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Sample records for egl-4 pkg acts

  1. Nuclear cGMP-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex.

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    Yan Hao

    2011-05-01

    Full Text Available Elevation of the second messenger cGMP by nitric oxide (NO activates the cGMP-dependent protein kinase PKG, which is key in regulating cardiovascular, intestinal, and neuronal functions in mammals. The NO-cGMP-PKG signaling pathway is also a major therapeutic target for cardiovascular and male reproductive diseases. Despite widespread effects of PKG activation, few molecular targets of PKG are known. We study how EGL-4, the Caenorhabditis elegans PKG ortholog, modulates foraging behavior and egg-laying and seeks the downstream effectors of EGL-4 activity. Using a combination of unbiased forward genetic screen and proteomic analysis, we have identified a conserved SAEG-1/SAEG-2/HDA-2 histone deacetylase complex that is specifically recruited by activated nuclear EGL-4. Gene expression profiling by microarrays revealed >40 genes that are sensitive to EGL-4 activity in a SAEG-1-dependent manner. We present evidence that EGL-4 controls egg laying via one of these genes, Y45F10C.2, which encodes a novel protein that is expressed exclusively in the uterine epithelium. Our results indicate that, in addition to cytoplasmic functions, active EGL-4/PKG acts in the nucleus via a conserved Class I histone deacetylase complex to regulate gene expression pertinent to behavioral and physiological responses to cGMP. We also identify transcriptional targets of EGL-4 that carry out discrete components of the physiological response.

  2. The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.

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    Xiao Xu

    Full Text Available Stress is a fundamental aspect of aging, as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan. In this study, we identify a conserved Caenorhabditis elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS, as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

  3. C. elegans HIM-8 functions outside of meiosis to antagonize EGL-13 Sox protein function.

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    Nelms, Brian L; Hanna-Rose, Wendy

    2006-05-15

    egl-13 encodes a Sox domain protein that is required for proper uterine seam cell development in Caenorhabditis elegans. We demonstrate that mutations of the C2H2 zinc fingers encoded by the him-8 (high incidence of males) gene partially suppress the egg-laying and connection-of-gonad morphology defects caused by incompletely penetrant alleles of egl-13. him-8 alleles have previously characterized recessive effects on recombination and segregation of the X chromosome during meiosis due to failure of X chromosome homolog pairing and subsequent synapsis. However, we show that him-8 alleles are semi-dominant suppressors of egl-13, and the semi-dominant effect is due to haplo-insufficiency of the him-8 locus. Thus, we conclude that the wild-type him-8 gene product acts antagonistically to EGL-13. Null alleles of egl-13 cannot be suppressed, suggesting that this antagonistic interaction most likely occurs either upstream of or in parallel with EGL-13. Moreover, we conclude that suppression of egl-13 is due to a meiosis-independent function of him-8 because suppression is observed in mutants that have severely reduced meiotic germ cell populations and suppression does not depend on the function of him-8 in the maternal germ line. We also show that the chromosomal context of egl-13 seems important in the him-8 suppression mechanism. Interactions between these genes can give insight into function of Sox family members, which are important in many aspects of metazoan development, and into functions of him-8 outside of meiosis.

  4. EGL-13/SoxD specifies distinct O2 and CO2 sensory neuron fates in Caenorhabditis elegans.

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    Jakob Gramstrup Petersen

    2013-05-01

    Full Text Available Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2 and carbon dioxide (CO2. In Caenorhabditis elegans, the O2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral responses to exquisite changes in O2 or CO2 levels via different sensory receptors. How the diversification of the O2- and CO2-sensing neurons is established is poorly understood. We show here that the molecular identity of both the BAG (O2/CO2-sensing and the URX (O2-sensing neurons is controlled by the phylogenetically conserved SoxD transcription factor homolog EGL-13. egl-13 mutant animals fail to fully express the distinct terminal gene batteries of the BAG and URX neurons and, as such, are unable to mount behavioral responses to changes in O2 and CO2. We found that the expression of egl-13 is regulated in the BAG and URX neurons by two conserved transcription factors-ETS-5(Ets factor in the BAG neurons and AHR-1(bHLH factor in the URX neurons. In addition, we found that EGL-13 acts in partially parallel pathways with both ETS-5 and AHR-1 to direct BAG and URX neuronal fate respectively. Finally, we found that EGL-13 is sufficient to induce O2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O2- and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms of neuronal diversification and the regulation of molecular factors that may be conserved in higher organisms.

  5. Equivalent glycemic load (EGL: a method for quantifying the glycemic responses elicited by low carbohydrate foods

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    Spolar Matt

    2006-08-01

    Full Text Available Abstract Background Glycemic load (GL is used to quantify the glycemic impact of high-carbohydrate (CHO foods, but cannot be used for low-CHO foods. Therefore, we evaluated the accuracy of equivalent-glycemic-load (EGL, a measure of the glycemic impact of low-CHO foods defined as the amount of CHO from white-bread (WB with the same glycemic impact as one serving of food. Methods Several randomized, cross-over trials were performed by a contract research organization using overnight-fasted healthy subjects drawn from a pool of 63 recruited from the general population by newspaper advertisement. Incremental blood-glucose response area-under-the-curve (AUC elicited by 0, 5, 10, 20, 35 and 50 g CHO portions of WB (WB-CHO and 3, 5, 10 and 20 g glucose were measured. EGL values of the different doses of glucose and WB and 4 low-CHO foods were determined as: EGL = (F-B/M, where F is AUC after food and B is y-intercept and M slope of the regression of AUC on grams WB-CHO. The dose-response curves of WB and glucose were used to derive an equation to estimate GL from EGL, and the resulting values compared to GL calculated from the glucose dose-response curve. The accuracy of EGL was assessed by comparing the GL (estimated from EGL values of the 4 doses of oral-glucose with the amounts actually consumed. Results Over 0–50 g WB-CHO (n = 10, the dose-response curve was non-linear, but over the range 0–20 g the curve was indistinguishable from linear, with AUC after 0, 5, 10 and 20 g WB-CHO, 10 ± 1, 28 ± 2, 58 ± 5 and 100 ± 6 mmol × min/L, differing significantly from each other (n = 48. The difference between GL values estimated from EGL and those calculated from the dose-response curve was 0 g (95% confidence-interval, ± 0.5 g. The difference between the GL values of the 4 doses of glucose estimated from EGL, and the amounts of glucose actually consumed was 0.2 g (95% confidence-interval, ± 1 g. Conclusion EGL, a measure of the glycemic impact of

  6. Revisiting the slow force response: the role of the PKG signaling pathway in the normal and the ischemic heart.

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    Castro-Ferreira, Ricardo; Neves, João Sérgio; Ladeiras-Lopes, Ricardo; Leite-Moreira, André M; Neiva-Sousa, Manuel; Almeida-Coelho, João; Ferreira-Martins, João; F Leite-Moreira, Adelino

    2014-09-01

    The myocardial response to acute stretch consists of a two-phase increase in contractility: an acute increase by the Frank-Starling mechanism and a gradual and time-dependent increase in force generated known as the slow force response (SFR). The SFR is actively modulated by different signaling pathways, but the role of protein kinase G (PKG) signaling is unknown. In this study we aim to characterize the role of the PKG signaling pathway in the SFR under normal and ischemic conditions. Rabbit papillary muscles were stretched from 92 to 100% of maximum length (Lmax) under basal conditions, in the absence (1) or presence of: a PKG agonist (2) and a PKG inhibitor (3); under ischemic conditions in the absence (4) or presence of: a PKG agonist (5); a nitric oxide (NO) donor (6) and a phosphodiesterase 5 (PDE5) inhibitor (7). Under normoxia, the SFR was significantly attenuated by inhibition of PKG and remained unaltered with PKG activation. Ischemia induced a progressive decrease in myocardial contractility after stretch. Neither the PKG agonist nor the NO donor altered the myocardial response to stretch under ischemic conditions. However, the use of a PDE5 inhibitor in ischemia partially reversed the progressive deterioration in contractility. PKG activity is essential for the SFR. During ischemia, a progressive decline in the force is observed in response to acute myocardial stretch. This dysfunctional response can be partially reversed by the use of PDE5 inhibitors. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  7. Examining a role for PKG Iα oxidation in the pathogenesis of cardiovascular dysfunction during diet-induced obesity.

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    Rudyk, Olena; Eaton, Philip

    2017-09-01

    Protein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state. Diet-induced obesity is associated with NOS uncoupling, which may in part contribute to the associated cardiovascular dysfunction due to exacerbated PKG Iα disulfide oxidation to the disulfide state. This is a rational hypothesis because PKG Iα oxidation is known to significantly contribute to heart failure that arises from chronic myocardial oxidative stress. Bovine arterial endothelial cells (BAECs) or smooth muscle cells (SMCs) were exposed to drugs that uncouple NOS. These included 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) which promotes its S-glutathiolation, 4-diamino-6-hydroxy-pyrimidine (DAHP) which inhibits guanosine-5'-triphosphate-cyclohydrolase 2 to prevent BH 4 synthesis or methotrexate (MTX) which inhibits the regeneration of BH 4 from BH 2 by dihydrofolate reductase. While all the drugs mentioned above induced robust PKG Iα disulfide dimerization in cells, exposure of BAECs to NOS inhibitor L-NMMA did not. Increased PKG Iα disulfide formation occurred in hearts and aortae from mice treated in vivo with DAHP (10mM in a drinking water for 3 weeks). Redox-dead C42S PKG Iα knock-in (KI) mice developed less pronounced cardiac posterior wall hypertrophy and did not develop cardiac dysfunction, assessed by echocardiography, compared to the wild-type (WT) mice after chronic DAHP treatment. WT or

  8. Egle Uljas parandas kaks korda Eesti rekordit / Ants Põldoja

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    Põldoja, Ants, 1959-

    2005-01-01

    USA-s õppiv ja harjutav Egle Uljas ületas Lincolnis toimunud üliõpilaste BIG 12 konverentsi kergejõustikumeistrivõistlustel Eesti siserekordi 400 m jooksus, saavutades eeljooksus aja 53,83 ja finaalis 53,61

  9. Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

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    Sherin Samuel

    2017-04-01

    Full Text Available Background/Aims: Vascular relaxation caused by Triiodothyronine (T3 involves direct activation of endothelial cells (EC and vascular smooth muscle cells (VSMC. Activation of protein kinase G (PKG has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP signaling pathway in VSMC. Methods: Human aortic endothelial cells (HAEC and VSMC were treated with T3 for short (2 to 60 minutes and long term (24 hours. Nitric oxide (NO production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh and sodium nitroprusside (SNP. Results: Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Conclusion: Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.

  10. Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells.

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    Samuel, Sherin; Zhang, Kuo; Tang, Yi-Da; Gerdes, A Martin; Carrillo-Sepulveda, Maria Alicia

    2017-01-01

    Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation. © 2017 The Author(s)Published by S. Karger AG, Basel.

  11. The nT1 translocation separates vulval regulatory elements from the egl-18 and elt-6 GATA factor genes.

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    Koh, Kyunghee; Bernstein, Yelena; Sundaram, Meera V

    2004-03-01

    egl-18 and elt-6 are partially redundant, adjacent genes encoding GATA factors essential for viability, seam cell development, and vulval development in Caenorhabditis elegans. The nT1 reciprocal translocation causes a strong Vulvaless phenotype, and an nT1 breakpoint was previously mapped to the left arm of LGIV, where egl-18/elt-6 are located. Here we present evidence that the nT1 vulval phenotype is due to a disruption of egl-18/elt-6 function specifically in the vulva. egl-18 mutations do not complement nT1 for vulval defects, and the nT1 breakpoint on LGIV is located within approximately 800 bp upstream of a potential transcriptional start site of egl-18. In addition, we have identified a approximately 350-bp cis-regulatory region sufficient for vulval expression just upstream of the nT1 breakpoint. By examining the fusion state and division patterns of the cells in the developing vulva of nT1 mutants, we demonstrate that egl-18/elt-6 prevent fusion and promote cell proliferation at multiple steps of vulval development.

  12. Egle Uljas jätkab kahe isanda teenimist / Ants Põldoja

    Index Scriptorium Estoniae

    Põldoja, Ants, 1959-

    2005-01-01

    USA-s õppiv ja harjutav Egle Uljas ületas Lincolnis toimunud üliõpilaste BIG 12 konverentsi kergejõustikumeistrivõistlustel Eesti siserekordi 400 m jooksus, saavutades eeljooksus aja 53,83 ja finaalis 53,61

  13. PKG in honey bees: spatial expression, Amfor gene expression, sucrose responsiveness, and division of labor.

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    Thamm, Markus; Scheiner, Ricarda

    2014-06-01

    Division of labor is a hallmark of social insects. In honey bees, division of labor involves transition of female workers from one task to the next. The most distinct tasks are nursing (providing food for the brood) and foraging (collecting pollen and nectar). The brain mechanisms regulating this form of behavioral plasticity have largely remained elusive. Recently, it was suggested that division of labor is based on nutrition-associated signaling pathways. One highly conserved gene associated with food-related behavior across species is the foraging gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Our analysis of this gene reveals the presence of alternative splicing in the honey bee. One isoform is expressed in the brain. Expression of this isoform is most pronounced in the mushroom bodies, the subesophageal ganglion, and the corpora allata. Division of labor and sucrose responsiveness in honey bees correlate significantly with foraging gene expression in distinct brain regions. Activating PKG selectively increases sucrose responsiveness in nurse bees to the level of foragers, whereas the same treatment does not affect responsiveness to light. These findings demonstrate a direct link between PKG signaling in distinct brain areas and division of labor. Furthermore, they demonstrate that the difference in sensory responsiveness between nurse bees and foragers can be compensated for by activating PKG. Our findings on the function of PKG in regulating specific sensory responsiveness and social organization offer valuable indications for the function of the cGMP/PKG pathway in many other insects and vertebrates. Copyright © 2013 Wiley Periodicals, Inc.

  14. Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory.

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    Shen, Fang; Li, Yi-Jing; Shou, Xiao-Jing; Cui, Cai-Lian

    2012-09-01

    Evidence suggests that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP dependent protein kinase (PKG) signaling pathway plays a key role in memory processing, but the actual participation of this signaling cascade in the hippocampal CA1 during morphine-induced reward memory remains unknown. In this study, we investigated the role of the NO/sGC/PKG signaling pathway in the CA1 on morphine-induced reward memory using a conditioned place preference (CPP) paradigm. We found that rats receiving an intraperitoneal (i.p.) injection of 4mg/kg morphine exhibited CPP, whereas rats treated with only 0.2mg/kg morphine failed to produce CPP. Intra-CA1 injection of the neuronal NO synthase (nNOS) inhibitor 7-NI, the sGC inhibitor ODQ or the PKG inhibitor Rp-8-Br-PET-cGMPS had no effect on the acquisition of CPP by 4mg/kg morphine. Intra-CA1 injection of 7-NI blocked the consolidation of CPP induced by 4mg/kg morphine, and this amnesic effect of 7-NI was mimicked by ODQ and Rp-8-Br-PET-cGMPS. Intra-CA1 injection of the NOS substrate L-arg or the sGC activator YC-1 with an ineffective dose of morphine (0.2mg/kg, i.p.) elicited CPP. This response induced by L-arg or YC-1 was reversed by pre-microinjection of Rp-8-Br-PET-cGMPS in the CA1. These results indicated that the activation of the NO/sGC/PKG signaling pathway in the CA1 is necessary for the consolidation of morphine-related reward memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. High Performance Molecular Visualization: In-Situ and Parallel Rendering with EGL

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    Stone, John E.; Messmer, Peter; Sisneros, Robert; Schulten, Klaus

    2016-01-01

    Large scale molecular dynamics simulations produce terabytes of data that is impractical to transfer to remote facilities. It is therefore necessary to perform visualization tasks in-situ as the data are generated, or by running interactive remote visualization sessions and batch analyses co-located with direct access to high performance storage systems. A significant challenge for deploying visualization software within clouds, clusters, and supercomputers involves the operating system software required to initialize and manage graphics acceleration hardware. Recently, it has become possible for applications to use the Embedded-system Graphics Library (EGL) to eliminate the requirement for windowing system software on compute nodes, thereby eliminating a significant obstacle to broader use of high performance visualization applications. We outline the potential benefits of this approach in the context of visualization applications used in the cloud, on commodity clusters, and supercomputers. We discuss the implementation of EGL support in VMD, a widely used molecular visualization application, and we outline benefits of the approach for molecular visualization tasks on petascale computers, clouds, and remote visualization servers. We then provide a brief evaluation of the use of EGL in VMD, with tests using developmental graphics drivers on conventional workstations and on Amazon EC2 G2 GPU-accelerated cloud instance types. We expect that the techniques described here will be of broad benefit to many other visualization applications. PMID:27747137

  16. Neuronal cell fate decisions:  O2 and CO2 sensing neurons require egl-13/Sox5

    DEFF Research Database (Denmark)

    Gramstrup Petersen, Jakob; Pocock, Roger David John

    2013-01-01

    We recently conducted a study that aimed to describe the differentiation mechanisms used to generate O2 and CO2 sensing neurons in C. elegans. We identified egl-13/Sox5 to be required for the differentiation of both O2 and CO2 sensing neurons. We found that egl-13 functions cell autonomously...

  17. Magnesium Lithospermate B, an Active Extract of Salvia miltiorrhiza, Mediates sGC/cGMP/PKG Translocation in Experimental Vasospasm

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    Chih-Zen Chang

    2014-01-01

    Full Text Available Background. Soluble guanylyl cyclases (sGCs and Ras homolog gene family, member A (rhoA/Ras homolog gene family kinase(rho-kinase plays a role in vascular smooth muscle relaxation in subarachnoid hemorrhage (SAH. It is of interest to examine the effect of MLB on rhoA/ROCK and sGC/cGMP/PKG expression. Methods. A rodent SAH model was employed. Tissue samples were for sGCα1, sGCβ1, PKG, rhoA, ROCK (Western blot, and cGMP (ELISA measurement. Results. MLB morphologically improved convolution of the internal elastic lamina, distortion of endothelial wall, and necrosis of the smooth muscle in the SAH rats. Expressed cGMP, sGCα1, sGCβ1, and PKG in the SAH groups were reduced (P<0.01, and MLB precondition significantly induced cGMP, sGCα1, sGCβ1, and PKG. L-NAME reversed the vasodilation effect of MLB, reduced the bioexpression of PKG and cGMP (P<0.01, and tends to reduce sGCα1 level and induce rhoA, ROCK level in MLB precondition + SAH groups. Conclusion. These results demonstrate that sGC/cGMP/PKG and NO/ET pathways play pivotal roles in SAH-induced vasospasm. Through activating sGC/cGMP/PKG pathway and partially by inactivating rho-kinase in a NO-dependent mechanism, MLB shows promise to be an effective strategy for the treatment of this disease entity.

  18. Synergistic activation of the CMV promoter by NF-κB P50 and PKG

    International Nuclear Information System (INIS)

    He Bin; Weber, Georg F.

    2004-01-01

    Several DNA binding NF-κB subunits are substrates for cGMP-dependent kinase (PKG) and their transactivation from cognate sites is induced by phosphorylation. This includes p50, which does not have a transcriptional activation domain and therefore needs to bind to other proteins to mediate gene expression. Here, we describe the synergistic transactivation by p50 and PKG from the CMV promoter. This is caused not only by phosphorylation of p50, leading to increased DNA binding, but also by PKG-dependent activation of CRE sites in the promoter. One of the CRE sites is located directly adjacent to a NF-κB site and is essential for p50-mediated induction of transcription. According to the binding of CREB to p50 in pull-down assays and according to the inhibition of p50-dependent transactivation by dominant-negative CREB, this reflects the formation of a transcription factor complex containing CREB and p50. The nuclear translocation of NF-κB is insufficient to distinguish among the multitude of promoters that harbor cognate recognition sites. The phosphorylation of multiple transcription factors by an upstream kinase, such as PKG, can lead to the formation of transcription factor complexes and differential transactivation from a subset of NF-κB sites. These interactions may be relevant for the activation of viral gene expression

  19. EGL-13/SoxD Specifies Distinct O2 and CO2 Sensory Neuron Fates in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Gramstrup Petersen, Jakob; Rojo Romanos, Teresa; Juozaityte, Vaida

    2013-01-01

    that EGL-13 is sufficient to induce O2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O2- and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms......Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2) and carbon dioxide (CO2). In Caenorhabditis elegans, the O2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral...

  20. The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

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    Carlos A. Díaz-Balzac

    2015-06-01

    Full Text Available Neurite branching is essential for correct assembly of neural circuits, yet it remains a poorly understood process. For example, the neural cell adhesion molecule KAL-1/anosmin-1, which is mutated in Kallmann syndrome, regulates neurite branching through mechanisms largely unknown. Here, we show that KAL-1/anosmin-1 mediates neurite branching as an autocrine co-factor with EGL-17/FGF through a receptor complex consisting of the conserved cell adhesion molecule SAX-7/L1CAM and the fibroblast growth factor receptor EGL-15/FGFR. This protein complex, which appears conserved in humans, requires the immunoglobulin (Ig domains of SAX-7/L1CAM and the FN(III domains of KAL-1/anosmin-1 for formation in vitro as well as function in vivo. The kinase domain of the EGL-15/FGFR is required for branching, and genetic evidence suggests that ras-mediated signaling downstream of EGL-15/FGFR is necessary to effect branching. Our studies establish a molecular pathway that regulates neurite branching during development of the nervous system.

  1. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

    KAUST Repository

    Kim, Jeong Joo

    2016-04-09

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

  2. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

    KAUST Repository

    Kim, Jeong  Joo; Lorenz, Robin; Arold, Stefan T.; Reger, Albert  S.; Sankaran, Banumathi; Casteel, Darren  E.; Herberg, Friedrich  W.; Kim, Choel

    2016-01-01

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

  3. C. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells.

    Science.gov (United States)

    Gorrepati, Lakshmi; Thompson, Kenneth W; Eisenmann, David M

    2013-05-01

    The C. elegans seam cells are lateral epithelial cells arrayed in a single line from anterior to posterior that divide in an asymmetric, stem cell-like manner during larval development. These asymmetric divisions are regulated by Wnt signaling; in most divisions, the posterior daughter in which the Wnt pathway is activated maintains the progenitor seam fate, while the anterior daughter in which the Wnt pathway is not activated adopts a differentiated hypodermal fate. Using mRNA tagging and microarray analysis, we identified the functionally redundant GATA factor genes egl-18 and elt-6 as Wnt pathway targets in the larval seam cells. EGL-18 and ELT-6 have previously been shown to be required for initial seam cell specification in the embryo. We show that in larval seam cell asymmetric divisions, EGL-18 is expressed strongly in the posterior seam-fated daughter. egl-18 and elt-6 are necessary for larval seam cell specification, and for hypodermal to seam cell fate transformations induced by ectopic Wnt pathway overactivation. The TCF homolog POP-1 binds a site in the egl-18 promoter in vitro, and this site is necessary for robust seam cell expression in vivo. Finally, larval overexpression of EGL-18 is sufficient to drive expression of a seam marker in other hypodermal cells in wild-type animals, and in anterior hypodermal-fated daughters in a Wnt pathway-sensitized background. These data suggest that two GATA factors that are required for seam cell specification in the embryo independently of Wnt signaling are reused downstream of Wnt signaling to maintain the progenitor fate during stem cell-like divisions in larval development.

  4. The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells.

    Science.gov (United States)

    Gorrepati, Lakshmi; Eisenmann, David M

    2015-01-01

    In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

  5. DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.

    Science.gov (United States)

    Mueller, Michael M; Castells-Roca, Laia; Babu, Vipin; Ermolaeva, Maria A; Müller, Roman-Ulrich; Frommolt, Peter; Williams, Ashley B; Greiss, Sebastian; Schneider, Jennifer I; Benzing, Thomas; Schermer, Bernhard; Schumacher, Björn

    2014-12-01

    Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

  6. Nitric oxide/cGMP/PKG signaling pathway activated by M1-type muscarinic acetylcholine receptor cascade inhibits Na+-activated K+ currents in Kenyon cells

    Science.gov (United States)

    Hasebe, Masaharu

    2016-01-01

    The interneurons of the mushroom body, known as Kenyon cells, are essential for the long-term memory of olfactory associative learning in some insects. Some studies have reported that nitric oxide (NO) is strongly related to this long-term memory in Kenyon cells. However, the target molecules and upstream and downstream NO signaling cascades are not completely understood. Here we analyzed the effect of the NO signaling cascade on Na+-activated K+ (KNa) channel activity in Kenyon cells of crickets (Gryllus bimaculatus). We found that two different NO donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl-dl-penicillamine (SNAP), strongly suppressed KNa channel currents. Additionally, this inhibitory effect of GSNO on KNa channel activity was diminished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), and KT5823, an inhibitor of protein kinase G (PKG). Next, we analyzed the role of ACh in the NO signaling cascade. ACh strongly suppressed KNa channel currents, similar to NO donors. Furthermore, this inhibitory effect of ACh was blocked by pirenzepine, an M1 muscarinic ACh receptor antagonist, but not by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) and mecamylamine, an M3 muscarinic ACh receptor antagonist and a nicotinic ACh receptor antagonist, respectively. The ACh-induced inhibition of KNa channel currents was also diminished by the PLC inhibitor U73122 and the calmodulin antagonist W-7. Finally, we found that ACh inhibition was blocked by the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME). These results suggested that the ACh signaling cascade promotes NO production by activating NOS and NO inhibits KNa channel currents via the sGC/cGMP/PKG signaling cascade in Kenyon cells. PMID:26984419

  7. 34 CFR 300.4 - Act.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Act. 300.4 Section 300.4 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES... Definitions Used in This Part § 300.4 Act. Act means the Individuals with Disabilities Education Act, as...

  8. β3-adrenergic receptor activation induces TGFβ1 expression in cardiomyocytes via the PKG/JNK/c-Jun pathway.

    Science.gov (United States)

    Xu, Zhongcheng; Wu, Jimin; Xin, Junzhou; Feng, Yenan; Hu, Guomin; Shen, Jing; Li, Mingzhe; Zhang, Youyi; Xiao, Han; Wang, Li

    2018-06-05

    In heart failure, the expression of cardiac β 3 -adrenergic receptors (β 3 -ARs) increases. However, the precise role of β 3 -AR signaling within cardiomyocytes remains unclear. Transforming growth factor β1 (TGFβ1) is a crucial cytokine mediating the cardiac remodeling that plays a causal role in the progression of heart failure. Here, we set out to determine the effect of β 3 -AR activation on TGFβ1 expression in rat cardiomyocytes and examine the underlying mechanism. The selective β 3 -AR agonist BRL37344 induced an increase in TGFβ1 expression and the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun in β 3 -AR-overexpressing cardiomyocytes. Those effects of BRL37344 were suppressed by a β 3 -AR antagonist. Moreover, the inhibition of JNK and c-Jun activity by a JNK inhibitor and c-Jun siRNA blocked the increase in TGFβ1 expression upon β 3 -AR activation. A protein kinase G (PKG) inhibitor also attenuated β 3 -AR-agonist-induced TGFβ1 expression and the phosphorylation of JNK and c-Jun. In conclusion, the β 3 -AR activation in cardiomyocytes increases the expression of TGFβ1 via the PKG/JNK/c-Jun pathway. These results help us further understand the role of β 3 -AR signaling in heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. 29 CFR 4.103 - The Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true The Act. 4.103 Section 4.103 Labor Office of the Secretary... Contract Act Introductory § 4.103 The Act. The McNamara-O'Hara Service Contract Act of 1965 (Pub. L. 89-286, 79 Stat. 1034, 41 U.S.C. 351 et seq.), hereinafter referred to as the Act, was approved by the...

  10. 29 CFR 4.105 - The Act as amended.

    Science.gov (United States)

    2010-07-01

    ... Contract Act Introductory § 4.105 The Act as amended. (a) The provisions of the Act (see §§ 4.102-4.103... section 2(a) of the Act requires a statement in the government service contract of the rates that would be... section 4 of the Act providing for the award of service contracts for terms not more than 5 years with...

  11. 29 CFR 4.102 - Administration of the Act.

    Science.gov (United States)

    2010-07-01

    ...'Hara Service Contract Act Introductory § 4.102 Administration of the Act. As provided by section 4 of the Act and under provisions of sections 4 and 5 of the Walsh-Healey Public Contracts Act (49 Stat... authorized and directed to administer and enforce the provisions of the McNamara-O'Hara Service Contract Act...

  12. Endogenous Nuclear RNAi Mediates Behavioral Adaptation to Odor

    DEFF Research Database (Denmark)

    Juang, Bi-Tzen; Gu, Chen; Starnes, Linda

    2013-01-01

    , an in vitro substrate of the EGL-4 kinase that promotes adaption, is necessary and sufficient for behavioral adaptation. Thus, environmental stimulation amplifies an endo-siRNA negative feedback loop to dynamically repress cognate gene expression and shape behavior. This class of siRNA may act broadly...

  13. Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells.

    Science.gov (United States)

    Haushalter, Kristofer J; Casteel, Darren E; Raffeiner, Andrea; Stefan, Eduard; Patel, Hemal H; Taylor, Susan S

    2018-03-23

    cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII (each having α and β isoforms), which keep the PKAc catalytic subunit in a catalytically inactive state until activation by cAMP. Previous reports showed that the RIα regulatory subunit is phosphorylated by cGMP-dependent protein kinase (PKG) in vitro , whereupon phosphorylated RIα no longer inhibits PKAc at normal (1:1) stoichiometric ratios. However, the significance of this phosphorylation as a mechanism for activating type I PKA holoenzymes has not been fully explored, especially in cellular systems. In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells. Analysis of a phosphomimetic substitution in RIα (S101E) showed that modification of this site increases PKAc activity in vitro and in cells, even without cAMP stimulation. Numerous techniques were used to show that although Ser 101 variants of RIα can bind PKAc, the modified linker region of the S101E mutant has a significantly reduced affinity for the PKAc active site. These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We have thus proposed a model to explain how PKG phosphorylation of RIα creates a "sensitized intermediate" state that is in effect primed to trigger PKAc activity.

  14. 29 CFR 6.4 - Subpoenas (Service Contract Act).

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Subpoenas (Service Contract Act). 6.4 Section 6.4 Labor... STANDARDS IN FEDERAL AND FEDERALLY ASSISTED CONSTRUCTION CONTRACTS AND FEDERAL SERVICE CONTRACTS General § 6.4 Subpoenas (Service Contract Act). All applications under the Service Contract Act for subpoenas ad...

  15. 32 CFR 806b.4 - Privacy Act complaints.

    Science.gov (United States)

    2010-07-01

    ... be identified, the local Privacy Act officer will assume these duties. Issues that cannot be resolved... 32 National Defense 6 2010-07-01 2010-07-01 false Privacy Act complaints. 806b.4 Section 806b.4 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT...

  16. 48 CFR 52.225-4 - Buy American Act-Free Trade Agreement-Israeli Trade Act Certificate.

    Science.gov (United States)

    2010-10-01

    ... Trade Agreement-Israeli Trade Act Certificate. 52.225-4 Section 52.225-4 Federal Acquisition Regulations... CLAUSES Text of Provisions and Clauses 52.225-4 Buy American Act—Free Trade Agreement—Israeli Trade Act... Agreement—Israeli Trade Act Certificate (JUN 2009) (a) The offeror certifies that each end product, except...

  17. Cloning, expression and characterization of a cold-adapted endo-1, 4-β-glucanase from Citrobacter farmeri A1, a symbiotic bacterium of Reticulitermes labralis

    Directory of Open Access Journals (Sweden)

    Xi Bai

    2016-11-01

    Full Text Available Background Many biotechnological and industrial applications can benefit from cold-adapted EglCs through increased efficiency of catalytic processes at low temperature. In our previous study, Citrobacter farmeri A1 which was isolated from a wood-inhabiting termite Reticulitermes labralis could secrete a cold-adapted EglC. However, its EglC was difficult to purify for enzymatic properties detection because of its low activity (0.8 U/ml. The objective of the present study was to clone and express the C. farmeri EglC gene in Escherichia coli to improve production level and determine the enzymatic properties of the recombinant enzyme. Methods The EglC gene was cloned from C. farmeri A1 by thermal asymmetric interlaced PCR. EglC was transformed into vector pET22b and functionally expressed in E. coli. The recombination protein EglC22b was purified for properties detection. Results SDS-PAGE revealed that the molecular mass of the recombinant endoglucanase was approximately 42 kDa. The activity of the E. coli pET22b-EglC crude extract was 9.5 U/ml. Additionally, it was active at pH 6.5–8.0 with an optimum pH of 7.0. The recombinant enzyme had an optimal temperature of 30–40 °C and exhibited >50% relative activity even at 5 °C, whereas it lost approximately 90% of its activity after incubation at 60 °C for 30 min. Its activity was enhanced by Co2+ and Fe3+, but inhibited by Cd2+, Zn2+, Li+, Triton X-100, DMSO, acetonitrile, Tween 80, SDS, and EDTA. Conclusion These biochemical properties indicate that the recombinant enzyme is a cold-adapted endoglucanase that can be used for various industrial applications.

  18. Spironolactone lowers portal hypertension by inhibiting liver fibrosis, ROCK-2 activity and activating NO/PKG pathway in the bile-duct-ligated rat.

    Directory of Open Access Journals (Sweden)

    Wei Luo

    Full Text Available OBJECTIVE: Aldosterone, one of the main peptides in renin angiotensin aldosterone system (RAAS, has been suggested to mediate liver fibrosis and portal hypertension. Spironolactone, an aldosterone antagonist, has beneficial effect on hyperdynamic circulation in clinical practice. However, the mechanisms remain unclear. The present study aimed to investigate the role of spionolactone on liver cirrhosis and portal hypertension. METHODS: Liver cirrhosis was induced by bile duct ligation (BDL. Spironolactone was administered orally (20 mg/kg/d after bile duct ligation was performed. Liver fibrosis was assessed by histology, Masson's trichrome staining, and the measurement of hydroxyproline and type I collagen content. The activation of HSC was determined by analysis of alpha smooth muscle actin (α-SMA expression. Protein expressions and protein phosphorylation were determined by immunohistochemical staining and Western blot analysis, Messenger RNA levels by quantitative real time polymerase chain reaction (Q-PCR. Portal pressure and intrahepatic resistance were examined in vivo. RESULTS: Treatment with spironolactone significantly lowered portal pressure. This was associated with attenuation of liver fibrosis, intrahepatic resistance and inhibition of HSC activation. In BDL rat liver, spironolactone suppressed up-regulation of proinflammatory cytokines (TNFα and IL-6. Additionally, spironolactone significantly decreased ROCK-2 activity without affecting expression of RhoA and Ras. Moreover, spironolactone markedly increased the levels of endothelial nitric oxide synthase (eNOS, phosphorylated eNOS and the activity of NO effector-protein kinase G (PKG in the liver. CONCLUSION: Spironolactone lowers portal hypertension by improvement of liver fibrosis and inhibition of intrahepatic vasoconstriction via down-regulating ROCK-2 activity and activating NO/PKG pathway. Thus, early spironolactone therapy might be the optional therapy in cirrhosis and

  19. Nitric oxide modulates sodium vitamin C transporter 2 (SVCT-2) protein expression via protein kinase G (PKG) and nuclear factor-κB (NF-κB).

    Science.gov (United States)

    Portugal, Camila Cabral; da Encarnação, Thaísa Godinho; Socodato, Renato; Moreira, Sarah Rodrigues; Brudzewsky, Dan; Ambrósio, António Francisco; Paes-de-Carvalho, Roberto

    2012-02-03

    Ascorbate is an important antioxidant, which also displays important functions in neuronal tissues, including the retina. The retina is responsible for the initial steps of visual processing, which is further refined in cerebral high-order centers. The retina is also a prototypical model for studying physiologic aspects of cells that comprise the nervous system. Of major importance also is the cellular messenger nitric oxide (NO). Previous studies have demonstrated the significance of NO for both survival and proliferation of cultured embryonic retinal cells. Cultured retinal cells express a high-affinity ascorbate transporter, and the release of ascorbate is delicately regulated by ionotropic glutamate receptors. Therefore, we proposed whether there is interplay between the ascorbate transport system and NO signaling pathway in retinal cells. Here we show compelling evidence that ascorbate uptake is tightly controlled by NO and its downstream signaling pathway in culture. NO also modulates the expression of SVCT-2, an effect mediated by cGMP and PKG. Kinetic studies suggest that NO increases the transport capacity for ascorbate, but not the affinity of SVCT-2 for its substrate. Interestingly, NO utilizes the NF-κB pathway, in a PKG-dependent manner, to modulate both SVCT-2 expression and ascorbate uptake. These results demonstrate that NO exerts a fine-tuned control of the availability of ascorbate to cultured retinal cells and strongly reinforces ascorbate as an important bioactive molecule in neuronal tissues.

  20. Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.

    Directory of Open Access Journals (Sweden)

    Louisa McRobert

    2008-06-01

    Full Text Available Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA, can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falciparum remain unknown. A role for cGMP was revealed by our observation that zaprinast (an inhibitor of phosphodiesterases that hydrolyse cGMP stimulates gametogenesis in the absence of XA. Using cGMP-dependent protein kinase (PKG inhibitors in conjunction with transgenic parasites expressing an inhibitor-insensitive mutant PKG enzyme, we demonstrate that PKG is essential for XA- and zaprinast-induced gametogenesis. Furthermore, we show that intracellular calcium (Ca2+ is required for differentiation and acts downstream of or in parallel with PKG activation. This work defines a key role for PKG in gametogenesis, elucidates the hierarchy of signalling events governing this process in P. falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle.

  1. Essential role of the NO signaling pathway in the hippocampal CA1 in morphine-associated memory depends on glutaminergic receptors.

    Science.gov (United States)

    Shen, Fang; Wang, Xue-Wei; Ge, Fei-Fei; Li, Yi-Jing; Cui, Cai-Lian

    2016-03-01

    The nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP-dependent protein kinase (PKG) signaling pathway has been reported to play a key role in memory processing. However, little is known about its role in drug-associated reward memory. Here, we report the following. 1) The NO pathway in the CA1 is critical for the retrieval of morphine-associated reward memory. Specifically, the nNOS, sGC and PKG protein levels in the CA1 were increased after the expression of morphine conditioned place preference (CPP). Intra-CA1 injection of an NOS, sGC or PKG inhibitor prevented morphine CPP expression. 2) The involvement of the NO pathway in morphine CPP requires NR2B-containing NMDA receptors (NR2B-NMDARs). NR2B-NMDAR expression was elevated in the CA1 following morphine CPP expression, and intra-CA1 injection of the NR2B-NMDAR antagonist Ro25-6981 not only blocked morphine CPP expression but also inhibited the up-regulation of nNOS, sGC and PKG. Moreover, the Ro25-6981-induced blockade of morphine CPP was abolished by intra-CA1 injection of a NOS substrate or an sGC activator. 3) The NR2B-NMDAR stimulated the NO pathway by up-regulating the phosphorylation of Akt(Ser473). Morphine CPP expression enhanced the pAkt(Ser473) level, which has been corroborated to regulate nNOS activity, and this effect was reversed by intra-CA1 injection of Ro25-6981. 4) GluR1 acted downstream of the NO pathway. The membrane level of GluR1 in the CA1 was increased after morphine CPP expression, and this effect was prevented by pre-injection of a PKG inhibitor into the CA1. Additionally, co-immunoprecipitation revealed an interaction between PKG and GluR1; this result further indicated a role of PKG in regulating GluR1 trafficking. Collectively, the results of our study demonstrated that the activation of the NR2B-NMDAR/NO/sGC/PKG signaling pathway is necessary for the retrieval of morphine-associated reward memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Human papillomavirus virus (HPV) genotype- and age-specific analyses of external genital lesions among men in the HPV Infection in Men (HIM) Study.

    Science.gov (United States)

    Ingles, Donna J; Pierce Campbell, Christine M; Messina, Jane A; Stoler, Mark H; Lin, Hui-Yi; Fulp, William J; Abrahamsen, Martha; Sirak, Bradley A; O'Keefe, Michael T; Papenfuss, Mary; Gage, Christine; Carvalho da Silva, Roberto; Gonzalez Sosa, Rossana; Rojas Juarez, Oscar; Villa, Luisa L; Lazcano Ponce, Eduardo; Giuliano, Anna R

    2015-04-01

    Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time with age. The genotype-specific incidence of EGL varied by pathological diagnoses, with high- and low-risk genotypes found in 15.6% and 73.2% of EGLs, respectively. Condyloma primarily contained HPV 6 or 11. While PeIN lesions primarily contained HPV 16, 1 PeIN III lesion was positive for HPV 6 only. Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Separate transcriptionally regulated pathways specify distinct classes of sister dendrites in a nociceptive neuron.

    Science.gov (United States)

    O'Brien, Barbara M J; Palumbos, Sierra D; Novakovic, Michaela; Shang, Xueying; Sundararajan, Lakshmi; Miller, David M

    2017-12-15

    The dendritic processes of nociceptive neurons transduce external signals into neurochemical cues that alert the organism to potentially damaging stimuli. The receptive field for each sensory neuron is defined by its dendritic arbor, but the mechanisms that shape dendritic architecture are incompletely understood. Using the model nociceptor, the PVD neuron in C. elegans, we determined that two types of PVD lateral branches project along the dorsal/ventral axis to generate the PVD dendritic arbor: (1) Pioneer dendrites that adhere to the epidermis, and (2) Commissural dendrites that fasciculate with circumferential motor neuron processes. Previous reports have shown that the LIM homeodomain transcription factor MEC-3 is required for all higher order PVD branching and that one of its targets, the claudin-like membrane protein HPO-30, preferentially promotes outgrowth of pioneer branches. Here, we show that another MEC-3 target, the conserved TFIIA-like zinc finger transcription factor EGL-46, adopts the alternative role of specifying commissural dendrites. The known EGL-46 binding partner, the TEAD transcription factor EGL-44, is also required for PVD commissural branch outgrowth. Double mutants of hpo-30 and egl-44 show strong enhancement of the lateral branching defect with decreased numbers of both pioneer and commissural dendrites. Thus, HPO-30/Claudin and EGL-46/EGL-44 function downstream of MEC-3 and in parallel acting pathways to direct outgrowth of two distinct classes of PVD dendritic branches. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Phosphorylation of rat aquaporin-4 at Ser(111) is not required for channel gating

    DEFF Research Database (Denmark)

    Assentoft, Mette; Kaptan, Shreyas; Fenton, Robert A.

    2013-01-01

    Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. AQP4 has been described as an important entry and exit site for water during formation of brain edema and regulation of AQP4 is theref......Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. AQP4 has been described as an important entry and exit site for water during formation of brain edema and regulation of AQP4...... is therefore of therapeutic interest. Phosphorylation of some aquaporins has been proposed to regulate their water permeability via gating of the channel itself. Protein kinase (PK)-dependent phosphorylation of Ser(111) has been reported to increase the water permeability of AQP4 expressed in an astrocytic...... of activators and inhibitors of PKG and PKA. Mutation of Ser(111) to alanine or aspartate (to prevent or mimic phosphorylation) did not change the water permeability of AQP4. PKG activation had no effect on the water permeability of AQP4 in primary cultures of rat astrocytes. Molecular dynamics simulations...

  5. 17 CFR 14.4 - Violation of Commodity Exchange Act.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Violation of Commodity Exchange Act. 14.4 Section 14.4 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION... Exchange Act. The Commission may deny, temporarily or permanently, the privilege of appearing or practicing...

  6. 50 CFR 17.4 - Pre-Act wildlife.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 2 2010-10-01 2010-10-01 false Pre-Act wildlife. 17.4 Section 17.4 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND...

  7. 29 CFR 785.4 - Application to Walsh-Healey Public Contracts Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Application to Walsh-Healey Public Contracts Act. 785.4... Considerations § 785.4 Application to Walsh-Healey Public Contracts Act. The principles set forth in this part... employees performing work subject to the provisions of the Walsh-Healey Public Contracts Act. [35 FR 15289...

  8. Ganoderma lucidum ethanol extract inhibits the inflammatory response by suppressing the NF-κB and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglial cells.

    Science.gov (United States)

    Yoon, Hyun-Min; Jang, Kyung-Jun; Han, Min Seok; Jeong, Jin-Woo; Kim, Gi Young; Lee, Jai-Heon; Choi, Yung Hyun

    2013-03-01

    Ganoderma lucidum is a traditional Oriental medicine that has been widely used as a tonic to promote longevity and health in Korea and other Asian countries. Although a great deal of work has been carried out on the therapeutic potential of this mushroom, the pharmacological mechanisms of its anti-inflammatory actions remain unclear. In this study, we evaluated the inhibitory effects of G. lucidum ethanol extract (EGL) on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglia. We also investigated the effects of EGL on the LPS-induced activation of nuclear factor kappaB (NF-κB) and upregulation of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Elevated levels of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and pro-inflammatory cytokine production were detected in BV2 microglia following LPS stimulation. We identifed that EGL significantly inhibits the excessive production of NO, PGE(2) and pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor-α in a concentration-dependent manner without causing cytotoxicity. In addition, EGL suppressed NF-κB translocation and transcriptional activity by blocking IκB degradation and inhibiting TLR4 and MyD88 expression in LPS-stimulated BV2 cells. Our results indicate that the inhibitory effects of EGL on LPS-stimulated inflammatory responses in BV2 microglia are associated with the suppression of the NF-κB and TLR signaling pathways. Therefore, EGL may be useful in the treatment of neurodegenerative diseases by inhibiting inflammatory mediator responses in activated microglia.

  9. 48 CFR 22.1002-4 - Application of the Fair Labor Standards Act minimum wage.

    Science.gov (United States)

    2010-10-01

    ... Labor Standards Act minimum wage. 22.1002-4 Section 22.1002-4 Federal Acquisition Regulations System... its employees working on the contract less than the minimum wage specified in section 6(a)(1) of the... Service Contract Act of 1965, as Amended 22.1002-4 Application of the Fair Labor Standards Act minimum...

  10. Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.

    Directory of Open Access Journals (Sweden)

    Mathieu Brochet

    2014-03-01

    Full Text Available Many critical events in the Plasmodium life cycle rely on the controlled release of Ca²⁺ from intracellular stores to activate stage-specific Ca²⁺-dependent protein kinases. Using the motility of Plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cGMP-dependent protein kinase, PKG, maintains the elevated level of cytosolic Ca²⁺ required for gliding motility. We find that the same PKG-dependent pathway operates upstream of the Ca²⁺ signals that mediate activation of P. berghei gametocytes in the mosquito and egress of Plasmodium falciparum merozoites from infected human erythrocytes. Perturbations of PKG signalling in gliding ookinetes have a marked impact on the phosphoproteome, with a significant enrichment of in vivo regulated sites in multiple pathways including vesicular trafficking and phosphoinositide metabolism. A global analysis of cellular phospholipids demonstrates that in gliding ookinetes PKG controls phosphoinositide biosynthesis, possibly through the subcellular localisation or activity of lipid kinases. Similarly, phosphoinositide metabolism links PKG to egress of P. falciparum merozoites, where inhibition of PKG blocks hydrolysis of phosphatidylinostitol (4,5-bisphosphate. In the face of an increasing complexity of signalling through multiple Ca²⁺ effectors, PKG emerges as a unifying factor to control multiple cellular Ca²⁺ signals essential for malaria parasite development and transmission.

  11. KCl cotransport regulation and protein kinase G in cultured vascular smooth muscle cells.

    Science.gov (United States)

    Adragna, N C; Zhang, J; Di Fulvio, M; Lincoln, T M; Lauf, P K

    2002-05-15

    K-Cl cotransport is activated by vasodilators in erythrocytes and vascular smooth muscle cells and its regulation involves putative kinase/phosphatase cascades. N-ethylmaleimide (NEM) activates the system presumably by inhibiting a protein kinase. Nitrovasodilators relax smooth muscle via cGMP-dependent activation of protein kinase G (PKG), a regulator of membrane channels and transporters. We investigated whether PKG regulates K-Cl cotransport activity or mRNA expression in normal, PKG-deficient-vector-only-transfected (PKG-) and PKG-catalytic-domain-transfected (PKG+) rat aortic smooth muscle cells. K-Cl cotransport was calculated as the Cl-dependent Rb influx, and mRNA was determined by semiquantitative RT-PCR. Baseline K-Cl cotransport was higher in PKG+ than in PKG- cells (p <0.01). At 0.5 mM, NEM stimulated K-Cl cotransport by 5-fold in PKG- but not in PKG+ cells. However, NEM was more potent although less effective to activate K-Cl cotransport in normal (passage 1-3) and PKG+ than in PKG- cells. In PKG- cells, [(dihydroindenyl) oxy] alkanoic acid (300 mM) but not furosemide (1 mM) inhibited K-Cl cotransport. Furthermore, no difference in K-Cl cotransport mRNA expression was observed between these cells. In conclusion, this study shows that manipulation of PKG expression in vascular smooth muscle cells affects K-Cl cotransport activity and its activation by NEM.

  12. Pro-survival Effects of 17β-Estradiol on Osteocytes Are Mediated by Nitric Oxide/cGMP via Differential Actions of cGMP-dependent Protein Kinases I and II*

    Science.gov (United States)

    Marathe, Nisha; Rangaswami, Hema; Zhuang, Shunhui; Boss, Gerry R.; Pilz, Renate B.

    2012-01-01

    Estrogens promote bone health in part by increasing osteocyte survival, an effect that requires activation of the protein kinases Akt and ERK1/2, but the molecular mechanisms involved are only partly understood. Because estrogens increase nitric oxide (NO) synthesis and NO can have anti-apoptotic effects, we examined the role of NO/cGMP signaling in estrogen regulation of osteocyte survival. Etoposide-induced death of MLO-Y4 osteocyte-like cells, assessed by trypan blue staining, caspase-3 cleavage, and TUNEL assays, was completely prevented when cells were pre-treated with 17β-estradiol. This protective effect was mimicked when cells were pre-treated with a membrane-permeable cGMP analog and blocked by pharmacological inhibitors of NO synthase, soluble guanylate cyclase, or cGMP-dependent protein kinases (PKGs), supporting a requirement for NO/cGMP/PKG signaling downstream of 17β-estradiol. siRNA-mediated knockdown and viral reconstitution of individual PKG isoforms demonstrated that the anti-apoptotic effects of estradiol and cGMP were mediated by PKG Iα and PKG II. Akt and ERK1/2 activation by 17β-estradiol required PKG II, and cGMP mimicked the effects of estradiol on Akt and ERK, including induction of ERK nuclear translocation. cGMP induced BAD phosphorylation on several sites, and experiments with phosphorylation-deficient BAD mutants demonstrated that the anti-apoptotic effects of cGMP and 17β-estradiol required BAD phosphorylation on Ser136 and Ser155; these sites were targeted by Akt and PKG I, respectively, and regulate BAD interaction with Bcl-2. In conclusion, 17β-estradiol protects osteocytes against apoptosis by activating the NO/cGMP/PKG cascade; PKG II is required for estradiol-induced activation of ERK and Akt, and PKG Iα contributes to pro-survival signaling by directly phosphorylating BAD. PMID:22117068

  13. cGMP-Dependent Protein Kinase Inhibitors in Health and Disease

    Directory of Open Access Journals (Sweden)

    Jens Schlossmann

    2013-02-01

    Full Text Available cGMP-dependent protein kinases (PKG exhibit diverse physiological functions in the mammalian system e.g., in vascular and gastrointestinal smooth muscles, in platelets, in kidney, in bone growth, nociception and in the central nervous system. Furthermore, PKG were found in insects and in the malaria parasite Plasmodium falciparum. Two different genes of PKG exist: a the PKG-I gene that is expressed as cytosolic PKG-Iα or PKG-Iβ isoform, and b the PKG-II gene, which expresses the membrane associated PKG-II protein. The enzyme kinetics, the localization and the substrates of these PKG enzymes differ utilizing different physiological functions. Various inhibitors of PKG were developed directed against diverse functional regions of the kinase. These inhibitors of PKG have been used to analyse the specific functions of these enzymes. The review article will summarize these different inhibitors regarding their specificity and their present applications in vitro and in vivo. Furthermore, it will be discussed that the distinct inhibition of the PKG enzymes could be used as a valuable pharmacological target e.g., in the treatment of cardiovascular diseases, diarrhea, cancer or malaria.

  14. 78 FR 51736 - Notice of FY 2013 Refugee Targeted Assistance Formula Awards to States and Wilson/Fish...

    Science.gov (United States)

    2013-08-21

    ... 78, No. 125, published on June 28, 2013, and at http://www.gpo.gov/fdsys/pkg/FR-2013-06-28/pdf/2013-15465.pdf . Statutory Authority: Section 412(c)(2)(A) of the Immigration and Nationality Act (INA) (8 U...

  15. Long term effect of reduced dietary phosphorus on feed intake and milk yield in dry and lactating dairy cows

    DEFF Research Database (Denmark)

    Puggaard, Liselotte; Lund, Peter; Liesegang, A.

    2014-01-01

    Eighteen multiparous Holstein cows were used to study the long term effect of reducing dietary P concentration on intake of DM and milk yield, on blood levels of inorganic phosphate (Pi), Ca, vitamin D3, parathyroid hormone (PTH) as well as assessing bone turnover by the use of bone formation......) (2.1g P/kg DM) and High P (HP) (2.5g P/kg DM). After parturition and throughout lactation treatments were LP (2.3g P/kg DM), MP (2.8g P/kg DM) and HP (3.4g P/kg DM). Differences in dietary P were obtained by adding 0.60 and 1.19% mono-sodium phosphate per kg DM to MP and HP, respectively. The cows...... were fed restrictively pre-partum and for ad libitum intake from one week before expected calving and throughout the experiment. Due to a high number of health problems, LP treatment was terminated after sampling in week 12, and cows were shifted to HP and continued on this treatment until week 36...

  16. Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study.

    Science.gov (United States)

    Sudenga, Staci L; Ingles, Donna J; Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William J; Messina, Jane L; Stoler, Mark H; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2016-01-01

    Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  17. Type II cGMP‑dependent protein kinase inhibits the migration, invasion and proliferation of several types of human cancer cells.

    Science.gov (United States)

    Wu, Min; Wu, Yan; Qian, Hai; Tao, Yan; Pang, Ji; Wang, Ying; Chen, Yongchang

    2017-10-01

    Previous studies have indicated that type II cyclic guanosine monophosphate (cGMP)‑dependent protein kinase (PKG II) could inhibit the proliferation and migration of gastric cancer cells. However, the effects of PKG II on the biological functions of other types of cancer cells remain to be elucidated. Therefore, the aim of the present study was to investigate the effects of PKG II on cancer cells derived from various types of human tissues, including A549 lung, HepG2 hepatic, OS‑RC‑2 renal, SW480 colon cancer cells and U251 glioma cells. Cancer cells were infected with adenoviral constructs coding PKG II (Ad‑PKG II) to up‑regulate PKG II expression, and treated with 8‑(4‑chlorophenylthio) (8‑pCPT)‑cGMP to activate the kinase. A Cell Counting kit 8 assay was used to detect cell proliferation. Cell migration was measured using a Transwell assay, whereas a terminal deoxynucleotidyl transferase 2'‑deoxyuridine, 5'‑triphosphate nick‑end labeling assay was used to detect cell apoptosis. A pull‑down assay was used to investigate the activation of Ras‑related C3 botulinum toxin substrate (Rac) 1 and western blotting was used to detect the expression of proteins of interest. The present results demonstrated that EGF (100 ng/ml, 24 h) promoted the proliferation and migration of cancer cells, and it suppressed their apoptosis. In addition, treatment with EGF enhanced the activation of Rac1, and up‑regulated the protein expression of proliferating cell nuclear antigen, matrix metalloproteinase (MMP)2, MMP7 and B‑cell lymphoma (Bcl)‑2, whereas it down‑regulated the expression of Bcl‑2‑associated X protein. Transfection of cancer cells with Ad‑PKG II, and PKG II activation with 8‑pCPT‑cGMP, was identified to counteract the effects triggered by EGF. The present results suggested that PKG II may exert inhibitory effects on the proliferation and migration of various types of cancer cells.

  18. 17 CFR 260.4d-9 - Exemption for Canadian Trust Indentures from Specified Provisions of the Act.

    Science.gov (United States)

    2010-04-01

    ...) The Canada Business Corporations Act, R. S. C. 1985; (b) The Bank Act, R. S. C. 1985; (c) The Business Corporations Act, 1982 (Ontario), S. O. 1982; or (d) The Company Act, R.S.B.C. 1979, C. 59. [56 FR 30077, July... Indentures from Specified Provisions of the Act. 260.4d-9 Section 260.4d-9 Commodity and Securities Exchanges...

  19. cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae.

    Science.gov (United States)

    Krill, Jennifer L; Dawson-Scully, Ken

    2016-01-01

    While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms. In this study, we characterize presynaptic calcium ([Ca2+]i) dynamics at the Drosophila larval NMJ to determine the effects of high temperature stress on synaptic transmission. We investigated the neuroprotective role of PKG modulation both genetically using RNA interference (RNAi), and pharmacologically, to determine if and how PKG affects presynaptic [Ca2+]i dynamics during hyperthermia. We found that PKG activity modulates presynaptic neuronal Ca2+ responses during acute hyperthermia, where PKG activation makes neurons more sensitive to temperature-induced failure of Ca2+ flux and PKG inhibition confers thermotolerance and maintains normal Ca2+ dynamics under the same conditions. Targeted motoneuronal knockdown of PKG using RNAi demonstrated that decreased PKG expression was sufficient to confer thermoprotection. These results demonstrate that the PKG pathway regulates presynaptic motoneuronal Ca2+ signaling to influence thermotolerance of presynaptic function during acute hyperthermia.

  20. DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans.

    Science.gov (United States)

    Reddien, Peter W; Andersen, Erik C; Huang, Michael C; Horvitz, H Robert

    2007-04-01

    The genes egl-1, ced-9, ced-4, and ced-3 play major roles in programmed cell death in Caenorhabditis elegans. To identify genes that have more subtle activities, we sought mutations that confer strong cell-death defects in a genetically sensitized mutant background. Specifically, we screened for mutations that enhance the cell-death defects caused by a partial loss-of-function allele of the ced-3 caspase gene. We identified mutations in two genes not previously known to affect cell death, dpl-1 and mcd-1 (modifier of cell death). dpl-1 encodes the C. elegans homolog of DP, the human E2F-heterodimerization partner. By testing genes known to interact with dpl-1, we identified roles in cell death for four additional genes: efl-1 E2F, lin-35 Rb, lin-37 Mip40, and lin-52 dLin52. mcd-1 encodes a novel protein that contains one zinc finger and that is synthetically required with lin-35 Rb for animal viability. dpl-1 and mcd-1 act with efl-1 E2F and lin-35 Rb to promote programmed cell death and do so by regulating the killing process rather than by affecting the decision between survival and death. We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death.

  1. Implications Enzymatic Degradation of the Endothelial Glycocalyx on the Microvascular Hemodynamics and the Arteriolar Red Cell Free Layer of the Rat Cremaster Muscle

    Directory of Open Access Journals (Sweden)

    Ozlem Yalcin

    2018-03-01

    Full Text Available The endothelial glycocalyx is a complex network of glycoproteins, proteoglycans, and glycosaminoglycans; it lines the vascular endothelial cells facing the lumen of blood vessels forming the endothelial glycocalyx layer (EGL. This study aims to investigate the microvascular hemodynamics implications of the EGL by quantifying changes in blood flow hydrodynamics post-enzymatic degradation of the glycocalyx layer. High-speed intravital microscopy videos of small arteries (around 35 μm of the rat cremaster muscle were recorded at various time points after enzymatic degradation of the EGL. The thickness of the cell free layer (CFL, blood flow velocity profiles, and volumetric flow rates were quantified. Hydrodynamic effects of the presence of the EGL were observed in the differences between the thickness of CFL in microvessels with an intact EGL and glass tubes of similar diameters. Maximal changes in the thickness of CFL were observed 40 min post-enzymatic degradation of the EGL. Analysis of the frequency distribution of the thickness of CFL allows for estimation of the thickness of the endothelial surface layer (ESL, the plasma layer, and the glycocalyx. Peak flow, maximum velocity, and mean velocity were found to statistically increase by 24, 27, and 25%, respectively, after enzymatic degradation of the glycocalyx. The change in peak-to-peak maximum velocity and mean velocity were found to statistically increase by 39 and 32%, respectively, after 40 min post-enzymatic degradation of the EGL. The bluntness of blood flow velocity profiles was found to be reduced post-degradation of the EGL, as the exclusion volume occupied by the EGL increased the effective volume impermeable to RBCs in microvessels. This study presents the effects of the EGL on microvascular hemodynamics. Enzymatic degradation of the EGL resulted in a decrease in the thickness of CFL, an increase in blood velocity, blood flow, and decrease of the bluntness of the blood flow

  2. Implications Enzymatic Degradation of the Endothelial Glycocalyx on the Microvascular Hemodynamics and the Arteriolar Red Cell Free Layer of the Rat Cremaster Muscle.

    Science.gov (United States)

    Yalcin, Ozlem; Jani, Vivek P; Johnson, Paul C; Cabrales, Pedro

    2018-01-01

    The endothelial glycocalyx is a complex network of glycoproteins, proteoglycans, and glycosaminoglycans; it lines the vascular endothelial cells facing the lumen of blood vessels forming the endothelial glycocalyx layer (EGL). This study aims to investigate the microvascular hemodynamics implications of the EGL by quantifying changes in blood flow hydrodynamics post-enzymatic degradation of the glycocalyx layer. High-speed intravital microscopy videos of small arteries (around 35 μm) of the rat cremaster muscle were recorded at various time points after enzymatic degradation of the EGL. The thickness of the cell free layer (CFL), blood flow velocity profiles, and volumetric flow rates were quantified. Hydrodynamic effects of the presence of the EGL were observed in the differences between the thickness of CFL in microvessels with an intact EGL and glass tubes of similar diameters. Maximal changes in the thickness of CFL were observed 40 min post-enzymatic degradation of the EGL. Analysis of the frequency distribution of the thickness of CFL allows for estimation of the thickness of the endothelial surface layer (ESL), the plasma layer, and the glycocalyx. Peak flow, maximum velocity, and mean velocity were found to statistically increase by 24, 27, and 25%, respectively, after enzymatic degradation of the glycocalyx. The change in peak-to-peak maximum velocity and mean velocity were found to statistically increase by 39 and 32%, respectively, after 40 min post-enzymatic degradation of the EGL. The bluntness of blood flow velocity profiles was found to be reduced post-degradation of the EGL, as the exclusion volume occupied by the EGL increased the effective volume impermeable to RBCs in microvessels. This study presents the effects of the EGL on microvascular hemodynamics. Enzymatic degradation of the EGL resulted in a decrease in the thickness of CFL, an increase in blood velocity, blood flow, and decrease of the bluntness of the blood flow velocity profile in

  3. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different training...

  4. Storage and Materials Handling

    Science.gov (United States)

    1979-09-01

    18 9 Beef, instant , dehydrated ..... Pkg 24 12 6 Beef, noodle , dehydrated ...... Pkg 24 12 6 Beef, vegetable, noodle , dehy- drated... noodle , dehydrated . Can 60 30 15 .............. Pkg 24 12 6 Condensed" ....................... Can 72 36 18 Cream of onion, instant , dehy- drated...6 Onion, instant , dehydrated ... Pkg 24 12 6 Ready to serve ................... Can 48 24 12 Tomato-vegetable w/ noodle , dehydrated

  5. Spatiotemporal and functional characterisation of the Plasmodium falciparum cGMP-dependent protein kinase.

    Directory of Open Access Journals (Sweden)

    Christine S Hopp

    Full Text Available Signalling by 3'-5'-cyclic guanosine monophosphate (cGMP exists in virtually all eukaryotes. In the apicomplexan parasite Plasmodium, the cGMP-dependent protein kinase (PKG has previously been reported to play a critical role in four key stages of the life cycle. The Plasmodium falciparum isoform (PfPKG is essential for the initiation of gametogenesis and for blood stage schizont rupture and work on the orthologue from the rodent malaria parasite P. berghei (PbPKG has shown additional roles in ookinete differentiation and motility as well as liver stage schizont development. In the present study, PfPKG expression and subcellular location in asexual blood stages was investigated using transgenic epitope-tagged PfPKG-expressing P. falciparum parasites. In Western blotting experiments and immunofluorescence analysis (IFA, maximal PfPKG expression was detected at the late schizont stage. While IFA suggested a cytosolic location, a degree of overlap with markers of the endoplasmic reticulum (ER was found and subcellular fractionation showed some association with the peripheral membrane fraction. This broad localisation is consistent with the notion that PfPKG, as with the mammalian orthologue, has numerous cellular substrates. This idea is further supported by the global protein phosphorylation pattern of schizonts which was substantially changed following PfPKG inhibition, suggesting a complex role for PfPKG during schizogony.

  6. Caenorhabditis elegans fibroblast growth factor receptor signaling can occur independently of the multi-substrate adaptor FRS2.

    Science.gov (United States)

    Lo, Te-Wen; Bennett, Daniel C; Goodman, S Jay; Stern, Michael J

    2010-06-01

    The components of receptor tyrosine kinase signaling complexes help to define the specificity of the effects of their activation. The Caenorhabditis elegans fibroblast growth factor receptor (FGFR), EGL-15, regulates a number of processes, including sex myoblast (SM) migration guidance and fluid homeostasis, both of which require a Grb2/Sos/Ras cassette of signaling components. Here we show that SEM-5/Grb2 can bind directly to EGL-15 to mediate SM chemoattraction. A yeast two-hybrid screen identified SEM-5 as able to interact with the carboxy-terminal domain (CTD) of EGL-15, a domain that is specifically required for SM chemoattraction. This interaction requires the SEM-5 SH2-binding motifs present in the CTD (Y(1009) and Y(1087)), and these sites are required for the CTD role of EGL-15 in SM chemoattraction. SEM-5, but not the SEM-5 binding sites located in the CTD, is required for the fluid homeostasis function of EGL-15, indicating that SEM-5 can link to EGL-15 through an alternative mechanism. The multi-substrate adaptor protein FRS2 serves to link vertebrate FGFRs to Grb2. In C. elegans, an FRS2-like gene, rog-1, functions upstream of a Ras/MAPK pathway for oocyte maturation but is not required for EGL-15 function. Thus, unlike the vertebrate FGFRs, which require the multi-substrate adaptor FRS2 to recruit Grb2, EGL-15 can recruit SEM-5/Grb2 directly.

  7. Act No. 430 of 7 June 1978 amending Sections 4 and 5

    International Nuclear Information System (INIS)

    1978-01-01

    Act No. 430 amends Sections 4 and 5 of the Atomic Energy Act of 25/10/57. Under Section 4 as amended, a permit issued by virtue of the Atomic Energy Act may now be granted for specified reasons for a stated period of time. The possibility of granting permits for a period is considered important in the light of the uncertainties relating to nuclear waste management. Such permits may be renewed permanently provided the reasons for their periodic validity have ceased to exist. Amended Section 5 lays down the manner in which the responsibility for nuclear waste has been divided between the waste producer and the State. The waste producer has overall responsibility for the expenses caused by nuclear waste management. The State may, however, take over the nuclear waste, provided that the conditions approved by the Council of State have been fulfilled and provision for payment of expenses arising from the treatment and disposal of such waste has been made in a satisfactory manner. (NEA) [fr

  8. 40 CFR 52.726 - Control strategy: Ozone.

    Science.gov (United States)

    2010-07-01

    ... Roselle Road) Awarded 0.030000 SIG COORD Higgins Road (Barrington to Roselle Road) Awarded 0.030000 SIG... Hanover Park Done 0.011840 Com. Pkg Worth Done 0.003530 Com. Pkg Roselle Done 0.007710 Com. Pkg Crystal...

  9. Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

    Science.gov (United States)

    2016-06-01

    parasites consistently produced only about half as many liver stages as the isogenic 273 PKG-HA control clone (Supplementary Fig 1F, Supplementary...amongst the nominally isogenic PKG T619Q-HA and 281 PKG-HA clones , although we find it more likely that PKG T619Q-HA is a hypomorphic 282 allele in...prophylaxis and transmission blocking approaches. 494 495 Experimental Procedures 496 497 Ethics Statement 498 All experiments were approved by

  10. 12 CFR 1510.4 - Who may act as the depositary and fiscal agent for the Funding Corporation?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Who may act as the depositary and fiscal agent for the Funding Corporation? 1510.4 Section 1510.4 Banks and Banking DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION RESOLUTION FUNDING CORPORATION OPERATIONS § 1510.4 Who may act as the...

  11. The supplementation of low-P diets with microbial 6-phytase expressed in Aspergillus oryzae increases P and Ca digestibility in growing pigs.

    Science.gov (United States)

    Torrallardona, D; Salvadó, R; Broz, J

    2012-12-01

    A trial was conducted to evaluate the dose response of a novel microbial 6-phytase expressed in Aspergillus oryzae (Ronozyme HiPhos; DSM Nutritional Products, Basel, Switzerland) in pigs. Forty-eight individually housed pigs (Landrace × Pietrain; 52 kg BW; 24 males and 24 females) were distributed among 6 experimental treatments consisting of a low-P diet (3.5 g P/kg; 1.1 g digestible P/kg), which was supplemented with 500, 1000, 2000, or 4000 units of phytase activity/kg, and a standard-P diet (4.5 g P/kg; 1.8 g digestible P/kg) that was supplemented with CaHPO(4). After 17 d, fresh feces were sampled from all pigs and the apparent total tract digestibility of DM, OM, ash, P, and Ca was measured using TiO(2) as indigestible marker. Blood samples were also obtained from each pig and serum was analyzed for P and Ca concentrations. The nonsupplemented low-P diet increased Ca and reduced P blood serum concentrations (P Phytase supplementation of the low-P diet reduced Ca (from 10.8 to 9.9 mg/dL; linear, P Phytase improved the total tract digestibility of P (from 29.0 to 62.3%; linear and quadratic, P phytase tested improves the apparent total tract digestibility of P in growing pigs and reduces P excretion in feces in a dose-dependent manner.

  12. The role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Wegener, Gregers; Brink, Christiaan

    not affect swimming or climbing. Lastly, locomotor activity was unaltered by all treatment conditions. Conclusions These results confirm cholinergic-cGMP-PK-G interactions in the antidepressant-like effects of sildenafil, putatively acting via noradrenergic mechanisms, whereas direct PK-G activation induces...... the antidepressant-like activity of sildenafil + atropine is mediated via the activation of PK-G, a downstream effector for cGMP, and whether this may target known pathways in antidepressant action. Purpose We investigated whether the antidepressant-like response of sildenafil ± atropine could be reversed by Rp-8-Br.......c.v.) ± atropine (1 mg/kg, i.p.), Rp-8-Br-PET-cGMP or atropine. Antidepressant-like activity was scored in terms of a reduction of immobility (in seconds) relative to vehicle-treated controls. Swimming and climbing behaviours were scored as an indication of serotonergic and noradrenergic mechanisms, respectively...

  13. Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

    International Nuclear Information System (INIS)

    Kucka, Marek; Pogrmic-Majkic, Kristina; Fa, Svetlana; Stojilkovic, Stanko S.; Kovacevic, Radmila

    2012-01-01

    Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of cAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on cAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s. -- Highlights: ► Atrazine stimulates cAMP accumulation in pituitary and Leydig cells. ► Atrazine also stimulates PRL and androgens secretion. ► Stimulatory effects of atrazine were abolished in cells with IBMX-inhibited PDEs. ► Atrazine specificity toward c

  14. Ultrafast charge transfer and radiationless relaxations from higher excited state (S2) of directly linked Zn-porphyrin (ZP)-acceptor dyads: investigations into fundamental problems of exciplex chemistry

    International Nuclear Information System (INIS)

    Mataga, Noboru; Taniguchi, Seiji; Chosrowjan, Haik; Osuka, Atsuhiro; Yoshida, Naoya

    2003-01-01

    We have investigated photoinduced electron transfer and related processes from the higher excited electronic state (S 2 ) of Zn-porphyrin-imide acceptor directly linked supramolecular systems (ZP-I) designed especially for the critical studies of the energy gap law (EGL) of the charge separation (CS) from the S 2 state and solvent effects upon EGL. We have confirmed the modification of the EGL by change of solvent polarity from acetonitrile (ACN), tetrahydrofuran (THF) to toluene (Tol) and methyl-cyclohexane (MCH), from rather typical bell-shaped one in ACN to that with less prominent normal region and prominent inverted region with moderate slope extending over wider range of -ΔG CS values in nonpolar solvent MCH. We have demonstrated that these solvent effects upon EGL affect delicately various radiationless relaxation processes from S 2 state. We have examined also effects of the hydrogen bonding solvent ethanol (EtOH) on the EGL for CS and found very specific effect controlling the CS reaction and related processes

  15. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression

    International Nuclear Information System (INIS)

    Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M.; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode

    2014-01-01

    Highlights: • We investigated the impact of cyclic nucleotide analogues on platelet activation. • Different time dependence were found for inhibition of platelet activation. • Additive effect was found using PKA- and PKG-activating analogues. • Our results may explain some of the discrepancies reported for cNMP signalling. - Abstract: In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation

  16. 15 CFR 921.4 - Relationship to other provisions of the Coastal Zone Management Act, and to the Marine Protection...

    Science.gov (United States)

    2010-01-01

    ... the Coastal Zone Management Act, and to the Marine Protection, Research and Sanctuaries Act. 921.4... provisions of the Coastal Zone Management Act, and to the Marine Protection, Research and Sanctuaries Act. (a... affecting the state's coastal zone, must be undertaken in a manner consistent to the maximum extent...

  17. Efficient expression and characterization of a cold-active endo-1, 4-β-glucanase from Citrobacter farmeri by co-expression of Myxococcus xanthus protein S

    Directory of Open Access Journals (Sweden)

    Xi Bai

    2016-11-01

    Conclusions: The ProS-EglC is promising in application of various biotechnological processes because of its cold-active characterizations. This study also suggests a useful strategy for the expression of foreign proteins in E. coli using a ProS tag.

  18. Role of Nitric Oxide, Nitric Oxide Synthase, Soluble Guanylyl Cyclase, and cGMP-Dependent Protein Kinase I in Mouse Stem Cell Cardiac Development

    Directory of Open Access Journals (Sweden)

    Valentina Spinelli

    2016-01-01

    Full Text Available Introduction and Aim. Nitric oxide (NO can trigger cardiac differentiation of embryonic stem cells (ESCs, indicating a cardiogenic function of the NO synthetizing enzyme(s (NOS. However, the involvement of the NO/NOS downstream effectors soluble guanylyl cyclase (sGC and cGMP activated protein kinase I (PKG-I is less defined. Therefore, we assess the involvement of the entire NO/NOS/sGC/PKG-I pathway during cardiac differentiation process. Methods. Mouse ESCs were differentiated toward cardiac lineages by hanging drop methodology for 21 days. NOS/sGC/PKG-I pathway was studied quantifying genes, proteins, enzymatic activities, and effects of inhibition during differentiation. Percentages of beating embryoid bodies (mEBs were evaluated as an index of cardiogenesis. Results and Discussion. Genes and protein expression of enzymes were increased during differentiation with distinctive kinetics and proteins possessed their enzymatic functions. Exogenous administered NO accelerated whereas the blockade of PKG-I strongly slowed cardiogenesis. sGC inhibition was effective only at early stages and NOS blockade ineffective. Of NOS/sGC/PKG-I pathway, PKG-I seems to play the prominent role in cardiac maturation. Conclusion. We concluded that exogenous administered NO and other pharmacological strategies able to increase the activity of PKG-I provide new tools to investigate and promote differentiation of cardiogenic precursors.

  19. The NO signaling pathway differentially regulates KCC3a and KCC3b mRNA expression.

    Science.gov (United States)

    Di Fulvio, Mauricio; Lauf, Peter K; Adragna, Norma C

    2003-11-01

    Nitric oxide (NO) donors and protein kinase G (PKG) acutely up-regulate K-Cl cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in vascular smooth muscle cells (VSMCs). Here, we report the presence, relative abundance, and regulation by sodium nitroprusside (SNP) of the novel KCC3a and KCC3b mRNAs, in primary cultures of rat VSMCs. KCC3a and KCC3b mRNAs were expressed in an approximate 3:1 ratio, as determined by semiquantitative RT-PCR analysis. SNP as well as YC-1 and 8-Br-cGMP, a NO-independent stimulator of soluble guanylyl cyclase (sGC) and PKG, respectively, increased KCC3a and KCC3b mRNA expression by 2.5-fold and 8.1-fold in a time-dependent manner, following a differential kinetics. Stimulation of the NO/sGC/PKG signaling pathway with either SNP, YC-1, or 8-Br-cGMP decreased the KCC3a/KCC3b ratio from 3.0+/-0.4 to 0.9+/-0.1. This is the first report on a differential regulation by the NO/sGC/PKG signaling pathway of a cotransporter and of KCC3a and KCC3b mRNA expression.

  20. Gαo and Gαq regulate the expression of daf-7, a TGFβ-like gene, in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Edith M Myers

    Full Text Available Caenorhabditis elegans enter an alternate developmental stage called dauer in unfavorable conditions such as starvation, overcrowding, or high temperature. Several evolutionarily conserved signaling pathways control dauer formation. DAF-7/TGFβ and serotonin, important ligands in these signaling pathways, affect not only dauer formation, but also the expression of one another. The heterotrimeric G proteins GOA-1 (Gα(o and EGL-30 (Gα(q mediate serotonin signaling as well as serotonin biosynthesis in C. elegans. It is not known whether GOA-1 or EGL-30 also affect dauer formation and/or daf-7 expression, which are both modulated in part by serotonin. The purpose of this study is to better understand the relationship between proteins important for neuronal signaling and developmental plasticity in both C. elegans and humans. Using promoter-GFP transgenic worms, it was determined that both goa-1 and egl-30 regulate daf-7 expression during larval development. In addition, the normal daf-7 response to high temperature or starvation was altered in goa-1 and egl-30 mutants. Despite the effect of goa-1 and egl-30 mutations on daf-7 expression in various environmental conditions, there was no effect of the mutations on dauer formation. This paper provides evidence that while goa-1 and egl-30 are important for normal daf-7 expression, mutations in these genes are not sufficient to disrupt dauer formation.

  1. Effect of decreasing dietary phosphorus supply on net recycling of inorganic phosphate in lactating dairy cows

    DEFF Research Database (Denmark)

    Puggaard, Liselotte; Kristensen, Niels Bastian; Sehested, Jens Jakob

    2011-01-01

    (LP; 2.4 g of P/kg of DM) and high P (HP; 3.4 g of P/kg of DM). The dietary total P (tP) concentrations were obtained by replacing 0.50% calcium carbonate in the LP diet with 0.50% monocalcium phosphate in the HP diet. Diets were fed for 14 d and cows were sampled on d 14 in each period. Cows were fed...... restrictively, resulting in equal dry matter intakes as well as milk, fat, and protein yields between treatments. Net Pi recycling (primarily salivary) was estimated as the difference between net portal plasma flux (net absorption of Pi) and apparently digested tP (feed – fecal tP difference). Phosphorus intake...

  2. Protein Kinase G facilitates EGFR-mediated cell death in MDA-MB-468 cells

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Nicole M.; Ceresa, Brian P., E-mail: brian.ceresa@louisville.edu

    2016-08-15

    The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase with critical implications in cell proliferation, migration, wound healing and the regulation of apoptosis. However, the EGFR has been shown to be hyper-expressed in a number of human malignancies. The MDA-MB-468 metastatic breast cell line is one example of this. This particular cell line hyper-expresses the EGFR and undergoes EGFR-mediated apoptosis in response to EGF ligand. The goal of this study was to identify the kinases that could be potential intermediates for the EGFR-mediated induction of apoptosis intracellularly. After identifying Cyclic GMP-dependent Protein Kinase G (PKG) as a plausible intermediate, we wanted to determine the temporal relationship of these two proteins in the induction of apoptosis. We observed a dose-dependent decrease in MDA-MB-468 cell viability, which was co-incident with increased PKG activity as measured by VASPSer239 phosphorylation. In addition, we observed a dose dependent decrease in cell viability, as well as an increase in apoptosis, in response to two different PKG agonists, 8-Bromo-cGMP and 8-pCPT-cGMP. MDA-MB-468 cells with reduced PKG activity had attenuated EGFR-mediated apoptosis. These findings indicate that PKG does not induce cell death via transphosphorylation of the EGFR. Instead, PKG activity occurs following EGFR activation. Together, these data indicate PKG as an intermediary in EGFR-mediated cell death, likely via apoptotic pathway.

  3. Aromatic amino acids in the cellulose binding domain of Penicillium crustosum endoglucanase EGL1 differentially contribute to the cellulose affinity of the enzyme.

    Directory of Open Access Journals (Sweden)

    Jiang-Ke Yang

    Full Text Available The cellulose binding domain (CBD of cellulase binding to cellulosic materials is the initiation of a synergistic action on the enzymatic hydrolysis of the most abundant renewable biomass resources in nature. The binding of the CBD domain to cellulosic substrates generally relies on the interaction between the aromatic amino acids structurally located on the flat face of the CBD domain and the glucose rings of cellulose. In this study, we found the CBD domain of a newly cloned Penicillium crustosum endoglucanase EGL1, which was phylogenetically related to Aspergillus, Fusarium and Rhizopus, and divergent from the well-characterized Trichoderma reeseis cellulase CBD domain, contain two conserved aromatic amino acid-rich regions, Y451-Y452 and Y477-Y478-Y479, among which three amino acids Y451, Y477, and Y478 structurally sited on a flat face of this domain. Cellulose binding assays with green fluorescence protein as the marker, adsorption isotherm assays and an isothermal titration calorimetry assays revealed that although these three amino acids participated in this process, the Y451-Y452 appears to contribute more to the cellulose binding than Y477-Y478-Y479. Further glycine scanning mutagenesis and structural modelling revealed that the binding between CBD domain and cellulosic materials might be multi-amino-acids that participated in this process. The flexible poly-glucose molecule could contact Y451, Y477, and Y478 which form the contacting flat face of CBD domain as the typical model, some other amino acids in or outside the flat face might also participate in the interaction. Thus, it is possible that the conserved Y451-Y452 of CBD might have a higher chance of contacting the cellulosic substrates, contributing more to the affinity of CBD than the other amino acids.

  4. The D4Z4 macrosatellite repeat acts as a CTCF and A-type lamins-dependent insulator in facio-scapulo-humeral dystrophy.

    Directory of Open Access Journals (Sweden)

    Alexandre Ottaviani

    2009-02-01

    Full Text Available Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD, which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the FSHD-associated gene(s through position effect mechanisms. We investigated this hypothesis by creating a large collection of constructs carrying 1 to >11 D4Z4 repeats integrated into the human genome, either at random sites or proximal to a telomere, mimicking thereby the organization of the 4q35 locus. We show that D4Z4 acts as an insulator that interferes with enhancer-promoter communication and protects transgenes from position effect. This last property depends on both CTCF and A-type Lamins. We further demonstrate that both anti-silencing activity of D4Z4 and CTCF binding are lost upon multimerization of the repeat in cells from FSHD patients compared to control myoblasts from healthy individuals, suggesting that FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats. We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients.

  5. 16 CFR 4.13 - Privacy Act rules.

    Science.gov (United States)

    2010-01-01

    ... assigned to the individual, such as a finger or voice print or a photograph, but does not include... Act or regulations established thereunder. Title 18 U.S.C. 1001, Crimes and Criminal Procedures, makes...

  6. The role of cGMP signalling in regulating life cycle progression of Plasmodium.

    OpenAIRE

    Hopp, CS; Bowyer, PW; Baker, DA

    2012-01-01

    The 3′-5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regu...

  7. Costs and outcome of assertive community treatment (ACT) in a rural area in Denmark: 4-year register-based follow-up.

    Science.gov (United States)

    Hastrup, Lene Halling; Aagaard, Jørgen

    2015-02-01

    Health economic evidence of assertive community treatment (ACT) in Denmark is limited. The aim of the study was to assess the costs and outcome of ACT among 174 patients with severe and persistent mental illness in a rural area of Denmark. The study was based on a quasi-experimental design with a control group from the neighbouring region. Costs and retention in mental health services were analysed by using register data 1 year before and 4 years after inclusion in the study. Data on the use of supportive housing were available for the year before baseline and the subsequent 2 years only. Seventy eight percent of the patients receiving ACT were in contact with psychiatric services at the 4-year follow-up, while 69% of the patients in the control group had contact with psychiatric services (P < 0.17). Days in supportive housing were lower for the ACT group before baseline and remained so (dropping to zero) for the subsequent 2 years. Over 4 years, the mean total costs per patient in the group receiving ACT were DDK 493,442 (SE = 34,292). Excluding costs of supportive housing, the mean total costs per patient of the control group were DDK 537,218 (SE = 59,371), P < 0.53. If these costs are included, however, the mean total costs for the ACT group are unchanged, whereas costs for the control group rise to DDK 671,500 (SE = 73,671), P < 0.03. While ACT appears to have resulted in a significant reduction in costs for psychiatric hospitalizations, baseline differences in use of supportive housing make the effects of ACT on overall costs more ambiguous. At worst, however, overall costs did not increase. Given the generally acknowledged clinical benefits of ACT over standard outpatient care, the results support further dissemination of ACT in Denmark.

  8. An endoglucanase is involved in infection of rice roots by the not-cellulose-metabolizing endophyte Azoarcus sp. strain BH72.

    Science.gov (United States)

    Reinhold-Hurek, Barbara; Maes, Tamara; Gemmer, Sabrina; Van Montagu, Marc; Hurek, Thomas

    2006-02-01

    The nitrogen-fixing endophyte Azoarcus sp. strain BH72 infects roots of Kallar grass and rice inter- and intra-cellularly and can spread systemically into shoots without causing symptoms of plant disease. Although cellulose or its breakdown products do not support growth, this strain expresses an endoglucanase, which might be involved in infection. Sequence analysis of eglA places the secreted 34-kDa protein into the glycosyl hydrolases family 5, with highest relatedness (40% identity) to endoglucanases of the phytopathogenic bacteria Xanthomonas campestris and Ralstonia solanacearum. Transcriptional regulation studied by eglA:: gusA fusion was not significantly affected by cellulose or its breakdown products or by microaerobiosis. Strongest induction (threefold) was obtained in bacteria grown in close vicinity to rice roots. Visible sites of expression were the emergence points of lateral roots and root tips, which are the primary regions of ingress into the root. To study the role in endophytic colonization, eglA was inactivated by transposon mutagenesis. Systemic spreading of the eglA mutant and of a pilAB mutant into the rice shoot could no longer be detected by polymerase chain reaction. Microscopic inspection of infection revealed that the intracellular colonization of root epidermis cells was significantly reduced in the eglA- mutant BHE6 compared with the wild type and partially restored in the complementation mutant BHRE2 expressing eglA. This provides evidence that Azoarcus sp. endoglucanase is an important determinant for successful endophytic colonization of rice roots, suggesting an active bacterial colonization process.

  9. Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis.

    Science.gov (United States)

    Zhang, Cheng-Gang; Zhang, Bin; Deng, Wen-Sheng; Duan, Ming; Chen, Wei; Wu, Zhi-Yong

    2016-05-14

    To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN

  10. High dietary zinc supply reduces the digestibility of phosphorus in pig diets1

    DEFF Research Database (Denmark)

    Poulsen, Hanne Damgaard; Blaabjerg, Karoline; Sørensen, Kristina Ulrich

    2016-01-01

    . However, divalent metal ions may bind phytate, leaving phytate less accessible to phytase-induced hydrolysis. The objective was to examine the effects of increased Zn supply on the apparent total tract digestibility (ATTD) of P in pig diets supplemented with microbial phytase. A wheat, barley, and soy–based...... diet (4.3 g P/kg DM, 3.1 g phytate P/kg DM, and no feed phosphate) were heat treated at 81°C (plant phytase diet was divided into 3 batches that were supplemented with 0, 100 or 2,500 mg...... a significant (P diet decreased the ATTD of plant P by about 16% in microbial phytase–supplemented diets....

  11. Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study.

    Science.gov (United States)

    Pierce Campbell, Christine M; Gheit, Tarik; Tommasino, Massimo; Lin, Hui-Yi; Torres, B Nelson; Messina, Jane L; Stoler, Mark H; Rollison, Dana E; Sirak, Bradley A; Abrahamsen, Martha; Carvalho da Silva, Roberto J; Sichero, Laura; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2016-10-01

    Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin. Copyright © 2016. Published by Elsevier Inc.

  12. Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition

    Directory of Open Access Journals (Sweden)

    Cristiana Perrotta

    2018-05-01

    Full Text Available Tumor microenvironment is fundamental for cancer progression and chemoresistance. Among stromal cells tumor-associated macrophages (TAMs represent the largest population of infiltrating inflammatory cells in malignant tumors, promoting their growth, invasion, and immune evasion. M2-polarized TAMs are endowed with the nitric oxide (NO-generating enzyme inducible nitric oxide synthase (iNOS. NO has divergent effects on tumors, since it can either stimulate tumor cells growth or promote their death depending on the source of it; likewise the role of iNOS in cancer differs depending on the cell type. The role of NO generated by TAMs has not been investigated. Using different tumor models in vitro and in vivo we found that NO generated by iNOS of M2-polarized TAMs is able to protect tumor cells from apoptosis induced by the chemotherapeutic agent cisplatin (CDDP. Here, we demonstrate that the protective effect of NO depends on the inhibition of acid sphingomyelinase (A-SMase, which is activated by CDDP in a pathway involving the death receptor CD95. Mechanistic insights indicate that NO actions occur via generation of cyclic GMP and activation of protein kinase G (PKG, inducing phosphorylation of syntaxin 4 (synt4, a SNARE protein responsible for A-SMase trafficking and activation. Noteworthy, phosphorylation of synt4 at serine 78 by PKG is responsible for the proteasome-dependent degradation of synt4, which limits the CDDP-induced exposure of A-SMase to the plasma membrane of tumor cells. This inhibits the cytotoxic mechanism of CDDP reducing A-SMase-triggered apoptosis. This is the first demonstration that endogenous NO system is a key mechanism through which TAMs protect tumor cells from chemotherapeutic drug-induced apoptosis. The identification of the pathway responsible for A-SMase activity downregulation in tumors leading to chemoresistance warrants further investigations as a means to identify new anti-cancer molecules capable of specifically

  13. Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

    Science.gov (United States)

    Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

    2014-01-01

    The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

  14. Contribution of a natural polymorphism, protein kinase G, modulates electroconvulsive seizure recovery in D. melanogaster.

    Science.gov (United States)

    Kelly, Stephanie P; Risley, Monica G; Miranda, Leonor E; Dawson-Scully, Ken

    2018-05-24

    Drosophila melanogaster is a well-characterized model for neurological disorders and is widely used for investigating causes of altered neuronal excitability leading to seizure-like behavior. One method used to analyze behavioral output of neuronal perturbance is recording the time to locomotor recovery from an electroconvulsive shock. Based on this behavior, we sought to quantify seizure susceptibility in larval D. melanogaster with differences in the enzymatic activity levels of a major protein, cGMP-dependent protein kinase (PKG). PKG, encoded by foraging , has two natural allelic variants and has previously been implicated in several important physiological characteristics including: foraging patterns, learning and memory, and environmental stress tolerance. The well-established NO/cGMP/PKG signaling pathway found in the fly, which potentially targets downstream K + channel(s), which ultimately impacts membrane excitability; leading to our hypothesis: altering PKG enzymatic activity modulates time to recovery from an electroconvulsive seizure. Our results show that by both genetically and pharmacologically increasing PKG enzymatic activity, we can decrease the locomotor recovery time from an electroconvulsive seizure in larval D. melanogaster . © 2018. Published by The Company of Biologists Ltd.

  15. 75 FR 34983 - Order (1) Pursuant to Section 4(c) of the Commodity Exchange Act, Permitting the Kansas City...

    Science.gov (United States)

    2010-06-21

    ... Act, Permitting the Kansas City Board of Trade Clearing Corporation To Clear Over-the-Counter Wheat Calendar Swaps and (2) Pursuant to Section 4d of the Commodity Exchange Act, Permitting Customer Positions... contract market, and its wholly- owned subsidiary corporation, the Kansas City Board of Trade Clearing...

  16. The role of cGMP signalling in regulating life cycle progression of Plasmodium.

    Science.gov (United States)

    Hopp, Christine S; Bowyer, Paul W; Baker, David A

    2012-08-01

    The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  17. 75 FR 34434 - Request To Amend an Existing Order Under Section 4(c) of the Commodity Exchange Act Permitting...

    Science.gov (United States)

    2010-06-17

    ...) pursuant to Section 4(c) of the Act, (a) to permit the clearing of coffee, sugar, and cocoa OTC swap..., ``a * * * commodity swap,'' which latter term includes swaps on agricultural products. While the...(c) of the Act, ICE Clear could not engage in the clearing of OTC swap contracts in cocoa, sugar and...

  18. 28 CFR Appendix to Part 55 - Jurisdictions Covered Under Sections 4(f)(4) and 203(c) of the Voting Rights Act of 1965, as Amended

    Science.gov (United States)

    2010-07-01

    ... REGARDING LANGUAGE MINORITY GROUPS Pt. 55, App. Appendix to Part 55—Jurisdictions Covered Under Sections 4(f...)(4) and 203(c) of the Voting Rights Act of 1965, as Amended [Applicable language minority group(s... (Chinese, Filipino, Japanese, Vietnamese), Spanish heritage. Merced County Spanish heritage Monterey County...

  19. Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation

    Directory of Open Access Journals (Sweden)

    Kate Fisher

    2013-10-01

    Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosin.

  20. Impairment of leaf photosynthesis after insect herbivory or mechanical injury on common milkweed, Asclepias syriaca.

    Science.gov (United States)

    Delaney, K J; Haile, F J; Peterson, R K D; Higley, L G

    2008-10-01

    Insect herbivory has variable consequences on plant physiology, growth, and reproduction. In some plants, herbivory reduces photosynthetic rate (Pn) activity on remaining tissue of injured leaves. We sought to better understand the influence of leaf injury on Pn of common milkweed, Asclepias syriaca (Asclepiadaceae), leaves. Initially, we tested whether Pn reductions occurred after insect herbivory or mechanical injury. We also (1) examined the duration of photosynthetic recovery, (2) compared mechanical injury with insect herbivory, (3) studied the relationship between leaf Pn with leaf injury intensity, and (4) considered uninjured leaf compensatory Pn responses neighboring an injured leaf. Leaf Pn was significantly reduced on mechanically injured or insect-fed leaves in all reported experiments except one, so some factor(s) (cardiac glycoside induction, reproductive investment, and water stress) likely interacts with leaf injury to influence whether Pn impairment occurs. Milkweed tussock moth larval herbivory, Euchaetes egle L. (Arctiidae), impaired leaf Pn more severely than mechanical injury in one experiment. Duration of Pn impairment lasted > 5 d to indicate high leaf Pn sensitivity to injury, but Pn recovery occurred within 13 d in one experiment. The degree of Pn reduction was more severe from E. egle herbivory than similar levels of mechanical tissue removal. Negative linear relationships characterized leaf Pn with percentage tissue loss from single E. egle-fed leaves and mechanically injured leaves and suggested that the signal to trigger leaf Pn impairment on remaining tissue of an injured leaf was amplified by additional tissue loss. Finally, neighboring uninjured leaves to an E. egle-fed leaf had a small (approximately 10%) degree of compensatory Pn to partly offset tissue loss and injured leaf Pn impairment.

  1. PÖFF / Egle Loo

    Index Scriptorium Estoniae

    Loo, Egle

    2010-01-01

    14. Pimedate Ööde filmifestivali filmidest: "Päris koopia" (Prantsuse-Itaalia-Iraani 2010), "Taevariik" (Rootsi-Taani 2010), "Teisel pool" (Rootsi-Soome 2010), "Tamara Drewe" (Inglise 2010), "Mesi" (Türgi-Saksa 2010), "Inimestest ja jumalatest" (Prantsuse 2010)

  2. Role for β-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions

    Science.gov (United States)

    Irazoqui, Javier E.; Ng, Aylwin; Xavier, Ramnik J.; Ausubel, Frederick M.

    2008-01-01

    We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans β-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-κB-dependent TLR2 signaling in epithelial cells. These data suggest that β-catenin and homeobox genes play an important and conserved role in innate immune defense. PMID:18981407

  3. Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions.

    Science.gov (United States)

    Irazoqui, Javier E; Ng, Aylwin; Xavier, Ramnik J; Ausubel, Frederick M

    2008-11-11

    We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans beta-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-kappaB-dependent TLR2 signaling in epithelial cells. These data suggest that beta-catenin and homeobox genes play an important and conserved role in innate immune defense.

  4. A cGMP-dependent protein kinase gene, foraging, modifies habituation-like response decrement of the giant fiber escape circuit in Drosophila.

    Science.gov (United States)

    Engel, J E; Xie, X J; Sokolowski, M B; Wu, C F

    2000-01-01

    The Drosophila giant fiber jump-and-flight escape response is a model for genetic analysis of both the physiology and the plasticity of a sensorimotor behavioral pathway. We previously established the electrically induced giant fiber response in intact tethered flies as a model for habituation, a form of nonassociative learning. Here, we show that the rate of stimulus-dependent response decrement of this neural pathway in a habituation protocol is correlated with PKG (cGMP-Dependent Protein Kinase) activity and foraging behavior. We assayed response decrement for natural and mutant rover and sitter alleles of the foraging (for) gene that encodes a Drosophila PKG. Rover larvae and adults, which have higher PKG activities, travel significantly farther while foraging than sitters with lower PKG activities. Response decrement was most rapid in genotypes previously shown to have low PKG activities and sitter-like foraging behavior. We also found differences in spontaneous recovery (the reversal of response decrement during a rest from stimulation) and a dishabituation-like phenomenon (the reversal of response decrement evoked by a novel stimulus). This electrophysiological study in an intact animal preparation provides one of the first direct demonstrations that PKG can affect plasticity in a simple learning paradigm. It increases our understanding of the complex interplay of factors that can modulate the sensitivity of the giant fiber escape response, and it defines a new adult-stage phenotype of the foraging locus. Finally, these results show that behaviorally relevant neural plasticity in an identified circuit can be influenced by a single-locus genetic polymorphism existing in a natural population of Drosophila.

  5. Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation

    International Nuclear Information System (INIS)

    Lund, Natalie; Henrion, Daniel; Tiede, Petra; Ziche, Marina; Schunkert, Heribert; Ito, Wulf D.

    2010-01-01

    The cytoskeleton plays a central role for the integration of biochemical and biomechanical signals across the cell required for complex cellular functions. Recent studies indicate that the intermediate filament vimentin is necessary for endothelial cell morphogenesis e.g. in the context of leukocyte transmigration. Here, we present evidence, that the scaffold provided by vimentin is essential for VASP localization and PKG mediated VASP phosphorylation and thus controls endothelial cell migration and proliferation. Vimentin suppression using siRNA technique significantly decreased migration velocity by 50% (videomicroscopy), diminished transmigration activity by 42.5% (Boyden chamber) and reduced proliferation by 43% (BrdU-incorporation). In confocal microscopy Vimentin colocalized with VASP and PKG in endothelial cells. Vimentin suppression was accompanied with a translocation of VASP from focal contacts to the perinuclear region. VASP/Vimentin and PKG/Vimentin colocalization appeared to be essential for proper PKG mediated VASP phosphorylation because we detected a diminished expression of PKG and p Ser239 -VASP in vimentin-suppressed cells, Furthermore, the induction of VASP phosphorylation in perfused arteries was markedly decreased in vimentin knockout mice compared to wildtypes. A link is proposed between vimentin, VASP phosphorylation and actin dynamics that delivers an explanation for the important role of vimentin in controlling endothelial cell morphogenesis.

  6. Homosexual Cohabitees Act, 18 June 1987.

    Science.gov (United States)

    1989-01-01

    The purpose of this Act is to place homosexual cohabitees in the same legal position as heterosexual cohabitees. It provides that if 2 persons are living together in a homosexual relationship, the following legal provisions relating to cohabitation shall apply to them: 1) the Cohabitees (Joint Homes) Act (1987:232), 2) the Inheritance Code, 3) the Real Property Code, 4) Chapter 10, section 9, of the Code of Judicial Procedure, 5) Chapter 4, section 19, 1st paragraph, of the Code of Execution, 6) section 19, 1st paragraph, section 35, subsection 4, and point 2a, 7th paragraph, of the regulations relating to Section 36 of the Municipal Tax Act (1928:370), 7) the Inheritance and Gift Taxes Act (1941:416), 8) Section 6 of the Court Procedures (Miscellaneous Business) Act (1946:807), 9) the Tenant Owner Act (1971:479), 10) section 10 of the Legal Aid Act (1972:429), and 11) the Notice to Unknown Creditors Act (1981:131).

  7. Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.

    Directory of Open Access Journals (Sweden)

    Christine R Collins

    2013-05-01

    Full Text Available The malaria parasite replicates within an intraerythrocytic parasitophorous vacuole (PV. Eventually, in a tightly regulated process called egress, proteins of the PV and intracellular merozoite surface are modified by an essential parasite serine protease called PfSUB1, whilst the enclosing PV and erythrocyte membranes rupture, releasing merozoites to invade fresh erythrocytes. Inhibition of the Plasmodium falciparum cGMP-dependent protein kinase (PfPKG prevents egress, but the underlying mechanism is unknown. Here we show that PfPKG activity is required for PfSUB1 discharge into the PV, as well as for release of distinct merozoite organelles called micronemes. Stimulation of PfPKG by inhibiting parasite phosphodiesterase activity induces premature PfSUB1 discharge and egress of developmentally immature, non-invasive parasites. Our findings identify the signalling pathway that regulates PfSUB1 function and egress, and raise the possibility of targeting PfPKG or parasite phosphodiesterases in therapeutic approaches to dysregulate critical protease-mediated steps in the parasite life cycle.

  8. Civil Code (Amendment) Act, 1988 (No. 4 of 1988), 21 May 1988.

    Science.gov (United States)

    1988-01-01

    This Act amends the Civil Code of Saint Lucia to do the following, among other things: 1) allow marriage to be celebrated by giving notice; 2) legalize divorce; 3) allow all children to be legitimated by the subsequent marriage of their parents; 4) remove differences in the treatment of children born within marriage and those born outside of marriage; 5) lower to 18 the age of majority and the age under which consent must be obtained in order to marry. A number of these changes are consolidations of earlier amendments made to the Civil Code. full text

  9. Leedu kunst on integratsioonivõimeline / Eha Komissarov

    Index Scriptorium Estoniae

    Komissarov, Eha, 1947-

    2004-01-01

    Leedu kaasaegse kunsti näitus "Omas mahlas" Tallinna Kunstihoones (Evaldas Jansas, Egle Rakauskaite) ja Rotermanni soolalaos (Loreta Bilinskaite-Burke, Laura Barbshtiene & Arturas Bumshteinas (G-Lab), Jonas Gasiunas, Arunas Gudaitis, Linas Jablonskis, Dainius Lishkevicius, Mindaugas Lukoshaitis, Gintaras Makarevicius, Deimantas Narkevicius, Egle Ridikaite, Irma Stanaityte, Laura Stasiulyte, Mindaugas Shimkus, Arturas Valiauga, Rimaldas Vikshraitis, Darius Zhiura). Kuraator Anders Kreuger leedu kunstniku kuvandiloomest

  10. EEG. Renewables Act. Comment. 4. new rev. and enl. ed.

    International Nuclear Information System (INIS)

    Frenz, Walter; Cosack, Tilman

    2015-01-01

    Unlike any other Act, the Renewable Energy Sources Act (EEG) changes continuously. Recently it has been fundamentally transformed with the amendment 2014. Comprehensive, readable and practice-oriented. The proven Berliner comment EEG is your reliable companion through the new regulatory regime. All provisions of the EEG 2014 thorough and easy to understand commented by experts of the matter. 2. The EEG Amending Act of 29.6.2015 has already been considered. A detailed introduction and contributions to the relevant European law and the antitrust aspects of the renewable energy sources to guarantee you a broad understanding of the rules. Valuable background information you provide, the digressions of the most important renewable energy technologies, will explain the pictures thanks to numerous the scientific and technical foundations. Moreover you the construction law aspects in the construction of photovoltaic and wind turbines are explained clearly. [de

  11. Act No. 25 of 31 January 1983 amending Act No. 1103 of 4 August 1965 and Decree No. 680 of 6 March 1968 on regulations governing the activities of technicians in medical radiology

    International Nuclear Information System (INIS)

    1983-01-01

    This Act amends Act No. 1103 of 4 August 1965 and Decree No. 680 of 6 March 1968 of the President of the Republic regulating the activities of auxiliary personnel engaged in medical radiology. It establishes new conditions for training and qualifications of such technicians in respect of radiodiagnosis, radiotherapy and nuclear medicine. (NEA) [fr

  12. 48 CFR 52.250-4 - SAFETY Act Pre-qualification Designation Notice.

    Science.gov (United States)

    2010-10-01

    ..., or fails to meet, the requirements of any solicitation issued by any Federal, State, local or tribal...) Definitions. As used in this provision— Act of terrorism means any act determined to have met the following... unlawful. (2) Causes harm, including financial harm, to a person, property, or entity, in the United States...

  13. Act no 388 to amend Section 15 of the Nuclear Liability Act

    International Nuclear Information System (INIS)

    1986-01-01

    Finland is ratifying the Montreal Protocols Nos 3 and 4 to the Warsaw Convention concerning carriage by air; protocol No 4 contains no exclusion clause for nuclear damage. This Act amends the 1972 Nuclear Liability Act to the effect that air carriers of nuclear substances have a right of recourse against the operator liable under nuclear legislation. In this way the principle of channelling liability onto the nuclear operator is maintained. (NEA) [fr

  14. 34 CFR 5.1 - Act.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Act. 5.1 Section 5.1 Education Office of the Secretary...-10) Definitions § 5.1 Act. As used in this part, Act means section 552 of title 5, United States Code, as amended by Pub. L. 90-23, codifying the Act of July 4, 1966, sometimes referred to as the “Freedom...

  15. A multi-angular mass spectrometric view at cyclic nucleotide signaling proteins : Structure/function and protein interactions of cAMP- and cGMP-dependent protein kinase

    NARCIS (Netherlands)

    Scholten, A.

    2006-01-01

    The primary focus of this thesis is the two kinases PKA and PKG, cAMP and cGMP dependent protein kinase respectively. PKA and PKG are studied both at structure/function level as well as at the level of interaction with other proteins in tissue. Our primary methods are all based on mass spectrometry.

  16. An ant-plant mutualism through the lens of cGMP-dependent kinase genes.

    Science.gov (United States)

    Malé, Pierre-Jean G; Turner, Kyle M; Doha, Manjima; Anreiter, Ina; Allen, Aaron M; Sokolowski, Marla B; Frederickson, Megan E

    2017-09-13

    In plant-animal mutualisms, how an animal forages often determines how much benefit its plant partner receives. In many animals, foraging behaviour changes in response to foraging gene expression or activation of the cGMP-dependent protein kinase (PKG) that foraging encodes. Here, we show that this highly conserved molecular mechanism affects the outcome of a plant-animal mutualism. We studied the two PKG genes of Allomerus octoarticulatus, an Amazonian ant that defends the ant-plant Cordia nodosa against herbivores. Some ant colonies are better 'bodyguards' than others. Working in the field in Peru, we found that colonies fed with a PKG activator recruited more workers to attack herbivores than control colonies. This resulted in less herbivore damage. PKG gene expression in ant workers correlated with whether an ant colony discovered an herbivore and how much damage herbivores inflicted on leaves in a complex way; natural variation in expression levels of the two genes had significant interaction effects on ant behaviour and herbivory. Our results suggest a molecular basis for ant protection of plants in this mutualism. © 2017 The Author(s).

  17. 76 FR 77558 - Sunshine Act Meeting; Notice

    Science.gov (United States)

    2011-12-13

    ... LEGAL SERVICES CORPORATION Sunshine Act Meeting; Notice DATES: Date and Time: The Legal Services Corporation's Operations & Regulations Committee will meet December 16, 2011. The meeting will commence at 4 p... Bylaws necessitated by the DC Nonprofit Corporation Act of 2010. 3. Public comment. 4. Consider and act...

  18. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice

    Directory of Open Access Journals (Sweden)

    Ganesh Rao

    2003-05-01

    Full Text Available Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cellsof-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh, a crucial determinant of embryonic pattern formation in the central nervous system. We modeled the ability of c-Myc and Shh to induce medulloblastoma in mice using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell type-specific manner. We targeted the expression of Shh and c-Myc to nestin-expressing neural progenitor cells by injecting replication-competent ALV splice acceptor (RCAS vectors into the cerebella of newborn mice. Following injection with RCAS-Shh alone, 3/32 (9% mice developed medulloblastomas and 5/32 showed multifocal hyperproliferation of the EGL, possibly a precursor stage of medulloblastoma. Following injection with RCAS-Shh plus RCAS-Myc, 9/39 (23% mice developed medulloblastomas. We conclude that nestin-expressing neural progenitors, present in the cerebellum at birth, can act as the cells-of-origin for medulloblastoma, and that c-Myc cooperates with Shh to enhance tumorigenicity.

  19. 45 CFR 2543.86 - Clean Air Act and the Federal Water Pollution Control Act.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Clean Air Act and the Federal Water Pollution... Water Pollution Control Act. Contracts and subgrants of amounts in excess of $100,000 shall contain a... regulations issued pursuant to the Clean Air Act (42 U.S.C. 7401 et seq.) and the Federal Water Pollution...

  20. The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on embryo development and cryopreservation.

    Directory of Open Access Journals (Sweden)

    Kátia R L Schwarz

    Full Text Available This study aimed to determine the influence of cyclic guanosine 3'5'-monophosphate (cGMP and cGMP-dependent kinase (PKG during in vitro maturation (IVM on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs, and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII, cGMP levels, lipid content in oocytes (OO, transcript abundance for genes involved in lipolysis (ATGL and lipid droplets (PLIN2 in cumulus cells (CC and OO, and presence of phosphorylated (active hormone sensitive lipase (HSLser563 in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme with 10-5M sildenafil (SDF during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05 and did not affect on maturation rate (84.3±6.4% MII. Fetal calf serum (FCS in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05. FCS increased lipid content in OO (40.1 FI, p<0.05 compared to BSA (34.6 FI, while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05. PKG inhibitor (KT5823 reversed this effect (38.9 FI, p<0.05. ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI compared to its use in either or none of the culture periods (34.2 FI, p<0.05. Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance.

  1. Characterization of the regulatory network of BoMYB2 in controlling anthocyanin biosynthesis in purple cauliflower.

    Science.gov (United States)

    Chiu, Li-Wei; Li, Li

    2012-10-01

    Purple cauliflower (Brassica oleracea L. var. botrytis) Graffiti represents a unique mutant in conferring ectopic anthocyanin biosynthesis, which is caused by the tissue-specific activation of BoMYB2, an ortholog of Arabidopsis PAP2 or MYB113. To gain a better understanding of the regulatory network of anthocyanin biosynthesis, we investigated the interaction among cauliflower MYB-bHLH-WD40 network proteins and examined the interplay of BoMYB2 with various bHLH transcription factors in planta. Yeast two-hybrid studies revealed that cauliflower BoMYBs along with the other regulators formed the MYB-bHLH-WD40 complexes and BobHLH1 acted as a bridge between BoMYB and BoWD40-1 proteins. Different BoMYBs exhibited different binding activity to BobHLH1. Examination of the BoMYB2 transgenic lines in Arabidopsis bHLH mutant backgrounds demonstrated that TT8, EGL3, and GL3 were all involved in the BoMYB2-mediated anthocyanin biosynthesis. Expression of BoMYB2 in Arabidopsis caused up-regulation of AtTT8 and AtEGL3 as well as a subset of anthocyanin structural genes encoding flavonoid 3'-hydroxylase, dihydroflavonol 4-reductase, and leucoanthocyanidin dioxygenase. Taken together, our results show that MYB-bHLH-WD40 network transcription factors regulated the bHLH gene expression, which may represent a critical feature in the control of anthocyanin biosynthesis. BoMYB2 together with various BobHLHs specifically regulated the late anthocyanin biosynthetic pathway genes for anthocyanin biosynthesis. Our findings provide additional information for the complicated regulatory network of anthocyanin biosynthesis and the transcriptional regulation of transcription factors in vegetable crops.

  2. Estimation of Dose Received in Decommissioning of Phosphate Acid Factory-Petro Kimia Gresik

    International Nuclear Information System (INIS)

    Lubis, Erwansyah; Heru Umbara; Agus Gindo S

    2007-01-01

    The estimation of dose received in decommissioning of Phosphate Acid Factory-Petro Kimia Gresik (PAF-PKG) was carried out. The external dose estimated base on the radiation rate in each working area of zona-1, 2, 3 and 4. The internal dose estimated base on the radionuclides activity and diameter of particulate exist in each working area. The calculation of the internal dose was carried out by LUDEP 2.0 computer code. The results indicated that in the normal activity of decommissioning, the effective dose will received by the worker per year were 0.27 mSv in zona-1, 1.23 mSv in zona-2, 1.37 mSv in zona-3 and 11.85 mSv in zona-4. The internal dose received when a worse accident happens in decommissioning activity is 21.06 mSv for lung organ or 4.2 % of the dose limit for that organ. Based on the discussion above, indicated that in the decommissioning of PAF-PKG the dose received by the workers is far lower than the dose limit. (author)

  3. Biotin increases glucokinase expression via soluble guanylate cyclase/protein kinase G, adenosine triphosphate production and autocrine action of insulin in pancreatic rat islets.

    Science.gov (United States)

    Vilches-Flores, Alonso; Tovar, Armando R; Marin-Hernandez, Alvaro; Rojas-Ochoa, Alberto; Fernandez-Mejia, Cristina

    2010-07-01

    Besides its role as a carboxylase prosthetic group, biotin has important effects on gene expression. However, the molecular mechanisms through which biotin exerts these effects are largely unknown. We previously found that biotin increases pancreatic glucokinase expression. We have now explored the mechanisms underlying this effect. Pancreatic islets from Wistar rats were treated with biotin, in the presence or absence of different types of inhibitors. Glucokinase mRNA and 18s rRNA abundance were determined by real-time PCR. Adenosine triphosphate (ATP) content was analyzed by fluorometry. Biotin treatment increased glucokinase mRNA abundance approximately one fold after 2 h; the effect was sustained up to 24 h. Inhibition of soluble guanylate cyclase or protein kinase G (PKG) signalling suppressed biotin-induced glucokinase expression. The cascade of events downstream of PKG in biotin-mediated gene transcription is not known. We found that inhibition of insulin secretion with diazoxide or nifedipine prevented biotin-stimulated glucokinase mRNA increase. Biotin treatment increased islet ATP content (control: 4.68+/-0.28; biotin treated: 6.62+/-0.26 pmol/islet) at 30 min. Inhibition of PKG activity suppressed the effects of biotin on ATP content. Insulin antibodies or inhibitors of phosphoinositol-3-kinase/Akt insulin signalling pathway prevented biotin-induced glucokinase expression. The nucleotide 8-Br-cGMP mimicked the biotin effects. We propose that the induction of pancreatic glucokinase mRNA by biotin involves guanylate cyclase and PKG activation, which leads to an increase in ATP content. This induces insulin secretion via ATP-sensitive potassium channels. Autocrine insulin, in turn, activates phosphoinositol-3-kinase/Akt signalling. Our results offer new insights into the pathways that participate in biotin-mediated gene expression. (c) 2010 Elsevier Inc. All rights reserved.

  4. Radioactive Substances Act 1960

    International Nuclear Information System (INIS)

    1960-01-01

    This Act regulates the keeping and use of radioactive material and makes provision for the disposal and storage of radioactive waste in the United Kingdom. It provides for a licensing system for such activities and for exemptions therefrom, in particular as concerns the United Kingdom Atomic Energy Authority. The Act repeals Section 4(5) of the Atomic Energy Authority Act, 1954 which made temporary provision for discharge of waste on or from premises occupied by the Authority. (NEA) [fr

  5. 26 CFR 31.6001-4 - Additional records under Federal Unemployment Tax Act.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Additional records under Federal Unemployment... Federal Unemployment Tax Act. (a) Records of employers. Every employer liable for tax under the Federal Unemployment Tax Act for any calendar year shall, with respect to each such year, keep such records as are...

  6. Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

    Directory of Open Access Journals (Sweden)

    Miguel Angel Burguillos

    2015-03-01

    Full Text Available Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4 in microglia’s inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3 released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.

  7. Kuidas tuvastada rahapesu / Egle Vainula

    Index Scriptorium Estoniae

    Vainula, Egle

    2017-01-01

    Rahapesu Andmebüroo (RAB) hiljutistest kontrollidest raamatupidamisteenust pakutavates ettevõtetes eesmärgiga teostada järelevalvet rahapesu ja terrorismi rahastamise tõkestamise seadusest tuleneva hoolsuskohustuse täitmise üle

  8. Slovak Republic Act of 11 February 1998 on the energetics and on alterations to Act No. 455/1991 Collection of Acts of CSFR on small business (trade Act) in version of posterior regulations

    International Nuclear Information System (INIS)

    1998-01-01

    This act constitute: (a) conditions of undertaking in electro-energetic, gas industry, and heat supply (in next only 'energetic' branches) ; (b) rights and responsibility of physical and act person undertaking in energetic branches; (c) rights and responsibility of customers of electricity, gas, and heat; counteract measures in the need situations, (d) and at prevention before need situations in energetic branches; (e) state regulation in energetic; (f) authority on keep of this act. The act is divided into for parts: (1) General constitutions, (2) Energetic branches; (3) The state authority; (4) Common, transient and invalidation constitutions.This act deals with the specific conditions for undertaking in nuclear power plants, too (licensing, security). This act shall into effect on 1 July 1998

  9. The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. III. Kinetics of cell proliferation in the external granular layer.

    Science.gov (United States)

    Lauder, J M

    1977-04-22

    The effects of early hypo- and hyperthyroidism on the rates of cell acquisition and proliferation have been studied in the external granular layer (EGL) of the developing rat cerebellar cortex at 10 days of age using quantitative autoradiographic methods. Both altered thyroid states reduce the rate of cell acquisition in the EGL, but appear to do so for different reasons. Hyperthyroidism shortens the average length of the cell cycle by decreasing the duration of the pre-DNA synthetic phase (G1), indicating that excess thyroxine may exert a direct effect on the EGL. This action involves the early onset of neuronal differentiation (cessation of proliferation)46 which presumably leads to the observed decrease in the rate of cell acquisition (increased doubling time). Such differentiating cells do not, however, leave the proliferative zone or the EGL prematurely, resulting in a reduced labeling index, mitotic index, and growth fraction as non-dividing cells dilute the proliferating cell population. Hypothyroidism, on the other hand, leads to no significant change in the length of the cell cycle or in the mitotic index, but causes a decreased labeling index and growth fraction, as well as a reduced rate of cell acquisition (increased doubling time). No significant change in the amount of cell death in the EGL could be found to explain this apparent discrepancy between the rate of cell proliferation (cell cycle length) and cell acqusiition. The answer to this puzzle appears to lie in the mitotic index, which is not affected to the same extent as the labeling index, although it is also slightly reduced. If cells were to remain longer in mitosis, this could result in a decreased labeling index and growth fraction but nearly normal mitotic index and cell cycle length (as measured using the % labeled mitoses method), since those cells dropping out of the cycling population would be counted as mitoses...

  10. Production and profitability of a beef herd on transitional ...

    African Journals Online (AJOL)

    In summer Treatment 1 (T1) consisted of a supplement containing 50 g phosphate (P)/kg and 150 g crude protein (CP)/kg. T2 and T3 both consisted of supplements containing 60 g P/kg and 0 g CP/kg. In winter, T1 consisted of a supplement containing 367 g CP/kg, 77.5% non-protein nitrogen (NPN) and metabolizable ...

  11. 29 CFR 1614.203 - Rehabilitation Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Rehabilitation Act. 1614.203 Section 1614.203 Labor... EMPLOYMENT OPPORTUNITY Provisions Applicable to Particular Complaints § 1614.203 Rehabilitation Act. (a... Rehabilitation Act of 1973, as amended (29 U.S.C. 791), has been violated in a complaint alleging nonaffirmative...

  12. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy.

    Science.gov (United States)

    Woodcock, T E; Woodcock, T M

    2012-03-01

    I.V. fluid therapy does not result in the extracellular volume distribution expected from Starling's original model of semi-permeable capillaries subject to hydrostatic and oncotic pressure gradients within the extracellular fluid. Fluid therapy to support the circulation relies on applying a physiological paradigm that better explains clinical and research observations. The revised Starling equation based on recent research considers the contributions of the endothelial glycocalyx layer (EGL), the endothelial basement membrane, and the extracellular matrix. The characteristics of capillaries in various tissues are reviewed and some clinical corollaries considered. The oncotic pressure difference across the EGL opposes, but does not reverse, the filtration rate (the 'no absorption' rule) and is an important feature of the revised paradigm and highlights the limitations of attempting to prevent or treat oedema by transfusing colloids. Filtered fluid returns to the circulation as lymph. The EGL excludes larger molecules and occupies a substantial volume of the intravascular space and therefore requires a new interpretation of dilution studies of blood volume and the speculation that protection or restoration of the EGL might be an important therapeutic goal. An explanation for the phenomenon of context sensitivity of fluid volume kinetics is offered, and the proposal that crystalloid resuscitation from low capillary pressures is rational. Any potential advantage of plasma or plasma substitutes over crystalloids for volume expansion only manifests itself at higher capillary pressures.

  13. Architectures, Concepts and Architectures for Service Oriented Computing : proceedings of the 1st International Workshop - ACT4SOC 2007

    NARCIS (Netherlands)

    van Sinderen, Marten J.; Unknown, [Unknown

    2007-01-01

    This volume contains the proceedings of the First International Workshop on Architectures, Concepts and Technologies for Service Oriented Computing (ACT4SOC 2007), held on July 22 in Barcelona, Spain, in conjunction with the Second International Conference on Software and Data Technologies (ICSOFT

  14. 29 CFR 1620.27 - Relationship to the Equal Pay Act of title VII of the Civil Rights Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship to the Equal Pay Act of title VII of the Civil... OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.27 Relationship to the Equal Pay Act of title VII of the Civil... equal pay under the Equal Pay Act has no relationship to whether the employee is in the lower paying job...

  15. Expresión diferencial de los genes de algunas enzimas lignocelulolíticas en biopelículas de Aspergillus niger

    Directory of Open Access Journals (Sweden)

    Gretty K. Villena

    2008-12-01

    Full Text Available Se realizó una evaluación génica preliminar a nivel transcripcional de biopelículas de Aspergillus niger ATCC 10864 desarrolladas sobre poliéster respecto a algunas enzimas lignocelulolíticas. El análisis de expresión de genes de enzimas lignocelulolíticas y genes reguladores mediante RT-PCR mostró que los genes eng1, eglC, exo y eglA, eglB y xynB son diferencialmente expresados ya sea temporalmente o mediante más de un transcripto en comparación con cultivos sumergidos. Asimismo, los genes reguladores xlnR y creA mostraron patrones temporales de expresión distintos en ambos sistemas. Los resultados obtenidos aportan la evidencia molecular inicial de expresión diferencial de genes en biopelículas así como patrones de regulación diferencial muy probablemente ligada a la adhesión celular.

  16. Sildenafil improves blood perfusion in steroid-induced avascular necrosis of femoral head in rabbits via a protein kinase G-dependent mechanism.

    Science.gov (United States)

    Song, Qichun; Ni, Jianlong; Jiang, Hongyuan; Shi, Zhibin

    2017-10-01

    The aim of the study were to evaluate the effect of sildenafil against avascular necrosis of femoral head (ANFH) in a rabbit model, and to study the role of protein kinase G (PKG) pathway and vascular endothelial growth factor (VEGF) in ANFH. Three weeks after inducing ANFH with methylprednisolone injection, 45 female adult New Zealand white rabbits were divided into three groups and treated as follows: group SI received daily intraperitoneal sildenafil with a dose of 10 mg/kg per day; group SD received daily sildenafil identically to group SI plus auricular vein injection DT3 (a specific PKG inhibitor); group NS received only normal saline. The blood perfusion function in the femoral head was measured by perfusion MRI and ink artery infusion. Bilateral femora heads were examined histopathologically for the presence of osteonecrosis; VEGF of tissue was examined by Western blot analysis; cGMP level and PKG activity were also measured. The incidence of ANFH in SI group was significantly lower than that observed in NS and SD groups (p < 0.05). VEGF in SI group was increased compared to NS group. cGMP level and PKG activity were also significantly different between NS and SI group (p < 0.05). However, these effects of sildenafil in SD group were all markedly inhibited by the administration of DT3 compared to SI group. Sildenafil appear to increase the perfusion of femoral head by up-regulating VEGF through PKG pathway. The increased perfusion of femoral head could prevent ANFH. Copyright © 2017 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

  17. Lead and zinc bioavailability to Eisenia fetida after phosphorus amendment to repository soils

    International Nuclear Information System (INIS)

    Ownby, David R.; Galvan, Kari A.; Lydy, Michael J.

    2005-01-01

    Four phosphorus forms were investigated as potential soil amendments to decrease the bioavailability of Pb and Zn in two repository soils to the earthworm, Eisenia fetida. Treatments were evaluated by examining differences in bioaccumulation factors between amended and non-amended soils. Triple super phosphate at 5000 mg P/kg decreased both Pb and Zn bioavailability in both soils. Rock phosphate at 5000 mg P/kg decreased Zn bioavailability, but not Pb bioavailability in both repository soils. Monocalcium phosphate and tricalcium phosphate at 5000 mg P/kg did not significantly decrease Pb or Zn bioavailability to earthworms in either repository soil. In order to optimize phosphorus amendments, additional phosphorus (up to 15,000 mg P/kg) and lowered pH were used in a series of tests. The combination of lowering the pH below 6.0 and increasing phosphorus concentrations caused complete mortality in all triple super phosphate amended soils and partial mortality in the highest rock phosphate amended soils. Results indicate that triple super phosphate and rock phosphate are viable soil amendments, but care should be taken when optimizing amendment quantity and pH so that adverse environmental effects are not a by-product. - Phosphorus form and pH were controlling factors in the effectiveness of phosphorus amendment in decreasing Pb and Zn bioavailability

  18. Lead and zinc bioavailability to Eisenia fetida after phosphorus amendment to repository soils

    Energy Technology Data Exchange (ETDEWEB)

    Ownby, David R. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University, Carbondale, IL 62901 (United States); Galvan, Kari A. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University, Carbondale, IL 62901 (United States); Lydy, Michael J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University, Carbondale, IL 62901 (United States)]. E-mail: mlydy@siu.edu

    2005-07-15

    Four phosphorus forms were investigated as potential soil amendments to decrease the bioavailability of Pb and Zn in two repository soils to the earthworm, Eisenia fetida. Treatments were evaluated by examining differences in bioaccumulation factors between amended and non-amended soils. Triple super phosphate at 5000 mg P/kg decreased both Pb and Zn bioavailability in both soils. Rock phosphate at 5000 mg P/kg decreased Zn bioavailability, but not Pb bioavailability in both repository soils. Monocalcium phosphate and tricalcium phosphate at 5000 mg P/kg did not significantly decrease Pb or Zn bioavailability to earthworms in either repository soil. In order to optimize phosphorus amendments, additional phosphorus (up to 15,000 mg P/kg) and lowered pH were used in a series of tests. The combination of lowering the pH below 6.0 and increasing phosphorus concentrations caused complete mortality in all triple super phosphate amended soils and partial mortality in the highest rock phosphate amended soils. Results indicate that triple super phosphate and rock phosphate are viable soil amendments, but care should be taken when optimizing amendment quantity and pH so that adverse environmental effects are not a by-product. - Phosphorus form and pH were controlling factors in the effectiveness of phosphorus amendment in decreasing Pb and Zn bioavailability.

  19. A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.

    Science.gov (United States)

    Baker, David A; Stewart, Lindsay B; Large, Jonathan M; Bowyer, Paul W; Ansell, Keith H; Jiménez-Díaz, María B; El Bakkouri, Majida; Birchall, Kristian; Dechering, Koen J; Bouloc, Nathalie S; Coombs, Peter J; Whalley, David; Harding, Denise J; Smiljanic-Hurley, Ela; Wheldon, Mary C; Walker, Eloise M; Dessens, Johannes T; Lafuente, María José; Sanz, Laura M; Gamo, Francisco-Javier; Ferrer, Santiago B; Hui, Raymond; Bousema, Teun; Angulo-Barturén, Iñigo; Merritt, Andy T; Croft, Simon L; Gutteridge, Winston E; Kettleborough, Catherine A; Osborne, Simon A

    2017-09-05

    To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC 50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC 50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P. falciparum SCID mouse model. The series targets both merozoite egress and erythrocyte invasion, but crucially, also blocks transmission of mature P. falciparum gametocytes to Anopheles stephensi mosquitoes. A co-crystal structure of PvPKG bound to ML10, reveals intimate molecular contacts that explain the high levels of potency and selectivity we have measured. The properties of this series warrant consideration for further development to produce an antimalarial drug.Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes.

  20. 1 CFR 15.4 - Reproduction and certification of copies of acts and documents.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Reproduction and certification of copies of... Reproduction and certification of copies of acts and documents. The Director of the Federal Register shall furnish to requesting agencies, at cost, reproductions or certified copies of original acts and documents...

  1. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination.

    Directory of Open Access Journals (Sweden)

    Yuna Kim

    2006-06-01

    Full Text Available The genes encoding members of the wingless-related MMTV integration site (WNT and fibroblast growth factor (FGF families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination. Loss of Fgf9 leads to XY sex reversal, whereas loss of Wnt4 results in partial testis development in XX gonads. However, the relationship between these signals and the male sex-determining gene, Sry, was unknown. We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9 and WNT4 act as opposing signals to regulate sex determination. In the mouse XY gonad, Sry normally initiates a feed-forward loop between Sox9 and Fgf9, which up-regulates Fgf9 and represses Wnt4 to establish the testis pathway. Surprisingly, loss of Wnt4 in XX gonads is sufficient to up-regulate Fgf9 and Sox9 in the absence of Sry. These data suggest that the fate of the gonad is controlled by antagonism between Fgf9 and Wnt4. The role of the male sex-determining switch--Sry in the case of mammals--is to tip the balance between these underlying patterning signals. In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways.

  2. Zebrafish hoxd4a acts upstream of meis1.1 to direct vasculogenesis, angiogenesis and hematopoiesis.

    Directory of Open Access Journals (Sweden)

    Aseervatham Anusha Amali

    Full Text Available Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior vertebral column, but are viable and fertile. Here, we report that zebrafish embryos having decreased function of the orthologous hoxd4a gene manifest striking perturbations in vasculogenesis, angiogenesis and primitive and definitive hematopoiesis. These defects are preceded by reduced expression of the hemangioblast markers scl1, lmo2 and fli1 within the posterior lateral plate mesoderm (PLM at 13 hours post fertilization (hpf. Epistasis analysis revealed that hoxd4a acts upstream of meis1.1 but downstream of cdx4 as early as the shield stage in ventral-most mesoderm fated to give rise to hemangioblasts, leading us to propose that loss of hoxd4a function disrupts hemangioblast specification. These findings place hoxd4a high in a genetic hierarchy directing hemangioblast formation downstream of cdx1/cdx4 and upstream of meis1.1. An additional consequence of impaired hoxd4a and meis1.1 expression is the deregulation of multiple Hox genes implicated in vasculogenesis and hematopoiesis which may further contribute to the defects described here. Our results add to evidence implicating key roles for Hox genes in their initial phase of expression early in gastrulation.

  3. Energy Policy Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Energy Policy Act (EPA) addresses energy production in the United States, including: (1) energy efficiency; (2) renewable energy; (3) oil and gas; (4) coal; (5)...

  4. Heavy metal phytoextraction by Sedum alfredii is affected by continual clipping and phosphorus fertilization amendment.

    Science.gov (United States)

    Huang, Huagang; Li, Tingqiang; Gupta, D K; He, Zhenli; Yang, Xiao-E; Ni, Bingnan; Li, Mao

    2012-01-01

    Improving the efficacy of phytoextraction is critical for its successful application in metal contaminated soils. Mineral nutrition affects plant growth and metal absorption and subsequently the accumulation of heavy metal through hyper-accumulator plants. This study assessed the effects of di-hydrogen phosphates (KH2PO4, Ca(H2PO4)2, NaH2PO4 and NH4H2PO4) application at three levels (22, 88 and 352 mg P/kg soil) on Sedum alfredii growth and metal uptake by three consecutive harvests on aged and Zn/Cd combined contaminated paddy soil. The addition of phosphates (P) significantly increased the amount of Zn taken up by S. alfredii due to increased shoot Zn concentration and dry matter yield (DMY) (P phytoextraction of Zn and Cd was observed in KH2PO4 and NH4H2PO4 treatment at 352 mg P/kg soil. The amount of Zn removed by phytoextraction increased in the order of 1st clipping < 2nd clipping < 3rd clipping, and for Cd extraction the order was 2nd clipping < 1st clipping < 3rd clipping. These results indicate that the application of P fertilizers coupled with multiple cuttings can enhance the removal of Zn and Cd from contaminated soils by S. alfredii, thus shortening the time needed for accomplishing remediation goals.

  5. 48 CFR 352.224-70 - Privacy Act.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Privacy Act. 352.224-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 352.224-70 Privacy Act. As prescribed in 324.103(b)(2), the Contracting Officer shall insert the following clause: Privacy Act (January...

  6. 29 CFR 1614.202 - Equal Pay Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Equal Pay Act. 1614.202 Section 1614.202 Labor Regulations... OPPORTUNITY Provisions Applicable to Particular Complaints § 1614.202 Equal Pay Act. (a) In its enforcement of the Equal Pay Act, the Commission has the authority to investigate an agency's employment practices on...

  7. Partial Key Grouping: Load-Balanced Partitioning of Distributed Streams

    OpenAIRE

    Nasir, Muhammad Anis Uddin; Morales, Gianmarco De Francisci; Garcia-Soriano, David; Kourtellis, Nicolas; Serafini, Marco

    2015-01-01

    We study the problem of load balancing in distributed stream processing engines, which is exacerbated in the presence of skew. We introduce PARTIAL KEY GROUPING (PKG), a new stream partitioning scheme that adapts the classical “power of two choices” to a distributed streaming setting by leveraging two novel techniques: key splitting and local load estimation. In so doing, it achieves better load balancing than key grouping while being more scalable than shuffle grouping. We test PKG on severa...

  8. Antibodies against the melanocortin-4 receptor act as inverse agonists in vitro and in vivo.

    Science.gov (United States)

    Peter, Jean-Christophe; Nicholson, Janet R; Heydet, Déborah; Lecourt, Anne-Catherine; Hoebeke, Johan; Hofbauer, Karl G

    2007-06-01

    Functionally active antibodies (Abs) against central G-protein-coupled receptors have not yet been reported. We selected the hypothalamic melanocortin-4 receptor (MC4-R) as a target because of its crucial role in the regulation of energy homeostasis. A 15 amino acid sequence of the N-terminal (NT) domain was used as an antigen. This peptide showed functional activity in surface plasmon resonance experiments and in studies on HEK-293 cells overexpressing the human MC4-R (hMC4-R). Rats immunized against the NT peptide produced specific antibodies, which were purified and characterized in vitro. In HEK-293 cells, rat anti-NT Abs showed specific immunofluorescence labeling of hMC4-R. They reduced the production of cAMP under basal conditions and after stimulation with a synthetic MC4-R agonist. Rats immunized against the NT peptide developed a phenotype consistent with MC4-R blockade, that is, increased food intake and body weight, increased liver and fat pad weight, and elevated plasma triglycerides. In a separate experiment in rats, an increase in food intake could be produced after injection of purified Abs into the third ventricle. Similar results were obtained in rats injected with anti-NT Abs raised in rabbits. Our data show for the first time that active immunization of rats against the NT sequence of the MC4-R results in specific Abs, which appear to stimulate food intake by acting as inverse agonists in the hypothalamus.

  9. H- ras deletion protects against angiotensin II-induced arterial hypertension and cardiac remodeling through protein kinase G-Iβ pathway activation.

    Science.gov (United States)

    Martín-Sánchez, Paloma; Luengo, Alicia; Griera, Mercedes; Orea, María Jesús; López-Olañeta, Marina; Chiloeches, Antonio; Lara-Pezzi, Enrique; de Frutos, Sergio; Rodríguez-Puyol, Manuel; Calleros, Laura; Rodríguez-Puyol, Diego

    2018-02-01

    Ras proteins regulate cell survival, growth, differentiation, blood pressure, and fibrosis in some organs. We have demonstrated that H- ras gene deletion produces mice hypotension via a soluble guanylate cyclase-protein kinase G (PKG)-dependent mechanism. In this study, we analyzed the consequences of H- ras deletion on cardiac remodeling induced by continuous angiotensin II (AngII) infusion and the molecular mechanisms implied. Left ventricular posterior wall thickness and mass and cardiomyocyte cross-sectional area were similar between AngII-treated H-Ras knockout (H -ras -/- ) and control wild-type (H -ras +/+ ) mice, as were extracellular matrix protein expression. Increased cardiac PKG-Iβ protein expression in H -ras -/- mice suggests the involvement of this protein in heart protection. Ex vivo experiments on cardiac explants could support this mechanism, as PKG blockade blunted protection against AngII-induced cardiac hypertrophy and fibrosis markers in H -ras -/- mice. Genetic modulation studies in cardiomyocytes and cardiac and embryonic fibroblasts revealed that the lack of H-Ras down-regulates the B-RAF/MEK/ERK pathway, which induces the glycogen synthase kinase-3β-dependent activation of the transcription factor, cAMP response element-binding protein, which is responsible for PKG-Iβ overexpression in H -ras -/- mouse embryonic fibroblasts. This study demonstrates that H- ras deletion protects against AngII-induced cardiac remodeling, possibly via a mechanism in which PKG-Iβ overexpression could play a partial role, and points to H-Ras and/or downstream proteins as potential therapeutic targets in cardiovascular disease.-Martín-Sánchez, P., Luengo, A., Griera, M., Orea, M. J., López-Olañeta, M., Chiloeches, A., Lara-Pezzi, E., de Frutos, S., Rodríguez-Puyol, M., Calleros, L., Rodríguez-Puyol, D. H- ras deletion protects against angiotensin II-induced arterial hypertension and cardiac remodeling through protein kinase G-Iβ pathway activation.

  10. 77 FR 32111 - Privacy Act System of Records

    Science.gov (United States)

    2012-05-31

    ... contacted in order to obtain that office's advice regarding obligations under the Privacy Act; 8. Breach... FEDERAL COMMUNICATIONS COMMISSION Privacy Act System of Records AGENCY: Federal Communications Commission. ACTION: Notice; one new Privacy Act system of records. SUMMARY: Pursuant to subsection (e)(4) of...

  11. 25 CFR 700.33 - Act (The Act).

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88 Stat...

  12. Download this PDF file

    African Journals Online (AJOL)

    Ref. Ago Stro Average Average Average Type of failure. Mark No. at test (mm) weight In maximum compressive and remarks. Cube. " TAUmum strength days air (kg) load (kN). (mm). PK, 7 150. 6.75. 126. 5.63 Normal Failure. PKG 7 150 6.36. 119. 5.27 Normal Failure. PKS. 150. 6,39. 108. 4.81 Normal Failure. PK 7 150.

  13. Australian Nuclear Science and Technology Organization (Transitional Provisions) Act 1987 - No 4 of 1987

    International Nuclear Information System (INIS)

    1987-01-01

    This Act implements certain transitional provisions consequent to the enactment of the ANSTO Act 1987. The legislation provides for the continuation of the body corporate from its present form as the Australian Atomic Energy Commission to the new body corporate, the Australian Nuclear Science and Technology Organization. (NEA) [fr

  14. 75 FR 75187 - Sunshine Act Meeting

    Science.gov (United States)

    2010-12-02

    ... SECURITIES AND EXCHANGE COMMISSION Sunshine Act Meeting Notice is hereby given, pursuant to the provisions of the Government in the Sunshine Act, Public Law 94-409, that the Securities and Exchange.... Elizabeth M. Murphy, Secretary. [FR Doc. 2010-30407 Filed 11-30-10; 4:15 pm] BILLING CODE 8011-01-P ...

  15. A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Bruce N Bagley

    Full Text Available Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL called Spontaneous dominant leukemia (Sdl. Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H. MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.

  16. A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis.

    Science.gov (United States)

    Bagley, Bruce N; Keane, Thomas M; Maklakova, Vilena I; Marshall, Jonathon G; Lester, Rachael A; Cancel, Michelle M; Paulsen, Alex R; Bendzick, Laura E; Been, Raha A; Kogan, Scott C; Cormier, Robert T; Kendziorski, Christina; Adams, David J; Collier, Lara S

    2012-01-01

    Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H)). MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H) to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.

  17. Clean Water Act (Section 404) and Rivers and Harbors Act (Sections 9 and 10). Environmental Guidance Program Reference Book, Revision 4

    Energy Technology Data Exchange (ETDEWEB)

    None

    1992-03-01

    This Reference Book contains a current copy of the Clean Water Act (Section 404) and the Rivers and Harbors Act (Sections 9 and 10) and those regulations that implement those sections of the statutes and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Updates that include important new requirements will be provided periodically. Questions concerning this Reference Book may be directed to Mark Petts, IH-231 (FTS 896-2609 or Commercial 202/586-2609).

  18. 34 CFR 80.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  19. 49 CFR 18.4 - Applicability.

    Science.gov (United States)

    2010-10-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  20. 21 CFR 1403.4 - Applicability.

    Science.gov (United States)

    2010-04-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

  1. 13 CFR 143.4 - Applicability.

    Science.gov (United States)

    2010-01-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  2. 28 CFR 66.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  3. 44 CFR 13.4 - Applicability.

    Science.gov (United States)

    2010-10-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  4. 45 CFR 1174.4 - Applicability.

    Science.gov (United States)

    2010-10-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  5. 45 CFR 1157.4 - Applicability.

    Science.gov (United States)

    2010-10-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  6. 22 CFR 135.4 - Applicability.

    Science.gov (United States)

    2010-04-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  7. 45 CFR 1183.4 - Applicability.

    Science.gov (United States)

    2010-10-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  8. 14 CFR 1273.4 - Applicability.

    Science.gov (United States)

    2010-01-01

    ... Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD of the Act); and (v... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State Administrative...

  9. 38 CFR 43.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... Assistance (Title IV-E of the Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD... following programs of The National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity... 3 of the Act), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State...

  10. 45 CFR 602.4 - Applicability.

    Science.gov (United States)

    2010-10-01

    ... Assistance (Title IV-E of the Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD... following programs of The National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity... 3 of the Act), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State...

  11. 40 CFR 31.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... Assistance (Title IV-E of the Act); (iv) Aid to the Aged, Blind, and Disabled (Titles I, X, XIV, and XVI-AABD... following programs of The National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity... 3 of the Act), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State...

  12. 29 CFR 1470.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... Assistance (title IV-E of the Act); (iv) Aid to the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD... following programs of The National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity... 3 of the Act), and (ii) School Breakfast (section 4 of the Act). (6) Entitlement grants for State...

  13. 78 FR 35533 - Suspension of Limitations Under the Jerusalem Embassy Act

    Science.gov (United States)

    2013-06-12

    ...-09 of June 4, 2013--Suspension of Limitations Under the Jerusalem Embassy Act Presidential.... 2013-09 of June 4, 2013 Suspension of Limitations Under the Jerusalem Embassy Act Memorandum for the... the United States, including section 7(a) of the Jerusalem Embassy Act of 1995 (Public Law 104-45...

  14. 75 FR 67397 - Sunshine Act Meeting; Notice

    Science.gov (United States)

    2010-11-02

    ... select from among those candidates for further consideration. 3. Consider and act on other business. 4... LEGAL SERVICES CORPORATION Sunshine Act Meeting; Notice Time and Date: The Legal Services Corporation Board of Directors' Search Committee for LSC President (``Search Committee'' or ``Committee...

  15. 48 CFR 352.237-70 - Pro-Children Act.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the Pro...

  16. Astragaloside IV Inhibits Oxidative Stress-Induced Mitochondrial Permeability Transition Pore Opening by Inactivating GSK-3β via Nitric Oxide in H9c2 Cardiac Cells

    Directory of Open Access Journals (Sweden)

    Yonggui He

    2012-01-01

    Full Text Available Objective. This study aimed to investigate whether astragaloside IV modulates the mitochondrial permeability transition pore (mPTP opening through glycogen synthase kinase 3β (GSK-3β in H9c2 cells. Methods. H9c2 cells were exposed to astragaloside IV for 20 min. GSK-3β (Ser9, Akt (Ser473, and VASP (Ser239 activities were determined with western blot. The mPTP opening was evaluated by measuring mitochondrial membrane potential (ΔΨm. Nitric oxide (NO generation was measured by 4-amino-5-methylamino-2′, 7′-difluorofluorescein (DAF-FM diacetate. Fluorescence images were obtained with confocal microscopy. Results. Astragaloside IV significantly enhanced GSK-3β phosphorylation and prevented H2O2-induced loss of ΔΨm. These effects of astragaloside IV were reversed by the phosphatidylinositol 3-kinase (PI3K inhibitor LY294002, the NO sensitive guanylyl cyclase selective inhibitor ODQ, and the PKG inhibitor KT5823. Astragaloside IV activated Akt and PKG. Astragaloside IV was also shown to increase NO production, an effect that was reversed by L-NAME and LY294002. Astragaloside IV applied at reperfusion reduced cell death caused by simulated ischemia/reperfusion, indicating that astragaloside IV can prevent reperfusion injury. Conclusions. These data suggest that astragaloside IV prevents the mPTP opening and reperfusion injury by inactivating GSK-3β through the NO/cGMP/PKG signaling pathway. NOS is responsible for NO generation and is activated by the PI3K/Akt pathway.

  17. 77 FR 74551 - Suspension of Limitations Under the Jerusalem Embassy Act

    Science.gov (United States)

    2012-12-14

    .... 2013-2 of December 4, 2012--Suspension of Limitations Under the Jerusalem Embassy Act #0; #0; #0.... 2013-2 of December 4, 2012 Suspension of Limitations Under the Jerusalem Embassy Act Memorandum for the... the United States, including section 7(a) of the Jerusalem Embassy Act of 1995 (Public Law 104-45...

  18. Investigation of electrostatic waves in the ion cyclotron range of frequencies in L-4 and ACT-1

    International Nuclear Information System (INIS)

    Ono, Masayuki.

    1993-05-01

    Electrostatic waves in the ion cyclotron range of frequencies (ICRF) were studied in the Princeton L-4 and ACT-1 devices for approximately ten years, from 1975 to 1985. The investigation began in the L-4 linear device, looking for the parametric excitation of electrostatic ion cyclotron waves in multi-ion-species plasmas. In addition, this investigation verified multi-ion-species effects on the electrostatic ion cyclotron wave dispersion religion including the ion-ion hybrid resonance. Finite-Larmor-radius modification of the wave dispersion relation was also observed, even for ion temperatures of T i ∼ 1/40 eV. Taking advantage of the relatively high field and long device length of L-4, the existence of the cold electrostatic ion cyclotron wave (CES ICW) was verified. With the arrival of the ACT-1 toroidal device, finite-Larmor-radius (FLR) waves were studied in a relatively collisionless warm-ion hydrogen plasma. Detailed investigations of ion Bernstein waves (IBW) included the verification of mode-transformation in their launching, their wave propagation characteristics, their absorption, and the resulting ion heating. This basic physics activity played a crucial role in developing a new reactor heating concept termed ion Bernstein wave heating. Experimental research in the lower hybrid frequency range confirmed the existence of FLR effects near the lower hybrid resonance, predicted by Stix in 1965. In a neon plasma with a carefully placed phased wave exciter, the neutralized ion Bernstein wave was observed for the first time. Using a fastwave ICRF antenna, two parasitic excitation processes for IBW -- parametric instability and density-gradient-driven excitation -- were also discovered. In the concluding section of this paper, a possible application of externally launched electrostatic waves is suggested for helium ash removal from fusion reactor plasmas

  19. Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

    Directory of Open Access Journals (Sweden)

    Tag-Adeen M

    2017-10-01

    Full Text Available Mohammed Tag-Adeen,1,2 Ahlam Mohamed Sabra,1 Yuko Akazawa,2 Ken Ohnita,2 Kazuhiko Nakao2 1Department of Internal Medicine, Qena School of Medicine, South Valley University, Qena, Egypt; 2Department of Gastroenterology and Hepatology, Nagasaki School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan Background: Liver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 predominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM improvement after successful HCV eradication.Patients and methods: The study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA treatment and after achieving sustained virologic response-24 (SVR-24. Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR. LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4, p-value <0.05 was statistically significant.Results: Following DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%, mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m2. Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of −5.8 occurred in F4 versus −2.79, −1.28 and +0.08 in F3, F2 and F0–F1 respectively (p<0.0001. At baseline, 41 patients were in the F4 group; only 16 (39% regressed to non-cirrhotic range (<12.5 kPa, while 25 (61% were still cirrhotic despite achieving SVR-24 (p<0.0001. Patients who achieved LSM improvement (n=64 have had significantly higher baseline aspartate transferase (AST and alanine transaminase (ALT. Also, those patients showed significant improvement in AST, AST/platelets ratio index

  20. Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea.

    Science.gov (United States)

    Takeda-Nakazawa, Hiroko; Harada, Narinobu; Shen, Jing; Kubo, Nobuo; Zenner, Hans-Peter; Yamashita, Toshio

    2007-08-01

    Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca2+-free solution. L-NG-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca2+ concentrations ([Ca2+]i) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca2+ response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca2+]i increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca2+ response via the NO-cGMP-PKG pathway by a feedback mechanism.

  1. The unity of Luke-Acts

    Directory of Open Access Journals (Sweden)

    J. Verheyden

    1999-12-01

    Full Text Available The article contains a summary of contributions delivered at he 47th Colloquium Biblicum Lovaniense (1998 held at the Catholic University, Leuven on the subject: "The unity of Luke-Acts". The opening address was delivered by J Verheyden (Leuven on "The Unity of Luke and Acts: What are we up to?". The contributors were: J Kremer (Vienna - "Die dreifache Wiedergabe des Damaskuserlebnis Pauli in der Apostelgeschichte: Eine Hilfe für das rechte Verständnis der lukanischen Osterevangelien"; D Marguerat (Lausanne -"Jusqu' où faut-il parler d'une "unité". Luc-Actes? Continuity et ruptures dans I'ævre de Luc"; JDelobel (Leuven - "The text of Luke-Acts: A confrontation of recent theories"; R L Brawley (Chicago - "Abrahamic covenant traditions and the characterization of God in Luke-Acts"; F W Horn (Mainz - "Die Haltung des Lukas zum römischen Staat im Evangelium und in der Apostelgeschichte"; J A Fitzmyer (Washington - "The role of theSpirit in Luke-Acts"; M Rese (Munster - "The Jews in Luke-Acts: Some secondthoughts"; J Taylor (Jerusalem - "La fraction du pain en Luc-Actes"; W Radl (Augs-burg - "Die Beziehungen der Vorgeschichte zur Apostelgeschichte, dargestellt an Lk 2:22-39; F Neirynck (Leuven - "Luke 4:16-30 and the unity of Luke-Acts"; C M Tuckett (Oxford - "The Christology of Luke-Acts"; O Mainville (Montreal - "Le messianisme de Jésus: Le rapport announce/accomplissement entre Lc 1,35 et Ac 2,33"; A Lindemann (Bethel-Bielefeld - "Form und Funktion von Reden und Wundererzählungen im Lukas-evangelium und in der Apostelgeschichte", A Denaux - The theme of divine visits and human (inhospitability in Luke-Acts and its Old Testament and Graeco-Roman antecedents.

  2. 29 CFR 97.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD of the Act); and (v) Medical Assistance... section 1903(a)(6)(B). (4) Entitlement grants under the following programs of The National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of the Act), (iii...

  3. 24 CFR 85.4 - Applicability.

    Science.gov (United States)

    2010-04-01

    ... the Aged, Blind, and Disabled (titles I, X, XIV, and XVI-AABD of the Act); and (v) Medical Assistance... section 1903(a)(6)(B). (4) Entitlement grants under the following programs of The National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of the Act), (iii...

  4. Image denoising via adaptive eigenvectors of graph Laplacian

    Science.gov (United States)

    Chen, Ying; Tang, Yibin; Xu, Ning; Zhou, Lin; Zhao, Li

    2016-07-01

    An image denoising method via adaptive eigenvectors of graph Laplacian (EGL) is proposed. Unlike the trivial parameter setting of the used eigenvectors in the traditional EGL method, in our method, the eigenvectors are adaptively selected in the whole denoising procedure. In detail, a rough image is first built with the eigenvectors from the noisy image, where the eigenvectors are selected by using the deviation estimation of the clean image. Subsequently, a guided image is effectively restored with a weighted average of the noisy and rough images. In this operation, the average coefficient is adaptively obtained to set the deviation of the guided image to approximately that of the clean image. Finally, the denoised image is achieved by a group-sparse model with the pattern from the guided image, where the eigenvectors are chosen in the error control of the noise deviation. Moreover, a modified group orthogonal matching pursuit algorithm is developed to efficiently solve the above group sparse model. The experiments show that our method not only improves the practicality of the EGL methods with the dependence reduction of the parameter setting, but also can outperform some well-developed denoising methods, especially for noise with large deviations.

  5. Sensitivity difference between anterior and posterior lobes of rat cerebellum to prenatal exposure to 2.5 Gy X-irradiation. A histological study

    International Nuclear Information System (INIS)

    Darmanto, W.; Hayasaka, Shizu; Takagishi, Yoshiko; Aolad, H.M.; Inouye, Minoru

    1997-01-01

    We investigated the histological differences in abnormality between anterior lobes (vermian lobules II, III and culmen IV, V) and posterior lobes (lobules IX, X) of the rat cerebellum following prenatal exposure to X-irradiation. Pregnant rats were exposed to 2.5 Gy X-irradiation at gestation day-21 (GD-21), and pups were sacrificed from birth through 15 days of age. Their cerebella were examined histologically and immunohistochemically for glial fibrillary acidic protein in Bergmann fibers. Extensive cell death was found in the external granular layer (EGL) of the cerebellum on the day of birth. In the anterior lobes, the number of cell deaths was higher than in the posterior lobes. During 5 days after birth, the recovery of EGL was earlier in the posterior lobes than in the anterior lobes. Seven days after birth, Bergmann fibers were more irregular in the anterior lobes than in the posterior lobes. The number of Purkinje cells in ectopic locations was higher in the anterior lobes than in the posterior lobes. The EGL and migrating Purkinje cells showed different responses to X-irradiation in the anterior than in the posterior lobes of the cerebellum. (author)

  6. Act of 4 August 1955 concerning State Security in the Nuclear Field

    International Nuclear Information System (INIS)

    1955-01-01

    This Act governing State security in the nuclear field lays down that the King may determine the security measures to be complied with concerning nuclear research, materials, methods of production used by establishments and legal or physical persons having in their possession information, documents or material obtained either directly from the Government or with its consent. The Act was supplemented by Royal Order of 14 March 1956 which amplified its provisions by laying down specific requirements regarding the classification of information and material, the security measures to be applied thereto, and to establishments involved in related research work. It also provides for the security clearance to be applied to persons who shall be authorised to obtain such information and classified material. A Royal Order of 18 October 1974 amends this Order in respect of the authorities responsible for its implementation. (NEA) [fr

  7. Some Thoughts on the Equal Pay Act and Coaching Salaries.

    Science.gov (United States)

    Boring, Phyllis

    This paper discusses the Equal Pay Act, Title VII of the Civil Rights Act of 1964, as it applies to women athletic coaches and physical education teachers. The following points are considered: (1) application of the Equal Pay Act; (2) advantage of voluntary compliance with the Equal Pay Act; (3) factors used to measure "equal work"; (4)…

  8. A dual-specificity isoform of the protein kinase inhibitor PKI produced by alternate gene splicing.

    Science.gov (United States)

    Kumar, Priyadarsini; Walsh, Donal A

    2002-03-15

    We have previously shown that the protein kinase inhibitor beta (PKIbeta) form of the cAMP-dependent protein kinase inhibitor exists in multiple isoforms, some of which are specific inhibitors of the cAMP-dependent protein kinase, whereas others also inhibit the cGMP-dependent enzyme [Kumar, Van Patten and Walsh (1997), J. Biol. Chem. 272, 20011-20020]. We have now demonstrated that the switch from a cAMP-dependent protein kinase (PKA)-specific inhibitor to one with dual specificity arises as a consequence of alternate gene splicing. We have confirmed using bacterially produced pure protein that a single inhibitor species has dual specificity for both PKA and cGMP-dependent protein kinase (PKG), inhibiting each with very high and closely similar inhibitory potencies. The gene splicing converted a protein with 70 amino acids into one of 109 amino acids, and did not change the inhibitory potency to PKA, but changed it from a protein that had no detectable PKG inhibitory activity to one that now inhibited PKG in the nanomolar range.

  9. The supplementation of low-P diets with microbial 6-phytase expressed in Aspergillus oryzae improves P digestibility in sows.

    Science.gov (United States)

    Torrallardona, D; Llauradó, L; Broz, J

    2012-12-01

    Two trials were conducted to evaluate a novel microbial 6-phytase expressed in Aspergillus oryzae (Ronozyme HiPhos; DSM Nutritional Products, Basel, Switzerland) in gestating and lactating sows. In the first trial, 24 sows (Duroc × Landrace; 223 kg BW) were offered, at 16 d of gestation, a low-P control diet (formulated to provide 4.0 g total P/kg; 1.5 g digestible P/kg) supplemented with 0, 500, or 1000 phytase activity (FYT)/kg of phytase. Two weeks later, fresh feces were sampled from all sows and the apparent total tract digestibility of P was measured using TiO(2) as indigestible marker. Phytase supplementation did not (P > 0.10) affect the total tract digestibility of P but reduced (P phytase. After 2 wk, fresh feces were sampled from all sows and the apparent total tract digestibility of P was measured using TiO(2) as indigestible marker. Phytase supplementation improved (P phytase tested increased the apparent total tract digestibility of P in sows and reduced P excretion in feces.

  10. Atomic Energy Commission Act, 2000 (Act 588)

    International Nuclear Information System (INIS)

    2000-01-01

    Act 588 of the Republic of Ghana entitled, Atomic Energy Commission Act, 2000, amends and consolidates the Atomic Energy Commission Act, 204 of 1963 relating to the establishment of the Atomic Energy Commission. Act 588 makes provision for the Ghana Atomic Energy Commission to establish more institutes for the purpose of research in furtherance of its functions and also promote the commercialization of its research and development results. (E.A.A.)

  11. 29 CFR 1614.408 - Civil action: Equal Pay Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Civil action: Equal Pay Act. 1614.408 Section 1614.408... EQUAL EMPLOYMENT OPPORTUNITY Appeals and Civil Actions § 1614.408 Civil action: Equal Pay Act. A..., three years of the date of the alleged violation of the Equal Pay Act regardless of whether he or she...

  12. 78 FR 16611 - Freedom of Information Act; Correction

    Science.gov (United States)

    2013-03-18

    ... FEDERAL TRADE COMMISSION 16 CFR Part 4 Freedom of Information Act; Correction AGENCY: Federal Trade Commission. ACTION: Final rule; correction. SUMMARY: The Federal Trade Commission published a... instruction in our final rule entitled ``Freedom of Information Act'' published February 28, 2013 (78 FR 13472...

  13. Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme.

    Science.gov (United States)

    Tucker, A S; Al Khamis, A; Sharpe, P T

    1998-08-01

    Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions. Bmp4 has been identified as a candidate signalling molecule in these interactions, initially as an epithelial signal and then later at the bud stage as a mesenchymal signal (Vainio et al. [1993] Cell 75:45-58). A target gene for Bmp4 signalling is the homeobox gene Msx-1, identified by the ability of recombinant Bmp4 protein to induce expression in mesenchyme. There is, however, no evidence that Bmp4 is the endogenous inducer of Msx-1 expression. Msx-1 and Bmp-4 show dynamic, interactive patterns of expression in oral epithelium and ectomesenchyme during the early stages of tooth development. In this study, we compare the temporal and spatial expression of these two genes to determine whether the changing expression patterns of these genes are consistent with interactions between the two molecules. We show that changes in Bmp-4 expression precede changes in Msx-1 expression. At embryonic day (E)10.5-E11.0, expression patterns are consistent with BMP4 from the epithelium, inducing or maintaining Msx-1 in underlying mesenchyme. At E11.5, Bmp-4 expression shifts from epithelium to mesenchyme and is rapidly followed by localised up-regulation of Msx-1 expression at the sites of Bmp-4 expression. Using cultured explants of developing mandibles, we confirm that exogenous BMP4 is capable of replacing the endogenous source in epithelium and inducing Msx-1 gene expression in mesenchyme. By using noggin, a BMP inhibitor, we show that endogenous Msx-1 expression can be inhibited at E10.5 and E11.5, providing the first evidence that endogenous Bmp-4 from the epithelium is responsible for regulating the early spatial expression of Msx-1. We also show that the mesenchymal shift in Bmp-4 is responsible for up-regulating Msx-1 specifically at the sites of future tooth formation. Thus, we establish that a reciprocal series of interactions act to restrict expression of both genes to future

  14. Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins

    Energy Technology Data Exchange (ETDEWEB)

    Hu Ting; Gibson, David P.; Carr, Gregory J.; Torontali, Suzanne M.; Tiesman, Jay P.; Chaney, Joel G.; Aardema, Marilyn J

    2004-05-18

    During the safety evaluation process of new drugs and chemicals, a battery of genotoxicity tests is conducted starting with in vitro genotoxicity assays. Obtaining positive results in in vitro genotoxicity tests is not uncommon. Follow-up studies to determine the biological relevance of positive genotoxicity results are costly, time consuming, and utilize animals. More efficient methods, especially for identifying a putative mode of action like an indirect mechanism of genotoxicity (where DNA molecules are not the initial primary targets), would greatly improve the risk assessment for genotoxins. To this end, we are participating in an International Life Sciences Institute (ILSI) project involving studies of gene expression changes caused by model genotoxins. The purpose of the work is to evaluate gene expression tools in general, and specifically for discriminating genotoxins that are direct-acting from indirect-acting. Our lab has evaluated gene expression changes as well as micronuclei (MN) in L5178Y TK{sup +/-} mouse lymphoma cells treated with six compounds. Direct-acting genotoxins (where DNA is the initial primary target) that were evaluated included the DNA crosslinking agents, mitomycin C (MMC) and cisplatin (CIS), and an alkylating agent, methyl methanesulfonate (MMS). Indirect-acting genotoxins included hydroxyurea (HU), a ribonucleotide reductase inhibitor, taxol (TXL), a microtubule inhibitor, and etoposide (ETOP), a DNA topoisomerase II inhibitor. Microarray gene expression analysis was conducted using Affymetrix mouse oligonucleotide arrays on RNA samples derived from cells which were harvested immediately after the 4 h chemical treatment, and 20 h after the 4 h chemical treatment. The evaluation of these experimental results yields evidence of differentially regulated genes at both 4 and 24 h time points that appear to have discriminating power for direct versus indirect genotoxins, and therefore may serve as a fingerprint for classifying chemicals

  15. The Creating Hope Act: what is old is new again

    Directory of Open Access Journals (Sweden)

    Tolbert JA

    2014-06-01

    Full Text Available Jaszianne A Tolbert,1,2 Jennifer L Goldman,2-4 Ralph E Kauffman,2,4 Susan M Abdel-Rahman2,41Division of Hematology/Oncology, 2Division of Clinical Pharmacology and Therapeutic Innovation, 3Division of Infectious Diseases, Children's Mercy Hospital, Kansas City, MO, USA; 4Department of Pediatrics, University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USAAbstract: The Creating Hope Act, passed as part of the Food and Drug Administration Safety and Innovation Act of 2012, is among the newest laws intended to foster drug development for rare and neglected diseases in children. The act expands the priority review voucher incentive that first appeared in the Food and Drug Administration Amendments Act of 2007 and was intended to stimulate the development of products for the prevention and treatment of tropical diseases. Notably, legislative and regulatory initiatives aimed at enhancing drug development both for use in children and for rare diseases have intermittently emerged over the past 3 decades. This manuscript provides an overview of related legislation that has preceded the Creating Hope Act and examines the potential impact of the new act in the context of the outcomes that have been observed with the earlier initiatives.Keywords: orphan drug, rare disease, pediatric, drug development, priority review voucher

  16. 29 CFR 1620.1 - Basic applicability of the Equal Pay Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Basic applicability of the Equal Pay Act. 1620.1 Section 1620.1 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.1 Basic applicability of the Equal Pay Act. (a) Since the Equal Pay Act, 29 U.S.C...

  17. X-ray-induced cell death by apoptosis in the immature rat cerebellum

    International Nuclear Information System (INIS)

    Harmon, B.V.; Allan, D.J.

    1988-01-01

    The cells of the external granular layer (EGL) of the developing cerebellum are known to be particularly sensitive to radiation. In the past, changes induced in this layer by irradiation have been referred to by non-specific terms such as pyknotic cells and the mode of cell death has been assumed to be necrosis. However, in published light micrographs of these dying cells, the appearance is suggestive of apoptosis, a distinctive mode of cell death which occurs spontaneously in normal adult and embryonic tissues and can also be triggered by certain pathological stimuli. This light and transmission electron microscopic study of control and irradiated (7 h post-irradiation) rat cerebellum from 18 day fetuses and 5 day-old neonates showed that the cell death was effected by apoptosis. The apoptosis was markedly enhanced by x-irradiation and quantification of the cell death in the EGL of 5 day-old rats exposed to 4, 8, 25, 100, and 400 cGy x-irradiation demonstrated that there was a positive dose response relationship. The extent of cell death by apoptosis which was 0.2% in control, ranged from 0.8% after 4 cGy to 62.3% after 400 cGy x-irradiation. The recognition that cell death by apoptosis can be a major component of x-irradiation damage has important implications for radiobiological studies

  18. Ponjat, prinjat, avtomatizirovat / Liza Denissova, Georgi Zhukovskas, Peteris Zirneklis

    Index Scriptorium Estoniae

    Denissova, Liza

    2003-01-01

    Enterprise Resource Planning (ERP) - ettevõtte ressursside planeerimissüsteem aitab tõsta Baltimaade ettevõtete konkurentsivõimet. Kommenteerivad Rolands Vetsvanags, Egle Bulotiene ja Jüri Kaljundi

  19. Cell culture compositions

    Science.gov (United States)

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yiao, Jian

    2014-03-18

    The present invention provides a novel endoglucanase nucleic acid sequence, designated egl6 (SEQ ID NO:1 encodes the full length endoglucanase; SEQ ID NO:4 encodes the mature form), and the corresponding endoglucanase VI amino acid sequence ("EGVI"; SEQ ID NO:3 is the signal sequence; SEQ ID NO:2 is the mature sequence). The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVI, recombinant EGVI proteins and methods for producing the same.

  20. Treatment-completion rates with olanzapine long-acting injection versus risperidone long-acting injection in a 12-month, open-label treatment of schizophrenia: indirect, exploratory comparisons

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2012-05-01

    Full Text Available Haya Ascher-Svanum1, William S Montgomery2, David P McDonnell3, Kristina A Coleman4, Peter D Feldman11Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly Australia Pty Ltd, West Ryde, New South Wales, Australia; 3Eli Lilly and Company, Cork, Ireland; 4OptumInsight, Lilyfield, New South Wales, AustraliaBackground: Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia.Methods: Indirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication's effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a “sensitivity analysis,” using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates.Results: Comparison of olanzapine long-acting injection data (931 patients with the pooled data from the nine

  1. Atomic Act amended

    International Nuclear Information System (INIS)

    Drabova, D.

    2002-01-01

    In the paper by the chairwoman of the Czech nuclear regulatory authority, the history of Czech nuclear legislation is outlined, the reasons for the amendment of the Atomic Act (Act No. 18/1997) are explained, and the amendments themselves are highlighted. The Act No. 13/2002 of 18 December 2001 is reproduced from the official Collection of Acts of the Czech Republic in the facsimile form. The following acts were thereby amended: Atomic Act No. 18/1997, Metrology Act No. 505/1990, Public Health Protection Act No. 258/2000, and Act No. 2/1969 on the Establishment of Ministries and Other Governmental Agencies of the Czech Republic. (P.A.)

  2. Intervention pursuant to article 4(h) of the Constitutive Act of the African Union without United Nations Security Council authorisation

    OpenAIRE

    Amvane, Gabriel

    2015-01-01

    Article 4(h) of the Constitutive Act of the African Union (AU) establishes the right of the Union to intervene in a member state to prevent grave violations of human rights. It does not state whether the AU should request prior authorisation from the United Nations (UN) Security Council, leading to many interpretations. Many articles were written on this issue at a time when the AU and the Security Council were not in confrontation. However, the situation has changed since the controversy ove...

  3. 75 FR 63703 - Privacy Act of 1974; Privacy Act Regulation

    Science.gov (United States)

    2010-10-18

    ... FEDERAL RESERVE SYSTEM 12 CFR Part 261a [Docket No. R-1313] Privacy Act of 1974; Privacy Act... implementing the Privacy Act of 1974 (Privacy Act). The primary changes concern the waiver of copying fees... records under the Privacy Act; the amendment of special procedures for the release of medical records to...

  4. Privacy Act

    Science.gov (United States)

    Learn about the Privacy Act of 1974, the Electronic Government Act of 2002, the Federal Information Security Management Act, and other information about the Environmental Protection Agency maintains its records.

  5. ACTS 2014

    DEFF Research Database (Denmark)

    Co-curator of ACTS 2014 together with Rasmus Holmboe, Judith Schwarzbart and Sanne Kofoed. ACTS is the Museum of Contemporary Art’s international bi-annual festival. ACTS was established in 2011 and, while the primary focus is on sound and performance art, it also looks toward socially oriented art....... For the 2014 festival, the museum has entered into a collaboration with the Department for Performance Design at Roskilde University – with continued focus on sound and performance art, and social art in public spaces. With ACTS, art moves out of its usual exhibition space and instead utilizes the city, its...... various possibilities and public spaces as a stage. ACTS takes place in and around the museum and diverse locations in Roskilde city. ACTS is partly curated by the museum staff and partly by guest curators. ACTS 2014 is supported by Nordea-fonden and is a part of the project The Museum goes downtown....

  6. Nuclear Regulatory Authority Act, 2015 (Act 895)

    International Nuclear Information System (INIS)

    2015-04-01

    An Act to establish a Nuclear Regulatory Authority in Ghana. This Act provides for the regulation and management of activities and practices for the peaceful use of nuclear material or energy, and to provide for the protection of persons and the environment against the harmful effects of radiation; and to ensure the effective implementation of the country’s international obligations and for related matters. This Act replaced the Radiation Protection Instrument, of 1993 (LI 1559).

  7. 75 FR 31440 - Privacy Act of 1974; Report of a New System of Records

    Science.gov (United States)

    2010-06-03

    ... Information Security Management Act of 2002; the Computer Fraud and Abuse Act of 1986; the E-Government Act of... Information Security Management Act of 2002; the Computer Fraud and Abuse Act of 1986; the E-Government Act of... by State law, or its fiscal agent; (3) support litigation involving the Department; (4) combat fraud...

  8. 39 CFR 4.4 - Deputy Postmaster General.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Deputy Postmaster General. 4.4 Section 4.4 Postal... described at 39 U.S.C. 202(d), 203. The Deputy Postmaster General shall act as Postmaster General during the.... The Governors set the compensation and benefits of the Deputy Postmaster General, subject to 39 U.S.C...

  9. Jauna tehniskā lignīna degradācijas produktu pētīšana

    OpenAIRE

    Ponomarenko, Jevgenija

    2006-01-01

    Darbā ir veikta parastās egles (Picea abies) koksnes lignīnu analīze, kas ir iegūti Zviedrijas Lundas Universitātes bioetanola ražošanas pilotiekārtā kā cieti atlikumi dažādās procesa stadijās. Salīdzināšanai ir izmantots egles koksnes Bjorkmana lignīns. Lignīnu pētīšanai ir izmantotas oksidatīvas degradācijas un analītiskās pirolīzes metodes. Produktu sadalīšanai un identifikācijai ir izmantotas gāzes hromatogrāfijas un masspektrometrijas metodes. Nitrobenzola oksidēšanas rezultātā kā galven...

  10. Phosphorus status and microbial community of paddy soil with the growth of annual ryegrass (Lolium multiflorum Lam.) under different phosphorus fertilizer treatments*

    Science.gov (United States)

    Guo, Hai-chao; Wang, Guang-huo

    2009-01-01

    Annual ryegrass (Lolium multiflorum Lam.) was grown in paddy soil in pots under different phosphorus (P) fertilizer treatments to investigate changes of P fractions and microbial community of the soil. The treatments included Kunyang phosphate rock (KPR) applications at 50 mg P/kg (KPR50) and 250 mg P/kg (KPR250), mono-calcium phosphate (MCP) application at 50 mg P/kg (MCP50), and the control without P application. The results showed that KPR50, KPR250, and MCP50 applications significantly increased the dry weight of the ryegrass by 13%, 38%, and 55%, and increased P uptake by 19%, 135%, and 324%, respectively. Compared with MCP50, the relative effectiveness of KPR50 and KPR250 treatments in ryegrass production was about 23% and 68%, respectively. After one season of ryegrass growth, the KPR50, KPR250, and MCP50 applications increased soil-available P by 13.4%, 26.8%, and 55.2%, respectively. More than 80% of the applied KPR-P remained as HCl-P fraction in the soil. Phospholipid fatty acid (PLFA) analysis showed that the total and bacterial PLFAs were significantly higher in the soils with KPR250 and MCP50 treatments compared with KPR50 and control. The latter had no significant difference in the total or bacterial PLFAs. The KPR50, KPR250, and MCP50 treatments increased fungal PLFA by 69%, 103%, and 69%, respectively. Both the principal component analysis and the cluster analysis of the PLFA data suggest that P treatments altered the microbial community composition of the soils, and that P availability might be an important contributor to the changes in the microbial community structure during the ryegrass growth in the paddy soils. PMID:19817001

  11. 50 CFR 82.4 - Authority.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Authority. 82.4 Section 82.4 Wildlife and... PROTECTION ACT OF 1972) Introduction § 82.4 Authority. The Secretary of the Interior has delegated to the Director, Fish and Wildlife Service, his authority under the Marine Mammal Protection Act to enter into...

  12. 75 FR 33355 - Sunshine Act Meeting

    Science.gov (United States)

    2010-06-11

    .... 2. Consider and act on revisions to the LSC Accounting Guide for LSC Recipients. 3. Public comment.... Batie, Corporate Secretary. [FR Doc. 2010-14171 Filed 6-9-10; 4:15 pm] BILLING CODE 7050-01-P ...

  13. 78 FR 64885 - Freedom of Information Act (FOIA); Miscellaneous Rules Redelegation of Authority To Determine...

    Science.gov (United States)

    2013-10-30

    ... FEDERAL TRADE COMMISSION 16 CFR Part 4 Freedom of Information Act (FOIA); Miscellaneous Rules... redelegate his or her authority to determine appeals related to the Freedom of Information Act (``FOIA... in 16 CFR Part 4 Administrative practice and procedure, Freedom of Information Act. For the reasons...

  14. 45 CFR 2508.3 - What is the Corporation's Privacy Act policy?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false What is the Corporation's Privacy Act policy? 2508... NATIONAL AND COMMUNITY SERVICE IMPLEMENTATION OF THE PRIVACY ACT OF 1974 § 2508.3 What is the Corporation's Privacy Act policy? It is the policy of the Corporation to protect, preserve, and defend the right of...

  15. Polititshesko-poetitsheskoje iskusstvo prinadlezhit narodu / Ilja Sundelevitsh

    Index Scriptorium Estoniae

    Sundelevitsh, Ilja

    2007-01-01

    Tallinna 14. graafikatriennaalist "Poliitiline/poeetiline" Kumus ja Tallinna Kunstihoones. Kuraator Anders Härm. Eelmise triennaali võitja Egle Kuckaite isikunäitus Tallinna Linnagaleriis. Triennaali peaauhinna sai kolumbia kunstnik Oscar Munos

  16. 36 CFR 1207.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ...); (iii) Foster Care and Adoption Assistance (title IV-E of the Act); (iv) Aid to the Aged, Blind, and...). (4) Entitlement grants under the following programs of The National School Lunch Act: (i) School... The Child Nutrition Act of 1966: (i) Special Milk (section 3 of the Act), and (ii) School Breakfast...

  17. 32 CFR 33.4 - Applicability.

    Science.gov (United States)

    2010-07-01

    ...); (iii) Foster Care and Adoption Assistance (title IV-E of the Act); (iv) Aid to the Aged, Blind, and...). (4) Entitlement grants under the following programs of The National School Lunch Act: (i) School... The Child Nutrition Act of 1966: (i) Special Milk (section 3 of the Act), and (ii) School Breakfast...

  18. 29 CFR 1977.4 - Persons prohibited from discriminating.

    Science.gov (United States)

    2010-07-01

    ... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 General § 1977.4 Persons prohibited from discriminating. Section 11....4 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... employee” because the employee has exercised rights under the Act. Section 3(4) of the Act defines “person...

  19. Phosphodiesterase inhibitor KMUP-3 displays cardioprotection via protein kinase G and increases cardiac output via G-protein-coupled receptor agonist activity and Ca2+ sensitization

    Directory of Open Access Journals (Sweden)

    Chung-Pin Liu

    2016-02-01

    Full Text Available KMUP-3 (7-{2-[4-(4-nitrobenzene piperazinyl]ethyl}-1, 3-dimethylxanthine displays cardioprotection and increases cardiac output, and is suggested to increase cardiac performance and improve myocardial infarction. To determine whether KMUP-3 improves outcomes in hypoperfused myocardium by inducing Ca2+ sensitization to oppose protein kinase (PKG-mediated Ca2+ blockade, we measured left ventricular systolic blood pressure, maximal rates of pressure development, mean arterial pressure and heart rate in rats, and measured contractility and expression of PKs/RhoA/Rho kinase (ROCKII in beating guinea pig left atria. Hemodynamic changes induced by KMUP-3 (0.5–3.0 mg/kg, intravenously were inhibited by Y27632 [(R-(+-trans-4-1-aminoethyl-N-(4-Pyridyl cyclohexane carboxamide] and ketanserin (1 mg/kg, intravenously. In electrically stimulated left guinea pig atria, positive inotropy induced by KMUP-3 (0.1–100μM was inhibited by the endothelial NO synthase (eNOS inhibitors N-nitro-l-arginine methyl ester (L-NAME and 7-nitroindazole, cyclic AMP antagonist SQ22536 [9-(terahydro-2-furanyl-9H-purin-6-amine], soluble guanylyl cyclase (sGC antagonist ODQ (1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one, RhoA inhibitor C3 exoenzyme, β-blocker propranolol, 5-hydroxytryptamine 2A antagonist ketanserin, ROCK inhibitor Y27632 and KMUP-1 (7-{2-[4-(2-chlorobenzene piperazinyl]ethyl}-1, 3-dimethylxanthine at 10μM. Western blotting assays indicated that KMUP-3 (0.1–10μM increased PKA, RhoA/ROCKII, and PKC translocation and CIP-17 (an endogenous 17-kDa inhibitory protein activation. In spontaneous right atria, KMUP-3 induced negative chronotropy that was blunted by 7-nitroindazole and atropine. In neonatal myocytes, L-NAME inhibited KMUP-3-induced eNOS phosphorylation and RhoA/ROCK activation. In H9c2 cells, Y-27632 (50μM and PKG antagonist KT5823 [2,3,9,10,11,12-hexahydro-10R- methoxy-2,9-dimethyl-1-oxo-9S,12R-epoxy-1H-diindolo(1,2,3-fg:3′,2′,1

  20. 44 CFR 59.4 - References.

    Science.gov (United States)

    2010-10-01

    ...) Housing and Urban Development Act of 1969 (Pub. L. 91-152, approved December 24, 1969). (3) Flood Disaster... of the Disaster Relief Act of 1974 (Pub. L. 93-288). (4) Coastal Zone Management Act (Pub. L. 92-583... these regulations are issued: (1) National Flood Insurance Act of 1968 (title XIII of the Housing and...

  1. 13 CFR 107.115 - 1940 Act and 1980 Act Companies.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false 1940 Act and 1980 Act Companies. 107.115 Section 107.115 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... Companies. A 1940 Act or 1980 Act Company is eligible to apply for an SBIC license, and an existing Licensee...

  2. Identification of a soluble guanylate cyclase in RBCs: preserved activity in patients with coronary artery disease.

    Science.gov (United States)

    Cortese-Krott, Miriam M; Mergia, Evanthia; Kramer, Christian M; Lückstädt, Wiebke; Yang, Jiangning; Wolff, Georg; Panknin, Christina; Bracht, Thilo; Sitek, Barbara; Pernow, John; Stasch, Johannes-Peter; Feelisch, Martin; Koesling, Doris; Kelm, Malte

    2018-04-01

    Endothelial dysfunction is associated with decreased NO bioavailability and impaired activation of the NO receptor soluble guanylate cyclase (sGC) in the vasculature and in platelets. Red blood cells (RBCs) are known to produce NO under hypoxic and normoxic conditions; however evidence of expression and/or activity of sGC and downstream signaling pathway including phopshodiesterase (PDE)-5 and protein kinase G (PKG) in RBCs is still controversial. In the present study, we aimed to investigate whether RBCs carry a functional sGC signaling pathway and to address whether this pathway is compromised in coronary artery disease (CAD). Using two independent chromatographic procedures, we here demonstrate that human and murine RBCs carry a catalytically active α 1 β 1 -sGC (isoform 1), which converts 32 P-GTP into 32 P-cGMP, as well as PDE5 and PKG. Specific sGC stimulation by NO+BAY 41-2272 increases intracellular cGMP-levels up to 1000-fold with concomitant activation of the canonical PKG/VASP-signaling pathway. This response to NO is blunted in α1-sGC knockout (KO) RBCs, but fully preserved in α2-sGC KO. In patients with stable CAD and endothelial dysfunction red cell eNOS expression is decreased as compared to aged-matched controls; by contrast, red cell sGC expression/activity and responsiveness to NO are fully preserved, although sGC oxidation is increased in both groups. Collectively, our data demonstrate that an intact sGC/PDE5/PKG-dependent signaling pathway exists in RBCs, which remains fully responsive to NO and sGC stimulators/activators in patients with endothelial dysfunction. Targeting this pathway may be helpful in diseases with NO deficiency in the microcirculation like sickle cell anemia, pulmonary hypertension, and heart failure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Protective effects of phosphodiesterase 2 inhibitor on depression- and anxiety-like behaviors: involvement of antioxidant and anti-apoptotic mechanisms.

    Science.gov (United States)

    Ding, Lianshu; Zhang, Chong; Masood, Anbrin; Li, Jianxin; Sun, Jiao; Nadeem, Ahmed; Zhang, Han-Ting; O' Donnell, James M; Xu, Ying

    2014-07-15

    Stress occurs in everyday life, but the relationship between stress and the onset or development of depression/anxiety remains unknown. Increasing evidence suggests that the impairment of antioxidant defense and the neuronal cell death are important in the process of emotional disorders. Chronic stress impairs the homeostasis of antioxidants/oxidation, which results in the aberrant stimulation of the cell cycle proteins where cGMP-PKG signaling is thought to have an inhibitory role. Phosphodiesterase 2 (PDE2) is linked to cGMP-PKG signaling and highly expressed in the limbic brain regions including hippocampus and amygdala, which may play important roles in the treatment of depression and anxiety. To address the possible effects of PDE2 inhibitors on depression-/anxiety-like behaviors and the underlying mechanisms, Bay 60-7550 (0.75, 1.5 and 3 mg/kg, i.p.) was administered 30 min before chronic stress. The results suggested that Bay 60-7550 not only restored the behavioral changes but also regulated Cu/Zn superoxide dismutase (SOD) levels differentially in hippocampus and amygdala, which were increased in the hippocampus while decreased in the amygdala. It was also significant that Bay 60-7550 regulated the abnormalities of pro- and anti-apoptotic components, such as Bax, Caspase 3 and Bcl-2, and the indicator of PKG signaling characterized by pVASP(ser239), in these two brain regions. The results suggested that Bay 60-7550 is able to alleviate oxidative stress and mediate part of the apoptotic machinery in neuronal cells possibly through SOD-cGMP/PKG-anti-apoptosis signaling and that inhibition of PDE2 may represent a novel therapeutic target for psychiatric disorders, such as depression and anxiety. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Gamma-radiation produces abnormal Bergmann fibers and ectopic granule cells in mouse cerebellar cortex

    International Nuclear Information System (INIS)

    Inouye, Minoru; Hayasaka, Shizu; Funahashi, Atsushi; Yamamura, Hideki

    1992-01-01

    Morphological changes in Bergmann glial fibers in the developing cerebellar cortex produced by exposure to gamma-rays were investigated in association with ectopic granule cells. Six-day-old mice that had been exposed to 3 Gy of gamma-radiation were killed 6 hours after exposure or at 7 through 30 days of age. Their cerebella were examined histologically and immunohistochemically for glial fibrillary acidic protein in Bergmann fibers. Extensive cell death took place in the external granular layer (EGL) of the cerebellum from 6 through 24 hours after exposure. This led to the thinning of the EGL and a decrease in the number of migrating cells in the molecular layer. The number of Bergmann cells was not decreased, but the fibers in the molecular layer were distorted; whereas, in the control these fibers were straight and perpendicular to the pial surface. The EGL began to recover 2 days after exposure, and abnormally oriented migrating cells were seen. At 17 days of age, some cell clustering was observed in the molecular layer of the irradiated cerebellum. Distortion of the Bergmann fibers was marked in regions where ectopic granule cells appeared at 30 days of age. These findings suggest that the distortion of Bergmann fibers leads to the production of ectopic granule cells after exposure to gamma-radiation. (author)

  5. Prevalence of Malaria Parasitemia and Purchase of Artemisinin-Based Combination Therapies (ACTs) among Drug Shop Clients in Two Regions in Tanzania with ACT Subsidies

    Science.gov (United States)

    Briggs, Melissa A.; Kalolella, Admirabilis; Bruxvoort, Katia; Wiegand, Ryan; Lopez, Gerard; Festo, Charles; Lyaruu, Pierre; Kenani, Mitya; Abdulla, Salim; Goodman, Catherine; Kachur, S. Patrick

    2014-01-01

    Background Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. Method and Findings A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6–18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was 5 years, experience (aOR: 2.8; 95% CI: 1.2–6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5–7.4). Conclusion Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops. PMID:24732258

  6. 25 CFR 275.4 - Implementing regulations.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Implementing regulations. 275.4 Section 275.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR INDIAN SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT PROGRAM STAFFING § 275.4 Implementing regulations. Regulations to implement section 105 of the Act...

  7. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling.

    Science.gov (United States)

    Wang, Gang; Chen, Ling; Pan, Xiaoyu; Chen, Jiechun; Wang, Liqun; Wang, Weijie; Cheng, Ruochuan; Wu, Fan; Feng, Xiaoqing; Yu, Yingcong; Zhang, Han-Ting; O'Donnell, James M; Xu, Ying

    2016-04-05

    Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling.

  8. 32 CFR 324.4 - Responsibilities.

    Science.gov (United States)

    2010-07-01

    ... Privacy Act Officer. (1) Establishes, issues and updates policy for the DFAS Privacy Act Program and... Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) PRIVACY PROGRAM DFAS PRIVACY ACT PROGRAM General information § 324.4 Responsibilities. (a) Director, DFAS. (1) Ensures...

  9. Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

    Science.gov (United States)

    Hong, Seung-Keun; Cha, Mee-Kyung; Choi, Yong-Soo; Kim, Won-Cheol; Kim, Il-Han

    2002-04-05

    We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.

  10. Formulation of enzyme blends to maximize the hydrolysis of alkaline peroxide pretreated alfalfa hay and barley straw by rumen enzymes and commercial cellulases.

    Science.gov (United States)

    Badhan, Ajay; Wang, Yuxi; Gruninger, Robert; Patton, Donald; Powlowski, Justin; Tsang, Adrian; McAllister, Tim

    2014-04-26

    Efficient conversion of lignocellulosic biomass to fermentable sugars requires the synergistic action of multiple enzymes; consequently enzyme mixtures must be properly formulated for effective hydrolysis. The nature of an optimal enzyme blends depends on the type of pretreatment employed as well the characteristics of the substrate. In this study, statistical experimental design was used to develop mixtures of recombinant glycosyl hydrolases from thermophilic and anaerobic fungi that enhanced the digestion of alkaline peroxide treated alfalfa hay and barley straw by mixed rumen enzymes as well as commercial cellulases (Accelerase 1500, A1500; Accelerase XC, AXC). Combinations of feruloyl and acetyl xylan esterases (FAE1a; AXE16A_ASPNG), endoglucanase GH7 (EGL7A_THITE) and polygalacturonase (PGA28A_ASPNG) with rumen enzymes improved straw digestion. Inclusion of pectinase (PGA28A_ASPNG), endoxylanase (XYN11A_THITE), feruloyl esterase (FAE1a) and β-glucosidase (E-BGLUC) with A1500 or endoglucanase GH7 (EGL7A_THITE) and β-xylosidase (E-BXSRB) with AXC increased glucose release from alfalfa hay. Glucose yield from straw was improved when FAE1a and endoglucanase GH7 (EGL7A_THITE) were added to A1500, while FAE1a and AXE16A_ASPNG enhanced the activity of AXC on straw. Xylose release from alfalfa hay was augmented by supplementing A1500 with E-BGLUC, or AXC with EGL7A_THITE and XYN11A_THITE. Adding arabinofuranosidase (ABF54B_ASPNG) and esterases (AXE16A_ASPNG; AXE16B_ASPNG) to A1500, or FAE1a and AXE16A_ASPNG to AXC enhanced xylose release from barley straw, a response confirmed in a scaled up assay. The efficacy of commercial enzyme mixtures as well as mixed enzymes from the rumen was improved through formulation with synergetic recombinant enzymes. This approach reliably identified supplemental enzymes that enhanced sugar release from alkaline pretreated alfalfa hay and barley straw.

  11. The Apoptosome: Heart and Soul of the Cell Death Machine

    Directory of Open Access Journals (Sweden)

    Arul M. Chinnaiyan

    1999-04-01

    Full Text Available Apoptosis is a fundamental biologic process by which metazoan cells orchestrate their own self-demise. Genetic analyses of the nematode C elegans identified three core components of the suicide apparatus which include CED-3, CED-4, and CED-9. An analogous set of core constituents exists in mammalian cells and includes caspase-9, Apaf-1, and bcl-2/xL, respectively. CED-3 and CED-4, along with their mammalian counterparts, function to kill cells, whereas CED-9 and its mammalian equivalents protect cells from death. These central components biochemically intermingle in a ternary complex recently dubbed the “apoptosome.” The C elegans protein EGL-1 and its mammalian counterparts, pro-apoptotic members of the bcl-2 family, induce cell death by disrupting apoptosome interactions. Thus, EGL-1 may represent a primordial signal integrator for the apoptosome. Various biochemical processes including oligomerization, adenosine triphosphate ATP/dATP binding, and cytochrome c interaction play a role in regulating the ternary death complex. Recent studies suggest that cell death receptors, such as CD95, may amplify their suicide signal by activating the apoptosome. These mutual associations by core components of the suicide apparatus provide a molecular framework in which diverse death signals likely interface. Understanding the apoptosome and its cellular connections will facilitate the design of novel therapeutic strategies for cancer and other disease states in which apoptosis plays a pivotal role.

  12. 18 CFR 4.101 - Applicability.

    Science.gov (United States)

    2010-04-01

    ... PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.101 Applicability... the Federal Power Act (Act), including licensing, for small hydroelectric power projects as defined in... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Applicability. 4.101...

  13. 20 CFR 202.4 - Control.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Control. 202.4 Section 202.4 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT EMPLOYERS UNDER THE ACT... and in any case in which a carrier is in fact exercising direction of the policies and business of...

  14. Now Those Who Were Scattered Went about Preaching the Word (Acts 8:4: The Migrant Church and Its Mission According to the Book of Acts

    Directory of Open Access Journals (Sweden)

    Stenschke, Christoph

    2016-03-01

    Full Text Available After a brief survey of migration in the Bible, this article examines migration be it voluntary or enforced in the Book of Acts. Acts describes in Stephen's speech in surprising detail experiences of migration in Israel's past and its theological implications. Acts also describes that many early Christian missionaries served in places that were not their places of origin, voluntarily or by force: the disciples ended up in Jerusalem and eventually at the ends of the earth rather than returning to Galilee. Others had come to Jerusalem from elsewhere even before encountering the Gospel and ministered throughout the Eastern Mediterranean world as they became involved in mission. Early Christian mission is closely related to migration and dislocation, voluntary or by force, led by the Spirit and for the sake of the Gospel. Repeatedly other missionaries had to flee in order to avoid persecution. Despite the tragedy and suffering involved, there were also great opportunities which were readily seized: the Gospel moved forward. Much of early Christian mission was accomplished by refugees. A final section reflects on the significance of this portrayal of early Christian mission for the church and its mission in the 21st century.

  15. Diabetes and the Affordable Care Act.

    Science.gov (United States)

    Burge, Mark R; Schade, David S

    2014-07-01

    The Affordable Care Act--"Obamacare"--is the most important federal medical legislation to be enacted since Medicare. Although the goal of the Affordable Care Act is to improve healthcare coverage, access, and quality for all Americans, people with diabetes are especially poised to benefit from the comprehensive reforms included in the act. Signed into law in 2010, this massive legislation will slowly be enacted over the next 10 years. In the making for at least a decade, it will affect every person in the United States, either directly or indirectly. In this review, we discuss the major changes in healthcare that will take place in the next several years, including (1) who needs to purchase insurance on the Web-based exchange, (2) the cost to individuals and the rebates that they may expect, (3) the rules and regulations for purchasing insurance, (4) the characteristics of the different "metallic" insurance plans that are available, and (5) the states that have agreed to participate. With both tables and figures, we have tried to make the Affordable Care Act both understandable and appreciated. The goal of this comprehensive review is to highlight aspects of the Affordable Care Act that are of importance to practitioners who care for people with diabetes by discussing both the positive and the potentially negative aspects of the program as they relate to diabetes care.

  16. 77 FR 15555 - Freedom of Information Act and Privacy Act Procedures

    Science.gov (United States)

    2012-03-16

    ... Freedom of Information Act and Privacy Act Procedures AGENCY: Special Inspector General for Afghanistan... Freedom of Information Act (FOIA) and the Privacy Act of 1974. These procedures will facilitate public..., Freedom of information, Privacy. Authority and Issuance For the reasons set forth above, SIGAR establishes...

  17. 76 FR 21373 - Privacy Act of 1974; Report of a New System of Records

    Science.gov (United States)

    2011-04-15

    ... Information Security Management Act of 2002; the Computer Fraud and Abuse Act of 1986; the Health Insurance... 1974; the Federal Information Security Management Act of 2002; the Computer Fraud and Abuse Act of 1986... established by State law; (3) support litigation involving the Agency; (4) combat fraud, waste, and abuse in...

  18. Sense, Reference, Speech Acts, Norms and Other Issues

    Czech Academy of Sciences Publication Activity Database

    Koťátko, Petr

    2015-01-01

    Roč. 22, č. 4 (2015), s. 546-576 ISSN 1335-0668 Institutional support: RVO:67985955 Keywords : meaning * sense * normativity * speech acts * conventions * communicative intentions * rigid designation * explicite performatives Subject RIV: AA - Philosophy ; Religion http://www.klemens.sav.sk/fiusav/doc/organon/2015/4/546-576.pdf

  19. 28 CFR 55.5 - Coverage under section 4(f)(4).

    Science.gov (United States)

    2010-07-01

    ... THE VOTING RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Nature of Coverage § 55.5 Coverage under section 4(f)(4). (a) Coverage formula. Section 4(f)(4) applies to any State or political subdivision in...) Coverage may be determined with regard to section 4(f)(4) on a statewide or political subdivision basis. (1...

  20. 7 CFR 3016.4 - Applicability.

    Science.gov (United States)

    2010-01-01

    ...); (iii) Foster Care and Adoption Assistance (Title IV-E of the Act); (iv) Aid to the Aged, Blind, and... part. (1) Entitlement grants under the following programs authorized by The National School Lunch Act: (i) National School Lunch Program, General Assistance (section 4 of the Act), (ii) Commodity...

  1. 76 FR 64115 - Privacy Act of 1974; Privacy Act System of Records

    Science.gov (United States)

    2011-10-17

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-092)] Privacy Act of 1974; Privacy Act... retirement of one Privacy Act system of records notice. SUMMARY: In accordance with the Privacy Act of 1974, NASA is giving notice that it proposes to cancel the following Privacy Act system of records notice...

  2. AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

    Energy Technology Data Exchange (ETDEWEB)

    Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp

    2015-11-20

    Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

  3. AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

    International Nuclear Information System (INIS)

    Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami

    2015-01-01

    Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

  4. 12 CFR 332.16 - Protection of Fair Credit Reporting Act.

    Science.gov (United States)

    2010-01-01

    ... GENERAL POLICY PRIVACY OF CONSUMER FINANCIAL INFORMATION Relation to Other Laws; Effective Date § 332.16 Protection of Fair Credit Reporting Act. Nothing in this part shall be construed to modify, limit, or... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Protection of Fair Credit Reporting Act. 332.16...

  5. 12 CFR 407.7 - Relationship to Freedom of Information Act.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Relationship to Freedom of Information Act. 407.7 Section 407.7 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES REGULATIONS GOVERNING PUBLIC OBSERVATION OF EX-IM BANK MEETINGS § 407.7 Relationship to Freedom of Information Act. Nothing in...

  6. 78 FR 59374 - Sunshine Act Meeting

    Science.gov (United States)

    2013-09-26

    ... Institutional Advancement Committee will meet telephonically on October 1, 2013. The meeting will commence at 4... meeting of the Institutional Advancement Committee. The transcript of any portion of the closed session... the 1973 Rehabilitation Act. Upon request, meeting notices and materials will be made available in...

  7. 78 FR 21978 - Sunshine Act Meeting

    Science.gov (United States)

    2013-04-12

    ... Institutional Advancement Committee will meet telephonically on April 23, 2013. The meeting will commence at 4... written transcript will be made of each closed session meeting of the Institutional Advancement Committee... the 1973 Rehabilitation Act. Upon request, meeting notices and materials will be made available in...

  8. 78 FR 50387 - Certain Frozen Warmwater Shrimp From the Socialist Republic of Vietnam: Final Affirmative...

    Science.gov (United States)

    2013-08-19

    ... Blanchard Seafood, Inc.; Dominick Seafood; Fisherman's Reef Packing Plant; Golden Gulf Coast Pkg. Co., Inc...-caught warmwater species include, but are not limited to, whiteleg shrimp (Penaeus vannemei), banana...

  9. Hommikueine Belgradis ja hallitav rukkileib / Anders Härm

    Index Scriptorium Estoniae

    Härm, Anders, 1977-

    2004-01-01

    Kunstipoliitikast Eestis ja Belgradis. Aastanäituse Oktoobrisalong (Oktobarski Salon) avamisest Belgradis, kuraator Anda Rottenberg. Rahvusvahelisel näitusel "Kontinental Breakfast" osalesid Ilja Kabakov, Emilia Kabakov, Christian Boltanski, Marina Abramovic, Esra Ersen, Anri Sala, Egle Raukaskaite

  10. 20 CFR 626.4 - Table of contents for the Job Training Partnership Act regulations.

    Science.gov (United States)

    2010-04-01

    .... 628.210State Job Training Coordinating Council. 628.215State Human Resource Investment Council... and for general program management. Subpart G [Reserved] Subpart H—Job Training Partnership Act... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Table of contents for the Job Training...

  11. 75 FR 62889 - Sunshine Act Meetings

    Science.gov (United States)

    2010-10-13

    ... report on: a. Virtual Board Manual. b. Board and Committee Self Evaluation process for 2010. c. New Board.... Presentation by Mattie Cohan, Senior Assistant General Counsel. 4. Consider and act on Draft Advanced Notice of... committees. a. Presentation by Mattie Cohan, Senior Assistant General Counsel. b. Comments by Laurie...

  12. 78 FR 20356 - Sunshine Act Meeting

    Science.gov (United States)

    2013-04-04

    ... Institutional Advancement Committee will meet telephonically on April 9, 2013. The meeting will commence at 4:00... verbatim written transcript will be made of each closed session meeting of the Institutional Advancement... Rehabilitation Act. Upon request, meeting notices and materials will be made available in alternative formats to...

  13. Triennaali peaauhind läks Leetu

    Index Scriptorium Estoniae

    2004-01-01

    Tallinna XIII graafikatriennaalil väljaantud preemiad: peaauhind - leedu graafik Egle Kuckaite, diplomid - eesti kunstirühmitus John Smith (projekt betoonkohvritega "100 John Smithi") ja Eve Kiiler (fotoseeria "Fantastiline realism"), kiituskiri - eesti rühmitus Anonymous Boh

  14. Development of whole core thermal-hydraulic analysis program ACT. 4. Simplified fuel assembly model and parallelization by MPI

    International Nuclear Information System (INIS)

    Ohshima, Hiroyuki

    2001-10-01

    A whole core thermal-hydraulic analysis program ACT is being developed for the purpose of evaluating detailed in-core thermal hydraulic phenomena of fast reactors including the effect of the flow between wrapper-tube walls (inter-wrapper flow) under various reactor operation conditions. As appropriate boundary conditions in addition to a detailed modeling of the core are essential for accurate simulations of in-core thermal hydraulics, ACT consists of not only fuel assembly and inter-wrapper flow analysis modules but also a heat transport system analysis module that gives response of the plant dynamics to the core model. This report describes incorporation of a simplified model to the fuel assembly analysis module and program parallelization by a message passing method toward large-scale simulations. ACT has a fuel assembly analysis module which can simulate a whole fuel pin bundle in each fuel assembly of the core and, however, it may take much CPU time for a large-scale core simulation. Therefore, a simplified fuel assembly model that is thermal-hydraulically equivalent to the detailed one has been incorporated in order to save the simulation time and resources. This simplified model is applied to several parts of fuel assemblies in a core where the detailed simulation results are not required. With regard to the program parallelization, the calculation load and the data flow of ACT were analyzed and the optimum parallelization has been done including the improvement of the numerical simulation algorithm of ACT. Message Passing Interface (MPI) is applied to data communication between processes and synchronization in parallel calculations. Parallelized ACT was verified through a comparison simulation with the original one. In addition to the above works, input manuals of the core analysis module and the heat transport system analysis module have been prepared. (author)

  15. 17 CFR 4.12 - Exemption from provisions of part 4.

    Science.gov (United States)

    2010-04-01

    ... part 4. 4.12 Section 4.12 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION... said Act; (B) Will generally and routinely engage in the buying and selling of securities and securities derived instruments; (C) Will not enter into commodity futures and commodity options contracts for...

  16. Long-acting reversible contraceptive acceptability and unintended pregnancy among women presenting for short-acting methods: a randomized patient preference trial.

    Science.gov (United States)

    Hubacher, David; Spector, Hannah; Monteith, Charles; Chen, Pai-Lien; Hart, Catherine

    2017-02-01

    participants, 43% chose randomization and 57% chose the preference option. Complete loss to follow-up at 12 months was method continuation probabilities were 63.3% (95% confidence interval, 58.9-67.3) (preference short-acting reversible contraception), 53.0% (95% confidence interval, 45.7-59.8) (randomized short-acting reversible contraception), and 77.8% (95% confidence interval, 71.0-83.2) (randomized long-acting reversible contraception) (P contraception), 7.7% (95% confidence interval, 3.3-12.1) (randomized short-acting reversible contraception), and 0.7% (95% confidence interval, 0.0-4.7) (randomized long-acting reversible contraception) (P = .01 when comparing randomized groups). In the secondary comparisons involving only short-acting reversible contraception users, the continuation probability was higher in the preference group compared with the randomized group (P = .04). However, the short-acting reversible contraception randomized group and short-acting reversible contraception preference group had statistically equivalent rates of unintended pregnancy (P = .77). Seventy-eight percent of randomized long-acting reversible contraception users were happy/neutral with their initial method, compared with 89% of randomized short-acting reversible contraception users (P method continuers at 12 months, all groups were equally happy/neutral (>90%). Even in a typical population of women who presented to initiate or continue short-acting reversible contraception, long-acting reversible contraception proved highly acceptable. One year after initiation, women randomized to long-acting reversible contraception had high continuation rates and consequently experienced superior protection from unintended pregnancy compared with women using short-acting reversible contraception; these findings are attributable to the initial technology and not underlying factors that often bias observational estimates of effectiveness. The similarly patterned experiences of the 2 short-acting

  17. Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO.

    Science.gov (United States)

    Coelho Cerqueira, Eduardo; Netz, Paulo Augusto; Diniz, Cristiane; Petry do Canto, Vanessa; Follmer, Cristian

    2011-12-15

    Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic and exogenous amines and its inhibitors have therapeutic value for several conditions including affective disorders, stroke, neurodegenerative diseases and aging. The discovery of 2,3,6-trimethyl-1,4-naphthoquinone (TMN) as a nonselective and reversible inhibitor of MAO, has suggested 1,4-naphthoquinone (1,4-NQ) as a potential scaffold for designing new MAO inhibitors. Combining molecular modeling tools and biochemical assays we evaluate the kinetic and molecular details of the inhibition of human MAO by 1,4-NQ, comparing it with TMN and menadione. Menadione (2-methyl-1,4-naphthoquinone) is a multitarget drug that acts as a precursor of vitamin K and an inducer of mitochondrial permeability transition. Herein we show that MAO-B was inhibited competitively by 1,4-NQ (K(i)=1.4 μM) whereas MAO-A was inhibited by non-competitive mechanism (K(i)=7.7 μM). Contrasting with TMN and 1,4-NQ, menadione exhibited a 60-fold selectivity for MAO-B (K(i)=0.4 μM) in comparison with MAO-A (K(i)=26 μM), which makes it as selective as rasagiline. Fluorescence and molecular modeling data indicated that these inhibitors interact with the flavin moiety at the active site of the enzyme. Additionally, docking studies suggest the phenyl side groups of Tyr407 and Tyr444 (for MAO-A) or Tyr398 and Tyr435 (for MAO-B) play an important role in the interaction of the enzyme with 1,4-NQ scaffold through forces of dispersion as verified for menadione, TMN and 1,4-NQ. Taken together, our findings reveal the molecular details of MAO inhibition by 1,4-NQ scaffold and show for the first time that menadione acts as a competitive and reversible inhibitor of human MAO. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. 75 FR 81205 - Privacy Act: Revision of Privacy Act Systems of Records

    Science.gov (United States)

    2010-12-27

    ... DEPARTMENT OF AGRICULTURE Office of the Secretary Privacy Act: Revision of Privacy Act Systems of Records AGENCY: Office of the Secretary, USDA. ACTION: Notice to Revise Privacy Act Systems of Records... two Privacy Act Systems of Records entitled ``Information on Persons Disqualified from the...

  19. Dealing with multicollinearity in predicting egg components from egg weight and egg dimension

    Directory of Open Access Journals (Sweden)

    Tarek M. Shafey

    2014-10-01

    Full Text Available Measurements of 174 eggs from meat-type breeder flock (Ross at 36 weeks of age were used to study the problem of multicollinearity (MC instability in the estimation of egg components of yolk weight (YKWT, albumen weight (ALBWT and eggshell weight (SHWT. Egg weight (EGWT, egg shape index (ESI=egg width (EGWD*100/egg length (EGL and their interaction (EGWTESI were used in the context of un-centred vs centred data and principal components regression (PCR models. The pairwise phenotypic correlations, variance inflation factor (VIF, eigenvalues, condition index (CI, and variance proportions were examined. Egg weight had positive correlations with EGWD and EGL (r=0.56 and 0.50, respectively; P<0.0001 and EGL had a negative correlation with ESI (r=-0.79; P<0.0001. The highest correlation was observed between EGWT and ALBWT (r=0.94; P<0.0001, while the lowest was between EGWD and SHWT (r=0.33; P<0.0001. Multicollinearity problems were found in EGWT, ESI and their interaction as shown by VIF (>10, eigenvalues (near zero, CI (>30 and high corresponding proportions of variance of EGWT, ESI and EGWTESI with respect to EGWTESI. Results from this study suggest that mean centring and PCR were appropriate to overcome the MC instability in the estimation of egg components from EGWT and ESI. These methods improved the meaning of intercept values and produced much lower standard error values for regression coefficients than those from un-centred data.

  20. 48 CFR 652.236-71 - Foreign Service Buildings Act, as Amended.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Foreign Service Buildings....236-71 Foreign Service Buildings Act, as Amended. As prescribed in 636.570(a), insert the following provision: Foreign Service Buildings Act, as Amended (APR 2004) (a) This solicitation is subject to Section...

  1. 45 CFR 2543.84 - Contract Work Hours and Safety Standards Act.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Contract Work Hours and Safety Standards Act. 2543... OTHER NON-PROFIT ORGANIZATIONS Statutory Compliance § 2543.84 Contract Work Hours and Safety Standards Act. Where applicable, all contracts awarded by recipients in excess of $2000 for construction...

  2. 78 FR 40515 - Privacy Act of 1974; Privacy Act System of Records

    Science.gov (United States)

    2013-07-05

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 13-071] Privacy Act of 1974; Privacy Act System of Records AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Privacy Act system of records. SUMMARY: Each Federal agency is required by the Privacy Act of 1974 to publish...

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 7901 - 7950 of 11090 ... ... of Zmda1-1 gene increases seed mass of corn, Abstract PDF ... gene in maize increases sethoxydim resistance and oil content, Abstract PDF ... and characterization of the Aspergillus niger endoglucanase, EglA, ...

  4. Williamson Act - The California Land Conservation Act of 1965

    Data.gov (United States)

    California Natural Resource Agency — The California Land Conservation Act of 1965 - commonly referred to as the Williamson Act - is the State's primary program for the conservation of private land in...

  5. The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating.

    Directory of Open Access Journals (Sweden)

    Chai Ann Ng

    Full Text Available Human ether-à-go-go-related gene (hERG K(+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4-S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4-S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4-S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4-S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4-S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4-S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel.

  6. Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

    Science.gov (United States)

    Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

    2017-02-20

    We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

  7. 78 FR 77503 - Privacy Act of 1974; Privacy Act System of Records

    Science.gov (United States)

    2013-12-23

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 13-149] Privacy Act of 1974; Privacy Act... proposed revisions to existing Privacy Act systems of records. SUMMARY: Pursuant to the provisions of the Privacy Act of 1974 (5 U.S.C. 552a), the National Aeronautics and Space Administration is issuing public...

  8. 76 FR 28426 - Applications for New Awards; Assistive Technology Act of 1998, as Amended (AT Act)-National...

    Science.gov (United States)

    2011-05-17

    ... resources; and (11) The level of customer satisfaction with the services provided; and (d) Help measure the... and referrals provided under section 4(e)(2)(D) of the AT Act, and an analysis of individuals with disabilities who have benefited from the demonstrations and referrals; (6)(i) The number and general...

  9. Initial Northwest Power Act Power Sales Contracts : Final Environmental Impact Statement. Volume 4, Comments and Responses.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1992-01-01

    This volume of the Initial Northwest Power Act Power Sales Contracts Final Environmental Impact Statement (Final EIS) contains public comments addressing the Initial Northwest Power Act Power Sales Contracts Draft EIS, August 1990 and Bonneville Power Administration`s (BPA) responses. The Introduction provides information about the process BPA follows in addressing these comments. Part I contains a listing of the Alternative Actions evaluated in the Final EIS; Part II is organized by Alternatives and includes summaries of the comments and BPA responses; Part III provides copies of the original comments letters, and, for ease of identification, are coded in the margins according to the alternative(s) addressed.

  10. 75 FR 36535 - Freedom of Information Act, Privacy Act of 1974; Implementation

    Science.gov (United States)

    2010-06-28

    ... DEPARTMENT OF THE TREASURY Office of the Secretary 31 CFR Part 1 Freedom of Information Act... Freedom of Information Act (FOIA) and its regulations concerning the Privacy Act of 1974 (Privacy Act). It... correct those errors. List of Subjects in 31 CFR Part 1 Freedom of Information; Privacy. 0 Accordingly...

  11. 76 FR 67763 - Privacy Act of 1974; Privacy Act System of Records

    Science.gov (United States)

    2011-11-02

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-109)] Privacy Act of 1974; Privacy Act... proposed revisions to an existing Privacy Act system of records. SUMMARY: Pursuant to the provisions of the Privacy Act of 1974 (5 U.S.C. 552a), the National Aeronautics and Space Administration is issuing public...

  12. 76 FR 64114 - Privacy Act of 1974; Privacy Act System of Records

    Science.gov (United States)

    2011-10-17

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-093)] Privacy Act of 1974; Privacy Act... proposed revisions to an existing Privacy Act system of records. SUMMARY: Pursuant to the provisions of the Privacy Act of 1974 (5 U.S.C. 552a), the National Aeronautics and Space Administration is issuing public...

  13. 77 FR 69898 - Privacy Act of 1974; Privacy Act System of Records

    Science.gov (United States)

    2012-11-21

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 12-100] Privacy Act of 1974; Privacy Act... proposed revisions to an existing Privacy Act system of records. SUMMARY: Pursuant to the provisions of the Privacy Act of 1974 (5 U.S.C. 552a), the National Aeronautics and Space Administration is issuing public...

  14. Tenth act amending the German atomic energy act

    International Nuclear Information System (INIS)

    Heller, W.

    2009-01-01

    On January 14, 2009, the German federal government introduced into parliament the 10th Act Amending the Atomic Energy Act. In the first reading in the federal parliament, Federal Minister for the Environment Gabriel emphasized 2 main points: Intensified protection of nuclear facilities and of transports of radioactive substances against unauthorized interventions; transfer by law to the Federal Office for Radiological Protection (BfS) of decommissioning of the Asse mine. Reliability review: The amendment to Sec.12 b of the Atomic Energy Act is to meet the different safety and security conditions after the terrorist attacks on September 11, 2001 in the United States and other terrorist activities afterwards (London, Madrid) also with respect to hazards arising to nuclear facilities and nuclear transports. The bill must be seen in conjunction with the Ordinance on Reliability Reviews under the Atomic Energy Act dated July 1, 1999 which covers reviews of reliability of persons holding special responsibilities. Asse II mine: The competence of the Federal Office for Radiological Protection is achieved by an amendment to Sec.23, Para.1, Number 2, Atomic Energy Act, in which the words ''and for the Asse II mine'' are added after the word ''waste.'' Further proceedings depend on the additional provision in a new Sec.57 b, Atomic Energy Act. Accordingly, the operation and decommissioning of the Asse II mine are subject to the regulations applicable to facilities of the federation pursuant to Sec.9a, Para.3. In this way, Asse II is given the same legal status as the federal waste management facilities. Moreover, it is stipulated that the mine is to be shut down immediately. (orig.)

  15. Act to amend cost regulations of the Atomic Energy Act

    International Nuclear Information System (INIS)

    1980-01-01

    Article 21 is replaced by articles 21 to 21b. According to this, fees or reimbursements for expenses for official acts (e.g. decisions, supervisory acts, safeguarding of nuclear fuels) as well as for the use of facilities according to article 9a, section 3, of the Atomic Energy Act (e.g. Laender facilities to collect nuclear waste). (HP) [de

  16. Ukraina kreekakatoliku kirik / Jüri Kuuskemaa, Egle Tamm

    Index Scriptorium Estoniae

    Kuuskemaa, Jüri, 1942-

    2002-01-01

    Ukraina kreekakatoliku Kolmkäsi Jumalaema kirik (Laboratooriumi 22) taastati 2000. a. sügiseks. Anatoli Ljutjuki kujundatud interjöörist. Lvovi kunstniku Petro Gumenjuki maalitud ikoonidega ikonostaas

  17. Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2012-02-01

    Full Text Available Nitric oxide (NO is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP and the cGMP-dependent kinase (PKG are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ were used. We observed that long-term exposure to the NO donor (24 h, NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner.

  18. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8... GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The... based on the Equal Pay Act may be raised in a proceeding under title VII. (c) Where such a defense is...

  19. 76 FR 56815 - Workforce Investment Act; Native American Employment and Training Council

    Science.gov (United States)

    2011-09-14

    ... Committee Act (FACA) (Pub. L. 92-463), as amended, and Section 166 (h)(4) of the Workforce Investment Act... submitted to Mrs. Evangeline M. Campbell, Designated Federal Official (DFO), U.S. Department of Labor, 200... CONTACT: Mrs. Evangeline M. Campbell, DFO, Division [[Page 56816

  20. Evaluation of the relative biological effectiveness of carbon ion beams in the cerebellum using the rat organotypic slice culture system

    International Nuclear Information System (INIS)

    Yoshida, Yukari; Katoh, Hiroyuki; Nakano, Takashi; Suzuki, Yoshiyuki; Al-Jahdari, Wael S.; Shirai, Katsuyuki; Hamada, Nobuyuki; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

    2012-01-01

    The purpose of this study was to clarify the relative biological effectiveness (RBE) values of carbon ion (C) beams in normal brain tissues, a rat organotypic slice culture system was used. The cerebellum was dissected from 10-day-old Wistar rats, cut parasagittally into approximately 600-μm-thick slices and cultivated using a membrane-based culture system with a liquid-air interface. Slices were irradiated with 140 kV X-rays and 18.3 MeV/amu C-beams (linear energy transfer=108 keV/μm). After irradiation, the slices were evaluated histopathologically using hematoxylin and eosin staining, and apoptosis was quantified using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Disorganization of the external granule cell layer (EGL) and apoptosis of the external granule cells (EGCs) were induced within 24 h after exposure to doses of more than 5 Gy from C-beams and X-rays. In the early postnatal cerebellum, morphological changes following exposure to C-beams were similar to those following exposure to X-rays. The RBEs values of C-beams using the EGL disorganization and the EGC TUNEL index endpoints ranged from 1.4 to 1.5. This system represents a useful model for assaying the biological effects of radiation on the brain, especially physiological and time-dependent phenomena. (author)

  1. Managing the nation's nuclear waste. Overview: Nuclear Waste Policy Act

    International Nuclear Information System (INIS)

    1985-10-01

    Signed into law by the President on January 7, 1983, the Nuclear Waste Policy Act established a national policy for safely storing, transporting, and disposing of spent nuclear fuel and high-level radioactive waste. This overview presents the following information on the Nuclear Waste Policy Act: (1) background; (2) permanent repository; (3) siting guidelines and mission plan; (4) monitored retrievable storage; and (5) nuclear waste funds. (DT)

  2. 16 CFR 1115.22 - Prohibited acts and sanctions.

    Science.gov (United States)

    2010-01-01

    ... (15 U.S.C. 2068(a)(4)). (c) Failure to make reports. The failure or refusal to make reports or provide... acts in the circumstances, including knowledge obtainable upon the exercise of due care to ascertain...

  3. Human Rights Act, 12 February 1987.

    Science.gov (United States)

    1987-01-01

    This document reprints major provisions of the Yukon's (Canada) 1987 Human Rights Act. The Act furthers the public policy that every individual is free and equal in dignity and rights, seeks to discourage and eliminate discrimination, and promotes the underlying principles of Canadian and international human rights instruments. Part 1 contains a Bill of Rights that protects the right to freedom of: 1) religion and conscience, 2) expression, 3) assembly and association, and 4) to enjoyment and disposition of property. Part 2 prohibits discrimination based on ancestry (including color and race), national origin, ethnic or linguistic background or origin, age, sex (including pregnancy), and marital or family status. Discrimination is also prohibited when offering services, goods, or facilities to the public; in connection with employment; in connection with membership in trade unions or trade, occupational, or professional associations; and in negotiation or performance of public contracts. The Bill of Rights lists reasonable causes for discrimination as well as exemptions, including preferential treatment for organization or family members or employment in a private home. Special programs and affirmative action programs are specifically not considered discrimination under this Act. The Act sets forth rules for providing equal pay for work of equal value and creates a Yukon Human Rights Commission to promote human rights and assist adjudication of complaints.

  4. 40 CFR 40.115-4 - Municipality.

    Science.gov (United States)

    2010-07-01

    ... 208 of the act. (b) Under the Resource Conservation and Recovery Act, a city, town, borough, county... subdivision thereof. (c) In all other cases, a city, town, borough, county, parish, district, or other public... DEMONSTRATION GRANTS § 40.115-4 Municipality. (a) Under the Federal Water Pollution Control Act, a city, town...

  5. Identification of a soluble guanylate cyclase in RBCs: preserved activity in patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Miriam M. Cortese-Krott

    2018-04-01

    Full Text Available Endothelial dysfunction is associated with decreased NO bioavailability and impaired activation of the NO receptor soluble guanylate cyclase (sGC in the vasculature and in platelets. Red blood cells (RBCs are known to produce NO under hypoxic and normoxic conditions; however evidence of expression and/or activity of sGC and downstream signaling pathway including phopshodiesterase (PDE-5 and protein kinase G (PKG in RBCs is still controversial. In the present study, we aimed to investigate whether RBCs carry a functional sGC signaling pathway and to address whether this pathway is compromised in coronary artery disease (CAD. Using two independent chromatographic procedures, we here demonstrate that human and murine RBCs carry a catalytically active α1β1-sGC (isoform 1, which converts 32P-GTP into 32P-cGMP, as well as PDE5 and PKG. Specific sGC stimulation by NO+BAY 41-2272 increases intracellular cGMP-levels up to 1000-fold with concomitant activation of the canonical PKG/VASP-signaling pathway. This response to NO is blunted in α1-sGC knockout (KO RBCs, but fully preserved in α2-sGC KO. In patients with stable CAD and endothelial dysfunction red cell eNOS expression is decreased as compared to aged-matched controls; by contrast, red cell sGC expression/activity and responsiveness to NO are fully preserved, although sGC oxidation is increased in both groups. Collectively, our data demonstrate that an intact sGC/PDE5/PKG-dependent signaling pathway exists in RBCs, which remains fully responsive to NO and sGC stimulators/activators in patients with endothelial dysfunction. Targeting this pathway may be helpful in diseases with NO deficiency in the microcirculation like sickle cell anemia, pulmonary hypertension, and heart failure. Keywords: cGMP, Nitric oxide, Protein kinase G, Signaling, Non -canonical functions of RBCs

  6. Control of Vascular Smooth Muscle Cell Growth by Connexin 43

    Directory of Open Access Journals (Sweden)

    Chintamani eJoshi

    2012-06-01

    Full Text Available Connexin 43 (Cx43, the principal gap junction protein in vascular smooth muscle cells (VSMCs, regulates movement of ions and other signaling molecules through gap junction intercellular communication (GJIC and plays important roles in maintaining normal vessel function; however, many of the signaling mechanisms controlling Cx43 in VSMCs are not clearly described. The goal of this study was to investigate mechanisms of Cx43 regulation with respect to VSMC proliferation. Treatment of rat primary VSMCs with the cAMP analog 8Br-cAMP, the soluble guanylate cyclase (sGC stimulator BAY 41-2272 (BAY, or the Cx inducer diallyl disulfide (DADS significantly reduced proliferation after 72 h compared to vehicle controls. Bromodeoxyuridine uptake revealed reduction (p<.001 in DNA synthesis after 6 h and flow cytometry showed reduced (40% S phase cell numbers after 16 h in DADS-treated cells compared to controls. Cx43 expression significantly increased after 270 min treatment with 8Br-cAMP, 8Br-cGMP, BAY or DADS. Inhibition of PKA, PKG or PKC reversed 8Br-cAMP-stimulated increases in Cx43 expression, whereas only PKG or PKC inhibition reversed 8Br-cGMP- and BAY-stimulated increases in total Cx43. Interestingly, stimulation of Cx43 expression by DADS was not dependent on PKA, PKG or PKC. Using fluorescence recovery after photobleaching, only 8Br-cAMP or DADS increased GJIC with 8Br-cAMP mediated by PKC and DADS mediated by PKG. Further, DADS significantly increased phosphorylation at the MAPK-sensitive serine (Ser255 and Ser279, the cell cycle regulatory kinase-sensitive Ser262 and the PKC-sensitive Ser368 after 30 min while 8Br-cAMP significantly increased phosphorylation only at Ser279 compared to controls. This study demonstrates that 8Br-cAMP- and DADS-enhanced GJIC rather than Cx43 expression and/or phosphorylation plays an important role in regulation of VSMC proliferation and provides new insights into the growth-regulatory capacities of Cx43 in VSMCs.

  7. 76 FR 8380 - Workforce Investment Act; Native American Employment and Training Council

    Science.gov (United States)

    2011-02-14

    ... Committee Act (FACA) (Pub. L. 92-463), as amended, and Section 166(h)(4) of the Workforce Investment Act.... Evangeline M. Campbell, Designated Federal Official (DFO), U.S. Department of Labor, 200 Constitution Avenue... Workgroup Reports; and (10) Council Recommendations. FOR FURTHER INFORMATION CONTACT: Mrs. Campbell, DFO...

  8. 45 CFR 1226.10 - Hatch Act restrictions.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Hatch Act restrictions. 1226.10 Section 1226.10 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY... candidates on canvassing or speaking tours. (12) Participation in or organizing a political parade. (13...

  9. An epigenetic signal encoded protection mechanism is activated by graphene oxide to inhibit its induced reproductive toxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Zhao, Yunli; Wu, Qiuli; Wang, Dayong

    2016-02-01

    Although many studies have suggested the adverse effects of engineered nanomaterials (ENMs), the self-protection mechanisms for organisms against ENMs toxicity are still largely unclear. Using Caenorhabditis elegans as an in vivo assay system, our results suggest the toxicity of graphene oxide in reducing reproductive capacity by inducing damage on gonad development. The observed reproductive toxicity of GO on gonad development was due to the combinational effect of germline apoptosis and cell cycle arrest, and DNA damage activation might act as an inducer for this combinational effect. For the underlying molecular mechanism of reproductive toxicity of GO, we raised a signaling cascade of HUS-1/CLK-2-CEP-1-EGL-1-CED-4-CED-3 to explain the roles of core apoptosis signaling pathway and DNA damage checkpoints. Moreover, we identified a miRNA regulation mechanism activated by GO to suppress its induced reproductive toxicity. A mir-360 regulation mechanism was activated by GO to suppress its induced DNA damage-apoptosis signaling cascade through affecting component of CEP-1. Our identified epigenetic signal encoded protection mechanism activated by GO suggests a novel self-protection mechanism for organisms against the ENMs toxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 76 FR 594 - Board of Governors; Sunshine Act Meeting

    Science.gov (United States)

    2011-01-05

    ... POSTAL SERVICE Board of Governors; Sunshine Act Meeting TIMES AND DATES: 4 p.m., Monday, January 10, 2011; and 9 a.m., Tuesday, January 11, 2011. PLACE: Long Beach, California, at the Renaissance Hotel, 111 East Ocean Boulevard. STATUS: (Closed). MATTERS TO BE CONSIDERED: Monday, January 10, at 4 p...

  11. 75 FR 33367 - Board of Governors; Sunshine Act Meeting

    Science.gov (United States)

    2010-06-11

    ... POSTAL SERVICE Board of Governors; Sunshine Act Meeting Times and Dates: 4 p.m., Monday, June 21... Broadway. Status: (Closed). Matters To Be Considered: Monday, June 21, at 4 p.m. (Closed) 1. Strategic...' Executive Session--Discussion of prior agenda items and Board Governance. Tuesday, June 22, at 10 a.m...

  12. Australian Radiation Protection and Nuclear Safety Act 1998. Act No 133

    International Nuclear Information System (INIS)

    1999-01-01

    A set of legislation consisting of three Acts in the field of radiation protection and nuclear safety was passed by both Houses of Parliament on 10 December 1998 and was proclaimed on 5 February 1999. Act No. 133 - Australian Radiation Protection and Nuclear Safety Act, which is a framework Law, established the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) as the regulatory body for radiation protection and nuclear safety, in place of the Nuclear Safety Bureau. The Chief Executive Officer of ARPANSA, who is appointed by the Governor-General for a term of up to 5 years, is obliged to submit annual and quarterly reports to the Minister on the operations of the Chief Executive Officer, ARPANSA, the Council, the Radiation Health Committee and the Nuclear Safety Committee. The Council is a consultative body which examines issues relating to radiation protection and nuclear safety and advises the Chief Executive Officer on these issues as well as on the adoption of recommendations, policies and codes. The Radiation Health Committee and the Nuclear Safety Committee are to be established as advisory committees to the Chief Executive Officer or the Council. Both committees should draft national policies, codes and standards in their respective fields and review their effectiveness periodically. The second in this series of legislation, Act No. 134, Australian Radiation Protection and Nuclear Safety (License Charges) Act requires holders of both facility and source licenses to pay an annual charge, to be prescribed by the regulations. The third, Act No. 135 , Australian Radiation Protection and Nuclear Safety (Consequential Amendments) Act repeals those provisions of the 1987 Australian Nuclear Science and Technology Organisation Act which concern the Nuclear Safety Bureau, and the 1978 Environment Protection Act as a whole

  13. Australian Radiation Protection and Nuclear Safety Act 1998. Act No 133

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-11-01

    A set of legislation consisting of three Acts in the field of radiation protection and nuclear safety was passed by both Houses of Parliament on 10 December 1998 and was proclaimed on 5 February 1999. Act No. 133 - Australian Radiation Protection and Nuclear Safety Act, which is a framework Law, established the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) as the regulatory body for radiation protection and nuclear safety, in place of the Nuclear Safety Bureau. The Chief Executive Officer of ARPANSA, who is appointed by the Governor-General for a term of up to 5 years, is obliged to submit annual and quarterly reports to the Minister on the operations of the Chief Executive Officer, ARPANSA, the Council, the Radiation Health Committee and the Nuclear Safety Committee. The Council is a consultative body which examines issues relating to radiation protection and nuclear safety and advises the Chief Executive Officer on these issues as well as on the adoption of recommendations, policies and codes. The Radiation Health Committee and the Nuclear Safety Committee are to be established as advisory committees to the Chief Executive Officer or the Council. Both committees should draft national policies, codes and standards in their respective fields and review their effectiveness periodically. The second in this series of legislation, Act No. 134, Australian Radiation Protection and Nuclear Safety (License Charges) Act requires holders of both facility and source licenses to pay an annual charge, to be prescribed by the regulations. The third, Act No. 135 , Australian Radiation Protection and Nuclear Safety (Consequential Amendments) Act repeals those provisions of the 1987 Australian Nuclear Science and Technology Organisation Act which concern the Nuclear Safety Bureau, and the 1978 Environment Protection Act as a whole

  14. 76 FR 64112 - Privacy Act of 1974; Privacy Act System of Records Appendices

    Science.gov (United States)

    2011-10-17

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-091)] Privacy Act of 1974; Privacy Act...: Revisions of NASA Appendices to Privacy Act System of Records. SUMMARY: Notice is hereby given that NASA is... Privacy Act of 1974. This notice publishes those amendments as set forth below under the caption...

  15. 7 CFR 65.100 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Act. 65.100 Section 65.100 Agriculture Regulations of... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) COUNTRY OF ORIGIN LABELING OF BEEF..., AND GINSENG General Provisions Definitions § 65.100 Act. Act means the Agricultural Marketing Act of...

  16. Curatorial Acts

    NARCIS (Netherlands)

    Bal, M.

    2012-01-01

    In a self-critical inquiry into my own recent work of co-curating and the experience of seeing my video work being curated by others, this article examines acts of framing as performative acts that seek to transform visitors' preconceptions. This affective effect is pursued by means of immersion,

  17. 12 CFR 303.5 - Effect of Community Reinvestment Act performance on filings.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Effect of Community Reinvestment Act performance on filings. 303.5 Section 303.5 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE... Reinvestment Act performance on filings. Among other factors, the FDIC takes into account the record of...

  18. 75 FR 13595 - Workforce Investment Act; Native American Employment and Training Council

    Science.gov (United States)

    2010-03-22

    ... Committee Act (FACA) (Pub. L. 92-463), as amended, and Section 166(h)(4) of the Workforce Investment Act.... Campbell, Designated Federal Official (DFO), U.S. Department of Labor, 200 Constitution Avenue, NW., Room S...: Mrs. Campbell, DFO, Indian and Native American Program, Employment and Training Administration, U.S...

  19. 77 FR 22003 - Workforce Investment Act; Native American Employment and Training Council

    Science.gov (United States)

    2012-04-12

    ... Committee Act (FACA) (Pub. L. 92-463), as amended, and Section 166 (h)(4) of the Workforce Investment Act.... Evangeline M. Campbell, Designated Federal Official (DFO), U.S. Department of Labor, 200 Constitution Avenue... INFORMATION CONTACT: Mrs. Evangeline M. Campbell, DFO, Division of Indian and Native American Programs...

  20. 75 FR 7524 - Workforce Investment Act; Native American Employment and Training Council

    Science.gov (United States)

    2010-02-19

    ... Committee Act (FACA) (Pub. L. 92-463), as amended, and Section 166(h)(4) of the Workforce Investment Act.... Evangeline M. Campbell, Designated Federal Official (DFO), U.S. Department of Labor, 200 Constitution Avenue... Recommendations. FOR FURTHER INFORMATION CONTACT: Mrs. Evangeline M. Campbell, DFO, Indian and Native American...

  1. 78 FR 69879 - Workforce Investment Act: Native American Employment and Training Council

    Science.gov (United States)

    2013-11-21

    ... Committee Act (FACA) (Pub. L. 92-463), as amended, and Section 166(h)(4) of the Workforce Investment Act... written statements to Mrs. Evangeline M. Campbell, Designated Federal Official (DFO), U.S. Department of... Recommendations. FOR FURTHER INFORMATION CONTACT: Mrs. Evangeline M. Campbell, DFO, Division of Indian and Native...

  2. Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4-5 chronic kidney disease: a meta-analysis.

    Science.gov (United States)

    Li, Tao; Qu, Yundong; Guo, Ying; Wang, Yan; Wang, Lei

    2017-07-01

    The aim of this study was to assess the efficacy and safety of direct-acting antivirals (DAA)-based antiviral therapies for HCV patients with stage 4-5 chronic kidney disease. We conducted a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time and language limitations. The search strategy used was "(End stage renal disease OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR dialysis) AND (sofosbuvir OR simeprevir OR grazoprevir OR elbasvir OR ombitasvir OR paritaprevir OR ritonavir OR dasabuvir OR daclatasvir OR asuparevir OR direct-acting antiviral OR DAA)". Sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs) and/or serious adverse events (SAEs) with 95% confidence intervals (CI) were pooled. Eleven studies, comprising a total of 264 patients were included for our meta-analysis. The pooled SVR12 rate were 93.2% (95% CI 89.9%-95.9%, I 2 =0.0%), 89.4% (95% CI 82.0%-95.0%, I 2 =0.0%) and 94.7% (95% CI 91.0%-97.5%, I 2 =0.0%) in total population, patients with sofosbuvir-based therapies and patients with non-sofosbuvir-based therapies respectively. For HCV genotype 1 patients, the pooled SVR12 rate was 93.1% (95% CI 88.3%-96.7%, I 2 =20.0%). The pooled incidence of SAEs was 12.1% (95% CI 6.2%-19.7%, I 2 =55.0%). The pooled discontinuation rate because of AEs or SAEs in our meta-analysis was 2.2% (95% CI 0.8%-4.4%, I 2 =0.0%). DAA-based antiviral therapies are effective and well-tolerated for HCV patients with stage 4-5 chronic kidney disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Comparison of double-acting and single-acting synthetic jets

    Czech Academy of Sciences Publication Activity Database

    Hsu, S.S.; Trávníček, Zdeněk; Chou, C.-C.; Chen, C. C.; Wang, A. B.

    2013-01-01

    Roč. 203, December (2013), s. 291-299 ISSN 0924-4247 Institutional support: RVO:61388998 Keywords : synthetic jet * double-acting & single acting machines * PIV Subject RIV: BK - Fluid Dynamics Impact factor: 1.943, year: 2013 http://dx.doi.org/10.1016/j.sna.2013.09.005

  4. Regulation of K-Cl cotransport: from function to genes.

    Science.gov (United States)

    Adragna, N C; Di Fulvio, M; Lauf, P K

    2004-10-01

    cotransporter and the cytoskeleton appears to depend on the cellular origin and experimental conditions. Pathophysiologically, K-Cl COT is altered in sickle cell anemia and neuropathies, and it has also been proposed to play a role in blood pressure control. Four closely related human genes code for KCCs (KCC1-4). Although considerable information is accumulating on tissue distribution, function and pathologies associated with the different isoforms, little is known about the genetic regulation of the KCC genes in terms of transcriptional and post-transcriptional regulation. A few reports indicate that the NO/cGMP/PKG signaling pathway regulates KCC1 and KCC3 mRNA expression in VSMCs at the post-transcriptional level. However, the detailed mechanisms of post-transcriptional regulation of KCC genes and of regulation of KCC2 and KCC4 mRNA expression are unknown. The K-Cl COT field is expected to expand further over the next decades, as new isoforms and/or regulatory pathways are discovered and its implication in health and disease is revealed.

  5. 7. I kell 18 avatakse Pärnu Muuseumi Aidas...

    Index Scriptorium Estoniae

    2006-01-01

    Urmas Viigi juhendatud EKA graafikaüliõpilaste tööde näitus, toimuvad ka Pink Pungi, Ernest Truely, Lexxxa, Ville-Karel Viirelaiu, Egle Veske, Remo Randveri, Toomas Kuusingu, Meeland Sepa, Sorge, Sirami (Mari Kartau), Billeneeve, Tanel Saare performance'id

  6. Act No. 732 of December 7, 1988. Act to amend the Act on civil liability for nuclear damage

    International Nuclear Information System (INIS)

    1988-01-01

    This Act amends Act No. 332 of June 19, 1974 on civil liability for nuclear damage, enabling Denmark to ratify the 1982 Protocols to amend the Paris Convention and the Brussels Supplementary Convention as well as the 1988 Joint Protocol relating to the application of the Vienna and the Paris Convention. The 1988 Act raises the nuclear operator's liability from 75 million DKr to 60 million SDRs while cover involving State funds is raised from 120 million units of account to 300 million SDRs. The Act entered into force on July 1, 1989 except for the provision on State funds which becomes effective when the 1982 Protocol amending the Brussels Convention comes into force. (NEA) [fr

  7. 33 CFR 221.1 - Investigation and supervision of hydropower projects under the Federal Power Act (ER 1140-2-4).

    Science.gov (United States)

    2010-07-01

    ... Permits for Activities in Navigable Waters or Ocean Waters. 2 33 CFR 209.120 was removed at 42 FR 37133... Federal Water Pollution Control Act (see paragraph (i)(2)) of this section. Such a permit is subject to a...) Responsibilities under section 404 of the Federal Water Pollution Control Act as amended in 1972 (33 U.S.C. 1151...

  8. ACT Reporting Category Interpretation Guide: Version 1.0. ACT Working Paper 2016 (05)

    Science.gov (United States)

    Powers, Sonya; Li, Dongmei; Suh, Hongwook; Harris, Deborah J.

    2016-01-01

    ACT reporting categories and ACT Readiness Ranges are new features added to the ACT score reports starting in fall 2016. For each reporting category, the number correct score, the maximum points possible, the percent correct, and the ACT Readiness Range, along with an indicator of whether the reporting category score falls within the Readiness…

  9. Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

    Science.gov (United States)

    Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

    2016-07-19

    Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

  10. Validation of the Brazilian version of the childhood asthma control test (c-ACT).

    Science.gov (United States)

    Oliveira, Suelen G; Sarria, Edgar E; Roncada, Cristian; Stein, Renato T; Pitrez, Paulo M; Mattiello, Rita

    2016-04-01

    Children's perception of their symptoms has proved reliable and relevant to disease management and should be considered when assessing their asthma control. The aim of the study is to validate the Brazilian Portuguese version of the Childhood Asthma Control Test (c-ACT) in children aged 4-11 years. This is a cross-sectional study in children diagnosed with asthma undergoing treatment in a pediatric pulmonology outpatient clinic in Porto Alegre, Brazil. The translation and linguistic adaptation of the instrument were performed in accordance with international recommendations for questionnaire validation. A total of 105 participants were included, aged 4-11 years. all correlations between the total score and items on the questionnaire were significant and obtained values of r ≥ 0.3, and c-ACT means showed statistically significant differences between the GINA categories (P ACT scores than those of uncontrolled asthma group (controlled 22.0 ± 2.9 vs. uncontrolled 16.3 ± 5.3 P ACT scores than those of uncontrolled asthma group (partially controlled 20.0 ± 4.0 vs. uncontrolled 16.3 ± 5.3 P = 0.03). Correlations between the c-ACT total score and spirometry and nitric oxide were poor (r = 0.020; P = 0.866 and r = 0.035; P = 0.753, respectively). Reliability: the α-C coefficient for the c-ACT total score was 0.677 (95%CI 0.573-0763). Sensitivity to change had an effect size of 0.8 and an intraclass correlation coefficient of 0.598. No floor or ceiling effects were observed. The Brazilian version of the Childhood Asthma Control Test proved to be valid and reliable in children aged 4-11 years. © 2015 Wiley Periodicals, Inc.

  11. Determinants of long acting and permanent contraceptive methods ...

    African Journals Online (AJOL)

    Introduction: In Ethiopia information on the level of utilization of the long term and ... determinant factors of long acting and permanent contraceptive methods use ... number of live children (AOR = 2.42, 95% CI: 1.46- 4.02), joint fertility related ...

  12. EEG. Renewables Act. Comment. 4. new rev. and enl. ed.; EEG. Erneuerbare-Energien-Gesetz. Kommentar

    Energy Technology Data Exchange (ETDEWEB)

    Frenz, Walter [RWTH Aachen Univ. (Germany). Lehr- und Forschungsgebiet Berg-, Umwelt- und Europarecht; Mueggenborg, Hans-Juergen [Technische Hochschule Aachen (Germany); Kassel Univ. (Germany); Cosack, Tilman [Hochschule Trier, Umwelt-Campus Birkenfeld (Germany). IREK - Inst. fuer das Recht der Erneuerbaren Energien, Energieeffizienzrecht und Klimaschutzrecht; Ekardt, Felix (ed.) [Forschungsstelle Nachhaltigkeit und Klimapolitik, Leipzig (Germany)

    2015-07-01

    Unlike any other Act, the Renewable Energy Sources Act (EEG) changes continuously. Recently it has been fundamentally transformed with the amendment 2014. Comprehensive, readable and practice-oriented. The proven Berliner comment EEG is your reliable companion through the new regulatory regime. All provisions of the EEG 2014 thorough and easy to understand commented by experts of the matter. 2. The EEG Amending Act of 29.6.2015 has already been considered. A detailed introduction and contributions to the relevant European law and the antitrust aspects of the renewable energy sources to guarantee you a broad understanding of the rules. Valuable background information you provide, the digressions of the most important renewable energy technologies, will explain the pictures thanks to numerous the scientific and technical foundations. Moreover you the construction law aspects in the construction of photovoltaic and wind turbines are explained clearly. [German] Wie kaum ein anderes Gesetz veraendert sich das Erneuerbare-Energien-Gesetz (EEG) laufend. Zuletzt wurde es mit der Novelle 2014 grundlegend umgestaltet. Umfassend, verstaendlich und praxisgerecht Der bewaehrte Berliner Kommentar EEG ist Ihr verlaesslicher Begleiter durch das neue Regelungsregime. Alle Vorschriften des EEG 2014 werden gruendlich und leicht verstaendlich von Kennern der Materie kommentiert. Das 2. EEG-Aenderungsgesetz vom 29.06.2015 ist bereits beruecksichtigt. Eine ausfuehrliche Einleitung sowie Beitraege zum einschlaegigen europaeischen Recht und zu den kartellrechtlichen Aspekten der erneuerbaren Energien verhelfen Ihnen zu einem breiten Verstaendnis der Vorschriften. Wertvolles Hintergrundwissen liefern Ihnen auch die Exkurse zu den wichtigsten Erneuerbare-Energien-Technologien, die Ihnen dank zahlreicher Abbildungen die naturwissenschaftlich-technischen Grundlagen erlaeutern. Zudem werden Ihnen die baurechtlichen Aspekte bei der Errichtung von Photovoltaik- und Windenergieanlagen

  13. 29 CFR 4.110 - What contracts are covered.

    Science.gov (United States)

    2010-07-01

    ...'Hara Service Contract Act Covered Contracts Generally § 4.110 What contracts are covered. The Act... mean that the contract is not within the coverage of the Act. The amount of the contract is not determinative of the Act's coverage, although the requirements are different for contracts in excess of $2,500...

  14. 29 CFR 4.121 - Contracts for individual services.

    Science.gov (United States)

    2010-07-01

    ... McNamara-O'Hara Service Contract Act Specific Exclusions § 4.121 Contracts for individual services. The Act... to an “employment contract” for “direct services,” makes it clear that the Act's application to... contract service, the exemption applies and the contract will not be subject to the Act's provisions. The...

  15. Hanford Site National Environmental Policy Act (NEPA) Characterization

    Energy Technology Data Exchange (ETDEWEB)

    Neitzel, Duane A.; Antonio, Ernest J.; Eschbach, Tara O.; Fowler, Richard A.; Goodwin, Shannon M.; Harvey, David W.; Hendrickson, Paul L.; Hoitink, Dana J.; Horton, Duane G.; Last, George V.; Poston, Ted M.; Prendergast, Ellen L.; Rohay, Alan C.; Thorne, Paul D.

    2001-09-01

    This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the thirteenth revision of the original document published in 1988 and is (until replaced by the fourteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities.

  16. Hanford Site National Environmental Policy Act (NEPA) Characterization

    Energy Technology Data Exchange (ETDEWEB)

    Neitzel, Duane A.; Bunn, Amoret L.; Duncan, Joanne P.; Eschbach, Tara O.; Fowler, Richard A.; Fritz, Brad G.; Goodwin, Shannon M.; Harvey, David W.; Hendrickson, Paul L.; Hoitink, Dana J.; Horton, Duane G.; Last, George V.; Poston, Ted M.; Prendergast-Kennedy, Ellen L.; Rohay, Alan C.; Scott, Michael J.; Thorne, Paul D.

    2002-09-01

    This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the thirteenth revision of the original document published in 1988 and is (until replaced by the fourteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities.

  17. 39 CFR 211.4 - Interim personnel regulations.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Interim personnel regulations. 211.4 Section 211.4... under the Postal Reorganization Act. (b) Continuation of Personnel Provisions of Former title 39, U.S.C... collective bargaining agreement under the Postal Reorganization Act, all provisions of former title 39, U.S.C...

  18. 18 CFR 4.10 - Valuation data.

    Science.gov (United States)

    2010-04-01

    ... PROJECT COSTS Determination of Fair Value of Constructed Projects, Under Section 23(a) of the Act § 4.10... Power Act that requires the determination of the fair value of a project already constructed, the...

  19. Development of whole core thermal-hydraulic analysis program ACT. 4. Incorporation of three-dimensional upper plenum model

    International Nuclear Information System (INIS)

    Ohshima, Hiroyuki

    2003-03-01

    The thermal-hydraulic analysis computer program ACT is under development for the evaluation of detailed flow and temperature fields in a core region of fast breeder reactors under various operation conditions. The purpose of this program development is to contribute not only to clarifying thermal hydraulic characteristics that cannot be revealed by experiments due to measurement difficulty but also to performing rational safety design and assessment. This report describes the incorporation of a three-dimensional upper plenum model to ACT and its verification study as part of the program development. To treat the influence of three-dimensional thermal-hydraulic behavior in a upper plenum on the in-core temperature field, the multi-dimensional general purpose thermal-hydraulic analysis program AQUA, which was developed and validated at JNC, was applied as the base of the upper plenum analysis module of ACT. AQUA enables to model the upper plenum configuration including immersed heat exchangers of the direct reactor auxiliary cooling system (DRACS). In coupling core analysis module that consists of the fuel-assembly and the inter-wrapper gap calculation parts with the upper plenum module, different types of computation mesh systems were jointed using the staggered quarter assembly mesh scheme. A coupling algorithm among core, upper plenum and heat transport system modules, which can keep mass, momentum and energy conservation, was developed and optimized in consideration of parallel computing. ACT was applied to analyzing a sodium experiment (PLANDTL-DHX) performed at JNC, which simulated the natural circulation decay heat removal under DRACS operation conditions for the program verification. From the calculation result, the validity of the improved program was confirmed. (author)

  20. 14 CFR 399.73 - Definition of small business for Regulatory Flexibility Act.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Definition of small business for Regulatory... Rulemaking Proceedings § 399.73 Definition of small business for Regulatory Flexibility Act. For the purposes... Flexibility Act), a direct air carrier or foreign air carrier is a small business if it provides air...

  1. 7 CFR 33.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices... AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.1 Act. Act and Export Apple Act are synonymous and mean “An act to promote the foreign trade of the United States in apples to protect the reputation of...

  2. 29 CFR 4.116 - Contracts for construction activity.

    Science.gov (United States)

    2010-07-01

    ... McNamara-O'Hara Service Contract Act Specific Exclusions § 4.116 Contracts for construction activity. (a... McNamara-O'Hara Service Contract Act indicates that the purpose of the provision is to avoid overlapping coverage of the two acts by excluding from the application of the McNamara-O'Hara Act those contracts to...

  3. Determinants of long acting and permanent contraceptive methods ...

    African Journals Online (AJOL)

    Introduction: in Ethiopia information on the level of utilization of the long-term and ... determinant factors of long-acting and permanent contraceptive methods use ... 95% CI: 1.46- 4.02), joint fertility related decision (AOR = 6.11, 95% CI: 2.29- ...

  4. 29 CFR 4.119 - Contracts for services of communications companies.

    Science.gov (United States)

    2010-07-01

    ... Application of the McNamara-O'Hara Service Contract Act Specific Exclusions § 4.119 Contracts for services of communications companies. The Act, in paragraph (4) of section 7, exempts from its provisions “any contract for... Communications Act of 1934.” This exemption is applicable to contracts with such companies for communication...

  5. 29 CFR 4.145 - Extended term contracts.

    Science.gov (United States)

    2010-07-01

    ...'Hara Service Contract Act Changes in Contract Coverage § 4.145 Extended term contracts. (a) Sometimes... purposes of this Act, a contract shall be deemed entered into upon the contract anniversary date which... period is a wholly new contract with respect to application of the Act's provisions and the regulations...

  6. 7 CFR 35.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Act. 35.1 Section 35.1 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices... Definitions § 35.1 Act. Act or Export Grape and Plum Act means “An Act to promote the foreign trade of the...

  7. 7 CFR 987.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 987.2 Section 987.2 Agriculture Regulations of... RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Definitions § 987.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of...

  8. EGVII endoglucanase and nucleic acids encoding the same

    Science.gov (United States)

    Dunn-Coleman, Nigel [Los Gatos, CA; Goedegebuur, Frits [Vlaardingen, NL; Ward, Michael [San Francisco, CA; Yao, Jian [Sunnyvale, CA

    2009-05-05

    The present invention provides an endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.

  9. Overexpression, purification and characterization of the Aspergillus ...

    African Journals Online (AJOL)

    Cellulases are industrially important hydrolytic enzymes applicable in the bioconversion of cellulosic biomass to simple sugars. In this work, an endoglucanase from Aspergillus niger ATCC 10574, EglA, was expressed in the methylotrophic yeast Pichia pastoris and the properties of the recombinant protein were ...

  10. 7 CFR 917.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 917.2 Section 917.2 Agriculture Regulations of... Order Regulating Handling Definitions § 917.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended, and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as...

  11. 7 CFR 1260.128 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1260.128 Section 1260.128 Agriculture... Promotion and Research Order Definitions § 1260.128 Act. Act means the Beef Promotion and Research Act of 1985, Title XVI, Subtitle A of the Food Security Act of 1985, Pub. L. 99-198 and any amendments thereto. ...

  12. 7 CFR 906.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 906.2 Section 906.2 Agriculture Regulations of... GRANDE VALLEY IN TEXAS Order Regulating Handling Definitions § 906.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as re-enacted and amended by the Agricultural Marketing Agreement Act of...

  13. 7 CFR 946.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 946.2 Section 946.2 Agriculture Regulations of... Regulating Handling Definitions § 946.2 Act. Act means Public Act No. 10, 73d Congress, as amended and reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as...

  14. 7 CFR 989.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 989.2 Section 989.2 Agriculture Regulations of... CALIFORNIA Order Regulating Handling Definitions § 989.2 Act. Act means Public Act No. 10, 73d Congress, as amended, and as re-enacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended...

  15. 7 CFR 922.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 922.2 Section 922.2 Agriculture Regulations of... WASHINGTON Order Regulating Handling Definitions § 922.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of...

  16. 10 CFR 1017.4 - Definitions.

    Science.gov (United States)

    2010-01-01

    ..., experimental, or research-related part, subsection, design, or material used in the manufacture or utilization... General Overview § 1017.4 Definitions. As used in this part: Atomic Energy Act means the Atomic Energy Act... material in the research, development, production, or testing of nuclear weapons, nuclear weapon components...

  17. 7 CFR 956.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 956.2 Section 956.2 Agriculture Regulations of... OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Definitions § 956.2 Act. Act means Public Act No. 10... Agreement Act of 1937, as amended (Sec. 1-19, 48 Stat. 31, as amended; 7 U.S.C. 601 et seq.). ...

  18. 7 CFR 983.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 983.2 Section 983.2 Agriculture Regulations of... NEW MEXICO Definitions § 983.2 Act. Act means Public Act No. 10, 73rd Congress (May 12, 1933), as amended and as re-enacted and amended by the Agricultural Marketing Order Act of 1937, as amended (48 Stat...

  19. 7 CFR 930.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 930.1 Section 930.1 Agriculture Regulations of... Definitions § 930.1 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended, and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as...

  20. 7 CFR 984.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 984.2 Section 984.2 Agriculture Regulations of... Handling Definitions § 984.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C. 601 et seq.). ...

  1. 7 CFR 925.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 925.2 Section 925.2 Agriculture Regulations of... SOUTHEASTERN CALIFORNIA Definitions § 925.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...

  2. 7 CFR 915.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 915.2 Section 915.2 Agriculture Regulations of... Regulating Handling Definitions § 915.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...

  3. 7 CFR 959.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 959.2 Section 959.2 Agriculture Regulations of... Handling Definitions § 959.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (sections 1-19, 48 Stat...

  4. 7 CFR 905.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 905.2 Section 905.2 Agriculture Regulations of... TANGELOS GROWN IN FLORIDA Order Regulating Handling Definitions § 905.2 Act. Act means Public Act No. 10... Agreement Act of 1937, as amended. (48 Stat. 31, as amended; 7 U.S.C. 601 et seq.; 68 Stat. 906, 1047.) ...

  5. 7 CFR 955.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 955.2 Section 955.2 Agriculture Regulations of... § 955.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (Sec. 1-19, 48 Stat. 31, as...

  6. 7 CFR 982.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 982.2 Section 982.2 Agriculture Regulations of... Order Regulating Handling Definitions § 982.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C...

  7. 7 CFR 932.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 932.2 Section 932.2 Agriculture Regulations of... Handling Definitions § 932.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933) as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31...

  8. 7 CFR 981.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 981.2 Section 981.2 Agriculture Regulations of... Handling Definitions § 981.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as amended...

  9. 7 CFR 966.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 966.2 Section 966.2 Agriculture Regulations of... Handling Definitions § 966.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as amended...

  10. 7 CFR 916.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 916.2 Section 916.2 Agriculture Regulations of... Regulating Handling Definitions § 916.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...

  11. 7 CFR 993.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 993.2 Section 993.2 Agriculture Regulations of... Regulating Handling Definitions § 993.2 Act. Act means Public Act No. 10, 73d Congress, as amended and reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C. 601 et seq.). ...

  12. 7 CFR 929.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 929.2 Section 929.2 Agriculture Regulations of... ISLAND IN THE STATE OF NEW YORK Order Regulating Handling Definitions § 929.2 Act. Act means Public Act... Marketing Agreement Act of 1937, as amended (secs. 1-19, 48 Stat. 31, as amended; 7 U.S.C. 601-674). ...

  13. 7 CFR 923.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 923.2 Section 923.2 Agriculture Regulations of... IN WASHINGTON Order Regulating Handling Definitions § 923.2 Act. Act means Public Act No. 10, 73d... Act of 1937, as amended (48 Stat. 31, as amended; 7 U.S.C. 601 et seq.; 68 Stat. 906, 1047). ...

  14. 7 CFR 927.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 927.2 Section 927.2 Agriculture Regulations of... Regulating Handling Definitions § 927.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...

  15. 7 CFR 1170.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Act. 1170.2 Section 1170.2 Agriculture Regulations of... Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PRODUCT MANDATORY REPORTING § 1170.2 Act. Act means the Agricultural Marketing Act of 1946, 7 U.S.C. 1621 et seq., as amended by the Dairy Market Enhancement Act of...

  16. 7 CFR 953.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 953.2 Section 953.2 Agriculture Regulations of... Order Regulating Handling Definitions § 953.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as re-enacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C...

  17. 7 CFR 1160.101 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Act. 1160.101 Section 1160.101 Agriculture Regulations... Definitions § 1160.101 Act. Act means the Fluid Milk Promotion Act of 1990, Subtitle H of Title XIX of the Food, Agriculture, Conservation, and Trade Act of 1990, Public Law 101-624, 7 U.S.C. 6401-6417, and any...

  18. 7 CFR 948.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 948.2 Section 948.2 Agriculture Regulations of... Regulating Handling Definitions § 948.2 Act. Act means Public Act No. 10 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (sections 1-19, 48...

  19. National Competitiveness Act of 1993. Report of the Senate Committee on Commerce, Science, and Transportation together with Additional Views on S.4. 103d Congress, 1st Session.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Senate Committee on Commerce, Science, and Transportation.

    This report is a recommendation for passage of Senate bill S.4, the National Competitiveness Act of 1993, with an amendment. The purpose of this bill is to promote the industrial competitiveness and economic growth of the United States by strengthening and expanding the civilian technology programs of the Department of Commerce and amending the…

  20. Federal Act on the peaceful uses of atomic energy and protection against radiation

    International Nuclear Information System (INIS)

    1959-12-01

    This is a framework Act regulating the peaceful uses of atomic energy in Switzerland. It establishes a licensing and control system for the construction and operation of nuclear installations, transport and possession of nuclear substances as well as for other nuclear activities. The Act also defines the measures for protection against ionizing radiation and contains a series of provisions sanctioning any actions jeopardising nuclear safety or violating the Act itself. Chapter 4 (Sec. 12-18) dealing with nuclear third party liability is repealed and replaced by the Act of 1979 on nuclear third party liability. (NEA) [fr

  1. Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

    Science.gov (United States)

    Li, Longhu; Haider, Husnain Kh.; Wang, Linlin; Lu, Gang

    2012-01-01

    We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction. PMID:22447941

  2. 78 FR 29659 - Forfeiture Procedures Under the Endangered Species Act and the Lacey Act Amendments

    Science.gov (United States)

    2013-05-21

    .... APHIS-2007-0086] RIN 0579-AD50 Forfeiture Procedures Under the Endangered Species Act and the Lacey Act... Endangered Species Act of 1973, as amended (ESA), and the Lacey Act Amendments of 1981, as amended, that... INFORMATION: Background The Endangered Species Act (ESA) of 1973, as amended (16 U.S.C. 1531 et seq.), was...

  3. 7 CFR 920.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 920.2 Section 920.2 Agriculture Regulations of... § 920.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as amended; 7 U.S.C...

  4. 7 CFR 947.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 947.2 Section 947.2 Agriculture Regulations of... Definitions § 947.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as amended; 7 U.S.C. 601 et...

  5. 12 CFR 225.104 - “Services” under section 4(c)(1) of Bank Holding Company Act.

    Science.gov (United States)

    2010-01-01

    ... of advertising, public relations, developing new business, organizations, operations, preparing tax... on the later bill (“advertising, public relations, developing new business, organization, operations... used in a broad and general sense, the legislative history of the Bank Holding Company Act indicates...

  6. 29 CFR 4.114 - Subcontracts.

    Science.gov (United States)

    2010-07-01

    ... Secretary of Labor LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Application of the McNamara-O'Hara Service Contract Act Covered Contracts Generally § 4.114 Subcontracts. (a) “Contractor” as including “subcontractor... contractor undertakes a contract subject to the Act, the contractor agrees to assume the obligation that the...

  7. 77 FR 59990 - Workforce Investment Act; Native American Employment and Training Council Meeting

    Science.gov (United States)

    2012-10-01

    ... Committee Act (FACA) (Pub. L. 92-463), as amended, and Section 166(h)(4) of the Workforce Investment Act... written statements to Mrs. Evangeline M. Campbell, Designated Federal Official (DFO), U.S. Department of.... FOR FURTHER INFORMATION CONTACT: Mrs. Evangeline M. Campbell, DFO, Division of Indian and Native...

  8. 77 FR 69491 - Privacy Act of 1974: System of Records; Secure Flight Records

    Science.gov (United States)

    2012-11-19

    ... page at http://www.regulations.gov ; (2) Accessing the Government Printing Office's Web page at http...) of the Intelligence Reform and Terrorism Prevention Act of 2004 (IRTPA),\\4\\ Congress directed TSA and... Intelligence Agency, the Secretary of the Treasury, and the Secretary of Defense. The Attorney General, acting...

  9. Foreign Direct Investment and China’s Productivity Growth during the 1997 Asian Financial Crisis

    Directory of Open Access Journals (Sweden)

    Fulgence Dominick Waryoba

    2017-09-01

    Full Text Available The study estimates the fixed effect model using cross–section weights to estimate panel EGLS for 7 years in 29 regions of China. Though for the sample period, foreign direct investment influences productivity positively, the effect is very lower compared to other factors in the model. Conversely, labor has a very high influence on productivity for the period under consideration. Nevertheless, the years after 1997 have shown more productivity growth compared to the years before 1997. This is probably due to the fact that the government acted quickly to recover by boosting the external demand. Consequently, the contribution of export on productivity growth is significantly large. As long as China’s productivity keeps growing, high technological foreign direct investments will continue to flow into the economy. Chinese government should continue to invest in human capital to match with high technology embodied in foreign direct investments for the economy to continue experiencing high productivity growth.

  10. Nuclear Installations Act 1965

    International Nuclear Information System (INIS)

    1965-01-01

    This Act governs all activities related to nuclear installations in the United Kingdom. It provides for the licensing procedure for nuclear installations, the duties of licensees, the competent authorities and carriers of nuclear material in respect of nuclear occurrences, as well as for the system of third party liability and compensation for nuclear damage. The Act repeals the Nuclear Installations (Licensing and Insurance) Act 1959 and the Nuclear Installations (Amendment Act) 1965 except for its Section 17(2). (NEA) [fr

  11. Compounds acting against HIV: Imidazo[1,2-a]pyridines as non-nucleoside reverse transcriptase inhibitors (NNRTIs)

    CSIR Research Space (South Africa)

    Bode, M

    2010-09-01

    Full Text Available .6 µM N N NH Cl Res Act = 3% IC50 = 2 µM MAGI IC50 = 0.2 µM N N NH Cl Res Act = 5% IC50 = 3.5 µM MAGI IC50 = 0.18 µM N N NH Cl Res Act = 13% IC50 = 8 µM MAGI IC50 = 0.6 µM N N NH Cl Cl Res Act = 4% IC50 = 1.5 µM MAGI IC50... 2010 www.csir.co.za N N NH N N NH Cl N N NH Cl CN IC50= 4.4 uM (RT) IC50= 0.16 uM (PBMC) IC50= 0.41 uM (MAGI) cf . Nevirapine IC50=0.67 uM (RT) IC50=0.033 uM (PBMC) IC50= 29 uM (RT) IC50= 41 uM (PBMC) cf...

  12. ACT-R Electronic Bookshelf: An Adaptive System To Support Learning ACT-R on the Web.

    Science.gov (United States)

    Brusilovsky, Peter; Anderson, John

    This paper describes the electronic ACT-R Bookshelf, a system which supports learning ACT-R, a well-known theory in the field of cognitive psychology, over the World Wide Web. ACT-R Bookshelf is a collection of electronic books on various aspects of ACT-R. The primary role of ACT-R Bookshelf is to serve as a 24-hour information resource for…

  13. 75 FR 39669 - Privacy Act of 1974; System of Records

    Science.gov (United States)

    2010-07-12

    ...In accordance with the Privacy Act of 1974, as amended (Privacy Act), the Department of Education (Department) publishes this notice proposing to revise the system of records notice for the Hotline Complaint Files of the Inspector General (18-10-04), 64 FR 30157-59 (June 4, 1999). The Department proposes to amend this system of records notice by: (1) Adding that a purpose of the system is to report on complaints and allegations related to American Recovery and Reinvestment Act of 2009 (ARRA) funds to the Recovery Accountability and Transparency Board (RATB) as established by the ARRA (Pub. L. 111- 5); (2) adding a new routine use to allow the disclosure of ARRA- related complaints and allegations to the RATB; (3) adding a new routine use to allow for disclosure of information in connection with response and remedial efforts in the event of a data breach in accordance with Office of Management and Budget (OMB) requirements in M-07-16 (May 22, 2007); (4) revising the routine use ``Disclosure to Public and Private Sources in Connection with the Higher Education Act of 1965, as amended (HEA)'' to allow the disclosure of information to an educational institution or a school that is or was a party to an agreement with the Secretary of Education pursuant to the HEA; and (5) updating the address of the System Manager.

  14. 75 FR 41239 - Sunshine Act; Notice of Meeting

    Science.gov (United States)

    2010-07-15

    ... LEGAL SERVICES CORPORATION Sunshine Act; Notice of Meeting TIME AND DATE: The Legal Services Corporation Board of Directors' Search Committee for LSC President (``Search Committee'' or ``Committee'') will meet on July 20, 2010. The meeting will begin at 4 p.m. (Central Daylight Savings Time) and...

  15. 29 CFR 1621.4 - Effect of opinions and interpretations of the Commission.

    Science.gov (United States)

    2010-07-01

    .... 1621.4 Section 1621.4 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURES-THE EQUAL PAY ACT § 1621.4 Effect of opinions and interpretations of the Commission. (a) Section 10 of the Portal to Portal Act of 1947, 29 U.S.C. 255, which applies to the Equal Pay Act of 1963...

  16. Radiological Protection Act 1970

    International Nuclear Information System (INIS)

    1970-01-01

    This Act provides for the establishment of a Radiological Protection Board to undertake research and advise on protection from radiation hazards. Its functions include provision of advice to Government departments with responsibilities in relation to protection of sectors of the community or the community as a whole against the hazards of ionizing radiation. The Act, which lays down that the Board shall replace certain departments concerned with radiation protection, repeals several Sections of the Radioactive Substances Act 1948 and the Science and Technology Act 1965. (NEA) [fr

  17. Chloroquinone Inhibits Cell Proliferation and Induces Apoptosis in ...

    African Journals Online (AJOL)

    Apoptosis in Nasopharyngeal Carcinoma Cell Lines. Xin-Qing ... However, this requires clinical investigation to ascertain its ... results to restrict the growth of tumors locally in addition ..... MEK1/ERK1/2/iNOS/sGC/PKG pathway associated with.

  18. A perspective on the PCPNDT Act

    Directory of Open Access Journals (Sweden)

    A Murali Mohan Patnaik

    2012-01-01

    Full Text Available Background: An important modern diagnostic tool, used for monitoring pregnancy and genetic defects; the ultrasound machine, has also become a selective killer of the female child. The male child preference in India was responsible for female infanticides in the past. With easy availability and accessibility of USG, a shift has occurred from infanticide to feticide, although female infanticides still continue. In the process doctors are blamed as "merchants of death". Peeved and pressed by national and internal agencies for the declining female child ratio (0-6 years, the Government of India reacted by enacting a stringent PC-PNDT Act almost solely aimed at doctors to prevent them from advertising and disclosing the sex of the fetus to the pregnant woman or her relatives. Since the enactment, hundreds of cases have been launched against the doctors. Aims: 1. In order to stand up to the law important sections and rules of the PC-PNDT Act have been analyzed for the benefit of our colleagues. 2. The Indian legal system rests the "burden of proof" on the prosecution. In two sections of The Act, these have been done away with. Instead, the accused doctor has to prove himself innocent. Therefore a demand has been made to make suitable amendments to The Act in this regard. 3. The inclusion of column numbers 9-19 in the form ′F′ is not relevant for USG clinics/ imaging centers; inaccurate filling of which may attract a prison sentence of 3 years. This irrelevance has to be deleted. 4. Some suggestions.

  19. 7 CFR 1250.302 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1250.302 Section 1250.302 Agriculture... Research and Promotion Order Definitions § 1250.302 Act. Act means the Egg Research and Consumer Information Act and as it may be amended (Pub. L. 93-428). ...

  20. 7 CFR 201.56-4 - Cucurbit family, (Cucurbitaceae).

    Science.gov (United States)

    2010-01-01

    ... SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Germination Tests in the Administration of the Act § 201.56-4... necrosis or decay. (Remove any attached seed coats at the end of the test period for evaluation of...

  1. 40 CFR 146.4 - Criteria for exempted aquifers.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General Provisions § 146.4 Criteria... of a permit application for a Class II or III operation to contain minerals or hydrocarbons that... public water system. (Clean Water Act, Safe Drinking Water Act, Clean Air Act, Resource Conservation and...

  2. Acts of Research

    DEFF Research Database (Denmark)

    Nelund, Sidsel

    place mostly in seminars and articles, in which knowledge is often discussed as an intrinsic quality of the artwork. Acts of Research, however, is devoted to studying the rise of knowledge production in contemporary art from the perspective of artistic, curatorial and educational research...... described as knowledge producers and exhibitions and art works as instances of knowledge production. Acts of Research: Knowledge Production in Contemporary Arts between Knowledge Economy and Critical Practices analyses this development. The academic discussion of knowledge production in the arts has taken...... with an awareness of larger political, economic, geographical and art-related aspects. The concept of ‘acts of research’ is suggested as a way to understand knowledge production as a creative act in which research carried out in relation to a specific material challenges and resists the protocols of conventional...

  3. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yinxia; Zhao, Yunli; Huang, Xu; Lin, Xingfeng; Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

    2013-01-01

    Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  4. 7 CFR 1205.302 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1205.302 Section 1205.302 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Research and Promotion Order Definitions § 1205.302 Act. Act means the Cotton Research and Promotion Act...

  5. 7 CFR 1220.600 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1220.600 Section 1220.600 Agriculture... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.600 Act. Act means the Soybean, Promotion, Research, and Consumer Information Act set forth in title XIX, subtitle E, of the Food...

  6. 7 CFR 1220.101 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1220.101 Section 1220.101 Agriculture... CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.101 Act. The term Act means the Soybean Promotion, Research, and Consumer Information Act, subtitle E of title XIX, of the Food...

  7. 34 CFR 303.6 - Act.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Act. 303.6 Section 303.6 Education Regulations of the..., Eligibility, and Other General Provisions § 303.6 Act. As used in this part, Act means the Individuals with Disabilities Education Act. (Authority: 20 U.S.C. 1400) ...

  8. Negative social acts and pain: evidence of a workplace bullying and 5-HTT genotype interaction.

    Science.gov (United States)

    Jacobsen, Daniel Pitz; Nielsen, Morten Birkeland; Einarsen, Ståle; Gjerstad, Johannes

    2018-05-01

    Objectives Long-term exposure to systematic negative acts at work, usually labeled workplace bullying, is a prevalent problem at many workplaces. The adverse effects of such exposure may range from psychological symptoms, such as depression and anxiety to somatic ailments like cardiovascular disease and musculoskeletal complaints. In this study, we examined the relationships among exposure to negative acts, genetic variability in the 5-HTT gene SLC6A4 and pain. Methods The study was based on a nationally representative survey of 987 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to bullying in the workplace was measured with the 9-item version of the Negative Acts Questionnaire - Revised (NAQ-R) inventory. Pain was rated using an 11-point (0-10) numeric rating scale (NRS). Genotyping with regard to SLC6A4 was carried out using a combination of gel-electrophoresis and TaqMan assay. Results The data revealed a significant interaction between exposure to negative acts and the SLC6A4 genotype with regard to pain (linear regression with 5000 resamples; age, sex, tobacco use and education were included as covariates). The relationship between negative acts and pain intensity was significantly stronger for subjects with the LALA genotype than for subjects with the SLA/LALG/SLG genotype. No significant difference between subjects with the LALA genotype and SS genotype was observed. Conclusions Our data demonstrated that the relationship between bullying and pain was modified by the 5-HTT genotype, ie, genetic variation in SLC6A4. The association between negative acts and health among vulnerable individuals appeared more potent than previously reported.

  9. The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Yun; Wang, Shunchang; Luo, Xun; Yang, Yanan; Jian, Fenglei; Wang, Xuemin; Xie, Lucheng

    2014-08-01

    The induction of apoptosis is recognized to be a major mechanism of tributyltin (TBT) toxicity. However, the underlying signaling pathways for TBT-induced apoptosis remain unclear. In this study, using the nematode Caenorhabditis elegans, we examined whether DNA damage response (DDR) pathway and mitogen-activated protein kinase (MAPK) signaling cascades are involved in TBT-induced germline apoptosis and cell cycle arrest. Our results demonstrated that exposing worms to TBT at the dose of 10nM for 6h significantly increased germline apoptosis in N2 strain. Germline apoptosis was absent in strains that carried ced-3 or ced-4 loss-of-function alleles, indicating that both caspase protein CED-3 and Apaf-1 protein CED-4 were required for TBT-induced apoptosis. TBT-induced apoptosis was blocked in the Bcl-2 gain-of-function strain ced-9(n1950), whereas TBT induced a minor increase in the BH3-only protein EGL-1 mutated strain egl-1(n1084n3082). Checkpoint proteins HUS-1 and CLK-2 exerted proapoptotic effects, and the null mutation of cep-1, the homologue of tumor suppressor gene p53, significantly inhibited TBT-induced apoptosis. Apoptosis in the loss-of-function strains of ERK, JNK and p38 MAPK signaling pathways were completely or mildly suppressed under TBT stress. These results were supported by the results of mRNA expression levels of corresponding genes. The present study indicated that TBT-induced apoptosis required the core apoptotic machinery, and that DDR genes and MAPK pathways played essential roles in signaling the processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. 12 CFR 225.109 - “Services” under section 4(c)(1) of Bank Holding Company Act.

    Science.gov (United States)

    2010-01-01

    ..., investment counseling”) and in the Committee Report on the later bill (“advertising, public relations... for exemption. The legislative history of the Act, however, as indicated in the relevant portion of... banking subsidiary of the holding company which the legislative history clearly indicates does not come...

  11. 7 CFR 1150.101 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Act. 1150.101 Section 1150.101 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Definitions § 1150.101 Act. Act means Title I, Subtitle B, of the Dairy and Tobacco Adjustment Act of 1983...

  12. 16 CFR 304.4 - Application of other law or regulation.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Application of other law or regulation. 304.4 Section 304.4 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE HOBBY PROTECTION ACT § 304.4 Application of other law or...

  13. 75 FR 41370 - Regulations Implementing the Freedom of Information Act

    Science.gov (United States)

    2010-07-16

    ... updates paragraph (a) to reflect the new maintenance of statistics requirements in the OPEN Government Act... 2201.4 is amended: 0 a. By revising paragraphs (c) introductory text, (c)(1), (3), (4), and (5); 0 b...) introductory text; 0 b. Adding paragraph (b)(2)(v); and 0 c. Revising paragraph (e). The revisions and addition...

  14. 7 CFR 1280.101 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1280.101 Section 1280.101 Agriculture... INFORMATION ORDER Lamb Promotion, Research, and Information Order Definitions § 1280.101 Act. Act means the Commodity Promotion, Research, and Information Act of 1996 (7 U.S.C. 7411-7425; Pub. L. 104-127; 110 Stat...

  15. 12 CFR 541.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Act. 541.2 Section 541.2 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY DEFINITIONS FOR REGULATIONS AFFECTING FEDERAL SAVINGS ASSOCIATIONS § 541.2 Act. The term Act means the Home Owners' Loan Act of 1933, as amended. ...

  16. 7 CFR 1207.302 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1207.302 Section 1207.302 Agriculture... Potato Research and Promotion Plan Definitions § 1207.302 Act. Act means the Potato Research and Promotion Act, Title III of Public Law 91-670, 91st Congress, approved January 11, 1971, 84 Stat. 2041, as...

  17. 7 CFR 985.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 985.2 Section 985.2 Agriculture Regulations of... SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Definitions § 985.2 Act. Act means Public Act No. 10, 73d Congress, as amended, and reenacted and amended by the Agricultural Marketing...

  18. 7 CFR 1230.601 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1230.601 Section 1230.601 Agriculture... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.601 Act. The term Act means the Pork Promotion, Research, and Consumer Information Act of 1985 (7 U.S.C. 4801-4819) and any...

  19. 29 CFR 401.17 - Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Act. 401.17 Section 401.17 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.17 Act. Act means the Labor-Management Reporting and Disclosure Act...

  20. 7 CFR 1221.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1221.1 Section 1221.1 Agriculture Regulations of... INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.1 Act. Act means the Commodity Promotion, Research, and Information Act of 1996 (7 U.S.C. 7411-7425), and any amendments thereto. ...

  1. 7 CFR 958.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 958.2 Section 958.2 Agriculture Regulations of... IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Definitions § 958.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing...

  2. Isolation of a novel promoter for efficient protein expression by Aspergillus oryzae in solid-state culture.

    Science.gov (United States)

    Bando, Hiroki; Hisada, Hiromoto; Ishida, Hiroki; Hata, Yoji; Katakura, Yoshio; Kondo, Akihiko

    2011-11-01

    A novel promoter from a hemolysin-like protein encoding the gene, hlyA, was characterized for protein overexpression in Aspergillus oryzae grown in solid-state culture. Using endo-1,4-β-glucanase from A. oryzae (CelA) as the reporter, promoter activity was found to be higher than that of the α-amylase (amyA) and manganese superoxide dismutase (sodM) genes not only in wheat bran solid-state culture but also in liquid culture. Expression of the A. oryzae endoglucanase CelB and two heterologous endoglucanases (TrEglI and TrEglIII from Trichoderma reesei) under the control of the hlyA promoter were also found to be stronger than under the control of the amyA promoter in A. oryzae grown in wheat bran solid-state culture, suggesting that the hlyA promoter may be useful for the overproduction of other proteins as well. In wheat bran solid-state culture, the productivity of the hlyA promoter in terms of protein produced was high when the cultivation temperature was 30°C or 37°C, when the water content was 0.6 or 0.8 ml/g wheat bran, and from 48 to 72 h after inoculation. Because A. oryzae sporulated actively under these conditions and because hemolysin has been reported to play a role in fungal fruiting body formation, high-level expression of hlyA may be related to sporulation.

  3. Hanford Site National Environmental Policy Act (NEPA) Characterization Report

    Energy Technology Data Exchange (ETDEWEB)

    Neitzel, Duane A.; Bunn, Amoret L.; Cannon, Sandra D.; Duncan, Joanne P.; Fowler, Richard A.; Fritz, Brad G.; Harvey, David W.; Hendrickson, Paul L.; Hoitink, Dana J.; Horton, Duane G.; Last, George V.; Poston, Ted M.; Prendergast-Kennedy, Ellen L.; Reidel, Steve P.; Rohay, Alan C.; Scott, Michael J.; Thorne, Paul D.

    2004-09-22

    This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the sixteenth revision of the original document published in 1988 and is (until replaced by the seventeenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety and health, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities.

  4. 12 CFR 404.6 - Release of records under the Freedom of Information Act.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Release of records under the Freedom of Information Act. 404.6 Section 404.6 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.6 Release of...

  5. 14 CFR 374.3 - Compliance with the Consumer Credit Protection Act and regulations.

    Science.gov (United States)

    2010-01-01

    ... requirements of the Consumer Credit Protection Act, 15 U.S.C. 1601-1693r. Any violation of the following... PROTECTION ACT WITH RESPECT TO AIR CARRIERS AND FOREIGN AIR CARRIERS § 374.3 Compliance with the Consumer... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Compliance with the Consumer Credit...

  6. 7 CFR 1218.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1218.1 Section 1218.1 Agriculture Regulations of... INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.1 Act. Act means the Commodity Promotion, Research, and Information Act of 1996 (7 U.S.C. 7401-7425; Pub. L. 104-127; 110 Stat...

  7. 7 CFR 1216.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1216.1 Section 1216.1 Agriculture Regulations of... ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.1 Act. Act means the Commodity Promotion, Research, and Information Act of 1996 (7 U.S.C. 7401-7425; Public Law 104-127, 110 Stat...

  8. 7 CFR 1206.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1206.1 Section 1206.1 Agriculture Regulations of... Mango Promotion, Research, and Information Order Definitions § 1206.1 Act. Act means the Commodity Promotion, Research, and Information Act of 1996 (7 U.S.C. 7411-7425; Public Law 104-127; 110 Stat. 1029...

  9. 7 CFR 1212.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1212.1 Section 1212.1 Agriculture Regulations of..., Consumer Education, and Industry Information Order Definitions § 1212.1 Act. “Act” means the Commodity Promotion, Research, and Information Act of 1996, (7 U.S.C. 7411-7425), and any amendments to that Act. ...

  10. 7 CFR 1219.1 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1219.1 Section 1219.1 Agriculture Regulations of... INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.1 Act. Act means the Hass Avocado Promotion, Research, and Information Act of 2000, Public Law 106-387, 7 U.S.C. 7801-7813...

  11. 7 CFR 945.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 945.2 Section 945.2 Agriculture Regulations of... COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Definitions § 945.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing...

  12. The Advanced Communications Technology Satellite (ACTS) capabilities for serving science

    Science.gov (United States)

    Meyer, Thomas R.

    1990-01-01

    Results of research on potential science applications of the NASA Advanced Communications Technology Satellite (ACTS) are presented. Discussed here are: (1) general research on communications related issues; (2) a survey of science-related activities and programs in the local area; (3) interviews of selected scientists and associated telecommunications support personnel whose projects have communications requirements; (4) analysis of linkages between ACTS functionality and science user communications activities and modes of operation; and (5) an analysis of survey results and the projection of conclusions to a national scale.

  13. Six Acts of Miscognition: Implications for Art Education

    Science.gov (United States)

    Tavin, Kevin M.

    2010-01-01

    Employing Lacanian theory as a necessary supplement to contemporary approaches in art education, this article provides a critique and response to art education discourse around "cognition." This response unfolds in six acts: (1) Unknown knowledge, (2) Unmeant knowledge, (3) Missing metaphors, (4) Stupidity, (5) Symptoms and sinthomes, and (6)…

  14. 77 FR 23173 - Privacy Act of 1974: Implementation

    Science.gov (United States)

    2012-04-18

    ... a significant economic impact on a substantial number of small entities. Paperwork Reduction Act The... governments, and the private sector. UMRA requires a written statement of economic and regulatory alternatives... subsections (c)(3); (d)(1), (2), (3) and (4); and (e)(1): (1) Air Intelligence Program (Justice/DEA-001) (2...

  15. The Radiation Protection Act

    International Nuclear Information System (INIS)

    Persson, L.

    1989-01-01

    The new Radiation Protection Act (1988:220) entered into force in Sweden on July 1st, 1988. This book presents the Act as well as certain regulations connected to it. As previously, the main responsibility for public radiation protection will rest with one central radiation protection authority. According to the 1988 Act, the general obligations with regard to radiation protection will place a greater responsibility than in the past on persons carrying out activities involving radiation. Under the act, it is possible to adjust the licensing and supervisory procedures to the level of danger of the radiation source and the need for adequate competence, etc. The Act recognises standardised approval procedures combined with technical regulations for areas where the risks are well known. The Act contains several rules providing for more effective supervision. The supervising authority may in particular decide on the necessary regulations and prohibitions for each individual case. The possibilities of using penal provisions have been extended and a rule on the mandatory execution of orders has been introduced. The Ordinance on Radiation Protection (1988:293) designates the National Institute of Radiation Protection (SSI) as the central authority referred to in the Radiation Protection Act. The book also gives a historic review of radiation protection laws in Sweden, lists regulations issued by SSI and presents explanations of radiation effects and international norms in the area. (author)

  16. Canada's Clean Air Act

    International Nuclear Information System (INIS)

    2006-01-01

    This paper provided an outline of Canada's Clean Air Act and examined some of the regulatory changes that will occur as a result of its implementation. The Act is being introduced to strengthen the legislative basis for taking action on reducing air pollution and GHGs, and will allow the government to regulate both indoor and outdoor air pollutants and GHGs. The Act will require the Ministers of the Environment and Health to establish national air quality objectives, as well as to monitor and report on their attainment. The Canadian Environmental Protection Act will be amended to enable the government to regulate the blending of fuels and their components. The Motor Vehicle Fuel Consumption Standards Act will also be amended to enhance the government's authority to regulate vehicle fuel efficiency. The Energy Efficiency Act will also be expanded to allow the government to set energy efficiency standards and labelling requirements for a wider range of consumer and commercial products. The Act will commit to short, medium and long-term industrial air pollution targets. Regulations will be proposed for emissions from industry; on-road and off-road vehicles and engines; and consumer and commercial products. It was concluded that the Government of Canada will continue to consult with provinces, territories, industries and Canadians to set and reach targets for the reduction of both indoor and outdoor air pollutants and GHG emissions. 6 figs

  17. 40 CFR 1508.2 - Act.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Act. 1508.2 Section 1508.2 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY TERMINOLOGY AND INDEX § 1508.2 Act. Act means the National Environmental Policy Act, as amended (42 U.S.C. 4321, et seq.) which is also referred to as “NEPA.” ...

  18. 22 CFR 901.10 - Act.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Act. 901.10 Section 901.10 Foreign Relations FOREIGN SERVICE GRIEVANCE BOARD GENERAL Meanings of Terms As Used in This Chapter § 901.10 Act. Act means the Foreign Service Act of 1980 (Pub. L. 96-465, October 17, 1980), as amended. [56 FR 55458, Oct. 28...

  19. 7 CFR 924.2 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 924.2 Section 924.2 Agriculture Regulations of... WASHINGTON AND IN UMATILLA COUNTY, OREGON Order Regulating Handling Definitions § 924.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as re-enacted and amended by the Agricultural...

  20. 7 CFR 1205.10 - Act.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1205.10 Section 1205.10 Agriculture Regulations... for Conduct of Sign-up Period Definitions § 1205.10 Act. The term Act means the Cotton Research and Promotion Act, as amended [7 U.S.C 2101-2118; Public Law 89-502, 80 Stat 279, as amended]. ...

  1. 75 FR 22320 - Regulations Implementing the Freedom of Information Act

    Science.gov (United States)

    2010-04-28

    ... reflect the new maintenance of statistics requirements in the OPEN Government Act. 5 U.S.C. 552(e). III... 2201.4 is amended: a. By revising paragraphs (c) introductory text, (c)(1), (3), (4), and (5); b. By.... Revising paragraphs (b)(1) and (b)(2) introductory text; b. Adding paragraph (b)(2)(v); and c. Revising...

  2. Protein kinase A-dependent Neuronal Nitric Oxide Synthase Activation Mediates the Enhancement of Baroreflex Response by Adrenomedullin in the Nucleus Tractus Solitarii of Rats

    Directory of Open Access Journals (Sweden)

    Ho I-Chun

    2011-05-01

    Full Text Available Abstract Background Adrenomedullin (ADM exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA, or neuronal nitric oxide synthase (nNOS. We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR response. It remains unclear whether ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS. Methods Intravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope. Results We found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM22-52 or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after intra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phosphorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons. Conclusions The novel finding of this study is that the signal transduction cascade that

  3. 75 FR 33608 - Privacy Act of 1974; System of Records

    Science.gov (United States)

    2010-06-14

    ...In accordance with the Privacy Act of 1974, as amended (Privacy Act), the Department of Education (Department) publishes this notice proposing to revise the system of records notice for the Investigative Files of the Inspector General (18-10-01), 68 FR 38154 (June 26, 2003). The Department proposes to amend this system of records notice by: (1) Adding a new routine use to allow reporting on the activities of the Inspector General regarding American Recovery and Reinvestment Act funds to the Recovery Accountability and Transparency Board (RATB) as established by the American Recovery and Reinvestment Act of 2009 (Pub. L. 111-5); (2) adding a new routine use to allow for disclosure of information in connection with response and remedial efforts in the event of a data breach in accordance with Office of Management and Budget (OMB) requirements in M-07-16 (May 22, 2007); (3) revising routine uses ``(12) Disclosure to the President's Council on Integrity and Efficiency'' and ``(13) Disclosure for Qualitative Assessment Reviews'' to allow reporting on the activities of the Inspector General to the Council of Inspectors General on Integrity and Efficiency (formerly the President's Council on Integrity and Efficiency) as established by the Inspector General Reform Act of 2008 (Pub. L. 110-409); (4) revising the routine use ``(4) Disclosure to Public and Private Sources in Connection with the Higher Education Act of 1965, as Amended (HEA)'' to allow the disclosure of information to an educational institution or a school that is or was a party to an agreement with the Secretary of Education pursuant to the HEA; and (5) updating the system location addresses. This system of records provides essential support for investigative activities of the Office of Inspector General (OIG) relating to the Department's programs and operations, enabling the OIG to secure and maintain the necessary information and to coordinate with other law enforcement agencies as appropriate.

  4. 32 CFR 292.4 - Specific policy.

    Science.gov (United States)

    2010-07-01

    ... INFORMATION ACT PROGRAM DEFENSE INTELLIGENCE AGENCY (DIA) FREEDOM OF INFORMATION ACT § 292.4 Specific policy... of source and object codes, regardless of medium are not agency records. (This does not include the... existing computer program or printout for retrieval of the requested information. (c) The prior application...

  5. 77 FR 36231 - Americans With Disabilities Act (ADA) and Architectural Barriers Act (ABA) Accessibility...

    Science.gov (United States)

    2012-06-18

    ...-0004] RIN 3014-AA39 Americans With Disabilities Act (ADA) and Architectural Barriers Act (ABA... (ADA) and Architectural Barriers Act (ABA) Accessibility Guidelines to specifically address emergency... ensure that newly constructed and altered emergency transportable housing units covered by the ADA or ABA...

  6. 75 FR 47312 - Board Meeting; Sunshine Act Meetings

    Science.gov (United States)

    2010-08-05

    ... INTER-AMERICAN FOUNDATION Board Meeting; Sunshine Act Meetings Time and Date: August 9, 2010, 8:30 a.m.-5:30 p.m.. Place: 101 Constitution Avenue, Washington, DC 20001. Status: Closed session as provided in 22 CFR 1004.4(f). Matters to be Considered: Executive Session. Portions to be Closed to the...

  7. Act No. 11/87 of 7 april - Basic environment act

    International Nuclear Information System (INIS)

    1987-04-01

    The purpose of this Act is to provide the basis for an environmental policy in Portugal. Section 25 of the Act deals with radioactive substances. It provides that any contamination likely to be caused by these substances should be controlled with a view to preventing its effects on the health and welfare of the population and specifies the methods for such control [fr

  8. 7 CFR 33.4 - Carrier.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Carrier. 33.4 Section 33.4 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.4 Carrier. Carrier means any common or...

  9. 36 CFR 705.4 - Reproduction.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Reproduction. 705.4 Section 705.4 Parks, Forests, and Public Property LIBRARY OF CONGRESS REPRODUCTION, COMPILATION, AND....4 Reproduction. (a) Library of Congress staff acting under the general authority of the Librarian of...

  10. DVD. Sweeney Todd : Fleet Streeti deemonlik habemeajaja / Egle Loo

    Index Scriptorium Estoniae

    Loo, Egle

    2008-01-01

    Lühiarvustus õudusmuusikalist "Sweeney Todd : The Demon Barber of Fleet Street" Stephen Sondheimi muusikali alusel : režissöör Tim Burton : peaosades Johnny Depp, Helena Bonham Carter : Ameerika Ühendriigid - Suurbritannia 2007

  11. Sõjast ei jää keegi puutumata / Egle Loo

    Index Scriptorium Estoniae

    Loo, Egle

    2010-01-01

    Režissöör Jim Sheridani film "Vennad" (USA, 2009), peaosades Jake Gyllenhaal ja Tobey Maguire. Film on Taani režissööri Susanne Bieri samanimelise filmi uusversioon (Taani-Suurbritannia-Rootsi-Norra, 2004)

  12. 75 FR 55618 - Board of Governors; Sunshine Act Meeting

    Science.gov (United States)

    2010-09-13

    ... POSTAL SERVICE Board of Governors; Sunshine Act Meeting DATES AND TIMES: Tuesday, September 21... 21, at 10 a.m. (Closed) 1. Strategic Issues. 2. Pricing. 3. Financial Matters. 4. Personnel Matters and Compensation Issues. 5. Governors' Executive Session--Discussion of prior agenda items and Board...

  13. Outer Continental Shelf Lands Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data represents geographic terms used within the Outer Continental Shelf Lands Act (OCSLA or Act). The Act defines the United States outer continental shelf...

  14. On the redshift distribution and physical properties of ACT-selected DSFGs

    Science.gov (United States)

    Su, T.; Marriage, T. A.; Asboth, V.; Baker, A. J.; Bond, J. R.; Crichton, D.; Devlin, M. J.; Dünner, R.; Farrah, D.; Frayer, D. T.; Gralla, M. B.; Hall, K.; Halpern, M.; Harris, A. I.; Hilton, M.; Hincks, A. D.; Hughes, J. P.; Niemack, M. D.; Page, L. A.; Partridge, B.; Rivera, J.; Scott, D.; Sievers, J. L.; Thornton, R. J.; Viero, M. P.; Wang, L.; Wollack, E. J.; Zemcov, M.

    2017-01-01

    We present multi-wavelength detections of nine candidate gravitationally lensed dusty star-forming galaxies (DSFGs) selected at 218 GHz (1.4 mm) from the Atacama Cosmology Telescope (ACT) equatorial survey. Among the brightest ACT sources, these represent the subset of the total ACT sample lying in Herschel SPIRE fields, and all nine of the 218 GHz detections were found to have bright Herschel counterparts. By fitting their spectral energy distributions (SEDs) with a modified blackbody model with power-law temperature distribution, we find the sample has a median redshift of z=4.1^{+1.1}_{-1.0} (68 per cent confidence interval), as expected for 218 GHz selection, and an apparent total infrared luminosity of log _{10}(μ L_IR/L_{odot }) = 13.86^{+0.33}_{-0.30}, which suggests that they are either strongly lensed sources or unresolved collections of unlensed DSFGs. The effective apparent diameter of the sample is sqrt{μ }d= 4.2^{+1.7}_{-1.0} kpc, further evidence of strong lensing or multiplicity, since the typical diameter of DSFGs is 1.0-2.5 kpc. We emphasize that the effective apparent diameter derives from SED modelling without the assumption of optically thin dust (as opposed to image morphology). We find that the sources have substantial optical depth (tau = 4.2^{+3.7}_{-1.9}) to dust around the peak in the modified blackbody spectrum (λobs ≤ 500 μm), a result that is robust to model choice.

  15. On the Redshift Distribution and Physical Properties of ACT-Selected DSFGs

    Science.gov (United States)

    Su, T.; Marriage, T. A.; Asboth, V.; Baker, A. J.; Bond, J. R.; Crichton, D.; Devlin, M. J.; Dunner, R.; Farrah, D.; Frayer, D. T.; hide

    2016-01-01

    We present multi-wavelength detections of nine candidate gravitationally-lensed dusty starforming galaxies (DSFGs) selected at 218 GHz (1.4 mm) from the ACT equatorial survey. Among the brightest ACT sources, these represent the subset of the total ACT sample lying in Herschel SPIRE fields, and all nine of the 218 GHz detections were found to have bright Herschel counterparts. By fitting their spectral energy distributions (SEDs) with a modified blackbody model with power-law temperature distribution, we find the sample has a median redshift of 4.1 (+ 1.1, -10) (68 percent confidence interval), as expected for 218 GHz selection and an apparent total infrared luminosity of log 10(uL(sub IR)/solar luminosity) = 13.86(+0.33, -0.30), which suggests that they are either strongly lensed sources or unresolved collections of unlensed DSFGs. The effective apparent diameter of the sample is square root of mu d = 4.2 (+ 1.7, -1.0) kpc, further evidence of strong lensing of multiplicity, since the typical diameter of dusty star-forming galaxies is 1.0-2.5 kpc. We emphasize that the effective apparent diameter derives from SED modeling without the assumption of opticaly thin dust (as opposed to image morphology). We find that the sources have substantial optical depth (tau = (4.2+, -1.9) of dust around the peak in the modified blackbody spectrum (lambda obs is less than 500 micrometers), a result that is robust to model choice.

  16. Collective speech acts

    NARCIS (Netherlands)

    Meijers, A.W.M.; Tsohatzidis, S.L.

    2007-01-01

    From its early development in the 1960s, speech act theory always had an individualistic orientation. It focused exclusively on speech acts performed by individual agents. Paradigmatic examples are ‘I promise that p’, ‘I order that p’, and ‘I declare that p’. There is a single speaker and a single

  17. Legislation on carriage of dangerous goods. Acts - directives - exemptions. 2. rev. ed.

    International Nuclear Information System (INIS)

    Vogt, H.W.

    1993-01-01

    This compact paperback edition presents the essential chapters of volume 3 'Acts, directives, exemptions' of the publication ''A handbook for dangerous goods officers''. Contents: (1) Act on the Carriage of Dangerous Goods. (2) Ordinance concerning Dangerous Goods Officers (GbV). (3) Legislative intent pursued with the GbV. (4) Instructions for implementation of the GbV. (5) Ordinance on Road Transport of Dangerous Goods (GGVS). (6) Annex A and B of the GGVS. The updating and amendment of the ADR provisions for harmonisation with the international classification schemes and hence the complete revision of categories 4.1, 4.2, 4.3, 5.1, 5.2, and 9, as well as the harmonisation of GGVS provisions with ADR provisions fall both under the 4th Amending Ordinance. This 4th Ordinance Amending the GGVS, passed by the Bundesrat on March 5, 1993 and announced on April 23, 1993, is, of course, part of this edition. Professional subscribers to the publication will prefer the loose-leaf edition of the Handbook for Dangerous Goods Officers, for easy updating of their reference source. (orig./HP) [de

  18. Roles of Endoplasmic Reticulum Stress in NECA-Induced Cardioprotection against Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Fengmei Xing

    2017-01-01

    Full Text Available Objective. This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R injury via glycogen synthase kinase 3β (GSK-3β and the mitochondrial permeability transition pore (mPTP through inhibition of endoplasmic reticulum stress (ERS. Methods and Results. H9c2 cells were exposed to H2O2 for 20 minutes. NECA significantly prevented H2O2-induced TMRE fluorescence reduction, indicating that NECA inhibited the mPTP opening. NECA blocked H2O2-induced GSK-3β phosphorylation and GRP94 expression. NECA increased GSK-3β phosphorylation and decreased GRP94 expression, which were prevented by both ERS inductor 2-DG and PKG inhibitor KT5823, suggesting that NECA may induce cardioprotection through GSK-3β and cGMP/PKG via ERS. In isolated rat hearts, both NECA and the ERS inhibitor TUDCA decreased myocardial infarction, increased GSK-3β phosphorylation, and reversed GRP94 expression at reperfusion, suggesting that NECA protected the heart by inhibiting GSK-3β and ERS. Transmission electron microscopy showed that NECA and TUDCA reduced mitochondrial swelling and endoplasmic reticulum expansion, further supporting that NECA protected the heart by preventing the mPTP opening and ERS. Conclusion. These data suggest that NECA prevents the mPTP opening through inactivation of GSK-3β via ERS inhibition. The cGMP/PKG signaling pathway is responsible for GSK-3β inactivation by NECA.

  19. 26 CFR 1.6072-3 - Income tax due dates postponed in case of China Trade Act corporations.

    Science.gov (United States)

    2010-04-01

    ... Trade Act corporations. 1.6072-3 Section 1.6072-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT... Documents § 1.6072-3 Income tax due dates postponed in case of China Trade Act corporations. (a) With... tax return of any corporation organized under the China Trade Act of 1922 (15 U.S.C. ch. 4), as...

  20. Learning dialog act processing

    OpenAIRE

    Wermter, Stefan; Löchel, Matthias

    1996-01-01

    In this paper we describe a new approach for learning dialog act processing. In this approach we integrate a symbolic semantic segmentation parser with a learning dialog act network. In order to support the unforeseeable errors and variations of spoken language we have concentrated on robust data-driven learning. This approach already compares favorably with the statistical average plausibility method, produces a segmentation and dialog act assignment for all utterances in a robust manner,...

  1. 78 FR 27233 - Clean Water Act: Availability of List Decisions

    Science.gov (United States)

    2013-05-09

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9811-4] Clean Water Act: Availability of List Decisions AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: This notice announces the availability of EPA's action identifying water quality limited segments and associated...

  2. 76 FR 59073 - Privacy Act

    Science.gov (United States)

    2011-09-23

    ... CENTRAL INTELLIGENCE AGENCY 32 CFR Part 1901 Privacy Act AGENCY: Central Intelligence Agency. ACTION: Proposed rule. SUMMARY: Consistent with the Privacy Act (PA), the Central Intelligence Agency...-1379. SUPPLEMENTARY INFORMATION: Consistent with the Privacy Act (PA), the CIA has undertaken and...

  3. ST–ACTS

    DEFF Research Database (Denmark)

    Gidofalvi, Gyozo; Pedersen, Torben Bach

    2006-01-01

    hot issue in the area of spatio–temporal databases [7]. While existing Moving Object Simulators (MOSs) address different physical aspects of mobility, they neglect the important social and geo–demographical aspects of it. This paper presents ST–ACTS, a Spatio–Temporal ACTivity Simulator that, using...... various geo–statistical data sources and intuitive principles, models the so far neglected aspects. ST–ACTS considers that (1) objects (representing mobile users) move from one spatio–temporal location to another with the objective of performing a certain activity at the latter location; (2) not all users...

  4. The CCR4 Deadenylase Acts with Nanos and Pumilio in the Fine-Tuning of Mei-P26 Expression to Promote Germline Stem Cell Self-Renewal

    Science.gov (United States)

    Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

    2013-01-01

    Summary Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation. PMID:24286029

  5. The CCR4 deadenylase acts with Nanos and Pumilio in the fine-tuning of Mei-P26 expression to promote germline stem cell self-renewal.

    Science.gov (United States)

    Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

    2013-01-01

    Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation.

  6. Inhibitor of differentiation 4 (Id4) is a potential tumor suppressor in prostate cancer

    International Nuclear Information System (INIS)

    Carey, Jason PW; Asirvatham, Ananthi J; Galm, Oliver; Ghogomu, Tandeih A; Chaudhary, Jaideep

    2009-01-01

    Inhibitor of differentiation 4 (Id4), a member of the Id gene family is also a dominant negative regulator of basic helix loop helix (bHLH) transcription factors. Some of the functions of Id4 appear to be unique as compared to its other family members Id1, Id2 and Id3. Loss of Id4 gene expression in many cancers in association with promoter hypermethylation has led to the proposal that Id4 may act as a tumor suppressor. In this study we provide functional evidence that Id4 indeed acts as a tumor suppressor and is part of a cancer associated epigenetic re-programming. Data mining was used to demonstrate Id4 expression in prostate cancer. Methylation specific polymerase chain reaction (MSP) analysis was performed to understand molecular mechanisms associated with Id4 expression in prostate cancer cell lines. The effect of ectopic Id4 expression in DU145 cells was determined by cell cycle analysis (3H thymidine incorporation and FACS), expression of androgen receptor, p53 and cyclin dependent kinase inhibitors p27 and p21 by a combination of RT-PCR, real time-PCR, western blot and immuno-cytochemical analysis. Id4 expression was down-regulated in prostate cancer. Id4 expression was also down-regulated in prostate cancer line DU145 due to promoter hyper-methylation. Ectopic Id4 expression in DU145 prostate cancer cell line led to increased apoptosis and decreased cell proliferation due in part by an S-phase arrest. In addition to S-phase arrest, ectopic Id4 expression in PC3 cells also resulted in prolonged G2/M phase. At the molecular level these changes were associated with increased androgen receptor (AR), p21, p27 and p53 expression in DU145 cells. The results suggest that Id4 acts directly as a tumor suppressor by influencing a hierarchy of cellular processes at multiple levels that leads to a decreased cell proliferation and change in morphology that is possibly mediated through induction of previously silenced tumor suppressors

  7. Resource Conservation and Recovery Act, Part B Permit Application

    International Nuclear Information System (INIS)

    1991-02-01

    The Waste Isolation Pilot Plant (WIPP) project was authorized by the Department of Energy National Security and Military Applications of Nuclear Energy Authorization Act of 1980 (Public Law 96-164) as a research and development facility to demonstrate the safe, environmentally sound disposal of transuranic (TRU) radioactive wastes derived from the defense activities of the United States. The WIPP facility is owned and operated by the US Department of Energy (DOE). The TRU waste to be received at WIPP consists largely of such items as laboratory glassware and utensils, tools, scrap metal, shielding, personnel protection equipment, and solidified sludges from the treatment of waste water. Approximately 60 percent of this waste is ''mixed,'' that is, it is also contaminated with hazardous waste or hazardous waste constituents as defined by the Resource Conservation and Recovery Act (RCRA) and by the New Mexico Hazardous Waste Management Regulations (HWMR-5). Therefore, emplacement of TRU mixed waste in the WIPP repository is subject to regulation under HWMR-5 and RCRA. The permit application under the Resource Conservation and Recovery Act for WIPP is divided into five volumes. This document, Volume 4, contains Appendices C3, C4, and D1--D10. These appendices cover information on environmental impacts, site characterization, geology and hydrology of the area, monitoring of the environment, compatibility of waste forms and containers, and removal of volatile organic compounds (VOC)

  8. 29 CFR 4.106 - [Reserved

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true [Reserved] 4.106 Section 4.106 Labor Office of the Secretary of Labor LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Application of the McNamara-O'Hara Service Contract Act Introductory § 4.106 [Reserved] Agencies Whose Contracts May Be Covered ...

  9. Bill C-5, an act to amend the radiation emitting devices act

    International Nuclear Information System (INIS)

    1984-01-01

    This Act, entitled Bill C-5, allows for a series of amendments to the Radiation Emitting Devices Act. The amendments relate to regulations concerned with the sale, lease or import, labelling, advertising, packaging, safety standards and inspection of radiation emitting devices

  10. 19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

    Science.gov (United States)

    2010-04-01

    ... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION... Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a) Plant... the plant quarantine regulations. (b) Federal Food, Drug, and Cosmetic Act. The entry of food products...

  11. The Price-Anderson Act

    International Nuclear Information System (INIS)

    Jones, R.

    2000-01-01

    The Price-Anderson Act establishes nuclear liability law in the United States. First passed in 1957, it has influenced other nuclear liability legislation around the world. The insurer response the nuclear accident at Three Mile Island in 1979 demonstrates the application of the Act in a real life situation. The Price-Anderson Act is scheduled to be renewed in 2002, and the future use of commercial nuclear power in tge United States will be influenced by this renewal. (author)

  12. The Nuclear Waste Policy Act, as amended, with appropriations acts appended. Revision 1

    International Nuclear Information System (INIS)

    1995-02-01

    This act provides for the development of repositories for the disposal of high-level radioactive wastes, low-level radioactive wastes, and spent nuclear fuels. In addition, it establishes research and development programs, as well as demonstration programs regarding the disposal of these wastes. This Act consists of the Act of Jan. 7, 1983 (Public Law 97-425; 96 Stat. 2201), as amended by Public Law 100-203 and Public Law 102-486

  13. 76 FR 12370 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-ASTM...

    Science.gov (United States)

    2011-03-07

    ... Production Act of 1993--ASTM International Standards Notice is hereby given that, on February 4, 2011... seq. (``the Act''), ASTM International Standards (``ASTM'') has filed written notifications.... Specifically, ASTM has provided an updated list of current, ongoing ASTM standards activities originating...

  14. No 592 - Radiation Act

    International Nuclear Information System (INIS)

    1991-01-01

    This Act will enter into force on 1 January 1992. The scope of the Act is extensive as, in addition to ionizing radiation, it will also apply to activities involving exposure to natural radiation and non-ionizing radiation. Its purpose is to prevent and restrict harmful effects to health resulting from radiation. The basic principles of the Act are that the practice involving radiation should be justified; radiation protection should be optimized; and radiation doses should be as low as reasonably achievable. Licensed organisations using radiation will be responsible for the safety of the activity involving exposure to radiation and for having available the appropriate expertise to this effect. The required so-called safety licence provides the regulatory control to ensure that radiation is used sensibly, that the equipment and shields are technically acceptable and the operating personnel is competent, and that the radioactive waste is dealt with appropriately. The Radiation Act will also apply to nuclear activities within the scope of the 1987 Nuclear Energy Act [fr

  15. 76 FR 17712 - Sunshine Act; Notice Of Agency Meeting

    Science.gov (United States)

    2011-03-30

    ... NATIONAL CREDIT UNION ADMINISTRATION Sunshine Act; Notice Of Agency Meeting TIME AND DATE: 9:30 a.m., Monday, April 4, 2011. PLACE: Westin San Diego Hotel, Board Room, 3rd Floor, 400 West Broadway, San Diego, CA 92101. STATUS: Closed. MATTERS TO BE CONSIDERED: 1. Consideration of Supervisory...

  16. The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases

    Science.gov (United States)

    Orchard, Sandra; Ammari, Mais; Aranda, Bruno; Breuza, Lionel; Briganti, Leonardo; Broackes-Carter, Fiona; Campbell, Nancy H.; Chavali, Gayatri; Chen, Carol; del-Toro, Noemi; Duesbury, Margaret; Dumousseau, Marine; Galeota, Eugenia; Hinz, Ursula; Iannuccelli, Marta; Jagannathan, Sruthi; Jimenez, Rafael; Khadake, Jyoti; Lagreid, Astrid; Licata, Luana; Lovering, Ruth C.; Meldal, Birgit; Melidoni, Anna N.; Milagros, Mila; Peluso, Daniele; Perfetto, Livia; Porras, Pablo; Raghunath, Arathi; Ricard-Blum, Sylvie; Roechert, Bernd; Stutz, Andre; Tognolli, Michael; van Roey, Kim; Cesareni, Gianni; Hermjakob, Henning

    2014-01-01

    IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org). PMID:24234451

  17. 75 FR 44811 - Sunshine Act Meeting of the Board of Directors and Five Board Committees

    Science.gov (United States)

    2010-07-29

    ... Virtual Board Manual 4. Consider and act on Committee Self-Evaluation Forms 5. Discussion of LSC research... i. Presentation by Mattie Cohan, Senior Assistant General Counsel ii. Comment by Laurie Tarantowicz, Assistant Inspector General and Legal Counsel iii. Public Comment 5. Consider and act on the proposed 2011...

  18. Environmental impact assessment modern dressed? To the amendment of the EIA act and other acts and regulations

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2017-01-01

    On 22 December 2016, the Federal Ministry for the Environment (BMUB) presented the ''Draft Act for the Modernization of the Act on the Environmental Impact Assessment'' within the framework of the association consultation, as well as the ''Draft first Ordinance Amending the Ordinance on the Approval Procedure - 9. BImSchV''. The EIA Modernization Act as well as the Atomic Act Procedure Regulation and the Federal Mining Act should be revised by terms of an omnibus act. The association consultation was held on 18 January 2017.

  19. Hanford Site National Environmental Policy Act (NEPA) Characterization, Revision 15

    Energy Technology Data Exchange (ETDEWEB)

    Neitzel, Duane A.; Bunn, Amoret L.; Burk, Kenneth W.; Cannon, Sandra D.; Duncan, Joanne P.; Fowler, Richard A.; Fritz, Brad G.; Harvey, David W.; Hendrickson, Paul L.; Horton, Duane G.; Last, George V.; Poston, Ted M.; Prendergast-Kennedy, Ellen L.; Reidel, Steve P.; Scott, Michael J.; Thorne, Paul D.; Woody, Dave M.

    2003-09-01

    This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the thirteenth revision of the original document published in 1988 and is (until replaced by the fourteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities.

  20. Pharmacokinetics of Short- and Long-acting Formulations of Oxytetracycline After Intramuscular Administration in Chickens.

    Science.gov (United States)

    Gberindyer, Aondover F; Okpeh, Ene R; Semaka, Asaaga A

    2015-12-01

    Both short- and long-acting formulations of oxytetracycline are commonly used in veterinary medicine to treat animals infected with gram-negative and gram-positive bacteria, rickettsiae, mycoplasma, and chlamydiae. To compare pharmacokinetics of short- and long-acting oxytetracycline in chickens, injectable formulations from the same pharmaceutical company were administered to healthy 6-week-old broiler chickens in accordance to the labeled instructions. Fourteen chickens were separated into 2 groups: chickens in group A (n = 7) were administered the short-acting formulation (10 mg/kg IM q24h) for 4 consecutive days, whereas those in group B (n = 7) were treated with a single dose (20 mg/kg IM) of the long-acting formulation. Blood samples were collected into heparinized tubes before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 24 hours after initial treatment. Thereafter, blood samples were taken every 24 hours up to 120 hours. Plasma concentrations of oxytetracycline were determined by competitive enzyme-linked immunoabsorbent assay, and pharmacokinetic parameters were obtained. Both formulations delivered therapeutic plasma concentrations of oxytetracycline for approximately 100% of their respective dosing intervals as recommended. However, considering the additional labor, patient stress, and mortalities associated with handling, in addition to rejection of the carcass due to tissue necrosis resulting from multiple injections, we recommend use of the long-acting instead of the short-acting injectable formulation in broiler chickens.

  1. 29 CFR 4.120 - Contracts for public utility services.

    Science.gov (United States)

    2010-07-01

    ... McNamara-O'Hara Service Contract Act Specific Exclusions § 4.120 Contracts for public utility services. The Act, in paragraph (5) of section 7, exempts from its provisions “any contract for public utility... regulation, are not exempt from the Act. Among the contracts included in the exemption would be those between...

  2. 75 FR 63204 - Sunshine Act Meeting of the Board of Directors and Its Committees; Amended Notice; Changes to...

    Science.gov (United States)

    2010-10-14

    ... the Audit Committee. 14. Consider and act on the report of the Operations & Regulations Committee 15. Consider and act on the report of the Governance & Performance Review Committee. 16. Consider and act on..., 2010. Patricia D. Batie, Corporate Secretary. [FR Doc. 2010-26078 Filed 10-12-10; 4:15 pm] BILLING CODE...

  3. Macoilin, a conserved nervous system-specific ER membrane protein that regulates neuronal excitability.

    Directory of Open Access Journals (Sweden)

    Fausto Arellano-Carbajal

    2011-03-01

    Full Text Available Genome sequence comparisons have highlighted many novel gene families that are conserved across animal phyla but whose biological function is unknown. Here, we functionally characterize a member of one such family, the macoilins. Macoilins are characterized by several highly conserved predicted transmembrane domains towards the N-terminus and by coiled-coil regions C-terminally. They are found throughout Eumetazoa but not in other organisms. Mutants for the single Caenorhabditis elegans macoilin, maco-1, exhibit a constellation of behavioral phenotypes, including defects in aggregation, O₂ responses, and swimming. MACO-1 protein is expressed broadly and specifically in the nervous system and localizes to the rough endoplasmic reticulum; it is excluded from dendrites and axons. Apart from subtle synapse defects, nervous system development appears wild-type in maco-1 mutants. However, maco-1 animals are resistant to the cholinesterase inhibitor aldicarb and sensitive to levamisole, suggesting pre-synaptic defects. Using in vivo imaging, we show that macoilin is required to evoke Ca²(+ transients, at least in some neurons: in maco-1 mutants the O₂-sensing neuron PQR is unable to generate a Ca²(+ response to a rise in O₂. By genetically disrupting neurotransmission, we show that pre-synaptic input is not necessary for PQR to respond to O₂, indicating that the response is mediated by cell-intrinsic sensory transduction and amplification. Disrupting the sodium leak channels NCA-1/NCA-2, or the N-,P/Q,R-type voltage-gated Ca²(+ channels, also fails to disrupt Ca²(+ responses in the PQR cell body to O₂ stimuli. By contrast, mutations in egl-19, which encodes the only Caenorhabditis elegans L-type voltage-gated Ca²(+ channel α1 subunit, recapitulate the Ca²(+ response defect we see in maco-1 mutants, although we do not see defects in localization of EGL-19. Together, our data suggest that macoilin acts in the ER to regulate assembly or

  4. Preschools Under the Fair Labor Standards Act, July 1972.

    Science.gov (United States)

    Employment Standards Administration (DOL), Washington, DC. Wage and Hour Div.

    This pamphlet provides general information concerning the application of the Fair Labor Standards Act to employees of preschool centers. Included is a discussion of: (1) Basic Monetary Requirements, including minimum wages and facilities furnished to the preschool employees, (2) Equal Pay Provisions, (3) Overtime, (4) Hours Worked, (5) Exemptions,…

  5. 12 CFR 404.4 - Request requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Request requirements. 404.4 Section 404.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.4 Request requirements. (a) Form. Requests...

  6. 29 CFR 1926.15 - Relationship to the Service Contract Act; Walsh-Healey Public Contracts Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Relationship to the Service Contract Act; Walsh-Healey Public Contracts Act. 1926.15 Section 1926.15 Labor Regulations Relating to Labor (Continued... FOR CONSTRUCTION General Interpretations § 1926.15 Relationship to the Service Contract Act; Walsh...

  7. 32 CFR 174.4 - Policy.

    Science.gov (United States)

    2010-07-01

    ... COMMUNITIES AND ADDRESSING IMPACTS OF REALIGNMENT Policy § 174.4 Policy. It is DoD policy to: (a) Act... 32 National Defense 1 2010-07-01 2010-07-01 false Policy. 174.4 Section 174.4 National Defense... will, when feasible, be accelerated to facilitate the transfer of real property for community reuse. In...

  8. 76 FR 18365 - Fair Credit Reporting Act and Bank Secrecy Act Compliance

    Science.gov (United States)

    2011-04-04

    ... Procedure Act (APA), an agency may, for good cause, find (and incorporate the finding and a brief statement... and comment procedures prescribed by the APA are unnecessary because the final rule makes technical... Asked Questions, and the FFIEC Bank Secrecy Act/Anti-Money Laundering Examination Manual. (iii...

  9. 29 CFR 4.142 - Contracts in an indefinite amount.

    Science.gov (United States)

    2010-07-01

    ... McNamara-O'Hara Service Contract Act Determining Amount of Contract § 4.142 Contracts in an indefinite amount. (a) Every contract subject to this Act which is indefinite in amount is required to contain the....), a case arising under the Walsh-Healey Public Contracts Act. Such a contract, which may be in the...

  10. Costs and outcome of assertive community treatment (ACT) in a rural area in Denmark

    DEFF Research Database (Denmark)

    Hastrup, Lene Halling; Aagaard, Jørgen

    2015-01-01

    Purpose: Health economic evidence of assertive community treatment (ACT) in Denmark is limited. The aim of the study was to assess the costs and outcome of ACT among 174 patients with severe and persistent mental illness in a rural area of Denmark. Methods: The study was based on a quasi-experime......Purpose: Health economic evidence of assertive community treatment (ACT) in Denmark is limited. The aim of the study was to assess the costs and outcome of ACT among 174 patients with severe and persistent mental illness in a rural area of Denmark. Methods: The study was based on a quasi...... only. Results: Seventy eight percent of the patients receiving ACT were in contact with psychiatric services at the 4-year follow-up, while 69% of the patients in the control group had contact with psychiatric services (P

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Therapeutics Lab Developing New Treatments The CF Foundation offers a number of resources for learning about clinical ... her father: Demonstrate and discuss common ACT therapies Offer their tips for fitting ACTs into daily life ...

  12. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

  13. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    In situ real-time evaluation of radiation-responsive promoters in the extremely radioresistant microbe Deinococcus radiodurans · Narasimha Anaganti Bhakti Basu Shree Kumar Apte · More Details Abstract Fulltext PDF. A third generation promoter probe shuttle vector pKG was constructed, using the green fluorescent ...

  14. 45 CFR 2508.19 - What Privacy Act exemptions or control of systems of records are exempt from disclosure?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false What Privacy Act exemptions or control of systems of records are exempt from disclosure? 2508.19 Section 2508.19 Public Welfare Regulations Relating to... ACT OF 1974 § 2508.19 What Privacy Act exemptions or control of systems of records are exempt from...

  15. 23 CFR 633.211 - Implementation of the Clean Air Act and the Federal Water Pollution Control Act.

    Science.gov (United States)

    2010-04-01

    ... Water Pollution Control Act. 633.211 Section 633.211 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT...) implementing requirements with respect to the Clean Air Act and the Federal Water Pollution Control Act are... Contracts (Appalachian Contracts) § 633.211 Implementation of the Clean Air Act and the Federal Water...

  16. 17 CFR 275.206(4)-4 - Financial and disciplinary information that investment advisers must disclose to clients.

    Science.gov (United States)

    2010-04-01

    ... information that investment advisers must disclose to clients. 275.206(4)-4 Section 275.206(4)-4 Commodity and... disclose to clients. (a) It shall constitute a fraudulent, deceptive, or manipulative act, practice, or... fail to disclose to any client or prospective client all material facts with respect to: (1) A...

  17. VizieR Online Data Catalog: ACT high significance 148 and 218GHz sources (Marsden+, 2014)

    Science.gov (United States)

    Marsden, D.; Gralla, M.; Marriage, T. A.; Switzer, E. R.; Partridge, B.; Massardi, M.; Morales, G.; Addison, G.; Bond, J. R.; Crichton, D.; Das, S.; Devlin, M.; Dunner, R.; Hajian, A.; Hilton, M.; Hincks, A.; Hughes, J. P.; Irwin, K.; Kosowsky, A.; Menanteau, F.; Moodley, K.; Niemack, M.; Page, L.; Reese, E. D.; Schmitt, B.; Sehgal, N.; Sievers, J.; Staggs, S.; Swetz, D.; Thornton, R.; Wollack, E.

    2014-11-01

    The ACT experiment (Swetz et al., 2011ApJS..194...41S) is situated on the slopes of Cerro Toco in the Atacama Desert of Chile at an elevation of 5190m. ACT's latitude gives access to both the northern and southern celestial hemispheres. Observations occurred simultaneously in three frequency bands, at 148GHz (2.0mm), 218GHz (1.4mm) and 277GHz (1.1mm) with angular resolutions of roughly 1.4 , 1.0 and 0.9-arcmin, respectively. (1 data file).

  18. Political insights on implementing the Nuclear Waste Policy Act of 1982

    International Nuclear Information System (INIS)

    Edwards, J.B.

    1986-01-01

    The author discusses the options available for implementing the Nuclear Waste Policy Act (NWPA) of 1982. The author concludes that the federal and state governments must cooperate because this is a political problem. Two sites must be selected because this gets the Western states supporting the act and provides a backup if problems develop at one site. The author says once 2-4 sites are chosen as finalists, an educational campaign must be done in those states to stress safety. Solving the waste problem will give the nuclear industry a brighter future

  19. Marine Mammal Protection Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Marine Mammal Protection Act (MMPA or Act) prohibits, with certain exceptions, the "take" of marine mammals in U.S. waters and by U.S. citizens on the high seas,...

  20. Atomic Energy Act (AtG) and subordinate legislation. 19. ed.

    International Nuclear Information System (INIS)

    Ziegler, E.

    1995-01-01

    This 19th edition covers the amendments added since the 17th edition ( March 1994 ) referring to the following: (1) AtG sections 7 and 9a (Artikelgesetz, as of 19.7. 1994, published in BGBl I, p. 1618 ff); (2) incorporation of the legal requirements governing the environmental impact statement (EIS) in compliance with the EIS Act (UVPG) into the Nuclear Installations Ordinance (BGBl I, p. 181 ff); (3) amendment of the Radiation Protection Ordinance (StrlSchV) in sections 6, 22, 31, 42, 87, sub-sec. 2, due to the new act on medical products, in section 41 due to the amended act on health care facilities and services, and in section 87, sub-sec. 1 due to section 7 of the 31st penal reform law - 2nd law to combat environmental crime; (4) amendment of the Preventive Radiation Protection Act in section 11, extension of competence of the BfS (Federal Rad. Prot. Office); (5) amendment of the Penal Code, environmental crime committed by release of ionizing radiation, or faulty construction of a nuclear installation; (6) update of provisions concerning competences of the federal states in implementation of nuclear laws. In the 19th edition of the commentary, the numbering of the various acts and ordinances, and the relevant page numbering have been completely revised. (HP) [de

  1. Radiation-induced apoptosis and developmental disturbance of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Inouye, Minoru [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1995-03-01

    The developing mammalian brain is highly susceptible to ionizing radiation. A significant increase in small head size and mental retardation has been noted in prenatally exposed survivors of the atomic bombing, with the highest risk in those exposed during 8-15 weeks after fertilization. This stage corresponds to day 13 of pregnancy for mice and day 15 for rats in terms of brain development. The initial damage produced by radiation at this stage is cell death in the ventricular zone (VZ) of the brain mantle, the radiosensitive germinal cell population. During histogenesis of the cerebellum the external granular layer (EGL) is also radiosensitive. Although extensive cell death results in microcephaly and histological abnormlity, both VZ and EGL have an ability to recover from a considerable cell loss and form the normal structure of the central nervous system. The number of cell deaths to induce tissue abnormalities in adult brain rises in the range of 15-25% of the germinal cell population; and the threshold doses are about 0.3 Gy for cerebral defects and 1 Gy for cerebellar anomalies in both mice and rats. A similar threshold level is suggested in human cases in induction of mental retardation. Radiation-induced cell death in the VZ and EGL has been revealed as apoptosis, by the nuclear and cytoplasmic condensation, transglutaminase activation, required macromolecular synthesis, and internucleosomal DNA cleavage. Apoptosis of the germinal cell is assumed to eliminate acquired genetic damage. Once an abnormality in DNA has been induced and fixed in a germinal cell, it would be greatly amplified during future proliferation. These cells would commit suicide when injured for replacement by healthy cells, rather than undertake DNA repair. In fact they show very slow repair of cellular damage. Thus the high sensitivity of undifferentiated neural cells to the lethal effect of radiation may constitute a biological defense mechanism. (author) 69 refs.

  2. Radiation-induced apoptosis and developmental disturbance of the brain

    International Nuclear Information System (INIS)

    Inouye, Minoru

    1995-01-01

    The developing mammalian brain is highly susceptible to ionizing radiation. A significant increase in small head size and mental retardation has been noted in prenatally exposed survivors of the atomic bombing, with the highest risk in those exposed during 8-15 weeks after fertilization. This stage corresponds to day 13 of pregnancy for mice and day 15 for rats in terms of brain development. The initial damage produced by radiation at this stage is cell death in the ventricular zone (VZ) of the brain mantle, the radiosensitive germinal cell population. During histogenesis of the cerebellum the external granular layer (EGL) is also radiosensitive. Although extensive cell death results in microcephaly and histological abnormlity, both VZ and EGL have an ability to recover from a considerable cell loss and form the normal structure of the central nervous system. The number of cell deaths to induce tissue abnormalities in adult brain rises in the range of 15-25% of the germinal cell population; and the threshold doses are about 0.3 Gy for cerebral defects and 1 Gy for cerebellar anomalies in both mice and rats. A similar threshold level is suggested in human cases in induction of mental retardation. Radiation-induced cell death in the VZ and EGL has been revealed as apoptosis, by the nuclear and cytoplasmic condensation, transglutaminase activation, required macromolecular synthesis, and internucleosomal DNA cleavage. Apoptosis of the germinal cell is assumed to eliminate acquired genetic damage. Once an abnormality in DNA has been induced and fixed in a germinal cell, it would be greatly amplified during future proliferation. These cells would commit suicide when injured for replacement by healthy cells, rather than undertake DNA repair. In fact they show very slow repair of cellular damage. Thus the high sensitivity of undifferentiated neural cells to the lethal effect of radiation may constitute a biological defense mechanism. (author) 69 refs

  3. Visbyst Lissaboni Stockholmi kaudu / Reet Varblane

    Index Scriptorium Estoniae

    Varblane, Reet, 1952-

    1998-01-01

    Nelja Läänemere regiooni naiskunstniku Ene-Liis Semperi (videoinstallatsioon "Endspiel"), Anita Zabilevska, Egle Rakauskaite ja Ann-Sofi Sidéni ühisnäitus "Kauged tuletornid" Portugalis Almadas galeriis "Fabrica". Näituse eellugu, kuraatorid. Kogu projekti kuraator Norbert Weber, eesti kuraator Ando Keskküla. Eksponeeritud töödest. Balti kunsti keskusest Visbyl

  4. Modulation of Caenorhabditis elegans transcription factor activity by HIM-8 and the related Zinc-Finger ZIM proteins.

    Science.gov (United States)

    Sun, Hongliu; Nelms, Brian L; Sleiman, Sama F; Chamberlin, Helen M; Hanna-Rose, Wendy

    2007-10-01

    The previously reported negative regulatory activity of HIM-8 on the Sox protein EGL-13 is shared by the HIM-8-related ZIM proteins. Furthermore, mutation of HIM-8 can modulate the effects of substitution mutations in the DNA-binding domains of at least four other transcription factors, suggesting broad regulatory activity by HIM-8.

  5. Isolation of a human anti-epidermal growth factor receptor Fab antibody, EG-19-11, with subnanomolar affinity from naïve immunoglobulin repertoires using a hierarchical antibody library system.

    Science.gov (United States)

    Hur, Byung-ung; Yoon, Jae-bong; Liu, Li-Kun; Cha, Sang-hoon

    2010-11-30

    Specific antibodies that possess a subnanomolar affinity are very difficult to obtain from human naïve immunoglobulin repertoires without the use of lengthy affinity optimization procedures. Here, we designed a hierarchical phage-displayed antibody library system to generate an enormous diversity of combinatorial Fab fragments (6×10(17)) and attempted to isolate high-affinity Fabs against the human epidermal growth factor receptor (EGFR). A primary antibody library, designated HuDVFab-8L, comprising 4.5×10(9) human naïve heavy chains and eight unspecified human naïve light chains was selected against the EGFR-Fc protein by biopanning, and four anti-EGFR Fab clones were isolated. Because one of the Fab clones, denoted EG-L2-11, recognized a native EGFR expressed on A431 cells, the heavy chain of the Fab was shuffled with a human naïve light chain repertoire with a diversity of 1.4×10(8) and selected a second time against the EGFR-Fc protein again. One EG-L2-11 variant, denoted EG-19-11, recognized an EGFR epitope that was almost the same as that bound by cetuximab and had a K(D) of approximately 540 pM for soluble EGFR, which is about 7-fold higher than that of the FabC225 derived from cetuximab. This variant was also internalized by A431 cells, likely via receptor-mediated endocytosis, and it efficiently inhibited EGF-mediated tyrosine phosphorylation of the EGFR. These results demonstrate that the use of our hierarchical antibody library system is advantageous in generating fully human antibodies especially with a therapeutic purpose. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. 16 CFR 1031.4 - Effect of voluntary standards activities on Commission activities.

    Science.gov (United States)

    2010-01-01

    ... Safety Act, the Federal Hazardous Substances Act, or the Flammable Fabrics Act, as may be applicable.... 2058, section 3(f) of the Federal Hazardous Substances Act, 15 U.S.C. 1262(f), or section 4(a) of the Flammable Fabrics Act, 15 U.S.C. 1193(g), as may be applicable. In commencing such a proceeding, the...

  7. overhauling the national industrial court act: a pathway to effective ...

    African Journals Online (AJOL)

    DJFLEX

    GLOBAL JOURNAL OF SOCIAL SCIENCES VOL 9, NO. 1, 2010: ... PATHWAY TO EFFECTIVE LABOUR DISPUTE SETTLEMENT IN ... For more than four (4) decades, labour ... settlement machinery provides meaningful approach to ..... economy. The National Industrial Court Act 2006 would have very positive effect on our ...

  8. Monitoring the persistence of a genetically modified strain of the Azorhizobium caulinodans in the rhizosphere of Triticum aestivum L.

    Directory of Open Access Journals (Sweden)

    Jan Jacek Slaski

    2013-01-01

    Full Text Available A protocol was developed to monitor persistence and spread of a genetically modified strain of the growth promoting diazotroph Azorhizobium caulinodans used to inoculate field grown wheat. The protocol was used to identify an endogluconase (egl overproducing strain of A. caulinodans isolated from inoculated soils. A detection limit of 2500 cfu g-1 and 108_1010cfu g-1 of soil was determined using the BIOLOG® fingerprinting method and PCR technique, respectively. Since none of the tested samples were positive for the bacteria or the Egl 1 gene construct, it was concluded that A. caulinodans ORS 571 pGV910-C1 did not persist or spread in any of the tested field locations. This result may be due to low soil temperatures and competition of indigenous microorganisms: environmental factors that were not favorable for the diazotroph to thrive in the test locations. The application of different inoculation methodologies, as well as the study of other rhizobial genera for the inoculation of wheat in further experiments, is strongly recommended. Key words: detection, diazotroph, endogluconase, ORS 571, wheat

  9. 9 CFR 4.11 - Stipulations.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Stipulations. 4.11 Section 4.11 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE ANIMAL WELFARE ACT Supplemental Rules of...

  10. Preventive Radiation Protection Act

    International Nuclear Information System (INIS)

    Roewer, H.

    1988-01-01

    The commentary is intended to contribute to protection of the population by a practice-oriented discussion and explanation of questions arising in connection with the Preventive Radiation Protection Act. Leaving aside discussions about abandonment of nuclear power, or criticism from any legal point of view, the commentary adopts the practical approach that accepts, and tries to help implementing, the act as it is. It is a guide for readers who are not experts in the law and gives a line of orientation by means of explanations and sometimes by citations from other acts (in footnotes). The commentary also presents the EURATOM Directive No. 3954/87 dated 22 December 1987, the EC Directive No. 3955/87 dated 22 December 1987, and the EC Directive No. 1983/88 dated 5 July 1988. A tabular survey shows the system of duties and competences defined by the Preventive Radiation Protection Act. (RST) [de

  11. Cerebellum developmental challenges: From morphology to molecular issues

    Directory of Open Access Journals (Sweden)

    Andrei Cosma

    2017-06-01

    Full Text Available Introduction: It is known that, throughout the development of the nervous system, the cellular migratory routes are an important part of its expansion; therefore, the cerebellum is ‘sprinkled’ with cellular changes during its growth. The aim of this study was to analyse the morphological features of the cerebellum cells in all the layers, during its development. Material and methods: We examined 14 cases of human cerebellum, ranging between 1 to 12 months by histopathology and immunohistochemistry. Results: Haematoxylin and eosin staining method confirmed the age-linked migration of the cells from the external granular layer into the internal granular layer. Moreover, immunohistochemical evaluation using PROX1 and NFAP showed positivity for the Purkinje cells. However, these cells exposed negativity on NSE stained specimens. On the other hand, the transience of the EGL was analyzed using OCT3/4, which showed the migration of the EGL cells through the molecular layer to the IGL. Also, GFAP and NFAP proved to be a useful tool for the identification of the climbing fibres and the variation of their density connected the age of the patient. Conclusions: The human cerebellum undergoes different morphological and molecular changes throughout its evolution during embryogenesis. The markers used in our study have proved to present a differential, stage-dependant reactivity and appeared as useful tools for the identification of different cerebellar structures. Our study is a challenging attempt to understand the basics of cerebellar development at a morphological and molecular level and may bring new perspectives for a better approach of cerebellar associated pathologies.

  12. CEREBELLUM DEVELOPMENTAL CHALLENGES: FROM MORPHOLOGY TO MOLECULAR ISSUES

    Directory of Open Access Journals (Sweden)

    Andrei Cosma ¹

    2017-10-01

    Full Text Available INTRODUCTION: It is known that, throughout the development of the nervous system, the cellular migratory routes are an important part of its expansion; therefore, the cerebellum is ‘sprinkled’ with cellular changes during its growth. The aim of this study was to analyse the morphological features of the cerebellum cells in all the layers, during its development. MATERIAL AND METHODS: We examined 14 cases of human cerebellum, ranging between 1 month to 12 years by histopathology and immunohistochemistry. RESULTS: Haematoxylin and eosin staining method confirmed the age-linked migration of the cells from the external granular layer into the internal granular layer. Moreover, immunohistochemical evaluation using PROX1 and NFAP showed positivity for the Purkinje cells. However, these cells exposed negativity on NSE stained specimens. On the other hand, the transience of the EGL was analysed using OCT3/4, which showed the migration of the EGL cells through the molecular layer to the IGL. Also, GFAP and NFAP proved to be a useful tool for the identification of the climbing fibres and the variation of their density connected the age of the patient. CONCLUSIONS: The human cerebellum undergoes different morphological and molecular changes throughout its evolution during embryogenesis. The markers used in our study have proved to present a differential, stage-dependant reactivity and appeared as useful tools for the identification of different cerebellar structures. Our study is a challenging attempt to understand the basics of cerebellar development at a morphological and molecular level and may bring new perspectives for a better approach of cerebellar associated pathologies.

  13. 28 CFR 49.4 - Deputy custodians.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Deputy custodians. 49.4 Section 49.4 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) ANTITRUST CIVIL PROCESS ACT § 49.4 Deputy custodians. Deputy custodians may perform such of the duties assigned to the custodian as may be authorized...

  14. 15 CFR 4.9 - Business Information.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Business Information. 4.9 Section 4.9... of Information Act § 4.9 Business Information. (a) In general. Business information obtained by the... the purposes of this section: (1) Business information means commercial or financial information...

  15. 15 CFR 4.8 - Classified Information.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Classified Information. 4.8 Section 4... INFORMATION Freedom of Information Act § 4.8 Classified Information. In processing a request for information..., the information shall be reviewed to determine whether it should remain classified. Ordinarily the...

  16. Atomic Energy Authority Act 1954

    International Nuclear Information System (INIS)

    1954-01-01

    This Act provides for the setting up of an Atomic Energy Authority for the United Kingdom. It also makes provision for the Authority's composition, powers, duties, rights and liabilities, and may amend, as a consequence of the establishment of the Authority and in connection therewith, the Atomic Energy Act, 1946, the Radioactive Substances Act 1948 and other relevant enactments. (NEA) [fr

  17. Act No. 18 of 7 August 1989 amending Articles 1 and 4 of and adding a new article to Act No. 6 of 1987.

    Science.gov (United States)

    1989-01-01

    This Act provides the following benefits to all Panamanians and foreigners resident in Panama who have reached the age of 55, if women, and 60, if men, as well as to those who are pensioned and those retired because of disability: 1) a 50% discount on recreation and entertainment activities; 2) a public transportation discount ranging from 25 to 30%; 3) a lodging discount of 50% during the week and 30% on weekends; 4) a 25% discount on restaurants of the 1st and 2nd class; 5) a 15% discount in fast food establishments that are part of a national or international franchise; 6) a 10% discount in private hospitals and clinics when the person does not have hospital insurance; 7) a 10% discount on prescription medicines; 8) a 20% discount on general medical consultations and a 10% discount on dental, optometry, ophthalmology, cardiology, psychiatric and psychological, geriatric, and surgical services; 9) a 10% discount on technical and professional services, including legal, architectural, physiotherapy, and nursing services; 10) a 10% discount on prostheses; 11) a 50% discount on expenses and commissions related to financial, banking, and credit transactions; 12) a 15% discount on the maximum interest on personal and commercial loans; 13) a reduction of 1 percentage point in the interest on personal housing loans; 14) the freezing of the property tax on a personal home, as long as that home is the person's only property; 15) exemption from payment of the appraisal fee due on the transfer of property under the same circumstances as in 14 above; 16) a 50% discount on passports; 17) a 25% discount on electric bills under certain circumstances; and 18) a 50% discount on airport taxes or fees.

  18. The Energy Act 1983

    International Nuclear Information System (INIS)

    1983-01-01

    Part II of This Act came into force on 1 September 1983 and is concerned with nuclear installations. Its main purpose is to amend the Nuclear Installations Act 1965 to give effect to the provisions of two Protocols amending the Paris Convention on nuclear third party liability and the Brussels Convention Supplementary to the Paris Convention respectively. The principal effect of these modifications is to increase the sums available to meet claims for nuclear damage. The United Kingdom is a Party to both Conventions and the provisions of the 1983 Act will enable it to ratify the Protocols. (NEA) [fr

  19. Inhibitor of differentiation 4 (Id4 is a potential tumor suppressor in prostate cancer

    Directory of Open Access Journals (Sweden)

    Carey Jason PW

    2009-06-01

    Full Text Available Abstract Background Inhibitor of differentiation 4 (Id4, a member of the Id gene family is also a dominant negative regulator of basic helix loop helix (bHLH transcription factors. Some of the functions of Id4 appear to be unique as compared to its other family members Id1, Id2 and Id3. Loss of Id4 gene expression in many cancers in association with promoter hypermethylation has led to the proposal that Id4 may act as a tumor suppressor. In this study we provide functional evidence that Id4 indeed acts as a tumor suppressor and is part of a cancer associated epigenetic re-programming. Methods Data mining was used to demonstrate Id4 expression in prostate cancer. Methylation specific polymerase chain reaction (MSP analysis was performed to understand molecular mechanisms associated with Id4 expression in prostate cancer cell lines. The effect of ectopic Id4 expression in DU145 cells was determined by cell cycle analysis (3H thymidine incorporation and FACS, expression of androgen receptor, p53 and cyclin dependent kinase inhibitors p27 and p21 by a combination of RT-PCR, real time-PCR, western blot and immuno-cytochemical analysis. Results Id4 expression was down-regulated in prostate cancer. Id4 expression was also down-regulated in prostate cancer line DU145 due to promoter hyper-methylation. Ectopic Id4 expression in DU145 prostate cancer cell line led to increased apoptosis and decreased cell proliferation due in part by an S-phase arrest. In addition to S-phase arrest, ectopic Id4 expression in PC3 cells also resulted in prolonged G2/M phase. At the molecular level these changes were associated with increased androgen receptor (AR, p21, p27 and p53 expression in DU145 cells. Conclusion The results suggest that Id4 acts directly as a tumor suppressor by influencing a hierarchy of cellular processes at multiple levels that leads to a decreased cell proliferation and change in morphology that is possibly mediated through induction of previously

  20. Review of the nuclear liability act

    International Nuclear Information System (INIS)

    1990-01-01

    There has always been concern that nuclear materials have the potential to cause injury and property damage. For this reason, nuclear operators have always been required by national regulatory authorities to exercise special precautions in the operation of their facilities. Federal legislation was drafted in Canada as the Nuclear Liability Act in 1970. The Act ensures that funds are available from all operators of nuclear facilities to provide financial compensation to third parties for injuries or damages suffered as a result of a nuclear incident; at the same time the Act provides protection to the operators by limiting their related liability. The Act also protects persons other than operators. The review of the Act has progressed in stages. The first stage was conducted by the staff of the Atomic Energy Control Board and catalogued previously identified difficulties with the Act. The second stage was a preliminary examination of the Act by an Interdepartmental Working Group. 2 figs