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Sample records for active gtp-bound state

  1. Identification of a second GTP-bound magnesium ion in archaeal initiation factor 2

    PubMed Central

    Dubiez, Etienne; Aleksandrov, Alexey; Lazennec-Schurdevin, Christine; Mechulam, Yves; Schmitt, Emmanuelle

    2015-01-01

    Eukaryotic and archaeal translation initiation processes involve a heterotrimeric GTPase e/aIF2 crucial for accuracy of start codon selection. In eukaryotes, the GTPase activity of eIF2 is assisted by a GTPase-activating protein (GAP), eIF5. In archaea, orthologs of eIF5 are not found and aIF2 GTPase activity is thought to be non-assisted. However, no in vitro GTPase activity of the archaeal factor has been reported to date. Here, we show that aIF2 significantly hydrolyses GTP in vitro. Within aIF2γ, H97, corresponding to the catalytic histidine found in other translational GTPases, and D19, from the GKT loop, both participate in this activity. Several high-resolution crystal structures were determined to get insight into GTP hydrolysis by aIF2γ. In particular, a crystal structure of the H97A mutant was obtained in the presence of non-hydrolyzed GTP. This structure reveals the presence of a second magnesium ion bound to GTP and D19. Quantum chemical/molecular mechanical simulations support the idea that the second magnesium ion may assist GTP hydrolysis by helping to neutralize the developing negative charge in the transition state. These results are discussed in light of the absence of an identified GAP in archaea to assist GTP hydrolysis on aIF2. PMID:25690901

  2. The GTP-bound and Sumoylated Form of the rab17 Small Molecular Weight GTPase Selectively Binds Syntaxin 2 in Polarized Hepatic WIF-B Cells.

    PubMed

    Striz, Anneliese C; Tuma, Pamela L

    2016-04-29

    A major focus for our laboratory is identifying the molecules and mechanisms that regulate polarized apical protein sorting in hepatocytes, the major epithelial cells of the liver. These trafficking pathways are regulated, in part, by small molecular weight rab GTPases. We chose to investigate rab17, whose expression is restricted to polarized epithelial cells, is enriched in liver, and has been implicated in regulating basolateral to apical transcytosis. To initiate our studies, we generated three recombinant adenoviruses expressing wild type, constitutively active (GTP bound), or dominant-negative (GDP bound) rab17. Immunoblotting revealed rab17 immunoreactive species at 25 kDa (the predicted rab17 molecular mass) and 40 kDa. We determined that mono-sumoylation of the 25-kDa rab17 is responsible for the shift in molecular mass, and that rab17 prenylation is required for sumoylation. We further determined that sumoylation selectively promotes interactions with syntaxin 2 (but not syntaxins 3 or 4) and that these interactions are nucleotide dependent. Furthermore, a K68R-mutated rab17 led to the redistribution of syntaxin 2 and 5' nucleotidase from the apical membrane to subapical puncta, whereas multidrug resistance protein 2 distributions were not changed. Together these data are consistent with the proposed role of rab17 in vesicle fusion with the apical plasma membrane and further implicate sumoylation as an important mediator of protein-protein interactions. The selectivity in syntaxin binding and apical protein redistribution further suggests that rab17 and syntaxin 2 mediate fusion of transcytotic vesicles at the apical surface. PMID:26957544

  3. Agonist-induced changes in RalA activities allows the prediction of the endocytosis of G protein-coupled receptors.

    PubMed

    Zheng, Mei; Zhang, Xiaohan; Guo, Shuohan; Zhang, Xiaowei; Min, Chengchun; Cheon, Seung Hoon; Oak, Min-Ho; Kim, Young Ran; Kim, Kyeong-Man

    2016-01-01

    GTP binding proteins are classified into two families: heterotrimeric large G proteins which are composed of three subunits, and one subunit of small G proteins. Roles of small G proteins in the intracellular trafficking of G protein-coupled receptors (GPCRs) were studied. Among various small G proteins tested, GTP-bound form (G23V) of RalA inhibited the internalization of dopamine D2 receptor independently of the previously reported downstream effectors of RalA, such as Ral-binding protein 1 and PLD. With high affinity for GRK2, active RalA inhibited the GPCR endocytosis by sequestering the GRK2 from receptors. When it was tested for several GPCRs including an endogenous GPCR, lysophosphatidic acid receptor 1, agonist-induced conversion of GTP-bound to GDP-bound RalA, which presumably releases the sequestered GRK2, was observed selectively with the GPCRs which have tendency to undergo endocytosis. Conversion of RalA from active to inactive state occurred by translocation of RGL, a guanine nucleotide exchange factor, from the plasma membrane to cytosol as a complex with Gβγ. These results suggest that agonist-induced Gβγ-mediated conversion of RalA from the GTP-bound form to the GDP-bound form could be a mechanism to facilitate agonist-induced internalization of GPCRs. PMID:26477566

  4. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    SciTech Connect

    Simonetti, Angelita; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Gualerzi, Claudio O.; Klaholz, Bruno P.

    2013-06-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

  5. Locking GTPases covalently in their functional states

    NASA Astrophysics Data System (ADS)

    Wiegandt, David; Vieweg, Sophie; Hofmann, Frank; Koch, Daniel; Li, Fu; Wu, Yao-Wen; Itzen, Aymelt; Müller, Matthias P.; Goody, Roger S.

    2015-07-01

    GTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase-acryl-nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins.

  6. Transglutaminase 2 Regulates the GTPase-activating Activity of Bcr*

    PubMed Central

    Yi, Sun-Ju; Groffen, John; Heisterkamp, Nora

    2009-01-01

    Transglutaminase 2 (TG2) is a multifunctional protein that has been implicated in numerous pathologies including that of neurodegeneration and celiac disease, but the molecular interactions that mediate its diverse activities are largely unknown. Bcr and the closely related Abr negatively regulate the small G-protein Rac: loss of their combined function in vivo results in increased reactivity of innate immune cells. Bcr and Abr are GTPase-activating proteins that catalyze the hydrolysis of the GTP bound to Rac. However, how the Bcr and Abr GTPase-activating activity is regulated is not precisely understood. We here report a novel mechanism of regulation through direct protein-protein interaction with TG2. TG2 bound to the Rac-binding pocket in the GTPase-activating domains of Bcr and Abr, blocked Bcr activity and, through this mechanism, increased levels of active GTP-bound Rac and EGF-stimulated membrane ruffling. TG2 exists in at least two different conformations. Interestingly, experiments using TG2 mutants showed that Bcr exhibits preferential binding to the non-compacted conformation of TG2, in which its catalytic domain is exposed, but transamidation is not needed for the interaction. Thus, TG2 regulates levels of cellular GTP-bound Rac and actin cytoskeletal reorganization through a new mechanism involving direct inhibition of Bcr GTPase-activating activity. PMID:19840940

  7. Locking GTPases covalently in their functional states

    PubMed Central

    Wiegandt, David; Vieweg, Sophie; Hofmann, Frank; Koch, Daniel; Li, Fu; Wu, Yao-Wen; Itzen, Aymelt; Müller, Matthias P.; Goody, Roger S.

    2015-01-01

    GTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase–acryl–nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins. PMID:26178622

  8. A New Use for a Familiar Fold: the X-Ray Crystal Structure of GTP-Bound GTP Cyclohydrolase III From Methanocaldococcus Jannaschii Reveals a Two Metal Ion Catalytic Mechanism

    SciTech Connect

    Morrison, S.D.; Roberts, S.A.; Zegeer, A.M.; Montfort, W.R.; Bandarian, V.

    2009-05-26

    GTP cyclohydrolase (GCH) III from Methanocaldococcus jannaschii, which catalyzes the conversion of GTP to 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (FAPy), has been shown to require Mg{sup 2+} for catalytic activity and is activated by monovalent cations such as K{sup +} and ammonium [Graham, D. E., Xu, H., and White, R. H. (2002) Biochemistry 41, 15074-15084]. The reaction is formally identical to that catalyzed by a GCH II ortholog (SCO 6655) from Streptomyces coelicolor; however, SCO 6655, like other GCH II proteins, is a zinc-containing protein. The structure of GCH III complexed with GTP solved at 2 {angstrom} resolution clearly shows that GCH III adopts a distinct fold that is closely related to the palm domains of phosphodiesterases, such as DNA polymerase I. GCH III is a tetramer of identical subunits; each monomer is composed of an N- and a C-terminal domain that adopt nearly superimposible structures, suggesting that the protein has arisen by gene duplication. Three metal ions were located in the active site, two of which occupy positions that are analogous to those occupied by divalent metal ions in the structures of a number of palm domain containing proteins, such as DNA polymerase I. Two conserved Asp residues that coordinate the metal ions, which are also found in palm domain containing proteins, are observed in GCH III. Site-directed variants (Asp{yields}Asn) of these residues in GCH III are less active than wild-type. The third metal ion, most likely a potassium ion, is involved in substrate recognition through coordination of O6 of GTP. The arrangement of the metal ions in the active site suggests that GCH III utilizes two metal ion catalysis. The structure of GCH III extends the repertoire of possible reactions with a palm fold to include cyclohydrolase chemistry.

  9. Determination of Rab5 activity in the cell by effector pull-down assay.

    PubMed

    Qi, Yaoyao; Liang, Zhimin; Wang, Zonghua; Lu, Guodong; Li, Guangpu

    2015-01-01

    Rab5 targets to early endosomes and is a master regulator of early endosome fusion and endocytosis in all eukaryotic cells. Like other GTPases, Rab5 functions as a molecular switch by alternating between GTP-bound and GDP-bound forms, with the former being biologically active via interactions with multiple effector proteins. Thus the Rab5-GTP level in the cell reflects Rab5 activity in promoting endosome fusion and endocytosis and is indicative of cellular endocytic activity. In this chapter, we describe a Rab5 activity assay by using GST fusion proteins with the Rab5 effectors such as Rabaptin-5, Rabenosyn-5, and EEA1 that specifically bind to GTP-bound Rab5. We compare the efficiencies of the three GST fusion proteins in the pull-down of mammalian and fungal Rab5 proteins. PMID:25800849

  10. Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

    PubMed Central

    Cook, Danielle R.; Rossman, Kent L.; Der, Channing J.

    2016-01-01

    The aberrant activity of Ras homologous (Rho) family small GTPases (20 human members) has been implicated in cancer and other human diseases. However, in contrast to the direct mutational activation of Ras found in cancer and developmental disorders, Rho GTPases are activated most commonly by indirect mechanisms in disease. One prevalent mechanism involves aberrant Rho activation via the deregulated expression and/or activity of Rho family guanine nucleotide exchange factors (RhoGEFs). RhoGEFs promote formation of the active GTP-bound state of Rho GTPases. The largest family of RhoGEFs is comprised of the Dbl family RhoGEFs with 70 human members. The multitude of RhoGEFs that activate a single Rho GTPase reflect the very specific role of each RhoGEF in controlling distinct signaling mechanisms involved in Rho activation. In this review, we summarize the role of Dbl RhoGEFs in development and disease, with a focus on Ect2, Tiam1, Vav and P-Rex1/2. PMID:24037532

  11. Minimal determinants for binding activated G-alpha from the structure of a G-alpha-i1/peptide dimer†

    PubMed Central

    Johnston, Christopher A.; Lobanova, Ekaterina S.; Shavkunov, Alexander S.; Low, Justin; Ramer, J. Kevin; Blaesius, Rainer; Fredericks, Zoey; Willard, Francis S.; Kuhlman, Brian; Arshavsky, Vadim Y.; Siderovski, David P.

    2008-01-01

    G-proteins cycle between an inactive GDP-bound state and active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage-display to identify a series of peptides that bind Gα subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069–1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP·AlF4−- and GTPγS-bound states of Gαi subunits. KB-1753 blocks interaction of Gαtransducin with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated Gα in vitro. The crystal structure of KB-1753 bound to Gαi1·GDP·AlF4− reveals binding to a conserved hydrophobic groove between switch II and α3 helices, and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for Gαi subunits. PMID:16981699

  12. Minimal Determinants for Binding Activated G alpha from the Structure of a G alpha i1-Peptide Dimer

    SciTech Connect

    Johnston,C.; Lobanova, E.; Shavkunov, A.; Low, J.; Ramer, J.; Blasesius, R.; Fredericks, Z.; willard, F.; Kuhlman, B.; et al.

    2006-01-01

    G-Proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G{alpha}subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069-1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP{center_dot}AlF{sub 4{sup -}}- and GTP{gamma}S-bound states of G{alpha}{sup i} subunits. KB-1753 blocks interaction of G{alpha}{sub transducin} with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated G{alpha} in vitro. The crystal structure of KB-1753 bound to G{alpha}{sub i1}-GDP{center_dot}AlF{sub 4{sup -}} reveals binding to a conserved hydrophobic groove between switch II and 3 helices and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for G{alpha}i subunits.

  13. Update: Influenza Activity - United States.

    PubMed

    Smith, Sophie; Blanton, Lenee; Kniss, Krista; Mustaquim, Desiree; Steffens, Craig; Reed, Carrie; Bramley, Anna; Flannery, Brendan; Fry, Alicia M; Grohskopf, Lisa A; Bresee, Joseph; Wallis, Teresa; Garten, Rebecca; Xu, Xiyan; Elal, Anwar Isa Abd; Gubareva, Larisa; Barnes, John; Wentworth, David E; Burns, Erin; Katz, Jacqueline; Jernigan, Daniel; Brammer, Lynnette

    2015-12-11

    CDC collects, compiles, and analyzes data on influenza activity year-round in the United States. The influenza season generally begins in the fall and continues through the winter and spring months; however, the timing and severity of circulating influenza viruses can vary by geographic location and season. Influenza activity in the United States remained low through October and November in 2015. Influenza A viruses have been most frequently identified, with influenza A (H3) viruses predominating. This report summarizes U.S. influenza activity for the period October 4-November 28, 2015. PMID:26656182

  14. Phospholipases as GTPase activity accelerating proteins (GAPs) in plants.

    PubMed

    Pandey, Sona

    2016-05-01

    GTPase activity accelerating proteins (GAPs) are key regulators of the G-protein signaling cycle. By facilitating effective hydrolysis of the GTP bound on Gα proteins, GAPs control the timing and amplitude of the signaling cycle and ascertain the availability of the inactive heterotrimer for the next round of activation. Until very recently, the studies of GAPs in plants were focused exclusively on the regulator of G-protein signaling (RGS) protein. We now show that phospholipase Dα1 (PLDα1) is also a bona fide GAP in plants and together with the RGS protein controls the level of active Gα protein. PMID:27124090

  15. Formation of a Trimeric Xpo1-Ran[GTP]-Ded1 Exportin Complex Modulates ATPase and Helicase Activities of Ded1.

    PubMed

    Hauk, Glenn; Bowman, Gregory D

    2015-01-01

    The DEAD-box RNA helicase Ded1, which is essential in yeast and known as DDX3 in humans, shuttles between the nucleus and cytoplasm and takes part in several basic processes including RNA processing and translation. A key interacting partner of Ded1 is the exportin Xpo1, which together with the GTP-bound state of the small GTPase Ran, facilitates unidirectional transport of Ded1 out of the nucleus. Here we demonstrate that Xpo1 and Ran[GTP] together reduce the RNA-stimulated ATPase and helicase activities of Ded1. Binding and inhibition of Ded1 by Xpo1 depend on the affinity of the Ded1 nuclear export sequence (NES) for Xpo1 and the presence of Ran[GTP]. Association with Xpo1/Ran[GTP] reduces RNA-stimulated ATPase activity of Ded1 by increasing the apparent KM for the RNA substrate. Despite the increased KM, the Ded1:Xpo1:Ran[GTP] ternary complex retains the ability to bind single stranded RNA, suggesting that Xpo1/Ran[GTP] may modulate the substrate specificity of Ded1. These results demonstrate that, in addition to transport, exportins such as Xpo1 also have the capability to alter enzymatic activities of their cargo. PMID:26120835

  16. Regulators of G-protein signaling accelerate GPCR signaling kinetics and govern sensitivity solely by accelerating GTPase activity.

    PubMed

    Lambert, Nevin A; Johnston, Christopher A; Cappell, Steven D; Kuravi, Sudhakiranmayi; Kimple, Adam J; Willard, Francis S; Siderovski, David P

    2010-04-13

    G-protein heterotrimers, composed of a guanine nucleotide-binding G alpha subunit and an obligate G betagamma dimer, regulate signal transduction pathways by cycling between GDP- and GTP-bound states. Signal deactivation is achieved by G alpha-mediated GTP hydrolysis (GTPase activity) which is enhanced by the GTPase-accelerating protein (GAP) activity of "regulator of G-protein signaling" (RGS) proteins. In a cellular context, RGS proteins have also been shown to speed up the onset of signaling, and to accelerate deactivation without changing amplitude or sensitivity of the signal. This latter paradoxical activity has been variably attributed to GAP/enzymatic or non-GAP/scaffolding functions of these proteins. Here, we validated and exploited a G alpha switch-region point mutation, known to engender increased GTPase activity, to mimic in cis the GAP function of RGS proteins. While the transition-state, GDP x AlF(4)(-)-bound conformation of the G202A mutant was found to be nearly identical to wild-type, G alpha(i1)(G202A) x GDP assumed a divergent conformation more closely resembling the GDP x AlF(4)(-)-bound state. When placed within Saccharomyces cerevisiae G alpha subunit Gpa1, the fast-hydrolysis mutation restored appropriate dose-response behaviors to pheromone signaling in the absence of RGS-mediated GAP activity. A bioluminescence resonance energy transfer (BRET) readout of heterotrimer activation with high temporal resolution revealed that fast intrinsic GTPase activity could recapitulate in cis the kinetic sharpening (increased onset and deactivation rates) and blunting of sensitivity also engendered by RGS protein action in trans. Thus G alpha-directed GAP activity, the first biochemical function ascribed to RGS proteins, is sufficient to explain the activation kinetics and agonist sensitivity observed from G-protein-coupled receptor (GPCR) signaling in a cellular context. PMID:20351284

  17. THE STATE TOBACCO ACTIVITIES TRACKING AND EVALUATION (STATE) SYSTEM

    EPA Science Inventory

    The State Tobacco Activities Tracking and Evaluation (STATE) System is an electronic data warehouse containing up-to-date and historical state-level data on tobacco use prevention and control. The STATE System is designed to integrate many data sources to provide comprehensive su...

  18. Generation of a Single Chain Antibody Variable Fragment (scFv) to Sense Selectively RhoB Activation

    PubMed Central

    Chinestra, Patrick; Olichon, Aurélien; Medale-Giamarchi, Claire; Lajoie-Mazenc, Isabelle; Gence, Rémi; Inard, Cyril; Ligat, Laetitia; Faye, Jean-Charles; Favre, Gilles

    2014-01-01

    Determining the cellular level of activated form of RhoGTPases is of key importance to understand their regulatory functions in cell physiopathology. We previously reported scFvC1, that selectively bind to the GTP-bound form of RhoA, RhoB and RhoC. In this present study we generate, by molecular evolution, a new phage library to isolate scFvs displaying high affinity and selectivity to RhoA and RhoB. Using phage display affinity maturation against the GTP-locked mutant RhoAL63, we isolated scFvs against RhoA active conformation that display Kd values at the nanomolar range, which corresponded to an increase of affinity of three orders of magnitude compared to scFvC1. Although a majority of these evolved scFvs remained selective towards the active conformation of RhoA, RhoB and RhoC, we identified some scFvs that bind to RhoA and RhoC but not to RhoB activated form. Alternatively, we performed a substractive panning towards RhoB, and isolated the scFvE3 exhibiting a 10 times higher affinity for RhoB than RhoA activated forms. We showed the peculiar ability of scFvE3 to detect RhoB but not RhoA GTP-bound form in cell extracts overexpressing Guanine nucleotide Exchange Factor XPLN as well as in EGF stimulated HeLa cells. Our results demonstrated the ability of scFvs to distinguish RhoB from RhoA GTP-bound form and provide new selective tools to analyze the cell biology of RhoB GTPase regulation. PMID:25365345

  19. Cdc42 and Rac1 activity is reduced in human pheochromocytoma and correlates with FARP1 and ARHGEF1 expression.

    PubMed

    Croisé, Pauline; Houy, Sébastien; Gand, Mathieu; Lanoix, Joël; Calco, Valérie; Tóth, Petra; Brunaud, Laurent; Lomazzi, Sandra; Paramithiotis, Eustache; Chelsky, Daniel; Ory, Stéphane; Gasman, Stéphane

    2016-04-01

    Among small GTPases from the Rho family, Cdc42, RAC, and Rho are well known to mediate a large variety of cellular processes linked with cancer biology through their ability to cycle between an inactive (GDP-bound) and an active (GTP-bound) state. Guanine nucleotide exchange factors (GEFs) stimulate the exchange of GDP for GTP to generate the activated form, whereas the GTPase-activating proteins (GAPs) catalyze GTP hydrolysis, leading to the inactivated form. Modulation of Rho GTPase activity following altered expression of RHO-GEFs and/or RHO-GAPs has already been reported in various human tumors. However, nothing is known about the Rho GTPase activity or the expression of their regulators in human pheochromocytomas, a neuroendocrine tumor (NET) arising from chromaffin cells of the adrenal medulla. In this study, we demonstrate, through an ELISA-based activity assay, that Rac1 and Cdc42 activities decrease in human pheochromocytomas (PCCs) compared with the matched adjacent non-tumor tissue. Furthermore, through quantitative mass spectrometry (MS) approaches, we show that the expression of two RHO-GEF proteins, namely ARHGEF1 and FARP1, is significantly reduced in tumors compared with matched non-tumor tissue, whereas ARHGAP36 expression is increased. Moreover, siRNA-based knockdown of ARHGEF1 and FARP1 in PC12 cells leads to a significant inhibition of Rac1 and Cdc42 activities, respectively. Finally, a principal component analysis (PCA) of our dataset was able to discriminate PCC from non-tumor tissue and indicates a close correlation between Cdc42/Rac1 activity and FARP1/ARHGEF1 expression. Altogether, our findings reveal for the first time the importance of modulation of Rho GTPase activities and expression of their regulators in human PCCs. PMID:26911374

  20. StARD13(Dlc-2) RhoGap mediates ceramide activation of phosphatidylglycerolphosphate synthase and drug response in Chinese hamster ovary cells.

    PubMed

    Hatch, Grant M; Gu, Yuan; Xu, Fred Y; Cizeau, Jeannick; Neumann, Shannon; Park, Ji-Seon; Loewen, Shauna; Mowat, Michael R A

    2008-03-01

    To identify genes involved in etoposide drug response, we used promoter trap mutagenesis to isolate an etoposide-resistant Chinese hamster ovary (CHO) cell line. This resistant CHO-K1 line, named E91, showed cross-resistance to C(2)-ceramide (N-acetylsphingosine). The promoter trap retrovirus was found integrated into intron 1-2 of the Dlc-2 (Stard13) RhoGap gene. The E91 cells showed elevated guanosine triphosphate (GTP)-bound RhoA levels compared with the parental line, suggesting that retrovirus integration had inactivated one of the Dlc-2 RhoGap alleles. To test whether E91 cells were impaired in an intracellular ceramide-regulated process not directly related to cell killing, we measured mitochondrial phosphatidylglycerolphosphate (PGP) synthase and phospholipase A2 enzyme activities in cells after C(2)-ceramide addition. Parental cells showed elevated enzyme activities after treatment with C(2)-ceramide or tumor necrosis factor alpha, but not the E91 cells. These results suggested that intracellular ceramide signaling was defective in E91 cells due to increased levels of active GTP-bound RhoA. RNA knockdown experiments of the Dlc2 RhoGap resulted in increased GTP-bound RhoA and reduced induction of PGP synthase after C(2)-ceramide addition compared with controls. Expression of a dominant-negative RhoA in the E91 cell line allowed induction of PGP synthase by ceramide. The RNA interference knockdown cell line also showed increased etoposide resistance. This study is the first report for the regulation of a phospholipid biosynthetic enzyme through RhoGap expression. PMID:18162584

  1. State Court Law-Related Education Activities.

    ERIC Educational Resources Information Center

    American Bar Association, Chicago, IL. Special Committee on Youth Education for Citizenship.

    This document lists the law-related education activities conducted by state courts. The listings are arranged by state. Entries list the name of the court, a list of activities provided, descriptions of unusual programs, guidelines for programs that some of the courts have developed, and the name, title or committee, address, and phone number of a…

  2. Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.

    PubMed

    Roney, Kelly E; O'Connor, Brian P; Wen, Haitao; Holl, Eda K; Guthrie, Elizabeth H; Davis, Beckley K; Jones, Stephen W; Jha, Sushmita; Sharek, Lisa; Garcia-Mata, Rafael; Bear, James E; Ting, Jenny P-Y

    2011-01-01

    Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/-) macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/-) macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing. PMID:21966369

  3. Diversity of Active States in TMT Opsins

    PubMed Central

    Sakai, Kazumi; Yamashita, Takahiro; Imamoto, Yasushi; Shichida, Yoshinori

    2015-01-01

    Opn3/TMT opsins belong to one of the opsin groups with vertebrate visual and non-visual opsins, and are widely distributed in eyes, brains and other internal organs in various vertebrates and invertebrates. Vertebrate Opn3/TMT opsins are further classified into four groups on the basis of their amino acid identities. However, there is limited information about molecular properties of these groups, due to the difficulty in preparing the recombinant proteins. Here, we successfully expressed recombinant proteins of TMT1 and TMT2 opsins of medaka fish (Oryzias latipes) in cultured cells and characterized their molecular properties. Spectroscopic and biochemical studies demonstrated that TMT1 and TMT2 opsins functioned as blue light-sensitive Gi/Go-coupled receptors, but exhibited spectral properties and photo-convertibility of the active state different from each other. TMT1 opsin forms a visible light-absorbing active state containing all-trans-retinal, which can be photo-converted to 7-cis- and 9-cis-retinal states in addition to the original 11-cis-retinal state. In contrast, the active state of TMT2 opsin is a UV light-absorbing state having all-trans-retinal and does not photo-convert to any other state, including the original 11-cis-retinal state. Thus, TMT opsins are diversified so as to form a different type of active state, which may be responsible for their different functions. PMID:26491964

  4. Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse

    PubMed Central

    2014-01-01

    Background Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model. Methods We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays. Results The presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary. Conclusion We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B. PMID:24628852

  5. Light activated solid-state opening switches

    SciTech Connect

    Petr, R.A.; Kachen, G.I.; Reilly, J.P.; Schaefer, R.B. ); Heyse, M.W. )

    1993-01-01

    Light-activated solid-state opening switches are shown to be a viable approach for switching inductive circuits. Measured photoswitch performance indicates that light-activated opening switches have the power density ratings needed to develop compact inductive power systems.

  6. Light activated solid-state opening switches

    NASA Astrophysics Data System (ADS)

    Petr, R. A.; Kachen, G. I.; Reilly, J. P.; Schaefer, R. B.; Heyse, M. W.

    1993-01-01

    The paper shows light-activated solid-state opening switches to be a viable approach for switching inductive circuits. Measured photoswitch performance indicates that light-activated opening switches have the power density ratings required to develop compact inductive power systems.

  7. Rho5p is involved in mediating the osmotic stress response in Saccharomyces cerevisiae, and its activity is regulated via Msi1p and Npr1p by phosphorylation and ubiquitination.

    PubMed

    Annan, Robert B; Wu, Cunle; Waller, Daniel D; Whiteway, Malcolm; Thomas, David Y

    2008-09-01

    Small GTPases of the Rho family act as molecular switches, and modulation of the GTP-bound state of Rho proteins is a well-characterized means of regulating their signaling activity in vivo. In contrast, the regulation of Rho-type GTPases by posttranslational modifications is poorly understood. Here, we present evidence of the control of the Saccharomyces cerevisiae Rho-type GTPase Rho5p by phosphorylation and ubiquitination. Rho5p binds to Ste50p, and the expression of the activated RHO5(Q91H) allele in an Deltaste50 strain is lethal under conditions of osmotic stress. An overexpression screen identified RGD2 and MSI1 as being high-copy suppressors of the osmotic sensitivity of this lethality. Rgd2p had been identified as being a possible Rho5p GTPase-activating protein based on an in vitro assay; this result supports its function as a regulator of Rho5p activity in vivo. MSI1 was previously identified as being a suppressor of hyperactive Ras/cyclic AMP signaling, where it antagonizes Npr1p kinase activity and promotes ubiquitination. Here, we show that Msi1p also acts via Npr1p to suppress activated Rho5p signaling. Rho5p is ubiquitinated, and its expression is lethal in a strain that is compromised for proteasome activity. These data identify Rho5p as being a target of Msi1p/Npr1p regulation and describe a regulatory circuit involving phosphorylation and ubiquitination. PMID:18621925

  8. The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase.

    PubMed Central

    Ishizaki, T; Maekawa, M; Fujisawa, K; Okawa, K; Iwamatsu, A; Fujita, A; Watanabe, N; Saito, Y; Kakizuka, A; Morii, N; Narumiya, S

    1996-01-01

    The small GTP-binding protein Rho functions as a molecular switch in the formation of focal adhesions and stress fibers, cytokinesis and transcriptional activation. The biochemical mechanism underlying these actions remains unknown. Using a ligand overlay assay, we purified a 160 kDa platelet protein that bound specifically to GTP-bound Rho. This protein, p160, underwent autophosphorylation at its serine and threonine residues and showed the kinase activity to exogenous substrates. Both activities were enhanced by the addition of GTP-bound Rho. A cDNA encoding p160 coded for a 1354 amino acid protein. This protein has a Ser/Thr kinase domain in its N-terminus, followed by a coiled-coil structure approximately 600 amino acids long, and a cysteine-rich zinc finger-like motif and a pleckstrin homology region in the C-terminus. The N-terminus region including a kinase domain and a part of coiled-coil structure showed strong homology to myotonic dystrophy kinase over 500 residues. When co-expressed with RhoA in COS cells, p160 was co-precipitated with the expressed Rho and its kinase activity was activated, indicating that p160 can associate physically and functionally with Rho both in vitro and in vivo. Images PMID:8617235

  9. Polyomavirus T Antigens Activate an Antiviral State

    PubMed Central

    Giacobbi, Nicholas S.; Gupta, Tushar; Coxon, Andrew; Pipas, James M.

    2014-01-01

    Ectopic expression of Simian Virus 40 (SV40) large T antigen (LT) in mouse embryonic fibroblasts (MEFs) increased levels of mRNAs encoding interferon stimulated genes (ISGs). The mechanism by which T antigen increases levels of ISGs in MEFs remains unclear. We present evidence that expression of T antigen from SV40, Human Polyomaviruses BK (BKV) or JC (JCV) upregulate production of ISGs in MEFs, and subsequently result in an antiviral state, as determined by inhibition of VSV or EMCV growth. The first 136 amino acids of LT are sufficient for these activities. Furthermore, increased ISG expression and induction of the antiviral state requires STAT1. Finally, the RB binding motif of LT is necessary for activation of STAT1. We conclude that the induction of the STAT1 mediated innate immune response in MEFs is a common feature shared by SV40, BKV and JCV. PMID:25589241

  10. An MENC Bicentennial Commission Report on State Activities

    ERIC Educational Resources Information Center

    Music Educators Journal, 1976

    1976-01-01

    The MENC Bicentennial Commission requested each state chairman to submit a list of projects that were representative of the activities in that state. Included here are 27 states and the music activities appropriate for the Bicentennial year. (Editor/RK)

  11. Edge states in confined active fluids

    NASA Astrophysics Data System (ADS)

    Souslov, Anton; Vitelli, Vincenzo

    Recently, topologically protected edge modes have been proposed and realized in both mechanical and acoustic metamaterials. In one class of such metamaterials, Time-Reversal Symmetry is broken, and, to achieve this TRS breaking in mechanical and acoustic systems, an external energy input must be used. For example, motors provide a driving force that uses energy and, thus, explicitly break TRS. As a result, motors have been used as an essential component in the design of topological metamaterials. By contrast, we explore the design of topological metamaterials that use a class of far-from-equilibrium liquids, called polar active liquids, that spontaneously break TRS. We thus envision the confinement of a polar active liquid to a prescribed geometry in order to realize topological order with broken time-reversal symmetry. We address the design of the requisite geometries, for example a regular honeycomb lattice composed of annular channels, in which the active liquid may be confined. We also consider the physical character of the active liquid that, when introduced into the prescribed geometry, will spontaneously form the flow pattern of a metamaterial with topologically protected edge states. Finally, we comment on potential experimental realizations of such metamaterials.

  12. Active State Model for Autonomous Systems

    NASA Technical Reports Server (NTRS)

    Park, Han; Chien, Steve; Zak, Michail; James, Mark; Mackey, Ryan; Fisher, Forest

    2003-01-01

    The concept of the active state model (ASM) is an architecture for the development of advanced integrated fault-detection-and-isolation (FDI) systems for robotic land vehicles, pilotless aircraft, exploratory spacecraft, or other complex engineering systems that will be capable of autonomous operation. An FDI system based on the ASM concept would not only provide traditional diagnostic capabilities, but also integrate the FDI system under a unified framework and provide mechanism for sharing of information between FDI subsystems to fully assess the overall health of the system. The ASM concept begins with definitions borrowed from psychology, wherein a system is regarded as active when it possesses self-image, self-awareness, and an ability to make decisions itself, such that it is able to perform purposeful motions and other transitions with some degree of autonomy from the environment. For an engineering system, self-image would manifest itself as the ability to determine nominal values of sensor data by use of a mathematical model of itself, and selfawareness would manifest itself as the ability to relate sensor data to their nominal values. The ASM for such a system may start with the closed-loop control dynamics that describe the evolution of state variables. As soon as this model was supplemented with nominal values of sensor data, it would possess self-image. The ability to process the current sensor data and compare them with the nominal values would represent self-awareness. On the basis of self-image and self-awareness, the ASM provides the capability for self-identification, detection of abnormalities, and self-diagnosis.

  13. Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

    SciTech Connect

    B McCray; E Skordalakes; J Taylor

    2011-12-31

    Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Through extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.

  14. 34 CFR 300.704 - State-level activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false State-level activities. 300.704 Section 300.704... Allotments, Grants, and Use of Funds § 300.704 State-level activities. (a) State administration. (1) For the... may be used for the administration of Part C of the Act, if the SEA is the lead agency for the...

  15. 34 CFR 300.704 - State-level activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true State-level activities. 300.704 Section 300.704... Allotments, Grants, and Use of Funds § 300.704 State-level activities. (a) State administration. (1) For the... may be used for the administration of Part C of the Act, if the SEA is the lead agency for the...

  16. 12 CFR 362.3 - Activities of insured State banks.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Activities of insured State banks. 362.3 Section 362.3 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY ACTIVITIES OF INSURED STATE BANKS AND INSURED SAVINGS ASSOCIATIONS Activities of...

  17. 12 CFR 362.3 - Activities of insured State banks.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Activities of insured State banks. 362.3 Section 362.3 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY ACTIVITIES OF INSURED STATE BANKS AND INSURED SAVINGS ASSOCIATIONS Activities of...

  18. Validity Evidence for the State Mindfulness Scale for Physical Activity

    ERIC Educational Resources Information Center

    Cox, Anne E.; Ullrich-French, Sarah; French, Brian F.

    2016-01-01

    Being attentive to and aware of one's experiences in the present moment with qualities of acceptance and openness reflects the state of mindfulness. Positive associations exist between state mindfulness and state autonomous motivation for everyday activities. Though this suggests that state mindfulness links with adaptive motivational experiences,…

  19. Physical coupling of activation and derepression activities to maintain an active transcriptional state at FLC.

    PubMed

    Yang, Hongchun; Howard, Martin; Dean, Caroline

    2016-08-16

    Establishment and maintenance of gene expression states is central to development and differentiation. Transcriptional and epigenetic mechanisms interconnect in poorly understood ways to determine these states. We explore these mechanisms through dissection of the regulation of Arabidopsis thaliana FLOWERING LOCUS C (FLC). FLC can be present in a transcriptionally active state marked by H3K36me3 or a silent state marked by H3K27me3. Here, we investigate the trans factors modifying these opposing histone states and find a physical coupling in vivo between the H3K36 methyltransferase, SDG8, and the H3K27me3 demethylase, ELF6. Previous modeling has predicted this coupling would exist as it facilitates bistability of opposing histone states. We also find association of SDG8 with the transcription machinery, namely RNA polymerase II and the PAF1 complex. Delivery of the active histone modifications is therefore likely to be through transcription at the locus. SDG8 and ELF6 were found to influence the localization of each other on FLC chromatin, showing the functional importance of the interaction. In addition, both influenced accumulation of the associated H3K27me3 and H3K36me3 histone modifications at FLC We propose the physical coupling of activation and derepression activities coordinates transcriptional activity and prevents ectopic silencing. PMID:27482092

  20. Physical coupling of activation and derepression activities to maintain an active transcriptional state at FLC

    PubMed Central

    Yang, Hongchun; Howard, Martin; Dean, Caroline

    2016-01-01

    Establishment and maintenance of gene expression states is central to development and differentiation. Transcriptional and epigenetic mechanisms interconnect in poorly understood ways to determine these states. We explore these mechanisms through dissection of the regulation of Arabidopsis thaliana FLOWERING LOCUS C (FLC). FLC can be present in a transcriptionally active state marked by H3K36me3 or a silent state marked by H3K27me3. Here, we investigate the trans factors modifying these opposing histone states and find a physical coupling in vivo between the H3K36 methyltransferase, SDG8, and the H3K27me3 demethylase, ELF6. Previous modeling has predicted this coupling would exist as it facilitates bistability of opposing histone states. We also find association of SDG8 with the transcription machinery, namely RNA polymerase II and the PAF1 complex. Delivery of the active histone modifications is therefore likely to be through transcription at the locus. SDG8 and ELF6 were found to influence the localization of each other on FLC chromatin, showing the functional importance of the interaction. In addition, both influenced accumulation of the associated H3K27me3 and H3K36me3 histone modifications at FLC. We propose the physical coupling of activation and derepression activities coordinates transcriptional activity and prevents ectopic silencing. PMID:27482092

  1. Luteinizing Hormone Receptor-Stimulated Progesterone Production by Preovulatory Granulosa Cells Requires Protein Kinase A-Dependent Activation/Dephosphorylation of the Actin Dynamizing Protein Cofilin

    PubMed Central

    Karlsson, Amelia B.; Maizels, Evelyn T.; Flynn, Maxfield P.; Jones, Jonathan C.; Shelden, Eric A.; Bamburg, James R.; Hunzicker-Dunn, Mary

    2010-01-01

    Activation of the LH receptor (LHR) on preovulatory granulosa cells stimulates the cAMP/protein kinase A (PKA) pathway to regulate expression of genes required for ovulation and luteinization. LHR signaling also initiates rearrangement of the actin cytoskeleton. Because disruption of the actin cytoskeleton has been causally linked to steroidogenesis in various cell models, we sought to identify the cellular mechanisms that may modulate reorganization of the actin cytoskeleton and to determine whether cytoskeletal reorganization is required for steroidogenesis. Herein we report that LHR signaling in preovulatory granulosa cells promotes rapid dephosphorylation of the actin-depolymerizing factor cofilin at Ser3 that is dependent on PKA. The LHR-stimulated dephosphorylation of cofilin(Ser3) switches on cofilin activity to bind actin filaments and enhance their dynamics. Basal phosphorylation of cofilin(Ser3) is mediated by active/GTP-bound Rho and downstream protein kinases; LHR signaling promotes a decrease in active/GTP-bound Rho by a PKA-dependent mechanism. LHR-dependent Rho inactivation and subsequent activation of cofilin does not involve ERK, epidermal growth factor receptor, or phosphatidylinositol 3-kinase pathways downstream of PKA. To understand the biological significance of cofilin activation, preovulatory granulosa cells were transduced with a mutant cofilin adenoviral vector in which Ser3 was mutated to Glu (S-E cofilin). Inactive S-E cofilin abolished LHR-mediated reorganization of the actin cytoskeleton and caused a 70% decrease in LHR-stimulated progesterone that is obligatory for ovulation. Taken together, these results show that LHR signaling via PKA activates a cofilin-regulated rearrangement of the actin cytoskeleton and that active cofilin is required to initiate progesterone secretion by preovulatory granulosa cells. PMID:20610540

  2. Mesolimbic neuronal activity across behavioral states.

    PubMed

    Woodward, D J; Chang, J Y; Janak, P; Azarov, A; Anstrom, K

    1999-06-29

    A goal of neurophysiology of the mesolimbic system is to determine the activity patterns within the regions in the prefrontal cortex, ventral neostriatum, and amygdala that regulate behavioral patterns to seek rewards. A new technology has been introduced in which arrays of microwires are implanted in different brain regions while activity patterns of ensembles of neurons are recorded for long periods of time during freely moving behaviors. Multichannel instrumentation and software is used for data acquisition and analysis. An initial hypothesis was that neural signals would be encountered in the nucleus accumbens and associated regions specifically related to reward. However, an initial study of neural activity and behavioral patterns during a simple lever press for intravenous cocaine (1 mg/kg) revealed that phasic excitatory or inhibitory neural activity patterns often appear prior to the reward phase. Individual neurons throughout the mesolimbic system appear to code information specific to sensory and motor events, tones, or lever presses in the chain of tasks leading to all rewards so far studied. Different spatial temporal patterns also appear within the same neural populations, as reward is changed from injected cocaine to heroin, from ingested pure water to ethanol in water or sucrose. Overall, patterns of activity for each neuron are found to shift dynamically during the operant task as changes are made in the target reward. Significant shifts in activity of mesolimbic neurons that are unrelated to specific sensory-motor events also appear during complex sessions, such as during a bout of ethanol consumption to reach satiation or during progressive ratio tasks with increasing difficulty. An emerging hypothesis is that some candidate neural elements in the mesolimbic system code the anticipated reward, whereas others serve internal logic functions of motivation that mediate extinction or resumption of specific goal-directed behaviors. PMID:10415645

  3. Tritium activities in the United States

    SciTech Connect

    Anderson, J.L.; LaMarche, P.

    1995-07-01

    There have been many significant changes in the status of tritium activities in the US since the 4th Tritium Conference in October, 1991. The replacement Tritium Facility (RTF) at Savannah River Site and the Weapons Engineering Tritium Facility (WETF) at the Los Alamos National Laboratory are now operational with tritium. The Tokamak Fusion Test Reactor (TFTR) has initiated a highly successful experimental campaign studying DT plasmas, and has produced more than 10 Megawatts (MW) of fusion power in a D-T plasma. Sandia National Laboratory has ceased tritium operations at the Tritium Research Laboratory (TRL) and many of the activities previously performed there have been transferred to Los Alamos and Savannah River. The tritium laboratory at Lawrence Livermore National Laboratory has reduced the tritium inventory to <5 grams. The Tritium Systems Test Assembly (TSTA) at Los Alamos continues to be at the forefront of tritium technology and safety development for the fusion energy program.

  4. State opportunities for action: Update of states' combined heat and power activities

    SciTech Connect

    Brown, Elizabeth; Elliott, R. Neal

    2003-10-01

    This report updates the review of state policies with regard to CHP that the American Council for and Energy Efficient Economy completed in 2002. It describes the current activities of states with programs during the initial survey and also reviews new programs offered by the states.

  5. 34 CFR 403.70 - How must funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... State Leadership Activities? 403.70 Section 403.70 Education Regulations of the Offices of the... the Basic Programs? State Programs and State Leadership Activities § 403.70 How must funds be used under the State Programs and State Leadership Activities? A State shall use funds reserved under...

  6. 34 CFR 403.70 - How must funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... State Leadership Activities? 403.70 Section 403.70 Education Regulations of the Offices of the... the Basic Programs? State Programs and State Leadership Activities § 403.70 How must funds be used under the State Programs and State Leadership Activities? A State shall use funds reserved under...

  7. 34 CFR 403.70 - How must funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... State Leadership Activities? 403.70 Section 403.70 Education Regulations of the Offices of the... the Basic Programs? State Programs and State Leadership Activities § 403.70 How must funds be used under the State Programs and State Leadership Activities? A State shall use funds reserved under...

  8. 34 CFR 403.70 - How must funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... State Leadership Activities? 403.70 Section 403.70 Education Regulations of the Offices of the... the Basic Programs? State Programs and State Leadership Activities § 403.70 How must funds be used under the State Programs and State Leadership Activities? A State shall use funds reserved under...

  9. Active Solid State Dosimetry for Lunar EVA

    NASA Technical Reports Server (NTRS)

    Wrbanek, John D.; Fralick, Gustave C.; Wrbanek, Susan Y.; Chen, Liang-Yu.

    2006-01-01

    The primary threat to astronauts from space radiation is high-energy charged particles, such as electrons, protons, alpha and heavier particles, originating from galactic cosmic radiation (GCR), solar particle events (SPEs) and trapped radiation belts in Earth orbit. There is also the added threat of secondary neutrons generated as the space radiation interacts with atmosphere, soil and structural materials.[1] For Lunar exploration missions, the habitats and transfer vehicles are expected to provide shielding from standard background radiation. Unfortunately, the Lunar Extravehicular Activity (EVA) suit is not expected to afford such shielding. Astronauts need to be aware of potentially hazardous conditions in their immediate area on EVA before a health and hardware risk arises. These conditions would include fluctuations of the local radiation field due to changes in the space radiation field and unknown variations in the local surface composition. Should undue exposure occur, knowledge of the dynamic intensity conditions during the exposure will allow more precise diagnostic assessment of the potential health risk to the exposed individual.[2

  10. [Nonequilibrium state of electrochemically activated water and its biological activity].

    PubMed

    Petrushanko, I Iu; Lobyshev, V I

    2001-01-01

    Changes in the physicochemical parameters (pH, redox potential and electroconductivity) of catholyte and anolyte produced by membrane electrolysis of distilled water and dilute (c < 10(-3) M) sodium chloride solutions were studied. The relaxation of these parameters after electrolysis and the influence of catholyte and anolyte on the growth of roots of Tradescantia viridis grafts, the development of duckweed, and the motive activity of infusoria Spirostomum ambiguum were investigated. It was found that the anolyte of distilled water stimulated development of these biological objects. The direction of shift of physicochemical parameters of catholyte and anolyte from equilibrium values and the type of their biological activity (stimulation or inhibition) depend on salt concentration in initial solution. Barbotage of initial distilled water with argon or nitrogen leads to a greater decrease in the redox potential of catholyte during electrolysis. The physicochemical parameters relax to equilibrium values, and the biological activity of catholite and anolyte decreases with time and practically disappears by the end of the day. It was found that the oxidation of reducing agent by atmospheric oxygen is not the sole cause of the relaxation of catalyte redox potential. The increase in the ionic strength of catholite and anolyte by the addition of concentrated sodium chloride after electrolysis decreases the rate of redox potential relaxation several times. The redox potential can be maintained for long periods by freezing. PMID:11449536

  11. Intrinsic Brain Activity in Altered States of Consciousness

    PubMed Central

    Boly, M.; Phillips, C.; Tshibanda, L.; Vanhaudenhuyse, A.; Schabus, M.; Dang-Vu, T.T.; Moonen, G.; Hustinx, R.; Maquet, P.; Laureys, S.

    2010-01-01

    Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain–behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto–cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level–dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark. PMID:18591474

  12. Exploring the Tensions between State Activism and School Autonomy.

    ERIC Educational Resources Information Center

    Malen, Betty; Muncey, Donna

    Since the 1970s, states have substantially and dramatically increased their involvement in education while simultaneously endorsing notions of local control. This paper focuses on the impact of such persistent and pervasive state activism on school autonomy. It describes how the proliferation and accumulation of education policies enacted at the…

  13. Monitoring Affect States during Effortful Problem Solving Activities

    ERIC Educational Resources Information Center

    D'Mello, Sidney K.; Lehman, Blair; Person, Natalie

    2010-01-01

    We explored the affective states that students experienced during effortful problem solving activities. We conducted a study where 41 students solved difficult analytical reasoning problems from the Law School Admission Test. Students viewed videos of their faces and screen captures and judged their emotions from a set of 14 states (basic…

  14. Education Finance Legislative Activity and Trends at the State Level.

    ERIC Educational Resources Information Center

    Crampton, Faith E.

    1999-01-01

    Reviews 1997 school finance legislation, comparing legislative activity levels from 1994 to 1997. In 1997, 32 states passed legislation pertaining to capital-outlay funding, tax bases, and taxation for education funding. Half passed legislation for state aid, technology, special-purpose education, budgeting/fiscal management, and school personnel…

  15. 34 CFR 300.704 - State-level activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false State-level activities. 300.704 Section 300.704 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH DISABILITIES Authorization,...

  16. 34 CFR 300.814 - Other State-level activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Other State-level activities. 300.814 Section 300.814 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION...

  17. 34 CFR 300.812 - Reservation for State activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Reservation for State activities. 300.812 Section 300.812 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION...

  18. State Activism in School Funding: Goals and Approaches.

    ERIC Educational Resources Information Center

    Theobald, Neil D.

    2000-01-01

    State activism in school funding extends far beyond increasing states' percentage of public-school revenues. However, local districts' share of funding has fallen dramatically over the last 7 decades. Equity-, efficiency-, and liberty-enhancing goals are explained, along with assistance-oriented, persuasive, and regulatory policy approaches.…

  19. Are Auditory Hallucinations Related to the Brain's Resting State Activity? A 'Neurophenomenal Resting State Hypothesis'

    PubMed Central

    2014-01-01

    While several hypotheses about the neural mechanisms underlying auditory verbal hallucinations (AVH) have been suggested, the exact role of the recently highlighted intrinsic resting state activity of the brain remains unclear. Based on recent findings, we therefore developed what we call the 'resting state hypotheses' of AVH. Our hypothesis suggest that AVH may be traced back to abnormally elevated resting state activity in auditory cortex itself, abnormal modulation of the auditory cortex by anterior cortical midline regions as part of the default-mode network, and neural confusion between auditory cortical resting state changes and stimulus-induced activity. We discuss evidence in favour of our 'resting state hypothesis' and show its correspondence with phenomenal, i.e., subjective-experiential features as explored in phenomenological accounts. Therefore I speak of a 'neurophenomenal resting state hypothesis' of auditory hallucinations in schizophrenia. PMID:25598821

  20. The Very Young and Education: 1974 State Activity.

    ERIC Educational Resources Information Center

    Hayas, Denise Kale; Ross, Doris M.

    This booklet contains more than 100 brief descriptions of early childhood projects, activities, studies, and legislation obtained from newsletters, bulletins, and the Education Commission of the States' (ECS) 1974 Annual Survey. Only legislation and activities that have been validated or newly reported are included. Bills which failed or were…

  1. Light-activated solid-state opening switch

    NASA Astrophysics Data System (ADS)

    Heyse, Mark W.; Petr, Rodney A.; Kachen, George I.; Reilly, James P.; Schaefer, Raymond B.

    1993-01-01

    Light-activated solid-state opening switches are shown to be a viable approach for switching inductive circuits. Measured photoswitch performance indicates that light-activated opening switches have the power density ratings needed to develop compact inductive power systems.

  2. On the way of classifying new states of active matter

    NASA Astrophysics Data System (ADS)

    Menzel, Andreas M.

    2016-07-01

    With ongoing research into the collective behavior of self-propelled particles, new states of active matter are revealed. Some of them are entirely based on the non-equilibrium character and do not have an immediate equilibrium counterpart. In their recent work, Romanczuk et al (2016 New J. Phys. 18 063015) concentrate on the characterization of smectic-like states of active matter. A new type, referred to by the authors as smectic P, is described. In this state, the active particles form stacked layers and self-propel along them. Identifying and classifying states and phases of non-equilibrium matter, including the transitions between them, is an up-to-date effort that will certainly extend for a longer period into the future.

  3. Electrical Activation of Dark Excitonic States in Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Uda, Takushi; Yoshida, Masahiro; Ishii, Akihiro; Kato, Yuichiro K.

    Electrical activation of optical transitions to parity-forbidden dark excitonic states in individual carbon nanotubes is reported. We examine electric field effects on various excitonic states by simultaneously measuring both photocurrent and photoluminescence. As the applied field increases, we observe an emergence of new absorption peaks in the excitation spectra. From the diameter dependence of the energy separation between the new peaks and the ground state of E11 excitons, we attribute the peaks to the dark excited states which became optically active due to the applied field. A simple field-induced exciton dissociation model is introduced to explain the photocurrent threshold fields, and the edge of the E11 continuum states have been identified using this model. Work supported by JSPS (KAKENHI 24340066, 26610080), MEXT (Photon Frontier Network Program, Nanotechnology Platform), Canon Foundation, and Asahi Glass Foundation.

  4. Pressure is not a state function for generic active fluids

    NASA Astrophysics Data System (ADS)

    Solon, A. P.; Fily, Y.; Baskaran, A.; Cates, M. E.; Kafri, Y.; Kardar, M.; Tailleur, J.

    2015-08-01

    Pressure is the mechanical force per unit area that a confined system exerts on its container. In thermal equilibrium, it depends only on bulk properties--such as density and temperature--through an equation of state. Here we show that in a wide class of active systems the pressure depends on the precise interactions between the active particles and the confining walls. In general, therefore, active fluids have no equation of state. Their mechanical pressure exhibits anomalous properties that defy the familiar thermodynamic reasoning that holds in equilibrium. The pressure remains a function of state, however, in some specific and well-studied active models that tacitly restrict the character of the particle-wall and/or particle-particle interactions.

  5. Resting state activity in patients with disorders of consciousness

    PubMed Central

    Soddu, Andrea; Vanhaudenhuyse, Audrey; Demertzi, Athena; Bruno, Marie-Aurélie; Tshibanda, Luaba; Di, Haibo; Boly, Mélanie; Papa, Michele; Laureys, Steven; Noirhomme, Quentin

    Summary Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients’ active collaboration in data acquisition. PMID:21693087

  6. Resting state activity in patients with disorders of consciousness.

    PubMed

    Soddu, Andrea; Vanhaudenhuyse, Audrey; Demertzi, Athena; Bruno, Marie-Aurélie; Tshibanda, Luaba; Di, Haibo; Mélanie, Boly; Papa, Michele; Laureys, Steven; Noirhomme, Quentin

    2011-01-01

    Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients' active collaboration in data acquisition. PMID:21693087

  7. Correspondence between Resting-State Activity and Brain Gene Expression.

    PubMed

    Wang, Guang-Zhong; Belgard, T Grant; Mao, Deng; Chen, Leslie; Berto, Stefano; Preuss, Todd M; Lu, Hanzhang; Geschwind, Daniel H; Konopka, Genevieve

    2015-11-18

    The relationship between functional brain activity and gene expression has not been fully explored in the human brain. Here, we identify significant correlations between gene expression in the brain and functional activity by comparing fractional amplitude of low-frequency fluctuations (fALFF) from two independent human fMRI resting-state datasets to regional cortical gene expression from a newly generated RNA-seq dataset and two additional gene expression datasets to obtain robust and reproducible correlations. We find significantly more genes correlated with fALFF than expected by chance and identify specific genes correlated with the imaging signals in multiple expression datasets in the default mode network. Together, these data support a population-level relationship between regional steady-state brain gene expression and resting-state brain activity. PMID:26590343

  8. Dynamics of multistable states during ongoing and evoked cortical activity.

    PubMed

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    2015-05-27

    Single-trial analyses of ensemble activity in alert animals demonstrate that cortical circuits dynamics evolve through temporal sequences of metastable states. Metastability has been studied for its potential role in sensory coding, memory, and decision-making. Yet, very little is known about the network mechanisms responsible for its genesis. It is often assumed that the onset of state sequences is triggered by an external stimulus. Here we show that state sequences can be observed also in the absence of overt sensory stimulation. Analysis of multielectrode recordings from the gustatory cortex of alert rats revealed ongoing sequences of states, where single neurons spontaneously attain several firing rates across different states. This single-neuron multistability represents a challenge to existing spiking network models, where typically each neuron is at most bistable. We present a recurrent spiking network model that accounts for both the spontaneous generation of state sequences and the multistability in single-neuron firing rates. Each state results from the activation of neural clusters with potentiated intracluster connections, with the firing rate in each cluster depending on the number of active clusters. Simulations show that the model's ensemble activity hops among the different states, reproducing the ongoing dynamics observed in the data. When probed with external stimuli, the model predicts the quenching of single-neuron multistability into bistability and the reduction of trial-by-trial variability. Both predictions were confirmed in the data. Together, these results provide a theoretical framework that captures both ongoing and evoked network dynamics in a single mechanistic model. PMID:26019337

  9. Dynamics of Multistable States during Ongoing and Evoked Cortical Activity

    PubMed Central

    Mazzucato, Luca

    2015-01-01

    Single-trial analyses of ensemble activity in alert animals demonstrate that cortical circuits dynamics evolve through temporal sequences of metastable states. Metastability has been studied for its potential role in sensory coding, memory, and decision-making. Yet, very little is known about the network mechanisms responsible for its genesis. It is often assumed that the onset of state sequences is triggered by an external stimulus. Here we show that state sequences can be observed also in the absence of overt sensory stimulation. Analysis of multielectrode recordings from the gustatory cortex of alert rats revealed ongoing sequences of states, where single neurons spontaneously attain several firing rates across different states. This single-neuron multistability represents a challenge to existing spiking network models, where typically each neuron is at most bistable. We present a recurrent spiking network model that accounts for both the spontaneous generation of state sequences and the multistability in single-neuron firing rates. Each state results from the activation of neural clusters with potentiated intracluster connections, with the firing rate in each cluster depending on the number of active clusters. Simulations show that the model's ensemble activity hops among the different states, reproducing the ongoing dynamics observed in the data. When probed with external stimuli, the model predicts the quenching of single-neuron multistability into bistability and the reduction of trial-by-trial variability. Both predictions were confirmed in the data. Together, these results provide a theoretical framework that captures both ongoing and evoked network dynamics in a single mechanistic model. PMID:26019337

  10. Antiviral Regulation in Porcine Monocytic Cells at Different Activation States

    PubMed Central

    Rowland, Raymond R. R.

    2014-01-01

    ABSTRACT Monocytic cells, including macrophages and dendritic cells, exist in different activation states that are critical to the regulation of antimicrobial immunity. Many pandemic viruses are monocytotropic, including porcine reproductive and respiratory syndrome virus (PRRSV), which directly infects subsets of monocytic cells and interferes with antiviral responses. To study antiviral responses in PRRSV-infected monocytic cells, we characterized inflammatory cytokine responses and genome-wide profiled signature genes to investigate response pathways in uninfected and PRRSV-infected monocytic cells at different activation states. Our findings showed suppressed interferon (IFN) production in macrophages in non-antiviral states and an arrest of lipid metabolic pathways in macrophages at antiviral states. Importantly, porcine monocytic cells at different activation states were susceptible to PRRSV and responded differently to viral infection. Based on Gene Ontology (GO) analysis, two approaches were used to potentiate antiviral activity: (i) pharmaceutical modulation of cellular lipid metabolism and (ii) in situ PRRSV replication-competent expression of interferon alpha (IFN-α). Both approaches significantly suppressed exogenous viral infection in monocytic cells. In particular, the engineered IFN-expressing PRRSV strain eliminated exogenous virus infection and sustained cell viability at 4 days postinfection in macrophages. These findings suggest an intricate interaction of viral infection with the activation status of porcine monocytic cells. An understanding and integration of antiviral infection with activation status of monocytic cells may provide a means of potentiating antiviral immunity. IMPORTANCE Activation statuses of monocytic cells, including monocytes, macrophages (Mϕs), and dendritic cells (DCs), are critically important for antiviral immunity. Unfortunately, the activation status of porcine monocytic cells or how cell activation status

  11. Limits of state activity in the interstate water market

    SciTech Connect

    Rodgers, A.B.

    1986-01-01

    In an effort to ensure future water supplies, many western states are becoming participants in the market for water. As market participants, states gain a proprietary interest in their water resources which more effectively secures their right to the water than mere regulation or claims of ownership under the public trust doctrine. As the author points out, however, the constitution imposes numerous limitations on state water market activity. The privileges and immunities clause, the commerce clause, the property clause, as well as the equal protection clause of the fourteenth amendment, all influence the manner in which states may behave. Most significantly, the author explains, these clauses prevent states from using their power as water market participants as a disguise for economic protectionism.

  12. Data inconsistencies from states with unconventional oil and gas activity.

    PubMed

    Malone, Samantha; Kelso, Matthew; Auch, Ted; Edelstein, Karen; Ferrar, Kyle; Jalbert, Kirk

    2015-01-01

    The quality and availability of unconventional oil and gas (O&G) data in the United States have never been compared methodically state-to-state. By conducting such an assessment, this study seeks to better understand private and publicly sourced data variability and to identify data availability gaps. We developed an exploratory data-grading tool - Data Accessibility and Usability Index (DAUI) - to guide the review of O&G data quality. Between July and October 2013, we requested, collected, and assessed 5 categories of unconventional O&G data (wells drilled, violations, production, waste, and Class II disposal wells) from 10 states with active drilling activity. We based our assessment on eight data quality parameters (accessibility, usability, point location, completeness, metadata, agency responsiveness, accuracy, and cost). Using the DAUI, two authors graded the 10 states and then averaged their scores. The average score received across all states, data categories, and parameters was 67.1 out of 100, largely insufficient for proper data transparency. By state, Pennsylvania received the highest average ( = 93.5) and ranked first in all but one data category. The lowest scoring state was Texas ( = 44) largely due to its policy of charging for certain data. This article discusses the various reasons for scores received, as well as methodological limitations of the assessment metrics. We argue that the significant variability of unconventional O&G data-and its availability to the public-is a barrier to regulatory and industry transparency. The lack of transparency also impacts public education and broader participation in industry governance. This study supports the need to develop a set of data best management practices (BMPs) for state regulatory agencies and the O&G industry, and suggests potential BMPs for this purpose. PMID:25734825

  13. Obesity, Health, and Physical Activity: Discourses from the United States

    ERIC Educational Resources Information Center

    Zieff, Susan G.; Veri, Maria J.

    2009-01-01

    This article examines the obesity, health, and physical activity discourses of the past 35 years in the context of the United States with particular reference to five social sectors: the biomedical domain; the popular media; nonprofit foundations, centers and agencies; various national and multinational corporations; and government at all levels.…

  14. The Current State of Marketing Activity among Higher Education Institutions.

    ERIC Educational Resources Information Center

    Newman, Cynthia M.

    2002-01-01

    Investigated the current state of marketing, marketing research, and planning practices at four-year higher education institutions. Builds upon previous studies by Blackburn (1979) and Goldgehn (1982 and 1989). Determined whether the use and apparent understanding of marketing and its attendant activities by admissions and enrollment management…

  15. Canada and the United States. Perspective. Learning Activity Packet.

    ERIC Educational Resources Information Center

    Maine Univ., Orono. New England - Atlantic Provinces - Quebec Center.

    The similarities and differences of Canada and the United States are explored in this Learning Activity Packet (LAP). Ten learning objectives are given which encourage students to examine: 1) the misconceptions Americans and Canadians have about each other and their ways of life; 2) the effect and influence of French and English exploration and…

  16. Examining Alignment between State Performance Assessment and Mathematics Classroom Activities

    ERIC Educational Resources Information Center

    Parke, Carol S.; Lane, Suzanne

    2008-01-01

    The authors describe research on the extent to which mathematics classroom activities in Maryland were aligned with Maryland learning outcomes and the Maryland School Performance Assessment Program (MSPAP; Maryland State Department of Education, 1995, 2000). The study was part of a larger research project (S. Lane, C. S. Parke, & C. A. Stone,…

  17. 12 CFR 362.3 - Activities of insured State banks.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Financial institution letters (FILs) are available in the FDIC Public Information Center, room 100, 801 17th... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Activities of insured State banks. 362.3 Section 362.3 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS...

  18. 12 CFR 362.3 - Activities of insured State banks.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Financial institution letters (FILs) are available in the FDIC Public Information Center, room 100, 801 17th... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Activities of insured State banks. 362.3 Section 362.3 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS...

  19. Nonequilibrium Equation of State in Suspensions of Active Colloids

    NASA Astrophysics Data System (ADS)

    Ginot, Félix; Theurkauff, Isaac; Levis, Demian; Ybert, Christophe; Bocquet, Lydéric; Berthier, Ludovic; Cottin-Bizonne, Cécile

    2015-01-01

    Active colloids constitute a novel class of materials composed of colloidal-scale particles locally converting chemical energy into motility, mimicking micro-organisms. Evolving far from equilibrium, these systems display structural organizations and dynamical properties distinct from thermalized colloidal assemblies. Harvesting the potential of this new class of systems requires the development of a conceptual framework to describe these intrinsically nonequilibrium systems. We use sedimentation experiments to probe the nonequilibrium equation of state of a bidimensional assembly of active Janus microspheres and conduct computer simulations of a model of self-propelled hard disks. Self-propulsion profoundly affects the equation of state, but these changes can be rationalized using equilibrium concepts. We show that active colloids behave, in the dilute limit, as an ideal gas with an activity-dependent effective temperature. At finite density, increasing the activity is similar to increasing adhesion between equilibrium particles. We quantify this effective adhesion and obtain a unique scaling law relating activity and effective adhesion in both experiments and simulations. Our results provide a new and efficient way to understand the emergence of novel phases of matter in active colloidal suspensions.

  20. Behavioral State Modulates the Activity of Brainstem Sensorimotor Neurons

    PubMed Central

    McArthur, Kimberly L.

    2011-01-01

    Sensorimotor processing must be modulated according to the animal's behavioral state. A previous study demonstrated that motion responses were strongly state dependent in birds. Vestibular eye and head responses were significantly larger and more compensatory during simulated flight, and a flight-specific vestibular tail response was also characterized. In the current study, we investigated the neural substrates for these state-dependent vestibular behaviors by recording extracellularly from neurons in the vestibular nuclear complex and comparing their spontaneous activity and sensory responses during default and simulated flight states. We show that motion-sensitive neurons in the lateral vestibular nucleus are state dependent. Some neurons increased their spontaneous firing rates during flight, though their increased excitability was not reflected in higher sensory gains. However, other neurons exhibited state-dependent gating of sensory inputs, responding to rotational stimuli only during flight. These results demonstrate that vestibular processing in the brainstem is state dependent and lay the foundation for future studies to investigate the synaptic mechanisms responsible for these modifications. PMID:22090497

  1. Dynamics of biomembranes with active multiple-state inclusions.

    PubMed

    Chen, Hsuan-Yi; Mikhailov, Alexander S

    2010-03-01

    Nonequilibrium dynamics of biomembranes with active multiple-state inclusions is considered. The inclusions represent protein molecules which perform cyclic internal conformational motions driven by the energy brought with adenosine triphosphate (ATP) ligands. As protein conformations cyclically change, this induces hydrodynamical flows and also directly affects the local curvature of a membrane. On the other hand, variations in the local curvature of the membrane modify the transition rates between conformational states in a protein, leading to a feedback in the considered system. Moreover, active inclusions can move diffusively through the membrane so that their surface concentration varies. The kinetic description of this system is constructed and the stability of the uniform stationary state is analytically investigated. We show that, as the rate of supply of chemical energy is increased above a certain threshold, this uniform state becomes unstable and stationary or traveling waves spontaneously develop in the system. Such waves are accompanied by periodic spatial variations of the membrane curvature and the inclusion density. For typical parameter values, their characteristic wavelengths are of the order of hundreds of nanometers. For traveling waves, the characteristic frequency is of the order of a thousand Hz or less. The predicted instabilities are possible only if at least three internal inclusion states are present. PMID:20365764

  2. Steady-state entanglement activation in optomechanical cavities

    NASA Astrophysics Data System (ADS)

    Farace, Alessandro; Ciccarello, Francesco; Fazio, Rosario; Giovannetti, Vittorio

    2014-02-01

    Quantum discord, and related indicators, are raising a relentless interest as a novel paradigm of nonclassical correlations beyond entanglement. Here, we discover a discord-activated mechanism yielding steady-state entanglement production in a realistic continuous-variable setup. This comprises two coupled optomechanical cavities, where the optical modes (OMs) communicate through a fiber. We first use a simplified model to highlight the creation of steady-state discord between the OMs. We show next that such discord improves the level of stationary optomechanical entanglement attainable in the system, making it more robust against temperature and thermal noise.

  3. Integrin Activation States and Eosinophil Recruitment in Asthma

    PubMed Central

    Johansson, Mats W.; Mosher, Deane F.

    2013-01-01

    Eosinophil arrest and recruitment to the airway in asthma are mediated, at least in part, by integrins. Eosinophils express α4β1, α6β1, αLβ2, αMβ2, αXβ2, αDβ2, and α4β7 integrins, which interact with counter-receptors on other cells or ligands in the extracellular matrix. Whether a given integrin-ligand pair mediates cell adhesion and migration depends on the activation state of the integrin. Integrins exist in an inactive bent, an intermediate-activity extended closed, and a high-activity extended open conformation. Integrin activation states can be monitored by conformation-specific monoclonal antibodies (mAbs). Studies in mice indicate that both β1 and β2 integrins mediate eosinophil recruitment to the lung. In vitro studies indicate that α4β1 and αMβ2 are the principal integrins mediating eosinophil adhesion, including to vascular cell adhesion molecule-1 and the novel αMβ2 ligand periostin. In vivo, blood eosinophils have intermediate-activity β1 integrins, as judged by mAb N29, apparently resulting from eosinophil binding of P-selectin on the surface of activated platelets, and have a proportion of their β2 integrins in the intermediate conformation, as judged by mAb KIM-127, apparently due to exposure to low concentrations of interleukin-5 (IL-5). Airway eosinophils recovered by bronchoalveolar lavage (BAL) after segmental antigen challenge have high-activity β1 integrins and high-activity αMβ2 that does not require IL-5. Here we review information on how the activation states of eosinophil β1 and β2 integrins correlate with measurements of eosinophil recruitment and pulmonary function in asthma. Blood eosinophil N29 reactivity is associated with decreased lung function under various circumstances in non-severe asthma and KIM-127 with BAL eosinophil numbers, indicating that intermediate-activity α4β1 and αMβ2 of blood eosinophils are important for eosinophil arrest and consequently for recruitment and aspects of asthma. PMID

  4. Active states and structure transformations in accreting white dwarfs

    NASA Astrophysics Data System (ADS)

    Boneva, Daniela; Kaygorodov, Pavel

    2016-07-01

    Active states in white dwarfs are usually associated with light curve's effects that concern to the bursts, flickering or flare-up occurrences. It is common that a gas-dynamics source exists for each of these processes there. We consider the white dwarf binary stars with accretion disc around the primary. We suggest a flow transformation modeling of the mechanisms that are responsible for ability to cause some flow instability and bring the white dwarfs system to the outburst's development. The processes that cause the accretion rate to sufficiently increase are discussed. Then the transition from a quiescent to an active state is realized. We analyze a quasi-periodic variability in the luminosity of white dwarf binary stars systems. The results are supported with an observational data.

  5. Mining Claim Activity on Federal Land in the United States

    USGS Publications Warehouse

    Causey, J. Douglas

    2007-01-01

    Several statistical compilations of mining claim activity on Federal land derived from the Bureau of Land Management's LR2000 database have previously been published by the U.S Geological Survey (USGS). The work in the 1990s did not include Arkansas or Florida. None of the previous reports included Alaska because it is stored in a separate database (Alaska Land Information System) and is in a different format. This report includes data for all states for which there are Federal mining claim records, beginning in 1976 and continuing to the present. The intent is to update the spatial and statistical data associated with this report on an annual basis, beginning with 2005 data. The statistics compiled from the databases are counts of the number of active mining claims in a section of land each year from 1976 to the present for all states within the United States. Claim statistics are subset by lode and placer types, as well as a dataset summarizing all claims including mill site and tunnel site claims. One table presents data by case type, case status, and number of claims in a section. This report includes a spatial database for each state in which mining claims were recorded, except North Dakota, which only has had two claims. A field is present that allows the statistical data to be joined to the spatial databases so that spatial displays and analysis can be done by using appropriate geographic information system (GIS) software. The data show how mining claim activity has changed in intensity, space, and time. Variations can be examined on a state, as well as a national level. The data are tied to a section of land, approximately 640 acres, which allows it to be used at regional, as well as local scale. The data only pertain to Federal land and mineral estate that was open to mining claim location at the time the claims were staked.

  6. [Activities of Center for Nondestructive Evaluation, Iowa State University

    NASA Technical Reports Server (NTRS)

    Gray, Joe

    2002-01-01

    The final report of NASA funded activities at Iowa State University (ISU) for the period between 1/96 and 1/99 includes two main areas of activity. The first is the development and delivery of an x-ray simulation package suitable for evaluating the impact of parameters affects the inspectability of an assembly of parts. The second area was the development of images processing tools to remove reconstruction artifacts in x-ray laminagraphy images. The x-ray simulation portion of this work was done by J. Gray and the x-ray laminagraphy work was done by J. Basart. The report is divided into two sections covering the two activities respectively. In addition to this work reported the funding also covered NASA's membership in the NSF University/Industrial Cooperative Research Center.

  7. EF-G Activation by Phosphate Analogs.

    PubMed

    Salsi, Enea; Farah, Elie; Ermolenko, Dmitri N

    2016-05-22

    Elongation factor G (EF-G) is a universally conserved translational GTPase that promotes the translocation of tRNA and mRNA through the ribosome. EF-G binds to the ribosome in a GTP-bound form and subsequently catalyzes GTP hydrolysis. The contribution of the ribosome-stimulated GTP hydrolysis by EF-G to tRNA/mRNA translocation remains debated. Here, we show that while EF-G•GDP does not stably bind to the ribosome and induce translocation, EF-G•GDP in complex with phosphate group analogs BeF3(-) and AlF4(-) promotes the translocation of tRNA and mRNA. Furthermore, the rates of mRNA translocation induced by EF-G in the presence of GTP and a non-hydrolyzable analog of GTP, GDP•BeF3(-) are similar. Our results are consistent with the model suggesting that GTP hydrolysis is not directly coupled to mRNA/tRNA translocation. Hence, GTP binding is required to induce the activated, translocation-competent conformation of EF-G while GTP hydrolysis triggers EF-G release from the ribosome. PMID:27063503

  8. Air pollution information activities at state and local agencies--United States, 1992

    SciTech Connect

    Not Available

    1993-01-08

    Because air pollution is a pervasive environmental health problem in the United States, one of the national health objectives for the year 2000 is to increase from 49.7% to 85.0% the proportion of persons who live in counties that have not exceeded any air quality standard during the previous 12 months (1). Public support for air pollution control efforts is critical if this national health objective is to be achieved. To characterize public health information activities related to air pollution, in 1992, the State and Territorial Air Pollution Program Administrators (STAPPA) and the Association of Local Air Pollution Control Officials (ALAPCO), with the assistance of CDC, conducted a survey of state and local air pollution control agencies. This report summarizes the findings of that survey.

  9. Two-temperature formalin fixation preserves activation states efficiently.

    PubMed

    Chafin, David

    2015-01-01

    Modern pathology is built around the principle of preserving tissues such that the in vivo molecular status is maintained at levels representative of the disease state. Tissues are immersed in a solution of fixative which slowly inactivates biological activities, thus preserving the sample. Further processing ultimately allows the tissue to be embedded into wax for thin sectioning and staining for interpretation microscopically. Every year, around 7 billion tissue samples are submitted for processing in the United States alone. With this huge workload, histology laboratories are looking for faster methods of performing fixation, which currently require from several hours to days to complete. Ideally, this procedure could be standardized and would be quicker with better preservation over a wide range of biologically relevant molecules. PMID:25636434

  10. A state-of-the-art assessment of active structures

    NASA Technical Reports Server (NTRS)

    1992-01-01

    A state-of-the-art assessment of active structures with emphasis towards the applications in aeronautics and space is presented. It is felt that since this technology area is growing at such a rapid pace in many different disciplines, it is not feasible to cover all of the current research but only the relevant work as relates to aeronautics and space. Research in smart actuation materials, smart sensors, and control of smart/intelligent structures is covered. In smart actuation materials, piezoelectric, magnetostrictive, shape memory, electrorheological, and electrostrictive materials are covered. For sensory materials, fiber optics, dielectric loss, and piezoelectric sensors are examined. Applications of embedded sensors and smart sensors are discussed.

  11. CO2 ice state during active Dark Spot

    NASA Astrophysics Data System (ADS)

    Andrieu, F.; Schmidt, F.; Douté, S.

    2013-09-01

    MOC and HiRISE high-resolution images permitted the identification of various active seasonal processes such as cold CO2 jets or dark flows [7] on Mars seasonal caps, triggered by the caps' seasonal variations [5]. The purpose of this work is to retrieve quantitative information about the CO2 ice physical state, and its evolution, to constrain the active processes. To this end, we perform a radiative transfer inversion of CRISM near-infrared spectra before, during and after the event. After atmospheric gas and aerosols contributions correction [3], we use a radiative transfer model [2] that simulates reflectance spectra of granular icy material to create a look up table, and then a spectral inversion based on the likelihood that allows taking into account possible bias in atmospheric correction [1]. Using that inversion method, we are able to retrieve the spatial and temporal evolutions of various parameters of the icy surface.

  12. Update on nutrition monitoring activities in the United States.

    PubMed

    Kuczmarski, M F; Moshfegh, A; Briefel, R

    1994-07-01

    This article provides an overview of planned and proposed nutrition monitoring activities of the National Nutrition Monitoring and Related Research (NNMRR) Program. Key provisions of the NNMRR Act of 1990 are described, including the roles and responsibilities of the Interagency Board of Nutrition Monitoring and Related Research (IBNMRR) and the National Nutrition Monitoring Advisory Council and the development of the Ten-Year Comprehensive Plan. The Plan, which was developed under the guidance of the IBNMRR and reviewed by the National Nutrition Monitoring Advisory Council, is the basis for planning and coordinating the monitoring activities of 22 federal agencies. Also discussed are the resources generated from nutrition monitoring activities, from publications to conferences, that are available to dietitians and nutritionists. Professionals view the scientific reports that describe the nutritional status of the US population and the directories of federal and state monitoring activities as valuable resources. Suggestions from users of nutrition monitoring data related to their information and research needs have been extremely helpful to federal agencies in the development of future monitoring publications and the Ten-Year Comprehensive Plan. Continued communication between dietitians and the federal agencies responsible for the NNMRR Program is important. PMID:8021417

  13. [Investigation of Aerosol Mixed State and CCN Activity in Nanjing].

    PubMed

    Zhu, Lin; Ma, Yan; Zheng, Jun; Li, Shi-zheng; Wang, Li-peng

    2016-04-15

    During 11-18 September 2014, the size-resolved aerosol Cloud Condensation Nuclei (CCN) activity and mixing state were measured using Cloud Condensation Nuclei Counter (CCNC), Aerosol Particle Mass (APM) and Scanning Mobility Particle Sizer (SMPS). The results showed that aerosols mainly existed as an internal mixture. For 76, 111, 138 and 181 nm particles, black carbon (BC) accounted for 5.4%, 10%, l0.7% and 6.7% of the particle mass, but as high as 51%, 57%, 70% and 59% of the particle number concentrations, respectively, suggesting that BC was a type of important condensation nuclei in the atmosphere and made significant contributions to particle numbers. The occasionally observed external mixtures were mainly present in 111 and 138 nm particles. The critical supersaturation was 0.25%, 0.13%, 0.06% and 0.015% for 76, 111, 138 and 181 nm particles, respectively. Precipitation and haze had significant effects on the particle CCN activity. The hygroscopicity parameter K was 0.37, 0.29 and 0.39 in rainy, clear and hazy days, respectively. Particle density and CCN activity were impacted by chemical compositions. Compared with clear days, higher contents of inorganic salts and lower contents of organics were found on hazy days, accompanied by lower particle density and higher CCN activity. PMID:27548938

  14. Role of carotenoid excited states and radicals in antioxidant activities

    NASA Astrophysics Data System (ADS)

    Lambert, Chris R.

    1995-05-01

    Carotenoids are linear polyenes that occur in nature and are known to have powerful antioxidant properties. They react efficiently with the excited states of many organic molecules. In the photosynthetic apparatus of plants they quench reactive excited states that may be formed and release the energy as heat. In photodynamic therapy they may be used to ameliorate the associated skin photosensitivity that is a consequence of many photosensitizers. This protection may be either through reaction with the sensitizer triplet state or through quenching of singlet oxygen. Carotenoids also form relatively stable radical species and react efficiently with the hydroxyl radical, superoxide and the solvated electron. In cells they are associated with the lipid core of the cell membrane and are effective against lipid peroxidation. The importance of the thermodynamic properties of these compounds and their organization within biological systems is pivotal to understanding carotenoid antioxidant activity. The present paper reviews some recent work on the energy level of (beta) -carotene, electron transfer involving the one electron reduced species and the resonance Raman spectra of some carotenoids in micellar solution.

  15. Diabetic state-induced activation of calcium-activated neutral proteinase in mouse skeletal muscle.

    PubMed

    Kobayashi, S; Fujihara, M; Hoshino, N; Kimura, I; Kimura, M

    1989-12-01

    The effect of a diabetic state in the diabetic KK-CAy mouse on calcium activated neutral proteinase (CANP) of hind-limb skeletal muscles was investigated. In the diabetic state, there was an increased sensitivity to activation of CANP by calcium (Ca). In addition, there was an enhancement of maximal activity of the enzyme. The effect was induced by secondary modification of the diabetic state, but not genetical factors. Several lines of evidence suggest that the CANP is responsible for 92 K dalton protein in diabetic skeletal muscles. Among the evidence are the following: a) The 92 K band in the diabetic muscles was lower than in the prediabetic mouse and restored by the addition of 2 mM EDTA and 2 mM EGTA. b) The band was reduced by increasing the Ca content and neutral pH in the non-diabetic normal muscles. c) E-64-C, a CANP inhibitor, restored the 92 K component reduced by the diabetic state. Since the band in denervated muscles was not changed by the Ca chelating agents, the reduction of the band in the diabetic muscles is related with musculotrophic factors, not diabetic neuropathy. These results suggest that diabetic amyotrophy may be regarded as a phenomenon linked to an increase in intracellular Ca ions and an increase in CANP activity. PMID:2561275

  16. Resting-State Brain Activity in Adult Males Who Stutter

    PubMed Central

    Zhu, Chaozhe; Wang, Liang; Yan, Qian; Lin, Chunlan; Yu, Chunshui

    2012-01-01

    Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them. PMID:22276215

  17. Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain

    PubMed Central

    Hsu, Jia-Wei; Chen, Kuan-Jung; Lee, Fang-Jen S.

    2015-01-01

    Active GTP-bound Arf GTPases promote eukaryotic cell membrane trafficking and cytoskeletal remodelling. Arf activation is accelerated by guanine nucleotide-exchange factors (GEFs) using the critical catalytic glutamate in all known Sec7 domain sequences. Yeast Arf3p, a homologue of mammalian Arf6, is required for yeast invasive responses to glucose depletion. Here we identify Snf1p as a GEF that activates Arf3p when energy is limited. SNF1 is the yeast homologue of AMP-activated protein kinase (AMPK), which is a key regulator of cellular energy homeostasis. As activation of Arf3p does not depend on the Snf1p kinase domain, assay of regulatory domain fragments yield evidence that the C-terminal hydrophobic α-helix core of Snf1p is a non-canonical GEF for Arf3p activation. Thus, our study reveals a novel mechanism for regulating cellular responses to energy deprivation, in particular invasive cell growth, through direct Arf activation by Snf1/AMPK. PMID:26198097

  18. Hypoxia Induces a Prothrombotic State Independently of the Physical Activity

    PubMed Central

    Ninivaggi, Marisa; de Laat, Marieke; Lancé, Marcus M. D.; Kicken, Cécile H.; Pelkmans, Leonie; Bloemen, Saartje; Dirks, Marlou L.; van Loon, Luc J. C.; Govers-Riemslag, José W. P.; Lindhout, Theo; Konings, Joke; de Laat, Bas

    2015-01-01

    Hypoxia (oxygen deprivation) is known to be associated with deep vein thrombosis and venous thromboembolism. We attempted to get a better comprehension of its mechanism by going to high altitude, thereby including the potential contributing role of physical activity. Two groups of 15 healthy individuals were exposed to hypoxia by going to an altitude of 3900 meters, either by climbing actively (active group) or transported passively by cable car (passive group). Both groups were tested for plasma fibrinogen, von Willebrand factor and factor VIII levels, fibrinolysis, thrombin generating capacity, heart rate, oxygen saturation levels and blood pressure. As a control for the passive group, 7 healthy volunteers stayed immobile in bed for 7 days at normoxic conditions. The heart rate increased and oxygen saturation levels decreased with increasing altitude. Fibrinolysis and fibrinogen levels were not affected. Factor VIII and von Willebrand factor levels levels increased significantly in the active group, but not in the passive group. Plasma thrombin generation remained unchanged in both the active and passive group with increasing altitude and during 7 days of immobility in healthy subjects. However, by applying whole blood thrombin generation, we found an increased peak height and endogenous thrombin potential, and a decreased lagtime and time-to-peak with increasing levels of hypoxia in both groups. In conclusion, by applying whole blood thrombin generation we demonstrated that hypoxia causes a prothrombotic state. As thrombin generation in plasma did not increase, our results suggest that the cellular part of the blood is involved in the prothrombotic phenotype induced by hypoxia. PMID:26516774

  19. What should be the roles of conscious States and brain States in theories of mental activity?

    PubMed

    Dulany, Donelson E

    2011-01-01

    Answers to the title's question have been influenced by a history in which an early science of consciousness was rejected by behaviourists on the argument that this entails commitment to ontological dualism and "free will" in the sense of indeterminism. This is, however, a confusion of theoretical assertions with metaphysical assertions. Nevertheless, a legacy within computational and information-processing views of mind rejects or de-emphasises a role for consciousness. This paper sketches a mentalistic metatheory in which conscious states are the sole carriers of symbolic representations, and thus have a central role in the explanation of mental activity and action-while specifying determinism and materialism as useful working assumptions. A mentalistic theory of causal learning, experimentally examined with phenomenal reports, is followed by examination of these questions: Are there common roles for phenomenal reports and brain imaging? Is there defensible evidence for unconscious brain states carrying symbolic representations? Are there interesting dissociations within consciousness? PMID:21694964

  20. Passive resting state and history of antagonist muscle activity shape active extensions in an insect limb.

    PubMed

    Ache, Jan M; Matheson, Thomas

    2012-05-01

    Limb movements can be driven by muscle contractions, external forces, or intrinsic passive forces. For lightweight limbs like those of insects or small vertebrates, passive forces can be large enough to overcome the effects of gravity and may even generate limb movements in the absence of active muscle contractions. Understanding the sources and actions of such forces is therefore important in understanding motor control. We describe passive properties of the femur-tibia joint of the locust hind leg. The resting angle is determined primarily by passive properties of the relatively large extensor tibiae muscle and is influenced by the history of activation of the fast extensor tibiae motor neuron. The resting angle is therefore better described as a history-dependent resting state. We selectively stimulated different flexor tibiae motor neurons to generate a range of isometric contractions of the flexor tibiae muscle and then stimulated the fast extensor tibiae motor neuron to elicit active tibial extensions. Residual forces in the flexor muscle have only a small effect on subsequent active extensions, but the effect is larger for distal than for proximal flexor motor neurons and varies with the strength of flexor activation. We conclude that passive properties of a lightweight limb make substantial and complex contributions to the resting state of the limb that must be taken into account in the patterning of neuronal control signals driving its active movements. Low variability in the effects of the passive forces may permit the nervous system to accurately predict their contributions to behavior. PMID:22357791

  1. Active output state of the Synechococcus Kai circadian oscillator

    PubMed Central

    Paddock, Mark L.; Boyd, Joseph S.; Adin, Dawn M.; Golden, Susan S.

    2013-01-01

    The mechanisms by which cellular oscillators keep time and transmit temporal information are poorly understood. In cyanobacteria, the timekeeping aspect of the circadian oscillator, composed of the KaiA, KaiB, and KaiC proteins, involves a cyclic progression of phosphorylation states at Ser431 and Thr432 of KaiC. Elucidating the mechanism that uses this temporal information to modulate gene expression is complicated by unknowns regarding the number, structure, and regulatory effects of output components. To identify oscillator signaling states without a complete description of the output machinery, we defined a simple metric, Kai-complex output activity (KOA), that represents the difference in expression of reporter genes between strains that carry specific variants of KaiC and baseline strains that lack KaiC. In the absence of the oscillator, expression of the class 1 paradigm promoter PkaiBC was locked at its usual peak level; conversely, that of the class 2 paradigm promoter PpurF was locked at its trough level. However, for both classes of promoters, peak KOA in wild-type strains coincided late in the circadian cycle near subjective dawn, when KaiC-pST becomes most prevalent (Ser431 is phosphorylated and Thr432 is not). Analogously, peak KOA was detected specifically for the phosphomimetic of KaiC-pST (KaiC-ET). Notably, peak KOA required KaiB, indicating that a KaiBC complex is involved in the output activity. We also found evidence that phosphorylated RpaA (regulator of phycobilisome associated) represses an RpaA-independent output of KOA. A simple mathematical expression successfully simulated two key features of the oscillator—the time of peak KOA and the peak-to-trough amplitude changes. PMID:24043774

  2. Low-dimensional dynamics of resting-state cortical activity.

    PubMed

    Mehrkanoon, Saeid; Breakspear, Michael; Boonstra, Tjeerd W

    2014-05-01

    Endogenous brain activity supports spontaneous human thought and shapes perception and behavior. Connectivity-based analyses of endogenous, or resting-state, functional magnetic resonance imaging (fMRI) data have revealed the existence of a small number of robust networks which have a rich spatial structure. Yet the temporal information within fMRI data is limited, motivating the complementary analysis of electrophysiological recordings such as electroencephalography (EEG). Here we provide a novel method based on multivariate time-frequency interdependence to reconstruct the principal resting-state network dynamics in human EEG data. The stability of network expression across subjects is assessed using resampling techniques. We report the presence of seven robust networks, with distinct topographic organizations and high frequency (∼ 5-45 Hz) fingerprints, nested within slow temporal sequences that build up and decay over several orders of magnitude. Interestingly, all seven networks are expressed concurrently during these slow dynamics, although there is a temporal asymmetry in the pattern of their formation and dissolution. These analyses uncover the complex temporal character of endogenous cortical fluctuations and, in particular, offer an opportunity to reconstruct the low dimensional linear subspace in which they unfold. PMID:24104726

  3. On-line, adaptive state estimator for active noise control

    NASA Technical Reports Server (NTRS)

    Lim, Tae W.

    1994-01-01

    Dynamic characteristics of airframe structures are expected to vary as aircraft flight conditions change. Accurate knowledge of the changing dynamic characteristics is crucial to enhancing the performance of the active noise control system using feedback control. This research investigates the development of an adaptive, on-line state estimator using a neural network concept to conduct active noise control. In this research, an algorithm has been developed that can be used to estimate displacement and velocity responses at any locations on the structure from a limited number of acceleration measurements and input force information. The algorithm employs band-pass filters to extract from the measurement signal the frequency contents corresponding to a desired mode. The filtered signal is then used to train a neural network which consists of a linear neuron with three weights. The structure of the neural network is designed as simple as possible to increase the sampling frequency as much as possible. The weights obtained through neural network training are then used to construct the transfer function of a mode in z-domain and to identify modal properties of each mode. By using the identified transfer function and interpolating the mode shape obtained at sensor locations, the displacement and velocity responses are estimated with reasonable accuracy at any locations on the structure. The accuracy of the response estimates depends on the number of modes incorporated in the estimates and the number of sensors employed to conduct mode shape interpolation. Computer simulation demonstrates that the algorithm is capable of adapting to the varying dynamic characteristics of structural properties. Experimental implementation of the algorithm on a DSP (digital signal processing) board for a plate structure is underway. The algorithm is expected to reach the sampling frequency range of about 10 kHz to 20 kHz which needs to be maintained for a typical active noise control

  4. Water-temperature data acquisition activities in the United States

    USGS Publications Warehouse

    Pauszek, F.H.

    1972-01-01

    Water Data Coordination, U.S. Geological Survey, and published in the "Catalog of Information on Water Data, Index to Water Quality Section, Edition 1970." This is one of four indexes, each of which is a separate section of the Catalog. Three of the indexes, "Index to Water-Quality Section," "Index to Surface-Water Section," and "Index to Ground-.Water Stations," contain information on data acquired on a recurrent basis at specific locations for a period of 3 years or more. The fourth section, "Index to Areal Investigations and Miscellaneous Activities," is concerned with specific projects or shorter-term data activities that involve field or laboratory measurements or observations not included in any other section of the Catalog. The Catalog is a record of activities throughout the country (and in some places along the international border between the United States and Canada) conducted by Federal and non-Federal agencies engaged in the acquisition of water data and who furnish such information for presentation in the Catalog. The Catalog itself is an outgrowth of an assignment to the Department of the Interior and in turn to the Geological Survey, by the Office of Management and Budget, through the medium of OMB Circular A-67. This Circular states in part that one of the assigned responsibilities will be maintenance of a "central catalog of information on...water data and on Federal activities being planned or conducted to acquire such data." As an extension of this activity, non-Federal agencies are solicited to participate in the program. In this report, information is presented by means of tables and illustrations preceded by brief explanations. It includes the agencies collecting the data, the number of stations located on surface and ground waters where temperature measurements are made, the distribution of stations by States and by the 21 regions of the Water Resources Council (WRC) (a Federal agency created in accordance with the Water Resources Planning Act of

  5. Nitrogen molecule activation by excited states of copper

    SciTech Connect

    Sanchez-Zamora, M.; Novaro, O.; Ruiz, M.E. )

    1990-04-05

    Ab initio molecular orbital studies that include variational (with a multiconfiguration reference state of 200 states) and perturbational (including over 3 million configurations) configuration interaction calculations were addressed to the interaction of nitrogen molecules with copper. The Cu ground state {sup 2}S and first two excited states {sup 2}P and {sup 2}D were studied as they interact in different geometrical approaches (including side-on and end-on geometries) with ground-state N{sub 2} molecules.

  6. What Should Be the Roles of Conscious States and Brain States in Theories of Mental Activity?**

    PubMed Central

    Dulany, Donelson E.

    2011-01-01

    Answers to the title’s question have been influenced by a history in which an early science of consciousness was rejected by behaviourists on the argument that this entails commitment to ontological dualism and “free will” in the sense of indeterminism. This is, however, a confusion of theoretical assertions with metaphysical assertions. Nevertheless, a legacy within computational and information-processing views of mind rejects or de-emphasises a role for consciousness. This paper sketches a mentalistic metatheory in which conscious states are the sole carriers of symbolic representations, and thus have a central role in the explanation of mental activity and action-while specifying determinism and materialism as useful working assumptions. A mentalistic theory of causal learning, experimentally examined with phenomenal reports, is followed by examination of these questions: Are there common roles for phenomenal reports and brain imaging? Is there defensible evidence for unconscious brain states carrying symbolic representations? Are there interesting dissociations within consciousness? PMID:21694964

  7. Destination state screening of active spaces in spin dynamics simulations

    NASA Astrophysics Data System (ADS)

    Krzystyniak, M.; Edwards, Luke J.; Kuprov, Ilya

    2011-06-01

    We propose a novel avenue for state space reduction in time domain Liouville space spin dynamics simulations, using detectability as a selection criterion - only those states that evolve into or affect other detectable states are kept in the simulation. This basis reduction procedure (referred to as destination state screening) is formally exact and can be applied on top of the existing state space restriction techniques. As demonstrated below, in many cases this results in further reduction of matrix dimension, leading to considerable acceleration of many spin dynamics simulation types. Destination state screening is implemented in the latest version of the Spinach library (http://spindynamics.org).

  8. EPAC activation inhibits acetaldehyde-induced activation and proliferation of hepatic stellate cell via Rap1.

    PubMed

    Yang, Yan; Yang, Feng; Wu, Xiaojuan; Lv, Xiongwen; Li, Jun

    2016-05-01

    Hepatic stellate cells (HSCs) activation represents an essential event during alcoholic liver fibrosis (ALF). Previous studies have demonstrated that the rat HSCs could be significantly activated after exposure to 200 μmol/L acetaldehyde for 48 h, and the cAMP/PKA signaling pathways were also dramatically upregulated in activated HSCs isolated from alcoholic fibrotic rat liver. Exchange protein activated by cAMP (EPAC) is a family of guanine nucleotide exchange factors (GEFs) for the small Ras-like GTPases Rap, and is being considered as a vital mediator of cAMP signaling in parallel with the principal cAMP target protein kinase A (PKA). Our data showed that both cAMP/PKA and cAMP/EPAC signaling pathways were involved in acetaldehyde-induced HSCs. Acetaldehyde could reduce the expression of EPAC1 while enhancing the expression of EPAC2. The cAMP analog Me-cAMP, which stimulates the EPAC/Rap1 pathway, could significantly decrease the proliferation and collagen synthesis of acetaldehyde-induced HSCs. Furthermore, depletion of EPAC2, but not EPAC1, prevented the activation of HSC measured as the production of α-SMA and collagen type I and III, indicating that EPAC1 appears to have protective effects on acetaldehyde-induced HSCs. Curiously, activation of PKA or EPAC perhaps has opposite effects on the synthesis of collagen and α-SMA: EPAC activation by Me-cAMP increased the levels of GTP-bound (activated) Rap1 while PKA activation by Phe-cAMP had no significant effects on such binding. These results suggested that EPAC activation could inhibit the activation and proliferation of acetaldehyde-induced HSCs via Rap1. PMID:26854595

  9. Student Activity Packet for the California State Capitol Museum.

    ERIC Educational Resources Information Center

    2001

    This packet contains materials to help fourth and fifth grade teachers provide their students with background information for field trips to the California State Capitol Museum (Sacramento). The working museum focuses on the theme areas of California history, the state government/legislative process, and state symbols. The packet presents teacher…

  10. Sector Activities and Lessons Learned Around Initial Implementation of the United States National Physical Activity Plan

    PubMed Central

    Evenson, Kelly R.; Satinsky, Sara B.

    2016-01-01

    Background National plans are increasingly common but infrequently evaluated. The 2010 United States National Physical Activity Plan (NPAP) provided strategies to increase population levels of physical activity. This paper describes (i) the initial accomplishments of the NPAP sector teams, and (ii) results from a process evaluation to determine how the sectors operated, their cross-sector collaboration, challenges encountered, and positive experiences. Methods During 2011, a quarterly reporting system was developed to capture sector-level activities. A year-end interview derived more detailed information. Interviews with 12 sector leads were recorded, transcribed verbatim, and analyzed for common themes. Results The 6 sectors worked on goals from the implementation plan that focused broadly on education, promotion, intervention, policy, collaboration, and evaluation. Through year-end interviews, themes were generated around operations, goal setting, and cross-sector collaboration. Challenges to the NPAP work included lack of funding and time, the need for marketing and promotion, and organizational support. Positive experiences included collaboration, efficiency of work, enhanced community dynamic, and accomplishments toward NPAP goals. Conclusions These initial results on the NPAP sector teams can be used as a baseline assessment for future monitoring. The lessons learned may be useful to other practitioners developing evaluations around state- or national-level plans. PMID:24176800

  11. 40 CFR 745.325 - Lead-based paint activities: State and Tribal program requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES State and Indian Tribal Programs § 745.325 Lead-based paint activities: State and... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Lead-based paint activities: State...

  12. 40 CFR 745.325 - Lead-based paint activities: State and Tribal program requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES State and Indian Tribal Programs § 745.325 Lead-based paint activities: State and... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Lead-based paint activities: State...

  13. 40 CFR 745.325 - Lead-based paint activities: State and Tribal program requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES State and Indian Tribal Programs § 745.325 Lead-based paint activities: State and... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Lead-based paint activities: State...

  14. 40 CFR 745.325 - Lead-based paint activities: State and Tribal program requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES State and Indian Tribal Programs § 745.325 Lead-based paint activities: State and... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Lead-based paint activities: State...

  15. Reap around the State: "Best of Reap" Activities.

    ERIC Educational Resources Information Center

    Indiana State Dept. of Education, Indianapolis. Learning Resources Unit.

    This booklet presents selected activities from elementary, middle, junior high, and senior high schools In Indiana, intended to encourage students to read. It offers ideas for 11 community activities (including guest readers, nursing home reading, and a young author celebration), 14 continuous activities (such as the great book graffiti wall and…

  16. Structure of an archaeal heterotrimeric initiation factor 2 reveals a nucleotide state between the GTP and the GDP states

    PubMed Central

    Yatime, Laure; Mechulam, Yves; Blanquet, Sylvain; Schmitt, Emmanuelle

    2007-01-01

    Initiation of translation in eukaryotes and in archaea involves eukaryotic/archaeal initiation factor (e/aIF)1 and the heterotrimeric initiation factor e/aIF2. In its GTP-bound form, e/aIF2 provides the initiation complex with Met–tRNAiMet. After recognition of the start codon by initiator tRNA, e/aIF1 leaves the complex. Finally, e/aIF2, now in a GDP-bound form, loses affinity for Met–tRNAiMet and dissociates from the ribosome. Here, we report a 3D structure of an aIF2 heterotrimer from the archeon Sulfolobus solfataricus obtained in the presence of GDP. Our report highlights how the two-switch regions involved in formation of the tRNA-binding site on subunit γ exchange conformational information with α and β. The zinc-binding domain of β lies close to the guanine nucleotide and directly contacts the switch 1 region. As a result, switch 1 adopts a not yet described conformation. Moreover, unexpectedly for a GDP-bound state, switch 2 has the “ON” conformation. The stability of these conformations is accounted for by a ligand, most probably a phosphate ion, bound near the nucleotide binding site. The structure suggests that this GDP–inorganic phosphate (Pi) bound state of aIF2 may be proficient for tRNA binding. Recently, it has been proposed that dissociation of eIF2 from the initiation complex is closely coupled to that of Pi from eIF2γ upon start codon recognition. The nucleotide state of aIF2 shown here is indicative of a similar mechanism in archaea. Finally, we consider the possibility that release of Pi takes place after e/aIF2γ has been informed of e/aIF1 dissociation by e/aIF2β. PMID:18000047

  17. Report to the Congress from The President of the United States. United States Aeronautics and Space Activities 1967.

    ERIC Educational Resources Information Center

    Johnson, Lyndon B.

    This report extensively reviews the progress of the United States in space during 1967, the tenth year of the space age. The first chapter of the report summarizes the 1967 space activities; and each of the remaining 13 chapters is devoted to reviewing the space-related activities of a particular federal agency (13 agencies included). Appendices…

  18. 78 FR 54637 - Agency Information Collection Activities; Comment Request; State Educational Agency, Local...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-05

    ... Agency Information Collection Activities; Comment Request; State Educational Agency, Local Educational... information technology. Please note that written comments received in response to this notice will be considered public records. Title of Collection: State Educational Agency, Local Educational Agency,...

  19. In-depth interviews with state public health practitioners on the United States National Physical Activity Plan

    PubMed Central

    2013-01-01

    Background The United States National Physical Activity Plan (NPAP; 2010), the country’s first national plan for physical activity, provides strategies to increase population-level physical activity to complement the 2008 physical activity guidelines. This study examined state public health practitioner awareness, dissemination, use, challenges, and recommendations for the NPAP. Methods In 2011–2012, we interviewed 27 state practitioners from 25 states. Interviews were recorded and transcribed verbatim. Transcripts were coded using a standard protocol, verified and reconciled by an independent coder, and input into qualitative software to facilitate development of common themes. Results NPAP awareness was high among state practitioners; dissemination to local constituents varied. Development of state-level strategies and goals was the most frequently reported use of the NPAP. Some respondents noted the usefulness of the NPAP for coalitions and local practitioners. Challenges to the plan included implementation cost, complexity, and consistency with other policies. The most frequent recommendation made was to directly link examples of implementation activities to the plan. Conclusions These results provide early evidence of NPAP dissemination and use, along with challenges encountered and suggestions for future iterations. Public health is one of eight sectors in the NPAP. Further efforts are needed to understand uptake and use by other sectors, as well as to monitor long-term relevance, progress, and collaboration across sectors. PMID:23731829

  20. Activism in Concrete: Student Union, San Francisco State University

    ERIC Educational Resources Information Center

    Progressive Architecture, 1978

    1978-01-01

    The San Francisco State University Student Union is a futurist design of two steel space-frame pyramids. Each contains a stairway leading to four partial floors that diminish in size as the pyramid tapers. (Author/MLF)

  1. A Cross Section Analysis of State Recreation Activity

    ERIC Educational Resources Information Center

    Seneca, Joseph J.; Davis, Robert K.

    1976-01-01

    Planning techniques provide a means of systematically evaluating and documenting the impact of alternative land use strategies, thereby enabling state recreational planners to develop policies and programs offensively, rather than as defensive reactions to deteriorating situations. (MB)

  2. Spindle Assembly in the Absence of a RanGTP Gradient Requires Localized CPC Activity

    PubMed Central

    Maresca, Thomas J.; Groen, Aaron C.; Gatlin, Jesse C.; Ohi, Ryoma; Mitchison, Timothy J.; Salmon, Edward D.

    2009-01-01

    Summary During animal cell division, a gradient of GTP-bound Ran is generated around mitotic chromatin [1, 2]. It is generally accepted that this RanGTP gradient is essential for organizing the spindle since it locally activates critical spindle assembly factors [3–5]. Here, we show in Xenopus egg extract, where the gradient is best characterized, that spindles can assemble in the absence of a RanGTP gradient. Gradient-free spindle assembly occurred around sperm nuclei but not around chromatin-coated beads and required the chromosomal passenger complex (CPC). Artificial enrichment of CPC activity within hybrid bead arrays containing both immobilized chromatin and the CPC supported local microtubule assembly even in the absence of a RanGTP gradient. We conclude that RanGTP and the CPC constitute the two major molecular signals that spatially promote microtubule polymerization around chromatin. Furthermore, we hypothesize that the two signals mainly originate from discreet physical sites on the chromosomes to localize microtubule assembly around chromatin: a RanGTP signal from any chromatin, and a CPC-dependent signal predominantly generated from centromeric chromatin. PMID:19540121

  3. A direct fluorescence-based assay for RGS domain GTPase accelerating activity.

    PubMed

    Willard, Francis S; Kimple, Adam J; Johnston, Christopher A; Siderovski, David P

    2005-05-15

    Diverse extracellular signals regulate seven transmembrane-spanning receptors to modulate cellular physiology. These receptors signal primarily through activation of heterotrimeric guanine nucleotide binding proteins (G proteins). A major determinant of heterotrimeric G protein signaling in vivo and in vitro is the intrinsic GTPase activity of the Galpha subunit. RGS (regulator of G protein signaling) domain-containing proteins are GTPase accelerating proteins specific for Galpha subunits. In this article, we describe the use of the ribose-conjugated fluorescent guanine nucleotide analog BODIPYFL-GTP as a spectroscopic probe to measure intrinsic and RGS protein-catalyzed nucleotide hydrolysis by Galphao. BODIPYFL-GTP bound to Galphao exhibits a 200% increase in fluorescence quantum yield. Hydrolysis of BODIPYFL-GTP to BODIPYFL-GDP reduces the quantum yield to 27% above its unbound value. We demonstrate that BODIPYFL-GTP can be used as a rapid real-time probe for measuring RGS domain-catalyzed GTP hydrolysis by Galphao. We demonstrate the effectiveness of this assay in the analysis of loss-of-function point mutants of both Galphao and RGS12. This assay should be useful in screening for and analyzing RGS protein inhibitory compounds. PMID:15840508

  4. Excited states in the active media of oxygen - iodine lasers

    SciTech Connect

    Azyazov, V N

    2009-11-30

    A review of investigations of kinetic processes in active media oxygen - iodine lasers (OILs) performed in the last decade is presented. The mechanisms of pumping and quenching of electronically and vibrationally excited O{sub 2} and I{sub 2} molecules are considered, and dissociation mechanisms of I{sub 2} in the active medium of the OIL are analysed. The values of kinetic constants of processes proceeding in the active media of OILs are recommended. (review)

  5. Illinois State Bar Association Law Day Activities Guide. 2001 Edition.

    ERIC Educational Resources Information Center

    Illinois State Bar Association, Springfield.

    These law-related lessons and activities can facilitate participation in a Law Day program. Following an introduction, this activities guide is divided into these sections: "Tips for Teachers" ("What Can a Lawyer Add to the Classroom?"; "So You Have Been Asked to Speak to Kids about the Law"; "A Checklist for Lawyers and Judges in the Classroom");…

  6. Heterogeneity of dopamine neuron activity across traits and states

    PubMed Central

    Marinelli, Michela; McCutcheon, James E.

    2014-01-01

    Midbrain dopamine neurons fire irregularly, with interspersed clusters of high-frequency spikes, commonly called ‘bursts’. In this review we examine such heterogeneity in activity, and provide insight into how it can participate in psychiatric conditions such as drug addiction. We first describe several techniques used to evaluate dopamine neuron activity, and comment on the different measures that each provides. We next describe the activity of dopamine neurons in ‘basal’ conditions. Specifically, we discuss how the use of anesthesia and reduced preparations may alter aspects of dopamine cell activity, and how there is heterogeneity across species and regions. We also describe how dopamine cell firing changes throughout the peri-adolescent period and how dopamine neuron activity differs across the population. In the final section, we discuss how dopamine neuron activity changes in response to life events. First, we focus attention on drugs of abuse. Drugs themselves change firing activity through a variety of mechanisms, with effects on firing while drug is present differing from those seen after drug discontinuation. We then review how stimuli that are rewarding, aversive, or salient can evoke changes in firing rate and discharge pattern of dopamine neurons, and provide behavioral relevance of dopamine signaling. Finally, we discuss how stress can modulate dopamine neuron firing and how this may contribute to the role that stressful experiences play in psychiatric disorders such as addiction and depression. PMID:25084048

  7. Heterogeneity of dopamine neuron activity across traits and states.

    PubMed

    Marinelli, M; McCutcheon, J E

    2014-12-12

    Midbrain dopamine neurons fire irregularly, with interspersed clusters of high-frequency spikes, commonly called 'bursts'. In this review we examine such heterogeneity in activity, and provide insight into how it can participate in psychiatric conditions such as drug addiction. We first describe several techniques used to evaluate dopamine neuron activity, and comment on the different measures that each provides. We next describe the activity of dopamine neurons in 'basal' conditions. Specifically, we discuss how the use of anesthesia and reduced preparations may alter aspects of dopamine cell activity, and how there is heterogeneity across species and regions. We also describe how dopamine cell firing changes throughout the peri-adolescent period and how dopamine neuron activity differs across the population. In the final section, we discuss how dopamine neuron activity changes in response to life events. First, we focus attention on drugs of abuse. Drugs themselves change firing activity through a variety of mechanisms, with effects on firing while drug is present differing from those seen after drug discontinuation. We then review how stimuli that are rewarding, aversive, or salient can evoke changes in firing rate and discharge pattern of dopamine neurons, and provide behavioral relevance of dopamine signaling. Finally, we discuss how stress can modulate dopamine neuron firing and how this may contribute to the role that stressful experiences play in psychiatric disorders such as addiction and depression. PMID:25084048

  8. An update of Utah State University's GAS activities

    NASA Technical Reports Server (NTRS)

    Megill, L. R.

    1986-01-01

    The highlights of the Utah State University's participation in the space program are listed. Proposed experiments include: a study of the velocity of a bubble in water under the influence of a temperature gradient; reflight of an experiment on surface tension driven convective flow; surface waves in zero-G; crystallization in zero-G (vapor phase and liquid phase); bio gas generation; and penicillum growth; study of undamped oscillations in a vacuum and zero-G. The effect that spinoffs have had on the Utah State University were discussed.

  9. Program activities, DOE state and local assistance programs, 1980 report

    SciTech Connect

    Chiogioji, Melvin H.

    1981-01-01

    Progress achieved by DOE State and Local Assistance Programs during FY 1980 and since they were established is summarized. These programs enable improved energy efficiency of industry, transportation, commercial establishments, public buildings, and residences. Eight programs (State Energy Conservation, Energy Extension Service, Weatherization Assistance, Institutional Buildings Grants, Energy-Related Inventions, Appropriate Technology Small Grants, Emergency Energy Conservation, Emergency Building Temperature Restrictions) are described. They provide the impetus for thousands of individual and organizational actions that have significantly affected national energy use patterns. (MCW)

  10. Steady-state heating of active fibres under optical pumping

    SciTech Connect

    Gainov, V V; Shaidullin, R I; Ryabushkin, Oleg A

    2011-07-31

    We have measured the temperature in the core of rare-earth-doped optical fibres under lasing conditions at high optical pump powers using a fibre Mach - Zehnder interferometer and probe light of wavelength far away from the absorption bands of the active ions. From the observed heating kinetics of the active medium, the heat transfer coefficient on the polymer cladding - air interface has been estimated. The temperature of the active medium is shown to depend on the thermal and optical properties of the polymer cladding. (fiber and integrated optics)

  11. Cdc42 Regulation of Kinase Activity and Signaling by the Yeast p21-Activated Kinase Ste20

    PubMed Central

    Lamson, Rachel E.; Winters, Matthew J.; Pryciak, Peter M.

    2002-01-01

    The Saccharomyces cerevisiae kinase Ste20 is a member of the p21-activated kinase (PAK) family with several functions, including pheromone-responsive signal transduction. While PAKs are usually activated by small G proteins and Ste20 binds Cdc42, the role of Cdc42-Ste20 binding has been controversial, largely because Ste20 lacking its entire Cdc42-binding (CRIB) domain retains kinase activity and pheromone response. Here we show that, unlike CRIB deletion, point mutations in the Ste20 CRIB domain that disrupt Cdc42 binding also disrupt pheromone signaling. We also found that Ste20 kinase activity is stimulated by GTP-bound Cdc42 in vivo and this effect is blocked by the CRIB point mutations. Moreover, the Ste20 CRIB and kinase domains bind each other, and mutations that disrupt this interaction cause hyperactive kinase activity and bypass the requirement for Cdc42 binding. These observations demonstrate that the Ste20 CRIB domain is autoinhibitory and that this negative effect is antagonized by Cdc42 to promote Ste20 kinase activity and signaling. Parallel results were observed for filamentation pathway signaling, suggesting that the requirement for Cdc42-Ste20 interaction is not qualitatively different between the mating and filamentation pathways. While necessary for pheromone signaling, the role of the Cdc42-Ste20 interaction does not require regulation by pheromone or the pheromone-activated Gβγ complex, because the CRIB point mutations also disrupt signaling by activated forms of the kinase cascade scaffold protein Ste5. In total, our observations indicate that Cdc42 converts Ste20 to an active form, while pathway stimuli regulate the ability of this active Ste20 to trigger signaling through a particular pathway. PMID:11940652

  12. Resting-State Oscillatory Activity in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Cornew, Lauren; Roberts, Timothy P. L.; Blaskey, Lisa; Edgar, J. Christopher

    2012-01-01

    Neural oscillatory anomalies in autism spectrum disorders (ASD) suggest an excitatory/inhibitory imbalance; however, the nature and clinical relevance of these anomalies are unclear. Whole-cortex magnetoencephalography data were collected while 50 children (27 with ASD, 23 controls) underwent an eyes-closed resting-state exam. A Fast Fourier…

  13. Objectively Assessed Physical Activity among Tongans in the United States

    ERIC Educational Resources Information Center

    Behrens, Timothy K.; Moy, Karen; Dinger, Mary K.; Williams, Daniel P.; Harbour, Vanessa J.

    2011-01-01

    Until recently, health statistics data for Native Hawaiians and Pacific Islanders (NHPI) in the United States were almost nonexistent, due to their being historically aggregated into one homogenous group with Asian Americans. However, recent studies on U.S. NHPI highlight a multitude of obesity-related health disparities indicating the necessity…

  14. State of the science: a focus on physical activity.

    PubMed

    Hills, Andrew P; Byrne, Nuala M

    2006-01-01

    Diet, exercise, behavioural support and for some obese individuals, pharmacotherapy, represent the set of lifestyle factors necessary for effective management of obesity. An on-going challenge in the prevention, treatment and management of obesity is to arm health professionals in particular, with the necessary knowledge and understanding and time to engage in meaningful weight management counseling. Despite the many barriers to effective management such as lack of relevant education in nutrition and physical activity, perceived patient non-compliance, perceived inability to change patient behaviours, and the cost of specialist behavioural support, there is increasing evidence of the value of behaviour modification techniques to both dietary and exercise counseling, particularly when focusing on current behaviour. Behavioural counseling addresses the barriers to compliance with diet and physical activity goals and also equips the individual with practical strategies and motivation to be more self-responsible. Commonly employed behavioural interventions include stimulus control, reinforcement techniques, self-monitoring, behavioural contracting, and social support programs. This paper addresses one of the key behavioural components in the treatment and management of obesity - physical activity. Higher levels of energy expenditure through increased physical activity are central to successful weight loss and long-term weight maintenance. The specific value derived from physical activity in the context of weight management for the overweight and obese is in large part associated with an appreciation of the role of both physical activity promotion and exercise prescription. PMID:16928660

  15. Antibiotic Binding Drives Catalytic Activation of Aminoglycoside Kinase APH(2″)-Ia.

    PubMed

    Caldwell, Shane J; Huang, Yue; Berghuis, Albert M

    2016-06-01

    APH(2″)-Ia is a widely disseminated resistance factor frequently found in clinical isolates of Staphylococcus aureus and pathogenic enterococci, where it is constitutively expressed. APH(2″)-Ia confers high-level resistance to gentamicin and related aminoglycosides through phosphorylation of the antibiotic using guanosine triphosphate (GTP) as phosphate donor. We have determined crystal structures of the APH(2″)-Ia in complex with GTP analogs, guanosine diphosphate, and aminoglycosides. These structures collectively demonstrate that aminoglycoside binding to the GTP-bound kinase drives conformational changes that bring distant regions of the protein into contact. These changes in turn drive a switch of the triphosphate cofactor from an inactive, stabilized conformation to a catalytically competent active conformation. This switch has not been previously reported for antibiotic kinases or for the structurally related eukaryotic protein kinases. This catalytic triphosphate switch presents a means by which the enzyme can curtail wasteful hydrolysis of GTP in the absence of aminoglycosides, providing an evolutionary advantage to this enzyme. PMID:27161980

  16. Non-equilibrium States of Active Filament Networks

    NASA Astrophysics Data System (ADS)

    Blackwell, Robert A.; Betterton, Meredith D.; Sweezy, Oliver M.; Glaser, Matthew A.

    2014-03-01

    Active networks of filamentous proteins and crosslinking motor proteins play a critical role in many cellular processes. Among the most important active networks is the mitotic spindle, an assembly of microtubules and crosslinking motor proteins that forms during cell division and that ultimately separates chromosomes into two daughter cells. To evolve a better understanding of spindle formation, structure, and dynamics, we have developed course-grained models of active networks composed of filaments, modeled as hard spherocylinders, in diffusive equilibrium with a reservoir of crosslinking motors, modeled as Hookean springs that can adsorb to microtubules and translocate at finite velocity along the microtubule axis. We explore the phase diagram and other characteristics of this model in two and three dimensions as a function of filament packing fraction, and of crosslink concentration, velocity, and adsorption and desorption rates. We observe a variety of interesting emergent behaviors including sorting of filaments into polar domains, generation of extensile stress, and superdiffusive transport. DMR-0820579

  17. United States Department of Energy Thermally Activated Heat Pump Program

    SciTech Connect

    Fiskum, R.J.; Adcock, P.W.; DeVault, R.C.

    1996-06-01

    The US Department of Energy (DOE) is working with partners from the gas heating and cooling industry to improve energy efficiency using advance absorption technologies, to eliminate chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs), to reduce global warming through more efficient combustion of natural gas, and to impact electric peak demand of air conditioning. To assist industry in developing these gas heating and cooling absorption technologies, the US DOE sponsors the Thermally Activated Heat Pump Program. It is divided into five key activities, addressing residential gas absorption heat pumps, large commercial chillers, advanced absorption fluids, computer-aided design, and advanced ``Hi-Cool`` heat pumps.

  18. Use of the United States Census in Social Studies Activities.

    ERIC Educational Resources Information Center

    Hardy, Charles

    1982-01-01

    Discusses how teachers can use U.S. census data in secondary U.S. history classes. Four census-based activities dealing with the themes of social mobility among Detroit and Alabama Blacks, definition of megalopolis, poverty in Boston, and Irish immigrants in Walpole, Massachusetts, in 1850 are described. (AM)

  19. Solid-state active media based on aminocoumarins

    SciTech Connect

    Kopylova, T N; Mayer, G V; Samsonova, L G; Svetlichnyi, Valerii A; Reznichenko, A V; Dolotov, S M; Ponomarenko, E P; Tavrizova, M A

    2003-06-30

    The lasing properties and photostability of eighteen aminocoumarins in polymethyl methacrylate, methyl methacrylate, and ethanol excited by an excimer XeCl laser are studied. It is shown that coumarins with a fluorinated methyl group and substituents in the third position of the molecule can be promising active media for lasers on polymer matrices doped with dyes. (lasers)

  20. Recognition of human activity characteristics based on state transitions modeling technique

    NASA Astrophysics Data System (ADS)

    Elangovan, Vinayak; Shirkhodaie, Amir

    2012-06-01

    Human Activity Discovery & Recognition (HADR) is a complex, diverse and challenging task but yet an active area of ongoing research in the Department of Defense. By detecting, tracking, and characterizing cohesive Human interactional activity patterns, potential threats can be identified which can significantly improve situation awareness, particularly, in Persistent Surveillance Systems (PSS). Understanding the nature of such dynamic activities, inevitably involves interpretation of a collection of spatiotemporally correlated activities with respect to a known context. In this paper, we present a State Transition model for recognizing the characteristics of human activities with a link to a prior contextbased ontology. Modeling the state transitions between successive evidential events determines the activities' temperament. The proposed state transition model poses six categories of state transitions including: Human state transitions of Object handling, Visibility, Entity-entity relation, Human Postures, Human Kinematics and Distance to Target. The proposed state transition model generates semantic annotations describing the human interactional activities via a technique called Casual Event State Inference (CESI). The proposed approach uses a low cost kinect depth camera for indoor and normal optical camera for outdoor monitoring activities. Experimental results are presented here to demonstrate the effectiveness and efficiency of the proposed technique.

  1. Allowance trading activity and state regulatory rulings: Evidence from the US Acid Rain Program

    SciTech Connect

    Bailey, E.M.

    1997-12-31

    The US Acid Rain Program is one of the first, and by far the most extensive, applications of a market based approach to pollution control. From the beginning, there has been concern whether utilities would participate in allowance trading, and whether regulatory activity at the state level would further complicate utilities` decision to trade allowances. This paper finds that public utility commission regulation has encouraged allowance trading activity in states with regulatory rulings, but that allowance trading activity has not been limited to states issuing regulations. Until there is evidence suggesting that significant additional cost savings could have been obtained if additional allowance trading activity had occurred in states without regulations or that utilities in states with regulations are still not taking advantage of all cost saving trading opportunities, this analysis suggests that there is little reason to believe that allowance trading activity is impeded by public utility commission regulations.

  2. The symbiotic star TX CVn has entered an active state

    NASA Astrophysics Data System (ADS)

    Munari, U.; Castellani, F.; Valisa, P.; Dallaporta, S.; Cherini, G.; Vagnozzi, A.; Righetti, G. L.; Belligoli, R.

    2014-01-01

    After the last active phase that begun in 2003, the symbiotic star TX CVn has now entered a new active phase. In 2003, TX CVn rose to B=10.5 and there it remained until the end of 2007 (Skopal 2007, AN 328, 909), when we started monitoring the variable with various ANS Collaboration telescopes in BVRI bands. Our observations show that the star has spent the following 6 years on a steady decline at a rate of 0.084 mag per year in the B band, that took it from B=10.55 on December 2007 to B=11.02 on September 2013, when the star begun a rapid brightening, reaching B=10.65 by early December 2013.

  3. Active tectonic studies in the United States, 1987-1990

    SciTech Connect

    Weldon, R.J., II )

    1991-01-01

    The techniques and instrumentation used in active tectonic studies are discussed, and recent results are reviewed. It is suggested that a critical mass of data on several particular regions has been accumulated, making possible critical debates and attempts to assess earthquake hazards. Particular attention is given to studies of the Pacific Northwest region, basin and range deformation studies, and distributed deformation and hidden earthquake sources. Also included is a comprehensive bibliography for the period.

  4. United States-Russia: Environmental management activities, Summer 1998

    SciTech Connect

    1998-09-01

    A Joint Coordinating Committee for Environmental Restoration and Waste Management (JCCEM) was formed between the US and Russia. This report describes the areas of research being studied under JCCEM, namely: Efficient separations; Contaminant transport and site characterization; Mixed wastes; High level waste tank remediation; Transuranic stabilization; Decontamination and decommissioning; and Emergency response. Other sections describe: Administrative framework for cooperation; Scientist exchange; Future actions; Non-JCCEM DOE-Russian activities; and JCCEM publications.

  5. 34 CFR 403.71 - In what additional ways may funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... agencies; (b) The support for tech-prep education as described in 34 CFR part 406; (c)(1) The support of... State Programs and State Leadership Activities? 403.71 Section 403.71 Education Regulations of the... Secretary Assist Under the Basic Programs? State Programs and State Leadership Activities § 403.71 In...

  6. 34 CFR 403.71 - In what additional ways may funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... agencies; (b) The support for tech-prep education as described in 34 CFR part 406; (c)(1) The support of... State Programs and State Leadership Activities? 403.71 Section 403.71 Education Regulations of the... Secretary Assist Under the Basic Programs? State Programs and State Leadership Activities § 403.71 In...

  7. A review of recent activity in the United States.

    USGS Publications Warehouse

    Cannon, H.L.; Petrie, W.L.

    1979-01-01

    Either an overabundance or a deficiency of trace metals in the food chain can ultimately affect adversely the health of livestock and man. Increasing interest in the United States in the distribution of metals in the environment and in metal pollutants has led to widespread interdisciplinary research sponsored by governmental, private and academic groups concerning the availability of trace elements for absorption by plants and animals, and the effects of trace elements throughout the food chain. Effects on the environment of coal-fired power plants, the mining and processing of metals, asbestos, and phosphate, and the disposal of industrial and nuclear wastes have also received much attention in the past few years.-Authors

  8. Altered baseline brain activity in children with bipolar disorder during mania state: a resting-state study

    PubMed Central

    Lu, Dali; Jiao, Qing; Zhong, Yuan; Gao, Weijia; Xiao, Qian; Liu, Xiaoqun; Lin, Xiaoling; Cheng, Wentao; Luo, Lanzhu; Xu, Chuanjian; Lu, Guangming; Su, Linyan

    2014-01-01

    Background Previous functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity in regions involved in emotion processing and regulation in pediatric bipolar disorder (PBD). Recent studies indicate, however, that task-dependent neural changes only represent a small fraction of the brain’s total activity. How the brain allocates the majority of its resources at resting state is still unknown. We used the amplitude of low-frequency fluctuation (ALFF) method of fMRI to explore the spontaneous neuronal activity in resting state in PBD patients. Methods Eighteen PBD patients during the mania phase and 18 sex-, age- and education-matched healthy subjects were enrolled in this study and all patients underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups. Correlation analysis was performed between the ALFF values and Young Mania Rating Scale scores. Results Compared with healthy controls, PBD patients presented increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF in left precuneus, left superior parietal lobule, and bilateral inferior occipital gyrus. Additionally, ALFF values in left pallidum were positively correlated with Young Mania Rating Scale score in PBD. Conclusion The abnormal resting-state neuronal activities of the basal ganglia, parietal cortex, and occipital cortex may play an important role in the pathophysiology in PBD patients. PMID:24570585

  9. United States data collection activities and requirements, volume 1

    NASA Technical Reports Server (NTRS)

    Hrin, S.; Mcgregor, D.

    1977-01-01

    The potential market for a data collection system was investigated to determine whether the user needs would be sufficient to support a satellite relay data collection system design. The activities of 107,407 data collections stations were studied to determine user needs in agriculture, climatology, environmental monitoring, forestry, geology, hydrology, meteorology, and oceanography. Descriptions of 50 distinct data collections networks are described and used to form the user data base. The computer program used to analyze the station data base is discussed, and results of the analysis are presented in maps and graphs. Information format and coding is described in the appendix.

  10. Activities on Facebook Reveal the Depressive State of Users

    PubMed Central

    Kwak, Jinah

    2013-01-01

    Background As online social media have become prominent, much effort has been spent on identifying users with depressive symptoms in order to aim at early diagnosis, treatment, and even prevention by using various online social media. In this paper, we focused on Facebook to discern any correlations between the platform’s features and users’ depressive symptoms. This work may be helpful in trying to reach and detect large numbers of depressed individuals more easily. Objective Our goal was to develop a Web application and identify depressive symptom–related features from users of Facebook, a popular social networking platform. Methods 55 Facebook users (male=40, female=15, mean age 24.43, SD 3.90) were recruited through advertisement fliers distributed to students in a large university in Korea. Using EmotionDiary, the Facebook application we developed, we evaluated depressive symptoms using the Center for Epidemiological Studies-Depression (CES-D) scale. We also provided tips and facts about depression to participants and measured their responses using EmotionDiary. To identify the Facebook features related to depression, correlation analyses were performed between CES-D and participants’ responses to tips and facts or Facebook social features. Last, we interviewed depressed participants (CES-D≥25) to assess their depressive symptoms by a psychiatrist. Results Facebook activities had predictive power in distinguishing depressed and nondepressed individuals. Participants’ response to tips and facts, which can be explained by the number of app tips viewed and app points, had a positive correlation (P=.04 for both cases), whereas the number of friends and location tags had a negative correlation with the CES-D scale (P=.08 and P=.045 respectively). Furthermore, in finding group differences in Facebook social activities, app tips viewed and app points resulted in significant differences (P=.01 and P=.03 respectively) between probably depressed and

  11. United States radiological health activities: inspection results of mammography facilities

    PubMed Central

    Spelic, DC; Kaczmarek, RV; Hilohi, M; Belella, S

    2007-01-01

    Purpose: The Mammography Quality Standards Act (MQSA) was enacted in 1992 to set national standards for high-quality mammography, including standards for mammographic X-ray equipment, patient dose, clinical image quality, and related technical parameters. The MQSA also requires minimum qualifications for radiologic technologists, interpreting physicians and medical physicists, mandates acceptable practices for quality-control, quality-assurance, and requires processes to audit medical outcomes. This paper presents the findings of MQSA inspections of facilities, which characterize significant factors affecting mammography quality in the United States. Materials and Methods: Trained inspectors collected data regarding X-ray technical factors, made exposure measurements for the determination of mean glandular dose (MGD), evaluated image quality, and inspected the quality of the film-processing environment. The average annual facility and total U.S. screening exam workloads were computed using workload data reported by facilities. Results: Mammography facilities have made technical improvements as evidenced by a narrower distribution of doses, higher phantom-film background optical densities associated with higher phantom image-quality scores, and better film processing. It is estimated that approximately 36 million screening mammography exams were conducted in 2006, a rate that is almost triple the exam volume estimated for 1997. Digital mammography (DM) is now in use at approximately 14% (1,191 of 8,834) of MQSA-certified mammography facilities. The results indicate that DM can offer lower dose to the patient while providing comparable or better image quality. PMID:21614276

  12. Women's income generation activities in Merowe Province, Northern State, Sudan.

    PubMed

    Pitamber, S; Osama, S

    1994-06-01

    Merowe province in rural northern Sudan has been divided into three local government council areas: Merowe, Karima, and Ed Debba. A government program was instituted to increase the welfare of residents and food production. A baseline survey of 490 respondents was conducted in order to ascertain how illiterate women viewed development in the area and to provide useful information for program design and implementation. Women from 24 villages were administered questionnaires, observed in their daily activities, and engaged in discussion in a local meeting place. Discussions were also held with members of the local Popular Committee. Demographic information was very sketchy about age, and 48% had no formal education in writing and reading. General reading and writing skills of the remainder were very poor. There were 500 female children and 502 male children, and the sex ratio varied among the 3 council areas. 52% were married and 14% were divorced or widowed and living with relatives. The average monthly income was from Ls. 700 to Ls. 3000 based on reports from only 59.3% of respondents. Most of the women had skills in food processing and 25.7% were skilled in handicrafts. Water was obtained primarily from local wells and not decontaminated before use. Pit latrines were the standard. One bathing facility was available in the compound for the entire council area. Health units were either in each village or within 20-30 minutes walk. Child mortality was 4.3% in Merowe province. 77 children 0-5 years old died out of a total of 1002 live births. Life expectancy was 41-50 years for women and 61-70 years for men. Cleanliness and healthful eating were observed. 58% owned no land; plots were under 5 feddans and usually half a feddan. 92.1% had no bank account and 90% had no experience with loans. 70.2% were indifferent about involvement in an income generation program. 26% were interested in part-time participation. Only 3.9% desired full-time participation. 8.6% said they

  13. EspT triggers formation of lamellipodia and membrane ruffles through activation of Rac-1 and Cdc42

    PubMed Central

    Bulgin, Richard R; Arbeloa, Ana; Chung, Jade C S; Frankel, Gad

    2009-01-01

    Subversion of the eukaryotic cell cytoskeleton is a virulence strategy employed by many bacterial pathogens. Due to the pivotal role of Rho GTPases in actin dynamics they are common targets of bacterial effector proteins and toxins. IpgB1, IpgB2 (Shigella), SifA, SifB (Salmonella) and Map and EspM (attaching and effacing pathogens) constitute a family of type III secretion system effectors that subverts small GTPase signalling pathways. In this study we identified and characterized EspT from Citrobacter rodentium that triggers formation of lamellipodia on Swiss 3T3 and membrane ruffles on HeLa cells, which are reminiscent of the membrane ruffles induced by IpgB1. Ectopic expression of EspT and IpgB1, but not EspM, resulted in a mitochondrial localization. Using dominant negative constructs we found that EspT-induced actin remodelling is dependent on GTP-bound Rac-1 and Cdc42 but not ELMO or Dock180, which are hijacked by IpgB1 in order to form a Rac-1 specific guanine nucleotide exchange factor. Using pull-down assays with the Rac-1 and Cdc42 binding domains of Pak and WASP we demonstrate that EspT is capable of activating both Rac-1 and Cdc42. These results suggest that EspT modulates the host cell cytoskeleton through coactivation of Rac-1 and Cdc42 by a distinct mechanism. PMID:19016787

  14. Dark/light transition and vigilance states modulate jaw-closing muscle activity level in mice.

    PubMed

    Katayama, Keisuke; Mochizuki, Ayako; Kato, Takafumi; Ikeda, Minako; Ikawa, Yasuha; Nakamura, Shiro; Nakayama, Kiyomi; Wakabayashi, Noriyuki; Baba, Kazuyoshi; Inoue, Tomio

    2015-12-01

    Bruxism is associated with an increase in the activity of the jaw-closing muscles during sleep and wakefulness. However, the changes in jaw-closing muscle activity across states of vigilance over a 24-h period are unclear. In this study, we investigated the effects of dark/light transition and sleep/wake state on EMG activity of the masseter (jaw-closing) muscle in comparison with the activity of the upper trapezius muscle (a neck muscle) over a 24-h period in mice. The activities of the masseter and neck muscles during wakefulness were much greater than during non-REM and REM sleep. In contrast, the activities of both muscles slightly, but significantly, decreased during the transition period from dark to light. Histograms of masseter activity during wakefulness and non-REM sleep showed bimodal distributions, whereas the neck muscle showed unimodal activation in all states. These results suggest that the activities of jaw-closing and neck muscles are modulated by both sleep/wake state and dark/light transition, with the latter being to a lesser degree. Furthermore, even during non-REM sleep, jaw-closing muscles display bimodal activation, which may contribute to the occurrence of exaggerated aberrant muscle activity, such as sleep bruxism. PMID:26188127

  15. A Bayesian Framework for the Classification of Microbial Gene Activity States

    PubMed Central

    Disselkoen, Craig; Greco, Brian; Cook, Kaitlyn; Koch, Kristin; Lerebours, Reginald; Viss, Chase; Cape, Joshua; Held, Elizabeth; Ashenafi, Yonatan; Fischer, Karen; Acosta, Allyson; Cunningham, Mark; Best, Aaron A.; DeJongh, Matthew; Tintle, Nathan

    2016-01-01

    Numerous methods for classifying gene activity states based on gene expression data have been proposed for use in downstream applications, such as incorporating transcriptomics data into metabolic models in order to improve resulting flux predictions. These methods often attempt to classify gene activity for each gene in each experimental condition as belonging to one of two states: active (the gene product is part of an active cellular mechanism) or inactive (the cellular mechanism is not active). These existing methods of classifying gene activity states suffer from multiple limitations, including enforcing unrealistic constraints on the overall proportions of active and inactive genes, failing to leverage a priori knowledge of gene co-regulation, failing to account for differences between genes, and failing to provide statistically meaningful confidence estimates. We propose a flexible Bayesian approach to classifying gene activity states based on a Gaussian mixture model. The model integrates genome-wide transcriptomics data from multiple conditions and information about gene co-regulation to provide activity state confidence estimates for each gene in each condition. We compare the performance of our novel method to existing methods on both simulated data and real data from 907 E. coli gene expression arrays, as well as a comparison with experimentally measured flux values in 29 conditions, demonstrating that our method provides more consistent and accurate results than existing methods across a variety of metrics. PMID:27555837

  16. Correlation between Cortical State and Locus Coeruleus Activity: Implications for Sensory Coding in Rat Barrel Cortex

    PubMed Central

    Fazlali, Zeinab; Ranjbar-Slamloo, Yadollah; Adibi, Mehdi; Arabzadeh, Ehsan

    2016-01-01

    Cortical state modulates the background activity of cortical neurons, and their evoked response to sensory stimulation. Multiple mechanisms are involved in switching between cortical states including various neuromodulatory systems. Locus Coeruleus (LC) is one of the major neuromodulatory nuclei in the brainstem with widespread projections throughout the brain and modulates the activity of cells and networks. Here, we quantified the link between the LC spontaneous activity, cortical state and sensory processing in the rat vibrissal somatosensory “barrel” cortex (BC). We simultaneously recorded unit activity from LC and BC along with prefrontal electroencephalogram (EEG) while presenting brief whisker deflections under urethane anesthesia. The ratio of low to high frequency components of EEG (referred to as the L/H ratio) was employed to identify cortical state. We found that the spontaneous activity of LC units exhibited a negative correlation with the L/H ratio. Cross-correlation analysis revealed that changes in LC firing preceded changes in the cortical state: the correlation of the LC firing profile with the L/H ratio was maximal at an average lag of −1.2 s. We further quantified BC neuronal responses to whisker stimulation during the synchronized and desynchronized states. In the desynchronized state, BC neurons showed lower stimulus detection threshold, higher response fidelity, and shorter response latency. The most prominent change was observed in the late phase of BC evoked activity (100–400 ms post stimulus onset): almost every BC unit exhibited a greater late response during the desynchronized state. Categorization of the BC evoked responses based on LC activity (into high and low LC discharge rates) resulted in highly similar response profiles compared to categorization based on the cortical state (low and high L/H ratios). These findings provide evidence for the involvement of the LC neuromodulatory system in desynchronization of cortical state

  17. A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking

    PubMed Central

    Woodruff, Prescott G.; Koth, Laura L.; Yang, Yee Hwa; Rodriguez, Madeleine W.; Favoreto, Silvio; Dolganov, Gregory M.; Paquet, Agnes C.; Erle, David J.

    2005-01-01

    Rationale: Macrophages are believed to play a central role in emphysema based largely on data from mouse models. However, the relevance of these models to smoking-related lung disease in humans is uncertain. Objectives: We sought to comprehensively characterize the effects of smoking on gene expression in human alveolar macrophages and to compare these with effects seen in transgenic mouse models of emphysema. Methods: We used DNA microarrays with genomewide coverage to analyze alveolar macrophages from 15 smokers, 15 nonsmokers, and 15 subjects with asthma (disease control). Selected gene expression changes were validated by polymerase chain reaction and ELISA. Expression changes were compared with those identified by microarray analysis of interleukin-13–overexpressing and integrin-β6–deficient mice, which both develop emphysema. Measurements and Main Results: All 15 smokers shared a common pattern of macrophage gene expression that distinguished them from nonsmokers, a finding not observed in subjects with asthma. We identified 110 genes as differentially expressed in smokers despite using conservative statistical methods. Matrix metalloproteinase 12, a proteinase that plays a critical role in mouse models, was the third most highly induced gene in smokers (ninefold, p < 0.0001). However, most changes in smokers were not reflected in mouse models. One such finding was increased osteopontin expression in smokers (fourfold, p = 0.006), which was confirmed at the protein level and correlated with the degree of airway obstruction. Conclusions: Smoking induces a remarkably consistent and distinctive pattern of alveolar macrophage activation. These studies identify aspects of mouse models that are directly relevant to human smokers and also reveal novel potential mediators of smoking-related diseases. PMID:16166618

  18. Catalysis and activation of magic states in fault-tolerant architectures

    SciTech Connect

    Campbell, Earl T.

    2011-03-15

    In many architectures for fault-tolerant quantum computing universality is achieved by a combination of Clifford group unitary operators and preparation of suitable nonstabilizer states, the so-called magic states. Universality is possible even for some fairly noisy nonstabilizer states, as distillation can convert many noisy copies into fewer purer magic states. Here we propose protocols that exploit multiple species of magic states in surprising ways. These protocols provide examples of previously unobserved phenomena that are analogous to catalysis and activation well known in entanglement theory.

  19. Activation by Cdc42 and Pip2 of Wiskott-Aldrich Syndrome Protein (Wasp) Stimulates Actin Nucleation by Arp2/3 Complex

    PubMed Central

    Higgs, Henry N.; Pollard, Thomas D.

    2000-01-01

    We purified native WASp (Wiskott-Aldrich Syndrome protein) from bovine thymus and studied its ability to stimulate actin nucleation by Arp2/3 complex. WASp alone is inactive in the presence or absence of 0.5 μM GTP-Cdc42. Phosphatidylinositol 4,5 bisphosphate (PIP2) micelles allowed WASp to activate actin nucleation by Arp2/3 complex, and this was further enhanced twofold by GTP-Cdc42. Filaments nucleated by Arp2/3 complex and WASp in the presence of PIP2 and Cdc42 concentrated around lipid micelles and vesicles, providing that Cdc42 was GTP-bound and prenylated. Thus, the high concentration of WASp in neutrophils (9 μM) is dependent on interactions with both acidic lipids and GTP-Cdc42 to activate actin nucleation by Arp2/3 complex. The results also suggest that membrane binding increases the local concentrations of Cdc42 and WASp, favoring their interaction. PMID:10995437

  20. Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state.

    PubMed

    Schokraie, Elham; Warnken, Uwe; Hotz-Wagenblatt, Agnes; Grohme, Markus A; Hengherr, Steffen; Förster, Frank; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas; Schnölzer, Martina

    2012-01-01

    Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state. PMID:23029181

  1. Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state

    PubMed Central

    Schokraie, Elham; Warnken, Uwe; Hotz-Wagenblatt, Agnes; Grohme, Markus A.; Hengherr, Steffen; Förster, Frank; Schill, Ralph O.; Frohme, Marcus; Dandekar, Thomas; Schnölzer, Martina

    2012-01-01

    Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state. PMID:23029181

  2. Using RSVP for analyzing state and previous activities for the Mars Exploration Rovers

    NASA Technical Reports Server (NTRS)

    Cooper, Brian K.; Wright, John; Hartman, Frank; Maxwell, Scott; Yen, Jeng

    2004-01-01

    This paper will discuss the tools and methodologies present in the RSVP suite for examining rover state, reviewing previous activities, visually comparing telemetered results to rehearse results, and reveiwing sciene and engineering imagery.

  3. 77 FR 37914 - Agency Information Collection Activities: Submission for OMB Review; Comment Request, State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-25

    ... Preparedness Report is a Web-based survey that is combined with the National Incident Management System... SECURITY Federal Emergency Management Agency Agency Information Collection Activities: Submission for OMB Review; Comment Request, State Preparedness Report AGENCY: Federal Emergency Management Agency,...

  4. 77 FR 21575 - Agency Information Collection Activities: Proposed Collection; Comment Request; State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-10

    ... combined with the National Incident Management System Compliance Assessment Support Tool (NIMSCAST) that... SECURITY Federal Emergency Management Agency Agency Information Collection Activities: Proposed Collection; Comment Request; State Preparedness Report AGENCY: Federal Emergency Management Agency, DHS....

  5. Trends in No Leisure-Time Physical Activity--United States, 1988-2010

    ERIC Educational Resources Information Center

    Moore, Latetia V.; Harris, Carmen D.; Carlson, Susan A.; Kruger, Judy; Fulton, Janet E.

    2012-01-01

    Purpose: The aim of this study was to examine trends in the prevalence of no leisure-time physical activity (LTPA) from 1988 to 2010. Method: Using the Behavioral Risk Factor Surveillance System data, 35 states and the District of Columbia reported information on no LTPA from 1988 to 1994; all states reported no LTPA from 1996 to 2010. Results: No…

  6. 78 FR 5793 - Agency Information Collection Activities; Comment Request; Evaluation of State Expanded Learning...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ... Agency Information Collection Activities; Comment Request; Evaluation of State Expanded Learning Time... State Expanded Learning Time. OMB Control Number: 1850-New. Type of Review: New information collection... 21st CCLC funds for expanded learning time (ELT). The interviews will be used to produce a...

  7. 40 CFR 745.325 - Lead-based paint activities: State and Tribal program requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Lead-based paint activities: State and Tribal program requirements. 745.325 Section 745.325 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES State and Indian...

  8. 15 CFR 930.74 - OCS activities subject to State agency review.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... COASTAL RESOURCE MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for... subject to State agency review. Except for States which do not anticipate coastal effects resulting from OCS activities, management program lists required pursuant to § 930.53 shall include a reference...

  9. 76 FR 61148 - Proposed Information Collection (Application for United States Flag for Burial Purposes) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-03

    ... AFFAIRS Proposed Information Collection (Application for United States Flag for Burial Purposes) Activity... comments on the information needed to determine eligibility for issuance of a burial flag for a deceased... information technology. Title: Application for United States Flag for Burial Purposes, VA Form 21-2008....

  10. Lecturers' Perception of Research Activities for Knowledge Production in Universities in Cross River State, Nigeria

    ERIC Educational Resources Information Center

    Uchendu, C. C.; Osim, R. O.; Odigwe, F. N.; Alade, F. N.

    2014-01-01

    This study examined lecturers' perception of research activities for knowledge production in universities in Cross River State, Nigeria. Two hypotheses were isolated to give direction to this investigation. 240 university lecturers were sampled from a population of 1,868 from the two universities in Cross River State, using stratified random…

  11. State of the art survey: active and semi-active suspension control

    NASA Astrophysics Data System (ADS)

    Tseng, H. Eric; Hrovat, Davor

    2015-07-01

    This survey paper aims to provide some insight into the design of suspension control system within the context of existing literature and share observations on current hardware implementation of active and semi-active suspension systems. It reviews the performance envelop of active, semi-active, and passive suspensions with a focus on linear quadratic-based optimisation including a specific example. The paper further discusses various design aspects including other design techniques, the decoupling of load and road disturbances, the decoupling of pitch and heave modes, the use of an inerter as an additional design element, and the application of preview. Various production and near production suspension systems were examined and described according to the features they offer, including self-levelling, variable damping, variable geometry, and anti-roll damping and stiffness. The lessons learned from these analytical insights and related hardware implementations are valuable and can be applied towards future active or semi-active suspension design.

  12. 34 CFR 403.71 - In what additional ways may funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false In what additional ways may funds be used under the... the required activities in § 403.70, a State may use funds reserved under section 102(a)(3) of the Act for the State Programs and State Leadership Activities in accordance with § 403.180(b)(3) for...

  13. Implementation of a School-Based State Policy to Increase Physical Activity

    ERIC Educational Resources Information Center

    Evenson, Kelly R.; Ballard, Kymm; Lee, Ginny; Ammerman, Alice

    2009-01-01

    Background: In 2005, the North Carolina State Board of Education updated the Healthy Active Children Policy to include a requirement that all kindergarten through eighth-grade children receive at least 30 minutes of moderate-to-vigorous physical activity each school day through physical education, recess, and other creative approaches. This study…

  14. Activities Using the New State of the World Atlas. Grades 7-12.

    ERIC Educational Resources Information Center

    Hursh, Heidi; Prevedel, Michael

    Teachers of social studies, foreign language, science, and journalism will find these learning activities useful in integrating "The New State of the World Atlas" (Simon and Schuster, 1984) into their curriculum. The book is organized into three sections. The first section uses an area studies approach. Activities focus on geopolitical and…

  15. Activities Using "The State of the World Atlas." Grades 7-12. International Understanding Series.

    ERIC Educational Resources Information Center

    Hursh, Heidi; Prevedel, Michael

    Secondary school teachers in a variety of disciplines will find the teaching activities in this handbook useful in integrating the "State of the World Atlas" into their curricula. Following an activity which introduces students to the atlas, content is divided into three sections focusing on area studies, issues, and research skills. Nine…

  16. Decreased Activation of Subcortical Brain Areas in the Motor Fatigue State: An fMRI Study.

    PubMed

    Hou, Li J; Song, Zheng; Pan, Zhu J; Cheng, Jia L; Yu, Yong; Wang, Jun

    2016-01-01

    One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264

  17. Behavioral state-specific inhibitory postsynaptic potentials impinge on cat lumbar motoneurons during active sleep.

    PubMed

    Morales, F R; Boxer, P; Chase, M H

    1987-11-01

    High-gain intracellular records were obtained from lumbar motoneurons in intact, undrugged cats during naturally occurring states of wakefulness, quiet sleep, and active sleep. Spontaneous, discrete, inhibitory postsynaptic potentials (IPSPs) were found to impinge on lumbar motoneurons during all states of sleep and wakefulness. IPSPs which occurred during wakefulness and quiet sleep were of relatively low amplitude and had a low frequency of occurrence. During the state of active sleep there occurred a great increase in inhibitory input. This was the result of the appearance of large-amplitude IPSPs and of an increase in the frequency of low-amplitude IPSPs which were indistinguishable from those recorded during wakefulness and quiet sleep. In addition to a difference in amplitude, the time course of the large IPSPs recorded during active sleep further differentiated them from the smaller IPSPs recorded during wakefulness, quiet sleep, and active sleep; i.e., their rise-time and half-width were of longer duration and their rate-of-rise was significantly faster. We suggest that the large, active sleep-specific IPSPs reflect the activity of a group of inhibitory interneurons which are inactive during wakefulness and quiet sleep and which discharge during active sleep. These as yet unidentified interneurons would then serve as the last link in the brain stem-spinal cord inhibitory system which is responsible for producing muscle atonia during the state of active sleep. PMID:3666087

  18. Natural Environments, Obesity, and Physical Activity in Nonmetropolitan Areas of the United States

    ERIC Educational Resources Information Center

    Michimi, Akihiko; Wimberly, Michael C.

    2012-01-01

    Purpose: To assess the associations of the natural environment with obesity and physical activity in nonmetropolitan areas of the United States among representative samples by using 2 indices of outdoor activity potential (OAP) at the county level. Methods: We used the data from 457,820 and 473,296 noninstitutionalized adults aged over 18 years…

  19. Decreased Activation of Subcortical Brain Areas in the Motor Fatigue State: An fMRI Study

    PubMed Central

    Hou, Li J.; Song, Zheng; Pan, Zhu J.; Cheng, Jia L.; Yu, Yong; Wang, Jun

    2016-01-01

    One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264

  20. Activities Using the "State of the World Atlas, 5th Edition."

    ERIC Educational Resources Information Center

    Hursh, Heidi

    This activity book highlights recent changes in international political and economic systems of the world. Teachers of geography, history, economics, political science, current issues, foreign languages, and journalism will find these activities useful in integrating the "State of the World Atlas" into their curriculum. Two introductory activities…

  1. 78 FR 78788 - Nondiscrimination in Programs or Activities Conducted by the United States Department of Agriculture

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ...The United States Department of Agriculture (USDA or Department) proposes to amend its regulation on nondiscrimination in programs or activities conducted by the Department. The changes are proposed to clarify the roles and responsibilities of USDA's Office of the Assistant Secretary for Civil Rights (OASCR) and USDA agencies in enforcing nondiscrimination in programs or activities conducted......

  2. The Kangaroo Book: Developmental Activities Related to the State Kindergarten Objectives.

    ERIC Educational Resources Information Center

    Corley, Rhonda; And Others

    Intended for use in conjunction with the guidebook, "Early Childhood Education in South Carolina," this book of experiential activities aims to help kindergarten teachers plan an appropriate program for their children. Each activity described realizes one of the 18 objectives for kindergarten that were adopted by the South Carolina State Board of…

  3. A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting.

    PubMed

    Byron, Adam; Askari, Janet A; Humphries, Jonathan D; Jacquemet, Guillaume; Koper, Ewa J; Warwood, Stacey; Choi, Colin K; Stroud, Matthew J; Chen, Christopher S; Knight, David; Humphries, Martin J

    2015-01-01

    Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling. PMID:25609142

  4. A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting

    PubMed Central

    Byron, Adam; Askari, Janet A.; Humphries, Jonathan D.; Jacquemet, Guillaume; Koper, Ewa J.; Warwood, Stacey; Choi, Colin K.; Stroud, Matthew J.; Chen, Christopher S.; Knight, David; Humphries, Martin J.

    2015-01-01

    Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling. PMID:25609142

  5. Electric-Field Induced Activation of Dark Excitonic States in Carbon Nanotubes.

    PubMed

    Uda, T; Yoshida, M; Ishii, A; Kato, Y K

    2016-04-13

    Electrical activation of optical transitions to parity-forbidden dark excitonic states in individual carbon nanotubes is reported. We examine electric-field effects on various excitonic states by simultaneously measuring photocurrent and photoluminescence. As the applied field increases, we observe an emergence of new absorption peaks in the excitation spectra. From the diameter dependence of the energy separation between the new peaks and the ground state of E11 excitons, we attribute the peaks to the dark excited states which became optically active due to the applied field. Field-induced exciton dissociation can explain the photocurrent threshold field, and the edge of the E11 continuum states has been identified by extrapolating to zero threshold. PMID:26999284

  6. The GTPase-Activating Protein Rga1 Interacts with Rho3 GTPase and May Regulate Its Function in Polarized Growth in Budding Yeast

    PubMed Central

    He, Fei; Nie, Wen-Chao; Tong, Zongtian; Yuan, Si-Min; Gong, Ting; Liao, Yuan; Bi, Erfei; Gao, Xiang-Dong

    2015-01-01

    In budding yeast, Rga1 negatively regulates the Rho GTPase Cdc42 by acting as a GTPase-activating protein (GAP) for Cdc42. To gain insight into the function and regulation of Rga1, we overexpressed Rga1 and an N-terminally truncated Rga1-C538 (a.a. 538-1007) segment. Overexpression of Rga1-C538 but not full-length Rga1 severely impaired growth and cell morphology in wild-type cells. We show that Rga1 is phosphorylated during the cell cycle. The lack of phenotype for full-length Rga1 upon overexpression may result from a negative regulation by G1-specific Pho85, a cyclin-dependent kinase (CDK). From a high-copy suppressor screen, we isolated RHO3, SEC9, SEC1, SSO1, SSO2, and SRO7, genes involved in exocytosis, as suppressors of the growth defect caused by Rga1-C538 overexpression. Moreover, we detected that Rga1 interacts with Rho3 in two-hybrid and bimolecular fluorescence complementation (BiFC) assays. Rga1 preferentially interacts with the GTP-bound form of Rho3 and the interaction requires the GAP domain and additional sequence upstream of the GAP domain. Our data suggest that the interaction of Rga1 with Rho3 may regulate Rho3’s function in polarized bud growth. PMID:25860339

  7. Modulation of spontaneous fMRI activity in human visual cortex by behavioral state

    PubMed Central

    Bianciardi, Marta; Fukunaga, Masaki; van Gelderen, Peter; Horovitz, Silvina G.; de Zwart, Jacco A.; Duyn, Jeff H.

    2009-01-01

    The phenomenon of spontaneous fMRI activity is increasingly being exploited to investigate the connectivity of functional networks in human brain with high spatial-resolution. Although mounting evidence points towards a neuronal contribution to this activity, its functional role and dependence on behavioral state remain unclear. In this work, we used BOLD fMRI at 7 T to study the modulation of spontaneous activity in occipital areas by various behavioral conditions, including resting with eyes closed, eyes open with visual fixation, and eyes open with fixation and focal visual stimulation. Spontaneous activity was separated from evoked activity and from signal fluctuations related to cardiac and respiratory cycles. We found that spontaneous activity in visual areas was substantially reduced (amplitude (44%) and coherence (25%)) with the fixation conditions relative to the eyes-closed condition. No significant further modulation was observed when the visual stimulus was added. The observed dependence on behavioral condition suggests that part of spontaneous fMRI signal fluctuations represents neuronal activity. Possible mechanisms for the modulation of spontaneous activity by behavioral state are discussed. The observed linear superposition of spontaneous fMRI activity with focal evoked activity related to visual processing has important implications for fMRI studies, which ideally should take into account the effect of spontaneous activity to properly define brain activations during task conditions. PMID:19028588

  8. Multiple conductance states of the light-activated channel of Limulus ventral photoreceptors. Alteration of conductance state during light

    PubMed Central

    1991-01-01

    The properties of light-dependent channels in Limulus ventral photoreceptors have been studied in cell-attached patches. Two sizes of single-channel events are seen during illumination. Previous work has characterized the large (40 pS) events; the goal of the current work was to characterize the small (15 pS) events and determine their relationship to the large events. The small events are activated by light rather than as a secondary result of the change in membrane voltage during light. The mean open time of the small events is 1.34 +/- 0.49 ms (mean +/- SD, n = 15), approximately 50% of that of the large events. The large and small events have the same reversal potential and a similar dependence of open-state probability on voltage. Evidence that these events are due to different conductance states of the same channel comes from analysis of relatively infrequent events showing a direct transition between the 15 and 40-pS levels. Furthermore, large and small events do not superpose, even at positive voltages when the probability of being open is very high, as would be predicted if the two-sized events were due to independent channels. Expression of the different conductance states is not random; during steady illumination there are alternating periods of several hundred milliseconds in which there are consecutive, sequential large events followed by periods in which there are consecutive, sequential small events. At early times during the response to a step of light, the large conductance state is preferentially expressed. At later times, there is an increase in the relative contribution of the low conductance state. These findings indicate that there is a process that changes the preferred conductance state of the channel. This alteration has functional importance in the process of light adaptation. PMID:1875187

  9. Patient specific proteolytic activity of monocyte-derived macrophages and osteoclasts predicted with temporal kinase activation states during differentiation

    PubMed Central

    Park, Keon-Young; Li, Weiwei A.; Platt, Manu O.

    2012-01-01

    Patient-to-patient variability in disease progression continues to complicate clinical decisions of treatment regimens for cardiovascular diseases, metastatic cancers and osteoporosis. Here, we investigated if monocytes, circulating white blood cells that enter tissues and contribute to disease progression by differentiating into macrophages or osteoclasts, could be useful in understanding this variability. Monocyte-derived macrophages and osteoclasts produce cysteine cathepsins, powerful extracellular matrix proteases which have been mechanistically linked to accelerated atherosclerotic, osteoporotic, and tumor progression. We hypothesized that multivariate analysis of temporal kinase activation states during monocyte differentiation could predict cathepsin proteolytic responses of monocyte-derived macrophages and osteoclasts in a patient-specific manner. Freshly isolated primary monocytes were differentiated with M-CSF or RANKL into macrophages or osteoclasts, respectively, and phosphorylation of ERK1/2, Akt, p38 MAPK, JNK, c-jun, and IκB-α were measured at days 1, 3, 6, and 9. In parallel, cell diameters and numbers of nuclei were measured, and multiplex cathepsin zymography was used to quantify cathepsins K, L, S, and V activity from cell extracts and conditioned media. There was extensive patient-to-patient variability in temporal kinase activation states, cell morphologies, and cathepsin K, L, S, and V proteolytic activity. Partial least squares regression models trained with temporal kinase activation states successfully predicted patient-specific morphological characteristics (mean cell diameter and number of nuclei) and patient-specific cathepsin proteolytic activity with predictability as high as 95%, even with the challenge of incorporating the complex, unknown cues from individual patients’ unique genetic and biochemical backgrounds. This personalized medicine approach considers patient variability in kinase signals to predict cathepsin activity

  10. Rod Visual Pigment Optimizes Active State to Achieve Efficient G Protein Activation as Compared with Cone Visual Pigments*

    PubMed Central

    Kojima, Keiichi; Imamoto, Yasushi; Maeda, Ryo; Yamashita, Takahiro; Shichida, Yoshinori

    2014-01-01

    Most vertebrate retinas contain two types of photoreceptor cells, rods and cones, which show different photoresponses to mediate scotopic and photopic vision, respectively. These cells contain different types of visual pigments, rhodopsin and cone visual pigments, respectively, but little is known about the molecular properties of cone visual pigments under physiological conditions, making it difficult to link the molecular properties of rhodopsin and cone visual pigments with the differences in photoresponse between rods and cones. Here we prepared bovine and mouse rhodopsin (bvRh and mRh) and chicken and mouse green-sensitive cone visual pigments (cG and mG) embedded in nanodiscs and applied time-resolved fluorescence spectroscopy to compare their Gt activation efficiencies. Rhodopsin exhibited greater Gt activation efficiencies than cone visual pigments. Especially, the Gt activation efficiency of mRh was about 2.5-fold greater than that of mG at 37 °C, which is consistent with our previous electrophysiological data of knock-in mice. Although the active state (Meta-II) was in equilibrium with inactive states (Meta-I and Meta-III), quantitative determination of Meta-II in the equilibrium showed that the Gt activation efficiency per Meta-II of bvRh was also greater than those of cG and mG. These results indicated that efficient Gt activation by rhodopsin, resulting from an optimized active state of rhodopsin, is one of the causes of the high amplification efficiency of rods. PMID:24375403

  11. Solid State Inflation Balloon Active Deorbiter: Scalable Low-Cost Deorbit System for Small Satellites

    NASA Technical Reports Server (NTRS)

    Huang, Adam

    2016-01-01

    The goal of the Solid State Inflation Balloon Active Deorbiter project is to develop and demonstrate a scalable, simple, reliable, and low-cost active deorbiting system capable of controlling the downrange point of impact for the full-range of small satellites from 1 kg to 180 kg. The key enabling technology being developed is the Solid State Gas Generator (SSGG) chip, generating pure nitrogen gas from sodium azide (NaN3) micro-crystals. Coupled with a metalized nonelastic drag balloon, the complete Solid State Inflation Balloon (SSIB) system is capable of repeated inflation/deflation cycles. The SSGG minimizes size, weight, electrical power, and cost when compared to the current state of the art.

  12. Catalytic activity of platinum on ruthenium electrodes with modified (electro)chemical states.

    PubMed

    Park, Kyung-Won; Sung, Yung-Eun

    2005-07-21

    Using Pt on Ru thin-film electrodes with various (electro)chemical states designed by the sputtering method, the effect of Ru states on the catalytic activity of Pt was investigated. The chemical and electrochemical properties of Pt/Ru thin-film samples were confirmed by X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry. In addition, Pt nanoparticles on Ru metal or oxide for an actual fuel cell system showed an effect of Ru states on the catalytic activity of Pt in methanol electrooxidation. Finally, it was concluded that such an enhancement of methanol electrooxidation on the Pt is responsible for Ru metallic and/or oxidation sites compared to pure Pt without any Ru state. PMID:16852701

  13. Unfolding the relationship between secreted molecular chaperones and macrophage activation states

    PubMed Central

    Henderson, Samantha

    2008-01-01

    Over the last 20 years, it has emerged that many molecular chaperones and protein-folding catalysts are secreted from cells and function, somewhat in the manner of cytokines, as pleiotropic signals for a variety of cells, with much attention being focused on the macrophage. During the last decade, it has become clear that macrophages respond to bacterial, protozoal, parasitic and host signals to generate phenotypically distinct states of activation. These activation states have been termed ‘classical’ and ‘alternative’ and represent not a simple bifurcation in response to external signals but a range of cellular phenotypes. From an examination of the literature, the hypothesis is propounded that mammalian molecular chaperones are able to induce a wide variety of alternative macrophage activation states, and this may be a system for relating cellular or tissue stress to appropriate macrophage responses to restore homeostatic equilibrium. PMID:18958583

  14. Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state.

    PubMed

    Jamart, Cécile; Naslain, Damien; Gilson, Hélène; Francaux, Marc

    2013-10-15

    Activation of autophagy in skeletal muscle has been reported in response to endurance exercise and food deprivation independently. The purpose of this study was to evaluate whether autophagy was more activated when both stimuli were combined, namely when endurance exercise was performed in a fasted rather than a fed state. Mice performed a low-intensity running exercise (10 m/min for 90min) in both dietary states after which the gastrocnemius muscles were removed. LC3b-II, a marker of autophagosome presence, increased in both conditions, but the increase was higher in the fasted state. Other protein markers of autophagy, like Gabarapl1-II and Atg12 conjugated form as well as mRNA of Lc3b, Gabarapl1, and p62/Sqstm1 were increased only when exercise was performed in a fasted state. The larger activation of autophagy by exercise in a fasted state was associated with a larger decrease in plasma insulin and phosphorylation of Akt(Ser473), Akt(Thr308), FoxO3a(Thr32), and ULK1(Ser757). AMPKα(Thr172), ULK1(Ser317), and ULK1(Ser555) remained unchanged in both conditions, whereas p38(Thr180/Tyr182) increased during exercise to a similar extent in the fasted and fed conditions. The marker of mitochondrial fission DRP1(Ser616) was increased by exercise independently of the nutritional status. Changes in mitophagy markers BNIP3 and Parkin suggest that mitophagy was increased during exercise in the fasted state. In conclusion, our results highlight a major implication of the insulin-Akt-mTOR pathway and its downstream targets FoxO3a and ULK1 in the larger activation of autophagy observed when exercise is performed in a fasted state compared with a fed state. PMID:23964069

  15. Neuronal activity of orexin and non-orexin waking-active neurons during wake-sleep states in the mouse.

    PubMed

    Takahashi, K; Lin, J-S; Sakai, K

    2008-05-15

    Using extracellular single unit recordings alone or in combination with neurobiotin juxtacellular labeling and orexin (hypocretin) immunohistochemistry in the mouse, we have recorded a total of 452 neurons in the orexin neuron field of the posterior hypothalamus. Of these, 76 exhibited tonic discharge highly specific to wakefulness, referred to as waking-active neurons. They showed differences from each other in terms of spike shape, activity profile, and response to an arousing sound stimulus and could be classified into three groups on the basis of spike shape as: 1) biphasic broad; 2) biphasic narrow; and 3) triphasic. Waking-active neurons characterized by biphasic broad spikes were orexin-immunopositive, whereas those characterized by either biphasic narrow or triphasic broad spikes were orexin-immunonegative. Unlike waking-specific histamine neurons, all orexin and non-orexin waking-active neurons exhibited slow (<10 Hz) tonic discharges during wakefulness and ceased firing shortly after the onset of electroencephalogram (EEG) synchronization (deactivation), the EEG sign of sleep (drowsy state). They remained virtually silent during slow-wave sleep, but displayed transient discharges during paradoxical (or rapid eye movement) sleep. During the transition from sleep to wakefulness, both orexin and triphasic non-orexin neurons fired in clusters prior to the onset of EEG activation, the EEG sign of wakefulness, and responded with a short latency to an arousing sound stimulus given during sleep. In contrast, the biphasic narrow non-orexin neurons fired in single spikes either prior to, or after, EEG activation during the same transition and responded to the stimulus with a longer latency. The activity of all waking-active neurons preceded the return of muscle tonus at the transition from paradoxical sleep to wakefulness. These data support the view that the activity of orexin and non-orexin waking-active neurons in the posterior hypothalamus plays an important

  16. Ground State Destabilization by Anionic Nucleophiles Contributes to the Activity of Phosphoryl Transfer Enzymes

    PubMed Central

    Andrews, Logan D.; Fenn, Tim D.; Herschlag, Daniel

    2013-01-01

    Enzymes stabilize transition states of reactions while limiting binding to ground states, as is generally required for any catalyst. Alkaline Phosphatase (AP) and other nonspecific phosphatases are some of Nature's most impressive catalysts, achieving preferential transition state over ground state stabilization of more than 1022-fold while utilizing interactions with only the five atoms attached to the transferred phosphorus. We tested a model that AP achieves a portion of this preference by destabilizing ground state binding via charge repulsion between the anionic active site nucleophile, Ser102, and the negatively charged phosphate monoester substrate. Removal of the Ser102 alkoxide by mutation to glycine or alanine increases the observed Pi affinity by orders of magnitude at pH 8.0. To allow precise and quantitative comparisons, the ionic form of bound Pi was determined from pH dependencies of the binding of Pi and tungstate, a Pi analog lacking titratable protons over the pH range of 5–11, and from the 31P chemical shift of bound Pi. The results show that the Pi trianion binds with an exceptionally strong femtomolar affinity in the absence of Ser102, show that its binding is destabilized by ≥108-fold by the Ser102 alkoxide, and provide direct evidence for ground state destabilization. Comparisons of X-ray crystal structures of AP with and without Ser102 reveal the same active site and Pi binding geometry upon removal of Ser102, suggesting that the destabilization does not result from a major structural rearrangement upon mutation of Ser102. Analogous Pi binding measurements with a protein tyrosine phosphatase suggest the generality of this ground state destabilization mechanism. Our results have uncovered an important contribution of anionic nucleophiles to phosphoryl transfer catalysis via ground state electrostatic destabilization and an enormous capacity of the AP active site for specific and strong recognition of the phosphoryl group in the transition

  17. Spin state transition in the active center of the hemoglobin molecule: DFT + DMFT study

    NASA Astrophysics Data System (ADS)

    Novoselov, D.; Korotin, Dm. M.; Anisimov, V. I.

    2016-05-01

    An ab initio study of electronic and spin configurations of the iron ion in the active center of the human hemoglobin molecule is presented. With a combination of the Density Functional Theory (DFT) method and the Dynamical Mean Field Theory (DMFT) approach, the spin state transition description in the iron ion during the oxidation process is significantly improved in comparison with previous attempts. It was found that the origin of the iron ion local moment behavior both for the high-spin and for the low-spin states in the hemoglobin molecule is caused by the presence of a mixture of several atomic states with comparable statistical probability.

  18. Compact acid-induced state of Clitoria ternatea agglutinin retains its biological activity.

    PubMed

    Naeem, A; Saleemuddin, M; Khan, R H

    2009-10-01

    The effects of pH on Clitoria ternatea agglutinin (CTA) were studied by spectroscopy, size-exclusion chromatography, and by measuring carbohydrate specificity. At pH 2.6, CTA lacks well-defined tertiary structure, as seen by fluorescence and near-UV CD spectra. Far-UV CD spectra show retention of 50% native-like secondary structure. The mean residue ellipticity at 217 nm plotted against pH showed a transition around pH 4.0 with loss of secondary structure leading to the formation of an acid-unfolded state. This state is relatively less denatured than the state induced by 6 M guanidine hydrochloride. With a further decrease in pH, this unfolded state regains ~75% secondary structure at pH 1.2, leading to the formation of the A-state with native-like near-UV CD spectral features. Enhanced 8-anilino-1-naphthalene-sulfonate binding was observed in A-state, indicating a "molten-globule" like conformation with exposed hydrophobic residues. Acrylamide quenching data exhibit reduced accessibility of quencher to tryptophan, suggesting a compact conformation at low pH. Size-exclusion chromatography shows the presence of a compact intermediate with hydrodynamic size corresponding to a monomer. Thermal denaturation of the native state was cooperative single-step transition and of the A-state was non-cooperative two-step transition. A-State regains 72% of the carbohydrate-binding activity. PMID:19916921

  19. Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation

    PubMed Central

    Wright, John; Kahn, Richard A.; Sztul, Elizabeth

    2016-01-01

    Eukaryotic cells require selective sorting and transport of cargo between intracellular compartments. This is accomplished at least in part by vesicles that bud from a donor compartment, sequestering a subset of resident protein “cargos” destined for transport to an acceptor compartment. A key step in vesicle formation and targeting is the recruitment of specific proteins that form a coat on the outside of the vesicle in a process requiring the activation of regulatory GTPases of the ARF family. Like all such GTPases, ARFs cycle between inactive, GDP-bound, and membrane-associated active, GTP-bound, conformations. And like most regulatory GTPases the activating step is slow and thought to be rate limiting in cells, requiring the use of ARF guanine nucleotide exchange factor (GEFs). ARF GEFs are characterized by the presence of a conserved, catalytic Sec7 domain, though they also contain motifs or additional domains that confer specificity to localization and regulation of activity. These domains have been used to define and classify five different sub-families of ARF GEFs. One of these, the BIG/GBF1 family, includes three proteins that are each key regulators of the secretory pathway. GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs and thus these GEFs are the upstream regulators that define the site and timing of vesicle production. Paradoxically, while we have detailed molecular knowledge of how GEFs activate ARFs, we know very little about how GEFs are recruited and/or activated at the right time and place to initiate transport. This review summarizes the current knowledge of GEF regulation and explores the still uncertain mechanisms that position GEFs at “budding ready” membrane sites to generate highly localized activated ARFs. PMID:24728583

  20. Steady-state hydrodynamic instabilities of active liquid crystals: Hybrid lattice Boltzmann simulations

    NASA Astrophysics Data System (ADS)

    Marenduzzo, D.; Orlandini, E.; Cates, M. E.; Yeomans, J. M.

    2007-09-01

    We report hybrid lattice Boltzmann (HLB) simulations of the hydrodynamics of an active nematic liquid crystal sandwiched between confining walls with various anchoring conditions. We confirm the existence of a transition between a passive phase and an active phase, in which there is spontaneous flow in the steady state. This transition is attained for sufficiently “extensile” rods, in the case of flow-aligning liquid crystals, and for sufficiently “contractile” ones for flow-tumbling materials. In a quasi-one-dimensional geometry, deep in the active phase of flow-aligning materials, our simulations give evidence of hysteresis and history-dependent steady states, as well as of spontaneous banded flow. Flow-tumbling materials, in contrast, rearrange themselves so that only the two boundary layers flow in steady state. Two-dimensional simulations, with periodic boundary conditions, show additional instabilities, with the spontaneous flow appearing as patterns made up of “convection rolls.” These results demonstrate a remarkable richness (including dependence on anchoring conditions) in the steady-state phase behavior of active materials, even in the absence of external forcing; they have no counterpart for passive nematics. Our HLB methodology, which combines lattice Boltzmann for momentum transport with a finite difference scheme for the order parameter dynamics, offers a robust and efficient method for probing the complex hydrodynamic behavior of active nematics.

  1. Cortical connective field estimates from resting state fMRI activity

    PubMed Central

    Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V.; Dumoulin, Serge O.; Renken, Remco; Ćurčić-Blake, Branislava; Cornelissen, Frans W.

    2014-01-01

    One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that—despite some variability in CF estimates between RS scans—neural properties such as CF maps and CF size can be derived from resting state data. PMID:25400541

  2. Steady-state hydrodynamic instabilities of active liquid crystals: hybrid lattice Boltzmann simulations.

    PubMed

    Marenduzzo, D; Orlandini, E; Cates, M E; Yeomans, J M

    2007-09-01

    We report hybrid lattice Boltzmann (HLB) simulations of the hydrodynamics of an active nematic liquid crystal sandwiched between confining walls with various anchoring conditions. We confirm the existence of a transition between a passive phase and an active phase, in which there is spontaneous flow in the steady state. This transition is attained for sufficiently "extensile" rods, in the case of flow-aligning liquid crystals, and for sufficiently "contractile" ones for flow-tumbling materials. In a quasi-one-dimensional geometry, deep in the active phase of flow-aligning materials, our simulations give evidence of hysteresis and history-dependent steady states, as well as of spontaneous banded flow. Flow-tumbling materials, in contrast, rearrange themselves so that only the two boundary layers flow in steady state. Two-dimensional simulations, with periodic boundary conditions, show additional instabilities, with the spontaneous flow appearing as patterns made up of "convection rolls." These results demonstrate a remarkable richness (including dependence on anchoring conditions) in the steady-state phase behavior of active materials, even in the absence of external forcing; they have no counterpart for passive nematics. Our HLB methodology, which combines lattice Boltzmann for momentum transport with a finite difference scheme for the order parameter dynamics, offers a robust and efficient method for probing the complex hydrodynamic behavior of active nematics. PMID:17930285

  3. Frontopolar activity and connectivity support dynamic conscious augmentation of creative state.

    PubMed

    Green, Adam E; Cohen, Michael S; Raab, Hillary A; Yedibalian, Christopher G; Gray, Jeremy R

    2015-03-01

    No ability is more valued in the modern innovation-fueled economy than thinking creatively on demand, and the "thinking cap" capacity to augment state creativity (i.e., to try and succeed at thinking more creatively) is of broad importance for education and a rich mental life. Although brain-based creativity research has focused on static individual differences in trait creativity, less is known about changes in creative state within an individual. How does the brain augment state creativity when creative thinking is required? Can augmented creative state be consciously engaged and disengaged dynamically across time? Using a novel "thin slice" creativity paradigm in 55 fMRI participants performing verb-generation, we successfully cued large, conscious, short-duration increases in state creativity, indexed quantitatively by a measure of semantic distance derived via latent semantic analysis. A region of left frontopolar cortex, previously associated with creative integration of semantic information, exhibited increased activity and functional connectivity to anterior cingulate gyrus and right frontopolar cortex during cued augmentation of state creativity. Individual differences in the extent of increased activity in this region predicted individual differences in the extent to which participants were able to successfully augment state creative performance after accounting for trait creativity and intelligence. PMID:25394198

  4. Can Specific Protein-Lipid Interactions Stabilize an Active State of the Beta 2 Adrenergic Receptor?

    PubMed

    Neale, Chris; Herce, Henry D; Pomès, Régis; García, Angel E

    2015-10-20

    G-protein-coupled receptors are eukaryotic membrane proteins with broad biological and pharmacological relevance. Like all membrane-embedded proteins, their location and orientation are influenced by lipids, which can also impact protein function via specific interactions. Extensive simulations totaling 0.25 ms reveal a process in which phospholipids from the membrane's cytosolic leaflet enter the empty G-protein binding site of an activated β2 adrenergic receptor and form salt-bridge interactions that inhibit ionic lock formation and prolong active-state residency. Simulations of the receptor embedded in an anionic membrane show increased lipid binding, providing a molecular mechanism for the experimental observation that anionic lipids can enhance receptor activity. Conservation of the arginine component of the ionic lock among Rhodopsin-like G-protein-coupled receptors suggests that intracellular lipid ingression between receptor helices H6 and H7 may be a general mechanism for active-state stabilization. PMID:26488656

  5. Molecular cloning of a cDNA for a small GTP binding protein, BRho, from the embryo of Bombyx mori and its characterization after expression and purification.

    PubMed

    Uno, T; Nakasuji, A; Hara, W; Aizono, Y

    2000-04-01

    A cDNA clone encoding a small GTP binding protein (Brho) was isolated from an embryonic cDNA library of Bombyx mori that encoded a polypeptide with 202 amino acids sharing 60-80% similarity with the Rho1 family of GTP binding proteins. The effector site and one of the guanine nucleotide binding sites differed from other members of the Rho family. To characterize the biochemical properties of Brho, the clone was expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein. The recombinant protein was purified to homogeneity with glutathione S-Sepharose. The fusion protein bound [(35)S] GTPgammaS and [(3)H] GDP with association constants of 11x10(6) M(-1) and 6.2x10(6) M(-1), respectively. The binding of [(35)S] GTPgammaS was inhibited by GTP and GDP, but by no other nucleotides. The calculated GTP-hydrolysis activity was 89.6 m mol/min/mol of Brho. Bound [(35)S] GTPgammaS and [(3)H] GDP were exchanged with GTPgammaS most efficiently in the presence of 6 mM MgCl(2). These results suggest that Brho has a higher affinity for GTP than GDP, converts from the GTP-bound state into the GDP-bound state by intrinsic GTP hydrolytic activity, and returns to the GTP-bound state with the exchange of GDP with GTP. Arch. PMID:10737920

  6. Molecular cloning of cDNA for BRab from the brain of Bombyx mori and biochemical properties of BRab expressed in Escherichia coli.

    PubMed

    Uno, T; Ueno, M; Nakajima, A; Shirai, Y; Aizono, Y

    1998-10-01

    From a brain cDNA library of Bombyx mori, we cloned cDNA for BRab, which encoded a 202-amino-acid polypeptide sharing 60-80% similarity with rab1 family members. To characterize its biochemical properties, cDNA for BRab was inserted into an expression vector (pGEX2T) and expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein. The recombinant protein was purified to homogeneity with glutathione S-Sepharose. The purified GST-BRab bound [35S]-GTP gamma S and [3H]-GDP with association constants of 1.5 x 10(6) M-1 and 0.58 x 10(6) M-1, respectively. The binding of [35S]-GTP gamma S was inhibited with GTP and GDP, but with no other nucleotides. The GTP-hydrolysis activity was evaluated to be 5 m mole/min/mole of BRab. In the presence of 6 mM MgCl2, bound [35S]-GTP gamma S and [3H]-GDP were exchanged with GTP gamma S most efficiently. These results suggest that BRab, having a higher affinity for GTP than GDP, converts from the GTP-bound state into the GDP-bound state by intrinsic GTP hydrolysis activity and returns to the GTP-bound state with the exchange of GDP with GTP. PMID:9836423

  7. Adults Eligible for Cardiovascular Disease Prevention Counseling and Participation in Aerobic Physical Activity - United States, 2013.

    PubMed

    Omura, John D; Carlson, Susan A; Paul, Prabasaj; Watson, Kathleen B; Loustalot, Fleetwood; Foltz, Jennifer L; Fulton, Janet E

    2015-09-25

    Cardiovascular disease (CVD) is the leading cause of death in the United States, and physical inactivity is a major risk factor (1). Health care professionals have a role in counseling patients about physical activity for CVD prevention. In August 2014, the U.S. Preventive Services Task Force (USPSTF) recommended that adults who are overweight or obese and have additional CVD risk factors be offered or referred to intensive behavioral counseling interventions to promote a healthful diet and physical activity for CVD prevention. Although the USPSTF recommendation does not specify an amount of physical activity, the 2008 Physical Activity Guidelines for Americans state that for substantial health benefits adults should achieve ≥150 minutes per week of moderate-intensity aerobic physical activity or ≥75 minutes per week of vigorous-intensity aerobic activity, or an equivalent combination of moderate- and vigorous-intensity aerobic physical activity. To assess the proportion of adults eligible for intensive behavioral counseling and not meeting the aerobic physical activity guideline, CDC analyzed data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS). This analysis indicated that 36.8% of adults were eligible for intensive behavioral counseling for CVD prevention. Among U.S. states and the District of Columbia (DC), the prevalence of eligible adults ranged from 29.0% to 44.6%. Nationwide, 19.9% of all adults were eligible and did not meet the aerobic physical activity guideline. These data can inform the planning and implementation of health care interventions for CVD prevention that are based on physical activity. PMID:26401758

  8. 34 CFR 403.71 - In what additional ways may funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false In what additional ways may funds be used under the State Programs and State Leadership Activities? 403.71 Section 403.71 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND...

  9. Reduction in cortical gamma synchrony during depolarized state of slow wave activity in mice

    PubMed Central

    Hwang, Eunjin; McNally, James M.; Choi, Jee Hyun

    2013-01-01

    EEG gamma band oscillations have been proposed to account for the neural synchronization crucial for perceptual integration. While increased gamma power and synchronization is generally observed during cognitive tasks performed during wake, several studies have additionally reported increased gamma power during sleep or anesthesia, raising questions about the characteristics of gamma oscillation during impaired consciousness and its role in conscious processing. Phase-amplitude modulation has been observed between slow wave activity (SWA, 0.5–4 Hz) and gamma oscillations during ketamine/xylazine anesthesia or sleep, showing increased gamma activity corresponding to the depolarized (ON) state of SWA. Here we divided gamma activity into its ON and OFF (hyperpolarized) state components based on the phase of SWA induced by ketamine/xylazine anesthesia and compared their power and synchrony with wake state levels in mice. We further investigated the state-dependent changes in both gamma power and synchrony across primary motor and primary somatosensory cortical regions and their interconnected thalamic regions throughout anesthesia and recovery. As observed previously, gamma power was as high as during wake specifically during the ON state of SWA. However, the synchrony of this gamma activity between somatosensory-motor cortical regions was significantly reduced compared to the baseline wake state. In addition, the somatosensory-motor cortical synchrony of gamma oscillations was reduced and restored in an anesthetic state-dependent manner, reflecting the changing depth of anesthesia. Our results provide evidence that during anesthesia changes in long-range information integration between cortical regions might be more critical for changes in consciousness than changes in local gamma oscillatory power. PMID:24379760

  10. Decreased electrophysiological activity represents the conscious state of emptiness in meditation.

    PubMed

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful "thoughtless emptiness (TE)," a "focused attention," and an "open monitoring" task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p < 0.05). Compared to open monitoring TE expressed decreased alpha and beta amplitudes, mainly in parietal areas (p < 0.01). TE presented significantly less delta (p < 0.001) and theta (p < 0.05) waves than a wakeful closed eyes resting condition. A group of participants with none or little meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness. PMID:24596562

  11. Decreased electrophysiological activity represents the conscious state of emptiness in meditation

    PubMed Central

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful “thoughtless emptiness (TE),” a “focused attention,” and an “open monitoring” task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p < 0.05). Compared to open monitoring TE expressed decreased alpha and beta amplitudes, mainly in parietal areas (p < 0.01). TE presented significantly less delta (p < 0.001) and theta (p < 0.05) waves than a wakeful closed eyes resting condition. A group of participants with none or little meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness. PMID:24596562

  12. Momentary Affective States Are Associated with Momentary Volume, Prospective Trends, and Fluctuation of Daily Physical Activity

    PubMed Central

    Kanning, Martina K.; Schoebi, Dominik

    2016-01-01

    Several interventions aiming to enhance physical activity in everyday life showed mixed effects. Affective constructs are thought to potentially support health behavior change. However, little is known about within-subject associations between momentary affect and subsequent physical activity in everyday life. This study analyzed the extent to which three dimensions of affective states (valence, calmness, and energetic arousal) were associated with different components of daily activity trajectories. Sixty-five undergraduates’ students (Age: M = 24.6; SD = 3.2; females: 57%) participated in this study. Physical activity was assessed objectively through accelerometers during 24 h. Affective states assessments were conducted randomly every 45 min using an e-diary with a six-item mood scale that was especially designed for ambulatory assessment. We conducted three-level multi-level analyses to investigate the extent to which momentary affect accounted for momentary volume, prospective trends, and stability vs. fluctuation of physical activity in everyday life. All three affect dimensions were significantly associated with momentary activity volumes and prospective trends over 45 min periods. Physical activity didn’t fluctuate freely, but featured significant autocorrelation across repeated measurements, suggesting some stability of physical activity across 5-min assessments. After adjusting for the autoregressive structure in physical activity assessments, only energetic arousal remained a significant predictor. Feeling energized and awake was associated with an increased momentary volume of activity and initially smaller but gradually growing decreases in subsequent activity within the subsequent 45 min. Although not related to trends in physical activity, higher valence predicted lower stability in physical activity across subsequent 45 min, suggesting more short-term fluctuations in daily activity the more participants reported positive affective valence. The

  13. Understanding the Role of Water in Modifying Particle Mixing States for CCN Activity

    NASA Astrophysics Data System (ADS)

    Vu, D. N.; Gao, S.; Pierce, J. R.; Asa-Awuku, A. A.

    2014-12-01

    CCN data sets from ambient and chamber studies, which consist of complex heterogeneous mixtures of organic and inorganic aerosol mixtures, may not show a single activation curve but instead can exhibit multiple activations not associated with doubly charged particles. It has been suggested that these activation curves may be representative of multiple externally mixed compounds, whereas single activation curves are representative of single component or multicomponent internally mixed aerosols. To characterize and modify mixing states, a new laminar flow tube apparatus was developed to control the extent of mixing of organic and inorganic fractions under different environmental conditions such as relative humidity. Data sets yielding multiple activation curves have been recreated by mixing multiple inorganic and organic compounds. Preliminary results suggest that aerosol water is a significant factor; under dry conditions, the aerosols remained externally mixed while humid conditions facilitated internal mixing. For example, ammonium sulfate (inorganic) and succinic acid (organic) when dry, maintained an external mixture and multiple activation curves were observed to be constant. Under humid conditions, external mixing was initially observed; however, the aerosol water promoted internal mixing and the activation curves were observed to converge into a single curve. The data agrees well with Köhler Theory and single parameter (kappa) theory thermodynamic predictions of droplet activation. Data sets are also compared with a diffusion based coagulation particle model to predict mixing behavior. The method of analysis and the effect of mixing states of multiple components on the supersaturated hygroscopic properties of aerosols are presented.

  14. An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility

    PubMed Central

    Costa, Marcello; Wiklendt, Lukasz; Arkwright, John W.; Spencer, Nicholas J.; Omari, Taher; Brookes, Simon J. H.; Dinning, Phil G.

    2013-01-01

    Excitatory and inhibitory enteric neural input to intestinal muscle acting on ongoing myogenic activity determines the rich repertoire of motor patterns involved in digestive function. The enteric neural activity cannot yet be established during movement of intact intestine in vivo or in vitro. We propose the hypothesis that is possible to deduce indirectly, but reliably, the state of activation of the enteric neural input to the muscle from measurements of the mechanical state of the intestinal muscle. The fundamental biomechanical model on which our hypothesis is based is the “three-element model” proposed by Hill. Our strategy is based on simultaneous video recording of changes in diameters and intraluminal pressure with a fiber-optic manometry in isolated segments of rabbit colon. We created a composite spatiotemporal map (DPMap) from diameter (DMap) and pressure changes (PMaps). In this composite map rhythmic myogenic motor patterns can readily be distinguished from the distension induced neural peristaltic contractions. Plotting the diameter changes against corresponding pressure changes at each location of the segment, generates “orbits” that represent the state of the muscle according to its ability to contract or relax actively or undergoing passive changes. With a software developed in MatLab, we identified twelve possible discrete mechanical states and plotted them showing where the intestine actively contracted and relaxed isometrically, auxotonically or isotonically, as well as where passive changes occurred or was quiescent. Clustering all discrete active contractions and relaxations states generated for the first time a spatio-temporal map of where enteric excitatory and inhibitory neural input to the muscle occurs during physiological movements. Recording internal diameter by an impedance probe proved equivalent to measuring external diameter, making possible to further develop similar strategy in vivo and humans. PMID:23596400

  15. Signaling Pathways That Control Rho Kinase Activity Maintain the Embryonic Epicardial Progenitor State

    PubMed Central

    Artamonov, Mykhaylo V.; Jin, Li; Franke, Aaron S.; Momotani, Ko; Ho, Ruoya; Dong, Xiu Rong; Majesky, Mark W.; Somlyo, Avril V.

    2015-01-01

    This study identifies signaling pathways that play key roles in the formation and maintenance of epicardial cells, a source of progenitors for coronary smooth muscle cells (SMCs). After epithelial to mesenchymal transition (EMT), mesenchymal cells invade the myocardium to form coronary SMCs. RhoA/Rho kinase activity is required for EMT and for differentiation into coronary SMCs, whereas cAMP activity is known to inhibit EMT in epithelial cells by an unknown mechanism. We use outgrowth of epicardial cells from E9.5 isolated mouse proepicardium (PE) explants, wild type and Epac1 null E12.5 mouse heart explants, adult rat epicardial cells, and immortalized mouse embryonic epicardial cells as model systems to identify signaling pathways that regulate RhoA activity to maintain the epicardial progenitor state. We demonstrate that RhoA activity is suppressed in the epicardial progenitor state, that the cAMP-dependent Rap1 GTP exchange factor (GEF), Epac, known to down-regulate RhoA activity through activation of Rap1 GTPase activity increased, that Rap1 activity increased, and that expression of the RhoA antagonistic Rnd proteins known to activate p190RhoGAP increased and associated with p190RhoGAP. Finally, EMT is associated with increased p63RhoGEF and RhoGEF-H1 protein expression, increased GEF-H1 activity, with a trend in increased p63RhoGEF activity. EMT is suppressed by partial silencing of p63RhoGEF and GEF-H1. In conclusion, we have identified new signaling molecules that act together to control RhoA activity and play critical roles in the maintenance of coronary smooth muscle progenitor cells in the embryonic epicardium. We suggest that their eventual manipulation could promote revascularization after myocardial injury. PMID:25733666

  16. Activation of sulfur active material in an all-solid-state lithium-sulfur battery

    NASA Astrophysics Data System (ADS)

    Nagata, Hiroshi; Chikusa, Yasuo

    2014-10-01

    Charge-discharge performance of all-solid-state Li/S batteries using several solid electrolytes to enhance energy density is investigated at 25 °C. The sulfur content in the positive composite electrode is 50 wt%. A correlation between the P/S ratio in a solid electrolyte and the reactivity of sulfur is observed. The capacity of a positive composite electrode using a Li1.5PS3.3{60Li2S-40P2S5(mol%)} electrolyte is 1096 mAh g-1 under 6.4 mA cm-2 at 25 °C. This value is much higher than the capacity for a Li4.0PS4.5{80Li2S-20P2S5} electrolyte (565 mAh g-1), although the ionic conductivity of Li1.5PS3.3 was lower than Li4.0PS4.5 (2 × 10-5 S cm-1, 5 × 10-4 S cm-1, respectively).

  17. A master equation formalism for macroscopic modeling of asynchronous irregular activity states.

    PubMed

    El Boustani, Sami; Destexhe, Alain

    2009-01-01

    Many efforts have been devoted to modeling asynchronous irregular (AI) activity states, which resemble the complex activity states seen in the cerebral cortex of awake animals. Most of models have considered balanced networks of excitatory and inhibitory spiking neurons in which AI states are sustained through recurrent sparse connectivity, with or without external input. In this letter we propose a mesoscopic description of such AI states. Using master equation formalism, we derive a second-order mean-field set of ordinary differential equations describing the temporal evolution of randomly connected balanced networks. This formalism takes into account finite size effects and is applicable to any neuron model as long as its transfer function can be characterized. We compare the predictions of this approach with numerical simulations for different network configurations and parameter spaces. Considering the randomly connected network as a unit, this approach could be used to build large-scale networks of such connected units, with an aim to model activity states constrained by macroscopic measurements, such as voltage-sensitive dye imaging. PMID:19210171

  18. Effects of Solar Magnetic Activity on the Charge States of Minor Ions of Solar Wind

    NASA Astrophysics Data System (ADS)

    Wang, Xuyu

    We present an investigation of the effects of solar magnetic activity on the charge states of minor ions (Fe, Si, Mg, Ne, O, C) in the solar wind using ACE solar wind data, the Current Sheet Source Surface (CSSS) model of the corona and SoHO/MDI data during the 23rd solar cycle. We found that the mean charge states indicate a clear trend to increase with the solar activity when the solar wind speed is above 550 km/s. Below this speed, no significant solar activity dependence is found. When displayed as a function of solar wind speed, iron is different from other elements in that it displays lower charge states in slow wind than in fast wind. The percentages of the high charge states for species with higher m/q (Fe) increase with the solar wind speed, while for the species with lower m/q (Si,Mg, O, C), the percentages of the high charge states decrease with the solar wind speed.

  19. TUNL XIX. Annual report, January 1-December 31, 1980. [North Carolina State Univ. activities at TUNL

    SciTech Connect

    1980-12-31

    Research performed by North Carolina State University personnel at TUNL is highlighted in this report, which is actually the complete TUNL progress report for 1980. Studies in the areas of neutron cross sections, neutron polarization, radiative capture, atomic physics and development activities are included. One may expect completed projects to be reported in physics journals or conference proceedings. (RWR)

  20. 75 FR 27575 - Agency Information Collection Activities: State Water Resources Research Institute Program Annual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    ... notice (74 FR 68860) announcing that we would submit this ICR to OMB for approval and soliciting comments... Geological Survey Agency Information Collection Activities: State Water Resources Research Institute Program... Water Resources Research Act of 1984, as amended (42 U.S.C. 10301 et seq.), authorizes a water...

  1. 78 FR 46597 - Agency Information Collection Activities: State Water Resources Research Institute Program Annual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ..., we published a Federal Register notice (78 FR 2422) announcing that we would submit this ICR to OMB....S. Geological Survey Agency Information Collection Activities: State Water Resources Research... Water Resources (NIWR) USGS Competitive Grant Program. As required by the Paperwork Reduction Act...

  2. Descriptive Analysis of Title VII-Funded State Education Agency Activities. Volume I.

    ERIC Educational Resources Information Center

    Nava, Hector; And Others

    Results of a national study of the use of funds provided by the 1974 amendments to Title VII of the Elementary and Secondary Education Act by the state education agencies (SEAs) are presented. The study was undertaken to (1) describe and analyze SEA policies and activities regarding bilingual education, (2) describe and analyze the SEA-level…

  3. Descriptive Analysis of Title VII-Funded State Education Agency Activities. Executive Summary.

    ERIC Educational Resources Information Center

    SRA Technologies, Inc., Arlington, VA.

    An executive summary of the results of a national study of the state education agencies' (SEAs) use of funds provided by the 1974 amendments to Title VII of the Elementary and Secondary Education Act are presented. The study was undertaken to (1) describe and analyze SEA policies and activities regarding bilingual education, (2) describe and…

  4. Descriptive Analysis of Title VII-Funded State Education Agency Activities. Volume II: Nine Case Studies.

    ERIC Educational Resources Information Center

    Nava, Hector; And Others

    Results of a national study of the use of funds provided by the 1974 amendments to Title VII of the Elementary and Secondary Education Act by the state education agencies (SEAs) are presented. The study was undertaken to (1) describe and analyze SEA policies and activities regarding bilingual education, (2) describe and analyze the SEA-level…

  5. 78 FR 22251 - Agency Information Collection Activities; Comment Request; IDEA Part B State Performance Plan...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... Performance Plan (SPP) and Annual Performance Report (APR). OMB Control Number: 1820-0624. Type of Review: a... Agency Information Collection Activities; Comment Request; IDEA Part B State Performance Plan (SPP) and Annual Performance Report (APR) AGENCY: Office of Special Education and Rehabilitative Services...

  6. 78 FR 22253 - Agency Information Collection Activities; Comment Request; IDEA Part C State Performance Plan...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... Performance Plan (SPP) and Annual Performance Report (APR). OMB Control Number: 1820-0578. Type of Review: a... Agency Information Collection Activities; Comment Request; IDEA Part C State Performance Plan (SPP) and Annual Performance Report (APR) AGENCY: Office of Special Education and Rehabilitative Services...

  7. Solid-state NMR and ESR studies of activated carbons produced from pecan shells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Activated carbon from pecan shells has shown promise as an adsorbent in water treatment and sugar refining. However, the chemistry of the material is complex and not fully understood. We report here the application of solid state NMR and ESR to study the chemical structure, mobility, and pore volu...

  8. Content and Activities for Teaching about Indians of Washington State, Grades K-6.

    ERIC Educational Resources Information Center

    Janda, Janet

    The purpose of this curriculum guide is to suggest content and appropriate activities for the study of Washington State Indians and is designed as a supplement to regular social studies curriculum for grades K-3 and 4-6. Objectives for studying about Indians in three geographic regions in Washington (the Coast, Puget Sound, and the Plateau) are to…

  9. Association and Diffusion of Nutrition and Physical Activity Policies on the State and District Level

    ERIC Educational Resources Information Center

    Taber, Daniel R.; Chriqui, Jamie F.; Chaloupka, Frank J.

    2012-01-01

    Background: School district wellness policies designed to reduce obesity and promote student health and well-being often lack specific requirements or any mandate that schools comply with the policy. Researchers, educators, and policymakers have called for states to take an active role in shaping district policies. The objective of this study was…

  10. Structure of a nanobody-stabilized active state of the β2 adrenoceptor

    PubMed Central

    Rasmussen, Søren G. F.; Choi, Hee-Jung; Fung, Juan Jose; Pardon, Els; Casarosa, Paola; Chae, Pil Seok; DeVree, Brian T.; Rosenbaum, Daniel M.; Thian, Foon Sun; Kobilka, Tong Sun; Schnapp, Andreas; Konetzki, Ingo; Sunahara, Roger K.; Gellman, Samuel H.; Pautsch, Alexander; Steyaert, Jan; Weis, William I.; Kobilka, Brian K.

    2010-01-01

    G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviors in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β2 adrenergic receptor (β2AR) that exhibits G protein-like behavior, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β2AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation. PMID:21228869

  11. Participation of Elderly Women in Community Welfare Activities in Akinyele Local Government, Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Odebode, Stella O.

    2009-01-01

    This paper assessed the participation of elderly women in community welfare activities in Oyo State, Nigeria. Simple random sampling technique was used to select 120 elderly women from six out of the twelve political wards in the study area. Both qualitative and quantitative methods of data collection were used to elicit information from the…

  12. 12 CFR 347.116 - Recordkeeping and supervision of foreign activities of insured state nonmember banks.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Recordkeeping and supervision of foreign activities of insured state nonmember banks. 347.116 Section 347.116 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  13. 12 CFR 347.116 - Recordkeeping and supervision of foreign activities of insured state nonmember banks.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Recordkeeping and supervision of foreign activities of insured state nonmember banks. 347.116 Section 347.116 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  14. 12 CFR 347.116 - Recordkeeping and supervision of foreign activities of insured state nonmember banks.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Recordkeeping and supervision of foreign activities of insured state nonmember banks. 347.116 Section 347.116 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  15. 12 CFR 347.116 - Recordkeeping and supervision of foreign activities of insured state nonmember banks.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Recordkeeping and supervision of foreign activities of insured state nonmember banks. 347.116 Section 347.116 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  16. 75 FR 32959 - Agency Information Collection Activities: United States-Caribbean Basin Trade Partnership Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    ... information collection was previously published in the Federal Register (75 FR 15446) on March 29, 2010... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: United States-Caribbean Basin Trade Partnership Act AGENCY: U.S. Customs and Border Protection, Department of...

  17. 78 FR 7739 - Agency Information Collection Activities: Proposed Collection; Comment Request-State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... Monitoring Branch, Food and Nutrition Service, U.S. Department of Agriculture, 3101 Park Center Drive, Room... Food and Nutrition Service Agency Information Collection Activities: Proposed Collection; Comment Request--State Administrative Expense Funds Regulations AGENCY: Food and Nutrition Service (FNS),...

  18. The Official-Language Movement in the United States: Contexts, Issues, and Activities.

    ERIC Educational Resources Information Center

    Amorose, Thomas

    1989-01-01

    Central concerns in the movement to make English the official language of the United States are reviewed, publications and activities of two major organizations supporting it are compared, and basic assumptions and directions of the movement are criticized. (21 references) (MSE)

  19. Let It Go and Open Up, an Ensemble of Ion Channel Active States.

    PubMed

    Minor, Daniel L

    2016-02-11

    Ligand binding usually moves the target protein from an ensemble of inactive states to a well-defined active conformation. Matthies et al. flip this scheme around, finding that, for the magnesium channel CorA, loss of ligand binding induces an ensemble of conformations that turn the channel on. PMID:26871624

  20. Alcohol, Sex and Illegal Activities: An Analysis of Selected Facebook Central Photos in Fifty States

    ERIC Educational Resources Information Center

    Watson, Sandy White; Smith, Zachary; Driver, Jennifer

    2006-01-01

    The purpose of this research study was to evaluate the central photos of 150 students in 50 states participating in Facebook for evidence of alcohol consumption, illegal activities and portrayal of sexually inappropriate behaviors (including nudity or partial nudity). Because the media has frequently reported evidence of these behaviors in…

  1. Teen Sexual Activity, Pregnancy and Childbearing among Latinos in the United States. Fact Sheet.

    ERIC Educational Resources Information Center

    National Campaign To Prevent Teen Pregnancy, Washington, DC.

    The Latino population is the fastest-growing major racial/ethnic group in the United States. By 2020, approximately 16 percent of the population will be Latino. This increase will be even more pronounced among teens. This fact sheet summarizes data from the National Vital Statistics Reports on reported sexual activity, pregnancy rates, and…

  2. Faculty Research, Publications, In-Service Activities at Northeastern Oklahoma State University.

    ERIC Educational Resources Information Center

    Northeastern Oklahoma State Univ., Tahlequah.

    Contained in this publication of Northeastern Oklahoma State University are faculty publications and research reports; abstracts fo faculty-student research projects; a list of individual and group inservice activities and research in progress by college department and divisions; and a bibliography of published articles, books, and creative works.…

  3. State Policies about Physical Activity Minutes in Physical Education or during School

    ERIC Educational Resources Information Center

    Carlson, Jordan A.; Sallis, James F.; Chriqui, Jamie F.; Schneider, Linda; McDermid, Lindsey C.; Agron, Peggy

    2013-01-01

    Background: School policies can change practices on a relatively permanent basis. This study investigated adoption and implementation of state-level policies specifying minutes (or percent) of physical activity in physical education (PE) or during school. Methods: Policies were identi?ed from existing databases and rated as having weak, moderate,…

  4. 77 FR 74471 - Agency Information Collection Activities; Comment Request; State of Preschool Survey 2013-2015

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Comment Request; State of Preschool Survey 2013-2015 AGENCY: Department of Education (ED), IES/NCES. ACTION: Notice. SUMMARY: In accordance with the Paperwork...

  5. Estimating repetitive spatiotemporal patterns from resting-state brain activity data.

    PubMed

    Takeda, Yusuke; Hiroe, Nobuo; Yamashita, Okito; Sato, Masa-Aki

    2016-06-01

    Repetitive spatiotemporal patterns in spontaneous brain activities have been widely examined in non-human studies. These studies have reported that such patterns reflect past experiences embedded in neural circuits. In human magnetoencephalography (MEG) and electroencephalography (EEG) studies, however, spatiotemporal patterns in resting-state brain activities have not been extensively examined. This is because estimating spatiotemporal patterns from resting-state MEG/EEG data is difficult due to their unknown onsets. Here, we propose a method to estimate repetitive spatiotemporal patterns from resting-state brain activity data, including MEG/EEG. Without the information of onsets, the proposed method can estimate several spatiotemporal patterns, even if they are overlapping. We verified the performance of the method by detailed simulation tests. Furthermore, we examined whether the proposed method could estimate the visual evoked magnetic fields (VEFs) without using stimulus onset information. The proposed method successfully detected the stimulus onsets and estimated the VEFs, implying the applicability of this method to real MEG data. The proposed method was applied to resting-state functional magnetic resonance imaging (fMRI) data and MEG data. The results revealed informative spatiotemporal patterns representing consecutive brain activities that dynamically change with time. Using this method, it is possible to reveal discrete events spontaneously occurring in our brains, such as memory retrieval. PMID:26979127

  6. Mining claim activity on federal land in the contiguous United States, 1976 through 2004

    USGS Publications Warehouse

    Causey, J. Douglas; Frank, David G.

    2006-01-01

    The data show how mining claim activity has changed in intensity, space, and time. Variations can be examined on a state, as well as a national level. The data are tied to a section of land, approximately 640 acres, which allows it to be used at regional, as well as local scale. It is restricted in that it only encompasses Federal land.

  7. 49 CFR 350.329 - How may a State or local agency qualify for High Priority or Border Activity Funds?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false How may a State or local agency qualify for High Priority or Border Activity Funds? 350.329 Section 350.329 Transportation Other Regulations Relating to... How may a State or local agency qualify for High Priority or Border Activity Funds? (a) States...

  8. 49 CFR 350.329 - How may a State or local agency qualify for High Priority or Border Activity Funds?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false How may a State or local agency qualify for High Priority or Border Activity Funds? 350.329 Section 350.329 Transportation Other Regulations Relating to... How may a State or local agency qualify for High Priority or Border Activity Funds? (a) States...

  9. Steady states and global dynamics of electrical activity in the cerebral cortex

    NASA Astrophysics Data System (ADS)

    Robinson, P. A.; Rennie, C. J.; Wright, J. J.; Bourke, P. D.

    1998-09-01

    Steady states and global dynamics of electrical activity in the cerebral cortex are investigated within the framework of a recent continuum model. It is shown that for a particular physiologically realistic class of models, at most three steady states can occur, two of which are stable. The global dynamics of spatially uniform activity states is studied and it is shown that in a physiologically realistic class of models, the adiabatic dynamics is governed by a second-order differential equation equivalent to that for the motion of a Newtonian particle in a potential in the presence of friction. This result is used to derive a simplified dynamical equation in the friction-dominated limit. Solutions of these equations are compared with those of the full global dynamics equations and it is found that they are adequate for time scales longer than approximately 100 ms provided dendritic integration times are less than approximately 10 ms.

  10. Sar1 GTPase Activity Is Regulated by Membrane Curvature*♦

    PubMed Central

    Hanna, Michael G.; Mela, Ioanna; Wang, Lei; Henderson, Robert M.; Chapman, Edwin R.; Edwardson, J. Michael; Audhya, Anjon

    2016-01-01

    The majority of biosynthetic secretory proteins initiate their journey through the endomembrane system from specific subdomains of the endoplasmic reticulum. At these locations, coated transport carriers are generated, with the Sar1 GTPase playing a critical role in membrane bending, recruitment of coat components, and nascent vesicle formation. How these events are appropriately coordinated remains poorly understood. Here, we demonstrate that Sar1 acts as the curvature-sensing component of the COPII coat complex and highlight the ability of Sar1 to bind more avidly to membranes of high curvature. Additionally, using an atomic force microscopy-based approach, we further show that the intrinsic GTPase activity of Sar1 is necessary for remodeling lipid bilayers. Consistent with this idea, Sar1-mediated membrane remodeling is dramatically accelerated in the presence of its guanine nucleotide-activating protein (GAP), Sec23-Sec24, and blocked upon addition of guanosine-5′-[(β,γ)-imido]triphosphate, a poorly hydrolysable analog of GTP. Our results also indicate that Sar1 GTPase activity is stimulated by membranes that exhibit elevated curvature, potentially enabling Sar1 membrane scission activity to be spatially restricted to highly bent membranes that are characteristic of a bud neck. Taken together, our data support a stepwise model in which the amino-terminal amphipathic helix of GTP-bound Sar1 stably penetrates the endoplasmic reticulum membrane, promoting local membrane deformation. As membrane bending increases, Sar1 membrane binding is elevated, ultimately culminating in GTP hydrolysis, which may destabilize the bilayer sufficiently to facilitate membrane fission. PMID:26546679

  11. Distinct spatiotemporal activity in principal neurons of the mouse olfactory bulb in anesthetized and awake states

    PubMed Central

    Blauvelt, David G.; Sato, Tomokazu F.; Wienisch, Martin; Murthy, Venkatesh N.

    2013-01-01

    The acquisition of olfactory information and its early processing in mammals are modulated by brain states through sniffing behavior and neural feedback. We imaged the spatiotemporal pattern of odor-evoked activity in a population of output neurons (mitral/tufted cells, MTCs) in the olfactory bulb (OB) of head-restrained mice expressing a genetically-encoded calcium indicator. The temporal dynamics of MTC population activity were relatively simple in anesthetized animals, but were highly variable in awake animals. However, the apparently irregular activity in awake animals could be predicted well using sniff timing measured externally, or inferred through fluctuations in the global responses of MTC population even without explicit knowledge of sniff times. The overall spatial pattern of activity was conserved across states, but odor responses had a diffuse spatial component in anesthetized mice that was less prominent during wakefulness. Multi-photon microscopy indicated that MTC lateral dendrites were the likely source of spatially disperse responses in the anesthetized animal. Our data demonstrate that the temporal and spatial dynamics of MTCs can be significantly modulated by behavioral state, and that the ensemble activity of MTCs can provide information about sniff timing to downstream circuits to help decode odor responses. PMID:23543674

  12. The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network

    PubMed Central

    Palhano-Fontes, Fernanda; Andrade, Katia C.; Tofoli, Luis F.; Santos, Antonio C.; Crippa, Jose Alexandre S.; Hallak, Jaime E. C.; Ribeiro, Sidarta; de Araujo, Draulio B.

    2015-01-01

    The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN. PMID:25693169

  13. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network.

    PubMed

    Palhano-Fontes, Fernanda; Andrade, Katia C; Tofoli, Luis F; Santos, Antonio C; Crippa, Jose Alexandre S; Hallak, Jaime E C; Ribeiro, Sidarta; de Araujo, Draulio B

    2015-01-01

    The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN. PMID:25693169

  14. Bursting Activity of Substantia Nigra pars Reticulata Neurons in Mouse Parkinsonism in Awake and Anesthetized States

    PubMed Central

    Lobb, CJ; Jaeger, D

    2015-01-01

    Electrophysiological changes in basal ganglia neurons are hypothesized to underlie motor dysfunction in Parkinson’s disease (PD). Previous results in head-restrained MPTP-treated non-human primates have suggested that increased bursting within the basal ganglia and related thalamic and cortical areas may be a hallmark of pathophysiological activity. In this study, we investigated whether there is increased bursting in substantia nigra pars reticulata (SNpr) output neurons in anesthetized and awake, head-restrained unilaterally lesioned 6-OHDA mice when compared to control mice. Confirming previous studies, we show that there are significant changes in the firing rate and pattern in SNpr neuron activity under urethane anesthesia. The regular firing pattern of control urethane-anesthetized SNpr neurons was not present in the 6-OHDA-lesioned group, as the latter neurons instead became phase locked with cortical slow wave activity (SWA). Next, we examined whether such robust electrophysiological changes between groups carried over to the awake state. SNpr neurons from both groups fired at much higher frequencies in the awake state than in the anesthetized state and surprisingly showed only modest changes between awake control and 6-OHDA groups. While there were no differences in firing rate between groups in the awake state, an increase in the coefficient of variation (CV) was observed in the 6-OHDA group. Contrary to the bursting hypothesis, this increased CV was not due to changes in bursting but was instead due to a mild increase in pausing. Together, these results suggest that differences in SNpr activity between control and 6-OHDA lesioned mice may be strongly influenced by changes in network activity during different arousal and behavioral states. PMID:25576395

  15. Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs.

    PubMed

    Santin, Joseph M; Hartzler, Lynn K

    2015-06-15

    Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current (I h) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451-R1464, 2013). This suggests an unlikely role for I h in generating cold activation, but led us to hypothesize that inhibition of I h by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs(+) (an I h antagonist) to isolate the role of I h in spontaneous firing and cold activation in neurons recorded with either control or I h agonist (cyclic AMP)-containing artificial intracellular fluid. I h did not contribute to the membrane potential (V m) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits I h, its lack of involvement in setting baseline firing and V m precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to I h activation. Our hypothesis was supported when the starting level of I h was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of I h facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net V m response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of I h activation state on neuronal firing varies in the poikilothermic neuronal environment. PMID:25833936

  16. Front motion and localized states in an asymmetric bistable activator-inhibitor system with saturation

    NASA Astrophysics Data System (ADS)

    Yochelis, Arik; Garfinkel, Alan

    2008-03-01

    We study the spatiotemporal properties of coherent states (peaks, holes, and fronts) in a bistable activator-inhibitor system that exhibits biochemical saturated autocatalysis, and in which fronts do not preserve spatial parity symmetry. Using the Gierer-Meinhardt prototype model, we find the conditions in which two distinct pinning regions are formed. The first pinning type is known in the context of variational systems while the second is structurally different due to the presence of a heteroclinic bifurcation between two uniform states. The bifurcation also separates the parameter regions of counterpropagating fronts, leading in turn to the growth or contraction of activator domains. These phenomena expand the range of pattern formation theory and its biomedical applications: activator domain retraction suggests potential therapeutic strategies for patterned pathologies, such as cardiovascular calcification.

  17. Two-State Reactivity Mechanism of Benzene C-C Activation by Trinuclear Titanium Hydride.

    PubMed

    Zhu, Bo; Guan, Wei; Yan, Li-Kai; Su, Zhong-Min

    2016-09-01

    The cleavage of inert C-C bonds is a central challenge in modern chemistry. Multinuclear transition metal complexes would be a desirable alternative because of the synergetic effect of multiple metal centers. In this work, carbon-carbon bond cleavage and rearrangement of benzene by a trinuclear titanium hydride were investigated using density functional theory. The reaction occurs via a novel "two-state reactivity" mechanism. The important elementary steps consist of hydride transfer, benzene coordination, dehydrogenation, oxidative addition, hydride-proton exchange, and reductive elimination. Most importantly, the ground-state potential energy surface switches from nearly degenerate triplet and antiferromagnetic singlet states to a closed-shell singlet state in the dearomatization of benzene, which effectively decreases the activation barrier. Furthermore, the roles of the transition metal centers and hydrides were clarified. PMID:27549571

  18. Electro-optical parameters in excited states of some spectrally active molecules

    NASA Astrophysics Data System (ADS)

    Benchea, Andreea Celia; Closca, Valentina; Rusu, Cristina Marcela; Morosanu, Cezarina; Dorohoi, Dana Ortansa

    2014-08-01

    The spectral shifts measured in different solvents are expressed as functions of the solvent macroscopic parameters. The value of the correlation coefficient multiplying the functions of electric permittivity was determined by statistical means. The correlation coefficient depends on the electric dipole moment of the spectrally active molecules. The electro-optical parameters in the ground state of the solute molecules can be approximated by molecular modeling. The excited state parameters are usually estimated using the results obtained both by HyperChem Programme and solvatochromic study. The importance of this approximate method is that it offers information about of the excited state of solute molecule for which our measuring possibilities are very restrictive. The information about the excited electronic state is affected by the limits in which the theories of liquid solutions are developed. Our results refer to two molecules of vitamins from B class, namely B3 and B6.

  19. Change-of-state determination to recognize mobility activities using a BlackBerry smartphone.

    PubMed

    Wu, Hui Hsien; Lemaire, Edward D; Baddour, Natalie

    2011-01-01

    A Wearable Mobility Monitoring System (WMMS) can be a useful tool for rehabilitation decision-making. This paper presents preliminary design and evaluation of a WMMS proof-of-concept system. Software was developed for the BlackBerry 9550, using the integrated three axes accelerometer, GPS, video camera, and timer to identify mobility changes-of-state (CoS) between static activities, walking-related activities, taking an elevator, bathroom activities, working in the kitchen, and meal preparation (five able-bodied subjects). This pilot project provides insight into new algorithms and features that recognize CoS and activities in real-time. Following features extraction from the sensor data, two decision trees were used to distinguish the CoS and activities. Real-time CoS identification triggered BlackBerry video recording for improved mobility context analysis during post-processing. PMID:22255522

  20. ACAP3 regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.

    PubMed

    Miura, Yuki; Hongu, Tsunaki; Yamauchi, Yohei; Funakoshi, Yuji; Katagiri, Naohiro; Ohbayashi, Norihiko; Kanaho, Yasunori

    2016-09-01

    ACAP3 (ArfGAP with coiled-coil, ankyrin repeat and pleckstrin homology domains 3) belongs to the ACAP family of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). However, its specificity to Arf isoforms and physiological functions remain unclear. In the present study, we demonstrate that ACAP3 plays an important role in neurite outgrowth of mouse hippocampal neurons through its GAP activity specific to Arf6. In primary cultured mouse hippocampal neurons, knockdown of ACAP3 abrogated neurite outgrowth, which was rescued by ectopically expressed wild-type ACAP3, but not by its GAP activity-deficient mutant. Ectopically expressed ACAP3 in HEK (human embryonic kidney)-293T cells showed the GAP activity specific to Arf6. In support of this observation, the level of GTP-bound Arf6 was significantly increased by knockdown of ACAP3 in hippocampal neurons. In addition, knockdown and knockout of Arf6 in mouse hippocampal neurons suppressed neurite outgrowth. These results demonstrate that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6. Furthermore, neurite outgrowth suppressed by ACAP3 knockdown was rescued by expression of a fast cycle mutant of Arf6 that spontaneously exchanges guanine nucleotides on Arf6, but not by that of wild-type, GTP- or GDP-locked mutant Arf6. Thus cycling between active and inactive forms of Arf6, which is precisely regulated by ACAP3 in concert with a guanine-nucleotide-exchange factor(s), seems to be required for neurite outgrowth of hippocampal neurons. PMID:27330119

  1. Electronic Word of Mouth on Twitter About Physical Activity in the United States: Exploratory Infodemiology Study

    PubMed Central

    Campo, Shelly; Janz, Kathleen F; Eckler, Petya; Yang, Jingzhen; Snetselaar, Linda G; Signorini, Alessio

    2013-01-01

    Background Twitter is a widely used social medium. However, its application in promoting health behaviors is understudied. Objective In order to provide insights into designing health marketing interventions to promote physical activity on Twitter, this exploratory infodemiology study applied both social cognitive theory and the path model of online word of mouth to examine the distribution of different electronic word of mouth (eWOM) characteristics among personal tweets about physical activity in the United States. Methods This study used 113 keywords to retrieve 1 million public tweets about physical activity in the United States posted between January 1 and March 31, 2011. A total of 30,000 tweets were randomly selected and sorted based on numbers generated by a random number generator. Two coders scanned the first 16,100 tweets and yielded 4672 (29.02%) tweets that they both agreed to be about physical activity and were from personal accounts. Finally, 1500 tweets were randomly selected from the 4672 tweets (32.11%) for further coding. After intercoder reliability scores reached satisfactory levels in the pilot coding (100 tweets separate from the final 1500 tweets), 2 coders coded 750 tweets each. Descriptive analyses, Mann-Whitney U tests, and Fisher exact tests were performed. Results Tweets about physical activity were dominated by neutral sentiments (1270/1500, 84.67%). Providing opinions or information regarding physical activity (1464/1500, 97.60%) and chatting about physical activity (1354/1500, 90.27%) were found to be popular on Twitter. Approximately 60% (905/1500, 60.33%) of the tweets demonstrated users’ past or current participation in physical activity or intentions to participate in physical activity. However, social support about physical activity was provided in less than 10% of the tweets (135/1500, 9.00%). Users with fewer people following their tweets (followers) (P=.02) and with fewer accounts that they followed (followings) (P=.04

  2. RINL, Guanine Nucleotide Exchange Factor Rab5-Subfamily, Is Involved in the EphA8-Degradation Pathway with Odin

    PubMed Central

    Kontani, Kenji; Katada, Toshiaki

    2012-01-01

    The Rab family of small guanosine triphosphatases (GTPases) plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs). Ras and Rab interactor (or Ras interaction/interference)-like (RINL), which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM) domain-containing (Anks) protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin. PMID:22291991

  3. RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin.

    PubMed

    Kajiho, Hiroaki; Fukushima, Shinichi; Kontani, Kenji; Katada, Toshiaki

    2012-01-01

    The Rab family of small guanosine triphosphatases (GTPases) plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs). Ras and Rab interactor (or Ras interaction/interference)-like (RINL), which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM) domain-containing (Anks) protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin. PMID:22291991

  4. Disorders of consciousness: Moving from passive to resting state and active paradigms.

    PubMed

    Bruno, M A; Soddu, A; Demertzi, A; Laureys, S; Gosseries, O; Schnakers, C; Boly, M; Noirhomme, Q; Thonnard, M; Chatelle, C; Vanhaudenhuyse, A

    2010-09-01

    Following coma, some patients will recover wakefulness without signs of consciousness (i.e., vegetative state) or may show nonreflexive movements but with no ability for functional communication (i.e., minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state. The increasing use of fMRI and EEG tools permits the clinical characterization of these patients to be improved. We first discuss "resting metabolism" and "passive activation" paradigms, used in neuroimaging and evoked potential studies, which merely identify neural activation reflecting "automatic" processing-that is, occurring without the patient's willful intervention. Secondly, we present an alternative approach consisting of instructing subjects to imagine well-defined sensory-motor or cognitive-mental actions. This strategy reflects volitional neural activation and, hence, witnesses awareness. Finally, we present results on blood-oxgen-level-dependent "default mode network"/resting state studies that might be a promising tool in the diagnosis of these challenging patients. PMID:24168335

  5. Polymodal activation of the TREK-2 K2P channel produces structurally distinct open states.

    PubMed

    McClenaghan, Conor; Schewe, Marcus; Aryal, Prafulla; Carpenter, Elisabeth P; Baukrowitz, Thomas; Tucker, Stephen J

    2016-06-01

    The TREK subfamily of two-pore domain (K2P) K(+) channels exhibit polymodal gating by a wide range of physical and chemical stimuli. Crystal structures now exist for these channels in two main states referred to as the "up" and "down" conformations. However, recent studies have resulted in contradictory and mutually exclusive conclusions about the functional (i.e., conductive) status of these two conformations. To address this problem, we have used the state-dependent TREK-2 inhibitor norfluoxetine that can only bind to the down state, thereby allowing us to distinguish between these two conformations when activated by different stimuli. Our results reconcile these previously contradictory gating models by demonstrating that activation by pressure, temperature, voltage, and pH produce more than one structurally distinct open state and reveal that channel activation does not simply involve switching between the up and down conformations. These results also highlight the diversity of structural mechanisms that K2P channels use to integrate polymodal gating signals. PMID:27241700

  6. Improving the activity of Trichoderma reesei cel7B through stabilizing the transition state.

    PubMed

    Wang, Yefei; Song, Xiangfei; Zhang, Shujun; Li, Jingwen; Shu, Zhiyu; He, Chunyan; Huang, Qingshan; Yao, Lishan

    2016-06-01

    Trichoderma reesei (Tr.) cellulases, which convert cellulose to reducing sugars, are a promising catalyst used in the lignocellulosic biofuel production. Improving Tr. cellulases activity, though very difficult, is highly desired due to the recalcitrance of lignocellulose. Meanwhile, it is preferable to enhance the cellulase's promiscuity so that substrates other than cellulose can also be hydrolyzed. In this work, an attempt is made to improve the catalytic activity of a major endogluanase Tr. Cel7B against xylan which crosslinks with cellulose in lignocellulose. By using quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations, the transition state of the xylo-oligosaccharide hydrolysis is identified. Then, mutations are introduced and their effect on the transition state stabilization is ranked based on the free energy calculations. Seven top ranked mutants are evaluated experimentally. Three mutants A208Q, A222D, and G230R show a higher activity than the wild-type Tr. Cel7B in the hydrolysis of xylan (by up to 47%) as well as filter paper (by up to 50%). The combination of the single mutants can further improve the enzyme activity. Our work demonstrates that the free energy method is effective in engineering the Tr. Cel7B activity against xylan and cellulose, and thus may also be useful for improving the activity of other Tr. cellulases. Biotechnol. Bioeng. 2016;113: 1171-1177. © 2015 Wiley Periodicals, Inc. PMID:26616246

  7. Engineering electrocatalytic activity in nanosized perovskite cobaltite through surface spin-state transition.

    PubMed

    Zhou, Shiming; Miao, Xianbing; Zhao, Xu; Ma, Chao; Qiu, Yuhao; Hu, Zhenpeng; Zhao, Jiyin; Shi, Lei; Zeng, Jie

    2016-01-01

    The activity of electrocatalysts exhibits a strongly dependence on their electronic structures. Specifically, for perovskite oxides, Shao-Horn and co-workers have reported a correlation between the oxygen evolution reaction activity and the eg orbital occupation of transition-metal ions, which provides guidelines for the design of highly active catalysts. Here we demonstrate a facile method to engineer the eg filling of perovskite cobaltite LaCoO3 for improving the oxygen evolution reaction activity. By reducing the particle size to ∼80 nm, the eg filling of cobalt ions is successfully increased from unity to near the optimal configuration of 1.2 expected by Shao-Horn's principle. Consequently, the activity is significantly enhanced, comparable to those of recently reported cobalt oxides with eg(∼1.2) configurations. This enhancement is ascribed to the emergence of spin-state transition from low-spin to high-spin states for cobalt ions at the surface of the nanoparticles, leading to more active sites with increased reactivity. PMID:27187067

  8. Engineering electrocatalytic activity in nanosized perovskite cobaltite through surface spin-state transition

    NASA Astrophysics Data System (ADS)

    Zhou, Shiming; Miao, Xianbing; Zhao, Xu; Ma, Chao; Qiu, Yuhao; Hu, Zhenpeng; Zhao, Jiyin; Shi, Lei; Zeng, Jie

    2016-05-01

    The activity of electrocatalysts exhibits a strongly dependence on their electronic structures. Specifically, for perovskite oxides, Shao-Horn and co-workers have reported a correlation between the oxygen evolution reaction activity and the eg orbital occupation of transition-metal ions, which provides guidelines for the design of highly active catalysts. Here we demonstrate a facile method to engineer the eg filling of perovskite cobaltite LaCoO3 for improving the oxygen evolution reaction activity. By reducing the particle size to ~80 nm, the eg filling of cobalt ions is successfully increased from unity to near the optimal configuration of 1.2 expected by Shao-Horn's principle. Consequently, the activity is significantly enhanced, comparable to those of recently reported cobalt oxides with eg~1.2 configurations. This enhancement is ascribed to the emergence of spin-state transition from low-spin to high-spin states for cobalt ions at the surface of the nanoparticles, leading to more active sites with increased reactivity.

  9. Engineering electrocatalytic activity in nanosized perovskite cobaltite through surface spin-state transition

    PubMed Central

    Zhou, Shiming; Miao, Xianbing; Zhao, Xu; Ma, Chao; Qiu, Yuhao; Hu, Zhenpeng; Zhao, Jiyin; Shi, Lei; Zeng, Jie

    2016-01-01

    The activity of electrocatalysts exhibits a strongly dependence on their electronic structures. Specifically, for perovskite oxides, Shao-Horn and co-workers have reported a correlation between the oxygen evolution reaction activity and the eg orbital occupation of transition-metal ions, which provides guidelines for the design of highly active catalysts. Here we demonstrate a facile method to engineer the eg filling of perovskite cobaltite LaCoO3 for improving the oxygen evolution reaction activity. By reducing the particle size to ∼80 nm, the eg filling of cobalt ions is successfully increased from unity to near the optimal configuration of 1.2 expected by Shao-Horn's principle. Consequently, the activity is significantly enhanced, comparable to those of recently reported cobalt oxides with eg∼1.2 configurations. This enhancement is ascribed to the emergence of spin-state transition from low-spin to high-spin states for cobalt ions at the surface of the nanoparticles, leading to more active sites with increased reactivity. PMID:27187067

  10. The steady states and dynamics of urokinase-mediated plasmin activation.

    PubMed

    Venkatraman, Lakshmi; Yu, Hanry; Bhowmick, Sourav S; Dewey, Forbes; Tucker-Kellogg, Lisa

    2010-01-01

    Plasmin and urokinase-type plasminogen activator (uPA) are ubiquitous proteases regulating the extracellular environment. They can activate each other via proteolytic cleavage, suggesting the potential for complex dynamic behaviors that could be elucidated by computational modeling. Ordinary differential equations are constructed to model the activation dynamics of plasminogen into plasmin, and single-chain uPA (scUPA) into two-chain uPA (tcUPA). Computational simulations and phase plane analysis reveal two stable steady states for the activation of each protein. Bifurcation analysis shows the in silico system to be bistable. Cell-free experiments verify the system to have ultrasensitive activation behavior, where scUPA is the stimulus and plasmin the output. Furthermore, two significantly different steady states could be seen in vitro for the same stimulus levels, depending on the initial activation level of the plasmin. The switch-like dynamics of the uPA-plasmin system could have potential relevance to many normal and disease processes including angiogenesis, migration and metastasis, wound healing and fibrosis. PMID:19908371

  11. Thermal activation of a group II intron ribozyme reveals multiple conformational states.

    PubMed

    Franzen, J S; Zhang, M; Chay, T R; Peebles, C L

    1994-09-20

    Conformational changes often accompany biological catalysis. Group II introns promote a variety of reactions in vitro that show an unusually sharp temperature dependence. This suggests that the chemical steps are accompanied by the conversion of a folded-but-inactive form to a differently folded active state. We report here the kinetic analysis of 5'-splice-junction hydrolysis (SJH) by E1:12345, a transcript containing the 5'-exon plus the first five of six intron secondary structure domains. The pseudo-first-order SJH reaction shows (1) activation by added KCl to 1.5 M; (2) cooperative activation by added MgCl2, nHill = 4.1-4.3, and [MgCl2]vmax/2 approximately 0.040 M; and (3) a rather high apparent activation energy, Ea approximately 50 kcal mol-l. In contrast, the 5'-terminal phosphodiester bond of a domain 5 transcript (GGD5) was hydrolyzed with Ea approximately 30 kcal mol-1 under SJH conditions; the 5'-GG leader dinucleotide presumably lacks secondary structure constraints. The effect of adding the chaotropic salt tetraethylammonium chloride (TEA) was also investigated. TEA reduced the melting temperatures of GGD5 and E1:12345. TEA also shifted the profile of rate versus temperature for SJH by E1:12345 toward lower temperatures without affecting the maximum rate. TEA had little effect on the rate of hydrolysis of the 5'-phosphodiester bond of GGD5. The high apparent activation enthalpy and entropy for SJH along with the effect of TEA on these parameters imply that conversion of an inactive form of E1:12345 to an active conformation accompanies enhanced occupation of the transition state as the temperature is raised to that for maximum SJH. Analytical modeling indicates that either a two-state model (open and disordered, with open being active) or a three-state model (compact, open, and disordered) could account for the temperature dependence of kSJH. However, the three-state model is clearly preferable, since it does not require that the activation parameters

  12. Sleep: A synchrony of cell activity-driven small network states

    PubMed Central

    Krueger, James M.; Huang, Yanhua; Rector, David M.; Buysse, Daniel J.

    2013-01-01

    We posit a bottom-up sleep regulatory paradigm in which state changes are initiated within small networks as a consequence of local cell activity. Bottom-up regulatory mechanisms are prevalent throughout nature, occurring in vastly different systems and levels of organization. Synchronization of state without top-down regulation is a fundamental property of large collections of small semi-autonomous entities. We posit that such synchronization mechanisms are sufficient and necessary for whole organism sleep onset. Within brain we posit that small networks of highly interconnected neurons and glia, e.g. cortical columns, are semi-autonomous units oscillating between sleep-like and wake-like states. We review evidence showing that cells, small networks, and regional areas of brain share sleep-like properties with whole animal sleep. A testable hypothesis focused on how sleep is initiated within local networks is presented. We posit that the release of cell activity-dependent molecules, such as ATP and nitric oxide, into the extracellular space initiates state changes within the local networks where they are produced. We review mechanisms of ATP induction of sleep regulatory substances (SRS) and their actions on receptor trafficking. Finally, we provide an example of how such local metabolic and state changes provide mechanistic explanations for clinical conditions such as insomnia. PMID:23651209

  13. Informal Face-to-Face Interaction Improves Mood State Reflected in Prefrontal Cortex Activity

    PubMed Central

    Watanabe, Jun-ichiro; Atsumori, Hirokazu; Kiguchi, Masashi

    2016-01-01

    Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS). We also observed that the verbal working memory (WM) task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC) activity accompanied by WM tasks measured by near-infrared spectroscopy (NIRS). PMID:27199715

  14. Informal Face-to-Face Interaction Improves Mood State Reflected in Prefrontal Cortex Activity.

    PubMed

    Watanabe, Jun-Ichiro; Atsumori, Hirokazu; Kiguchi, Masashi

    2016-01-01

    Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS). We also observed that the verbal working memory (WM) task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC) activity accompanied by WM tasks measured by near-infrared spectroscopy (NIRS). PMID:27199715

  15. Theoretical models for cooperative steady-state ATPase activity of myosin subfragment-1 on regulated actin.

    PubMed Central

    Hill, T L; Eisenberg, E; Chalovich, J M

    1981-01-01

    Recent theoretical work on the cooperative equilibrium binding of myosin subfragment-1-ADP to regulated actin, as influenced by Ca2+, is extended here to the cooperative steady-state ATPase activity of myosin subfragment-1 on regulated actin. Exact solution of the general steady-state problem will require Monte Carlo calculations. Three interrelated special cases are discussed in some detail and sample computer (not Monte Carlo) solutions are given. The eventual objective is to apply these considerations to in vitro experimental data and to in vivo muscle models. PMID:6455170

  16. Resting-state activity in development and maintenance of normal brain function

    PubMed Central

    Pizoli, Carolyn E.; Snyder, Abraham Z.; Shimony, Joshua S.; Limbrick, David D.; Schlaggar, Bradley L.; Smyth, Matthew D.

    2011-01-01

    One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level–dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization. PMID:21709227

  17. Ground state destabilization by anionic nucleophiles contributes to the activity of phosphoryl transfer enzymes.

    PubMed

    Andrews, Logan D; Fenn, Tim D; Herschlag, Daniel

    2013-07-01

    Enzymes stabilize transition states of reactions while limiting binding to ground states, as is generally required for any catalyst. Alkaline Phosphatase (AP) and other nonspecific phosphatases are some of Nature's most impressive catalysts, achieving preferential transition state over ground state stabilization of more than 10²²-fold while utilizing interactions with only the five atoms attached to the transferred phosphorus. We tested a model that AP achieves a portion of this preference by destabilizing ground state binding via charge repulsion between the anionic active site nucleophile, Ser102, and the negatively charged phosphate monoester substrate. Removal of the Ser102 alkoxide by mutation to glycine or alanine increases the observed Pi affinity by orders of magnitude at pH 8.0. To allow precise and quantitative comparisons, the ionic form of bound P(i) was determined from pH dependencies of the binding of Pi and tungstate, a P(i) analog lacking titratable protons over the pH range of 5-11, and from the ³¹P chemical shift of bound P(i). The results show that the Pi trianion binds with an exceptionally strong femtomolar affinity in the absence of Ser102, show that its binding is destabilized by ≥10⁸-fold by the Ser102 alkoxide, and provide direct evidence for ground state destabilization. Comparisons of X-ray crystal structures of AP with and without Ser102 reveal the same active site and P(i) binding geometry upon removal of Ser102, suggesting that the destabilization does not result from a major structural rearrangement upon mutation of Ser102. Analogous Pi binding measurements with a protein tyrosine phosphatase suggest the generality of this ground state destabilization mechanism. Our results have uncovered an important contribution of anionic nucleophiles to phosphoryl transfer catalysis via ground state electrostatic destabilization and an enormous capacity of the AP active site for specific and strong recognition of the phosphoryl group in

  18. States and the (Not So) New Standards--Where Are They Now? State Academic Standards: Activity around the Common Core

    ERIC Educational Resources Information Center

    Salazar, Tonette; Christie, Kathy

    2014-01-01

    States began adopting the Common Core State Standards (CCSS) in 2010 after they were launched by the Council of Chief State School Officers and the National Governors Association. Five years later, policymakers in numerous states continue to debate the Common Core and related elements, such as how to assess the standards. This brief provides a…

  19. Di-Ras2 Protein Forms a Complex with SmgGDS Protein in Brain Cytosol in Order to Be in a Low Affinity State for Guanine Nucleotides.

    PubMed

    Ogita, Yoshitaka; Egami, Sachiko; Ebihara, Arisa; Ueda, Nami; Katada, Toshiaki; Kontani, Kenji

    2015-08-14

    The Ras family of small GTPases function in a wide variety of biological processes as "molecular switches" by cycling between inactive GDP-bound and active GTP-bound forms. Di-Ras1 and Di-Ras2 were originally identified as small GTPases forming a distinct subgroup of the Ras family. Di-Ras1/Di-Ras2 mRNAs are detected predominantly in brain and heart tissues. Biochemical analysis of Di-Ras1/Di-Ras2 has revealed that they have little GTPase activity and that their intrinsic guanine-nucleotide exchange rates are much faster than that of H-Ras. Yet little is known about the biological role(s) of Di-Ras1/Di-Ras2 or of how their activities are regulated. In the present study we found that endogenous Di-Ras2 co-purifies with SmgGDS from rat brain cytosol. Size-exclusion chromatography of purified recombinant proteins showed that Di-Ras2 forms a high affinity complex with SmgGDS. SmgGDS is a guanine nucleotide exchange factor with multiple armadillo repeats and has recently been shown to specifically activate RhoA and RhoC. In contrast to the effect on RhoA, SmgGDS does not act as a guanine nucleotide exchange factor for Di-Ras2 but instead tightly associates with Di-Ras2 to reduce its binding affinity for guanine nucleotides. Finally, pulse-chase analysis revealed that Di-Ras2 binds, in a C-terminal CAAX motif-dependent manner, to SmgGDS immediately after its synthesis. This leads to increased Di-Ras2 stability. We thus propose that isoprenylated Di-Ras2 forms a tight complex with SmgGDS in cytosol immediately after its synthesis, which lowers its affinity for guanine nucleotides. PMID:26149690

  20. Economic impacts of anthropogenic activities on coastlines of the United States

    USGS Publications Warehouse

    Magoon, Orville T.; Williams, S. Jeffress; Lent, Linda K.; Richmond, James A.; Treadwell, Donald D.; Douglass, Scott L.; Edge, Billy L.; Ewing, Lesley C.; Pratt, Anthony P.

    2004-01-01

    Anthropogenic activities primarily impact coasts by reducing sediment inputs, altering sediment transport processes, and accelerating sediment losses to the offshore. These activities include: sand and gravel extraction, navigation and shore protection works; non-structural shoreline management strategies such as beach nourishment, sand by-passing and beach scraping, dams and flood control works; channel and inlet dredging; subsidence caused by fluid extraction and reduction of carbonate beach material. Although many of these activities have improved the quality of life, they also have had unintended effects on the coast. The issues that arise from human alterations of the coast are common to many coastal regions around the world; this paper draws from several areas of the United States to present an overview and provisional assessment of the economic consequences of anthropogenic activities along the Pacific coast.

  1. Determination of Chemical States of Mercury on Activated Carbon Using XANES

    SciTech Connect

    Takaoka, Masaki; Takeda, Nobuo; Oshita, Kazuyuki; Yamamoto, Takashi; Tanaka, Tsunehiro; Uruga, Tomoya

    2007-02-02

    Although the adsorption of mercury vapor onto activated carbon is a widely used technology to prevent environmental release, the adsorption mechanism is not clearly understood. In this study, we determined the chemical states of mercury on two kinds of activated carbon using X-ray absorption near-edge spectroscopy (XANES) to elucidate the adsorption mechanism. The adsorption experiments of elemental mercury onto activated carbon were conducted under air and nitrogen atmospheres at temperatures of 20 and 160 deg. C. Two types of activated carbon were prepared. X-ray absorption fine structure (XAFS) measurements were carried out on beamline BL01B1 at SPring-8. Hg-LIII edge XANES spectra suggested that chemical adsorption of elemental mercury on the activated carbon occurred in the 20-160 deg. C temperature range. According to the XANES spectra, a difference occurred in the chemical states of mercury between AC no. 1 and AC no. 2. The Hg XANES spectra on AC no. 1 were similar to those of Hg2Cl2 and HgS, and the Hg XANES spectra on AC no. 2 were similar to that of HgO, which suggested that nitric acid treatment removed sulfur from AC no. 1 and functional groups that were strong oxidizers on the surface of AC no. 2 created HgO. According to the EXAFS oscillation, a difference occurred in the chemical states of mercury on AC no. 1 between 20 and 160 deg. C. We found that impurities and oxidant functional groups on activated carbon play key roles in mercury adsorption.

  2. EEG spectra, behavioral states and motor activity in rats exposed to acetylcholinesterase inhibitor chlorpyrifos.

    PubMed

    Timofeeva, Olga A; Gordon, Christopher J

    2002-06-01

    Exposure to organophosphates (OP) has been associated with sleep disorders such as insomnia and "excessive dreaming." The central mechanisms of these effects are not well understood. OPs inhibit acetylcholinesterase (AChE) activity, leading to a hyperactivity of the brain cholinergic systems that are involved in sleep regulation. We studied alterations in the EEG, behavioral states, motor activity and core temperature in rats orally administered with 10 or 40 mg/kg of the OP insecticide chlorpyrifos (CHP). Occipital EEG, motor activity and core temperature were recorded with telemetric transmitters. Behavioral sleep-wake states were visually scored. Both doses of CHP produced alterations of the EEG (decrease in power of sigma/beta and increase in slow theta and fast gamma bands) characteristic of arousal. EEG alterations were consistent with behavioral changes such as an increase in wakefulness and a decrease in sleep. Waking immobility was a prevalent behavior. We did not detect any overt signs of CHP toxicity, such as an abnormal posture or gait, suggesting that reduced locomotion can be a result of central effects of CHP (such as activation of cholinergic motor inhibitory system) rather than peripheral (such as an impairment of neuromuscular function). Changes in the EEG and behavior occurred independently of the decrease in core temperature. Increased wakefulness together with reduced motor activity after exposure to CHP seems to be a result of hyperactivity in brain cholinergic neuronal networks. PMID:12175464

  3. c-Abl Tyrosine Kinase Adopts Multiple Active Conformational States in Solution

    PubMed Central

    2016-01-01

    Protein tyrosine kinases of the Abl family have diverse roles in normal cellular regulation and drive several forms of leukemia as oncogenic fusion proteins. In the crystal structure of the inactive c-Abl kinase core, the SH2 and SH3 domains dock onto the back of the kinase domain, resulting in a compact, assembled state. This inactive conformation is stabilized by the interaction of the myristoylated N-cap with a pocket in the C-lobe of the kinase domain. Mutations that perturb these intramolecular interactions result in kinase activation. Here, we present X-ray scattering solution structures of multidomain c-Abl kinase core proteins modeling diverse active states. Surprisingly, the relative positions of the regulatory N-cap, SH3, and SH2 domains in an active myristic acid binding pocket mutant (A356N) were virtually identical to those of the assembled wild-type kinase core, indicating that Abl kinase activation does not require dramatic reorganization of the downregulated core structure. In contrast, the positions of the SH2 and SH3 domains in a clinically relevant imatinib-resistant gatekeeper mutant (T315I) appear to be reconfigured relative to their positions in the wild-type protein. Our results demonstrate that c-Abl kinase activation can occur either with (T315I) or without (A356N) global allosteric changes in the core, revealing the potential for previously unrecognized signaling diversity. PMID:27166638

  4. Using RSVP for analyzing state and previous activities for the Mars Exploration Rovers

    NASA Technical Reports Server (NTRS)

    Cooper, Brian K.; Hartman, Frank; Maxwell, Scott; Wright, John; Yen, Jeng

    2004-01-01

    Current developments in immersive environments for mission planning include several tools which make up a system for performing and rehearsing missions. This system, known as the Rover Sequencing and Visualization Program (RSVP), includes tools for planning long range sorties for highly autonomous rovers, tools for planning operations with robotic arms, and advanced tools for visualizing telemetry from remote spacecraft and landers. One of the keys to successful planning of rover activities is knowing what the rover has accomplished to date and understanding the current rover state. RSVP builds on the lessons learned and the heritage of the Mars Pathfinder mission This paper will discuss the tools and methodologies present in the RSVP suite for examining rover state, reviewing previous activities, visually comparing telemetered results to rehearsed results, and reviewing science and engineering imagery. In addition we will present how this tool suite was used on the Mars Exploration Rovers (MER) project to explore the surface of Mars.

  5. Active-Space Coupled-Cluster Study of Electronic States of Be₃

    SciTech Connect

    Kowalski, Karol; Hirata, So; Wloch, M W.; Piecuch, Piotr; Windus, Theresa L.

    2005-08-15

    An automated implementation of the active-space coupled-cluster (CC) and equation-of-motion (EOM) CC methods with all singles and doubles, and triples defined via active orbitals (CCSDt, EOMCCSDt) employing Tensor Contraction Engine (TCE), is reported. The TCE-generated CCSDt/ codes are parallel and applicable to closed-and open-shell references. The effectiveness of the new code in describing electronic quasi-degeneracies is illustrated by the CCSDt / EOMCCSDt) calculations for the challenging Be₃system, which is characterized by a large number of low-lying excited states dominated by two-electron transitions and significant high order correlation effects in the ground electronic state. Different strategies for defining triple excitation s within the CCSDt / EOMCCSDt) approach are discussed.

  6. Spontaneous ordering and vortex states of active fluids in circular confinement

    NASA Astrophysics Data System (ADS)

    Theillard, Maxime; Ezhilan, Barath; Saintillan, David

    2015-11-01

    Recent experimental, theoretical and simulation studies have shown that confinement can profoundly affect self-organization in active suspensions leading to striking features such as directed fluid pumping in planar confinement, formation of steady and spontaneous vortices in radial confinement. Motivated by this, we study the dynamics in a suspension of biologically active particles confined in spherical geometries using a mean-field kinetic theory for which we developed a novel numerical solver. In the case of circular confinement, we conduct a systematic exploration of the entire parameter space and distinguish 3 broad states: no-flow, stable vortex and chaotic and several interesting sub-states. Our efficient numerical framework is also employed to study 3D effects and dynamics in more complex geometries.

  7. Quasi-optical solid-state power combining for millimeter-wave active seeker applications

    NASA Astrophysics Data System (ADS)

    Halladay, R. H.; Terrill, S. D.; Bowling, D. R.; Gagnon, D. R.

    1992-05-01

    Consideration is given to quasi-optical power combining techniques, state-of-the-art demonstrated performance, and system issues as they apply to endoatmospheric homing seeker insertion. Quasi-optical power combining is based on combining microwave and millimeter-wave solid-state device power in space through the use of antennas and lenses. It is concluded that quasi-optical power combining meets the severe electrical requirements and packaging constraints of active MMW seekers for endoatmospheric hit-to-kill missiles. The approach provides the possibility of wafer-scale integration of major components for low cost production and offers high reliability. Critical issues include thermal loading and system integration, which must be resolved before the quasi-optical power combining technology will be applied to an active MMW seeker.

  8. Quasi-optical solid-state power combining for millimeter-wave active seeker applications

    SciTech Connect

    Halladay, R.H.; Terrill, S.D.; Bowling, D.R.; Gagnon, D.R. U.S. Navy, Naval Air Warfare Center, China Lake, CA )

    1992-05-01

    Consideration is given to quasi-optical power combining techniques, state-of-the-art demonstrated performance, and system issues as they apply to endoatmospheric homing seeker insertion. Quasi-optical power combining is based on combining microwave and millimeter-wave solid-state device power in space through the use of antennas and lenses. It is concluded that quasi-optical power combining meets the severe electrical requirements and packaging constraints of active MMW seekers for endoatmospheric hit-to-kill missiles. The approach provides the possibility of wafer-scale integration of major components for low cost production and offers high reliability. Critical issues include thermal loading and system integration, which must be resolved before the quasi-optical power combining technology will be applied to an active MMW seeker. 18 refs.

  9. Is Nox4 a key regulator of the activated state of fibroblasts in systemic sclerosis?

    PubMed

    Böhm, Markus; Dosoki, Heba; Kerkhoff, Claus

    2014-09-01

    The family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases consists of phagocytic gp91(phox) and six-related isoforms. Recent evidence indicates that the NADPH oxidase isoform Nox4 controls vascular, renal and pulmonary injury. We propose that Nox4 is an intrinsic regulator of the activated state of dermal fibroblasts in systemic sclerosis (SSc). Profibrotic cytokines on the one hand and antifibrogenic factors such as α-melanocyte-stimulating hormone on the other hand may target Nox4 as an intracellular nodal point. Via increased or decreased generation of reactive oxygen species and/or hydrogen peroxide, Nox4 could orchestrate collagen synthesis, differentiation of dermal fibroblasts into a profibrotic myofibroblast phenotype and thus dermal fibrosis. Confirmation of this hypothesis will have important consequences in our understanding of the activated state of dermal fibroblasts in SSc. Based on the availability of clinically useful Nox4 inhibitors, novel antifibrotic therapies of SSc can be envisioned. PMID:25040787

  10. Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation

    SciTech Connect

    Yamano, Noriko; Kimura, Tohru; Watanabe-Kushima, Shoko; Shinohara, Takashi; Nakano, Toru

    2010-02-12

    Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation. We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes. Sphere cell transfer to the original feeder-free ESC cultures resulted in chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was observed. These results indicate that Akt signaling promotes a novel metastable and pluripotent state that is intermediate to those of ESCs and PGCs.

  11. Solid state structural and theoretical investigations of a biologically active chalcone

    NASA Astrophysics Data System (ADS)

    Abbas, Asghar; Gökce, Halil; Bahceli, Semiha; Bolte, Michael; Naseer, Muhammad Moazzam

    2016-05-01

    The computational methods are presently emerging as an efficient and reliable tool for predicting structural properties of biologically important compounds. In the present manuscript, the solid state structural and theoretical investigations of a biologically active chalcone i-e (E)-3-(4-(hexyloxy)phenyl)-1-phenylprop-2-en-1-one (6c) have been reported. The solid state structure of 6c was measured by X-ray crystallographic technique whereas the optimized molecular geometry, vibrational frequencies, the simulated UV-vis spectra (in gas and in methanol solvent), 1H and 13C NMR chemical shift (in gas and in chloroform solvent) values, HOMO-LUMO analysis, the molecular electrostatic potential (MEP) surface and thermodynamic parameters were calculated by using DFT/B3LYP method with 6-311++G(d,p) basis set in ground state. The results of the theoretical investigations were found to be in good agreement with experimental data.

  12. Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity

    PubMed Central

    Nixon-Abell, Jonathon; Berwick, Daniel C.; Grannó, Simone; Spain, Victoria A.; Blackstone, Craig; Harvey, Kirsten

    2016-01-01

    Mutations in LRRK2 are a common cause of familial and idiopathic Parkinson’s disease (PD). Recently, the LRRK2 GTPase domain R1398H variant was suggested in genetic studies to confer protection against PD but mechanistic data supporting this is lacking. Here, we present evidence that R1398H affects GTPase function, axon outgrowth, and Wnt signaling in a manner opposite to pathogenic LRRK2 mutations. LRRK2 R1398H GTPase domain dimerization and GTP hydrolysis were increased whereas GTP binding was reduced, leading to a decrease in active GTP-bound LRRK2. This protective variant also increased axon length of primary cortical neurones in comparison to wild-type LRRK2, whereas the R1441G LRRK2 pathogenic mutant decreased axon outgrowth. Importantly, R1398H enhanced the stimulatory effect of LRRK2 on canonical Wnt signaling whereas the G2385R risk variant, in accordance with all previously tested pathogenic LRRK2 mutants, had the opposite effect. Molecular modeling placed R1398H in close proximity to PD-causing mutations suggesting that this protective LRRK2 variant, like familial mutations, affects intramolecular RocCOR domain interactions. Thus, our data suggest that R1398H LRRK2 is a bona fide protective variant. The opposite effects of protective versus PD associated LRRK2 variants on GTPase function and canonical Wnt signaling activity also suggests that regulation of these two basic signaling mechanisms is important for neuronal function. We conclude that LRRK2 mediated Wnt signaling and GTPase function are fundamental in conferring disease susceptibility and have clear implications for therapeutic target identification. PMID:27013965

  13. States Lack Physical Activity Policies in Child Care That Are Consistent with National Recommendations

    PubMed Central

    Slining, Meghan M.; Benjamin Neelon, Sara E.

    2014-01-01

    Abstract Background: Child care facilities' policies can importantly impact health behaviors of toddlers and preschoolers. Our aim was to assess state regulations promoting physical activity (PA) in child care and compare regulations to national recommendations. Methods: We reviewed licensing and administrative regulations related to promoting PA for all states and territories for child care centers (centers) and family child care homes (homes). Three reviewers searched two sources (a publically available website and WestlawNext™) and compared regulations with 15 Institute of Medicine recommendations. We used Pearson's and Spearman's correlations to assess associations between geographic region, year of last update, and number of regulations consistent with the recommendations. Results: The average number and range of regulations in centers and homes was 4.1 (standard deviation [SD], 1.4; range, 0–8) and 3.8 (SD, 1.5; range, 0–7), respectively. Nearly all states had regulations consistent with providing an outdoor (centers, 98%; homes, 95%) and indoor (centers, 94%, homes, 92%) environment “with a variety of portable play equipment and adequate space.” No state had regulations for staff joining children, avoiding punishment for being physically active, yearly consultation from a PA expert, or providing training/education on PA for providers. Conclusions: There is room for improvement in child care regulations around PA for young children; PA promotion should be included with future updates to regulations. PMID:25354331

  14. Altered Hemodynamic Activity in Conduct Disorder: A Resting-State fMRI Investigation

    PubMed Central

    Zhou, Jiansong; Yao, Nailin; Fairchild, Graeme; Zhang, Yingdong; Wang, Xiaoping

    2015-01-01

    Background Youth with conduct disorder (CD) not only inflict serious physical and psychological harm on others, but are also at greatly increased risk of sustaining injuries, developing depression or substance abuse, and engaging in criminal behaviors. The underlying neurobiological basis of CD remains unclear. Objective The present study investigated whether participants with CD have altered hemodynamic activity under resting-state conditions. Methods Eighteen medication-naïve boys with CD and 18 age- and sex- matched typically developing (TD) controls underwent functional magnetic resonance imaging (MRI) scans in the resting state. The amplitude of low-frequency fluctuations (ALFF) was measured and compared between the CD and TD groups. Results Compared with the TD participants, the CD participants showed lower ALFF in the bilateral amygdala/parahippocampus, right lingual gyrus, left cuneus and right insula. Higher ALFF was observed in the right fusiform gyrus and right thalamus in the CD participants compared to the TD group. Conclusions Youth with CD displayed widespread functional abnormalities in emotion-related and visual cortical regions in the resting state. These results suggest that deficits in the intrinsic activity of resting state networks may contribute to the etiology of CD. PMID:25816069

  15. Relationship between observed upper mantle structures and recent tectonic activity across the Southeastern United States

    NASA Astrophysics Data System (ADS)

    Biryol, C. Berk; Wagner, Lara S.; Fischer, Karen M.; Hawman, Robert B.

    2016-05-01

    The lithospheric structure of the Southeastern United States is a product of earlier episodes of continental collision and breakup. The region is located in the interior of the North American Plate, away from active plate margins. However, there is ongoing tectonism in the region with multiple zones of seismicity, uplifting arches, and Cenozoic intraplate volcanism. The mechanisms controlling this activity and the state of stress remain enigmatic. Two important factors are plate strength and preexisting, inherited structures. Here we present new tomographic images of the upper mantle beneath the Southeastern United States, revealing large-scale structural variations in the upper mantle. Examples include the relatively thick lithospheric mantle of stable North America that abruptly thins beneath the Paleozoic Appalachian orogeny, and the slow upper mantle of the Proterozoic Reelfoot rift. Our results also indicate fast seismic velocity patterns that can be interpreted as ongoing lithospheric foundering. This provides a viable explanation for seismicity, uplifting, and young intraplate volcanism. We postulate that not only tectonic inheritance but also continuing lithospheric foundering may control the ongoing activity of the region long after it became a passive margin. Based on distinct variations in the geometry and thickness of the lithospheric mantle and foundered lithosphere, we propose that piecemeal delamination has occurred beneath the region throughout the Cenozoic, removing a significant amount of reworked/deformed mantle lithosphere. Ongoing lithospheric foundering beneath the eastern margin of stable North America explains significant variations in thickness of lithospheric mantle across the former Grenville deformation front.

  16. Detection rates of the MODIS active fire product in the United States

    USGS Publications Warehouse

    Hawbaker, T.J.; Radeloff, V.C.; Syphard, A.D.; Zhu, Z.; Stewart, S.I.

    2008-01-01

    MODIS active fire data offer new information about global fire patterns. However, uncertainties in detection rates can render satellite-derived fire statistics difficult to interpret. We evaluated the MODIS 1??km daily active fire product to quantify detection rates for both Terra and Aqua MODIS sensors, examined how cloud cover and fire size affected detection rates, and estimated how detection rates varied across the United States. MODIS active fire detections were compared to 361 reference fires (??? 18??ha) that had been delineated using pre- and post-fire Landsat imagery. Reference fires were considered detected if at least one MODIS active fire pixel occurred within 1??km of the edge of the fire. When active fire data from both Aqua and Terra were combined, 82% of all reference fires were found, but detection rates were less for Aqua and Terra individually (73% and 66% respectively). Fires not detected generally had more cloudy days, but not when the Aqua data were considered exclusively. MODIS detection rates decreased with fire size, and the size at which 50% of all fires were detected was 105??ha when combining Aqua and Terra (195??ha for Aqua and 334??ha for Terra alone). Across the United States, detection rates were greatest in the West, lower in the Great Plains, and lowest in the East. The MODIS active fire product captures large fires in the U.S. well, but may under-represent fires in areas with frequent cloud cover or rapidly burning, small, and low-intensity fires. We recommend that users of the MODIS active fire data perform individual validations to ensure that all relevant fires are included. ?? 2008 Elsevier Inc. All rights reserved.

  17. Rsr1 Focuses Cdc42 Activity at Hyphal Tips and Promotes Maintenance of Hyphal Development in Candida albicans

    PubMed Central

    Pulver, Rebecca; Heisel, Timothy; Gonia, Sara; Robins, Robert; Norton, Jennifer; Haynes, Paula

    2013-01-01

    The extremely elongated morphology of fungal hyphae is dependent on the cell's ability to assemble and maintain polarized growth machinery over multiple cell cycles. The different morphologies of the fungus Candida albicans make it an excellent model organism in which to study the spatiotemporal requirements for constitutive polarized growth and the generation of different cell shapes. In C. albicans, deletion of the landmark protein Rsr1 causes defects in morphogenesis that are not predicted from study of the orthologous protein in the related yeast Saccharomyces cerevisiae, thus suggesting that Rsr1 has expanded functions during polarized growth in C. albicans. Here, we show that Rsr1 activity localizes to hyphal tips by the differential localization of the Rsr1 GTPase-activating protein (GAP), Bud2, and guanine nucleotide exchange factor (GEF), Bud5. In addition, we find that Rsr1 is needed to maintain the focused localization of hyphal polarity structures and proteins, including Bem1, a marker of the active GTP-bound form of the Rho GTPase, Cdc42. Further, our results indicate that tip-localized Cdc42 clusters are associated with the cell's ability to express a hyphal transcriptional program and that the ability to generate a focused Cdc42 cluster in early hyphae (germ tubes) is needed to maintain hyphal morphogenesis over time. We propose that in C. albicans, Rsr1 “fine-tunes” the distribution of Cdc42 activity and that self-organizing (Rsr1-independent) mechanisms of polarized growth are not sufficient to generate narrow cell shapes or to provide feedback to the transcriptional program during hyphal morphogenesis. PMID:23223038

  18. Quantitative Proteomic Analysis Reveals Molecular Adaptations in the Hippocampal Synaptic Active Zone of Chronic Mild Stress-Unsusceptible Rats

    PubMed Central

    Zhou, Jian; Liu, Zhao; Yu, Jia; Han, Xin; Fan, Songhua; Shao, Weihua; Chen, Jianjun; Qiao, Rui

    2016-01-01

    Background: While stressful events are recognized as an important cause of major depressive disorder, some individuals exposed to life stressors maintain normal psychological functioning. The molecular mechanism(s) underlying this phenomenon remain unclear. Abnormal transmission and plasticity of hippocampal synapses have been implied to play a key role in the pathoetiology of major depressive disorder. Methods: A chronic mild stress protocol was applied to separate susceptible and unsusceptible rat subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation coupled with tandem mass spectrometry was performed to identify differential proteins in enriched hippocampal synaptic junction preparations. Results: A total of 4318 proteins were quantified, and 89 membrane proteins were present in differential amounts. Of these, SynaptomeDB identified 81 (91%) having a synapse-specific localization. The unbiased profiles identified several candidate proteins within the synaptic junction that may be associated with stress vulnerability or insusceptibility. Subsequent functional categorization revealed that protein systems particularly involved in membrane trafficking at the synaptic active zone exhibited a positive strain as potential molecular adaptations in the unsusceptible rats. Moreover, through STRING and immunoblotting analysis, membrane-associated GTP-bound Rab3a and Munc18-1 appear to coregulate syntaxin-1/SNAP25/VAMP2 assembly at the hippocampal presynaptic active zone of unsusceptible rats, facilitating SNARE-mediated membrane fusion and neurotransmitter release, and may be part of a stress-protection mechanism in actively maintaining an emotional homeostasis. Conclusions: The present results support the concept that there is a range of potential protein adaptations in the hippocampal synaptic active zone of unsusceptible rats, revealing new investigative targets that may contribute to a better understanding of stress

  19. 34 CFR 403.71 - In what additional ways may funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... agencies; (b) The support for tech-prep education as described in 34 CFR part 406; (c)(1) The support of... 34 Education 3 2010-07-01 2010-07-01 false In what additional ways may funds be used under the State Programs and State Leadership Activities? 403.71 Section 403.71 Education Regulations of...

  20. 1974 State Education Legislation and Activity: General Governance and Administration. A survey of the States. Research Brief, Vol. 3, No. 5.

    ERIC Educational Resources Information Center

    Hayas, Denise Kale; Ross, Doris M.

    This report, fifth in a series, is a collection of information on 1974 state education legislation and activity. The raw data information, rapidly processed for early release, includes 700 legislative items related to general governance and administration of elementary and secondary schools. The legislation from all 50 states reported has been…

  1. Downregulation of the Ras–Mitogen-Activated Protein Kinase Pathway by the EphB2 Receptor Tyrosine Kinase Is Required for Ephrin-Induced Neurite Retraction

    PubMed Central

    Elowe, Sabine; Holland, Sacha J.; Kulkarni, Sarang; Pawson, Tony

    2001-01-01

    Activation of the EphB2 receptor tyrosine kinase by clustered ephrin-B1 induces growth cone collapse and neurite retraction in differentiated NG108 neuronal cells. We have investigated the cytoplasmic signaling events associated with EphB2-induced cytoskeletal reorganization in these neuronal cells. We find that unlike other receptor tyrosine kinases, EphB2 induces a pronounced downregulation of GTP-bound Ras and consequently of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. A similar inhibition of the Ras-MAPK pathway was observed on stimulation of endogenous EphB2 in COS-1 cells. Inactivation of Ras, induced by ephrin B1 stimulation of NG108 neuronal cells, requires EphB2 tyrosine kinase activity and is blocked by a truncated form of p120-Ras GTPase-activating protein (p120-RasGAP), suggesting that EphB2 signals through the SH2 domain protein p120-RasGAP to inhibit the Ras-MAPK pathway. Suppression of Ras activity appears functionally important, since expression of a constitutively active variant of Ras impaired the ability of EphB2 to induce neurite retraction. In addition, EphB2 attenuated the elevation in ERK activation induced by attachment of NG108 cells to fibronectin, indicating that the EphB2 receptor can modulate integrin signaling to the Ras GTPase. These results suggest that a primary function of EphB2, a member of the most populous family of receptor tyrosine kinases, is to inactivate the Ras-MAPK pathway in a fashion that contributes to cytoskeletal reorganization and adhesion responses in neuronal growth cones. PMID:11585923

  2. Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis

    PubMed Central

    Kumar, Atul; Aguirre, Jacob D; Condos, Tara EC; Martinez-Torres, R Julio; Chaugule, Viduth K; Toth, Rachel; Sundaramoorthy, Ramasubramanian; Mercier, Pascal; Knebel, Axel; Spratt, Donald E; Barber, Kathryn R; Shaw, Gary S; Walden, Helen

    2015-01-01

    The PARK2 gene is mutated in 50% of autosomal recessive juvenile parkinsonism (ARJP) cases. It encodes parkin, an E3 ubiquitin ligase of the RBR family. Parkin exists in an autoinhibited state that is activated by phosphorylation of its N-terminal ubiquitin-like (Ubl) domain and binding of phosphoubiquitin. We describe the 1.8 Å crystal structure of human parkin in its fully inhibited state and identify the key interfaces to maintain parkin inhibition. We identify the phosphoubiquitin-binding interface, provide a model for the phosphoubiquitin–parkin complex and show how phosphorylation of the Ubl domain primes parkin for optimal phosphoubiquitin binding. Furthermore, we demonstrate that the addition of phosphoubiquitin leads to displacement of the Ubl domain through loss of structure, unveiling a ubiquitin-binding site used by the E2∼Ub conjugate, thus leading to active parkin. We find the role of the Ubl domain is to prevent parkin activity in the absence of the phosphorylation signals, and propose a model for parkin inhibition, optimization for phosphoubiquitin recruitment, release of inhibition by the Ubl domain and engagement with an E2∼Ub conjugate. Taken together, this model provides a mechanistic framework for activating parkin. PMID:26254304

  3. Altered resting-state brain activity at functional MRI during automatic memory consolidation of fear conditioning.

    PubMed

    Feng, Tingyong; Feng, Pan; Chen, Zhencai

    2013-07-26

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of automatic memory consolidation of fear conditioning is still unclear. To address this question, we measured brain activity following fear acquisition using resting-state functional magnetic resonance imaging (rs-fMRI). In the current study, we used a marker of fMRI, amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to quantify the spontaneous brain activity. Brain activity correlated to fear memory consolidation was observed in parahippocampus, insula, and thalamus in resting-state. Furthermore, after acquired fear conditioning, compared with control group some brain areas showed ALFF increased in ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) in the experimental group, whereas some brain areas showed decreased ALFF in striatal regions (caudate, putamen). Moreover, the change of ALFF in vmPFC was positively correlated with the subjective fear ratings. These findings suggest that the parahippocampus, insula, and thalamus are the neural substrates of fear memory consolidation. The difference in activity could be attributed to a homeostatic process in which the vmPFC and ACC were involved in the fear recovery process, and change of ALFF in vmPFC predicts subjective fear ratings. PMID:23726994

  4. Altered Spontaneous Brain Activity in Patients with Hemifacial Spasm: A Resting-State Functional MRI Study

    PubMed Central

    Tu, Ye; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei

    2015-01-01

    Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS. PMID:25603126

  5. State Special Education Outcomes, 2001: A Report on State Activities at the Beginning of a New Decade.

    ERIC Educational Resources Information Center

    Thompson, Sandra; Thurlow, Martha

    This report summarizes the eighth survey of state directors of special education by the National Center on Educational Outcomes at the University of Minnesota. Results include all 50 states and the Bureau of Indian Affairs, American Samoa, and Palau. State directors report increased participation rates of students with disabilities in state…

  6. Update: Influenza Activity--United States, October 4, 2015-February 6, 2016.

    PubMed

    Russell, Kate; Blanton, Lenee; Kniss, Krista; Mustaquim, Desiree; Smith, Sophie; Cohen, Jessica; Garg, Shikha; Flannery, Brendan; Fry, Alicia M; Grohskopf, Lisa A; Bresee, Joseph; Wallis, Teresa; Sessions, Wendy; Garten, Rebecca; Xu, Xiyan; Elal, Anwar Isa Abd; Gubareva, Larisa; Barnes, John; Wentworth, David E; Burns, Erin; Katz, Jacqueline; Jernigan, Daniel; Brammer, Lynnette

    2016-02-19

    From October through mid-December 2015, influenza activity remained low in most regions of the United States. Activity began to increase in late December 2015 and continued to increase slowly through early February 2016. Influenza A viruses have been most frequently identified, with influenza A (H3N2) viruses predominating during October until early December, and influenza A (H1N1)pdm09 viruses predominating from mid-December until early February. Most of the influenza viruses characterized during that time are antigenically similar to vaccine virus strains recommended for inclusion in the 2015-16 Northern Hemisphere vaccines. This report summarizes U.S. influenza activity* during October 4, 2015-February 6, 2016, and updates the previous summary (1). PMID:26891596

  7. 78 FR 44467 - Political Activity-State or Local Officers or Employees; Federal Employees Residing in Designated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-24

    ...; Federal Register #0; #0; #0;This section of the FEDERAL REGISTER contains notices to the public of #0;the...; ] OFFICE OF PERSONNEL MANAGEMENT 5 CFR Parts 151, 733, and 734 RIN 3206-AM87 Political Activity--State or...: The Hatch Act, codified at 5 U.S.C. 1501- 1508, concerns the political activities of State and...

  8. 20 CFR 404.417 - Deductions because of noncovered remunerative activity outside the United States; 45 hour and 7...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... activity outside the United States; 45 hour and 7-day work test. 404.417 Section 404.417 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950... activity outside the United States; 45 hour and 7-day work test. (a) Deductions because of...

  9. A Cautionary Tale About Conducting Research on Abstinence Education: How Do State Abstinence Coordinators Define "Sexual Activity?"

    ERIC Educational Resources Information Center

    Bailey, William; Young, Michael; Knickerbocker, Cliff; Doan, Tam

    2002-01-01

    Investigated how state coordinators of abstinence education programs defined "sexual activity." Researchers surveyed Title V abstinence education coordinators from the 50 states, the District of Columbia, and three territories. Of the 17 coordinators providing at least partial responses, none reported having a definition of sexual activity. The…

  10. Matching Element Symbols with State Abbreviations: A Fun Activity for Browsing the Periodic Table of Chemical Elements

    ERIC Educational Resources Information Center

    Woelk, Klaus

    2009-01-01

    A classroom activity is presented in which students are challenged to find matches between the United States two-letter postal abbreviations for states and chemical element symbols. The activity aims to lessen negative apprehensions students might have when the periodic table of the elements with its more than 100 combinations of letters is first…

  11. High salt primes a specific activation state of macrophages, M(Na).

    PubMed

    Zhang, Wu-Chang; Zheng, Xiao-Jun; Du, Lin-Juan; Sun, Jian-Yong; Shen, Zhu-Xia; Shi, Chaoji; Sun, Shuyang; Zhang, Zhiyuan; Chen, Xiao-Qing; Qin, Mu; Liu, Xu; Tao, Jun; Jia, Lijun; Fan, Heng-Yu; Zhou, Bin; Yu, Ying; Ying, Hao; Hui, Lijian; Liu, Xiaolong; Yi, Xianghua; Liu, Xiaojing; Zhang, Lanjing; Duan, Sheng-Zhong

    2015-08-01

    High salt is positively associated with the risk of many diseases. However, little is known about the mechanisms. Here we showed that high salt increased proinflammatory molecules, while decreased anti-inflammatory and proendocytic molecules in both human and mouse macrophages. High salt also potentiated lipopolysaccharide-induced macrophage activation and suppressed interleukin 4-induced macrophage activation. High salt induced the proinflammatory aspects by activating p38/cFos and/or Erk1/2/cFos pathways, while inhibited the anti-inflammatory and proendocytic aspects by Erk1/2/signal transducer and activator of transcription 6 pathway. Consistent with the in vitro results, high-salt diet increased proinflammatory gene expression of mouse alveolar macrophages. In mouse models of acute lung injury, high-salt diet aggravated lipopolysaccharide-induced pulmonary macrophage activation and inflammation in lungs. These results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na). PMID:26206316

  12. 14 CFR 1204.1507 - Communicating with State and local officials concerning the Agency's programs and activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... early in a program planning cycle as is reasonably feasible to explain specific plans and actions. (b... in a state of proposed direct Federal development if: (1) The state has not adopted a process under the Order; or (2) The development involves a program or activity not selected for the state...

  13. Binding of Gq protein stabilizes the activated state of the muscarinic receptor type 1.

    PubMed

    Tateyama, Michihiro; Kubo, Yoshihiro

    2013-02-01

    Activation of G protein coupled receptors (GPCRs) induces various cellular responses through interactions with G proteins. The key trigger of GPCR activation is agonist binding. It is reportedly known that the agonist-bound active conformation of the GPCRs, such as the muscarinic acetylcholine receptor type 1 (M(1)R), can be affected by the coupling of G proteins and by depolarization of the membrane potential. Here we aimed at investigating their effects on the structural rearrangements of the M(1)Rs between the active and quiescent states, using the fluorescence resonance energy transfer (FRET) technique. For this purpose, fluorescent M(1)R constructs that maintained intact activation of the Gq pathway and interaction with Gq were used. We captured the agonist-induced conformational changes of the M(1)R as the FRET decreases and found that the FRET decreases were enhanced by co-expression of the Gq subunits. In addition, co-expression of the Gq subunits decelerated the recovery of the declined FRET upon removal of the agonists, which was slower than the dissociation of the Gq subunits from the receptor. These results suggested that Gq binding stabilizes the agonist-induced activated conformation of the M(1)R. We also found that depolarization of the membrane potential slightly but significantly enhanced the agonist-induced FRET decrease, by accelerating the agonist-induced conformational changes. Thus, structural rearrangement analyses by FRET revealed that Gq coupling stabilizes the active conformation of the M(1)R and also suggested that depolarization accelerates the transition from quiescent to activation conformation. PMID:23085334

  14. Prevalence and correlates of local health department activities to address mental health in the United States.

    PubMed

    Purtle, Jonathan; Klassen, Ann C; Kolker, Jennifer; Buehler, James W

    2016-01-01

    Mental health has been recognized as a public health priority for nearly a century. Little is known, however, about what local health departments (LHDs) do to address the mental health needs of the populations they serve. Using data from the 2013 National Profile of Local Health Departments - a nationally representative survey of LHDs in the United States (N=505) - we characterized LHDs' engagement in eight mental health activities, factors associated with engagement, and estimated the proportion of the U.S. population residing in jurisdictions where these activities were performed. We used Handler's framework of the measurement of public health systems to select variables and examined associations between LHD characteristics and engagement in mental health activities using bivariate analyses and multilevel, multivariate logistic regression. Assessing gaps in access to mental healthcare services (39.3%) and implementing strategies to improve access to mental healthcare services (32.8%) were the most common mental health activities performed. LHDs that provided mental healthcare services were significantly more likely to perform population-based mental illness prevention activities (adjusted odds ratio: 7.1; 95% CI: 5.1, 10.0) and engage in policy/advocacy activities to address mental health (AOR: 3.9; 95% CI: 2.7, 5.6). Our study suggests that many LHDs are engaged in activities to address mental health, ranging from healthcare services to population-based interventions, and that LHDs that provide healthcare services are more likely than others to perform mental health activities. These findings have implications as LHDs reconsider their roles in the era of the Patient Protection and Affordable Care Act and LHD accreditation. PMID:26582210

  15. Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness.

    PubMed

    Chow, Ho Ming; Horovitz, Silvina G; Carr, Walter S; Picchioni, Dante; Coddington, Nate; Fukunaga, Masaki; Xu, Yisheng; Balkin, Thomas J; Duyn, Jeff H; Braun, Allen R

    2013-06-18

    Rapid eye movement (REM) sleep constitutes a distinct "third state" of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects "level of consciousness," we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation. PMID:23733938

  16. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis

    PubMed Central

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J.; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  17. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis.

    PubMed

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl's gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  18. Processing communications events in parallel active messaging interface by awakening thread from wait state

    DOEpatents

    Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

    2013-10-22

    Processing data communications events in a parallel active messaging interface (`PAMI`) of a parallel computer that includes compute nodes that execute a parallel application, with the PAMI including data communications endpoints, and the endpoints are coupled for data communications through the PAMI and through other data communications resources, including determining by an advance function that there are no actionable data communications events pending for its context, placing by the advance function its thread of execution into a wait state, waiting for a subsequent data communications event for the context; responsive to occurrence of a subsequent data communications event for the context, awakening by the thread from the wait state; and processing by the advance function the subsequent data communications event now pending for the context.

  19. Multi-scale integration and predictability in resting state brain activity

    PubMed Central

    Kolchinsky, Artemy; van den Heuvel, Martijn P.; Griffa, Alessandra; Hagmann, Patric; Rocha, Luis M.; Sporns, Olaf; Goñi, Joaquín

    2014-01-01

    The human brain displays heterogeneous organization in both structure and function. Here we develop a method to characterize brain regions and networks in terms of information-theoretic measures. We look at how these measures scale when larger spatial regions as well as larger connectome sub-networks are considered. This framework is applied to human brain fMRI recordings of resting-state activity and DSI-inferred structural connectivity. We find that strong functional coupling across large spatial distances distinguishes functional hubs from unimodal low-level areas, and that this long-range functional coupling correlates with structural long-range efficiency on the connectome. We also find a set of connectome regions that are both internally integrated and coupled to the rest of the brain, and which resemble previously reported resting-state networks. Finally, we argue that information-theoretic measures are useful for characterizing the functional organization of the brain at multiple scales. PMID:25104933

  20. Quantitative super-resolution imaging of Bruchpilot distinguishes active zone states

    NASA Astrophysics Data System (ADS)

    Ehmann, Nadine; van de Linde, Sebastian; Alon, Amit; Ljaschenko, Dmitrij; Keung, Xi Zhen; Holm, Thorge; Rings, Annika; Diantonio, Aaron; Hallermann, Stefan; Ashery, Uri; Heckmann, Manfred; Sauer, Markus; Kittel, Robert J.

    2014-08-01

    The precise molecular architecture of synaptic active zones (AZs) gives rise to different structural and functional AZ states that fundamentally shape chemical neurotransmission. However, elucidating the nanoscopic protein arrangement at AZs is impeded by the diffraction-limited resolution of conventional light microscopy. Here we introduce new approaches to quantify endogenous protein organization at single-molecule resolution in situ with super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM). Focusing on the Drosophila neuromuscular junction (NMJ), we find that the AZ cytomatrix (CAZ) is composed of units containing ~137 Bruchpilot (Brp) proteins, three quarters of which are organized into about 15 heptameric clusters. We test for a quantitative relationship between CAZ ultrastructure and neurotransmitter release properties by engaging Drosophila mutants and electrophysiology. Our results indicate that the precise nanoscopic organization of Brp distinguishes different physiological AZ states and link functional diversification to a heretofore unrecognized neuronal gradient of the CAZ ultrastructure.

  1. Neuropeptidergic Signaling and Active Feeding State Inhibit Nociception in Caenorhabditis elegans.

    PubMed

    Ezcurra, Marina; Walker, Denise S; Beets, Isabel; Swoboda, Peter; Schafer, William R

    2016-03-16

    Food availability and nutritional status are important cues affecting behavioral states. Here we report that, in Caenorhabditis elegans, a cascade of dopamine and neuropeptide signaling acts to inhibit nociception in food-poor environments. In the absence of food, animals show decreased sensitivity and increased adaptation to soluble repellents sensed by the polymodal ASH nociceptors. The effects of food on adaptation are affected by dopamine and neuropeptide signaling; dopamine acts via the DOP-1 receptor to decrease adaptation on food, whereas the neuropeptide receptors NPR-1 and NPR-2 act to increase adaptation off food. NPR-1 and NPR-2 function cell autonomously in the ASH neurons to increase adaptation off food, whereas the DOP-1 receptor controls neuropeptide release from interneurons that modulate ASH activity indirectly. These results indicate that feeding state modulates nociception through the interaction of monoamine and neuropeptide signaling pathways. PMID:26985027

  2. Solid state photon upconversion utilizing thermally activated delayed fluorescence molecules as triplet sensitizer

    SciTech Connect

    Wu, Tony C.; Congreve, Daniel N.; Baldo, Marc A.

    2015-07-20

    The ability to upconvert light is useful for a range of applications, from biological imaging to solar cells. But modern technologies have struggled to upconvert incoherent incident light at low intensities. Here, we report solid state photon upconversion employing triplet-triplet exciton annihilation in an organic semiconductor, sensitized by a thermally activated-delayed fluorescence (TADF) dye. Compared to conventional phosphorescent sensitizers, the TADF dye maximizes the wavelength shift in upconversion due to its small singlet-triplet splitting. The efficiency of energy transfer from the TADF dye is 9.1%, and the conversion yield of sensitizer exciton pairs to singlet excitons in the annihilator is 1.1%. Our results demonstrate upconversion in solid state geometries and with non-heavy metal-based sensitizer materials.

  3. Neuropeptidergic Signaling and Active Feeding State Inhibit Nociception in Caenorhabditis elegans

    PubMed Central

    Ezcurra, Marina; Walker, Denise S.; Beets, Isabel; Swoboda, Peter

    2016-01-01

    Food availability and nutritional status are important cues affecting behavioral states. Here we report that, in Caenorhabditis elegans, a cascade of dopamine and neuropeptide signaling acts to inhibit nociception in food-poor environments. In the absence of food, animals show decreased sensitivity and increased adaptation to soluble repellents sensed by the polymodal ASH nociceptors. The effects of food on adaptation are affected by dopamine and neuropeptide signaling; dopamine acts via the DOP-1 receptor to decrease adaptation on food, whereas the neuropeptide receptors NPR-1 and NPR-2 act to increase adaptation off food. NPR-1 and NPR-2 function cell autonomously in the ASH neurons to increase adaptation off food, whereas the DOP-1 receptor controls neuropeptide release from interneurons that modulate ASH activity indirectly. These results indicate that feeding state modulates nociception through the interaction of monoamine and neuropeptide signaling pathways. PMID:26985027

  4. Evaluating amphibian responses in wetlands impacted by mining activities in the western United States

    SciTech Connect

    Linder, G.; Wyant, J.; Meganck, R.; Williams, B.

    1991-01-01

    An increasing awareness of declining amphibian populations in the United States requires that the authors develop strategies for evaluating anthropogenic impacts on wetlands and the biota dependent upon these habitats. For example, in the western United States, mining activities may impact a wetland and its biota directly through habitat destruction or run-off of sediments and contaminants generated during mining operations. Amphibians which frequent these transition zones between terrestrial and aquatic habitats may be key biological indicators of a wetland's status. Through a demonstration project located in the mining regions of western Montana, the authors are currently using laboratory and field methods for a wetland evaluation required within a Superfund ecological risk assessment.

  5. Solid state photon upconversion utilizing thermally activated delayed fluorescence molecules as triplet sensitizer

    NASA Astrophysics Data System (ADS)

    Wu, Tony C.; Congreve, Daniel N.; Baldo, Marc A.

    2015-07-01

    The ability to upconvert light is useful for a range of applications, from biological imaging to solar cells. But modern technologies have struggled to upconvert incoherent incident light at low intensities. Here, we report solid state photon upconversion employing triplet-triplet exciton annihilation in an organic semiconductor, sensitized by a thermally activated-delayed fluorescence (TADF) dye. Compared to conventional phosphorescent sensitizers, the TADF dye maximizes the wavelength shift in upconversion due to its small singlet-triplet splitting. The efficiency of energy transfer from the TADF dye is 9.1%, and the conversion yield of sensitizer exciton pairs to singlet excitons in the annihilator is 1.1%. Our results demonstrate upconversion in solid state geometries and with non-heavy metal-based sensitizer materials.

  6. Dynamics of the Thermal State of Active Layer at the Alaska North Slope and Northern Yakutia

    NASA Astrophysics Data System (ADS)

    Kholodov, A. L.; Romanovsky, V. E.; Marchenko, S.; Shiklomanov, N. I.; Fedorov-Davydov, D.

    2010-12-01

    Dynamics of the active layer is one of the most important indexes, reflecting permafrost response to the modern climate changes. Monitoring of active layer thickness dynamics is the main goal of CALM (Circumpolar Active Layer Monitoring) project. But, from different points of view, it is very important to know not only maximal depth of seasonal thawing but also dynamics of thermal field of active layer and duration of its staying in the unfrozen state. Current research was aimed on the analyzing data of temperature measurements have been done during the more then 10 years at the North Slope of Brooks Range (Alaska) and 2 years at the selected sites at the Northern Yakutia (Russia) and its comparison with the 17 to 10 years records of active layer thickness dynamics at the corresponding sites (http://www.udel.edu/Geography/calm/data/north.html). The area of investigation characterized by the typical tundra landscape and different kinds of micro topography. Reported observation sites located at the latitudinal range from 68.5 to 70.3N in Alaska and 70.5 to 71.75N in the Northern Yakutia. Observation have been done using the 1 meter long MRC probe with 11 sensors (every 10 cm) and single Campbell SCI A107 sensors in Alaska and 2-channel HOBO U23 data loggers with TMC-HD thermistors in the Northern Yakutia. Analyses of CALM data show what most observation sites in Alaska (except located near the Brooks Range and at the Arctic Ocean coast) do not subjected to the significant sustainable changes of active layer thickness over the last 10 years. At the same time active layer thickness at the Yakutian sites was increasing. Temperature observations show decreasing of the mean annual temperature at the average depth of active layer bottom at the Alaskan sites. But, because of general trend to increasing of period of thawing it does not lead to the decreasing of active layer thickness. Recent equipment deployment at the Tiksi and Allaikha sites (Northern Yakutia) does not

  7. Independent Component Analysis of Resting State Activity in Pediatric Obsessive-Compulsive Disorder

    PubMed Central

    Gruner, Patricia; Vo, An; Argyelan, Miklos; Ikuta, Toshikazu; Degnan, Andrew J.; John, Majnu; Peters, Bart D.; Malhotra, Anil K.; Uluğ, Aziz M.; Szeszko, Philip R.

    2014-01-01

    Obsessive-compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared to healthy volunteers and their clinical correlates. Twenty-three pediatric OCD patients and 23 healthy volunteers (age range 9–17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children’s Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified 3 components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component expression scores were significantly higher in patients compared to healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention. PMID:24867148

  8. Nanosilver induces a non-culturable but metabolically active state in Pseudomonas aeruginosa

    PubMed Central

    Königs, Alexa M.; Flemming, Hans-Curt; Wingender, Jost

    2015-01-01

    The antimicrobial properties of silver nanoparticles (AgNPs) have raised expectations for the protection of medical devices and consumer products against biofilms. The effect of silver on bacteria is commonly determined by culture-dependent methods. It is as yet unknown if silver-exposed bacteria can enter a metabolically active but non-culturable state. In this study, the efficacy of chemically synthesized AgNPs and silver as silver nitrate (AgNO3) against planktonic cells and biofilms of Pseudomonas aeruginosa AdS was investigated in microtiter plate assays, using cultural as well as culture-independent methods. In liquid medium, AgNPs and AgNO3 inhibited both planktonic growth and biofilm formation. The efficacy of AgNPs and AgNO3 against established, 24 h-old biofilms and planktonic stationary-phase cells was compared by exposure to silver in deionized water. Loss of culturability of planktonic cells was always higher than that of the attached biofilms. However, resuspended biofilm cells became more susceptible to AgNPs and AgNO3 than attached biofilms. Thus, the physical state of bacteria within biofilms rendered them more tolerant to silver compared with the planktonic state. Silver-exposed cells that had become unculturable still displayed signs of viability: they contained rRNA, determined by fluorescent in situ hybridization, as an indicator for potential protein synthesis, maintained their membrane integrity as monitored by differential live/dead staining, and displayed significant levels of adenosine triphosphate. It was concluded that AgNPs and AgNO3 in concentrations at which culturability was inhibited, both planktonic and biofilm cells of P. aeruginosa were still intact and metabolically active, reminiscent of the viable but non-culturable state known to be induced in pathogenic bacteria in response to stress conditions. This observation is important for a realistic assessment of the antimicrobial properties of AgNPs. PMID:25999929

  9. Management and climate contributions to satellite-derived active fire trends in the contiguous United States

    NASA Astrophysics Data System (ADS)

    Lin, Hsiao-Wen; McCarty, Jessica L.; Wang, Dongdong; Rogers, Brendan M.; Morton, Douglas C.; Collatz, G. James; Jin, Yufang; Randerson, James T.

    2014-04-01

    Fires in croplands, plantations, and rangelands contribute significantly to fire emissions in the United States, yet are often overshadowed by wildland fires in efforts to develop inventories or estimate responses to climate change. Here we quantified decadal trends, interannual variability, and seasonality of Terra Moderate Resolution Imaging Spectroradiometer (MODIS) observations of active fires (thermal anomalies) as a function of management type in the contiguous U.S. during 2001-2010. We used the Monitoring Trends in Burn Severity database to identify active fires within the perimeter of large wildland fires and land cover maps to identify active fires in croplands. A third class of fires defined as prescribed/other included all residual satellite active fire detections. Large wildland fires were the most variable of all three fire types and had no significant annual trend in the contiguous U.S. during 2001-2010. Active fires in croplands, in contrast, increased at a rate of 3.4% per year. Cropland and prescribed/other fire types combined were responsible for 77% of the total active fire detections within the U.S and were most abundant in the south and southeast. In the west, cropland active fires decreased at a rate of 5.9% per year, likely in response to intensive air quality policies. Potential evaporation was a dominant regulator of the interannual variability of large wildland fires, but had a weaker influence on the other two fire types. Our analysis suggests it may be possible to modify landscape fire emissions within the U.S. by influencing the way fires are used in managed ecosystems.

  10. Management and climate contributions to satellite-derived active fire trends in the contiguous United States

    PubMed Central

    Lin, Hsiao-Wen; McCarty, Jessica L; Wang, Dongdong; Rogers, Brendan M; Morton, Douglas C; Collatz, G James; Jin, Yufang; Randerson, James T

    2014-01-01

    Fires in croplands, plantations, and rangelands contribute significantly to fire emissions in the United States, yet are often overshadowed by wildland fires in efforts to develop inventories or estimate responses to climate change. Here we quantified decadal trends, interannual variability, and seasonality of Terra Moderate Resolution Imaging Spectroradiometer (MODIS) observations of active fires (thermal anomalies) as a function of management type in the contiguous U.S. during 2001–2010. We used the Monitoring Trends in Burn Severity database to identify active fires within the perimeter of large wildland fires and land cover maps to identify active fires in croplands. A third class of fires defined as prescribed/other included all residual satellite active fire detections. Large wildland fires were the most variable of all three fire types and had no significant annual trend in the contiguous U.S. during 2001–2010. Active fires in croplands, in contrast, increased at a rate of 3.4% per year. Cropland and prescribed/other fire types combined were responsible for 77% of the total active fire detections within the U.S and were most abundant in the south and southeast. In the west, cropland active fires decreased at a rate of 5.9% per year, likely in response to intensive air quality policies. Potential evaporation was a dominant regulator of the interannual variability of large wildland fires, but had a weaker influence on the other two fire types. Our analysis suggests it may be possible to modify landscape fire emissions within the U.S. by influencing the way fires are used in managed ecosystems. Key Points Wildland, cropland, and prescribed fires had different trends and patterns Sensitivity to climate varied with fire type Intensity of air quality regulation influenced cropland burning trends PMID:26213662

  11. Cancer Internet Search Activity on a Major Search Engine, United States 2001-2003

    PubMed Central

    Cooper, Crystale Purvis; Mallon, Kenneth P; Leadbetter, Steven; Peipins, Lucy A

    2005-01-01

    Background To locate online health information, Internet users typically use a search engine, such as Yahoo! or Google. We studied Yahoo! search activity related to the 23 most common cancers in the United States. Objective The objective was to test three potential correlates of Yahoo! cancer search activity—estimated cancer incidence, estimated cancer mortality, and the volume of cancer news coverage—and to study the periodicity of and peaks in Yahoo! cancer search activity. Methods Yahoo! cancer search activity was obtained from a proprietary database called the Yahoo! Buzz Index. The American Cancer Society's estimates of cancer incidence and mortality were used. News reports associated with specific cancer types were identified using the LexisNexis “US News” database, which includes more than 400 national and regional newspapers and a variety of newswire services. Results The Yahoo! search activity associated with specific cancers correlated with their estimated incidence (Spearman rank correlation, ρ = 0.50, P = .015), estimated mortality (ρ = 0.66, P = .001), and volume of related news coverage (ρ = 0.88, P < .001). Yahoo! cancer search activity tended to be higher on weekdays and during national cancer awareness months but lower during summer months; cancer news coverage also tended to follow these trends. Sharp increases in Yahoo! search activity scores from one day to the next appeared to be associated with increases in relevant news coverage. Conclusions Media coverage appears to play a powerful role in prompting online searches for cancer information. Internet search activity offers an innovative tool for passive surveillance of health information–seeking behavior. PMID:15998627

  12. Evaluation of Force Degradation Pattern of Elastomeric Ligatures and Elastomeric Separators in Active Tieback State

    PubMed Central

    Mohammadi, Amir; Mahmoodi, Farhang

    2015-01-01

    Background and aims. The purpose of this study was to evaluate initial force and force decay of commercially available elastomeric ligatures and elastomeric separators in active tieback state in a simulated oral environment. Materials and methods. A total of 288 elastomeric ligatures and elastomeric separators from three manufacturers (Dentaurum, RMO, 3M Unitek) were stretched to 100% and 150% of their original inner diameter. Force levels were measured initially and at 3-minute, 24-hour, and 1-, 2-, 3- and 4-week intervals. Data were analyzed by univariate analysis of variance and a post hoc Tukey test. Results. The means of initial forces of elastomeric ligatures and separators from three above-mentioned companies, when stretched to 100% of their inner diameters, were 199, 305 and 284 g, and 330, 416, 330 g; when they were stretched to 150% of their inner diameters the values were 286, 422 and 375 g, and 433, 540 and 504 g, respectively. In active tieback state, 11-18% of the initial force of the specimens was lost within the first 3 minutes and 29-63% of the force decay occurred in the first 24 hours; then force decay rate decreased. 62-81% of the initial force was lost in 4 weeks. Although force decay pattern was identical in all the products, the initial force and force decay of Dentaurum elastomeric products were less than the similar products of other companies (P<0.05). Under the same conditions, the force of elastomeric separators was greater than elastomeric ligatures of the same company. Conclusion. Regarding the force pattern of elastomeric ligatures and separators and optimal force for tooth movement, many of these products can be selected for applying orthodontic forces in active tieback state. PMID:26889363

  13. Evaluation of Force Degradation Pattern of Elastomeric Ligatures and Elastomeric Separators in Active Tieback State.

    PubMed

    Mohammadi, Amir; Mahmoodi, Farhang

    2015-01-01

    Background and aims. The purpose of this study was to evaluate initial force and force decay of commercially available elastomeric ligatures and elastomeric separators in active tieback state in a simulated oral environment. Materials and methods. A total of 288 elastomeric ligatures and elastomeric separators from three manufacturers (Dentaurum, RMO, 3M Unitek) were stretched to 100% and 150% of their original inner diameter. Force levels were measured initially and at 3-minute, 24-hour, and 1-, 2-, 3- and 4-week intervals. Data were analyzed by univariate analysis of variance and a post hoc Tukey test. Results. The means of initial forces of elastomeric ligatures and separators from three above-mentioned companies, when stretched to 100% of their inner diameters, were 199, 305 and 284 g, and 330, 416, 330 g; when they were stretched to 150% of their inner diameters the values were 286, 422 and 375 g, and 433, 540 and 504 g, respectively. In active tieback state, 11-18% of the initial force of the specimens was lost within the first 3 minutes and 29-63% of the force decay occurred in the first 24 hours; then force decay rate decreased. 62-81% of the initial force was lost in 4 weeks. Although force decay pattern was identical in all the products, the initial force and force decay of Dentaurum elastomeric products were less than the similar products of other companies (P<0.05). Under the same conditions, the force of elastomeric separators was greater than elastomeric ligatures of the same company. Conclusion. Regarding the force pattern of elastomeric ligatures and separators and optimal force for tooth movement, many of these products can be selected for applying orthodontic forces in active tieback state. PMID:26889363

  14. Auditory Power-Law Activation Avalanches Exhibit a Fundamental Computational Ground State.

    PubMed

    Stoop, Ruedi; Gomez, Florian

    2016-07-15

    The cochlea provides a biological information-processing paradigm that we are only beginning to understand in its full complexity. Our work reveals an interacting network of strongly nonlinear dynamical nodes, on which even a simple sound input triggers subnetworks of activated elements that follow power-law size statistics ("avalanches"). From dynamical systems theory, power-law size distributions relate to a fundamental ground state of biological information processing. Learning destroys these power laws. These results strongly modify the models of mammalian sound processing and provide a novel methodological perspective for understanding how the brain processes information. PMID:27472144

  15. Auditory Power-Law Activation Avalanches Exhibit a Fundamental Computational Ground State

    NASA Astrophysics Data System (ADS)

    Stoop, Ruedi; Gomez, Florian

    2016-07-01

    The cochlea provides a biological information-processing paradigm that we are only beginning to understand in its full complexity. Our work reveals an interacting network of strongly nonlinear dynamical nodes, on which even a simple sound input triggers subnetworks of activated elements that follow power-law size statistics ("avalanches"). From dynamical systems theory, power-law size distributions relate to a fundamental ground state of biological information processing. Learning destroys these power laws. These results strongly modify the models of mammalian sound processing and provide a novel methodological perspective for understanding how the brain processes information.

  16. Integrating computational activities into the upper-level Paradigms in Physics curriculum at Oregon State University

    NASA Astrophysics Data System (ADS)

    McIntyre, David H.; Tate, Janet; Manogue, Corinne A.

    2008-04-01

    The Paradigms in Physics project at Oregon State University has reformed the entire upper-level physics curriculum. The reform has involved a rearrangement of content to better reflect the way physicists think about the field and the use of several new pedagogies that place responsibility for learning more firmly in the hands of the students. In particular, we employ a wide variety of computational examples and problems throughout the courses. Students use MAPLE, MATHEMATICA, JAVA, and other software packages to do calculations, visualizations, and simulations that develop their intuition and physical reasoning. These computational activities are indispensable to the success of the curriculum.

  17. Cellular and circuit models of increased resting-state network gamma activity in schizophrenia.

    PubMed

    White, R S; Siegel, S J

    2016-05-01

    Schizophrenia (SCZ) is a disorder characterized by positive symptoms (hallucinations, delusions), negative symptoms (blunted affect, alogia, reduced sociability, and anhedonia), as well as persistent cognitive deficits (memory, concentration, and learning). While the biology underlying subjective experiences is difficult to study, abnormalities in electroencephalographic (EEG) measures offer a means to dissect potential circuit and cellular changes in brain function. EEG is indispensable for studying cerebral information processing due to the introduction of techniques for the decomposition of event-related activity into its frequency components. Specifically, brain activity in the gamma frequency range (30-80Hz) is thought to underlie cognitive function and may be used as an endophenotype to aid in diagnosis and treatment of SCZ. In this review we address evidence indicating that there is increased resting-state gamma power in SCZ. We address how modeling this aspect of the illness in animals may help treatment development as well as providing insights into the etiology of SCZ. PMID:26577758

  18. Detection of glucose based on the peroxidase-like activity of reduced state carbon dots.

    PubMed

    Long, Yijuan; Wang, Xiliang; Shen, Dongjun; Zheng, Huzhi

    2016-10-01

    It was found that reduced state carbon dots (r-CDs) possessed intrinsic peroxidase-like activity, and could catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction. The effects of temperature, pH, incubating time and the concentration of H2O2 and TMB on catalytic activity of r-CDs were investigated. Finally we calculated the kinetic constant was ca. 0.00729min(-1) and applied r-CDs to glucose sensing by coupling glucose oxidase. As low as 2µM H2O2 could be detected with a linear range from 0.010 to 0.40mM via this method. This study offered a simple, sensitive, and high selectivity method for glucose determination even in serum. PMID:27474288

  19. Continuous Activation of Autoreactive CD4+ CD25+ Regulatory T Cells in the Steady State

    PubMed Central

    Fisson, Sylvain; Darrasse-Jèze, Guillaume; Litvinova, Elena; Septier, Franck; Klatzmann, David; Liblau, Roland; Salomon, Benoît L.

    2003-01-01

    Despite a growing interest in CD4+ CD25+ regulatory T cells (Treg) that play a major role in self-tolerance and immunoregulation, fundamental parameters of the biology and homeostasis of these cells are poorly known. Here, we show that this population is composed of two Treg subsets that have distinct phenotypes and homeostasis in normal unmanipulated mice. In the steady state, some Treg remain quiescent and have a long lifespan, in the order of months, whereas the other Treg are dividing extensively and express multiple activation markers. After adoptive transfer, tissue-specific Treg rapidly divide and expand preferentially in lymph nodes draining their target self-antigens. These results reveal the existence of a cycling Treg subset composed of autoreactive Treg that are continuously activated by tissue self-antigens. PMID:12939344

  20. Active Particles with Soft and Curved Walls: Equation of State, Ratchets, and Instabilities.

    PubMed

    Nikola, Nikolai; Solon, Alexandre P; Kafri, Yariv; Kardar, Mehran; Tailleur, Julien; Voituriez, Raphaël

    2016-08-26

    We study, from first principles, the pressure exerted by an active fluid of spherical particles on general boundaries in two dimensions. We show that, despite the nonuniform pressure along curved walls, an equation of state is recovered upon a proper spatial averaging. This holds even in the presence of pairwise interactions between particles or when asymmetric walls induce ratchet currents, which are accompanied by spontaneous shear stresses on the walls. For flexible obstacles, the pressure inhomogeneities lead to a modulational instability as well as to the spontaneous motion of short semiflexible filaments. Finally, we relate the force exerted on objects immersed in active baths to the particle flux they generate around them. PMID:27610886

  1. Influence of Protonation State on the Excited State Dynamics of a Photobiologically Active Ru(II) Dyad.

    PubMed

    Reichardt, Christian; Sainuddin, Tariq; Wächtler, Maria; Monro, Susan; Kupfer, Stephan; Guthmuller, Julien; Gräfe, Stefanie; McFarland, Sherri; Dietzek, Benjamin

    2016-08-18

    The influence of ligand protonation on the photophysics of a ruthenium (Ru) dyad bearing the 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]-phenanthroline (ippy) ligand was investigated by time-resolved transient absorption spectroscopy. It was found that changes in the protonation state of the imidazole group led to changes in the electronic configuration of the lowest lying excited state. Formation of the fully deprotonated imidazole anion resulted in excited state signatures that were consistent with a low-lying intraligand (IL) triplet state. This assignment was supported by time-dependent density functional theory (TDDFT) calculations. IL triplet states have been suggested to be potent mediators of photodynamic effects. Thus, these results are of interest in the design of Ru metal complexes as photosensitizers (PSs) for photodynamic therapy (PDT). PMID:27459188

  2. Sport for All? Insight into Stratification and Compensation Mechanisms of Sporting Activity in the 27 European Union Member States

    ERIC Educational Resources Information Center

    Van Tuyckom, Charlotte; Scheerder, Jeroen

    2010-01-01

    Physical activity is an important public health issue and the benefits of an active lifestyle in relation to well-being and health have been strongly emphasised in recent years in Europe, as well as in most parts of the world. However, previous research has shown that physical activity within Europe and its member states is stratified. The present…

  3. Preservice Secondary Teachers' Conceptions from a Mathematical Modeling Activity and Connections to the Common Core State Standards

    ERIC Educational Resources Information Center

    Stohlmann, Micah; Maiorca, Cathrine; Olson, Travis A.

    2015-01-01

    Mathematical modeling is an essential integrated piece of the Common Core State Standards. However, researchers have shown that mathematical modeling activities can be difficult for teachers to implement. Teachers are more likely to implement mathematical modeling activities if they have their own successful experiences with such activities. This…

  4. Driving reactions: Surmounting activation barriers in solid state chemistry using hydroxide melts and RF plasmas

    NASA Astrophysics Data System (ADS)

    Friedman, Todd Lawrence

    1997-11-01

    This thesis explores several techniques for surmounting activation barriers in solid state chemistry. The two major issues addressed are the use of a solution-based molten hydroxide system to increase the rate of reactant diffusion over that in the solid state, and the use of an RF plasma to break bonds in gaseous reactants for subsequent reaction with a solid. Part I describes the use of molten alkali metal hydroxides as a low-temperature solvent system for both electrodeposition and precipitation of high valent copper oxides. Cyclic voltammetry was used to determine the effects of various reaction conditions on copper dissolved in the melts, including copper activity, temperature, and atmosphere composition. The results of this study indicate that copper oxide phases become less soluble at higher copper activities, temperatures, and pHsb2O values. Also, the Cu(II)/Cu(III) redox wave, important for the electrodeposition of cuprate phases with high copper formal oxidation states, is observed below 300sp°C in air and at 350sp°C in dry argon. NaCuOsb2 was electrodeposited under constant current conditions. Iodometric titrations and annealing studies indicate that NaCuOsb2 is oxygen deficient and tends to lose additional oxygen on heating. The hydroxide method was also successful in the deposition of thin films of superconducting EuBasb2Cusb4Osb8 on SrTiOsb3 substrates. The films were found to be superconducting with a Tsbc of 75 K in the absence of annealing. In Part II, the idea of circumventing activation energy barriers is applied to the problem of environmentally harmful perfluorocarbons (PFCs). Mass spectrometry was used to determine the PFC emissions from two semiconductor manufacturing processes: oxide etch and post-CVD chamber clean. Because of radical recombination to thermodynamically stable species, most of the PFCs used in these processes are emitted to the atmosphere. A prototype abatement device which uses an RF plasma to provide the activation energy

  5. Aerosol mixing state, hygroscopic growth and cloud activation efficiency during MIRAGE 2006

    NASA Astrophysics Data System (ADS)

    Lance, S.; Raatikainen, T.; Onasch, T. B.; Worsnop, D. R.; Yu, X.-Y.; Alexander, M. L.; Stolzenburg, M. R.; McMurry, P. H.; Smith, J. N.; Nenes, A.

    2013-05-01

    Observations of aerosol hygroscopic growth and CCN activation spectra for submicron particles are reported for the T1 ground site outside of Mexico City during the MIRAGE 2006 campaign. κ-Köhler theory is used to evaluate the characteristic hygroscopicity parameter, κ*, for the CCN active aerosol population using both size-resolved HTMDA and size-resolved CCNc measurements. Organic mass fractions (forg) are evaluated from size-resolved aerosol mass spectrometer (AMS) measurements, from which predictions of the hygroscopicity parameter are compared against κ*. Strong diurnal changes in aerosol water uptake parameters and aerosol composition are observed. We find that new particle formation (NPF) events are correlated with an increased κ* and CCN-active fraction during the daytime, with greater impact on smaller particles. During NPF events, the number concentration of 40 nm particles acting as CCN at 0.51% ± 0.06% supersaturation can surpass by more than a factor of two the corresponding concentrations of 100 nm particles. We also find that at 06:00-08:00 LT throughout the campaign, fresh traffic emissions result in substantial changes to the chemical distribution of the aerosol, with on average 65% externally mixed fraction for 40 nm particles and 30% externally mixed fraction for 100 nm particles, whereas at midday nearly all particles of both sizes can be described as "internally mixed". Average activation spectra and growth factor distributions are analyzed for different time periods characterizing the daytime (with and without NPF events), the early morning "rush hour" and the entire campaign. We show that κ* derived from CCNc measurements decreases as a function of size during all time periods, while the CCN-active fraction increases as a function of size. Size-resolved AMS measurements do not predict the observed trend for κ* versus particle size, which can be attributed to unresolved mixing state and the presence of refractory material not measured

  6. Preferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors

    PubMed Central

    Yanamala, Naveena; Tirupula, Kalyan C; Klein-Seetharaman, Judith

    2008-01-01

    Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiological and pathological processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects – enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, we propose the hypothesis that positive and negative modulators will differentially stabilize the active and inactive conformations of the receptors, respectively. To test this hypothesis, we have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the inactive, dark state of rhodopsin as template and the active conformation was created based on a recent model of the light-activated state of rhodopsin. Ligands for which the nature of their allosteric effects on mGluRs is experimentally known were docked to the modeled mGluR structures using ArgusLab and Autodock softwares. We find that the allosteric ligand binding pockets of mGluRs are overlapping with the retinal binding pocket of rhodopsin, and that ligands have strong preferences for the active and inactive states depending on their modulatory nature. In 8 out of 14 cases (57%), the negative modulators bound the inactive conformations with significant preference using both docking programs, and 6 out of 9 cases (67%), the positive modulators bound the active conformations. Considering results by the individual programs only, even higher correlations were observed: 12/14 (86%) and 8/9 (89%) for ArgusLab and 10/14 (71%) and 7/9 (78%) for AutoDock. These findings strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of different conformations analogous to those identified in rhodopsin where they are induced by photochemical isomerization

  7. Cerebral activity during the anesthesia-like state induced by mesopontine microinjection of pentobarbital.

    PubMed

    Abulafia, Ruth; Zalkind, Vladimir; Devor, Marshall

    2009-05-27

    Microinjection of pentobarbital into a restricted region of rat brainstem, the mesopontine tegmental anesthesia area (MPTA), induces a reversible anesthesia-like state characterized by loss of the righting reflex, atonia, antinociception, and loss of consciousness as assessed by electroencephalogram synchronization. We examined cerebral activity during this state using FOS expression as a marker. Animals were anesthetized for 50 min with a series of intracerebral microinjections of pentobarbital or with systemic pentobarbital and intracerebral microinjections of vehicle. FOS expression was compared with that in awake animals microinjected with vehicle. Neural activity was suppressed throughout the cortex whether anesthesia was induced by systemic or MPTA routes. Changes were less consistent subcortically. In the zona incerta and the nucleus raphe pallidus, expression was strongly suppressed during systemic anesthesia, but only mildly during MPTA-induced anesthesia. Dissociation was seen in the tuberomammillary nucleus where suppression occurred during systemic-induced anesthesia only, and in the lateral habenular nucleus where activity was markedly increased during systemic-induced anesthesia but not following intracerebral microinjection. Several subcortical nuclei previously associated with cerebral arousal were not affected. In the MPTA itself FOS expression was suppressed during systemic anesthesia. Differences in the pattern of brain activity in the two modes of anesthesia are consistent with the possibility that anesthetic endpoints might be achieved by alternative mechanisms: direct drug action for systemic anesthesia or via ascending pathways for MPTA-induced anesthesia. However, it is also possible that systemically administered agents induce anesthesia, at least in part, by a primary action in the MPTA with cortical inhibition occurring secondarily. PMID:19474332

  8. Conformational transition in signal transduction: metastable states and transition pathways in the activation of a signaling protein.

    PubMed

    Banerjee, Rahul; Yan, Honggao; Cukier, Robert I

    2015-06-01

    Signal transduction is of vital importance to the growth and adaptation of living organisms. The key to understand mechanisms of biological signal transduction is elucidation of the conformational dynamics of its signaling proteins, as the activation of a signaling protein is fundamentally a process of conformational transition from an inactive to an active state. A predominant form of signal transduction for bacterial sensing of environmental changes in the wild or inside their hosts is a variety of two-component systems, in which the conformational transition of a response regulator (RR) from an inactive to an active state initiates responses to the environmental changes. Here, RR activation has been investigated using RR468 as a model system by extensive unbiased all-atom molecular dynamics (MD) simulations in explicit solvent, starting from snapshots along a targeted MD trajectory that covers the conformational transition. Markov state modeling, transition path theory, and geometric analyses of the wealth of the MD data have provided a comprehensive description of the RR activation. It involves a network of metastable states, with one metastable state essentially the same as the inactive state and another very similar to the active state that are connected via a small set of intermediates. Five major pathways account for >75% of the fluxes of the conformational transition from the inactive to the active-like state. The thermodynamic stability of the states and the activation barriers between states are found, to identify rate-limiting steps. The conformal transition is initiated predominantly by movements of the β3α3 loop, followed by movements of the β4α4-loop and neighboring α4 helix region, and capped by additional movements of the β3α3 loop. A number of transient hydrophobic and hydrogen bond interactions are revealed, and they may be important for the conformational transition. PMID:25945797

  9. Resting state activity and the "stream of consciousness" in schizophrenia--neurophenomenal hypotheses.

    PubMed

    Northoff, Georg

    2015-01-01

    Schizophrenia is a multifaceted disorder with various symptoms including auditory hallucinations, egodisturbances, passivity phenomena, and delusions. Recent neurobiological approaches have focused on, especially, the abnormal contents of consciousness, the "substantive parts" as James said, to associate them with the neural mechanisms related to sensory, motor, and cognitive functions, and the brain's underlying stimulus-induced or task-evoked activity. This leaves open, however, the neural mechanisms that provide the temporal linkage or glue between the various contents, the transitive parts that makes possible the "stream of consciousness." Interestingly, schizophrenic patients seem to suffer from abnormalities specifically in the "transitive parts" when they experience contents as temporally disconnected or fragmented which in phenomenological psychiatry has been described as "temporal fragmentation." The aim of this article is to develop so-called neurophenomenal hypothesis about the direct relationship between phenomenal features of the "stream of consciousness," the "transitive parts," and the specific neuronal mechanisms in schizophrenia as based on healthy subjects. Rather than emphasizing stimulus-induced and task-evoked activity and sensory and lateral prefrontal cortical regions as in neurocognitive approaches with their focus on the "substantive parts," the focus shifts here to the brain's intrinsic activity, its resting state activity, which may account for the temporal linkage or glue between the contents of consciousness, the transitive parts. PMID:25150784

  10. An automated method to quantify microglia morphology and application to monitor activation state longitudinally in vivo.

    PubMed

    Kozlowski, Cleopatra; Weimer, Robby M

    2012-01-01

    Microglia are specialized immune cells of the brain. Upon insult, microglia initiate a cascade of cellular responses including a characteristic change in cell morphology. To study the dynamics of microglia immune response in situ, we developed an automated image analysis method that enables the quantitative assessment of microglia activation state within tissue based solely on cell morphology. Per cell morphometric analysis of fluorescently labeled microglia is achieved through local iterative threshold segmentation, which reduces errors caused by signal-to-noise variation across large volumes. We demonstrate, utilizing systemic application of lipopolysaccharide as a model of immune challenge, that several morphological parameters, including cell perimeter length, cell roundness and soma size, quantitatively distinguish resting versus activated populations of microglia within tissue comparable to traditional immunohistochemistry methods. Furthermore, we provide proof-of-concept data that monitoring soma size enables the longitudinal assessment of microglia activation in the mouse neocortex imaged via 2-photon in vivo microscopy. The ability to quantify microglia activation automatically by shape alone allows unbiased and rapid analysis of both fixed and in vivo central nervous system tissue. PMID:22457705

  11. Reversible amorphization and the catalytically active state of crystalline Co3O4 during oxygen evolution.

    PubMed

    Bergmann, Arno; Martinez-Moreno, Elias; Teschner, Detre; Chernev, Petko; Gliech, Manuel; de Araújo, Jorge Ferreira; Reier, Tobias; Dau, Holger; Strasser, Peter

    2015-01-01

    Water splitting catalysed by earth-abundant materials is pivotal for global-scale production of non-fossil fuels, yet our understanding of the active catalyst structure and reactivity is still insufficient. Here we report on the structurally reversible evolution of crystalline Co3O4 electrocatalysts during oxygen evolution reaction identified using advanced in situ X-ray techniques. At electrode potentials facilitating oxygen evolution, a sub-nanometre shell of the Co3O4 is transformed into an X-ray amorphous CoOx(OH)y which comprises di-μ-oxo-bridged Co(3+/4+) ions. Unlike irreversible amorphizations, here, the formation of the catalytically-active layer is reversed by re-crystallization upon return to non-catalytic electrode conditions. The Co3O4 material thus combines the stability advantages of a controlled, stable crystalline material with high catalytic activity, thanks to the structural flexibility of its active amorphous oxides. We propose that crystalline oxides may be tailored for generating reactive amorphous surface layers at catalytic potentials, just to return to their stable crystalline state under rest conditions. PMID:26456525

  12. Reversible amorphization and the catalytically active state of crystalline Co3O4 during oxygen evolution

    NASA Astrophysics Data System (ADS)

    Bergmann, Arno; Martinez-Moreno, Elias; Teschner, Detre; Chernev, Petko; Gliech, Manuel; de Araújo, Jorge Ferreira; Reier, Tobias; Dau, Holger; Strasser, Peter

    2015-10-01

    Water splitting catalysed by earth-abundant materials is pivotal for global-scale production of non-fossil fuels, yet our understanding of the active catalyst structure and reactivity is still insufficient. Here we report on the structurally reversible evolution of crystalline Co3O4 electrocatalysts during oxygen evolution reaction identified using advanced in situ X-ray techniques. At electrode potentials facilitating oxygen evolution, a sub-nanometre shell of the Co3O4 is transformed into an X-ray amorphous CoOx(OH)y which comprises di-μ-oxo-bridged Co3+/4+ ions. Unlike irreversible amorphizations, here, the formation of the catalytically-active layer is reversed by re-crystallization upon return to non-catalytic electrode conditions. The Co3O4 material thus combines the stability advantages of a controlled, stable crystalline material with high catalytic activity, thanks to the structural flexibility of its active amorphous oxides. We propose that crystalline oxides may be tailored for generating reactive amorphous surface layers at catalytic potentials, just to return to their stable crystalline state under rest conditions.

  13. Reversible amorphization and the catalytically active state of crystalline Co3O4 during oxygen evolution

    PubMed Central

    Bergmann, Arno; Martinez-Moreno, Elias; Teschner, Detre; Chernev, Petko; Gliech, Manuel; de Araújo, Jorge Ferreira; Reier, Tobias; Dau, Holger; Strasser, Peter

    2015-01-01

    Water splitting catalysed by earth-abundant materials is pivotal for global-scale production of non-fossil fuels, yet our understanding of the active catalyst structure and reactivity is still insufficient. Here we report on the structurally reversible evolution of crystalline Co3O4 electrocatalysts during oxygen evolution reaction identified using advanced in situ X-ray techniques. At electrode potentials facilitating oxygen evolution, a sub-nanometre shell of the Co3O4 is transformed into an X-ray amorphous CoOx(OH)y which comprises di-μ-oxo-bridged Co3+/4+ ions. Unlike irreversible amorphizations, here, the formation of the catalytically-active layer is reversed by re-crystallization upon return to non-catalytic electrode conditions. The Co3O4 material thus combines the stability advantages of a controlled, stable crystalline material with high catalytic activity, thanks to the structural flexibility of its active amorphous oxides. We propose that crystalline oxides may be tailored for generating reactive amorphous surface layers at catalytic potentials, just to return to their stable crystalline state under rest conditions. PMID:26456525

  14. Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states

    PubMed Central

    Little, Joshua W.; Ford, Amanda; Symons-Liguori, Ashley M.; Chen, Zhoumou; Janes, Kali; Doyle, Timothy; Xie, Jennifer; Luongo, Livio; Tosh, Dillip K.; Maione, Sabatino; Bannister, Kirsty; Dickenson, Anthony H.; Vanderah, Todd W.; Porreca, Frank; Jacobson, Kenneth A.

    2015-01-01

    Chronic pain is a global burden that promotes disability and unnecessary suffering. To date, efficacious treatment of chronic pain has not been achieved. Thus, new therapeutic targets are needed. Here, we demonstrate that increasing endogenous adenosine levels through selective adenosine kinase inhibition produces powerful analgesic effects in rodent models of experimental neuropathic pain through the A3 adenosine receptor (A3AR, now known as ADORA3) signalling pathway. Similar results were obtained by the administration of a novel and highly selective A3AR agonist. These effects were prevented by blockade of spinal and supraspinal A3AR, lost in A3AR knock-out mice, and independent of opioid and endocannabinoid mechanisms. A3AR activation also relieved non-evoked spontaneous pain behaviours without promoting analgesic tolerance or inherent reward. Further examination revealed that A3AR activation reduced spinal cord pain processing by decreasing the excitability of spinal wide dynamic range neurons and producing supraspinal inhibition of spinal nociception through activation of serotonergic and noradrenergic bulbospinal circuits. Critically, engaging the A3AR mechanism did not alter nociceptive thresholds in non-neuropathy animals and therefore produced selective alleviation of persistent neuropathic pain states. These studies reveal A3AR activation by adenosine as an endogenous anti-nociceptive pathway and support the development of A3AR agonists as novel therapeutics to treat chronic pain. PMID:25414036

  15. Hemodynamic low-frequency oscillation reflects resting-state neuronal activity in rodent brain

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Liu, Peng; Li, James; Pan, Yingtian; Du, Congwu

    2015-03-01

    Brain functional connectivity is mapped using spontaneous low-frequency oscillations (LFOs) in blood-oxygen-leveldependent (BOLD) signals using fMRI. However, the origin of spontaneous BOLD oscillations remains elusive. Specifically, the coupling of regional hemodynamic LFOs to neuronal activity in a resting brain is rarely examined directly. Here we present a method based on instantaneous-frequency (IF) analysis to detect regional LFOs of cerebral blood flow (CBF) along with local-field potential (LFP) changes of neurons in resting state to study neurovascular coupling. CBF and LFP were simultaneously acquired using laser Doppler flowmetry (LDF) and electroencephalography in the rat's somatosensory cortex with high temporal resolution (i.e., 20Hz for CBF and 2kHz for LDF, respectively). Instead of fast Fourier transform analysis, a peak-detection algorithm was used to define the LFP activities and CBF spontaneous oscillations in the time domain and the time lapses were used to calculate the IFs of hemodynamic (i.e., CBF) oscillations and neuronal (i.e., LFP) activities. Our results showed that the CBF mostly oscillated at ~0.1Hz with a full-half-bandwidth of [0.08Hz, 0.15Hz]. In addition, the maximal frequency of LFP firings was also approximately at 0.1Hz, which collaborated with to the frequency of CBF oscillations. Interestingly, CBF increased linearly with the LFP activity up to 0.15Hz (r=0.93), and both signals then decreased rapidly as a function of activity frequency. This indicates the spontaneous hemodynamic LFOs were associated with neuronal activities, thus confirming the neuronal origin of the hemodynamic oscillations.

  16. Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss

    PubMed Central

    Zhao, Fu; Wang, Zhenmin; Ge, Jianqiao; Zhang, Kai; Gao, Zhixian; Gao, Jia-Hong; Yang, Yihong; Fan, Jin; Zou, Qihong; Liu, Pinan

    2014-01-01

    The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting–state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network. PMID:24788317

  17. State observer-based sliding mode control for semi-active hydro-pneumatic suspension

    NASA Astrophysics Data System (ADS)

    Ren, Hongbin; Chen, Sizhong; Zhao, Yuzhuang; Liu, Gang; Yang, Lin

    2016-02-01

    This paper proposes an improved virtual reference model for semi-active suspension to coordinate the vehicle ride comfort and handling stability. The reference model combines the virtues of sky-hook with ground-hook control logic, and the hybrid coefficient is tuned according to the longitudinal and lateral acceleration so as to improve the vehicle stability especially in high-speed condition. Suspension state observer based on unscented Kalman filter is designed. A sliding mode controller (SMC) is developed to track the states of the reference model. The stability of the SMC strategy is proven by means of Lyapunov function taking into account the nonlinear damper characteristics and sprung mass variation of the vehicle. Finally, the performance of the controller is demonstrated under three typical working conditions: the random road excitation, speed bump road and sharp acceleration and braking. The simulation results indicated that, compared with the traditional passive suspension, the proposed control algorithm can offer a better coordination between vehicle ride comfort and handling stability. This approach provides a viable alternative to costlier active suspension control systems for commercial vehicles.

  18. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States

    PubMed Central

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan

    2016-01-01

    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA’s influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence—influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being. PMID:27548195

  19. Quantitative proteomics analyses of activation states of human THP-1 macrophages.

    PubMed

    Meijer, Kees; Weening, Desiree; de Vries, Marcel P; Priebe, Marion G; Vonk, Roel J; Roelofsen, Han

    2015-10-14

    Macrophages display large functional and phenotypical plasticity. They can adopt a broad range of activation states depending on their microenvironment. Various surface markers are used to characterize these differentially polarized macrophages. However, this is not informative for the functions of the macrophage. In order to have a better understanding of the functional changes of macrophages upon differential polarization, we studied differences in LPS- and IL4-stimulated macrophages. The THP-1 human monocytic cell line, was used as a model system. Cells were labeled, differentiated and stimulated with either LPS or IL-4 in a quantitative SILAC proteomics set-up. The resulting sets of proteins were functionally clustered. LPS-stimulated macrophages show increased secretion of proinflammatory peptides, leading to increased pressure on protein biosynthesis and processing. IL4-stimulated macrophages show upregulation of cell adhesion and extracellular matrix remodeling. Our approach provides an integrated view of polarization-induced functional changes and proves useful for studying functional differences between subsets of macrophages. Moreover, the identified polarization specific proteins may contribute to a better characterization of different activation states in situ and their role in various inflammatory processes. PMID:26200757

  20. Walking Associated With Public Transit: Moving Toward Increased Physical Activity in the United States

    PubMed Central

    Banerjee, Shailendra N.; Dannenberg, Andrew L.; Wendel, Arthur M.

    2013-01-01

    Objectives. We assessed changes in transit-associated walking in the United States from 2001 to 2009 and documented their importance to public health. Methods. We examined transit walk times using the National Household Travel Survey, a telephone survey administered by the US Department of Transportation to examine travel behavior in the United States. Results. People are more likely to transit walk if they are from lower income households, are non-White, and live in large urban areas with access to rail systems. Transit walkers in large urban areas with a rail system were 72% more likely to transit walk 30 minutes or more per day than were those without a rail system. From 2001 to 2009, the estimated number of transit walkers rose from 7.5 million to 9.6 million (a 28% increase); those whose transit-associated walking time was 30 minutes or more increased from approximately 2.6 million to 3.4 million (a 31% increase). Conclusions. Transit walking contributes to meeting physical activity recommendations. Study results may contribute to transportation-related health impact assessment studies evaluating the impact of proposed transit systems on physical activity, potentially influencing transportation planning decisions. PMID:23327281

  1. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States.

    PubMed

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan

    2016-01-01

    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA's influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence-influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being. PMID:27548195

  2. Microwave heating enhances antioxidant and emulsifying activities of ovalbumin glycated with glucose in solid-state.

    PubMed

    Tu, Zong-Cai; Hu, Yue-Ming; Wang, Hui; Huang, Xiao-Qin; Xia, Shi-Qi; Niu, Pei-Pei

    2015-03-01

    The aim of this study was to characterize the properties of ovalbumin (OVA) after glycated with glucose under microwave heating. For this purpose, microwave at 480 and 640 W power levels were used for heating the OVA-glucose system in solid-state for 0, 5, 10, 15, 20 and 25 min, respectively. The results indicated that the protein molecular weight was increased after glycated with glucose under microwave treatment, the pH of the system was decreased with the increase of microwave treatment power and time, while the UV absorbance, browning intensity, antioxidant activities as well as the emulsifying activity and emulsion stability of the Maillard reaction products (MRPs) were increased in according with the raise of microwave treatment power and time. The reaction time of microwave treatment is much shorter than those using traditional methods, suggesting that microwave irradiation is a novel and efficient approach to promote Maillard reaction (MR) in dry state and improve protein antioxidant and functional properties. PMID:25745213

  3. Anatomical connectivity and the resting state activity of large cortical networks

    PubMed Central

    Pinotsis, D.A.; Hansen, E.; Friston, K.J.; Jirsa, V.K.

    2013-01-01

    This paper uses mathematical modelling and simulations to explore the dynamics that emerge in large scale cortical networks, with a particular focus on the topological properties of the structural connectivity and its relationship to functional connectivity. We exploit realistic anatomical connectivity matrices (from diffusion spectrum imaging) and investigate their capacity to generate various types of resting state activity. In particular, we study emergent patterns of activity for realistic connectivity configurations together with approximations formulated in terms of neural mass or field models. We find that homogenous connectivity matrices, of the sort of assumed in certain neural field models give rise to damped spatially periodic modes, while more localised modes reflect heterogeneous coupling topologies. When simulating resting state fluctuations under realistic connectivity, we find no evidence for a spectrum of spatially periodic patterns, even when grouping together cortical nodes into communities, using graph theory. We conclude that neural field models with translationally invariant connectivity may be best applied at the mesoscopic scale and that more general models of cortical networks that embed local neural fields, may provide appropriate models of macroscopic cortical dynamics over the whole brain. PMID:23085498

  4. Preformed Soluble Chemoreceptor Trimers That Mimic Cellular Assembly States and Activate CheA Autophosphorylation

    PubMed Central

    2015-01-01

    Bacterial chemoreceptors associate with the histidine kinase CheA and coupling protein CheW to form extended membrane arrays that receive and transduce environmental signals. A receptor trimers-of-dimers resides at each vertex of the hexagonal protein lattice. CheA is fully activated and regulated when it is integrated into the receptor assembly. To mimic these states in solution, we have engineered chemoreceptor cytoplasmic kinase-control modules (KCMs) based on the Escherichia coli aspartate receptor Tar that are covalently fused and trimerized by a foldon domain (TarFO). Small-angle X-ray scattering, multi-angle light scattering, and pulsed-dipolar electron spin resonance spectroscopy of spin-labeled proteins indicate that the TarFO modules assemble into homogeneous trimers wherein the protein interaction regions closely associate at the end opposite to the foldon domains. The TarFO variants greatly increase the saturation levels of phosphorylated CheA (CheA-P), indicating that the association with a trimer of receptor dimers changes the fraction of active kinase. However, the rate constants for CheA-P formation with the Tar variants are low compared to those for autophosphorylation by free CheA, and net phosphotransfer from CheA to CheY does not increase commensurately with CheA autophosphorylation. Thus, the Tar variants facilitate slow conversion to an active form of CheA that then undergoes stable autophosphorylation and is capable of subsequent phosphotransfer to CheY. Free CheA is largely incapable of phosphorylation but contains a small active fraction. Addition of TarFO to CheA promotes a planar conformation of the regulatory domains consistent with array models for the assembly state of the ternary complex and different from that observed with a single inhibitory receptor. Introduction of TarFO into E. coli cells activates endogenous CheA to produce increased clockwise flagellar rotation, with the effects increasing in the presence of the chemotaxis

  5. Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

    NASA Astrophysics Data System (ADS)

    Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

    2002-04-01

    Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

  6. Right Frontoinsular Cortex and Subcortical Activity to Infant Cry Is Associated with Maternal Mental State Talk

    PubMed Central

    Phillips, Mary L.; Swain, James E.; Moses-Kolko, Eydie L.

    2015-01-01

    The study objective was to examine neural correlates of a specific component of human caregiving: maternal mental state talk, reflecting a mother's proclivity to attribute mental states and intentionality to her infant. Using a potent, ecologically relevant stimulus of infant cry during fMRI, we tested hypotheses that postpartum neural response to the cry of “own” versus a standard “other” infant in the right frontoinsular cortex (RFIC) and subcortical limbic network would be associated with independent observations of maternal mental state talk. The sample comprised 76 urban-living, low socioeconomic mothers (82% African American) and their 4-month-old infants. Before the fMRI scan, mothers were filmed in face-to-face interaction with their infant, and maternal behaviors were coded by trained researchers unaware of all other information about the participants. The results showed higher functional activity in the RFIC to own versus other infant cry at the group level. In addition, RFIC and bilateral subcortical neural activity (e.g., thalamus, amygdala, hippocampus, putamen) was associated positively with maternal mental state talk but not with more global aspects of observed caregiving. These findings held when accounting for perceptual and contextual covariates, such as maternal felt distress, urge to help, depression severity, and recognition of own infant cry. Our results highlight the need to focus on specific components of caregiving to advance understanding of the maternal brain. Future work will examine the predictive utility of this neural marker for mother–child function. SIGNIFICANCE STATEMENT The current study advances extant literature examining the neural underpinning of early parenting behavior. The findings highlight the special functional importance of the right frontoinsular cortex–thalamic–limbic network in a mother's proclivity to engage in mental state talk with her preverbal infant, a circumscribed aspect of maternal caregiving

  7. Global metabolite analysis of the land snail Theba pisana hemolymph during active and aestivated states.

    PubMed

    Bose, U; Centurion, E; Hodson, M P; Shaw, P N; Storey, K B; Cummins, S F

    2016-09-01

    The state of metabolic dormancy has fascinated people for hundreds of years, leading to research exploring the identity of natural molecular components that may induce and maintain this state. Many animals lower their metabolism in response to high temperatures and/or arid conditions, a phenomenon called aestivation. The biological significance for this is clear; by strongly suppressing metabolic rate to low levels, animals minimize their exposure to stressful conditions. Understanding blood or hemolymph metabolite changes that occur between active and aestivated animals can provide valuable insights relating to those molecular components that regulate hypometabolism in animals, and how they afford adaptation to their different environmental conditions. In this study, we have investigated the hemolymph metabolite composition from the land snail Theba pisana, a remarkably resilient mollusc that displays an annual aestivation period. Using LC-MS-based metabolomics analysis, we have identified those hemolymph metabolites that show significant changes in relative abundance between active and aestivated states. We show that certain metabolites, including some phospholipids [e.g. LysoPC(14:0)], and amino acids such as l-arginine and l-tyrosine, are present at high levels within aestivated snails. Further investigation of our T. pisana RNA-sequencing data elucidated the entire repertoire of phospholipid-synthesis genes in the snail digestive gland, as a precursor towards future comparative investigation between the genetic components of aestivating and non-aestivating species. In summary, we have identified a large number of metabolites that are elevated in the hemolymph of aestivating snails, supporting their role in protecting against heat or desiccation. PMID:27318654

  8. KIR channel activation contributes to onset and steady-state exercise hyperemia in humans.

    PubMed

    Crecelius, Anne R; Luckasen, Gary J; Larson, Dennis G; Dinenno, Frank A

    2014-09-01

    We tested the hypothesis that activation of inwardly rectifying potassium (KIR) channels and Na(+)-K(+)-ATPase, two pathways that lead to hyperpolarization of vascular cells, contributes to both the onset and steady-state hyperemic response to exercise. We also determined whether after inhibiting these pathways nitric oxide (NO) and prostaglandins (PGs) are involved in the hyperemic response. Forearm blood flow (FBF; Doppler ultrasound) was determined during rhythmic handgrip exercise at 10% maximal voluntary contraction for 5 min in the following conditions: control [saline; trial 1 (T1)]; with combined inhibition of KIR channels and Na(+)-K(+)-ATPase alone [via barium chloride (BaCl2) and ouabain, respectively; trial 2 (T2)]; and with additional combined nitric oxide synthase (N(G)-monomethyl-l-arginine) and cyclooxygenase inhibition [ketorolac; trial 3 (T3)]. In T2, the total hyperemic responses were attenuated ~50% from control (P < 0.05) at exercise onset, and there was minimal further effect in T3 (protocol 1; n = 11). In protocol 2 (n = 8), steady-state FBF was significantly reduced during T2 vs. T1 (133 ± 15 vs. 167 ± 17 ml/min; Δ from control: -20 ± 3%; P < 0.05) and further reduced during T3 (120 ± 15 ml/min; -29 ± 3%; P < 0.05 vs. T2). In protocol 3 (n = 8), BaCl2 alone reduced FBF during onset (~50%) and steady-state exercise (~30%) as observed in protocols 1 and 2, respectively, and addition of ouabain had no further impact. Our data implicate activation of KIR channels as a novel contributing pathway to exercise hyperemia in humans. PMID:24973385

  9. Cortical network models of impulse firing in the resting and active states predict cortical energetics.

    PubMed

    Bennett, Maxwell R; Farnell, Les; Gibson, William G; Lagopoulos, Jim

    2015-03-31

    Measurements of the cortical metabolic rate of glucose oxidation [CMR(glc(ox))] have provided a number of interesting and, in some cases, surprising observations. One is the decline in CMR(glc(ox)) during anesthesia and non-rapid eye movement (NREM) sleep, and another, the inverse relationship between the resting-state CMR(glc(ox)) and the transient following input from the thalamus. The recent establishment of a quantitative relationship between synaptic and action potential activity on the one hand and CMR(glc(ox)) on the other allows neural network models of such activity to probe for possible mechanistic explanations of these phenomena. We have carried out such investigations using cortical models consisting of networks of modules with excitatory and inhibitory neurons, each receiving excitatory inputs from outside the network in addition to intermodular connections. Modules may be taken as regions of cortical interest, the inputs from outside the network as arising from the thalamus, and the intermodular connections as long associational fibers. The model shows that the impulse frequency of different modules can differ from each other by less than 10%, consistent with the relatively uniform CMR(glc(ox)) observed across different regions of cortex. The model also shows that, if correlations of the average impulse rate between different modules decreases, there is a concomitant decrease in the average impulse rate in the modules, consistent with the observed drop in CMR(glc(ox)) in NREM sleep and under anesthesia. The model also explains why a transient thalamic input to sensory cortex gives rise to responses with amplitudes inversely dependent on the resting-state frequency, and therefore resting-state CMR(glc(ox)). PMID:25775588

  10. 12 CFR 211.29 - Applications by state branches and state agencies to conduct activities not permissible for...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... compliance with 12 CFR 346.19 (Pledge of Assets) and 12 CFR 346.20 (Asset Maintenance); (ii) That it has... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Applications by state branches and state... determined by the FDIC, pursuant to 12 CFR 362.4(c)(3)(i) through (c)(3)(ii)(A), not to present a...

  11. 12 CFR 211.29 - Applications by state branches and state agencies to conduct activities not permissible for...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... compliance with 12 CFR 346.19 (Pledge of Assets) and 12 CFR 346.20 (Asset Maintenance); (ii) That it has... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Applications by state branches and state... determined by the FDIC, pursuant to 12 CFR 362.4(c)(3)(i) through (c)(3)(ii)(A), not to present a...

  12. Glycosylation at Asn211 Regulates the Activation State of the Discoidin Domain Receptor 1 (DDR1)*

    PubMed Central

    Fu, Hsueh-Liang; Valiathan, Rajeshwari R.; Payne, Leo; Kumarasiri, Malika; Mahasenan, Kiran V.; Mobashery, Shahriar; Huang, Paul; Fridman, Rafael

    2014-01-01

    Discoidin domain receptor 1 (DDR1) belongs to a unique family of receptor tyrosine kinases that signal in response to collagens. DDR1 undergoes autophosphorylation in response to collagen binding with a slow and sustained kinetics that is unique among members of the receptor tyrosine kinase family. DDR1 dimerization precedes receptor activation suggesting a structural inhibitory mechanism to prevent unwarranted phosphorylation. However, the mechanism(s) that maintains the autoinhibitory state of the DDR1 dimers is unknown. Here, we report that N-glycosylation at the Asn211 residue plays a unique role in the control of DDR1 dimerization and autophosphorylation. Using site-directed mutagenesis, we found that mutations that disrupt the conserved 211NDS N-glycosylation motif, but not other N-glycosylation sites (Asn260, Asn371, and Asn394), result in collagen I-independent constitutive phosphorylation. Mass spectrometry revealed that the N211Q mutant undergoes phosphorylation at Tyr484, Tyr520, Tyr792, and Tyr797. The N211Q traffics to the cell surface, and its ectodomain displays collagen I binding with an affinity similar to that of the wild-type DDR1 ectodomain. However, unlike the wild-type receptor, the N211Q mutant exhibits enhanced receptor dimerization and sustained activation upon ligand withdrawal. Taken together, these data suggest that N-glycosylation at the highly conserved 211NDS motif evolved to act as a negative repressor of DDR1 phosphorylation in the absence of ligand. The presence of glycan moieties at that site may help to lock the collagen-binding domain in the inactive state and prevent unwarranted signaling by receptor dimers. These studies provide a novel insight into the structural mechanisms that regulate DDR activation. PMID:24509848

  13. Revealing the Functional States in the Active Site of BLUF Photoreceptors from Electrochromic Shift Calculations

    PubMed Central

    2014-01-01

    Photoexcitation with blue light of the flavin chromophore in BLUF photoreceptors induces a switch into a metastable signaling state that is characterized by a red-shifted absorption maximum. The red shift is due to a rearrangement in the hydrogen bond pattern around Gln63 located in the immediate proximity of the isoalloxazine ring system of the chromophore. There is a long-lasting controversy between two structural models, named Q63A and Q63J in the literature, on the local conformation of the residues Gln63 and Tyr21 in the dark state of the photoreceptor. As regards the mechanistic details of the light-activation mechanism, rotation of Gln63 is opposed by tautomerism in the Q63A and Q63J models, respectively. We provide a structure-based simulation of electrochromic shifts of the flavin chromophore in the wild type and in various site-directed mutants. The excellent overall agreement between experimental and computed data allows us to evaluate the two structural models. Compelling evidence is obtained that the Q63A model is incorrect, whereas the Q63J is fully consistent with the present computations. Finally, we confirm independently that a keto–enol tautomerization of the glutamine at position 63, which was proposed as molecular mechanism for the transition between the dark and the light-adapted state, explains the measured 10 to 15 nm red shift in flavin absorption between these two states of the protein. We believe that the accurateness of our results provides evidence that the BLUF photoreceptors absorption is fine-tuned through electrostatic interactions between the chromophore and the protein matrix, and finally that the simplicity of our theoretical model is advantageous as regards easy reproducibility and further extensions. PMID:25153778

  14. Yeast allosteric chorismate mutase is locked in the activated state by a single amino acid substitution

    SciTech Connect

    Schmidheini, T.; Moesch, H.U.; Braus, G. ); Evans, J.N.S. )

    1990-04-17

    Chorismate mutase, a branch-point enzyme in the aromatic amino acid pathway of Saccharomyces cerevisiae, and also a mutant chorismate mutase with a single amino acid substitution in the C-terminal part of the protein have been purified approximately 20-fold and 64-fold from overproducing strains, respectively. The wild-type enzyme is activated by tryptophan and subject to feedback inhibition by tyrosine, whereas the mutant enzyme does not respond to activation by tryptophan nor inhibition by tyrosine. Both enzymes are dimers consisting of two identical subunits of M{sub r} 30,000, each one capable of binding one substrate and one activator molecule. Each subunit of the wild-type enzyme also binds one inhibitor molecule, whereas the mutant enzyme lost this ability. The enzyme reaction was observed by {sup 1}H NMR and shows a direct and irreversible conversion of chorismate to prephenate without the accumulation of any enzyme-free intermediates. The kinetic data of the wild-type chorismate mutase show positive cooperativity toward the substrate with a Hill coefficient of 1.71 and a (S){sub 0.5} value of 4.0 mM. In the presence of the activator tryptophan, the cooperativity is lost. The enzyme has an (S){sub 0.5} value of 1.2 mM in the presence of 10 {mu}M tryptophan and an increased (S){sub 0.5} value of 8.6 mM in the presence of 300 {mu}M tyrosine. In the mutant enzyme, a loss of the cooperativity was observed, and (S){sub 0.5} was reduced to 1.0 mM. This enzyme is therefore locked in the activated state by a single amino acid substitution.

  15. Simulation of a Novel Active Target for Neutron-Unbound State Measurements

    NASA Astrophysics Data System (ADS)

    Frank, Nathan; MoNA Collaboration

    2013-10-01

    Measurement of nuclei at extreme ratios of protons to neutrons is challenging due to the low production rate. New facilities will increase the production of neutron-rich isotopes, but still not reach the neutron dripline for heavier nuclei. We simulated a carbon-based active target system that could be constructed to both increase statistics while preserving the experimental resolution. This simulation is an adaptation of the in-house MoNA Collaboration C + + based simulation tool to extract the decay energy of neutron-unbound states. A number of experiments of this type have been carried out at the National Superconducting Cyclotron Laboratory (NSCL). In most experiments, we produce neutron-unbound nuclei by bombarding a Beryllium target with a radioactive beam. The nucleus of interest immediately decays into a charged particle and one or more neutrons. In this simulation, we have constructed a carbon-based active target that provides a measurement of energy loss, which is used to calculate the nuclear interaction point within the target. This additional information is used to improve the resolution or preserve the resolution of a thinner target while increasing statistics. This presentation will cover some aspects of the simulation process as well as show a resolution improvement of up to about 4 with a ~700 mg/cm2 active target compared to a Be-target. The simulation utilized experimental settings from published work. Work supported by National Science Foundation Grant #0969173.

  16. Dynamic Multiscale Modes of Resting State Brain Activity Detected by Entropy Field Decomposition.

    PubMed

    Frank, Lawrence R; Galinsky, Vitaly L

    2016-09-01

    The ability of functional magnetic resonance imaging (FMRI) to noninvasively measure fluctuations in brain activity in the absence of an applied stimulus offers the possibility of discerning functional networks in the resting state of the brain. However, the reconstruction of brain networks from these signal fluctuations poses a significant challenge because they are generally nonlinear and nongaussian and can overlap in both their spatial and temporal extent. Moreover, because there is no explicit input stimulus, there is no signal model with which to compare the brain responses. A variety of techniques have been devised to address this problem, but the predominant approaches are based on the presupposition of statistical properties of complex brain signal parameters, which are unprovable but facilitate the analysis. In this article, we address this problem with a new method, entropy field decomposition, for estimating structure within spatiotemporal data. This method is based on a general information field-theoretic formulation of Bayesian probability theory incorporating prior coupling information that allows the enumeration of the most probable parameter configurations without the need for unjustified statistical assumptions. This approach facilitates the construction of brain activation modes directly from the spatial-temporal correlation structure of the data. These modes and their associated spatial-temporal correlation structure can then be used to generate space-time activity probability trajectories, called functional connectivity pathways, which provide a characterization of functional brain networks. PMID:27391678

  17. On the borders: surgeons and their activities in the Venetian State (1540-1640).

    PubMed

    Bartolini, Donatella

    2015-01-01

    Through the biographies of a dynasty of practitioners who were active in some of the mountainous villages of the Venetian Terraferma the article brings to light unknown aspects of the professional world of surgeons. Their activities were profoundly influenced by the economic and geographic peculiarities of the territory where they lived and worked. Provincial towns and their territories offered professional opportunities both to licensed and to non-university trained practitioners. However, it was generally in small villages, especially those situated in border areas and part of the main commercial networks, that surgeons preferred to establish their practices, thus supplementing the medical services supplied by the town. Normally their knowledge was largely empirical and was transmitted from father to son. The apprenticeship-based training does not appear alternative to the academic education typical of learned practitioners: much evidence points to the existence of 'scientific autodidacts', self-taught practitioners who possessed and read medical texts or had attended academic courses, even if only in part. Practising surgery in this area was a highly mobile activity, stretching from the village to the neighbouring valleys, and even to areas outside the boundaries of the city and across the border of the Venetian state. Surgeons, furthermore, were able to transfer their skills and knowledge across a range of different occupations such as shoemakers, leather workers and tailors, a fact that confirms their close ties with the local artisan milieu. PMID:25498439

  18. Theorems and Application of Local Activity of CNN with Five State Variables and One Port

    PubMed Central

    Xiong, Gang; Dong, Xisong; Xie, Li; Yang, Thomas

    2012-01-01

    Coupled nonlinear dynamical systems have been widely studied recently. However, the dynamical properties of these systems are difficult to deal with. The local activity of cellular neural network (CNN) has provided a powerful tool for studying the emergence of complex patterns in a homogeneous lattice, which is composed of coupled cells. In this paper, the analytical criteria for the local activity in reaction-diffusion CNN with five state variables and one port are presented, which consists of four theorems, including a serial of inequalities involving CNN parameters. These theorems can be used for calculating the bifurcation diagram to determine or analyze the emergence of complex dynamic patterns, such as chaos. As a case study, a reaction-diffusion CNN of hepatitis B Virus (HBV) mutation-selection model is analyzed and simulated, the bifurcation diagram is calculated. Using the diagram, numerical simulations of this CNN model provide reasonable explanations of complex mutant phenomena during therapy. Therefore, it is demonstrated that the local activity of CNN provides a practical tool for the complex dynamics study of some coupled nonlinear systems. PMID:22611440

  19. On the Borders: Surgeons and their Activities in the Venetian State (1540–1640)

    PubMed Central

    Bartolini, Donatella

    2015-01-01

    Through the biographies of a dynasty of practitioners who were active in some of the mountainous villages of the Venetian Terraferma the article brings to light unknown aspects of the professional world of surgeons. Their activities were profoundly influenced by the economic and geographic peculiarities of the territory where they lived and worked. Provincial towns and their territories offered professional opportunities both to licensed and to non-university trained practitioners. However, it was generally in small villages, especially those situated in border areas and part of the main commercial networks, that surgeons preferred to establish their practices, thus supplementing the medical services supplied by the town. Normally their knowledge was largely empirical and was transmitted from father to son. The apprenticeship-based training does not appear alternative to the academic education typical of learned practitioners: much evidence points to the existence of ‘scientific autodidacts’, self-taught practitioners who possessed and read medical texts or had attended academic courses, even if only in part. Practising surgery in this area was a highly mobile activity, stretching from the village to the neighbouring valleys, and even to areas outside the boundaries of the city and across the border of the Venetian state. Surgeons, furthermore, were able to transfer their skills and knowledge across a range of different occupations such as shoemakers, leather workers and tailors, a fact that confirms their close ties with the local artisan milieu. PMID:25498439

  20. Rho GTPase Transcriptome Analysis Reveals Oncogenic Roles for Rho GTPase-Activating Proteins in Basal-like Breast Cancers.

    PubMed

    Lawson, Campbell D; Fan, Cheng; Mitin, Natalia; Baker, Nicole M; George, Samuel D; Graham, David M; Perou, Charles M; Burridge, Keith; Der, Channing J; Rossman, Kent L

    2016-07-01

    The basal-like breast cancer (BLBC) subtype accounts for a disproportionately high percentage of overall breast cancer mortality. The current therapeutic options for BLBC need improvement; hence, elucidating signaling pathways that drive BLBC growth may identify novel targets for the development of effective therapies. Rho GTPases have previously been implicated in promoting tumor cell proliferation and metastasis. These proteins are inactivated by Rho-selective GTPase-activating proteins (RhoGAP), which have generally been presumed to act as tumor suppressors. Surprisingly, RNA-Seq analysis of the Rho GTPase signaling transcriptome revealed high expression of several RhoGAP genes in BLBC tumors, raising the possibility that these genes may be oncogenic. To evaluate this, we examined the roles of two of these RhoGAPs, ArhGAP11A (also known as MP-GAP) and RacGAP1 (also known as MgcRacGAP), in promoting BLBC. Both proteins were highly expressed in human BLBC cell lines, and knockdown of either gene resulted in significant defects in the proliferation of these cells. Knockdown of ArhGAP11A caused CDKN1B/p27-mediated arrest in the G1 phase of the cell cycle, whereas depletion of RacGAP1 inhibited growth through the combined effects of cytokinesis failure, CDKN1A/p21-mediated RB1 inhibition, and the onset of senescence. Random migration was suppressed or enhanced by the knockdown of ArhGAP11A or RacGAP1, respectively. Cell spreading and levels of GTP-bound RhoA were increased upon depletion of either RhoGAP. We have established that, via the suppression of RhoA, ArhGAP11A and RacGAP1 are both critical drivers of BLBC growth, and propose that RhoGAPs can act as oncogenes in cancer. Cancer Res; 76(13); 3826-37. ©2016 AACR. PMID:27216196

  1. Activation of the RhoB Signaling Pathway by Thyroid Hormone Receptor β in Thyroid Cancer Cells

    PubMed Central

    Ichijo, Sayaka; Furuya, Fumihiko; Shimura, Hiroki; Hayashi, Yoshitaka; Takahashi, Kazuya; Ohta, Kazuyasu; Kobayashi, Tetsuro; Kitamura, Kenichiro

    2014-01-01

    Thyroid hormone receptor (TR) mediates the crucial effects of the thyroid hormone (T3) on cellular growth, development, and differentiation. Decreased expression or inactivating somatic mutations of TRs have been found in human cancers of the liver, breast, lung, and thyroid. The mechanisms of TR-associated carcinogenesis are still not clear. To establish the function of TRβ in thyroid cancer cell proliferation, we constructed a recombinant adenovirus vector, AdTRβ, which expresses human TRβ1 cDNA. Thyroid cancer cell lines in which TRβ protein levels were significantly decreased as compared to intact thyroid tissues were infected with AdTRβ and the function of TRβ on cell proliferation and migration was analyzed. Ligand-bound TRβ induced HDAC1 and HDAC3 dissociation from, and histone acetylation associated with the RhoB promoter and enhanced the expression of RhoB mRNA and protein. In AdTRβ-infected cells, T3 and farnesyl transferase inhibitor (FTI)-treatment induced the distribution of RhoB on the cell membrane and enhanced the abundance of active GTP-bound RhoB. This RhoB protein led to p21-associated cell-cycle arrest in the G0/G1 phase, following inhibition of cell proliferation and invasion. Conversely, lowering cellular RhoB by small interfering RNA knockdown in AdTRβ-infected cells led to downregulation of p21 and inhibited cell-cycle arrest. The growth of BHP18-21v tumor xenografts in vivo was significantly inhibited by AdTRβ injection with FTIs-treatment, as compared to control virus-injected tumors. This novel signaling pathway triggered by ligand-bound TRβ provides insight into possible mechanisms of proliferation and invasion of thyroid cancer and may provide new therapeutic targets for thyroid cancers. PMID:25548921

  2. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs

    PubMed Central

    Rahman, Anisur; Lamberty, Yves; Bordet, Regis; Richardson, Jill C.; Forloni, Gianluigi; Drinkenburg, Wilhelmus; Lopez, Susanna; Aujard, Fabienne; Babiloni, Claudio; Pifferi, Fabien

    2015-01-01

    The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8–12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7–9 Hz) during passive state. During active state, there was a reduction in alpha power density (8–12 Hz) and an increase of power density at slow frequencies (1–4 Hz). Relative EMG activity was related to EEG power density at 2–4 Hz (positive correlation) and at 8–12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology. PMID:26618512

  3. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs.

    PubMed

    Infarinato, Francesco; Rahman, Anisur; Del Percio, Claudio; Lamberty, Yves; Bordet, Regis; Richardson, Jill C; Forloni, Gianluigi; Drinkenburg, Wilhelmus; Lopez, Susanna; Aujard, Fabienne; Babiloni, Claudio; Pifferi, Fabien

    2015-01-01

    The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7-9 Hz) during passive state. During active state, there was a reduction in alpha power density (8-12 Hz) and an increase of power density at slow frequencies (1-4 Hz). Relative EMG activity was related to EEG power density at 2-4 Hz (positive correlation) and at 8-12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology. PMID:26618512

  4. Selected Laws, Rules and State-Level Activities in Wisconsin Related to Acquired Immunodeficiency Syndrome. Information Memorandum 87-4.

    ERIC Educational Resources Information Center

    Sweet, Richard

    This information memorandum describes the selected laws, rules, and state-level activities in Wisconsin related to acquired immunodeficiency syndrome (AIDS) and tests for antibodies to the virus (HIV) that causes AIDS. A section on current state laws on AIDS and HIV antibody testing describes laws related to informed consent for testing,…

  5. Monitoring the Impact of Testing and Evaluation Innovations Project: State Activity and Interest Concerning Performance-Based Assessment.

    ERIC Educational Resources Information Center

    Center for Research on Evaluation, Standards, and Student Testing, Los Angeles, CA.

    Information was gathered about current state interest, activity, and concerns related to performance assessment for students. The Center for Research on Evaluation, Standards, and Student Testing of the University of California (Los Angeles) conducted telephone interviews with directors of testing in each of the 50 states in the spring of 1990.…

  6. 77 FR 64386 - Agency Information Collection Activities (Per Diem for Nursing Home Care of Veterans in State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... AFFAIRS Agency Information Collection Activities (Per Diem for Nursing Home Care of Veterans in State Homes; Per Diem for Adult Day Care of Veterans in State Homes) Under OMB Review AGENCY: Veterans Health... day health services care to Veterans. VA requires facilities providing nursing home and adult...

  7. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  8. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  9. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  10. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  11. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  12. Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

    PubMed

    Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

    2015-01-22

    Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition. PMID:25450956

  13. Abnormal Resting State fMRI Activity Predicts Processing Speed Deficits in First-Episode Psychosis

    PubMed Central

    Argyelan, Miklos; Gallego, Juan A; Robinson, Delbert G; Ikuta, Toshikazu; Sarpal, Deepak; John, Majnu; Kingsley, Peter B; Kane, John; Malhotra, Anil K; Szeszko, Philip R

    2015-01-01

    Little is known regarding the neuropsychological significance of resting state functional magnetic resonance imaging (rs-fMRI) activity early in the course of psychosis. Moreover, no studies have used different approaches for analysis of rs-fMRI activity and examined gray matter thickness in the same cohort. In this study, 41 patients experiencing a first-episode of psychosis (including N=17 who were antipsychotic drug-naive at the time of scanning) and 41 individually age- and sex-matched healthy volunteers completed rs-fMRI and structural MRI exams and neuropsychological assessments. We computed correlation matrices for 266 regions-of-interest across the brain to assess global connectivity. In addition, independent component analysis (ICA) was used to assess group differences in the expression of rs-fMRI activity within 20 predefined publicly available templates. Patients demonstrated lower overall rs-fMRI global connectivity compared with healthy volunteers without associated group differences in gray matter thickness assessed within the same regions-of-interest used in this analysis. Similarly, ICA revealed worse rs-fMRI expression scores across all 20 networks in patients compared with healthy volunteers, with posthoc analyses revealing significant (p<0.05; corrected) abnormalities within the caudate nucleus and planum temporale. Worse processing speed correlated significantly with overall lower global connectivity using the region-of-interest approach and lower expression scores within the planum temporale using ICA. Our findings implicate dysfunction in rs-fMRI activity in first-episode psychosis prior to extensive antipsychotic treatment using different analytic approaches (in the absence of concomitant gray matter structural differences) that predict processing speed. PMID:25567423

  14. Relationships Between Physical Education Students’ Motivational Profiles, Enjoyment, State Anxiety, and Self-Reported Physical Activity

    PubMed Central

    Yli-Piipari, Sami; Watt, Anthony; Jaakkola, Timo; Liukkonen, Jarmo; Nurmi, Jari-Erik

    2009-01-01

    The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000) and how these profiles are related to physical education students’ enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213) completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1) the “High motivation profile”, in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the “Low motivation profile”, in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education. Key points Two motivational profiles were revealed: 1) the “High motivation profile”, in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the “Low motivation profile”, in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first profile enjoyed physical education more and were physically more active than the students in the second profile. Moreover, the representatives of the “High motivation profile ”experienced greater anxiety toward physical education than the representatives of the “Low motivation profile” These findings raised an interesting question whether students engaging in physical education benefit more from the presence of both self-determined and non-self-determined forms of motivation, or are the benefits higher if students are primarily self-determined? PMID:24149994

  15. A high state of activity of the quasar 3C454.3

    NASA Astrophysics Data System (ADS)

    Jorstad, S.; Larionov, V.; Mokrushina, A.; Troitsky, I.; Morozova, D.

    2015-08-01

    The quasar 3c454.3 shows a new state of high activity. According to the Fermi LAT Collaboration it is brighter than 1.0e-05 ph/cm2/sec at gamma-rays: TITLE: GCN/FERMI NOTICE NOTICE_DATE: Fri 21 Aug 15 14:47:48 UT NOTICE_TYPE: Fermi-LAT Monitor SOURCE_OBJ: 3C454.3 CURR_FLUX: 1.40e-05 +- 6.09e-07 [ph/cm2/sec] BASE_FLUX: 2.60e-06 +- 4.59e-07 [ph/cm2/sec] The BU group monitors the source with the VLBA at 43 GHz.

  16. Resources for physical activity in cancer centers in the United States.

    PubMed

    Karvinen, Kristina H; Carr, Lucas J; Stevinson, Clare

    2013-12-01

    Physical activity (PA) has many benefits for cancer survivors. However, the available PA resources for survivors at cancer centers throughout the United States are undocumented. The current study surveyed major cancer centers concerning the availability and types (e.g., facilities, programs, counseling, information resources) of PA resources available. Of supportive care services, PA resources were the least commonly reported. Significant correlations were found among availability of PA resources and other supportive care services. Although many cancer centers reported offering PA programming, formal and informal PA guidance and support seem to fall on oncology nurses and other clinicians. Oncology nurses should be reminded that they may be one of the only sources of PA guidance available to survivors at cancer centers. PMID:24305494

  17. Exchange interactions of spin-active metallofullerenes in solid-state carbon networks

    NASA Astrophysics Data System (ADS)

    Zaka, Mujtaba; Warner, Jamie H.; Ito, Yasuhiro; Morton, John J. L.; Rümmeli, Mark H.; Pichler, Thomas; Ardavan, Arzhang; Shinohara, Hisanori; Briggs, G. Andrew D.

    2010-02-01

    The electron paramagnetic resonance (EPR) of spin-active metallofullerenes (MFs) La@C82 and Sc@C82 diluted in solid-state C60 crystalline matrices with molar concentrations varying from 0.4% to 100% are investigated. For dilute concentrations, the hyperfine structure of the MFs is resolved, and as the concentration increases exchange narrowing is observed leading to a single peak in the EPR. Sc@C82 MFs are inserted into single-walled carbon nanotubes to form peapods with concentrations of 10% and 0.1%, diluted with C60 . For the case of peapods containing 10% Sc@C82 a strong narrow peak is observed in X -band CW EPR, but not pulsed measurements. Peapods containing Ce@C82 MFs are prepared and these also show similar CW EPR to the Sc@C82 , indicating the peak arises from charge transfer with the SWNT.

  18. Enzyme Activities and Substrate Degradation by Fungal Isolates on Cassava Waste During Solid State Fermentation

    PubMed Central

    Eyini, M.

    2007-01-01

    The growth and bioconversion potential of selected strains growing on cassava waste substrate during solid state fermentation were assessed. Rhizopus stolonifer showed the highest and the fastest utilization of starch and cellulose in the cassava waste substrate. It showed 70% starch utilization and 81% cellulose utilization within eight days. The release of reducing sugars indicating the substrate saccharification or degradation potential of the organisms reached the highest value of 406.5 mg/g by R. stolonifer on cassava waste during the eighth day of fermentation. The protein content was gradually increased (89.4 mg/g) on the eighth day of fermentation in cassava waste by R. stolonifer. The cellulase and amylase activity is higher in R. stolonifer than A. niger and P. chrysosporium. The molecular mass of purified amylase and cellulase seemed to be 75 KDal, 85 KDal respectively. PMID:24015097

  19. generation of picosecond pulses in solid-state lasers using new active media

    SciTech Connect

    Lisitsyn, V.N.; Matrosov, V.N.; Pestryakov, E.V.; Trunov, V.I.

    1986-07-01

    Results are reported of investigations aimed at generating nanosecond radiation pulses in solid-state lasers using new active media having broad gain lines. Passive mode locking is accomplished for the first time in a BeLa:Nd/sup 3/ laser at a wavelength 1.354 microm, and in a YAG:Nd/sup 3/ laser on a 1.32-microm transition. The free lasing and mode-locking regimes were investigated in an alexandrite (BeA1/sub 2/O/sub 4/:Cr/sup 3/) laser in the 0.72-0.78-microm range and in a synchronously pumped laser on F/sub 2//sup -/ centers in LiF in the 1.12-1.24-microm region. The features of nonlinear perception of IR radiation by the eye, using a developed picosecond laser on F/sub 2//sup -/ centers, are investigated for the first time.

  20. Agreement governing the activities of states on the Moon and other celestial bodies

    NASA Technical Reports Server (NTRS)

    Gaggero, E. D.; Ripoll, R. P.

    1981-01-01

    The treaty on the Moon is not revolutionary but it embodies the legal rule for future activities of man on the Moon as opposed to the Space Treaty of 1967 which was too general. The new text is conservative but still allows some room for the developing States as in the law of the sea. The Moon is declared the "Common Heritage of Mankind" but the regime of exploitation of its resources is still blurred with imprecise guidelines still needing to be developed. The two superpowers cannot as in the past, ignore the rest of the world in the conquest of space and the fact that the U.N. is the depositary for ratifications, and not the two superpowers as in previous treaties, is the first sign of wider participation in the creation of Space Law.

  1. Validation of the activity expansion method with ultrahigh pressure shock equations of state

    NASA Astrophysics Data System (ADS)

    Rogers, Forrest J.; Young, David A.

    1997-11-01

    Laser shock experiments have recently been used to measure the equation of state (EOS) of matter in the ultrahigh pressure region between condensed matter and a weakly coupled plasma. Some ultrahigh pressure data from nuclear-generated shocks are also available. Matter at these conditions has proven very difficult to treat theoretically. The many-body activity expansion method (ACTEX) has been used for some time to calculate EOS and opacity data in this region, for use in modeling inertial confinement fusion and stellar interior plasmas. In the present work, we carry out a detailed comparison with the available experimental data in order to validate the method. The agreement is good, showing that ACTEX adequately describes strongly shocked matter.

  2. Enzyme activities and substrate degradation by fungal isolates on cassava waste during solid state fermentation.

    PubMed

    Pothiraj, C; Eyini, M

    2007-12-01

    The growth and bioconversion potential of selected strains growing on cassava waste substrate during solid state fermentation were assessed. Rhizopus stolonifer showed the highest and the fastest utilization of starch and cellulose in the cassava waste substrate. It showed 70% starch utilization and 81% cellulose utilization within eight days. The release of reducing sugars indicating the substrate saccharification or degradation potential of the organisms reached the highest value of 406.5 mg/g by R. stolonifer on cassava waste during the eighth day of fermentation. The protein content was gradually increased (89.4 mg/g) on the eighth day of fermentation in cassava waste by R. stolonifer. The cellulase and amylase activity is higher in R. stolonifer than A. niger and P. chrysosporium. The molecular mass of purified amylase and cellulase seemed to be 75 KDal, 85 KDal respectively. PMID:24015097

  3. Pneumocytes Assemble Lung Surfactant as Highly Packed/Dehydrated States with Optimal Surface Activity.

    PubMed

    Cerrada, Alejandro; Haller, Thomas; Cruz, Antonio; Pérez-Gil, Jesús

    2015-12-01

    Pulmonary surfactant (PS) is an essential complex of lipids and specific proteins synthesized in alveolar type II pneumocytes, where it is assembled and stored intracellularly as multilayered organelles known as lamellar bodies (LBs). Once secreted upon physiological stimulation, LBs maintain a densely packed structure in the form of lamellar body-like particles (LBPs), which are efficiently transferred into the alveolar air-water interface, lowering surface tension to avoid lung collapse at end-expiration. In this work, the structural organization of membranes in LBs and LBPs freshly secreted by primary cultures of rat ATII cells has been compared with that of native lung surfactant membranes isolated from porcine bronchoalveolar lavage. PS assembles in LBs as crystalline-like highly ordered structures, with a highly packed and dehydrated state, which is maintained at supraphysiological temperatures. This relatively ordered/packed state is retained in secreted LBPs. The micro- and nanostructural examination of LBPs suggests the existence of high levels of structural complexity in comparison with the material purified from lavages, which may contain partially inactivated or spent structures. Additionally, freshly secreted surfactant LBPs exhibit superior activity when generating interfacial films and a higher intrinsic resistance to inactivating agents, such as serum proteins or meconium. We propose that LBs are assembled as an energy-activated structure competent to form very efficient interfacial films, and that the organization of lipids and proteins and the properties displayed by the films formed by LBPs are likely similar to those established at the alveolar interface and represent the actual functional structure of surfactant as it sustains respiration. PMID:26636941

  4. Computational State Space Models for Activity and Intention Recognition. A Feasibility Study

    PubMed Central

    Krüger, Frank; Nyolt, Martin; Yordanova, Kristina; Hein, Albert; Kirste, Thomas

    2014-01-01

    Background Computational state space models (CSSMs) enable the knowledge-based construction of Bayesian filters for recognizing intentions and reconstructing activities of human protagonists in application domains such as smart environments, assisted living, or security. Computational, i. e., algorithmic, representations allow the construction of increasingly complex human behaviour models. However, the symbolic models used in CSSMs potentially suffer from combinatorial explosion, rendering inference intractable outside of the limited experimental settings investigated in present research. The objective of this study was to obtain data on the feasibility of CSSM-based inference in domains of realistic complexity. Methods A typical instrumental activity of daily living was used as a trial scenario. As primary sensor modality, wearable inertial measurement units were employed. The results achievable by CSSM methods were evaluated by comparison with those obtained from established training-based methods (hidden Markov models, HMMs) using Wilcoxon signed rank tests. The influence of modeling factors on CSSM performance was analyzed via repeated measures analysis of variance. Results The symbolic domain model was found to have more than states, exceeding the complexity of models considered in previous research by at least three orders of magnitude. Nevertheless, if factors and procedures governing the inference process were suitably chosen, CSSMs outperformed HMMs. Specifically, inference methods used in previous studies (particle filters) were found to perform substantially inferior in comparison to a marginal filtering procedure. Conclusions Our results suggest that the combinatorial explosion caused by rich CSSM models does not inevitably lead to intractable inference or inferior performance. This means that the potential benefits of CSSM models (knowledge-based model construction, model reusability, reduced need for training data) are available without performance

  5. Bacterial chemoreceptor dynamics correlate with activity state and are coupled over long distances

    PubMed Central

    Samanta, Dipanjan; Borbat, Peter P.; Dzikovski, Boris; Freed, Jack H.; Crane, Brian R.

    2015-01-01

    Dynamics are hypothesized to play an important role in the transmission of signals across membranes by receptors. Bacterial chemoreceptors are long helical proteins that consist of a periplasmic ligand-binding domain; a transmembrane region; a cytoplasmic HAMP (histidine kinase, adenylyl cyclases, methyl-accepting chemotaxis proteins, and phosphatases) domain; and a kinase-control module (KCM). The KCM is further composed of adaptation, hinge, and protein interaction regions (PIRs), the latter of which binds the histidine kinase CheA and adaptor CheW. Fusions of the Escherichia coli aspartate receptor KCM to HAMP domains of defined structure (H1-Tar vs. H1-2-Tar) give opposite responses in phosphotransfer and cellular assays, despite similar binding to CheA and CheW. Pulsed dipolar ESR spectroscopy (PDS) of these isolated on and off dimeric effectors reveals that, in the kinase-on state, the HAMP is more conformationally destabilized compared with the PIR, whereas in the kinase-off state, the HAMP is more compact, and the PIR samples a greater breadth of conformations. On and off HAMP states produce different conformational effects at the KCM junction, but these differences decrease through the adaptation region and into the hinge only to return with the inverted relationship in the PIR. Continuous wave–ESR of the spin-labeled proteins confirms that broader PDS distance distributions correlate with increased rates of dynamics. Conformational breadth in the adaptation region changes with charge alterations caused by modification enzymes. Activating modifications broaden the HAMP conformational ensemble but correspondingly, compact the PIR. Thus, chemoreceptors behave as coupled units, in which dynamics in regions proximal and distal to the membrane change coherently but with opposite sign. PMID:25675479

  6. Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse.

    PubMed

    Lehrmann, E; Oyler, J; Vawter, M P; Hyde, T M; Kolachana, B; Kleinman, J E; Huestis, M A; Becker, K G; Freed, W J

    2003-01-01

    CNS-focused cDNA microarrays were used to examine gene expression profiles in dorsolateral prefrontal cortex (dlPFC, Area 46) from seven individual sets of age- and post-mortem interval-matched male cocaine abusers and controls. The presence of cocaine and related metabolites was confirmed by gas chromatography-mass spectrometry. Sixty-five transcripts were differentially expressed, indicating alterations in energy metabolism, mitochondria and oligodendrocyte function, cytoskeleton and related signaling, and neuronal plasticity. There was evidence for two distinct states of transcriptional regulation, with increases in gene expression predominating in subjects testing positive for a metabolite indicative of recent 'crack' cocaine abuse and decreased expression profiles in the remaining cocaine subjects. This pattern was confirmed by quantitative polymerase chain reaction for select transcripts. These data suggest that cocaine abuse targets a distinct subset of genes in the dlPFC, resulting in either a state of acute activation in which increased gene expression predominates, or a relatively destimulated, refractory phase. PMID:12629581

  7. Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning.

    PubMed

    Nokia, Miriam S; Mikkonen, Jarno E; Penttonen, Markku; Wikgren, Jan

    2012-01-01

    Oscillations in hippocampal local-field potentials (LFPs) reflect the crucial involvement of the hippocampus in memory trace formation: theta (4-8 Hz) oscillations and ripples (~200 Hz) occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs), hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval (ITI), when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs. PMID:23316148

  8. Increasing eolian dust deposition in the western United States linked to human activity

    NASA Astrophysics Data System (ADS)

    Neff, J. C.; Ballantyne, A. P.; Farmer, G. L.; Mahowald, N. M.; Conroy, J. L.; Landry, C. C.; Overpeck, J. T.; Painter, T. H.; Lawrence, C. R.; Reynolds, R. L.

    2008-03-01

    Mineral aerosols from dust are an important influence on climate and on marine and terrestrial biogeochemical cycles. These aerosols are generated from wind erosion of surface soils. The amount of dust emission can therefore be affected by human activities that alter surface sediments. However, changes in regional- and global-scale dust fluxes following the rapid expansion of human populations and settlements over the past two centuries are not well understood. Here we determine the accumulation rates and geochemical properties of alpine lake sediments from the western interior United States for the past 5,000 years. We find that dust load levels increased by 500% above the late Holocene average following the increased western settlement of the United States during the nineteenth century. We suggest that the increased dust deposition is caused by the expansion of livestock grazing in the early twentieth century. The larger dust flux, which persists into the early twenty-first century, results in a more than fivefold increase in inputs of K, Mg, Ca, N and P to the alpine ecosystems, with implications for surface-water alkalinity, aquatic productivity and terrestrial nutrient cycling.

  9. Spontaneous brain activity following fear reminder of fear conditioning by using resting-state functional MRI

    PubMed Central

    Feng, Pan; Zheng, Yong; Feng, Tingyong

    2015-01-01

    Although disrupting reconsolidation may be a promising approach to attenuate or erase the expression of fear memory, it is not clear how the neural state following fear reminder contribute to the following fear extinction. To address this question, we used resting-state functional magnetic resonance imaging (rs-fMRI) to measure spontaneous neuronal activity and functional connectivity (RSFC) following fear reminder. Some brain regions such as dorsal anterior cingulate (dACC) and ventromedial prefrontal cortex (vmPFC) showed increased amplitude of LFF (ALFF) in the fear reminder group than the no reminder group following fear reminder. More importantly, there was much stronger functional connectivity between the amygdala and vmPFC in the fear reminder group than those in the no reminder group. These findings suggest that the strong functional connectivity between vmPFC and amygdala following a fear reminder could serve as a key role in the followed-up fear extinction stages, which may contribute to the erasing of fear memory. PMID:26576733

  10. Oscillatory brain activity in vegetative and minimally conscious state during a sentence comprehension task.

    PubMed

    Schabus, Manuel; Pelikan, Christoph; Chwala-Schlegel, Nicole; Weilhart, Katharina; Roehm, Dietmar; Donis, Johann; Michitsch, Gabriele; Pichler, Gerald; Klimesch, Wolfgang

    2011-01-01

    Patients with altered states of consciousness continue to constitute a major challenge in terms of clinical assessment, treatment and daily management. Furthermore, the exploration of brain function in severely brain-damaged patients represents a unique lesional approach to the scientific study of consciousness. Electroencephalography is one means of identifying covert behaviour in the absence of motor activity in these critically ill patients. Here we focus on a language processing task which assesses whether vegetative (n=10) and minimally conscious state patients (n=4) (vs control subjects, n=14) understand semantic information on a sentence level ("The opposite of black is... white/yellow/nice"). Results indicate that only MCS but not VS patients show differential processing of unrelated ("nice") and antonym ("white") words in the form of parietal alpha (10-12Hz) event-related synchronization and desynchronization (ERS/ERD), respectively. Controls show a more typical pattern, characterized by alpha ERD in response to unrelated words and alpha ERS in response to antonyms. PMID:21693086

  11. The protonation state of catalytic residues in the resting state of KasA revisited: detailed mechanism for the activation of KasA by its own substrate.

    PubMed

    Lee, Wook; Engels, Bernd

    2014-02-11

    Mycobacterium tuberculosis is the causative pathogen of tuberculosis, the second leading cause of death from an infectious disease globally. β-Ketoacyl ACP synthase I (KasA) is essential for the survival of M. tuberculosis, because it is one of the key enzymes in the biosynthetic pathway of mycolic acid, the building block of the cell wall in M. tuberculosis. To distinguish among the various suggested mechanisms of KasA that are based on different protonation states of the active site, we characterize its resting state by various theoretical approaches ranging from first-principle-based quantum mechanical/molecular mechanical molecular dynamics simulations (QM/MM MD) with large QM parts to force field-based MD and free energy perturbation computations. In contrast to a previous study that used less reliable semiempirical approaches in combination with smaller QM parts, our improved computations predict that the most important active site residues, Cys171 and His311, are neutral. Because the neutral catalytic residues are too unreactive to attack the substrate, the question of how their activation is achieved arises. Combining our computed results with structural information about the malonyl binding pocket, we devised a detailed model about the activation mechanism. A conformational change of Phe404 possibly triggered by the substrate is central for the activation because it switches KasA to the sufficiently reactive zwitterionic state. PMID:24479625

  12. Communication: Smoothing out excited-state dynamics: Analytical gradients for dynamically weighted complete active space self-consistent field

    SciTech Connect

    Glover, W. J.

    2014-11-07

    State averaged complete active space self-consistent field (SA-CASSCF) is a workhorse for determining the excited-state electronic structure of molecules, particularly for states with multireference character; however, the method suffers from known issues that have prevented its wider adoption. One issue is the presence of discontinuities in potential energy surfaces when a state that is not included in the state averaging crosses with one that is. In this communication I introduce a new dynamical weight with spline (DWS) scheme that mimics SA-CASSCF while removing energy discontinuities due to unweighted state crossings. In addition, analytical gradients for DWS-CASSCF (and other dynamically weighted schemes) are derived for the first time, enabling energy-conserving excited-state ab initio molecular dynamics in instances where SA-CASSCF fails.

  13. How active site protonation state influences the reactivity and ligation of the heme in chlorite dismutase

    PubMed Central

    Streit, Bennett R.; Blanc, Béatrice; Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.; DuBois, Jennifer L.

    2010-01-01

    Chlorite dismutase catalyzes O2 release from chlorite with exquisite efficiency and specificity. The spectroscopic properties, ligand binding affinities, and steady state kinetics of chlorite dismutase from Dechloromonas aromatica were examined over pH 3–11.5 to gain insight into how the protonation state of the heme environment influences dioxygen formation. An acid/base transition was observed by UV/visible and resonance Raman spectroscopy with a pKa of 8.7, 2–3 pH units below analogous transitions observed in typical His-ligated peroxidases. This transition marks the conversion of a five coordinate high spin Fe(III) to a mixed high/low spin ferric-hydroxide, as confirmed by resonance Raman (rR) spectroscopy. The two Fe–OH stretching frequencies are quite low, consistent with a weak Fe–OH bond, despite the nearly neutral imidazole side chain of the proximal histidine ligand. The hydroxide is proposed to interact strongly with a distal H-bond donor, thereby weakening the Fe–OH bond. The rR spectra of Cld-CO as a function of pH reveal two forms of the complex, one in which there is minimal interaction of distal residues with the carbonyl oxygen and another, acidic form in which the oxygen is under the influence of positive charge. Recent crystallographic data reveal arginine 183 as the lone H-bond donating residue in the distal pocket. It is likely that this Arg is the strong, positively charged H-bond donor implicated by vibrational data to interact with exogenous axial heme ligands. The same Arg in its neutral (pKa ~ 6.5) form also appears to act as the active site base in binding reactions of protonated ligands, such as HCN, to ferric Cld. The steady state profile for the rate of chlorite decomposition is characterized by these same pKas. The 5 coordinate high spin acidic Cld is more active than the alkaline hydroxide-bound form. The acid form decomposes chlorite most efficiently when the distal Arg is protonated/cationic (maximum kcat = 2.0 (±0.6)

  14. Will Global Warming Cause a Rise in Sea Level? A Simple Activity about the States of Water

    ERIC Educational Resources Information Center

    Oguz, Ayse

    2009-01-01

    In this activity, a possible problem related to global warming is clarified by the principle of states of water. The activity consists of an experiment that includes three scientific principles: Archimedes' Principle, the Law of Conservation of Matter, and the fluidity of liquids. The experiment helps students raise questions and open new horizons…

  15. A Window into Different Cultural Worlds: Young Children's Everyday Activities in the United States, Brazil, and Kenya

    ERIC Educational Resources Information Center

    Tudge, Jonathan R. H.; Doucet, Fabienne; Odero, Dolphine; Sperb, Tania M.; Piccinini, Cesar A.; Lopes, Rita S.

    2006-01-01

    A powerful means to understand young children's normative development in context is to examine their everyday activities. The daily activities of 79 children (3 years old) were observed, for 20 hr each, in their usual settings. Children were selected from 4 cultural groups: European American and African American (Greensboro, United States), Luo…

  16. Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity

    PubMed Central

    Miendlarzewska, Ewa A.; Eryilmaz, Hamdi; Vuilleumier, Patrik

    2015-01-01

    Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity. PMID:24603023

  17. Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site.

    PubMed

    Roston, Daniel; Demapan, Darren; Cui, Qiang

    2016-06-15

    A reaction's transition state (TS) structure plays a critical role in determining reactivity and has important implications for the design of catalysts, drugs, and other applications. Here, we explore TS structure in the enzyme alkaline phosphatase using hybrid Quantum Mechanics/Molecular Mechanics simulations. We find that minor perturbations to the substrate have major effects on TS structure and the way the enzyme stabilizes the TS. Substrates with good leaving groups (LGs) have little cleavage of the phosphorus-LG bond at the TS, while substrates with poor LGs have substantial cleavage of that bond. The results predict nonlinear free energy relationships for a single rate-determining step, and substantial differences in kinetic isotope effects for different substrates; both trends were observed in previous experimental studies, although the original interpretations differed from the present model. Moreover, due to different degrees of phosphorus-LG bond cleavage at the TS for different substrates, the LG is stabilized by different interactions at the TS: while a poor LG is directly stabilized by an active site zinc ion, a good LG is mainly stabilized by active site water molecules. Our results demonstrate the considerable plasticity of TS structure and stabilization in enzymes. Furthermore, perturbations to reactivity that probe TS structure experimentally (i.e., substituent effects) may substantially perturb the TS they aim to probe, and thus classical experimental approaches such as free energy relations should be interpreted with care. PMID:27186960

  18. A state feedback electro-acoustic transducer for active control of acoustic impedance

    NASA Astrophysics Data System (ADS)

    Samejima, Toshiya

    2003-03-01

    In this paper, a new control system in which the acoustic impedance of an electro-acoustic transducer diaphragm can be actively varied by modifying design parameters is presented and its effectiveness is theoretically investigated. The proposed control system is based on a state-space description of the control system derived from an electrical equivalent circuit of an electro-acoustic transducer to which a differentiating circuit is connected, and is designed using modern control theory. The optimal quadratic regulator is used in the control system design, with its quadratic performance index formulated for producing desired acoustic impedance. Computer simulations indicate that the acoustic impedance of the diaphragm can be significantly varied over a wide frequency range that includes the range below the resonance frequency of the electro-acoustic transducer. A computer model of the proposed control system is used to illustrate its application to semi-active noise control in a duct. It is demonstrated that the proposed control system provides substantial reductions in the noise radiating from the outlet of the duct, both in the stiffness control range and in the mass control range.

  19. Rates of intra- and intermolecular electron transfers in hydrogenase deduced from steady-state activity measurements.

    PubMed

    Dementin, Sébastien; Burlat, Bénédicte; Fourmond, Vincent; Leroux, Fanny; Liebgott, Pierre-Pol; Abou Hamdan, Abbas; Léger, Christophe; Rousset, Marc; Guigliarelli, Bruno; Bertrand, Patrick

    2011-07-01

    Electrons are transferred over long distances along chains of FeS clusters in hydrogenases, mitochondrial complexes, and many other respiratory enzymes. It is usually presumed that electron transfer is fast in these systems, despite the fact that there has been no direct measurement of rates of FeS-to-FeS electron transfer in any respiratory enzyme. In this context, we propose and apply to NiFe hydrogenase an original strategy that consists of quantitatively interpreting the variations of steady-state activity that result from changing the nature of the FeS clusters which connect the active site to the redox partner, and/or the nature of the redox partner. Rates of intra- and intermolecular electron transfer are deduced from such large data sets. The mutation-induced variations of electron transfer rates cannot be explained by changes in intercenter distances and reduction potentials. This establishes that FeS-to-FeS rate constants are extremely sensitive to the nature and coordination of the centers. PMID:21615141

  20. In vitro antimalarial activity of six Aspidosperma species from the state of Minas Gerais (Brazil).

    PubMed

    Dolabela, Maria Fâni; Oliveira, Salma G; Peres, José M; Nascimento, José M S; Póvoa, Marinete M; Oliveira, Alaide B

    2012-12-01

    Ethnomedicinal informations point to some Aspidosperma species (Apocynaceae) as antimalarial plants in Brazil and have motivated the evaluation of six species which were collected in the state of Minas Gerais: A. cylindrocarpon Müll. Arg., A. parvifolium A. DC., A. olivaceum Müll. Arg., A. ramiflorum Müll. Arg., A. spruceanum Benth. ex Müll. Arg. and A. tomentosum Mart.. A total of 23 extracts of different plant parts in different solvents were assayed in vitro against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. All the extracts were shown to be active with IC50 values in the range of 5.0 ± 0 2.8 µg/mL to 65.0 ± 4.2 µg/mL. TLC profile of the extracts revealed the presence of alkaloids in the six species assayed. These results seem to confirm the popular use of Aspidosperma species to treat human malaria in Brazil and seem point to alkaloids as the putative active compounds of the assayed species. PMID:23207699

  1. Improved solid-state NMR quantifications of active principles in pharmaceutical formulations.

    PubMed

    Sanchez, Stéphanie; Ziarelli, Fabio; Viel, Stéphane; Delaurent, Corinne; Caldarelli, Stefano

    2008-08-01

    The facility of implementation reached by solid-state nuclear magnetic resonance (ssNMR) spectroscopy makes this technique increasingly popular in pharmaceutical sciences, and more specifically for the dosage of active principles in pharmaceutical formulations, since about 80% of the formulations currently available on the market are present in the solid form. In this case, analysis by MAS NMR allows faster and simplified protocols, as a solubilization step is not required. However, the specificity of the ssNMR experiments should be explicitly taken into account when designing an accurate measurement procedure. In this work we show that, by using a combination of external concentration referencing and a properly designed sample preparation optimized for quantitative determinations, quantification of active principles in pharmaceutical formulations can be performed with both speed and precision. The method is illustrated by reinvestigating the dosage of Meprobamate, an anxiolytic agent typically prescribed in case of anxiety or muscular soreness, present in a commercial formulation (Equanil). Specifically, with respect to previously proposed analytical protocols, the procedure outlined here allows fast quantification with excellent precision. PMID:18479881

  2. What makes the dorsomedial frontal cortex active during reading the mental states of others?

    PubMed

    Isoda, Masaki; Noritake, Atsushi

    2013-01-01

    The dorsomedial frontal part of the cerebral cortex is consistently activated when people read the mental states of others, such as their beliefs, desires, and intentions, the ability known as having a theory of mind (ToM) or mentalizing. This ubiquitous finding has led many researchers to conclude that the dorsomedial frontal cortex (DMFC) constitutes a core component in mentalizing networks. Despite this, it remains unclear why the DMFC becomes active during ToM tasks. We argue that key psychological and behavioral aspects in mentalizing are closely associated with DMFC functions. These include executive inhibition, distinction between self and others, prediction under uncertainty, and perception of intentions, all of which are important for predicting others' intention and behavior. We review the literature supporting this claim, ranging in fields from developmental psychology to human neuroimaging and macaque electrophysiology. Because perceiving intentions in others' actions initiates mentalizing and forms the basis of virtually all types of social interaction, the fundamental issue in social neuroscience is to determine the aspects of physical entities that make an observer perceive that they are intentional beings and to clarify the neurobiological underpinnings of the perception of intentionality in others' actions. PMID:24367287

  3. Robust system state estimation for active suspension control in high-speed tilting trains

    NASA Astrophysics Data System (ADS)

    Zhou, Ronghui; Zolotas, Argyrios; Goodall, Roger

    2014-05-01

    The interaction between the railway vehicle body roll and lateral dynamics substantially influences the tilting system performance in high-speed tilting trains, which results in a potential poor ride comfort and high risk of motion sickness. Integrating active lateral secondary suspension into the tilting control system is one of the solutions to provide a remedy to roll-lateral interaction. It improves the design trade-off for the local tilt control (based only upon local vehicle measurements) between straight track ride comfort and curving performance. Advanced system state estimation technology can be applied to further enhance the system performance, i.e. by using the estimated vehicle body lateral acceleration (relative to the track) and true cant deficiency in the configuration of the tilt and lateral active suspension controllers, thus to further attenuate the system dynamics coupling. Robust H∞ filtering is investigated in this paper aiming to offer a robust estimation (i.e. estimation in the presence of uncertainty) for the required variables, In particular, it can minimise the maximum estimation error and thus be more robust to system parametric uncertainty. Simulation results illustrate the effectiveness of the proposed schemes.

  4. The Effect of Cellulose Crystal Structure and Solid-State Morphology on the Activity of Cellulases

    SciTech Connect

    Stipanovic, Arthur J

    2014-11-17

    Consistent with the US-DOE and USDA “Roadmap” objective of producing ethanol and chemicals from cellulosic feedstocks more efficiently, a three year research project entitled “The Effect of Cellulose Crystal Structure and Solid-State Morphology on the Activity of Cellulases” was initiated in early 2003 under DOE sponsorship (Project Number DE-FG02-02ER15356). A three year continuation was awarded in June 2005 for the period September 15, 2005 through September 14, 2008. The original goal of this project was to determine the effect of cellulose crystal structure, including allomorphic crystalline form (Cellulose I, II, III, IV and sub-allomorphs), relative degree of crystallinity and crystallite size, on the activity of different types of genetically engineered cellulase enzymes to provide insight into the mechanism and kinetics of cellulose digestion by “pure” enzymes rather than complex mixtures. We expected that such information would ultimately help enhance the accessibility of cellulose to enzymatic conversion processes thereby creating a more cost-effective commercial process yielding sugars for fermentation into ethanol and other chemical products. Perhaps the most significant finding of the initial project phase was that conversion of native bacterial cellulose (Cellulose I; BC-I) to the Cellulose II (BC-II) crystal form by aqueous NaOH “pretreatment” provided an increase in cellulase conversion rate approaching 2-4 fold depending on enzyme concentration and temperature, even when initial % crystallinity values were similar for both allomorphs.

  5. Active Surveillance for Influenza A Virus among Swine, Midwestern United States, 2009–2011

    PubMed Central

    Corzo, Cesar A.; Juleen, Kevin; Stigger-Rosser, Evelyn; Ducatez, Mariette F.; Webby, Richard J.; Lowe, James F.

    2013-01-01

    Veterinary diagnostic laboratories identify and characterize influenza A viruses primarily through passive surveillance. However, additional surveillance programs are needed. To meet this need, an active surveillance program was conducted at pig farms throughout the midwestern United States. From June 2009 through December 2011, nasal swab samples were collected monthly from among 540 groups of growing pigs and tested for influenza A virus by real-time reverse transcription PCR. Of 16,170 samples, 746 were positive for influenza A virus; of these, 18.0% were subtype H1N1, 16.0% H1N2, 7.6% H3N2, and 14.5% (H1N1)pdm09. An influenza (H3N2) and (H1N1)pdm09 virus were identified simultaneously in 8 groups. This active influenza A virus surveillance program provided quality data and increased the understanding of the current situation of circulating viruses in the midwestern US pig population. PMID:23735740

  6. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    PubMed Central

    Chen, Yu-Chen; Zhang, Jian; Li, Xiao-Wei; Xia, Wenqing; Feng, Xu; Gao, Bo; Ju, Sheng-Hong; Wang, Jian; Salvi, Richard; Teng, Gao-Jun

    2014-01-01

    Objective The neural mechanisms that give rise to the phantom sound of tinnitus are poorly understood. This study aims to investigate whether aberrant spontaneous brain activity exists in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI) technique. Materials and methods A total of 31 patients with chronic tinnitus patients and 32 healthy age-, sex-, and education-matched healthy controls were prospectively examined. Both groups had normal hearing thresholds. We calculated the amplitude of low-frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between fMRI information and clinical data of tinnitus. Results Compared with healthy controls, we observed significant increased ALFF within several selected regions including the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular gyrus; decreased ALFF was detected in the left cuneus, right middle occipital gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively with increased ALFF in right MTG and right SFG; tinnitus duration correlated positively with higher ALFF values in right SFG. Conclusions The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients. PMID:25379434

  7. Spatiotemporal psychopathology I: No rest for the brain's resting state activity in depression? Spatiotemporal psychopathology of depressive symptoms.

    PubMed

    Northoff, Georg

    2016-01-15

    Despite intense neurobiological investigation in psychiatric disorders like major depressive disorder (MDD), the basic disturbance that underlies the psychopathological symptoms of MDD remains, nevertheless, unclear. Neuroimaging has focused mainly on the brain's extrinsic activity, specifically task-evoked or stimulus-induced activity, as related to the various sensorimotor, affective, cognitive, and social functions. Recently, the focus has shifted to the brain's intrinsic activity, otherwise known as its resting state activity. While various abnormalities have been observed during this activity, their meaning and significance for depression, along with its various psychopathological symptoms, are yet to be defined. Based on findings in healthy brain resting state activity and its particular spatial and temporal structure - defined in a functional and physiological sense rather than anatomical and structural - I claim that the various depressive symptoms are spatiotemporal disturbances of the resting state activity and its spatiotemporal structure. This is supported by recent findings that link ruminations and increased self-focus in depression to abnormal spatial organization of resting state activity. Analogously, affective and cognitive symptoms like anhedonia, suicidal ideation, and thought disorder can be traced to an increased focus on the past, increased past-focus as basic temporal disturbance o the resting state. Based on these findings, I conclude that the various depressive symptoms must be conceived as spatiotemporal disturbances of the brain's resting state's activity and its spatiotemporal structure. Importantly, this entails a new form of psychopathology, "Spatiotemporal Psychopathology" that directly links the brain and psyche, therefore having major diagnostic and therapeutic implications for clinical practice. PMID:26048657

  8. An active state of the BL Lacertae object Markarian 421 detected by INTEGRAL in April 2013

    NASA Astrophysics Data System (ADS)

    Pian, E.; Türler, M.; Fiocchi, M.; Boissay, R.; Bazzano, A.; Foschini, L.; Tavecchio, F.; Bianchin, V.; Castignani, G.; Ferrigno, C.; Raiteri, C. M.; Villata, M.; Beckmann, V.; D'Ammando, F.; Hudec, R.; Malaguti, G.; Maraschi, L.; Pursimo, T.; Romano, P.; Soldi, S.; Stamerra, A.; Treves, A.; Ubertini, P.; Vercellone, S.; Walter, R.

    2014-10-01

    Aims: Multiwavelength variability of blazars offers indirect, but very effective, insight into their powerful engines and on the mechanisms through which energy is propagated from the centre down the jet. The BL Lac object Mkn 421 is a TeV emitter, a bright blazar at all wavelengths, and therefore an excellent target for variability studies. Methods: We activated INTEGRAL observations of Mkn 421 in an active state on 16-21 April 2013, and complemented them with Fermi-LAT data. Results: We obtained well sampled optical, soft, and hard X-ray light curves that show the presence of two flares and time-resolved spectra in the 3.5-60 keV (JEM-X and IBIS/ISGRI) and 0.1-100 GeV (Fermi-LAT) ranges. The average flux in the 20-100 keV range is 9.1 × 10-11 erg s-1 cm-2 (~4.5 mCrab) and the nuclear average apparent magnitude, corrected for Galactic extinction, is V ≃ 12.2. In the time-resolved X-ray spectra, which are described by broken power laws and, marginally better, by log-parabolic laws, we see a hardening that correlates with flux increase, as expected in refreshed energy injections in a population of electrons that later cool via synchrotron radiation. The hardness ratios between the JEM-X fluxes in two different bands and between the JEM-X and IBIS/ISGRI fluxes confirm this trend. During the observation, the variability level increases monotonically from the optical to the hard X-rays, while the large LAT errors do not allow a significant assessment of the MeV-GeV variability. The cross-correlation analysis during the onset of the most prominent flare suggests a monotonically increasing delay of the lower frequency emission with respect to that at higher frequency, with a maximum time-lag of about 70 min, that is however not well constrained. The spectral energy distributions from the optical to the TeV domain were compared to homogeneous models of blazar emission based on synchrotron radiation and synchrotron self-Compton scattering. They represent a satisfactory

  9. Enhancement of wheat grain antioxidant activity by solid state fermentation with Grifola spp.

    PubMed

    Postemsky, Pablo; Curvetto, Néstor

    2014-05-01

    Grifola frondosa, Grifola gargal, and Grifola sordulenta are edible and medicinal mushrooms with antioxidant properties. To obtain wheat flour (Wf ) with a higher antioxidant activity than the one exhibited by regular Wf, solid state fermentation (SSF) of wheat grains with mycelia of those Grifola spp. was used to obtain biotransformed wheat grain (BWG) flour. The methanolic extract of control Wf and BWG flour of G. gargal, G. sordulenta, and G. frondosa (GfWG, GgWG, and GsWG, respectively) were studied for their radical scavenging (RS) activity against 2,2-diphenyl-1-picrylhydracyl (DPPH) and their Fe(III) reducing power (RP). The values for RS-EC50 decreased in BWG flour, therefore presenting a higher antioxidant activity: GgWG (0.56 mg/mL), GfWG (0.81 mg/mL), and GsWG (5.80 mg/mL) in comparison to Wf (57.60 mg/mL). The antioxidant content for this RS activity in terms of ascorbic acid content (RS-EQAA) was highest in GfWG, followed by GgWG and GsWG (71.73, 14.46, and 3.02 mg/g, respectively) and lowest in Wf (0.25 mg/g). The RP-EC50 values in GgWG, GfWG, and GsWG were low (0.55, 0.64, and 4.20 mg/mL, respectively) with respect to Wf (55.00 mg/mL). Compared with Wf (0.56 mg/g), the RP capacity in terms of ascorbic acid content (RP-EQAA) was very high in GfWG (193.67 mg/g) followed by GgWG and GsWG (31.42 and 8.74 mg/g, respectively). The high content in gallic acid equivalents was consistent with RS-EQ(AA) and RP-EQ(AA) contents. TLC revealed that antioxidant activity in BWG could be related to the presence of phenolic compounds. Thus, a valuable food alternative can easily be obtained with wheat grains, that is, by markedly increasing their antioxidant value through SSF with Grifola spp. PMID:24552201

  10. Effect of Hinoki and Meniki Essential Oils on Human Autonomic Nervous System Activity and Mood States.

    PubMed

    Chen, Chi-Jung; Kumar, K J Senthil; Chen, Yu-Ting; Tsao, Nai-Wen; Chien, Shih-Chang; Chang, Shang-Tzen; Chu, Fang-Hua; Wang, Sheng-Yang

    2015-07-01

    Meniki (Chamecyparis formosensis) and Hinoki (C. obtusa) are precious conifers with excellent wood properties and distinctive fragrances that make these species popular in Taiwan for construction, interiors and furniture. In the present study, the compositions of essential oils prepared from Meniki and Hinoki were analyzed by gas chromatography-mass spectrometry (GC/MS). Thirty-six compounds were identified from the wood essential oil of Meniki, including Δ-cadinene, γ-cadinene, Δ-cadinol, α-muurolene, calamenene, linalyl acetate and myrtenol; 29 compounds were identified from Hinoki, including α-terpineol, α-pinene, Δ-cadinene, borneol, terpinolene, and limonene. Next, we examined the effect of Meniki and Hinoki essential oils on human autonomic nervous system activity. Sixteen healthy adults received Meniki or Hinoki by inhalation for 5 min, and the physiological and psychological effects were examined. After inhaling Meniki essential oil, participant's systolic blood pressure and heart rate (HR) were decreased, and diastolic blood pressure increased. In addition, sympathetic nervous activity (SNS) was significantly decreased, and parasympathetic activity (PSNS) was significantly increased. On the other hand, after inhaling Hinoki essential oil, systolic blood pressure, heart rate and PSNS were decreased, whereas SNA was increased. Indeed, both Meniki and Hinoki essential oils increased heart rate variability (HRV) in tested adults. Furthermore, in the Profile of Mood States (POMS) test, both Meniki and Hinoki wood essential oils stimulated a pleasant mood status. Our results strongly suggest that Meniki and Hinoki essential oils could be suitable agents for the development of regulators of sympathetic nervous system dysfunctions. PMID:26411036

  11. High-Resolution Seismic Reflection Studies of Active Faults: a Case Study from Washington State

    NASA Astrophysics Data System (ADS)

    Liberty, L. M.; Pratt, T. L.

    2007-12-01

    In the past five years, new high-resolution seismic surveys have filled in gaps in our understanding of active structures beneath the Puget Lowland region of Washington State. The extensive forests have made recognition of active faults difficult, but new Light Distance and Ranging (LIDAR) detailed topographic data have made a major breakthrough in mapping active faults. Extensive regional and high-resolution marine seismic surveys have been fundamental to understanding the tectonic framework of the area. These marine profiles, however, lack coverage beneath water bodies that large ships cannot navigate and beneath city streets underlain by late Pleistocene glacial deposits that are missing from the waterways. Recent land surveys and profiles in restricted waterways can therefore bridge the gap between paleoseismic and marine geophysical studies, and test elements of models proposed by regional-scale geophysical studies. We have also been venturing into more congested areas to seismically image faults in key urban locations. Results from recent surveys have: 1) documented new faults that had long been suspected in the Olympia area; 2) clarified the relationship between the LIDAR scarps and observed structures across the Tacoma fault zone; 3) provided a window into structures beneath the north and eastern portions of the western Tacoma fault zone; 4) documented deformation along the Seattle fault near a paleoseismic trench; 5) mapped the eastern part the Seattle fault zone beyond its previously mapped limits; and 6) documented multiple fault strands in the Seattle fault zone in the cities of Bellevue and Seattle. The results better constrain interpretations of paleoseismic data collected on these faults, and provide targets for future paleoseismic studies.

  12. Altered Resting-State Brain Activity and Connectivity in Depressed Parkinson's Disease.

    PubMed

    Hu, Xiao; Song, Xiaopeng; Li, Erfeng; Liu, Jiajia; Yuan, Yonggui; Liu, Weiguo; Liu, Yijun

    2015-01-01

    Depressive symptoms are common in Parkinson's disease (PD), but the neurophysiological mechanisms of depression in PD are poorly understood. The current study attempted to examine disrupted spontaneous local brain activities and functional connectivities that underlie the depression in PD. We recruited a total of 20 depressed PD patients (DPD), 40 non-depressed PD patients (NDPD) and 43 matched healthy controls (HC). All the subjects underwent neuropsychological tests and resting-state fMRI scanning. The between-group differences in the amplitude of low frequency fluctuations (ALFF) of BOLD signals were examined using post-hoc tests after the analysis of covariance. Compared with the NDPD and HC, the DPD group showed significantly increased ALFF in the left median cingulated cortex (MCC). The functional connectivity (FC) between left MCC and all the other voxels in the brain were then calculated. Compared with the HC and NDPD group, the DPD patients showed stronger FC between the left MCC and some of the major nodes of the default mode network (DMN), including the post cingulated cortex/precuneus, medial prefrontal cortex, inferior frontal gyrus, and cerebellum. Correlation analysis revealed that both the ALFF values in the left MCC and the FC between the left MCC and the nodes of DMN were significantly correlated with the Hamilton Depression Rating Scale score. Moreover, higher local activities in the left MCC were associated with increased functional connections between the MCC and the nodes of DMN in PD. These abnormal activities and connectivities of the limbic-cortical circuit may indicate impaired high-order cortical control or uncontrol of negative mood in DPD, which suggested a possible neural mechanism of the depression in PD. PMID:26147571

  13. Oil and gas technology transfer activities and potential in eight major producing states. Volume 1

    SciTech Connect

    Not Available

    1993-07-01

    In 1990, the Interstate Oil and Gas Compact Commission (the Compact) performed a study that identified the structure and deficiencies of the system by which oil and gas producers receive information about the potential of new technologies and communicate their problems and technology needs back to the research community. The conclusions of that work were that major integrated companies have significantly more and better sources of technology information than independent producers. The majors also have significantly better mechanisms for communicating problems to the research and development (R&D) community. As a consequence, the Compact recommended analyzing potential mechanisms to improve technology transfer channels for independents and to accelerate independents acceptance and use of existing and emerging technologies. Building on this work, the Compact, with a grant from the US Department Energy, has reviewed specific technology transfer organizations in each of eight major oil producing states to identify specific R&D and technology transfer organizations, characterize their existing activities, and identify potential future activities that could be performed to enhance technology transfer to oil and gas producers. The profiles were developed based on information received from organizations,follow-up interviews, site visit and conversations, and participation in their sponsored technology transfer activities. The results of this effort are reported in this volume. In addition, the Compact has also developed a framework for the development of evaluation methodologies to determine the effectiveness of technology transfer programs in performing their intended functions and in achieving desired impacts impacts in the producing community. The results of that work are provided in a separate volume.

  14. Pausing and activating thread state upon pin assertion by external logic monitoring polling loop exit time condition

    DOEpatents

    Chen, Dong; Giampapa, Mark; Heidelberger, Philip; Ohmacht, Martin; Satterfield, David L; Steinmacher-Burow, Burkhard; Sugavanam, Krishnan

    2013-05-21

    A system and method for enhancing performance of a computer which includes a computer system including a data storage device. The computer system includes a program stored in the data storage device and steps of the program are executed by a processer. The processor processes instructions from the program. A wait state in the processor waits for receiving specified data. A thread in the processor has a pause state wherein the processor waits for specified data. A pin in the processor initiates a return to an active state from the pause state for the thread. A logic circuit is external to the processor, and the logic circuit is configured to detect a specified condition. The pin initiates a return to the active state of the thread when the specified condition is detected using the logic circuit.

  15. Relationship between the tonic elevator mandibular activity and the vertical dimension during the states of vigilance and hypnosis.

    PubMed

    Manns, A; Zuazola, R V; Sirhan, R M; Quiroz, M; Rocabado, M

    1990-04-01

    The variation of the tonic EMG elevator mandibular activity was studied as well as the consequent variation of the vertical dimension in two different experimental states: those of vigilance and hypnosis. In the state of vigilance, normal values of tonic EMG activity were recorded and a space of inocclusion (X = 2.22 mm) coincident with the postural mandibular position. Under hypnosis a significant reduction of the tonic EMG activity was observed (43 to 50%), together with a great increase of the inocclusion space (X = 8.90 mm). PMID:2073696

  16. 34 CFR 403.70 - How must funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....180(b)(3) to conduct programs, projects, services, and activities that include— (a) Professional... students, including corrections educators and counselors and educators and counselors in community-based..., including integration of vocational and academic curricula, with particular emphasis on training of...

  17. Dynamical state of the network determines the efficacy of single neuron properties in shaping the network activity

    PubMed Central

    Sahasranamam, Ajith; Vlachos, Ioannis; Aertsen, Ad; Kumar, Arvind

    2016-01-01

    Spike patterns are among the most common electrophysiological descriptors of neuron types. Surprisingly, it is not clear how the diversity in firing patterns of the neurons in a network affects its activity dynamics. Here, we introduce the state-dependent stochastic bursting neuron model allowing for a change in its firing patterns independent of changes in its input-output firing rate relationship. Using this model, we show that the effect of single neuron spiking on the network dynamics is contingent on the network activity state. While spike bursting can both generate and disrupt oscillations, these patterns are ineffective in large regions of the network state space in changing the network activity qualitatively. Finally, we show that when single-neuron properties are made dependent on the population activity, a hysteresis like dynamics emerges. This novel phenomenon has important implications for determining the network response to time-varying inputs and for the network sensitivity at different operating points. PMID:27212008

  18. Dynamical state of the network determines the efficacy of single neuron properties in shaping the network activity.

    PubMed

    Sahasranamam, Ajith; Vlachos, Ioannis; Aertsen, Ad; Kumar, Arvind

    2016-01-01

    Spike patterns are among the most common electrophysiological descriptors of neuron types. Surprisingly, it is not clear how the diversity in firing patterns of the neurons in a network affects its activity dynamics. Here, we introduce the state-dependent stochastic bursting neuron model allowing for a change in its firing patterns independent of changes in its input-output firing rate relationship. Using this model, we show that the effect of single neuron spiking on the network dynamics is contingent on the network activity state. While spike bursting can both generate and disrupt oscillations, these patterns are ineffective in large regions of the network state space in changing the network activity qualitatively. Finally, we show that when single-neuron properties are made dependent on the population activity, a hysteresis like dynamics emerges. This novel phenomenon has important implications for determining the network response to time-varying inputs and for the network sensitivity at different operating points. PMID:27212008

  19. Aerosol mixing-state, hygroscopic growth and cloud activation efficiency during MIRAGE 2006

    NASA Astrophysics Data System (ADS)

    Lance, S.; Raatikainen, T.; Onasch, T.; Worsnop, D. R.; Yu, X.-Y.; Alexander, M. L.; Stolzenburg, M. R.; McMurry, P. H.; Smith, J. N.; Nenes, A.

    2012-06-01

    Observations of aerosol hygroscopic growth and CCN activation spectra for submicron particles are reported for the T1 ground site outside of Mexico City during the MIRAGE 2006 campaign. κ-Köhler theory is used to evaluate the characteristic water uptake coefficient, κ*, for the CCN active aerosol population using both size-resolved HTDMA and size-resolved CCNc measurements. Organic mass fractions, forg, are evaluated from size-resolved aerosol mass spectrometer (AMS) measurements, from which κAMS is inferred and compared against κ*. Strong diurnal profiles of aerosol water uptake parameters and aerosol composition are observed. We find that new particle formation (NPF) events are correlated with an increased κ* and CCN-active fraction during the daytime, with greater impact on smaller particles. During NPF events, the number concentration of 40 nm particles acting as CCN can surpass by more than a factor of two the concentrations of 100 nm particles acting as CCN, at supersaturations of 0.51% ± 0.06%. We also find that at 06:00-08:00 in the morning throughout the campaign, fresh traffic emissions result in substantial changes to the chemical distribution of the aerosol, with on average 65% externally-mixed fraction for 40 nm particles and 30% externally-mixed fraction for 100 nm particles, whereas at midday nearly all particles of both sizes can be described as internally-mixed. Average activation spectra and growth factor distributions are analyzed for different time periods characterizing the daytime (with and without NPF events), the early morning "rush hour", and the entire campaign. We show that κ* derived from CCNc measurements decreases as a function of size during all time periods, while the CCN-active fraction increases as a function of size. Size-resolved AMS measurements do not predict the observed trend for κ* versus particle size, which can be attributed to unresolved mixing-state and the presence of refractory material not measured by the AMS

  20. 76 FR 44904 - Agency Information Collection Activities; Proposed Collection; Comment Request; State Water...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-27

    ... Quality Program Management Resource Analysis; EPA ICR No. 2433.01 AGENCY: Environmental Protection Agency... are state governments. Title: State Water Quality Program Management Resource Analysis. ICR numbers... with states, is conducting the State Water Quality Program Management Resource Analysis to...

  1. Update on 2005-06 State Financial Aid Program Activity and 2006-07 Estimates

    ERIC Educational Resources Information Center

    Washington Higher Education Coordinating Board, 2006

    2006-01-01

    The state of Washington is committed to higher education opportunity for all students, regardless of income, through its state financial aid programs. The purpose of this report is to provide the members of the Higher Education Coordinating Board (HECB) with an overview of state and federal financial aid in Washington, an update on state financial…

  2. Control of Polarized Growth by the Rho Family GTPase Rho4 in Budding Yeast: Requirement of the N-Terminal Extension of Rho4 and Regulation by the Rho GTPase-Activating Protein Bem2

    PubMed Central

    Gong, Ting; Liao, Yuan; He, Fei; Yang, Yang; Yang, Dan-Dan; Chen, Xiang-Dong

    2013-01-01

    In the budding yeast Saccharomyces cerevisiae, Rho4 GTPase partially plays a redundant role with Rho3 in the control of polarized growth, as deletion of RHO4 and RHO3 together, but not RHO4 alone, caused lethality and a loss of cell polarity at 30°C. Here, we show that overexpression of the constitutively active rho4Q131L mutant in an rdi1Δ strain caused a severe growth defect and generated large, round, unbudded cells, suggesting that an excess of Rho4 activity could block bud emergence. We also generated four temperature-sensitive rho4-Ts alleles in a rho3Δ rho4Δ strain. These mutants showed growth and morphological defects at 37°C. Interestingly, two rho4-Ts alleles contain mutations that cause amino acid substitutions in the N-terminal region of Rho4. Rho4 possesses a long N-terminal extension that is unique among the six Rho GTPases in the budding yeast but is common in Rho4 homologs in other yeasts and filamentous fungi. We show that the N-terminal extension plays an important role in Rho4 function since rho3Δ rho4Δ61 cells expressing truncated Rho4 lacking amino acids (aa) 1 to 61 exhibited morphological defects at 24°C and a growth defect at 37°C. Furthermore, we show that Rho4 interacts with Bem2, a Rho GTPase-activating protein (RhoGAP) for Cdc42 and Rho1, by yeast two-hybrid, bimolecular fluorescence complementation (BiFC), and glutathione S-transferase (GST) pulldown assays. Bem2 specifically interacts with the GTP-bound form of Rho4, and the interaction is mediated by its RhoGAP domain. Overexpression of BEM2 aggravates the defects of rho3Δ rho4 mutants. These results suggest that Bem2 might be a novel GAP for Rho4. PMID:23264647

  3. Dissociation between mental fatigue and motivational state during prolonged mental activity.

    PubMed

    Gergelyfi, Mónika; Jacob, Benvenuto; Olivier, Etienne; Zénon, Alexandre

    2015-01-01

    Mental fatigue (MF) is commonly observed following prolonged cognitive activity and can have major repercussions on the daily life of patients as well as healthy individuals. Despite its important impact, the cognitive processes involved in MF remain largely unknown. An influential hypothesis states that MF does not arise from a disruption of overused neural processes but, rather, is caused by a progressive decrease in motivation-related task engagement. Here, to test this hypothesis, we measured various neural, autonomic, psychometric and behavioral signatures of MF and motivation (EEG, ECG, pupil size, eye blinks, Skin conductance responses (SCRs), questionnaires and performance in a working memory (WM) task) in healthy volunteers, while MF was induced by Sudoku tasks performed for 120 min. Moreover extrinsic motivation was manipulated by using different levels of monetary reward. We found that, during the course of the experiment, the participants' subjective feeling of fatigue increased and their performance worsened while their blink rate and heart rate variability (HRV) increased. Conversely, reward-induced EEG, pupillometric and skin conductance signal changes, regarded as indicators of task engagement, remained constant during the experiment, and failed to correlate with the indices of MF. In addition, MF did not affect a simple reaction time task, despite the strong influence of extrinsic motivation on this task. Finally, alterations of the motivational state through monetary incentives failed to compensate the effects of MF. These findings indicate that MF in healthy subjects is not caused by an alteration of task engagement but is likely to be the consequence of a decrease in the efficiency, or availability, of cognitive resources. PMID:26217203

  4. Dissociation between mental fatigue and motivational state during prolonged mental activity

    PubMed Central

    Gergelyfi, Mónika; Jacob, Benvenuto; Olivier, Etienne; Zénon, Alexandre

    2015-01-01

    Mental fatigue (MF) is commonly observed following prolonged cognitive activity and can have major repercussions on the daily life of patients as well as healthy individuals. Despite its important impact, the cognitive processes involved in MF remain largely unknown. An influential hypothesis states that MF does not arise from a disruption of overused neural processes but, rather, is caused by a progressive decrease in motivation-related task engagement. Here, to test this hypothesis, we measured various neural, autonomic, psychometric and behavioral signatures of MF and motivation (EEG, ECG, pupil size, eye blinks, Skin conductance responses (SCRs), questionnaires and performance in a working memory (WM) task) in healthy volunteers, while MF was induced by Sudoku tasks performed for 120 min. Moreover extrinsic motivation was manipulated by using different levels of monetary reward. We found that, during the course of the experiment, the participants’ subjective feeling of fatigue increased and their performance worsened while their blink rate and heart rate variability (HRV) increased. Conversely, reward-induced EEG, pupillometric and skin conductance signal changes, regarded as indicators of task engagement, remained constant during the experiment, and failed to correlate with the indices of MF. In addition, MF did not affect a simple reaction time task, despite the strong influence of extrinsic motivation on this task. Finally, alterations of the motivational state through monetary incentives failed to compensate the effects of MF. These findings indicate that MF in healthy subjects is not caused by an alteration of task engagement but is likely to be the consequence of a decrease in the efficiency, or availability, of cognitive resources. PMID:26217203

  5. Coupled interactions between volatile activity and Fe oxidation state during arc crustal processes

    USGS Publications Warehouse

    Humphreys, Madeleine C.S.; Brooker, R; Fraser, D.C.; Burgisser, A; Mangan, Margaret T.; McCammon, C

    2015-01-01

    Arc magmas erupted at the Earth’s surface are commonly more oxidized than those produced at mid-ocean ridges. Possible explanations for this high oxidation state are that the transfer of fluids during the subduction process results in direct oxidation of the sub-arc mantle wedge, or that oxidation is caused by the effect of later crustal processes, including protracted fractionation and degassing of volatile-rich magmas. This study sets out to investigate the effect of disequilibrium crustal processes that may involve coupled changes in H2O content and Fe oxidation state, by examining the degassing and hydration of sulphur-free rhyolites. We show that experimentally hydrated melts record strong increases in Fe3+/∑Fe with increasing H2O concentration as a result of changes in water activity. This is relevant for the passage of H2O-undersaturated melts from the deep crust towards shallow crustal storage regions, and raises the possibility that vertical variations in fO2 might develop within arc crust. Conversely, degassing experiments produce an increase in Fe3+/∑Fe with decreasing H2O concentration. In this case the oxidation is explained by loss of H2 as well as H2O into bubbles during decompression, consistent with thermodynamic modelling, and is relevant for magmas undergoing shallow degassing en route to the surface. We discuss these results in the context of the possible controls on fO2 during the generation, storage and ascent of magmas in arc settings, in particular considering the timescales of equilibration relative to observation as this affects the quality of the petrological record of magmatic fO2.

  6. The Activities and Impact of State Programs to Address Hereditary Breast and Ovarian Cancer, 2011–2014

    PubMed Central

    Trivers, Katrina F.; Rodriguez, Juan L.; Cox, Summer L.; Crane, Barbara E.; Duquette, Debra

    2015-01-01

    In 2011, the Division of Cancer Prevention and Control (DCPC), at the United States Centers for Disease Control and Prevention (CDC), released a three-year funding opportunity announcement (FOA) for a competitive, non-research cooperative agreement. The agreement enhanced the capacities of state health departments to promote the application of best practices for evidence-based breast cancer genomics through education, surveillance, and policy activities. The FOA required that applicants focus on activities related to hereditary breast and ovarian cancer (HBOC). The DCPC funded three states: Georgia, Michigan, and Oregon. Georgia was a first-time recipient of cancer genomics funding, whereas Michigan and Oregon had long standing activities in cancer genomics and had received CDC funding in the past. By the end of the funding period, each state had well-functioning and impactful state-based programs in breast cancer genomics. This article highlights the impact of a few key state activities by using CDC’s Science Impact Framework. There were challenges to implementing public health genomics programs, including the need to develop relevant partnerships, the highly technical nature of the subject matter, a lack of genetic services in certain areas, and the difficulty in funding genetic services. Georgia, Michigan, and Oregon have served as models for others interested in initiating or expanding cancer genomics programs, and they helped to determine what works well for promoting and integrating public health genomics into existing systems. PMID:27417805

  7. On the Structure of Neuronal Population Activity under Fluctuations in Attentional State

    PubMed Central

    Denfield, George H.; Bethge, Matthias; Tolias, Andreas S.

    2016-01-01

    Attention is commonly thought to improve behavioral performance by increasing response gain and suppressing shared variability in neuronal populations. However, both the focus and the strength of attention are likely to vary from one experimental trial to the next, thereby inducing response variability unknown to the experimenter. Here we study analytically how fluctuations in attentional state affect the structure of population responses in a simple model of spatial and feature attention. In our model, attention acts on the neural response exclusively by modulating each neuron's gain. Neurons are conditionally independent given the stimulus and the attentional gain, and correlated activity arises only from trial-to-trial fluctuations of the attentional state, which are unknown to the experimenter. We find that this simple model can readily explain many aspects of neural response modulation under attention, such as increased response gain, reduced individual and shared variability, increased correlations with firing rates, limited range correlations, and differential correlations. We therefore suggest that attention may act primarily by increasing response gain of individual neurons without affecting their correlation structure. The experimentally observed reduction in correlations may instead result from reduced variability of the attentional gain when a stimulus is attended. Moreover, we show that attentional gain fluctuations, even if unknown to a downstream readout, do not impair the readout accuracy despite inducing limited-range correlations, whereas fluctuations of the attended feature can in principle limit behavioral performance. SIGNIFICANCE STATEMENT Covert attention is one of the most widely studied examples of top-down modulation of neural activity in the visual system. Recent studies argue that attention improves behavioral performance by shaping of the noise distribution to suppress shared variability rather than by increasing response gain. Our work

  8. Altered Vision-Related Resting-State Activity in Pituitary Adenoma Patients with Visual Damage

    PubMed Central

    Qian, Haiyan; Wang, Xingchao; Wang, Zhongyan; Wang, Zhenmin; Liu, Pinan

    2016-01-01

    Objective To investigate changes of vision-related resting-state activity in pituitary adenoma (PA) patients with visual damage through comparison to healthy controls (HCs). Methods 25 PA patients with visual damage and 25 age- and sex-matched corrected-to-normal-vision HCs underwent a complete neuro-ophthalmologic evaluation, including automated perimetry, fundus examinations, and a magnetic resonance imaging (MRI) protocol, including structural and resting-state fMRI (RS-fMRI) sequences. The regional homogeneity (ReHo) of the vision-related cortex and the functional connectivity (FC) of 6 seeds within the visual cortex (the primary visual cortex (V1), the secondary visual cortex (V2), and the middle temporal visual cortex (MT+)) were evaluated. Two-sample t-tests were conducted to identify the differences between the two groups. Results Compared with the HCs, the PA group exhibited reduced ReHo in the bilateral V1, V2, V3, fusiform, MT+, BA37, thalamus, postcentral gyrus and left precentral gyrus and increased ReHo in the precuneus, prefrontal cortex, posterior cingulate cortex (PCC), anterior cingulate cortex (ACC), insula, supramarginal gyrus (SMG), and putamen. Compared with the HCs, V1, V2, and MT+ in the PAs exhibited decreased FC with the V1, V2, MT+, fusiform, BA37, and increased FC primarily in the bilateral temporal lobe (especially BA20,21,22), prefrontal cortex, PCC, insular, angular gyrus, ACC, pre-SMA, SMG, hippocampal formation, caudate and putamen. It is worth mentioning that compared with HCs, V1 in PAs exhibited decreased or similar FC with the thalamus, whereas V2 and MT+ exhibited increased FCs with the thalamus, especially pulvinar. Conclusions In our study, we identified significant neural reorganization in the vision-related cortex of PA patients with visual damage compared with HCs. Most subareas within the visual cortex exhibited remarkable neural dysfunction. Some subareas, including the MT+ and V2, exhibited enhanced FC with the thalamic

  9. Two Active States of the Narrow-Line Gamma-Ray-Loud AGN GB 1310 + 487

    NASA Technical Reports Server (NTRS)

    Sokolovsky, K. V.; Schinzel, F. K.; Tanaka, Y. T.; Abolmasov, P. K.; Angelakis, E.; Bulgarelli, A.; Carrasco, L.; Cenko, S. B.; Cheung, C. C.; Clubb, K. I.; D'Ammando, F.; Escande, L.; Fegan, S. J.; Filippenko, A. V.; Finke, J. D.; Fuhrmann, L.; Fukazawa, Y.; Hays, E.; Healey, S. E.; Ikejiri, Y.; Itoh, R.; Kawabata, K. S.; Komatsu, T.; Kovalev, Yu. A.; Kovalev, Y. Y.; Krichbaum, T. P.

    2014-01-01

    Context. Previously unremarkable, the extragalactic radio source GB1310 487 showed gamma-ray flare on 2009 November 18, reaching a daily flux of approximately 10(exp -6) photons cm(exp -2) s(exp -1) at energies E greater than 100MeV and became one of the brightest GeV sources for about two weeks. Its optical spectrum shows strong forbidden-line emission while lacking broad permitted lines, which is not typical for a blazar. Instead, the spectrum resembles those of narrow emission-line galaxies. Aims. We investigate changes in the object's radio-to-GeV spectral energy distribution (SED) during and after the prominent gamma-ray flare with the aim of determining the nature of the object and of constraining the origin of the variable high-energy emission. Methods. The data collected by the Fermi and AGILE satellites at gamma-ray energies; Swift at X-ray and ultraviolet (UV); the Kanata, NOT, and Keck telescopes at optical; OAGH and WISE at infrared (IR); and IRAM30m, OVRO 40m, Effelsberg 100m, RATAN-600, and VLBA at radio are analyzed together to trace the SED evolution on timescales of months. Results. The gamma-ray radio-loud narrow-line active galactic nucleus (AGN) is located at redshift z = 0.638. It shines through an unrelated foreground galaxy at z = 0.500. The AGN light is probably amplified by gravitational lensing. The AGN SED shows a two-humped structure typical of blazars and gamma-ray-loud narrow-line Seyfert 1 galaxies, with the high-energy (inverse-Compton) emission dominating by more than an order of magnitude over the low-energy (synchrotron) emission during gamma-ray flares. The difference between the two SED humps is smaller during the low-activity state. Fermi observations reveal a strong correlation between the gamma-ray flux and spectral index, with the hardest spectrum observed during the brightest gamma-ray state. The gamma-ray flares occurred before and during a slow rising trend in the radio, but no direct association between gamma-ray and

  10. Participating in politics resembles physical activity: general action patterns in international archives, United States archives, and experiments.

    PubMed

    Noguchi, Kenji; Handley, Ian M; Albarracín, Dolores

    2011-02-01

    A series of studies examined whether political participation can emerge from general patterns of indiscriminate activity. In the first two studies, general action tendencies were measured by combining national and state-level indicators of high activity (e.g., impulsiveness, pace of life, and physical activity) from international and U.S. data. This action-tendency index positively correlated with a measure of political participation that consisted of voting behaviors and participation in political demonstrations. The following two experimental studies indicated that participants exposed to action words (e.g., go, move) had stronger intentions to vote in an upcoming election and volunteered more time to make phone calls on behalf of a university policy than participants exposed to inaction words did (e.g., relax, stop). These studies suggest that political participation can be predicted from general tendencies toward activity present at the national and state levels, as well as from verbal prompts suggestive of activity. PMID:21177515

  11. Participating in Politics Resembles Physical Activity: General Action Patterns in International Archives, United States Archives, and Experiments

    PubMed Central

    Noguchi, Kenji; Handley, Ian M.; Albarracín, Dolores

    2016-01-01

    A series of studies examined whether political participation can emerge from general patterns of indiscriminate activity. In the first two studies, general action tendencies were measured by combining national and state-level indicators of high activity (e.g., impulsiveness, pace of life, and physical activity) from international and U.S. data. This action-tendency index positively correlated with a measure of political participation that consisted of voting behaviors and participation in political demonstrations. The following two experimental studies indicated that participants exposed to action words (e.g., go, move) had stronger intentions to vote in an upcoming election and volunteered more time to make phone calls on behalf of a university policy than participants exposed to inaction words did (e.g., relax, stop). These studies suggest that political participation can be predicted from general tendencies toward activity present at the national and state levels, as well as from verbal prompts suggestive of activity. PMID:21177515

  12. Quantification of the Fragmentation of Rest-Activity Patterns in Elderly Individuals Using a State Transition Analysis

    PubMed Central

    Lim, Andrew S.P.; Yu, Lei; Costa, Madalena D.; Buchman, Aron S.; Bennett, David A.; Leurgans, Sue E.; Saper, Clifford B.

    2011-01-01

    Objectives: Recent interest in the temporal dynamics of behavioral states has spurred the development of analytical approaches for their quantification. Several analytical approaches for polysomnographic data have been described. However, polysomnography is cumbersome, perturbs behavior, and is limited to short recordings. Although less physiologically comprehensive than polysomnography, actigraphy is nonintrusive, amenable to long recordings, and suited to use in subjects' natural environments, and provides an indirect measure of behavioral state. We developed a probabilistic state transition model to quantify the fragmentation of human rest-activity patterns from actigraphic data. We then applied this to the study of the temporal dynamics of rest-activity patterns in older individuals. Design: Cross-sectional. Setting: Community-based. Participants: 621 community-dwelling individuals without dementia participating in the Rush Memory and Aging Project. Measurements and Results: We analyzed actigraphic data collected for up to 11 days. We processed each record to give a series of transitions between the states of rest and activity, calculated the probabilities of such transitions, and described their evolution as a function of time. From these analyses, we derived metrics of the fragmentation of rest or activity at scales of seconds to minutes. Regression modeling of the relationship of these metrics with clinical variables revealed significant associations with age, even after adjusting for sex, body mass index, and a broad range of medical comorbidities. Conclusions: Probabilistic analyses of the transition dynamics of rest-activity data provide a high-throughput, automated, quantitative, and noninvasive method of assessing the fragmentation of behavioral states suitable for large scale human and animal studies; these methods reveal age-associated changes in the fragmentation of rest-activity patterns akin to those described using polysomnographic methods

  13. Activation of the methylation cycle in cells reprogrammed into a stem cell-like state

    PubMed Central

    Bosch-Barrera, Joaquim; Alarcón, Tomás; Joven, Jorge; Menendez, Javier A.

    2015-01-01

    Generation of induced pluripotent stem (iPS) cells and cancer biogenesis share similar metabolic switches. Most studies have focused on how the establishment of a cancer-like glycolytic phenotype is necessary for the optimal routing of somatic cells for achieving stemness. However, relatively little effort has been dedicated towards elucidating how one-carbon (1C) metabolism is retuned during acquisition of stem cell identity. Here we used ultra-high pressure liquid chromatography coupled to an electrospray ionization source and a triple-quadrupole mass spectrometer [UHPLC-ESI-QqQ-MS/MS] to quantitatively examine the methionine/folate bi-cyclic 1C metabolome during nuclear reprogramming of somatic cells into iPS cells. iPS cells optimize the synthesis of the universal methyl donor S-adenosylmethionine (SAM), apparently augment the ability of the redox balance regulator NADPH in SAM biosynthesis, and greatly increase their methylation potential by triggering a high SAM:S-adenosylhomocysteine (SAH) ratio. Activation of the methylation cycle in iPS cells efficiently prevents the elevation of homocysteine (Hcy), which could alter global DNA methylation and induce mitochondrial toxicity, oxidative stress and inflammation. In this regard, the methyl donor choline is also strikingly accumulated in iPS cells, suggesting perhaps an overactive intersection of the de novo synthesis of choline with the methionine-Hcy cycle. Activation of methylogenesis and maintenance of an optimal SAM:Hcy ratio might represent an essential function of 1C metabolism to provide a labile pool of methyl groups and NADPH-dependent redox products required for successfully establishing and maintaining an embryonic-like DNA methylation imprint in stem cell states. PMID:26909364

  14. Roles and strategies of state organizations related to school-based physical education and physical activity policies.

    PubMed

    Cradock, Angie L; Barrett, Jessica L; Carnoske, Cheryl; Chriqui, Jamie F; Evenson, Kelly R; Gustat, Jeanette; Healy, Isobel B; Heinrich, Katie M; Lemon, Stephenie C; Tompkins, Nancy Oʼhara; Reed, Hannah L; Zieff, Susan G

    2013-01-01

    School-based physical education (PE) and physical activity (PA) policies can improve PA levels of students and promote health. Studies of policy implementation, communication, monitoring, enforcement, and evaluation are lacking. To describe how states implement, communicate, monitor, enforce, and evaluate key school-based PE and PA policies, researchers interviewed 24 key informants from state-level organizations in 9 states, including representatives from state departments of health and education, state boards of education, and advocacy/professional organizations. These states educate 27% of the US student population. Key informants described their organizations' roles in addressing 14 school-based PE and PA state laws and regulations identified by the Bridging the Gap research program and the National Cancer Institute's Classification of Laws Associated with School Students (C.L.A.S.S.) system. On average, states had 4 of 14 school-based PE and PA laws and regulations, and more than one-half of respondents reported different policies in practice besides the "on the books" laws. Respondents more often reported roles implementing and communicating policies compared with monitoring, enforcing, and evaluating them. Implementation and communication strategies used included training, technical assistance, and written communication of policy to local education agency administrators and teachers. State-level organizations have varying roles in addressing school-based PE and PA policies. Opportunities exist to focus state-level efforts on compliance with existing laws and regulations and evaluation of their impact. PMID:23529053

  15. CCK activates RhoA and Rac1 differentially through Gα13 and Gαq in mouse pancreatic acini

    PubMed Central

    Bi, Yan; Ji, Baoan; Ernst, Stephen A.; Williams, John A.

    2010-01-01

    Cholecystokinin (CCK) has been shown to activate RhoA and Rac1, as well as reorganize the actin cytoskeleton and, thereby, modify acinar morphology and amylase secretion in mouse pancreatic acini. The aim of the present study was to determine which heterotrimeric G proteins activate RhoA and Rac1 upon CCK stimulation. Gα13, but not Gα12, was identified in mouse pancreatic acini by RT-PCR and Western blotting. Using specific assays for RhoA and Rac1 activation, we showed that only active Gα13 activated RhoA. By contrast, active Gα13 and Gαq, but not Gαs, slightly increased GTP-bound Rac1 levels. A greater increase in Rac1 activation was observed when active Gα13 and active Gαq were coexpressed. Gαi was not required for CCK-induced RhoA or Rac1 activation. The regulator of G protein signaling (RGS) domain of p115-Rho guanine nucleotide exchange factor (p115-RGS), a specific inhibitor of Gα12/13-mediated signaling, abolished CCK-stimulated RhoA activation. By contrast, both RGS-2, an inhibitor of Gαq, and p115-RGS abolished CCK-induced Rac1 activation, which was PLC pathway-independent. Active Gαq and Gα13, but not Gαs, induced morphological changes and actin redistribution similar to 1 nM CCK. CCK-induced actin cytoskeletal reorganization was inhibited by RGS-2, but not by p115-RGS, whereas CCK-induced amylase secretion was blocked by both inhibitors. Together, these findings indicate that, in mouse pancreatic acini, Gα13 links CCK stimulation to the activation of RhoA, whereas both Gα13 and Gαq link CCK stimulation to the activation of Rac1. CCK-induced actin cytoskeletal reorganization is mainly mediated by Gαq. By contrast, Gα13 and Gαq signaling are required for CCK-induced amylase secretion. PMID:19940064

  16. Receiver domains control the active state stoichiometry of Aquifex aeolicus σ54 activator NtrC4, as revealed by electrospray mass spectrometry

    PubMed Central

    Batchelor, Joseph D.; Sterling, Harry J.; Hong, Eunmi; Williams, Evan R.; Wemmer, David E.

    2009-01-01

    A common challenge with studies of proteins in vitro is determining which constructs and conditions are most physiologically relevant. σ54 activators are proteins that undergo regulated assembly to form an active ATPase ring that enables transcription by σ54-polymerase. Previous studies of the AAA+ ATPase domains from σ54 activators have shown that some are heptamers, while others are hexamers. Because the active oligomers assemble from off-state dimers, it was thought that even-numbered oligomers should dominate, and that heptamer formation might occur when individual domains of the activators were studied rather than the intact proteins. Here we present results from electrospray mass spectrometry experiments that characterize the assembly states of intact NtrC4 (a σ54 activator from Aquifex aeolicus, an extreme thermophile) as well as its ATPase domain alone, and regulatory-ATPase and ATPase-DNA binding domain combinations. We show that the full-length and activated regulatory-ATPase proteins form hexamers, whereas the isolated ATPase domain, unactivated regulatory-ATPase and ATPase-DNA binding domain form heptamers. Activation of the N-terminal regulatory domain is the key factor stabilizing the hexamer form of the ATPase, relative to the heptamer. PMID:19699748

  17. Levansucrase optimization using solid state fermentation and levan biological activities studies.

    PubMed

    Esawy, Mona A; Abdel-Fattah, Azza M; Ali, Mamdouh M; Helmy, Wafaa A; Salama, Bassem M; Taie, Hanan A A; Hashem, Amal M; Awad, Ghada E A

    2013-07-01

    Bacillus subtilis NRC1aza produced levansucrase under solid state fermentation using starch as support. A sequential optimization strategy, based on statistical experimental designs is employed to enhance enzyme productivity. First, a 2-level Plackett-Burman design was applied for bioprocess parameters screen that significantly increase levansucrase production. Second optimization step was performed using fractional factorial design in order to optimize the amounts of highest positive variables that had significant effect on levansucrase productivity. Maximal enzyme productivity of 170 U/gds was achieved in presence of glucose, yeast extract, and pH 8. In vitro, experiments confirmed that LevCR and LevQT had an antitumor activity against different animal and human cancer cell lines by demonstrating inhibitory effects on growth of Ehrlich ascites carcinoma cell line, human MCF-7 breast and liver HepG2 cancer cell lines, in particular LevQT was found to be efficacious compared to anticancer drug, cisplatin. Result focused in LevCR as strong fibrinolytic agent. PMID:23688489

  18. Uses of Research Evidence in the State Legislative Process to Promote Active Environments in Minnesota

    PubMed Central

    Kite, Hanna A.; Gollust, Sarah E.; Callanan, Rachel A.; Weisman, Susan R.; Benning, Sara J.; Nanney, Marilyn S.

    2014-01-01

    Purpose To describe how research evidence and non–research-based information are used in testimony and other legislative documents used in arguments for and against physical activity–related bills in Minnesota. Design Content analysis Setting Documents and oral testimony archived by the Minnesota State Legislature from 2007 to 2011. Subjects Not applicable. Measures A coding instrument was developed to measure descriptive features of materials (e.g., length, document type) and the presence or absence of certain types of research evidence and non–research-based information. Analysis Frequencies of variables and measures of associations using Pearson χ2 tests. Results Over a third (36%) of the sample contained research evidence, and 88% of the sample contained non–research-based information. Compared to materials related to physical activity, materials related to built environment were significantly less likely to reference research evidence. Conclusion Despite an abundance of evidence, research evidence was present in only about one-third of the sample. There may be opportunities during legislative discussions on the built environment for obesity-related data to help make the case for sound policies. PMID:24380464

  19. Intensive training induces longitudinal changes in meditation state-related EEG oscillatory activity

    PubMed Central

    Saggar, Manish; King, Brandon G.; Zanesco, Anthony P.; MacLean, Katherine A.; Aichele, Stephen R.; Jacobs, Tonya L.; Bridwell, David A.; Shaver, Phillip R.; Rosenberg, Erika L.; Sahdra, Baljinder K.; Ferrer, Emilio; Tang, Akaysha C.; Mangun, George R.; Wallace, B. Alan; Miikkulainen, Risto; Saron, Clifford D.

    2012-01-01

    The capacity to focus one's attention for an extended period of time can be increased through training in contemplative practices. However, the cognitive processes engaged during meditation that support trait changes in cognition are not well characterized. We conducted a longitudinal wait-list controlled study of intensive meditation training. Retreat participants practiced focused attention (FA) meditation techniques for three months during an initial retreat. Wait-list participants later undertook formally identical training during a second retreat. Dense-array scalp-recorded electroencephalogram (EEG) data were collected during 6 min of mindfulness of breathing meditation at three assessment points during each retreat. Second-order blind source separation, along with a novel semi-automatic artifact removal tool (SMART), was used for data preprocessing. We observed replicable reductions in meditative state-related beta-band power bilaterally over anteriocentral and posterior scalp regions. In addition, individual alpha frequency (IAF) decreased across both retreats and in direct relation to the amount of meditative practice. These findings provide evidence for replicable longitudinal changes in brain oscillatory activity during meditation and increase our understanding of the cortical processes engaged during meditation that may support long-term improvements in cognition. PMID:22973218

  20. Active Immunization in the United States: Developments over the Past Decade

    PubMed Central

    Dennehy, Penelope H.

    2001-01-01

    The Centers for Disease Control and Prevention has identified immunization as the most important public health advance of the 20th century. The purpose of this article is to review the changes that have taken place in active immunization in the United States over the past decade. Since 1990, new vaccines have become available to prevent five infectious diseases: varicella, rotavirus, hepatitis A, Lyme disease, and Japanese encephalitis virus infection. Improved vaccines have been developed to prevent Haemophilus influenzae type b, pneumococcus, pertussis, rabies, and typhoid infections. Immunization strategies for the prevention of hepatitis B, measles, meningococcal infections, and poliomyelitis have changed as a result of the changing epidemiology of these diseases. Combination vaccines are being developed to facilitate the delivery of multiple antigens, and improved vaccines are under development for cholera, influenza, and meningococcal disease. Major advances in molecular biology have enabled scientists to devise new approaches to the development of vaccines against diseases ranging from respiratory viral to enteric bacterial infections that continue to plague the world's population. PMID:11585789

  1. Production and regulation of lipase activity from Penicillium restrictum in submerged and solid-state fermentations.

    PubMed

    de Azeredo, Luciana A I; Gomes, Patrícia M; Sant'Anna, Geraldo L; Castilho, Leda R; Freire, Denise M G

    2007-05-01

    Different carbon (C) sources, mainly carbohydrates and lipids, have been screened for their capacity to support growth and lipase production by Penicillium restrictum in submerged fermentation (SmF) and in solid-state fermentation (SSF). Completely different physiological behaviors were observed after the addition of easily (oleic acid and glucose) and complex (olive oil and starch) assimilable C sources to the liquid and solid media. Maximal lipolytic activities (12.1 U/mL and 17.4 U/g) by P. restrictum were obtained with olive oil in SmF and in SSF, respectively. Biomass levels in SmF (12.2-14.1 mg/mL) and SSF (7.0-8.0 mg/g) did not varied greatly with the distinct C sources used. High lipase production (12.3 U/g) using glucose was only attained in SSF, perhaps due to the ability of this fermentation process to minimize catabolite repression. PMID:17457647

  2. Kinetic energy budget during strong jet stream activity over the eastern United States

    NASA Technical Reports Server (NTRS)

    Fuelberg, H. E.; Scoggins, J. R.

    1980-01-01

    Kinetic energy budgets are computed during a cold air outbreak in association with strong jet stream activity over the eastern United States. The period is characterized by large generation of kinetic energy due to cross-contour flow. Horizontal export and dissipation of energy to subgrid scales of motion constitute the important energy sinks. Rawinsonde data at 3 and 6 h intervals during a 36 h period are used in the analysis and reveal that energy fluctuations on a time scale of less than 12 h are generally small even though the overall energy balance does change considerably during the period in conjunction with an upper level trough which moves through the region. An error analysis of the energy budget terms suggests that this major change in the budget is not due to random errors in the input data but is caused by the changing synoptic situation. The study illustrates the need to consider the time and space scales of associated weather phenomena in interpreting energy budgets obtained through use of higher frequency data.

  3. Crystal structure of plant light-harvesting complex shows the active, energy-transmitting state

    PubMed Central

    Barros, Tiago; Royant, Antoine; Standfuss, Jörg; Dreuw, Andreas; Kühlbrandt, Werner

    2009-01-01

    Plants dissipate excess excitation energy as heat by non-photochemical quenching (NPQ). NPQ has been thought to resemble in vitro aggregation quenching of the major antenna complex, light harvesting complex of photosystem II (LHC-II). Both processes are widely believed to involve a conformational change that creates a quenching centre of two neighbouring pigments within the complex. Using recombinant LHC-II lacking the pigments implicated in quenching, we show that they have no particular role. Single crystals of LHC-II emit strong, orientation-dependent fluorescence with an emission maximum at 680 nm. The average lifetime of the main 680 nm crystal emission at 100 K is 1.31 ns, but only 0.39 ns for LHC-II aggregates under identical conditions. The strong emission and comparatively long fluorescence lifetimes of single LHC-II crystals indicate that the complex is unquenched, and that therefore the crystal structure shows the active, energy-transmitting state of LHC-II. We conclude that quenching of excitation energy in the light-harvesting antenna is due to the molecular interaction with external pigments in vitro or other pigment–protein complexes such as PsbS in vivo, and does not require a conformational change within the complex. PMID:19131972

  4. Control of nitric oxide dynamics by guanylate cyclase in its activated state.

    PubMed

    Négrerie, M; Bouzhir, L; Martin, J L; Liebl, U

    2001-12-14

    Soluble guanylate cyclase (sGC) is the target of nitric oxide (NO) released by nitric-oxide synthase in endothelial cells, inducing an increase of cGMP synthesis in response. This heterodimeric protein possesses a regulatory subunit carrying a heme where NO binding occurs, while the second subunit harbors the catalytic site. The binding of NO and the subsequent breaking of the bond between the proximal histidine and the heme-Fe(2+) are assumed to induce conformational changes, which are the origin of the catalytic activation. At the molecular level, the activation and deactivation mechanisms are unknown, as is the dynamics of NO once in the heme pocket. Using ultrafast time-resolved absorption spectroscopy, we measured the kinetics of NO rebinding to sGC after photodissociation. The main spectral transient in the Soret band does not match the equilibrium difference spectrum of NO-liganded minus unliganded sGC, and the geminate rebinding was found to be monoexponential and ultrafast (tau = 7.5 ps), with a relative amplitude close to unity (0.97). These characteristics, so far not observed in other hemoproteins, indicate that NO encounters a high energy barrier for escaping from the heme pocket once the His-Fe(2+) bond has been cleaved; this bond does not reform before NO recombination. The deactivation of isolated sGC cannot occur by only simple diffusion of NO from the heme; therefore, several allosteric states may be inferred, including a desensitized one, to induce NO release. Thus, besides the structural change leading to activation, a consequence of the decoupling of the proximal histidine may also be to induce a change of the heme pocket distal geometry, which raises the energy barrier for NO escape, optimizing the efficiency of NO trapping. The non-single exponential character of the NO picosecond rebinding coexists only with the presence of the protein structure surrounding the heme, and the single exponential rate observed in sGC is very likely to be due to

  5. Using Active Video Games for Physical Activity Promotion: A Systematic Review of the Current State of Research

    ERIC Educational Resources Information Center

    Peng, Wei; Crouse, Julia C.; Lin, Jih-Hsuan

    2013-01-01

    This systematic review evaluates interventions using active video games (AVGs) to increase physical activity and summarizes laboratory studies quantifying intensity of AVG play among children and adults. Databases (Cochrane Library, PsychInfo, PubMed, SPORTDiscus, Web of Science) and forward citation and reference list searches were used to…

  6. 76 FR 71339 - Agency Information Collection Activities; Proposed Collection; Comment Request; State Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... Business Stationary Source Technical and Environmental Compliance Assistance Programs (SBTCP) Annual... this action are the State Small Business Stationary Source Technical and Environmental Compliance Assistance Programs (SBTCP). Title: State Small Business Stationary Source Technical and...

  7. Stimulus-induced and state-dependent sustained gamma activity is tightly coupled to the hemodynamic response in humans.

    PubMed

    Koch, Stefan P; Werner, Peter; Steinbrink, Jens; Fries, Pascal; Obrig, Hellmuth

    2009-11-01

    A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus-response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35-70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging. PMID:19890006

  8. Dispute Resolution Activities-State Data Collection. Quick Turn Around (QTA).

    ERIC Educational Resources Information Center

    National Association of State Directors of Special Education, Alexandria, VA.

    This report discusses the outcomes of a survey that investigated data collection efforts of state special education dispute resolution contacts in all 50 states. Results indicate that all states maintain some level (directly or through contractual arrangements) of basic information on the number and location of formal complaints, mediations, and…

  9. THE ROLE AND POLICYMAKING ACTIVITIES OF STATE BOARDS OF EDUCATION. REPORT ON A SPECIAL STUDY PROJECT.

    ERIC Educational Resources Information Center

    SCHWEICKHARD, DEAN M.

    SPONSORED BY STATE BOARDS OF EDUCATION IN ELEVEN REPRESENTATIVE STATES (ARKANSAS, COLORADO, CONNECTICUT, GEORGIA, NEW MEXICO, OHIO, OREGON, PENNSYLVANIA, SOUTH DAKOTA, MINNESOTA, AND WEST VIRGINIA), THIS STUDY CENTERS AROUND SEVEN BASIC PROBLEMS--(1) CONCEPTS OF "POLICY" AND "POLICYMAKING" IN STATE AND LOCAL EDUCATIONAL ADMINISTRATION ARE NOT…

  10. Fe, O, and C Charge States Associated with Quiescent Versus Active Current Sheets in the Solar Wind

    NASA Technical Reports Server (NTRS)

    Suess, S. T.; Ko, Y.-K.; vonSteiger, R.

    2008-01-01

    Ulysses MAG data were used to locate the heliospheric current sheet in data from 1991 through 2006. The purpose was to characterize typical charge states for Fe, O, and C in the vicinity of the current sheet and provide insight into the physical sources for these charge states in the corona. A study of He/H around the current sheets has led to a clear distinction between quiescent current sheets at times of low solar activity and active current sheets associated with magnetic clouds (and, presumably, ICMES). It has been shown that high ionization state Fe is produced in the corona in current sheets associated with CMEs through spectroscopic observations of the corona and through in situ detection at Ulysses. Here we show that the ionization state of Fe is typically only enhanced around active current sheets while the ionization states of O and C are commonly enhanced around both quiescent and active current sheets. This is consistent with UV coronal spectroscopy, which has shown that reconnection in current sheets behind CMEs leads to high temperatures not typically seen above quiet streamers.

  11. Summary report, low-level radioactive waste management activities in the states and compacts. Vol. 4. No. 1

    SciTech Connect

    1996-01-01

    `Low-Level Radioactive Waste Management Activities in the States and Compacts` is a supplement to `LLW Notes` and is distributed periodically by Afton Associates, Inc. to state, compact and federal officials that receive `LLW Notes`. The Low-Level Radioactive Waste Forum (LLW Forum) is an association of state and compact representatives, appointed by governors and compact commissions, established to facilitate state and compact implementation of the Low- Level Radioactive Waste Policy Act of 1980 and the Low-Level Radioactive Waste Policy Amendments Act of 1985 and to promote the objectives of low-level radioactive waste regional compacts. The LLW Forum provides an opportunity for state and compact officials to share information with one another and to exchange views with officials of federal agencies and other interested parties.

  12. Summary report. Low-level radioactive waste management activities in the states and compacts. Volume 4, No. 2

    SciTech Connect

    1996-08-01

    `Low-Level Radioactive Waste Management Activities in the States and Compacts` is a supplement to `LLW Notes` and is distributed periodically by Afton Associates, Inc. to state, compact and federal officials that receive `LLW Notes`. The Low-Level Radioactive Waste Forum (LLW Forum) is an association of state and compact representatives, appointed by governors and compact commissions, established to facilitate state and compact implementation of the Low- Level Radioactive Waste Policy Act of 1980 and the Low-Level Radioactive Waste Policy Amendments Act of 1985 and to promote the objectives of low-level radioactive waste regional compacts. The LLW Forum provides an opportunity for state and compact officials to share information with one another and to exchange views with officials of federal agencies and other interested parties.

  13. Direct observation of intersystem crossing in a thermally activated delayed fluorescence copper complex in the solid state.

    PubMed

    Bergmann, Larissa; Hedley, Gordon J; Baumann, Thomas; Bräse, Stefan; Samuel, Ifor D W

    2016-01-01

    Intersystem crossing in thermally activated delayed fluorescence (TADF) materials is an important process that controls the rate at which singlet states convert to triplets; however, measuring this directly in TADF materials is difficult. TADF is a significant emerging technology that enables the harvesting of triplets as well as singlet excited states for emission in organic light emitting diodes. We have observed the picosecond time-resolved photoluminescence of a highly luminescent, neutral copper(I) complex in the solid state that shows TADF. The time constant of intersystem crossing is measured to be 27 picoseconds. Subsequent overall reverse intersystem crossing is slow, leading to population equilibration and TADF with an average lifetime of 11.5 microseconds. These first measurements of intersystem crossing in the solid state in this class of mononuclear copper(I) complexes give a better understanding of the excited-state processes and mechanisms that ensure efficient TADF. PMID:26767194

  14. Direct observation of intersystem crossing in a thermally activated delayed fluorescence copper complex in the solid state

    PubMed Central

    Bergmann, Larissa; Hedley, Gordon J.; Baumann, Thomas; Bräse, Stefan; Samuel, Ifor D. W.

    2016-01-01

    Intersystem crossing in thermally activated delayed fluorescence (TADF) materials is an important process that controls the rate at which singlet states convert to triplets; however, measuring this directly in TADF materials is difficult. TADF is a significant emerging technology that enables the harvesting of triplets as well as singlet excited states for emission in organic light emitting diodes. We have observed the picosecond time-resolved photoluminescence of a highly luminescent, neutral copper(I) complex in the solid state that shows TADF. The time constant of intersystem crossing is measured to be 27 picoseconds. Subsequent overall reverse intersystem crossing is slow, leading to population equilibration and TADF with an average lifetime of 11.5 microseconds. These first measurements of intersystem crossing in the solid state in this class of mononuclear copper(I) complexes give a better understanding of the excited-state processes and mechanisms that ensure efficient TADF. PMID:26767194

  15. Active Control of Sound Field Using State-Space Model and Feedback Control Theory: a Numerical Simulation.

    NASA Astrophysics Data System (ADS)

    Wu, Zhen

    Active sound filed control techniques have received growing attention since they provide alternative solutions to low-frequency sound control, where the conventional passive methods have not been very successful. They have wide industrial and military applications such as noise reduction, room acoustics design, acoustic measurements, underwater acoustic camouflage, etc. An appropriate model of an acoustical system serves as the basis of control law synthesis and active control system design. A classical system model describes the dynamics of an acoustic system in a view of input/output relation through transfer functions. On the other hand, a time-domain based state-space model equivalently describes the system dynamics in terms of internal system variables and provides a direct physical insight of active control of sound. Furthermore, based on a state-space model, one can take advantage of modern control analysis and synthesis tools to design an optimal control system for broadband, global sound absorption. This thesis explores state-space feedback control in unbounded acoustic systems. State-space models are developed for unbounded one-dimensional acoustic systems using a finite-difference method with special boundary treatments. State feedback control algorithms including state estimations are developed using optimal control theory (LQG). Numerical simulation results of the closed-loop system responses demonstrate the optimal performance of active control systems considering the trade-off between the high reflection reduction and limited sensing/actuating power. Two numerical examples, an active underwater sound absorbing coating system, and an active noise control system in a duct, are studied. For the active underwater sound absorbing system, a feedback control system involving two sensors and one actuator is designed. Numerical simulation of the closed-loop response indicates a substantial and broadband reflection (echo) reduction for this design. A variety

  16. On the State of a Solar Active Region Before Flares and CMEs

    NASA Astrophysics Data System (ADS)

    Korsós, M. B.; Erdélyi, R.

    2016-06-01

    Several attempts have been made to find reliable diagnostic tools to determine the state prior to flares and related coronal mass ejections (CMEs) in solar active regions (ARs). Characterization of the level of mixed states is carried out using the Debrecen sunspot Data for 116 flaring ARs. Conditional flare probabilities (CFPs) are calculated for different flaring classes. The association with slow/fast CMEs is examined. Two precursor parameters are introduced: (i) the sum of the (daily averaged) horizontal magnetic gradient G S (G DS ) and (ii) the separation parameter {S}l-f. We found that if {S}l-f≤slant 1 for a flaring AR then the CFP of the expected highest-intensity flare being X-class is more than 70%. If 1≤slant {S}l-f≤slant 3 the CFP is more than 45% for the highest-intensity flare(s) to be M-class, and if 3≤slant {S}l-f≤slant 13 there is larger than 60% CFP that C-class flare(s) may have the strongest intensity within 48 hr. Next, from analyzing G S for determining CFP we found: if 5.5≤slant {log}({G}S) ≤slant 6.5, then it is very likely that C-class flare(s) may be the most intense; if 6.5≤slant {log}({G}S)≤slant 7.5 then there is ∼45% CFP that M-class could have the highest intensity; finally, if 7.5≤slant {log}({G}S) then there is at least 70% chance that the strongest energy release will be X-class in the next 48 hr. ARs are unlikely to produce X-class flare(s) if 13≤slant {S}l-f and log(G S ) ≤slant 5.5. Finally, in terms of providing an estimate of an associated slow/fast CME, we found that, if {log}({S}l-f) ≥slant 0.4 or {log}({G}{DS}) ≤slant 6.5, there is no accompanying fast CME in the following 24 hr.

  17. PRENATAL ALCOHOL EXPOSURE ALTERS STEADY-STATE AND ACTIVATED GENE EXPRESSION IN THE ADULT RAT BRAIN

    PubMed Central

    Stepien, Katarzyna A.; Lussier, Alexandre A.; Neumann, Sarah M.; Pavlidis, Paul; Kobor, Michael S.; Weinberg, Joanne

    2016-01-01

    Background Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems . We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freund’s adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression

  18. Survey of Physical Activity in Elementary School Classrooms in the State of Virginia

    ERIC Educational Resources Information Center

    Elmakis, Gail Smith

    2010-01-01

    Elementary school age children engage in levels of physical activity that are well below recommended guidelines. It has been suggested that classroom teachers can assist in remedying the problem by providing physical activity breaks and physical activity embedded in instruction. This study utilized the instrument, Physical Activity in the…

  19. Energy Conservation Education for New York State. Interdisciplinary Learning Activities. Grades 7-12.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany.

    Provided in this document are 18 energy conservation activities designed to supplement regular classroom learning activities. A matrix correlating activity number with grade level and subject areas is included. Titles of activities are: puzzles; energy quiz; energy-related careers; reading a meter; trading calories for kilo-watts; conserving home…

  20. What graph theory actually tells us about resting state interictal MEG epileptic activity

    PubMed Central

    Niso, Guiomar; Carrasco, Sira; Gudín, María; Maestú, Fernando; del-Pozo, Francisco; Pereda, Ernesto

    2015-01-01

    Graph theory provides a useful framework to study functional brain networks from neuroimaging data. In epilepsy research, recent findings suggest that it offers unique insight into the fingerprints of this pathology on brain dynamics. Most studies hitherto have focused on seizure activity during focal epilepsy, but less is known about functional epileptic brain networks during interictal activity in frontal focal and generalized epilepsy. Besides, it is not clear yet which measures are most suitable to characterize these networks. To address these issues, we recorded magnetoencephalographic (MEG) data using two orthogonal planar gradiometers from 45 subjects from three groups (15 healthy controls (7 males, 24 ± 6 years), 15 frontal focal (8 male, 32 ± 16 years) and 15 generalized epileptic (6 male, 27 ± 7 years) patients) during interictal resting state with closed eyes. Then, we estimated the total and relative spectral power of the largest principal component of the gradiometers, and the degree of phase synchronization between each sensor site in the frequency range [0.5–40 Hz]. We further calculated a comprehensive battery of 15 graph-theoretic measures and used the affinity propagation clustering algorithm to elucidate the minimum set of them that fully describe these functional brain networks. The results show that differences in spectral power between the control and the other two groups have a distinctive pattern: generalized epilepsy presents higher total power for all frequencies except the alpha band over a widespread set of sensors; frontal focal epilepsy shows higher relative power in the beta band bilaterally in the fronto-central sensors. Moreover, all network indices can be clustered into three groups, whose exemplars are the global network efficiency, the eccentricity and the synchronizability. Again, the patterns of differences were clear: the brain network of the generalized epilepsy patients presented greater efficiency and lower

  1. What graph theory actually tells us about resting state interictal MEG epileptic activity.

    PubMed

    Niso, Guiomar; Carrasco, Sira; Gudín, María; Maestú, Fernando; Del-Pozo, Francisco; Pereda, Ernesto

    2015-01-01

    Graph theory provides a useful framework to study functional brain networks from neuroimaging data. In epilepsy research, recent findings suggest that it offers unique insight into the fingerprints of this pathology on brain dynamics. Most studies hitherto have focused on seizure activity during focal epilepsy, but less is known about functional epileptic brain networks during interictal activity in frontal focal and generalized epilepsy. Besides, it is not clear yet which measures are most suitable to characterize these networks. To address these issues, we recorded magnetoencephalographic (MEG) data using two orthogonal planar gradiometers from 45 subjects from three groups (15 healthy controls (7 males, 24 ± 6 years), 15 frontal focal (8 male, 32 ± 16 years) and 15 generalized epileptic (6 male, 27 ± 7 years) patients) during interictal resting state with closed eyes. Then, we estimated the total and relative spectral power of the largest principal component of the gradiometers, and the degree of phase synchronization between each sensor site in the frequency range [0.5-40 Hz]. We further calculated a comprehensive battery of 15 graph-theoretic measures and used the affinity propagation clustering algorithm to elucidate the minimum set of them that fully describe these functional brain networks. The results show that differences in spectral power between the control and the other two groups have a distinctive pattern: generalized epilepsy presents higher total power for all frequencies except the alpha band over a widespread set of sensors; frontal focal epilepsy shows higher relative power in the beta band bilaterally in the fronto-central sensors. Moreover, all network indices can be clustered into three groups, whose exemplars are the global network efficiency, the eccentricity and the synchronizability. Again, the patterns of differences were clear: the brain network of the generalized epilepsy patients presented greater efficiency and lower

  2. Longitudinal changes in resting-state brain activity in a capsular infarct model

    PubMed Central

    Kim, Donghyeon; Kim, Ra Gyung; Kim, Hyung-Sun; Kim, Jin-Myung; Jun, Sung Chan; Lee, Boreom; Jo, Hang Joon; Neto, Pedro R; Lee, Min-Cheol; Kim, Hyoung-Ihl

    2015-01-01

    Strokes attributable to subcortical infarcts have been increasing recently in elderly patients. To gain insight how this lesion influences the motor outcome and responds to rehabilitative training, we used circumscribed photothrombotic capsular infarct models on 36 Sprague-Dawley rats (24 experimental and 12 sham-operated). We used 2-deoxy-2-[18F]-fluoro-D-glucose-micro positron emission tomography (FDG-microPET) to assess longitudinal changes in resting-state brain activity (rs-BA) and daily single-pellet reaching task (SPRT) trainings to evaluate motor recovery. Longitudinal FDG-microPET results showed that capsular infarct resulted in a persistent decrease in rs-BA in bilateral sensory and auditory cortices, and ipsilesional motor cortex, thalamus, and inferior colliculus (P<0.0025, false discovery rate (FDR) q<0.05). The decreased rs-BA is compatible with diaschisis and contributes to manifest the malfunctions of lesion-specific functional connectivity. In contrast, capsular infarct resulted in increase of rs-BA in the ipsilesional internal capsule, and contralesional red nucleus and ventral hippocampus in recovery group (P<0.0025, FDR q<0.05), implying that remaining subcortical structures have an important role in conducting the recovery process in capsular infarct. The SPRT training facilitated motor recovery only in rats with an incomplete destruction of the posterior limb of the internal capsule (PLIC) (Pearson's correlation, P<0.05). Alternative therapeutic interventions are required to enhance the potential for recovery in capsular infarct with complete destruction of PLIC. PMID:25352047

  3. Longitudinal changes in resting-state brain activity in a capsular infarct model.

    PubMed

    Kim, Donghyeon; Kim, Ra Gyung; Kim, Hyung-Sun; Kim, Jin-Myung; Jun, Sung Chan; Lee, Boreom; Jo, Hang Joon; Neto, Pedro R; Lee, Min-Cheol; Kim, Hyoung-Ihl

    2015-01-01

    Strokes attributable to subcortical infarcts have been increasing recently in elderly patients. To gain insight how this lesion influences the motor outcome and responds to rehabilitative training, we used circumscribed photothrombotic capsular infarct models on 36 Sprague-Dawley rats (24 experimental and 12 sham-operated). We used 2-deoxy-2-[(18)F]-fluoro-D-glucose-micro positron emission tomography (FDG-microPET) to assess longitudinal changes in resting-state brain activity (rs-BA) and daily single-pellet reaching task (SPRT) trainings to evaluate motor recovery. Longitudinal FDG-microPET results showed that capsular infarct resulted in a persistent decrease in rs-BA in bilateral sensory and auditory cortices, and ipsilesional motor cortex, thalamus, and inferior colliculus (P<0.0025, false discovery rate (FDR) q<0.05). The decreased rs-BA is compatible with diaschisis and contributes to manifest the malfunctions of lesion-specific functional connectivity. In contrast, capsular infarct resulted in increase of rs-BA in the ipsilesional internal capsule, and contralesional red nucleus and ventral hippocampus in recovery group (P<0.0025, FDR q<0.05), implying that remaining subcortical structures have an important role in conducting the recovery process in capsular infarct. The SPRT training facilitated motor recovery only in rats with an incomplete destruction of the posterior limb of the internal capsule (PLIC) (Pearson's correlation, P<0.05). Alternative therapeutic interventions are required to enhance the potential for recovery in capsular infarct with complete destruction of PLIC. PMID:25352047

  4. Regulation of Paramyxovirus Fusion Activation: the Hemagglutinin-Neuraminidase Protein Stabilizes the Fusion Protein in a Pretriggered State

    PubMed Central

    Salah, Zuhair W.; Gui, Long; DeVito, Ilaria; Jurgens, Eric M.; Lu, Hong; Yokoyama, Christine C.; Palermo, Laura M.; Lee, Kelly K.

    2012-01-01

    The hemagglutinin (HA)-neuraminidase protein (HN) of paramyxoviruses carries out three discrete activities, each of which affects the ability of HN to promote viral fusion and entry: receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein. Binding of HN to its sialic acid receptor on a target cell triggers its activation of the fusion protein (F), which then inserts into the target cell and mediates the membrane fusion that initiates infection. We provide new evidence for a fourth function of HN: stabilization of the F protein in its pretriggered state before activation. Influenza virus hemagglutinin protein (uncleaved HA) was used as a nonspecific binding protein to tether F-expressing cells to target cells, and heat was used to activate F, indicating that the prefusion state of F can be triggered to initiate structural rearrangement and fusion by temperature. HN expression along with uncleaved HA and F enhances the F activation if HN is permitted to engage the receptor. However, if HN is prevented from engaging the receptor by the use of a small compound, temperature-induced F activation is curtailed. The results indicate that HN helps stabilize the prefusion state of F, and analysis of a stalk domain mutant HN reveals that the stalk domain of HN mediates the F-stabilization effect. PMID:22993149

  5. Activism in an age of restraint: the resiliency of administrative structure in implementing the State Children's Health Insurance Program.

    PubMed

    Plein, L Christopher

    2004-01-01

    This article examines state efforts to build administrative structures and outreach networks in the State Children's Health Insurance Program (CHIP) through a comparative review of 18 states that have been the subject of ongoing research by the Nelson A. Rockefeller Institute of Government. The article explores the role that institutional structures play at the state level in shaping the implementation and administration of federal policy choices. States have generally opted to rely largely on existing Medicaid bureaucracies in order to implement the new CHIP programs. As a result, CHIP programs have been tightly integrated into existing Medicaid structures. Rarely put forward as exemplars of responsiveness and, these bureaucracies have nonetheless played a crucial role in building and managing CHIP programs across the United States. As this analysis will show, this has even been the case in those few states that have opted to officially house CHIP administration outside of the Medicaid bureaucracy. Furthermore, existing Medicaid systems have often been active as partners and participants in efforts to publicize and promote the CHIP program through outreach and education efforts. As part of these initiatives, efforts have been made to portray CHIP as a form of health insurance rather than a welfare benefit. A slight paradox results where key actors in the health and human services bureaucracy play an active role in program management while making efforts to dissassociate the program from the traditional welfare system. These efforts have been largely successful. And in doing so, not only have children been brought into the CHIP program but more families have been connected to the Medicaid program. In short, a review of state experiences reveals the resiliency and flexibility of existing state administrative systems in responding to and addressing substantive policy change. PMID:15962917

  6. 10 CFR 50.13 - Attacks and destructive acts by enemies of the United States; and defense activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Attacks and destructive acts by enemies of the United States; and defense activities. 50.13 Section 50.13 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC... the effects of (a) attacks and destructive acts, including sabotage, directed against the facility...

  7. Motivational Activities for High School Economics, Keyed to the New York State Syllabus "Economics and Economic Decision Making."

    ERIC Educational Resources Information Center

    Dawson, George G.

    This manual provides secondary school teachers with ideas for relating economics to student needs, interests, and experiences. The tentative syllabus "Economics and Economic Decision Making," designed for 12th grade social studies by the New York State Education Department in 1987, is used as a guide. Motivational activities for the 18 topics in…

  8. 10 CFR 50.13 - Attacks and destructive acts by enemies of the United States; and defense activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Attacks and destructive acts by enemies of the United States; and defense activities. 50.13 Section 50.13 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC... the effects of (a) attacks and destructive acts, including sabotage, directed against the facility...

  9. 10 CFR 50.13 - Attacks and destructive acts by enemies of the United States; and defense activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Attacks and destructive acts by enemies of the United States; and defense activities. 50.13 Section 50.13 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC... the effects of (a) attacks and destructive acts, including sabotage, directed against the facility...

  10. 10 CFR 50.13 - Attacks and destructive acts by enemies of the United States; and defense activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Attacks and destructive acts by enemies of the United States; and defense activities. 50.13 Section 50.13 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC... the effects of (a) attacks and destructive acts, including sabotage, directed against the facility...

  11. 10 CFR 50.13 - Attacks and destructive acts by enemies of the United States; and defense activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Attacks and destructive acts by enemies of the United States; and defense activities. 50.13 Section 50.13 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC... the effects of (a) attacks and destructive acts, including sabotage, directed against the facility...

  12. 7 CFR 621.41 - Participation in Federal-State policy and planning activities at the regional level.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Participation in Federal-State policy and planning activities at the regional level. 621.41 Section 621.41 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER...

  13. Warm-Up Activities of Middle and High School Band Directors Participating in State-Level Concert Band Assessments

    ERIC Educational Resources Information Center

    Ward, Justin P.; Hancock, Carl B.

    2016-01-01

    The purpose of this study was to examine the warm-ups chosen by concert band directors participating in state-level performance assessments. We observed 29 middle and high school bands and coded the frequency and duration of warm-up activities and behaviors. Results indicated that most bands rehearsed music and played scales, long tones, and…

  14. State Longitudinal Data Systems for Tracking Outcomes for Students with Disabilities through Postsecondary Activities. inForum

    ERIC Educational Resources Information Center

    Muller, Eve

    2010-01-01

    In recent years, an increasing number of states have been moving towards the development and implementation of longitudinal data systems for tracking the progress of individual K-12 students with disabilities across their academic careers up to and including their postsecondary activities. In an effort to avoid duplication of data collection…

  15. 12 CFR 347.115 - Permissible activities for a foreign branch of an insured state nonmember bank.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... authorized by this section, but that are authorized by 12 CFR 211.4 or FRB interpretations of activities... principal (defined by reference to section 362.1(b) of this chapter), and that are not authorized by 12 CFR... an insured state nonmember bank. 347.115 Section 347.115 Banks and Banking FEDERAL DEPOSIT...

  16. 12 CFR 347.115 - Permissible activities for a foreign branch of an insured state nonmember bank.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... authorized by this section, but that are authorized by 12 CFR 211.4 or FRB interpretations of activities... principal (defined by reference to section 362.1(b) of this chapter), and that are not authorized by 12 CFR... an insured state nonmember bank. 347.115 Section 347.115 Banks and Banking FEDERAL DEPOSIT...

  17. 12 CFR 347.115 - Permissible activities for a foreign branch of an insured state nonmember bank.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... authorized by this section, but that are authorized by 12 CFR 211.4 or FRB interpretations of activities... principal (defined by reference to section 362.1(b) of this chapter), and that are not authorized by 12 CFR... an insured state nonmember bank. 347.115 Section 347.115 Banks and Banking FEDERAL DEPOSIT...

  18. 12 CFR 347.115 - Permissible activities for a foreign branch of an insured state nonmember bank.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... authorized by this section, but that are authorized by 12 CFR 211.4 or FRB interpretations of activities... principal (defined by reference to section 362.1(b) of this chapter), and that are not authorized by 12 CFR... an insured state nonmember bank. 347.115 Section 347.115 Banks and Banking FEDERAL DEPOSIT...

  19. 12 CFR 347.115 - Permissible activities for a foreign branch of an insured state nonmember bank.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... authorized by this section, but that are authorized by 12 CFR 211.4 or FRB interpretations of activities... principal (defined by reference to section 362.1(b) of this chapter), and that are not authorized by 12 CFR... an insured state nonmember bank. 347.115 Section 347.115 Banks and Banking FEDERAL DEPOSIT...

  20. Interaction of Rio1 Kinase with Toyocamycin Reveals a Conformational Switch That Controls Oligomeric State and Catalytic Activity

    SciTech Connect

    Kiburu, Irene N.; LaRonde-LeBlanc, Nicole

    2012-10-10

    Rio1 kinase is an essential ribosome-processing factor required for proper maturation of 40 S ribosomal subunit. Although its structure is known, several questions regarding its functional remain to be addressed. We report that both Archaeoglobus fulgidus and human Rio1 bind more tightly to an adenosine analog, toyocamycin, than to ATP. Toyocamycin has antibiotic, antiviral and cytotoxic properties, and is known to inhibit ribosome biogenesis, specifically the maturation of 40 S. We determined the X-ray crystal structure of toyocamycin bound to Rio1 at 2.0 {angstrom} and demonstrated that toyocamycin binds in the ATP binding pocket of the protein. Despite this, measured steady state kinetics were inconsistent with strict competitive inhibition by toyocamycin. In analyzing this interaction, we discovered that Rio1 is capable of accessing multiple distinct oligomeric states and that toyocamycin may inhibit Rio1 by stabilizing a less catalytically active oligomer. We also present evidence of substrate inhibition by high concentrations of ATP for both archaeal and human Rio1. Oligomeric state studies show both proteins access a higher order oligomeric state in the presence of ATP. The study revealed that autophosphorylation by Rio1 reduces oligomer formation and promotes monomerization, resulting in the most active species. Taken together, these results suggest the activity of Rio1 may be modulated by regulating its oligomerization properties in a conserved mechanism, identifies the first ribosome processing target of toyocamycin and presents the first small molecule inhibitor of Rio1 kinase activity.