The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis
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
Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII
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
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.
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.
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
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.
The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy
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
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 plasmin activate factor XII; kallikrein is 20 times more potent on a molar basis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
The activation of plasminogen by Hageman factor (Factor XII) and Hageman factor fragments.
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
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.
Discovery of host-targeted covalent inhibitors of dengue virus
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
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 ways of blocking stress-induced hypercoagulability and hypertension. Hypercoagulability could be targeted by monoclonal antibodies directed against the platelet-specific alpha-2 adrenergic receptor or the (putative) platelet receptor for Factor XII; hypertension could be treated with monoclonal antibodies directed against the beta-adrenergic receptor in the juxtaglomerular apparatus or by surgical denervation of the kidneys, either of which would decrease the renin release which helps drive the hypertension.
Factor XI and XII as antithrombotic targets.
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.
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
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
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
Future prospects for contact factors as therapeutic targets
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
Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.
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 50% at D2 compared to the basal levels, and these reductions in plasma activity for both factors were consistent with our RT-PCR findings. In contrast, the plasma activities of the other coagulation factors (fibrinogen, factors V, VII, XIII, and VWF) were not significantly reduced, despite the reduction in the liver mRNA levels. Unlike the other factors, FX showed a temporal increase in its plasma activity, with significant increases (P<0.05) detected at D1. Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions.
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 receptors with AP5 had no effect on the modulation of XII nerve activity by SPNK1. In conclusion, SPNK1 modulates XII motoneuron responses to inspiratory drive primarily through inhibition of a resting, postsynaptic K+ leak conductance. The results establish the functional significance of SP in controlling upper airway tone during early postnatal life and indicate differential modulation of motoneurons controlling airway and pump muscles by SP. PMID:11454963
Evaluation of thromboelastography in two factor XII-deficient cats.
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.
Factor XI and Contact Activation as Targets for Antithrombotic Therapy
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
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.
The Secondary Structure of Human Hageman Factor (Factor XII) and its Alteration by Activating Agents
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
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.
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.
Evaluation of thromboelastography in two factor XII-deficient cats
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
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 structure of ProP, reveal the dimerization interface, and show that the structure of TM XII influences the osmolality at which ProP activates.
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
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.
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.
Expression of hypoxia-inducible carbonic anhydrases in brain tumors
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
[Effects of various adsorbants on coagulation factors (author's transl)].
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.
Retinal venous thrombosis in a young patient with coagulation factor XII deficiency.
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.
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.
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
Factor XII (Hageman factor) deficiency
... 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 ...
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 Space Science through the SR&T Program and the SEC Guest Investigator Program.
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.
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
Contact Activation of Blood Plasma and Factor XII by Ion-exchange Resins
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:21982294
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.
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.
Double-stabilized neurotensin analogues as potential radiopharmaceuticals for NTR-positive tumors.
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.
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.
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 hantavirus infection and could have profound implications for treatment of hantavirus infections. PMID:23874198
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 origin. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
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.
Contact system activation and high thrombin generation in hyperthyroidism.
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 activation and abundant NET formation occurred in the high thrombin generation state in hyperthyroidism and were correlated with free T4 level. © 2017 European Society of Endocrinology.
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.
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.
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.
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...
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...
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
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
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.
... 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 ...
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.
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...
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...
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...
Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population.
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 expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.
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
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
Contact activation: a revision.
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.
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...
Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.
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.
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.
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,…
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...
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: Condensed Matter will help foster further progress in the study of DIET processes. Since the field remains vibrant and exciting, the workshop series will continue with DIET XIII. Professor Richard Palmer (University of Birmingham, UK) will chair DIET XIII in the UK in early summer 2012. We gratefully acknowledge financial support from SPECS, HIDEN Analytical, BRUKER, The United States National Science Foundation, Georgia Institute of Technology and The State University of New Jersey, Rutgers.
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...
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...
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...
Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides.
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.
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.
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 "adsorption-dilution" effect that blocks FXII contact with hydrophobic activator surfaces. The adsorption-dilution effect explains the apparent specificity for hydrophilic activators pursued by earlier investigators. Finally a comparison of FXII autoactivation in buffer, serum, protein cocktail, and plasma solutions is shown herein. Activation of blood plasma coagulation in vitro by contact with material surfaces is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. However, activation of factor XII 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 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.
Autotransfusion from experimental hemothorax: levels of coagulation factors.
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.
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
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...
48 CFR Appendix F to Chapter 7 - Use of Collaborative Assistance Method for Title XII Activities
Code of Federal Regulations, 2010 CFR
2010-10-01
... AIDAR 715.613-71. 2. Purpose The collaborative assistance system is designed to: (a) Increase the joint..., including the design stage of a technical assistance project. 3. Policy The collaborative assistance... joint research and development—including training. In such an activity, the difficulty in defining, in...
48 CFR Appendix F to Chapter 7 - Use of Collaborative Assistance Method for Title XII Activities
Code of Federal Regulations, 2013 CFR
2013-10-01
... AIDAR 715.613-71. 2. Purpose The collaborative assistance system is designed to: (a) Increase the joint..., including the design stage of a technical assistance project. 3. Policy The collaborative assistance... joint research and development—including training. In such an activity, the difficulty in defining, in...
48 CFR Appendix F to Chapter 7 - Use of Collaborative Assistance Method for Title XII Activities
Code of Federal Regulations, 2014 CFR
2014-10-01
... AIDAR 715.613-71. 2. Purpose The collaborative assistance system is designed to: (a) Increase the joint..., including the design stage of a technical assistance project. 3. Policy The collaborative assistance... joint research and development—including training. In such an activity, the difficulty in defining, in...
48 CFR Appendix F to Chapter 7 - Use of Collaborative Assistance Method for Title XII Activities
Code of Federal Regulations, 2012 CFR
2012-10-01
... AIDAR 715.613-71. 2. Purpose The collaborative assistance system is designed to: (a) Increase the joint..., including the design stage of a technical assistance project. 3. Policy The collaborative assistance... joint research and development—including training. In such an activity, the difficulty in defining, in...
48 CFR Appendix F to Chapter 7 - Use of Collaborative Assistance Method for Title XII Activities
Code of Federal Regulations, 2011 CFR
2011-10-01
... AIDAR 715.613-71. 2. Purpose The collaborative assistance system is designed to: (a) Increase the joint..., including the design stage of a technical assistance project. 3. Policy The collaborative assistance... joint research and development—including training. In such an activity, the difficulty in defining, in...
1969-11-21
S69-59525 (19 Nov. 1969) --- Overall view of activity in the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC), Building 30, during the Apollo 12 lunar landing mission. When this picture was made the first Apollo 12 extravehicular activity (EVA) was being televised from the surface of the moon. Photo credit: NASA
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.
ERIC Educational Resources Information Center
Conway, Lorraine
Based on the idea that active participation stimulates the processes by which learning takes place, this document provides teachers and students with a variety of information and learning activities that deal with plants and animals in nature. Basic concepts are presented through the use of laboratory experiments, worksheet exercises, diagrams,…
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.
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...
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...
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.
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...
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.
Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases.
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.
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...
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...
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...
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...
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...
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...
The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis
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
ERIC Educational Resources Information Center
Vernon, Ralph J.; And Others
This report summarizes research findings which resulted in development of curricula for occupational safety and health professions based on task/activity analyses and related performance objectives. The first seven chapters focus on the seven objectives. Chapter 1, Literature Review and Selection of Employers, concerns tasks required for…
Role of plasma kallikrein in diabetes and metabolism.
Feener, E P; Zhou, Q; Fickweiler, W
2013-09-01
Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.
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.
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.
Fenik, V; Davies, R O; Pack, A I; Kubin, L
1998-10-01
Microinjections of carbachol into the pontine tegmentum of decerebrate cats have been used to study the mechanisms underlying the suppression of postural and respiratory motoneuronal activity during the resulting rapid eye movement (REM) sleep-like atonia. During REM sleep, distinct respiratory muscles are differentially affected; e.g., the activity of the diaphragm shows little suppression, whereas the activity of some upper airway muscles is quite strong. To determine the pattern of the carbachol-induced changes in the activity of different groups of upper airway motoneurons, we simultaneously recorded the efferent activity of the recurrent laryngeal nerve (RL), pharyngeal branch of the vagus nerve (Phar), and genioglossal branch of the hypoglossal (XII) and phrenic (Phr) nerves in 12 decerebrate, paralyzed, vagotomized, and artificially ventilated cats. Pontine carbachol caused a stereotyped suppression of the spontaneous activity that was significantly larger in Phar expiratory (to 8.3% of control) and XII inspiratory motoneurons (to 15%) than in Phr inspiratory (to 87%), RL inspiratory (to 79%), or RL expiratory motoneurons (to 72%). The suppression in upper airway motor output was significantly greater than the depression caused by a level of hypocapnia that reduced Phr activity as much as carbachol. We conclude that pontine carbachol evokes a stereotyped pattern of suppression of upper airway motor activity. Because carbachol evokes a state having many neurophysiological characteristics similar to those of REM sleep, it is likely that pontine cholinoceptive neurons have similar effects on the activity of upper airway motoneurons during both states.
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.
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.
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.
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…
Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.
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.
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...
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...
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.
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
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.
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.
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…
AID and Universities Have Yet to Forge an Effective Partnership to Combat World Food Problems.
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
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:…
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...
Influence of blood lipids on global coagulation test results.
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.
Influence of Blood Lipids on Global Coagulation Test Results
Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon
2015-01-01
Background 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). Methods 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). Results 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. Conclusion 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. PMID:25553275
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.
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.
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…
ERIC Educational Resources Information Center
Scott, John W., Ed.; Seidman, Laurence, Ed.
1992-01-01
"Folksong in the Classroom" is a newsletter of a network of teachers of history, literature, music, and the humanities. Each issue contains songs, background information, classroom activities, and ideas for teachers to use in integrating folksongs into their teaching. Three issues of "Folksong in the Classroom" are included in…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Klein, Fred W.
A significant seismic hazard exists in south Hawaii from large tectonic earthquakes that can reach magnitude 8 and intensity XII. This paper quantifies the hazard by estimating the horizontal peak ground acceleration (PGA) in south Hawaii which occurs with a 90% probability of not being exceeded during exposure times from 10 to 250 years. The largest earthquakes occur beneath active, unbuttressed and mobile flanks of volcanoes in their shield building stage.
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
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.
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.
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
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.
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…
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...
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.
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...
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
Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.
Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen
2016-06-01
Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (-7%, P = 0.009; -7.8%, P < 0.0001; -6.9%, P < 0.0001; and -4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.
C46 `ASTRONOMY Education and Development': a Peculiar Commission
NASA Astrophysics Data System (ADS)
de Greve, Jean-Pierre; García, Beatriz; Gerbaldi, Michèle; Ferlet, Roger; Guinan, Edward; Hearnshaw, John; Jones, Barrie; Marschall, Laurence; Miley, George; Pasachoff, Jay; Ros, Rosa; Stavinschi, Magda; Torres-Peimbert, Silvia
2016-04-01
C46 was a Commission of the Executive Committee of the IAU under Division XII (Union-Wide Activities), then after 2012 under Division C (Education, Outreach, and Heritage). It was the only commission dealing exclusively with astronomy education; a previous Commission 38 (Exchange of Astronomers), which allocated travel grants to astronomers who needed them, and a Working Group on the Worldwide Development of Astronomy, have been absorbed by Commission 46.
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
[Pathogenic factors of vibrios with special emphasis on Vibrio vulnificus].
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.
Propagation of thrombosis by neutrophils and extracellular nucleosome networks
Pfeiler, Susanne; Stark, Konstantin; Massberg, Steffen; Engelmann, Bernd
2017-01-01
Neutrophils, early mediators of the innate immune defense, are recruited to developing thrombi in different types of thrombosis. They amplify intravascular coagulation by stimulating the tissue factor-dependent extrinsic pathway via inactivation of endogenous anticoagulants, enhancing factor XII activation or decreasing plasmin generation. Neutrophil-dependent prothrombotic mechanisms are supported by the externalization of decondensed nucleosomes and granule proteins that together form neutrophil extracellular traps. These traps, either in intact or fragmented form, are causally involved in various forms of experimental thrombosis as first indicated by their role in the enhancement of both microvascular thrombosis during bacterial infection and carotid artery thrombosis. Neutrophil extracellular traps can be induced by interactions of neutrophils with activated platelets; vice versa, these traps enhance adhesion of platelets via von Willebrand factor. Neutrophil-induced microvascular thrombus formation can restrict the dissemination and survival of blood-borne bacteria and thereby sustain intravascular immunity. Dysregulation of this innate immune pathway may support sepsis-associated coagulopathies. Notably, neutrophils and extracellular nucleosomes, together with platelets, critically promote fibrin formation during flow restriction-induced deep vein thrombosis. Neutrophil extracellular traps/extracellular nucleosomes are increased in thrombi and in the blood of patients with different vaso-occlusive pathologies and could be therapeutically targeted for the prevention of thrombosis. Thus, during infections and in response to blood vessel damage, neutrophils and externalized nucleosomes are major promoters of intravascular blood coagulation and thrombosis. PMID:27927771
2001-06-01
Corrège Buffet Active Control - Experimental and Numerical Results 15 by C. Despré, D. Caruana, A. Mignosi, O. Reberga, M. Corrège, H. Gassot, J.C...Park and S. Menon An Experimental Examination of the Relationship Between Chemiluminescent Light 20 Emissions and Heat-Release Rate Under Non -Adiabatic...D.A. Santavicca An Experimental Study on Actively Controlled Dump Combustors 36 by K. Yu, K.J. Wilson, T.P. Parr and K.C. Schadow xii Theme The
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.
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
Forces necessary for the disruption of the cisternal segments of cranial nerves II through XII.
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.
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...
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.
Analysis of aggregation of platelets in thrombosis
NASA Astrophysics Data System (ADS)
Ahuja, Suresh
Platelets are key players in thrombus formation by first rolling over collagen bound von Willebrand factor followed by formation of a stable interaction with collagen. The first adhered platelets bind additional platelets until the whole injury is sealed off by a platelet aggregate. The coagulation system stabilizes the formed platelet plug by creating a tight fibrin network, and then wound contraction takes place because of morphological changes in platelets. Coagulation takes place by platelet activation and aggregation mainly through fibrinogen polymerization into fibrin fibers. The process includes multiple factors, such as thrombin, plasmin, and local shear-rate which regulate and control the process. Coagulation can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by the exposure of a negatively charged. It is able to activate factor XII, using a complex reaction that includes prekallikrein and high-molecular-weight kininogen as cofactors.. Thrombin is the final enzyme that is needed to convert fibrinogen into fibrin. The extrinsic pathway starts with the exposure of tissue factor to the circulating blood, which is the major initiator of coagulation. There are several feedback loops that reinforce the coagulation cascade, resulting in large amounts of thrombin. It is dependent on the presence of pro-coagulant surfaces of cells expressing negatively charged phospholipids--which include phosphatidylserine (PS)--on their outer membrane. PS-bearing surfaces are able to increase the efficiency of the reactions by concentrating and co-localizing coagulation factors.. Aggregation of platelets are analyzed and compared to adhesion of platelet to erythrocyte and to endothelial cells. This abstract is replacing MAR16-2015-020003.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brosius, Jeffrey W.; Daw, Adrian N.; Rabin, D. M., E-mail: Jeffrey.W.Brosius@nasa.gov
2014-08-01
We present spatially resolved EUV spectroscopic measurements of pervasive, faint Fe XIX 592.2 Å line emission in an active region observed during the 2013 April 23 flight of the Extreme Ultraviolet Normal Incidence Spectrograph (EUNIS-13) sounding rocket instrument. With cooled detectors, high sensitivity, and high spectral resolution, EUNIS-13 resolves the lines of Fe XIX at 592.2 Å (formed at temperature T ≈ 8.9 MK) and Fe XII at 592.6 Å (T ≈ 1.6 MK). The Fe XIX line emission, observed over an area in excess of 4920 arcsec{sup 2} (2.58 × 10{sup 9} km{sup 2}, more than 60% of themore » active region), provides strong evidence for the nanoflare heating model of the solar corona. No GOES events occurred in the region less than 2 hr before the rocket flight, but a microflare was observed north and east of the region with RHESSI and EUNIS during the flight. The absence of significant upward velocities anywhere in the region, particularly the microflare, indicates that the pervasive Fe XIX emission is not propelled outward from the microflare site, but is most likely attributed to localized heating (not necessarily due to reconnection) consistent with the nanoflare heating model of the solar corona. Assuming ionization equilibrium we estimate Fe XIX/Fe XII emission measure ratios of ∼0.076 just outside the AR core and ∼0.59 in the core.« less
Semi-aromatic polyesters based on a carbohydrate-derived rigid diol for engineering plastics.
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.
Functional Interactions between Mammalian Respiratory Rhythmogenic and Premotor Circuitry
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 incompletely understood. Here we applied network modeling and numerical simulation to discover respiratory circuit configurations that successfully replicate photonic cell ablation experiments targeting either the core oscillator or premotor network, respectively. If premotor neurons are interconnected in a so-called “small-world” network with a fixed number of incoming synapses balanced between premotor and rhythmogenic neurons, then our simulations match their experimental benchmarks. These results provide a framework of experimentally testable predictions regarding the rudimentary structure and function of respiratory rhythm- and pattern-generating circuits in the brainstem of mammals. PMID:27383596
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
[XII National Forum on Health Education].
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.
ERIC Educational Resources Information Center
de Celis, Margarita
This Child Development Associate (CDA) training module, the twelfth in a series of 16, is designed for preschool teachers and paraprofessional trainees and contains (in four separate sections) games, stories, songs and rhymes in Spanish that can be used in a bilingual, multicultural classroom setting. The module, written in Spanish, offers…
Comparative Study of the Effects of Combined Oral Contraceptives in Hemostatic Variables
Stocco, Bianca; Fumagalli, Helen F.; Franceschini, Silvio A.; Martinez, Edson Z.; Marzocchi-Machado, Cleni M.; de Sá, Marcos Felipe S.; Toloi, Maria Regina T.
2015-01-01
Abstract Thrombotic risk is associated with the estrogen dose and type of progestin in combined oral contraceptives. Studies published since 1990 showed that third-generation progestins have larger risk to contribute to thrombosis development than the second-generation. However, there are conflicts in the literature regarding the thrombotic risk associated to the drospirenone progestin. So, this study aimed to evaluate the effects of 3 formulations of contraceptives containing ethinylestradiol (EE) (20 and 30 μg) combined with drospirenone versus levonorgestrel combined with EE (30 μg) in hemostatic parameters. This cross-sectional study included 70 healthy women between 18 and 30 years, BMI 19 to 30 kg/m2, not pregnant, non-smokers, and users or non-users (control) of contraceptives for a minimum period of 6 months. The following parameters were assessed: prothrombin time (PT), Factor VII, activated partial thromboplastin time (aPTT), Factor XII, fibrinogen, Factor 1 + 2, Protein C, Protein S, antithrombin, D-dimers, and plasminogen activator inhibitor-1. Significant alterations were found in PT, aPTT, fibrinogen, D-dimers, and protein S, all favoring a state of hypercoagulation for contraceptive containing DRSP/20EE. Both contraceptives containing DRSP/30EE and LNG/30EE promoted changes that favor the hypercoagulability in the coagulant variable PT and in the anticoagulant variables Protein S and Protein C, respectively. We suggest that the progestin drospirenone can contribute to an inadequate balance among procoagulant, anticoagulant, and fibrinolytic factors, since that the contraceptive containing the lowest dose of estrogen and drospirenone (DRSP/20EE) caused a higher number of hemostatic changes. PMID:25634167
LRR-RLK family from two Citrus species: genome-wide identification and evolutionary aspects.
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 evolutionary analysis of the LRR-RLKs in Citrus. A large expansion of LRR-XII in Citrus genomes suggests that it might play a key role in adaptive responses in host-pathogen co-evolution, related to the perennial life cycle and domestication of the citrus crop species.
NASA Astrophysics Data System (ADS)
Bhatia, V. B.
Tradition of astronomy in India goes back to ancient times. Many festivals and rituals are associated with astronomical phenomena. Indian children start learning rudiments of astronomy from primary classes. But primary teachers are not equipped to handle this subject so not much learning actually takes place. The first serious interface with astronomy occurs when children reach class X when they are 15 years old. Till last year astronomy was there in class XII also but it has now been dropped. This is a serious setback for the study of astronomy. In class X astronomy forms part of general science. Since children at this stage are not proficient in physics and mathematics the subject remains descriptive though there are useful activities for children to do. However the teachers are not equipped to handle this subject and there is no help in the form of visual material. So the subject remains neglected. The Indian astronomical community can help by training teachers and providing visual material. It must also urge authorities to reintroduce astronomy in class XII if astronomy is to flourish in India. Moreover India needs to network with developing countries share experiences with them and evolve a strategy that promotes astronomy.
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.
Biological basis and pathological relevance of microvascular thrombosis.
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.
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.
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
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.
TESIS experiment on EUV imaging spectroscopy of the Sun
NASA Astrophysics Data System (ADS)
Kuzin, S. V.; Bogachev, S. A.; Zhitnik, I. A.; Pertsov, A. A.; Ignatiev, A. P.; Mitrofanov, A. M.; Slemzin, V. A.; Shestov, S. V.; Sukhodrev, N. K.; Bugaenko, O. I.
2009-03-01
TESIS is a set of solar imaging instruments in development by the Lebedev Physical Institute of the Russian Academy of Science, to be launched aboard the Russian spacecraft CORONAS-PHOTON in December 2008. The main goal of TESIS is to provide complex observations of solar active phenomena from the transition region to the inner and outer solar corona with high spatial, spectral and temporal resolution in the EUV and Soft X-ray spectral bands. TESIS includes five unique space instruments: the MgXII Imaging Spectroheliometer (MISH) with spherical bent crystal mirror, for observations of the Sun in the monochromatic MgXII 8.42 Å line; the EUV Spectoheliometer (EUSH) with grazing incidence difraction grating, for the registration of the full solar disc in monochromatic lines of the spectral band 280-330 Å; two Full-disk EUV Telescopes (FET) with multilayer mirrors covering the band 130-136 and 290-320 Å; and the Solar EUV Coronagraph (SEC), based on the Ritchey-Chretien scheme, to observe the inner and outer solar corona from 0.2 to 4 solar radii in spectral band 290-320 Å. TESIS experiment will start at the rising phase of the 24th cycle of solar activity. With the advanced capabilities of its instruments, TESIS will help better understand the physics of solar flares and high-energy phenomena and provide new data on parameters of solar plasma in the temperature range 10-10K. This paper gives a brief description of the experiment, its equipment, and its scientific objectives.
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.
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.
Zhu, Shu; Diamond, Scott L
2014-12-01
Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm(2))/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposition followed by fibrin formation. At venous wall shear rate (100 s(-1)), kaolin accelerated onset of fibrin formation by ~100 sec when compared to collagen alone (250 sec vs. 350 sec), with little effect on platelet deposition. Even with kaolin present, arterial wall shear rate (1000 s(-1)) delayed and suppressed fibrin formation compared to venous wall shear rate. A comparison of surfaces for extrinsic activation (tissue factor TF/collagen) versus contact activation (kaolin/collagen) that each generated equal platelet deposition at 100 s(-1) revealed: (1) TF surfaces promoted much faster fibrin onset (at 100 sec) and more endpoint fibrin at 600 sec at either 100 s(-1) or 1000 s(-1), and (2) kaolin and TF surfaces had a similar sensitivity for reduced fibrin deposition at 1000 s(-1) (compared to fibrin formed at 100 s(-1)) despite differing coagulation triggers. Anti-platelet drugs inhibiting P2Y1, P2Y12, cyclooxygenase-1 or activating IP-receptor or guanylate cyclase reduced platelet and fibrin deposition on kaolin/collagen. Since FXIIa or FXIa inhibition may offer safe antithrombotic therapy, especially for biomaterial thrombosis, these defined collagen/kaolin surfaces may prove useful in drug screening tests or in clinical diagnostic assays of blood under flow conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.
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
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
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
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.
Relativistic MR–MP Energy Levels for L-shell Ions of Silicon
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
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.
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).
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
Novoselova, E G; Parfeniuk, S B; Glushkova, O V; Khrenov, M O; Novoselova, T V; Lunin, S M; Fesenko, E E
2012-01-01
Effects of four inhibitors of NF-kappaB, SAPK/JNK and TLR4 signaling, namely, inhibitor XII, SP600125, CLI-095 and Oxpapc on a macrophage response to low dose ammonium were studied in RAW 264.7 cells. Low dose ammonium induced pro-inflammatory response in cells as judged from enhanced production of TNF-alpha, IF-gamma, and IL-6, and by activation of signal cascades. The increase in production of cytokines, namely TNF, IFN, and IL-6, demonstrated that low-dose ammonium induced a pro-inflammatory cellular response. In addition, an activation of NF-kappaB and SAPK/JNK cascades, as well as enhancement of TLR4 expression was shown. Each of used inhibitors reduced to a variable degree the pro-inflammatory response of RAW 264.7 cells on chemical toxin by decreasing cytokine production. The inhibitor of NF-kappaB cascade, IKK Inhibitor XII, was more effective, and not only prevented the development of pro-inflammatory response induced by ammonium, but also decreased cytokine production below control values. The inhibitor of extra cellular domains of TLR2 and TLR4 (OxPAPC) had almost the same anti-inflammatory effect, and an addition of the inhibitor of JNK cascade (SP600125) to cell culture practically neutralized effect of ammonium ions by decreasing cytokine production to control level. Inhibitory analysis showed that activation of RAW 264.7 cells induced by chemical toxin coincide incompletely with intracellular signaling pathways that were early determined regarding macrophage's response to toxin from gram-negative bacteria. Nevertheless, application of the inhibitors defended RAW 264.7 from toxic effect of the low dose ammonium.
APOLLO XII - LAUNCH DAY ACTIVITIES - LAUNCH COMPLEX 39A - KSC
1969-11-14
S69-58880 (14 Nov. 1969) --- Astronaut Alan L. Bean, Apollo 12 lunar module pilot, suits up in the Kennedy Space Center's (KSC) Manned Spacecraft Operations Building during the Apollo 12 prelaunch countdown. Minutes later astronauts Bean; Charles Conrad Jr., commander; and Richard F. Gordon Jr., command module pilot, rode a special transport van over to Pad A, Launch Complex 39, where their spacecraft awaited. The Apollo 12 liftoff occurred at 11:22 a.m. (EST), Nov. 14, 1969. Apollo 12 is the United States' second lunar landing mission.
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.
Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII.
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.
A novel slice preparation to study medullary oromotor and autonomic circuits in vitro
Nasse, Jason S.
2014-01-01
Background The medulla is capable of controlling and modulating ingestive behavior and gastrointestinal function. These two functions, which are critical to maintaining homeostasis, are governed by an interconnected group of nuclei dispersed throughout the medulla. As such, in vitro experiments to study the neurophysiologic details of these connections have been limited by spatial constraints of conventional slice preparations. New method This study demonstrates a novel method of sectioning the medulla so that sensory, integrative, and motor nuclei that innervate the gastrointestinal tract and the oral cavity remain intact. Results: Immunohistochemical staining against choline-acetyl-transferase and dopamine-β-hydroxylase demonstrated that within a 450 μm block of tissue we are able to capture sensory, integrative and motor nuclei that are critical to oromotor and gastrointestinal function. Within slice tracing shows that axonal projections from the NST to the reticular formation and from the reticular formation to the hypoglossal motor nucleus (mXII) persist. Live-cell calcium imaging of the slice demonstrates that stimulation of either the rostral or caudal NST activates neurons throughout the NST, as well as the reticular formation and mXII. Comparison with existing methods This new method of sectioning captures a majority of the nuclei that are active when ingesting a meal. Tradition planes of section, i.e. coronal, horizontal or sagittal, contain only a limited portion of the substrate. Conclusions Our results demonstrate that both anatomical and physiologic connections of oral and visceral sensory nuclei that project to integrative and motor nuclei remain intact with this new plane of section. PMID:25196216
Nucleolar asymmetry and the importance of septin integrity upon cell cycle arrest
Rai, Urvashi; Najm, Fadi
2017-01-01
Cell cycle arrest can be imposed by inactivating the anaphase promoting complex (APC). In S. cerevisiae this arrest has been reported to stabilize a metaphase-like intermediate in which the nuclear envelope spans the bud neck, while chromatin repeatedly translocates between the mother and bud domains. The present investigation was undertaken to learn how other features of nuclear organization are affected upon depletion of the APC activator, Cdc20. We observe that the spindle pole bodies and the spindle repeatedly translocate across the narrow orifice at the level of the neck. Nevertheless, we find that the nucleolus (organized around rDNA repeats on the long right arm of chromosome XII) remains in the mother domain, marking the polarity of the nucleus. Accordingly, chromosome XII is polarized: TelXIIR remains in the mother domain and its centromere is predominantly located in the bud domain. In order to learn why the nucleolus remains in the mother domain, we studied the impact of inhibiting rRNA synthesis in arrested cells. We observed that this fragments the nucleolus and that these fragments entered the bud domain. Taken together with earlier observations, the restriction of the nucleolus to the mother domain therefore can be attributed to its massive structure. We also observed that inactivation of septins allowed arrested cells to complete the cell cycle, that the alternative APC activator, Cdh1, was required for completion of the cell cycle and that induction of Cdh1 itself caused arrested cells to progress to the end of the cell cycle. PMID:28339487
A novel slice preparation to study medullary oromotor and autonomic circuits in vitro.
Nasse, Jason S
2014-11-30
The medulla is capable of controlling and modulating ingestive behavior and gastrointestinal function. These two functions, which are critical to maintaining homeostasis, are governed by an interconnected group of nuclei dispersed throughout the medulla. As such, in vitro experiments to study the neurophysiologic details of these connections have been limited by spatial constraints of conventional slice preparations. This study demonstrates a novel method of sectioning the medulla so that sensory, integrative, and motor nuclei that innervate the gastrointestinal tract and the oral cavity remain intact. Immunohistochemical staining against choline-acetyl-transferase and dopamine-β-hydroxylase demonstrated that within a 450 μm block of tissue we are able to capture sensory, integrative and motor nuclei that are critical to oromotor and gastrointestinal function. Within slice tracing shows that axonal projections from the NST to the reticular formation and from the reticular formation to the hypoglossal motor nucleus (mXII) persist. Live-cell calcium imaging of the slice demonstrates that stimulation of either the rostral or caudal NST activates neurons throughout the NST, as well as the reticular formation and mXII. This new method of sectioning captures a majority of the nuclei that are active when ingesting a meal. Tradition planes of section, i.e. coronal, horizontal or sagittal, contain only a limited portion of the substrate. Our results demonstrate that both anatomical and physiologic connections of oral and visceral sensory nuclei that project to integrative and motor nuclei remain intact with this new plane of section. Published by Elsevier B.V.
Identification of Genetic Defects Underlying FXII Deficiency in Four Unrelated Chinese Patients.
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.
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.
NASA Astrophysics Data System (ADS)
Tian, T.; Zhang, J.; Jiang, W.
2017-12-01
The North South Seismic Belt is located in the middle of China, and this seismic belt can be divided into 12 tectonic zones, including the South West Yunnan (I), the Sichuan Yunnan (II), the Qiang Tang (III), the Bayan Har (IV), the East Kunlun Qaidam (V), the Qi Lian Mountain (VI), the Tarim(VII), the East Alashan (VIII), the East Sichuan (IX), the Ordos(X), the Middle Yangtze River (XI) and the Edge of Qinghai Tibet Block (XII) zone. Based on the Bouguer Gravity data calculated from the EGM2008 model, the Euler deconvolution was used to obtain the edge of tectonic zone to amend the traditional tectonic divisions. In every tectonic zone and the whole research area, the logarithm of the total energy of seismic was calculated. The Time Series Analysis (TSA) for all tectonic zones and the whole area were progressed in R, and 12 equal divisions were made (A1-3, B1-3, C1-3, D1-3) by latitude and longitude as a control group. A simple linear trend fitting of time was used, and the QQ figure was used to show the residual distribution features. Among the zones according to Gravity anomalies, I, II and XII show similar statistical characteristic, with no earthquake free year (on which year there was no earthquake in the zone), and it shows that the more seismic activity area is more similar in statistical characteristic as the large area, no matter how large the zone is or how many earthquakes are in the zone. Zone IV, V, IX, III, VII and VIII show one or several seismic free year during 1970s (IV, V and IX) and 1980s (III, VII and VIII), which may implicate the earthquake activity were low decades ago or the earthquake catalogue were not complete in these zones, or both. Zone VI, X and XI show many earthquake free years even in this decade, which means in these zones the earthquake activity were very low even if the catalogue were not complete. In the control group, the earthquake free year zone appeared random and independent of the seismic density, and in all equal divided zones with seismic free years, the seismic free years all appeared in 1970s, which only related to the incompleteness of the earthquake catalogue in the west area of China. In conclusion, the tectonic divisions based on Gravity anomalies can provide a more efficient way to add space factor in the time series analysis with specific tectonic implications.
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. Phytoplasma solani'; STOL11 is designated the reference strain.
Siritapetawee, Jaruwan; Thammasirirak, Sompong
2011-01-01
Plant latex has many health benefits and has been used in folk medicine. In this study, the biological effect of Artocarpus heterophyllus (jackfruit) latex on human blood coagulation was investigated. By a combination of heat precipitation and ion-exchange chromatography, a heat stable heteromultimeric glycoprotein (HSGPL1) was purified from jackfruit milky latex. The apparent molecular masses of the monomeric proteins on SDS/PAGE were 33, 31 and 29 kDa. The isoelectric points (pIs) of the monomers were 6.63, 6.63 and 6.93, respectively. Glycosylation and deglycosylation tests confirmed that each subunit of HSGPL1 formed the native multimer by sugar-based interaction. Moreover, the multimer of HSGPL1 also resisted 2-mercaptoethanol action. Peptide mass fingerprint analysis indicated that HSGPL1 was a complex protein related to Hsps/chaperones. HSGPL1 has an effect on intrinsic pathways of the human blood coagulation system by significantly prolonging the activated partial thrombin time (APTT). In contrast, it has no effect on the human extrinsic blood coagulation system using the prothrombin time (PT) test. The prolonged APTT resulted from the serine protease inhibitor property of HSGPL1, since it reduced activity of human blood coagulation factors XI(a) and α-XII(a).
Active region upflows. I. Multi-instrument observations
NASA Astrophysics Data System (ADS)
Vanninathan, K.; Madjarska, M. S.; Galsgaard, K.; Huang, Z.; Doyle, J. G.
2015-12-01
Context. We study upflows at the edges of active regions, called AR outflows, using multi-instrument observations. Aims: This study intends to provide the first direct observational evidence of whether chromospheric jets play an important role in furnishing mass that could sustain coronal upflows. The evolution of the photospheric magnetic field, associated with the footpoints of the upflow region and the plasma properties of active region upflows is investigated with the aim of providing information for benchmarking data-driven modelling of this solar feature. Methods: We spatially and temporally combine multi-instrument observations obtained with the Extreme-ultraviolet Imaging Spectrometer on board the Hinode, the Atmospheric Imaging Assembly and the Helioseismic Magnetic Imager instruments on board the Solar Dynamics Observatory and the Interferometric BI-dimensional Spectro-polarimeter installed at the National Solar Observatory, Sac Peak, to study the plasma parameters of the upflows and the impact of the chromosphere on active region upflows. Results: Our analysis shows that the studied active region upflow presents similarly to those studied previously, i.e. it displays blueshifted emission of 5-20 kms-1 in Fe xii and Fe xiii and its average electron density is 1.8 × 109 cm-3 at 1 MK. The time variation of the density is obtained showing no significant change (in a 3σ error). The plasma density along a single loop is calculated revealing a drop of 50% over a distance of ~20 000 km along the loop. We find a second velocity component in the blue wing of the Fe xii and Fe xiii lines at 105 kms-1 reported only once before. For the first time we study the time evolution of this component at high cadence and find that it is persistent during the whole observing period of 3.5 h with variations of only ±15 kms-1. We also, for the first time, study the evolution of the photospheric magnetic field at high cadence and find that magnetic flux diffusion is responsible for the formation of the upflow region. High cadence Hα observations are used to study the chromosphere at the footpoints of the upflow region. We find no significant jet-like (spicule/rapid blue excursion) activity to account for several hours/days of plasma upflow. The jet-like activity in this region is not continuous and blueward asymmetries are a bare minimum. Using an image enhancement technique for imaging and spectral data, we show that the coronal structures seen in the AIA 193 Å channel are comparable to the EIS Fe xii images, while images in the AIA 171 Å channel reveal additional loops that are a result of contribution from cooler emission to this channel. Conclusions: Our results suggest that at chromospheric heights there are no signatures that support the possible contribution of spicules to active region upflows. We suggest that magnetic flux diffusion is responsible for the formation of the coronal upflows. The existence of two velocity components possibly indicates the presence of two different flows, which are produced by two different physical mechanisms, e.g. magnetic reconnection and pressure-driven jets. Movies associated to Figs. A.1-A.3 are available in electronic form at http://www.aanda.org
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
A cross-sectional study of factors associated with adolescent sexual activity.
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.
Unraveling and engineering the production of 23,24-bisnorcholenic steroids in sterol metabolism
Xu, Li-Qin; Liu, Yong-Jun; Yao, Kang; Liu, Hao-Hao; Tao, Xin-Yi; Wang, Feng-Qing; Wei, Dong-Zhi
2016-01-01
The catabolism of sterols in mycobacteria is highly important due to its close relevance in the pathogenesis of pathogenic strains and the biotechnological applications of nonpathogenic strains for steroid synthesis. However, some key metabolic steps remain unknown. In this study, the hsd4A gene from Mycobacterium neoaurum ATCC 25795 was investigated. The encoded protein, Hsd4A, was characterized as a dual-function enzyme, with both 17β-hydroxysteroid dehydrogenase and β-hydroxyacyl-CoA dehydrogenase activities in vitro. Using a kshAs-null strain of M. neoaurum ATCC 25795 (NwIB-XII) as a model, Hsd4A was further confirmed to exert dual-function in sterol catabolism in vivo. The deletion of hsd4A in NwIB-XII resulted in the production of 23,24-bisnorcholenic steroids (HBCs), indicating that hsd4A plays a key role in sterol side-chain degradation. Therefore, two competing pathways, the AD and HBC pathways, were proposed for the side-chain degradation. The proposed HBC pathway has great value in illustrating the production mechanism of HBCs in sterol catabolism and in developing HBCs producing strains for industrial application via metabolic engineering. Through the combined modification of hsd4A and other genes, three HBCs producing strains were constructed that resulted in promising productivities of 0.127, 0.109 and 0.074 g/l/h, respectively. PMID:26898409
Unraveling and engineering the production of 23,24-bisnorcholenic steroids in sterol metabolism.
Xu, Li-Qin; Liu, Yong-Jun; Yao, Kang; Liu, Hao-Hao; Tao, Xin-Yi; Wang, Feng-Qing; Wei, Dong-Zhi
2016-02-22
The catabolism of sterols in mycobacteria is highly important due to its close relevance in the pathogenesis of pathogenic strains and the biotechnological applications of nonpathogenic strains for steroid synthesis. However, some key metabolic steps remain unknown. In this study, the hsd4A gene from Mycobacterium neoaurum ATCC 25795 was investigated. The encoded protein, Hsd4A, was characterized as a dual-function enzyme, with both 17β-hydroxysteroid dehydrogenase and β-hydroxyacyl-CoA dehydrogenase activities in vitro. Using a kshAs-null strain of M. neoaurum ATCC 25795 (NwIB-XII) as a model, Hsd4A was further confirmed to exert dual-function in sterol catabolism in vivo. The deletion of hsd4A in NwIB-XII resulted in the production of 23,24-bisnorcholenic steroids (HBCs), indicating that hsd4A plays a key role in sterol side-chain degradation. Therefore, two competing pathways, the AD and HBC pathways, were proposed for the side-chain degradation. The proposed HBC pathway has great value in illustrating the production mechanism of HBCs in sterol catabolism and in developing HBCs producing strains for industrial application via metabolic engineering. Through the combined modification of hsd4A and other genes, three HBCs producing strains were constructed that resulted in promising productivities of 0.127, 0.109 and 0.074 g/l/h, respectively.
Abazari, Reza; Mahjoub, Ali Reza
2018-03-05
A visible light-driven amine-functionalized Al-based MOF # @ y x Sm 2 O 3 -ZnO nanocomposite (NH 2 -MOF # @ y x Sm 2 O 3 -ZnO NCP) was synthesized as an effective photocatalyst for AMX degradation in the presence of ultrasound, in which # is MOF synthesis conditions from MOF I to MOF XII and x and y stand for the weight percentages of Sm 2 O 3 -to-ZnO and Sm 2 O 3 -ZnO-to-MOF, respectively. The β-lactam antibiotic AMX, which is widely used for treating Gram-positive and Gram-negative bacterial infections in both animals and humans, was employed as a model pollutant. Using different detection techniques, the synthesized materials were characterized. Furthermore, effects of different synthesis methods, ultrasonic time, precursor concentration, sonication amplitude, and modulators on the MOFs photocatalytic behavior were taken into account. Also, catalytic dose and recycling, H 2 O 2 usage, and operating pH effects were investigated. Compared to the pure forms of NH 2 -MOF-53(Al) and Sm 2 O 3 -ZnO, the NCPs having the optimal Sm 2 O 3 -ZnO and NH 2 -MOF-53(Al) contents highly influenced the photocatalytic activity due to the synergetic impacts of the high charge mobility and the red shift in the NH 2 -MOF@Sm 2 O 3 -ZnO NCPs absorption edge compared to the Sm 2 O 3 -ZnO nanoflowers. We used a TOC analyzer, UV/vis spectroscopy, and HPLC chromatogram to estimate the rate of AMX elimination in water over NH 2 -MOF XII @ 30 7 Sm 2 O 3 -ZnO NCPs as our optimal sample. In addition, after the AMX pollutant degradation, the NH 2 -MOF@Sm 2 O 3 -ZnO NCPs were structurally stable and maintained the majority of their photocatalytic properties even after five runs of recycling process The NH 2 -MOF XII @ 30 7 Sm 2 O 3 -ZnO NCPs as the superior photocatalysts were more examined and a mechanism for the AMX degradation was suggested. As a suggestion, our obtained results can be used as a starting point for the preparation of the other heterogeneous MOF-based NCPs combined with the Sm 2 O 3 -ZnO for a variety of applications such as the environmental remediation.
NASA Astrophysics Data System (ADS)
Lee, K.; Imada, S.; Moon, Y.; Lee, J.
2013-12-01
We investigate spectral properties of a cool loop and a dark lane over a limb active region on 2007 March 14 by the Hinode/EUV Imaging Spectrometer. The cool loop is clearly seen in the spectral lines formed at the transition region temperature. The dark lane is characterized by an elongated faint structure in coronal spectral lines and rooted on a bright point. We determine their electron densities, Doppler velocities, and non-thermal velocities with height over the limb. We derived electron densities using the density sensitive line pairs of Mg VII, Si X, Fe XII, Fe XIII and Fe XIV spectra. Under the hydrostatic equilibrium and isothermal assumption, we determine their temperatures from the density scale height. Comparing the scale height temperatures to the peak formation temperatures of the spectral lines, we note that the scale height temperature of the cool loop is consistent with a peak formation temperature of the Fe XII and the scale height temperatures of the dark lane from each spectral lines are much lower than their peak formation temperatures. The non-thermal velocity in the cool loop slightly decreases along the loop while that in the dark lane sharply falls off with height. The variation of non-thermal velocity with height in the cool loop and the dark lane is contrast to that in off-limb polar coronal holes which are considered as source of the solar wind. Such a decrease in the non-thermal velocity may be explained by wave damping near the solar surface or turbulence due to magnetic reconnection near the bright point.
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...
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...
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...
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...
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...
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...
A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis.
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.
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...
Prezoto, B C; Tanaka-Azevedo, A M; Marcelino, J R; Tashima, A K; Nishiduka, E S; Kapronezai, J; Mota, J O; Rocha, M M T; Serino-Silva, C; Oguiura, N
2018-06-15
The assessment of the capacity of antivenoms to neutralize the lethal activity of snake venoms still relies on traditional rodent in vivo lethality assay. ED 50 and LD 50 assays require large quantities of venoms and antivenoms, and besides leading to animal suffering. Therefore, in vitro tests should be introduced for assessing antivenom neutralizing capacity in intermediary steps of antivenom production. This task is facilitated when one key lethal toxin is identified. A good example is crotoxin, a β-neurotoxin phospholipase A 2 -like toxin that presents anticoagulant activity in vitro and is responsible for the lethality of venoms of Crotalus durissus snakes. By using rotational thromboelastometry, we reported recently one sensitive coagulation assay for assessing relative potency of the anti-bothropic serum in neutralizing procoagulant activity of Bothrops jararaca venom upon recalcified factor-XII-deficient chicken plasma samples (CPS). In this study, we stablished conditions for determining relative potency of four batches of the anti-crotalic serum (ACS) (antagonist) in inactivating crotoxin anticoagulant activity in CPS (target) simultaneously treated with one classical activator of coagulation (agonists). The correlation coefficient (r) between values related the ACS potency in inactivating both in vitro crotoxin anticoagulant activity and the in vivo lethality of whole venom (ED 50 ) was 0.94 (p value < 0.05). In conclusion, slowness in spontaneous thrombin/fibrin generation even after recalcification elicit time lapse sufficient for elaboration of one dose-response curve to pro- or anti-coagulant agonists in CPS. We propose this methodology as an alternative and sensitive assay for assessing antivenom neutralizing ability in plasma of immunized horses as well as for in-process quality control. Copyright © 2018 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xie, Haixia; Li, Bo; Huang, Zhenghua
How the solar corona is heated to high temperatures remains an unsolved mystery in solar physics. In the present study we analyze observations of 50 whole active region loops taken with the Extreme-ultraviolet Imaging Spectrometer on board the Hinode satellite. Eleven loops were classified as cool loops (<1 MK) and 39 as warm loops (1–2 MK). We study their plasma parameters, such as densities, temperatures, filling factors, nonthermal velocities, and Doppler velocities. We combine spectroscopic analysis with linear force-free magnetic field extrapolation to derive the 3D structure and positioning of the loops, their lengths and heights, and the magnetic fieldmore » strength along the loops. We use density-sensitive line pairs from Fe xii, Fe xiii, Si x, and Mg vii ions to obtain electron densities by taking special care of intensity background subtraction. The emission measure loci method is used to obtain the loop temperatures. We find that the loops are nearly isothermal along the line of sight. Their filling factors are between 8% and 89%. We also compare the observed parameters with the theoretical Rosner–Tucker–Vaiana (RTV) scaling law. We find that most of the loops are in an overpressure state relative to the RTV predictions. In a follow-up study, we will report a heating model of a parallel-cascade-based mechanism and will compare the model parameters with the loop plasma and structural parameters derived here.« less
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...
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...
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 motivation and success in physics courses and may have long-term implications on the quality of physics education in schools, colleges. and universities and the scientific research aspirations of the country.
Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S
2010-05-01
We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.
48 CFR 715.370-1 - Title XII selection procedure-general.
Code of Federal Regulations, 2013 CFR
2013-10-01
... essential, a statement of work, estimate of personnel requirements, special requirements (logistic support... statement of work, an estimate of the personnel required, and special provisions (such as logistic support...
48 CFR 715.370-1 - Title XII selection procedure-general.
Code of Federal Regulations, 2014 CFR
2014-10-01
... essential, a statement of work, estimate of personnel requirements, special requirements (logistic support... statement of work, an estimate of the personnel required, and special provisions (such as logistic support...
48 CFR 715.370-1 - Title XII selection procedure-general.
Code of Federal Regulations, 2012 CFR
2012-10-01
... essential, a statement of work, estimate of personnel requirements, special requirements (logistic support... statement of work, an estimate of the personnel required, and special provisions (such as logistic support...
[Concepts in anticoagulant therapy - past, present, and future].
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.
A cross-sectional study of factors associated with adolescent sexual activity
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
[Pregnancy outcome during the bombing of Yugoslavia from March 24 to June 9, 1999].
Krstić, Dragan; Marinković, Darko; Mirković, Ljiljana; Krstić, Jelena
2006-04-01
The aim of this study was to evaluate pregnancy outcome during the bombing of Yugoslavia in the period from March 24 to June 9, 1999. A retrospective study included a total of 81 spontaneous abortion following XII gestation week, and 1448 deliveries, hospitalized in the regional hospital. The analyzed were: the incidence of spontaneous abortion, Cesarean section, post-term delivery, vaginal delivery following the previous Cesarean section within the period from March 24 to June 9, 1999, and compared to the same periods in 1998 and 2000 by the use of chi2 and Kolgomorov-Smirnov tests. Under the conditions of a three-month stress imposed by the bombing, significantly increased were the incidence of spontaneous abortion and vaginal delivery following the previous Cesarean section, while the incidence of Cesarean section and post-term delivery were decreased, but the incidence of perinatal outcome was paradoxically improved. The analysis of findings on admittance revealed that iterative Cesarean section was performed electively, close to the expected term of delivery, and vaginal delivery following the previous Cesarean section mainly two weeks before that term with the admittance finding confirming a high active stage pregnancy. Within the bombing, statistically significantly was increased the percentage of abortions after XII gestation week, and the biological duration of pregnancy was reduced. The reduced duration of pregnancy complete with the accelerated fetal mutation (also caused by the stress) resulted in better perinatal outcome, and statistically significantly lower percentage of Cesarean section.
Conlon, J M; Platzack, B; Marra, L E; Youson, J H; Olson, K R
1995-01-01
The holostean fish occupy an important position in vertebrate phylogeny as extant representatives of a ancient group of ray-finned fish with evolutionary connections to present-day teleosts. Incubation of heat-denatured plasma from the bowfin Amia calva with trypsin generated bradykinin-like immunoreactivity. The primary structure of bowfin bradykinin was established as Ala-Pro-Pro-Gly-Trp-Ser-Pro-Phe-Arg. This amino acid sequence contains one amino acid substitution (Phe5 --> Trp) compared with mammalian bradykinin. The same peptide was generated in heat-denatured plasma from the longnosed gar Lepisosteus osseus. Treatment of plasma from either the bowfin or gar with glass beads under conditions previously shown to activate Factor XII in the plasma of mammals and reptiles did not generate bradykinin. Bolus injections of synthetic bowfin bradykinin (0.1, 0.3, and 1.0 nmol/kg) into the bulbus arteriosus of unanesthetized bowfin resulted in an immediate fall in arterial blood pressure of 5-10 min duration that was followed by a dose-dependent rise in pressure that was sustained for 30-60 min. There was no change in heart rate following bradykinin administration. The data suggest that the kallikrein-kinin system may predate the appearance of teleosts and may play a role in cardiovascular regulation in holosteans.
Désormeaux, Anik; Moreau, Marie Eve; Lepage, Yves; Chanard, Jacques; Adam, Albert
2008-03-01
The combination of negatively-charged membranes and angiotensin I-converting enzyme inhibitors (ACEi) evokes hypersensitivity reactions (HSR) during hemodialysis and bradykinin (BK)-related peptides have been hypothesized as being responsible for these complications. In this study, we tested the effects of neutralizing the membrane electronegativity (zeta potential) of polyacrylonitrile AN69 membranes by coating a polyethyleneimine layer (AN69-ST membranes) over the generation of kinins induced by blood contact with synthetic membranes. We used minidialyzers with AN69 or AN69-ST membranes in an ex vivo model of plasma and we showed that plasma dialysis with AN69 membranes led to significant BK and des-Arg(9)-BK release, which was potentiated by ACEi. This kinin formation was dramatically decreased by AN69-ST membranes, even in the presence of an ACEi, and kinin recovery in the dialysates was also significantly lower with these membranes. High molecular weight kininogen and factor XII detection by immunoblotting of the protein layer coating both membranes corroborated the results: binding of these proteins and contact system activation on AN69-ST membranes were reduced. This ex vivo experimental model applied to the plasma, dialysate and dialysis membrane could be used for the characterization of the kinin-forming capacity of any biomaterial potentially used in vivo in combination with drugs which modulate the pharmacological activity of kinins.
Enzymatic and chemical synthesis of new anticoagulant peptides.
Origone, Anabella; Bersi, Grisel; Illanes, Andrés; Sturniolo, Héctor; Liggieri, Constanza; Guzmán, Fanny; Barberis, Sonia
2018-06-08
In this study we report the enzymatic synthesis of N-α-[Carbobenzyloxy]-Tyr-Gln-Gln (Z-YQQ), a new anticoagulant tripeptide. It was obtained using phytoproteases from the stems and petioles of Asclepias curassavica L. as catalyst in an aqueous-organic biphasic system formed by 50% (v/v) ethyl acetate and 0.1 M Tris - HCl buffer pH 8. The resulting peptide was compared with the analogous peptide Tyr-Gln-Gln (YQQ) produced by solid-phase chemical synthesis. The in vitro anticoagulant activity of the above mentioned peptides was determined using Wiener Lab Test (Wiener, Argentina). The toxicological activity of the peptides was also determined. The enzymatically synthesized Z-YQQ peptide acted on the extrinsic pathway of the coagulation cascade, delaying the conversion time of prothrombin to thrombin and fibrinogen to fibrin by 136% and 50%, respectively, with respect to the controls. The chemically synthesized YQQ peptide acted specifically on the intrinsic pathway of the coagulation cascade, affecting factors VIII, IX, XI and XII from such cascade, and increasing the coagulation time by 105% with respect to the control. The results suggest that two new anticoagulant peptides (Z-YQQ and YQQ) can be useful for safe pharmaceutical applications. Nevertheless, some aspects related to peptide production should be optimized. This article is protected by copyright. All rights reserved. © 2018 American Institute of Chemical Engineers.
Désormeaux, Anik; Moreau, Marie Eve; Lepage, Yves; Chanard, Jacques; Adam, Albert
2014-01-01
The combination of negatively-charged membranes and angiotensin I-converting enzyme inhibitors (ACEi) evokes hypersensitivity reactions (HSR) during hemodialysis and bradykinin (BK)-related peptides have been hypothesized as being responsible for these complications. In this study, we tested the effects of neutralizing the membrane electronegativity (zeta potential) of polyacrylonitrile AN69 membranes by coating a polyethyleneimine layer (AN69-ST membranes) over the generation of kinins induced by blood contact with synthetic membranes. We used minidialyzers with AN69 or AN69-ST membranes in an ex vivo model of plasma and we showed that plasma dialysis with AN69 membranes led to significant BK and des-Arg9-BK release, which was potentiated by ACEi. This kinin formation was dramatically decreased by AN69-ST membranes, even in the presence of an ACEi, and kinin recovery in the dialysates was also significantly lower with these membranes. High molecular weight kininogen and factor XII detection by immunoblotting of the protein layer coating both membranes corroborated the results: binding of these proteins and contact system activation on AN69-ST membranes were reduced. This ex vivo experimental model applied to the plasma, dialysate and dialysis membrane could be used for the characterization of the kinin-forming capacity of any biomaterial potentially used in vivo in combination with drugs which modulate the pharmacological activity of kinins. PMID:18078988
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...
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...
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...
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...
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...
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...
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...
Unstable transpositions of his4 in yeast.
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
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.
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...
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...
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...
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...
Pashmakova, Medora B; Barr, James W; Bishop, Micah A
2015-05-01
To compare stability of hemostatic proteins in canine fresh-frozen plasma (FFP) thawed with a modified commercial microwave warmer (MCM) or warm water bath (37°C; WWB) or at room temperature (22°C). Fresh-frozen plasma obtained from 8 canine donors of a commercial blood bank. A commercial microwave warmer was modified with a thermocouple to measure surface temperature of bags containing plasma. The MCM and a WWB were each used to concurrently thaw a 60-mL bag of plasma obtained from the same donor. Two 3-mL control aliquots of FFP from each donor were thawed to room temperature without use of a heating device. Concentrations of hemostatic proteins, albumin, and D-dimers; prothrombin time (PT); and activated partial thromboplastin time (aPTT) were determined for all samples. Significant decreases in concentrations of factors II, IX, X, XI, fibrinogen, von Willebrand factor, antithrombin, protein C, and albumin and significant increases in PT and aPTT were detected for plasma thawed with the MCM, compared with results for samples thawed with the WWB. Concentrations of factors VII, VIII, and XII were not significantly different between plasma thawed with the MCM and WWB. Concentrations of D-dimers were above the reference range for all thawed samples regardless of thawing method. No significant differences in factor concentrations were detected between control and WWB-thawed samples. Significant differences in hemostatic protein concentrations and coagulation times were detected for plasma thawed with an MCM but not between control and WWB-thawed samples. Clinical importance of these changes should be investigated.
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...
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...
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...
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...
25 CFR 36.32 - Standard XII-Graduation requirements for a high school diploma.
Code of Federal Regulations, 2011 CFR
2011-04-01
... general science area. (ii) One (1) unit in laboratory science areas, i.e., chemistry, physics, biology, zoology, laboratory anatomy. (5) Physical education—one (1) unit. (6) Practical arts—one (1) unit. Credit...
25 CFR 36.32 - Standard XII-Graduation requirements for a high school diploma.
Code of Federal Regulations, 2014 CFR
2014-04-01
... general science area. (ii) One (1) unit in laboratory science areas, i.e., chemistry, physics, biology, zoology, laboratory anatomy. (5) Physical education—one (1) unit. (6) Practical arts—one (1) unit. Credit...
25 CFR 36.32 - Standard XII-Graduation requirements for a high school diploma.
Code of Federal Regulations, 2013 CFR
2013-04-01
... general science area. (ii) One (1) unit in laboratory science areas, i.e., chemistry, physics, biology, zoology, laboratory anatomy. (5) Physical education—one (1) unit. (6) Practical arts—one (1) unit. Credit...
25 CFR 36.32 - Standard XII-Graduation requirements for a high school diploma.
Code of Federal Regulations, 2012 CFR
2012-04-01
... general science area. (ii) One (1) unit in laboratory science areas, i.e., chemistry, physics, biology, zoology, laboratory anatomy. (5) Physical education—one (1) unit. (6) Practical arts—one (1) unit. Credit...
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.
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.
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.
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 palsy respond well to RT. That the time course of neurologic recovery is variable and can be protracted indicates a need for continuous and close neurologic surveillance. The poorer neurologic outcome associated with a longer duration of CN symptoms may be related to a more severe longterm CN compression that results in irreversible damage. Timely diagnosis of NPC and fast institution of therapy are therefore critical to improving the neurologic outcome.
In-Situ Remediation of MTBE Contaminated Aquifers Using Propane Biosparging. Revision 1
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
Adaptation to vestibular disorientation. XII, Habituation of vestibular responses : an overview.
DOT National Transportation Integrated Search
1974-03-01
Vestibular and visual mechanisms are critical sensing systems in spatial orientation and in spatial disorientation. In aviation or space environments in particular, the role of the vestibular system is central to the problems of spatial disorientatio...
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...
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...
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...
Girolami, Antonio; Vidal, Josè; Sabagh, Marcela; Salagh, Marcela; Gervan, Nora; Parody, Maria; Peroni, Edoardo; Sambado, Luisa; Guglielmone, Hugo
2014-07-01
Prekallikrein (PK) is one of the clotting factors involved in the contact phase of blood. PK has an important historical role as its deficiency state represents the second instance of a clotting defect without bleeding manifestations, the first one being factor XII deficiency. PK deficiency is a rare clotting disorder. Moreover, only 11 patients have been investigated so far by molecular biology techniques. In this article, we briefly review some of the history around PK and also present some recent data on a newly identified family from Argentina suffering from PK deficiency. Two patients are homozygous whereas other family members are heterozygous. PK activity and antigen are 1% of normal in the homozygotes and around 60 to 70% of normal in the heterozygotes. As expected, all patients are asymptomatic of bleeding or thrombosis presentations. However, the two homozygotes showed essential hypertension. The PK deficiency in this family is due to a new mutation (Arg541Gln) in exon 14. The defect segregates together with a known polymorphism, Asn124Ser, in exon 5. The significance of the presence of hypertension in the two homozygotes is discussed in view of the extra coagulation effects of PK on vasodilation, vessel permeability, and the control of blood pressure. Structure function analysis indicates that the substitution of Arg with Gln probably impedes the transmembrane diffusion of the molecule, which therefore cannot be secreted in the homozygotes. The presence of hypertension in patients with PK deficiency has been previously reported in some but not all patients. Future research activities will probably concentrate on the effect of PK and other contact phase factors on the vascular system. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Human plasma kallikrein-kinin system: Physiological and biochemical parameters
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
[Stability of disintegration in health food].
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.
Nichols, Nicole L.; Satriotomo, Irawan; Harrigan, Daniel J.; Mitchell, Gordon S.
2015-01-01
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated superoxide dismutase-1 (SOD1G93A), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1G93A (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600µM; 12µL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms preserving/enhancing the capacity for pLTF in MT rats are not known. PMID:26287750
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.
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...
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.
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...
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...
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...
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...
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...
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...
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...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-01
... parts of the National Board Inspection Code at http://www.nationalboard.org . DATES: The comment period... edition of the National Board Inspection Code for public review at www.nationalboard.org . Both documents...
Division XII / Commission 46 / Program Group Teaching for Astronomy Development
NASA Astrophysics Data System (ADS)
Guinan, Edward F.; Marschall, Laurence A.
Annual reports of the IAU Commission 46 Program Group Teaching for Astronomy Development (TAD) for the years 2006 and 2007 have been published in IAU Information Bulletin 100, 47; and 101, 40. Here the 2008 report is presented.
Wickström, H R; Holgert, H; Hökfelt, T; Lagercrantz, H
1999-02-05
In situ hybridization was used to characterize respiration-related areas of the brainstem activated around the time of birth as well as their postnatal sensitivity to CO2. Levels of mRNA corresponding to the immediate early genes (IEG), c-fos and c-jun, and of substance P precursor, ppt-A, were determined in rat fetuses (E21) and neonatal pups (1 h, 1 day and 6 days after normal birth) and after exposure to hypercapnia (12% CO2 for 1 h). Transient increases in c-fos mRNA were observed in the central chemoreceptor area of the ventral medullary surface (VMS), in the lateral reticular nucleus (LRN), in the nucleus of the solitary tract (NTS), and in the nucleus raphé pallidus (RPA) 1 h after birth. Increased expression of c-fos mRNA in the VMS could also be evoked by hypercapnia and this response was particularly pronounced 1 day after birth. On the other hand, c-jun mRNA could be detected already at E21 in the hypoglossal nucleus (XII) and LRN and these levels were not significantly altered at 1 h after birth. There was, however, an increase in the expression of c-jun mRNA in the pia mater surrounding the brainstem after birth. At 1 day after birth, c-jun mRNA levels had decreased in the LRN and pia mater, and later on (6 days after birth) in XII. Furthermore, the ppt-A mRNA level in NTS increased immediately after birth and remained high 1 and 6 days later. These results suggest that (a) the central chemoreceptor area of the VMS, as well as the NTS, LRN, RPA and pia mater are activated following birth; (b) the VMS, but not the other structures examined, can be activated immediately after birth by hypercapnia; and (c) increased expression of ppt-A mRNA may be related to the transition of respiratory control at birth. Copyright 1998 Elsevier Science B.V.
Kaplan, Allen P
2014-01-01
Diseases which have been demonstrated to be caused by increased plasma levels of bradykinin all have angioedema as the common major clinical manifestation. Angioedema due to therapy with angiotensin-converting enzyme (ACE) inhibitors is caused by suppressed bradykinin degradation so that it accumulates. This occurs because ACE metabolizes bradykinin by removal of Phe-Arg from the C-terminus, which inactivates it. By contrast, angioedema due to C1 inhibitor deficiency (either hereditary types I and II, or acquired) is caused by bradykinin overproduction. C1 inhibitor inhibits factor XIIa, kallikrein and activity associated with the prekallikrein-HK (high-molecular-weight kininogen) complex. In its absence, uncontrolled activation of the plasma bradykinin cascade is seen once there has been an initiating stimulus. C4 levels are low in all types of C1 inhibitor deficiency due to the instability of C1 (C1r, in particular) such that some activated C1 always circulates and depletes C4. In the hereditary disorder, formation of factor XIIf (factor XII fragment) during attacks of swelling causes C4 levels to drop toward zero, and C2 levels decline. A kinin-like molecule, once thought to be a cleavage product derived from C2 that contributes to the increased vascular permeability seen in hereditary angioedema (HAE), is now thought to be an artifact, i.e. no such molecule is demonstrable. The acquired C1 inhibitor deficiency is associated with clonal disorders of B cell hyperreactivity, including lymphoma and monoclonal gammopathy. Most cases have an IgG autoantibody to C1 inhibitor which inactivates it so that the presentation is strikingly similar to type I HAE. New therapies for types I and II HAE include C1 inhibitor replacement therapy, ecallantide, a kallikrein antagonist, and icatibant, a B2 receptor antagonist. A newly described type III HAE has normal C1 inhibitor, although it is thought to be mediated by bradykinin, as is an antihistamine-resistant subpopulation of patients with 'idiopathic' angioedema. The mechanism(s) for the formation of bradykinin in these disorders is unknown. © 2014 S. Karger AG, Basel.
Analysis of Several PLA2 mRNA in Human Meningiomas
Denizot, Yves; De Armas, Rafael; Durand, Karine; Robert, Sandrine; Moreau, Jean-Jacques; Caire, François; Weinbreck, Nicolas; Labrousse, François
2009-01-01
In view of the important oncogenic action of phospholipase A2(PLA2) we investigated PLA2 transcripts in human meningiomas. Real-time PCR was used to investigate PLA2 transcripts in 26 human meningioma tumors. Results indicated that three Ca2+-dependent high molecular weight PLA2 (PLA2-IVA, PLA2-IVB, PLA2-IVC), one Ca2+-independent high molecular weight PLA2 (PLA2-VI) and five low molecular weight secreted forms of PLA2 (PLA2-IB, PLA2-IIA, PLA2-III, PLA2-V, and PLA2-XII) are expressed with PLA2-IVA, PLA2-IVB, PLA2-VI, and PLA2-XIIA as the major expressed forms. PLA2-IIE, PLA2-IIF, PLA2-IVD, and PLA2-XIIB are not detected. Plasma (PLA2-VIIA) and intracellular (PLA2-VIIB) platelet-activating factor acetylhydrolase transcripts are expressed in human meningiomas. However no difference was found for PLA2 transcript amounts in relation to the tumor grade, the subtype of meningiomas, the presence of inflammatory infiltrated cells, of an associated edema, mitosis, brain invasion, vascularisation or necrosis. In conclusion numerous genes encoding multiples forms of PLA2 are expressed in meningiomas where they might act on the phospholipid remodeling and on the local eicosanoid and/or cytokine networks. PMID:20339511
Arterial thrombosis is accelerated in mice deficient in histidine-rich glycoprotein
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
Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K
2001-09-01
1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.
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...
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...
An isolated right hypoglossal nerve palsy in association with infectious mononucleosis.
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
Concerning the flow about ring-shaped cowlings XII : two new classes of circular cowls
NASA Technical Reports Server (NTRS)
Kuchemann, Dietrich; Weber, Johanna
1953-01-01
For application in practice for annular radiator fairings and similar arrangements, two new classes of circular cowls are developed by theoretical method, and investigated in a systematic test series regarding their behavior under various working conditions.
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...
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...
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...
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...
Electromagnetic Environment Measurements of PRT Systems at "TRANSPO 72" : Volume XII
DOT National Transportation Integrated Search
1974-01-01
The report covers the measurements of the broadband conducted noise present on the A.C. power lines feeding the Personalized Rapid Transit (PRT) systems with all four systems operating simultaneously. The purpose of the measurement effort was to eval...
Large-Scale Coronal Heating, Clustering of Coronal Bright Points, and Concentration of Magnetic Flux
NASA Technical Reports Server (NTRS)
Falconer, D. A.; Moore, R. L.; Porter, J. G.; Hathaway, D. H.
1998-01-01
By combining quiet-region Fe XII coronal images from SOHO/EIT with magnetograms from NSO/Kitt Peak and from SOHO/MDI, we show that on scales larger than a supergranule the population of network coronal bright points and the magnetic flux content of the network are both markedly greater under the bright half of the quiet corona than under the dim half. These results (1) support the view that the heating of the entire corona in quiet regions and coronal holes is driven by fine-scale magnetic activity (microflares, explosive events, spicules) seated low in the magnetic network, and (2) suggest that this large-scale modulation of the magnetic flux and coronal heating is a signature of giant convection cells.
Alpha Centauri at a Crossroads
NASA Astrophysics Data System (ADS)
Ayres, Thomas
2014-09-01
Nearby Alpha Centauri (G2V+K1V) contains the two best characterized solar-like dwarf stars, which also have the best studied X-ray activity cycles, extending back to the 1970's. Objective is to continue tracking the evolving multi-decadal high-energy narrative of Alpha Cen with semiannual HRC-I pointings in Cycles 16-18, as the system reaches a coronal crossroads: solar twin A rising toward cycle maximum, K-type companion B sinking into a minimum. HST/STIS UV spectra will support and leverage the X-ray measurements by probing subcoronal dynamics, with connection to the corona through the FUV Fe XII forbidden line. Only Chandra can resolve the AB X-ray sources as the Alpha Cen orbit also reaches a crossroads in 2016.
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...
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),…
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...
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...
48 CFR 715.370-2 - Title XII selection procedure-collaborative assistance.
Code of Federal Regulations, 2010 CFR
2010-10-01
... AGENCY FOR INTERNATIONAL DEVELOPMENT CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION... contracting system is appropriate. See AIDR sppendix F (of this chapter)—Use of Collaborative Assistance... initiating any contract actions under the collaborative assistance method: (1) The cognizant technical office...
48 CFR 715.370-2 - Title XII selection procedure-collaborative assistance.
Code of Federal Regulations, 2011 CFR
2011-10-01
... AGENCY FOR INTERNATIONAL DEVELOPMENT CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION... contracting system is appropriate. See AIDR sppendix F (of this chapter)—Use of Collaborative Assistance... initiating any contract actions under the collaborative assistance method: (1) The cognizant technical office...
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.
Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy.
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.
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.
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.
Ferrite Loaded Coils for Improved Wireless Power Transfer Efficiency
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
Assessing the Totalitarian Islamists: A Strategy of Alliances
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
48 CFR 715.370-1 - Title XII selection procedure-general.
Code of Federal Regulations, 2010 CFR
2010-10-01
... essential, a statement of work, estimate of personnel requirements, special requirements (logistic support... statement of work, an estimate of the personnel required, and special provisions (such as logistic support, government furnished equipment, and so forth), a proposed contract format, and evaluation criteria. No cost...
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...
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...
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...
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...
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...
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...
USDA-ARS?s Scientific Manuscript database
The CRI (chromophore release and identification) method isolates well-defined chromophoric substances from different cellulosic matrices, such as highly bleached pulps, cotton linters, bacterial cellulose, viscose or lyocell fibers, and cellulose acetates. The chromophores are present only in extrem...
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...
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...
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...
Involving Corporations in Dispensing During Mass Prophylaxis
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
The Sunset Supply Base: Long Term COTS Supportability, Implementing Affordable Methods and Processes
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 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] ...
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] ...
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] ...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
Overview of the Lambda-* Performance Reasoning Frameworks
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
Koizumi, Hidehiko; Koshiya, Naohiro; Chia, Justine X.; Cao, Fang; Nugent, Joseph; Zhang, Ruli
2013-01-01
We comparatively analyzed cellular and circuit properties of identified rhythmic excitatory and inhibitory interneurons within respiratory microcircuits of the neonatal rodent pre-Bötzinger complex (pre-BötC), the structure generating inspiratory rhythm in the brainstem. We combined high-resolution structural–functional imaging, molecular assays for neurotransmitter phenotype identification in conjunction with electrophysiological property phenotyping, and morphological reconstruction of interneurons in neonatal rat and mouse slices in vitro. This approach revealed previously undifferentiated structural–functional features that distinguish excitatory and inhibitory interneuronal populations. We identified distinct subpopulations of pre-BötC glutamatergic, glycinergic, GABAergic, and glycine-GABA coexpressing interneurons. Most commissural pre-BötC inspiratory interneurons were glutamatergic, with a substantial subset exhibiting intrinsic oscillatory bursting properties. Commissural excitatory interneurons projected with nearly planar trajectories to the contralateral pre-BötC, many also with axon collaterals to areas containing inspiratory hypoglossal (XII) premotoneurons and motoneurons. Inhibitory neurons as characterized in the present study did not exhibit intrinsic oscillatory bursting properties, but were electrophysiologically distinguished by more pronounced spike frequency adaptation properties. Axons of many inhibitory neurons projected ipsilaterally also to regions containing inspiratory XII premotoneurons and motoneurons, whereas a minority of inhibitory neurons had commissural axonal projections. Dendrites of both excitatory and inhibitory interneurons were arborized asymmetrically, primarily in the coronal plane. The dendritic fields of inhibitory neurons were more spatially compact than those of excitatory interneurons. Our results are consistent with the concepts of a compartmental circuit organization, a bilaterally coupled excitatory rhythmogenic kernel, and a role of pre-BötC inhibitory neurons in shaping inspiratory pattern as well as coordinating inspiratory and expiratory activity. PMID:23407957
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 relationship between CrRLK1L and Pto group. It will be exciting to verify if sensu strictu Pto are present in taxonomic groups other than Solanaceae, in order to further clarify the evolutionary link with CrRLK1L.We obtained a first valuable resource useful for an in-depth study on stress perception systems.
G Protein-Coupled Kinin Receptors and Immunity Against Pathogens.
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 from studies of kinin receptor function in experimental infections have shed light on the complex proteolytic circuits that, acting at the endothelial interface, reciprocally couple immunity to the proinflammatory KKS. © 2017 Elsevier Inc. All rights reserved.
EGF domain of coagulation factor IX is conducive to exposure of phosphatidylserine.
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.
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...
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...
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...
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...
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...
DOT National Transportation Integrated Search
2005-12-01
This volume provides an overview of the six studies that compose Phase II of the Enhanced Night Visibility project and the experimental plan for its third and final portion, Phase III. The Phase II studies evaluated up to 12 vision enhancement system...
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…
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
[Book Review] Waterfowl ecology and management by Guy A. Baldassarre and Eric G. Bolen
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
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...
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...
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...
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...
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...
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...
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...
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…
1966-10-01
S66-09382 (1 Oct. 1966) --- Gemini-12 Experiment MSC-7 Bremsstrahlung Spectrometer-Spectrometer Analyzer processor installed in cabin. Objective of experiment is to determine the gamma and beta flux and energy spectra induced inside the spacecraft by exterior electrons. Photo credit: NASA
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
Environmental Education. Catalogue of Resources for Grades I to XII.
ERIC Educational Resources Information Center
Houghton, J. R.
Environmental education resources are presented in three categories: (1) print materials; (2) non-print materials; and (3) physical resources. The print material category is subdivided into two sections: books, booklets, and card sets; and magazines, reports, and pamphlets. Entries, arranged alphabetically by title within each section, include…
48 CFR 715.370-1 - Title XII selection procedure-general.
Code of Federal Regulations, 2011 CFR
2011-10-01
... INTERNATIONAL DEVELOPMENT CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Source Selection 715..., government furnished property, and so forth) for the contracting officer's use in preparing the request for...) through (iii) of this section, with the “Action” copy of the PIO/T to the contracting officer, requesting...
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
Federal Register 2010, 2011, 2012, 2013, 2014
2013-12-30
... Rulemaking Division, (202) 366-8553, or Stanley Staniszewski, Engineering and Research [[Page 79364... increased capacity to transport product. A review of previous research by PHMSA's Engineering and Research..., knowledge-sharing, and skill development across all engineering disciplines. ASME is recognized globally for...
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)…
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…
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
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...
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...
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...
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...
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...
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...
DOT National Transportation Integrated Search
1991-12-01
Polymeric aircraft cabin materials have the potential to produce toxic gases in fires. Lethality (LC50) in animal models is a standard index to rank polymers on the basis of their combustion product toxicity. However, the use of times-toincapacitatio...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
Network Routing Using the Network Tasking Order, a Chron Approach
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
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...
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...
Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika
2016-12-01
Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.
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...
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...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-23
... requirement for allowable peak secondary stresses for MC 331 cargo tanks. 4. Rational Design of Non-circular... the design, construction, and certification of cargo tank motor vehicles, cryogenic portable tanks and... CTMV: Cargo Tank Motor Vehicle DCE: Design Certifying Engineer FMCSA: Federal Motor Carrier Safety...
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...
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...
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...
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...
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…
25 CFR 36.32 - Standard XII-Graduation requirements for a high school diploma.
Code of Federal Regulations, 2010 CFR
2010-04-01
..., zoology, laboratory anatomy. (5) Physical education—one (1) unit. (6) Practical arts—one (1) unit. Credit... diploma. 36.32 Section 36.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY...
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...
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…
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…
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...
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...
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...
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…
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...
Evaluation Policy on Assistance Program Bidikmisi Higher Education in Private Kopertis Region XII
ERIC Educational Resources Information Center
Wasahua, Tahir; Koesmaryono, Yonny; Sailah, Illah
2018-01-01
One of the governments' policy through Directoral General of Learning and Student Affair, Ministry of Research, Technology and Higher Education in improving the access for new students namely the bidikmisi program. Program bidikmisi is a tuition fee subsidy program allocated to selected new students who possess excellent academic capability yet…
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...
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...
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...
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...
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...
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...
On-Chip Out-of-Plane High-Q Inductors
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
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...
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...
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...
Multiscale Modeling of Non-crystalline Ceramics (Glass)
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
USDA-ARS?s Scientific Manuscript database
While all Newcastle disease viruses (NDV) are contained within one serotype and different NDV provide cross-protection against others, antigenically matched strains have been shown to decrease viral shedding. Therefore, using recombinant technology, some companies have directed efforts in developin...
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...
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...
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...
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...
Experimental Analysis of Dampened Breathing Mode Oscillation on Hall Thruster Performance
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
U. S. Naval Forces, Vietnam Monthly Historical Summary for July 1970
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
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...
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...
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...
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] ...
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] ...
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] ...
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] ...
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] ...
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 ...
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…
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…
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.
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...
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...
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...
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...
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.
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.
Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy
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
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.
Arterial thrombosis is accelerated in mice deficient in histidine-rich glycoprotein.
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.
Sosnovsky, G; Li, S W
1985-04-15
The spin labeled nitrosourea 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6- tetramethyl-piperidinyl)-1-nitrosourea (SLCNU, 4) and its analogues 5-7 were synthesized either by a regio-selective method or by a conventional route via the nitrosation of the spin labeled intermediates (11a-e). Nitrosation of the ureas 11a-e with dinitrogen tetraoxide resulted in better yields than those obtained with sodium nitrite. The nitrosoureas 4-8 were tested for their anticancer activity against the lymphocytic leukemia P388 in mice. Thus, either at the equal molar dose or at the dose of equal toxicity level, the SLCNU (4) was found to be more active than the clinically used CCNU (1). Unlike CCNU (1) whose LD50 is 56 mg/kg, the SLCNU (4) possesses a low toxicity (LD50 123 mg/kg). Therefore, SLCNU (4) is a promising new entry into the nitrosourea class of anticancer drugs.
Bacterial resistance modifying tetrasaccharide agents from Ipomoea murucoides.
Chérigo, Lilia; Pereda-Miranda, Rogelio; Gibbons, Simon
2009-01-01
As part of an ongoing project to identify oligosaccharides which modulate bacterial multidrug resistance, the CHCl(3)-soluble extract from flowers of a Mexican arborescent morning glory, Ipomoea murucoides, through preparative-scale recycling HPLC, yielded five lipophilic tetrasaccharide inhibitors of Staphylococcusaureus multidrug efflux pumps, murucoidins XII-XVI (1-5). The macrocyclic lactone-type structures for these linear hetero-tetraglycoside derivatives of jalapinolic acid were established by spectroscopic methods. These compounds were tested for in vitro antibacterial and resistance modifying activity against strains of Staphylococcus aureus possessing multidrug resistance efflux mechanisms. Only murucoidin XIV (3) displayed antimicrobial activity against SA-1199B (MIC 32microg/ml), a norfloxacin-resistant strain that over-expresses the NorA MDR efflux pump. The four microbiologically inactive (MIC>512microg/ml) tetrasaccharides increased norfloxacin susceptibility of this strain by 4-fold (8microg/ml from 32microg/ml) at concentrations of 25microg/ml, while murucoidin XIV (3) exerted the same potentiation effect at a concentration of 5microg/ml.
Coordinated Observations of AR 11726 by Hinode/EIS and EUNIS-2013
NASA Astrophysics Data System (ADS)
Ancheta, A. J.; Daw, A. N.; Brosius, J. W.
2016-12-01
The Extreme-Ultraviolet Normal-Incidence Spectrograph (EUNIS) sounding rocket payload was flown on 2013 April 23 with two independent channels covering the 300-370 A and 525-635 A wavebands. EUNIS-2013 observed two targets on the solar disk that included quiet sun, active regions, a flare, and a micro-flare. The active region AR 11726 was co-observed with the EUV Imaging Spectrometer (EIS) on Hinode. The radiometric response of EUNIS is measured in the laboratory using a NIST-calibrated photodiode and hollow cathode discharge lamp. A density- and temperature- insensitive line intensity ratio technique can be used to derive an in-flight calibration update of Hinode/EIS. Measurements of EIS emission lines with respect to EUNIS lines, including Fe X to Fe XII and Si X, provide a comparison between the calibrations of the two instruments. The radiometric calibration of EUNIS-2013 is also validated using the same insensitive ratio technique with emission lines such as Mg VIII, Fe XI, Fe XVI, and Si IX.
Spectroscopic Study of a Dark Lane and a Cool Loop in a Solar Limb Active Region by Hinode/EIS
NASA Astrophysics Data System (ADS)
Lee, K.; Imada, S.; Moon, Y.; Lee, J.
2012-12-01
We investigate a cool loop and a dark lane over a limb active region on 2007 March 14 by the Hinode/EUV Imaging Spectrometer (EIS). The cool loop is clearly seen in the EIS spectral lines formed at the transition region temperature (log T = 5.8). The dark lane is characterized by an elongated faint structure in coronal spectral lines (log T = 5.8 - 6.1) and rooted on a bright point. We examine their electron densities, Doppler velocities, and non-thermal velocities as a function of distance from the limb using the spectral lines formed at different temperatures (log T = 5.4 - 6.4). The electron densities of the cool loop and the dark lane are derived from the density sensitive line pairs of Mg VII, Fe XII, and Fe XIV spectra. Under the hydrostatic equilibrium and isothermal assumption, we determine their temperatures from the density scale height. Comparing the scale height temperatures to the peak formation temperatures of the spectral lines, we note that the scale height temperature of the cool loop is consistent with a peak formation temperature of the Mg VII (log T = 5.8) and the scale height temperature of the dark lane is close to a peak formation temperature of the Fe XII and Fe XIII (log T = 6.1 - 6.2). It is interesting to note that the structures of the cool loop and the dark lane are most visible in these temperature lines. While the non-thermal velocity in the cool loop slightly decreases (less than 7 km {s-1}) along the loop, that in the dark lane sharply falls off with height. The variation of non-thermal velocity with height in the cool loop and the dark lane is contrast to that in off-limb polar coronal holes which are considered as source of the fast solar wind. Such a decrease in the non-thermal velocity may be explained by wave damping near the solar surface or turbulence due to magnetic reconnection near the bright point.
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.
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...
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...
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...
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...
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...
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...
Architectural Survey of Seven Wyoming Army National Guard Armories, 1961-1974: Volume 1
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
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...
H-Bomb Development: Decision on the Merits or Political Necessity
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
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...
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...
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...
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...
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...
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...
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…
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…
Selecting Electricity Generation Sources in Remote Locations
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
Code of Federal Regulations, 2012 CFR
2012-07-01
... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...
Code of Federal Regulations, 2014 CFR
2014-07-01
... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...
Code of Federal Regulations, 2010 CFR
2010-07-01
... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...
Code of Federal Regulations, 2013 CFR
2013-07-01
... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...
Code of Federal Regulations, 2011 CFR
2011-07-01
... sweepings Air filters Electroplating bath filters Wastewater filter media Wood pallets Disposable clothing... cartridge filters Paper hand towels B. Exempt Nickel or Chromium-Bearing Materials when Generated by Any... Nickel, chromium, and iron catalysts Nickel-cadmium and nickel-iron batteries Filter cake from wet...
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...
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...
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...
ERIC Educational Resources Information Center
Chandler, David, Comp.; And Others
This unit is part of a Mississippi program designed to provide exploratory experiences and training for handicapped students, to determine if these students are capable of further vocational training or are poor risks for further occupational training, and to train students for basal skill occupations. The materials included in this unit on…
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...
ERIC Educational Resources Information Center
National Highway Traffic Safety Administration (DOT), Washington, DC.
This instructor's lesson plan guide on pediatrics and neonatal transport is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Five units of study are presented: (1) approach to the pediatric patient including patient assessment; (2) pathophysiology and management of problems unique to the…
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 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...
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...
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...
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,…
Research Linking Teacher Preparation and Student Performance: Teacher Education Yearbook XII
ERIC Educational Resources Information Center
Guyton, Edith M., Ed.; Dangel, Julie Rainer, Ed.
2004-01-01
The case studies, research, and projects presented here strike at the very heart of effective teaching. The specific practices to improve student performance will spark classroom discussion and improve teacher practice. After a foreword by Frances van Tassell and an introduction by Edith M. Guyton and Julie Rainer Dangel, this book is divided into…
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...
Medical Management of Radiological Casualties, Second Edition, Handbook
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
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...
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...