primary Beam (Neutrons); Part VIII. The Background; Part IX. Systematic Errors in Measuring Relative Integrated Intensities; Part X. Procedure for Measuring Integrated Intensities; Part XI. Derivation and Accuracy of Structure Factors; Part XII. Computer Programs and On-line Control; Appendix; References; Index.

  18. Medical Selection and Physiological Training of Future Fighter Aircrew. Conference Proceedings of the Aerospace Medical Panel Symposium Held in Athens, Greece on 25-26 April 1985

    DTIC Science & Technology

    1985-12-01

    over the last decade is largely due to a reduction in the " LOC Rate" (Logistics/Maintenance Factors) - 1.6/100,000 in 1975, 0.5 in 1983 and 1984...taujourc d’eztrascyetalee icaldec cane doublets xii calvoes.j r ~ Leos e*naliec do conduction A-V cant rocidoc toujoura mineurec (siuple silangement nc...tracti, landis quo. Leo troubles veniricolalrca no soni obsncvts que stir 31 tracts. Urt certain noc- bre de tracds prtsontsnt A Is fots den troubles do

  19. The AAF in Northwest Africa. An Account of the Twelfth Air Force in the Northwest African Landing and the Battle for Tunisia

    DTIC Science & Technology

    1992-01-01

    29 echelon of XII Fighter Command; the Moroccan Composite Wing operated in Morocco . All wings were activated 26 January 1943. XII Fighter Command’s...satellites, would raise Allied morale, and would encourage those ele - ments in the Axis-occupied countries which were working as best they could toward...news of the invasion, in order to fore- stall an Allied breaching of the southern coast of France, to establish submarine and air bases , and to control

  20. Boron Hydrides

    DTIC Science & Technology

    1946-07-01

    4cCdocmpcsiti- a c~f wntrca * s~r,,np1. Z P. R. XII, 6; XVII, 4.. 1. i~eu~u~ioa ýf hy,’-.r-ijn pr-babl’ ný.t -h s:bizu£ctr P. R. xII, ý;s XVII!, -1. 2. Vrt ...hour at 200OCr, brown dccozzposition preducts ~were depositod uniformly over tho hoatcd G1aiss surfae* The tube vrts opened and the hydro~cni vns renoved

  1. EGF domain of coagulation factor IX is conducive to exposure of phosphatidylserine.

    PubMed

    Hidai, Chiaki; Fujiwara, Yusuke; Kokubun, Shinichiro; Kitano, Hisataka

    2017-04-01

    Lipid rafts are an initiation site for many different signals. Recently, we reported that an EGF domain in activated coagulation factor IX (EGF-F9) increases lipid raft formation and accelerates cell migration. However, the detailed mechanism is not well understood. This study aimed to evaluate the effects of EGF-F9 on the cell membrane. A431 cells (derived from human squamous cell carcinoma) were treated with recombinant EGF-F9. Cells were immunocytochemically stained with probes for lipid rafts or phosphatidylserine (PS). After 3 min of treatment with EGF-F9, cholera toxin subunit B (CTxB) binding domains emerged at the adhesive tips of filopodia. Subsequently, CTxB staining was observed on the filopodial shaft. Finally, large clusters of CTxB domains were observed at the edge of cell bodies. Markers for lipid rafts, such as caveolin-1 and a GPI anchored protein, co-localized with CTxB. Staining with annexin V and XII revealed that PS was exposed at the tips of filopodia, translocated on filopodial shafts, and co-localized with CTxB at the rafts. Immunocytochemistry showed that scramblase-1 protein was present at the filopodial tips. Our data indicates that EGF-F9 accelerates PS exposure around the filopodial adhesion complex and induces clustering of lipid rafts in the cell body. PS exposure is thought to occur on cells undergoing apoptosis. Further study of the function of the EGF-F9 motif in mediating signal transduction is necessary because it is shared by a number of proteins. © 2017 International Federation for Cell Biology.

  2. Inhalation Toxicology. 12. Comparison of Toxicity Rankings of Six Polymers by Lethality and by Incapacitation in Rats

    DTIC Science & Technology

    1991-12-01

    DOT/FAA/AM-91/17 Inhalation Toxicology : XII. Comparison of Toxicity Office of Aviation Medicine Rankings of Six Polymers by \\Vashington, D.C. 20591...Subtitil $I Report Oat. INHALATION TOXICOLOGY : XII. COMPARISON OF TOXICITY. December 1991 RANKINGS OF SIX POLYMERS BY LETHALITY AND BY 6. Performing...the ts (min) at LC50s, the polymers were grouped into III & V (10.5, 11.0); I, II & V1 (14.1-15.0); and IV (19.5). The two toxicological end points

  3. Population Inversion and Gain Measurements for Soft X-Ray Laser Development in a Magnetically Confined Plasma Column.

    DTIC Science & Technology

    1985-09-01

    initial conditions for gas target and solid targets. (2) As in (a) but for the Li-like ions CIV, OVI, FVII , NeVIII, AtXI, and SiXII. r,," (3) To...directions indicated an enhancement of CVI 182A line intensity in the axial direction, and population inversion for Li-like CIV, OVI, FVII and NeVII ions12...lines (particularly OVI 173 A line) increased by a factor of 2-3 in comparison to our earlier data.12 Most of the measurements of line intensities

  4. Hypoglossal-facial nerve anastomosis and rehabilitation in patients with complete facial palsy: cohort study of 30 patients followed up for three years

    PubMed Central

    Toffola, Elena Dalla; Pavese, Chiara; Cecini, Miriam; Petrucci, Lucia; Ricotti, Susanna; Bejor, Maurizio; Salimbeni, Grazia; Biglioli, Federico; Klersy, Catherine

    2014-01-01

    Summary Our study evaluates the grade and timing of recovery in 30 patients with complete facial paralysis (House-Brackmann grade VI) treated with hypoglossal-facial nerve (XII-VII) anastomosis and a long-term rehabilitation program, consisting of exercises in facial muscle activation mediated by tongue movement and synkinesis control with mirror feedback. Reinnervation after XII-VII anastomosis occurred in 29 patients, on average 5.4 months after surgery. Three years after the anastomosis, 23.3% of patients had grade II, 53.3% grade III, 20% grade IV and 3.3% grade VI ratings on the House-Brackmann scale. Time to reinnervation was associated with the final House-Brackmann grade. Our study demonstrates that patients undergoing XII-VII anastomosis and a long-term rehabilitation program display a significant recovery of facial symmetry and movement. The recovery continues for at least three years after the anastomosis, meaning that prolonged follow-up of these patients is advisable. PMID:25473738

  5. Semi-aromatic polyesters based on a carbohydrate-derived rigid diol for engineering plastics.

    PubMed

    Wu, Jing; Eduard, Pieter; Thiyagarajan, Shanmugam; Noordover, Bart A J; van Es, Daan S; Koning, Cor E

    2015-01-01

    New carbohydrate-based polyesters were prepared from isoidide-2,5-dimethanol (extended isoidide, XII) through melt polymerization with dimethyl esters of terephthalic acid (TA) and furan-2,5-dicarboxylic acid (FDCA), yielding semi-crystalline prepolymers. Subsequent solid-state post-condensation (SSPC) gave high molecular weight (Mn =30 kg mol(-1) for FDCA) materials, the first examples of high Mn , semi-aromatic homopolyesters containing isohexide derivatives obtained via industrially relevant procedures. NMR spectroscopy showed that the stereo-configuration of XII was preserved under the applied conditions. The polyesters are thermally stable up to 380 °C. The TA- and FDCA-based polyesters have high Tg (105 °C and 94 °C, resp.) and Tm (284 °C and 250 °C, resp.) values. Its reactivity, stability, and ability to afford high Tg and Tm polyesters make XII a promising diol for the synthesis of engineering polymers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The XII Century Towers, a Benchmark of the Rome Countryside almost Cancelled: the Safeguard Plan by Low Cost Uav and Terrestrial Dsm Photogrammetry Surveying and 3d Web GIS Applications

    NASA Astrophysics Data System (ADS)

    Barelli, L.; Paolini, P.; Forti, G.

    2017-11-01

    "Giving a bird-fly look at the Rome countryside, throughout the Middle Age central period, it would show as if the multiple city towers has been widely spread around the territory" on a radial range of maximum thirty kilometers far from the Capitol Hill center (Carocci and Vendittelli, 2004). This is the consequence of the phenomenon identified with the "Incasalamento" neologism, described in depth in the following paper, intended as the general process of expansion of the urban society interests outside the downtown limits, started from the half of the XII and developed through all the XIII century, slowing down and ending in the following years. From the XIX century till today the architectural finds of this reality have raised the interest of many national and international scientists, which aimed to study and catalog them all to create a complete framework that, cause of its extension, didn't allow yet attempting any element by element detailed analysis. From the described situation has started our plan of intervention, we will apply integrated survey methods and technologies of terrestrial and UAV near stereo-photogrammetry, by the use of low cost drones, more than action cameras and reflex on extensible rods, integrated and referenced with GPS and topographic survey. In the final project we intend to produce some 3D scaled and textured surface models of any artifact (almost two hundreds were firstly observed still standing), to singularly study the dimensions and structure, to analyze the building materials and details and to formulate an hypothesis about any function, based even on the position along the territory. These models, successively georeferenced, will be imported into a 2D and 3D WebGIS and organized in layers made visible on basemaps of reference, as much as on historical maps.

  7. Functional Interactions between Mammalian Respiratory Rhythmogenic and Premotor Circuitry

    PubMed Central

    Song, Hanbing; Hayes, John A.; Vann, Nikolas C.; Wang, Xueying; LaMar, M. Drew

    2016-01-01

    Breathing in mammals depends on rhythms that originate from the preBötzinger complex (preBötC) of the ventral medulla and a network of brainstem and spinal premotor neurons. The rhythm-generating core of the preBötC, as well as some premotor circuits, consist of interneurons derived from Dbx1-expressing precursors (Dbx1 neurons), but the structure and function of these networks remain incompletely understood. We previously developed a cell-specific detection and laser ablation system to interrogate respiratory network structure and function in a slice model of breathing that retains the preBötC, the respiratory-related hypoglossal (XII) motor nucleus and XII premotor circuits. In spontaneously rhythmic slices, cumulative ablation of Dbx1 preBötC neurons decreased XII motor output by ∼50% after ∼15 cell deletions, and then decelerated and terminated rhythmic function altogether as the tally increased to ∼85 neurons. In contrast, cumulatively deleting Dbx1 XII premotor neurons decreased motor output monotonically but did not affect frequency nor stop XII output regardless of the ablation tally. Here, we couple an existing preBötC model with a premotor population in several topological configurations to investigate which one may replicate the laser ablation experiments best. If the XII premotor population is a “small-world” network (rich in local connections with sparse long-range connections among constituent premotor neurons) and connected with the preBötC such that the total number of incoming synapses remains fixed, then the in silico system successfully replicates the in vitro laser ablation experiments. This study proposes a feasible configuration for circuits consisting of Dbx1-derived interneurons that generate inspiratory rhythm and motor pattern. SIGNIFICANCE STATEMENT To produce a breathing-related motor pattern, a brainstem core oscillator circuit projects to a population of premotor interneurons, but the assemblage of this network remains

  8. Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides.

    PubMed

    Supuran, Claudiu T

    2008-01-01

    The widely clinically used benzothiadiazines and high ceiling diuretics, such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide, contain SO(2)NH(2) moieties acting as an effective zinc-binding function in carbonic anhydrases (CAs, EC 4.2.1.1) inhibitors. These drugs were launched in a period when only isoform CA II was known and considered physiologically/pharmacologically relevant. Although acting as moderate-weak inhibitors of CA II, all these drugs considerably inhibit other CA isozymes known nowadays to be involved in critical physiologic processes, among the 16 CAs present in vertebrates. Some low nanomolar (or even subnanomolar) inhibitors against such isoforms were recently detected, such as metholazone against CA VII, XII and XIII, chlorthalidone against CA VB, VII, IX, XII and XIII, indapamide against CA VII, IX, XII and XIII, furosemide against CA I, II and XIV, and bumethanide against CA IX and XII. The X-ray crystal structure of the CA II-indapamide adduct was also reported recently, revealing interesting aspects useful for the drug design of CA inhibitors. It has also been proposed that the recently observed beneficial effect of indapamide for the treatment of patients with hypertension and type 2 diabetes might be due to its potent inhibition of CA isoforms present in kidneys and blood vessels, which would thus explain both the blood pressure lowering effects as well as organ-protective activity of the drug. Thus, these old drugs may be useful as leads for new applications.

  9. Micro Coronal Bright Points Observed in the Quiet Magnetic Network by SOHO/EIT

    NASA Technical Reports Server (NTRS)

    Falconer, D. A.; Moore, R. L.; Porter, J. G.

    1997-01-01

    When one looks at SOHO/EIT Fe XII images of quiet regions, one can see the conventional coronal bright points (> 10 arcsec in diameter), but one will also notice many smaller faint enhancements in brightness (Figure 1). Do these micro coronal bright points belong to the same family as the conventional bright points? To investigate this question we compared SOHO/EIT Fe XII images with Kitt Peak magnetograms to determine whether the micro bright points are in the magnetic network and mark magnetic bipoles within the network. To identify the coronal bright points, we applied a picture frame filter to the Fe XII images; this brings out the Fe XII network and bright points (Figure 2) and allows us to study the bright points down to the resolution limit of the SOHO/EIT instrument. This picture frame filter is a square smoothing function (hlargelyalf a network cell wide) with a central square (quarter of a network cell wide) removed so that a bright point's intensity does not effect its own background. This smoothing function is applied to the full disk image. Then we divide the original image by the smoothed image to obtain our filtered image. A bright point is defined as any contiguous set of pixels (including diagonally) which have enhancements of 30% or more above the background; a micro bright point is any bright point 16 pixels or smaller in size. We then analyzed the bright points that were fully within quiet regions (0.6 x 0.6 solar radius) centered on disk center on six different days.

  10. LRR-RLK family from two Citrus species: genome-wide identification and evolutionary aspects.

    PubMed

    Magalhães, Diogo M; Scholte, Larissa L S; Silva, Nicholas V; Oliveira, Guilherme C; Zipfel, Cyril; Takita, Marco A; De Souza, Alessandra A

    2016-08-12

    Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subfamily of plant RLKs. The functions of most LRR-RLKs have remained undiscovered, and a few that have been experimentally characterized have been shown to have important roles in growth and development as well as in defense responses. Although RLK subfamilies have been previously studied in many plants, no comprehensive study has been performed on this gene family in Citrus species, which have high economic importance and are frequent targets for emerging pathogens. In this study, we performed in silico analysis to identify and classify LRR-RLK homologues in the predicted proteomes of Citrus clementina (clementine) and Citrus sinensis (sweet orange). In addition, we used large-scale phylogenetic approaches to elucidate the evolutionary relationships of the LRR-RLKs and further narrowed the analysis to the LRR-XII group, which contains several previously described cell surface immune receptors. We built integrative protein signature databases for Citrus clementina and Citrus sinensis using all predicted protein sequences obtained from whole genomes. A total of 300 and 297 proteins were identified as LRR-RLKs in C. clementina and C. sinensis, respectively. Maximum-likelihood phylogenetic trees were estimated using Arabidopsis LRR-RLK as a template and they allowed us to classify Citrus LRR-RLKs into 16 groups. The LRR-XII group showed a remarkable expansion, containing approximately 150 paralogs encoded in each Citrus genome. Phylogenetic analysis also demonstrated the existence of two distinct LRR-XII clades, each one constituted mainly by RD and non-RD kinases. We identified 68 orthologous pairs from the C. clementina and C. sinensis LRR-XII genes. In addition, among the paralogs, we identified a subset of 78 and 62 clustered genes probably derived from tandem duplication events in the genomes of C. clementina and C. sinensis, respectively. This work provided the first comprehensive

  11. Relativistic MR–MP Energy Levels for L-shell Ions of Silicon

    DOE PAGES

    Santana, Juan A.; Lopez-Dauphin, Nahyr A.; Beiersdorfer, Peter

    2018-01-15

    Level energies are reported for Si v, Si vi, Si vii, Si viii, Si ix, Si x, Si xi, and Si xii. The energies have been calculated with the relativistic Multi-Reference Møller–Plesset Perturbation Theory method and include valence and K-vacancy states with nl up to 5f. The accuracy of the calculated level energies is established by comparison with the recommended data listed in the National Institute of Standards and Technology (NIST) online database. The average deviation of valence level energies ranges from 0.20 eV in Si v to 0.04 eV in Si xii. For K-vacancy states, the available values recommendedmore » in the NIST database are limited to Si xii and Si xiii. The average energy deviation is below 0.3 eV for K-vacancy states. The extensive and accurate data set presented here greatly augments the amount of available reference level energies. Here, we expect our data to ease the line identification of L-shell ions of Si in celestial sources and laboratory-generated plasmas, and to serve as energy references in the absence of more accurate laboratory measurements.« less

  12. Relativistic MR–MP Energy Levels for L-shell Ions of Silicon

    NASA Astrophysics Data System (ADS)

    Santana, Juan A.; Lopez-Dauphin, Nahyr A.; Beiersdorfer, Peter

    2018-01-01

    Level energies are reported for Si V, Si VI, Si VII, Si VIII, Si IX, Si X, Si XI, and Si XII. The energies have been calculated with the relativistic Multi-Reference Møller–Plesset Perturbation Theory method and include valence and K-vacancy states with nl up to 5f. The accuracy of the calculated level energies is established by comparison with the recommended data listed in the National Institute of Standards and Technology (NIST) online database. The average deviation of valence level energies ranges from 0.20 eV in Si V to 0.04 eV in Si XII. For K-vacancy states, the available values recommended in the NIST database are limited to Si XII and Si XIII. The average energy deviation is below 0.3 eV for K-vacancy states. The extensive and accurate data set presented here greatly augments the amount of available reference level energies. We expect our data to ease the line identification of L-shell ions of Si in celestial sources and laboratory-generated plasmas, and to serve as energy references in the absence of more accurate laboratory measurements.

  13. VizieR Online Data Catalog: Relativistic MR-MP energy levels for Si (Santana+, 2018)

    NASA Astrophysics Data System (ADS)

    Santana, J. A.; Lopez-Dauphin, N. A.; Beiersdorfer, P.

    2018-03-01

    Level energies are reported for Si V, Si VI, Si VII, Si VIII, Si IX, Si X, Si XI, and Si XII. The energies have been calculated with the relativistic Multi- Reference Moller-Plesset Perturbation Theory method and include valence and K-vacancy states with nl up to 5f. The accuracy of the calculated level energies is established by comparison with the recommended data listed in the National Institute of Standards and Technology (NIST) online database. The average deviation of valence level energies ranges from 0.20eV in SiV to 0.04eV in SiXII. For K-vacancy states, the available values recommended in the NIST database are limited to Si XII and Si XIII. The average energy deviation is below 0.3eV for K-vacancy states. The extensive and accurate data set presented here greatly augments the amount of available reference level energies. We expect our data to ease the line identification of L-shell ions of Si in celestial sources and laboratory-generated plasmas, and to serve as energy references in the absence of more accurate laboratory measurements. (1 data file).

  14. Relativistic MR–MP Energy Levels for L-shell Ions of Silicon

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

    Santana, Juan A.; Lopez-Dauphin, Nahyr A.; Beiersdorfer, Peter

    Level energies are reported for Si v, Si vi, Si vii, Si viii, Si ix, Si x, Si xi, and Si xii. The energies have been calculated with the relativistic Multi-Reference Møller–Plesset Perturbation Theory method and include valence and K-vacancy states with nl up to 5f. The accuracy of the calculated level energies is established by comparison with the recommended data listed in the National Institute of Standards and Technology (NIST) online database. The average deviation of valence level energies ranges from 0.20 eV in Si v to 0.04 eV in Si xii. For K-vacancy states, the available values recommendedmore » in the NIST database are limited to Si xii and Si xiii. The average energy deviation is below 0.3 eV for K-vacancy states. The extensive and accurate data set presented here greatly augments the amount of available reference level energies. Here, we expect our data to ease the line identification of L-shell ions of Si in celestial sources and laboratory-generated plasmas, and to serve as energy references in the absence of more accurate laboratory measurements.« less

  15. PREFACE: XII Latin American workshop on plasma physics (17-21 September 2007, Caracas, Venezuela)

    NASA Astrophysics Data System (ADS)

    Puerta, Julio

    2008-10-01

    Some years ago a group of Latin American physicists took the initiative to consult about the viability of organizing a meeting on plasma physics for researchers and students of the region. The result was that it was not only a good idea, but a necessity in order to show and share everyone's work, and to keep updated on latest advances and technologies on plasma physics. It was decided that for new researchers as well as students of Physics, it would prove to be the best way to keep them posted on such matters. This was the birth of a series of meetings known as Latin American workshops on plasma physics that take place every two years in a different Latin American country. In Venezuela we have had the opportunity to organize two editions of this interesting and important reunion of physicists. The first of these Latin American workshops on plasma physics was held in Cambuquira (Brazil) in 1982. After organizing the first six editions of the workshop, the VII LAWPP meeting was realized in Caracas in January 1997. It was designed with a structure similar to the first edition. It developed in two stages, a first week devoted to short courses with lecturers in different fields of plasma physics and a second week for contributed and invited presentations. Participants from sixteen different countries were present, half of them from this continent and the other half from overseas, demonstrating the international character of this meeting. There have been four more editions of the workshop and once again, we have had the opportunity to organize this latest edition of the series: the XII Latin American workshop on plasma physics, which took place in Caracas, Venezuela from the 17th to the 21st of September 2007. The structure was modified, because contributed and review papers were together during the first stage, with short courses realized during the second one, called mini-courses, and given by several high level contributors such as José Boedo, Leopoldo Soto, Claude

  16. [Disseminated intravascular coagulation induced by endotoxin in rabbits: effect of treatment with t-PA and urokinase].

    PubMed

    Paloma, M J; Páramo, J A; Rifón, J; Rocha, E

    1992-12-01

    To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system, such as tissue plasminogen activator (t-PA) and urokinase (UK) on endotoxin-induced disseminated intravascular coagulation (DIC) in the rabbit. DIC was induced by intravenous administration of endotoxin, 20 micrograms/kg/hr during 6 hr. Four different groups were established: a) control group, receiving only saline solution; b) t-PA group receiving 0.2 mg/kg; c) t-PA group receiving 0.7 mg/kg, and d) UK group, which was given 3,000 IU/kg/hr for 6 hr. Blood samples were drawn before and after 2 hr and 6 hr of endotoxin administration. Platelet count, and fibrinogen, factor XII and antithrombin III concentrations, were assessed in each sample. Mean, standard deviation and percentage of increase or decrease with respect to the basal value, this considered 100%, were used to evaluate the findings. For comparison of values, Student's t and Mann Whitney's U were used; the Fisher test was used for mortality studies. No statistical differences appeared for any of the values in the rabbits under basal conditions. The rabbits in the control group developed DIC. No doses of t-PA modified the changes appearing in blood coagulation. UK reduced the fibrinogen and factor XII consumption induced by endotoxin. The mortality rate in the control group reached 70%. High-dose t-PA decreased such figure to 50%, while low-dose t-PA or UK failed to reduce mortality. High-dose t-PA has beneficial effects on endotoxin-induced DIC in rabbits. UK failed to achieve such effect at the doses given in this experimental DIC model.

  17. APOLLO XII - ART CONCEPT - COMMAND MODULE

    NASA Image and Video Library

    1969-11-10

    S69-58005 (10 Nov. 1969) --- An artist's concept of the Apollo 12 Command Module's (CM) interior, with the command module pilot at the controls. The Apollo 12 Lunar Module (LM) and a portion of the lunar surface are seen out of the window. Astronaut Richard F. Gordon Jr. will maneuver the Apollo 12 Command and Service Modules (CSM) in lunar orbit while astronauts Charles Conrad Jr., commander, and Alan L. Bean, lunar module pilot, explore the moon.

  18. 7 CFR 614.3 - Decisions subject to informal appeal procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Program; and (x) Conservation Innovation Grants. (2) Non-Title XII conservation programs or provisions, including: (i) Agriculture Management Assistance Program; (ii) Emergency Watershed Protection Program; (iii...

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

    Zelenak, Kamil, E-mail: zelenak@unm.sk; Zelenakova, Jana; DeRiggo, Julius

    Internal carotid artery (ICA) lesions in the parapharyngeal space (a dissection and a pseudoaneurysm) may present as isolated lower cranial nerves (IX, X, XI, and XII) palsy (Collet-Sicard syndrome). Some arteriopathies such as fibromuscular dysplasia and tortuosity make a vessel predisposed to dissection. Extreme vessel tortuosity makes the treatment by a stent graft impossible. Two Silk stents were used in a 46 year-old man with left lower cranial nerves (IX-XII) palsy for the treatment of left ICA spontaneous dissection with pseudoaneurysm. A follow-up angiogram 5 months later confirmed pseudoaneurysm thrombosis and patency of the left ICA. The patient recovered completelymore » from the deficits.« less

  20. Effect of calcium chloride solution immersion on surface hardness of restorative glass ionomer cements.

    PubMed

    Shiozawa, Maho; Takahashi, Hidekazu; Iwasaki, Naohiko; Uo, Motohiro

    2013-01-01

    The objective of this study was to evaluate the effect of the concentration of calcium chloride (CaCl2) solution on the surface hardness of restorative glass ionomer cements (GICs). Two high-viscosity GICs, Fuji IX GP and GlasIonomer FX-II, were immersed in several concentrations of CaCl2 solution for 1 day and 1 week. The immersed specimen surfaces were evaluated using microhardness testing, grazing incidence X-ray diffraction, and energy-dispersive X-ray spectroscopy. Immersion in a higher concentration of CaCl2 solution produced a greater increase in the surface hardness. No crystalline substance was observed on the immersed surface. Calcium ions were selectively absorbed in the matrix of the GIC surface after immersion. They reacted with the non-reacted carboxylic acid groups remaining in the cement matrix. These reactions were considered to cause an increase in the surface hardness of the GICs.

  1. 77 FR 68155 - Sunshine Act Meeting Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-15

    ...-Quality Control Compliance/3rd Party CPA XII. National Foreclosure Mitigation Counseling (NFMC) Compliance Update XIII. OHTS Watch List and Overview of Organizational Assessment Review Process XIV. Adjournment...

  2. 40 CFR 61.104 - Reporting requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... residence, school, business or office and the nearest farms producing vegetables, milk, and meat. (x) The... which these quantities were determined. (xii) The volumetric flow, diameter, effluent temperature, and...

  3. 32 CFR 865.114 - Decisional document.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Awards and decorations. (ix) Educational level. (x) Aptitude test scores. (xi) Incidents of punishment... punishment). (xii) Conviction by court-martial. (xiii) Prior military service and type of discharge received...

  4. 32 CFR 865.114 - Decisional document.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) Awards and decorations. (ix) Educational level. (x) Aptitude test scores. (xi) Incidents of punishment... punishment). (xii) Conviction by court-martial. (xiii) Prior military service and type of discharge received...

  5. 32 CFR 865.114 - Decisional document.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) Awards and decorations. (ix) Educational level. (x) Aptitude test scores. (xi) Incidents of punishment... punishment). (xii) Conviction by court-martial. (xiii) Prior military service and type of discharge received...

  6. 32 CFR 865.114 - Decisional document.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Awards and decorations. (ix) Educational level. (x) Aptitude test scores. (xi) Incidents of punishment... punishment). (xii) Conviction by court-martial. (xiii) Prior military service and type of discharge received...

  7. 49 CFR 1572.103 - Disqualifying criminal offenses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... controlled substance. (viii) Arson. (ix) Kidnapping or hostage taking. (x) Rape or aggravated sexual abuse. (xi) Assault with intent to kill. (xii) Robbery. (xiii) Fraudulent entry into a seaport as described...

  8. 49 CFR 1572.103 - Disqualifying criminal offenses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... controlled substance. (viii) Arson. (ix) Kidnapping or hostage taking. (x) Rape or aggravated sexual abuse. (xi) Assault with intent to kill. (xii) Robbery. (xiii) Fraudulent entry into a seaport as described...

  9. Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor 1 (PAC1) in the human infant brain and changes in the Sudden Infant Death Syndrome (SIDS).

    PubMed

    Huang, J; Waters, K A; Machaalani, R

    2017-07-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) and its complementary receptor, PAC1, are crucial in central respiratory control. PACAP Knockout (KO) mice exhibit a SIDS-like phenotype, with an inability to overcome noxious insults, compression of baseline ventilation, and death in the early post-neonatal period. PAC1 KO demonstrate similar attributes to PACAP-null mice, but with the addition of increased pulmonary artery pressure, consequently leading to heart failure and death. This study establishes a detailed interpretation of the neuroanatomical distribution and localization of both PACAP and PAC1 in the human infant brainstem and hippocampus, to determine whether any changes in expression are evident in infants who died of Sudden Infant Death Syndrome (SIDS) and any relationships to risk factors of SIDS including smoke exposure and sleep related parameters. Immunohistochemistry for PACAP and PAC1 was performed on formalin fixed and paraffin embedded human infant brain tissue of SIDS (n=32) and non-SIDS (n=12). The highest expression of PACAP was found in the hypoglossal (XII) of the brainstem medulla and lowest expression in the subiculum of the hippocampus. Highest expression of PAC1 was also found in XII of the medulla and lowest in the midbrain dorsal raphe (MBDR) and inferior colliculus. SIDS compared to non-SIDS had higher PACAP in the MBDR (p<0.05) and lower PAC1 in the medulla arcuate nucleus (p<0.001). Correlations were found between PACAP and PAC1 with the risk factors of smoke exposure, bed sharing, upper respiratory tract infection (URTI) and seasonal temperatures. The findings of this study show for the first time that some abnormalities of the PACAP system are evident in the SIDS brain and could contribute to the mechanisms of infants succumbing to SIDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Contact system activation and high thrombin generation in hyperthyroidism.

    PubMed

    Kim, Namhee; Gu, Ja-Yoon; Yoo, Hyun Ju; Han, Se Eun; Kim, Young Il; Nam-Goong, Il Sung; Kim, Eun Sook; Kim, Hyun Kyung

    2017-05-01

    Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extracellular traps (NET) has emerged as an important trigger of thrombosis, we hypothesized that the contact system is activated along with active NET formation in hyperthyroidism and that their markers correlate with disease severity. In 61 patients with hyperthyroidism and 40 normal controls, the levels of coagulation factors (fibrinogen, and factor VII, VIII, IX, XI and XII), D-dimer, thrombin generation assay (TGA) markers, NET formation markers (histone-DNA complex, double-stranded DNA and neutrophil elastase) and contact system markers (activated factor XII (XIIa), high-molecular-weight kininogen (HMWK), prekallikrein and bradykinin) were measured. Patients with hyperthyroidism showed higher levels of fibrinogen (median (interquartile range), 315 (280-344) vs 262 (223-300), P  = 0.001), D-dimer (103.8 (64.8-151.5) vs 50.7 (37.4-76.0), P  < 0.001), peak thrombin (131.9 (102.2-159.4) vs 31.6 (14.8-83.7), P  < 0.001) and endogenous thrombin potential (649 (538-736) vs 367 (197-1147), P  = 0.021) in TGA with 1 pM tissue factor, neutrophil elastase (1.10 (0.39-2.18) vs 0.23 (0.20-0.35), P  < 0.001), factor XIIa (66.9 (52.8-87.0) vs 73.0 (57.1-86.6), P  < 0.001), HMWK (6.11 (4.95-7.98) vs 3.83 (2.60-5.68), P  < 0.001), prekallikrein (2.15 (1.00-6.36) vs 1.41 (0.63-2.22), P  = 0.026) and bradykinin (152.4 (137.6-180.4) vs 118.3 (97.1-137.9), P  < 0.001) than did normal controls. In age- and sex-adjusted logistic regression analysis, fibrinogen, factor VIII, IX and XIIa, D-dimer, peak thrombin, neutrophil elastase, HMWK and bradykinin showed significant odds ratios representing hyperthyroidism's contribution to coagulation and contact system activation. Free T4 was significantly correlated with factors VIII and IX, D-dimer, double-stranded DNA and bradykinin. This study demonstrated that contact system

  11. 8 CFR 214.4 - Denial of certification, denial of recertification or withdrawal of SEVP certification.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...). (xii) Failure to operate as a bona fide institution of learning. (xiii) Failure to employ adequate...) Failure to maintain the physical plant, curriculum, and teaching staff in the manner represented in the...

  12. 78 FR 48901 - National Register of Historic Places; Notification of Pending Nominations and Related Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-12

    ..., 13000637 NORTH DAKOTA Grand Forks County Hariman Sanatorium, 2002 University Ave., Grand Forks, 13000633... Municipal de la Playa de Ponce, 28 Alfonso XII St., Ponce, 13000639 UTAH Salt Lake County Bennion, Howard...

  13. DNA Barcoding for Identification of ‘Candidatus Phytoplasmas’ Using a Fragment of the Elongation Factor Tu Gene

    PubMed Central

    Makarova, Olga; Contaldo, Nicoletta; Paltrinieri, Samanta; Kawube, Geofrey; Bertaccini, Assunta; Nicolaisen, Mogens

    2012-01-01

    Background Phytoplasmas are bacterial phytopathogens responsible for significant losses in agricultural production worldwide. Several molecular markers are available for identification of groups or strains of phytoplasmas. However, they often cannot be used for identification of phytoplasmas from different groups simultaneously or are too long for routine diagnostics. DNA barcoding recently emerged as a convenient tool for species identification. Here, the development of a universal DNA barcode based on the elongation factor Tu (tuf) gene for phytoplasma identification is reported. Methodology/Principal Findings We designed a new set of primers and amplified a 420–444 bp fragment of tuf from all 91 phytoplasmas strains tested (16S rRNA groups -I through -VII, -IX through -XII, -XV, and -XX). Comparison of NJ trees constructed from the tuf barcode and a 1.2 kbp fragment of the 16S ribosomal gene revealed that the tuf tree is highly congruent with the 16S rRNA tree and had higher inter- and intra- group sequence divergence. Mean K2P inter−/intra- group divergences of the tuf barcode did not overlap and had approximately one order of magnitude difference for most groups, suggesting the presence of a DNA barcoding gap. The use of the tuf barcode allowed separation of main ribosomal groups and most of their subgroups. Phytoplasma tuf barcodes were deposited in the NCBI GenBank and Q-bank databases. Conclusions/Significance This study demonstrates that DNA barcoding principles can be applied for identification of phytoplasmas. Our findings suggest that the tuf barcode performs as well or better than a 1.2 kbp fragment of the 16S rRNA gene and thus provides an easy procedure for phytoplasma identification. The obtained sequences were used to create a publicly available reference database that can be used by plant health services and researchers for online phytoplasma identification. PMID:23272216

  14. 20 CFR 606.22 - Application for cap.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief From Tax Credit... payable in such 12-month period, including the effect of interaction among program actions, and with...

  15. 20 CFR 606.22 - Application for cap.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief From Tax Credit... payable in such 12-month period, including the effect of interaction among program actions, and with...

  16. 20 CFR 606.22 - Application for cap.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief From Tax Credit... payable in such 12-month period, including the effect of interaction among program actions, and with...

  17. 20 CFR 606.22 - Application for cap.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief From Tax Credit... payable in such 12-month period, including the effect of interaction among program actions, and with...

  18. 20 CFR 606.22 - Application for cap.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief From Tax Credit... payable in such 12-month period, including the effect of interaction among program actions, and with...

  19. 'Candidatus Phytoplasma solani', a novel taxon associated with stolbur- and bois noir-related diseases of plants.

    PubMed

    Quaglino, Fabio; Zhao, Yan; Casati, Paola; Bulgari, Daniela; Bianco, Piero Attilio; Wei, Wei; Davis, Robert Edward

    2013-08-01

    Phytoplasmas classified in group 16SrXII infect a wide range of plants and are transmitted by polyphagous planthoppers of the family Cixiidae. Based on 16S rRNA gene sequence identity and biological properties, group 16SrXII encompasses several species, including 'Candidatus Phytoplasma australiense', 'Candidatus Phytoplasma japonicum' and 'Candidatus Phytoplasma fragariae'. Other group 16SrXII phytoplasma strains are associated with stolbur disease in wild and cultivated herbaceous and woody plants and with bois noir disease in grapevines (Vitis vinifera L.). Such latter strains have been informally proposed to represent a separate species, 'Candidatus Phytoplasma solani', but a formal description of this taxon has not previously been published. In the present work, stolbur disease strain STOL11 (STOL) was distinguished from reference strains of previously described species of the 'Candidatus Phytoplasma' genus based on 16S rRNA gene sequence similarity and a unique signature sequence in the 16S rRNA gene. Other stolbur- and bois noir-associated ('Ca. Phytoplasma solani') strains shared >99 % 16S rRNA gene sequence similarity with strain STOL11 and contained the signature sequence. 'Ca. Phytoplasma solani' is the only phytoplasma known to be transmitted by Hyalesthes obsoletus. Insect vectorship and molecular characteristics are consistent with the concept that diverse 'Ca. Phytoplasma solani' strains share common properties and represent an ecologically distinct gene pool. Phylogenetic analyses of 16S rRNA, tuf, secY and rplV-rpsC gene sequences supported this view and yielded congruent trees in which 'Ca. Phytoplasma solani' strains formed, within the group 16SrXII clade, a monophyletic subclade that was most closely related to, but distinct from, that of 'Ca. Phytoplasma australiense'-related strains. Based on distinct molecular and biological properties, stolbur- and bois noir-associated strains are proposed to represent a novel species level taxon, 'Ca

  20. Methylxanthines do not affect rhythmogenic preBötC inspiratory network activity but impair bursting of preBötC-driven motoneurons.

    PubMed

    Panaitescu, B; Kuribayashi, J; Ruangkittisakul, A; Leung, V; Iizuka, M; Ballanyi, K

    2013-01-01

    Clinical stimulation of preterm infant breathing with methylxanthines like caffeine and theophylline can evoke seizures. It is unknown whether underlying neuronal hyperexcitability involves the rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) in the brainstem or preBötC-driven motor networks. Inspiratory-related preBötC interneuronal plus spinal (cervical/phrenic) or cranial hypoglossal (XII) motoneuronal bursting was studied in newborn rat en bloc brainstem-spinal cords and brainstem slices, respectively. Non-respiratory bursting perturbed inspiratory cervical nerve activity in en bloc models at >0.25mM theophylline or caffeine. Rhythm in the exposed preBötC of transected en bloc preparations was less perturbed by 10mM theophylline than cervical root bursting which was more affected than phrenic nerve activity. In the preBötC of slices, even 10mM methylxanthine did not evoke seizure-like bursting whereas >1mM masked XII rhythm via large amplitude 1-10Hz oscillations. Blocking A-type γ-aminobutyric (GABAA) receptors evoked seizure-like cervical activity whereas in slices neither XII nor preBötC rhythm was disrupted. Methylxanthines (2.5-10mM), but not blockade of adenosine receptors, phosphodiesterase-4 or the sarcoplasmatic/endoplasmatic reticulum ATPase countered inspiratory depression by muscimol-evoked GABAA receptor activation that was associated with a hyperpolarization and input resistance decrease silencing preBötC neurons in slices. The latter blockers did neither affect preBötC or cranial/spinal motor network bursting nor evoke seizure-like activity or mask corresponding methylxanthine-evoked discharges. Our findings show that methylxanthine-evoked hyperexcitability originates from motor networks, leaving preBötC activity largely unaffected, and suggest that GABAA receptors contribute to methylxanthine-evoked seizure-like perturbation of spinal motoneurons whereas non-respiratory XII motoneuron oscillations are of different

  1. 12 CFR 544.2 - Charter amendments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... assumption of control by a mutual account holder of the association, or the removal of incumbent management... regulations of the Office; (xi) To wind up and dissolve, merge, consolidate, convert, or reorganize; (xii) To...

  2. 12 CFR 544.2 - Charter amendments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... assumption of control by a mutual account holder of the association, or the removal of incumbent management... regulations of the Office; (xi) To wind up and dissolve, merge, consolidate, convert, or reorganize; (xii) To...

  3. 50 CFR 23.84 - What are the roles of the Secretariat and the committees?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... functions are listed in Article XII of the Treaty and include: (1) Arranging and staffing meetings of the... effective implementation of the Convention. (5) Bringing to the attention of the Parties matters relevant to...

  4. In-Situ Remediation of MTBE Contaminated Aquifers Using Propane Biosparging. Revision 1

    DTIC Science & Technology

    2003-01-03

    above MTBE’s odor and taste threshold of 40 µg/L. Compared to other gasoline constituents, relatively few studies have been conducted to address the...xii MICROCOSM STUDY RESULTS...16 3.4.2 Microcosm Studies

  5. [Concepts in anticoagulant therapy - past, present, and future].

    PubMed

    Graf, L

    2012-11-01

    The understanding of the clotting system emerged in parallel to the development of anticoagulants. In contrast to vitamin K-antagonists and heparins that where discovered by chance, new anticoagulants have been systematically designed to specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and thrombin play a crucial role within the new cell-based model of hemostasis. Thus it is obvious that FXa and thrombin turned out to be ideal targets for anticoagulation. The proof of the concept of selective inhibition of thrombin and FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole group of new oral anticoagulants has been licensed: the direct FXa-inhibitors rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from the so far licensed products mainly in pharmacokinetics are in an advanced phase of development. A further innovative concept of anticoagulation that entered its clinical phase of development is the inhibition of factor VIII. Other new concepts such as inhibition of initiation of coagulation by blocking factor VIIa, inhibition of contact factor XII, or inhibition of factor IX are in an early phase of development.

  6. 38 CFR 21.4263 - Approval of flight training courses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., and aircraft identification number; (xi) An accounts receivable ledger; (xii) Individual instructor.... (Authority: 10 U.S.C. 16136(b); 38 U.S.C. 3034(d), 3241(c), 3680A(d)) (The Office of Management and Budget...

  7. 38 CFR 21.4263 - Approval of flight training courses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., and aircraft identification number; (xi) An accounts receivable ledger; (xii) Individual instructor.... (Authority: 10 U.S.C. 16136(b); 38 U.S.C. 3034(d), 3241(c), 3680A(d)) (The Office of Management and Budget...

  8. 38 CFR 21.4263 - Approval of flight training courses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., and aircraft identification number; (xi) An accounts receivable ledger; (xii) Individual instructor.... (Authority: 10 U.S.C. 16136(b); 38 U.S.C. 3034(d), 3241(c), 3680A(d)) (The Office of Management and Budget...

  9. 38 CFR 21.4263 - Approval of flight training courses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., and aircraft identification number; (xi) An accounts receivable ledger; (xii) Individual instructor.... (Authority: 10 U.S.C. 16136(b); 38 U.S.C. 3034(d), 3241(c), 3680A(d)) (The Office of Management and Budget...

  10. 78 FR 76328 - Notice of Approval of Indiana's Application for a Waiver of the Additional Credit Reduction That...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ...) provide that employers in a state that has an outstanding balance of advances under Title XII of the... such January 1 occurs, if a balance of advances remains at the beginning of November 10 of that year...

  11. 78 FR 76328 - Notice of Approval of South Carolina's Application for a Waiver of the Additional Credit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ...) provide that employers in a state that has an outstanding balance of advances under Title XII of the... such January 1 occurs, if a balance of advances remains at the beginning of November 10 of that year...

  12. Immunohistochemical localization of c-fos in the nuclei of the medulla oblongata in relation to asphyxia.

    PubMed

    Nogami, M; Takatsu, A; Endo, N; Ishiyama, I

    1999-01-01

    The immediately early gene product c-fos is known to be induced in neurons under noxious stimuli. Therefore, the immunohistochemistry of c-fos expression in human brains might offer information on the localization of stimulated neurons. In this study, the immunohistochemical localization of c-fos was studied in the neurons of the hypoglossal nucleus (XII), the dorsal motor nucleus of the vagal nerve (X), the nucleus solitarius (Sol), the accessory cuneate nucleus (Cun), the spinal trigeminal nucleus (V) and the inferior olive (Oli) of the human medulla oblongata from forensic autopsy cases. The neurons in the X nucleus showed the highest percentage of positive reactions for c-fos, followed in descending order by the Cun, V, Oli, XII and Sol. The c-fos immunoreactivity in the Cun and X was statistically significantly higher than in the Sol, XII and Oli. Although neurons in the Sol are known to be involved in respiration, there was no statistically significant difference in the c-fos immunoreactivity in the neurons in the Sol between asphyxia and non-asphyxia cases. On the other hand, the percentage of neurons positive for the c-fos immunoreactivity was statistically significantly higher in the Oli of asphyxia cases than of non-asphyxia cases. Our results indicate the difference in the immunoreactivity of c-fos among the nuclei of the human medulla oblongata and that the c-fos immunoreactivity in the Oli might assist the diagnosis of asphyxia.

  13. 7 CFR 1400.401 - Eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... made available under Title I of the Food, Conservation, and Energy Act of 2008, the Agricultural Market Transition Act, the Commodity Credit Corporation Charter Act (15 U.S.C. 714-714o), or subtitle D of Title XII...

  14. 7 CFR 1400.401 - Eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... made available under Title I of the Food, Conservation, and Energy Act of 2008, the Agricultural Market Transition Act, the Commodity Credit Corporation Charter Act (15 U.S.C. 714-714o), or subtitle D of Title XII...

  15. 7 CFR 1400.401 - Eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... made available under Title I of the Food, Conservation, and Energy Act of 2008, the Agricultural Market Transition Act, the Commodity Credit Corporation Charter Act (15 U.S.C. 714-714o), or subtitle D of Title XII...

  16. 7 CFR 1400.401 - Eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... made available under Title I of the Food, Conservation, and Energy Act of 2008, the Agricultural Market Transition Act, the Commodity Credit Corporation Charter Act (15 U.S.C. 714-714o), or subtitle D of Title XII...

  17. Unstable transpositions of his4 in yeast.

    PubMed Central

    Greer, H; Fink, G R

    1979-01-01

    Unstable transpositions in yeast have been selected in which the his4C gene from chromosome III is inserted into chromosome XII. This event is associated with the generation of a recessive lethal mutation, resulting from the integration of his4C into an essential gene. Strains with these transpositions are viable as diploids or aneuploids for chromosome XII. The event that generates the transpositions does not lead reciprocally to a deletion on chromosome III, implying that synthesis of a new copy of his4C and subsequent transposition may have occurred. The his4C transpositions are unstable and give rise to C- segregants at a high frequency, as a result of either precise excision of the his4C gene (restoring function of the gene into which insertion had occurred) or chromosome loss. PMID:386353

  18. An isolated right hypoglossal nerve palsy in association with infectious mononucleosis.

    PubMed Central

    Wright, G. D.; Lee, K. D.

    1980-01-01

    Following an upper respiratory tract infection, a teenage girl developed an isolated right XII nerve palsy; subsequently she was shown to have infectious mononucleosis. After 24 weeks her tongue had virtually recovered. Images Fig. 1 Fig. 2 PMID:6248842

  19. 40 CFR 93.153 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... operation to activities currently being conducted. (xii) Planning, studies, and provision of technical... control activities and adopting approach, departure, and enroute procedures for aircraft operations above... (e) of this section. (3) Research, investigations, studies, demonstrations, or training (other than...

  20. 40 CFR 93.153 - Applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... operation to activities currently being conducted. (xii) Planning, studies, and provision of technical... control activities and adopting approach, departure, and enroute procedures for aircraft operations above... (e) of this section. (3) Research, investigations, studies, demonstrations, or training (other than...

  1. 40 CFR 93.153 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... operation to activities currently being conducted. (xii) Planning, studies, and provision of technical... control activities and adopting approach, departure, and enroute procedures for aircraft operations above... (e) of this section. (3) Research, investigations, studies, demonstrations, or training (other than...

  2. 26 CFR 1.897-6T - Nonrecognition exchanges applicable to corporations, their shareholders, and other taxpayers, and...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... section 897 and the regulations thereunder, except as provided by Articles XII (9) and XXX (5) of the... regard to Article XXX (5) the Income Tax Treaty with Canada, see, Rev. Rul. 85-76, 1985-1 C.B. 409. (b...

  3. 26 CFR 1.897-6T - Nonrecognition exchanges applicable to corporations, their shareholders, and other taxpayers, and...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... section 897 and the regulations thereunder, except as provided by Articles XII (9) and XXX (5) of the... regard to Article XXX (5) the Income Tax Treaty with Canada, see, Rev. Rul. 85-76, 1985-1 C.B. 409. (b...

  4. 26 CFR 1.897-6T - Nonrecognition exchanges applicable to corporations, their shareholders, and other taxpayers, and...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... section 897 and the regulations thereunder, except as provided by Articles XII (9) and XXX (5) of the... regard to Article XXX (5) the Income Tax Treaty with Canada, see, Rev. Rul. 85-76, 1985-1 C.B. 409. (b...

  5. 78 FR 16302 - Sunshine Act Meeting; Regular Board of Directors Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-14

    ..., Washington, DC 20005. STATUS: Open. CONTACT PERSON FOR MORE INFORMATION: Erica Hall, Assistant Corporate... Discussion IV. Financial Report V. DC Office Move VI. NCST Board VII. Homeownership Challenges..., NFMC & EHLP Reports XII. Executive Session XIII. Adjournment Erica Hall, Assistant Corporate Secretary...

  6. 45 CFR 307.11 - Functional requirements for computerized support enforcement systems in operation by October 1...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... violence or child abuse); (xi) Indication of an order; (xii) Locate request type (optional); (xiii) Locate... to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT ENFORCEMENT PROGRAM), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES COMPUTERIZED SUPPORT...

  7. 45 CFR 307.11 - Functional requirements for computerized support enforcement systems in operation by October 1...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... violence or child abuse); (xi) Indication of an order; (xii) Locate request type (optional); (xiii) Locate... to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT ENFORCEMENT PROGRAM), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES COMPUTERIZED SUPPORT...

  8. 45 CFR 307.11 - Functional requirements for computerized support enforcement systems in operation by October 1...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... violence or child abuse); (xi) Indication of an order; (xii) Locate request type (optional); (xiii) Locate... to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT ENFORCEMENT PROGRAM), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES COMPUTERIZED SUPPORT...

  9. 7 CFR 610.24 - Responsibilities of State Technical Committees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... programs under Title XII of the Food Security Act of 1985 including, but not limited to, the Conservation Reserve Program, Wetlands Reserve Program, Conservation Security Program, Conservation Stewardship Program, Farm and Ranch Lands Protection Program, Grassland Reserve Program, Environmental Quality Incentives...

  10. 7 CFR 610.24 - Responsibilities of State Technical Committees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... programs under Title XII of the Food Security Act of 1985 including, but not limited to, the Conservation Reserve Program, Wetlands Reserve Program, Conservation Security Program, Conservation Stewardship Program, Farm and Ranch Lands Protection Program, Grassland Reserve Program, Environmental Quality Incentives...

  11. 7 CFR 610.24 - Responsibilities of State Technical Committees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... programs under Title XII of the Food Security Act of 1985 including, but not limited to, the Conservation Reserve Program, Wetlands Reserve Program, Conservation Security Program, Conservation Stewardship Program, Farm and Ranch Lands Protection Program, Grassland Reserve Program, Environmental Quality Incentives...

  12. 7 CFR 610.24 - Responsibilities of State Technical Committees.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... programs under Title XII of the Food Security Act of 1985 including, but not limited to, the Conservation Reserve Program, Wetlands Reserve Program, Conservation Security Program, Conservation Stewardship Program, Farm and Ranch Lands Protection Program, Grassland Reserve Program, Environmental Quality Incentives...

  13. The Sunset Supply Base: Long Term COTS Supportability, Implementing Affordable Methods and Processes

    DTIC Science & Technology

    2003-03-01

    7 D. BENEFITS OF THE SSB SYSTEM...69 Table 11: Summary of SSB Financial and Non-Financial Benefits ................................. 73 Table 12: Alignment with...SSB Specific Goals to Derived Benefits ................................ 74 xi THIS PAGE INTENTIONALLY LEFT BLANK xii LIST OF ABBREVIATIONS AND

  14. 42 CFR 1003.100 - Basis and purpose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Social Security Act; sections 421(c) and 427(b)(2) of Pub. L. 99-660; and section 201(i) of Pub. L. 107... Act); (xii) Offer inducements that they know or should know are likely to influence Medicare or State...

  15. 75 FR 42000 - Requirements for Fingerprint-Based Criminal History Records Checks for Individuals Seeking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-20

    ... Compatibility VIII. Plain Language IX. Voluntary Consensus Standards X. Finding of No Significant Environmental Impact: Availability XI. Paperwork Reduction Act Statement XII. Regulatory Analysis: Availability XIII... received seven comment letters from interested parties: Four from RTR licensees, one from the Nuclear...

  16. 33 CFR 104.210 - Company Security Officer (CSO).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... operational limitations; (vi) Methods of conducting audits, inspection and control and monitoring techniques... threats and patterns; (ix) Recognition and detection of dangerous substances and devices; (x) Recognition...) Techniques used to circumvent security measures; (xii) Methods of physical screening and non-intrusive...

  17. 33 CFR 104.210 - Company Security Officer (CSO).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... operational limitations; (vi) Methods of conducting audits, inspection and control and monitoring techniques... threats and patterns; (ix) Recognition and detection of dangerous substances and devices; (x) Recognition...) Techniques used to circumvent security measures; (xii) Methods of physical screening and non-intrusive...

  18. 33 CFR 104.210 - Company Security Officer (CSO).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... operational limitations; (vi) Methods of conducting audits, inspection and control and monitoring techniques... threats and patterns; (ix) Recognition and detection of dangerous substances and devices; (x) Recognition...) Techniques used to circumvent security measures; (xii) Methods of physical screening and non-intrusive...

  19. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases.

    PubMed

    Massberg, Steffen; Grahl, Lenka; von Bruehl, Marie-Luise; Manukyan, Davit; Pfeiler, Susanne; Goosmann, Christian; Brinkmann, Volker; Lorenz, Michael; Bidzhekov, Kiril; Khandagale, Avinash B; Konrad, Ildiko; Kennerknecht, Elisabeth; Reges, Katja; Holdenrieder, Stefan; Braun, Siegmund; Reinhardt, Christoph; Spannagl, Michael; Preissner, Klaus T; Engelmann, Bernd

    2010-08-01

    Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.

  20. Cranial nerve involvement in nasopharyngeal carcinoma: response to radiotherapy and its clinical impact.

    PubMed

    Li, Jian-Cheng; Mayr, Nina A; Yuh, William T C; Wang, Jian Z; Jiang, Guo-Liang

    2006-05-01

    To evaluate the cranial nerve (CN) palsy associated with nasopharyngeal carcinoma (NPC), we studied factors that influenced the neurologic outcome of radiotherapy (RT), and the patterns and time course of neurologic recovery of CN palsy. Between July 1987 and July 1989, 93 patients who presented with CN palsy at the time of diagnosis of NPC were studied. All patients underwent external-beam RT with either cobalt-60 or 6-MV photon beams to a dose of 69 to 84 Gy at 2 Gy per fraction. The time course and pattern of neurologic recovery (complete, partial, or none) from CN palsy were evaluated. Age, sex, stage, histology, incidence and distribution of types of CNs involved, duration of CN palsy, and time course of tumor response during RT were correlated with the patterns and the time course of neurologic CN recovery by univariate and multivariate analyses. The cases of CN palsy most commonly involved CN V (38%), CN VI (26%), and CN XII (11%), which accounted for the majority of the cases (75%). The time course of CN recovery was variable and protracted. Most patients showed significant improvement upon completion of RT (51%, 19%, and 30% complete, partial, and no recovery, respectively) and further improvement 6 months after RT (58%, 17%, and 25%, respectively). Cranial nerves V, VI, and XII accounted for 75% of cases with no recovery. Recovery was best for CNs II, IX, and XI and the sympathetic nerve (100%, 87%, 100%, and 100%, respectively) and worst for CNs IV, VII, and XII (67%, 60%, and 40%, respectively, with no recovery). Neurologic CN recovery correlated significantly with the pretherapy duration (<3 months versus > or =3 months) of CN palsy (88% versus 62%; p = .002, multivariate analysis), the time course of clinical tumor regression, and neurologic symptom improvement during RT. Age, sex, T stage, N stage, histology, anterior versus posterior CN palsies, and base of skull involvement were not significant. According to our limited data, most patients with CN

  1. Students' epistemological beliefs, expectations, and learning physics: An international comparison

    NASA Astrophysics Data System (ADS)

    Sharma, Sapna; Ahluwalia, P. K.; Sharma, S. K.

    2013-06-01

    It has been established by physics education researchers that there is a correlation between the learner’s behavior, their epistemological beliefs with which they come to the classrooms, and their success in a course. This study of Indian students and teachers explores expectations and beliefs in learning physics at the secondary and tertiary levels by making use of the Maryland Physics Expectation (MPEX) survey, which has been tested for both its validity and its reliability. The MPEX was administered to a sample of 265 Indian students at three different levels of study: (i) XII standard (high school), (ii) undergraduate (Bachelor of Science), and (iii) master’s degree (Master of Science in Physics, MS). In India, a pre-post instruction difference between the attitudes of class XII, undergraduate, and master’s students is observed with favorable improvement in master’s students as compared to deterioration in both class XII and undergraduate students. A comparison of these results with those reported in similar studies conducted in four other countries (U.S., Turkey, Philippines, and Thailand) indicates that there is a difference between the U.S. students and those of the other three countries and also between U.S. experts and Indian teachers. In all countries (U.S., India, Turkey, Thailand, and Philippines) the basic trend of expectation from pre to post test remained the same—there was a deterioration observed in all levels of students. Indian MS students were an exception. A significant difference was observed in the expectations of U.S. experts and Indian teachers. The score of favorable views of Indian class XII and undergraduate students was observed to be less than U.S. students in many clusters. No significant difference was found between Indian male and female students’ expectations at any level of study. This study shows that most Indian students have nowhere near an expert’s expectations even after instruction, which might affect their

  2. 40 CFR 60.53c - Operator training and qualification requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and types of emissions; (ii) Basic combustion principles, including products of combustion; (iii) Operation of the type of incinerator to be used by the operator, including proper startup, waste charging... procedures; (xii) Pre-startup inspections; and (xiii) Recordkeeping requirements. (2) An examination designed...

  3. 40 CFR 60.53c - Operator training and qualification requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and types of emissions; (ii) Basic combustion principles, including products of combustion; (iii) Operation of the type of incinerator to be used by the operator, including proper startup, waste charging... procedures; (xii) Pre-startup inspections; and (xiii) Recordkeeping requirements. (2) An examination designed...

  4. [Book Review] Waterfowl ecology and management by Guy A. Baldassarre and Eric G. Bolen

    USGS Publications Warehouse

    Olsen, Glenn H.

    2007-01-01

    A review of: Waterfowl Ecology and Management. Second Edition. By Guy A Baldassarre and , Eric G Bolen; illustrated by , Tamara R Sayre. Malabar (Florida): Krieger Publishing. $112.50. xii + 567 p; ill.; index. ISBN: 1‐57524‐260‐5. 2006

  5. 76 FR 76634 - Establishment of the Indian Oil Valuation Negotiated Rulemaking Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-08

    ... DEPARTMENT OF THE INTERIOR Office of Natural Resources Revenue 30 CFR Chapter XII [Docket No. ONRR... Natural Resources Revenue, Interior. ACTION: Notice. SUMMARY: On January 31, 2011, the Department.... FOR FURTHER INFORMATION CONTACT: Mr. Karl Wunderlich, Office of Natural Resources Revenue (ONRR...

  6. Association for International Agricultural and Extension Education 1994 Conference Papers. Annual Conference (10th, Arlington, Virginia, March 24-26, 1994).

    ERIC Educational Resources Information Center

    Steele, Roger E., Comp.

    Selected papers are as follows: "Member Perceptions of the Association for International Agricultural & Extension Education" (Eaton et al.); "Historical Review of U.S. Involvement in International Agricultural Education between World War II and Enactment of Title XII" (Thuemmel, Meaders); "Educational Needs of…

  7. 42 CFR 441.464 - State assurances.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... services, supports, and resources. (xii) Development of risk management agreements. (xiii) Development of... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... protect the health and welfare of individuals furnished services under the program and to assure the...

  8. 42 CFR 441.464 - State assurances.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... services, supports, and resources. (xii) Development of risk management agreements. (xiii) Development of... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... protect the health and welfare of individuals furnished services under the program and to assure the...

  9. 42 CFR 441.464 - State assurances.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... services, supports, and resources. (xii) Development of risk management agreements. (xiii) Development of... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... protect the health and welfare of individuals furnished services under the program and to assure the...

  10. 78 FR 2214 - Enhanced Weapons, Firearms Background Checks, and Security Event Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-10

    .... Voluntary Consensus Standards XI. Finding of No Significant Environmental Impact XII. Paperwork Reduction... ML110480470 of Nuclear Energy Institute, on the proposed ``Enhanced Weapons, Firearms Background Checks and... consensus standards. XI. Finding of No Significant Environmental Impact In the proposed rule published on...

  11. 76 FR 6199 - Enhanced Weapons, Firearms Background Checks, and Security Event Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-03

    ... XI. Voluntary Consensus Standards XII. Finding of No Significant Environmental Impact XIII. Paperwork... potential advantages to NRC licensees and certificate holders to enhance security. The first advantage is... advantage is that security personnel of certain licensees or certificate holders will be permitted to...

  12. Mapping QTLs for resistance against Globodera pallida (Stone) Pa2/3 in a diploid potato progeny originating from Solanum spegazzinii.

    PubMed

    Caromel, B; Mugniéry, D; Lefebvre, V; Andrzejewski, S; Ellissèche, D; Kerlan, M C; Rousselle, P; Rousselle-Bourgeois, F

    2003-05-01

    A "F1" diploid population between Solanum tuberosum 2 x and the wild Solanum spegazzinii was studied. It segregated for resistance against the potato cyst nematode Globodera pallida derived from the wild species. The inheritance had a quantitative nature. Linkage maps of AFLP and RFLP markers were constructed for both parents. Three QTLs were identified on the map of the resistant parent on chromosomes V, VI and XII, respectively. The first one had a major effect and explained more than 50% of the total variance of resistance. It is located in a cluster of resistance genes and may be the same locus as Gpa which has been described formerly. The two others explained about 20% of the total variance each. The QTL on chromosome XII is also in a cluster of resistance genes, and in an orthologous position with resistance genes against nematodes in tomato and pepper.

  13. Effects of In Vitro Osteogenic Induction on In Vivo Tissue Regeneration by Dental Pulp and Periodontal Ligament Stem Cells.

    PubMed

    Cha, Yoonsun; Jeon, Mijeong; Lee, Hyo-Seol; Kim, Seunghye; Kim, Seong-Oh; Lee, Jae-Ho; Song, Je Seon

    2015-09-01

    The aim of this study was to determine the effects of in vitro odontogenic/cementogenic differentiation on the in vivo tissue regeneration of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). DPSCs and PDLSCs were predifferentiated for 0, 4, or 8 days with an odontogenic/cementogenic medium and then transplanted into subcutaneous pockets in immunocompromised mice. The transplants were harvested 9 weeks after transplantation, and the characteristics of the newly formed tissues in vivo were analyzed by histologic staining; examining alkaline phosphate activity; immunohistochemical staining for osteocalcin, dentin sialoprotein, and type XII collagen; and quantitative real-time polymerase chain reaction to analyze the expression patterns of the following genes: RUNX2, OC, DMP1, DSPP, POSTN, CP23, and Col XII. In DPSC transplants, the amount of new tissues was similar in all groups, whereas in predifferentiated transplants the OC and DSPP expression were higher than undifferentiated transplants. Predifferentiated PDLSC transplants generated more hard tissue and expressed higher alkaline phosphatase activity than undifferentiated transplants. In particular, 8-day predifferentiated PDLSC transplants formed tissue closer to the cementum/PDL complex in vivo as confirmed by the higher expression levels of POSTN, CP23, and Col XII. Although there was no significant increase in tissue-forming ability among DPSCs after predifferentiation, predifferentiated DPSCs generated hard tissue closer to dentin. Also, predifferentiated PDLSCs appeared to be able to generate higher-quality and greater amounts of tissue for dental regeneration than undifferentiated PDLSCs. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  14. 40 CFR 70.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: (i) Coal cleaning plants (with thermal dryers); (ii) Kraft pulp mills; (iii) Portland cement plants... plants; (xii) Phosphate rock processing plants; (xiii) Coke oven batteries; (xiv) Sulfur recovery plants...) totaling more than 250 million British thermal units per hour heat input; (xxii) Petroleum storage and...

  15. 40 CFR 71.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: (i) Coal cleaning plants (with thermal dryers); (ii) Kraft pulp mills; (iii) Portland cement plants... plants; (xii) Phosphate rock processing plants; (xiii) Coke oven batteries; (xiv) Sulfur recovery plants...) totaling more than 250 million British thermal units per hour heat input; (xxii) Petroleum storage and...

  16. Ferrite Loaded Coils for Improved Wireless Power Transfer Efficiency

    DTIC Science & Technology

    2015-09-01

    visible in yellow, from [4]. ..........................................................................................4  Figure 4.  The Odyssey AUV ...47  Figure 35.  System mockup of AUV in docking/charging station...42  xii THIS PAGE INTENTIONALLY LEFT BLANK xiii LIST OF ACRONYMS AND ABBREVIATIONS AUV Autonomous Underwater Vehicle CST

  17. 78 FR 22659 - Revisions to the Export Administration Regulations: Initial Implementation of Export Control Reform

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-16

    ... Designed'' Definition B. Other Definitions XXIV. Part 774--The Commerce Control List A. Product Group... Changes H. Country Groups XII. Part 742--Control Policy A. National Security (NS) Review Policy B...-all controls on parts, components, accessories, and attachments specifically designed or modified for...

  18. 42 CFR 88.1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... sites in the respiratory system and intrathoracic organs. (xi) Mesothelioma. (xii) Malignant neoplasms of the peripheral nerves and autonomic nervous system, and other connective and soft tissue. (xiii... disorder means a chronic or recurrent disorder of the musculoskeletal system caused by heavy lifting or...

  19. 42 CFR 9.3 - Sanctuary policies and responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... decree for, any violation of the Animal Welfare Act; (vii) Create a safe and species-appropriate physical... not prohibit educational activities that may involve limited viewing of chimpanzees in their... importance to the ecological system that does not adversely affect the chimpanzees' routine.); (xii) Staff...

  20. 15 CFR 30.3 - Electronic Export Information filer requirements, parties to export transactions, and...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .../units of measure. (ix) Value. (x) Export Control Classification Number (ECCN) or sufficient technical information to determine the ECCN. (xi) All licensing information necessary to file the EEI for commodities... export. (xi) Foreign port of unloading. (xii) Shipping weight. (xiii) ECCN. (xiv) License or license...

  1. 15 CFR 30.3 - Electronic Export Information filer requirements, parties to export transactions, and...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .../units of measure. (ix) Value. (x) Export Control Classification Number (ECCN) or sufficient technical information to determine the ECCN. (xi) All licensing information necessary to file the EEI for commodities... export. (xi) Foreign port of unloading. (xii) Shipping weight. (xiii) ECCN. (xiv) License or license...

  2. 15 CFR 30.3 - Electronic Export Information filer requirements, parties to export transactions, and...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .../units of measure. (ix) Value. (x) Export Control Classification Number (ECCN) or sufficient technical information to determine the ECCN. (xi) All licensing information necessary to file the EEI for commodities... export. (xi) Foreign port of unloading. (xii) Shipping weight. (xiii) ECCN. (xiv) License or license...

  3. 15 CFR 30.3 - Electronic Export Information filer requirements, parties to export transactions, and...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .../units of measure. (ix) Value. (x) Export Control Classification Number (ECCN) or sufficient technical information to determine the ECCN. (xi) All licensing information necessary to file the EEI for commodities... export. (xi) Foreign port of unloading. (xii) Shipping weight. (xiii) ECCN. (xiv) License or license...

  4. 15 CFR 30.3 - Electronic Export Information filer requirements, parties to export transactions, and...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .../units of measure. (ix) Value. (x) Export Control Classification Number (ECCN) or sufficient technical information to determine the ECCN. (xi) All licensing information necessary to file the EEI for commodities... export. (xi) Foreign port of unloading. (xii) Shipping weight. (xiii) ECCN. (xiv) License or license...

  5. 14 CFR 61.68 - Category III pilot authorization requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... height, as applicable, including use of a radar altimeter; (iii) Recognition of and proper reaction to...; and (xii) Recognition of, and reaction to, airborne or ground system faults or abnormalities... adverse lateral touchdown displacement allowing a safe landing on the runway; and (D) In weather...

  6. 14 CFR 61.68 - Category III pilot authorization requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... height, as applicable, including use of a radar altimeter; (iii) Recognition of and proper reaction to...; and (xii) Recognition of, and reaction to, airborne or ground system faults or abnormalities... adverse lateral touchdown displacement allowing a safe landing on the runway; and (D) In weather...

  7. 14 CFR 61.68 - Category III pilot authorization requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... height, as applicable, including use of a radar altimeter; (iii) Recognition of and proper reaction to...; and (xii) Recognition of, and reaction to, airborne or ground system faults or abnormalities... adverse lateral touchdown displacement allowing a safe landing on the runway; and (D) In weather...

  8. 26 CFR 513.11 - Refund of income tax withheld during 1951.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., royalties, natural resource royalties, real property rentals, pensions, or life annuities is in excess of... items of income were derived, (i) a nonresident alien (including a nonresident alien individual... of pensions or life annuities entitled to the benefit of Article XII of the convention, the...

  9. 26 CFR 513.11 - Refund of income tax withheld during 1951.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., royalties, natural resource royalties, real property rentals, pensions, or life annuities is in excess of... items of income were derived, (i) a nonresident alien (including a nonresident alien individual... of pensions or life annuities entitled to the benefit of Article XII of the convention, the...

  10. 26 CFR 513.11 - Refund of income tax withheld during 1951.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., royalties, natural resource royalties, real property rentals, pensions, or life annuities is in excess of... items of income were derived, (i) a nonresident alien (including a nonresident alien individual... of pensions or life annuities entitled to the benefit of Article XII of the convention, the...

  11. 26 CFR 513.11 - Refund of income tax withheld during 1951.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., royalties, natural resource royalties, real property rentals, pensions, or life annuities is in excess of... items of income were derived, (i) a nonresident alien (including a nonresident alien individual... of pensions or life annuities entitled to the benefit of Article XII of the convention, the...

  12. 26 CFR 513.11 - Refund of income tax withheld during 1951.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., royalties, natural resource royalties, real property rentals, pensions, or life annuities is in excess of... items of income were derived, (i) a nonresident alien (including a nonresident alien individual... of pensions or life annuities entitled to the benefit of Article XII of the convention, the...

  13. 32 CFR 505.7 - Disclosure of personal information to other agencies and third parties.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for federal employment); (xii) Social Security Number (SSN); and (xiii) The information that would... released if their positions or duties require frequent interaction with the public. (3) Disclosure of.... (g) Social rosters. (1) Before including personal information such as a spouse's name, home addresses...

  14. 15 CFR 1180.11 - Relation to other laws and procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... XII); (5) Compliance with requirements to distribute publications through the Depository Library... secret in the interest of national defense or foreign policy and are in fact properly classified pursuant...). (d) In order to facilitate cooperation between agencies and the Depository Libraries— (1) NTIS will...

  15. 75 FR 43865 - Licenses, Certifications, and Approvals for Material Licensees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    .... Environmental Impact--Categorical Exclusion X. Paperwork Reduction Act Statement XI. Regulatory Analysis XII... the briefing, the Commission received a letter from the Nuclear Energy Institute (NEI) dated March 3... that such activities were conducted so as to minimize their environmental impact, and to conform the...

  16. Studies in Reaction to Disability. XII: Structure of Attitudes toward the Physically Disabled; Disability Factor Scales--Amputation, Blindness, Cosmetic Conditions.

    ERIC Educational Resources Information Center

    Siller, Jerome; And Others

    To describe and to develop instruments to measure attitudes toward amputees, the blind, and those with cosmetic conditions, three groups of subjects responded to one of three large pools of items tapping attitudes toward the three disability conditions. Three new groups of about 500 subjects of diverse demographic characteristics were given one of…

  17. [Stability of disintegration in health food].

    PubMed

    Ma, Lan; Zhao, Xin; Zhou, Shuang; Yang, Dajin

    2012-11-01

    To study the change of disintegration of different formulation samples which stored in the artificial climate box or room temperature and provide the technical support for health food monitoring. According to the method of Chinese Pharmacopoeia and British Pharmacopoeia. Appendix XII A. Disintegration 2010. Disintegration of the non-accelerate, accelerated after 1, 2 and 3 months samples were determined by the disintegrator, respectively. Sample properties, the ingredients of the samples, the proportions of the capsule and treatment methods have some effect on the stability of the disintegration. The disintegration time of health food will be changed particularly after they were accelerated under the condition of (38 +/- 1) degrees C/75% RH. Especially the disintegration time of soft capsules were significantly prolonged. The composition and properties of samples were the main factors that affected the disintegration.

  18. The status of Fast Ignition Realization Experiment (FIREX) and prospects for inertial fusion energy

    NASA Astrophysics Data System (ADS)

    Azechi, H.; FIREX Project Team

    2016-05-01

    Here we report recent progress for the fast ignition inertial confinement fusion demonstration. The fraction of low energy (< 1 MeV) component of the relativistic electron beam (REB), which efficiently heats the fuel core, increases by a factor of 4 by enhancing pulse contrast of heating laser and removing preformed plasma sources. Kilo-tesla magnetic field is studied to guide the diverging REB to the fuel core. The transport simulation of the REB accelerated by the heating laser in the externally applied and compressed magnetic field indicates that the REB can be guided efficiently to the fuel core. The integrated simulation shows > 4% of the heating efficiency and > 4 keV of ion temperature are achievable by using GEKKO-XII and LFEX, properly designed cone-fuel and an external magnetic field.

  19. 26 CFR 301.6103(j)(1)-1 - Disclosures of return information reflected on returns to officers and employees of the...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., and information derived from the Social Security Administration and other sources for the purposes of...) Total Social Security benefits. (x) Adjusted gross income. (xi) Type of tax return filed. (xii) Entity.... (xiv) Posting cycle date relative to filing. (xv) Social Security benefits. (xvi) Earned Income (as...

  20. 26 CFR 301.6103(j)(1)-1 - Disclosures of return information reflected on returns to officers and employees of the...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., and information derived from the Social Security Administration and other sources for the purposes of...) Total Social Security benefits. (x) Adjusted gross income. (xi) Type of tax return filed. (xii) Entity.... (xiv) Posting cycle date relative to filing. (xv) Social Security benefits. (xvi) Earned Income (as...

  1. 26 CFR 301.6103(j)(1)-1 - Disclosures of return information reflected on returns to officers and employees of the...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., and information derived from the Social Security Administration and other sources for the purposes of...) Total Social Security benefits. (x) Adjusted gross income. (xi) Type of tax return filed. (xii) Entity.... (xiv) Posting cycle date relative to filing. (xv) Social Security benefits. (xvi) Earned Income (as...

  2. 26 CFR 301.6103(j)(1)-1 - Disclosures of return information reflected on returns to officers and employees of the...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., and information derived from the Social Security Administration and other sources for the purposes of...) Total Social Security benefits. (x) Adjusted gross income. (xi) Type of tax return filed. (xii) Entity.... (xiv) Posting cycle date relative to filing. (xv) Social Security benefits. (xvi) Earned Income (as...

  3. 40 CFR Table 8 to Subpart Zzzz of... - Applicability of General Provisions to Subpart ZZZZ.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... predictable SSM Yes. § 63.8(c)(1)(ii) SSM not in Startup Shutdown Malfunction Plan Yes. § 63.8(c)(1)(iii...)-(v) Records related to SSM No. § 63.10(b)(2)(vi)-(xi) Records Yes. § 63.10(b)(2)(xii) Record when...

  4. 40 CFR Table 8 to Subpart Zzzz of... - Applicability of General Provisions to Subpart ZZZZ.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... predictable SSM Yes. § 63.8(c)(1)(ii) SSM not in Startup Shutdown Malfunction Plan Yes. § 63.8(c)(1)(iii...)-(v) Records related to SSM No. § 63.10(b)(2)(vi)-(xi) Records Yes. § 63.10(b)(2)(xii) Record when...

  5. Assessing the Totalitarian Islamists: A Strategy of Alliances

    DTIC Science & Technology

    2008-01-01

    org> (11 January 2008). 26 6 Irakly G. Areshidze, "Helping Georgia?," Perspective (Boston University) XII, March/April (2002). 7 Andrew E. Kramer...John Rollins, and Steven Woehrel. "Islamist Extremism in Europe." Congressional Research Service, 29 July 2005. Areshidze, Irakly G. "Helping Georgia

  6. 26 CFR 301.6103(j)(1)-1 - Disclosures of return information reflected on returns to officers and employees of the...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., and information derived from the Social Security Administration and other sources for the purposes of...) Total Social Security benefits. (x) Adjusted gross income. (xi) Type of tax return filed. (xii) Entity.... (xiv) Posting cycle date relative to filing. (xv) Social Security benefits. (xvi) Earned Income (as...

  7. 44 CFR 206.437 - State administrative plan.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... requests for advances of funds and reimbursement; (vii) Monitor and evaluate the progress and completion of... technical assistance as required to subgrantee(s); (xi) Comply with the administrative and audit requirements of 44 CFR parts 13 and 206; (xii) Provide quarterly progress reports to the Regional Administrator...

  8. 44 CFR 206.437 - State administrative plan.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... requests for advances of funds and reimbursement; (vii) Monitor and evaluate the progress and completion of... technical assistance as required to subgrantee(s); (xi) Comply with the administrative and audit requirements of 44 CFR parts 13 and 206; (xii) Provide quarterly progress reports to the Regional Administrator...

  9. 44 CFR 361.3 - Project description.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the Earthquake Hazards Reduction Act is to develop, in areas of seismic risk, improved understanding... retrofitting existing structures that pose threats to life or would suffer major damage in the event of a... (xii) Organization and management. (3) Public awareness/earthquake education activities are designed to...

  10. 31 CFR 16.3 - Basis for civil penalties and assessments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Development or the Secretary of Agriculture; (vii) Benefits under the special supplemental food program for women, infants, and children established under section 17 of the Child Nutrition Act of 1966; (viii... the Social Security Act; (xii) Aid to families with dependent children under a State plan approved...

  11. 31 CFR 16.3 - Basis for civil penalties and assessments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Development or the Secretary of Agriculture; (vii) Benefits under the special supplemental food program for women, infants, and children established under section 17 of the Child Nutrition Act of 1966; (viii... the Social Security Act; (xii) Aid to families with dependent children under a State plan approved...

  12. 31 CFR 16.3 - Basis for civil penalties and assessments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Development or the Secretary of Agriculture; (vii) Benefits under the special supplemental food program for women, infants, and children established under section 17 of the Child Nutrition Act of 1966; (viii... the Social Security Act; (xii) Aid to families with dependent children under a State plan approved...

  13. 31 CFR 16.3 - Basis for civil penalties and assessments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Development or the Secretary of Agriculture; (vii) Benefits under the special supplemental food program for women, infants, and children established under section 17 of the Child Nutrition Act of 1966; (viii... the Social Security Act; (xii) Aid to families with dependent children under a State plan approved...

  14. 31 CFR 16.3 - Basis for civil penalties and assessments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Development or the Secretary of Agriculture; (vii) Benefits under the special supplemental food program for women, infants, and children established under section 17 of the Child Nutrition Act of 1966; (viii... the Social Security Act; (xii) Aid to families with dependent children under a State plan approved...

  15. 75 FR 6229 - Consolidated Tape Association; Notice of Filing of the Fifteenth Substantive Amendment to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... Plan (``Amendments'') would amend the Plans to provide that the Participants pay the Network B Administrator a fixed annual fee in exchange for its performance of Network B administrator functions under the... Amendments Network Administrator Fees under the Plans. Section XII (``Financial Matters'') of the CTA and...

  16. 3 CFR 13605 - Executive Order 13605 of April 13, 2012. Supporting Safe and Responsible Development of...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... primary regulators of onshore oil and gas activities, the Federal Government has an important role to play... important for effective implementation of these programs and activities. To formalize and promote ongoing... Council on Environmental Quality; (xi) the Office of Science and Technology Policy; (xii) the Office of...

  17. 26 CFR 1.1031(a)-2 - Additional rules for exchanges of personal property.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Common Nontaxable Exchanges § 1.1031(a)-2...), (viii) Heavy general purpose trucks (asset class 00.242), (ix) Railroad cars and locomotives, except...-road (asset class 00.26), (xi) Trailers and trailer-mounted containers (asset class 00.27), (xii...

  18. Stolbur Phytoplasma Transmission to Maize by Reptalus panzeri and the Disease Cycle of Maize Redness in Serbia

    USDA-ARS?s Scientific Manuscript database

    Maize redness (MR), induced by stolbur phytoplasma (Candidatus Phytoplasma solani, subgroup 16SrXII-A), is characterized by midrib, leaf and stalk reddening and abnormal ear development. MR has been reported from Serbia, Romania and Bulgaria for 50 years, and recent epiphytotics reduced yields by 4...

  19. 15 CFR 742.9 - Anti-terrorism: Syria.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... will generally be denied: (i) Items that are controlled for chemical and biological weapons... fertilizers containing ammonium nitrate, controlled under ECCN 1C997. (xi) Technology for the production of Chemical Weapons Convention (CWC) Schedule 2 and 3 chemicals controlled under ECCN 1E355. (xii) Concealed...

  20. Involving Corporations in Dispensing During Mass Prophylaxis

    DTIC Science & Technology

    2007-03-01

    BLANK xi LIST OF TABLES Table 3.1 SWOT for Current Public Health Response Option............................ 34 Table 3.2 SWOT for the Postal...Service Option .................................................. 36 Table 3.3 SWOT for the Corporate Support Option...39 Table 3.4 SWOT for the Composite Support Option .......................................... 41 xii

  1. Leadership, Self-Efficacy, and Student Achievement

    ERIC Educational Resources Information Center

    Grayson, Kristin

    2013-01-01

    This study examined the relationships between teacher leadership, science teacher self-efficacy, and fifth-grade science student achievement in diverse schools in a San Antonio, Texas, metropolitan school district. Teachers completed a modified version of the "Leadership Behavior Description Question" (LBDQ) Form XII by Stogdill (1969),…

  2. 20 CFR 606.5 - Verification of estimates and review of determinations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Verification of estimates and review of determinations. 606.5 Section 606.5 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL...

  3. 20 CFR 606.44 - Notification of determinations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Notification of determinations. 606.44 Section 606.44 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from...

  4. 20 CFR 606.34 - Reports of interest payable. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Reports of interest payable. [Reserved] 606.34 Section 606.34 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT...

  5. 20 CFR 606.35 - Order of application for repayments. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Order of application for repayments. [Reserved] 606.35 Section 606.35 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL...

  6. 40 CFR 82.16 - Phaseout schedule of class II controlled substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... uses or defense applications. (8) A formulator for, or an agency, department, or instrumentality of the... exemption allowances. (1) Effective January 21, 2003, a formulator of HCFC-141b, an agency, department, or... continuing investigations into and progress on possible alternatives and substitutes; (xii) A list of...

  7. 40 CFR 82.16 - Phaseout schedule of class II controlled substances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... uses or defense applications. (8) A formulator for, or an agency, department, or instrumentality of the... exemption allowances. (1) Effective January 21, 2003, a formulator of HCFC-141b, an agency, department, or... continuing investigations into and progress on possible alternatives and substitutes; (xii) A list of...

  8. Overview of the Lambda-* Performance Reasoning Frameworks

    DTIC Science & Technology

    2009-02-01

    Developing Software with Predictable Behavior,” 949-950. ICSE Companion ’08: Companion of the 30th International Conference on Software Engineering...Julio Luis; & Drake, Jose M. “Sim-MAST: Simulador de Sis- temas Distribuidos de Tiempo Real.” XII Jornadas de Concurrencia y Sistemas Distribuidos, 2004

  9. 21 CFR 330.12 - Status of over-the-counter (OTC) drugs previously reviewed under the Drug Efficacy Study (DESI).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... in the Federal Register of November 19, 1972 (37 FR 25249). (xii) Certain OTC Multiple-Vitamin Preparations for Oral Use containing excessive amounts of vitamin D and/or vitamin A (DESI 97), for which... the products into conformity with current medical knowledge and experience. (d) Manufacturers and...

  10. 21 CFR 330.12 - Status of over-the-counter (OTC) drugs previously reviewed under the Drug Efficacy Study (DESI).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... in the Federal Register of November 19, 1972 (37 FR 25249). (xii) Certain OTC Multiple-Vitamin Preparations for Oral Use containing excessive amounts of vitamin D and/or vitamin A (DESI 97), for which... the products into conformity with current medical knowledge and experience. (d) Manufacturers and...

  11. 21 CFR 330.12 - Status of over-the-counter (OTC) drugs previously reviewed under the Drug Efficacy Study (DESI).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... in the Federal Register of November 19, 1972 (37 FR 25249). (xii) Certain OTC Multiple-Vitamin Preparations for Oral Use containing excessive amounts of vitamin D and/or vitamin A (DESI 97), for which... the products into conformity with current medical knowledge and experience. (d) Manufacturers and...

  12. Network Routing Using the Network Tasking Order, a Chron Approach

    DTIC Science & Technology

    2015-03-26

    57  Figure 4.6: Maximum bandwidth possible. ..................................................................... 58  Figure 4.7: MikroTik Router...iv xii RouterOS MikroTik Router Operating System...traffic through the network. Within the ESXi platform, four MikroTik Router Operating Systems (RouterOS) are installed. Within ESXi, the network

  13. Planck 2015 results. XII. Full focal plane simulations

    NASA Astrophysics Data System (ADS)

    Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Bartlett, J. G.; Bartolo, N.; Battaner, E.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bock, J. J.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bucher, M.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cardoso, J.-F.; Castex, G.; Catalano, A.; Challinor, A.; Chamballu, A.; Chiang, H. C.; Christensen, P. R.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Couchot, F.; Coulais, A.; Crill, B. P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Dickinson, C.; Diego, J. M.; Dolag, K.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Ducout, A.; Dupac, X.; Efstathiou, G.; Elsner, F.; Enßlin, T. A.; Eriksen, H. K.; Fergusson, J.; Finelli, F.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Frejsel, A.; Galeotta, S.; Galli, S.; Ganga, K.; Ghosh, T.; Giard, M.; Giraud-Héraud, Y.; Gjerløw, E.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Hansen, F. K.; Hanson, D.; Harrison, D. L.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huffenberger, K. M.; Hurier, G.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Karakci, A.; Keihänen, E.; Keskitalo, R.; Kiiveri, K.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lamarre, J.-M.; Lasenby, A.; Lattanzi, M.; Lawrence, C. R.; Leonardi, R.; Lesgourgues, J.; Levrier, F.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; Lindholm, V.; López-Caniego, M.; Lubin, P. M.; Macías-Pérez, J. F.; Maggio, G.; Maino, D.; Mandolesi, N.; Mangilli, A.; Maris, M.; Martin, P. G.; Martínez-González, E.; Masi, S.; Matarrese, S.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Melin, J.-B.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Moss, A.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paoletti, D.; Pasian, F.; Patanchon, G.; Pearson, T. J.; Perdereau, O.; Perotto, L.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Roman, M.; Rosset, C.; Rossetti, M.; Roudier, G.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Santos, D.; Savelainen, M.; Scott, D.; Seiffert, M. D.; Shellard, E. P. S.; Spencer, L. D.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Tuovinen, J.; Valenziano, L.; Valiviita, J.; Van Tent, B.; Vielva, P.; Villa, F.; Wade, L. A.; Wandelt, B. D.; Wehus, I. K.; Welikala, N.; Yvon, D.; Zacchei, A.; Zonca, A.

    2016-09-01

    We present the 8th full focal plane simulation set (FFP8), deployed in support of the Planck 2015 results. FFP8 consists of 10 fiducial mission realizations reduced to 18 144 maps, together with the most massive suite of Monte Carlo realizations of instrument noise and CMB ever generated, comprising 104 mission realizations reduced to about 106 maps. The resulting maps incorporate the dominant instrumental, scanning, and data analysis effects, and the remaining subdominant effects will be included in future updates. Generated at a cost of some 25 million CPU-hours spread across multiple high-performance-computing (HPC) platforms, FFP8 is used to validate and verify analysis algorithms and their implementations, and to remove biases from and quantify uncertainties in the results of analyses of the real data.

  14. Environmental Education Manual for Grades I to XII.

    ERIC Educational Resources Information Center

    Houghton, J. R.

    This manual focuses on the interdisciplinary approach to environmental education for grades 1 to 12 by providing curriculum models for each grade level. Models, presented in a three-column format, display relationships between concepts and ideas with an environmental focus and various subjects/disciplines. The central column (headed Environmental…

  15. Planck 2015 results: XII. Full focal plane simulations

    DOE PAGES

    Ade, P. A. R.; Aghanim, N.; Arnaud, M.; ...

    2016-09-20

    In this paper, we present the 8th full focal plane simulation set (FFP8), deployed in support of the Planck 2015 results. FFP8 consists of 10 fiducial mission realizations reduced to 18 144 maps, together with the most massive suite of Monte Carlo realizations of instrument noise and CMB ever generated, comprising 10 4 mission realizations reduced to about 10 6 maps. The resulting maps incorporate the dominant instrumental, scanning, and data analysis effects, and the remaining subdominant effects will be included in future updates. Finally, generated at a cost of some 25 million CPU-hours spread across multiple high-performance-computing (HPC) platforms,more » FFP8 is used to validate and verify analysis algorithms and their implementations, and to remove biases from and quantify uncertainties in the results of analyses of the real data.« less

  16. Mid-Infrared Optoelectronics: Materials and Devices. MIOMD-XII

    DTIC Science & Technology

    2014-10-01

    current. An enhancement of the QEPAS signal can be achieved when two metallic tubes acting as a micro‐ resonator (mR) are added to the QTF sensor ...spectrophone configuration using a 5.8 mm long micro‐ resonator with an inner diameter of 0.80 mm [3]. In order to test and validate the developed QEPAS sensor ...materials, photodetectors, sensors and applications have been discussed in other sessions. The papers were submitted by researchers representing 107

  17. International Congress on Glass XII (in several languages)

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

    Doremus, R H; LaCourse, W C; Mackenzie, J D

    1980-01-01

    A total of 158 papers are included under nine headings: structure and glass formation; optical properties; electrical and magnetic properties; mechanical properties and relaxation; mass transport; chemical durability and surfaces; nucleation; crystallization; and glass ceramics; processing; and automatic controls. Separate abstracts were prepared for eight papers; four of the remaining papers had been processed previously for the data base. (DLC)

  18. Innovation Abstracts: Volume XII, Numbers 1-30, 1990.

    ERIC Educational Resources Information Center

    Roueche, Susanne D., Ed.

    1990-01-01

    This series of one- to two-page abstracts highlights a variety of innovative approaches to teaching and learning in the community college. Topics covered in the abstracts include: (1) academic partnerships pairing "high-risk" students with a concerned faculty member, counselor, or administrator; (2) teacher-to-teacher learning partnerships; (3)…

  19. Division XII / Commission 41 / Working Group Historical Instruments

    NASA Astrophysics Data System (ADS)

    Pigatto, Luisa; Il-Seong, Nha; Hamel, Jürgen; Johnson, Kevin; Kochhar, Rajesh K.; Nakamura, Tsuko; Orchiston, Wayne; Pettersen, Bjørn R.; Schechner, Sara J.; Yunli, Shi

    The Historical Instruments Working Group (WG-HI) and Commission 41 started planning an interdisciplinary conference titled Astronomy and its instruments before and after Galileo since January 2007. This conference, as an IYA2009 initiative, aims “to highlight mankind's path toward an improved knowledge of the sky using mathematical and mechanical tools as well as monuments and buildings, giving rise, in doing so, to scientific astronomy”. Commission 46 and Commission 55 also support this conference, to be held on the Isle of San Servolo, Venice (Italy), 27 September 3 October 2009. As a fact of history, it was in Venice that Galileo was advised and got material (glass) to make his telescope, and in Venice he presented an working instrument to Venetian Doge in August 1609. The conference is co-sponsored by IAU as a Joint Symposium with the INAF Astronomical Observatory of Padova, Italy.

  20. Tabulation of comet observations.

    NASA Astrophysics Data System (ADS)

    1985-04-01

    Concerning comets: 1961 VIII Seki, 1962 III Seki-Lines, 1963 I Ikeya, 1963 III Alcock, 1964 VIII Ikeya, 1965 VIII Ikeya-Seki, 1966 V Kilston, 1967 II Rudnicki, 1968 I Ikeya-Seki, 1968 VI Honda, 1969 IX Tago-Sato-Kosaka, 1970 II Bennett, 1971 V Toba, 1973 XII Kohoutek, 1974 II P/Schwassmann-Wachmann 1, 1974 III Bradfield, 1975 IX Kobayashi-Berger-Milon, 1975 X Suzuki-Saigusa-Mori, 1975 XII Mori-Sato-Fujikawa, 1976 VI West, 1976 XI P/d'Arrest, 1979 X Bradfield, 1980 XI P/Encke, 1980 XIII P/Tuttle, 1980 XV Bradfield, 1981 II Panther, 1982i P/Halley, 1983 XIII P/Kopff, 1983n P/Crommelin, 1983v P/Hartley-IRAS, 1983w P/Clark, 1984c P/Neujmin, 1984f Shoemaker, 1984g P/Wolf-Harrington, 1984h P/Faye, 1984i Austin, 1984j P/Takamizawa, 1984k P/Arend-Rigaux, 1984m P/Schaumasse, 1984p Tsuchinshan 1, 1984q P/Shoemaker 1, 1984s Shoemaker, 1984t Levy-Rudenko.

  1. Identification of hydrogenlike and heliumlike transitions in the spectrum of laser-produced magnesium plasmas

    NASA Technical Reports Server (NTRS)

    Moreno, J. C.; Goldsmith, S.; Griem, H. R.; Cohen, Leonard; Knauer, J.

    1990-01-01

    Nonresonance spectral lines of Mg XII and Mg XI emitted by magnesium laser-produced plasmas have been observed in the extreme-vacuum-ultraviolet region and their transitions classified. As many as eight beams of the Omega laser system of the Laboratory for Laser Energetics at the University of Rochester were linearly focused onto magnesium-coated flat targets to produce linear plasma radiation sources from 3 to 6 mm long. The spectra were photographed end-on with a grazing-incidence spectrograph. The identified Mg XII lines are classified as 2s-3p, 2p-3d, 2s-4p, 2p-4d, and 3d-4f transitions. The identified Mg XI lines are classified as 1s2s-1s3p, 1s2p-1s3d, 1s2p-1s4d, 1s3p-1s4d, and 1s3d-1s4f.

  2. 40 CFR Table 8 to Subpart Zzzz of... - Applicability of General Provisions to Subpart ZZZZ.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... predictable SSM No § 63.8(c)(1)(ii) SSM not in Startup Shutdown Malfunction Plan Yes. § 63.8(c)(1)(iii... SSM No. § 63.10(b)(2)(vi)-(xi) Records Yes. § 63.10(b)(2)(xii) Record when under waiver Yes. § 63.10(b...

  3. 40 CFR Table 8 to Subpart Zzzz of... - Applicability of General Provisions to Subpart ZZZZ.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... predictable SSM No § 63.8(c)(1)(ii) SSM not in Startup Shutdown Malfunction Plan Yes. § 63.8(c)(1)(iii... SSM No. § 63.10(b)(2)(vi)-(xi) Records Yes. § 63.10(b)(2)(xii) Record when under waiver Yes. § 63.10(b...

  4. 7 CFR 1485.13 - Application process and strategic plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... business cards; (viii) The cost of seasonal greeting cards; (ix) Fees for office parking; (x) The cost of subscriptions to publications; (xi) The cost of activities conducted overseas; (xii) Credit card fees; (xiii... fees or similar sales expenditures; (x) Membership fees in clubs and social organizations; and (xi) Any...

  5. 77 FR 74276 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ... Department of the Treasury is planning to submit the following information collection request to the Office... Louisa M. Quittman, Director, Financial Education, Office of Consumer Policy, U.S. Department of the... Financial Capability Outcomes. Abstract: Pursuant to the Title XII of the Dodd-Frank Wall Street Reform and...

  6. 46 CFR 154.1810 - Cargo manual.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... leakage. (4) The use of the firefighting systems on the vessel. (5) The features of the cargo containment... detection systems. (x) Alarm or safety indication systems. (xi) Cargo jettisoning system. (xii) The system...) A description of gas detection systems and alarm or safety systems. (15) A description of the...

  7. 38 CFR 36.4340 - Underwriting standards, processing procedures, lender responsibility, and lender certification.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... equity in refinancing loans; (vii) Little or no increase in shelter expense; (viii) Military benefits...; (xii) Tax credits of a continuing nature, such as tax credits for child care; and (xiii) Tax benefits... supplied in the Consumer Expenditure Survey (CES) published by the Department of Labor's Bureau of Labor...

  8. 38 CFR 36.4340 - Underwriting standards, processing procedures, lender responsibility, and lender certification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... equity in refinancing loans; (vii) Little or no increase in shelter expense; (viii) Military benefits...; (xii) Tax credits of a continuing nature, such as tax credits for child care; and (xiii) Tax benefits... supplied in the Consumer Expenditure Survey (CES) published by the Department of Labor's Bureau of Labor...

  9. 38 CFR 36.4340 - Underwriting standards, processing procedures, lender responsibility, and lender certification.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... equity in refinancing loans; (vii) Little or no increase in shelter expense; (viii) Military benefits...; (xii) Tax credits of a continuing nature, such as tax credits for child care; and (xiii) Tax benefits... supplied in the Consumer Expenditure Survey (CES) published by the Department of Labor's Bureau of Labor...

  10. 27 CFR 9.108 - Ozark Mountain.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Creek; (xii) Then northeastward along Rock Creek to Petit Jean Creek; (xiii) Then generally northeastward and eastward along Petit Jean Creek until it becomes the Petit Jean River (on the Russellville map); (xiv) Then generally eastward along the Petit Jean River, flowing through Blue Mountain Lake, until the...

  11. 27 CFR 9.108 - Ozark Mountain.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Creek; (xii) Then northeastward along Rock Creek to Petit Jean Creek; (xiii) Then generally northeastward and eastward along Petit Jean Creek until it becomes the Petit Jean River (on the Russellville map); (xiv) Then generally eastward along the Petit Jean River, flowing through Blue Mountain Lake, until the...

  12. 27 CFR 9.108 - Ozark Mountain.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Creek; (xii) Then northeastward along Rock Creek to Petit Jean Creek; (xiii) Then generally northeastward and eastward along Petit Jean Creek until it becomes the Petit Jean River (on the Russellville map); (xiv) Then generally eastward along the Petit Jean River, flowing through Blue Mountain Lake, until the...

  13. 27 CFR 9.108 - Ozark Mountain.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Creek; (xii) Then northeastward along Rock Creek to Petit Jean Creek; (xiii) Then generally northeastward and eastward along Petit Jean Creek until it becomes the Petit Jean River (on the Russellville map); (xiv) Then generally eastward along the Petit Jean River, flowing through Blue Mountain Lake, until the...

  14. Current Status, Planning and Prospects of the 1202 State Postsecondary Commissions.

    ERIC Educational Resources Information Center

    Fenske, Robert H., Ed.; Romesburg, Kerry D., Ed.

    With the passage of the Education Amendments of 1972, the Congress of the United States introduced to the nation's educators a new academic and educational environment. Included in those amendments, under Title XII, General Provisions, was Section 1202 pertaining to the establishment of state postsecondary education commissions, signifying an…

  15. 77 FR 28393 - Proposed Information Collection Activity; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-14

    ... include the IAATP Trainee Pretest Survey and the IAATP Trainee Follow-up Survey. Title XII, Subtitle A, of... their subsequent work with pregnant women. Extension of the pretest and follow-up data collection... increasing awareness of community resources for adoption. Pretest and follow-up versions of the survey...

  16. 14 CFR 135.125 - Aircraft security.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Aircraft security. 135.125 Section 135.125....125 Aircraft security. Certificate holders conducting operators conducting operations under this part must comply with the applicable security requirements in 49 CFR chapter XII. [67 FR 8350, Feb. 22, 2002] ...

  17. 14 CFR 135.125 - Aircraft security.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Aircraft security. 135.125 Section 135.125....125 Aircraft security. Certificate holders conducting operators conducting operations under this part must comply with the applicable security requirements in 49 CFR chapter XII. [67 FR 8350, Feb. 22, 2002] ...

  18. 14 CFR 135.125 - Aircraft security.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Aircraft security. 135.125 Section 135.125....125 Aircraft security. Certificate holders conducting operators conducting operations under this part must comply with the applicable security requirements in 49 CFR chapter XII. [67 FR 8350, Feb. 22, 2002] ...

  19. Experimental Analysis of Dampened Breathing Mode Oscillation on Hall Thruster Performance

    DTIC Science & Technology

    2013-03-01

    38 4.5 Analysis of Discharge RMS Effect on Breathing Mode Amplitude...20 xii EXPERIMENTAL ANALYSIS OF DAMPENED BREATHING MODE OSCILLATION ON HALL EFFECT THRUSTER...the large error in the data presented above prevents many conclusions from being drawn. 4.5 Analysis of Discharge RMS Effect on Breathing Mode

  20. U. S. Naval Forces, Vietnam Monthly Historical Summary for July 1970

    DTIC Science & Technology

    1970-09-22

    o o- e ... " ......... CURRENT OPERATIONS ......... ............ I* USN OPERATIONS .7 - Operation Sea Float / Tran I-Tung Dao III...Fleet 21......................... .............. 19 VNN OPERATIONS . Tran Hung Dao I............ .................... 21 Tran Hung Dao II...24 Tran Hung Dao V .................................... 28Tran Hung Dao XI 30 Tran Hung Dao XII (Special Operation

  1. 20 CFR 606.40 - May/September delay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false May/September delay. 606.40 Section 606.40 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest...

  2. 20 CFR 606.31 - Due dates for payment of interest. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Due dates for payment of interest. [Reserved] 606.31 Section 606.31 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY...

  3. 20 CFR 606.26 - Application for waiver and substitution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief From Tax Credit Reduction § 606.26 Application for waiver and substitution. (a) Application. The... year, will notify the applicant and the Secretary of the Treasury of the resulting tax credit reduction...

  4. Kinase domain-targeted isolation of defense-related receptor-like kinases (RLK/Pelle) in Platanus×acerifolia: phylogenetic and structural analysis.

    PubMed

    Pilotti, Massimo; Brunetti, Angela; Uva, Paolo; Lumia, Valentina; Tizzani, Lorenza; Gervasi, Fabio; Iacono, Michele; Pindo, Massimo

    2014-12-08

    Plant receptor-like kinase (RLK/Pelle) family regulates growth and developmental processes and interaction with pathogens and symbionts.Platanaceae is one of the earliest branches of Eudicots temporally located before the split which gave rise to Rosids and Asterids. Thus investigations into the RLK family in Platanus can provide information on the evolution of this gene family in the land plants.Moreover RLKs are good candidates for finding genes that are able to confer resistance to Platanus pathogens. Degenerate oligonucleotide primers targeting the kinase domain of stress-related RLKs were used to isolate for the first time 111 RLK gene fragments in Platanus×acerifolia. Sequences were classified as candidates of the following subfamilies: CrRLK1L, LRR XII, WAK-like, and LRR X-BRI1 group. All the structural features typical of the RLK kinase domain were identified, including the non-RD motif which marks potential pathogen recognition receptors (PRRs). The LRR XII candidates, whose counterpart in Arabidopsis and rice comprises non-RD PRRs, were mostly non-RD kinases, suggesting a group of PRRs. Region-specific signatures of a relaxed purifying selection in the LRR XII candidates were also found, which is novel for plant RLK kinase domain and further supports the role of LRR XII candidates as PRRs. As we obtained CrRLK1L candidates using primers designed on Pto of tomato, we analysed the phylogenetic relationship between CrRLK1L and Pto-like of plant species. We thus classified all non-solanaceous Pto-like genes as CrRLK1L and highlighted for the first time the close phylogenetic vicinity between CrRLK1L and Pto group. The origins of Pto from CrRLK1L is proposed as an evolutionary mechanism. The signatures of relaxed purifying selection highlight that a group of RLKs might have been involved in the expression of phenotypic plasticity and is thus a good candidate for investigations into pathogen resistance.Search of Pto-like genes in Platanus highlighted the close

  5. 7 CFR 1485.16 - Contribution rules.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... business cards that target a foreign audience; (viii) The cost of seasonal greeting cards; (ix) Fees for... conducted overseas; (xii) Credit card fees; (xiii) The cost of any independent evaluation or audit that is...) Membership fees in clubs and social organizations; and (xi) Any expenditure for an activity prior to CCC's...

  6. 7 CFR 1485.16 - Contribution rules.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... business cards that target a foreign audience; (viii) The cost of seasonal greeting cards; (ix) Fees for... conducted overseas; (xii) Credit card fees; (xiii) The cost of any independent evaluation or audit that is...) Membership fees in clubs and social organizations; and (xi) Any expenditure for an activity prior to CCC's...

  7. 10 CFR 50.55a - Codes and standards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... commitments must be applied to Section XI activities. (xi) [Reserved] (xii) Underwater welding. The provisions in IWA-4660, “Underwater Welding,” of Section XI, 1997 Addenda through the latest edition and addenda... performed by welding or brazing on a pressure retaining boundary using the 2003 Addenda through the latest...

  8. 10 CFR 50.55a - Codes and standards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... commitments must be applied to Section XI activities. (xi) [Reserved] (xii) Underwater welding. The provisions in IWA-4660, “Underwater Welding,” of Section XI, 1997 Addenda through the latest edition and addenda... performed by welding or brazing on a pressure retaining boundary using the 2003 Addenda through the latest...

  9. 46 CFR 56.01-10 - Plan approval.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ballast piping. (vii) Tank cleaning piping. (viii) Condenser circulating water piping. (ix) Vent, sound....) (xii) Cargo piping. (xiii) Hot water heating systems if the temperature is greater than 121 °C(250 °F... substantiate their compliance with the regulations of this subchapter; (3) A thermal stress analysis is not...

  10. 10 CFR 851.27 - Reference sources.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) American Society of Mechanical Engineers (ASME), P.O. Box 2300 Fairfield, NJ 07007. Telephone: 800-843-2763... Electrical Code,” (2005). (5) NFPA 70E, “Standard for Electrical Safety in the Workplace,” (2004). (6... Engineers (ASME) Boilers and Pressure Vessel Code, sections I through XII including applicable Code Cases...

  11. 10 CFR 851.27 - Reference sources.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) American Society of Mechanical Engineers (ASME), P.O. Box 2300 Fairfield, NJ 07007. Telephone: 800-843-2763... Electrical Code,” (2005). (5) NFPA 70E, “Standard for Electrical Safety in the Workplace,” (2004). (6... Engineers (ASME) Boilers and Pressure Vessel Code, sections I through XII including applicable Code Cases...

  12. 20 CFR 606.6 - Information, reports, and studies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Information, reports, and studies. 606.6... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT General § 606.6 Information, reports, and studies. A State shall furnish to the Secretary of Labor such...

  13. 20 CFR 606.6 - Information, reports, and studies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Information, reports, and studies. 606.6... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT General § 606.6 Information, reports, and studies. A State shall furnish to the Secretary of Labor such...

  14. 20 CFR 606.6 - Information, reports, and studies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Information, reports, and studies. 606.6... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT General § 606.6 Information, reports, and studies. A State shall furnish to the Secretary of Labor such...

  15. 26 CFR 509.115 - Visiting professors or teachers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 19 2010-04-01 2010-04-01 false Visiting professors or teachers. 509.115...) REGULATIONS UNDER TAX CONVENTIONS SWITZERLAND General Income Tax § 509.115 Visiting professors or teachers. (a) General. Pursuant to Article XII of the convention, a professor or teacher, a nonresident alien who is a...

  16. 46 CFR 58.25-60 - Non-duplicated hydraulic rudder actuators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Non-duplicated hydraulic rudder actuators. 58.25-60... actuators. Non-duplicated hydraulic rudder actuators may be installed in the steering-gear control systems on each vessel of less than 100,000 deadweight tons. These actuators must meet IMO A.467(XII...

  17. Ethical Perspectives: Leadership Subscales Applied to Education.

    ERIC Educational Resources Information Center

    Gable, Sherry K.; Kavich, Larry L.

    Ethical perspectives are needed to gain insight into the history of leader behavior, especially as related to the current emphasis on contingency and Path-Goal Theories. An instrument to help select professionals who reflect ethical traits is the Leadership Behavior Description Questionnaire with 12 leadership subscales (LBDQ, Form XII). Selected…

  18. 22 CFR 401.19 - Reducing or extending time and dispensing with statements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... statements. 401.19 Section 401.19 Foreign Relations INTERNATIONAL JOINT COMMISSION, UNITED STATES AND CANADA... any case where the Commission considers that such action would be in the public interest and not prejudicial to the right of interested persons to be heard in accordance with Article XII of the Treaty, the...

  19. 77 FR 21819 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-11

    ... of Purpose of, and Statutory Basis for, the Proposed Rule Change Under Article VI, Section 11 of the... purpose. Interpretation and Policy .01 (``Interpretation'') under Article VI, Section 11A of OCC's By-Laws... under Section 3 of Article XII (applicable to security futures), under which the Committee could under...

  20. 20 CFR 606.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT General § 606.3 Definitions. For the purposes of the Acts cited and this part— (a) Act means as appropriate the Federal Unemployment Tax Act (26...

  1. 40 CFR 82.16 - Phaseout schedule of class II controlled substances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... defense applications. (8) A formulator for, or an agency, department, or instrumentality of the U.S.; or a..., 2003, a formulator of HCFC-141b, an agency, department, or instrumentality of the U.S., or a non... investigations into and progress on possible alternatives and substitutes; (xii) A list of alternatives...

  2. 40 CFR 82.16 - Phaseout schedule of class II controlled substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... defense applications. (8) A formulator for, or an agency, department, or instrumentality of the U.S.; or a..., 2003, a formulator of HCFC-141b, an agency, department, or instrumentality of the U.S., or a non... investigations into and progress on possible alternatives and substitutes; (xii) A list of alternatives...

  3. 40 CFR 82.16 - Phaseout schedule of class II controlled substances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... defense applications. (8) A formulator for, or an agency, department, or instrumentality of the U.S.; or a..., 2003, a formulator of HCFC-141b, an agency, department, or instrumentality of the U.S., or a non... investigations into and progress on possible alternatives and substitutes; (xii) A list of alternatives...

  4. 20 CFR 606.41 - High unemployment deferral.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false High unemployment deferral. 606.41 Section... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.41 High unemployment deferral. (a) Applicability. Subsection (b)(3)(C) of section...

  5. 20 CFR 606.33 - No payment of interest from unemployment fund. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false No payment of interest from unemployment fund... LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Interest on Advances § 606.33 No payment of interest from unemployment fund. [Reserved] ...

  6. 20 CFR 606.42 - High unemployment delay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false High unemployment delay. 606.42 Section 606... THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.42 High unemployment delay. (a) Applicability. Paragraph (9) of section 1202 (b) of...

  7. 20 CFR 606.41 - High unemployment deferral.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false High unemployment deferral. 606.41 Section... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.41 High unemployment deferral. (a) Applicability. Subsection (b)(3)(C) of section...

  8. 20 CFR 606.42 - High unemployment delay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false High unemployment delay. 606.42 Section 606... THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.42 High unemployment delay. (a) Applicability. Paragraph (9) of section 1202 (b) of...

  9. 20 CFR 606.33 - No payment of interest from unemployment fund. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false No payment of interest from unemployment fund... LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Interest on Advances § 606.33 No payment of interest from unemployment fund. [Reserved] ...

  10. 20 CFR 606.33 - No payment of interest from unemployment fund. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false No payment of interest from unemployment fund... LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Interest on Advances § 606.33 No payment of interest from unemployment fund. [Reserved] ...

  11. 20 CFR 606.42 - High unemployment delay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false High unemployment delay. 606.42 Section 606... THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.42 High unemployment delay. (a) Applicability. Paragraph (9) of section 1202 (b) of...

  12. 20 CFR 606.41 - High unemployment deferral.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false High unemployment deferral. 606.41 Section... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.41 High unemployment deferral. (a) Applicability. Subsection (b)(3)(C) of section...

  13. 20 CFR 606.41 - High unemployment deferral.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false High unemployment deferral. 606.41 Section... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.41 High unemployment deferral. (a) Applicability. Subsection (b)(3)(C) of section...

  14. 20 CFR 606.42 - High unemployment delay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false High unemployment delay. 606.42 Section 606... THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.42 High unemployment delay. (a) Applicability. Paragraph (9) of section 1202 (b) of...

  15. 20 CFR 606.33 - No payment of interest from unemployment fund. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false No payment of interest from unemployment fund... LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Interest on Advances § 606.33 No payment of interest from unemployment fund. [Reserved] ...

  16. 20 CFR 606.33 - No payment of interest from unemployment fund. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false No payment of interest from unemployment fund... LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Interest on Advances § 606.33 No payment of interest from unemployment fund. [Reserved] ...

  17. 20 CFR 606.42 - High unemployment delay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false High unemployment delay. 606.42 Section 606... THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.42 High unemployment delay. (a) Applicability. Paragraph (9) of section 1202 (b) of...

  18. 20 CFR 606.41 - High unemployment deferral.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false High unemployment deferral. 606.41 Section... UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief from Interest Payment § 606.41 High unemployment deferral. (a) Applicability. Subsection (b)(3)(C) of section...

  19. 14 CFR Appendix A to Part 43 - Major Alterations, Major Repairs, and Preventive Maintenance

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... hub design. (iii) Changes in the governor or control design. (iv) Installation of a propeller governor.... (iv) Engine mounts. (v) Control system. (vi) Landing gear. (vii) Hull or floats. (viii) Elements of an... of gravity limits of the aircraft. (xii) Changes to the basic design of the fuel, oil, cooling...

  20. 12 CFR 544.2 - Charter amendments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... requirements of its charter in adopting such amendments: (1) Purpose and powers. Add a second paragraph to section 4, as follows: Section 4. Purpose and powers. * * * The association shall have the express power... regulations of the Office; (xi) To wind up and dissolve, merge, consolidate, convert, or reorganize; (xii) To...

  1. 12 CFR 544.2 - Charter amendments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... requirements of its charter in adopting such amendments: (1) Purpose and powers. Add a second paragraph to section 4, as follows: Section 4. Purpose and powers. * * * The association shall have the express power... regulations of the Office; (xi) To wind up and dissolve, merge, consolidate, convert, or reorganize; (xii) To...

  2. Field calibration of submerged sluice gates in irrigation canals

    USDA-ARS?s Scientific Manuscript database

    Four rectangular sluice gates were calibrated for submerged-flow conditions using nearly 16,000 field-measured data points on Canal B of the B-XII irrigation scheme in Lebrija, Spain. Water depth and gate opening values were measured using acoustic sensors at each of the gate structures, and the dat...

  3. 76 FR 49810 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... Change Relating to Rebates and Fees for Adding and Removing Liquidity in Select Symbols August 5, 2011... in Select Symbols.'' The text of the proposed rule change is available on the Exchange's Web site at.... (''JPM''); (x) iShares Silver Trust (''SLV''); (xi) Financial Select Sector SPDR (''XLF''); and (xii...

  4. Evaluation of the Q analyzer, a new cap-piercing fully automated coagulometer with clotting, chromogenic, and immunoturbidometric capability.

    PubMed

    Kitchen, Steve; Woolley, Anita

    2013-01-01

    The Q analyzer is a recently launched fully automated photo-optical analyzer equipped with primary tube cap-piercing and capable of clotting, chromogenic, and immunoturbidometric tests. The purpose of the present study was to evaluate the performance characteristics of the Q analyzer with reagents from the instrument manufacturer. We assessed precision and throughput when performing coagulation screening tests, prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen assay by Clauss assay. We compared results with established reagent instrument combinations in widespread use. Precision of PT/INR and APTT was acceptable as indicated by total precision of around 3%. The time to first result was 3  min for an INR and 5  min for PT/APTT. The system produced 115 completed samples per hour when processing only INRs and 60 samples (120 results) per hour for PT/APTT combined. The sensitivity of the DG-APTT Synth/Q method to mild deficiency of factor VIII (FVIII), IX, and XI was excellent (as indicated by APTTs being prolonged above the upper limit of the reference range). The Q analyzer was associated with high precision, acceptable throughput, and good reliability. When used in combination with DG-PT reagent and manufacturer's instrument-specific international sensitivity index, the INRs obtained were accurate. The Q analyzer with DG-APTT Synth reagent demonstrated good sensitivity to isolated mild deficiency of FVIII, IX, and XI and had the advantage of relative insensitivity to mild FXII deficiency. Taken together, our data indicate that the Q hemostasis analyzer was suitable for routine use in combination with the reagents evaluated.

  5. 40 CFR 63.2386 - What reports must I submit and when and what information is to be submitted in each?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SSM during the reporting period and you took actions consistent with your SSM plan, the Compliance... information in paragraphs (d)(1)(i) through (xii) of this section. This includes periods of SSM. (i) The date... whether each deviation occurred during a period of SSM, or during another period. (v) A summary of the...

  6. Architectural Survey of Seven Wyoming Army National Guard Armories, 1961-1974: Volume 1

    DTIC Science & Technology

    2017-09-01

    criteria. The following is a brief description of each of the four NRHP Criteria for Evaluation , excerpted from National Register Bulletin #15: How...Cheyenne, WY 82009 Under Project No. 455557, “Wyoming Armories Historical Context and Building Evaluation ” ERDC/CERL TR-17-36, Vol. 1 ii Abstract...xii 1 Project Description

  7. XIX Tactical Air Command and Ultra: Patton’s Force Enhancers in the 1944 Campaign in France

    DTIC Science & Technology

    2000-06-01

    forces in Montargis, Eddy did “keep going,” and his 4th Armored Division drove forty miles to the outskirts of Troyes , defeating the German forces there...then proceeded to Reims. Further to the south, XII Corps traveled from Troyes to Vitry-le-Francois with little difficulty, and then crossed the Marne

  8. Increasing Activeness and Learning Outcomes by Developing Borland Delphi 7.0 Application as Instructional Media

    ERIC Educational Resources Information Center

    Setyorini, Dyna; Churiyah, Madziatul

    2016-01-01

    This study aims to produce instructional media of petty cash fund with Borland Delphi 7.0 application in the Finance Administration subject, Managing Petty Cash Fund material in class XII APK in Vocational High School (SMK) Negeri 1 Pasuruan, East Java, Indonesia. This study used "Research and Development" (R&D) design procedures…

  9. 40 CFR 63.1366 - Monitoring and inspection requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... scenario is implemented based on process knowledge and representative operating data. The procedures used... control scenarios in paragraphs (b)(1)(ii) through (xii) of this section, and are summarized in Table 3 of... also be monitored once a day. The minimum scrubber liquid flow rate or pressure drop shall be based on...

  10. AID and Universities Have Yet to Forge an Effective Partnership to Combat World Food Problems.

    DTIC Science & Technology

    1981-10-16

    1979, and (3) beans and cowpeas started in October 1980. These 3 CRSPs involve 30 title XII universities and institutions. Each CRSP 27 activity is...establish firm links with develop- ing countries. An official from the beans and cowpeas CRSP said that CRSP is not incorporated as part of AID host-country

  11. Prevalence of Depressive Symptoms among Urban Adolescents of South India

    ERIC Educational Resources Information Center

    Mohanraj, Rani; Subbaiah, Karunanidhi

    2010-01-01

    Aim: This study aimed to find the prevalence of depressive symptoms among adolescents studying in schools in Chennai. Settings and Design: The study was a school based cross-sectional survey in which data were collected through a self-administered questionnaire from adolescents studying in classes X, XI and XII. Material: Beck Depression Inventory…

  12. 32 CFR 865.114 - Decisional document.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... punishment). (xii) Conviction by court-martial. (xiii) Prior military service and type of discharge received. (3) A list of the type of documents submitted by or on behalf of the applicant (including a written... documentary evidence), if any. (4) A statement whether the applicant testified, and a list of the type of...

  13. 20 CFR 606.32 - Types of advances subject to interest.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... under title XII of the Social Security Act. (b) Cash flow loans—(1) Availability of interest-free advances. Advances are deemed cash flow loans and shall be free of interest provided that: (i) The advances... calendar year of those loans deemed to be cash flow loans and not subject to interest. This notification...

  14. 20 CFR 606.32 - Types of advances subject to interest.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... under title XII of the Social Security Act. (b) Cash flow loans—(1) Availability of interest-free advances. Advances are deemed cash flow loans and shall be free of interest provided that: (i) The advances... calendar year of those loans deemed to be cash flow loans and not subject to interest. This notification...

  15. 20 CFR 606.32 - Types of advances subject to interest.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... under title XII of the Social Security Act. (b) Cash flow loans—(1) Availability of interest-free advances. Advances are deemed cash flow loans and shall be free of interest provided that: (i) The advances... calendar year of those loans deemed to be cash flow loans and not subject to interest. This notification...

  16. Observational Learning on Industry Work Practices toward Job Readiness

    ERIC Educational Resources Information Center

    Rojuli, Subkhan; Rahayu, Agus; Disman

    2017-01-01

    This research aims to find out the influence of observational learning on job readiness based on some indicators and variables. This is a quantitative research in which Structural Equation Modeling (SEM) was used. The research method is survey. The participants of this research are the Grade XII students of Accountancy Department of State…

  17. 12 CFR 1026.55 - Limitations on increasing annual percentage rates, fees, and charges.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... PROTECTION TRUTH IN LENDING (REGULATION Z) Special Rules Applicable to Credit Card Accounts and Open-End...)(2)(iii), or (b)(2)(xii) on a credit card account under an open-end (not home-secured) consumer credit plan. (b) Exceptions. A card issuer may increase an annual percentage rate or a fee or charge...

  18. 12 CFR 1026.55 - Limitations on increasing annual percentage rates, fees, and charges.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... PROTECTION TRUTH IN LENDING (REGULATION Z) Special Rules Applicable to Credit Card Accounts and Open-End...)(2)(iii), or (b)(2)(xii) on a credit card account under an open-end (not home-secured) consumer credit plan. (b) Exceptions. A card issuer may increase an annual percentage rate or a fee or charge...

  19. 12 CFR 1026.55 - Limitations on increasing annual percentage rates, fees, and charges.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... PROTECTION TRUTH IN LENDING (REGULATION Z) Special Rules Applicable to Credit Card Accounts and Open-End...)(2)(iii), or (b)(2)(xii) on a credit card account under an open-end (not home-secured) consumer credit plan. (b) Exceptions. A card issuer may increase an annual percentage rate or a fee or charge...

  20. 40 CFR 266.100 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the following requirements, except that an owner or operator of a lead or a nickel-chromium recovery... operator of a lead or nickel-chromium or mercury recovery furnace (except for owners or operators of lead... listed in appendix XII of this part must contain recoverable levels of nickel or chromium, a waste listed...

  1. 40 CFR 266.100 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the following requirements, except that an owner or operator of a lead or a nickel-chromium recovery... operator of a lead or nickel-chromium or mercury recovery furnace (except for owners or operators of lead... listed in appendix XII of this part must contain recoverable levels of nickel or chromium, a waste listed...

  2. 20 CFR 606.32 - Types of advances subject to interest.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... under title XII of the Social Security Act. (b) Cash flow loans—(1) Availability of interest-free advances. Advances are deemed cash flow loans and shall be free of interest provided that: (i) The advances... calendar year of those loans deemed to be cash flow loans and not subject to interest. This notification...

  3. On-Chip Out-of-Plane High-Q Inductors

    DTIC Science & Technology

    2002-01-01

    and leaves the substrate available for circuits. Magnetic forces [2] and the surface tension of a molten dot of solder [3] or polymer [4] have been...and P. Renaud, "High aspect ratio planar coils embedded in SU8 photoepoxy for MEMS applications," Tech. Digest Eurosensors XII, Southampton, Sep. 13-16

  4. LOGWAR 15: Analysis Report

    DTIC Science & Technology

    2016-04-01

    Sanitation, and Hygiene WFP World Food Programme WHO World Health Organization Unclassified Unclassified xii This page intentionally left blank...Insurgency Natural Disaster Contamination Visibility Disposition Distribution Sourcing Prioritization Security Financial U.S. Military Services Combatant...supply; restrictions on sourcing; contamination concerns (IV solutions) Small in size; multiple variants with limited interchangeability; requires

  5. 20 CFR 606.25 - Waiver of and substitution for additional tax credit reduction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT Relief From Tax Credit Reduction § 606.25 Waiver of and substitution for additional tax credit reduction. A provision of subsection (c)(2) of section 3302 of FUTA provides that, for a...

  6. 76 FR 53833 - Magnuson-Stevens Act Provisions; Fisheries Off West Coast States; Pacific Coast Groundfish...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... Fishery Management Plan or PCGFMP'', ``Person'', ``Processing or to process'' introductory text and... under the terms of 46 U.S.C. 12102(a). Processing or to process means the preparation or packaging of... considered to be processing fish (See Sec. 660.112(b)(1)(xii)(A))). Processor means a person, vessel, or...

  7. 29 CFR 1910.111 - Storage and handling of anhydrous ammonia.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 1,200 gallons water capacity. (viii) Filling density. the percent ratio of the weight of the gas in... ammonia. (xi) Capacity. Total volume of the container in standard U.S. gallons. (xii) DOT specifications... allowable water level to which the container may be filled for test purposes. (vii) With the density of the...

  8. 29 CFR 1910.111 - Storage and handling of anhydrous ammonia.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 1,200 gallons water capacity. (viii) Filling density. the percent ratio of the weight of the gas in... ammonia. (xi) Capacity. Total volume of the container in standard U.S. gallons. (xii) DOT specifications... allowable water level to which the container may be filled for test purposes. (vii) With the density of the...

  9. 29 CFR 1910.111 - Storage and handling of anhydrous ammonia.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 1,200 gallons water capacity. (viii) Filling density. the percent ratio of the weight of the gas in... ammonia. (xi) Capacity. Total volume of the container in standard U.S. gallons. (xii) DOT specifications... allowable water level to which the container may be filled for test purposes. (vii) With the density of the...

  10. Investigating the Mercalli Intensity Scale through "Lived Experience"

    ERIC Educational Resources Information Center

    Jones, Richard

    2012-01-01

    The modified Mercalli (MM) intensity scale is composed of 12 increasing levels of intensity that range from imperceptible shaking to catastrophic destruction and is designated by Roman numerals I through XII. Although qualitative in nature, it can provide a more concrete model for middle and high school students striving to understand the dynamics…

  11. 20 CFR 606.1 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... standards for grant of such relief in the form of— (i) A cap on tax credit reduction, (ii) Avoidance of tax... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE FEDERAL UNEMPLOYMENT TAX ACT; ADVANCES UNDER TITLE XII OF THE SOCIAL SECURITY ACT General § 606.1 Purpose...

  12. Hosts of stolbur phytoplasmas in maize redness affected fields

    USDA-ARS?s Scientific Manuscript database

    The plant host range of a phytoplasma is strongly dependent on the host range of its insect vector. Maize redness in Serbia is caused by stolbur phytoplasma (subgroup 16SrXII-A) and is transmitted by the cixiid planthoper, Reptalus panzeri (Löw). R. panzeri was the only potential vector found to be ...

  13. Contact activation: a revision.

    PubMed

    Schmaier, A H

    1997-07-01

    In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.

  14. Perspectivas Pedagogicas. Documentos-Ponencias Y Ensayos Proyecto Teacher Corps, Ciclo XII (Pedagogical Perspectives. Documents, Papers and Essays, Teacher Corps Project, Cycle XII).

    ERIC Educational Resources Information Center

    Albino, Isidra, Ed.; Davila, Sonia, Ed.

    The purpose of this book is to stimulate ideas leading to a sharing of approaches, strategies, and methodologies applicable to the education of Puerto Ricans. Following introductory material, 18 papers are presented, the first 10 of which are in Spanish. Titles and authors are: (1) "El maestro que Puerto Rico necesita," Leonides Santos…

  15. Factors related to commercial production of the walleye in Red Lakes, Minnesota

    USGS Publications Warehouse

    Smith, Lloyd L.; Pycha, Richard L.

    1961-01-01

    Growth of the walleye (Stizostedion vitreum vitreum) in Red Lakes, Minnesota, over a 17-year period was slower than in other waters of the Great Lakes region and fluctuated annually from 30.7 percent above to 42.2 percent below mean growth. Individual year classes varied considerably in growth rate. Age distribution in 3 1/2-inch stretch-measure commercial nets varied extremely in 9 years' collections and was related to year-class strength and fishing intensity during periods when classes were available for catch. Abundance of different classes varied 23-fold. Annulus formation and resumption of growth occurred from mid-June to late July. Effective growing season did not exceed 4 months and for some individuals in some years was 2 months or less. The catch contained age-groups II-XII but consisted principally of groups IV-VIII. Seasonal changes in age distribution were dependent on growth rate and fishing effort. Total catch was strongly influenced by growth and seasonal distribution of fishing effort. Maximum availability to commercial nets was at a total length of 15.1 inches, but a large percentage of the catch was smaller fish. Total annual mortality rate after fish attained 15.1 inches total length was 0.66, but continued recruitment through group VIII caused apparent change in mortality rate with increasing age up to IX. Maximum harvest could be attained by concentrating fishing effort in the latter part of the growing season. Abundance indices derived from commercial catch will be strongly influenced by the seasonal pattern of fishing.

  16. [The use of free-of-charge prescription contraceptives among women : Results of a pilot project in the German federal state of Mecklenburg-Western Pomerania].

    PubMed

    Ulbricht, Sabina; Beyer, Angelika; John, Ulrich

    2018-04-01

    There is a connection between the receipt of unemployment benefits and the failure to use contraceptives in Germany. This study aims to understand the use of contraceptives among women entitled to unemployment benefits under the Sozialgesetzbuch II or XII (SGB II or SGB XII), prior and during an offer of contraceptives free of charge (CFOC). The criteria for the use of CFOC (pill, intrauterine device, or ring) over a 12-month period were: age between 20 and 35 years, resident in predefined urban or rural postal codes in the German federal state of Mecklenburg-Western Pomerania, and participation in a self-administered survey. Data about participants' age, education, number of children, relationship status, period of payment according to SGB II or SGB XII, the use and barriers to use of contraceptives during every occurrence of sexual intercourse, as well as the kind of contraceptives used. From a total of 418 women: 40.9% were single-mothers, 39.0% did not graduate school, 21.1% were childless, and 57.9% had received unemployment benefits for at least three years. Further, 21.1% rated their type of contraceptive as "less safe" or "unsafe." The most commonly cited reasons for nonregular use of contraceptives were: they are too expensive or their use is forgotten. A change in contraceptives was made by 30.9% due to the offer of CFOC. The change was associated with the number of children and the exclusive use of less safe contraceptives. CFOC seems to be attractive, especially for women with children and those who receive long-term unemployment benefits. Changing demands concerning the safety of birth control during the lives of women should be considered in the discussion about common rules for the access to CFOC.

  17. Mediated Debate, Historical Framing, and Public Art: The Juan de Onate Controversy in El Paso

    ERIC Educational Resources Information Center

    Perez, Frank G.; Ortega, Carlos F.

    2008-01-01

    In 1988, the El Paso, Texas, city council accepted a proposal to build twelve statues of historically important individuals as part of a downtown revitalization initiative. Juan de Onate was selected as the centerpiece statue of the XII Travelers Memorial of the Southwest. The decision to honor the Spanish colonizer triggered a local controversy…

  18. Investigating Visual Alerting in the Maritime Domain; Report on 3 Experiments, With Supporting Documentation

    DTIC Science & Technology

    2010-04-01

    Methodological Results / Details ................................................ 24 4.1.3.1 Clock Synchronization , Network & Temporal Resolution...xii DRDC Atlantic CR 2010-058 Acknowledgements Special thanks to Carl Helmick, Patti Devlin, Mike Taber, and the Dalhousie lab...Methodological Results / Details 4.1.3.1 Clock Synchronization , Network & Temporal Resolution Due to drift in computer clock times, especially laptop

  19. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO A.468(XII...

  20. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO A.468(XII...

  1. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO A.468(XII...

  2. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO A.468(XII...

  3. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO A.468(XII...

  4. The Effect of Executive Order 13269 on Noncitizen Enlisted Accessions in the U.S. Military

    DTIC Science & Technology

    2013-03-01

    heteroscedasticity by using both White and Breusch - Pagan Tests (Woolridge, 2009). The test results showed that there was significant heteroscedasticy in...39  C.  JOINT-HYPOTHESIS TEST AND SIGNIFICANCE OF THE MODELS...Accessions Regression Results ........................... 40  Table 8.  The Authors’ R Square and F Test Results of DMDC Data ................ 42  xii

  5. 78 FR 74121 - Office of the Secretary

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ..., CO 80011- 9066. FOR FURTHER INFORMATION CONTACT: Elan Green, Medical Benefits and Reimbursement... Care Act (PPACA) which amended section 1886(b)(3)(B) of the Social Security Act, and (2) a 0.3 percent point adjustment as required by section 1886(b)(3)(B)(xii) of the Act as added and amended by sections...

  6. 20 CFR 606.1 - Purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Purpose and scope. 606.1 Section 606.1... and scope. (a) In general. The regulations in this part 606 are issued to implement the tax credit... title XII of the Social Security Act. (b) Scope. This part 606 covers general matters relating to this...

  7. Libraries and Development.

    ERIC Educational Resources Information Center

    Findley, Paul

    These keynote remarks review some of the origins of Title XII of the Foreign Assistance Act. This legislation, whose goal is to conquer famine and malnutrition worldwide, was signed into law by President Ford in 1975. Senator Hubert Humphrey's address at the 1977 Famine Prevention Symposium in Washington, DC, is recounted with emphasis on his…

  8. 40 CFR 63.11564 - What are my notification, recordkeeping, and reporting requirements?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) through (b)(4) of this section. (1) If you are using a control device to comply with the emission limits... mixers, coaters). If you are not using a control device to comply with the emission limits, the... brief description of the CPMS. (xi) The date of the latest CPMS certification or audit. (xii) A...

  9. Civil Law Study Guide.

    DTIC Science & Technology

    1987-10-01

    Occupational Field . 12. A pattern of discreditable involvement with military or *- civilian authorities, notwithstanding the fact that such misconduct has...AUTHORITIES .... ......... 10-1 CHAPTER XI ....... FREEDOM OF EXPRESSION IN THE MILITARY ......... 11-1 CHAPTER XII . . . CLAIMS...2-3 0204 WHAT CONSTITUTES MISCONDUCT. .. ............. .. 2-4 A. General rule .. .. .............. ...... 2-4 *B. No military duty can require

  10. 49 CFR 572.180 - Incorporated materials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Drawing No. 175-3000, Shoulder Assembly; (v) Drawing No. 175-3500, Arm Assembly, Left; (vi) Drawing No.... 175-6000 Pelvis Assembly; (xi) Drawing No. 175-7000-1, Leg Assembly—left; (xii) Drawing No. 175-7000-2... Operations, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590, telephone (202) 366-9826, and at...

  11. 49 CFR 572.190 - Incorporated materials.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Complete; (ix) Drawing No. 180-5000-1, Complete Leg Assembly, Left; (x) Drawing No. 180-5000-2, Complete Leg Assembly, Right; (xi) Drawing No. 180-6000-1, Arm Assembly Left Molded; (xii) Drawing No. 180-6000..., Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590, telephone (202) 366-9826, and at the...

  12. 49 CFR 572.190 - Incorporated materials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Complete; (ix) Drawing No. 180-5000-1, Complete Leg Assembly, Left; (x) Drawing No. 180-5000-2, Complete Leg Assembly, Right; (xi) Drawing No. 180-6000-1, Arm Assembly Left Molded; (xii) Drawing No. 180-6000..., Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590, telephone (202) 366-9826, and at the...

  13. 49 CFR 572.180 - Incorporated materials.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Drawing No. 175-3000, Shoulder Assembly; (v) Drawing No. 175-3500, Arm Assembly, Left; (vi) Drawing No.... 175-6000 Pelvis Assembly; (xi) Drawing No. 175-7000-1, Leg Assembly—left; (xii) Drawing No. 175-7000-2... Operations, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590, telephone (202) 366-9826, and at...

  14. Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy.

    PubMed

    Nwabo Kamdje, A H; Bassi, G; Pacelli, L; Malpeli, G; Amati, E; Nichele, I; Pizzolo, G; Krampera, M

    2012-05-01

    Stromal cells are essential components of the bone marrow (BM) microenvironment that regulate and support the survival of different tumors, including chronic lymphocytic leukemia (CLL). In this study, we investigated the role of Notch signaling in the promotion of survival and chemoresistance of human CLL cells in coculture with human BM-mesenchymal stromal cells (hBM-MSCs) of both autologous and allogeneic origin. The presence of BM-MSCs rescued CLL cells from apoptosis both spontaneously and following induction with various drugs, including Fludarabine, Cyclophosphamide, Bendamustine, Prednisone and Hydrocortisone. The treatment with a combination of anti-Notch-1, Notch-2 and Notch-4 antibodies or γ-secretase inhibitor XII (GSI XII) reverted this protective effect by day 3, even in presence of the above-mentioned drugs. Overall, our findings show that stromal cell-mediated Notch-1, Notch-2 and Notch-4 signaling has a role in CLL survival and resistance to chemotherapy. Therefore, its blocking could be an additional tool to overcome drug resistance and improve the therapeutic strategies for CLL.

  15. Test and Evaluation of the Surveyor 3 Television Camera Returned from the Moon by Apollo 12. Volume 1

    NASA Technical Reports Server (NTRS)

    1970-01-01

    Results are presented of engineering tests of the Surveyor III television camera, which resided on the moon for 2 and 1/2 years before being brought back to earth by the Apollo XII astronauts. Electric circuits, electrical, mechanical, and optical components and subsystems, the vidicon tube, and a variety of internal materials and surface coatings were examined to determine the effects of lunar exposure. Anomalies and failures uncovered were analyzed. For the most part, the camera parts withstood the extreme environment exceedingly well except where degradation of obsolete parts or suspect components had been anticipated. No significant evidence of cold welding was observed, and the anomalies were largely attributable to causes other than lunar exposure. Very little evidence of micrometeoroid impact was noted. Discoloration of material surfaces -- one of the major effects noted--was found to be due to lunar dust contamination and radiation damage. The extensive test data contained in this report are supplemented by results of tests of other Surveyor parts retrieved by the Apollo XII astronauts, which are contained in a companion report.

  16. Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy

    PubMed Central

    Kamdje, A H Nwabo; Bassi, G; Pacelli, L; Malpeli, G; Amati, E; Nichele, I; Pizzolo, G; Krampera, M

    2012-01-01

    Stromal cells are essential components of the bone marrow (BM) microenvironment that regulate and support the survival of different tumors, including chronic lymphocytic leukemia (CLL). In this study, we investigated the role of Notch signaling in the promotion of survival and chemoresistance of human CLL cells in coculture with human BM-mesenchymal stromal cells (hBM-MSCs) of both autologous and allogeneic origin. The presence of BM-MSCs rescued CLL cells from apoptosis both spontaneously and following induction with various drugs, including Fludarabine, Cyclophosphamide, Bendamustine, Prednisone and Hydrocortisone. The treatment with a combination of anti-Notch-1, Notch-2 and Notch-4 antibodies or γ-secretase inhibitor XII (GSI XII) reverted this protective effect by day 3, even in presence of the above-mentioned drugs. Overall, our findings show that stromal cell-mediated Notch-1, Notch-2 and Notch-4 signaling has a role in CLL survival and resistance to chemotherapy. Therefore, its blocking could be an additional tool to overcome drug resistance and improve the therapeutic strategies for CLL. PMID:22829975

  17. A cross-sectional study of factors associated with adolescent sexual activity

    PubMed Central

    Shashikumar, R.; Das, R. C.; Prabhu, H. R. A.; Srivastava, K.; Bhat, P. S.; Prakash, J.; Seema, P.

    2012-01-01

    Context: Adolescents constitute about 20% of our population and increasingly more of them are initiating sexual activity at an early age. Several behaviors associated with adolescence like masturbation, expression of masculinity/femininity, lifestyle habits like attending late night parties, and consumption of alcohol have been variously implicated in initiating sexual activities. Sexual abuse can also lead to premature sexualization. In view of few worthwhile studies from India that have dealt with these issues this study was undertaken. Aims: To elicit information from two co-education schools adolescent boys and girls on matters related to pubescence, sexual experiences, and sexual health. Settings and Design: Study subjects involved students from class IX to XII in two co-education schools. Consent of parents was taken to administer the questionnaire to their wards. Materials and Methods: A total of 586 out of 1580 students completed a self-reporting questionnaire on matters related to sexuality. Statistical Analysis EpiInfo6 Software was used. Results: Significant association was found among those holding the view that having sex proves their masculinity, being sexually abused, masturbation among boys, and sexual activity. A significantly large number of boys and girls are unaware of role of alcohol on sexual activity and that pregnancy can be caused by single intercourse. Conclusions: This was probably the first such comparative study from India. Mechanisms need to be evaluated to help adolescents understand their sexual attitudes and situations that are likely to provoke sexual activity. Therefore, not only more detailed and longitudinal studies are needed to understand these relations in a better perspective, but also a well-planned educational program for adolescents is a need of the hour. PMID:22988320

  18. A cross-sectional study of factors associated with adolescent sexual activity.

    PubMed

    Shashikumar, R; Das, R C; Prabhu, H R A; Srivastava, K; Bhat, P S; Prakash, J; Seema, P

    2012-04-01

    Adolescents constitute about 20% of our population and increasingly more of them are initiating sexual activity at an early age. Several behaviors associated with adolescence like masturbation, expression of masculinity/femininity, lifestyle habits like attending late night parties, and consumption of alcohol have been variously implicated in initiating sexual activities. Sexual abuse can also lead to premature sexualization. In view of few worthwhile studies from India that have dealt with these issues this study was undertaken. To elicit information from two co-education schools adolescent boys and girls on matters related to pubescence, sexual experiences, and sexual health. Study subjects involved students from class IX to XII in two co-education schools. Consent of parents was taken to administer the questionnaire to their wards. A total of 586 out of 1580 students completed a self-reporting questionnaire on matters related to sexuality. Statistical Analysis EpiInfo6 Software was used. Significant association was found among those holding the view that having sex proves their masculinity, being sexually abused, masturbation among boys, and sexual activity. A significantly large number of boys and girls are unaware of role of alcohol on sexual activity and that pregnancy can be caused by single intercourse. This was probably the first such comparative study from India. Mechanisms need to be evaluated to help adolescents understand their sexual attitudes and situations that are likely to provoke sexual activity. Therefore, not only more detailed and longitudinal studies are needed to understand these relations in a better perspective, but also a well-planned educational program for adolescents is a need of the hour.

  19. The Muslim Brotherhood and Modern Education: How Will the Muslim Brotherhood Address Egypt’s Failing Education System?

    DTIC Science & Technology

    2012-09-01

    Thesis Advisor: Robert Springborg Second Reader: Mohammed M. Hafez THIS PAGE INTENTIONALLY LEFT BLANK i REPORT DOCUMENTATION PAGE Form...of secular subjects. vi THIS PAGE INTENTIONALLY LEFT BLANK vii TABLE OF CONTENTS I . INTRODUCTION...understanding, this thesis would not have been possible. xii THIS PAGE INTENTIONALLY LEFT BLANK 1 I . INTRODUCTION A. MAJOR RESEARCH QUESTION The

  20. 78 FR 35545 - Delegation of Certain Functions and Authorities Under the Iran Freedom and Counter-Proliferation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ...-Proliferation Act of 2012 Memorandum for the Secretary of State[,] the Secretary of the Treasury[,] the Attorney... Act of 2012 (subtitle D of title XII of Public Law 112-239) (22 U.S.C. 8801 et seq.) (IFCA), as... section 1248(b)(1)(A) of IFCA; Section 1252(a) to the Director of National Intelligence, in consultation...

  1. H-Bomb Development: Decision on the Merits or Political Necessity

    DTIC Science & Technology

    2015-05-23

    Army attempted to solidify its control of atomic energy in the post-war United States through the...capability to prevent the Soviet army from overrunning Western Europe.84 Reliance on atomic weapons combined with the recent...Robert Oppenheimer, Vol. XII, Transcript of hearing before the Personnel Security Board (Washington, DC: US Atomic Energy Commission, April 27, 1954

  2. 27 CFR 21.65 - Formula No. 38-B.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... Cinnamic aldehyde, N.F. IX. Cinnamon oil, N.F. Citronella oil, natural. Clove oil, N.F. Coal tar, U.S.P..., terpeneless. Spike lavender oil, natural. Storax, U.S.P. Thyme oil, N.F. XII. Thymol, N.F. Tolu balsam, U.S.P... the denaturant for analysis. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations...

  3. 27 CFR 21.65 - Formula No. 38-B.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Cinnamic aldehyde, N.F. IX. Cinnamon oil, N.F. Citronella oil, natural. Clove oil, N.F. Coal tar, U.S.P..., terpeneless. Spike lavender oil, natural. Storax, U.S.P. Thyme oil, N.F. XII. Thymol, N.F. Tolu balsam, U.S.P... the denaturant for analysis. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations...

  4. 27 CFR 21.65 - Formula No. 38-B.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Cinnamic aldehyde, N.F. IX. Cinnamon oil, N.F. Citronella oil, natural. Clove oil, N.F. Coal tar, U.S.P..., terpeneless. Spike lavender oil, natural. Storax, U.S.P. Thyme oil, N.F. XII. Thymol, N.F. Tolu balsam, U.S.P... the denaturant for analysis. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations...

  5. 27 CFR 21.65 - Formula No. 38-B.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Cinnamic aldehyde, N.F. IX. Cinnamon oil, N.F. Citronella oil, natural. Clove oil, N.F. Coal tar, U.S.P..., terpeneless. Spike lavender oil, natural. Storax, U.S.P. Thyme oil, N.F. XII. Thymol, N.F. Tolu balsam, U.S.P... the denaturant for analysis. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations...

  6. 27 CFR 21.65 - Formula No. 38-B.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Cinnamic aldehyde, N.F. IX. Cinnamon oil, N.F. Citronella oil, natural. Clove oil, N.F. Coal tar, U.S.P..., terpeneless. Spike lavender oil, natural. Storax, U.S.P. Thyme oil, N.F. XII. Thymol, N.F. Tolu balsam, U.S.P... the denaturant for analysis. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations...

  7. 75 FR 34291 - Federal Acquisition Regulation; Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... ADMINISTRATION 48 CFR Parts 31, 49 and 52 [FAC 2005-42; Item XII; Docket 2010-0078; Sequence 2] Federal... Subjects in 48 CFR Parts 31, 49, and 52 Government procurement. Dated: June 2, 2010. Edward Loeb, Acting Director, Acquisition Policy Division. 0 Therefore, DoD, GSA, and NASA amend 48 CFR parts 31, 49, and 52 as...

  8. On Understanding the Notion of Limits and Infinitesimal Quantities

    ERIC Educational Resources Information Center

    Parameswaran, Revathy

    2007-01-01

    In this paper we explore the influence of students' personalized notion of "small" numbers based on real life experiences on their understanding of limits. Tests were conducted on two samples of students. The first sample, consisting of students in the XII grade, had been taught limits using an informal approach (i.e., without recourse to the…

  9. Giving More Realistic Definitions of Trigonometric Ratios II

    ERIC Educational Resources Information Center

    Bhattacharjee, Pramode Ranjan

    2014-01-01

    This paper being an extension of Bhattacharjee (2012) is very much relevant to Year 9 to Year 10A in the "Australian Curriculum: Mathematics". It also falls within the purview of class IX to class XII curriculum of Mathematics in India (Revised NCERT curriculum) for students aged 14-17 years. In Bhattacharjee (2012), the discovery of…

  10. 75 FR 2905 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ... Registration Fee from $50 to $100; (xi) increase the current Order Entry Port from $250 to $500 and only charge per mnemonic instead of per mnemonic per port; (xii) amend the SQF Port Fee to assess a $500 per month per SQF port in lieu of the current structure of $250 for the first five ports and $1000 for...

  11. Detecting Potentially Compromised Credentials in a Large-Scale Production Single-Signon System

    DTIC Science & Technology

    2014-06-01

    Attention Deficit Hyperactivity Disorder ( ADHD ), Post-Traumatic Stress Disorder (PTSD), anxiety, they are neurotic, and have memory issues. They... Deficit Hyperactivity Disorder API Application Programming Interface CAC Common Access Card CBL Composite Blocking List CDF Cumulative Distribution...Service Logons (DSLs) system . . . . . . . . . . . . . . . . 49 xi THIS PAGE INTENTIONALLY LEFT BLANK xii List of Acronyms and Abbreviations ADHD Attention

  12. 48 CFR 52.244-6 - Subcontracts for Commercial Items.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Labor Relations Act (DEC 2010) (E.O. 13496), if flow down is required in accordance with paragraph (f) of FAR clause 52.222-40. (ix) 52.222-50, Combating Trafficking in Persons (FEB 2009) (22 U.S.C. 7104... 2013), if flow down is required in accordance with paragraph (c) of FAR clause 52.232-40. (xii) 52.247...

  13. Cultural Landscape Analysis of Existing Historic Districts: Picatinny Arsenal, New Jersey

    DTIC Science & Technology

    2016-03-01

    district, site, building, structure , or object. Especially relevant is Section 110 of the National Historic Preservation Act, which re- quires federal...82 Figure 79. Noncontributing structures in the Administrative and Research Historic District Boundary (ERDC-CERL, 2012...East side of Cannon Gate structure (ERDC-CERL, 2012). ............................. 142 ERDC/CERL TR-16-4 xii Figure 150. Stone wall that extends

  14. 12 CFR 226.55 - Limitations on increasing annual percentage rates, fees, and charges.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Rules Applicable to Credit Card Accounts and Open-End Credit Offered to College Students § 226.55... required to be disclosed under § 226.6(b)(2)(ii), (b)(2)(iii), or (b)(2)(xii) on a credit card account under an open-end (not home-secured) consumer credit plan. (b) Exceptions. A card issuer may increase an...

  15. 12 CFR 226.55 - Limitations on increasing annual percentage rates, fees, and charges.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Applicable to Credit Card Accounts and Open-End Credit Offered to College Students § 226.55 Limitations on... required to be disclosed under § 226.6(b)(2)(ii), (b)(2)(iii), or (b)(2)(xii) on a credit card account under an open-end (not home-secured) consumer credit plan. (b) Exceptions. A card issuer may increase an...

  16. 12 CFR 226.55 - Limitations on increasing annual percentage rates, fees, and charges.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Rules Applicable to Credit Card Accounts and Open-End Credit Offered to College Students § 226.55... required to be disclosed under § 226.6(b)(2)(ii), (b)(2)(iii), or (b)(2)(xii) on a credit card account under an open-end (not home-secured) consumer credit plan. (b) Exceptions. A card issuer may increase an...

  17. 12 CFR 226.55 - Limitations on increasing annual percentage rates, fees, and charges.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Applicable to Credit Card Accounts and Open-End Credit Offered to College Students § 226.55 Limitations on... required to be disclosed under § 226.6(b)(2)(ii), (b)(2)(iii), or (b)(2)(xii) on a credit card account under an open-end (not home-secured) consumer credit plan. (b) Exceptions. A card issuer may increase an...

  18. Test Plan Framework for Cross Domain Solution (CDS) Devices

    DTIC Science & Technology

    2010-06-01

    modification to the CASTER software to reflect the latest changes to RDAC is being discussed by the developers with input by the independent labs and NSA...7 xii THIS PAGE INTENTIONALLY LEFT BLANK xiii LIST OF ABBREVIATIONS AND ACRONYMS CASTER Certification...protecting information and information systems from unauthorized access, use, disclosure, disruption, modification , or destruction. While this is a

  19. 76 FR 72911 - TRICARE, Formerly Known as the Civilian Health and Medical Program of the Uniformed Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ...: Elan Green, Medical Benefits and Reimbursement Branch, TMA, telephone (303) 676-3907. SUPPLEMENTARY... 1886(b)(3)(B) of the Social Security Act, and (2) a 0.1 percent point adjustment as required by section 1886(b)(3)(B)(xii) of the Act as added and amended by sections 3401 and 10319(a) of the PPACA. These...

  20. Educational Studies of Cosmic Rays with a Telescope of Geiger-Muller Counters

    ERIC Educational Resources Information Center

    Wibig, T.; Kolodziejczak, K.; Pierzynski, R.; Sobczak, R.

    2006-01-01

    A group of high school students (XII Liceum) in the framework of the Roland Maze Project has built a compact telescope of three Geiger-Muller counters. The connection between the telescope and a PC computer was also created and programmed by students involved in the Project. This has allowed students to use their equipment to perform serious…

  1. 20 CFR 606.32 - Types of advances subject to interest.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... provided in paragraph (b) of this section each State shall pay interest on any advance made to such State under title XII of the Social Security Act. (b) Cash flow loans. Advances repaid in full prior to October 1 of the calendar year in which made are deemed cash flow loans and shall be free of interest...

  2. To Set One's Heart in a Violent World

    ERIC Educational Resources Information Center

    Tran, Mai-Anh Le

    2015-01-01

    Mai-Anh Le Tran is Associate Professor of Christian Education at Eden Theological Seminary in St. Louis, Missouri, and is president of the Religious Education Association. Here she begins with a saying attributed to Hindu mystic and guru Sri Ramakrishna (Love 2007, xii; cf. Cousineau 2003), "Religion is like a cow. It kicks but it gives milk,…

  3. Fragmentation of DHS Public Corruption Investigations: Options to Leverage Overlapping Jurisdiction and Enhance Collaboration

    DTIC Science & Technology

    2011-12-01

    LAPD Los Angeles Police Department MOU Memorandum of Understanding xii NCA National Crime Agency OIG Office of Inspector General OPR Office...that police departments should not be afforded the same privilege. In 2008, Ramona Ripston, Executive Director of the Los Angeles Chapter of the ...American Civil Liberties Union, praised outgoing Los Angeles Police Department ( LAPD ) Chief

  4. Medical Management of Radiological Casualties, Second Edition, Handbook

    DTIC Science & Technology

    2003-04-01

    neutropenia and fever) in irradiated persons is similar to that used for other febrile neutropenic patients, such as solid tumor patients receiving...of cytokines xii for patients expected to experience severe neutropenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Table 3...toms of tissue injuries can mimic and obscure those caused by acute radiation effects. Conventional Therapy for Neutropenia and Infection The

  5. Multiscale Modeling of Non-crystalline Ceramics (Glass)

    DTIC Science & Technology

    2013-03-01

    of infinite regions using a perfectly matched layer, SEM XII Congress & Exposition on Experimental and Applied Mechanics, May, 2012, Costa Mesa , CA...MCCAULEY (10 HCS) P PLOSTINS P BAKER RDRL WML J NEWILL M ZOLTOSKI RDRL WML B I BATYREV (1 HC) S IZVYEKOV (1 HC) B RICE (1 HC) R PESCE RODRIGUEZ D TAYLOR N

  6. [Growth of the neurocranium].

    PubMed

    Hodacová, Z; Skalská, H

    1998-01-01

    The present study demonstrates the results of evaluation of growth changes of the neurocranium in a set of 98 human skulls of immature individuals aged 6-18/20/ years from the XIII.-XVIII. century. Craniometric values were matched with the corresponding values measured on the skulls of the same age groups from the IX. century and IX.-XII. centuries.

  7. Influence of blood lipids on global coagulation test results.

    PubMed

    Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung

    2015-01-01

    High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

  8. Division XII: Commission 55: Communicating Astronomy with the Public

    NASA Astrophysics Data System (ADS)

    Christensen, Lars Lindberg; Russo, Pedro; Robson, Ian; Arcand, Kimberly Kowal; Fienberg, Richard Tresch; Ödman-Govender, Carolina; Sekiguchi, Kazuhiro; Wheeler, Pete; Zhu, Jin

    2015-08-01

    A good fraction of the Commission 55 (C55) Organizing Committee met in Beijing in August at the XXVIII IAU General Assembly, where C55 organized Special Session 14 (SpS14) entitled ``Communicating Astronomy with the Public for Scientists.'' During our C55 business meeting, and again during an impromptu gathering a few days later, we discussed changes in the IAU's organizational and programmatic structure and how these changes might affect C55. This report summarizes key points and offers some ideas about what we're calling ``C55 v2.0.'' For background and reference, see the C55 website at http://www.communicatingastronomy.org.

  9. XII Multifrequency Behaviour of High Energy Cosmic Sources Workshop

    NASA Astrophysics Data System (ADS)

    2017-06-01

    This is the twelfth edition of the series of Frascati Workshops on "Multifrequency Behaviour of High Energy Cosmic Sources" which is undoubtedly a largely accepted biennial meeting in which an updated experimental and theoretical panorama will be depicted. This edition comes at the 33rd anniversary of the first historical "multifrequency" workshop about "Multifrequency Behaviour of GalacticAccreting Sources", held in Vulcano in September 1984. This surely renders the Frascati Workshop Series the oldest among the many devoted to "Multifrequency Studies of Cosmic Sources". The study of the physics governing the cosmic sources will be the main goal of the workshop. A session devoted to the ongoing and next generation ground- and space-based experiments will give the actual prospects for the first decades of this millennium. The following items will be reviewed: Cosmology: Cosmic Background, Clusters of Galaxies Extragalactic Sources: Active Galaxies, Normal Galaxies Gamma-Rays Burst: Experiments versus Theories Galactic Sources: Pre-Main-Sequence and Main-Sequence Stars, Cataclysmic Variables and Novae, Supernovae and SNRs, X-Ray Binary Systems, Pulsars, Black Holes, Gamma-Ray Sources,Nucleosynthesis. The Astrophysics with the Ongoing and Future Experiments: Space-Based Experiments,Ground-Based Experiments. The workshop will include few 30-minute general review talks to introduce the current problems, and typically 20-minute talks discussing new experimental and theoretical results. A series of 20-minute talks will discuss the ongoing and planned ground- and space- based experiments. The cadence of the workshop is biennial. The participation will be only by invitation. All participants are kindly invited to attend the whole workshop. However, to keep alive the workshop it was decided that all presentations should be compulsorily given to the LOC, so that they can be inserted into the web page of the workshop. These presentations will form the basis for writing the papers to be published in the proceedings of the Frascati Workshop 2017 in electronic form by the Proceedings of Science (PoS-SISSA), after a peer referee process, and they will be freely available at once in the NASA- ADS. The editor of the proceedings will be Franco Giovannelli and Lola Sabau-Graziati.

  10. Chinese-Mandarin: Basic Course. Volume XII: Lessons 120-131.

    ERIC Educational Resources Information Center

    Defense Language Inst., Monterey, CA.

    This is the twelfth of 16 volumes of audiolingual classroom instruction in Mandarin Chinese. The course is designed to train native English speakers to Level 3 Foreign Service Institute proficiency in comprehension and speaking, and to Level 2 proficiency in reading and writing Mandarin. Facility in reading, writing, and translating texts written…

  11. Division XII / Commission 46 / Program Group Exchnage of Astronomers

    NASA Astrophysics Data System (ADS)

    Percy, John R.; Leung, Kam-Ching; Tolbert, Charles R.

    The Commission 46 Program Group Exchange of Astronomers (PG-EA) provides travel grants to astronomers and advanced students for research or study trips of at least three months duration. Highest priority is given to applicants from developing countries whose visits will benefit them, their institution and country, and the institution visited. This program, if used strategically, has the potential to support other Commission 46 programs such as Teaching for Astronomical Development (PG-TAD) and World Wide Development of Astronomy (PG-WWDA). Complete information about the program, and the application procedure, can be found at .

  12. Analytic Couple Modeling Introducing Device Design Factor, Fin Factor, Thermal Diffusivity Factor, and Inductance Factor

    NASA Technical Reports Server (NTRS)

    Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

    2014-01-01

    A set of convenient thermoelectric device solutions have been derived in order to capture a number of factors which are previously only resolved with numerical techniques. The concise conversion efficiency equations derived from governing equations provide intuitive and straight-forward design guidelines. These guidelines allow for better device design without requiring detailed numerical modeling. The analytical modeling accounts for factors such as i) variable temperature boundary conditions, ii) lateral heat transfer, iii) temperature variable material properties, and iv) transient operation. New dimensionless parameters, similar to the figure of merit, are introduced including the device design factor, fin factor, thermal diffusivity factor, and inductance factor. These new device factors allow for the straight-forward description of phenomenon generally only captured with numerical work otherwise. As an example a device design factor of 0.38, which accounts for thermal resistance of the hot and cold shoes, can be used to calculate a conversion efficiency of 2.28 while the ideal conversion efficiency based on figure of merit alone would be 6.15. Likewise an ideal couple with efficiency of 6.15 will be reduced to 5.33 when lateral heat is accounted for with a fin factor of 1.0.

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

    Parvinen, M.; Soeder, O.M.; Mali, P.

    Levels of rat testicular interleukin-1-like factor (tIL-1) have been shown to correlate with DNA synthetic activity during the cycle of the rat seminiferous epithelium, suggesting its role as a spermatogonial or meiotic growth factor. To explore this further, a new in vitro model system was developed. Rat seminiferous tubule segments from stages I, V, VIIa, and VIII-IX of the cycle were isolated by transillumination-assisted microdissection, cultured in chemically defined serum-free medium supplemented with human recombinant IL-1 {alpha}, and labeled with (3H)thymidine. During incubation, spontaneous progression of spermatogenesis was noted. Inactive stage VIIa tubule segments differentiated to stage VIII and initiatedmore » DNA synthesis, and concomitantly started to secrete IL-1-like factor. DNA synthesis of stages VIII-IX ceased through differentiation of spermatocytes to leptotene-zygotene (stages XII-XIII of the cycle). IL-1 {alpha} stimulated DNA synthesis significantly in spermatogonia of stage I. Meiotic DNA synthesis at stage VIIa was stimulated (48 h/34 C) and maintained at stages VIII-IX (48 h/34 C). IL-1 {alpha} seems to act as a regulator of spermatogenic DNA synthesis in both mitotic and meiotic phases. It has mainly stimulating and maintaining effects, but it may also be inhibitory under certain conditions.« less

  14. Securing, Stabilizing, and Rebuilding Iraq: Key Issues for Congressional Oversight

    DTIC Science & Technology

    2007-01-01

    Been Constrained by Security, Management , and Funding Challenges 72 U.S. Military Readiness 79 Enclosure XII: Extended Operations Have Had...Forces Have Resulted in Shortages of Critical Items 92 Improving Acquisition Outcomes 97 Enclosure XV: DOD Needs to Improve Its Capacity to Manage ...International Monetary Fund IRMO Iraq Reconstruction Management Office IRRF Iraqi Relief and Reconstruction Fund ISF Iraqi security forces ISFF

  15. Human Trafficking And U.S. Government Responses Post-9/11

    DTIC Science & Technology

    2016-09-01

    DeCeoursty 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School Monterey, CA 93943-5000 8. PERFORMING ORGANIZATION REPORT...Trafficking Unit ICE Immigration and Customs Enforcement ILAB Bureau of International Labor Affairs ILO International Labor Organization IRTPA...Intelligence Reform and Terrorism Prevention Act List List of Goods Produced by Child Labor or Forced Labor xii NGO non-governmental organization NHTRC

  16. Russian Energy Policy vis-a-vis Europe: Natural Resources as a Means of Foreign Policy

    DTIC Science & Technology

    2012-06-01

    that lag. For instance, after the March 2011 Fukushima disaster , German political leadership decided...memories for the rest of my life. xii THIS PAGE INTENTIONALLY LEFT BLANK 1 I. INTRODUCTION A. BACKGROUND After the resignation of Boris Yeltsin...the first president of the Russian Federation after the dissolution of the USSR, on December 31, 1999, and de facto appointment of his successor

  17. Screw-Thread Standards for Federal Services, 1957. Handbook H28 (1957), Part 3

    DTIC Science & Technology

    1957-09-01

    MOUNTING THREADS PHOTOGRAPHIC EQUIPMENT THREADS ISO METRIC THREADS; MISCELLANEOUS THREADS CLASS 5 INTERFERENCE-FIT THREADS, TRIAL STANDARD WRENCH...Bibliography on measurement of pitch diameter by means of wires 60 Appendix 14. Metric screw-thread standards 61 1. ISO thread profiles...61 2. Standard series for ISO metric threads 62 3. Designations for ISO metric threads 62 Tables Page Table XII. 1.—Basic

  18. Tourism in Peru: The Missing Strategy for Economic and Social Development

    DTIC Science & Technology

    2006-06-01

    Lima , 1970-1996.......................................12 xii THIS PAGE INTENTIONALLY LEFT BLANK xiii...time. Not two miles outside of Lima did things not only change, but they changed drastically. High rise buildings, upscale hotels, and very chic...natural resources. This is the case for Peru. Not only does the country hold a wealth of minerals, but it also possesses a plethora of beaches

  19. Budget Scoring of Alternative Financing Methods for Defense Requirements

    DTIC Science & Technology

    2007-06-01

    28 Table 3. Public vs . Private Operating Lease Determination ..........................................32 xii...asset to another party (lessee). For example, the rental of an automobile from Avis implies no ownership . However, leases can be structured in an... Ownership of the asset remains with the lessor during the term of the lease and is not transferred to the Government at or shortly after the end of

  20. 21 CFR 520.2380c - Thiabendazole bolus.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Limitations. As a single oral dose; may repeat once in 2 to 3 weeks; do not treat animals within 3 days of...) Chemical name. 2-(4-Thiazolyl) benzimidazole. (b) Specifications. Conforms to N.F. XII. (c) Sponsor. See No...) Limitations. As a single oral dose; as a drench or bolus; may repeat once in 2 to 3 weeks; do not treat...

  1. 21 CFR 520.2380c - Thiabendazole bolus.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Limitations. As a single oral dose; may repeat once in 2 to 3 weeks; do not treat animals within 3 days of...) Chemical name. 2-(4-Thiazolyl) benzimidazole. (b) Specifications. Conforms to N.F. XII. (c) Sponsor. See No...) Limitations. As a single oral dose; as a drench or bolus; may repeat once in 2 to 3 weeks; do not treat...

  2. An Evaluation of Solar Air Heating at United States Air Force Installations

    DTIC Science & Technology

    2009-03-01

    Collector (UTC) technology, more commonly known as SolarWalls®. This thesis sought to determine if UTC systems are an economically and environmentally...States Green Building Council UTC – Unglazed Transpired Collector xii List of Figures Page Figure 1: Revenue Passenger Kilometers by...95 Table 9: UTC Utilization Rate - Percent of Month Used ............................................. 100 Table 10: Solar Collector Fan Flow

  3. 40 CFR Table 2 to Subpart Rrrrr of... - Applicability of General Provisions to Subpart RRRRR of Part 63

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Definitions Yes. § 63.3 Units and Abbreviations Yes. § 63.4 Prohibited Activities Yes. § 63.5 Construction...) requirements in § 63.8(c)(5) and (6) apply only to COMS for dry electrostatic precipitators. § 63.8(a)(4... for dry electrostatic precipitators. § 63.10(a), (b)(1)-(2)(xii), (b)(2)(xiv), (b)(3), (c)(1)-(6), (c...

  4. 75 FR 11967 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... Order Entry Port from $250 to $500 and only charge per mnemonic instead of per mnemonic per port; (xii) amend the SQF Port Fee to assess a $500 per month per SQF port in lieu of the existing structure of $250 for the first five ports and $1000 for additional port thereafter and also rename the SQF Port Fee as...

  5. Selecting Electricity Generation Sources in Remote Locations

    DTIC Science & Technology

    2007-03-01

    A.N., & Chubb, T.J. (2005). Optimization of a PV with Diesel- Battery System for Remote Villages. International Solar Energy Journal , 6, 107- 118...List of Figures Page Figure 1. Electrification Rates by Region, 1970-2003 ( International , 2002) .................. 25 Figure 2. World Bank...xii List of Tables Page Table 1. Countries in 2000 with Low Electrification Rates ( International , 2002) .......... 13

  6. Korean Immigration Commemorative Coin Act

    THOMAS, 113th Congress

    Rep. Andrews, Robert E. [D-NJ-1

    2013-12-12

    House - 02/27/2014 Ms. Meng asked unanimous consent that she be considered the first sponsor of H.R. 3729, a bill originally introduced by Representative Andrews of New Jersey, for the purposes of adding cosponsors and requesting reprintings pursuant to clause 7 or rule XII. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  7. The Joint Effects-Based Contracting Execution System: A Proposed Enabling Concept for Future Joint Expeditionary Contracting Execution

    DTIC Science & Technology

    2008-12-01

    average 1 hour per response, including the time for reviewing instruction, searching existing data sources , gathering and maintaining the data needed...Representative for the Contracting Officer on five contracts whose value xii exceeded $200 million and participated on four source selection committees...roles on source selection boards; Consolidated Husbanding Services for all Pacific Ports, Consolidated MWR services for the Pacific, Software

  8. Defense Data Network/TOPS-20 Tutorial. An Interative Computer Program.

    DTIC Science & Technology

    1985-12-01

    33 XI. ELECTRONIC MAIL HOST ( EMH )-------------------------- 34 XII. EMACS...contents of text buffer to a file X EXCHANGE , used to search for and replace text Z ZAP, puts your entire file into the print buffer 23 - -° SWITCH...prompt USC-ISIE.ARPA> Sample foreign host command level prompt FTP COMMAND LEVEL COMMANDS COMMAND USE(S) FTP Invokes the FTP protocol CONNECT Connects

  9. Accomplishing American Strategic Goals in the Middle East through Persistent Special Operations

    DTIC Science & Technology

    2011-06-01

    LIST OF TABLES Table 1. Utility of SOF Vs . GPF in Various Conflicts ..................................................27 xii THIS PAGE...Headquarters and Support Company , 3 rd Battalion, 5 th Special Forces Group (Airborne) who have tirelessly stayed in the fight. xviii THIS... franchise industry by extending ties to regional extremist groups through financing and training. Al Qaeda Arabian Peninsula (AQAP) and Iranian influence

  10. Explorations on Just War: Has It Ever Existed?

    DTIC Science & Technology

    2006-06-01

    II . C. WORLD WAR II Pope Pius XII, in an address to the United Nations in 1952, said “The enormous violence of modern warfare means that...to the global community, Pope John Paul II cited “conscience of humanity and international humanity law” and claimed that nations and the...Unclassified 19. SECURITY CLASSIFICATION OF ABSTRACT Unclassified 20. LIMITATION OF ABSTRACT UL ii

  11. 40 CFR 75.58 - General recordkeeping provisions for specific situations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... C to this part, for each hour of missing SO2 concentration or volumetric flow data: (i) The information required in § 75.57(c) for SO2 concentration and volumetric flow, if either one of these monitors... SO2 concentration and volumetric flow using Codes 1-55 in Table 4a of § 75.57; and (xii) Inlet and...

  12. Southeast Asian Space Programs: Motives, Cooperation, and Competition

    DTIC Science & Technology

    2014-09-01

    LEO low Earth orbit MTCR Missile Technology Control Regime NAMRIA National Mapping and Resource Information Authority NASA National Aeronautics and...Technology’s role 27 Leo Marx and Merritt Roe Smith, “Introduction,” in Does Technology Drive History: The...Dilemma of Technological Determinism, ed. Merritt Roe Smith and Leo Marx (Cambridge, MA: The MIT Press, 1994), xii. 28 Donald MacKenzie and Judy

  13. Strategy for Upgrading Preparedness in Small and Rural Communities to Meet National Preparedness Standards

    DTIC Science & Technology

    2010-12-01

    National Academy of Public Administration NEMA National Emergency Managers Association xii NICC National Infrastructure Coordinating Center NIMS...2003, p. 3). A blunt conclusion stated succinctly in the 2008 study conducted by the National Emergency Managers Association ( NEMA ) on barriers to...NIMS compliance speaks to the heart of the issue: “Poorer, rural states can’t meet implementation, training, compliance requirements” ( NEMA , 2008

  14. 40 CFR 721.5185 - Morpholine, 4-(1-oxo-2-propenyl)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...), (a)(5)(i), (a)(5)(ii), (a)(5)(iii), (a)(5)(xii), (a)(5)(xiii), (a)(5)(xiv), (a)(5)(xv), (a)(6)(v), (b) (concentration set at 0. 1 percent), and (c). The following material has been tested in accordance with the American Society for Testing Materials (ASTM) F739 method and found by EPA to satisfy the consent order's...

  15. Effects of Clozapine and Alprazolam on Cognitive Deficits and Anxiety-Like Behaviors in a Ketamine-Induced Rat Model of Schizophrenia

    DTIC Science & Technology

    2005-01-01

    xii LIST OF TABLES Table 1. DSM-IV-TR Criteria for Schizophrenia (abbreviated) Table 2. Experimental Design Table 3. Experiment #1... Experimental Timeline Table 4. Experiment #2: Experimental Timeline Table 5. Experiment #1: Results of MANOVAs for Prepulse Inhibition Variables...rats. Please see Table 2 for a description of treatments and cell sizes for each experiment . Table 2. Experimental Design Ketamine (mg/kg

  16. Oceanic Impact: Mechanisms and Environmental Perturbations

    NASA Technical Reports Server (NTRS)

    Gersonde, Rainer (Editor); Deutsch, Alex (Editor); Ivanov, Boris A. (Editor); Kyte, Frank T. (Editor)

    2002-01-01

    The contents include the following: Oceanic impacts-a growing field of fundamental geoscience. Shock metamorphism on the ocean floor (numerical simulations). Numerical modeling of impact-induced modifications of the deep-sea floor. Computer modelling of the water resurge at a marine impact: the Lockne crater, Sweden. Experimental investigation of the role of water in impact vaporization chemistry. Calcareous plankton stratigraphy around the Pliocene Eltanin asteroid impact area (SE Pacific): documentation and application for geological and paleoceanographic reconstruction. Composition of impact melt debris from the Eltanin impact strewn field, Bellingshausen Sea. Iridium concentrations and abundances of meteoritic ejecta from the Eltanin impact in sediment cores from Polarstern expedition ANT XII/4. Unmelted meteoritic debris collected from Eltanin ejecta in Polarstern cores from expedition ANT XII/4. Impact tsunami-Eltanin. Ancient impact structures on modern continental shelves: The Chesapeake Bay, Montagnais, and Toms Canyon craters, Atlantic margin of North America. The Mjolnir marine impact crater porosity anomaly. Kardla (Hiiu-maa Island, Estonia) - the buried and well-preserved Ordovician marine impact structure. Long-term effect of the Kardla crater (Hiiu-maa, Estonia) on Late Ordovician carbonate sedimentation. The middle Devonian Kaluga impact crater (Russia): new interpretation of marine setting.

  17. Observation and numerical modeling of chromospheric evaporation during the impulsive phase of a solar flare

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

    Imada, Shinsuke, E-mail: shinimada@stelab.nagoya-u.ac.jp; Murakami, Izumi, E-mail: murakami.izumi@nifs.ac.jp; Department of Fusion Science, SOKENDAI

    2015-10-15

    We have studied the chromospheric evaporation flow during the impulsive phase of the flare by using the Hinode/EUV Imaging Spectrometer observation and 1D hydrodynamic numerical simulation coupled to the time-dependent ionization. The observation clearly shows that the strong redshift can be observed at the base of the flaring loop only during the impulsive phase. We performed two different numerical simulations to reproduce the strong downflows in FeXII and FeXV during the impulsive phase. By changing the thermal conduction coefficient, we carried out the numerical calculation of chromospheric evaporation in the thermal conduction dominant regime (conductivity coefficient κ{sub 0} = classical value) andmore » the enthalpy flux dominant regime (κ{sub 0} = 0.1 × classical value). The chromospheric evaporation calculation in the enthalpy flux dominant regime could reproduce the strong redshift at the base of the flare during the impulsive phase. This result might indicate that the thermal conduction can be strongly suppressed in some cases of flare. We also find that time-dependent ionization effect is important to reproduce the strong downflows in Fe XII and Fe XV.« less

  18. Genetic and physical mapping of homologues of the virus resistance gene Rx1 and the cyst nematode resistance gene Gpa2 in potato.

    PubMed

    Bakker, E; Butterbach, P; Rouppe van der Voort, J; van der Vossen, E; van Vliet, J; Bakker, J; Goverse, A

    2003-05-01

    Nine resistance gene homologues (RGHs) were identified in two diploid potato clones (SH and RH), with a specific primer pair based on conserved motifs in the LRR domain of the potato cyst nematode resistance gene Gpa2 and the potato virus X resistance gene Rx1. A modified AFLP method was used to facilitate the genetic mapping of the RGHs in the four haplotypes under investigation. All nine RGHs appeared to be located in the Gpa2/ Rx1 cluster on chromosome XII. Construction of a physical map using bacterial artificial chromosome (BAC) clones for both the Solanum tuberosum ssp. tuberosum and the S. tuberosum ssp. andigena haplotype of SH showed that the RGHs are located within a stretch of less than 200 kb. Sequence analysis of the RGHs revealed that they are highly similar (93 to 95%) to Gpa2 and Rx1. The sequence identities among all RGHs range from 85 to 100%. Two pairs of RGHs are identical, or nearly so (100 and 99.9%), with each member located in a different genotype. Southern-blot analysis on genomic DNA revealed no evidence for additional homologues outside the Gpa2/ Rx1 cluster on chromosome XII.

  19. Selective primary health care: strategies for control of disease in the developing world. XII. Ascariasis and trichuriasis.

    PubMed

    Arfaa, F

    1984-01-01

    Ascariasis and trichuriasis are the most prevalent and widespread intestinal helminthiases. Transmission of disease occurs by ingestion or inhalation of Ascaris and Trichuris eggs embryonated in the soil. During the migration of Ascaris to the lungs, pneumonic symptoms may develop. The intestinal stage of the parasite can cause severe symptoms and complications when the worm burden is high. High numbers of Trichuris may cause diarrhea. The poor standard of hygiene, the biology of the parasite (which is such that a high number of very resistant eggs are produced), and the habits of the host (such as the use of night soil) are factors causing a high prevalence of infection in many countries in Asia, Africa, South America, and Europe. The mechanism of the transmission of Ascaris varies in different communities. The peak of infection is among children aged four to 14 years. Worm burden is normally low, and only a small segment of the population harbors a high proportion of the worms present in a community. Control of infections due to Ascaris and Trichuris is feasible by a combination of mass chemotherapy with the effective drugs now available, safe disposal of excreta, destruction of the eggs, and health education.

  20. Biological basis and pathological relevance of microvascular thrombosis.

    PubMed

    Pfeiler, Susanne; Massberg, Steffen; Engelmann, Bernd

    2014-05-01

    Microvascular thrombosis indicates a pathological occlusion of microvessels by fibrin- and/or platelet-rich thrombi. It is observed during systemic infections, cancer, myocardial infarction, stroke, neurodegenerative diseases and in thrombotic microangiopathies. Microvessel thrombosis can cause greatly differing symptoms that range from limited changes in plasma coagulation markers to severe multi-organ failure. Because microvessel thrombi are difficult to detect and often occur only transiently, their importance for disease development and host biology is likely markedly under-appreciated. Recently, clear indications for a biological basis of microvascular thrombosis have been obtained. During systemic infections microvessel thrombosis can mediate an intravascular innate immune response (immunothrombosis). This biological form of thrombosis is based on the generation of fibrin inside blood vessels and is critically triggered by neutrophils and their interactions with platelets which result in the release of neutrophil extracellular traps (extracellular nucleosomes). Immunothrombosis is critically supported by neutrophil elastase and the activator molecules of blood coagulation tissue factor and factor XII. Identification of the biological driving forces of microvascular thrombosis should help to elucidate the mechanisms promoting pathological vessel occlusions in both microvessels and large vessels. Copyright © 2014 Elsevier Ltd. All rights reserved.