Science.gov

Sample records for active highly selective

  1. Activities Selected from the High School Geography Project.

    ERIC Educational Resources Information Center

    Natoli, Salvatore J., Ed.; And Others

    Out of approximately 50 activities which were, for a variety of reasons, not included in the final version of the High School Geography Project course, Geography in an Urban Age, the HSGP staff selected eight which would be useful in many secondary school classrooms. The activities included here are: 1) Operation Bigger Beef (on themes of cultural…

  2. Selection of quiescent Escherichia coli with high metabolic activity.

    PubMed

    Sonderegger, Marco; Schümperli, Michael; Sauer, Uwe

    2005-01-01

    Sustained metabolic activity in non-growing, quiescent cells can increase the operational life-span of bio-processes and improve process economics by decoupling production from cell growth. Because of the ill-defined molecular nature of this phenotype, we developed selection protocols for the evolution of quiescent Escherichia coli mutants that exhibit high metabolic activity in ammonium starvation-induced stationary phase. The best enrichment procedures were continuously or discontinuously fed ammonium-limited chemostat cultures with a very low dilution rate of 0.03 h(-1). After 40 generations of selection, improved mutants with up to doubled catabolic rates in stationary phase were isolated. The metabolically most active clones were identified by screening for high specific glucose uptake rates during ammonium starvation-induced stationary phase in deep-well microtiter plates. PMID:15721805

  3. Metabolism of a highly selective gelatinase inhibitor generates active metabolite.

    PubMed

    Lee, Mijoon; Villegas-Estrada, Adriel; Celenza, Giuseppe; Boggess, Bill; Toth, Marta; Kreitinger, Gloria; Forbes, Christopher; Fridman, Rafael; Mobashery, Shahriar; Chang, Mayland

    2007-11-01

    (4-Phenoxyphenylsulfonyl)methylthiirane (inhibitor 1) is a highly selective inhibitor of gelatinases (matrix metalloproteinases 2 and 9), which is showing considerable promise in animal models for cancer and stroke. Despite demonstrated potent, selective, and effective inhibition of gelatinases both in vitro and in vivo, the compound is rapidly metabolized, implying that the likely activity in vivo is due to a metabolite rather than the compound itself. To this end, metabolism of inhibitor 1 was investigated in in vitro systems. Four metabolites were identified by LC/MS-MS and the structures of three of them were further validated by comparison with authentic synthetic samples. One metabolite, 4-(4-thiiranylmethanesulfonylphenoxy)phenol (compound 21), was generated by hydroxylation of the terminal phenyl group of 1. This compound was investigated in kinetics of inhibition of several matrix metalloproteinases. This metabolite was a more potent slow-binding inhibitor of gelatinases (matrix metalloproteinase-2 and matrix metalloproteinase-9) than the parent compound 1, but it also served as a slow-binding inhibitor of matrix metalloproteinase-14, the upstream activator of matrix metalloproteinase-2. PMID:17927722

  4. Novel Antimicrobial Peptides with High Anticancer Activity and Selectivity

    PubMed Central

    Chen, Kuan-Hao; Yu, Hui-Yuan; Chih, Ya-Han; Cheng, Hsi-Tsung; Chou, Yu-Ting; Cheng, Jya-Wei

    2015-01-01

    We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics. PMID:25970292

  5. Highly Selective Synthesis of Catalytically Active Monodisperse Rhodium Nanocubes

    SciTech Connect

    Zhang, Y.; Grass, M.E.; Kuhn, J.N.; Tao, F.; Habas, S.E.; Huang, W.; Yang, P.; Somorjai, G.A.

    2009-02-21

    Synthesis of monodisperse and shape-controlled colloidal inorganic nanocrystals (NCs) is of increasing scientific interest and technological significance. Recently, shape control of Pt, Pd, Ag, Au, and Rh NCs has been obtained by tuning growth kinetics in various solution-phase approaches, including modified polyol methods, seeded growth by polyol reduction, thermolysis of organometallics, and micelle techniques. Control of reduction kinetics of the noble metal precursors and regulation of the relative growth rates of low-index planes (i.e. {l_brace}100{r_brace} and {l_brace}111{r_brace}) via selective adsorption of selected chemical species are two keys for achieving shape modification of noble metal NCs. One application for noble metal NCs of well-defined shape is in understanding how NC faceting (determines which crystallographic planes are exposed) affects catalytic performance. Rh NCs are used in many catalytic reactions, including hydrogenation, hydroformylation, hydrocarbonylation, and combustion reactions. Shape manipulation of Rh NCs may be important in understanding how faceting on the nanoscale affects catalytic properties, but such control is challenging and there are fewer reports on the shape control of Rh NCs compared to other noble metals. Xia and coworkers obtained Rh multipods exhibiting interesting surface plasmonic properties by a polyol approach. The Somorjai and Tilley groups synthesized crystalline Rh multipods, cubes, horns and cuboctahedra, via polyol seeded growth. Son and colleagues prepared catalytically active monodisperse oleylamine-capped tetrahedral Rh NCs for the hydrogenation of arenes via an organometallic route. More recently, the Somorjai group synthesized sizetunable monodisperse Rh NCs using a one-step polyol technique. In this Communication, we report the highly selective synthesis of catalytically active, monodisperse Rh nanocubes of < 10 nm by a seedless polyol method. In this approach, Br{sup -} ions from trimethyl

  6. High School Girls' Perceptions of Selected Fitness Activities

    ERIC Educational Resources Information Center

    Wilkinson, Carol; Bretzing, Robyn

    2011-01-01

    High school students, and particularly girls, are not very active (Centers for Disease Control and Prevention, 2006). To help girls develop the abilities to enjoy lifetime, healthy physical activity, physical educators need to provide curricula that will achieve this goal. In the process, they need to make sure they are aligned with the current…

  7. Highly selective antibacterial activities of silver nanoparticles against Bacillus subtilis.

    PubMed

    Li, Ju; Rong, Kaifeng; Zhao, Huiping; Li, Fei; Lu, Zhong; Chen, Rong

    2013-10-01

    Silver nanoparticles (AgNPs) with different sizes (5, 15 and 55 nm) were synthesized via simple method, and characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive X-ray microanalysis (EDX) and ultraviolet-visible absorption spectroscopy (UV-Vis). The antibacterial activities of the prepared AgNPs against Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis) were evaluated by inhibition zone, inhibition curve, and colony counting methods. The results showed that the AgNPs exhibited obvious bacterium-selective and size-dependent antibacterial activities. The Gram-positive bacteria S. aureus and B. subtilis were more sensitive to AgNPs than Gram-negative bacterium E. coli. Interestingly, AgNPs displayed remarkably antibacterial activities against B. subtilis among Gram-positive bacteria, regardless of whether in separately or cocultured bacteria. It also showed that AgNPs with 5 nm in size presented the highest antibacterial activity against both Gram-negative and Gram-positive bacteria. The effects of AgNPs on the membrane leakage of the reducing sugars from three bacteria were also measured by 3,5-dinitrosalicylic acid method. The leakage amount of reducing sugars from B. subtilis was the highest among the tested bacteria, indicating that AgNPs could damage the structure of bacteria cell membrane and resulted in the leakage of reducing sugars, leading to the death of bacteria. PMID:24245147

  8. Enzymatically active high-flux selectively gas-permeable membranes

    DOEpatents

    Jiang, Ying-Bing; Cecchi, Joseph L.; Rempe, Susan; FU, Yaqin; Brinker, C. Jeffrey

    2016-01-26

    An ultra-thin, catalyzed liquid transport medium-based membrane structure fabricated with a porous supporting substrate may be used for separating an object species such as a carbon dioxide object species. Carbon dioxide flux through this membrane structures may be several orders of magnitude higher than traditional polymer membranes with a high selectivity to carbon dioxide. Other gases such as molecular oxygen, molecular hydrogen, and other species including non-gaseous species, for example ionic materials, may be separated using variations to the membrane discussed.

  9. Lifecycle Prognostics Architecture for Selected High-Cost Active Components

    SciTech Connect

    N. Lybeck; B. Pham; M. Tawfik; J. B. Coble; R. M. Meyer; P. Ramuhalli; L. J. Bond

    2011-08-01

    There are an extensive body of knowledge and some commercial products available for calculating prognostics, remaining useful life, and damage index parameters. The application of these technologies within the nuclear power community is still in its infancy. Online monitoring and condition-based maintenance is seeing increasing acceptance and deployment, and these activities provide the technological bases for expanding to add predictive/prognostics capabilities. In looking to deploy prognostics there are three key aspects of systems that are presented and discussed: (1) component/system/structure selection, (2) prognostic algorithms, and (3) prognostics architectures. Criteria are presented for component selection: feasibility, failure probability, consequences of failure, and benefits of the prognostics and health management (PHM) system. The basis and methods commonly used for prognostics algorithms are reviewed and summarized. Criteria for evaluating PHM architectures are presented: open, modular architecture; platform independence; graphical user interface for system development and/or results viewing; web enabled tools; scalability; and standards compatibility. Thirteen software products were identified and discussed in the context of being potentially useful for deployment in a PHM program applied to systems in a nuclear power plant (NPP). These products were evaluated by using information available from company websites, product brochures, fact sheets, scholarly publications, and direct communication with vendors. The thirteen products were classified into four groups of software: (1) research tools, (2) PHM system development tools, (3) deployable architectures, and (4) peripheral tools. Eight software tools fell into the deployable architectures category. Of those eight, only two employ all six modules of a full PHM system. Five systems did not offer prognostic estimates, and one system employed the full health monitoring suite but lacked operations and

  10. Highly active ozonides selected against drug resistant malaria.

    PubMed

    Lobo, Lis; Sousa, Bruno de; Cabral, Lília; Cristiano, Maria Ls; Nogueira, Fátima

    2016-06-01

    Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites. PMID:27276364

  11. Highly active ozonides selected against drug resistant malaria

    PubMed Central

    Lobo, Lis; de Sousa, Bruno; Cabral, Lília; Cristiano, Maria LS; Nogueira, Fátima

    2016-01-01

    Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites. PMID:27276364

  12. Design of a high activity and selectivity alcohol catalyst

    SciTech Connect

    Foley, H.C.; Mills, G.A.

    1992-02-07

    Results of the pyridine adsorption, studies on native and K-doped alumina provide fundamental grounding for the observed methanol dehydration activity of these samples. Both the reactor studies and the pyridine adsorption studies support the conclusion that the K-doped sample had reduced Lewis acidity. Moreover, we were able to measurably alter the acidity of the support surface by our ion exchange treatment. More significantly, when reactor results for transition-metal loaded samples are reconsidered in combination with their surface characteristics suggested by our pyridine adsorption studies, our hypothesis that Rh and Mo have ultimately titrated the support surface seems all the more convincing. Hence, in light of the pyridine adsorption results, the attenuation of a transition-metal based decomposition pathway for methanol on the metal-loaded samples-as seen in the reactor testing-is all the more reasonable.

  13. Pyridazinone derivatives displaying highly potent and selective inhibitory activities against c-Met tyrosine kinase.

    PubMed

    Liu, Yang; Jin, Shiyu; Peng, Xia; Lu, Dong; Zeng, Limin; Sun, Yiming; Ai, Jing; Geng, Meiyu; Hu, Youhong

    2016-01-27

    Over activation of c-Met tyrosine kinase is known to promote tumorigenesis and metastasis, as well as to cause therapeutic resistance. Herein we describe the design, synthesis and biological activities of novel, ATP-competitive, c-Met tyrosine kinase inhibitors that are members of the 6-aryl-2-(3-(heteroarylamino)benzyl)pyridazinone family. A structure-activity relationship (SAR) study of these substances led to identification of pyridazinone 19 as a highly selective and potent c-Met tyrosine inhibitor, which displays favorable pharmacokinetic properties in mice and significant antitumor activity against a c-Met driven EBC-1 tumor xenograft. PMID:26698536

  14. A highly selective, reversible inhibitor identified by comparative chemoproteomics modulates diacylglycerol lipase activity in neurons

    PubMed Central

    Baggelaar, Marc P.; Chameau, Pascal J. P.; Kantae, Vasudev; Hummel, Jessica; Hsu, Ku-Lung; Janssen, Freek; van der Wel, Tom; Soethoudt, Marjolein; Deng, Hui; den Dulk, Hans; Allarà, Marco; Florea, Bogdan I.; Di Marzo, Vincenzo; Wadman, Wytse J.; Kruse, Chris G.; Overkleeft, Herman S.; Hankemeier, Thomas; Werkman, Taco R.; Cravatt, Benjamin F.; van der Stelt, Mario

    2016-01-01

    Diacylglycerol lipase (DAGL)-α and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective and reversible inhibitors are required to study the function of DAGLs in neuronal cells in an acute and temporal fashion, but they are currently lacking. Here, we describe the identification of a highly selective DAGL inhibitor using structure-guided and a chemoproteomics strategy to characterize the selectivity of the inhibitor in complex proteomes. Key to the success of this approach is the use of comparative and competitive activity-based proteome profiling (ABPP), in which broad-spectrum and tailor-made activity-based probes are combined to report on the inhibition of a protein family in its native environment. Competitive ABPP with broad-spectrum fluorophosphonate-based probes and specific β-lactone-based probes led to the discovery of α-ketoheterocycle LEI105 as a potent, highly selective and reversible dual DAGL-α/DAGL-β inhibitor. LEI105 did not affect other enzymes involved in endocannabinoid metabolism including abhydrolase domain-containing protein 6, abhydrolase domain-containing protein 12, monoacylglycerol lipase and fatty acid amide hydrolase and did not display affinity for the cannabinoid CB1 receptor. Targeted lipidomics revealed that LEI105 concentration-dependently reduced 2-AG levels, but not anandamide levels, in Neuro2A cells. We show that cannabinoid CB1-receptor-mediated short-term synaptic plasticity in a mouse hippocampal slice model can be reduced by LEI105. Thus, we have developed a highly selective DAGL inhibitor and provide new pharmacological evidence to support the hypothesis that ‘on demand biosynthesis’ of 2-AG is responsible for retrograde signaling. PMID:26083464

  15. Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations

    PubMed Central

    Cui, Yuanyuan; Yang, Fan; Cao, Xu; Yarov-Yarovoy, Vladimir

    2012-01-01

    The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate. PMID:22412190

  16. Discovery of Isonicotinamides as Highly Selective, Brain Penetrable, and Orally Active Glycogen Synthase Kinase-3 Inhibitors.

    PubMed

    Luo, Guanglin; Chen, Ling; Burton, Catherine R; Xiao, Hong; Sivaprakasam, Prasanna; Krause, Carol M; Cao, Yang; Liu, Nengyin; Lippy, Jonathan; Clarke, Wendy J; Snow, Kimberly; Raybon, Joseph; Arora, Vinod; Pokross, Matt; Kish, Kevin; Lewis, Hal A; Langley, David R; Macor, John E; Dubowchik, Gene M

    2016-02-11

    GSK-3 is a serine/threonine kinase that has numerous substrates. Many of these proteins are involved in the regulation of diverse cellular functions, including metabolism, differentiation, proliferation, and apoptosis. Inhibition of GSK-3 may be useful in treating a number of diseases including Alzheimer's disease (AD), type II diabetes, mood disorders, and some cancers, but the approach poses significant challenges. Here, we present a class of isonicotinamides that are potent, highly kinase-selective GSK-3 inhibitors, the members of which demonstrated oral activity in a triple-transgenic mouse model of AD. The remarkably high kinase selectivity and straightforward synthesis of these compounds bode well for their further exploration as tool compounds and therapeutics. PMID:26751161

  17. RV-23, a Melittin-Related Peptide with Cell-Selective Antibacterial Activity and High Hemocompatibility.

    PubMed

    Zhang, Shi-Kun; Ma, Qian; Li, Su-Bo; Gao, Hong-Wei; Tan, Ying-Xia; Gong, Feng; Ji, Shou-Ping

    2016-06-28

    RV-23 is a melittin-related antibacterial peptide (MRP) with lower cytotoxicity than either melittin or AR-23, another MRP. The aim of this study was to explore the mechanism of RV- 23's antibacterial selectivity and its hemocompatibility. The results showed that all the peptides exhibited lytic activity against Staphylococcus aureus and Escherichia coli, with RV-23 showing the highest potency. Moreover, RV-23 had lower cytotoxicity than melittin or AR-23 at their minimal inhibitory concentration. In addition, CD experiments showed that melittin, RV-23, and AR-23 all had a typical α-helical structure, and RV-23 had the lowest α-helix content. The structural information showed that RV-23 has the lowest hydrophobicity and highest hydrophobic moment. Because hydrophobicity and α-helix content are believed to correlate with hemolysis, the results indicate that the selective lytic activity against bacteria of RV-23 may be due to its low hydrophobicity and α-helicity, which lead to low cytotoxicity without affecting antibacterial activity. Furthermore, RV-23 did not affect the structure and function of blood components such as red blood cells, platelets, albumin, and the blood coagulation system. In conclusion, RV-23 is a cell-selective antibacterial peptide with high hemocompatibility due to its unique structure. PMID:26975766

  18. Selective enrichment and production of highly urease active bacteria by non-sterile (open) chemostat culture.

    PubMed

    Cheng, Liang; Cord-Ruwisch, Ralf

    2013-10-01

    In general, bioprocesses can be subdivided into naturally occurring processes, not requiring sterility (e.g., beer brewing, wine making, lactic acid fermentation, or biogas digestion) and other processes (e.g., the production of enzymes and antibiotics) that typically require a high level of sterility to avoid contaminant microbes overgrowing the production strain. The current paper describes the sustainable, non-sterile production of an industrial enzyme using activated sludge as inoculum. By using selective conditions (high pH, high ammonia concentration, and presence of urea) for the target bacterium, highly active ureolytic bacteria, physiologically resembling Sporosarcina pasteurii were reproducibly enriched and then continuously produced via chemostat operation of the bioreactor. When using a pH of 10 and about 0.2 M urea in a yeast extract-based medium, ureolytic bacteria developed under aerobic chemostat operation at hydraulic retention times of about 10 h with urease levels of about 60 μmol min⁻¹ ml⁻¹ culture. For cost minimization at an industrial scale the costly protein-rich yeast extract medium could be replaced by commercial milk powder or by lysed activated sludge. Glutamate, molasses, or glucose-based media did not result in the enrichment of ureolytic bacteria by the chemostat. The concentration of intracellular urease was sufficiently high such that the produced raw effluent from the reactor could be used directly for biocementation in the field. PMID:23892419

  19. Two-dimensional gold nanostructures with high activity for selective oxidation of carbon-hydrogen bonds.

    PubMed

    Wang, Liang; Zhu, Yihan; Wang, Jian-Qiang; Liu, Fudong; Huang, Jianfeng; Meng, Xiangju; Basset, Jean-Marie; Han, Yu; Xiao, Feng-Shou

    2015-01-01

    Efficient synthesis of stable two-dimensional (2D) noble metal catalysts is a challenging topic. Here we report the facile synthesis of 2D gold nanosheets via a wet chemistry method, by using layered double hydroxide as the template. Detailed characterization with electron microscopy and X-ray photoelectron spectroscopy demonstrates that the nanosheets are negatively charged and [001] oriented with thicknesses varying from single to a few atomic layers. X-ray absorption spectroscopy reveals unusually low gold-gold coordination numbers. These gold nanosheets exhibit high catalytic activity and stability in the solvent-free selective oxidation of carbon-hydrogen bonds with molecular oxygen. PMID:25902034

  20. Two-dimensional gold nanostructures with high activity for selective oxidation of carbon–hydrogen bonds

    PubMed Central

    Wang, Liang; Zhu, Yihan; Wang, Jian-Qiang; Liu, Fudong; Huang, Jianfeng; Meng, Xiangju; Basset, Jean-Marie; Han, Yu; Xiao, Feng-Shou

    2015-01-01

    Efficient synthesis of stable two-dimensional (2D) noble metal catalysts is a challenging topic. Here we report the facile synthesis of 2D gold nanosheets via a wet chemistry method, by using layered double hydroxide as the template. Detailed characterization with electron microscopy and X-ray photoelectron spectroscopy demonstrates that the nanosheets are negatively charged and [001] oriented with thicknesses varying from single to a few atomic layers. X-ray absorption spectroscopy reveals unusually low gold–gold coordination numbers. These gold nanosheets exhibit high catalytic activity and stability in the solvent-free selective oxidation of carbon–hydrogen bonds with molecular oxygen. PMID:25902034

  1. Two-dimensional gold nanostructures with high activity for selective oxidation of carbon-hydrogen bonds

    NASA Astrophysics Data System (ADS)

    Wang, Liang; Zhu, Yihan; Wang, Jian-Qiang; Liu, Fudong; Huang, Jianfeng; Meng, Xiangju; Basset, Jean-Marie; Han, Yu; Xiao, Feng-Shou

    2015-04-01

    Efficient synthesis of stable two-dimensional (2D) noble metal catalysts is a challenging topic. Here we report the facile synthesis of 2D gold nanosheets via a wet chemistry method, by using layered double hydroxide as the template. Detailed characterization with electron microscopy and X-ray photoelectron spectroscopy demonstrates that the nanosheets are negatively charged and [001] oriented with thicknesses varying from single to a few atomic layers. X-ray absorption spectroscopy reveals unusually low gold-gold coordination numbers. These gold nanosheets exhibit high catalytic activity and stability in the solvent-free selective oxidation of carbon-hydrogen bonds with molecular oxygen.

  2. Impact of high-risk conjunctions on Active Debris Removal target selection

    NASA Astrophysics Data System (ADS)

    Lidtke, Aleksander A.; Lewis, Hugh G.; Armellin, Roberto

    2015-10-01

    Space debris simulations show that if current space launches continue unchanged, spacecraft operations might become difficult in the congested space environment. It has been suggested that Active Debris Removal (ADR) might be necessary in order to prevent such a situation. Selection of objects to be targeted by ADR is considered important because removal of non-relevant objects will unnecessarily increase the cost of ADR. One of the factors to be used in this ADR target selection is the collision probability accumulated by every object. This paper shows the impact of high-probability conjunctions on the collision probability accumulated by individual objects as well as the probability of any collision occurring in orbit. Such conjunctions cannot be predicted far in advance and, consequently, not all the objects that will be involved in such dangerous conjunctions can be removed through ADR. Therefore, a debris remediation method that would address such events at short notice, and thus help prevent likely collisions, is suggested.

  3. Neurobiology of Mice Selected for High Voluntary Wheel-running Activity.

    PubMed

    Rhodes, Justin S; Gammie, Stephen C; Garland, Theodore

    2005-06-01

    Selective breeding of house mice has been used to study the evolution of locomotor behavior. Our model consists of 4 replicate lines selectively bred for high voluntary wheel running (High-Runner) and 4 bred randomly (Control). The major changes in High-Runner lines appear to have taken place in the brain rather than in capacities for exercise. Their neurobiological profile resembles features of human Attention Deficit Hyperactivity Disorder (ADHD) and is also consistent with high motivation for exercise as a natural reward. Both ADHD and motivation for natural rewards (such as food and sex), as well as drugs of abuse, have been associated with alterations in function of the neuromodulator dopamine, and High-Runner mice respond differently to dopamine drugs. In particular, drugs that block the dopamine transporter protein (such as Ritalin and cocaine) reduce the high-intensity running of High-Runner mice but have little effect on Control mice. In preliminary studies of mice exercised on a treadmill, brain dopamine concentrations did not differ, suggesting that changes in the dopamine system may have occurred downstream of dopamine production (e.g., receptor expression or transduction). Brain imaging by immunohistochemical detection of c-Fos identified several key regions (prefrontal cortex, nucleus accumbens, caudate-putamen, lateral hypothalamus) that appear to play a role in the differential response to Ritalin and in the increased motivation for running in High-Runner mice. The activation of other brain regions, such as the hippocampus, was closely associated with wheel running itself. Chronic wheel running (several weeks) also increased the production of new neurons to apparently maximal levels in the hippocampus, but impaired learning in High-Runner mice. We discuss the biomedical implications of these findings. PMID:21676789

  4. Running behavior and its energy cost in mice selectively bred for high voluntary locomotor activity.

    PubMed

    Rezende, Enrico L; Gomes, Fernando R; Chappell, Mark A; Garland, Theodore

    2009-01-01

    Locomotion is central to behavior and intrinsic to many fitness-critical activities (e.g., migration, foraging), and it competes with other life-history components for energy. However, detailed analyses of how changes in locomotor activity and running behavior affect energy budgets are scarce. We quantified these effects in four replicate lines of house mice that have been selectively bred for high voluntary wheel running (S lines) and in their four nonselected control lines (C lines). We monitored wheel speeds and oxygen consumption for 24-48 h to determine daily energy expenditure (DEE), resting metabolic rate (RMR), locomotor costs, and running behavior (bout characteristics). Daily running distances increased roughly 50%-90% in S lines in response to selection. After we controlled for body mass effects, selection resulted in a 23% increase in DEE in males and a 6% increase in females. Total activity costs (DEE - RMR) accounted for 50%-60% of DEE in both S and C lines and were 29% higher in S males and 5% higher in S females compared with their C counterparts. Energetic costs of increased daily running distances differed between sexes because S females evolved higher running distances by running faster with little change in time spent running, while S males also spent 40% more time running than C males. This increase in time spent running impinged on high energy costs because the majority of running costs stemmed from "postural costs" (the difference between RMR and the zero-speed intercept of the speed vs. metabolic rate relationship). No statistical differences in these traits were detected between S and C females, suggesting that large changes in locomotor behavior do not necessarily effect overall energy budgets. Running behavior also differed between sexes: within S lines, males ran with more but shorter bouts than females. Our results indicate that selection effects on energy budgets can differ dramatically between sexes and that energetic constraints in S

  5. Patients treated with high-dose intravenous immunoglobulin show selective activation of regulatory T cells

    PubMed Central

    Tjon, A S W; Tha-In, T; Metselaar, H J; van Gent, R; van der Laan, L J W; Groothuismink, Z M A; te Boekhorst, P A W; van Hagen, P M; Kwekkeboom, J

    2013-01-01

    Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (Tregs) in humans in vivo. Blood was collected from IVIg-treated patients with immunodeficiency or autoimmune disease who were treated with low-dose (n = 12) or high-dose (n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4+CD25+forkhead box protein 3 (FoxP3+) Tregs and of conventional CD4+FoxP3− T-helper cells (Tconv) were measured. The suppressive capacity of Tregs purified from blood collected at the time-points indicated was determined in an ex-vivo assay. High-dose, but not low-dose, IVIg treatment enhanced the activation status of circulating Tregs, as shown by increased FoxP3 and human leucocyte antigen D-related (HLA-DR) expression, while numbers of circulating Tregs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified Tregs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of Tconv was not affected by IVIg. We conclude that high-dose IVIg treatment activates Tregs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders. PMID:23607448

  6. High levels of absorption in orientation-unbiased, radio-selected 3CR Active Galaxies

    NASA Astrophysics Data System (ADS)

    Wilkes, Belinda J.; Haas, Martin; Barthel, Peter; Leipski, Christian; Kuraszkiewicz, Joanna; Worrall, Diana; Birkinshaw, Mark; Willner, Steven P.

    2014-08-01

    A critical problem in understanding active galaxies (AGN) is the separation of intrinsic physical differences from observed differences that are due to orientation. Obscuration of the active nucleus is anisotropic and strongly frequency dependent leading to complex selection effects for observations in most wavebands. These can only be quantified using a sample that is sufficiently unbiased to test orientation effects. Low-frequency radio emission is one way to select a close-to orientation-unbiased sample, albeit limited to the minority of AGN with strong radio emission.Recent Chandra, Spitzer and Herschel observations combined with multi-wavelength data for a complete sample of high-redshift (1 24.2) = 2.5:1.4:1 in these high-luminosity (log L(0.3-8keV) ~ 44-46) sources. These ratios are consistent with current expectations based on modelingthe Cosmic X-ray Background. A strong correlation with radio orientation constrains the geometry of the obscuring disk/torus to have a ~60 degree opening angle and ~12 degree Compton-thick cross-section. The deduced ~50% obscured fraction of the population contrasts with typical estimates of ~20% obscured in optically- and X-ray-selected high-luminosity samples. Once the primary nuclear emission is obscured, AGN X-ray spectra are frequently dominated by unobscured non-nuclear or scattered nuclear emission which cannot be distinguished from direct nuclear emission with a lower obscuration level unless high quality data is available. As a result, both the level of obscuration and the estimated instrinsic luminosities of highly-obscured AGN are likely to be significantly (*10-1000) underestimated for 25-50% of the population. This may explain the lower obscured fractions reported for optical and X-ray samples which have no independent measure of the AGN

  7. Active frequency selective surfaces

    NASA Astrophysics Data System (ADS)

    Buchwald, Walter R.; Hendrickson, Joshua; Cleary, Justin W.; Guo, Junpeng

    2013-05-01

    Split ring resonator arrays are investigated for use as active elements for the realization of voltage controllable frequency selective surfaces. Finite difference time domain simulations suggest the absorptive and reflective properties of such surfaces can be externally controlled through modifications of the split ring resonator gap impedance. In this work, such voltage-controlled resonance tuning is obtained through the addition of an appropriately designed high electron mobility transistor positioned across the split ring resonator gap. It is shown that a 0.5μm gate length high electron mobility transistor allows voltage controllable switching between the two resonant conditions associated with a split ring resonator and that of a closed loop geometry when the surface is illuminated with THz radiation. Partial switching between these two resonant conditions is observed at larger gate lengths. Such active frequency selective surfaces are proposed, for example, for use as modulators in THz detection schemes and as RF filters in radar applications when scaled to operate at GHz frequencies.

  8. Redox-Active Metal-Organic Composites for Highly Selective Oxygen Separation Applications.

    PubMed

    Zhang, Wen; Banerjee, Debasis; Liu, Jian; Schaef, Herbert T; Crum, Jarrod V; Fernandez, Carlos A; Kukkadapu, Ravi K; Nie, Zimin; Nune, Satish K; Motkuri, Radha K; Chapman, Karena W; Engelhard, Mark H; Hayes, James C; Silvers, Kurt L; Krishna, Rajamani; McGrail, B Peter; Liu, Jun; Thallapally, Praveen K

    2016-05-01

    A redox-active metal-organic composite material shows improved and selective O2 adsorption over N2 with respect to individual components (MIL-101 and ferrocene). The O2 sensitivity of the composite material arises due to the formation of maghemite nanoparticles with the pore of the metal-organic framework material. PMID:26953336

  9. Artificial selection for high activity favors mighty mini-muscles in house mice.

    PubMed

    Houle-Leroy, Philippe; Guderley, Helga; Swallow, John G; Garland, Theodore

    2003-02-01

    After 14 generations of selection for voluntary wheel running, mice from the four replicate selected lines ran, on average, twice as many revolutions per day as those from the four unselected control lines. To examine whether the selected lines followed distinct strategies in the correlated responses of the size and metabolic capacities of the hindlimb muscles, we examined mice from selected lines, housed for 8 wk in cages with access to running wheels that were either free to rotate ("wheel access" group) or locked ("sedentary"). Thirteen of twenty individuals in one selected line (line 6) and two of twenty in another (line 3) showed a marked reduction ( approximately 50%) in total hindlimb muscle mass, consistent with the previously described expression of a small-muscle phenotype. Individuals with these "mini-muscles" were not significantly smaller in total body mass compared with line-mates with normal-sized muscles. Access to free wheels did not affect the relative mass of the mini-muscles, but did result in typical mammalian training effects for mitochondrial enzyme activities. Individuals with mini-muscles showed a higher mass-specific muscle aerobic capacity as revealed by the maximal in vitro rates of citrate synthase and cytochrome c oxidase. Moreover, these mice showed the highest activities of hexokinase and carnitine palmitoyl transferase. Females with mini-muscles showed the highest levels of phosphofructokinase, and males with mini-muscles the highest levels of pyruvate dehydrogenase. As shown by total muscle enzyme contents, the increase in mass-specific aerobic capacity almost completely compensated for the reduction caused by the "loss" of muscle mass. Moreover, the mini-muscle mice exhibited the lowest contents of lactate dehydrogenase and glycogen phosphorylase. Interestingly, metabolic capacities of mini-muscled mice resemble those of muscles after endurance training. Overall, our results demonstrate that during selection for voluntary wheel

  10. A new experimental setup for high-pressure catalytic activity measurements on surface deposited mass-selected Pt clusters

    SciTech Connect

    Watanabe, Yoshihide; Isomura, Noritake

    2009-09-15

    A new experimental setup to study catalytic and electronic properties of size-selected clusters on metal oxide substrates from the viewpoint of cluster-support interaction and to formulate a method for the development of heterogeneous catalysts such as automotive exhaust catalysts has been developed. The apparatus consists of a size-selected cluster source, a photoemission spectrometer, a scanning tunneling microscope (STM), and a high-pressure reaction cell. The high-pressure reaction cell measurements provided information on catalytic properties in conditions close to practical use. The authors investigated size-selected platinum clusters deposited on a TiO{sub 2}(110) surface using a reaction cell and STM. Catalytic activity measurements showed that the catalytic activities have a cluster-size dependency.

  11. Selective attention modulates high-frequency activity in the face-processing network.

    PubMed

    Müsch, Kathrin; Hamamé, Carlos M; Perrone-Bertolotti, Marcela; Minotti, Lorella; Kahane, Philippe; Engel, Andreas K; Lachaux, Jean-Philippe; Schneider, Till R

    2014-11-01

    Face processing depends on the orchestrated activity of a large-scale neuronal network. Its activity can be modulated by attention as a function of task demands. However, it remains largely unknown whether voluntary, endogenous attention and reflexive, exogenous attention to facial expressions equally affect all regions of the face-processing network, and whether such effects primarily modify the strength of the neuronal response, the latency, the duration, or the spectral characteristics. We exploited the good temporal and spatial resolution of intracranial electroencephalography (iEEG) and recorded from depth electrodes to uncover the fast dynamics of emotional face processing. We investigated frequency-specific responses and event-related potentials (ERP) in the ventral occipito-temporal cortex (VOTC), ventral temporal cortex (VTC), anterior insula, orbitofrontal cortex (OFC), and amygdala when facial expressions were task-relevant or task-irrelevant. All investigated regions of interest (ROI) were clearly modulated by task demands and exhibited stronger changes in stimulus-induced gamma band activity (50-150 Hz) when facial expressions were task-relevant. Observed latencies demonstrate that the activation is temporally coordinated across the network, rather than serially proceeding along a processing hierarchy. Early and sustained responses to task-relevant faces in VOTC and VTC corroborate their role for the core system of face processing, but they also occurred in the anterior insula. Strong attentional modulation in the OFC and amygdala (300 msec) suggests that the extended system of the face-processing network is only recruited if the task demands active face processing. Contrary to our expectation, we rarely observed differences between fearful and neutral faces. Our results demonstrate that activity in the face-processing network is susceptible to the deployment of selective attention. Moreover, we show that endogenous attention operates along the whole

  12. The crystal structure of a bimorphinan with highly selective kappa opioid receptor antagonist activity

    NASA Astrophysics Data System (ADS)

    Urbańczyk-Lipkowska, Zofia; Etter, Margaret C.; Lipkowski, Andrzej W.; Portoghese, Philip S.

    1987-07-01

    The crystal structure of the dihydrobromide heptahydrate of nor-binaltorphimine (17, 17'-bis(cyclopropylmethyl)-6,6',7,7'-tetrahydro-4,5α: 4',5'α-diepoxy-6,6'-imino[7,7' bimorphinan]-3,3',14,14'-tetraol)is presented. This structure is the first reported structure of a rigid bivalent opioid ligand. Two morphinan pharmacophores are connected by a rigid spacer, the pyrrole ring. The nor-binaltorphimine structure itself shows unique, high selectivity as a kappa opioid receptor antagonist. Crystal data: P3 2, Z = 3, a = b = 20.223 (4), c = 9.541(7) Å, α = β = 90°, γ = 120°; R = 0.079 (1765 reflections, Fobs > 1σ( F)).

  13. Four minutes of in-class high-intensity interval activity improves selective attention in 9- to 11-year olds.

    PubMed

    Ma, Jasmin K; Le Mare, Lucy; Gurd, Brendon J

    2015-03-01

    The amount of time allocated to physical activity in schools is declining. Time-efficient physical activity solutions that demonstrate their impact on academic achievement-related outcomes are needed to prioritize physical activity within the school curricula. "FUNtervals" are 4-min, high-intensity interval activities that use whole-body actions to complement a storyline. The purpose of this study was to (i) explore whether FUNtervals can improve selective attention, an executive function posited to be essential for learning and academic success; and (ii) examine whether this relationship is predicted by students' classroom off-task behaviour. Seven grade 3-5 classes (n = 88) were exposed to a single-group, repeated cross-over design where each student's selective attention was compared between no-activity and FUNtervals days. In week 1, students were familiarized with the d2 test of attention and FUNterval activities, and baseline off-task behaviour was observed. In both weeks 2 and 3 students completed the d2 test of attention following either a FUNterval break or a no-activity break. The order of these breaks was randomized and counterbalanced between weeks. Neither motor nor passive off-task behaviour predicted changes in selective attention following FUNtervals; however, a weak relationship was observed for verbal off-task behaviour and improvements in d2 test performance. More importantly, students made fewer errors during the d2 test following FUNtervals. In supporting the priority of physical activity inclusion within schools, FUNtervals, a time efficient and easily implemented physical activity break, can improve selective attention in 9- to 11-year olds. PMID:25675352

  14. Palladium-silver-activated ZnO surface: highly selective methane sensor at reasonably low operating temperature.

    PubMed

    Ghosh, Sugato; Roychaudhuri, Chirasree; Bhattacharya, Raghunath; Saha, Hiranmay; Mukherjee, Nillohit

    2014-03-26

    Metal oxide semiconductors (MOS) are well known as reducing gas sensors. However, their selectivity and operating temperature have major limitations. Most of them show cross sensitivity and the operating temperatures are also relatively higher than the value reported here. To resolve these problems, here, we report the use of palladium-silver (70-30%) activated ZnO thin films as a highly selective methane sensor at low operating temperature (∼100 °C). Porous ZnO thin films were deposited on fluorine-doped tin oxide (FTO)-coated glass substrates by galvanic technique. X-ray diffraction showed polycrystalline nature of the films, whereas the morphological analyses (field emission scanning electron microscopy) showed flake like growth of the grains mainly on xy plane with high surface roughness (107 nm). Pd-Ag (70-30%) alloy was deposited on such ZnO films by e-beam evaporation technique with three different patterns, namely, random dots, ultrathin (∼1 nm) layer and thin (∼5 nm) layer as the activation layer. ZnO films with Pd-Ag dotted pattern were found show high selectivity towards methane (with respect to H2S and CO) and sensitivity (∼80%) at a comparatively low operating temperature of about 100°C. This type of sensor was found to have higher methane selectivity in comparison to other commercially available reducing gas sensor. PMID:24564703

  15. Gold nanoparticles supported on mesoporous silica: origin of high activity and role of Au NPs in selective oxidation of cyclohexane.

    PubMed

    Wu, Pingping; Bai, Peng; Yan, Zifeng; Zhao, George X S

    2016-01-01

    Homogeneous immobilization of gold nanoparticles (Au NPs) on mesoporous silica has been achieved by using a one-pot synthesis method in the presence of organosilane mercapto-propyl-trimethoxysilane (MPTMS). The resultant Au NPs exhibited an excellent catalytic activity in the solvent-free selective oxidation of cyclohexane using molecular oxygen. By establishing the structure-performance relationship, the origin of the high activity of mesoporous supported Au catalyst was identified to be due to the presence of low-coordinated Au (0) sites with high dispersion. Au NPs were confirmed to play a critical role in the catalytic oxidation of cyclohexane by promoting the activation of O2 molecules and accelerating the formation of surface-active oxygen species. PMID:26729288

  16. Gold nanoparticles supported on mesoporous silica: origin of high activity and role of Au NPs in selective oxidation of cyclohexane

    PubMed Central

    Wu, Pingping; Bai, Peng; Yan, Zifeng; Zhao, George X. S.

    2016-01-01

    Homogeneous immobilization of gold nanoparticles (Au NPs) on mesoporous silica has been achieved by using a one-pot synthesis method in the presence of organosilane mercapto-propyl-trimethoxysilane (MPTMS). The resultant Au NPs exhibited an excellent catalytic activity in the solvent-free selective oxidation of cyclohexane using molecular oxygen. By establishing the structure-performance relationship, the origin of the high activity of mesoporous supported Au catalyst was identified to be due to the presence of low-coordinated Au (0) sites with high dispersion. Au NPs were confirmed to play a critical role in the catalytic oxidation of cyclohexane by promoting the activation of O2 molecules and accelerating the formation of surface-active oxygen species. PMID:26729288

  17. Asymmetric triplex metallohelices with high and selective activity against cancer cells

    NASA Astrophysics Data System (ADS)

    Faulkner, Alan D.; Kaner, Rebecca A.; Abdallah, Qasem M. A.; Clarkson, Guy; Fox, David J.; Gurnani, Pratik; Howson, Suzanne E.; Phillips, Roger M.; Roper, David I.; Simpson, Daniel H.; Scott, Peter

    2014-09-01

    Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli.

  18. A highly calcium-selective cation current activated by intracellular calcium release in MDCK cells.

    PubMed

    Delles, C; Haller, T; Dietl, P

    1995-08-01

    methods, stimulates La(3+)-inhibitable Ca2+ entry in MDCK cells. Ca2+ entry is at least, in part, mediated by a cation current, which is highly, but not exclusively, selective for Ca2+ over Na+ and insensitive to SK&F 96365. PMID:7473219

  19. Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity.

    PubMed

    Liu, Peihong; Du, Yongli; Song, Lianhua; Shen, Jingkang; Li, Qunyi

    2016-08-01

    Protein tyrosine phosphatase 1B (PTP1B) as a key negative regulator of both insulin and leptin receptor pathways has been an attractive therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. With the goal of enhancing potency and selectivity of the PTP1B inhibitors, a series of methyl salicylate derivatives as ABC type PTP1B inhibitors (P1-P7) were discovered. More importantly, compound P6 exhibited high potent inhibitory activity (IC50 = 50 nM) for PTP1B with 15-fold selectivity over T-cell PTPase (TCPTP). Further studies on cellular activities revealed that compound P6 could enhance insulin-mediated insulin receptor β (IRβ) phosphorylation and insulin-stimulated glucose uptake. PMID:27123900

  20. Selective fovea-related deprived activation in retinotopic and high-order visual cortex of human amblyopes.

    PubMed

    Lerner, Y; Hendler, T; Malach, R; Harel, M; Leiba, H; Stolovitch, C; Pianka, P

    2006-10-15

    Amblyopia is a visual disorder starting at early childhood and characterized by reduced visual acuity not of optical origin or due to any eye disease. One expression of such an anomalous early visual experience is abnormal foveal vision. In a previous fMRI study, faces that were presented to amblyopic eyes evoked little response compared to houses in high-order visual areas. Patients also demonstrated reduced recognition of facial expression, raising the possibility that these face-selective abnormalities are related to foveal vision deficit. Whether this deficit originates in low-level processing or is mediated by compromised activation in high-order visual areas is unresolved. In the present functional magnetic resonance imaging (fMRI) study, we explored the impact of amblyopia on the representation of object images presented in foveally biased central versus peripheral retinotopic eccentricities through manipulation of object size. Small and large pictures were correlated to visual acuities of 6/6 and 6/60, respectively. In low-level visual areas, the amblyopic eye showed significantly reduced activation for centrally placed, small pictures than the sound eye, while activation to large pictures was only slightly reduced. Similarly, in high-order visual areas, the amblyopic eye showed marked reduction in activation in the fusiform gyrus, with normal activation in the collateral sulcus. The center/periphery size-related amblyopic outcomes of this study support a "bottom-up" nature of the center-periphery effect observed in high-order visual areas. Taken together, these findings point to the regional extent and functional selectivity of fovea-related cortical reorganization that is related to abnormal visual development of one eye. PMID:16919483

  1. Selective breeding for high anxiety introduces a synonymous SNP that increases neuropeptide S receptor activity.

    PubMed

    Slattery, David A; Naik, Roshan R; Grund, Thomas; Yen, Yi-Chun; Sartori, Simone B; Füchsl, Andrea; Finger, Beate C; Elfving, Betina; Nordemann, Uwe; Guerrini, Remo; Calo, Girolamo; Wegener, Gregers; Mathé, Aleksander A; Singewald, Nicolas; Czibere, Ludwig; Landgraf, Rainer; Neumann, Inga D

    2015-03-18

    Neuropeptide S (NPS) has generated substantial interest due to its anxiolytic and fear-attenuating effects in rodents, while a corresponding receptor polymorphism associated with increased NPS receptor (NPSR1) surface expression and efficacy has been implicated in an increased risk of panic disorder in humans. To gain insight into this paradox, we examined the NPS system in rats and mice bred for high anxiety-related behavior (HAB) versus low anxiety-related behavior, and, thereafter, determined the effect of central NPS administration on anxiety- and fear-related behavior. The HAB phenotype was accompanied by lower basal NPS receptor (Npsr1) expression, which we could confirm via in vitro dual luciferase promoter assays. Assessment of shorter Npsr1 promoter constructs containing a sequence mutation that introduces a glucocorticoid receptor transcription factor binding site, confirmed via oligonucleotide pull-down assays, revealed increased HAB promoter activity-an effect that was prevented by dexamethasone. Analogous to the human NPSR1 risk isoform, functional analysis of a synonymous single nucleotide polymorphism in the coding region of HAB rodents revealed that it caused a higher cAMP response to NPS stimulation. Assessment of the behavioral consequence of these differences revealed that intracerebroventricular NPS reversed the hyperanxiety of HAB rodents as well as the impaired cued-fear extinction in HAB rats and the enhanced fear expression in HAB mice, respectively. These results suggest that alterations in the NPS system, conserved across rodents and humans, contribute to innate anxiety and fear, and that HAB rodents are particularly suited to resolve the apparent discrepancy between the preclinical and clinical findings to date. PMID:25788677

  2. Effect of Selection for High Activity-Related Metabolism on Membrane Phospholipid Fatty Acid Composition in Bank Voles.

    PubMed

    Stawski, Clare; Valencak, Teresa G; Ruf, Thomas; Sadowska, Edyta T; Dheyongera, Geoffrey; Rudolf, Agata; Maiti, Uttaran; Koteja, Paweł

    2015-01-01

    Endothermy, high basal metabolic rates (BMRs), and high locomotor-related metabolism were important steps in the evolution of mammals. It has been proposed that the composition of membrane phospholipid fatty acids plays an important role in energy metabolism and exercise muscle physiology. In particular, the membrane pacemaker theory of metabolism suggests that an increase in cell membrane fatty acid unsaturation would result in an increase in BMR. We aimed to determine whether membrane phospholipid fatty acid composition of heart, liver, and gastrocnemius muscles differed between lines of bank voles selected for high swim-induced aerobic metabolism-which also evolved an increased BMR-and unselected control lines. Proportions of fatty acids significantly differed among the organs: liver was the least unsaturated, whereas the gastrocnemius muscles were most unsaturated. However, fatty acid proportions of the heart and liver did not differ significantly between selected and control lines. In gastrocnemius muscles, significant differences between selection directions were found: compared to control lines, membranes of selected voles were richer in saturated C18:0 and unsaturated C18:2n-6 and C18:3n-3, whereas the pattern was reversed for saturated C16:0 and unsaturated C20:4n-6. Neither unsaturation index nor other combined indexes of fatty acid proportions differed between lines. Thus, our results do not support the membrane pacemaker hypothesis. However, the differences between selected and control lines in gastrocnemius muscles reflect chain lengths rather than number of double bonds and are probably related to differences in locomotor activity per se rather than to differences in the basal or routine metabolic rate. PMID:26658414

  3. Highly selective plasma-activated copper catalysts for carbon dioxide reduction to ethylene

    NASA Astrophysics Data System (ADS)

    Mistry, Hemma; Varela, Ana Sofia; Bonifacio, Cecile S.; Zegkinoglou, Ioannis; Sinev, Ilya; Choi, Yong-Wook; Kisslinger, Kim; Stach, Eric A.; Yang, Judith C.; Strasser, Peter; Cuenya, Beatriz Roldan

    2016-06-01

    There is an urgent need to develop technologies that use renewable energy to convert waste products such as carbon dioxide into hydrocarbon fuels. Carbon dioxide can be electrochemically reduced to hydrocarbons over copper catalysts, although higher efficiency is required. We have developed oxidized copper catalysts displaying lower overpotentials for carbon dioxide electroreduction and record selectivity towards ethylene (60%) through facile and tunable plasma treatments. Herein we provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. Operando X-ray absorption spectroscopy and cross-sectional scanning transmission electron microscopy show that copper oxides are surprisingly resistant to reduction and copper+ species remain on the surface during the reaction. Our results demonstrate that the roughness of oxide-derived copper catalysts plays only a partial role in determining the catalytic performance, while the presence of copper+ is key for lowering the onset potential and enhancing ethylene selectivity.

  4. Highly selective plasma-activated copper catalysts for carbon dioxide reduction to ethylene.

    PubMed

    Mistry, Hemma; Varela, Ana Sofia; Bonifacio, Cecile S; Zegkinoglou, Ioannis; Sinev, Ilya; Choi, Yong-Wook; Kisslinger, Kim; Stach, Eric A; Yang, Judith C; Strasser, Peter; Cuenya, Beatriz Roldan

    2016-01-01

    There is an urgent need to develop technologies that use renewable energy to convert waste products such as carbon dioxide into hydrocarbon fuels. Carbon dioxide can be electrochemically reduced to hydrocarbons over copper catalysts, although higher efficiency is required. We have developed oxidized copper catalysts displaying lower overpotentials for carbon dioxide electroreduction and record selectivity towards ethylene (60%) through facile and tunable plasma treatments. Herein we provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. Operando X-ray absorption spectroscopy and cross-sectional scanning transmission electron microscopy show that copper oxides are surprisingly resistant to reduction and copper(+) species remain on the surface during the reaction. Our results demonstrate that the roughness of oxide-derived copper catalysts plays only a partial role in determining the catalytic performance, while the presence of copper(+) is key for lowering the onset potential and enhancing ethylene selectivity. PMID:27356485

  5. Highly selective plasma-activated copper catalysts for carbon dioxide reduction to ethylene

    PubMed Central

    Mistry, Hemma; Varela, Ana Sofia; Bonifacio, Cecile S.; Zegkinoglou, Ioannis; Sinev, Ilya; Choi, Yong-Wook; Kisslinger, Kim; Stach, Eric A.; Yang, Judith C.; Strasser, Peter; Cuenya, Beatriz Roldan

    2016-01-01

    There is an urgent need to develop technologies that use renewable energy to convert waste products such as carbon dioxide into hydrocarbon fuels. Carbon dioxide can be electrochemically reduced to hydrocarbons over copper catalysts, although higher efficiency is required. We have developed oxidized copper catalysts displaying lower overpotentials for carbon dioxide electroreduction and record selectivity towards ethylene (60%) through facile and tunable plasma treatments. Herein we provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. Operando X-ray absorption spectroscopy and cross-sectional scanning transmission electron microscopy show that copper oxides are surprisingly resistant to reduction and copper+ species remain on the surface during the reaction. Our results demonstrate that the roughness of oxide-derived copper catalysts plays only a partial role in determining the catalytic performance, while the presence of copper+ is key for lowering the onset potential and enhancing ethylene selectivity. PMID:27356485

  6. The ionophore nigericin transports Pb2+ with high activity and selectivity: a comparison to monensin and ionomycin.

    PubMed

    Hamidinia, Shawn A; Tan, Bo; Erdahl, Warren L; Chapman, Clifford J; Taylor, Richard W; Pfeiffer, Douglas R

    2004-12-21

    The K(+) ionophore nigericin is shown to be highly effective as an ionophore for Pb(2+) but not other divalent cations, including Cu(2+), Zn(2+), Cd(2+), Mn(2+), Co(2+), Ca(2+), Ni(2+), and Sr(2+). Among this group a minor activity for Cu(2+) transport is seen, while for the others activity is near or below the limit of detection. The selectivity of nigericin for Pb(2+) exceeds that of ionomycin or monensin and arises, at least in part, from a high stability of nigericin-Pb(2+) complexes. Plots of log rate vs log Pb(2+) or log ionophore concentration, together with the pH dependency, indicate that nigericin transports Pb(2+) via the species NigPbOH and by a mechanism that is predominately electroneutral. As with monensin and ionomycin, a minor fraction of activity may be electrogenic, based upon a stimulation of rate that is produced by agents which prevent the formation of transmembrane electrical potentials. Nigericin-catalyzed Pb(2+) transport is not inhibited by physiological concentrations of Ca(2+) or Mg(2+) and is only modestly affected by K(+) and Na(+) concentrations in the range of 0-100 mM. These characteristics, together with higher selectivity and efficiency, suggest that nigericin may be more useful than monensin in the treatment of Pb intoxication. PMID:15595852

  7. Synthesis and pharmacological evaluation of a potent and selective σ1 receptor antagonist with high antiallodynic activity.

    PubMed

    Utech, Tina; Köhler, Jens; Buschmann, Helmut; Holenz, Jörg; Vela, Jose Miguel; Wünsch, Bernhard

    2011-07-01

    Based on the pharmacophore model of Glennon the conformationally restricted σ(1) receptor ligand 2 with a 1,3-dioxane moiety has been designed and synthesized. The three step synthesis (transacetalization with pentane-1,3,5-triol, tosylation, and nucleophilic substitution with benzylamine) provided diastereoselectively the cis-configured 1,3-dioxane 2 in good yields. The 1,3-dioxane 2 represents a potent σ(1) receptor ligand (K(i) = 19 nM) with moderate selectivity over the σ(2) subtype (K(i) = 92 nM) and excellent selectivity against more than 60 other targets. Additionally the hERG K(+) channel is not affected by 2. In the capsaicin assay 2 showed extraordinarily high analgesic activity with more than 70% analgesia at the very low dose of 0.25 mg/kg body weight, which indicates σ(1) antagonistic activity. Since 2 does only interact with σ(1) receptors, the in-vivo antiallodynic activity of 2 must be attributed to the σ(1) antagonistic activity. PMID:21598296

  8. Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes.

    PubMed

    Bachovchin, Daniel A; Brown, Steven J; Rosen, Hugh; Cravatt, Benjamin F

    2009-04-01

    High-throughput screening to discover small-molecule modulators of enzymes typically relies on highly tailored substrate assays, which are not available for poorly characterized enzymes. Here we report a general, substrate-free method for identifying inhibitors of uncharacterized enzymes. The assay measures changes in the kinetics of covalent active-site labeling with broad-spectrum, fluorescent probes in the presence of inhibitors by monitoring the fluorescence polarization signal. We show that this technology is applicable to enzymes from at least two mechanistic classes, regardless of their degree of functional annotation, and can be coupled with secondary proteomic assays that use competitive activity-based profiling to rapidly determine the specificity of screening hits. Using this method, we identify the bioactive alkaloid emetine as a selective inhibitor of the uncharacterized cancer-associated hydrolase RBBP9. Furthermore, we show that the detoxification enzyme GSTO1, also implicated in cancer, is inhibited by several electrophilic compounds found in public libraries, some of which display high selectivity for this protein. PMID:19329999

  9. Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi.

    PubMed

    Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L; Moreira, Vânia M; Alakurtti, Sami

    2016-02-26

    Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease. PMID:26849852

  10. Highly selective plasma-activated copper catalysts for carbon dioxide reduction to ethylene

    DOE PAGESBeta

    Mistry, Hemma; Varela, Ana Sofia; Bonifacio, Cecile S.; Zegkinoglou, Ioannis; Sinev, Ilya; Choi, Yong-Wook; Kisslinger, Kim; Stach, Eric A.; Yang, Judith C.; Strasser, Peter; et al

    2016-06-30

    There is an urgent need to develop technologies that use renewable energy to convert waste products such as carbon dioxide into hydrocarbon fuels. Carbon dioxide can be electrochemically reduced to hydrocarbons over copper catalysts, although higher efficiency is required. We have developed oxidized copper catalysts displaying lower overpotentials for carbon dioxide electroreduction and record selectivity towards ethylene (60%) through facile and tunable plasma treatments. Herein we provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. Operando X-ray absorption spectroscopy and cross-sectional scanning transmission electron microscopy show that copper oxides aremore » surprisingly resistant to reduction and copper+ species remain on the surface during the reaction. Furthermore, our results demonstrate that the roughness of oxide-derived copper catalysts plays only a partial role in determining the catalytic performance, while the presence of copper+ is key for lowering the onset potential and enhancing ethylene selectivity.« less

  11. Target-Cell Contact Activates a Highly Selective Capacitative Calcium Entry Pathway in Cytotoxic T Lymphocytes

    PubMed Central

    Zweifach, Adam

    2000-01-01

    Calcium influx is critical for T cell activation. Evidence has been presented that T cell receptor–stimulated calcium influx in helper T lymphocytes occurs via channels activated as a consequence of depletion of intracellular calcium stores, a mechanism known as capacitative Ca2+ entry (CCE). However, two key questions have not been addressed. First, the mechanism of calcium influx in cytotoxic T cells has not been examined. While the T cell receptor–mediated early signals in helper and cytotoxic T cells are similar, the physiology of the cells is strikingly different, raising the possibility that the mechanism of calcium influx is also different. Second, contact of T cells with antigen-presenting cells or targets involves a host of intercellular interactions in addition to those between antigen–MHC and the T cell receptor. The possibility that calcium influx pathways in addition to those activated via the T cell receptor may be activated by contact with relevant cells has not been addressed. We have used imaging techniques to show that target-cell–stimulated calcium influx in CTLs occurs primarily through CCE. We investigated the permeability of the CTL influx pathway for divalent cations, and compared it to the permeability of CCE in Jurkat human leukemic T cells. CCE in CTLs shows a similar ability to discriminate between calcium, barium, and strontium as CCE in Jurkat human leukemic T lymphocytes, where CCE is likely to mediated by Ca2+ release–activated Ca2+ current (CRAC) channels, suggesting that CRAC channels also underlie CCE in CTLs. These results are the first determination of the mechanism of calcium influx in cytotoxic T cells and the first demonstration that cell contact–mediated calcium signals in T cells occur via depletion-activated channels. PMID:10662784

  12. Design of a high activity and selectivity alcohol catalyst. Final status report and summary of accomplishments

    SciTech Connect

    Foley, H.C.; Mills, G.A.

    1994-07-15

    This final DOE report for grant award number DE-FG22-90PC 90291 presents the results of our efforts to better understand the Rh-Mo/{gamma}-Al{sub 2}O3 catalytic system for the hydrogenation of carbon monoxide and carbon dioxide to selectively form oxygenated products. The content of this report is divided into three major sections and a fourth, concluding section which addresses our major research accomplishments, as well as documents the most significant publications and presentations associated with this grant. The three main sections which make up the body of this report are presented in the in form of manuscripts which, in turn, summarize our progress in three areas of this project. The three body sections are organized as follows: Section I--Evidence for site isolation in Rh-Mo bimetallic catalysts derived from organometallic clusters; Section II--Surface Chemistry of Rh-Mo/{gamma}-Al{sub 2}O{sub 3}: An analysis of surface acidity; and Section III--Comparative study of Rh/Al{sub 2}O{sub 3} and Rh-Mo/Al{sub 2}O{sub 3} Catalysts. Section IV summarizes major accomplishments. The content of this final report is meant to generally highlight our progress in both characterizing the nature of the Rh-Mo/Al{sub 2}O{sub 3} system and probing its reactivity for insight on the oxygenate synergy present in this class of catalysts.

  13. A novel perovskite based catalyst with high selectivity and activity for partial oxidation of methane for fuel cell applications.

    PubMed

    Staniforth, J; Evans, S E; Good, O J; Darton, R J; Ormerod, R M

    2014-10-28

    Solid oxide fuel cells (SOFCs) have the potential to revolutionise the present fuel economy due to their higher fuel conversion efficiency compared with standard heat engines and the possibility of utilizing the heat produced in a combined heat and power system. One of the reasons they have yet to fulfil this potential is that the conventional anode material of choice, a nickel/yttria-stabilised zirconia cermet, requires a high temperature production process and under operating conditions is susceptible to carbon and sulphur poisoning. Perovskite-based materials have been proposed as potential anode materials for SOFCs due to their potentially high electronic conductivity and catalytic properties. One of the problems in realizing this potential has been their low catalytic activity towards methane reforming compared to conventional nickel based cermet materials. A nickel doped strontium zirconate material produced by low temperature hydrothermal synthesis is described which has high activity for methane reforming and high selectivity towards partial oxidation of methane as opposed to total oxidation products. Initial studies show a very low level of carbon formation which does not increase over time. PMID:25069597

  14. Selection of a Bacillus pumilus Strain Highly Active against Ceratitis capitata (Wiedemann) Larvae▿

    PubMed Central

    Molina, C. Alfonso; Caña-Roca, Juan F.; Osuna, Antonio; Vilchez, Susana

    2010-01-01

    Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), the Mediterranean fruit fly (medfly), is one of the most important fruit pests worldwide. The medfly is a polyphagous species that causes losses in many crops, which leads to huge economic losses. Entomopathogenic bacteria belonging to the genus Bacillus have been proven to be safe, environmentally friendly, and cost-effective tools to control pest populations. As no control method for C. capitata based on these bacteria has been developed, isolation of novel strains is needed. Here, we report the isolation of 115 bacterial strains and the results of toxicity screening with adults and larvae of C. capitata. As a result of this analysis, we obtained a novel Bacillus pumilus strain, strain 15.1, that is highly toxic to C. capitata larvae. The toxicity of this strain for C. capitata was related to the sporulation process and was observed only when cultures were incubated at low temperatures before they were used in a bioassay. The mortality rate for C. capitata larvae ranged from 68 to 94% depending on the conditions under which the culture was kept before the bioassay. Toxicity was proven to be a special characteristic of the newly isolated strain, since other B. pumilus strains did not have a toxic effect on C. capitata larvae. The results of the present study suggest that B. pumilus 15.1 could be considered a strong candidate for developing strategies for biological control of C. capitata. PMID:20038689

  15. Evolution of high cellulolytic activity in symbiotic Streptomyces through selection of expanded gene content and coordinated gene expression

    DOE PAGESBeta

    Book, Adam J.; Lewin, Gina R.; McDonald, Bradon R.; Takasuka, Taichi E.; Wendt-Pienkowski, Evelyn; Doering, Drew T.; Suh, Steven; Raffa, Kenneth F.; Fox, Brian G.; Currie, Cameron R.

    2016-06-08

    In this study, the evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil andmore » symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology.« less

  16. Evolution of High Cellulolytic Activity in Symbiotic Streptomyces through Selection of Expanded Gene Content and Coordinated Gene Expression.

    PubMed

    Book, Adam J; Lewin, Gina R; McDonald, Bradon R; Takasuka, Taichi E; Wendt-Pienkowski, Evelyn; Doering, Drew T; Suh, Steven; Raffa, Kenneth F; Fox, Brian G; Currie, Cameron R

    2016-06-01

    The evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil and symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology. PMID:27276034

  17. Evolution of High Cellulolytic Activity in Symbiotic Streptomyces through Selection of Expanded Gene Content and Coordinated Gene Expression

    PubMed Central

    McDonald, Bradon R.; Takasuka, Taichi E.; Wendt-Pienkowski, Evelyn; Doering, Drew T.; Raffa, Kenneth F.; Fox, Brian G.; Currie, Cameron R.

    2016-01-01

    The evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil and symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology. PMID:27276034

  18. A high-performance liquid chromatographic assay with improved selectivity for cisplatin and active platinum (II) complexes in plasma ultrafiltrate.

    PubMed

    Andrews, P A; Wung, W E; Howell, S B

    1984-11-15

    cis-Diamminedichloroplatinum(II) (DDP) was measured in plasma ultrafiltrate following derivatization with sodium diethyldithiocarbamate (DDTC) by quantitation against a nickel chloride internal standard. A chloroform extract containing the Pt(DDTC)2 and Ni(DDTC)2 complexes was separated by reversed-phase high-performance liquid chromatography on a C18 radial compression column. The complex was eluted with methanol/water, 4/1, at a flow rate of 1.5 ml/min, and was detected at 254 nm. The limit of sensitivity was 0.1 microgram/ml DDP in the ultrafiltrate. This analytical approach was validated by comparison to graphite furnace atomic absorption spectrophotometric determinations of duplicate samples. There was clearly a component of the ultrafiltrable platinum present that was resistant to derivatization by DDTC. Evidence is presented that this component, presumably Pt(II) complexed with endogenous small molecules, is non cytotoxic and, hence, that this method may be selective for "active Pt(II)." This method offers an advantage over atomic absorption determination of total platinum in ultrafiltrate which does not discriminate between active and inactive forms, and over off-line FAA detection of parent DDP in HPLC eluates which ignores other active forms. Using this technique we have measured the pharmacokinetics of DDTC-reactive Pt(II) in humans after either i.v. infusion or infusion of DDP into the peritoneal cavity of patients with ovarian carcinoma. PMID:6099065

  19. UV activation of polymeric high aspect ratio microstructures: ramifications in antibody surface loading for circulating tumor cell selection.

    PubMed

    Jackson, Joshua M; Witek, Małgorzata A; Hupert, Mateusz L; Brady, Charles; Pullagurla, Swathi; Kamande, Joyce; Aufforth, Rachel D; Tignanelli, Christopher J; Torphy, Robert J; Yeh, Jen Jen; Soper, Steven A

    2014-01-01

    The need to activate thermoplastic surfaces using robust and efficient methods has been driven by the fact that replication techniques can be used to produce microfluidic devices in a high production mode and at low cost, making polymer microfluidics invaluable for in vitro diagnostics, such as circulating tumor cell (CTC) analysis, where device disposability is critical to mitigate artifacts associated with sample carryover. Modifying the surface chemistry of thermoplastic devices through activation techniques can be used to increase the wettability of the surface or to produce functional scaffolds to allow for the covalent attachment of biologics, such as antibodies for CTC recognition. Extensive surface characterization tools were used to investigate UV activation of various surfaces to produce uniform and high surface coverage of functional groups, such as carboxylic acids in microchannels of different aspect ratios. We found that the efficiency of the UV activation process is highly dependent on the microchannel aspect ratio and the identity of the thermoplastic substrate. Colorimetric assays and fluorescence imaging of UV-activated microchannels following EDC/NHS coupling of Cy3-labeled oligonucleotides indicated that UV-activation of a PMMA microchannel with an aspect ratio of ~3 was significantly less efficient toward the bottom of the channel compared to the upper sections. This effect was a consequence of the bulk polymer's damping of the modifying UV radiation due to absorption artifacts. In contrast, this effect was less pronounced for COC. Moreover, we observed that after thermal fusion bonding of the device's cover plate to the substrate, many of the generated functional groups buried into the bulk rendering them inaccessible. The propensity of this surface reorganization was found to be higher for PMMA compared to COC. As an example of the effects of material and microchannel aspect ratios on device functionality, thermoplastic devices for the

  20. In vitro selection of RNase P RNA reveals optimized catalytic activity in a highly conserved structural domain.

    PubMed

    Frank, D N; Ellington, A E; Pace, N R

    1996-12-01

    In vitro selection techniques are useful means of dissecting the functions of both natural and artificial ribozymes. Using a self-cleaving conjugate containing the Escherichia coli ribonuclease P RNA and its substrate, pre-tRNA (Frank DN, Harris ME, Pace NR, 1994, Biochemistry 33:10800-10808), we have devised a method to select for catalytically active variants of the RNase P ribozyme. A selection experiment was performed to probe the structural and sequence constraints that operate on a highly conserved region of RNase P: the J3/4-P4-J2/4 region, which lies within the core of RNase P and is thought to bind catalytically essential magnesium ions (Harris ME et al., 1994, EMBO J 13:3953-3963; Hardt WD et al., 1995, EMBO J 14:2935-2944; Harris ME, Pace NR, 1995, RNA 1:210-218). We sought to determine which, if any, of the nearly invariant nucleotides within J3/4-P4-J2/4 are required for ribozyme-mediated catalysis. Twenty-two residues in the J3/4-P4-J2/4 component of RNase P RNA were randomized and, surprisingly, after only 10 generations, each of the randomized positions returned to the wild-type sequence. This indicates that every position in J3/4-P4-J2/4 contributes to optimal catalytic activity. These results contrast sharply with selections involving other large ribozymes, which evolve improved catalytic function readily in vitro (Chapman KB, Szostak JW, 1994, Curr Opin Struct Biol 4:618-622; Joyce GF, 1994, Curr Opin Struct Biol 4:331-336; Kumar PKR, Ellington AE, 1995, FASEB J 9:1183-1195). The phylogenetic conservation of J3/4-P4-J2/4, coupled with the results reported here, suggests that the contribution of this structure to RNA-mediated catalysis was optimized very early in evolution, before the last common ancestor of all life. PMID:8972768

  1. High Selectivity Oxygen Delignification

    SciTech Connect

    Arthur J. Ragauskas Lucian A. Lucia Hasan Jameel

    2005-09-30

    The overall objective of this program was to develop improved extended oxygen delignification (EOD) technologies for current U.S. pulp mill operations. This was accomplished by: (1) Identifying pulping conditions that optimize O and OO performance; (2) Identifying structural features of lignin that enhance reactivity towards EOD of high kappa pulps; (3) Identifying factors minimizing carbohydrate degradation and improve pulp strength of EOD high kappa pulps; (4) Developing a simple, reproducible method of quantifying yield gains from EOD; and (5) Developing process conditions that significantly reduce the capital requirements of EOD while optimizing the yield benefits. Key research outcomes included, demonstrating the use of a mini-O sequence such as (E+O)Dkf:0.05(E+O) or Dkf:0.05(E+O)(E+O) without interstage washing could capture approximately 60% of the delignification efficiency of a conventional O-stage without the major capital requirements associated with an O-stage for conventional SW kraft pulps. The rate of formation and loss of fiber charge during an O-stage stage can be employed to maximize net fiber charge. Optimal fiber charge development and delignification are two independent parameters and do not parallel each other. It is possible to utilize an O-stage to enhance overall cellulosic fiber charge of low and high kappa SW kraft pulps which is beneficial for physical strength properties. The application of NIR and multi-variant analysis was developed into a rapid and simple method of determining the yield of pulp from an oxygen delignification stage that has real-world mill applications. A focus point of this program was the demonstration that Kraft pulping conditions and oxygen delignification of high and low-kappa SW and HW pulps are intimately related. Improved physical pulp properties and yield can be delivered by controlling the H-factor and active alkali charge. Low AA softwood kraft pulp with a kappa number 30 has an average improvement of 2% in

  2. Highly selective water channel activity measured by voltage clamp: Analysis of planar lipid bilayers reconstituted with purified AqpZ

    PubMed Central

    Pohl, Peter; Saparov, Sapar M.; Borgnia, Mario J.; Agre, Peter

    2001-01-01

    Aquaporins are membrane channels selectively permeated by water or water plus glycerol. Conflicting reports have described ion conductance associated with some water channels, raising the question of whether ion conductance is a general property of the aquaporin family. To clarify this question, a defined system was developed to simultaneously measure water permeability and ion conductance. The Escherichia coli water channel aquaporin-Z (AqpZ) was studied, because it is a highly stable tetramer. Planar lipid bilayers were formed from unilamellar vesicles containing purified AqpZ. The hydraulic conductivity of bilayers made from the total extract of E. coli lipids increased 3-fold if reconstituted with AqpZ, but electric conductance was unchanged. No channel activity was detected under voltage-clamp conditions, indicating that less than one in 109 transport events is electrogenic. Microelectrode measurements were simultaneously undertaken adjacent to the membrane. Changes in sodium concentration profiles accompanying transmembrane water flow permitted calculation of the activation energies: 14 kcal/mol for protein-free lipid bilayers and 4 kcal/mol for lipid bilayers containing AqpZ. Neither the water permeability nor the electric conductivity exhibited voltage dependence. This sensitive system demonstrated that AqpZ is permeated by water but not charged ions and should permit direct analyses of putative electrogenic properties of other aquaporins. PMID:11493683

  3. Morphometry, ultrastructure, myosin isoforms, and metabolic capacities of the "mini muscles" favoured by selection for high activity in house mice.

    PubMed

    Guderley, Helga; Houle-Leroy, Philippe; Diffee, Gary M; Camp, Dana M; Garland, Theodore

    2006-07-01

    Prolonged selective breeding of mice (Mus musculus) for high levels of voluntary wheel running has favoured an unusual phenotype ("mini muscles"), apparently caused by a single Mendelian recessive allele, in which most hind-limb muscles are markedly reduced in mass, but have increased mass-specific activities of mitochondrial enzymes. We examined whether these changes reflect changes in fibre size, number or ultrastructure in normal and "mini-muscle" mice within the two (of four) selectively bred lines (lab designations L3 and L6) that exhibit the phenotype at generations 26 and 27. In both lines, the gastrocnemius and plantaris muscles are smaller in mass (by >50% and 20%, respectively) in affected individuals. The mass-specific activities of mitochondrial enzymes in the gastrocnemius and plantaris muscles were increased in the mini phenotype in both lines, with stronger effects in the gastrocnemius muscle. In the gastrocnemius, the % myosin heavy chain (MHC) IIb was reduced by 50% in L3 and by 30% in L6, whereas the % MHC IIa and I were higher, particularly in L3. Fibre number in the plantaris muscle did not significantly differ between mini and normal muscles, although muscle mass was a significant positive correlate of fibre number. Small fibres were more abundant in mini than normal muscles in L3. Mitochondrial volume density was significantly higher in mini than normal muscle fibres in L3, but not in L6. Microscopy revealed a surprising attribute of the mini muscles: an abundance of small, minimally differentiated, myofibril-containing cells positioned in a disorderly fashion, particularly in the surface layer. We hypothesise that these unusual cells may be satellite cells or type IIb fibres that did not complete their differentiation. Together, these observations suggest that mice with the mini phenotype have reduced numbers of type IIb fibres in many of their hind-limb muscles, leading to a decrease in mass and an increase in mass-specific aerobic capacity

  4. High Selectivity Oxygen Delignification

    SciTech Connect

    Lucian A. Lucia

    2005-11-15

    Project Objective: The objectives of this project are as follows: (1) Examine the physical and chemical characteristics of a partner mill pre- and post-oxygen delignified pulp and compare them to lab generated oxygen delignified pulps; (2) Apply the chemical selectivity enhancement system to the partner pre-oxygen delignified pulps under mill conditions (with and without any predetermined amounts of carryover) to determine how efficiently viscosity is preserved, how well selectivity is enhanced, if strength is improved, measure any yield differences and/or bleachability differences; and (3) Initiate a mill scale oxygen delignification run using the selectivity enhancement agent, collect the mill data, analyze it, and propose any future plans for implementation.

  5. Design, synthesis, and structure-activity relationship studies of novel 3-alkylindole derivatives as selective and highly potent myeloperoxidase inhibitors.

    PubMed

    Soubhye, Jalal; Aldib, Iyas; Elfving, Betina; Gelbcke, Michel; Furtmüller, Paul G; Podrecca, Manuel; Conotte, Raphaël; Colet, Jean-Marie; Rousseau, Alexandre; Reye, Florence; Sarakbi, Ahmad; Vanhaeverbeek, Michel; Kauffmann, Jean-Michel; Obinger, Christian; Nève, Jean; Prévost, Martine; Zouaoui Boudjeltia, Karim; Dufrasne, Francois; Van Antwerpen, Pierre

    2013-05-23

    Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases. Thus MPO is an attractive target in drug design. (Aminoalkyl)fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range. Via structure-based drug design, a new series of MPO inhibitors derived from 3-alkylindole were synthesized and their effects were assessed on MPO-mediated taurine chlorination and low-density lipoprotein oxidation as well as on inhibition of SERT. The fluoroindole compound with three carbons in the side chain and one amide group exhibited a selectivity index of 35 (Ki/IC50) with high inhibition of MPO activity (IC50 = 18 nM), whereas its effect on SERT was in the micromolar range. Structure-function relationships, mechanism of action, and safety of the molecule are discussed. PMID:23581551

  6. Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening.

    PubMed

    Dighe, Satish N; Deora, Girdhar Singh; De la Mora, Eugenio; Nachon, Florian; Chan, Stephen; Parat, Marie-Odile; Brazzolotto, Xavier; Ross, Benjamin P

    2016-08-25

    Structure-based virtual screening of two libraries containing 567 981 molecules was used to discover novel, selective BuChE inhibitors, which are potentially superior symptomatic treatments in late-stage Alzheimer's disease. Compound 16 was identified as a highly selective submicromolar inhibitor of BuChE (huBuChE IC50 = 0.443 μM) with high permeability in the PAMPA-BBB model. The X-ray crystal structure of huBuChE in complex with 16 revealed the atomic-level interactions and offers opportunities for further development of the series. PMID:27405689

  7. High lift selected concepts

    NASA Technical Reports Server (NTRS)

    Henderson, M. L.

    1979-01-01

    The benefits to high lift system maximum life and, alternatively, to high lift system complexity, of applying analytic design and analysis techniques to the design of high lift sections for flight conditions were determined and two high lift sections were designed to flight conditions. The influence of the high lift section on the sizing and economics of a specific energy efficient transport (EET) was clarified using a computerized sizing technique and an existing advanced airplane design data base. The impact of the best design resulting from the design applications studies on EET sizing and economics were evaluated. Flap technology trade studies, climb and descent studies, and augmented stability studies are included along with a description of the baseline high lift system geometry, a calculation of lift and pitching moment when separation is present, and an inverse boundary layer technique for pressure distribution synthesis and optimization.

  8. Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors

    PubMed Central

    2014-01-01

    From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure. PMID:25589934

  9. Platinum-Promoted Ga/Al2O3 as Highly Active, Selective, and Stable Catalyst for the Dehydrogenation of Propane**

    PubMed Central

    Sattler, Jesper J H B; Gonzalez-Jimenez, Ines D; Luo, Lin; Stears, Brien A; Malek, Andrzej; Barton, David G; Kilos, Beata A; Kaminsky, Mark P; Verhoeven, Tiny W G M; Koers, Eline J; Baldus, Marc; Weckhuysen, Bert M

    2014-01-01

    A novel catalyst material for the selective dehydrogenation of propane is presented. The catalyst consists of 1000 ppm Pt, 3 wt % Ga, and 0.25 wt % K supported on alumina. We observed a synergy between Ga and Pt, resulting in a highly active and stable catalyst. Additionally, we propose a bifunctional active phase, in which coordinately unsaturated Ga3+ species are the active species and where Pt functions as a promoter. PMID:24989975

  10. A Curriculum Activities Guide to Selected Environmental Topics for Use With Elementary and Junior High School Students.

    ERIC Educational Resources Information Center

    Sexton, Alan D., Ed.

    This guide contains learning activities in environmental education developed by teachers and intended for use at the elementary or junior high school levels. Topics covered include: water, esthetics, air, soil and sediment, solid waste, energy, noise, population, and transportation. Generally, each activity contains an introduction, a listing of…

  11. Influence of the support on the activity and selectivity of high dispersion Fe catalysts in the Fischer-Tropsch reaction

    SciTech Connect

    Cagnoli, M.V.; Marchetti, S.G.; Gallegos, N.G.; Alvarez, A.M.; Mercader, R.C.; Yeramian, A.A. Facultad de Ciencias Exactas, La Plata )

    1990-05-01

    In order to study the influence of the support on high dispersion catalysts used for the CO hydrogenation reaction, two catalysts, Fe/SiO{sub 2} and Fe/Al{sub 2}O{sub 3}, were prepared by the dry impregnation method. Selective chemisorption of CO, volumetric oxidation, and Moessbauer spectroscopy were used to determine the Fe species present as well as the metallic crystal size, the degree of dispersion, and the reduction percentage. The presence of small Fe{sup 0} crystallites with high dispersion was determined in both catalysts. Reaction rates were measured in a differential reactor and significant differences, about one order of magnitude less for the Al{sub 2}O{sub 3} than for the SiO{sub 2} supported catalysts, were found in the methane turnover frequencies. They are attributed to the interaction between the metal and the supports. The selectivity differences is also discussed in connection with distinct surface properties.

  12. Selection for low or high primary dormancy in Lolium rigidum Gaud seeds results in constitutive differences in stress protein expression and peroxidase activity

    PubMed Central

    Goggin, Danica E.; Powles, Stephen B.; Steadman, Kathryn J.

    2011-01-01

    Seed dormancy in wild Lolium rigidum Gaud (annual ryegrass) populations is highly variable and not well characterized at the biochemical level. To identify some of the determinants of dormancy level in these seeds, the proteomes of subpopulations selected for low and high levels of primary dormancy were compared by two-dimensional polyacrylamide gel electrophoresis of extracts from mature, dry seeds. High-dormancy seeds showed higher expression of small heat shock proteins, enolase, and glyoxalase I than the low-dormancy seeds. The functional relevance of these differences in protein expression was confirmed by the fact that high-dormancy seeds were more tolerant to high temperatures imposed at imbibition and had consistently higher glyoxalase I activity over 0–42 d dark stratification. Higher expression of a putative glutathione peroxidase in low-dormancy seeds was not accompanied by higher activity, but these seeds had a slightly more oxidized glutathione pool and higher total peroxidase activity. Overall, these biochemical and physiological differences suggest that L. rigidum seeds selected for low dormancy are more prepared for rapid germination via peroxidase-mediated cell wall weakening, whilst seeds selected for high dormancy are constitutively prepared to survive environmental stresses, even in the absence of stress during seed development. PMID:20974739

  13. High frequency ultrasound as a selective advanced oxidation process to remove penicillinic antibiotics and eliminate its antimicrobial activity from water.

    PubMed

    Serna-Galvis, Efraim A; Silva-Agredo, Javier; Giraldo-Aguirre, Ana L; Flórez-Acosta, Oscar A; Torres-Palma, Ricardo A

    2016-07-01

    This work studies the sonochemical degradation of a penicillinic antibiotic (oxacillin) in simulated pharmaceutical wastewater. High frequency ultrasound was applied to water containing the antibiotic combined with mannitol or calcium carbonate. In the presence of additives, oxacillin was efficiently removed through sonochemical action. For comparative purposes, the photo-Fenton, TiO2 photocatalysis and electrochemical oxidation processes were also tested. Therefore, the evolution of the antibiotic and its associated antimicrobial activity (AA) were monitored. A high inhibition was found for the other three oxidation processes in the elimination of the antimicrobial activity caused by the additives; while for the ultrasonic treatment, a negligible effect was observed. The sonochemical process was able to completely degrade the antibiotic, generating solutions without AA. In fact, the elimination of antimicrobial activity showed an excellent performance adjusted to exponential kinetic-type decay. The main sonogenerated organic by-products were determined by means of HPLC-MS. Four intermediaries were identified and they have modified the penicillinic structure, which is the moiety responsible for the antimicrobial activity. Additionally, the possible oxacillin sonodegradation mechanism was proposed based on the evolution of the by-products and their chemical structure. Furthermore, the high-frequency ultrasound action over 120 min readily removed oxacillin and eliminated its antimicrobial activity. However, the pollutant was not mineralized even after a long period of ultrasonic irradiation (360 min). Interestingly, the previously sonicated water containing oxacillin and both additives was completely mineralized using non-adapted microorganisms from a municipal wastewater treatment plant. These results show that the sonochemical treatment transformed the initial pollutant into substances that are biotreatable with a typical aerobic biological system. PMID:26964950

  14. Nanogold supported on manganese oxide doped alumina microspheres as a highly active and selective catalyst for CO oxidation in a H2-rich stream.

    PubMed

    Miao, Yu-Xin; Li, Wen-Cui; Sun, Qiang; Shi, Lei; He, Lei; Wang, Jing; Deng, Gao-Ming; Lu, An-Hui

    2015-12-28

    Manganese oxide-doped Al2O3 microspheres were synthesized via a redox method, and were then deposited with Au nanoparticles using a deposition-precipitation method. The obtained catalyst is not only highly active and selective for the preferential oxidation of CO in a H2-rich stream, but also shows excellent stability in the co-presence of H2O and CO2 at 80 °C. PMID:26489890

  15. Highly selective anti-Prelog synthesis of optically active aryl alcohols by recombinant Escherichia coli expressing stereospecific alcohol dehydrogenase.

    PubMed

    Li, Ming; Nie, Yao; Mu, Xiao Qing; Zhang, Rongzhen; Xu, Yan

    2016-07-01

    Biocatalytic asymmetric synthesis has been widely used for preparation of optically active chiral alcohols as the important intermediates and precursors of active pharmaceutical ingredients. However, the available whole-cell system involving anti-Prelog specific alcohol dehydrogenase is yet limited. A recombinant Escherichia coli system expressing anti-Prelog stereospecific alcohol dehydrogenase from Candida parapsilosis was established as a whole-cell system for catalyzing asymmetric reduction of aryl ketones to anti-Prelog configured alcohols. Using 2-hydroxyacetophenone as the substrate, reaction factors including pH, cell status, and substrate concentration had obvious impacts on the outcome of whole-cell biocatalysis, and xylose was found to be an available auxiliary substrate for intracellular cofactor regeneration, by which (S)-1-phenyl-1,2-ethanediol was achieved with an optical purity of 97%e.e. and yield of 89% under the substrate concentration of 5 g/L. Additionally, the feasibility of the recombinant cells toward different aryl ketones was investigated, and most of the corresponding chiral alcohol products were obtained with an optical purity over 95%e.e. Therefore, the whole-cell system involving recombinant stereospecific alcohol dehydrogenase was constructed as an efficient biocatalyst for highly enantioselective anti-Prelog synthesis of optically active aryl alcohols and would be promising in the pharmaceutical industry. PMID:26178068

  16. Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized Female Rats Selectively Bred for High and Low Aerobic Capacity.

    PubMed

    Liu, Tzu-Wen; Park, Young-Min; Holscher, Hannah D; Padilla, Jaume; Scroggins, Rebecca J; Welly, Rebecca; Britton, Steven L; Koch, Lauren G; Vieira-Potter, Victoria J; Swanson, Kelly S

    2015-01-01

    The gut microbiota is considered a relevant factor in obesity and associated metabolic diseases, for which postmenopausal women are particularly at risk. Increasing physical activity has been recognized as an efficacious approach to prevent or treat obesity, yet the impact of physical activity on the microbiota remains under-investigated. We examined the impacts of voluntary exercise on host metabolism and gut microbiota in ovariectomized (OVX) high capacity (HCR) and low capacity running (LCR) rats. HCR and LCR rats (age = 27 wk) were OVX and fed a high-fat diet (45% kcal fat) ad libitum and housed in cages equipped with (exercise, EX) or without (sedentary, SED) running wheels for 11 wk (n = 7-8/group). We hypothesized that increased physical activity would hinder weight gain, increase metabolic health and shift the microbiota of LCR rats, resulting in populations more similar to that of HCR rats. Animals were compared for characteristic metabolic parameters including body composition, lipid profile and energy expenditure; whereas cecal digesta were collected for DNA extraction. 16S rRNA gene-based amplicon Illumina MiSeq sequencing was performed, followed by analysis using QIIME 1.8.0 to assess cecal microbiota. Voluntary exercise decreased body and fat mass, and normalized fasting NEFA concentrations of LCR rats, despite only running one-third the distance of HCR rats. Exercise, however, increased food intake, weight gain and fat mass of HCR rats. Exercise clustered the gut microbial community of LCR rats, which separated them from the other groups. Assessments of specific taxa revealed significant (p<0.05) line by exercise interactions including shifts in the abundances of Firmicutes, Proteobacteria, and Cyanobacteria. Relative abundance of Christensenellaceae family was higher (p = 0.026) in HCR than LCR rats, and positively correlated (p<0.05) with food intake, body weight and running distance. These findings demonstrate that exercise differentially impacts

  17. Enzymatic Regulation of Self-Assembling Peptide A9K2 Nanostructures and Hydrogelation with Highly Selective Antibacterial Activities.

    PubMed

    Bai, Jingkun; Chen, Cuixia; Wang, Jingxin; Zhang, Yu; Cox, Henry; Zhang, Jing; Wang, Yuming; Penny, Jeffrey; Waigh, Thomas; Lu, Jian R; Xu, Hai

    2016-06-22

    Hydrogels offer great potential for many biomedical and technological applications. For clinical uses, hydrogels that act as scaffold materials for cell culture, regenerative medicine, and drug delivery are required to have bactericidal properties. The amphiphilic peptide A9K2 was designed to effectively inhibit bacterial growth via a mechanism of membrane permeabilization. The present study demonstrated that addition of fetal bovine serum (FBS) or plasma amine oxidase (PAO) induced a sol-gel transition in A9K2 aqueous solutions. The transformation of A9K2 molecules catalyzed by lysyl oxidase (LO) in FBS or PAO accounted for the hydrogelation. Importantly, the enzymatic A9K2 hydrogel displayed high antibacterial ability against both Gram-negative and Gram-positive bacterial strains while showing extremely low mammalian cell cytotoxicity, thus demonstrating good biocompatibility. Under established coculture conditions, the peptide hydrogel showed excellent selectivity by favoring the adherence and spreading of mammalian cells, while killing pathogenic bacteria, thus avoiding bacterial contamination. These advantages endow the enzymatic A9K2 hydrogel with great potential for biomedical applications. PMID:27243270

  18. Effects of voluntary exercise and genetic selection for high activity levels on HSP72 expression in house mice.

    PubMed

    Belter, Jason G; Carey, Hannah V; Garland, Theodore

    2004-04-01

    We studied expression of heat shock protein 72 (HSP72) in female mice from four replicate lines that had been selectively bred for high voluntary wheel running (S) and from four random-bred control lines (C). Mice from generation 23 were sampled after 6 days of wheel access, and those from generation 14 were sampled after 8 wk of access to wheels either free to rotate or locked. Mice from S lines ran approximately 2.6 times as many revolutions per day as did those from C lines. Western blotting of tissues from generation 23 mice indicated that S mice had elevated HSP72 expression in triceps surae muscle, but levels in spleen, kidney, heart, and lung were similar in S and C mice. HSP72 expression in triceps surae from generation 14 mice was measured by ELISA and analyzed with a two-way analysis of covariance. The interaction between wheel type and line type (S vs. C) was statistically significant, and subsequent analyses indicated that S mice had significantly elevated HSP72 expression only when housed with free wheels. Mice with the previously described mini-muscle phenotype (Houle-Leroy P, Guderley H, Swallow JG, and Garland T Jr. Am J Physiol Regul Integr Comp Physiol 284: R433-R443, 2003) occurred in both generations and had elevated HSP72 expression in triceps surae. For the generation 23 sample, wheel running as a covariate had a significant negative association with HSP72 expression, and the effect of line type was still statistically significant. Therefore, the increased HSP72 expression of S mice is not a simple proximate effect of their increased wheel running. PMID:14672969

  19. Selecting Music for High School Pop Groups.

    ERIC Educational Resources Information Center

    Santy, Jeff

    1990-01-01

    Describes the criteria a high school music teacher used to select music for a new non-traditional class titled "Pop Band." Lists criteria that each song must have: playability, special feature, popular appeal, variety, artist's qualification, and appropriateness. Students took an active role in the decision-making process. (GG)

  20. Structure-activity relationships of 2-arylquinazolin-4-ones as highly selective and potent inhibitors of the tankyrases.

    PubMed

    Nathubhai, Amit; Haikarainen, Teemu; Hayward, Penelope C; Muñoz-Descalzo, Silvia; Thompson, Andrew S; Lloyd, Matthew D; Lehtiö, Lari; Threadgill, Michael D

    2016-08-01

    Tankyrases (TNKSs), members of the PARP (Poly(ADP-ribose)polymerases) superfamily of enzymes, have gained interest as therapeutic drug targets, especially as they are involved in the regulation of Wnt signalling. A series of 2-arylquinazolin-4-ones with varying substituents at the 8-position was synthesised. An 8-methyl group (compared to 8-H, 8-OMe, 8-OH), together with a 4'-hydrophobic or electron-withdrawing group, provided the most potency and selectivity towards TNKSs. Co-crystal structures of selected compounds with TNKS-2 revealed that the protein around the 8-position is more hydrophobic in TNKS-2 compared to PARP-1/2, rationalising the selectivity. The NAD(+)-binding site contains a hydrophobic cavity which accommodates the 2-aryl group; in TNKS-2, this has a tunnel to the exterior but the cavity is closed in PARP-1. 8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one was identified as a potent and selective inhibitor of TNKSs and Wnt signalling. This compound and analogues could serve as molecular probes to study proliferative signalling and for development of inhibitors of TNKSs as drugs. PMID:27163581

  1. High temperature size selective membranes

    SciTech Connect

    Yates, S.F.; Swamikannu, A.X.

    1993-09-01

    The high temperature membrane, capable of operation above 550{degree}C, is designed to be a composite membrane composed of a thin layer of a size selective membrane supported by a microporous ceramic support. The kinetic diameters of H{sub 2} and CO{sub 2} are 2.96 {Angstrom} and 4.00 {Angstrom}. The thin layer will be made from CMS whose pore size will be controlled to be less than 4 {Angstrom}. The membrane will be truly size selective and be impermeable to carbon dioxide. The membrane will have higher selectivity than membranes which operate on Knudsen diffusion mechanism. The ceramic support will be fabricated from Allied Signal`s proprietary Blackglas{trademark} resin. The ceramic material, noted for its high thermal and oxidative resistance, has a coefficient of thermal expansion which matches closely that of CMS. The close match will insure mechanical integrity when the membrane is subjected to thermal cycles. The CMS layer will be produced by controlled pyrolysis of polymeric precursors. Pore size will be suitably modified by post-treatments to the carbon. The composite membrane will be tested for its permeation properties at 550{degree}C or higher. Thermal, mechanical and chemical stability of the membrane will be assessed. We have produced several samples of CMS from polymeric precursors. We have initiated work also on the preparation of microporous supports from Blackglas{trademark} resin. We have completed the design of the high temperature membrane pilot plant. The membrane cell was fabricated out of two kinds of stainless steel. The inner parts are made of SS 316 and the outer ring made of SS 420. The greater thermal expansion of the SS 316 will help obtain a leak free seal at the operating temperatures.

  2. Discovery of novel tetrahydroisoquinoline derivatives as orally active N-type calcium channel blockers with high selectivity for hERG potassium channels.

    PubMed

    Ogiyama, Takashi; Inoue, Makoto; Honda, Shugo; Yamada, Hiroyoshi; Watanabe, Toshihiro; Gotoh, Takayasu; Kiso, Tetsuo; Koakutsu, Akiko; Kakimoto, Shuichiro; Shishikura, Jun-ichi

    2014-12-15

    N-type calcium channels represent a promising target for the treatment of neuropathic pain. The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration. We identified tetrahydroisoquinoline derivative 1a as a novel potent N-type calcium channel blocker. However, this compound also exhibited potent inhibitory activity against hERG channels. Structural optimizations led to identification of (1S)-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-{[(1-hydroxycyclohexyl)methyl]amino}ethanone ((S)-1h), which exhibited high selectivity for hERG channels while retaining potency for N-type calcium channel inhibition. (S)-1h went on to demonstrate in vivo efficacy as an orally available N-type calcium channel blocker in a rat spinal nerve ligation model of neuropathic pain. PMID:25456079

  3. The Influence of a High Intensity Physical Activity Intervention on a Selection of Health Related Outcomes: An Ecological Approach

    ClinicalTrials.gov

    2009-12-04

    To Assess the Impact of the HIT Intervention on Physiological Responses; To Assess the Role of a Secondary High School as a Setting for Promoting Healthy Eating and PA Behaviours; To Determine the Associations Between CVD Risk Factors at Baseline in 15 - 18 Year Old Youth

  4. Design of a high activity and selectivity alcohol catalyst. Sixth quarterly report, November 7, 1991--February 7, 1992

    SciTech Connect

    Foley, H.C.; Mills, G.A.

    1992-02-07

    Results of the pyridine adsorption, studies on native and K-doped alumina provide fundamental grounding for the observed methanol dehydration activity of these samples. Both the reactor studies and the pyridine adsorption studies support the conclusion that the K-doped sample had reduced Lewis acidity. Moreover, we were able to measurably alter the acidity of the support surface by our ion exchange treatment. More significantly, when reactor results for transition-metal loaded samples are reconsidered in combination with their surface characteristics suggested by our pyridine adsorption studies, our hypothesis that Rh and Mo have ultimately titrated the support surface seems all the more convincing. Hence, in light of the pyridine adsorption results, the attenuation of a transition-metal based decomposition pathway for methanol on the metal-loaded samples-as seen in the reactor testing-is all the more reasonable.

  5. The Mass-Pitch Angle Relation for Three High Redshift Active Galaxies Selected from the GOODS Field

    NASA Astrophysics Data System (ADS)

    Hughes, John

    As we continue to investigate and ponder the heavens, we have come to realize the presence of highly energetic gravitational wells at the center of all galaxies. These supermassive black holes at a galaxies nucleus formed in the company of the other features making up the galaxy, particularly spiral arms. With nearby galaxies showing a relationship between the spiral arm pitch angle and that central mass, here we push that relationship out to distances of redshift one. With three galaxies at this distance we find that they also hold to the same relationship of tighter spiral arms corresponding to more massive central black holes. We find that these three galaxies near a redshift of one also fit the equation log (n/a) = (8.21 +/- 0.16) -- (0.062 +/- 0.009) P given by Berrier et al. (2013) for nearby spiral galaxies. Further investigation of higher signal to noise spectroscopic observations will increase this confidence and demonstrate the robustness of the M -- P relationship at greater distances.

  6. COLOR-MAGNITUDE RELATIONS OF ACTIVE AND NON-ACTIVE GALAXIES IN THE CHANDRA DEEP FIELDS: HIGH-REDSHIFT CONSTRAINTS AND STELLAR-MASS SELECTION EFFECTS

    SciTech Connect

    Xue, Y. Q.; Brandt, W. N.; Luo, B.; Rafferty, D. A.; Schneider, D. P.; Alexander, D. M.; Lehmer, B. D.; Bauer, F. E.; Silverman, J. D.

    2010-09-01

    -mass-matched samples where there is apparent AGN clustering in the CMD and the AGN fraction generally increases as the color becomes redder. We also find, for mass-matched samples, that the star formation rates of AGN hosts are typically a factor of {approx} 2-3 larger than those of non-AGN galaxies at z {approx} 0-1, whereas this difference diminishes at z {approx} 1-3. With mass-selection effects taken into account, we find that almost all of the results obtained in this work can reasonably be explained by two main ingredients, color-mass correlation (i.e., X-ray AGNs preferentially reside in massive galaxies that generally tend to be redder than less-massive galaxies) and passive or secular evolution of galaxies. Our results show that the presence of moderate-luminosity AGN activity does not have a significant effect on the colors of galaxies and thus tightly constrain any effects from moderate-luminosity AGN feedback upon color-magnitude properties over the {approx} 80% of cosmic time during which most of galaxy formation occurred.

  7. Floriculture. Selected Learning Activity Packages.

    ERIC Educational Resources Information Center

    Clemson Univ., SC. Vocational Education Media Center.

    This series of learning activity packages is based on a catalog of performance objectives, criterion-referenced measures, and performance guides for gardening/groundskeeping developed by the Vocational Education Consortium of States (V-TECS). Learning activity packages are presented in four areas: (1) preparation of soils and planting media, (2)…

  8. Visible-Light-Active Plasmonic Ag-SrTiO3 Nanocomposites for the Degradation of NO in Air with High Selectivity.

    PubMed

    Zhang, Qian; Huang, Yu; Xu, Lifeng; Cao, Jun-ji; Ho, Wingkei; Lee, Shun Cheng

    2016-02-17

    Harnessing inexhaustible solar energy for photocatalytic disposal of nitrogen oxides is of great significance nowadays. In this study, Ag-SrTiO3 nanocomposites (Ag-STO) were synthesized via one-pot solvothermal method for the first time. The deposition of Ag nanoparticles incurs a broad plasmonic resonance absorption in the visible light range, resulting in enhanced visible light driven activity on NO removal in comparison with pristine SrTiO3. The Ag loading amount has a significant influence on light absorption properties of Ag-STO, which further affects the photocatalytic efficiency. It was shown that 0.5% Ag loading onto SrTiO3 (in mass ratio) could remove 30% of NO in a single reaction path under visible light irradiation, which is twice higher than that achieved on pristine SrTiO3. Most importantly, the generation of harmful intermediate (NO2) is largely inhibited over SrTiO3 and Ag-STO nanocomposites, which can be ascribed to the basic surface property of strontium sites. As identified by electron spin resonance (ESR) spectra,·O2(-) and ·OH radicals are the major reactive species for NO oxidation. Essentially speaking, the abundance of reactive oxygen radicals produced over Ag-STO nanocomposites are responsible for the improved photocatalytic activity. This work provides a facile and controllable route to fabricate plasmonic Ag-SrTiO3 nanocomposite photocatalyst featuring high visible light activity and selectivity for NO abatement. PMID:26796511

  9. Efficient CRISPR/Cas9-mediated biallelic gene disruption and site-specific knockin after rapid selection of highly active sgRNAs in pigs

    PubMed Central

    Wang, Xianlong; Zhou, Jinwei; Cao, Chunwei; Huang, Jiaojiao; Hai, Tang; Wang, Yanfang; Zheng, Qiantao; Zhang, Hongyong; Qin, Guosong; Miao, Xiangnan; Wang, Hongmei; Cao, Suizhong; Zhou, Qi; Zhao, Jianguo

    2015-01-01

    Genetic engineering in livestock was greatly enhanced by the emergence of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), which can be programmed with a single-guide RNA (sgRNA) to generate site-specific DNA breaks. However, the uncertainties caused by wide variations in sgRNA activity impede the utility of this system in generating genetically modified pigs. Here, we described a single blastocyst genotyping system to provide a simple and rapid solution to evaluate and compare the sgRNA efficiency at inducing indel mutations for a given gene locus. Assessment of sgRNA mutagenesis efficiencies can be achieved within 10 days from the design of the sgRNA. The most effective sgRNA selected by this system was successfully used to induce site-specific insertion through homology-directed repair at a frequency exceeding 13%. Additionally, the highly efficient gene deletion via the selected sgRNA was confirmed in pig fibroblast cells, which could serve as donor cells for somatic cell nuclear transfer. We further showed that direct cytoplasmic injection of Cas9 mRNA and the favorable sgRNA into zygotes could generate biallelic knockout piglets with an efficiency of up to 100%. Thus, our method considerably reduces the uncertainties and expands the practical possibilities of CRISPR/Cas9-mediated genome engineering in pigs. PMID:26293209

  10. Infusing and selecting V&V activities

    NASA Technical Reports Server (NTRS)

    Feather, M. S.

    2002-01-01

    The evolving nature of software development poses a continuing series of challenges for V&V. In response, the V&V community selectively adapts the use of existing V&V activities, and introduces new and improved ones.

  11. The origin of high activity but low CO(2) selectivity on binary PtSn in the direct ethanol fuel cell.

    PubMed

    Jin, Jia-Mei; Sheng, Tian; Lin, Xiao; Kavanagh, Richard; Hamer, Philip; Hu, Peijun; Hardacre, Christopher; Martinez-Bonastre, Alex; Sharman, Jonathan; Thompsett, David; Lin, Wen-Feng

    2014-05-28

    The most active binary PtSn catalyst for direct ethanol fuel cell applications has been studied at 20 °C and 60 °C, using variable temperature electrochemical in situ FTIR. In comparison with Pt, binary PtSn inhibits ethanol dissociation to CO(a), but promotes partial oxidation to acetaldehyde and acetic acid. Increasing the temperature from 20 °C to 60 °C facilitates both ethanol dissociation to CO(a) and then further oxidation to CO2, leading to an increased selectivity towards CO2; however, acetaldehyde and acetic acid are still the main products. Potential-dependent phase diagrams for surface oxidants of OH(a) formation on Pt(111), Pt(211) and Sn modified Pt(111) and Pt(211) surfaces have been determined using density functional theory (DFT) calculations. It is shown that Sn promotes the formation of OH(a) with a lower onset potential on the Pt(111) surface, whereas an increase in the onset potential is found upon modification of the (211) surface. In addition, Sn inhibits the Pt(211) step edge with respect to ethanol C-C bond breaking compared with that found on the pure Pt, which reduces the formation of CO(a). Sn was also found to facilitate ethanol dehydrogenation and partial oxidation to acetaldehyde and acetic acid which, combined with the more facile OH(a) formation on the Pt(111) surface, gives us a clear understanding of the experimentally determined results. This combined electrochemical in situ FTIR and DFT study provides, for the first time, an insight into the long-term puzzling features of the high activity but low CO2 production found on binary PtSn ethanol fuel cell catalysts. PMID:24722871

  12. Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

    SciTech Connect

    Chen, Aiqiong; Du, Dan; Lin, Yuehe

    2012-02-09

    Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

  13. Selection of active spaces for multiconfigurational wavefunctions

    NASA Astrophysics Data System (ADS)

    Keller, Sebastian; Boguslawski, Katharina; Janowski, Tomasz; Reiher, Markus; Pulay, Peter

    2015-06-01

    The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F2, ozone, and NO2), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr2). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions are discussed

  14. Selection of active spaces for multiconfigurational wavefunctions.

    PubMed

    Keller, Sebastian; Boguslawski, Katharina; Janowski, Tomasz; Reiher, Markus; Pulay, Peter

    2015-06-28

    The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F2, ozone, and NO2), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr2). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions are discussed

  15. Selection of active spaces for multiconfigurational wavefunctions

    SciTech Connect

    Keller, Sebastian; Boguslawski, Katharina; Reiher, Markus; Janowski, Tomasz; Pulay, Peter

    2015-06-28

    The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F{sub 2}, ozone, and NO{sub 2}), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr{sub 2}). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions

  16. High temperature solar selective coatings

    DOEpatents

    Kennedy, Cheryl E

    2014-11-25

    Improved solar collectors (40) comprising glass tubing (42) attached to bellows (44) by airtight seals (56) enclose solar absorber tubes (50) inside an annular evacuated space (54. The exterior surfaces of the solar absorber tubes (50) are coated with improved solar selective coatings {48} which provide higher absorbance, lower emittance and resistance to atmospheric oxidation at elevated temperatures. The coatings are multilayered structures comprising solar absorbent layers (26) applied to the meta surface of the absorber tubes (50), typically stainless steel, topped with antireflective Savers (28) comprising at least two layers 30, 32) of refractory metal or metalloid oxides (such as titania and silica) with substantially differing indices of refraction in adjacent layers. Optionally, at least one layer of a noble metal such as platinum can be included between some of the layers. The absorbent layers cars include cermet materials comprising particles of metal compounds is a matrix, which can contain oxides of refractory metals or metalloids such as silicon. Reflective layers within the coating layers can comprise refractory metal silicides and related compounds characterized by the formulas TiSi. Ti.sub.3SiC.sub.2, TiAlSi, TiAN and similar compounds for Zr and Hf. The titania can be characterized by the formulas TiO.sub.2, Ti.sub.3O.sub.5. TiOx or TiO.sub.xN.sub.1-x with x 0 to 1. The silica can be at least one of SiO.sub.2, SiO.sub.2x or SiO.sub.2xN.sub.1-x with x=0 to 1.

  17. CHF6001 I: a novel highly potent and selective phosphodiesterase 4 inhibitor with robust anti-inflammatory activity and suitable for topical pulmonary administration.

    PubMed

    Moretto, Nadia; Caruso, Paola; Bosco, Raffaella; Marchini, Gessica; Pastore, Fiorella; Armani, Elisabetta; Amari, Gabriele; Rizzi, Andrea; Ghidini, Eleonora; De Fanti, Renato; Capaldi, Carmelida; Carzaniga, Laura; Hirsch, Emilio; Buccellati, Carola; Sala, Angelo; Carnini, Chiara; Patacchini, Riccardo; Delcanale, Maurizio; Civelli, Maurizio; Villetti, Gino; Facchinetti, Fabrizio

    2015-03-01

    This study examined the pharmacologic characterization of CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a novel phosphodiesterase (PDE)4 inhibitor designed for treating pulmonary inflammatory diseases via inhaled administration. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity (IC50 = 0.026 ± 0.006 nM). CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (i.e., >40) and displayed >20,000-fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively inhibited (subnanomolar IC50 values) the release of tumor necrosis factor-α from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). Moreover, CHF6001 potently inhibited the activation of oxidative burst in neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon-γ from CD4(+) T cells. In all these functional assays, CHF6001 was more potent than previously described PDE4 inhibitors, including roflumilast, UK-500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide]. When administered intratracheally to rats as a micronized dry powder, CHF6001 inhibited liposaccharide-induced pulmonary neutrophilia (ED50 = 0.205 μmol/kg) and leukocyte infiltration (ED50 = 0.188 μmol/kg) with an efficacy comparable to a high dose of budesonide (1 μmol/kg i.p.). In sum, CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including

  18. MECHANISTIC STUDIES AND DESIGN OF HIGHLY ACTIVE CUPRATE CATALYSTS FOR THE DIRECT DECOMPOSITION AND SELECTIVE REDUCTION OF NITRIC OXIDE AND HYDROCARBONS TO NITROGEN FOR ABATEMENT OF STACK EMISSIONS

    SciTech Connect

    1998-04-30

    A flow trough type catalytic reactor system was adequately modified for NO related catalytic and adsorption measurements, including the on-line connection of a digital chemiluminescent NO-NO{sub x} analyzer to the reactor outlet system. Moreover, we have largely completed the installation of an FTIR coupled catalytic system containing a HTEC cell for high temperature DRIFT studies. Three different barium cuprate samples, Ba{sub 2}CuO{sub 3}, BaCuO{sub 2}, and Ba{sub 2}Cu{sub 3}O{sub 5} were synthesized and characterized by powder XRD for catalytic tests. Prior to catalytic studies over these cuprates, a new, liquid indium based supported molten metal catalyst (In-SMMC) was tested in the reduction of NO by various reductants. In the presence of excess O{sub 2} and H{sub 2}O, the In-SMMC proved to be more active for the selective catalytic reduction (SCR) of NO to N{sub 2} by ethanol than most other catalysts. Using C{sub 1}-C{sub 3} alcohols as reductants, self sustained periodic oscillations observed in the NO{sub x} concentrations of reactor effluents indicated the first time that radical intermediates can be involved in the SCR of NO by alcohols. Further, In-SMMC is the only effective and water tolerant SCR catalyst reported thus far which contains SiO{sub 2} support. Thus, this novel catalyst opens up a promising new alternative for developing an effective and durable catalyst for NO{sub x} abatement in stack emission.

  19. Highly Active Au/δ-MoC and Cu/δ-MoC Catalysts for the Conversion of CO2: The Metal/C Ratio as a Key Factor Defining Activity, Selectivity, and Stability.

    PubMed

    Posada-Pérez, Sergio; Ramírez, Pedro J; Evans, Jaime; Viñes, Francesc; Liu, Ping; Illas, Francesc; Rodriguez, José A

    2016-07-01

    The ever growing increase of CO2 concentration in the atmosphere is one of the main causes of global warming. Thus, CO2 activation and conversion toward valuable added compounds is a major scientific challenge. A new set of Au/δ-MoC and Cu/δ-MoC catalysts exhibits high activity, selectivity, and stability for the reduction of CO2 to CO with some subsequent selective hydrogenation toward methanol. Sophisticated experiments under controlled conditions and calculations based on density functional theory have been used to study the unique behavior of these systems. A detailed comparison of the behavior of Au/β-Mo2C and Au/δ-MoC catalysts provides evidence of the impact of the metal/carbon ratio in the carbide on the performance of the catalysts. The present results show that this ratio governs the chemical behavior of the carbide and the properties of the admetal, up to the point of being able to switch the rate and mechanism of the process for CO2 conversion. A control of the metal/carbon ratio paves the road for an efficient reutilization of this environmental harmful greenhouse gas. PMID:27308923

  20. Identifying and applying a highly selective probe to simultaneously determine the O-glucuronidation activity of human UGT1A3 and UGT1A4

    PubMed Central

    Jiang, Li; Liang, Si-Cheng; Wang, Chao; Ge, Guang-Bo; Huo, Xiao-Kui; Qi, Xiao-Yi; Deng, Sa; Liu, Ke-Xin; Ma, Xiao-Chi

    2015-01-01

    Glucuronidation mediated by uridine 5′-diphospho (UDP)-glucuronosyltransferase is an important detoxification pathway. However, identifying a selective probe of UDP- glucuronosyltransferase is complicated because of the significant overlapping substrate specificity displayed by the enzyme. In this paper, desacetylcinobufagin (DACB) 3-O- and 16-O-glucuronidation were found to be isoform-specific probe reactions for UGT1A4 and UGT1A3, respectively. DACB was well characterized as a probe for simultaneously determining the catalytic activities of O-glucuronidation mediated by UGT1A3 and UGT1A4 from various enzyme sources, through a sensitive analysis method. PMID:25884245

  1. Discovery of a highly selective PLD2 inhibitor (ML395): a new probe with improved physiochemical properties and broad spectrum antiviral activity against influenza strains

    PubMed Central

    O’Reilly, Matthew C.; Oguin, Thomas H.; Scott, Sarah A.; Thomas, Paul G.; Locuson, Charles W.; Morrison, Ryan D.; Daniels, J. Scott; Brown, H. Alex

    2014-01-01

    Further chemical optimization of the halopemide-derived family of dual PLD1/2 inhibitors afforded ML395 (VU0468809), a potent, >80-fold PLD2 selective allosteric inhibitor (cellular PLD1, IC50 >30,000 nM, cellular PLD2, IC50 = 360 nM). Moreover, ML395 possesses an attractive in vitro DMPK profile, improved physiochemical properties, ancillary pharmacology (Eurofins Panel) cleaner than any other reported PLD inhibitor, and has been found to possess interesting activity as an antiviral agent in cellular assays against a range of influenza strains (H1, H3, H5 and H7). PMID:25210004

  2. Development of a Multiplex Assay for Studying Functional Selectivity of Human Serotonin 5-HT2A Receptors and Identification of Active Compounds by High-Throughput Screening.

    PubMed

    Iglesias, Alba; Lage, Sonia; Cadavid, Maria Isabel; Loza, Maria Isabel; Brea, José

    2016-09-01

    G protein-coupled receptors (GPCRs) exist as collections of conformations in equilibrium, and the efficacy of drugs has been proposed to be associated with their absolute and relative affinities for these different conformations. The serotonin 2A (5-HT2A) receptor regulates multiple physiological functions, is involved in the pathophysiology of schizophrenia, and serves as an important target of atypical antipsychotic drugs. This receptor was one of the first GPCRs for which the functional selectivity phenomenon was observed, with its various ligands exerting differential effects on the phospholipase A2 (PLA2) and phospholipase C (PLC) signaling pathways. We aimed to develop a multiplex functional assay in 96-well plates for the simultaneous measurement of the PLA2 and PLC pathways coupled to 5-HT2A receptors; this approach enables the detection of either functional selectivity or cooperativity phenomena in early drug screening stages. The suitability of the method for running screening campaigns was tested using the Prestwick Chemical Library, and 22 confirmed hits with activities of more than 90% were identified; 11 of these hits produced statistically significant differences between the two effector pathways. Thus, we have developed a miniaturized multiplex assay in 96-well plates to measure functional selectivity for 5-HT2A receptors in the early stages of the drug discovery process. PMID:27095818

  3. High specific selectivity and Membrane-Active Mechanism of the synthetic centrosymmetric α-helical peptides with Gly-Gly pairs

    PubMed Central

    Wang, Jiajun; Chou, Shuli; Xu, Lin; Zhu, Xin; Dong, Na; Shan, Anshan; Chen, Zhihui

    2015-01-01

    We used a template-assisted approach to develop synthetic antimicrobial peptides, which differ from naturally occurring antimicrobial peptides that can compromise host natural defenses. Previous researches have demonstrated that symmetrical distribution patterns of amino acids contribute to the antimicrobial activity of natural peptides. However, there is little research describing such design ideas for synthetic α-helical peptides. Therefore, here, we established a centrosymmetric α-helical sequence template (y + hhh + y)n (h, hydrophobic amino acid; +, cationic amino acid; y, Gly or hydrophobic amino acid), which contributed to amphipathicity, and a series of centrosymmetric peptides was designed with pairs of small amino acids (Ala and Gly), which were utilized to modulate the biological activity. The centrosymmetric peptides with 3 repeat units exhibited strong antimicrobial activity; in particular, the Gly-rich centrosymmetric peptide GG3 showed stronger selectivity for gram-negative bacteria without hemolysis. Furthermore, beyond our expectation, fluorescence spectroscopy and electron microscopy analyses indicated that the GG3, which possessed poor α-helix conformation, dramatically exhibited marked membrane destruction via inducing bacterial membrane permeabilization, pore formation and disruption, even bound DNA to further exert antimicrobial activity. Collectively, the Gly-rich centrosymmetric peptide GG3 was an ideal candidate for commercialization as a clinical therapeutic to treat gram-negative bacterial infections. PMID:26530005

  4. High Dimensional Variable Selection with Error Control.

    PubMed

    Kim, Sangjin; Halabi, Susan

    2016-01-01

    Background. The iterative sure independence screening (ISIS) is a popular method in selecting important variables while maintaining most of the informative variables relevant to the outcome in high throughput data. However, it not only is computationally intensive but also may cause high false discovery rate (FDR). We propose to use the FDR as a screening method to reduce the high dimension to a lower dimension as well as controlling the FDR with three popular variable selection methods: LASSO, SCAD, and MCP. Method. The three methods with the proposed screenings were applied to prostate cancer data with presence of metastasis as the outcome. Results. Simulations showed that the three variable selection methods with the proposed screenings controlled the predefined FDR and produced high area under the receiver operating characteristic curve (AUROC) scores. In applying these methods to the prostate cancer example, LASSO and MCP selected 12 and 8 genes and produced AUROC scores of 0.746 and 0.764, respectively. Conclusions. We demonstrated that the variable selection methods with the sequential use of FDR and ISIS not only controlled the predefined FDR in the final models but also had relatively high AUROC scores. PMID:27597974

  5. High Dimensional Variable Selection with Error Control

    PubMed Central

    2016-01-01

    Background. The iterative sure independence screening (ISIS) is a popular method in selecting important variables while maintaining most of the informative variables relevant to the outcome in high throughput data. However, it not only is computationally intensive but also may cause high false discovery rate (FDR). We propose to use the FDR as a screening method to reduce the high dimension to a lower dimension as well as controlling the FDR with three popular variable selection methods: LASSO, SCAD, and MCP. Method. The three methods with the proposed screenings were applied to prostate cancer data with presence of metastasis as the outcome. Results. Simulations showed that the three variable selection methods with the proposed screenings controlled the predefined FDR and produced high area under the receiver operating characteristic curve (AUROC) scores. In applying these methods to the prostate cancer example, LASSO and MCP selected 12 and 8 genes and produced AUROC scores of 0.746 and 0.764, respectively. Conclusions. We demonstrated that the variable selection methods with the sequential use of FDR and ISIS not only controlled the predefined FDR in the final models but also had relatively high AUROC scores. PMID:27597974

  6. Highly Selective Ruthenium Metathesis Catalysts for Ethenolysis

    PubMed Central

    Thomas, Renee M.; Keitz, Benjamin K.; Champagne, Timothy M.; Grubbs, Robert H.

    2011-01-01

    N-aryl, N-alkyl N-heterocyclic carbene (NHC) ruthenium metathesis catalysts are highly selective toward the ethenolysis of methyl oleate, giving selectivity as high as 95% for the kinetic, ethenolysis products over the thermodynamic, self-metathesis products. The examples described herein represent some of the most selective NHC-based ruthenium catalysts for ethenolysis reactions to date. Furthermore, many of these catalysts show unusual preference and stability toward propagating as a methylidene species, and provide good yields and turnover numbers (TONs) at relatively low catalyst loading (<500 ppm). A catalyst comparison showed that ruthenium complexes bearing sterically hindered NHC substituents afforded greater selectivity and stability, and exhibited longer catalyst lifetime during reactions. Comparative analysis of the catalyst preference for kinetic versus thermodynamic product formation was achieved via evaluation of their steady-state conversion in the cross-metathesis reaction of terminal olefins. These results coincided with the observed ethenolysis selectivities, in which the more selective catalysts reach a steady-state characterized by lower conversion to cross-metathesis products compared to less selective catalysts, which show higher conversion to cross-metathesis products. PMID:21510645

  7. Stochastic cycle selection in active flow networks.

    PubMed

    Woodhouse, Francis G; Forrow, Aden; Fawcett, Joanna B; Dunkel, Jörn

    2016-07-19

    Active biological flow networks pervade nature and span a wide range of scales, from arterial blood vessels and bronchial mucus transport in humans to bacterial flow through porous media or plasmodial shuttle streaming in slime molds. Despite their ubiquity, little is known about the self-organization principles that govern flow statistics in such nonequilibrium networks. Here we connect concepts from lattice field theory, graph theory, and transition rate theory to understand how topology controls dynamics in a generic model for actively driven flow on a network. Our combined theoretical and numerical analysis identifies symmetry-based rules that make it possible to classify and predict the selection statistics of complex flow cycles from the network topology. The conceptual framework developed here is applicable to a broad class of biological and nonbiological far-from-equilibrium networks, including actively controlled information flows, and establishes a correspondence between active flow networks and generalized ice-type models. PMID:27382186

  8. Selective Activation of the Infraspinatus Muscle

    PubMed Central

    Ha, Sung-Min; Kwon, Oh-Yun; Cynn, Heon-Seock; Lee, Won-Hwee; Kim, Su-Jung; Park, Kyue-Nam

    2013-01-01

    Context: To improve selective infraspinatus muscle strength and endurance, researchers have recommended selective shoulder external-rotation exercise during rehabilitation or athletic conditioning programs. Although selective strengthening of the infraspinatus muscle is recommended for therapy and training, limited information is available to help clinicians design a selective strengthening program. Objective: To determine the most effective of 4 shoulder external-rotation exercises for selectively stimulating infraspinatus muscle activity while minimizing the use of the middle trapezius and posterior deltoid muscles. Design: Cross-sectional study. Setting: University research laboratory. Patients or Other Participants: A total of 30 healthy participants (24 men, 6 women; age = 22.6 ± 1.7 years, height = 176.2 ± 4.5 cm, mass = 65.6 ± 7.4 kg) from a university population. Intervention(s): The participants were instructed to perform 4 exercises: (1) prone horizontal abduction with external rotation (PER), (2) side-lying wiper exercise (SWE), (3) side-lying external rotation (SER), and (4) standing external-rotation exercise (STER). Main Outcome Measure(s): Surface electromyography signals were recorded from the infraspinatus, middle trapezius, and posterior deltoid muscles. Differences among the exercise positions were tested using a 1-way repeated-measures analysis of variance with Bonferroni adjustment. Results: The infraspinatus muscle activity was greater in the SWE (55.98% ± 18.79%) than in the PER (46.14% ± 15.65%), SER (43.38% ± 22.26%), and STER (26.11% ± 15.00%) (F3,87 = 19.97, P < .001). Furthermore, the SWE elicited the least amount of activity in the middle trapezius muscle (F3,87 = 20.15, P < .001). Posterior deltoid muscle activity was similar in the SWE and SER but less than that measured in the PER and STER (F3,87 = 25.10, P < .001). Conclusions: The SWE was superior to the PER, SER, and STER in maximizing infraspinatus activity with the least

  9. Aggregation-Induced Emission Active Metal-Free Chemosensing Platform for Highly Selective Turn-On Sensing and Bioimaging of Pyrophosphate Anion.

    PubMed

    Gogoi, Abhijit; Mukherjee, Sandipan; Ramesh, Aiyagari; Das, Gopal

    2015-07-01

    We report the synthesis of a metal-free chemosensor for highly selective sensing of pyrophosphate (PPi) anion in physiological medium. The novel phenylbenzimidazole functionalized imine containing chemosensor (L; [2,6-bis(((4-(1H-benzo[d]imidazol-2-yl)phenyl)imino) methyl)-4 methyl phenol]) could sense PPi anion through "turn-on" colorimetric and fluorimetric responses in a very competitive environment. The overall sensing mechanism is based on the aggregation-induced emission (AIE) phenomenon. Moreover, a real time in-field device application was demonstrated by sensing PPi in paper strips coated with L. Interestingly, detection of intracellular PPi ions in model human cells could also be possible by fluorescence microscopic studies without any toxicity to these cells. PMID:26059015

  10. Merging rhodium-catalysed C-H activation and hydroamination in a highly selective [4+2] imine/alkyne annulation.

    PubMed

    Manan, Rajith S; Zhao, Pinjing

    2016-01-01

    Catalytic C-H activation and hydroamination represent two important strategies for eco-friendly chemical synthesis with high atom efficiency and reduced waste production. Combining both C-H activation and hydroamination in a cascade process, preferably with a single catalyst, would allow rapid access to valuable nitrogen-containing molecules from readily available building blocks. Here we report a single metal catalyst-based approach for N-heterocycle construction by tandem C-H functionalization and alkene hydroamination. A simple catalyst system of cationic rhodium(I) precursor and phosphine ligand promotes redox-neutral [4+2] annulation between N-H aromatic ketimines and internal alkynes to form multi-substituted 3,4-dihydroisoquinolines (DHIQs) in high chemoselectivity over competing annulation processes, exclusive cis-diastereoselectivity, and distinct regioselectivity for alkyne addition. This study demonstrates the potential of tandem C-H activation and alkene hydrofunctionalization as a general strategy for modular and atom-efficient assembly of six-membered heterocycles with multiple chirality centres. PMID:27321650

  11. Merging rhodium-catalysed C–H activation and hydroamination in a highly selective [4+2] imine/alkyne annulation

    PubMed Central

    Manan, Rajith S.; Zhao, Pinjing

    2016-01-01

    Catalytic C–H activation and hydroamination represent two important strategies for eco-friendly chemical synthesis with high atom efficiency and reduced waste production. Combining both C–H activation and hydroamination in a cascade process, preferably with a single catalyst, would allow rapid access to valuable nitrogen-containing molecules from readily available building blocks. Here we report a single metal catalyst-based approach for N-heterocycle construction by tandem C–H functionalization and alkene hydroamination. A simple catalyst system of cationic rhodium(I) precursor and phosphine ligand promotes redox-neutral [4+2] annulation between N–H aromatic ketimines and internal alkynes to form multi-substituted 3,4-dihydroisoquinolines (DHIQs) in high chemoselectivity over competing annulation processes, exclusive cis-diastereoselectivity, and distinct regioselectivity for alkyne addition. This study demonstrates the potential of tandem C–H activation and alkene hydrofunctionalization as a general strategy for modular and atom-efficient assembly of six-membered heterocycles with multiple chirality centres. PMID:27321650

  12. Senior English in Selected High Schools.

    ERIC Educational Resources Information Center

    Trammell, Robert Thomas

    In this study, 50 teachers of senior English were surveyed regarding their academic preparation and the English programs and curricular practices in their schools (18 selected high schools in Alabama). An analysis of existing professional literature was made to determine the status of current senior English programs and to ascertain what criteria…

  13. Highly Selective Anti-Cancer Activity of Cholesterol-Interacting Agents Methyl-β-Cyclodextrin and Ostreolysin A/Pleurotolysin B Protein Complex on Urothelial Cancer Cells.

    PubMed

    Resnik, Nataša; Repnik, Urška; Kreft, Mateja Erdani; Sepčić, Kristina; Maček, Peter; Turk, Boris; Veranič, Peter

    2015-01-01

    Cholesterol content can vary distinctly between normal and cancer cells, with elevated levels in cancer cells. Here, we investigated cholesterol sequestration with methyl-β-cyclodextrin (MCD), and pore-formation with the ostreolysin A/pleurotolysin B (OlyA/PlyB) protein complex that binds to cholesterol/sphingomyelin-rich membrane domains. We evaluated the effects on viability of T24 invasive and RT4 noninvasive human urothelial cancer cells and normal porcine urothelial (NPU) cells. Cholesterol content strongly correlated with cancerous transformation, as highest in the T24 high-grade invasive urothelial cancer cells, and lowest in NPU cells. MCD treatment induced prominent cell death of T24 cells, whereas OlyA/PlyB treatment resulted in greatly decreased viability of the RT4 low-grade noninvasive carcinoma cells. Biochemical and transmission electron microscopy analyses revealed that MCD and OlyA/PlyB induce necrotic cell death in these cancer cells, while viability of NPU cells was not significantly affected by either treatment. We conclude that MCD is more toxic for T24 high-grade invasive urothelial cancer cells, and OlyA/PlyB for RT4 low-grade noninvasive urothelial cancer cells, and neither is toxic for NPU cells. The cholesterol and cholesterol/sphingomyelin-rich membrane domains in urothelial cancer cells thus constitute a selective therapeutic target for elimination of urothelial cancer cells. PMID:26361392

  14. Highly Selective Anti-Cancer Activity of Cholesterol-Interacting Agents Methyl-β-Cyclodextrin and Ostreolysin A/Pleurotolysin B Protein Complex on Urothelial Cancer Cells

    PubMed Central

    Resnik, Nataša; Repnik, Urška; Kreft, Mateja Erdani; Sepčić, Kristina; Maček, Peter; Turk, Boris; Veranič, Peter

    2015-01-01

    Cholesterol content can vary distinctly between normal and cancer cells, with elevated levels in cancer cells. Here, we investigated cholesterol sequestration with methyl-β-cyclodextrin (MCD), and pore-formation with the ostreolysin A/pleurotolysin B (OlyA/PlyB) protein complex that binds to cholesterol/sphingomyelin-rich membrane domains. We evaluated the effects on viability of T24 invasive and RT4 noninvasive human urothelial cancer cells and normal porcine urothelial (NPU) cells. Cholesterol content strongly correlated with cancerous transformation, as highest in the T24 high-grade invasive urothelial cancer cells, and lowest in NPU cells. MCD treatment induced prominent cell death of T24 cells, whereas OlyA/PlyB treatment resulted in greatly decreased viability of the RT4 low-grade noninvasive carcinoma cells. Biochemical and transmission electron microscopy analyses revealed that MCD and OlyA/PlyB induce necrotic cell death in these cancer cells, while viability of NPU cells was not significantly affected by either treatment. We conclude that MCD is more toxic for T24 high-grade invasive urothelial cancer cells, and OlyA/PlyB for RT4 low-grade noninvasive urothelial cancer cells, and neither is toxic for NPU cells. The cholesterol and cholesterol/sphingomyelin-rich membrane domains in urothelial cancer cells thus constitute a selective therapeutic target for elimination of urothelial cancer cells. PMID:26361392

  15. Selective Activation of Microglia Facilitates Synaptic Strength

    PubMed Central

    Clark, Anna K.; Gruber-Schoffnegger, Doris; Drdla-Schutting, Ruth; Gerhold, Katharina J.; Malcangio, Marzia

    2015-01-01

    Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1β from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states. PMID:25788673

  16. Dynamics of Active Sensing and Perceptual Selection

    PubMed Central

    Schroeder, Charles E; Wilson, Donald A.; Radman, Thomas; Scharfman, Helen; Lakatos, Peter

    2010-01-01

    Sensory processing is often regarded as a passive process in which a biological sensors like photo- and mechanoreceptors transducer physical energy into a neural code. Recent findings, however, suggest that: 1) most sensory processing is active, and largely determined by motor/attentional sampling routines, 2) due to rhythmicity in the motor routine, as well as to its entrainment of ambient rhythms in sensory regions, sensory inflow tends to be rhythmic, and 3) attentional manipulation of rhythms in sensory pathways is instrumental to perceptual selection. These observations outline the essentials of an Active Sensing paradigm, and argue for increased emphasis on the study of sensory processes as specific to the dynamic motor/attentional context in which inputs are acquired. PMID:20307966

  17. Dynamics of Active Sensing and perceptual selection.

    PubMed

    Schroeder, Charles E; Wilson, Donald A; Radman, Thomas; Scharfman, Helen; Lakatos, Peter

    2010-04-01

    Sensory processing is often regarded as a passive process in which biological receptors like photoreceptors and mechanoreceptors transduce physical energy into a neural code. Recent findings, however, suggest that: first, most sensory processing is active, and largely determined by motor/attentional sampling routines; second, owing to rhythmicity in the motor routine, as well as to its entrainment of ambient rhythms in sensory regions, sensory inflow tends to be rhythmic; third, attentional manipulation of rhythms in sensory pathways is instrumental to perceptual selection. These observations outline the essentials of an Active Sensing paradigm, and argue for increased emphasis on the study of sensory processes as specific to the dynamic motor/attentional context in which inputs are acquired. PMID:20307966

  18. 15 CFR 922.21 - Selection of active candidates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites... standards set forth in section 303 of the Act. (b) Selection of a site as an Active Candidate shall...

  19. Selected Technology Lab Activities Implementation Guide.

    ERIC Educational Resources Information Center

    Portland Public Schools, OR.

    These materials supplement state guides for junior high or middle school technology education programs. The materials show instructors how to implement 81 hours of new technology-related activities into existing programs. Introductory materials include a rationale, philosophy, and goals for technology education. Areas of instruction are as…

  20. Antibacterial activity of selected Malaysian honey

    PubMed Central

    2013-01-01

    Background Antibacterial activity of honey is mainly dependent on a combination of its peroxide activity and non-peroxide components. This study aims to investigate antibacterial activity of five varieties of Malaysian honey (three monofloral; acacia, gelam and pineapple, and two polyfloral; kelulut and tualang) against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. Methods Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed for semi-quantitative evaluation. Agar well diffusion assay was used to investigate peroxide and non-peroxide activities of honey. Results The results showed that gelam honey possessed lowest MIC value against S. aureus with 5% (w/v) MIC and MBC of 6.25% (w/v). Highest MIC values were shown by pineapple honey against E. coli and P. aeruginosa as well as acacia honey against E. coli with 25% (w/v) MIC and 50% (w/v) MBC values. Agar inhibition assay showed kelulut honey to possess highest total antibacterial activity against S. aureus with 26.49 equivalent phenol concentrations (EPC) and non-peroxide activity of 25.74 EPC. Lowest antibacterial activity was observed in acacia honey against E. coli with total activity of 7.85 EPC and non-peroxide activity of 7.59 EPC. There were no significant differences (p > 0.05) between the total antibacterial activities and non-peroxide activities of Malaysian honey. The intraspecific correlation between MIC and EPC of E. coli (r = -0.8559) was high while that between MIC and EPC of P. aeruginosa was observed to be moderate (r = -0.6469). S. aureus recorded a smaller correlation towards the opposite direction (r = 0.5045). In contrast, B.cereus showed a very low intraspecific correlation between MIC and EPC (r = -0.1482). Conclusions Malaysian honey, namely gelam, kelulut and tualang, have high antibacterial potency derived from total and non-peroxide activities, which implies that both peroxide and other

  1. Solar Selective Coatings for High Temperature Applications

    NASA Technical Reports Server (NTRS)

    Jaworske, Donald A.; Shumway, Dean A.

    2003-01-01

    Solar selective coatings are envisioned for use on minisatellites, for applications where solar energy is to be used to power heat engines or to provide thermal energy for remote regions in the interior of the spacecraft. These coatings are designed to have the combined properties of high solar absorptance and low infrared emittance. The coatings must be durable at elevated temperatures. For thermal bus applications, the temperature during operation is likely to be near 100 C. For heat engine applications. the temperature is expected to be much greater. The objective of this work was to screen candidate solar selective coatings for their high temperature durability. Candidate solar selective coatings were composed of molecular mixtures of metal and dielectric, including: nickel and aluminum oxide, titanium and aluminum oxide, and platinum and aluminum oxide. To identify high temperature durability, the solar absorptance and infrared emittance of the candidate coatings were evaluated initially, and after heating to temperatures in the range of 400 C to 700 C. The titanium and aluminum oxide molecular mixture was found to be the most durable.

  2. Blockade of uptake for dopamine, but not norepinephrine or 5-HT, increases selection of high effort instrumental activity: Implications for treatment of effort-related motivational symptoms in psychopathology.

    PubMed

    Yohn, Samantha E; Errante, Emily E; Rosenbloom-Snow, Aaron; Somerville, Matthew; Rowland, Margaret; Tokarski, Kristin; Zafar, Nadia; Correa, Merce; Salamone, John D

    2016-10-01

    Deficits in behavioral activation, exertion of effort, and other psychomotor/motivational symptoms are frequently seen in people with depression and other disorders. Depressed people show a decision bias towards selection of low effort activities, and animal tests of effort-related decision making are being used as models of motivational dysfunctions seen in psychopathology. The present studies investigated the ability of drugs that block dopamine transport (DAT), norepinephrine transport (NET), and serotonin transport (SERT) to modulate work output in rats responding on a test of effort-related decision making (i.e., a progressive ratio (PROG)/chow feeding choice task). With this task, rats choose between working for a preferred food (high carbohydrate pellets) by lever pressing on a PROG schedule vs. obtaining a less preferred lab chow that is freely available in the chamber. The present studies focused on the effects of the selective DAT inhibitor GBR12909, the selective SERT inhibitor fluoxetine, and the selective NET inhibitors desipramine and atomoxetine. Acute and repeated administration of GBR12909 shifted choice behavior, increasing measures of PROG lever pressing but decreasing chow intake. In contrast, fluoxetine, desipramine and atomoxetine failed to increase lever pressing output, and actually decreased it at higher doses. In the behaviorally effective dose range, GBR12909 elevated extracellular dopamine levels in accumbens core as measured by microdialysis, but fluoxetine, desipramine and atomoxetine decreased extracellular dopamine. Thus, blockade of DAT increases selection of the high effort instrumental activity, while inhibition of SERT or NET does not. These results have implications for the use of monoamine uptake inhibitors for the treatment of effort-related psychiatric symptoms in humans. PMID:27329556

  3. Coevolution of active vision and feature selection.

    PubMed

    Floreano, Dario; Kato, Toshifumi; Marocco, Davide; Sauser, Eric

    2004-03-01

    We show that complex visual tasks, such as position- and size-invariant shape recognition and navigation in the environment, can be tackled with simple architectures generated by a coevolutionary process of active vision and feature selection. Behavioral machines equipped with primitive vision systems and direct pathways between visual and motor neurons are evolved while they freely interact with their environments. We describe the application of this methodology in three sets of experiments, namely, shape discrimination, car driving, and robot navigation. We show that these systems develop sensitivity to a number of oriented, retinotopic, visual-feature-oriented edges, corners, height, and a behavioral repertoire to locate, bring, and keep these features in sensitive regions of the vision system, resembling strategies observed in simple insects. PMID:15052484

  4. Nanostructured electrocatalysts with tunable activity and selectivity

    NASA Astrophysics Data System (ADS)

    Mistry, Hemma; Varela, Ana Sofia; Kühl, Stefanie; Strasser, Peter; Cuenya, Beatriz Roldan

    2016-04-01

    The field of electrocatalysis has undergone tremendous advancement in the past few decades, in part owing to improvements in catalyst design at the nanoscale. These developments have been crucial for the realization of and improvement in alternative energy technologies based on electrochemical reactions such as fuel cells. Through the development of novel synthesis methods, characterization techniques and theoretical methods, rationally designed nanoscale electrocatalysts with tunable activity and selectivity have been achieved. This Review explores how nanostructures can be used to control electrochemical reactivity, focusing on three model reactions: O2 electroreduction, CO2 electroreduction and ethanol electrooxidation. The mechanisms behind nanoscale control of reactivity are discussed, such as the presence of low-coordinated sites or facets, strain, ligand effects and bifunctional effects in multimetallic materials. In particular, studies of how particle size, shape and composition in nanostructures can be used to tune reactivity are highlighted.

  5. Analysis of prasugrel active metabolite R-138727 in human plasma: a sensitive, highly selective and fast LC-MS/MS method.

    PubMed

    Kakarla, Sreekanth; Datla, Peda Varma; Kodali, Geetha; Seru, Ganapaty

    2016-05-01

    A cost effective, sensitive, simple, and rapid high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of the prasugrel metabolite in human plasma. Following solid phase extraction, the analyte (prasugrel active metabolite; R-138727) and internal standard (emtricitabine) were separated using a mobile phase in an isocratic elution mode on a reverse phase C18 column and were analyzed by an LC-MS/MS in the multiple reaction monitoring mode using the respective [M+H](+) ions, m/z 498.3-206.0 for R-138727 and m/z 248.2-130.1 for the internal standard. The assay exhibited a linear dynamic range of 0.2-120ng/mL. The lower limit of quantification was 0.2ng/mL with a relative standard deviation of 5.0%. This LC-MS/MS method was validated with intra-batch and inter-batch precision and accuracy. Results for precision and accuracy are in range of 3.9-9.6% and 95.2-102.2% respectively. This validated method is simple and repeatable to use in bioequivalence/pharmacokinetic studies. PMID:27038402

  6. High-quality elliptical iron glycolate nanosheets: selective synthesis and chemical conversion into FexOy nanorings, porous nanosheets, and nanochains with enhanced visible-light photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Tong, Guoxiu; Liu, Yun; Wu, Tong; Ye, Yucheng; Tong, Chaoli

    2015-10-01

    This paper describes an original and facile polyol-mediated solvothermal synthesis of elliptical iron glycolate nanosheets (IGNSs) combined with precursor thermal conversion into γ-Fe2O3 and α-Fe2O3/γ-Fe2O3 porous nanosheets (PNSs), α-Fe2O3 nanochains (NCs), and elliptical Fe3O4 nanorings (NRs). The IGNSs were produced via the oxidation-reduction and co-precipitation reactions in the presence of iron(iii) salts, ethylene glycol, polyethylene glycol, and ethylenediamine. Control over Fe3+ concentration, temperature, and time can considerably modulate the size and phase of the products. The IGNSs can be transformed to γ-Fe2O3 and α-Fe2O3/γ-Fe2O3 PNSs, α-Fe2O3 NCs, and elliptical Fe3O4 NRs by heat treatment under various annealing temperatures and ambiences. The PNSs and NCs exhibited high soft magnetic properties and coercivity, respectively. Visible-light photocatalytic activity toward RhB in the presence of H2O2 by PNSs and NCs was phase-, SBET, size-, porosity-, and local structure-dependent, following the order: α-Fe2O3 NCs > α-Fe2O3/γ-Fe2O3 PNSs > γ-Fe2O3 PNSs > IGNSs. In particular, α-Fe2O3/γ-Fe2O3 PNSs possessed significantly enhanced photocatalytic activity with good recyclability and could be conveniently separated by an applied magnetic field because of high magnetization. We believe that the as-prepared α-Fe2O3/γ-Fe2O3 PNSs have potential practical use in waste water treatment and microwave absorption.This paper describes an original and facile polyol-mediated solvothermal synthesis of elliptical iron glycolate nanosheets (IGNSs) combined with precursor thermal conversion into γ-Fe2O3 and α-Fe2O3/γ-Fe2O3 porous nanosheets (PNSs), α-Fe2O3 nanochains (NCs), and elliptical Fe3O4 nanorings (NRs). The IGNSs were produced via the oxidation-reduction and co-precipitation reactions in the presence of iron(iii) salts, ethylene glycol, polyethylene glycol, and ethylenediamine. Control over Fe3+ concentration, temperature, and time can

  7. Heterogeneous metasurface for high temperature selective emission

    SciTech Connect

    Woolf, D. Hensley, J.; Cederberg, J. G.; Bethke, D. T.; Grine, A. D.; Shaner, E. A.

    2014-08-25

    We demonstrate selective emission from a heterogeneous metasurface that can survive repeated temperature cycling at 1300 K. Simulations, fabrication, and characterization were performed for a cross-over-a-backplane metasurface consisting of platinum and alumina layers on a sapphire substrate. The structure was stabilized for high temperature operation by an encapsulating alumina layer. The geometry was optimized for integration into a thermophotovoltaic (TPV) system, and was designed to have its emissivity matched to the external quantum efficiency spectrum of 0.6 eV InGaAs TPV material. We present spectral measurements of the metasurface that result in a predicted 22% optical-to-electrical power conversion efficiency in a simplified model at 1300 K. Furthermore, this broadly adaptable selective emitter design can be easily integrated into full-scale TPV systems.

  8. Selected micronutrient levels and response to highly active antiretroviral therapy (HAART) among HIV/AIDS patients attending a teaching Hospital in Addis Ababa, Ethiopia.

    PubMed

    Eshetu, Amare; Tsegaye, Aster; Petros, Beyene

    2014-12-01

    Poor micronutrient levels are associated with an increased risk of progression to AIDS and are also suggested to influence outcome of highly active antiretroviral therapy (HAART), though existing data are inconclusive to support the latter. Few published data are available on micronutrient levels in Ethiopian HIV/AIDS patients taking HAART. The objective of the study was to determine the association of micronutrient levels and response to HAART (CD4(+) T cell count) among adult HIV/AIDS patients attending a teaching Hospital in Addis Ababa. CD4(+) T cell counts and micronutrient (retinol, zinc, and iron) levels for 171 subjects were determined using standard procedures. Some proportions of the study participants were found deficient for retinol (14.03 %), zinc (47.3 %), and iron (2.8 %). Patients who were deficient in retinol had a significantly lower median CD4(+) T cell counts (P = 0.002) compared to non-deficient subjects. Association of micronutrient quartiles with CD4+ T cell count was assessed using adjusted multivariate regression by taking quartile 4 as a reference category. Accordingly, patients who had retinol levels in quartile 4 had a significantly lower mean CD4(+) T cell count compared to quartile 3 (P = 0.02). The significantly higher CD4(+) T cell counts in patients who were non-deficient in retinol imply the role of retinol in improving the production of CD4(+) T cells. However, both lower and higher retinol levels were associated with suppressed immunity (CD4 < 200 cells/mm(3)), suggesting an adverse effect of higher retinol levels. Thus, retinol may be potentially harmful depending on the dose, emphasizing the need for optimized level of retinol in nutrient supplements in patients taking HAART. PMID:25256923

  9. Effects of size, sex, and voluntary running speeds on costs of locomotion in lines of laboratory mice selectively bred for high wheel-running activity.

    PubMed

    Rezende, Enrico L; Kelly, Scott A; Gomes, Fernando R; Chappell, Mark A; Garland, Theodore

    2006-01-01

    Selective breeding for over 35 generations has led to four replicate (S) lines of laboratory house mice (Mus domesticus) that run voluntarily on wheels about 170% more than four random-bred control (C) lines. We tested whether S lines have evolved higher running performance by increasing running economy (i.e., decreasing energy spent per unit of distance) as a correlated response to selection, using a recently developed method that allows for nearly continuous measurements of oxygen consumption (VO2) and running speed in freely behaving animals. We estimated slope (incremental cost of transport [COT]) and intercept for regressions of power (the dependent variable, VO2/min) on speed for 49 males and 47 females, as well as their maximum VO2 and speeds during wheel running, under conditions mimicking those that these lines face during the selection protocol. For comparison, we also measured COT and maximum aerobic capacity (VO2max) during forced exercise on a motorized treadmill. As in previous studies, the increased wheel running of S lines was mainly attributable to increased average speed, with males also showing a tendency for increased time spent running. On a whole-animal basis, combined analysis of males and females indicated that COT during voluntary wheel running was significantly lower in the S lines (one-tailed P=0.015). However, mice from S lines are significantly smaller and attain higher maximum speeds on the wheels; with either body mass or maximum speed (or both) entered as a covariate, the statistical significance of the difference in COT is lost (one-tailed P> or =0.2). Thus, both body size and behavior are key components of the reduction in COT. Several statistically significant sex differences were observed, including lower COT and higher resting metabolic rate in females. In addition, maximum voluntary running speeds were negatively correlated with COT in females but not in males. Moreover, males (but not females) from the S lines exhibited

  10. High Altitude Ballooning and Site Selection

    NASA Astrophysics Data System (ADS)

    Metcalf, John

    2008-10-01

    High altitude ballooning provides a near-space platform for amateur research projects in science and engineering. This venue allows new experiments, otherwise not conducted from costs or lack of transportation, from WSU and surrounding areas to be flown into the upper atmosphere. A highly skilled and motivated group of scientist and engineering students from WSU have contrived its own high altitude balloon to lift payload capsules filled with experiments and tracking equipment up to 120,000 feet where it then bursts and payload capsules are parachuted into a landing zone. Launch site selection is based upon the safety of those that come within the balloons projected flight path and terrain accessibility from the launch and landing zones. Restricted ground and airspace, mountainous regions, lakes and rivers, and densely populated or high air traffic areas were obstacles to be avoided. Computer flight simulations and region analysis show that there are several viable launch and recovery sites in Utah as well as SE Idaho, SW Wyoming, and NW Colorado.

  11. Selected advanced aerodynamic and active control concepts development

    NASA Technical Reports Server (NTRS)

    1980-01-01

    A summary is presented of results obtained during analysis, design and test activities on six selected technical tasks directed at exploratory improvement of fuel efficiency for new and derivative transports. The work included investigations into the potential offered by natural laminar flow, improved surface coatings and advanced high lift concepts. Similar investigations covering optimum low-energy flight path control, integrated application of active controls and evaluation of primary flight control systems reliability and maintenance are also summarized. Recommendations are included for future work needed to exploit potential advancements.

  12. Selecting activated carbon for water and wastewater treatability studies

    SciTech Connect

    Zhang, W.; Chang, Q.G.; Liu, W.D.; Li, B.J.; Jiang, W.X.; Fu, L.J.; Ying, W.C.

    2007-10-15

    A series of follow-up investigations were performed to produce data for improving the four-indicator carbon selection method that we developed to identify high-potential activated carbons effective for removing specific organic water pollutants. The carbon's pore structure and surface chemistry are dependent on the raw material and the activation process. Coconut carbons have relatively more small pores than large pores; coal and apricot nutshell/walnut shell fruit carbons have the desirable pore structures for removing adsorbates of all sizes. Chemical activation, excessive activation, and/or thermal reactivation enlarge small pores, resulting in reduced phenol number and higher tannic acid number. Activated carbon's phenol, iodine, methylene blue, and tannic acid numbers are convenient indicators of its surface area and pore volume of pore diameters < 10, 10-15, 15-28, and > 28 angstrom, respectively. The phenol number of a carbon is also a good indicator of its surface acidity of oxygen-containing organic functional groups that affect the adsorptive capacity for aromatic and other small polar organics. The tannic acid number is an indicator of carbon's capacity for large, high-molecular-weight natural organic precursors of disinfection by-products in water treatment. The experimental results for removing nitrobenzene, methyl-tert-butyl ether, 4,4-bisphenol, humic acid, and the organic constituents of a biologically treated coking-plant effluent have demonstrated the effectiveness of this capacity-indicator-based method of carbon selection.

  13. 38 CFR 40.6 - Selection of programs and activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Selection of programs and... Selection of programs and activities. (a) A State may select any program or activity published in the.... (b) Each State that adopts a process shall notify the Secretary of the VA's programs and...

  14. 15 CFR 922.21 - Selection of active candidates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Selection of active candidates. 922.21...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of...

  15. Identification of noncovalent proteasome inhibitors with high selectivity for chymotrypsin-like activity by a multistep structure-based virtual screening.

    PubMed

    Di Giovanni, Carmen; Ettari, Roberta; Sarno, Serena; Rotondo, Archimede; Bitto, Alessandra; Squadrito, Francesco; Altavilla, Domenica; Schirmeister, Tanja; Novellino, Ettore; Grasso, Silvana; Zappalà, Maria; Lavecchia, Antonio

    2016-10-01

    Noncovalent proteasome inhibitors introduce an alternative mechanism of inhibition to that of covalent inhibitors, e.g. carfilzomib, used in cancer therapy. A multistep hierarchical structure-based virtual screening (SBVS) of the 65,375 NCI lead-like compound library led to the identification of two compounds (9 and 28) which noncovalently inhibited the chymotrypsin-like (ChT-L) activity (Ki = 2.18 and 2.12 μM, respectively) with little or no effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and post-glutamyl peptide hydrolase (PGPH) activities. A subsequent hierarchical similarity search over the full NCI database with the most active tripeptide-based inhibitor 9 resulted in the discovery of the β5/β6-specific tripeptide derivative 38 that noncovalently binds the ChT-L site (Ki = 0.42 μM). The solution structure of 9 and 38 was solved by (1)H NMR spectroscopy and the binding mode of the inhibitors was elucidated by docking experiments using the yeast 20S proteasome. Compound 38 (IC50 = 26.7 μM) is slightly more potent than 9 (IC50 = 34.3 μM) at inhibiting survival of dexamethasone-resistant (MM.1R) human multiple myeloma cells. The identified ligand thus provides valuable insights for the future structure-based design of subtype-specific proteasome inhibitors. PMID:27318981

  16. Glycoalkaloid Levels in Solanum Microdontum and S. Jamesii Accessions: A Consideration in Parental Selection When Breeding for High Antioxidant Activity in Potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antioxidants are useful in reducing risk of several diseases associated with free radicals. While potatoes are not as high in antioxidants as fruits, the fact that large quantities of potatoes are consumed (~130 lbs per capita) suggests that any increase in tuber antioxidants would greatly benefit h...

  17. Design, Synthesis, and Structure-Activity Relationship, Molecular Modeling, and NMR Studies of a Series of a Phenyl Alkyl Ketones as Highly Potent and Selective Phosphodiesterase-4 Inhibitors

    SciTech Connect

    Zheng, S.; Kaur, G; Wang, H; Li, M; MacNaughtan, M; Yang, X; Reid, S; Prestegard, J; Wang, B; et. al.

    2008-01-01

    Phosphodiesterase 4 catalyzes the hydrolysis of cyclic AMP and is a target for the development of anti-inflammatory agents. We have designed and synthesized a series of phenyl alkyl ketones as PDE4 inhibitors. Among them, 13 compounds were identified as having submicromolar IC{sub 50} values. The most potent compounds have IC50 values of in the mid- to low-nanomolar range. Compound 5v also showed preference for PDE4 with selectivity of >2000-fold over PDE7, PDE9, PDE2, and PDE5. Docking of 5v, 5zf, and 5za into the binding pocket of the PDE4 catalytic domain revealed a similar binding profile to PDE4 with rolipram except that the fluorine atoms of the difluoromethyl groups of 5v, 5za, and 5zf are within a reasonable range for hydrogen bond formation with the amide hydrogen of Thr 333 and the long alkyl chain bears additional van der Waals interactions with His 160, Asp 318, and Tyr 159.

  18. Synthesis of superparamagnetic carbon nanotubes immobilized Pt and Pd pincer complexes: highly active and selective catalysts towards cyclohexane oxidation with dioxygen.

    PubMed

    Machado, Kelly; Mishra, Jaya; Suzuki, Shinzo; Mishra, Gopal S

    2014-12-14

    Single-walled carbon nanotubes (SWNTs) with Ni/Co have been prepared using an arc discharge technique and Ni/Co-carbon composite rods in an inert atmosphere and were surface modified using 3-aminophenyl trimethoxysilane. These NH2-functionalized magnetic carbon nanotubes have been used as a novel support for Pd((II)) and Pt((II)) pincer complexes immobilized as magnetic nano-catalysts. The morphology of the support and the catalysts have been characterized by IR, EPR, SEM, TGA, TEM, XRD, AAS and EDS analysis. These magnetic nano-catalysts have been tested on the industrially important cyclohexane (Cy-hx) oxidation with O2 and significantly high TONs of 1678 to 1946 were achieved under solvent free and relatively mild conditions. The SWNTs/Pd catalyst provided the best conversion, 22.7%, but the SWNTs/Pt system also provided a good conversion of 20.7%. PMID:25340475

  19. High Temperature Reactor (HTR) Deep Burn Core and Fuel Analysis: Design Selection for the Prismatic Block Reactor With Results from FY-2011 Activities

    SciTech Connect

    Michael A. Pope

    2011-10-01

    The Deep Burn (DB) Project is a U.S. Department of Energy sponsored feasibility study of Transuranic Management using high burnup fuel in the high temperature helium cooled reactor (HTR). The DB Project consists of seven tasks: project management, core and fuel analysis, spent fuel management, fuel cycle integration, TRU fuel modeling, TRU fuel qualification, and HTR fuel recycle. In the Phase II of the Project, we conducted nuclear analysis of TRU destruction/utilization in the HTR prismatic block design (Task 2.1), deep burn fuel/TRISO microanalysis (Task 2.3), and synergy with fast reactors (Task 4.2). The Task 2.1 covers the core physics design, thermo-hydraulic CFD analysis, and the thermofluid and safety analysis (low pressure conduction cooling, LPCC) of the HTR prismatic block design. The Task 2.3 covers the analysis of the structural behavior of TRISO fuel containing TRU at very high burnup level, i.e. exceeding 50% of FIMA. The Task 4.2 includes the self-cleaning HTR based on recycle of HTR-generated TRU in the same HTR. Chapter IV contains the design and analysis results of the 600MWth DB-HTR core physics with the cycle length, the average discharged burnup, heavy metal and plutonium consumptions, radial and axial power distributions, temperature reactivity coefficients. Also, it contains the analysis results of the 450MWth DB-HTR core physics and the analysis of the decay heat of a TRU loaded DB-HTR core. The evaluation of the hot spot fuel temperature of the fuel block in the DB-HTR (Deep-Burn High Temperature Reactor) core under full operating power conditions are described in Chapter V. The investigated designs are the 600MWth and 460MWth DB-HTRs. In Chapter VI, the thermo-fluid and safety of the 600MWth DB-HTRs has been analyzed to investigate a thermal-fluid design performance at the steady state and a passive safety performance during an LPCC event. Chapter VII describes the analysis results of the TRISO fuel microanalysis of the 600MWth and 450

  20. Selected Science Activities in Consumer Decision Making.

    ERIC Educational Resources Information Center

    Sagness, Richard L.; Sagness, Rebecca L.

    This publication has been designed for use by teachers wishing to incorporate consumer education activities into their science program. Each activity is classified by grade level most appropriate for use, area of consumer education involved, specific topic, and consumer education concept involved. Activities are designated as suitable for grades…

  1. Iridium-Catalyzed Branch-Selective Hydroarylation of Vinyl Ethers via C-H Bond Activation.

    PubMed

    Ebe, Yusuke; Nishimura, Takahiro

    2015-05-13

    Iridium-catalyzed hydroarylation of vinyl ethers via a directed C-H bond activation of aromatic compounds gave high yields of the corresponding addition products with high branch selectivity. PMID:25928127

  2. Selective Activation and Disengagement of Moral Control.

    ERIC Educational Resources Information Center

    Bandura, Albert

    1990-01-01

    Analyzes psychological mechanisms by which moral control is selectively disengaged from inhumane conduct in ordinary and unusual circumstances. Explores the symptoms of moral exclusion as described in the literature. Presents categories that unify theory on moral exclusion and contribute practical classifications for use in empirical studies. (JS)

  3. In The Mainstream: Selected Music Activities.

    ERIC Educational Resources Information Center

    McCoy, Martha

    1982-01-01

    Discusses classroom management techniques and music activities for handicapped children in mainstreamed and special education classes. Classroom techniques are designed around students' poor reading and concentration abilities, multisensory experiences, and consistent discipline using positive reinforcement. Music activities are used to reinforce…

  4. Cytotoxic activity of selected Nigerian plants.

    PubMed

    Sowemimo, A; van de Venter, M; Baatjies, L; Koekemoer, T

    2009-01-01

    Cancer is one of the most prominent human diseases which has stimulated scientific and commercial interest in the discovery of new anticancer agents from natural sources. The current study investigates the cytotoxic activity of ethanolic extracts of sixteen Nigerian plants used locally for the treatment of cancer using the MTT assay on the HeLa cell line. Sapium ellipticum leaves showed activity comparable to the reference compound Cisplatin and greater cytotoxic activity than Combretum paniculatum, Celosia trigyna, Drymaria cordata, Cyathula achyranthoides and Cyathula prostata. Justica extensa, Pupalia lappacea, Hedranthera barteri leaves, Alternanthera sessilis, Ethulia conyzoides leaves, Combretum zenkeri root, Sapium ellipticum stembark and Lannea nigritana stembark showed very low activity while Combretum molle, Adenanthera parvoniana and Lannea acida showed no activity. The results justify the use of Sapium, Combretum, Celosia, Drymaria and Cyathula in traditional treatment of cancer. PMID:20606772

  5. A novel method to fabricate high permeance, high selectivity thin-film composite membranes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report a thin-film composite (TFC) membrane fabrication method based on transfer of a pre-formed, cured active layer onto a microporous support. This method can be used with supports of relatively high pore size and porosity, thus reducing mass transfer resistance from the support. Ethanol-select...

  6. Highly Fluorinated Ir(III)-2,2':6',2″-Terpyridine-Phenylpyridine-X Complexes via Selective C-F Activation: Robust Photocatalysts for Solar Fuel Generation and Photoredox Catalysis.

    PubMed

    Porras, Jonathan A; Mills, Isaac N; Transue, Wesley J; Bernhard, Stefan

    2016-08-01

    A series of fluorinated Ir(III)-terpyridine-phenylpyridine-X (X = anionic monodentate ligand) complexes were synthesized by selective C-F activation, whereby perfluorinated phenylpyridines were readily complexed. The combination of fluorinated phenylpyridine ligands with an electron-rich tri-tert-butyl terpyridine ligand generates a "push-pull" force on the electrons upon excitation, imparting significant enhancements to the stability, electrochemical, and photophysical properties of the complexes. Application of the complexes as photosensitizers for photocatalytic generation of hydrogen from water and as redox photocatalysts for decarboxylative fluorination of several carboxylic acids showcases the performance of the complexes in highly coordinating solvents, in some cases exceeding that of the leading photosensitizers. Changes in the photophysical properties and the nature of the excited states are observed as the compounds increase in fluorination as well as upon exchange of the ancillary chloride ligand to a cyanide. These changes in the excited states have been corroborated using density functional theory modeling. PMID:27387149

  7. Recurrent Selection for Transgene Activity Levels in Maize Results in Proxy Selection for a Native Gene with the Same Promoter

    PubMed Central

    Bodnar, Anastasia L.; Schroder, Megan N.; Scott, M. Paul

    2016-01-01

    High activity levels of a transgene can be very useful, making a transgene easier to evaluate for safety and efficacy. High activity levels can also increase the economic benefit of the production of high value proteins in transgenic plants. The goal of this research is to determine if recurrent selection for activity of a transgene will result in higher activity, and if selection for activity of a transgene controlled by a native promoter will also increase protein levels of the native gene with the same promoter. To accomplish this goal we used transgenic maize containing a construct encoding green fluorescent protein controlled by the promoter for the maize endosperm-specific 27kDa gamma zein seed storage protein. We carried out recurrent selection for fluorescence intensity in two breeding populations. After three generations of selection, both selected populations were significantly more fluorescent and had significantly higher levels of 27kDa gamma zein than the unselected control populations. These higher levels of the 27kDa gamma zein occurred independently of the presence of the transgene. The results show that recurrent selection can be used to increase activity of a transgene and that selection for a transgene controlled by a native promoter can increase protein levels of the native gene with the same promoter via proxy selection. Moreover, the increase in native gene protein level is maintained in the absence of the transgene, demonstrating that proxy selection can be used to produce non-transgenic plants with desired changes in gene expression. PMID:26895451

  8. Biological activities of selected basidiomycetes from Yemen.

    PubMed

    Al-Fatimi, M; Schröder, G; Kreisel, H; Lindequist, U

    2013-03-01

    In a previous paper we demonstrated the results of biological screening of Yemeni basidiomycetes. The present study was aimed to investigate the antimicrobial and the antioxidant activity of further basidiomycetes collected in Yemen. Dichloromethane, methanol and aqueous extracts of the fruiting bodies of 25 species were screened in vitro for their antibacterial activities against three Gram-positive bacteria (Staphyloccocus aureus, Bacillus subtilis, Micrococcus flavus) and two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), against six human fungal pathogens (Candida albicans, Candida krusei, Aspergillus fumigatus, Mucor sp., Microsporum gypseum, Trichophyton mentagrophytes) and against one non human pathogenic fungus (Candida maltosa). The results indicated that 75 extracts exhibited activity against one or more of the bacteria. The methanol extracts of Agaricus cf. bernardii, Agrocybe pediades, Chlorophyllum molybdites, Coriolopsis polyzona, Ganoderma xylonoides, Pycnoporus sanguineus, Trametes lactinea and Trametes cingulata showed activity against all tested bacteria. The highest antibacterial activity was exhibited by methanol extracts from Chlorophyllum molybdites, Ganoderma xylonoides and Trametes cingulata and Agaricus cf. bernardii, Agrocybe pediades, Coriolopsis polyzona, Pycnoporus sanguineus and Trametes lactinea. The methanol extracts of Chlorophyllum molybdites, Ganoderma xylonoides and Pycnoporus sanguineus showed considerable antifungal activities against the tested fungal strains. Strong antioxidative effects employing the DPPH assay were exhibited by methanol extracts from Chlorophyllum molybdites, Ganoderma xylonoides, Hexagonia velutina, Pycnoporus sanguineus, Trametes lactinea and Trametes cingulata. Our previous and presented studies about 48 basidiomycetes collected in Yemen provide evidence that basidiomycetes from the Arabic region so far should attract more attention as potential source for new biologically active

  9. Fate of selected pharmaceutically active compounds during simulated riverbank filtration.

    PubMed

    D'Alessio, Matteo; Yoneyama, Bunnie; Ray, Chittaranjan

    2015-02-01

    The objective of this study was to investigate the effect of temperature, oxygen, and organic matter on the removal of selected pharmaceutically active compounds (PhACs) during simulated riverbank filtration (RBF). The behavior of six PhACs (caffeine, carbamazepine, 17-β estradiol [E2], estrone [E1], gemfibrozil, and phenazone) was evaluated by small flow-through column experiments. Results from our study showed that RBF can be used to treat many of the PhACs found in environmental waters. Local conditions at the RBF site, however, can affect the removal of PhACs and should be investigated. Biodegradation and sorption represented the predominant mechanisms involved during the removal of the selected PhACs. All selected PhACs showed limited and slower removal during the winter. Phenazone was highly impacted by the level of oxygen; complete depletion of phenazone below the analytical limit occurred only under aerobic conditions (dissolved oxygen >8 mg L(-1)). Caffeine and E2 were highly impacted by the presence of humic acid in the feed water. Caffeine and E2 were depleted below the detection limit in the presence of humic acid regardless of the temperature and the level of oxygen. E1 was impacted by the different environmental conditions and depletion below the detection limit occurred only during the summer under aerobic conditions. Carbamazepine (10%) and gemfibrozil (<30%) showed limited removal regardless of the different levels of temperature, oxygen and humic acid. PMID:25461064

  10. Screening antifungal activities of selected medicinal plants.

    PubMed

    Quiroga, E N; Sampietro, A R; Vattuone, M A

    2001-01-01

    Plants synthesise a vast array of secondary metabolites that are gaining importance for their biotechnological applications. The antifungal activity of the ethanolic extracts of ten Argentinean plants used in native medicine is reported. Antifungal assays included radial growth inhibition, disk and well diffusion assays and growth inhibition by broth dilution tests. The chosen test fungi were yeasts, microfungi and wood-rot causing Basidiomycetes. Extracts of Larrea divaricata, Zuccagnia punctata and Larrea cuneifolia displayed remarkable activity in the assays against the majority of the test fungi. In addition to the former plants, Prosopanche americana also inhibited yeast growth. PMID:11137353

  11. The Effectiveness of Selected Dissemination Activities.

    ERIC Educational Resources Information Center

    Chapman, David W.; Johnson, Russell H.

    1981-01-01

    The dissemination activities through which college admissions officers heard about Project CHOICE, a three-year project to help colleges improve the information they provided to prospective students, were investigated. The study involved determining how well various dissemination methods (newsletter, journal articles, conference presentations,…

  12. Selected studies of magnetism at high pressure

    SciTech Connect

    Hearne, G.R.; Pasternak, M.P.; Taylor, R.D.

    1995-09-01

    Most previous studies of magnetism in various compounds under extreme conditions have been conducted over a wide pressure range at room temperature or over a wide range of cryogenic temperatures at pressures below 20 GPa (200 kbar). We present some of the most recent studies of magnetism over an extended range of temperatures and pressures far beyond 20 GPa, i.e., in regions of pressure-temperature (P-T) where magnetism has been largely unexplored. Recent techniques have permitted investigations of magnetism in selected 3d transition metal compounds in regions of P-T where physical properties may be drastically modified; related effects have often been seen in selected doping studies at ambient pressures.

  13. Anticancer activity of selected Colocasia gigantia fractions.

    PubMed

    Pornprasertpol, Apichai; Sereemaspun, Amornpun; Sooklert, Kanidta; Satirapipatkul, Chutimon; Sukrong, Suchada

    2015-01-01

    The objective of this study is to investigate the anticancer potential of the extract of Colocasia gigantea C. gigantea), a plant member of the Araceae family. In the present study, we investigated the cytotoxic activity of C. gigantea extract on cervical cancer (Hela) and human white blood cells (WBC) in vitro. The authors then identified the bioactive ingredients that demonstrated cytotoxicity on tested cells and evaluated those bioactive ingredients using the bioassay-guided fractionation method. The results showed that not all parts of C. gigantea promote cytotoxic activity. The dichloromethane leaf fraction showed significant cell proliferation effect on Hela cells, but not on WBCs. Only the n-hexane tuber fraction (Fr. 1T) exhibited significant cytotoxicity on Hela cells (IC50 = 585 μg/ml) and encouraged WBC cell proliferation. From GC-Mass spectrometry, 4,22-Stigmastadiene-3-one, Diazoprogesterone, 9-Octadecenoic acid (Z)-, hexyl ester and Oleic Acid were the components of Fr 1T that demonstrated cytotoxic potential. In conclusion, C. gigantea's Fr 1T shows potential for cervical cancer treatment. PMID:25764620

  14. Selected demonstration and educational products/activities

    SciTech Connect

    Williams, R.J.; Mann, H.C.

    1992-07-01

    The information in this paper was assembled for several informal presentations to a variety of visitor groups during the summer of 1992. A number of staff members at TVA`s National Fertilizer and Environmental Research Center (NFERC) found it useful as a quick overview for their use and for their sharing with external colleagues and customers. The paper is not meant to be an exhaustive list or explanation of all products and services available from NFERC. However, the authors believe it will give a flavor and tenor of some of the ongoing activities of the Center, especially those activities relating to the retail fertilizer dealer. Programs over the years have focused on key aspects of nutrient efficiency and management. TVA is uniquely positioned to assist the fertilizer industry and US agriculture in protecting the environment from potential adverse environmental impacts of agriculture, especially for fertilizer and the attendant agrichemicals. TVA has the technical base and an ongoing working relationship with the fertilizer industry in technology development and introduction. Dealer education is very important in TVA programs in two aspects: (1) education for the dealer in meeting new environmental stewardship challenges from an operational perspective; and (2) education for the dealer in meeting the site-specific information needs of the farmer.

  15. Emotion disrupts neural activity during selective attention in psychopathy.

    PubMed

    Sadeh, Naomi; Spielberg, Jeffrey M; Heller, Wendy; Herrington, John D; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

    2013-03-01

    Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes. PMID:22210673

  16. High-level expression of biologically active glycoprotein hormones in Pichia pastoris strains—selection of strain GS115, and not X-33, for the production of biologically active N-glycosylated 15N-labeled phCG

    PubMed Central

    Blanchard, Véronique; Gadkari, Rupali A.; George, Albert V. E.; Roy, Satarupa; Gerwig, Gerrit J.; Leeflang, Bas R.; Dighe, Rajan R.; Boelens, Rolf

    2008-01-01

    The methylotrophic yeast Pichia pastoris is widely used for the production of recombinant glycoproteins. With the aim to generate biologically active 15N-labeled glycohormones for conformational studies focused on the unravelling of the NMR structures in solution, the P. pastoris strains GS115 and X-33 were explored for the expression of human chorionic gonadotropin (phCG) and human follicle-stimulating hormone (phFSH). In agreement with recent investigations on the N-glycosylation of phCG, produced in P. pastoris GS115, using ammonia/glycerol-methanol as nitrogen/carbon sources, the N-glycosylation pattern of phCG, synthesized using NH4Cl/glucose–glycerol–methanol, comprised neutral and charged, phosphorylated high-mannose-type N-glycans (Man8–15GlcNAc2). However, the changed culturing protocol led to much higher amounts of glycoprotein material, which is of importance for an economical realistic approach of the aimed NMR research. In the context of these studies, attention was also paid to the site specific N-glycosylation in phCG produced in P. pastoris GS115. In contrast to the rather simple N-glycosylation pattern of phCG expressed in the GS115 strain, phCG and phFSH expressed in the X-33 strain revealed, besides neutral high-mannose-type N-glycans, also high concentrations of neutral hypermannose-type N-glycans (Manup-to-30GlcNAc2). The latter finding made the X-33 strain not very suitable for generating 15N-labeled material. Therefore, 15N-phCG was expressed in the GS115 strain using the new optimized protocol. The 15N-enrichment was evaluated by 15N-HSQC NMR spectroscopy and GLC-EI/MS. Circular dichroism studies indicated that 15N-phCG/GS115 had the same folding as urinary hCG. Furthermore, 15N-phCG/GS115 was found to be similar to the unlabeled protein in every respect as judged by radioimmunoassay, radioreceptor assays, and in vitro bioassays. PMID:18274893

  17. Discrimination of Swiss cheese from 5 different factories by high impact volatile organic compound profiles determined by odor activity value using selected ion flow tube mass spectrometry and odor threshold.

    PubMed

    Taylor, Kaitlyn; Wick, Cheryl; Castada, Hardy; Kent, Kyle; Harper, W James

    2013-10-01

    Swiss cheese contains more than 200 volatile organic compounds (VOCs). Gas chromatography-mass spectrometry has been utilized for the analysis of volatile compounds in food products; however, it is not sensitive enough to measure VOCs directly in the headspace of a food at low concentrations. Selected ion flow tube mass spectrometry (SIFT-MS) provides a basis for determining the concentrations of VOCs in the head space of the sample in real time at low concentration levels of parts per billion/trillion by volume. Of the Swiss cheese VOCs, relatively few have a major impact on flavor quality. VOCs with odor activity values (OAVs) (concentration/odor threshold) greater than one are considered high-impact flavor compounds. The objective of this study was to utilize SIFT-MS concentrations in conjunction with odor threshold values to determine OAVs thereby identifying high-impact VOCs to use for differentiating Swiss cheese from five factories and identify the factory variability. Seventeen high-impact VOCs were identified for Swiss cheese based on an OAV greater than one in at least 1 of the 5 Swiss cheese factories. Of these, 2,3-butanedione was the only compound with significantly different OAVs in all factories; however, cheese from any pair of factories had multiple statistically different compounds based on OAV. Principal component analysis using soft independent modeling of class analogy statistical differentiation plots, with all of the OAVs, showed differentiation between the 5 factories. Overall, Swiss cheese from different factories was determined to have different OAV profiles utilizing SIFT-MS to determine OAVs of high impact compounds. PMID:24106758

  18. Silica dust exposures during selected construction activities.

    PubMed

    Flanagan, Mary Ellen; Seixas, Noah; Majar, Maria; Camp, Janice; Morgan, Michael

    2003-01-01

    This study characterized exposure for dust-producing construction tasks. Eight common construction tasks were evaluated for quartz and respirable dust exposure by collecting 113 personal task period samples for cleanup; demolition with handheld tools; concrete cutting; concrete mixing; tuck-point grinding; surface grinding; sacking and patching concrete; and concrete floor sanding using both time-integrating filter samples and direct-reading respirable dust monitors. The geometric mean quartz concentration was 0.10 mg/m(3) (geometric standard deviation [GSD]=4.88) for all run time samples, with 71% exceeding the threshold limit value. Activities with the highest exposures were surface grinding, tuck-point grinding, and concrete demolition (GM[GSD] of 0.63[4.12], 0.22[1.94], and 0.10[2.60], respectively). Factors recorded each minute were task, tool, work area, respiratory protection and controls used, estimated cross draft, and whether anyone nearby was making dust. Factors important to exposure included tool used, work area configuration, controls employed, cross draft, and in some cases nearby dust. More protective respirators were employed as quartz concentration increased, although respiratory protection was found to be inadequate for 42% of exposures. Controls were employed for only 12% of samples. Exposures were reduced with three controls: box fan for surface grinding and floor sanding, and vacuum/shroud for surface grinding, with reductions of 57, 50, and 71%, respectively. Exposures were higher for sweeping compound, box fan for cleanup, ducted fan dilution, and wetted substrate. Construction masons and laborers are frequently overexposed to silica. The usual protection method, respirators, was not always adequate, and engineering control use was infrequent and often ineffective. PMID:12809537

  19. (D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity

    SciTech Connect

    Knapp, R.J.; Sharma, S.D.; Toth, G.; Duong, M.T.; Fang, L.; Bogert, C.L.; Weber, S.J.; Hunt, M.; Davis, T.P.; Wamsley, J.K. )

    1991-09-01

    (D-Pen2,4{prime}-125I-Phe4,D-Pen5)enkephalin ((125I)DPDPE) is a highly selective radioligand for the delta opioid receptor with a specific activity (2200 Ci/mmol) that is over 50-fold greater than that of tritium-labeled DPDPE analogs. (125I)DPDPE binds to a single site in rat brain membranes with an equilibrium dissociation constant (Kd) value of 421 {plus minus} 67 pM and a receptor density (Bmax) value of 36.4 {plus minus} 2.7 fmol/mg protein. The high affinity of this site for delta opioid receptor ligands and its low affinity for mu or kappa receptor-selective ligands are consistent with its being a delta opioid receptor. The distribution of these sites in rat brain, observed by receptor autoradiography, is also consistent with that of delta opioid receptors. Association and dissociation binding kinetics of 1.0 nM (125I) DPDPE are monophasic at 25 degrees C. The association rate (k + 1 = 5.80 {plus minus} 0.88 {times} 10(7) M-1 min-1) is about 20- and 7-fold greater than that measured for 1.0 nM (3H) DPDPE and 0.8 nM (3H) (D-Pen2,4{prime}-Cl-Phe4, D-Pen5)enkephalin, respectively. The dissociation rate of (125I)DPDPE (0.917 {plus minus} 0.117 {times} 10(-2) min-1) measured at 1.0 nM is about 3-fold faster than is observed for either of the other DPDPE analogs. The rapid binding kinetics of (125I)DPDPE is advantageous because binding equilibrium is achieved with much shorter incubation times than are required for other cyclic enkephalin analogs. This, in addition to its much higher specific activity, makes (125I)DPDPE a valuable new radioligand for studies of delta opioid receptors.

  20. N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester: a novel, high selective and optimal chromogenic active site titrant for human and bovine alpha-, beta- and gamma-thrombin.

    PubMed

    Balliano, G; Milla, P; Giordano, C; Gallina, C; Coletta, M; Menegatti, E; Rizzi, M; Bolognesi, M; Ascenzi, P

    1996-08-14

    The serine proteinase catalyzed hydrolysis of N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p- nitrophenyl ester (Eoc-D-Phe-Pro-azaLys-ONp) was investigated at pH 6.2 and 21.0 degrees C. The results are consistent with the minimum three-step catalytic mechanism. The acylation step is rate limiting for human (Lys 77 species) and porcine plasmin, and for bovine beta-trypsin, the deacylation rate being limiting, on the other hand, for human and bovine alpha-, beta- and gamma-thrombin. Moreover the M(r) 33,000 species of human urokinase and the neuraminidase-treated porcine pancreatic beta-kallikrein-B do not catalyze the hydrolysis of the tripeptide. According to the specificity properties of the serine proteinases considered. Eoc-D-Phe- Pro-azaLys-ONp shows the characteristics of a novel, high selective and optimal chromogenic active site titrant for human and bovine alpha-, beta- and gamma-thrombin. PMID:8753800

  1. A selection of high gradient cavity experiments

    SciTech Connect

    Peter Kneisel

    1998-01-01

    In the two years since the 7th SRF workshop, a variety of cavity tests have been carried out with the objective to reproducibly achieve surface electric rf fields above 40 MV/m with no or only very little electron loading. This paper reports about a collection of tests on single cell and multi-cell cavities, which received standard surface treatments such as buffered chemical polishing and high pressure ultrapure water rinsing, but no heat treatments. Often the cavities were limited by quenches, posting a limit of 700 to 1,000 Oersted on achievable peak magnetic fields of high purity niobium RRR values between 200 and 250. In a seamless single cell cavity fabricated by V. Palmieri of INFN Legnaro by spinning, a very promising gradient of E{sub acc}=25 MV/m was measured. In collaboration with CERN, several tests on sputtering niobium prepared at CERN were also carried out, and accelerating gradients up to 25 MV/m were achieved. A single cell cavity, electron beam welded after electrochemical buffing, showed only good performance--E{sub p} > 50 MV/m--after the removal of more than 100 {micro}m of material. However, this cavity showed rather heavy Q disease even when cooled down rapidly; the Q degradation could be partially reversed by diffusing the oxygen from an anodized Nb{sub 2}O{sub 5} layer into the niobium by heating the cavity in-situ at T=250 C.

  2. Direct Activation of Epac by Sulfonylurea is Isoform Selective

    PubMed Central

    Herbst, Katie J.; Coltharp, Carla; Amzel, L. Mario; Zhang, Jin

    2011-01-01

    Summary Commonly used as a treatment for Type II diabetes, sulfonylureas (SUs) stimulate insulin secretion from pancreatic β cells by binding to sulfonylurea receptors. Recently, SUs have been shown to also activate exchange protein directly activated by cAMP 2 (Epac2), however little is known about this molecular action. Using biosensor imaging and biochemical analysis, we show that SUs activate Epac2 and the downstream signaling via direct binding to Epac2. We further identify R447 of Epac2 to be critically involved in SU binding. This distinct binding site from cAMP points to a new mode of allosteric activation of Epac2. We also show that SUs selectively activate Epac2 isoform, but not the closely related Epac1, further establishing SUs as a new class of isoform-selective enzyme activators. PMID:21338921

  3. Tips for selecting highly efficient cyclones

    SciTech Connect

    Amrein, D.L.

    1995-05-01

    Cyclone dust collectors have been used--and misused--all over the world for more than 100 years. One reason for the misuse is a common perception among users that all cyclones are created equal--that is, as long as a cyclone resembles a cylinder with an attached cone, it will do its job. However, to maximize separation efficiency in a specific application requires a precise cyclone design, engineered to exact fit many possible variables. A well-designed cyclone, for instance, can achieve efficiencies as high s 99.9+% when operated properly within the envelope of its specifications. Nonetheless, cyclones are often used only as first-stage filters for performing crude separations, with final collections being carried out by more-costly baghouses and scrubbers. Compared with baghouses and scrubbers, cyclones have two important considerations in their favor. One, they are almost invariably safer--in terms of the potential for generating fires and explosions--than fabric filters. Second, cyclones have lower maintenance costs since there are no filter media to replace. The paper discusses the operation, design, and troubleshooting of cyclones.

  4. High Throughput Screening and Selection Methods for Directed Enzyme Evolution

    PubMed Central

    2015-01-01

    Successful evolutionary enzyme engineering requires a high throughput screening or selection method, which considerably increases the chance of obtaining desired properties and reduces the time and cost. In this review, a series of high throughput screening and selection methods are illustrated with significant and recent examples. These high throughput strategies are also discussed with an emphasis on compatibility with phenotypic analysis during directed enzyme evolution. Lastly, certain limitations of current methods, as well as future developments, are briefly summarized. PMID:26074668

  5. Activated sludge studies of selected contaminants of PFH wastewater

    SciTech Connect

    Dudley, S.K.; Bustamante, R.B.; Bonner, W.P.

    1991-12-31

    Acetone, propionitrile, pyrrole, and thiocyanate were selected as representative compounds of wastewater expected from pressurized, fluidized-bed hydroretorting (PFH) of Eastern oil shales. The PFH process has been the subject of investigation by the Institute of Gas Technology, under contract with the United States Department of Energy, for the purpose of obtaining higher oil yields from Eastern shales than has been possible using conventional retorting methods. Preliminary batch experiments illustrated that acetone, propionitrile, pyrrole, and thiocyanate are aerobically biodegradable by heterogeneous microbiological cultures. Three continuous flow activated sludge reactors were used to further evaluate the biological treatability of the synthetic waste. The studies revealed that the compounds could be removed at hydraulic residence times of as low as one day. Three one-day experiments demonstrated that biological system`s capability to accept organic shock loadings without a change in effluent quality. A no-recycle reactor illustrated that the flocculent microbiological population had a high resistance to solids washout. Because a supplementary nitrogen source was not included in synthetic waste treated by the no-recycle unit, it was shown that propionitrile, pyrrole, and/or thiocyanate supplied the nitrogen necessary for biological activity.

  6. Activated sludge studies of selected contaminants of PFH wastewater

    SciTech Connect

    Dudley, S.K. ); Bustamante, R.B.; Bonner, W.P. )

    1991-01-01

    Acetone, propionitrile, pyrrole, and thiocyanate were selected as representative compounds of wastewater expected from pressurized, fluidized-bed hydroretorting (PFH) of Eastern oil shales. The PFH process has been the subject of investigation by the Institute of Gas Technology, under contract with the United States Department of Energy, for the purpose of obtaining higher oil yields from Eastern shales than has been possible using conventional retorting methods. Preliminary batch experiments illustrated that acetone, propionitrile, pyrrole, and thiocyanate are aerobically biodegradable by heterogeneous microbiological cultures. Three continuous flow activated sludge reactors were used to further evaluate the biological treatability of the synthetic waste. The studies revealed that the compounds could be removed at hydraulic residence times of as low as one day. Three one-day experiments demonstrated that biological system's capability to accept organic shock loadings without a change in effluent quality. A no-recycle reactor illustrated that the flocculent microbiological population had a high resistance to solids washout. Because a supplementary nitrogen source was not included in synthetic waste treated by the no-recycle unit, it was shown that propionitrile, pyrrole, and/or thiocyanate supplied the nitrogen necessary for biological activity.

  7. Correlations between surface structure and catalytic activity/selectivity

    SciTech Connect

    Goodman, D.W.

    1992-10-01

    Objective is to address the keys to understanding the relation between surface structure and catalytic activity/selectivity. Of concern are questions related to enhanced catalytic properties of mixed-metal catalysts and critical active site requirements for molecular synthesis and rearrangement. The experimental approach utilizes a microcatalytic reactor contiguous to a surface analysis system, an arrangement which allows in vacuo transfer of the catalyst from one chamber to the other. Surface techniques being used include Auger (AES), UV and X-ray photoemission spectroscopy (UPS and XPS), temperature programmed desorption (TPD), low energy electron diffraction (LEED), high resolution electron energy loss spectroscopy (HREELS) and infrared reflection-absorption spectroscopy (IRAS). Our research program builds upon our previous experience relating the results of single crystal kinetic measurements with the results obtained with supported analogs. As well we are exploiting our recent work on the preparation, the characterization, and the determination of the catalytic properties of ultra-thin metal and metal oxide films. The program is proceeding toward the study of the unique catalytic properties of ultrathin metal films; the investigation of the critical ensemble size requirements for principal catalytic reaction types; and the modelling of supported catalysts using ultra-thin planar oxide surfaces.

  8. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2003-10-28

    A process for the selective production and isolation of high specific activity Cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  9. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2002-12-03

    A process for the selective production and isolation of high specific activity cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  10. Highly Multiplexed RNA Aptamer Selection using a Microplate-based Microcolumn Device

    PubMed Central

    Reinholt, Sarah J.; Ozer, Abdullah; Lis, John T.; Craighead, Harold G.

    2016-01-01

    We describe a multiplexed RNA aptamer selection to 19 different targets simultaneously using a microcolumn-based device, MEDUSA (Microplate-based Enrichment Device Used for the Selection of Aptamers), as well as a modified selection process, that significantly reduce the time and reagents needed for selections. We exploited MEDUSA’s reconfigurable design between parallel and serially-connected microcolumns to enable the use of just 2 aliquots of starting library, and its 96-well microplate compatibility to enable the continued use of high-throughput techniques in downstream processes. Our modified selection protocol allowed us to perform the equivalent of a 10-cycle selection in the time it takes for 4 traditional selection cycles. Several aptamers were discovered with nanomolar dissociation constants. Furthermore, aptamers were identified that not only bound with high affinity, but also acted as inhibitors to significantly reduce the activity of their target protein, mouse decapping exoribonuclease (DXO). The aptamers resisted DXO’s exoribonuclease activity, and in studies monitoring DXO’s degradation of a 30-nucleotide substrate, less than 1 μM of aptamer demonstrated significant inhibition of DXO activity. This aptamer selection method using MEDUSA helps to overcome some of the major challenges with traditional aptamer selections, and provides a platform for high-throughput selections that lends itself to process automation. PMID:27432610

  11. Highly Multiplexed RNA Aptamer Selection using a Microplate-based Microcolumn Device.

    PubMed

    Reinholt, Sarah J; Ozer, Abdullah; Lis, John T; Craighead, Harold G

    2016-01-01

    We describe a multiplexed RNA aptamer selection to 19 different targets simultaneously using a microcolumn-based device, MEDUSA (Microplate-based Enrichment Device Used for the Selection of Aptamers), as well as a modified selection process, that significantly reduce the time and reagents needed for selections. We exploited MEDUSA's reconfigurable design between parallel and serially-connected microcolumns to enable the use of just 2 aliquots of starting library, and its 96-well microplate compatibility to enable the continued use of high-throughput techniques in downstream processes. Our modified selection protocol allowed us to perform the equivalent of a 10-cycle selection in the time it takes for 4 traditional selection cycles. Several aptamers were discovered with nanomolar dissociation constants. Furthermore, aptamers were identified that not only bound with high affinity, but also acted as inhibitors to significantly reduce the activity of their target protein, mouse decapping exoribonuclease (DXO). The aptamers resisted DXO's exoribonuclease activity, and in studies monitoring DXO's degradation of a 30-nucleotide substrate, less than 1 μM of aptamer demonstrated significant inhibition of DXO activity. This aptamer selection method using MEDUSA helps to overcome some of the major challenges with traditional aptamer selections, and provides a platform for high-throughput selections that lends itself to process automation. PMID:27432610

  12. Thinking Outside the Box: Rectilinear Shapes Selectively Activate Scene-Selective Cortex

    PubMed Central

    Echavarria, Cesar E.; Tootell, Roger B.H.

    2014-01-01

    Fifteen years ago, an intriguing area was found in human visual cortex. This area (the parahippocampal place area [PPA]) was initially interpreted as responding selectively to images of places. However, subsequent studies reported that PPA also responds strongly to a much wider range of image categories, including inanimate objects, tools, spatial context, landmarks, objectively large objects, indoor scenes, and/or isolated buildings. Here, we hypothesized that PPA responds selectively to a lower-level stimulus property (rectilinear features), which are common to many of the above higher-order categories. Using a novel wavelet image filter, we first demonstrated that rectangular features are common in these diverse stimulus categories. Then we tested whether PPA is selectively activated by rectangular features in six independent fMRI experiments using progressively simplified stimuli, from complex real-world images, through 3D/2D computer-generated shapes, through simple line stimuli. We found that PPA was consistently activated by rectilinear features, compared with curved and nonrectangular features. This rectilinear preference was (1) comparable in amplitude and selectivity, relative to the preference for category (scenes vs faces), (2) independent of known biases for specific orientations and spatial frequency, and (3) not predictable from V1 activity. Two additional scene-responsive areas were sensitive to a subset of rectilinear features. Thus, rectilinear selectivity may serve as a crucial building block for category-selective responses in PPA and functionally related areas. PMID:24828628

  13. ENSEMBLE VARIABILITY OF NEAR-INFRARED-SELECTED ACTIVE GALACTIC NUCLEI

    SciTech Connect

    Kouzuma, S.; Yamaoka, H. E-mail: yamaoka@phys.kyushu-u.ac.jp

    2012-03-01

    We present the properties of the ensemble variability V for nearly 5000 near-infrared active galactic nuclei (AGNs) selected from the catalog of Quasars and Active Galactic Nuclei (13th Edition) and the SDSS-DR7 quasar catalog. From three near-infrared point source catalogs, namely, Two Micron All Sky Survey (2MASS), Deep Near Infrared Survey (DENIS), and UKIDSS/LAS catalogs, we extract 2MASS-DENIS and 2MASS-UKIDSS counterparts for cataloged AGNs by cross-identification between catalogs. We further select variable AGNs based on an optimal criterion for selecting the variable sources. The sample objects are divided into subsets according to whether near-infrared light originates by optical emission or by near-infrared emission in the rest frame; and we examine the correlations of the ensemble variability with the rest-frame wavelength, redshift, luminosity, and rest-frame time lag. In addition, we also examine the correlations of variability amplitude with optical variability, radio intensity, and radio-to-optical flux ratio. The rest-frame optical variability of our samples shows negative correlations with luminosity and positive correlations with rest-frame time lag (i.e., the structure function, SF), and this result is consistent with previous analyses. However, no well-known negative correlation exists between the rest-frame wavelength and optical variability. This inconsistency might be due to a biased sampling of high-redshift AGNs. Near-infrared variability in the rest frame is anticorrelated with the rest-frame wavelength, which is consistent with previous suggestions. However, correlations of near-infrared variability with luminosity and rest-frame time lag are the opposite of these correlations of the optical variability; that is, the near-infrared variability is positively correlated with luminosity but negatively correlated with the rest-frame time lag. Because these trends are qualitatively consistent with the properties of radio-loud quasars reported

  14. A Deterministic Approach to Active Debris Removal Target Selection

    NASA Astrophysics Data System (ADS)

    Lidtke, A.; Lewis, H.; Armellin, R.

    2014-09-01

    Many decisions, with widespread economic, political and legal consequences, are being considered based on space debris simulations that show that Active Debris Removal (ADR) may be necessary as the concerns about the sustainability of spaceflight are increasing. The debris environment predictions are based on low-accuracy ephemerides and propagators. This raises doubts about the accuracy of those prognoses themselves but also the potential ADR target-lists that are produced. Target selection is considered highly important as removal of many objects will increase the overall mission cost. Selecting the most-likely candidates as soon as possible would be desirable as it would enable accurate mission design and allow thorough evaluation of in-orbit validations, which are likely to occur in the near-future, before any large investments are made and implementations realized. One of the primary factors that should be used in ADR target selection is the accumulated collision probability of every object. A conjunction detection algorithm, based on the smart sieve method, has been developed. Another algorithm is then applied to the found conjunctions to compute the maximum and true probabilities of collisions taking place. The entire framework has been verified against the Conjunction Analysis Tools in AGIs Systems Toolkit and relative probability error smaller than 1.5% has been achieved in the final maximum collision probability. Two target-lists are produced based on the ranking of the objects according to the probability they will take part in any collision over the simulated time window. These probabilities are computed using the maximum probability approach, that is time-invariant, and estimates of the true collision probability that were computed with covariance information. The top-priority targets are compared, and the impacts of the data accuracy and its decay are highlighted. General conclusions regarding the importance of Space Surveillance and Tracking for the

  15. A Dioxane Template for Highly Selective Epoxy Alcohol Cyclizations

    PubMed Central

    Mousseau, James J.; Morten, Christopher J.

    2013-01-01

    Ladder polyether natural products are a class of natural products denoted by their high functional group density and large number of well-defined stereocenters. They comprise the toxic component of harmful algal blooms (HABs), having significant negative economic and environmental ramifications. However, their mode of action, namely blocking various cellular ion channels, also denotes their promise as potential anticancer agents. Understanding their potential mode of biosynthesis will not only help with developing ways to limit the damage of HABs, but would also facilitate the synthesis of a range of analogues with interesting biological activity. 1,3-Dioxan-5-ol substrates display remarkable ‘enhanced template effects’ in water-promoted epoxide cyclization processes en route to the synthesis of these ladder polyether natural products. In many cases they provide near complete endo to exo selectivity in the cyclization of epoxy alcohols, thereby strongly favouring the formation of tetrahydropyran (THP) over tetrahydrofuran (THF) rings. The effects of various Brønsted and Lewis acidic and basic conditions are explored to demonstrate the superior selectivity of the template over the previously reported THP-based epoxy alcohols. In addition, the consideration of other synthetic routes are also considered with the goal of gaining rapid access to a plethora of potential starting materials applicable towards the synthesis of ladder polyethers. Finally, cascade sequences with polyepoxides are investigated, further demonstrating the versatility of this new reaction template. PMID:23775936

  16. Discovery of a Highly Selective STK16 Kinase Inhibitor.

    PubMed

    Liu, Feiyang; Wang, Jinhua; Yang, Xingxing; Li, Binhua; Wu, Hong; Qi, Shuang; Chen, Cheng; Liu, Xiaochuan; Yu, Kailin; Wang, Wenchao; Zhao, Zheng; Wang, Aoli; Chen, Yongfei; Wang, Li; Gray, Nathanael S; Liu, Jing; Zhang, Xin; Liu, Qingsong

    2016-06-17

    STK16, a serine/threonine protein kinase, is ubiquitously expressed and is conserved among all eukaryotes. STK16 has been implicated to function in a variety of cellular processes such as VEGF and cargo secretion, but the pathways through which these effects are mediated remain to be elucidated. Through screening of our focused library of kinase inhibitors, we discovered a highly selective ATP competitive inhibitor, STK16-IN-1, which exhibits potent inhibitory activity against STK16 kinase (IC50: 0.295 μM) with excellent selectivity across the kinome as assessed using the KinomeScan profiling assay (S score (1) = 0.0). In MCF-7 cells, treatment with STK16-IN-1 results in a reduction in cell number and accumulation of binucleated cells, which can be recapitulated by RNAi knockdown of STK16. Co-treatment of STK16-IN-1 with chemotherapeutics such as cisplatin, doxorubicin, colchicine, and paclitaxel results in a slight potentiation of the antiproliferative effects of the chemotherapeutics. STK16-IN-1 provides a useful tool compound for further elucidating the biological functions of STK16. PMID:27082499

  17. A Model for Investigating Predictive Validity at Highly Selective Institutions.

    ERIC Educational Resources Information Center

    Gross, Alan L.; And Others

    A statistical model for investigating predictive validity at highly selective institutions is described. When the selection ratio is small, one must typically deal with a data set containing relatively large amounts of missing data on both criterion and predictor variables. Standard statistical approaches are based on the strong assumption that…

  18. Neuronal activity biases axon selection for myelination in vivo

    PubMed Central

    Hines, Jacob H.; Ravanelli, Andrew M.; Schwindt, Rani; Scott, Ethan K.; Appel, Bruce

    2015-01-01

    An essential feature of vertebrate neural development is ensheathment of axons with myelin, an insulating membrane formed by oligodendrocytes. Not all axons are myelinated, but mechanisms directing myelination of specific axons are unknown. Using zebrafish we show that activity-dependent secretion stabilizes myelin sheath formation on select axons. When VAMP2-dependent exocytosis is silenced in single axons, oligodendrocytes preferentially ensheath neighboring axons. Nascent sheaths formed on silenced axons are shorter in length, but when activity of neighboring axons is also suppressed, inhibition of sheath growth is relieved. Using in vivo time-lapse microscopy, we show that only 25% of oligodendrocyte processes that initiate axon wrapping are stabilized during normal development, and that initiation does not require activity. Instead, oligodendrocyte processes wrapping silenced axons are retracted more frequently. We propose that axon selection for myelination results from excessive and indiscriminate initiation of wrapping followed by refinement that is biased by activity-dependent secretion from axons. PMID:25849987

  19. Selective high affinity polydentate ligands and methods of making such

    SciTech Connect

    DeNardo, Sally; DeNardo, Gerald; Balhorn, Rodney

    2010-02-16

    This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

  20. Structural basis for selective activation of ABA receptors

    SciTech Connect

    Peterson, Francis C.; Burgie, E. Sethe; Park, Sang-Youl; Jensen, Davin R.; Weiner, Joshua J.; Bingman, Craig A.; Chang, Chia-En A.; Cutler, Sean R.; Phillips, Jr., George N.; Volkman, Brian F.

    2010-11-01

    Changing environmental conditions and lessening fresh water supplies have sparked intense interest in understanding and manipulating abscisic acid (ABA) signaling, which controls adaptive responses to drought and other abiotic stressors. We recently discovered a selective ABA agonist, pyrabactin, and used it to discover its primary target PYR1, the founding member of the PYR/PYL family of soluble ABA receptors. To understand pyrabactin's selectivity, we have taken a combined structural, chemical and genetic approach. We show that subtle differences between receptor binding pockets control ligand orientation between productive and nonproductive modes. Nonproductive binding occurs without gate closure and prevents receptor activation. Observations in solution show that these orientations are in rapid equilibrium that can be shifted by mutations to control maximal agonist activity. Our results provide a robust framework for the design of new agonists and reveal a new mechanism for agonist selectivity.

  1. Leisure-Time Activities in Selected Nursing Homes.

    ERIC Educational Resources Information Center

    Tague, Jean Ruth

    This study sought to identify leisure interests and participation patterns of residents over 65 in selected nursing homes in Los Angeles County, California, together with general and professional beliefs of nursing home administrators and authorities on aging as to leisure activities for aged nursing home patients. Interviews were held with 107…

  2. Advanced aerodynamics and active controls. Selected NASA research

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Aerodynamic and active control concepts for application to commercial transport aircraft are discussed. Selected topics include in flight direct strike lightning research, triply redundant digital fly by wire control systems, tail configurations, winglets, and the drones for aerodynamic and structural testing (DAST) program.

  3. Automated frame selection process for high-resolution microendoscopy

    NASA Astrophysics Data System (ADS)

    Ishijima, Ayumu; Schwarz, Richard A.; Shin, Dongsuk; Mondrik, Sharon; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

    2015-04-01

    We developed an automated frame selection algorithm for high-resolution microendoscopy video sequences. The algorithm rapidly selects a representative frame with minimal motion artifact from a short video sequence, enabling fully automated image analysis at the point-of-care. The algorithm was evaluated by quantitative comparison of diagnostically relevant image features and diagnostic classification results obtained using automated frame selection versus manual frame selection. A data set consisting of video sequences collected in vivo from 100 oral sites and 167 esophageal sites was used in the analysis. The area under the receiver operating characteristic curve was 0.78 (automated selection) versus 0.82 (manual selection) for oral sites, and 0.93 (automated selection) versus 0.92 (manual selection) for esophageal sites. The implementation of fully automated high-resolution microendoscopy at the point-of-care has the potential to reduce the number of biopsies needed for accurate diagnosis of precancer and cancer in low-resource settings where there may be limited infrastructure and personnel for standard histologic analysis.

  4. 1990 Nationwide Truck Activity and Commodity Survey selected tabulations

    SciTech Connect

    Not Available

    1993-06-01

    The Nationwide Truck Activity and Commodity Survey (NTACS) provides detailed activity data for a sample of trucks covered in the 1987 Truck Inventory and Use Survey (TIUS) for days selected at random over a 12-month period ending in 1990. The NTACS was conducted by the US Bureau of the Census for the US Department of Transportation (DOT). A Public Use File for the NTACS was developed by Oak Ridge National Laboratory (ORNL) under a reimbursable agreement with the DOT. The content of the Public Use File and the detailed design of the NTACS are described in the ORNL Report [open quotes]Technical Documentation for the 1990 Nationwide Truck Activity and Commodity Survey Public Use File[close quotes]. (1992). ORNL Technical Report No. TM-12188, Oak Ridge National Laboratory, Oak Ridge, TN 37831. The main purpose of this summary report is to provide selected tables based on the public use file.

  5. High specific activity silicon-32

    DOEpatents

    Phillips, D.R.; Brzezinski, M.A.

    1996-06-11

    A process for preparation of silicon-32 is provided and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidation state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  6. High specific activity silicon-32

    DOEpatents

    Phillips, Dennis R.; Brzezinski, Mark A.

    1996-01-01

    A process for preparation of silicon-32 is provided and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  7. A Selective Overview of Variable Selection in High Dimensional Feature Space

    PubMed Central

    Fan, Jianqing

    2010-01-01

    High dimensional statistical problems arise from diverse fields of scientific research and technological development. Variable selection plays a pivotal role in contemporary statistical learning and scientific discoveries. The traditional idea of best subset selection methods, which can be regarded as a specific form of penalized likelihood, is computationally too expensive for many modern statistical applications. Other forms of penalized likelihood methods have been successfully developed over the last decade to cope with high dimensionality. They have been widely applied for simultaneously selecting important variables and estimating their effects in high dimensional statistical inference. In this article, we present a brief account of the recent developments of theory, methods, and implementations for high dimensional variable selection. What limits of the dimensionality such methods can handle, what the role of penalty functions is, and what the statistical properties are rapidly drive the advances of the field. The properties of non-concave penalized likelihood and its roles in high dimensional statistical modeling are emphasized. We also review some recent advances in ultra-high dimensional variable selection, with emphasis on independence screening and two-scale methods. PMID:21572976

  8. A Selective Overview of Variable Selection in High Dimensional Feature Space.

    PubMed

    Fan, Jianqing; Lv, Jinchi

    2010-01-01

    High dimensional statistical problems arise from diverse fields of scientific research and technological development. Variable selection plays a pivotal role in contemporary statistical learning and scientific discoveries. The traditional idea of best subset selection methods, which can be regarded as a specific form of penalized likelihood, is computationally too expensive for many modern statistical applications. Other forms of penalized likelihood methods have been successfully developed over the last decade to cope with high dimensionality. They have been widely applied for simultaneously selecting important variables and estimating their effects in high dimensional statistical inference. In this article, we present a brief account of the recent developments of theory, methods, and implementations for high dimensional variable selection. What limits of the dimensionality such methods can handle, what the role of penalty functions is, and what the statistical properties are rapidly drive the advances of the field. The properties of non-concave penalized likelihood and its roles in high dimensional statistical modeling are emphasized. We also review some recent advances in ultra-high dimensional variable selection, with emphasis on independence screening and two-scale methods. PMID:21572976

  9. Transcriptional Activation of Inflammatory Genes: Mechanistic Insight into Selectivity and Diversity

    PubMed Central

    Ahmed, Afsar U.; Williams, Bryan R. G.; Hannigan, Gregory E.

    2015-01-01

    Acute inflammation, an integral part of host defence and immunity, is a highly conserved cellular response to pathogens and other harmful stimuli. An inflammatory stimulation triggers transcriptional activation of selective pro-inflammatory genes that carry out specific functions such as anti-microbial activity or tissue healing. Based on the nature of inflammatory stimuli, an extensive exploitation of selective transcriptional activations of pro-inflammatory genes is performed by the host to ensure a defined inflammatory response. Inflammatory signal transductions are initiated by the recognition of inflammatory stimuli by transmembrane receptors, followed by the transmission of the signals to the nucleus for differential gene activations. The differential transcriptional activation of pro-inflammatory genes is precisely controlled by the selective binding of transcription factors to the promoters of these genes. Among a number of transcription factors identified to date, NF-κB still remains the most prominent and studied factor for its diverse range of selective transcriptional activities. Differential transcriptional activities of NF-κB are dictated by post-translational modifications, specificities in dimer formation, and variability in activation kinetics. Apart from the differential functions of transcription factors, the transcriptional activation of selective pro-inflammatory genes is also governed by chromatin structures, epigenetic markers, and other regulators as the field is continuously expanding. PMID:26569329

  10. Transcriptional Activation of Inflammatory Genes: Mechanistic Insight into Selectivity and Diversity.

    PubMed

    Ahmed, Afsar U; Williams, Bryan R G; Hannigan, Gregory E

    2015-01-01

    Acute inflammation, an integral part of host defence and immunity, is a highly conserved cellular response to pathogens and other harmful stimuli. An inflammatory stimulation triggers transcriptional activation of selective pro-inflammatory genes that carry out specific functions such as anti-microbial activity or tissue healing. Based on the nature of inflammatory stimuli, an extensive exploitation of selective transcriptional activations of pro-inflammatory genes is performed by the host to ensure a defined inflammatory response. Inflammatory signal transductions are initiated by the recognition of inflammatory stimuli by transmembrane receptors, followed by the transmission of the signals to the nucleus for differential gene activations. The differential transcriptional activation of pro-inflammatory genes is precisely controlled by the selective binding of transcription factors to the promoters of these genes. Among a number of transcription factors identified to date, NF-κB still remains the most prominent and studied factor for its diverse range of selective transcriptional activities. Differential transcriptional activities of NF-κB are dictated by post-translational modifications, specificities in dimer formation, and variability in activation kinetics. Apart from the differential functions of transcription factors, the transcriptional activation of selective pro-inflammatory genes is also governed by chromatin structures, epigenetic markers, and other regulators as the field is continuously expanding. PMID:26569329

  11. Customized cooking method improves total antioxidant activity in selected vegetables.

    PubMed

    Ng, Zhi-Xiang; Chai, Jen-Wai; Kuppusamy, Umah Rani

    2011-03-01

    The present study compares water-soluble phenolic content (WPC) and antioxidant activities in Chinese long bean (Vigna unguiculata), bitter gourd (Momordica charantia), water convolvulus (Ipomoea aquatica) and broccoli (Brassica olearacea) prior to and after subjecting to boiling, microwaving and pressure cooking. The total antioxidant activity was increased in cooked water convolvulus, broccoli and bitter gourd, estimated based on the ferric reducing antioxidant power, the Trolox equivalent antioxidant capacity and 2,2-diphenyl-1-picryl-hydrazyl radical scavenging activity. Pressure cooking did not cause any significant decline in the antioxidant property. Boiling generally improved the overall antioxidant activity in all the vegetables. Correlation analysis suggests that WPC contributed to significant antioxidant activities in these vegetables. Thus, prudence in selecting an appropriate cooking method for different vegetables may improve or preserve their nutritional value. PMID:21250903

  12. Super-surface selective nanomembranes providing simultaneous high permeation flux and high selectivity

    DOEpatents

    Hu, Michael Z.; Simpson, John T.; Aytug, Tolga; Paranthaman, Mariappan Parans; Sturgeon, Matthew R.

    2016-04-12

    Superhydrophobic membrane structures having a beneficial combination of throughput and a selectivity. The membrane structure can include a porous support substrate; and a membrane layer adherently disposed on and in contact with the porous support substrate. The membrane layer can include a nanoporous material having a superhydrophobic surface. The superhydrophobic surface can include a textured surface, and a modifying material disposed on the textured surface. Methods of making and using the membrane structures.

  13. A theoretical study on cellular antioxidant activity of selected flavonoids

    NASA Astrophysics Data System (ADS)

    Rong, Yuzhi; Wang, Zhengwu; Wu, Jinhong; Zhao, Bo

    The antioxidant capacities of the selected flavonoids quercetin, luteolin and taxifolin have been investigated at density functional level of theory with the aim of verifying the cellular antioxidant activity (CAA) values representative of experimental findings. The selected flavonoids were believed to act through the H-atom transfer mechanism. Their potentiality of hydrogen abstraction was evaluated by computing the Osbnd H bond dissociation enthalpy (BDE) in gas-phase and in dimethylsulfoxide solution. Results indicate that the order of antioxidant efficacies calculated in this work is in agreement with that reported by experimental results of CAA. Time-dependent density functional theory (TDDFT) calculations were also performed both in gas-phase and in dimethylsulfoxide to reproduce the electronic UV-vis spectra of the selected flavonoids.

  14. Surprisingly high activity for oxygen reduction reaction of selected oxides lacking long oxygen-ion diffusion paths at intermediate temperatures: a case study of cobalt-free BaFeO(3-δ).

    PubMed

    Dong, Feifei; Chen, Yubo; Chen, Dengjie; Shao, Zongping

    2014-07-23

    The widespread application of solid oxide fuel cell technology requires the development of innovative electrodes with high activity for oxygen reduction reaction (ORR) at intermediate temperatures. Here, we demonstrate that a cobalt-free parent oxide BaFeO(3-δ) (BF), which lacks long-range oxygen-ion diffusion paths, has surprisingly high electrocatalytic activity for ORR. Both in situ high-temperature X-ray diffraction analysis on room-temperature powder and transmission electron microscopy on quenched powder are applied to investigate the crystal structure of BF. Despite the lack of long oxygen-ion diffusion paths, the easy redox of iron cations as demonstrated by thermal gravimetric analysis (TGA) and oxygen temperature-programmed desorption and the high oxygen vacancy concentration as supported by iodometric titration and TGA benefit the reduction of oxygen to oxygen ions. Moreover, the electrical conductivity relaxation technique in conjunction with a transient thermogravimetric study reveals very high surface exchange kinetics of BF oxide. At 700 °C, the area specific resistance of BF cathode, as expressed by a symmetrical cell configuration, is only ∼0.021 Ω cm(2), and the derived single fuel cell achieves high power output with a peak power density of 870 mW cm(-2). It suggests that an undoped BF parent oxide can be used as a high-efficiency catalyst for ORR. PMID:24978102

  15. Recent progress in research on peroxisome proliferator-activated receptor alpha-selective ligands.

    PubMed

    Miyachi, Hiroyuki

    2004-08-01

    The understanding of the functions of the nuclear receptor peroxisome proliferator-activated receptor a (PPARalpha) as a regulator of lipid and lipoprotein homeostasis, and the rapid development of parallel high-throughput screening assays to evaluate the activity toward other PPAR subtypes (PPARdelta and PPARgamma), have provided an opportunity to develop novel PPARalpha-selective, PPARalpha/gamma dual and PPAR pan agonists for the treatment of various metabolic diseases. This review focuses on the molecular pharmacology of PPARalpha, and summarizes recent literature and patent applications disclosing medicinal chemistry strategies to identify new PPARalpha-selective agonists. The species selectivity of some classes of PPARalpha-selective agonists in response to in vitro PPARalpha transactivation activity is also reported. PMID:15334308

  16. Antibacterial Activity of Barringtonia acutangula against Selected Urinary Tract Pathogens.

    PubMed

    Sahoo, S; Panda, P K; Mishra, S R; Parida, R K; Ellaiah, P; Dash, S K

    2008-09-01

    Barringtonia acutangula (L.) Gaertn belonging to family Barringtoniaceae was investigated to evaluate In vitro antibacterial activity of aqueous, ethanolic, petroleum ether and chloroform extracts against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecalis and Escherichia coli the major urinary tract infection causing pathogens were tested by disc diffusion assay method and the minimum inhibitory concentration was evaluated. Ethanol (95%) extract exhibited broader spectrum of inhibition followed by chloroform, petroleum ether and aqueous extracts against the urinary tract pathogens under test. An attempt has been made to compare the activity of extracts with standard antibiotics against selected urinary tract infection causing pathogens. PMID:21394275

  17. Antibacterial Activity of Barringtonia acutangula against Selected Urinary Tract Pathogens

    PubMed Central

    Sahoo, S.; Panda, P. K.; Mishra, S. R.; Parida, R. K.; Ellaiah, P.; Dash, S. K.

    2008-01-01

    Barringtonia acutangula (L.) Gaertn belonging to family Barringtoniaceae was investigated to evaluate In vitro antibacterial activity of aqueous, ethanolic, petroleum ether and chloroform extracts against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecalis and Escherichia coli the major urinary tract infection causing pathogens were tested by disc diffusion assay method and the minimum inhibitory concentration was evaluated. Ethanol (95%) extract exhibited broader spectrum of inhibition followed by chloroform, petroleum ether and aqueous extracts against the urinary tract pathogens under test. An attempt has been made to compare the activity of extracts with standard antibiotics against selected urinary tract infection causing pathogens. PMID:21394275

  18. Antioxidant activity of various extracts of selected gourd vegetables.

    PubMed

    Yadav, Baljeet S; Yadav, Roshanlal; Yadav, Ritika B; Garg, Munish

    2016-04-01

    Study was conducted to evaluate the antioxidative activity of methanolic (ME), ethanolic (EE) and butanolic extracts (BE) of selected gourd vegetables. The antioxidant activity was investigated using different assays namely ferric thiocyanate test (FTC), thiobarbituric acid test (TBA), ferric reducing antioxidant power (FRAP) and DPPH free radicals scavenging test. A densitometric HPTLC analysis was performed for the analysis of phenolic acids and flavonoids. Different extracts of the selected gourd vegetables revealed different antioxidant activity. Different extracts of Lagenaria siceraria, Momordica charantia and Luffa cylindrica revealed significantly higher (p < 0.05) concentrations of total phenols, flavonids, tannins and carotenoids content and also the antioxidant activity in comparison to remaining vegetable extracts. Correlation studies indicated that FRAP test best described the antioxidant activity of phenols, flavonoids and carotenoids (r = 0.854, 0.692 and 0.915 respectively). HPTLC profiles revealed the presence of maximum number of phenolic acids and flavonoids in L. siceraria and M. charantia. PMID:27413209

  19. Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy.

    PubMed

    Sollet, Jean-Pierre; Garber, Gary E

    2002-12-01

    Selecting patients for drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) therapy outside of a clinical trial setting requires knowledge of the rationale that led the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) investigators to select the various entry criteria for the trial. Enrollment criteria for the study included a known or suspected infection, presence of at least 3 systemic inflammatory response syndrome (SIRS) criteria, and dysfunction of > or =1 organ or system. The infection criteria used in PROWESS were designed to be straightforward and were based on common clinical and radiological data. Although previous definitions of sepsis required only 2 SIRS criteria, the PROWESS trial investigators required the presence of > or =3 SIRS criteria to improve the sensitivity and specificity of these criteria for the diagnosis of sepsis. Acute organ dysfunction, the diagnostic criterion for severe sepsis, was used to define the study population because it identifies patients at significant risk of death. Characteristics of drotrecogin alfa (activated)-treated patients, including infection, modified SIRS criteria, and organ dysfunction, were similar to those of the placebo group and the general sepsis population. Proper clinical judgment and use of the these inclusion criteria as a guide will help clinicians select and treat sepsis patients with drotrecogin alfa (activated). PMID:12521613

  20. Patient Selection and Activity Planning Guide for Selective Internal Radiotherapy With Yttrium-90 Resin Microspheres

    SciTech Connect

    Lau, Wan-Yee; Kennedy, Andrew S.; Kim, Yun Hwan; Lai, Hee Kit; Lee, Rheun-Chuan; Leung, Thomas W.T.; Liu, Ching-Sheng; Salem, Riad; Sangro, Bruno; Shuter, Borys; Wang, Shih-Chang

    2012-01-01

    Purpose: Selective internal radiotherapy (SIRT) with yttrium-90 ({sup 90}Y) resin microspheres can improve the clinical outcomes for selected patients with inoperable liver cancer. This technique involves intra-arterial delivery of {beta}-emitting microspheres into hepatocellular carcinomas or liver metastases while sparing uninvolved structures. Its unique mode of action, including both {sup 90}Y brachytherapy and embolization of neoplastic microvasculature, necessitates activity planning methods specific to SIRT. Methods and Materials: A panel of clinicians experienced in {sup 90}Y resin microsphere SIRT was convened to integrate clinical experience with the published data to propose an activity planning pathway for radioembolization. Results: Accurate planning is essential to minimize potentially fatal sequelae such as radiation-induced liver disease while delivering tumoricidal {sup 90}Y activity. Planning methods have included empiric dosing according to degree of tumor involvement, empiric dosing adjusted for the body surface area, and partition model calculations using Medical Internal Radiation Dose principles. It has been recommended that at least two of these methods be compared when calculating the microsphere activity for each patient. Conclusions: Many factors inform {sup 90}Y resin microsphere SIRT activity planning, including the therapeutic intent, tissue and vasculature imaging, tumor and uninvolved liver characteristics, previous therapies, and localization of the microsphere infusion. The influence of each of these factors has been discussed.

  1. Highly efficient, selective, sensitive and stability indicating RP-HPLC-UV method for the quantitative determination of potential impurities and characterization of four novel impurities in eslicarbazepine acetate active pharmaceutical ingredient by LC/ESI-IT/MS/MS.

    PubMed

    Thomas, Saji; Bharti, Amber; Maddhesia, Pawan Kumar; Shandilya, Sanjeev; Agarwal, Ashutosh; Dharamvir; Biswas, Sujay; Bhansal, Vikas; Gupta, Ashish Kumar; Tewari, Praveen Kumar; Mathela, Chandra S

    2012-03-01

    A novel, sensitive, selective and stability indicating LC-UV method was developed for the determination of potential impurities of eslicarbazepine acetate. High performance liquid chromatographic investigation of eslicarbazepine acetate laboratory sample revealed the presence of several impurities. Three impurities were characterized rapidly and four impurities were found to be unknown. The unknown impurities were identified by liquid chromatography coupled with electrospray ionization, ion trap mass spectrometry (LC/ESI-IT/MS/MS). Structural confirmation of these impurities was unambiguously carried out by synthesis followed by characterization using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (FT-IR) and mass spectrometry (MS). Based on the spectroscopic, spectrometric and elemental analysis data unknown impurities were characterized as 5-acetyl-5,11-dihydro-10H-dibenzo [b,f]azepin-10-one, N-acetyl-5H-dibenzo[b,f]azepine-5-carboxamide, 5-acetyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate and 5-acetyl-5H-dibenzo[b,f]azepin-10-yl acetate. The newly developed LC-UV method was validated according to ICH guidelines considering eleven potential impurities and four new impurities to demonstrate specificity, precision, linearity, accuracy and stability indicating nature of the method. The newly developed method was found to be highly efficient, selective, sensitive and stability indicating. A plausible pathway for the formation of four new impurities is proposed. PMID:22178334

  2. Activated Sludge. Selected Instructional Activities and References. Instructional Resources Monograph Series.

    ERIC Educational Resources Information Center

    Shepard, Clinton L.; Walasek, James B.

    This monograph contains a variety of selected materials related to wastewater treatment and water quality education and instruction. Part I presents a brief discussion of the activated sludge process in wastewater treatment operations. Part II, Instructional Units, contains selected portions of existing programs which may be utilized in…

  3. Synthetic promoter elements obtained by nucleotide sequence variation and selection for activity

    PubMed Central

    Edelman, Gerald M.; Meech, Robyn; Owens, Geoffrey C.; Jones, Frederick S.

    2000-01-01

    Eukaryotic transcriptional regulation in different cells involves large numbers and arrangements of cis and trans elements. To survey the number of cis regulatory elements that are active in different contexts, we have devised a high-throughput selection procedure permitting synthesis of active cis motifs that enhance the activity of a minimal promoter. This synthetic promoter construction method (SPCM) was used to identify >100 DNA sequences that showed increased promoter activity in the neuroblastoma cell line Neuro2A. After determining DNA sequences of selected synthetic promoters, database searches for known elements revealed a predominance of eight motifs: AP2, CEBP, GRE, Ebox, ETS, CREB, AP1, and SP1/MAZ. The most active of the selected synthetic promoters contain composites of a number of these motifs. Assays of DNA binding and promoter activity of three exemplary motifs (ETS, CREB, and SP1/MAZ) were used to prove the effectiveness of SPCM in uncovering active sequences. Up to 10% of 133 selected active sequences had no match in currently available databases, raising the possibility that new motifs and transcriptional regulatory proteins to which they bind may be revealed by SPCM. The method may find uses in constructing databases of active cis motifs, in diagnostics, and in gene therapy. PMID:10725347

  4. Highly selective enrichment of phosphopeptides with high-index facets exposed octahedral tin dioxide nanoparticles for mass spectrometric analysis.

    PubMed

    Ma, Rongna; Hu, Junjie; Cai, Zongwei; Ju, Huangxian

    2014-02-01

    High-index facets exposed octahedral tin dioxide (SnO2) nanoparticles were successfully synthesized and applied to selectively enrich phosphopeptides for mass spectrometric analysis. The high selectivity and capacity of the octahedral SnO2 nanoparticles were demonstrated by effectively enriching phosphopeptides from digests of phosphoprotein (α- or β-casein), protein mixtures of β-casein and bovine serum albumin, milk, and human serum samples. The unique octahedral SnO2 with abundant unsaturated coordination Sn atoms exhibited enhanced affinity and selective coordination ability with phosphopeptides due to their high chemical activity. The strong affinity led to highly selective capture and enrichment of phosphopeptides for sensitive detection through the bidentate bonds formed between surface atoms and phosphate. The phosphopeptides could be detected in β-casein down to 4 × 10(-9)M or in the mixture of β-casein and BSA with a molar ratio of even 1:100. The performance in selective enrichment of phosphopeptides from drinking milk and human serum showed powerful evidence of high selectivity and efficiency in identifying the low-abundant phosphopeptides from complicated biological samples. This work provided a way to improve the physical and chemical properties of materials by tailoring their exposed facets for selective enrichment of phosphopeptides. PMID:24401440

  5. In vitro antitrypanosomal activity of ethnopharmacologically selected Beninese plants.

    PubMed

    Hoet, Sara; Opperdoes, Frederik; Brun, Reto; Adjakidjé, Victor; Quetin-Leclercq, Joëlle

    2004-03-01

    The in vitro antitrypanosomal activity of methylene chloride, methanol and aqueous extracts of the leaves and twigs of five plant species traditionally used in Benin for the treatment of sleeping sickness were evaluated on Trypanosoma brucei brucei and their selectivity was analysed on Leishmania mexicana mexicana and J774 macrophage-like murine cells. The results showed that the four most active extracts had MIC values < or =19 microg/ml (Hymenocardia acida twig and leaf, Strychnos spinosa leaf, Trichilia emetica leaf methylene chloride extracts). All these extracts had a lower activity on L. m. mexicana and J774 cells. Determination of the IC50 values of the methylene chloride leaf extracts on two strains of trypanosomes (T. b. brucei and T. b. rhodesiense) and two mammalian cell lines (L6 and J774 cells) showed that all extracts possessed some antitrypanosomal activity with IC50's ranging from 1.5 to 39 microg/ml. All were also toxic to the mammalian cells, but usually with higher IC50's. The only exception was the S. spinosa methylene chloride leaf extract which had no toxicity on J774 cells. Although tannins have been identified in most of the species studied, they could not be detected in the most active extracts, just as alkaloids. The presence of flavonoids and quinones may at least in part explain the observed activities of some of the active extracts. PMID:15036465

  6. Perceptual expectation evokes category-selective cortical activity.

    PubMed

    Esterman, Michael; Yantis, Steven

    2010-05-01

    Selective visual attention directed to a location (even in the absence of a stimulus) increases activity in the corresponding regions of visual cortex and enhances the speed and accuracy of target perception. We further explored top-down influences on perceptual representations by manipulating observers' expectations about the category of an upcoming target. Observers viewed a display in which an object (either a face or a house) gradually emerged from a state of phase-scrambled noise; a cue established expectation about the object category. Observers were faster to categorize faces (gender discrimination) or houses (structural discrimination) when the category of the partially scrambled object matched their expectation. Functional magnetic resonance imaging revealed that this expectation was associated with anticipatory increases in category-specific visual cortical activity, even in the absence of object- or category-specific visual information. Expecting a face evoked increased activity in face-selective cortical regions in the fusiform gyrus and superior temporal sulcus. Conversely, expecting a house increased activity in parahippocampal gyrus. These results suggest that visual anticipation facilitates subsequent perception by recruiting, in advance, the same cortical mechanisms as those involved in perception. PMID:19759124

  7. Selection of active member locations in adaptive structures

    NASA Technical Reports Server (NTRS)

    Chen, G.-S.; Bruno, R.; Salama, M.

    1989-01-01

    The effective use of multiple passive and active members in adaptive structures necessitates that these members be optimally distributed throughout the structure. In truss structures, the problem falls into the class of combinatorial optimization for which the solution becomes exceedingly intractable as the problem size increases. This is overcome by using the simulated annealing algorithm to obtain near optimal locations for passive and/or active members. The maximization of the rate of energy dissipation over a finite time period as the measure of optimality is adopted. The selection of optimal locations for both passive and active members is consistently treated through the use of the energy dissipation rate criterion within the simulated annealing algorithm. Numerical examples are used to illustrate the effectiveness of the methodology for large truss structures.

  8. Grafting of activated carbon cloths for selective adsorption

    NASA Astrophysics Data System (ADS)

    Gineys, M.; Benoit, R.; Cohaut, N.; Béguin, F.; Delpeux-Ouldriane, S.

    2016-05-01

    Chemical functionalization of an activated carbon cloth with 3-aminophthalic acid and 4-aminobenzoic acid groups by the in situ formation of the corresponding diazonium salt in aqueous acidic solution is reported. The nature and amount of selected functions on an activated carbon surface, in particular the grafted density, were determined by potentiometric titration, elemental analysis and X-ray photoelectron spectroscopy (XPS). The nanotextural properties of the modified carbon were explored by gas adsorption. Functionalized activated carbon cloth was obtained at a discrete grafting level while preserving interesting textural properties and a large porous volume. Finally, the grafting homogeneity of the carbon surface and the nature of the chemical bonding were investigated using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) technique.

  9. Selecting Reading Materials for High School Students. ERIC Research Summary.

    ERIC Educational Resources Information Center

    Smith, Carl B., Ed.

    This topical bibliography and commentary discusses resource aids that help educators evaluate and select high quality reading materials for young adults. It discusses general resource articles as aids. Examples are: specific themes, booklists, and school system aids. It concludes that there are no succinct lists of criteria or resources; rather,…

  10. Toxicity and mutagenic activity of some selected Nigerian plants.

    PubMed

    Sowemimo, A A; Fakoya, F A; Awopetu, I; Omobuwajo, O R; Adesanya, S A

    2007-09-25

    The toxicity and mutagenic potential of most African plants implicated in the management of cancer have not been investigated. The ethanolic extracts of selected Nigerian plants were subsequently studied using the brine shrimp lethality tests, inhibition of telomerase activity and induction of chromosomal aberrations in vivo in rat lymphocytes. Morinda lucida root bark, Nymphaea lotus whole plant and Garcinia kola root were active in the three test systems. Bryophyllum calycinum whole plant, Annona senegalensis root, Hymenocardia acida stem bark, Erythrophleum suaveolens leaves and Spondiathus preussii stem bark were toxic to brine shrimps and caused chromosomal damage in rat lymphocytes. Ficus exasperata leaves, Chrysophyllum albidum root bark and Hibiscus sabdariffa leaves were non-toxic to all the three test systems. Chenopodium ambrosioides whole plant was non-toxic to brine shrimps and rat lymphocyte chromosomes but showed inhibition in the conventional telomerase assay indicating a possible selectivity for human chromosomes. The result justified the use of the first eight plants and Chenopodium ambrosioides in the management of cancer in south west Nigeria although they appear to be non-selective and their mode of action may be different from plant to plant. All these plants except Chenopodium ambrosioides are also mutagenic and cytotoxic. PMID:17707603

  11. High-flow frequencies for selected streams in Oklahoma

    USGS Publications Warehouse

    Huntzinger, Thomas L.

    1978-01-01

    Streamflow records are analyzed statistically to determine high-flow characteristics of selected streams in Oklahoma. Tables are included which show the 2-, 5-, 10-, 25-, 50-, and 100-year high-flow frequencies for durations of 1, 3, 7, 30, 90, and 365 days. The log-Pearson Type III frequency distribution was used in the computations. Streamflow records used include data extending from 1903 to 1974.

  12. Quantitative selection of DNA aptamers through microfluidic selection and high-throughput sequencing

    PubMed Central

    Cho, Minseon; Xiao, Yi; Nie, Jeff; Stewart, Ron; Csordas, Andrew T.; Oh, Seung Soo; Thomson, James A.; Soh, H. Tom

    2010-01-01

    We describe the integration of microfluidic selection with high-throughput DNA sequencing technology for rapid and efficient discovery of nucleic acid aptamers. The Quantitative Selection of Aptamers through Sequencing method tracks the copy number and enrichment-fold of more than 10 million individual sequences through multiple selection rounds, enabling the identification of high-affinity aptamers without the need for the pool to fully converge to a small number of sequences. Importantly, this method allows the discrimination of sequences that arise from experimental biases rather than true high-affinity target binding. As a demonstration, we have identified aptamers that specifically bind to PDGF-BB protein with Kd < 3 nM within 3 rounds. Furthermore, we show that the aptamers identified by Quantitative Selection of Aptamers through Sequencing have ∼3–8-fold higher affinity and ∼2–4-fold higher specificity relative to those discovered through conventional cloning methods. Given that many biocombinatorial libraries are encoded with nucleic acids, we extrapolate that our method may be extended to other types of libraries for a range of molecular functions. PMID:20705898

  13. Effects of surface diffusion on high temperature selective emitters.

    PubMed

    Peykov, Daniel; Yeng, Yi Xiang; Celanovic, Ivan; Joannopoulos, John D; Schuh, Christopher A

    2015-04-20

    Using morphological and optical simulations of 1D tantalum photonic crystals at 1200K, surface diffusion was determined to gradually reduce the efficiency of selective emitters. This was attributed to shifting resonance peaks and declining emissivity caused by changes to the cavity dimensions and the aperture width. Decreasing the structure's curvature through larger periods and smaller cavity widths, as well as generating smoother transitions in curvature through the introduction of rounded cavities, was found to alleviate this degradation. An optimized structure, that shows both high efficiency selective emissivity and resistance to surface diffusion, was presented. PMID:25969039

  14. Development and Testing of High-Temperature Solar Selective Coatings

    SciTech Connect

    Kennedy, C.; Price, H.

    2005-01-01

    The Solar Energy Technologies Program is working to reduce the cost of parabolic trough solar power technology. System studies show that increasing the operating temperature of the solar field from 390 to >450 C will result in improved performance and cost reductions. This requires the development of new more-efficient selective coatings that have both high solar absorptance (>0.96) and low thermal emittance (<0.07) and are thermally stable above 450 C, ideally in air. Potential selective coatings were modeled, identified for laboratory prototyping, and manufactured at NREL. Optimization of the samples and high-temperature durability testing will be performed. Development of spectrally selective materials depends on reliable characterization of their optical properties. Protocols for testing the thermal/optical properties of selective coatings were developed and a round-robin experiment was conducted to verify and document the reflectance and high-temperature emittance measurements. The development, performance, and durability of these materials and future work will be described.

  15. Antimycobacterial and cytotoxic activity of selected medicinal plant extracts

    PubMed Central

    Nguta, Joseph M.; Appiah-Opong, Regina; Nyarko, Alexander K.; Yeboah-Manu, Dorothy; Addo, Phyllis G.A.; Otchere, Isaac; Kissi-Twum, Abena

    2016-01-01

    Ethnopharmacological relevance Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Several medicinal plants are used traditionally to treat tuberculosis in Ghana. The current study was designed to investigate the antimycobacterial activity and cytotoxicity of crude extracts from five selected medicinal plants. Material and methods The microplate alamar blue assay (MABA) was used for antimycobacterial studies while the CellTiter 96® AQueous Assay, which is composed of solutions of a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron coupling reagent (phenazine methosulfate) PMS, was used for cytotoxic studies. Correlation coefficients were used to compare the activity of crude extracts against nonpathogenic strains and the pathogenic Mycobacterium tuberculosis subsp.tuberculosis. Results Results of the MIC determinations indicated that all the crude extracts were active on all the three tested mycobacterial strains. Minimum inhibitory concentration values as low as 156.3 µg/mL against M. tuberculosis; Strain H37Ra (ATCC® 25,177™) were recorded from the leaves of Solanum torvum Sw. (Solanaceae). Cytotoxicity of the extracts varied, and the leaves from S. torvum had the most promising selectivity index. Activity against M. tuberculosis; Strain H37Ra was the best predictor of activity against pathogenic Mycobacterium tuberculosis subsp.tuberculosis (correlation coefficient=0.8). Conclusion The overall results of the present study provide supportive data on the use of some medicinal plants for tuberculosis treatment. The leaves of Solanum torvum are a potential source of anti-TB natural products and deserve further investigations to develop novel anti-TB agents against sensitive and drug resistant strains of M. tuberculosis. PMID:26875647

  16. ULTRASENSITIVE HIGH-TEMPERATURE SELECTIVE GAS DETECTION USING PIEZOELECTRIC MICROCANTILEVERS

    SciTech Connect

    Wan Y. Shih; Tejas Patil; Qiang Zhao; Yi-Shi Chiu; Wei-Heng Shih

    2004-03-05

    We have obtained very promising results in the Phase I study. Specifically, for temperature effects, we have established that piezoelectric cantilever sensors could retain their resonance peak strength at high temperatures, i.e., the Q values of the resonance peaks remained above 10 even when the temperature was very close to the Curie temperature. This confirms that a piezoelectric cantilever sensor can be used as a sensor up to its Curie temperature. Furthermore, we have shown that the mass detection sensitivity remained unchanged at different temperatures. For selective gas detection, we have demonstrated selective NH{sub 3} detection using piezoelectric cantilever sensors coated with mesoporous SiO{sub 2}. For high-temperature sensor materials development, we have achieved highly oriented Sr-doped lead titanate thin films that possessed superior dielectric and ferroelectric properties. Such highly oriented films can be microfabricated into high-performance piezoelectric microcantilever sensors that can be used up to 490 C. We have accomplished the goal of Phase I study in exploring the various aspects of a high-temperature gas sensor. We propose to continue the study in Phase II to develop a sensor that is suitable for high-temperature applications using piezoelectrics with a high Curie temperature and by controlling the effects of temperature. The lead titanate based thin film developed in Phase I is good for applications up to 490 C. In phase II, we will develop lithium niobate thin film based cantilevers for applications up to 1000 C.

  17. Selection and preparation of activated carbon for fuel gas storage

    DOEpatents

    Schwarz, James A.; Noh, Joong S.; Agarwal, Rajiv K.

    1990-10-02

    Increasing the surface acidity of active carbons can lead to an increase in capacity for hydrogen adsorption. Increasing the surface basicity can facilitate methane adsorption. The treatment of carbons is most effective when the carbon source material is selected to have a low ash content i.e., below about 3%, and where the ash consists predominantly of alkali metals alkali earth, with only minimal amounts of transition metals and silicon. The carbon is washed in water or acid and then oxidized, e.g. in a stream of oxygen and an inert gas at an elevated temperature.

  18. Non-coordinating-Anion-Directed Reversal of Activation Site: Selective C-H Bond Activation of N-Aryl Rings.

    PubMed

    Wang, Dawei; Yu, Xiaoli; Xu, Xiang; Ge, Bingyang; Wang, Xiaoli; Zhang, Yaxuan

    2016-06-13

    An Rh-catalyzed selective C-H bond activation of diaryl-substituted anilides is described. In an attempt to achieve C-H activation of C-aryl rings, we unexpectedly obtained an N-aryl ring product under non-coordinating anion conditions, whereas the C-aryl ring product was obtained in the absence of a non-coordinating anion. This methodology has proved to be an excellent means of tuning and adjusting selective C-H bond activation of C-aryl and N-aryl rings. The approach has been rationalized by mechanistic studies and theoretical calculations. In addition, it has been found and verified that the catalytic activity of the rhodium catalyst is obviously improved by non-coordinating anions, which provides an efficient strategy for obtaining a highly chemoselective catalyst. Mechanistic experiments also unequivocally ruled out the possibility of a so-called "silver effect" in this transformation involving silver. PMID:27159169

  19. Participation of people with disabilities in selected activities.

    PubMed

    Dowler, J M; Jordan-Simpson, D A

    1990-01-01

    The Health and Activity Limitation Survey (HALS) surveyed disabled Canadians. The survey measured participation in selected cultural and leisure activities, the satisfaction of disabled people with their level of participation, and barriers to participation. Of those surveyed, 98.0% reported doing one or a combination of the following: watching television; listening to radio, records or tapes; reading. Those with speaking and "other" limitations used the telephone less than those with other types of limitations; similarly, those with severe disabilities used the telephone less than those with less-severe disabilities. Participation decreased with age for activities such as doing arts or crafts, gardening, and talking on the telephone. Those aged 65 and over were more likely to be satisfied with their activity than younger people. Overall, 47.4% of those with a severe disability wanted to do more, compared to 34.0% with a moderate disability and 26.2% with a slight disability. The physical inability to do more was the most-often cited barrier to increasing activity: 53.9% of men and 55.7% of women said it was a barrier. PMID:2151649

  20. Antifungal activity of essential oils against selected terverticillate penicillia.

    PubMed

    Felšöciová, Soňa; Kačániová, Miroslava; Horská, Elena; Vukovič, Nenad; Hleba, Lukáš; Petrová, Jana; Rovná, Katarina; Stričík, Michal; Hajduová, Zuzana

    2015-01-01

    The aim of this study was to screen 15 essential oils of selected plant species, viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L., Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Thymus vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum, Penicillium expansum and Penicillium griseofulvum. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against Penicillium fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum vulgare L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The lowest level of antifungal activity was demonstrated by the oils Pinus mungo var. pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Rosmarinus officinalis. PMID:25780826

  1. Activity of selected hydrolytic enzymes in Allium sativum L. anthers.

    PubMed

    Winiarczyk, Krystyna; Gębura, Joanna

    2016-05-01

    The aim of the study was to determine enzymatic activity in sterile Allium sativum anthers in the final stages of male gametophyte development (the stages of tetrads and free microspores). The analysed enzymes were shown to occur in the form of numerous isoforms. In the tetrad stage, esterase activity was predominant, which was manifested by the greater number of isoforms of the enzyme. In turn, in the microspore stage, higher numbers of isoforms of acid phosphatases and proteases were detected. The development of sterile pollen grains in garlic is associated with a high level of protease and acid phosphatase activity and lower level of esterase activities in the anther locule. Probably this is the first description of the enzymes activity (ACPH, EST, PRO) in the consecutives stages of cell wall formation which is considered to be one of the causes of male sterility in flowering plant. PMID:26901781

  2. Peptide fibrils with altered stability, activity, and cell selectivity

    PubMed Central

    Chen, Long; Liang, Jun F.

    2014-01-01

    Peptides have some unique and superior features compared to proteins. However, the use of peptides as therapeutics is hampered by their low stability and cell selectivity. In this study, a new lytic peptide (CL-1, FLGALFRALSRLL) was constructed. Under the physiological condition, peptide CL-1 self-assembled into dynamically stable aggregates with fibrils-like structures. Aggregated CL-1 demonstrated dramatically altered activity and stability in comparison with single molecule CL-1 and other lytic peptides: when incubated with co-cultured bacteria and tissue cells, CL-1 aggregates killed bacteria selectively but spared co-cultured human cells; CL-1 aggregates kept intact in human serum for more than five hours. Peptide-cell interaction studies performed on lipid monolayers and live human tissue cells revealed that in comparison with monomeric CL-1, aggregated CL-1 had decreased cell affinity and membrane insertion capability on tissue cells. A dynamic process involving aggregate dissociation and rearrangement seemed to be an essential step for membrane bound CL-1 aggregates to realize its cytotoxicity to tissue cells. Our study suggests that peptide aggregation could be as important as the charge and secondary structure of a peptide in affecting peptide-cell interactions. Controlling peptide self-assembly represents a new way to increase the stability and cell selectivity of bioactive peptides for wide biomedical applications. PMID:23713839

  3. Fermi Observations of TeV-Selected Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Abdo, A. A.; Ackermann, M.; Ajello, M.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Baring, M. G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Berenji, B.; Bloom, E. D.; Bonamente, E.; Borgland, A. W.; Bregeon, J.; Brez, A.; Brigida, M.; Bruel, P.; Burnett, T. H.; Caliandro, G. A.; Cameron, R. A.; Caraveo, P. A.; Casandjian, J. M.; Cavazzuti, E.; Cecchi, C.; Çelik, Ö.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Cominsky, L. R.; Conrad, J.; Cutini, S.; de Angelis, A.; de Palma, F.; Di Bernardo, G.; Silva, E. do Couto e.; Drell, P. S.; Drlica-Wagner, A.; Dubois, R.; Dumora, D.; Farnier, C.; Favuzzi, C.; Fegan, S. J.; Finke, J.; Focke, W. B.; Fortin, P.; Foschini, L.; Frailis, M.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giavitto, G.; Giebels, B.; Giglietto, N.; Giommi, P.; Giordano, F.; Glanzman, T.; Godfrey, G.; Grenier, I. A.; Grondin, M.-H.; Grove, J. E.; Guillemot, L.; Guiriec, S.; Hanabata, Y.; Hayashida, M.; Hays, E.; Horan, D.; Hughes, R. E.; Jackson, M. S.; Jóhannesson, G.; Johnson, A. S.; Johnson, R. P.; Johnson, W. N.; Kamae, T.; Katagiri, H.; Kataoka, J.; Kawai, N.; Kerr, M.; Knödlseder, J.; Kocian, M. L.; Kuss, M.; Lande, J.; Latronico, L.; Lemoine-Goumard, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Madejski, G. M.; Makeev, A.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Meurer, C.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Moiseev, A. A.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nolan, P. L.; Norris, J. P.; Nuss, E.; Ohsugi, T.; Omodei, N.; Orlando, E.; Ormes, J. F.; Ozaki, M.; Paneque, D.; Panetta, J. H.; Parent, D.; Pelassa, V.; Pepe, M.; Pesce-Rollins, M.; Piron, F.; Porter, T. A.; Rainò, S.; Rando, R.; Razzano, M.; Reimer, A.; Reimer, O.; Reposeur, T.; Reyes, L. C.; Ritz, S.; Rochester, L. S.; Rodriguez, A. Y.; Roth, M.; Ryde, F.; Sadrozinski, H. F.-W.; Sanchez, D.; Sander, A.; Saz Parkinson, P. M.; Scargle, J. D.; Schalk, T. L.; Sellerholm, A.; Sgrò, C.; Shaw, M. S.; Siskind, E. J.; Smith, D. A.; Smith, P. D.; Spandre, G.; Spinelli, P.; Strickman, M. S.; Suson, D. J.; Tajima, H.; Takahashi, H.; Takahashi, T.; Tanaka, T.; Tanaka, Y.; Thayer, J. B.; Thayer, J. G.; Thompson, D. J.; Tibaldo, L.; Torres, D. F.; Tosti, G.; Tramacere, A.; Uchiyama, Y.; Usher, T. L.; Vasileiou, V.; Vilchez, N.; Vitale, V.; Waite, A. P.; Wang, P.; Winer, B. L.; Wood, K. S.; Ylinen, T.; Ziegler, M.

    2009-12-01

    We report on observations of TeV-selected active galactic nuclei (AGNs) made during the first 5.5 months of observations with the Large Area Telescope (LAT) on-board the Fermi Gamma-ray Space Telescope (Fermi). In total, 96 AGNs were selected for study, each being either (1) a source detected at TeV energies (28 sources) or (2) an object that has been studied with TeV instruments and for which an upper limit has been reported (68 objects). The Fermi observations show clear detections of 38 of these TeV-selected objects, of which 21 are joint GeV-TeV sources, and 29 were not in the third EGRET catalog. For each of the 38 Fermi-detected sources, spectra and light curves are presented. Most can be described with a power law of spectral index harder than 2.0, with a spectral break generally required to accommodate the TeV measurements. Based on an extrapolation of the Fermi spectrum, we identify sources, not previously detected at TeV energies, which are promising targets for TeV instruments. Evidence for systematic evolution of the γ-ray spectrum with redshift is presented and discussed in the context of interaction with the extragalactic background light.

  4. Immunomodulatory and anti-inflammatory activity of selected osthole derivatives.

    PubMed

    Zimecki, Michał; Artym, Jolanta; Cisowski, Wojciech; Mazol, Irena; Włodarczyk, Maciej; Gleńsk, Michał

    2009-01-01

    From osthole [7-methoxy-8-(3-methyl-but-2-enyl)-chromen-2-one] (I), obtained by selective extraction of Peucedanum ostruthium (L.) W. Koch roots, ostholic acid (II) was synthetized as a result of its oxidation with chromium trioxide. From ostholic acid, through its chloride, four amides were obtained: the morpholide 1, the p-chloro-benzylamide 2, the piperidine 3 and the N-methyl-piperazide 4. Except for 1, other compounds have not been described before. The amides 1-4 and their precursor osthole (I) were tested for their potential activities in selected immunological assays. The compounds showed moderate inhibitory activity in the humoral immune response to sheep erythrocytes in mice in vitro, and 4 was the most suppressive. The effects of 1 and 3 on concanavalin A- and pokeweed mitogen-induced mouse splenocyte proliferation were inhibitory and those of 4 stimulatory. The compounds were also tested for their activity on tumour necrosis factor a and interleukin 6 production, induced by lipopolysaccharide, in cultures of rat peritoneal cells and human peripheral blood mononuclear cells. Compounds 1, 3 and 4 inhibited tumour necrosis factor a (rat cells), whereas compound 2 stimulated the production of both cytokines. Compounds 1, 2 and 3 were also strongly inhibitory on tumour necrosis factor a production in human blood cells (73, 78 and 80% inhibition at 10 microg/ml, respectively). On the other hand, 2 and 4 stimulated the interleukin 6 production (2- to 3-fold stimulation). In addition, 2 and 4 suppressed the carrageenan-induced inflammation in mice (56.5% and 68.3% inhibition, respectively). In summary, the compounds predominantly displayed suppressive and antiinflammatory activities in the investigated models. PMID:19678539

  5. Can Programmed or Self-Selected Physical Activity Affect Physical Fitness of Adolescents?

    PubMed Central

    Neto, Cláudio F.; Neto, Gabriel R.; Araújo, Adenilson T.; Sousa, Maria S. C.; Sousa, Juliana B. C.; Batista, Gilmário R.; Reis, Victor M. M. R.

    2014-01-01

    The aim of this study was to verify the effects of programmed and self-selected physical activities on the physical fitness of adolescents. High school adolescents, aged between 15 and 17 years, were divided into two experimental groups: a) a self-selected physical activity group (PAS) with 55 students (aged 15.7 ± 0.7 years), who performed physical activities with self-selected rhythm at the following sports: basketball, volleyball, handball, futsal and swimming; and b) a physical fitness training group (PFT) with 53 students (aged 16.0 ± 0.7 years), who performed programmed physical fitness exercises. Both types of activity were developed during 60 min classes. To assess physical fitness the PROESP-BR protocol was used. The statistical analysis was performed by repeated measures ANOVA. The measurements of pre and post-tests showed significantly different values after PFT in: 9 minute running test, medicine ball throw, horizontal jump, abdominal endurance, running speed and flexibility. After PAS differences were detected in abdominal endurance, agility, running speed and flexibility. The intervention with programmed physical activity promoted more changes in the physical abilities; however, in the self-selected program, agility was improved probably because of the practice of sports. Therefore, physical education teachers can use PFT to improve cardiorespiratory fitness and power of lower and upper limbs and PAS to improve agility of high school adolescents. PMID:25713652

  6. Vibrational spectra and antimicrobial activity of selected bivalent cation benzoates

    NASA Astrophysics Data System (ADS)

    Borawska, M. H.; Koczoń, P.; Piekut, J.; Świsłocka, R.; Lewandowski, W.

    2009-02-01

    Selected bands of FT-IR spectra of Mg(II), Ca(II), Cu(II) and Zn(II) benzoates of both solid state and water solution, were assigned to appropriate molecular vibrations. Next evaluation of electronic charge distribution in both carboxylic anion and aromatic ring of studied compounds was performed. Classical plate tests and turbidimetry measurements, monitoring growth of bacteria Escherichia coli, Bacillus subtilis and yeasts Pichia anomala and Saccharomyces cerevisiae during 24 h of incubation, in optimal growth conditions (control) and in medium with addition of studied benzoate (concentration of 0.01% expressed as the concentration of benzoic acid), proved antimicrobial activity of studied compounds against investigated micro-organisms. PLS (partially least square) and PCR (principal component regression) techniques were applied to build a model, correlating spectral data reflecting molecular structure of studied compounds, with degree of influence of those compounds on growth of studied micro-organisms. Statistically significant correlation within cross validation diagnostic of PLS-1 calibration was found, when log 1/T of selected spectral regions of water solution samples were used as input data. The correlation coefficients between predicted with PLS calibration based on created 1, 2 or 3 factor models, and actual values of antimicrobial activity were: 0.70; 0.76, 0.81 for P. anomala, B. subtilis, and E. coli, respectively. Log(PRESS) values of appropriate models were 2.10, 2,39 and 3.23 for P. anomala, B. subtilis, and E. coli, respectively.

  7. Active link selection for efficient semi-supervised community detection

    PubMed Central

    Yang, Liang; Jin, Di; Wang, Xiao; Cao, Xiaochun

    2015-01-01

    Several semi-supervised community detection algorithms have been proposed recently to improve the performance of traditional topology-based methods. However, most of them focus on how to integrate supervised information with topology information; few of them pay attention to which information is critical for performance improvement. This leads to large amounts of demand for supervised information, which is expensive or difficult to obtain in most fields. For this problem we propose an active link selection framework, that is we actively select the most uncertain and informative links for human labeling for the efficient utilization of the supervised information. We also disconnect the most likely inter-community edges to further improve the efficiency. Our main idea is that, by connecting uncertain nodes to their community hubs and disconnecting the inter-community edges, one can sharpen the block structure of adjacency matrix more efficiently than randomly labeling links as the existing methods did. Experiments on both synthetic and real networks demonstrate that our new approach significantly outperforms the existing methods in terms of the efficiency of using supervised information. It needs ~13% of the supervised information to achieve a performance similar to that of the original semi-supervised approaches. PMID:25761385

  8. Active link selection for efficient semi-supervised community detection.

    PubMed

    Yang, Liang; Jin, Di; Wang, Xiao; Cao, Xiaochun

    2015-01-01

    Several semi-supervised community detection algorithms have been proposed recently to improve the performance of traditional topology-based methods. However, most of them focus on how to integrate supervised information with topology information; few of them pay attention to which information is critical for performance improvement. This leads to large amounts of demand for supervised information, which is expensive or difficult to obtain in most fields. For this problem we propose an active link selection framework, that is we actively select the most uncertain and informative links for human labeling for the efficient utilization of the supervised information. We also disconnect the most likely inter-community edges to further improve the efficiency. Our main idea is that, by connecting uncertain nodes to their community hubs and disconnecting the inter-community edges, one can sharpen the block structure of adjacency matrix more efficiently than randomly labeling links as the existing methods did. Experiments on both synthetic and real networks demonstrate that our new approach significantly outperforms the existing methods in terms of the efficiency of using supervised information. It needs ~13% of the supervised information to achieve a performance similar to that of the original semi-supervised approaches. PMID:25761385

  9. Environmental Activities, Junior High School.

    ERIC Educational Resources Information Center

    Edwards, William C.; Larson, Robert J.

    This guide, for use at the junior high level, is aimed at helping our youth become more knowledgeable concerning the environment and associated problems, thus making them aware of how to solve these problems and motivating them to work toward their solution. Among the subjects discussed are art in nature, erosion, body pollution, water pollution,…

  10. Development of second generation EP2 antagonists with high selectivity

    PubMed Central

    Ganesh, Thota; Jiang, Jianxiong; Dingledine, Ray

    2014-01-01

    EP2 receptor has emerged as an important biological target for therapeutic intervention. In particular, it has been shown to exacerbate disease progression of a variety of CNS and peripheral diseases. Deletion of the EP2 receptor in mouse models recapitulates several features of the COX-2 inhibition, thus presenting a new avenue for anti-inflammatory therapy which could bypass some of the adverse side effects observed by the COX-2 inhibition therapy. We have recently reported a cinnamic amide class of EP2 antagonists with high potency, but these compounds exhibited a moderate selectivity against prostanoid receptor DP1. Moreover they possess acrylamide moiety in the structure, which may result in liver toxicity over longer period of use in a chronic disease model. Thus, we now developed a second generation compounds that devoid of the acrylamide functionality and possess high potency and improved (>1000-fold) selectivity to EP2 over other prostanoid receptors. PMID:24937185

  11. Evaluation and selection of candidate high-level waste forms

    SciTech Connect

    Bernadzikowski, T. A.; Allender, J. S.; Butler, J. L.; Gordon, D. E.; Gould, Jr., T. H.; Stone, J. A.

    1982-03-01

    Seven candidate waste forms being developed under the direction of the Department of Energy's National High-Level Waste (HLW) Technology Program, were evaluated as potential media for the immobilization and geologic disposal of high-level nuclear wastes. The evaluation combined preliminary waste form evaluations conducted at DOE defense waste-sites and independent laboratories, peer review assessments, a product performance evaluation, and a processability analysis. Based on the combined results of these four inputs, two of the seven forms, borosilicate glass and a titanate based ceramic, SYNROC, were selected as the reference and alternative forms for continued development and evaluation in the National HLW Program. Both the glass and ceramic forms are viable candidates for use at each of the DOE defense waste-sites; they are also potential candidates for immobilization of commercial reprocessing wastes. This report describes the waste form screening process, and discusses each of the four major inputs considered in the selection of the two forms.

  12. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues.

    PubMed

    Stompor, Monika; Żarowska, Barbara

    2016-01-01

    The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group-all of them have it at the C-4 position-demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones). The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4'-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4'-methoxychalcones or its replacement by a halogen atom (-Cl, -Br), nitro group (-NO₂), ethoxy group (-OCH₂CH₃), or aliphatic substituent (-CH₃, -CH₂CH₃) resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4-hydroxy-4'-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra. PMID:27187329

  13. Fluoride release and antibacterial activity of selected dental materials.

    PubMed

    Marczuk-Kolada, Grazyna; Jakoniuk, Piotr; Mystkowska, Joanna; Łuczaj-Cepowicz, Elzbieta; Waszkiel, Danuta; Dabrowski, Jan Ryszard; Leszczyńska, Katarzyna

    2006-01-01

    The aim of the study was to assess the fluoride ion release and antibacterial activities of the glassionomer cement Fuji IX and the compomer (composite modified polyacid) Dyract AP. Fluoride ion release was measured using direct potentiometry with an Orion fluoride ion selective electrode. The measurement was carried out after 1, 4, 7, 14, 30, and 60 days of storage in phosphate buffer at pH 6.8. The antibacterial activity of the materials was evaluated against the bacteria Streptococcus mutans ATCC 35668, Streptococcus salivarius ATCC 13419, Streptococcus sanguis ATCC 10556, and Lactobacillus casei subsp. casei ATCC 393. The agar diffusion test was applied. The material specimens were assessed twice: after setting and seven days later. Zones of bacterial growth inhibition were measured in millimeters after 24 hours. The results of the study showed that both materials released ion fluoride, with a higher emission of Fuji IX than Dyract AP. The highest level of emission was observed on the seventh day of the study in both materials. After 24 hours of bonding there was inhibition of bacterial growth by Fuji IX, whereas Dyract AP did not show similar activity. On the eighth day after polymerization, Dyract AP was significantly more active towards Streptococcus sanguis and salivarius. PMID:18493226

  14. Semantic Wavelet-Induced Frequency-Tagging (SWIFT) Periodically Activates Category Selective Areas While Steadily Activating Early Visual Areas

    PubMed Central

    Koenig-Robert, Roger; VanRullen, Rufin; Tsuchiya, Naotsugu

    2015-01-01

    Primate visual systems process natural images in a hierarchical manner: at the early stage, neurons are tuned to local image features, while neurons in high-level areas are tuned to abstract object categories. Standard models of visual processing assume that the transition of tuning from image features to object categories emerges gradually along the visual hierarchy. Direct tests of such models remain difficult due to confounding alteration in low-level image properties when contrasting distinct object categories. When such contrast is performed in a classic functional localizer method, the desired activation in high-level visual areas is typically accompanied with activation in early visual areas. Here we used a novel image-modulation method called SWIFT (semantic wavelet-induced frequency-tagging), a variant of frequency-tagging techniques. Natural images modulated by SWIFT reveal object semantics periodically while keeping low-level properties constant. Using functional magnetic resonance imaging (fMRI), we indeed found that faces and scenes modulated with SWIFT periodically activated the prototypical category-selective areas while they elicited sustained and constant responses in early visual areas. SWIFT and the localizer were selective and specific to a similar extent in activating category-selective areas. Only SWIFT progressively activated the visual pathway from low- to high-level areas, consistent with predictions from standard hierarchical models. We confirmed these results with criterion-free methods, generalizing the validity of our approach and show that it is possible to dissociate neural activation in early and category-selective areas. Our results provide direct evidence for the hierarchical nature of the representation of visual objects along the visual stream and open up future applications of frequency-tagging methods in fMRI. PMID:26691722

  15. Highly selective vagotomy in the treatment of peptic ulcer diathesis.

    PubMed

    Kaushik, S P; Kohli, P; Kumar, P; Pradeep, R; Saxena, R; Choudhary, S R; Suresh, A

    1990-09-01

    The results of highly selective vagotomy in 174 Indian patients have been analysed. Compared to other procedures on the stomach, HSV has a definite advantage both on long term as well as on short term basis. HSV has therefore become the procedure of choice in the treatment of duodenal ulcer disease provided the expertise is available locally. HSV has also been used now in the treatment of ulcer complications and benign gastric ulcer disease. PMID:2092027

  16. High-temperature corrosion: Issues in alloy selection

    NASA Astrophysics Data System (ADS)

    Lai, George Y.

    1991-11-01

    This article examines the modes of high-temperature corrosion that are often responsible for equipment failures in a variety of industries, including aerospace and gas turbines; heat treating; mineral and metallurgical processing; chemical processing; refining and petrochemical processing; ceramic, electronic, and glass manufacturing; automotive; pulp and paper; waste incineration; and power generation and energy conversion. Corrosion data related to each corrosion mode are reviewed to provide readers with a brief materials selection guide.

  17. Highly hydrophobic and oleophilic foam for selective absorption

    NASA Astrophysics Data System (ADS)

    Su, Changhong

    2009-12-01

    In this article, both highly hydrophobic and oleophilic foam were fabricated by coating inner surface of polyurethane (PU) foam with a super-hydrophobic film. The contact angle of the foam is large as 152.2° for water, and 0° for kerosene. The foam can absorb kerosene selectively from kerosene-water mixture and be regenerated easily. The foam may be used to reclaim oil from polluted natural water area resulted from shipwreck or leakage.

  18. MESOPOROUS IRON PHOSPHATE AS AN ACTIVE, SELECTIVE AND RECYCLABLE CATALYST FOR THE SYNTHESIS OF NOPOL BY PRINS CONDENSATION

    EPA Science Inventory


    Mesoporous iron phosphate is found to be a highly active and recyclable heterogeneous catalyst for the selective synthesis of nopol by Prins condensation of ?-pinene and paraformaldehyde in acetonitrile at 80 oC.



  19. High density transcriptional mapping of chromosome 21 by hybridization selection

    SciTech Connect

    Tassone, F.; Wade, H.; Gardiner, K.

    1994-09-01

    A transcriptional map of human chromosome 21 is important for the study of Down syndrome, development processes and genome organization. To construct a high density transcriptional map, the technique of cDNA hybrid selection is being applied to a minimal tiling path of YAC clones that span 21q. The cDNA used for selection represents a complex pool of sequences obtained from a variety of fetal and adult tissues and cell lines. Approximately 70-80 YAC clones are sufficient to span 21q; each is individually processed through the selection procedure to obtain a YAC-specific {open_quotes}selected cDNA library{close_quotes}. Survey analysis of each library includes determination of levels of ribosomal contamination, verification of enrichment of control genes, identification of a preliminary number of novel unique sequences, and verification that novel sequences map to the correct YAC and chromosomal regions. This analysis has been completed for 19 YACs that together comprise approximately 10 Mb of non-overlapping DNA, 25% of the long arm. Ribosomal cDNA contamination is low (<10%) and all known genes of appropriate tissue specificity of expression have been recovered, as well as new genes from each YAC. Libraries of expression have been recovered, as well as new genes from each YAC. Libraries from 8 of these YACs are now being subjected to exhaustive analysis to identify all novel genes contained within them and to obtain complete cDNAs and expression analysis for each. Not all regions of the chromosome, however, are equally amenable to these analyses. Selected cDNA libraries from the centromeric YACs are yielding apparently novel genes, but confirmation of map position is problematic. Also of interest is a region of several megabases within the Giemsa dark band, 21q21. Selected cDNA libraries from these YACs so far have yielded no novel genes and support the idea of a genuinely very gene-poor region.

  20. Elevated temperature creep properties for selected active metal braze alloys

    SciTech Connect

    Stephens, J.J.

    1997-02-01

    Active metal braze alloys reduce the number of processes required for the joining of metal to ceramic components by eliminating the need for metallization and/or Ni plating of the ceramic surfaces. Titanium (Ti), V, and Zr are examples of active element additions which have been used successfully in such braze alloys. Since the braze alloy is expected to accommodate thermal expansion mismatch strains between the metal and ceramic materials, a knowledge of its elevated temperature mechanical properties is important. In particular, the issue of whether or not the creep strength of an active metal braze alloy is increased or decreased relative to its non-activated counterpart is important when designing new brazing processes and alloy systems. This paper presents a survey of high temperature mechanical properties for two pairs of conventional braze alloys and their active metal counterparts: (a) the conventional 72Ag-28Cu (Cusil) alloy, and the active braze alloy 62.2Ag- 36.2Cu-1.6Ti (Cusil ABA), and (b) the 82Au-18Ni (Nioro) alloy and the active braze alloy Mu-15.5M-0.75Mo-1.75V (Nioro ABA). For the case of the Cusil/Cusil ABA pair, the active metal addition contributes to solid solution strengthening of the braze alloy, resulting in a higher creep strength as compared to the non-active alloy. In the case of the Nioro/Nioro ABA pair, the Mo and V additions cause the active braze alloy to have a two-phase microstructure, which results in a reduced creep strength than the conventional braze alloy. The Garofalo sinh equation has been used to quantitatively describe the stress and temperature dependence of the deformation behavior. It will be observed that the effective stress exponent in the Garofalo sinh equation is a function of the instantaneous value of the stress argument.

  1. Antitumor activity of levan polysaccharides from selected microorganisms.

    PubMed

    Yoo, Sang-Ho; Yoon, Eun Ju; Cha, Jaeho; Lee, Hyeon Gyu

    2004-04-01

    Levans were isolated from the cultures of Gluconoacetobacter xylinus (G-levan; Mw = 40,000), Microbacterium laevaniformans (M; Mw = 710,000), Rahnella aquatilis (R; Mw = 380,000), and Zymomonas mobilis (Z; Mw = 570,000). The levans were composed mainly of fructose residues when analyzed by TLC and HPLC, and their main backbones were beta-(2,6)-linkages with beta-(2,1)-branches by GC-MS and NMR. In the in vitro antitumor activity test of the levans against eight different tumor cell lines, relatively stronger activity was observed from the SNU-1 and HepG2. The M- (52.54-62.05%) and R-levan (52.15-58.58%) showed the significantly high activity against SNU-1, while M-levan showed the highest (49.93-61.82%) activity against HepG2. During the in vivo analysis of inhibitory activity of the levans against Sarcoma-180 growth, M-, R- and Z-levans showed strong antitumor activity (average 66%) but G-levan (42%) had significantly lower activity. PMID:15178007

  2. Active surfaces engineered by immobilizing protein-polymer nanoreactors for selectively detecting sugar alcohols.

    PubMed

    Zhang, Xiaoyan; Lomora, Mihai; Einfalt, Tomaz; Meier, Wolfgang; Klein, Noreen; Schneider, Dirk; Palivan, Cornelia G

    2016-05-01

    We introduce active surfaces generated by immobilizing protein-polymer nanoreactors on a solid support for sensitive sugar alcohols detection. First, such selective nanoreactors were engineered in solution by simultaneous encapsulation of specific enzymes in copolymer polymersomes, and insertion of membrane proteins for selective conduct of sugar alcohols. Despite the artificial surroundings, and the thickness of the copolymer membrane, functionality of reconstituted Escherichia coli glycerol facilitator (GlpF) was preserved, and allowed selective diffusion of sugar alcohols to the inner cavity of the polymersome, where encapsulated ribitol dehydrogenase (RDH) enzymes served as biosensing entities. Ribitol, selected as a model sugar alcohol, was detected quantitatively by the RDH-nanoreactors with GlpF-mediated permeability in a concentration range of 1.5-9 mM. To obtain "active surfaces" for detecting sugar alcohols, the nanoreactors optimized in solution were then immobilized on a solid support: aldehyde groups exposed at the compartment external surface reacted via an aldehyde-amino reaction with glass surfaces chemically modified with amino groups. The nanoreactors preserved their architecture and activity after immobilization on the glass surface, and represent active biosensing surfaces for selective detection of sugar alcohols, with high sensitivity. PMID:26950167

  3. Niobium phosphates as new highly selective catalysts for the oxidative dehydrogenation of ethane.

    PubMed

    Weng, Weihao; Davies, Mathew; Whiting, Gareth; Solsona, Benjamin; Kiely, Christopher J; Carley, Albert F; Taylor, Stuart H

    2011-10-14

    Several niobium phosphate phases have been prepared, fully characterized and tested as catalysts for the selective oxidation of ethane to ethylene. Three distinct niobium phosphate catalysts were prepared, and each was comprised predominantly of a different bulk phase, namely Nb(2)P(4)O(15), NbOPO(4) and Nb(1.91)P(2.82)O(12). All of the niobium phosphate catalysts showed high selectivity towards ethylene, but the best catalyst was Nb(1.91)P(2.82)O(12), which was produced from the reduction of niobium oxide phosphate (NbOPO(4)) by hydrogen. It was particularly selective for ethylene, giving ca. 95% selectivity at 5% conversion, decreasing to ca. 90% at 15% conversion, and only produced low levels of carbon oxides. It was also determined that the only primary product from ethane oxidation over this catalyst was ethylene. Catalyst activity also increased with time-on-line, and this behaviour was ascribed to an increase of the concentration of the Nb(1.91)P(2.82)O(12) phase, as partially transformed NbOPO(4), formed during preparation, was converted to Nb(1.91)P(2.82)O(12) during use. Catalysts with predominant phases of Nb(2)P(4)O(15) and NbOPO(4) also showed appreciable activity and selectivities to ethylene with values around 75% and 85% respectively at 5% ethane conversion. The presence of phosphorous is required to achieve high ethylene selectivity, as orthorhombic and monoclinic Nb(2)O(5) catalysts showed similar activity, but displayed selectivities to ethylene that were <20% under the same reaction conditions. To the best of our knowledge, this is the first time that niobium phosphates have been shown to be highly selective catalysts for the oxidation of ethane to ethylene, and demonstrates that they are worthy candidates for further study. PMID:21881631

  4. A Primer on High-Throughput Computing for Genomic Selection

    PubMed Central

    Wu, Xiao-Lin; Beissinger, Timothy M.; Bauck, Stewart; Woodward, Brent; Rosa, Guilherme J. M.; Weigel, Kent A.; Gatti, Natalia de Leon; Gianola, Daniel

    2011-01-01

    High-throughput computing (HTC) uses computer clusters to solve advanced computational problems, with the goal of accomplishing high-throughput over relatively long periods of time. In genomic selection, for example, a set of markers covering the entire genome is used to train a model based on known data, and the resulting model is used to predict the genetic merit of selection candidates. Sophisticated models are very computationally demanding and, with several traits to be evaluated sequentially, computing time is long, and output is low. In this paper, we present scenarios and basic principles of how HTC can be used in genomic selection, implemented using various techniques from simple batch processing to pipelining in distributed computer clusters. Various scripting languages, such as shell scripting, Perl, and R, are also very useful to devise pipelines. By pipelining, we can reduce total computing time and consequently increase throughput. In comparison to the traditional data processing pipeline residing on the central processors, performing general-purpose computation on a graphics processing unit provide a new-generation approach to massive parallel computing in genomic selection. While the concept of HTC may still be new to many researchers in animal breeding, plant breeding, and genetics, HTC infrastructures have already been built in many institutions, such as the University of Wisconsin–Madison, which can be leveraged for genomic selection, in terms of central processing unit capacity, network connectivity, storage availability, and middleware connectivity. Exploring existing HTC infrastructures as well as general-purpose computing environments will further expand our capability to meet increasing computing demands posed by unprecedented genomic data that we have today. We anticipate that HTC will impact genomic selection via better statistical models, faster solutions, and more competitive products (e.g., from design of marker panels to realized

  5. High speed hybrid active system

    NASA Astrophysics Data System (ADS)

    Gonzalez, Ignacio F.; Chang, Fu-Kuo; Qing, Peter X.; Kumar, Amrita; Zhang, David

    2005-05-01

    A novel piezoelectric/fiber-optic system is developed for long-term health monitoring of aerospace vehicles and structures. The hybrid diagnostic system uses the piezoelectric actuators to input a controlled excitation to the structure and the fiber optic sensors to capture the corresponding structural response. The aim of the system is to detect changes in structures such as those found in aerospace applications (damage, cracks, aging, etc.). This system involves the use of fiber Bragg gratings, which may be either bonded to the surface of the material or embedded within it in order to detect the linear strain component produced by the excitation waves generate by an arbitrary waveform generator. Interrogation of the Bragg gratings is carried out using a high speed fiber grating demodulation unit and a high speed data acquisition card to provide actuation input. With data collection and information processing; is able to determine the condition of the structure. The demands on a system suitable for detecting ultrasonic acoustic waves are different than for the more common strain and temperature systems. On the one hand, the frequency is much higher, with typical values for ultrasonic frequencies used in non-destructive testing ranging from 100 kHz up to several MHz. On the other hand, the related strain levels are much lower, normally in the μstrain range. Fiber-optic solutions for this problem do exist and are particularly attractive for ultrasonic sensing as the sensors offer broadband detection capability.

  6. Tricyclic covalent inhibitors selectively target Jak3 through an active site thiol.

    PubMed

    Goedken, Eric R; Argiriadi, Maria A; Banach, David L; Fiamengo, Bryan A; Foley, Sage E; Frank, Kristine E; George, Jonathan S; Harris, Christopher M; Hobson, Adrian D; Ihle, David C; Marcotte, Douglas; Merta, Philip J; Michalak, Mark E; Murdock, Sara E; Tomlinson, Medha J; Voss, Jeffrey W

    2015-02-20

    The action of Janus kinases (JAKs) is required for multiple cytokine signaling pathways, and as such, JAK inhibitors hold promise for treatment of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging. We have designed and characterized substituted, tricyclic Jak3 inhibitors that selectively avoid inhibition of the other JAKs. This is accomplished through a covalent interaction between an inhibitor containing a terminal electrophile and an active site cysteine (Cys-909). We found that these ATP competitive compounds are irreversible inhibitors of Jak3 enzyme activity in vitro. They possess high selectivity against other kinases and can potently (IC50 < 100 nm) inhibit Jak3 activity in cell-based assays. These results suggest irreversible inhibitors of this class may be useful selective agents, both as tools to probe Jak3 biology and potentially as therapies for autoimmune diseases. PMID:25552479

  7. Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol*

    PubMed Central

    Goedken, Eric R.; Argiriadi, Maria A.; Banach, David L.; Fiamengo, Bryan A.; Foley, Sage E.; Frank, Kristine E.; George, Jonathan S.; Harris, Christopher M.; Hobson, Adrian D.; Ihle, David C.; Marcotte, Douglas; Merta, Philip J.; Michalak, Mark E.; Murdock, Sara E.; Tomlinson, Medha J.; Voss, Jeffrey W.

    2015-01-01

    The action of Janus kinases (JAKs) is required for multiple cytokine signaling pathways, and as such, JAK inhibitors hold promise for treatment of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging. We have designed and characterized substituted, tricyclic Jak3 inhibitors that selectively avoid inhibition of the other JAKs. This is accomplished through a covalent interaction between an inhibitor containing a terminal electrophile and an active site cysteine (Cys-909). We found that these ATP competitive compounds are irreversible inhibitors of Jak3 enzyme activity in vitro. They possess high selectivity against other kinases and can potently (IC50 < 100 nm) inhibit Jak3 activity in cell-based assays. These results suggest irreversible inhibitors of this class may be useful selective agents, both as tools to probe Jak3 biology and potentially as therapies for autoimmune diseases. PMID:25552479

  8. Influence of selected physicochemical parameters on microbiological activity of mucks.

    NASA Astrophysics Data System (ADS)

    Całka, A.; Sokołowska, Z.; Warchulska, P.; Dąbek-Szreniawska, M.

    2009-04-01

    One of the basic factor decided about soil fertility are microorganisms that together with flora, determine trend and character of biochemical processes as well totality of fundamental transformations connected with biogeochemistry and physicochemical properties of soil. Determination of general bacteria number, quantity of selected groups of microorganisms and investigation of respiration intensity let estimate microbiological activity of soil. Intensity of microbiological processes is directly connected with physicochemical soil parameters. In that case, such structural parameters as bulk density, porosity, surface or carbon content play significant role. Microbiological activity also changes within the bounds of mucks with different stage of humification and secondary transformation. Knowledge of relations between structural properties, microorganism activity and degree of transformation and humification can lead to better understanding microbiological processes as well enable to estimate microbiological activity at given physicochemical conditions and at progressing process of soil transformation. The study was carried out on two peaty-moorsh (muck) soils at different state of secondary transformation and humification degree. Soil samples were collected from Polesie Lubelskie (layer depth: 5 - 25 cm). Investigated mucks originated from soils formed from low peatbogs. Soil sample marked as I belonged to muck group weakly secondary transformed. Second sample (II) represented soil group with middle stage of secondary transformation. The main purpose of the research was to examine the relations between some physicochemical and surface properties and their biological activity. Total number and respiration activity of microorganisms were determined. The effectiveness of utilizing the carbon substances from the soil by the bacteria increased simultaneously with the transformation state of the peat-muck soils. Quantity of organic carbon decreased distinctly in the soil

  9. Activity in X-ray-selected late-type stars

    NASA Technical Reports Server (NTRS)

    Takalo, Leo O.; Nousek, J. A.

    1988-01-01

    A spectroscopic study has been conducted of nine X-ray bright late-type stars selected from two Einstein X-ray surveys: the Columbia Astrophysical Laboratory Survey (five stars) and the CFA Medium Sensitivity Survey (MSS; four stars). Spectral classes were determined and radial and V sin(i) velocities were measured for the stars. Four of the Columbia Survey stars were found to be new RS CVn-type binaries. The fifth Columbia survey star was found to be an active G dwarf star without evidence for binarity. None of the four MSS stars were found to be either binaries or optically active stars. Activity in these stars was assessed by measuring the excess emission in H-alpha and the Ca II IRT (8498, 8542) lines in comparison with inactive stars of similar spectral types. A correlation was found between X-ray luminosity and V sin(i) and H-alpha line excess. The measured excess line emission in H-alpha was also correlated with V sin(i) but not with the IRT line excess.

  10. Rhodium Nanoparticle-mesoporous Silicon Nanowire Nanohybrids for Hydrogen Peroxide Detection with High Selectivity

    NASA Astrophysics Data System (ADS)

    Song, Zhiqian; Chang, Hucheng; Zhu, Weiqin; Xu, Chenlong; Feng, Xinjian

    2015-01-01

    Developing nanostructured electrocatalysts, with low overpotential, high selectivity and activity has fundamental and technical importance in many fields. We report here rhodium nanoparticle and mesoporous silicon nanowire (RhNP@mSiNW) hybrids for hydrogen peroxide (H2O2) detection with high electrocatalytic activity and selectivity. By employing electrodes that loaded with RhNP@mSiNW nanohybrids, interference caused from both many electroactive substances and dissolved oxygen were eliminated by electrochemical assaying at an optimal potential of +75 mV. Furthermore, the electrodes exhibited a high detection sensitivity of 0.53 μA/mM and fast response (< 5 s). This high-performance nanohybrid electrocatalyst has great potential for future practical application in various oxidase-base biosensors.

  11. Rhodium Nanoparticle-mesoporous Silicon Nanowire Nanohybrids for Hydrogen Peroxide Detection with High Selectivity

    PubMed Central

    Song, Zhiqian; Chang, Hucheng; Zhu, Weiqin; Xu, Chenlong; Feng, Xinjian

    2015-01-01

    Developing nanostructured electrocatalysts, with low overpotential, high selectivity and activity has fundamental and technical importance in many fields. We report here rhodium nanoparticle and mesoporous silicon nanowire (RhNP@mSiNW) hybrids for hydrogen peroxide (H2O2) detection with high electrocatalytic activity and selectivity. By employing electrodes that loaded with RhNP@mSiNW nanohybrids, interference caused from both many electroactive substances and dissolved oxygen were eliminated by electrochemical assaying at an optimal potential of +75 mV. Furthermore, the electrodes exhibited a high detection sensitivity of 0.53 μA/mM and fast response (< 5 s). This high-performance nanohybrid electrocatalyst has great potential for future practical application in various oxidase-base biosensors. PMID:25588953

  12. Diarylacylhydrazones: Clostridium-Selective Antibacterials with Activity Against Stationary-Phase Cells

    PubMed Central

    Casadei, Gabriele; Bremner, John B.; Lewis, Kim; Kelso, Michael J.

    2014-01-01

    Current antibiotics for treating Clostridium difficile infections (CDI), i.e. metronidazole, vancomycin and more recently fidaxomicin, are mostly effective but treatment failure and disease relapse remain as significant clinical problems. The shortcomings of these agents are attributed to their low selectivity for C. difficile over normal gut microflora and their ineffectiveness against C. difficile spores. This paper reports that certain diarylacylhydrazones identified during a high-throughput screening/counter-screening campaign show selective activity against two Clostridium species (C. difficile and C. perfringens) over common gut commensals. Representative examples are shown to possess activity similar to vancomycin against clinical C. difficile strains and to kill stationary-phase C. difficile cells, which are responsible for spore production. Structure-activity relationships with additional synthesised analogues suggested a protonophoric mechanism may play a role in the observed activity/selectivity and this was supported by the well-known protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) showing selective anti-Clostridium effects and activity similar to diarylacylhydrazones against stationary-phase C. difficile cells. Two diarylacylhydrazones were shown to be non-toxic towards human FaDu and Hep G2 cells indicating that further studies with the class are warranted towards new drugs for CDI. PMID:24360560

  13. Phenolic profile and antioxidant activity in selected seeds and sprouts.

    PubMed

    Pająk, Paulina; Socha, Robert; Gałkowska, Dorota; Rożnowski, Jacek; Fortuna, Teresa

    2014-01-15

    The aim of this study was to investigate the effect of germination on the phenolic acids and flavonoids profile, as well as antioxidant activity (AA), in selected edible seeds of mung beans, radish, broccoli and sunflower. Germination increased the total phenolic (TP) and flavonoid (TF) levels, as well as the AA of the seeds, and influenced the profile of free and bound phenolic compounds. Among the samples, mung bean was characterised by lowest levels of TP and TF, as well as AA, evaluated using ABTS, DPPH and FRAP assays. Sunflower and radish sprouts were the most rich in phenolic compounds. Insignificant amounts of free phenolic acids were found in the free phenolic acid fraction; alkaline hydrolysis of the seeds and sprouts extracts provided the majority of the phenolic acids. The amounts of free and bound flavonoids were inconsiderable both for seeds and sprouts. PMID:24054243

  14. Photometric Selection of High-Redshift Type Ia Supernova Candidates

    NASA Astrophysics Data System (ADS)

    Sullivan, M.; Howell, D. A.; Perrett, K.; Nugent, P. E.; Astier, P.; Aubourg, E.; Balam, D.; Basa, S.; Carlberg, R. G.; Conley, A.; Fabbro, S.; Fouchez, D.; Guy, J.; Hook, I.; Lafoux, H.; Neill, J. D.; Pain, R.; Palanque-Delabrouille, N.; Pritchet, C. J.; Regnault, N.; Rich, J.; Taillet, R.; Aldering, G.; Baumont, S.; Bronder, J.; Filiol, M.; Knop, R. A.; Perlmutter, S.; Tao, C.

    2006-02-01

    We present a method for selecting high-redshift Type Ia supernovae (SNe Ia) located via rolling SN searches. The technique, using both color and magnitude information of events from only two to three epochs of multiband real-time photometry, is able to discriminate between SNe Ia and core-collapse SNe. Furthermore, for SNe Ia the method accurately predicts the redshift, phase, and light-curve parameterization of these events based only on pre-maximum-light data. We demonstrate the effectiveness of the technique on a simulated survey of SNe Ia and core-collapse SNe, where the selection method effectively rejects most core-collapse SNe while retaining SNe Ia. We also apply the selection code to real-time data acquired as part of the Canada-France-Hawaii Telescope Supernova Legacy Survey (SNLS). During the period 2004 May to 2005 January in the SNLS, 440 SN candidates were discovered, of which 70 were confirmed spectroscopically as SNe Ia and 15 as core-collapse events. For this test data set, the selection technique correctly identifies 100% of the identified SNe II as non-SNe Ia with only a 1%-2% false rejection rate. The predicted parameterization of the SNe Ia has a precision of Δz/(1+zspec)<0.09 in redshift and +/-2-3 rest-frame days in phase, providing invaluable information for planning spectroscopic follow-up observations. We also investigate any bias introduced by this selection method on the ability of surveys such as SNLS to measure cosmological parameters (e.g., w and ΩM) and find any effect to be negligible.

  15. Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents.

    PubMed

    Wu, Yuelin; Min, Xiao; Zhuang, Chunlin; Li, Jin; Yu, Zhiliang; Dong, Guoqiang; Yao, Jiangzhong; Wang, Shengzheng; Liu, Yang; Wu, Shanchao; Zhu, Shiping; Sheng, Chunquan; Wei, Yunyang; Zhang, Huojun; Zhang, Wannian; Miao, Zhenyuan

    2014-07-23

    In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity. PMID:24937186

  16. Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

    PubMed

    Manoj Kumar, Palanivelu; Karthikeyan, Chandrabose; Hari Narayana Moorthy, Narayana Subbiah; Trivedi, Piyush

    2006-11-01

    In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition. PMID:17077558

  17. Structure-Guided Design of Group I Selective p21-Activated Kinase Inhibitors.

    PubMed

    Crawford, James J; Lee, Wendy; Aliagas, Ignacio; Mathieu, Simon; Hoeflich, Klaus P; Zhou, Wei; Wang, Weiru; Rouge, Lionel; Murray, Lesley; La, Hank; Liu, Ning; Fan, Peter W; Cheong, Jonathan; Heise, Christopher E; Ramaswamy, Sreemathy; Mintzer, Robert; Liu, Yanzhou; Chao, Qi; Rudolph, Joachim

    2015-06-25

    The p21-activated kinases (PAKs) play important roles in cytoskeletal organization, cellular morphogenesis, and survival and have generated significant attention as potential therapeutic targets for cancer. Following a high-throughput screen, we identified an aminopyrazole scaffold-based series that was optimized to yield group I selective PAK inhibitors. A structure-based design effort aimed at targeting the ribose pocket for both potency and selectivity led to much-improved group I vs II selectivity. Early lead compounds contained a basic primary amine, which was found to be a major metabolic soft spot with in vivo clearance proceeding predominantly via N-acetylation. We succeeded in identifying replacements with improved metabolic stability, leading to compounds with lower in vivo rodent clearance and excellent group I PAK selectivity. PMID:26030457

  18. Frustrated magnets in high magnetic fields—selected examples

    NASA Astrophysics Data System (ADS)

    Wosnitza, J.; Zvyagin, S. A.; Zherlitsyn, S.

    2016-07-01

    An indispensable parameter to study strongly correlated electron systems is the magnetic field. Application of high magnetic fields allows the investigation, modification and control of different states of matter. Specifically for magnetic materials experimental tools applied in such fields are essential for understanding their fundamental properties. Here, we focus on selected high-field studies of frustrated magnetic materials that have been shown to host a broad range of fascinating new and exotic phases. We will give brief insights into the influence of geometrical frustration on the critical behavior of triangular-lattice antiferromagnets, the accurate determination of exchange constants in the high-field saturated state by use of electron spin resonance measurements, and the coupling of magnetic degrees of freedom to the lattice evidenced by ultrasound experiments. The latter technique as well allowed new, partially metastable phases in strong magnetic fields to be revealed.

  19. Frustrated magnets in high magnetic fields-selected examples.

    PubMed

    Wosnitza, J; Zvyagin, S A; Zherlitsyn, S

    2016-07-01

    An indispensable parameter to study strongly correlated electron systems is the magnetic field. Application of high magnetic fields allows the investigation, modification and control of different states of matter. Specifically for magnetic materials experimental tools applied in such fields are essential for understanding their fundamental properties. Here, we focus on selected high-field studies of frustrated magnetic materials that have been shown to host a broad range of fascinating new and exotic phases. We will give brief insights into the influence of geometrical frustration on the critical behavior of triangular-lattice antiferromagnets, the accurate determination of exchange constants in the high-field saturated state by use of electron spin resonance measurements, and the coupling of magnetic degrees of freedom to the lattice evidenced by ultrasound experiments. The latter technique as well allowed new, partially metastable phases in strong magnetic fields to be revealed. PMID:27310818

  20. The impact of materials selection on long-term activation in fusion power plants

    NASA Astrophysics Data System (ADS)

    Taylor, N. P.; Forty, C. B. A.; Petti, D. A.; McCarthy, K. A.

    2000-12-01

    Neutron-induced transmutation of materials in a D-T fusion power plant will give rise to the potential for long-term activation. To ensure that the attractive safety and environmental characteristics of fusion power are not degraded, careful design choices are necessary. An aim of optimising power plant design must be to minimise both the level of activation and the total volume of active material that might ultimately be categorised as waste requiring disposal. Materials selection is central to this optimisation. In this paper we assess the influence of materials choices for a power plant on the waste volume and the potential to clear (i.e. remove from regulatory control) and recycle material. Although the use of low activation materials in regions of high neutron flux is an important part of the strategy to minimise the level of activation, different choices may result from a strategy aimed at minimising the volume of active waste.

  1. ERP markers of target selection discriminate children with high vs. low working memory capacity

    PubMed Central

    Shimi, Andria; Nobre, Anna Christina; Scerif, Gaia

    2015-01-01

    Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM) system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults’ selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children’s selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults’ selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc). However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the “adult time-window” related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children’s neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM performance in

  2. High-temperature waste-heat-stream selection and characterization

    SciTech Connect

    Wikoff, P.M.; Wiggins, D.J.; Tallman, R.L.; Forkel, C.E.

    1983-08-01

    Four types of industrial high-temperature, corrosive waste heat streams are selected that could yield significant energy savings if improved heat recovery systems were available. These waste heat streams are the flue gases from steel soaking pits, steel reheat furnaces, aluminum remelt furnaces, and glass melting furnaces. Available information on the temperature, pressure, flow, and composition of these flue gases is given. Also reviewed are analyses of corrosion products and fouling deposits resulting from the interaction of these flue gases with materials in flues and heat recovery systems.

  3. Band Selection Procedure for Reduction of High Resolution Spectra

    NASA Astrophysics Data System (ADS)

    Pasztor, L.; Csillag, F.

    In this paper we present a technique for reduction of spectra based on the methods of multivariate statistical analysis. The procedure was developed for general processing of digital, high resolution spectra. The recursive band selection method can be applied in studies for weighting (original) spectral bands according their sensitivity to a predefined classification scheme. Additionally, definition of medium and broad band systems is possible, which can efficiently substitute the original spectrum. According to the characteristics of the method resulted from a remote sensing application (convergence, robustness), it is suggested for use in different (radio, UV, X-ray etc.) astronomical studies as well.

  4. Extremely high-dimensional feature selection via feature generating samplings.

    PubMed

    Li, Shutao; Wei, Dan

    2014-06-01

    To select informative features on extremely high-dimensional problems, in this paper, a sampling scheme is proposed to enhance the efficiency of recently developed feature generating machines (FGMs). Note that in FGMs O(mlogr) time complexity should be taken to order the features by their scores; the entire computational cost of feature ordering will become unbearable when m is very large, for example, m > 10(11) , where m is the feature dimensionality and r is the size of the selected feature subset. To solve this problem, in this paper, we propose a feature generating sampling method, which can reduce this computational complexity to O(Gslog(G)+G(G+log(G))) while preserving the most informative features in a feature buffer, where Gs is the maximum number of nonzero features for each instance and G is the buffer size. Moreover, we show that our proposed sampling scheme can be deemed as the birth-death process based on random processes theory, which guarantees to include most of the informative features for feature selections. Empirical studies on real-world datasets show the effectiveness of the proposed sampling method. PMID:23864272

  5. Highly selective agonists for substance P receptor subtypes.

    PubMed Central

    Wormser, U; Laufer, R; Hart, Y; Chorev, M; Gilon, C; Selinger, Z

    1986-01-01

    The existence of a third tachykinin receptor (SP-N) in the mammalian nervous system was demonstrated by development of highly selective agonists. Systematic N-methylation of individual peptide bonds in the C-terminal hexapeptide of substance P gave rise to agonists which specifically act on different receptor subtypes. The most selective analog of this series, succinyl-[Asp6,Me-Phe8]SP6-11, elicits half-maximal contraction of the guinea pig ileum through the neuronal SP-N receptor at a concentration of 0.5 nM. At least 60,000-fold higher concentrations of this peptide are required to stimulate the other two tachykinin receptors (SP-P and SP-E). The action of selective SP-N agonists in the guinea pig ileum is antagonized by opioid peptides, suggesting a functional counteraction between opiate and SP-N receptors. These results indicate that the tachykinin receptors are distinct entities which may mediate different physiological functions. PMID:2431898

  6. Engineering High-Fidelity Residue Separations for Selective Harvest

    SciTech Connect

    Kevin L. Kenney; Christopher T. Wright; Reed L. Hoskinson; J. Rochard Hess; David J. Muth, Jr.

    2006-07-01

    Composition and pretreatment studies of corn stover and wheat stover anatomical fractions clearly show that some corn and wheat stover anatomical fractions are of higher value than others as a biofeedstock. This premise, along with soil sustainability and erosion control concerns, provides the motivation for the selective harvest concept for separating and collecting the higher value residue fractions in a combine during grain harvest. This study recognizes the analysis of anatomical fractions as theoretical feedstock quality targets, but not as practical targets for developing selective harvest technologies. Rather, practical quality targets were established that identified the residue separation requirements of a selective harvest combine. Data are presented that shows that a current grain combine is not capable of achieving the fidelity of residue fractionation established by the performance targets. However, using a virtual engineering approach, based on an understanding of the fluid dynamics of the air stream separation, the separation fidelity can be significantly improved without significant changes to the harvester design. A virtual engineering model of a grain combine was developed and used to perform simulations of the residue separator performance. The engineered residue separator was then built into a selective harvest test combine, and tests performed to evaluate the separation fidelity. Field tests were run both with and without the residue separator installed in the test combine, and the chaff and straw residue streams were collected during harvest of Challis soft white spring wheat. The separation fidelity accomplished both with and without the residue separator was quantified by laboratory screening analysis. The screening results showed that the engineered baffle separator did a remarkable job of effecting high-fidelity separation of the straw and chaff residue streams, improving the chaff stream purity and increasing the straw stream yield.

  7. High-throughput epitope binning assays on label-free array-based biosensors can yield exquisite epitope discrimination that facilitates the selection of monoclonal antibodies with functional activity.

    PubMed

    Abdiche, Yasmina Noubia; Miles, Adam; Eckman, Josh; Foletti, Davide; Van Blarcom, Thomas J; Yeung, Yik Andy; Pons, Jaume; Rajpal, Arvind

    2014-01-01

    Here, we demonstrate how array-based label-free biosensors can be applied to the multiplexed interaction analysis of large panels of analyte/ligand pairs, such as the epitope binning of monoclonal antibodies (mAbs). In this application, the larger the number of mAbs that are analyzed for cross-blocking in a pairwise and combinatorial manner against their specific antigen, the higher the probability of discriminating their epitopes. Since cross-blocking of two mAbs is necessary but not sufficient for them to bind an identical epitope, high-resolution epitope binning analysis determined by high-throughput experiments can enable the identification of mAbs with similar but unique epitopes. We demonstrate that a mAb's epitope and functional activity are correlated, thereby strengthening the relevance of epitope binning data to the discovery of therapeutic mAbs. We evaluated two state-of-the-art label-free biosensors that enable the parallel analysis of 96 unique analyte/ligand interactions and nearly ten thousand total interactions per unattended run. The IBIS-MX96 is a microarray-based surface plasmon resonance imager (SPRi) integrated with continuous flow microspotting technology whereas the Octet-HTX is equipped with disposable fiber optic sensors that use biolayer interferometry (BLI) detection. We compared their throughput, versatility, ease of sample preparation, and sample consumption in the context of epitope binning assays. We conclude that the main advantages of the SPRi technology are its exceptionally low sample consumption, facile sample preparation, and unparalleled unattended throughput. In contrast, the BLI technology is highly flexible because it allows for the simultaneous interaction analysis of 96 independent analyte/ligand pairs, ad hoc sensor replacement and on-line reloading of an analyte- or ligand-array. Thus, the complementary use of these two platforms can expedite applications that are relevant to the discovery of therapeutic mAbs, depending

  8. A selection assay for haloalkane dehalogenase activity based on toxic substrates.

    PubMed

    Fibinger, Michael P C; Davids, Timo; Böttcher, Dominique; Bornscheuer, Uwe T

    2015-11-01

    Based on natural selection and the survival of the fittest by evolutionary adaption, a smart high-throughput system was developed to select active haloalkane dehalogenase variants from a large mutant library. Only active enzyme variants can hydrolyse toxic halogenated alkanes to promote growth, whereas inactive mutants starve or die due to the toxic compound. With this powerful tool, huge enzyme mutant libraries can be screened within a few days. The selection is done without any artificial substrates that are hard to synthesize and they also resemble typical ones for haloalkane dehalogenases. Three saturation libraries, with a size of more than 10(6) cells, based on inactive variants of the haloalkane dehalogenases DhaA or DhlA were successfully screened to retrieve active enzymes. The enrichment of the active wild-type enzyme in contrast to the inactive variants was about 340-fold. In addition, this selection approach can be applied for continuous directed evolution experiments for the enrichment of cells expressing adapted haloalkane dehalogenases. PMID:25998660

  9. Tc-99 Adsorption on Selected Activated Carbons - Batch Testing Results

    SciTech Connect

    Mattigod, Shas V.; Wellman, Dawn M.; Golovich, Elizabeth C.; Cordova, Elsa A.; Smith, Ronald M.

    2010-12-01

    CH2M HILL Plateau Remediation Company (CHPRC) is currently developing a 200-West Area groundwater pump-and-treat system as the remedial action selected under the Comprehensive Environmental Response, Compensation, and Liability Act Record of Decision for Operable Unit (OU) 200-ZP-1. This report documents the results of treatability tests Pacific Northwest National Laboratory researchers conducted to quantify the ability of selected activated carbon products (or carbons) to adsorb technetium-99 (Tc-99) from 200-West Area groundwater. The Tc-99 adsorption performance of seven activated carbons (J177601 Calgon Fitrasorb 400, J177606 Siemens AC1230AWC, J177609 Carbon Resources CR-1240-AW, J177611 General Carbon GC20X50, J177612 Norit GAC830, J177613 Norit GAC830, and J177617 Nucon LW1230) were evaluated using water from well 299-W19-36. Four of the best performing carbons (J177606 Siemens AC1230AWC, J177609 Carbon Resources CR-1240-AW, J177611 General Carbon GC20X50, and J177613 Norit GAC830) were selected for batch isotherm testing. The batch isotherm tests on four of the selected carbons indicated that under lower nitrate concentration conditions (382 mg/L), Kd values ranged from 6,000 to 20,000 mL/g. In comparison. Under higher nitrate (750 mg/L) conditions, there was a measureable decrease in Tc-99 adsorption with Kd values ranging from 3,000 to 7,000 mL/g. The adsorption data fit both the Langmuir and the Freundlich equations. Supplemental tests were conducted using the two carbons that demonstrated the highest adsorption capacity to resolve the issue of the best fit isotherm. These tests indicated that Langmuir isotherms provided the best fit for Tc-99 adsorption under low nitrate concentration conditions. At the design basis concentration of Tc 0.865 µg/L(14,700 pCi/L), the predicted Kd values from using Langmuir isotherm constants were 5,980 mL/g and 6,870 mL/g for for the two carbons. These Kd values did not meet the target Kd value of 9,000 mL/g. Tests

  10. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site

    PubMed Central

    Rumpf, Tobias; Schiedel, Matthias; Karaman, Berin; Roessler, Claudia; North, Brian J.; Lehotzky, Attila; Oláh, Judit; Ladwein, Kathrin I.; Schmidtkunz, Karin; Gajer, Markus; Pannek, Martin; Steegborn, Clemens; Sinclair, David A.; Gerhardt, Stefan; Ovádi, Judit; Schutkowski, Mike; Sippl, Wolfgang; Einsle, Oliver; Jung, Manfred

    2015-01-01

    Sirtuins are a highly conserved class of NAD+-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far. Here we present high-resolution structures of human Sirt2 in complex with highly selective drug-like inhibitors that show a unique inhibitory mechanism. Potency and the unprecedented Sirt2 selectivity are based on a ligand-induced structural rearrangement of the active site unveiling a yet-unexploited binding pocket. Application of the most potent Sirtuin-rearranging ligand, termed SirReal2, leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1, consistent with Sirt2 inhibition in vivo. Our structural insights into this unique mechanism of selective sirtuin inhibition provide the basis for further inhibitor development and selective tools for sirtuin biology. PMID:25672491

  11. High efficiency cell-specific targeting of cytokine activity

    NASA Astrophysics Data System (ADS)

    Garcin, Geneviève; Paul, Franciane; Staufenbiel, Markus; Bordat, Yann; van der Heyden, José; Wilmes, Stephan; Cartron, Guillaume; Apparailly, Florence; de Koker, Stefaan; Piehler, Jacob; Tavernier, Jan; Uzé, Gilles

    2014-01-01

    Systemic toxicity currently prevents exploiting the huge potential of many cytokines for medical applications. Here we present a novel strategy to engineer immunocytokines with very high targeting efficacies. The method lies in the use of mutants of toxic cytokines that markedly reduce their receptor-binding affinities, and that are thus rendered essentially inactive. Upon fusion to nanobodies specifically binding to marker proteins, activity of these cytokines is selectively restored for cell populations expressing this marker. This ‘activity-by-targeting’ concept was validated for type I interferons and leptin. In the case of interferon, activity can be directed to target cells in vitro and to selected cell populations in mice, with up to 1,000-fold increased specific activity. This targeting strategy holds promise to revitalize the clinical potential of many cytokines.

  12. MID-INFRARED SELECTION OF ACTIVE GALACTIC NUCLEI WITH THE WIDE-FIELD INFRARED SURVEY EXPLORER. I. CHARACTERIZING WISE-SELECTED ACTIVE GALACTIC NUCLEI IN COSMOS

    SciTech Connect

    Stern, Daniel; Assef, Roberto J.; Eisenhardt, Peter; Benford, Dominic J.; Blain, Andrew; Cutri, Roc; Griffith, Roger L.; Jarrett, T. H.; Masci, Frank; Tsai, Chao-Wei; Yan, Lin; Dey, Arjun; Lake, Sean; Petty, Sara; Wright, E. L.; Stanford, S. A.; Harrison, Fiona; Madsen, Kristin

    2012-07-01

    The Wide-field Infrared Survey Explorer (WISE) is an extremely capable and efficient black hole finder. We present a simple mid-infrared color criterion, W1 - W2 {>=} 0.8 (i.e., [3.4]-[4.6] {>=}0.8, Vega), which identifies 61.9 {+-} 5.4 active galactic nucleus (AGN) candidates per deg{sup 2} to a depth of W2 {approx} 15.0. This implies a much larger census of luminous AGNs than found by typical wide-area surveys, attributable to the fact that mid-infrared selection identifies both unobscured (type 1) and obscured (type 2) AGNs. Optical and soft X-ray surveys alone are highly biased toward only unobscured AGNs, while this simple WISE selection likely identifies even heavily obscured, Compton-thick AGNs. Using deep, public data in the COSMOS field, we explore the properties of WISE-selected AGN candidates. At the mid-infrared depth considered, 160 {mu}Jy at 4.6 {mu}m, this simple criterion identifies 78% of Spitzer mid-infrared AGN candidates according to the criteria of Stern et al. and the reliability is 95%. We explore the demographics, multiwavelength properties and redshift distribution of WISE-selected AGN candidates in the COSMOS field.

  13. Calibration of high flow rate thoracic-size selective samplers.

    PubMed

    Lee, Taekhee; Thorpe, Andrew; Cauda, Emanuele; Harper, Martin

    2016-01-01

    High flow rate respirable size selective samplers, GK4.126 and FSP10 cyclones, were calibrated for thoracic-size selective sampling in two different laboratories. The National Institute for Occupational Safety and Health (NIOSH) utilized monodisperse ammonium fluorescein particles and scanning electron microscopy to determine the aerodynamic particle size of the monodisperse aerosol. Fluorescein intensity was measured to determine sampling efficiencies of the cyclones. The Health Safety and Laboratory (HSL) utilized a real time particle sizing instrument (Aerodynamic Particle Sizer) and polydisperse glass sphere particles and particle size distributions between the cyclone and reference sampler were compared. Sampling efficiency of the cyclones were compared to the thoracic convention defined by the American Conference of Governmental Industrial Hygienists (ACGIH)/Comité Européen de Normalisation (CEN)/International Standards Organization (ISO). The GK4.126 cyclone showed minimum bias compared to the thoracic convention at flow rates of 3.5 l min(-1) (NIOSH) and 2.7-3.3 l min(-1) (HSL) and the difference may be from the use of different test systems. In order to collect the most dust and reduce the limit of detection, HSL suggested using the upper end in range (3.3 l min(-1)). A flow rate of 3.4 l min(-1) would be a reasonable compromise, pending confirmation in other laboratories. The FSP10 cyclone showed minimum bias at the flow rate of 4.0 l min(-1) in the NIOSH laboratory test. The high flow rate thoracic-size selective samplers might be used for higher sample mass collection in order to meet analytical limits of quantification. PMID:26891196

  14. Calibration of high flow rate thoracic-size selective samplers

    PubMed Central

    Lee, Taekhee; Thorpe, Andrew; Cauda, Emanuele; Harper, Martin

    2016-01-01

    High flow rate respirable size selective samplers, GK4.126 and FSP10 cyclones, were calibrated for thoracic-size selective sampling in two different laboratories. The National Institute for Occupational Safety and Health (NIOSH) utilized monodisperse ammonium fluorescein particles and scanning electron microscopy to determine the aerodynamic particle size of the monodisperse aerosol. Fluorescein intensity was measured to determine sampling efficiencies of the cyclones. The Health Safety and Laboratory (HSL) utilized a real time particle sizing instrument (Aerodynamic Particle Sizer) and poly-disperse glass sphere particles and particle size distributions between the cyclone and reference sampler were compared. Sampling efficiency of the cyclones were compared to the thoracic convention defined by the American Conference of Governmental Industrial Hygienists (ACGIH)/Comité Européen de Normalisation (CEN)/International Standards Organization (ISO). The GK4.126 cyclone showed minimum bias compared to the thoracic convention at flow rates of 3.5 l min−1 (NIOSH) and 2.7–3.3 l min−1 (HSL) and the difference may be from the use of different test systems. In order to collect the most dust and reduce the limit of detection, HSL suggested using the upper end in range (3.3 l min−1). A flow rate of 3.4 l min−1 would be a reasonable compromise, pending confirmation in other laboratories. The FSP10 cyclone showed minimum bias at the flow rate of 4.0 l min−1 in the NIOSH laboratory test. The high flow rate thoracic-size selective samplers might be used for higher sample mass collection in order to meet analytical limits of quantification. PMID:26891196

  15. High School Extracurricular Activities & College Grades.

    ERIC Educational Resources Information Center

    Rombokas, Mary; And Others

    Many factors influence the development and socialization of American adolescents including peers, schools, family, and the community. This paper examines how the relationship of extracurricular participation influences academic growth. To determine if selected personal and academic variables during high school currently affect college academic…

  16. Plans, Patterns, and Move Categories Guiding a Highly Selective Search

    NASA Astrophysics Data System (ADS)

    Trippen, Gerhard

    In this paper we present our ideas for an Arimaa-playing program (also called a bot) that uses plans and pattern matching to guide a highly selective search. We restrict move generation to moves in certain move categories to reduce the number of moves considered by the bot significantly. Arimaa is a modern board game that can be played with a standard Chess set. However, the rules of the game are not at all like those of Chess. Furthermore, Arimaa was designed to be as simple and intuitive as possible for humans, yet challenging for computers. While all established Arimaa bots use alpha-beta search with a variety of pruning techniques and other heuristics ending in an extensive positional leaf node evaluation, our new bot, Rat, starts with a positional evaluation of the current position. Based on features found in the current position - supported by pattern matching using a directed position graph - our bot Rat decides which of a given set of plans to follow. The plan then dictates what types of moves can be chosen. This is another major difference from bots that generate "all" possible moves for a particular position. Rat is only allowed to generate moves that belong to certain categories. Leaf nodes are evaluated only by a straightforward material evaluation to help avoid moves that lose material. This highly selective search looks, on average, at only 5 moves out of 5,000 to over 40,000 possible moves in a middle game position.

  17. IDENTIFYING LUMINOUS ACTIVE GALACTIC NUCLEI IN DEEP SURVEYS: REVISED IRAC SELECTION CRITERIA

    SciTech Connect

    Donley, J. L.; Koekemoer, A. M.; Brusa, M.; Salvato, M.; Capak, P.; Cardamone, C. N.; Civano, F.; Ilbert, O.; Impey, C. D.; Kartaltepe, J. S.; Miyaji, T.; Sanders, D. B.; Trump, J. R.

    2012-04-01

    Spitzer/IRAC selection is a powerful tool for identifying luminous active galactic nuclei (AGNs). For deep IRAC data, however, the AGN selection wedges currently in use are heavily contaminated by star-forming galaxies, especially at high redshift. Using the large samples of luminous AGNs and high-redshift star-forming galaxies in COSMOS, we redefine the AGN selection criteria for use in deep IRAC surveys. The new IRAC criteria are designed to be both highly complete and reliable, and incorporate the best aspects of the current AGN selection wedges and of infrared power-law selection while excluding high-redshift star-forming galaxies selected via the BzK, distant red galaxy, Lyman-break galaxy, and submillimeter galaxy criteria. At QSO luminosities of log L{sub 2-10keV}(erg s{sup -1}) {>=}44, the new IRAC criteria recover 75% of the hard X-ray and IRAC-detected XMM-COSMOS sample, yet only 38% of the IRAC AGN candidates have X-ray counterparts, a fraction that rises to 52% in regions with Chandra exposures of 50-160 ks. X-ray stacking of the individually X-ray non-detected AGN candidates leads to a hard X-ray signal indicative of heavily obscured to mildly Compton-thick obscuration (log N{sub H} (cm{sup -2}) = 23.5 {+-} 0.4). While IRAC selection recovers a substantial fraction of luminous unobscured and obscured AGNs, it is incomplete to low-luminosity and host-dominated AGNs.

  18. Search of antimicrobial activity of selected non-antibiotic drugs.

    PubMed

    Kruszewska, Hanna; Zareba, Tomasz; Tyski, Stefan

    2002-01-01

    A variety of pharmaceutical preparations, which are applied in the management of non-infectious diseases, have shown in vitro some antimicrobial activity. These drugs are called "non-antibiotics". The aim of this study was to detect and characterise the antimicrobial activity of non-antibiotic drugs. selected from the preparations analysed during state control performed at the Drug Institute in Poland. Over 160 pharmaceutical preparations were randomly chosen from different groups of drugs. The surveillance study was performed on standard ATCC microbial strains used for drug control: S aureus, E. coil, P. aeruginosa and C. albicans. It was shown that the drugs listed below inhibited growth of at least one of the examined strains:acyclovir (Awirol 5%, cream), alendronate (Alenato 5 mg, tabl.), alverine (Meteospasmyl 20 mg, caps.), butorphanole (Butamidor 10 mg/ml, amp.), clodronate (Sindronat 400 mg, caps), diclofenac (Olfen 75 mg, amp.), emadastine (Emadine 0.05%, eye dr.), etodolac (Febret 200 mg, caps.), fluvastatine (Lescol 40 mg, tabl.), ketamine (Ketamidor 10%, amp.), levocabastine (Histimet 0.5 mg/ml, eye dr.), losartan (Lorista 50 mg, tabl.), matipranolol (Betaman 0.3% eye dr.), mesalazine (Pentasa 1%, susp.), naproxen (Nalgesin 550 mg, tabl.), oxaprosine (Reumax 600 mg, tabl.), oxymethazoline (Nasivin 0.025%, nose dr.), proxymetacaine (Alcaine 0.5%, eye dr.), ribavirin (Rebetol 200 mg, caps.), rutoside with ascorbic acid (Cerutin 20+200 mg, tabl.), sulodexide (Vessel due F, 250 LSU, caps.), tegaserole (Zelmac 50 mg, tabl.), telmisartan (Pritor 20 mg, tabl.), temosolomide (Temodal 100 mg, caps.), ticlopidine (Ticlid 250 mg, tabl.), tolfenamic acid (Migea rapid 200 mg, tabl.), tramadole (Tramundin 100 mg, tabl.), tropicamide (Tropicamidum 1%, eye dr.). Staphylococcus aureus was susceptible to most of the drugs listed above. Ticlopidine showed activity against S. aureus, E. coli and C. albicans (MICs equal to: 0.45; 0.45 and 0.65 mg/ml, respectively

  19. A highly selective telomerase inhibitor limiting human cancer cell proliferation

    PubMed Central

    Damm, Klaus; Hemmann, Ulrike; Garin-Chesa, Pilar; Hauel, Norbert; Kauffmann, Iris; Priepke, Henning; Niestroj, Claudia; Daiber, Christine; Enenkel, Barbara; Guilliard, Bernd; Lauritsch, Ines; Müller, Elfriede; Pascolo, Emanuelle; Sauter, Gabriele; Pantic, Milena; Martens, Uwe M.; Wenz, Christian; Lingner, Joachim; Kraut, Norbert; Rettig, Wolfgang J.; Schnapp, Andreas

    2001-01-01

    Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues. Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation. We describe novel chemical compounds which selectively inhibit telomerase in vitro and in vivo. Treatment of cancer cells with these inhibitors leads to progressive telomere shortening, with no acute cytotoxicity, but a proliferation arrest after a characteristic lag period with hallmarks of senescence, including morphological, mitotic and chromosomal aberrations and altered patterns of gene expression. Telomerase inhibition and telomere shortening also result in a marked reduction of the tumorigenic potential of drug-treated tumour cells in a mouse xenograft model. This model was also used to demonstrate in vivo efficacy with no adverse side effects and uncomplicated oral administration of the inhibitor. These findings indicate that potent and selective, non-nucleosidic telomerase inhibitors can be designed as novel cancer treatment modalities. PMID:11742973

  20. Examination of antimicrobial activity of selected non-antibiotic drugs.

    PubMed

    Kruszewska, Hanna; Zareba, Tomasz; Tyski, Stefan

    2004-12-01

    A variety of pharmaceutical preparations, which are applied in the management of non-infectious diseases, have shown in vitro some antimicrobial activity. These drugs are called "non-antibiotics". The aim of this study was to detect and characterize the antimicrobial activity of non-antibiotic drugs, selected from the preparations analysed during state control performed in the National Institute of Public Health in Poland. Over 180 of pharmaceutical preparations were randomly chosen from different groups of drugs. A surveillance study was performed on standard ATCC microbial strains used for drug control: S. aureus, E. coli, P. aeruginosa and C. albicans. It was shown that the drugs listed below inhibited growth of at least one of the examined strains: Actonel 5 mg tabl. (risedronate), Aldan 10 mg tabl. (amlodipine), Aleras 10 mg tabl. (cetirisine), Aspicam 15 mg tabl. (meloxicam), Baikadent 6 mg/g gel (flavons of Scutellariae), Debretin 100 mg tabl. (trimebutine), Ferro-Duo 100 mg tabl. (ferrum), Gastrovent 145 mg caps. (bismuth citrate), Ibum 200 mg caps., Upfen 200 mg tabl. (ibuprofen), Lastet 100 mg caps. (etoposide), Legalon 70 mg tabl. (sylimarin), Madopar 125 tabl. (benserazide, levodopa), Moxenil 100 mg tabl. (nimesulide), Neurotin 800 mg tabl. (gabapentin), Propranolol 40 mg tabl. (propranolol), Rexetin 20 mg tabl. (paroxetine), Salipax 20 mg caps. (fluoxetine), Selofen 10 mg caps. (zaleplon) Stenorol 0.6% powder (halofuginone), Stimuloton 50 mg tabl. (sertraline), Superoptim 0.3 mg tabl. (hipericine), Uversan 50 mg tabl. (arbutine from Arctostaphylos uva ursi). S. aureus strain was susceptible to the most of the drugs listed above. The lowest inhibitory concentration was found for sertraline and hipericine (0.16 and 0.075 mg/mL, respectively). PMID:15909927

  1. A Highly Selective Ratiometric Two-Photon Fluorescent Probe for Human Cytochrome P450 1A.

    PubMed

    Dai, Zi-Ru; Ge, Guang-Bo; Feng, Lei; Ning, Jing; Hu, Liang-Hai; Jin, Qiang; Wang, Dan-Dan; Lv, Xia; Dou, Tong-Yi; Cui, Jing-Nan; Yang, Ling

    2015-11-18

    Cytochrome P450 1A (CYP1A), one of the most important phase I drug-metabolizing enzymes in humans, plays a crucial role in the metabolic activation of procarcinogenic compounds to their ultimate carcinogens. Herein, we reported the development of a ratiometric two-photon fluorescent probe NCMN that allowed for selective and sensitive detection of CYP1A for the first time. The probe was designed on the basis of substrate preference of CYP1A and its high capacity for O-dealkylation, while 1,8-naphthalimide was selected as fluorophore because of its two-photon absorption properties. To achieve a highly selective probe for CYP1A, a series of 1,8-naphthalimide derivatives were synthesized and used to explore the potential structure-selectivity relationship, by using a panel of human CYP isoforms for selectivity screening. After screening and optimization, NCMN displayed the best combination of selectivity, sensitivity and ratiometric fluorescence response following CYP1A-catalyzed O-demetylation. Furthermore, the probe can be used to real-time monitor the enzyme activity of CYP1A in complex biological systems, and it has the potential for rapid screening of CYP1A modulators using tissue preparation as enzyme sources. NCMN has also been successfully used for two-photon imaging of intracellular CYP1A in living cells and tissues, and showed high ratiometric imaging resolution and deep-tissue imaging depth. In summary, a two-photon excited ratiometric fluorescent probe NCMN has been developed and well-characterized for sensitive and selective detection of CYP1A, which holds great promise for bioimaging of endogenous CYP1A in living cells and for further investigation on CYP1A associated biological functions in complex biological systems. PMID:26488456

  2. High Temperature Irradiation Effects in Selected Generation IV Structural Alloys

    SciTech Connect

    Nanstad, Randy K; McClintock, David A; Hoelzer, David T; Tan, Lizhen; Allen, Todd R.

    2009-01-01

    In the Generation IV Materials Program cross-cutting task, irradiation and testing were carried out to address the issue of high temperature irradiation effects with selected current and potential candidate metallic alloys. The materials tested were (1) a high-nickel iron-base alloy (Alloy 800H); (2) a nickel-base alloy (Alloy 617); (3) two advanced nano-structured ferritic alloys (designated 14YWT and 14WT); and (4) a commercial ferritic-martensitic steel (annealed 9Cr-1MoV). Small tensile specimens were irradiated in rabbit capsules in the High-Flux Isotope Reactor at temperatures from about 550 to 700 C and to irradiation doses in the range 1.2 to 1.6 dpa. The Alloy 800H and Alloy 617 exhibited significant hardening after irradiation at 580 C; some hardening occurred at 660 C as well, but the 800H showed extremely low tensile elongations when tested at 700 C. Notably, the grain boundary engineered 800H exhibited even greater hardening at 580 C and retained a high amount of ductility. Irradiation effects on the two nano-structured ferritic alloys and the annealed 9Cr-1MoV were relatively slight at this low dose.

  3. Novel class of highly selective divanillin-based PACs

    NASA Astrophysics Data System (ADS)

    Medina, Arturo N.; Ferreira, Lawrence; Tadros, Sobhy P.; Sizensky, Joseph J.; Fregeolle, M.; Blakeney, Andrew J.; Toukhy, Medhat A.

    1996-06-01

    A new class of diazonaphthoquinone (DNQ) photoactive compounds (PACs) based on the divanillin core is introduced in this paper. The general structure of these PAC backbones is shown in Formula 1. The divanillin structure possesses unique electronic characteristics which influence its DNQ-SO2Cl esterification reactions to be highly selective. The most reactive site for esterification in Formula 1 is one of the divanillin hydroxyls despite the typically higher steric hindrance. Surprisingly, the esterification product is then significantly deactivated towards esterification at the other previously equivalent divanillin OH. The result of using 3 equivalents of DNQ-SO2Cl to esterify tetraphenolic species is the formation of high percentages of the specific triester in which the second divanillyl OH remains unesterified. The deactivation of the second divanillin OH after the initial esterification indicates some interaction between the two o,o-biphenol rings despite its inability to be coplanar for conjugation of (pi) electrons because of steric hindrance. Possible explanations for this interaction are explored using molecular simulation tools. Diverse members of the divanillin PAC family have been prepared from phenols of varying structure and hydrophobicities. These PACs were tested lithographically and the results correlated with PAC backbone structure. The characteristic dissolution rate behavior of the resist formulations based on triesterified PACs, measured as a function of exposure dose, generally show high discrimination and strong inhibition, even with the more hydrophilic PACs. These formulations typically exhibited high resolution, wide focus latitude, and exposure margins greater than 2.0 in lithographic screening.

  4. Highly Efficient, Selective, and Stable CO2 Electroreduction on a Hexagonal Zn Catalyst.

    PubMed

    Won, Da Hye; Shin, Hyeyoung; Koh, Jaekang; Chung, Jaehoon; Lee, Hee Sang; Kim, Hyungjun; Woo, Seong Ihl

    2016-08-01

    Electrocatalytic CO2 conversion into fuel is a prospective strategy for the sustainable energy production. However, still many parts of the catalyst such as low catalytic activity, selectivity, and stability are challenging. Herein, a hierarchical hexagonal Zn catalyst showed highly efficient and, more importantly, stable performance as an electrocatalyst for selectively producing CO. Moreover, we found that its high selectivity for CO is attributed to morphology. In electrochemical analysis, Zn (101) facet is favorable to CO formation whereas Zn (002) facet favors the H2 evolution during CO2 electrolysis. Indeed, DFT calculations showed that (101) facet lowers a reduction potential for CO2 to CO by more effectively stabilizing a (.) COOH intermediate than (002) facet. This further suggests that tuning the crystal structure to control (101)/(002) facet ratio of Zn can be considered as a key design principle to achieve a desirable product from Zn catalyst. PMID:27352078

  5. Selected advanced aerodynamic and active control concepts development

    NASA Technical Reports Server (NTRS)

    1981-01-01

    A task for the Energy Efficient Transport program conducted: (1) The design and wind tunnel development of high-aspect-ratio supercritical wings, investigating the cruise speed regime and also high-lift. (2) The preliminary design and evaluation of an aircraft combining a high-aspect-ratio supercritical wing with a winglet. (3) Active Controls: The determination of criteria, configuration, and flying qualities associated with augmented longitudinal stability of a level likely to be acceptable for the next generation transport; and the design of a practical augmentation system. The baseline against which the work was performed and evaluated was the Douglas DC-X-200 twin engine derivative of the DC-10 transport. The supercritical wing development showed that the cruise and buffet requirements could be achieved and that the wing could be designed to realize a sizable advantage over today's technology. Important advances in high lift performance were shown. The design study of an aircraft with supercritical wing and winglet suggested advantages in weight and fuel economy could be realized. The study of augmented stability, conducted with the aid of a motion base simulator, concluded that a negative static margin was acceptable for the baseline unaugmented aircraft.

  6. Activity and selectivity of molybdenum catalysts in coal liquefaction reactions

    SciTech Connect

    Curtis, C.W.; Pellegrino, J.L. )

    1988-01-01

    The purpose of this work is to evaluate how effectively three different molybdenum catalysts promote reactions involving heteroatom removal and cleavage of alkyl bridge hydrodeoxygenation (HDO), hydrodesulfurization (HDS), hydrodenitrogenation (HDN) and hydrocracking (HYC). Both model and coal liquefaction reactions were performed to test the activity and selectivity of three different molybdenum catalysts. The three catalysts used were molybdenum naphthenate, molybdenum supported on gamma alumina (Mo/Al{sub 2}O{sub 3}) and precipitated, poorly crystalline molybdenum disulfide (MoS{sub 2}). The model compounds, chosen to mimic coal structure, on which the effectiveness of the catalysts for the model reactions was tested were: 1-methylnaphthalene, representing aromatic hydrocarbons, for hydrogenation; 1-naphthol, representing oxygen containing compounds, for deoxygenation; benzothiophene, representing sulfur containing compounds, for desulfurization; indole, representing nitrogen containing compounds, for denitrogenation; and bibenzyl, representing alkyl bridging structures, for hydrocracking. Catalytic reactions of combinations of reactants were performed to simulate a complex coal matrix. Thermal and catalytic coal liquefaction reactions were performed using Illinois No. 6 coal with anthracene as a solvent. The efficacy of the catalysts was determined by comparing the product and compound class fractions obtained from the liquefaction reactions.

  7. Activity and selectivity of molybdenum catalysts in coal liquefaction reactions

    SciTech Connect

    Curtis, C.W.; Pellegrino, J.L. )

    1988-06-01

    During coal liquefaction, coal fragments forming a liquid product with reduced heteroatom content. Coal can be considered to be a large network of polynuclear aromatic species connected by heteroatoms and alkyl bridging structures. Predominant heteroatoms contained in coal are sulfur, oxygen, and nitrogen. Predominant alkyl bridges are methylene and ethylene structures. The purpose of this work is to evaluate how effectively three different molybdenum catalysts promote reactions involving heteroatom removal and cleavage of alkyl bridge structures. The reactions studied include: hydrogenation (HYD), hydrodeoxygenation (HDO), hydrosulfurization (HDS), hydrodenitrogenation (HDN) and hydrocracking (HYC). Both model and coal liquefaction reactions were performed to test the activity and selectivity of three different molybdenum catalysts. The three catalysts used were molybdenum napththenate, molybdenum supported on gamma alumina (Mo/Al/sub 2/O/sub 3/) and precipitated, poorly crystalline molybdenum disulfide (MoS/sub 2/). The model compounds, chosen to mimic coal structure, on which the effectiveness of the catalysts for the model reactions was tested were: 1-methylnaphthalene, representing aromatic hydrocarbons, for hydrogenation; 1-naphthol, representing oxygen containing compounds, for deoxygenation; benzothiophene, representing sulfur containing compounds, for desulfurization; indole, representing nitrogen containing compounds, for denitrogenation; and bibenzyl, representing alkyl bridging structures, for hydrocracking. Catalytic reactions of combinations of reactants were performed to simulate a complex coal matrix. Thermal and catalytic coal liquefaction reactions were performed using Illinois No. 6 coal with anthracene as a solvent. The efficacy of the catalysts was determined by comparing the product and compound class fractions obtained from the liquefaction reactions.

  8. Neuronal activity is not required for the initial formation and maturation of visual selectivity.

    PubMed

    Hagihara, Kenta M; Murakami, Tomonari; Yoshida, Takashi; Tagawa, Yoshiaki; Ohki, Kenichi

    2015-12-01

    Neuronal activity is important for the functional refinement of neuronal circuits in the early visual system. At the level of the cerebral cortex, however, it is still unknown whether the formation of fundamental functions such as orientation selectivity depends on neuronal activity, as it has been difficult to suppress activity throughout development. Using genetic silencing of cortical activity starting before the formation of orientation selectivity, we found that the orientation selectivity of neurons in the mouse visual cortex formed and matured normally despite a strong suppression of both spontaneous and visually evoked activity throughout development. After the orientation selectivity formed, the distribution of the preferred orientations of neurons was reorganized. We found that this process required spontaneous activity, but not visually evoked activity. Thus, the initial formation and maturation of orientation selectivity is largely independent of neuronal activity, and the initial selectivity is subsequently modified depending on neuronal activity. PMID:26523644

  9. Energy Activities for Junior High Science.

    ERIC Educational Resources Information Center

    Beaver, David; And Others

    This document is a collection of six energy education activities for junior high school science. Its purpose is to help promote knowledge about energy, provide laboratory experiences, provoke inquiry, and relate energy to society through the science curriculum. The six activities are designed to take one to three class periods. Two of the…

  10. Purpose and Meaning in Highly Active Seniors

    ERIC Educational Resources Information Center

    Penick, Jeffrey M.; Fallshore, Marte

    2005-01-01

    The authors investigated the sources of meaning for active seniors. Results indicated that seniors who were most active were relatively high in a wide range of sources of meaning as well as in life satisfaction in general. The importance of meaning and purpose in relation to counseling with older adults is discussed.

  11. A Calcium Coordination Framework Having Permanent Porosity and High CO2/N2 Selectivity

    SciTech Connect

    Banerjee D.; Parise J.; Zhang, Z.; Plonka, A.M.; Li, J.

    2012-03-15

    A thermally stable, microporous calcium coordination network shows a reversible 5.75 wt % CO{sub 2} uptake at 273 K and 1 atm pressure, with an enthalpy of interaction of {approx}31 kJ/mol and a CO{sub 2}/N{sub 2} selectivity over 45 under ideal flue gas conditions. The absence of open metal sites in the activated material suggests a different mechanism for selectivity and high interaction energy compared to those for frameworks with open metal sites.

  12. Stereochemical Assignment of Strigolactone Analogues Confirms Their Selective Biological Activity.

    PubMed

    Artuso, Emma; Ghibaudi, Elena; Lace, Beatrice; Marabello, Domenica; Vinciguerra, Daniele; Lombardi, Chiara; Koltai, Hinanit; Kapulnik, Yoram; Novero, Mara; Occhiato, Ernesto G; Scarpi, Dina; Parisotto, Stefano; Deagostino, Annamaria; Venturello, Paolo; Mayzlish-Gati, Einav; Bier, Ariel; Prandi, Cristina

    2015-11-25

    Strigolactones (SLs) are new plant hormones with various developmental functions. They are also soil signaling chemicals that are required for establishing beneficial mycorrhizal plant/fungus symbiosis. In addition, SLs play an essential role in inducing seed germination in root-parasitic weeds, which are one of the seven most serious biological threats to food security. There are around 20 natural SLs that are produced by plants in very low quantities. Therefore, most of the knowledge on SL signal transduction and associated molecular events is based on the application of synthetic analogues. Stereochemistry plays a crucial role in the structure-activity relationship of SLs, as compounds with an unnatural D-ring configuration may induce biological effects that are unrelated to SLs. We have synthesized a series of strigolactone analogues, whose absolute configuration has been elucidated and related with their biological activity, thus confirming the high specificity of the response. Analogues bearing the R-configured butenolide moiety showed enhanced biological activity, which highlights the importance of this stereochemical motif. PMID:26502774

  13. Anti-inflammatory activities of selected synthetic homoisoflavanones.

    PubMed

    Shaikh, Mahidansha M; Kruger, Hendrik G; Bodenstein, Johannes; Smith, Peter; du Toit, Karen

    2012-01-01

    Four homoisoflavanones of the 3-benzylidene-4-chromanone type, some of which were previously isolated from Caesalpinia pulcherrima, were synthesised to determine their anti-inflammatory activity and cytotoxicity. A range of four different homoisoflavanones (compounds 4a-4d) were synthesised from the corresponding substituted phenols. ¹H- and ¹³C-NMR data together with high-resolution mass spectroscopy data were employed to elucidate the structures. Anti-inflammatory activity was determined in mice with acute croton oil-induced auricular dermatitis. In vitro cytotoxicity was tested against a Chinese hamster ovarian cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Compound 4a exhibited a tendency to inhibit oedema in a dose-dependent manner after 3 and 6 h of treatment. Compounds 4b-4d also inhibited oedema, although a clear dose-response relationship was not observed. Compounds 4a-4c were found to be less cytotoxic than compound 4d. Compound 4b was the least cytotoxic. Compounds 4a-4d exhibited anti-inflammatory activity and varying levels of cytotoxicity. PMID:21950651

  14. A four-dimensional virtual hand brain–machine interface using active dimension selection

    NASA Astrophysics Data System (ADS)

    Rouse, Adam G.

    2016-06-01

    Objective. Brain–machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. Approach. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Main results. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s‑1 for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. Significance. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

  15. Selected classes of minimised hammerhead ribozyme have very high cleavage rates at low Mg2+ concentration.

    PubMed Central

    Conaty, J; Hendry, P; Lockett, T

    1999-01-01

    In vitro selection was used to enrich for highly efficient RNA phosphodiesterases within a size-constrained (18 nt) ribonucleotide domain. The starting population (g0) was directed in trans against an RNA oligonucleotide substrate immobilised to an avidin-magnetic phase. Four rounds of selection were conducted using 20 mM Mg2+to fractionate the population on the basis of divalent metal ion-dependent phosphodiesterase activity. The resulting generation 4 (g4) RNA was then directed through a further two rounds of selection using low concentrations of Mg2+. Generation 6 (g6) was composed of sets of active, trans cleaving minimised ribozymes, containing recognised hammerhead motifs in the conserved nucleotides, but with highly variable linker domains (loop II-L.1-L.4). Cleavage rate constants in the g6 population ranged from 0.004 to 1.3 min-1at 1 mM Mg2+(pH 8.0, 37 degrees C). Selection was further used to define conserved positions between G(10.1) and C(11.1) required for high cleavage activity at low Mg2+concentration. At 10 mM MgCl2the kinetic phenotype of these molecules was comparable to a hammerhead ribozyme with 4 bp in helix II. At low Mg2+concentration, the disparity in cleavage rate constants increases in favour of the minimised ribozymes. Favourable kinetic traits appeared to be a general property for specific selected linker sequences, as the high rates of catalysis were transferable to a different substrate system. PMID:10325431

  16. High-density nanopore array for selective biomolecule transport.

    SciTech Connect

    Patel, Kamlesh D.

    2011-11-01

    Development of sophisticated tools capable of manipulating molecules at their own length scale enables new methods for chemical synthesis and detection. Although nanoscale devices have been developed to perform individual tasks, little work has been done on developing a truly scalable platform: a system that combines multiple components for sequential processing, as well as simultaneously processing and identifying the millions of potential species that may be present in a biological sample. The development of a scalable micro-nanofluidic device is limited in part by the ability to combine different materials (polymers, metals, semiconductors) onto a single chip, and the challenges with locally controlling the chemical, electrical, and mechanical properties within a micro or nanochannel. We have developed a unique construct known as a molecular gate: a multilayered polymer based device that combines microscale fluid channels with nanofluidic interconnects. Molecular gates have been demonstrated to selectively transport molecules between channels based on size or charge. In order to fully utilize these structures, we need to develop methods to actively control transport and identify species inside a nanopore. While previous work has been limited to creating electrical connections off-channel or metallizing the entire nanopore wall, we now have the ability to create multiple, separate conductive connections at the interior surface of a nanopore. These interior electrodes will be used for direct sensing of biological molecules, probing the electrical potential and charge distribution at the surface, and to actively turn on and off electrically driven transport of molecules through nanopores.

  17. Selective extraction, structural characterisation and antifungal activity assessment of napins from an industrial rapeseed meal.

    PubMed

    Nioi, Claudia; Kapel, Romain; Rondags, Emmanuel; Marc, Ivan

    2012-10-15

    This article reports an extraction-purification of napins from an industrial rapeseed meal and the assessment of their antimicrobial activity against Fusarium langsethiae. The best extraction conditions are observed at pH 2, 12% (w/w) of rapeseed meal after 15 min of extraction in water at room temperature. Under these conditions the extraction is highly selective, allowing a simple purification process (ammonium sulfate precipitation followed by desalting size exclusion chromatography) to get purified napins. These napins possessed significant anti-Fusarium activity (IC(50)=70 μM) and a compact secondary structure rich in α-helix, which may explain this bioactivity. PMID:23442668

  18. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2.

    PubMed

    Verma, Sharad K; Tian, Xinrong; LaFrance, Louis V; Duquenne, Céline; Suarez, Dominic P; Newlander, Kenneth A; Romeril, Stuart P; Burgess, Joelle L; Grant, Seth W; Brackley, James A; Graves, Alan P; Scherzer, Daryl A; Shu, Art; Thompson, Christine; Ott, Heidi M; Aller, Glenn S Van; Machutta, Carl A; Diaz, Elsie; Jiang, Yong; Johnson, Neil W; Knight, Steven D; Kruger, Ryan G; McCabe, Michael T; Dhanak, Dashyant; Tummino, Peter J; Creasy, Caretha L; Miller, William H

    2012-12-13

    The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2. PMID:24900432

  19. Improvement of aromatic thiol release through the selection of yeasts with increased β-lyase activity.

    PubMed

    Belda, Ignacio; Ruiz, Javier; Navascués, Eva; Marquina, Domingo; Santos, Antonio

    2016-05-16

    The development of a selective medium for the rapid differentiation of yeast species with increased aromatic thiol release activity has been achieved. The selective medium was based on the addition of S-methyl-l-cysteine (SMC) as β-lyase substrate. In this study, a panel of 245 strains of Saccharomyces cerevisiae strains was tested for their ability to grow on YCB-SMC medium. Yeast strains with an increased β-lyase activity grew rapidly because of their ability to release ammonium from SMC in comparison to others, and allowed for the easy isolation and differentiation of yeasts with promising properties in oenology, or another field, for aromatic thiol release. The selective medium was also helpful for the discrimination between those S. cerevisiae strains, which present a common 38-bp deletion in the IRC7 sequence (present in around 88% of the wild strains tested and are likely to be less functional for 4-mercapto-4-methylpentan-2-one (4MMP) production), and those S. cerevisiae strains homozygous for the full-length IRC7 allele. The medium was also helpful for the selection of non-Saccharomyces yeasts with increased β-lyase activity. Based on the same medium, a highly sensitive, reproducible and non-expensive GC-MS method for the evaluation of the potential volatile thiol release by different yeast isolates was developed. PMID:26971012

  20. Selective activity of deguelin identifies therapeutic targets for androgen receptor-positive breast cancer.

    PubMed

    Robles, Andrew J; Cai, Shengxin; Cichewicz, Robert H; Mooberry, Susan L

    2016-06-01

    Triple-negative breast cancers (TNBC) are aggressive malignancies with no effective targeted therapies. Recent gene expression profiling of these heterogeneous cancers and the classification of cell line models now allows for the identification of compounds with selective activities against molecular subtypes of TNBC. The natural product deguelin was found to have selective activity against MDA-MB-453 and SUM-185PE cell lines, which both model the luminal androgen receptor (LAR) subtype of TNBC. Deguelin potently inhibited proliferation of these cells with GI50 values of 30 and 61 nM, in MDA-MB-453 and SUM-185PE cells, respectively. Deguelin had exceptionally high selectivity, 197 to 566-fold, for these cell lines compared to cell lines representing other TNBC subtypes. Deguelin's mechanisms of action were investigated to determine how it produced these potent and selective effects. Our results show that deguelin has dual activities, inhibiting PI3K/Akt/mTOR signaling, and decreasing androgen receptor levels and nuclear localization. Based on these data, we hypothesized that the combination of the mTOR inhibitor rapamycin and the antiandrogen enzalutamide would have efficacy in LAR models. Rapamycin and enzalutamide showed additive effects in MDA-MB-453 cells, and both drugs had potent antitumor efficacy in a LAR xenograft model. These results suggest that the combination of antiandrogens and mTOR inhibitors might be an effective strategy for the treatment of androgen receptor-expressing TNBC. PMID:27255535

  1. Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors

    PubMed Central

    Rüben, Katharina; Wurzlbauer, Anne; Walte, Agnes; Sippl, Wolfgang; Bracher, Franz; Becker, Walter

    2015-01-01

    DYRK1A is a pleiotropic protein kinase with diverse functions in cellular regulation, including cell cycle control, neuronal differentiation, and synaptic transmission. Enhanced activity and overexpression of DYRK1A have been linked to altered brain development and function in Down syndrome and neurodegenerative diseases such as Alzheimer’s disease. The β-carboline alkaloid harmine is a high affinity inhibitor of DYRK1A but suffers from the drawback of inhibiting monoamine oxidase A (MAO-A) with even higher potency. Here we characterized a series of novel harmine analogs with minimal or absent MAO-A inhibitory activity. We identified several inhibitors with submicromolar potencies for DYRK1A and selectivity for DYRK1A and DYRK1B over the related kinases DYRK2 and HIPK2. An optimized inhibitor, AnnH75, inhibited CLK1, CLK4, and haspin/GSG2 as the only off-targets in a panel of 300 protein kinases. In cellular assays, AnnH75 dose-dependently reduced the phosphorylation of three known DYRK1A substrates (SF3B1, SEPT4, and tau) without negative effects on cell viability. AnnH75 inhibited the cotranslational tyrosine autophosphorylation of DYRK1A and threonine phosphorylation of an exogenous substrate protein with similar potency. In conclusion, we have characterized an optimized β-carboline inhibitor as a highly selective chemical probe that complies with desirable properties of drug-like molecules and is suitable to interrogate the function of DYRK1A in biological studies. PMID:26192590

  2. Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.

    PubMed

    Rüben, Katharina; Wurzlbauer, Anne; Walte, Agnes; Sippl, Wolfgang; Bracher, Franz; Becker, Walter

    2015-01-01

    DYRK1A is a pleiotropic protein kinase with diverse functions in cellular regulation, including cell cycle control, neuronal differentiation, and synaptic transmission. Enhanced activity and overexpression of DYRK1A have been linked to altered brain development and function in Down syndrome and neurodegenerative diseases such as Alzheimer's disease. The β-carboline alkaloid harmine is a high affinity inhibitor of DYRK1A but suffers from the drawback of inhibiting monoamine oxidase A (MAO-A) with even higher potency. Here we characterized a series of novel harmine analogs with minimal or absent MAO-A inhibitory activity. We identified several inhibitors with submicromolar potencies for DYRK1A and selectivity for DYRK1A and DYRK1B over the related kinases DYRK2 and HIPK2. An optimized inhibitor, AnnH75, inhibited CLK1, CLK4, and haspin/GSG2 as the only off-targets in a panel of 300 protein kinases. In cellular assays, AnnH75 dose-dependently reduced the phosphorylation of three known DYRK1A substrates (SF3B1, SEPT4, and tau) without negative effects on cell viability. AnnH75 inhibited the cotranslational tyrosine autophosphorylation of DYRK1A and threonine phosphorylation of an exogenous substrate protein with similar potency. In conclusion, we have characterized an optimized β-carboline inhibitor as a highly selective chemical probe that complies with desirable properties of drug-like molecules and is suitable to interrogate the function of DYRK1A in biological studies. PMID:26192590

  3. Overcoming mutagenicity and ion channel activity: optimization of selective spleen tyrosine kinase inhibitors.

    PubMed

    Ellis, J Michael; Altman, Michael D; Bass, Alan; Butcher, John W; Byford, Alan J; Donofrio, Anthony; Galloway, Sheila; Haidle, Andrew M; Jewell, James; Kelly, Nancy; Leccese, Erica K; Lee, Sandra; Maddess, Matthew; Miller, J Richard; Moy, Lily Y; Osimboni, Ekundayo; Otte, Ryan D; Reddy, M Vijay; Spencer, Kerrie; Sun, Binyuan; Vincent, Stella H; Ward, Gwendolyn J; Woo, Grace H C; Yang, Chiming; Houshyar, Hani; Northrup, Alan B

    2015-02-26

    Development of a series of highly kinome-selective spleen tyrosine kinase (Syk) inhibitors with favorable druglike properties is described. Early leads were discovered through X-ray crystallographic analysis, and a systematic survey of cores within a selected chemical space focused on ligand binding efficiency. Attenuation of hERG ion channel activity inherent within the initial chemotype was guided through modulation of physicochemical properties including log D, PSA, and pKa. PSA proved most effective for prospective compound design. Further profiling of an advanced compound revealed bacterial mutagenicity in the Ames test using TA97a Salmonella strain, and subsequent study demonstrated that this mutagenicity was pervasive throughout the series. Identification of intercalation as a likely mechanism for the mutagenicity-enabled modification of the core scaffold. Implementation of a DNA binding assay as a prescreen and models in DNA allowed resolution of the mutagenicity risk, affording molecules with favorable potency, selectivity, pharmacokinetic, and off-target profiles. PMID:25625541

  4. Stochastic electrotransport selectively enhances the transport of highly electromobile molecules.

    PubMed

    Kim, Sung-Yon; Cho, Jae Hun; Murray, Evan; Bakh, Naveed; Choi, Heejin; Ohn, Kimberly; Ruelas, Luzdary; Hubbert, Austin; McCue, Meg; Vassallo, Sara L; Keller, Philipp J; Chung, Kwanghun

    2015-11-17

    Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1-3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion. PMID:26578787

  5. High Resolution K-Band Spectroscopy of Selected M Dwarfs

    NASA Astrophysics Data System (ADS)

    Nakajima, Tadashi

    2013-06-01

    We propose to obtain high-resolution K-band spectra of selected M dwarfs to study stellar properties such as effective temperature and metallicity. M dwarfs are under scrutiny as potential planet hosts. They have sufficiently low masses and small radii that exoplanets induce considerably larger reflex velocities and transit depths than an identical planet would around larger, more massive hosts. The low temperatures of M dwarfs imply short-period planets are in the habitable zone. However, due to the cool atmosphere, the characterization of M dwarfs at visible wavelengths has been rather difficult and the previously known stellar parameters have been rather crude. Recently a new method to use medium resolution K-band spectroscopy to determine the effective temperature and metallicity was devised. The purposes of this proposal is to examine the validity of the new method with a spectral resolution one order of magnitude higher and, if possible, to find a better method to determine the stellar properties.

  6. High Power Selective Laser Melting (HP SLM) of Aluminum Parts

    NASA Astrophysics Data System (ADS)

    Buchbinder, D.; Schleifenbaum, H.; Heidrich, S.; Meiners, W.; Bültmann, J.

    Selective Laser Melting (SLM) is one of the Additive Manufacturing (AM) technologies that enables the production of light weight structured components with series identical mechanical properties without the need for part specific tooling or downstream sintering processes, etc. Especially aluminum is suited for such eco-designed components due to its low weight and superior mechanical and chemical properties. However, SLM's state-of-the-art process and cost efficiency is not yet suited for series-production. In order to improve this efficiency it is indispensable to increase the build rate significantly. Thus, aluminum is qualified for high build rate applications using a new prototype machine tool including a 1 kW laser and a multi-beam system.

  7. High dispersion observations of selected regions in the Orion Nebula

    NASA Astrophysics Data System (ADS)

    Boeshaar, G. O.; Harvel, C. A.; Mallama, A. D.; Perry, P. M.; Thompson, R. W.; Turnrose, B.

    High resolution spectral observations were made of several regions of the Orion Nebula near theta (2) Ori A using the IUE. The positions were selected using a moderate spatial resolution map from a previous low dispersion IUE survery of this section of the nebula. With the SWP and LWR cameras, 28 pectra were obtained of the bright bar, three Taylor-Munch cloudlets, and several surrounding locations. Emission lines of He, C, N, O, Mg, and Si allow a characterization of these cloudlets and of the gas in and around the bar. Small aperture observations provide radial velocity information for the ultraviolet emission of these features. These data show ionization variations from region to region and are suggestive of stellar wind interactions between the cloudlets and theta(2) Ori A.

  8. Stochastic electrotransport selectively enhances the transport of highly electromobile molecules

    PubMed Central

    Kim, Sung-Yon; Cho, Jae Hun; Murray, Evan; Bakh, Naveed; Choi, Heejin; Ohn, Kimberly; Ruelas, Luzdary; Hubbert, Austin; McCue, Meg; Vassallo, Sara L.; Keller, Philipp J.; Chung, Kwanghun

    2015-01-01

    Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1–3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion. PMID:26578787

  9. Identification of selective and potent inhibitors of fibroblast activation protein and prolyl oligopeptidase.

    PubMed

    Poplawski, Sarah E; Lai, Jack H; Li, Youhua; Jin, Zhiping; Liu, Yuxin; Wu, Wengen; Wu, Yong; Zhou, Yuhong; Sudmeier, James L; Sanford, David G; Bachovchin, William W

    2013-05-01

    Fibroblast activation protein (FAP) is a serine protease selectively expressed on reactive stromal fibroblasts of epithelial carcinomas. It is widely believed to play a role in tumor invasion and metastasis and therefore to represent a potential new drug target for cancer. Investigation into its biological function, however, has been hampered by the current unavailability of selective inhibitors. The challenge has been in identifying inhibitors that are selective for FAP over both the dipeptidyl peptidases (DPPs), with which it shares exopeptidase specificity, and prolyl oligopeptidase (PREP), with which it shares endopeptidase specificity. Here, we report the first potent FAP inhibitor with selectivity over both the DPPs and PREP, N-(pyridine-4-carbonyl)-d-Ala-boroPro (ARI-3099, 6). We also report a similarly potent and selective PREP inhibitor, N-(pyridine-3-carbonyl)-Val-boroPro (ARI-3531, 22). Both are boronic acid based inhibitors, demonstrating that high selectivity can be achieved using this electrophile. The inhibitors are stable, easy to synthesize, and should prove to be useful in helping to elucidate the biological functions of these two unique and interesting enzymes, as well as their potential as drug targets. PMID:23594271

  10. Identification of Selective and Potent Inhibitors of Fibroblast Activation Protein and Prolyl Oligopeptidase

    PubMed Central

    Poplawski, Sarah E.; Lai, Jack H.; Li, Youhua; Jin, Zhiping; Liu, Yuxin; Wu, Wengen; Wu, Yong; Zhou, Yuhong; Sudmeier, James L.; Sanford, David G.; Bachovchin, William W.

    2014-01-01

    Fibroblast activation protein (FAP) is a serine protease selectively expressed on reactive stromal fibroblasts of epithelial carcinomas. It is widely believed to play a role in tumor invasion and metastasis and therefore to represent a potential new drug target for cancer. Investigation into its biological function, however, has been hampered by the current unavailability of selective inhibitors. The challenge has been in identifying inhibitors that are selective for FAP over both the dipeptidyl peptidases (DPPs), with which it shares exopeptidase specificity, and prolyl oligopeptidase (PREP), with which it shares endopeptidase specificity. Here, we report the first potent FAP inhibitor with selectivity over both the DPPs and PREP, N-(pyridine-4-carbonyl)-d-Ala-boroPro (ARI-3099, 6). We also report a similarly potent and selective PREP inhibitor, N-(pyridine-3-carbonyl)-Val-boroPro (ARI-3531, 22). Both are boronic acid based inhibitors, demonstrating that high selectivity can be achieved using this electrophile. The inhibitors are stable, easy to synthesize, and should prove to be useful in helping to elucidate the biological functions of these two unique and interesting enzymes, as well as their potential as drug targets. PMID:23594271

  11. Optimum selection of high performance mirror substrates for diamond finishing

    NASA Astrophysics Data System (ADS)

    Woodard, Kenneth S.; Comstock, Lovell E.; Wamboldt, Leonard; Sutherland, James S.

    2016-05-01

    Due to advances in manufacturing processes, the substrate options for high performance diamond machined mirrors are expanding. Fewer compromises have to be made to achieve the needed weight, stiffness and finish while maintaining reasonable costs. In addition to the traditional mirror materials like aluminum and beryllium, there are some less common materials that can now be included in the trade space that fill the cost and performance continuum between wrought aluminum and beryllium mirrors. Aluminum and beryllium, respectively, had been the low cost/fair performance and very high cost/very high performance bounds for substrate selection. These additional substrates provide multiple near net shape blank options and processes, mostly within these bounds, that can be considered in a mirror cost versus performance trade analysis. This paper will include a summary of some advances in manufacturing processes that provide more substrate options for diamond machined mirrors with some sample performance analysis and data. This is merged with the traditional substrate options to illustrate the now larger mirror substrate trade space. Some benchmark structural analysis is provided to back up a generic mirror design trade study.

  12. Selective nonoperative management of high grade splenic trauma.

    PubMed

    Branco, Bernardino C; Tang, Andrew L; Rhee, Peter; Fraga, Gustavo Pereira; Nascimento, Bartolomeu; Rizoli, Sandro; O'Keeffe, Terence

    2013-01-01

    The "Evidence-based Telemedicine - Trauma & Acute Care Surgery" (EBT-TACS) Journal Club performed a critical review of the literature and selected three up-to-date articles on the management of splenic trauma. Our focus was on high-grade splenic injuries, defined as AAST injury grade III-V. The first paper was an update of the 2003 Eastern Association for the Surgery of Trauma (EAST) practice management guidelines for nonoperative management of injury to the spleen. The second paper was an American Association for the Surgery of Trauma (AAST) 2012 plenary paper evaluating the predictive role of contrast blush on CT scan in AAST grade IV and V splenic injuries. Our last article was from Europe and investigates the effects of angioembolization of splenic artery on splenic function after high-grade splenic trauma (AAST grade III-V). The EBT-TACS Journal Club elaborated conclusions and recommendations for the management of high-grade splenic trauma. PMID:23912375

  13. Activity Cycles in Stars with Highly Active Chromospheres

    NASA Astrophysics Data System (ADS)

    Guinan, Edward F.

    The extended lifetime of the IUE satellite has provided an unique and unanticipated opportunity to examine the long-term evolution of magnetic activity on active chromospheric stars. We propose to obtain further IUE observations of the highly active RS CVn stars V711 Tauri, lambda Andromedae, II Pegasi, and UX Arietis in conjunction with groundbased optical and radio observations, and possibly ROSAT X-ray observations. In addition we would continue IUE observations of the unusual rapidly rotating early G giant, FK Comae, which, although not in the RS CVn category, shares a similarly high level of magnetic activity. These five stars have the most extensive IUE archival coverage for stars of their type and have almost continuous ground-based photometric coverage from about 1975 onward. We aim to trace the long-term development of magnetic activity on these stars: a detailed study of the UV emission-like fluxes will enable us to follow the variations in chromospheric and transition-region activity over an interval of 12-16 years. Optical observations reveal variations in photospheric (starspot) activity: the starspot regions are large (up to 30% of the stellar surface) and vary significantly with time. The main aim of the proposed research is to examine the relationship between chromospheric, transition-region, and photospheric active regions. Elucidation of the role of white-light faculae vis-a-vis spots in effecting stellar irradiance changes is also desirable.

  14. Educational Activity Sites for High School Students

    ERIC Educational Resources Information Center

    Troutner, Joanne

    2005-01-01

    Finding quality Internet resources for high school students is a continuing challenge. Several high-quality web sites are presented for educators and students. These sites offer activities to learn how an art conservator looks at paintings, create a newspaper, research and develop an end product, build geometry and physics skills, explore science…

  15. Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor.

    PubMed

    Henderson, Jaclyn L; Kormos, Bethany L; Hayward, Matthew M; Coffman, Karen J; Jasti, Jayasankar; Kurumbail, Ravi G; Wager, Travis T; Verhoest, Patrick R; Noell, G Stephen; Chen, Yi; Needle, Elie; Berger, Zdenek; Steyn, Stefanus J; Houle, Christopher; Hirst, Warren D; Galatsis, Paul

    2015-01-01

    Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD) by genome-wide association studies (GWAS). The most common LRRK2 mutation, G2019S, which is relatively rare in the total population, gives rise to increased kinase activity. As such, LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the discovery and optimization of a novel series of potent LRRK2 inhibitors, focusing on improving kinome selectivity using a surrogate crystallography approach. This resulted in the identification of 14 (PF-06447475), a highly potent, brain penetrant and selective LRRK2 inhibitor which has been further profiled in in vivo safety and pharmacodynamic studies. PMID:25353650

  16. Selective photo-activation analysis with laser-driven x-rays

    NASA Astrophysics Data System (ADS)

    Banerjee, Sudeep; Golovin, Grigory; Powers, Nathan; Liu, Cheng; Chen, Shouyuan; Petersen, Chad; Zhang, Jun; Ghebregziabher, Isaac; Zhao, Baozhen; Brown, Kevin; Mills, Jared; Umstadter, Donald; Haden, Dan; Silano, Jack; Karwowski, Hugon

    2013-04-01

    We discuss a technique for the identification of nuclear isotopes by selective photo-activation analysis. A narrow divergence beam of high-energy photons is produced when a laser driven electron beam Compton backscatters off a counter-propagating high-intensity laser pulse. The x-rays from this compact laser-driven synchrotron light source are MeV energy, narrow-bandwidth, tunable, polarized, and bright (10^8 photons s-1). Such characteristics make these x-rays well-suited for nuclear interrogation by means of triggering (γ,f) and (γ,xn) reactions. The narrow bandwidth of the x-ray light can be exploited to selectively activate nuclei with isotopic sensitivity, without causing unwanted background from collateral activation. Additionally, the polarized nature of the x-rays can be used to study anisotropy of neutron emission, for precise identification of isotopes. Activation by laser-driven synchrotron x-rays will be compared with activation by bremsstrahlung.

  17. High Speed Data Bus Active Coupler

    NASA Astrophysics Data System (ADS)

    Herrmann, James J.

    The author discusses the HSDB (high speed data bus) active coupler which provides a typical 13-dB power margin for HSDB systems installed in military aircraft. This high-power margin ensures reliable HSDB operation through fiber-optic component degradation. The active coupler performs optical amplification and signal reshaping functions such that an incoming signal is modified only in amplitude. Signal distortion and jitter are removed by a retiming ASIC (application-specific integrated circuit). The active coupler is modular in design, and plug-in growth for a 38 x 38 user interface is available. The active coupler achieves better than -27 dBm sensitivity at 5 x 10 exp -11 bit error rate and outputs -8 to -12 dBm optical power. The active coupler unit weighs only 6.25 lbs and has a predicted mean time between failure of over 21,000 h.

  18. Excellent activity and selectivity of Cu-SSZ-13 in the selective catalytic reduction of NOx with NH3

    SciTech Connect

    Kwak, Ja Hun; Tonkyn, Russell G.; Kim, Do Heui; Szanyi, Janos; Peden, Charles HF

    2010-10-21

    Superior activity and selectivity of a Cu ion-exchanged SSZ-13 zeolite in the selective catalytic reduction (SCR) of NOx with NH3 were observed, in comparison to Cu-beta and Cu-ZSM-5 zeolites. Cu-SSZ-13 was not only more active in the NOx SCR reaction over the entire temperature range studied (up to 550 °C), but also more selective toward nitrogen formation, resulting in significantly lower amounts of NOx by-products (i.e., NO2 and N2O) than the other two zeolites. In addition, Cu-SSZ-13 demonstrated the highest activity and N2 formation selectivity in the oxidation of NH3. The results of this study strongly suggest that Cu-SSZ-13 is a promising candidate as a catalyst for NOx SCR with great potential in after-treatment systems for either mobile or stationary sources.

  19. 3-Amido-3-aryl-piperidines: A Novel Class of Potent, Selective, and Orally Active GlyT1 Inhibitors

    PubMed Central

    2014-01-01

    3-Amido-3-aryl-piperidines were discovered as a novel structural class of GlyT1 inhibitors. The structure–activity relationship, which was developed, led to the identification of highly potent compounds exhibiting excellent selectivity against the GlyT2 isoform, drug-like properties, and in vivo activity after oral administration. PMID:24900853

  20. A controlled, randomized trial of highly selective vagotomy versus selective vagotomy and pyloroplasty in the treatment of duodenal ulcer.

    PubMed Central

    Kronborg, O; Madsen, P

    1975-01-01

    The results of highly selective vagotomy without drainage and selective vagotomy with pyloroplasty for duodenal ulcer were compared in a randomized, controlled trial of a series of 100 patients. The frequency of dumping, diarrhoea, and epigastric fullness was significantly lower after highly selective (6, 6, and 8 percent) than after selective vagotomy (30, 20, and 28 percent) one year after the operations. Recurrent and persisting duodenal ulcers appearing from one to four years after the operations were significantly more frequent after highly selective (22 percent) than after selective vagotomy (8 percent). No significant relationships were found between recurrent ulceration and gastric acid secretion measurements after the two operations. The Hollander response was early positive in 28 percent and late positive in 30 percent of the patients subjected to highly selective vagotomy, while the corresponding figures after selective vagotomy were 26 and 32 percent. The overall clinical results of the two operations were not different according to the classification of Visick. Excluding the patients with recurrence resulted in significantly better clinical results after highly selective vagotomy. PMID:1093947

  1. Efficacy of oxonia active against selected spore formers.

    PubMed

    Blakistone, B; Chuyate, R; Kautter, D; Charbonneau, J; Suit, K

    1999-03-01

    Alternatives to hydrogen peroxide are being sought for use in aseptic packaging systems because this sterilant is efficacious at temperatures higher than some of the newer packaging materials can tolerate. Earlier in this century, peracetic acid was known to be bactericidal, sporicidal, and virucidal but was not widely used because of handling, toxicity, and stability problems. Sanitizer suppliers have capitalized on the efficacy of hydrogen peroxide, acetic acid, and peracetic acid stabilized with a sequestering agent. Formulations have been improved and marketed as Oxonia Active, and its use as an alternative sterilant to hydrogen peroxide merits evaluation. Oxonia was assessed at a concentration of 2% and a temperature of 40 degrees C against a number of spore-forming organisms, including foodborne pathogens. Spores tested in aqueous suspension showed an order of sensitivity (least to greatest) to Oxonia as follows: Bacillus cereus > B. subtilis A > B. stearothermophilus > B. subtilis var. globigii > B. coagulans > Clostridium sporogenes (PA3679) > C. butyricum > C. botulinum type B (nonproteolytic) > C. botulinum type B (proteolytic) = C. botulinum type A = C. botulinum type E. B. subtilis A and B. stearothermophilus spores tested in the dry state were less sensitive to Oxonia than when tested in aqueous suspension. B. cereus, a foodborne pathogen, proved to be markedly less sensitive to Oxonia under the described test conditions. The decreased sensitivity to Oxonia by the foodborne pathogen B. cereus raises concern about the efficacy of the sterilant for aseptic packaging of low-acid foods. Further work will be needed to determine if this decreased sensitivity is an inherent property of the organism that affords unusual protection against Oxonia or if the challenge parameters selected were at the minimum conditions for efficacy. PMID:10090246

  2. Melanogenesis and Antityrosinase Activity of Selected South African Plants

    PubMed Central

    Mapunya, Manyatja Brenda; Nikolova, Roumiana Vassileva; Lall, Namrita

    2012-01-01

    Melanin is the pigment that is responsible for the colour of eyes, hair, and skin in humans. Tyrosinase is known to be the key enzyme in melanin biosynthesis. Overactivity of this enzyme leads to dermatological disorders such as age spots, melanoma and sites of actinic damage. Ten plants belonging to four families (Asphodelaceae, Anacardiaceae, Oleaceae, and Rutaceae) were investigated for their effect on tyrosinase using both L-tyrosine and L-DOPA as substrates. Ethanol leaf extracts (500 μg/mL) of Aloe ferox, Aloe aculeata, Aloe pretoriensis, and Aloe sessiliflora showed 60%, 31%, 17%, and 13% inhibition of tyrosinase activity respectively, when L-tyrosine was used as a substrate. Harpephyllum caffrum (leaves) at a concentration of 500 μg/mL had an inhibitory effect of 70% on tyrosinase when L-DOPA was used as a substrate. The IC50 of Harpephyllum caffrum (leaves and bark) were found to be 51 ± 0.002 and 40 ± 0.035 μg/mL, respectively. Following the results obtained from the tyrosinase assay, extracts from Harpephyllum caffrum were selected for further testing on their effect on melanin production and their cytotoxicity on melanocytes in vitro. The IC50 of both extracts was found to be 6.25 μg/mL for melanocyte cells. Bark extract of Harpephyllum caffrum showed 26% reduction in melanin content of melanocyte cells at a concentration of 6.25 μg/mL. The leaf extract of this plant showed some toxicity on melanocyte cells. Therefore, the bark extract of Harpephyllum caffrum could be considered as an antityrosinase agent for dermatological disorders such as age spots and melasoma. PMID:22611429

  3. Acoustic gaze adjustments during active target selection in echolocating porpoises.

    PubMed

    Wisniewska, Danuta Maria; Johnson, Mark; Beedholm, Kristian; Wahlberg, Magnus; Madsen, Peter Teglberg

    2012-12-15

    Visually dominant animals use gaze adjustments to organize perceptual inputs for cognitive processing. Thereby they manage the massive sensory load from complex and noisy scenes. Echolocation, as an active sensory system, may provide more opportunities to control such information flow by adjusting the properties of the sound source. However, most studies of toothed whale echolocation have involved stationed animals in static auditory scenes for which dynamic information control is unnecessary. To mimic conditions in the wild, we designed an experiment with captive, free-swimming harbor porpoises tasked with discriminating between two hydrophone-equipped targets and closing in on the selected target; this allowed us to gain insight into how porpoises adjust their acoustic gaze in a multi-target dynamic scene. By means of synchronized cameras, an acoustic tag and on-target hydrophone recordings we demonstrate that porpoises employ both beam direction control and range-dependent changes in output levels and pulse intervals to accommodate their changing spatial relationship with objects of immediate interest. We further show that, when switching attention to another target, porpoises can set their depth of gaze accurately for the new target location. In combination, these observations imply that porpoises exert precise vocal-motor control that is tied to spatial perception akin to visual accommodation. Finally, we demonstrate that at short target ranges porpoises narrow their depth of gaze dramatically by adjusting their output so as to focus on a single target. This suggests that echolocating porpoises switch from a deliberative mode of sensorimotor operation to a reactive mode when they are close to a target. PMID:23175527

  4. Active surveillance for prostate cancer: patient selection and management

    PubMed Central

    Klotz, L.

    2010-01-01

    Screening for prostate cancer using prostate-specific antigen (psa) has been appealing. However, the significant associated decline in prostate cancer mortality comes at the cost of a very high rate of diagnosis, and many patients with indolent, non-life-threatening cancer are exposed to the risk of significant side effects from radical treatment. Most men with favourable-risk prostate cancer are not destined to die of their disease, even in the absence of treatment. The challenge is to identify the subset that harbour more aggressive disease early enough that curative therapy is still a possibility, thereby allowing the others to enjoy improved quality of life, free from the side effects of treatment. This article reviews current research into active surveillance in favourable-risk disease and some of the issues that arise when prostate cancer is monitored rather than being treated immediately. PMID:20882126

  5. BVRI Standard Stars Near Selected Very High Energy Blazars

    NASA Astrophysics Data System (ADS)

    Pace, Cameron; Pearson, R.; Moody, J. W.; Joner, M. D.

    2010-01-01

    The nature of blazar variability is a test of the standard model of Active Galactic Nuclei (AGN). To be useful, measurements of blazar intensity must be compared to standard stars that have been tied into a standard photometric system. To aid the long-term study of blazars, we have measured BVRI magnitudes for six to eight comparison stars near the eight northern Very High Energy (VHE) blazars published by Horan & Weekes (2008). Our magnitudes have been tied into the standard stars published by Landolt (2009). The stars we have measured bracket the expected range of magnitudes between active and inactive phases of the blazars. Preliminary analysis of our results indicates an RMS error better than 0.02 magnitudes in all bands. Our measurements of comparison stars generally agree very well with previously published values. We are grateful to Brigham Young University and the National Science Foundation for their financial support.

  6. An effective selection method for low-mass active black holes and first spectroscopic identification

    NASA Astrophysics Data System (ADS)

    Morokuma, Tomoki; Tominaga, Nozomu; Tanaka, Masaomi; Yasuda, Naoki; Furusawa, Hisanori; Taniguchi, Yuki; Kato, Takahiro; Jiang, Ji-an; Nagao, Tohru; Kuncarayakti, Hanindyo; Morokuma-Matsui, Kana; Ikeda, Hiroyuki; Blinnikov, Sergei; Nomoto, Ken'ichi; Kokubo, Mitsuru; Doi, Mamoru

    2016-06-01

    We present a new method for effectively selecting objects which may be low-mass active black holes (BHs) at galaxy centers using high-cadence optical imaging data, and our first spectroscopic identification of an active 2.7 × 106 M⊙ BH at z = 0.164. This active BH was originally selected due to its rapid optical variability, from a few hours to a day, based on Subaru Hyper Suprime-Cam g-band imaging data taken with a 1 hr cadence. Broad and narrow Hα lines and many other emission ones are detected in our optical spectra taken with Subaru FOCAS, and the BH mass is measured via the broad Hα emission line width (1880 km s-1) and luminosity (4.2 × 1040 erg s-1) after careful correction to the atmospheric absorption around 7580-7720 Å. We measure the Eddington ratio and find it to be as low as 0.05, considerably smaller than those in a previous SDSS sample with similar BH mass and redshift, which indicates one of the special potentials of our Subaru survey. The g - r color and morphology of the extended component indicate that the host galaxy is a star-forming galaxy. We also show the effectiveness of our variability selection for low-mass active BHs.

  7. An effective selection method for low-mass active black holes and first spectroscopic identification

    NASA Astrophysics Data System (ADS)

    Morokuma, Tomoki; Tominaga, Nozomu; Tanaka, Masaomi; Yasuda, Naoki; Furusawa, Hisanori; Taniguchi, Yuki; Kato, Takahiro; Jiang, Ji-an; Nagao, Tohru; Kuncarayakti, Hanindyo; Morokuma-Matsui, Kana; Ikeda, Hiroyuki; Blinnikov, Sergei; Nomoto, Ken'ichi; Kokubo, Mitsuru; Doi, Mamoru

    2016-04-01

    We present a new method for effectively selecting objects which may be low-mass active black holes (BHs) at galaxy centers using high-cadence optical imaging data, and our first spectroscopic identification of an active 2.7 × 106 M⊙ BH at z = 0.164. This active BH was originally selected due to its rapid optical variability, from a few hours to a day, based on Subaru Hyper Suprime-Cam g-band imaging data taken with a 1 hr cadence. Broad and narrow Hα lines and many other emission ones are detected in our optical spectra taken with Subaru FOCAS, and the BH mass is measured via the broad Hα emission line width (1880 km s-1) and luminosity (4.2 × 1040 erg s-1) after careful correction to the atmospheric absorption around 7580-7720 Å. We measure the Eddington ratio and find it to be as low as 0.05, considerably smaller than those in a previous SDSS sample with similar BH mass and redshift, which indicates one of the special potentials of our Subaru survey. The g - r color and morphology of the extended component indicate that the host galaxy is a star-forming galaxy. We also show the effectiveness of our variability selection for low-mass active BHs.

  8. 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

  9. ZnO nanopellets have selective anticancer activity.

    PubMed

    Gopala Krishna, Prashanth; Paduvarahalli Ananthaswamy, Prashanth; Yadavalli, Tejabhiram; Bhangi Mutta, Nagabhushana; Sannaiah, Ananda; Shivanna, Yogisha

    2016-05-01

    This research work presents the synthesis of ZnO nanopellets (ZNPs) by low temperature hydrothermal approach and evaluation of their antibacterial activity, cytotoxicity in vitro and in vivo. Structural and morphological studies conducted on the sample reveal hexagonal ZNPs in the size range of 250-500nm. Surface area measurements showed high porosity of the sample compared to conventional ZnO nanoparticles. Antimicrobial studies revealed their bactericidal nature against both Gram-negative and Gram-positive bacteria. Furthermore, to better understand the parameters that affect the interactions between our ZNPs and mammalian cells, and thus their biocompatibility, we have examined the impact of cell culture conditions as well as of material properties on cytotoxicity by DPPH, blood hemolysis and MTT assay. The results showed good antioxidant capacity and biocompatibility of ZNPs at higher concentrations. MTT assay revealed the anticancer activity of ZNPs against prostate and breast cancer cell lines. Acute toxicity tests on Swiss albino mice showed no evident toxicity over a 14 days period. PMID:26952499

  10. Grazing by protozoa as selection factor for activated sludge bacteria.

    PubMed

    Güde, H

    1979-09-01

    In continuous culture enrichments that were inoculated with activated sludge and were fed with polymeric substrates, freely dispersed single-celled bacteria belonging to theCytophaga group dominated among the initial populations, irrespective of the activated sludge source. These populations were grazed by flagellated protozoa which after several days reached high cell densities. Other morphologic bacterial groups such as spiral-shaped or filamentous bacteria then became dominant. In defined mixed culture experiments with bacterial isolates from the enrichment cultures, it was shown that a "grazing-resistant"Microcyclus strain outgrew aCytophaga strain in the presence of grazing protozoa. In contrast, theCytophaga strain competed successfully with theMicrocyclus strain and with other "grazing-resistant" strains under protozoa-free conditions. Furthermore, it was demonstrated that assumed grazing resistance factors such as floccing or filamentous growth were lost by some of the strains when they were grown for several generations in continuous culture under the same conditions, but in the absence of protozoa. PMID:24232496

  11. Dual fluorescent molecular substrates selectively report the activation, sustainability and reversibility of cellular PKB/Akt activity

    NASA Astrophysics Data System (ADS)

    Shen, Duanwen; Bai, Mingfeng; Tang, Rui; Xu, Baogang; Ju, Xiaoming; Pestell, Richard G.; Achilefu, Samuel

    2013-04-01

    Using a newly developed near-infrared (NIR) dye that fluoresces at two different wavelengths (dichromic fluorescence, DCF), we discovered a new fluorescent substrate for Akt, also known as protein kinase B, and a method to quantitatively report this enzyme's activity in real time. Upon insulin activation of cellular Akt, the enzyme multi-phosphorylated a single serine residue of a diserine DCF substrate in a time-dependent manner, culminating in monophospho- to triphospho-serine products. The NIR DCF probe was highly selective for the Akt1 isoform, which was demonstrated using Akt1 knockout cells derived from MMTV-ErbB2 transgenic mice. The DCF mechanism provides unparalleled potential to assess the stimulation, sustainability, and reversibility of Akt activation longitudinally. Importantly, NIR fluorescence provides a pathway to translate findings from cells to living organisms, a condition that could eventually facilitate the use of these probes in humans.

  12. 40 CFR 60.2115 - What if I do not use a wet scrubber, fabric filter, activated carbon injection, selective...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., fabric filter, activated carbon injection, selective noncatalytic reduction, an electrostatic... filter, activated carbon injection, selective noncatalytic reduction, an electrostatic precipitator, or a... than a wet scrubber, activated carbon injection, selective noncatalytic reduction, fabric filter,...

  13. Antiplasmodial activity of selected medicinal plants used to treat malaria in Ghana.

    PubMed

    Komlaga, Gustav; Cojean, Sandrine; Dickson, Rita A; Beniddir, Mehdi A; Suyyagh-Albouz, Soulaf; Mensah, Merlin L K; Agyare, Christian; Champy, Pierre; Loiseau, Philippe M

    2016-08-01

    The use of medicinal plants for the treatment of diseases including malaria is commonplace in Ghanaian traditional medicine, though the therapeutic claims for most plants remain unvalidated. Antiplasmodial activity of the aqueous extracts and successively obtained petroleum ether, ethyl acetate and methanol fractions of the whole Phyllanthus fraternus plant, the leaves of Tectona grandis, Terminalia ivorensis and Bambusa vulgaris, and roots of Senna siamea were studied against Plasmodium falciparum chloroquine-sensitive 3D7 and chloroquine-resistant W2 strains. The aqueous extracts were assessed against human umbilical vein endothelial cells (HUVECs) for cytotoxicity, and the organic solvent fractions against human O(+) erythrocytes for haemolytic effect. Both extracts and fractions demonstrated antiplasmodial activity to varied extents. The aqueous extract of T. ivorensis was the most active (3D7, IC50 0.64 ± 0.14; and W2, IC50 10.52 ± 3.55 μg/mL), and together with P. fraternus displayed cytotoxicity (CC50 6.25 ± 0.40 and 31.11 ± 3.31 μg/mL, respectively). The aqueous extracts were generally selective for 3D7 strain of P. falciparum (selectivity indexes (SIs) ≥3.48) but only that of S. siamea was selective for the W2 strain (SI > 2.1). The organic solvent fractions also displayed antiplasmodial activity with the methanol fractions of P. fraternus and T. grandis, and the fractions of B. vulgaris showing activity with IC50 below 1 μg/mL against P. falciparum 3D7 strain; some fractions showed haemolytic effect but with low to high selectivity indexes (SI ≥ 4). The results while justifying the traditional use of the plant materials in the treatment of malaria, however, suggest their cautious use. PMID:27174028

  14. Resting high frequency heart rate variability selectively predicts cooperative behavior.

    PubMed

    Beffara, Brice; Bret, Amélie G; Vermeulen, Nicolas; Mermillod, Martial

    2016-10-01

    This study explores whether the vagal connection between the heart and the brain is involved in prosocial behaviors. The Polyvagal Theory postulates that vagal activity underlies prosocial tendencies. Even if several results suggest that vagal activity is associated with prosocial behaviors, none of them used behavioral measures of prosociality to establish this relationship. We recorded the resting state vagal activity (reflected by High Frequency Heart Rate Variability, HF-HRV) of 48 (42 suitale for analysis) healthy human adults and measured their level of cooperation during a hawk-dove game. We also manipulated the consequence of mutual defection in the hawk-dove game (severe vs. moderate). Results show that HF-HRV is positively and linearly related to cooperation level, but only when the consequence of mutual defection is severe (compared to moderate). This supports that i) prosocial behaviors are likely to be underpinned by vagal functioning ii) physiological disposition to cooperate interacts with environmental context. We discuss these results within the theoretical framework of the Polyvagal Theory. PMID:27343804

  15. Structure-Activity Relationships for the Antifungal Activity of Selective Estrogen Receptor Antagonists Related to Tamoxifen

    PubMed Central

    Butts, Arielle; Martin, Jennifer A.; DiDone, Louis; Bradley, Erin K.; Mutz, Mitchell; Krysan, Damian J.

    2015-01-01

    Cryptococcosis is one of the most important invasive fungal infections and is a significant contributor to the mortality associated with HIV/AIDS. As part of our program to repurpose molecules related to the selective estrogen receptor modulator (SERM) tamoxifen as anti-cryptococcal agents, we have explored the structure-activity relationships of a set of structurally diverse SERMs and tamoxifen derivatives. Our data provide the first insights into the structural requirements for the antifungal activity of this scaffold. Three key molecular characteristics affecting anti-cryptococcal activity emerged from our studies: 1) the presence of an alkylamino group tethered to one of the aromatic rings of the triphenylethylene core; 2) an appropriately sized aliphatic substituent at the 2 position of the ethylene moiety; and 3) electronegative substituents on the aromatic rings modestly improved activity. Using a cell-based assay of calmodulin antagonism, we found that the anti-cryptococcal activity of the scaffold correlates with calmodulin inhibition. Finally, we developed a homology model of C. neoformans calmodulin and used it to rationalize the structural basis for the activity of these molecules. Taken together, these data and models provide a basis for the further optimization of this promising anti-cryptococcal scaffold. PMID:26016941

  16. Dynamic model for selective metabolic activation in chemical carcinogenesis

    SciTech Connect

    Selkirk, J.K.; MacLeod, M.C.

    1980-01-01

    Theoretical calculations predict the relative ease of formation of carbonium ions from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene-9,10-oxide or from either of the 2 symmetrical bay regions of B(e)P, and suggest their attraction to cellular nucleophiles. When both isomers were metabolized by hamster embryo fibroblasts (HEF) and the products analyzed, the results showed that the probable reason for benzo(e)pyrene's lack of carcinogenicity was its metabolic preference to attack the molecule away from the bay-region area. Particularly striking was the absence of any evidence for the formation of a significant amount of B(e)P-9,10-dihydrodiol. This suggests a metabolic basis for the relative lack of carcinogenic and mutagenic activity of B(e)P. The reason for this is not clear but may be due to physical or chemical factors such as membrane solubility or stereochemical requirements of the active site of the enzyme. The bay-region theory of PAH carcinogenesis predicts that carbonium ion formation from 9,10-dihydro-9,10-dihydroxybenzo(e)pyrene-11, 12-oxide, if formed, would be energetically favorable. Thus, the inability of HEF and microcomes to form B(e)P-9,10-dihydrodiol, the precursor of its potentially highly reactive diol-epoxide, would explain the relative inertness of B(e)P in several biological systems. As the subtle biochemical interactions of the various carcinogen intermediates become clarified, it becomes apparent that susceptibility and resistance to malignant transformation are based on a complex set of both chemical and physical parameters. It is becoming clear that metabolism kinetics, membrane interaction, and the role of nuclear metabolism help dictate the passage of the carcinogen and its reactive intermediates into and through the metabolic machinery of the cell. (ERB)

  17. Mycobactericidal activity of selected disinfectants using a quantitative suspension test.

    PubMed

    Griffiths, P A; Babb, J R; Fraise, A P

    1999-02-01

    In this study, a quantitative suspension test carried out under both clean and dirty conditions was used to assess the activity of various instrument and environmental disinfectants against the type strain NCTC 946 and an endoscope washer disinfector isolate of Mycobacterium chelonae, Mycobacterium fortuitum NCTC 10,394, Mycobacterium tuberculosis H37 Rv NCTC 7416 and a clinical isolate of Mycobacterium avium-intracellulare (MAI). The disinfectants tested were; a chlorine releasing agent, sodium dichloroisocyanurate (NaDCC) at 1000 ppm and 10,000 ppm av Cl; chlorine dioxide at 1100 ppm av ClO2 (Tristel, MediChem International Limited); 70% industrial methylated spirits (IMS); 2% alkaline glutaraldehyde (Asep, Galan); 10% succinedialdehyde and formaldehyde mixture (Gigasept, Schulke & Mayr); 0.35% peracetic acid (NuCidex, Johnson & Johnson); and a peroxygen compound at 1% and 3% (Virkon, Antec International). Results showed that the clinical isolate of MAI was much more resistant than M. tuberculosis to all the disinfectants, while the type strains of M. chelonae and M. fortuitum were far more sensitive. The washer disinfector isolate of M. chelonae was extremely resistant to 2% alkaline activated glutaraldehyde and appeared to be slightly more resistant than the type strain to Nu-Cidex, Gigasept, Virkon and the lower concentration of NaDCC. This study has shown peracetic acid (Nu-Cidex), chlorine dioxide (Tristel), alcohol (IMS) and high concentrations of a chlorine releasing agent (NaDCC) are rapidly mycobactericidal. Glutaraldehyde, although effective, is a slow mycobactericide. Gigasept and Virkon are poor mycobactericidal agents and are not therefore recommended for instruments or spillage if mycobacteria are likely to be present. PMID:10063473

  18. Active insecticides for Diaphania hyalinata selective for the natural enemy Solenopsis saevissima.

    PubMed

    Aguiar, Alex R; Alvarenga, Elson S; Lopes, Mayara C; Santos, Izailda B Dos; Galdino, Tarcisio V; Picanço, Marcelo C

    2016-09-01

    The objective of this study was to determine the toxicity of the nine synthetic dienamides against the insect pest Diaphania hyalinata (melonworm) and the selectivity of these substances for the predator Solenopsis saevissima (fire ant). Four bioassays were conducted. To begin with, the dienamides that caused high mortality of D. hyalinata have been selected. In the second bioassay the dose-mortality curves of the selected dienamides have been constructed. In the third bioassay, the survival curves for D. hyalinata and the elapsed time to kill 50% of their population have been determined. In the fourth biological test, the selectivity of the substances to the predator S. saevissima has been evaluated. The most active (2E,4E)-N-butylhexa-2,4-dienamide 3d has killed 95% of the melonworm, D. hyalinata, and less than 10% of the natural enemy S. saevissima. The results presented by this compound are superior to the outcome displayed by the commercial insecticide Malathion®. Three of the dienamides prepared in this manuscript have proven to be selective in killing the pest, but not the beneficial insect. PMID:27192015

  19. Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation*

    PubMed Central

    Alvarez-Flores, Miryam Paola; Furlin, Daniel; Ramos, Oscar H. P.; Balan, Andrea; Konno, Katsuhiro; Chudzinski-Tavassi, Ana Marisa

    2011-01-01

    Envenoming by the contact of human skin with Lonomia obliqua caterpillars promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy. Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of L. obliqua that is probably partially responsible for the observed syndrome because it activates factor X and is recognized by an effective antilonomic serum. Here we unveil the proteolytic activity of Losac and demonstrate the feasibility of its recombinant production. On the other hand, Losac has no homology to known proteases, but it can be inhibited by PMSF, a serine protease inhibitor. Instead, it shows closer homology to members of the hemolin family of proteins, a group of cell adhesion molecules. The recombinant protein (rLosac) shortened the coagulation time of normal and deficient plasmas, whereas it was ineffective in factor X-deficient plasma unless reconstituted with this protein. rLosac was able to activate factor X in a dose- and time-dependent manner but not γ-carboxyglutamic acid domainless factor X. Moreover, phospholipids and calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or fibrinogen, indicating its specificity for blood coagulation activation. Linear double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics. Cleavage of factor X by rLosac resulted in fragments that are compatible with those generated by RVV-X (a well known factor X activator). Together, our results validate Losac as the first protein from the hemolin family exhibiting procoagulant activity through selective proteolysis on coagulation factor X. PMID:21177860

  20. Extensive training leads to temporal and spatial shifts of cortical activity underlying visual category selectivity.

    PubMed

    Kietzmann, Tim C; Ehinger, Benedikt V; Porada, Danja; Engel, Andreas K; König, Peter

    2016-07-01

    The human visual system is able to distinguish naturally occurring categories with exceptional speed and accuracy. At the same time, it exhibits substantial plasticity, permitting the seamless and fast learning of entirely novel categories. Here we investigate the interplay of these two processes by asking how category selectivity emerges and develops from initial to extended category learning. For this purpose, we combine a rapid event-related MEG adaptation paradigm, an extension of fMRI adaptation to high temporal resolution, a novel spatiotemporal analysis approach to separate adaptation effects from other effect origins, and source localization. The results demonstrate a spatiotemporal shift of cortical activity underlying category selectivity: after initial category acquisition, the onset of category selectivity was observed starting at 275ms together with stronger activity in prefrontal cortex. Following extensive training over 22 sessions, adding up to more than 16.600 trials, the earliest category effects occurred at a markedly shorter latency of 113ms and were accompanied by stronger occipitotemporal activity. Our results suggest that the brain balances plasticity and efficiency by relying on different mechanisms to recognize new and re-occurring categories. PMID:27063060

  1. Energy Expenditure of Selected Household Activities during Pregnancy

    ERIC Educational Resources Information Center

    Chasan-Taber, Lisa; Freedson, Patty S.; Roberts, Dawn E.; Schmidt, Michael D.; Fragala, Maren S.

    2007-01-01

    Accurately measuring pregnancy physical activity is critical to assess the percentage of pregnant women meeting the American College of Obstetricians and Gynecologists (ACOG) guidelines. In addition, valid assessment of pregnancy physical activity is important for epidemiologic studies assessing the relationship between physical activity and…

  2. Chemical Engineering of Enzymes: Altered Catalytic Activity, Predictable Selectivity and Exceptional Stability of the Semisynthetic Peroxidase Seleno-Subtilisin

    NASA Astrophysics Data System (ADS)

    Häring, Dietmar; Schreier, Peter

    The increasing demand for enzymes as highly selective, mild, and environmentally benign catalysts is often limited by the lack of an enzyme with the desired catalytic activity or substrate selectivity and by their instability in biotechnological processes. The previous answers to these problems comprised genetically engineered enzymes and several classes of enzyme mimics. Here we describe the potential of chemical enzyme engineering: native enzymes can be modified by merely chemical means and basic equipment yielding so-called semisynthetic enzymes. Thus, the high substrate selectivity of the enzymatic peptide framework is combined with the catalytic versatility of a synthetic active site. We illustrate the potential of chemically engineered enzymes with the conception of the semisynthetic peroxidase seleno-subtilisin. First, the serine endoprotease subtilisin was crystallized and cross-linked with glutaraldehyde to give cross-linked enzyme crystals which were found to be insoluble in water or organic solvents and highly stable. Second, serine 221 in the active site (Enz-OH) was chemically converted into an oxidized derivative of selenocystein (Enz-SeO2H). As a consequence, the former proteolytic enzyme gained peroxidase activity and catalyzed the selective reduction of hydroperoxides. Due to the identical binding sites of the semisynthetic peroxidase and the protease, the substrate selectivity of seleno-subtilisin was predictable in view of the well-known selectivity of subtilisin.

  3. High level waste interim storge architecture selection - decision report

    SciTech Connect

    Calmus, R.B.

    1996-09-27

    The U.S. Department of Energy (DOE) has embarked upon a course to acquire Hanford Site tank waste treatment and immobilization services using privatized facilities (RL 1996a). This plan contains a two-phased approach. Phase I is a proof-of-principle/connnercial demonstration- scale effort and Phase II is a fiill-scale production effort. In accordance with the planned approach, interim storage and disposal of various products from privatized facilities are to be DOE fumished. The high-level waste (BLW) interim storage options, or alternative architectures, were identified and evaluated to provide the framework from which to select the most viable method of Phase I BLW interim storage (Calmus 1996). This evaluation, hereafter referred to as the Alternative Architecture Evaluation, was performed to established performance and risk criteria (technical merit, cost, schedule, etc.). Based on evaluation results, preliminary architectures and path forward reconunendations were provided for consideration in the architecture decision- maldng process. The decision-making process used for selection of a Phase I solidified BLW interim storage architecture was conducted in accordance with an approved Decision Plan (see the attachment). This decision process was based on TSEP-07,Decision Management Procedure (WHC 1995). The established decision process entailed a Decision Board, consisting of Westinghouse Hanford Company (VY`HC) management staff, and included appointment of a VTHC Decision Maker. The Alternative Architecture Evaluation results and preliminary recommendations were presented to the Decision Board members for their consideration in the decision-making process. The Alternative Architecture Evaluation was prepared and issued before issuance of @C-IP- 123 1, Alternatives Generation and Analysis Procedure (WI-IC 1996a), but was deemed by the Board to fully meet the intent of WHC-IP-1231. The Decision Board members concurred with the bulk of the Alternative Architecture

  4. Cooperative Activities between High Schools and Colleges.

    ERIC Educational Resources Information Center

    Brown, Peggy, Ed.

    1983-01-01

    Some of the ways in which colleges can work with high schools to enrich secondary school experiences and increase access to and success in higher education, are described, and an essay on successful cooperative activities is presented. In "Pieces and Parts," James Herbert notes efforts to improve the preparation of students for college by…

  5. Solar Energy Project, Activities: Junior High Science.

    ERIC Educational Resources Information Center

    Tullock, Bruce, Ed.; And Others

    This guide contains lesson plans and outlines of science activities which present concepts of solar energy in the context of the junior high science curriculum. Each unit presents an introduction; objectives; skills and knowledge needed; materials; methods; questions; recommendations for further work; and a teacher information sheet. The teacher…

  6. Energy Activities for Junior High Social Studies.

    ERIC Educational Resources Information Center

    Minnesota State Energy Agency, St. Paul.

    The document contains seven learning activities for junior high students on the energy situation. Objectives are to help students gain understanding and knowledge about the relationships between humans and their social and physical environments; solve problems and clarify issues; examine personal beliefs and values; and recognize the relationships…

  7. High-activity liquid packaging design criteria

    SciTech Connect

    Not Available

    1994-05-01

    In recent studies, it has been acknowledged that there is an emerging need for packaging to transport high-activity liquid off the Hanford Site to support characterization and process development activities of liquid waste stored in underground tanks. These studies have dealt with specimen testing needs primarily at the Hanford Site; however, similar needs appear to be developing at other US Department of Energy (DOE) sites. The need to ship single and multiple specimens to offsite laboratories is anticipated because it is predicted that onsite laboratories will be overwhelmed by an increasing number and size (volume) of samples. Potentially, the specimen size could range from 250 mL to greater than 50 L. Presently, no certified Type-B packagings are available for transport of high-activity liquid radioactive specimens in sizes to support Site missions.

  8. Chromatographic Purification of Highly Active Yeast Ribosomes

    PubMed Central

    Meskauskas, Arturas; Leshin, Jonathan A.; Dinman, Jonathan D.

    2011-01-01

    Eukaryotic ribosomes are much more labile as compared to their eubacterial and archael counterparts, thus posing a significant challenge to researchers. Particularly troublesome is the fact that lysis of cells releases a large number of proteases and nucleases which can degrade ribosomes. Thus, it is important to separate ribosomes from these enzymes as quickly as possible. Unfortunately, conventional differential ultracentrifugation methods leaves ribosomes exposed to these enzymes for unacceptably long periods of time, impacting their structural integrity and functionality. To address this problem, we utilize a chromatographic method using a cysteine charged Sulfolink resin. This simple and rapid application significantly reduces co-purifying proteolytic and nucleolytic activities, producing high yields of intact, highly biochemically active yeast ribosomes. We suggest that this method should also be applicable to mammalian ribosomes. The simplicity of the method, and the enhanced purity and activity of chromatographically purified ribosome represents a significant technical advancement for the study of eukaryotic ribosomes. PMID:22042245

  9. Sensitive and selective tumor imaging with novel and highly activatable fluorescence strategies

    NASA Astrophysics Data System (ADS)

    Urano, Yasuteru

    2008-02-01

    Nowadays, several tumor imaging modalities such as MRI, PET and fluorescence imaging techniques have been extensively investigated. One of the central problems associated with these conventional tumor-targeted imaging methods, however, is the fact that the signal contrast between tumor and surrounding tissues relies on the efficient targeting to the tumor and the rapid sequestration or excretion of unbound agent. Among these modalities, only fluorescence imaging technique has a significant feature, in that great signal activation could be achieved which potentially leads to the selective imaging of cancer with higher tumor-to-background ratio. In this symposium, I will present some examples of fluorescence cancer imaging based on highly activatable strategies with using precisely designed novel fluorescence probes. Recently, we developed highly sensitive fluorescence probes for β-galactosidase which is applicable for living cell system. By utilizing these probes, we could establish a novel and highly activatable strategy for sensitive and selective optical imaging of imbedded tumor in the peritoneum. We took a two step procedure in that a lectin is used to localize β-galactosidase to cancer cells as an activating enzyme, and subsequent administration of a highly-sensitive fluorescence probe for the enzyme have afforded remarkable fluorescence activation selectively in tumor mass. Since the tumor-targeted enzyme can catalyze numerous substrate turnovers, a great number of fluorescent molecules could be produced and hence the rapid and sensitive detection of tumor in vivo with high tumor-to-background ratio could be achieved. Moreover, the consequent close-up investigation using fluorescence microscopy revealed that cancer microfoci as small as 200 μm could be successfully visualized.

  10. Selective Activation of Neuronal Targets With Sinusoidal Electric Stimulation

    PubMed Central

    Freeman, Daniel K.; Eddington, Donald K.; Rizzo, Joseph F.

    2010-01-01

    Electric stimulation of the CNS is being evaluated as a treatment modality for a variety of neurological, psychiatric, and sensory disorders. Despite considerable success in some applications, existing stimulation techniques offer little control over which cell types or neuronal substructures are activated by stimulation. The ability to more precisely control neuronal activation would likely improve the clinical outcomes associated with these applications. Here, we show that specific frequencies of sinusoidal stimulation can be used to preferentially activate certain retinal cell types: photoreceptors are activated at 5 Hz, bipolar cells at 25 Hz, and ganglion cells at 100 Hz. In addition, low-frequency stimulation (≤25 Hz) did not activate passing axons but still elicited robust synaptically mediated responses in ganglion cells; therefore, elicited neural activity is confined to within a focal region around the stimulating electrode. Our results suggest that sinusoidal stimulation provides significantly improved control over elicited neural activity relative to conventional pulsatile stimulation. PMID:20810683

  11. In vitro phytotoxicity and antioxidant activity of selected flavonoids.

    PubMed

    De Martino, Laura; Mencherini, Teresa; Mancini, Emilia; Aquino, Rita Patrizia; De Almeida, Luiz Fernando Rolim; De Feo, Vincenzo

    2012-01-01

    The knowledge of flavonoids involved in plant-plant interactions and their mechanisms of action are poor and, moreover, the structural characteristics required for these biological activities are scarcely known. The objective of this work was to study the possible in vitro phytotoxic effects of 27 flavonoids on the germination and early radical growth of Raphanus sativus L. and Lepidium sativum L., with the aim to evaluate the possible structure/activity relationship. Moreover, the antioxidant activity of the same compounds was also evaluated. Generally, in response to various tested flavonoids, germination was only slightly affected, whereas significant differences were observed in the activity of the various tested flavonoids against radical elongation. DPPH test confirms the antioxidant activity of luteolin, quercetin, catechol, morin, and catechin. The biological activity recorded is discussed in relation to the structure of compounds and their capability to interact with cell structures and physiology. No correlation was found between phytotoxic and antioxidant activities. PMID:22754304

  12. Highly concentrated active nonlinear media based on oxides

    SciTech Connect

    Bakin, D.V.; Dorozhkin, L.M.; Krasilov, Yu.I.; Kuznetsov, N.T.; Potemkin, A.V.; Tadzhi-Aglaev, K.S.; Shestakov, A.V.

    1987-07-01

    Important characteristics of highly concentrated active nonlinear media were studied which were based on oxide compounds of phosphates, niobates, tantalates, and titanates of neodymium with alkaline earth metals. Compounds of the indicated classes were synthesized and their spectral luminescent and nonlinear optical properties were studied. Single crystals were grown from the selected compounds (5-8mm) and preliminary measurements of the laser and nonlinear optical parameters were taken. Formulas are given for materials that demonstrated high nonlinear and luminescent properties simultaneously. Spectroscopic and nonlinear optical properties of some oxygen compounds of rare earth elements are shown.

  13. Selecting the Highly Gifted for Science: Israeli Sciempiad Model.

    ERIC Educational Resources Information Center

    Nevo, Baruch

    1993-01-01

    Israel's Sciempiad is an annual nationwide science competition for students ages 14 to 15, designed to stimulate interest in science and identify students with potential to become leading researchers. This article discusses how the selection procedure was determined and outlines steps in the selection process. (JDD)

  14. Pre-Selection Test to Identify High Responder Donor Goats.

    PubMed

    Balaro, Mfa; Brandão, F Z; Maia, Alrs; Souza-Fabjan, Jmg; Cueto, M I; Gibbons, A E; Fonseca, J F

    2016-06-01

    The aim of the study was to evaluate the feasibility of pre-selection of high or low responder does prior to the superovulatory protocols. Twenty Saanen does received 800 IU of equine chorionic gonadotropin (eCG) at the end of long-term progestogen treatment. Fourteen days later, a second progestogen protocol associated with a multiple-dose follicle stimulation hormone (FSH) treatment (5 IU/kg of FSH, in six decreasing doses between days 4 to 6 of the protocol) was administered. Transrectal ultrasound was used to assess the follicular status at the beginning of superovulatory treatments, at the oestrous onset and on the seventh day of the oestrous cycle for counting corpora lutea (CL). A significant lower number of CL was obtained in eCG-treated in comparision with FSH-treated does (p < 0.05). A quartic regression was able to explain the relationship between the number of CL in response to both treatments (r(2) =0.50; p < 0.05). Seventy per cent (14 of 20) of does maintained the same ovulatory response (high or low) after treatments. The Kappa (κ = 0.40; p < 0.05) and Spearman (rs = 0.39; p = 0.08) coefficients were able to show a relationship between treatments. Regarding the follicular status, there is a significant relationship between the number of small follicles (r = 0.71; r(2) =0.47; p < 0.01) and total follicles (r = 0.60; p < 0.01) at eCG and first FSH dose with the number of CL. Moreover, it was found a negative relationship between the presence of large follicles and the number of CL in response to eCG treatment (r = -0.44; p < 0.05), but not from FSH (p > 0.05). In conclusion, the screening test with eCG has the potential to identify Saanen does that will better respond to the superovulatory protocol with FSH. In addition, it highlighted the importance of an ultrasound evaluation prior to the beginning of superovulatory treatments with FSH to characterize the follicular status and identify the potential donors of high

  15. Selective Gold Recovery and Catalysis in a Highly Flexible Methionine-Decorated Metal-Organic Framework.

    PubMed

    Mon, Marta; Ferrando-Soria, Jesús; Grancha, Thais; Fortea-Pérez, Francisco R; Gascon, Jorge; Leyva-Pérez, Antonio; Armentano, Donatella; Pardo, Emilio

    2016-06-29

    A novel chiral 3D bioMOF exhibiting functional channels with thio-alkyl chains derived from the natural amino acid l-methionine (1) has been rationally prepared. The well-known strong affinity of gold for sulfur derivatives, together with the extremely high flexibility of the thioether "arms" decorating the channels, account for a selective capture of gold(III) and gold(I) salts in the presence of other metal cations typically found in electronic wastes. The X-ray single-crystal structures of the different gold adsorbates Au(III)@1 and Au(I)@1 suggest that the selective metal capture occurs in a metal ion recognition process somehow mimicking what happens in biological systems and protein receptors. Both Au(III)@1 and Au(I)@1 display high activity as heterogeneous catalyst for the hydroalkoxylation of alkynes, further expanding the application of these novel hybrid materials. PMID:27295383

  16. Variability-based active galactic nucleus selection using image subtraction in the SDSS and LSST era

    SciTech Connect

    Choi, Yumi; Gibson, Robert R.; Becker, Andrew C.; Ivezić, Željko; Connolly, Andrew J.; Ruan, John J.; Anderson, Scott F.; MacLeod, Chelsea L.

    2014-02-10

    With upcoming all-sky surveys such as LSST poised to generate a deep digital movie of the optical sky, variability-based active galactic nucleus (AGN) selection will enable the construction of highly complete catalogs with minimum contamination. In this study, we generate g-band difference images and construct light curves (LCs) for QSO/AGN candidates listed in Sloan Digital Sky Survey Stripe 82 public catalogs compiled from different methods, including spectroscopy, optical colors, variability, and X-ray detection. Image differencing excels at identifying variable sources embedded in complex or blended emission regions such as Type II AGNs and other low-luminosity AGNs that may be omitted from traditional photometric or spectroscopic catalogs. To separate QSOs/AGNs from other sources using our difference image LCs, we explore several LC statistics and parameterize optical variability by the characteristic damping timescale (τ) and variability amplitude. By virtue of distinguishable variability parameters of AGNs, we are able to select them with high completeness of 93.4% and efficiency (i.e., purity) of 71.3%. Based on optical variability, we also select highly variable blazar candidates, whose infrared colors are consistent with known blazars. One-third of them are also radio detected. With the X-ray selected AGN candidates, we probe the optical variability of X-ray detected optically extended sources using their difference image LCs for the first time. A combination of optical variability and X-ray detection enables us to select various types of host-dominated AGNs. Contrary to the AGN unification model prediction, two Type II AGN candidates (out of six) show detectable variability on long-term timescales like typical Type I AGNs. This study will provide a baseline for future optical variability studies of extended sources.

  17. Selection of enhanced antimicrobial activity posing lactic acid bacteria characterised by (GTG)5-PCR fingerprinting.

    PubMed

    Šalomskienė, Joana; Abraitienė, Asta; Jonkuvienė, Dovilė; Mačionienė, Irena; Repečkienė, Jūratė

    2015-07-01

    The aim of the study was a detail evaluation of genetic diversity among the lactic acid bacteria (LAB) strains having an advantage of a starter culture in order to select genotypically diverse strains with enhanced antimicrobial effect on some harmfull and pathogenic microorganisms. Antimicrobial activity of LAB was performed by the agar well diffusion method and was examined against the reference strains and foodborne isolates of Bacillus cereus, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. Antifungal activity was tested against the foodborne isolates of Candida parapsilosis, Debaromyces hansenii, Kluyveromyces marxianus, Pichia guilliermondii, Yarowia lipolytica, Aspergillus brasiliensis, Aspergillus versicolor, Cladosporium herbarum, Penicillium chrysogenum and Scopulariopsis brevicaulis. A total 40 LAB strains representing Lactobacillus (23 strains), Lactococcus (13 strains) and Streptococcus spp. (4 strains) were characterised by repetitive sequence based polymerase chain reaction fingerprinting which generated highly discriminatory profiles, confirmed the identity and revealed high genotypic heterogeneity among the strains. Many of tested LAB demonstrated strong antimicrobial activity specialised against one or few indicator strains. Twelve LAB strains were superior in suppressing growth of the whole complex of pathogenic bacteria and fungi. These results demonstrated that separate taxonomic units offered different possibilities of selection for novel LAB strains could be used as starter cultures enhancing food preservation. PMID:26139877

  18. Feature diagnosticity and task context shape activity in human scene-selective cortex.

    PubMed

    Lowe, Matthew X; Gallivan, Jason P; Ferber, Susanne; Cant, Jonathan S

    2016-01-15

    Scenes are constructed from multiple visual features, yet previous research investigating scene processing has often focused on the contributions of single features in isolation. In the real world, features rarely exist independently of one another and likely converge to inform scene identity in unique ways. Here, we utilize fMRI and pattern classification techniques to examine the interactions between task context (i.e., attend to diagnostic global scene features; texture or layout) and high-level scene attributes (content and spatial boundary) to test the novel hypothesis that scene-selective cortex represents multiple visual features, the importance of which varies according to their diagnostic relevance across scene categories and task demands. Our results show for the first time that scene representations are driven by interactions between multiple visual features and high-level scene attributes. Specifically, univariate analysis of scene-selective cortex revealed that task context and feature diagnosticity shape activity differentially across scene categories. Examination using multivariate decoding methods revealed results consistent with univariate findings, but also evidence for an interaction between high-level scene attributes and diagnostic visual features within scene categories. Critically, these findings suggest visual feature representations are not distributed uniformly across scene categories but are shaped by task context and feature diagnosticity. Thus, we propose that scene-selective cortex constructs a flexible representation of the environment by integrating multiple diagnostically relevant visual features, the nature of which varies according to the particular scene being perceived and the goals of the observer. PMID:26541082

  19. Evidence for Classical Cholinergic Toxicity Associated with Selective Activation of M1 Muscarinic Receptors.

    PubMed

    Alt, Andrew; Pendri, Annapurna; Bertekap, Robert L; Li, Guo; Benitex, Yulia; Nophsker, Michelle; Rockwell, Kristin L; Burford, Neil T; Sum, Chi Shing; Chen, Jing; Herbst, John J; Ferrante, Meredith; Hendricson, Adam; Cvijic, Mary Ellen; Westphal, Ryan S; O'Connell, Jonathan; Banks, Martyn; Zhang, Litao; Gentles, Robert G; Jenkins, Susan; Loy, James; Macor, John E

    2016-02-01

    The muscarinic acetylcholine receptor subtype 1 (M1) receptors play an important role in cognition and memory, and are considered to be attractive targets for the development of novel medications to treat cognitive impairments seen in schizophrenia and Alzheimer's disease. Indeed, the M1 agonist xanomeline has been shown to produce beneficial cognitive effects in both Alzheimer's disease and schizophrenia patients. Unfortunately, the therapeutic utility of xanomeline was limited by cholinergic side effects (sweating, salivation, gastrointestinal distress), which are believed to result from nonselective activation of other muscarinic receptor subtypes such as M2 and M3. Therefore, drug discovery efforts targeting the M1 receptor have focused on the discovery of compounds with improved selectivity profiles. Recently, allosteric M1 receptor ligands have been described, which exhibit excellent selectivity for M1 over other muscarinic receptor subtypes. In the current study, the following three compounds with mixed agonist/positive allosteric modulator activities that are highly functionally selective for the M1 receptor were tested in rats, dogs, and cynomologous monkeys: (3-((1S,2S)-2-hydrocyclohexyl)-6-((6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)methyl)benzo[h]quinazolin-4(3H)-one; 1-((4-cyano-4-(pyridin-2-yl)piperidin-1-yl)methyl)-4-oxo-4H-quinolizine-3-carboxylic acid; and (R)-ethyl 3-(2-methylbenzamido)-[1,4'-bipiperidine]-1'-carboxylate). Despite their selectivity for the M1 receptor, all three compounds elicited cholinergic side effects such as salivation, diarrhea, and emesis. These effects could not be explained by activity at other muscarinic receptor subtypes, or by activity at other receptors tested. Together, these results suggest that activation of M1 receptors alone is sufficient to produce unwanted cholinergic side effects such as those seen with xanomeline. This has important implications for the development of M1 receptor-targeted therapeutics since it

  20. Highly Efficient Selective Hydrogenation of Cinnamaldehyde to Cinnamyl Alcohol over Gold Supported on Zinc Oxide Materials

    DOE PAGESBeta

    Chen, Hangning; Cullen, David A.; Larese, J. Z.

    2015-11-30

    We used Au/ZnO catalysts for liquid-phase selective hydrogenation of cinnamaldehyde to cinnamyl alcohol and compared with Au/Fe2O3 catalysts. To investigate the influence of the support on the hydrogenation activity and selectivity, three different Au/ZnO catalysts were synthesized, including Au/rod-tetrapod ZnO, Au/porous ZnO, and Au/ZnO-CP prepared using a coprecipitation method. Moreover, the influence of calcination temperature was also systematically investigated in this study. The characterization of Au/ZnO catalysts was performed using ICP, N2 adsorption/desorption isotherms, X-ray diffraction, scanning transmission electron microscopy, and X-ray photoelectron spectroscopy. Among all the supported Au catalysts prepared in this study, Au/ZnO-CP exhibits both the highest hydrogenationmore » activity and selectivity. Using a 1.5% Au/ZnO-CP catalyst, 100% selectivity could be achieved with 94.9% conversion. Finally, we find that the Au particle (size and shape), the ZnO support (size and surface texture) and the interaction between Au and ZnO are three important parameters for achieving a highly efficient Au/ZnO catalyst.« less

  1. Highly Efficient Selective Hydrogenation of Cinnamaldehyde to Cinnamyl Alcohol over Gold Supported on Zinc Oxide Materials

    SciTech Connect

    Chen, Hangning; Cullen, David A.; Larese, J. Z.

    2015-11-30

    We used Au/ZnO catalysts for liquid-phase selective hydrogenation of cinnamaldehyde to cinnamyl alcohol and compared with Au/Fe2O3 catalysts. To investigate the influence of the support on the hydrogenation activity and selectivity, three different Au/ZnO catalysts were synthesized, including Au/rod-tetrapod ZnO, Au/porous ZnO, and Au/ZnO-CP prepared using a coprecipitation method. Moreover, the influence of calcination temperature was also systematically investigated in this study. The characterization of Au/ZnO catalysts was performed using ICP, N2 adsorption/desorption isotherms, X-ray diffraction, scanning transmission electron microscopy, and X-ray photoelectron spectroscopy. Among all the supported Au catalysts prepared in this study, Au/ZnO-CP exhibits both the highest hydrogenation activity and selectivity. Using a 1.5% Au/ZnO-CP catalyst, 100% selectivity could be achieved with 94.9% conversion. Finally, we find that the Au particle (size and shape), the ZnO support (size and surface texture) and the interaction between Au and ZnO are three important parameters for achieving a highly efficient Au/ZnO catalyst.

  2. Radio observations of a hard X-ray selected sample of active galaxies

    NASA Technical Reports Server (NTRS)

    Unger, S. W.; Lawrence, A.; Wilson, A. S.; Elvis, M.; Wright, A. E.

    1987-01-01

    Radio observations of a hard X-ray selected sample of active galaxies obtained with the VLA and Parkes radio telescopes are discussed, and the ratio of the radio to X-ray flux density is used to determine the degree of radio-loudness of the galaxies. A continuous distribution of the degree of radio loudness is found amongst the sample galaxies, and no evidence for distinct radio-quiet and radio-loud populations is noted. The X-ray and radio luminosity is shown to be nonlinearly correlated, with the radio-loud objects all having high X-ray luminosity.

  3. Synthesis and biological activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry†

    PubMed Central

    Wang, Lei; Cherian, Christina; Desmoulin, Sita Kugel; Polin, Lisa; Deng, Yijun; Wu, Jianmei; Hou, Zhanjun; White, Kathryn; Kushner, Juiwanna; Matherly, Larry H.; Gangjee, Aleem

    2010-01-01

    2-Amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines with a thienoyl side chain and 4-6 carbon bridge lengths (compounds 1-3) were synthesized as substrates for folate receptors (FRs) and the proton-coupled folate transporter (PCFT). Conversion of acetylene carboxylic acids to α-bromomethylketones and condensation with 2,4-diamino-6-hydroxypyrimidine afforded the 6-substituted pyrrolo[2,3-d]pyrimidines. Sonogashira coupling with (S)-2-[(5-bromo-thiophene-2-carbonyl)-amino]-pentanedioic acid diethyl ester, followed by hydrogenation and saponification, afforded 1-3. Compounds 1 and 2 potently inhibited KB and IGROV1 human tumor cells that express FRα, reduced folate carrier (RFC), and PCFT. The analogs were selective for FR- and PCFT over RFC. Glycinamide ribonucleotide formyltransferase was the principal cellular target. In SCID mice with KB tumors, 1 was highly active against both early (3.5 log kill, 1/5 cures) and advanced (3.7 log kill, 4/5 complete remissions) stage tumors. Our results demonstrate potent in vitro and in vivo antitumor activity for 1 due to selective transport by FRs and PCFT over RFC. PMID:20085328

  4. The cosmological evolution and luminosity function of X-ray selected active galactic nuclei

    NASA Technical Reports Server (NTRS)

    Maccacaro, T.; Gioia, I. M.; Avni, Y.; Giommi, P.; Griffiths, R. E.; Liebert, J.; Stocke, J.; Danziger, J.

    1983-01-01

    The cosmological evolution and the X-ray luminosity function of X-ray selected active galactic nuclei (AGNs) are derived and discussed. The sample used consists of 31 AGNs extracted from a fully identified sample of X-ray sources from the Einstein Observatory Medium Sensitivity Survey and is therefore exclusively defined by its X-ray properties. The distribution in space is found to be strongly nonuniform. The amount of cosmological evolution required by the X-ray data is derived in the framework of pure luminosity evolution and is found to be smaller than the amount determined from optically selected samples. The X-ray luminosity function is derived. It can be satisfactorily represented by a single power law only over a limited range of absolute luminosities. Evidence that the luminosity function flattens at low luminosity or steepens at high luminosity, or both, is presented and discussed.

  5. Total Synthesis and Selective Activity of a NewClass of Conformationally Restrained Epothilones

    PubMed Central

    Alhamadsheh, Mamoun M.; Gupta, Shuchi; Hudson, Richard A.; Perera, Lalith

    2009-01-01

    Stereoselective total syntheses of two novel conformationally restrained epothilone analogues are described. Evans asymmetric alkylation, Brown allylation, and a diastereoselective aldol reaction served as the key steps in the stereoselective synthesis of one of the two key fragments of the convergent synthetic approach.Enzyme resolution was employed to obtain the second fragment as a single enantiomer. The molecules were assembled by esterification, followed by ring-closing metathesis. In preliminary cytotoxicity studies, one of the analogues showed strong and selective growth inhibitory activity against two leukemia cell lines over solid human tumor cell lines. The precise biological mechanism of action and high degree of selectivity of this analogue remain to be examined. PMID:17955508

  6. Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold.

    PubMed

    Jansen, Koen; Heirbaut, Leen; Cheng, Jonathan D; Joossens, Jurgen; Ryabtsova, Oxana; Cos, Paul; Maes, Louis; Lambeir, Anne-Marie; De Meester, Ingrid; Augustyns, Koen; Van der Veken, Pieter

    2013-05-01

    Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp(2) hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>10(3)) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory. PMID:24900696

  7. Evaluation of mycobactericidal activity of selected chemical disinfectants and antiseptics according to European standards

    PubMed Central

    Bocian, Ewa; Grzybowska, Wanda; Tyski, Stefan

    2014-01-01

    Background The history of the investigation of standardized mycobactericidal activity of disinfectants and antiseptics is not very long. There is growing interest among the manufacturers of disinfectants in carrying out research on the antimicrobial activities in accordance with European standards (EN). This research could facilitate the introduction of high-quality disinfectants to the market. The aim of this study was to evaluate the mycobactericidal activity of selected chemical disinfectants and antiseptics used in the medical and veterinary fields. Material/Methods This study included 19 products submitted to the National Medicines Institute in Poland for evaluation of mycobactericidal activity. These products contain in their composition active substances belonging to different chemical groups, including aldehydes, alcohols, amines, quaternary ammonium compounds, phenols, guanidine, and oxidizing compounds. This study, conducted according to the manufacturers’ description of the preparations, was carried out in accordance with European standards, which also met the Polish standards: PN-EN 14204: 2013, PN-EN 14348: 2006, and PN-EN 14563: 2012. Results Tested products for disinfection and antiseptics containing active substances from different chemical groups showed high mycobactericidal activity and met the requirements of the appropriate European standards in most cases. In the case of products containing guanidine and amine compounds, the concentration of active ingredients used in the test and the test conditions specified by the manufacturer did not provide the mycobactericidal activity required by the standards. Conclusions Prior to the launch of a new product on the market, it is important to establish the appropriate usage and testing conditions of the preparation, such as its practical concentration, contact time, and environment condition (clean or dirty). PMID:24755666

  8. Active interrogation of highly enriched uranium

    SciTech Connect

    Moss, C. E.; Hollas, C. L.; Myers, W. L.

    2004-01-01

    Active interrogation techniques provide reliable detection of highly enriched uranium (HEU) even when passive detection is difficult. We use 50-Hz pulsed beams of bremsstrahlung photons from a 10-MeV linac or 14-MeV neutrons from a neutron generator for interrogation, thus activating the HEU. Detection of neutrons between pulses is a positive indicator of the presence of fissionable material. We detect the neutrons with three neutron detector designs based on {sup 3}He tubes. This report shows examples of the responses in these three detectors, for unshielded and shielded kilogram quantities of HEU, in containers as large as cargo containers.

  9. Selected Energy Education Activities for Pennsylvania Middle School Grades. Draft.

    ERIC Educational Resources Information Center

    Hack, Nancy; And Others

    These activities are intended to help increase awareness and understanding of the energy situation and to encourage students to become energy conservationists. The document is divided into sections according to discipline area. A final section is devoted to interdisciplinary activities involving several discipline areas integrated with the energy…

  10. Mediator protein mutations that selectively abolish activated transcription.

    PubMed

    Myers, L C; Gustafsson, C M; Hayashibara, K C; Brown, P O; Kornberg, R D

    1999-01-01

    Deletion of any one of three subunits of the yeast Mediator of transcriptional regulation, Med2, Pgd1 (Hrs1), and Sin4, abolished activation by Gal4-VP16 in vitro. By contrast, other Mediator functions, stimulation of basal transcription and of TFIIH kinase activity, were unaffected. A different but overlapping Mediator subunit dependence was found for activation by Gcn4. The genetic requirements for activation in vivo were closely coincident with those in vitro. A whole genome expression profile of a Deltamed2 strain showed diminished transcription of a subset of inducible genes but only minor effects on "basal" transcription. These findings make an important connection between transcriptional activation in vitro and in vivo, and identify Mediator as a "global" transcriptional coactivator. PMID:9874773

  11. How targets select activation or repression in response to Wnt.

    PubMed

    Murgan, Sabrina; Bertrand, Vincent

    2015-01-01

    In metazoans, the Wnt signaling pathway plays a key role in the regulation of binary decisions during development. During this process different sets of target genes are activated in cells where the Wnt pathway is active (classic target genes) versus cells where the pathway is inactive (opposite target genes). While the mechanism of transcriptional activation is well understood for classic target genes, how opposite target genes are activated in the absence of Wnt remains poorly characterized. Here we discuss how the key transcriptional mediator of the Wnt pathway, the TCF family member POP-1, regulates opposite target genes during C. elegans development. We examine recent findings suggesting that the direction of the transcriptional output (activation or repression) can be determined by the way TCF is recruited and physically interacts with its target gene. PMID:27123368

  12. Highly selective medium for isolation of Listeria monocytogenes from food.

    PubMed Central

    al-Zoreky, N; Sandine, W E

    1990-01-01

    A new selective medium (Al-Zoreky-Sandine listeria medium [ASLM]) was formulated to recover Listeria monocytogenes from food specimens; the medium completely inhibited common food microflora. Recognition of Listeria colonies is evident by black discoloration of the medium due to esculin hydrolysis without need for special illuminating equipment. The medium contains acriflavin, ceftazidime, and moxalactam as selective agents. Compared with Listeria Selective Agar, ASLM was equally effective in recovering L. monocytogenes. However, ASLM inhibited micrococci, enterococci, and gram-negative bacteria, especially a strain that mimicked L. monocytogenes on Listeria Selective Agar. The new medium was able to recover heat injured cells with only 15% less count than the nonselective medium. Images PMID:2126701

  13. Effect of size of catalytically active phases in the dehydrogenation of alcohols and the challenging selective oxidation of hydrocarbons.

    PubMed

    Zhang, Qinghong; Deng, Weiping; Wang, Ye

    2011-09-01

    The size of the active phase is one of the most important factors in determining the catalytic behaviour of a heterogeneous catalyst. This Feature Article focuses on the size effects in two types of reactions, i.e., the metal nanoparticle-catalysed dehydrogenation of alcohols and the metal oxide nanocluster-catalysed selective oxidation of hydrocarbons (including the selective oxidation of methane and ethane and the epoxidation of propylene). For Pd or Au nanoparticle-catalysed oxidative or non-oxidative dehydrogenation of alcohols, the size of metal nanoparticles mainly controls the catalytic activity by affecting the activation of reactants (either alcohol or O(2)). The size of oxidic molybdenum species loaded on SBA-15 determines not only the activity but also the selectivity of oxygenates in the selective oxidation of ethane; highly dispersed molybdenum species are suitable for acetaldehyde formation, while molybdenum oxide nanoparticles exhibit higher formaldehyde selectivity. Cu(II) and Fe(III) isolated on mesoporous silica are highly efficient for the selective oxidation of methane to formaldehyde, while the corresponding oxide clusters mainly catalyse the complete oxidation of methane. The lattice oxygen in iron or copper oxide clusters is responsible for the complete oxidation, while the isolated Cu(I) or Fe(II) generated during the reaction can activate molecular oxygen forming active oxygen species for the selective oxidation of methane. Highly dispersed Cu(I) and Fe(II) species also function for the epoxidation of propylene by O(2) and N(2)O, respectively. Alkali metal ions work as promoters for the epoxidation of propylene by enhancing the dispersion of copper or iron species and weakening the acidity. PMID:21629889

  14. High-affinity selective inhibitor against phospholipase A2 (PLA2): a computational study.

    PubMed

    Chinnasamy, Sathishkumar; Chinnasamy, Selvakkumar; Muthusamy, Karthikeyan

    2016-04-01

    Phospholipase A2 (PLA2) is the most abundant protein found in snake venom. PLA2 induces a variety of pharmacological effects such as neurotoxicity, myotoxicity and cardiotoxicity as well as anticoagulant, hemolytic, anti-platelet, hypertensive, hemorrhagic and edema inducing effects. In this study, the three dimensional structure of PLA2 of Naja sputatrix (Malayan spitting cobra) was modeled by I-TASSER, SWISS-MODEL, PRIME and MODELLER programs. The best model was selected based on overall stereo-chemical quality. Further, molecular dynamics simulation was performed to know the stability of the modeled protein using Gromacs software. Average structure was generated during the simulation period of 10 ns. High throughput virtual screening was employed through different databases (Asinex, Hit finder, Maybridge, TOSLab and ZINC databases) against PLA2. The top seven compounds were selected based on the docking score and free energy binding calculations. These compounds were analyzed by quantum polarized ligand docking, induced fit docking and density functional theory calculation. Furthermore, the stability of lead molecules in the active site of PLA2 was employed by MD simulation. The results show that selected lead molecules were highly stable in the active site of PLA2. PMID:26422703

  15. Selective catalytic conversion of bio-oil over high-silica zeolites.

    PubMed

    Widayatno, Wahyu Bambang; Guan, Guoqing; Rizkiana, Jenny; Du, Xiao; Hao, Xiaogang; Zhang, Zhonglin; Abudula, Abuliti

    2015-03-01

    Four high silica zeolites, i.e., HSZ-385, 890, 960, and 990 were utilized for the selective catalytic conversion of bio-oil from Fallopia japonica to certain chemicals in a fixed-bed reactor. The Beta-type HSZ-960 zeolite showed the highest selectivity to hydrocarbons, especially to aromatics as well as PAH compounds with the lowest unwanted chemicals while HSZ-890 showed high selectivity to aromatics. NH3-Temperature Programmed Desorption (TPD) analysis indicated that different amounts of acid sites in different zeolites determined the catalytic activity for the oxygen removal from bio-oil, in which the acid sites at low temperature (LT) region gave more contribution within the utilized temperature region. The reusability test of HSZ-960 showed the stability of hydrocarbons yield at higher temperature due to the significant contribution of coke gasification which assisted further deoxygenation of bio-oil. These results provide a guidance to select suitable zeolite catalysts for the upgrading of bio-oil in a practical process. PMID:25576987

  16. Highly Selective Synthesis of Halomon, Plocamenone, and Isoplocamenone

    PubMed Central

    Bucher, Cyril; Deans, Richard M.; Burns, Noah Z.

    2015-01-01

    Over 160 chiral vicinal bromochlorinated natural products have been identified, however a lack of synthetic methods for the selective incorporation of halogens into organic molecules has hindered their synthesis. Here we disclose the first total synthesis and structural confirmation of isoplocamenone and plocamenone, as well as the first selective and scaleable synthesis of the preclinical anticancer natural product halomon. The synthesis of these interhalogenated compounds has been enabled by our recently developed chemo-, regio-, and enantioselective dihalogenation reaction. PMID:26394844

  17. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation.

    PubMed

    Ma, Lei; Seager, Matthew A; Seager, Matthew; Wittmann, Marion; Jacobson, Marlene; Bickel, Denise; Burno, Maryann; Jones, Keith; Graufelds, Valerie Kuzmick; Xu, Guangping; Pearson, Michelle; McCampbell, Alexander; Gaspar, Renee; Shughrue, Paul; Danziger, Andrew; Regan, Christopher; Flick, Rose; Pascarella, Danette; Garson, Susan; Doran, Scott; Kreatsoulas, Constantine; Veng, Lone; Lindsley, Craig W; Shipe, William; Kuduk, Scott; Sur, Cyrille; Kinney, Gene; Seabrook, Guy R; Ray, William J

    2009-09-15

    The forebrain cholinergic system promotes higher brain function in part by signaling through the M(1) muscarinic acetylcholine receptor (mAChR). During Alzheimer's disease (AD), these cholinergic neurons degenerate, therefore selectively activating M(1) receptors could improve cognitive function in these patients while avoiding unwanted peripheral responses associated with non-selective muscarinic agonists. We describe here benzyl quinolone carboxylic acid (BQCA), a highly selective allosteric potentiator of the M(1) mAChR. BQCA reduces the concentration of ACh required to activate M(1) up to 129-fold with an inflection point value of 845 nM. No potentiation, agonism, or antagonism activity on other mAChRs is observed up to 100 microM. Furthermore studies in M(1)(-/-) mice demonstrates that BQCA requires M(1) to promote inositol phosphate turnover in primary neurons and to increase c-fos and arc RNA expression and ERK phosphorylation in the brain. Radioligand-binding assays, molecular modeling, and site-directed mutagenesis experiments indicate that BQCA acts at an allosteric site involving residues Y179 and W400. BQCA reverses scopolamine-induced memory deficits in contextual fear conditioning, increases blood flow to the cerebral cortex, and increases wakefulness while reducing delta sleep. In contrast to M(1) allosteric agonists, which do not improve memory in scopolamine-challenged mice in contextual fear conditioning, BQCA induces beta-arrestin recruitment to M(1), suggesting a role for this signal transduction mechanism in the cholinergic modulation of memory. In summary, BQCA exploits an allosteric potentiation mechanism to provide selectivity for the M(1) receptor and represents a promising therapeutic strategy for cognitive disorders. PMID:19717450

  18. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation

    PubMed Central

    Ma, Lei; Seager, Matthew A.; Wittmann, Marion; Jacobson, Marlene; Bickel, Denise; Burno, Maryann; Jones, Keith; Graufelds, Valerie Kuzmick; Xu, Guangping; Pearson, Michelle; McCampbell, Alexander; Gaspar, Renee; Shughrue, Paul; Danziger, Andrew; Regan, Christopher; Flick, Rose; Pascarella, Danette; Garson, Susan; Doran, Scott; Kreatsoulas, Constantine; Veng, Lone; Lindsley, Craig W.; Shipe, William; Kuduk, Scott; Sur, Cyrille; Kinney, Gene; Seabrook, Guy R.; Ray, William J.

    2009-01-01

    The forebrain cholinergic system promotes higher brain function in part by signaling through the M1 muscarinic acetylcholine receptor (mAChR). During Alzheimer's disease (AD), these cholinergic neurons degenerate, therefore selectively activating M1 receptors could improve cognitive function in these patients while avoiding unwanted peripheral responses associated with non-selective muscarinic agonists. We describe here benzyl quinolone carboxylic acid (BQCA), a highly selective allosteric potentiator of the M1 mAChR. BQCA reduces the concentration of ACh required to activate M1 up to 129-fold with an inflection point value of 845 nM. No potentiation, agonism, or antagonism activity on other mAChRs is observed up to 100 μM. Furthermore studies in M1−/− mice demonstrates that BQCA requires M1 to promote inositol phosphate turnover in primary neurons and to increase c-fos and arc RNA expression and ERK phosphorylation in the brain. Radioligand-binding assays, molecular modeling, and site-directed mutagenesis experiments indicate that BQCA acts at an allosteric site involving residues Y179 and W400. BQCA reverses scopolamine-induced memory deficits in contextual fear conditioning, increases blood flow to the cerebral cortex, and increases wakefulness while reducing delta sleep. In contrast to M1 allosteric agonists, which do not improve memory in scopolamine-challenged mice in contextual fear conditioning, BQCA induces β-arrestin recruitment to M1, suggesting a role for this signal transduction mechanism in the cholinergic modulation of memory. In summary, BQCA exploits an allosteric potentiation mechanism to provide selectivity for the M1 receptor and represents a promising therapeutic strategy for cognitive disorders. PMID:19717450

  19. A novel channel selection method for multiple motion classification using high-density electromyography

    PubMed Central

    2014-01-01

    Background Selecting an appropriate number of surface electromyography (EMG) channels with desired classification performance and determining the optimal placement of EMG electrodes would be necessary and important in practical myoelectric control. In previous studies, several methods such as sequential forward selection (SFS) and Fisher-Markov selector (FMS) have been used to select the appropriate number of EMG channels for a control system. These exiting methods are dependent on either EMG features and/or classification algorithms, which means that when using different channel features or classification algorithm, the selected channels would be changed. In this study, a new method named multi-class common spatial pattern (MCCSP) was proposed for EMG selection in EMG pattern-recognition-based movement classification. Since MCCSP is independent on specific EMG features and classification algorithms, it would be more convenient for channel selection in developing an EMG control system than the exiting methods. Methods The performance of the proposed MCCSP method in selecting some optimal EMG channels (designated as a subset) was assessed with high-density EMG recordings from twelve mildly-impaired traumatic brain injury (TBI) patients. With the MCCSP method, a subset of EMG channels was selected and then used for motion classification with pattern recognition technique. In order to justify the performance of the MCCSP method against different electrode configurations, features and classification algorithms, two electrode configurations (unipolar and bipolar) as well as two EMG feature sets and two types of pattern recognition classifiers were considered in the study, respectively. And the performance of the proposed MCCSP method was compared with that of two exiting channel selection methods (SFS and FMS) in EMG control system. Results The results showed that in comparison with the previously used SFS and FMS methods, the newly proposed MCCSP method had better

  20. Mallard blue: a high-affinity selective heparin sensor that operates in highly competitive media.

    PubMed

    Bromfield, Stephen M; Barnard, Anna; Posocco, Paola; Fermeglia, Maurizio; Pricl, Sabrina; Smith, David K

    2013-02-27

    We report the simple synthesis and full investigation of a novel heparin binding dye, mallard blue, an arginine-functionalized thionine. This dye binds heparin in highly competitive media, including water with high levels of competitive electrolyte, buffered aqueous solution and human serum. The dye reports on heparin levels by a significant change in its UV-vis spectroscopic profile. Molecular dynamics modeling provides detailed insight into the binding mode. Heparin binding is shown to be selective over other glycosaminoglycans, such as hyaluronic acid and chondroitin sulfate. Importantly, we demonstrate that, in the most competitive conditions, mallard blue outperforms standard dyes used for heparin sensing such as azure A. PMID:23406254

  1. Cell type-selective disease-association of genes under high regulatory load.

    PubMed

    Galhardo, Mafalda; Berninger, Philipp; Nguyen, Thanh-Phuong; Sauter, Thomas; Sinkkonen, Lasse

    2015-10-15

    We previously showed that disease-linked metabolic genes are often under combinatorial regulation. Using the genome-wide ChIP-Seq binding profiles for 93 transcription factors in nine different cell lines, we show that genes under high regulatory load are significantly enriched for disease-association across cell types. We find that transcription factor load correlates with the enhancer load of the genes and thereby allows the identification of genes under high regulatory load by epigenomic mapping of active enhancers. Identification of the high enhancer load genes across 139 samples from 96 different cell and tissue types reveals a consistent enrichment for disease-associated genes in a cell type-selective manner. The underlying genes are not limited to super-enhancer genes and show several types of disease-association evidence beyond genetic variation (such as biomarkers). Interestingly, the high regulatory load genes are involved in more KEGG pathways than expected by chance, exhibit increased betweenness centrality in the interaction network of liver disease genes, and carry longer 3' UTRs with more microRNA (miRNA) binding sites than genes on average, suggesting a role as hubs integrating signals within regulatory networks. In summary, epigenetic mapping of active enhancers presents a promising and unbiased approach for identification of novel disease genes in a cell type-selective manner. PMID:26338775

  2. Cell type-selective disease-association of genes under high regulatory load

    PubMed Central

    Galhardo, Mafalda; Berninger, Philipp; Nguyen, Thanh-Phuong; Sauter, Thomas; Sinkkonen, Lasse

    2015-01-01

    We previously showed that disease-linked metabolic genes are often under combinatorial regulation. Using the genome-wide ChIP-Seq binding profiles for 93 transcription factors in nine different cell lines, we show that genes under high regulatory load are significantly enriched for disease-association across cell types. We find that transcription factor load correlates with the enhancer load of the genes and thereby allows the identification of genes under high regulatory load by epigenomic mapping of active enhancers. Identification of the high enhancer load genes across 139 samples from 96 different cell and tissue types reveals a consistent enrichment for disease-associated genes in a cell type-selective manner. The underlying genes are not limited to super-enhancer genes and show several types of disease-association evidence beyond genetic variation (such as biomarkers). Interestingly, the high regulatory load genes are involved in more KEGG pathways than expected by chance, exhibit increased betweenness centrality in the interaction network of liver disease genes, and carry longer 3′ UTRs with more microRNA (miRNA) binding sites than genes on average, suggesting a role as hubs integrating signals within regulatory networks. In summary, epigenetic mapping of active enhancers presents a promising and unbiased approach for identification of novel disease genes in a cell type-selective manner. PMID:26338775

  3. Selection of head and whisker coordination strategies during goal-oriented active touch.

    PubMed

    Schroeder, Joseph B; Ritt, Jason T

    2016-04-01

    In the rodent whisker system, a key model for neural processing and behavioral choices during active sensing, whisker motion is increasingly recognized as only part of a broader motor repertoire employed by rodents during active touch. In particular, recent studies suggest whisker and head motions are tightly coordinated. However, conditions governing the selection and temporal organization of such coordinated sensing strategies remain poorly understood. We videographically reconstructed head and whisker motions of freely moving mice searching for a randomly located rewarded aperture, focusing on trials in which animals appeared to rapidly "correct" their trajectory under tactile guidance. Mice orienting after unilateral contact repositioned their whiskers similarly to previously reported head-turning asymmetry. However, whisker repositioning preceded head turn onsets and was not bilaterally symmetric. Moreover, mice selectively employed a strategy we term contact maintenance, with whisking modulated to counteract head motion and facilitate repeated contacts on subsequent whisks. Significantly, contact maintenance was not observed following initial contact with an aperture boundary, when the mouse needed to make a large corrective head motion to the front of the aperture, but only following contact by the same whisker field with the opposite aperture boundary, when the mouse needed to precisely align its head with the reward spout. Together these results suggest that mice can select from a diverse range of sensing strategies incorporating both knowledge of the task and whisk-by-whisk sensory information and, moreover, suggest the existence of high level control (not solely reflexive) of sensing motions coordinated between multiple body parts. PMID:26792880

  4. Development of selected advanced aerodynamics and active control concepts for commercial transport aircraft

    NASA Technical Reports Server (NTRS)

    Taylor, A. B.

    1984-01-01

    Work done under the Energy Efficient Transport project in the field of advanced aerodynamics and active controls is summarized. The project task selections focused on the following: the investigation of long-duct nacelle shape variation on interference drag; the investigation of the adequacy of a simple control law for the elastic modes of a wing; the development of the aerodynamic technology at cruise and low speed of high-aspect-ratio supercritical wings of high performance; and the development of winglets for a second-generation jet transport. All the tasks involved analysis and substantial wind tunnel testing. The winglet program also included flight evaluation. It is considered that the technology base has been built for the application of high-aspect-ratio supercritical wings and for the use of winglets on second-generation transports.

  5. Pd/Norbornene: A Winning Combination for Selective Aromatic Functionalization via C-H Bond Activation.

    PubMed

    Della Ca', Nicola; Fontana, Marco; Motti, Elena; Catellani, Marta

    2016-07-19

    Direct C-H bond activation is an important reaction in synthetic organic chemistry. This methodology has the potential to simplify reactions by avoiding the use of prefunctionalized reagents. However, selectivity, especially site selectivity, remains challenging. Sequential reactions, in which different molecules or groups are combined in an ordered sequence, represent a powerful tool for the construction of complex molecules in a single operation. We have discovered and developed a synthetic methodology that combines selective C-H bond activation with sequential reactions. This procedure, which is now known as the "Catellani reaction", enables the selective functionalization of both the ortho and ipso positions of aryl halides. The desired molecules are obtained with high selectivity from a pool of simple precursors. These molecules are assembled under the control of a palladacycle, which is formed through the joint action of a metal (Pd) and an olefin such as norbornene. These two species act cooperatively with an aryl halide to construct the palladacycle, which is formed through ortho-C-H activation of the original aryl halide. The resulting complex acts as a scaffold to direct the reaction (via Pd(IV)) of other species, such as alkyl or aryl halides and amination or acylation agents, toward the sp(2) C-Pd bond. At the end of this process, because of steric hindrance, the scaffold is dismantled by norbornene extrusion. Pd(0) is cleaved from the organic product through C-C, C-H, C-N, C-O, or C-B coupling, in agreement with the well-known reactivity of aryl-Pd complexes. The cycle involves Pd(0), Pd(II), and Pd(IV) species. In particular, our discovery relates to alkylation and arylation reactions. Recently, remarkable progress has been made in the following areas: (a) the installation of an amino or an acyl group at the ortho position of aryl halides, (b) the formation of a C-B bond at the ipso position, (c) the achievement of meta-C-H bond activation of aryl

  6. Production of high specific activity silicon-32

    SciTech Connect

    Phillips, D.R.; Brzezinski, M.A.

    1998-12-31

    This is the final report of a three-year, Laboratory Directed Research and Development Project (LDRD) at Los Alamos National Laboratory (LANL). There were two primary objectives for the work performed under this project. The first was to take advantage of capabilities and facilities at Los Alamos to produce the radionuclide {sup 32}Si in unusually high specific activity. The second was to combine the radioanalytical expertise at Los Alamos with the expertise at the University of California to develop methods for the application of {sup 32}Si in biological oceanographic research related to global climate modeling. The first objective was met by developing targetry for proton spallation production of {sup 32}Si in KCl targets and chemistry for its recovery in very high specific activity. The second objective was met by developing a validated field-useable, radioanalytical technique, based upon gas-flow proportional counting, to measure the dynamics of silicon uptake by naturally occurring diatoms.

  7. The unfolded protein response selectively targets active smoothened mutants.

    PubMed

    Marada, Suresh; Stewart, Daniel P; Bodeen, William J; Han, Young-Goo; Ogden, Stacey K

    2013-06-01

    The Hedgehog signaling pathway, an essential regulator of developmental patterning, has been implicated in playing causative and survival roles in a range of human cancers. The signal-transducing component of the pathway, Smoothened, has revealed itself to be an efficacious therapeutic target in combating oncogenic signaling. However, therapeutic challenges remain in cases where tumors acquire resistance to Smoothened antagonists, and also in cases where signaling is driven by active Smoothened mutants that exhibit reduced sensitivity to these compounds. We previously demonstrated that active Smoothened mutants are subjected to prolonged endoplasmic reticulum (ER) retention, likely due to their mutations triggering conformation shifts that are detected by ER quality control. We attempted to exploit this biology and demonstrate that deregulated Hedgehog signaling driven by active Smoothened mutants is specifically attenuated by ER stressors that induce the unfolded protein response (UPR). Upon UPR induction, active Smoothened mutants are targeted by ER-associated degradation, resulting in attenuation of inappropriate pathway activity. Accordingly, we found that the UPR agonist thapsigargin attenuated mutant Smoothened-induced phenotypes in vivo in Drosophila melanogaster. Wild-type Smoothened and physiological Hedgehog patterning were not affected, suggesting that UPR modulation may provide a novel therapeutic window to be evaluated for targeting active Smoothened mutants in disease. PMID:23572559

  8. Da0324, an inhibitor of nuclear factor-κB activation, demonstrates selective antitumor activity on human gastric cancer cells

    PubMed Central

    Jin, Rong; Xia, Yiqun; Chen, Qiuxiang; Li, Wulan; Chen, Dahui; Ye, Hui; Zhao, Chengguang; Du, Xiaojing; Shi, Dengjian; Wu, Jianzhang; Liang, Guang

    2016-01-01

    Background The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. Methods The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. Results High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation

  9. Substrate-Free High-Throughput Screening Identifies Selective Inhibitors for Uncharacterized Enzymes

    PubMed Central

    Bachovchin, Daniel A.; Brown, Steven J.; Rosen, Hugh; Cravatt, Benjamin F.

    2009-01-01

    Target-based high-throughput screening (HTS) is essential for the discovery of small-molecule modulators of proteins. Typical screening methods for enzymes rely on extensively tailored substrate assays, which are not available for targets of poorly characterized biochemical activity. Here, we report a general, substrate-free platform for HTS that overcomes this problem by monitoring the reaction of broad-spectrum, activity-based probes with enzymes using fluorescence polarization. We show that this platform is applicable to enzymes from multiple mechanistic classes, regardless of their degree of functional annotation, and can be coupled with secondary competitive activity-based proteomic assays to rapidly determine the specificity of screening hits. Using this platform, we identified the bioactive alkaloid emetine as a selective inhibitor of the uncharacterized cancer-associated hydrolase RBBP9. We furthermore show that the detoxification enzyme GSTO1, also implicated in cancer, is inhibited by several electrophilic compounds found in public libraries, some of which display high selectivity for this enzyme. PMID:19329999

  10. Binuclear Rhodium(II) Complexes With Selective Antibacterial Activity.

    PubMed

    Bień, M; Lachowicz, T M; Rybka, A; Pruchnik, F P; Trynda, L

    1997-01-01

    Binuclear rhodium(II) complexes [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] {R = H, Me; N-N = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen)} and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) (R = Me, Et;) have been synthesized and their structure and properties have been studied by electronic, IR and (1)H NMR spectroscopy. Antibacterial activity of these complexes against Escherichia coli and Staphylococcus aureus has been investigated. The most active antibacterial agents against E. coli were [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) {R = H and Me} which were considerably more active than the appropriate nitrogen ligands. The complexes show low activity against S. aureus. The activity of the complexes [Rh(2)(OOCR)(2)(N-N)(2)(H(2)O)(2)](OOCR)(2) against E. coli decreases in the series: R=H congruent withCH(3)>C(2)H(5)>C(3)H(7) congruent withC(4)H(9). The reverse order was found in the case of S. aureus. PMID:18475773

  11. Attitudes Toward Selected Concepts Among Junior High Science Teachers

    ERIC Educational Resources Information Center

    Simpson, Ronald D.; Brown, Dean R.

    1970-01-01

    Reports use of semantic differential instrument to measure junior high school science teachers attitudes toward education, science, evolution, religion, high school teachers, and college teachers. (BR)

  12. Noria: A Highly Xe-Selective Nanoporous Organic Solid.

    PubMed

    Patil, Rahul S; Banerjee, Debasis; Simon, Cory M; Atwood, Jerry L; Thallapally, Praveen K

    2016-08-26

    Separation of xenon and krypton is of industrial and environmental concern; the existing technologies use cryogenic distillation. Thus, a cost-effective, alternative technology for the separation of Xe and Kr and their capture from air is of significant importance. Herein, we report the selective Xe uptake in a crystalline porous organic oligomeric molecule, noria, and its structural analogue, PgC-noria, under ambient conditions. The selectivity of noria towards Xe arises from its tailored pore size and small cavities, which allows a directed non-bonding interaction of Xe atoms with a large number of carbon atoms of the noria molecular wheel in a confined space. PMID:27377260

  13. Selective Electrocatalytic Activity of Ligand Stabilized Copper Oxide Nanoparticles

    SciTech Connect

    Kauffman, Douglas R; Ohodnicki, Paul R; Kail, Brian W; Matranga, Christopher

    2011-01-01

    Ligand stabilization can influence the surface chemistry of Cu oxide nanoparticles (NPs) and provide unique product distributions for electrocatalytic methanol (MeOH) oxidation and CO{sub 2} reduction reactions. Oleic acid (OA) stabilized Cu{sub 2}O and CuO NPs promote the MeOH oxidation reaction with 88% and 99.97% selective HCOH formation, respectively. Alternatively, CO{sub 2} is the only reaction product detected for bulk Cu oxides and Cu oxide NPs with no ligands or weakly interacting ligands. We also demonstrate that OA stabilized Cu oxide NPs can reduce CO{sub 2} into CO with a {approx}1.7-fold increase in CO/H{sub 2} production ratios compared to bulk Cu oxides. The OA stabilized Cu oxide NPs also show 7.6 and 9.1-fold increases in CO/H{sub 2} production ratios compared to weakly stabilized and non-stabilized Cu oxide NPs, respectively. Our data illustrates that the presence and type of surface ligand can substantially influence the catalytic product selectivity of Cu oxide NPs.

  14. A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells.

    PubMed

    He, Huan; Li, Dong-Wei; Yang, Li-Yun; Fu, Li; Zhu, Xun-Jin; Wong, Wai-Kwok; Jiang, Feng-Lei; Liu, Yi

    2015-01-01

    Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment. PMID:26337336

  15. A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells

    PubMed Central

    He, Huan; Li, Dong-Wei; Yang, Li-Yun; Fu, Li; Zhu, Xun-Jin; Wong, Wai-Kwok; Jiang, Feng-Lei; Liu, Yi

    2015-01-01

    Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment. PMID:26337336

  16. Atmospheric Aerosols: Cloud Condensation Nucleus Activity of Selected Organic Molecules

    NASA Astrophysics Data System (ADS)

    Rosenorn, T.; Henning, S.; Hartz, K. H.; Kiss, G.; Pandis, S.; Bilde, M.

    2005-12-01

    Gas/particle partitioning of vapors in the atmosphere plays a major role in both climate through micro meteorology and in the physical and chemical processes of a single particle. This work has focused on the cloud droplet activation of a number of pure and mixed compounds. The means used to investigate these processes have been the University of Copenhagen cloud condensation nucleus counter setup and the Carnegie Mellon University CCNC setup. The importance of correct water activity modeling has been addressed and it has been pointed out that the molecular mass is an important parameter to consider when choosing model compounds for cloud activation models. It was shown that both traditional Kohler theory and Kohler theory modified to account for limited solubility reproduce measurements of soluble compounds well. For less soluble compounds it is necessary to use Kohler theory modified to account for limited solubility. It was also shown that this works for mixtures of compounds containing both inorganic salts and dicarboxylic acids. It has also been shown that particle phase and humidity history is important for activation behavior of particles consisting of two slightly soluble organic substances (succinic and adipic acid) and a soluble salt (NaCl). Model parameters for terpene oxidation product cloud activation have been derived. These are based on two sets of average parameters covering monoterpene oxidation products and sesquiterpene oxidation products. All parameters except the solubility were estimated and an effective solubility was calculated as the fitting parameter. The average solubility of the model compound found for mono terpene oxidation products is similar to those of sodium chloride and ammonium sulfate; however the higher molecular weight leads to a slightly higher activation diameter at fixed supersaturation. On a molar basis the monoterpene oxidation products show a 1.5 times higher effective solubility than the sesquiterpene oxidation products.

  17. Screening of selected ethnomedicinal plants from South Africa for larvicidal activity against the mosquito Anopheles arabiensis

    PubMed Central

    2012-01-01

    Background This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito larvicidal properties. Methods Extracts of a selection of plant taxa sourced in South Africa were tested for larvicidal properties in an applicable assay. Thirty 3rd instar Anopheles arabiensis larvae were exposed to various extract types (dichloromethane, dichloromethane/methanol) (1:1), methanol and purified water) of each species investigated. Mortality was evaluated relative to the positive control Temephos (Mostop; Agrivo), an effective emulsifiable concentrate larvicide. Results Preliminary screening of crude extracts revealed substantial variation in toxicity with 24 of the 381 samples displaying 100% larval mortality within the seven day exposure period. Four of the high activity plants were selected and subjected to bioassay guided fractionation. The results of the testing of the fractions generated identified one fraction of the plant, Toddalia asiatica as being very potent against the An. arabiensis larvae. Conclusion The present study has successfully identified a plant with superior larvicidal activity at both the crude and semi pure fractions generated through bio-assay guided fractionation. These results have initiated further research into isolating the active compound and developing a malaria vector control tool. PMID:22963538

  18. Comparative study on the antiviral activity of selected monoterpenes derived from essential oils.

    PubMed

    Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

    2010-05-01

    Essential oils are complex natural mixtures, their main constituents, e.g. terpenes and phenylpropanoids, being responsible for their biological properties. Essential oils from eucalyptus, tea tree and thyme and their major monoterpene compounds alpha-terpinene, gamma-terpinene, alpha-pinene, p-cymene, terpinen-4-ol, alpha-terpineol, thymol, citral and 1,8-cineole were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. These essential oils were able to reduce viral infectivity by >96%, the monoterpenes inhibited HSV by about >80%. The mode of antiviral action has been determined, only moderate antiviral effects were revealed by essential oils and monoterpenes when these drugs were added to host cells prior to infection or after entry of HSV into cells. However, both essential oils and monoterpenes exhibited high anti-HSV-1 activity by direct inactivation of free virus particles. All tested drugs interacted in a dose-dependent manner with herpesvirus particles thereby inactivating viral infection. Among the analysed compounds, monoterpene hydrocarbons were slightly superior to monoterpene alcohols in their antiviral activity, alpha-pinene and alpha-terpineol revealed the highest selectivity index. However, mixtures of different monoterpenes present in natural tea tree essential oil revealed a ten-fold higher selectivity index and a lower toxicity than its isolated single monoterpenes. PMID:19653195

  19. Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug

    PubMed Central

    Brunetti, Jlenia; Pillozzi, Serena; Falciani, Chiara; Depau, Lorenzo; Tenori, Eleonora; Scali, Silvia; Lozzi, Luisa; Pini, Alessandro; Arcangeli, Annarosa; Menichetti, Stefano; Bracci, Luisa

    2015-01-01

    Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian and breast cancer. However, treatment with paclitaxel is associated with severe side effects, including sensory axonal neuropathy, and its poor solubility in water complicates its formulation. In this paper we report the in vitro and in vivo activity of a new form of paclitaxel, modified for conjugation with a tumor-selective tetrabranched peptide carrier (NT4). NT4 selectively targets tumor cells by binding to membrane sulfated glycosaminoglycans (GAG) and to endocytic receptors, like LRP1 and LRP6, which are established tumor markers. Biological activity of NT4-paclitaxel was tested in vitro on MDA-MB 231 and SKOV-3 cell lines, representing breast and ovarian cancer, respectively, and in vivo in an orthotopic mouse model of human breast cancer. Using in vivo bioluminescence imaging, we found that conjugation of paclitaxel with the NT4 peptide led to increased therapeutic activity of the drug in vivo. NT4-paclitaxel induced tumor regression, whereas treatment with unconjugated paclitaxel only produced a reduction in tumor growth. Moreover, unlike paclitaxel, NT4-paclitaxel is very hydrophilic, which may improve its pharmacokinetic profile and allow the use of less toxic dilution buffers, further decreasing its general chemotherapic toxicity. PMID:26626158

  20. Importance of surface carbide formation on the activity and selectivity of Pd surfaces in the selective hydrogenation of acetylene

    NASA Astrophysics Data System (ADS)

    Yang, Bo; Burch, Robbie; Hardacre, Christopher; Hu, P.; Hughes, Philip

    2016-04-01

    A recent experimental investigation (Kim et al. J. Catal. 306 (2013) 146-154) on the selective hydrogenation of acetylene over Pd nanoparticles with different shapes concluded that Pd(100) showed higher activity and selectivity than Pd(111) for acetylene hydrogenation. However, our recent density functional calculations (Yang et al. J. Catal. 305 (2013) 264-276) observed that the clean Pd(111) surface should result in higher activity and ethylene selectivity compared with the clean Pd(100) surface for acetylene hydrogenation. In the current work, using density functional theory calculations, we find that Pd(100) in the carbide form gives rise to higher activity and selectivity than Pd(111) carbide. These results indicate that the catalyst surface is most likely in the carbide form under the experimental reaction conditions. Furthermore, the adsorption energies of hydrogen atoms as a function of the hydrogen coverage at the surface and subsurface sites over Pd(100) are compared with those over Pd(111), and it is found that the adsorption of hydrogen atoms is always less favoured on Pd(100) over the whole coverage range. This suggests that the Pd(100) hydride surface will be less stable than the Pd(111) hydride surface, which is also in accordance with the experimental results reported.

  1. Selective Activation of Transcription by a Novel CCAAT Binding Factor

    NASA Astrophysics Data System (ADS)

    Maity, Sankar N.; Golumbek, Paul T.; Karsenty, Gerard; de Crombrugghe, Benoit

    1988-07-01

    A novel CCAAT binding factor (CBF) composed of two different subunits has been extensively purified from rat liver. Both subunits are needed for specific binding to DNA. Addition of this purified protein to nuclear extracts of NIH 3T3 fibroblasts stimulates transcription from several promoters including the α 2(I) collagen, the α 1(I) collagen, the Rous sarcoma virus long terminal repeat (RSV-LTR), and the adenovirus major late promoter. Point mutations in the CCAAT motif that show either no binding or a decreased binding of CBF likewise abolish or reduce activation of transcription by CBF. Activation of transcription requires, therefore, the specific binding of CBF to its recognition sites.

  2. Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) γ Activators and Pan-PPAR Partial Agonists

    PubMed Central

    Ayers, Steven D.; Lin, Jean Z.; Cvoro, Aleksandra; Silveira, Rodrigo L.; Martínez, Leandro; Souza, Paulo C. T.; Saidemberg, Daniel; Deng, Tuo; Amato, Angela Angelica; Togashi, Marie; Hsueh, Willa A.; Phillips, Kevin; Palma, Mário Sérgio; Neves, Francisco A. R.; Skaf, Munir S.; Webb, Paul; Polikarpov, Igor

    2012-01-01

    Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) γ to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPARγ ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8–C10) bind the PPARγ LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPARγ LBD, stronger partial agonists with full length PPARγ and exhibit full blockade of PPARγ phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPARγ also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/β-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARγ modulators with useful clinical profiles among natural products. PMID:22649490

  3. Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection

    PubMed Central

    Ertelt, James M; Johanns, Tanner M; Mysz, Margaret A; Nanton, Minelva R; Rowe, Jared H; Aguilera, Marijo N; Way, Sing Sing

    2011-01-01

    Typhoid fever is a persistent infection caused by host-adapted Salmonella strains adept at circumventing immune-mediated host defences. Given the importance of T cells in protection, the culling of activated CD4+ T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen-specific CD4+ T cells after virulent Salmonella infection requires SPI-2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella-expressed antigens, but extends to CD4+ T cells primed to expand by co-infection with recombinant Listeria monocytogenes. Unexpectedly, however, the loss of activated CD4+ T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4+ T cells was not reproduced among the endogenous repertoire of antigen-specific CD4+ T cells identified with MHC class II tetramer. Analysis of T-cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4+ T-cell subsets after Salmonella co-infection that is associated with the purging of antigen-specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4+ T-cell subsets, which re-shapes the repertoire of antigen-specific T cells that persist later after infection. PMID:22044420

  4. Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor.

    PubMed

    Ma, Ming-Liang; Li, Ming; Gou, Jiao-Jiao; Ruan, Tian-Yu; Jin, Hai-Shan; Zhang, Ling-Hong; Wu, Liang-Chun; Li, Xiao-Yan; Hu, Ying-He; Wen, Ke; Zhao, Zheng

    2014-11-01

    Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure-activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2'-fluoride group in ring B were essential for this class of compounds to be active against NMU2R. PMID:25262941

  5. Design of Highly Selective Platinum Nanoparticle Catalysts for the Aerobic Oxidation of KA-Oil using Continuous-Flow Chemistry.

    PubMed

    Gill, Arran M; Hinde, Christopher S; Leary, Rowan K; Potter, Matthew E; Jouve, Andrea; Wells, Peter P; Midgley, Paul A; Thomas, John M; Raja, Robert

    2016-03-01

    Highly active and selective aerobic oxidation of KA-oil to cyclohexanone (precursor for adipic acid and ɛ-caprolactam) has been achieved in high yields using continuous-flow chemistry by utilizing uncapped noble-metal (Au, Pt & Pd) nanoparticle catalysts. These are prepared using a one-step in situ methodology, within three-dimensional porous molecular architectures, to afford robust heterogeneous catalysts. Detailed spectroscopic characterization of the nature of the active sites at the molecular level, coupled with aberration-corrected scanning transmission electron microscopy, reveals that the synthetic methodology and associated activation procedures play a vital role in regulating the morphology, shape and size of the metal nanoparticles. These active centers have a profound influence on the activation of molecular oxygen for selective catalytic oxidations. PMID:26833972

  6. Highly selective luminescent nanostructures for mitochondrial imaging and targeting.

    PubMed

    Fanizza, E; Iacobazzi, R M; Laquintana, V; Valente, G; Caliandro, G; Striccoli, M; Agostiano, A; Cutrignelli, A; Lopedota, A; Curri, M L; Franco, M; Depalo, N; Denora, N

    2016-02-14

    Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents. PMID:26763470

  7. Active low-valent niobium catalysts from NbCl5 and hydrosilanes for selective intermolecular cycloadditions.

    PubMed

    Satoh, Yasushi; Obora, Yasushi

    2011-10-21

    An active niobium catalyst was developed via a simple and nontoxic reduction method from NbCl(5)/hydrosilane and utilized for the selective [2 + 2 + 2] cycloaddition reaction of terminal alkynes and alkenes/α,ω-dienes, to give 1,3-cyclohexadiene derivatives in high yields with excellent chemo- and regioselectivity. PMID:21919436

  8. Antioxidant activities of selective gluten free ancient grains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ancient grains were known for special nutritional values along with gluten free qualities. Amaranth, quinoa, teff, buckwheat flours were evaluated for pasting properties, water holding capacity, phenolic contents, and antioxidant activities (free and bound). They all had higher water holding capacit...

  9. ACTIVATED CARBON TREATMENT OF INDUSTRIAL WASTEWATERS: SELECTED TECHNICAL PAPERS

    EPA Science Inventory

    Because of the tremendous interest in the organic constituent removal by activated carbon, the two industrial categories displaying the most interest are the petroleum refining and petrochemical industries. EPA's Office of Research and Development has co-sponsored two technical s...

  10. Analysis of Selection Activities to Supplement Approval Plans.

    ERIC Educational Resources Information Center

    Loup, Jean L.; Snoke, Helen Lloyd

    1991-01-01

    Describes two surveys of libraries by the Association of Research Libraries (ARL) that were conducted to compare approval plans and to determine alternative acquisitions methods for materials in philosophy and political science. Time spent by selectors is examined, collection evaluation activities are described, and implications for resource…

  11. Thrombomodulin Binding Selects the Catalytically Active Form of Thrombin.

    PubMed

    Handley, Lindsey D; Treuheit, Nicholas A; Venkatesh, Varun J; Komives, Elizabeth A

    2015-11-01

    Human α-thrombin is a serine protease with dual functions. Thrombin acts as a procoagulant, cleaving fibrinogen to make the fibrin clot, but when bound to thrombomodulin (TM), it acts as an anticoagulant, cleaving protein C. A minimal TM fragment consisting of the fourth, fifth, and most of the sixth EGF-like domain (TM456m) that has been prepared has much improved solubility, thrombin binding capacity, and anticoagulant activity versus those of previous TM456 constructs. In this work, we compare backbone amide exchange of human α-thrombin in three states: apo, D-Phe-Pro-Arg-chloromethylketone (PPACK)-bound, and TM456m-bound. Beyond causing a decreased level of amide exchange at their binding sites, TM and PPACK both cause a decreased level of amide exchange in other regions including the γ-loop and the adjacent N-terminus of the heavy chain. The decreased level of amide exchange in the N-terminus of the heavy chain is consistent with the historic model of activation of serine proteases, which involves insertion of this region into the β-barrel promoting the correct conformation of the catalytic residues. Contrary to crystal structures of thrombin, hydrogen-deuterium exchange mass spectrometry results suggest that the conformation of apo-thrombin does not yet have the N-terminus of the heavy chain properly inserted for optimal catalytic activity, and that binding of TM allosterically promotes the catalytically active conformation. PMID:26468766

  12. Effects of selected surfactants on soil microbial activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Surfactants (surface-active agents) facilitate and accentuate the emulsifying, dispersing, spreading, and wetting properties of liquids. Surfactants are used in industry to reduce the surface tension of liquid and to solubilize compounds. For agricultural pest management, surfactants are an import...

  13. Highly recyclable superhydrophobic sponge suitable for the selective sorption of high viscosity oil from water.

    PubMed

    Wang, Jintao; Geng, Guihong

    2015-08-15

    Inspired by the adhesion of marine mussels, a kind of superhydrophobic oil sorbent was successfully fabricated by robustly immobilizing the micro/nanostructure layer onto the sponge skeleton. The as-prepared sponges possess excellent hydrophobicity with the water contact angle of 154°, which enables the sponge to selectively absorb various oils floating on water surface. The oil sorption capacities of as-prepared sponge for a series of oils can reach 18.3-46.8g/g. The absorbed oil can be recovered by mechanical squeezing and the resulting sponge can be recycled more than 70 cycles while still keeping high oil sorption capability. More importantly, the obtained sponge has excellent affinity to the high viscosity oils. Therefore, the as-prepared sponge might find practical applications in the large-scale removal of oils especially high viscosity oils from water surface. PMID:26092604

  14. Comparison of the Electromyographic Activation Level and Unilateral Selectivity of Erector Spinae during Different Selected Movements

    ERIC Educational Resources Information Center

    Guo, Lan-Yuen; Wang, Yu-Lin; Huang, Yu-Han; Yang, Chich-Haung; Hou, Yi-You; Harn, Hans I-Chen; You, Yu-Lin

    2012-01-01

    For patients with scoliosis, core stabilization exercises may be beneficial in improving muscle strength and trunk dynamic control. However, few studies have examined whether the erector spinae (ES) activation status during unilateral spinal extensor strengthening meets the guideline for patients with spinal scoliosis. To determine ES activation…

  15. Self-Directed Activity-Based Learning and Achievement in High School Chemistry

    ERIC Educational Resources Information Center

    Bassett, Meighan M.; Martinez, James; Martin, Ellice P.

    2014-01-01

    The effects of student-directed activity-based learning (SDABL) were examined in two high school chemistry classes. Students in the SDABL class were given pretest results, a list of standards to be mastered, and a chart of learning activities categorized by difficulty level. They selected activities to meet their needs and preferences.…

  16. Identification of a novel 2-pyridyl-benzensulfonamide derivative, RQ-00203078, as a selective and orally active TRPM8 antagonist.

    PubMed

    Ohmi, Masashi; Shishido, Yuji; Inoue, Tadashi; Ando, Kazuo; Fujiuchi, Akiyoshi; Yamada, Akiko; Watanabe, Shuzo; Kawamura, Kiyoshi

    2014-12-01

    A novel series of 2-pyridyl-benzensulfonamide derivatives have been identified as selective and orally active TRPM8 antagonists via high throughput screening (HTS). Exploration of the structure-activity relationships of compound 1 has led to the identification of RQ-00203078 (compound 36) as a highly selective, potent and orally available TRPM8 antagonist. RQ-00203078 demonstrated excellent in vivo activity in a dose dependent manner with an ED50 value of 0.65 mg/kg in the icilin-induced wet-dog shakes model in rats after oral administration and may become an important pharmacological tool for fully assessing the potential therapeutic use of the targets activated by cold stimulation. PMID:25455182

  17. Novel arylalkylamine compounds exhibits potent selective antiparasitic activity against Leishmania major

    PubMed Central

    Iniguez, Eva A.; Perez, Andrea; Maldonado, Rosa A.; Skouta, Rachid

    2015-01-01

    Leishmania major (L. major) is a protozoan parasite causal agent of Leishmaniasis. It is estimated that 12 million people are currently infected and around 2 million infections occur each year. Current treatments suffer of high toxicity for the patient, low efficacy toward the parasite, high cost, and are losing effectiveness due to parasite resistance. Discovering novel small molecule with high specificity/selectivity and drug-like properties for anti-leishmanial activity remains a significant challenge. The purpose of this study is to communicate the design and synthesis strategies of novel chemical compounds based of the arylalkylamine scaffold with selective toxicity towards L. major and less toxicity to human cells in vitro. Here, we have developed a structure activity relationship (SAR) study of arylalkylamine AA1 in order to study their anti-parasitic effect in L. major. Overall, 27 arylalkylamine compounds derived from AA1 were synthesized and purified by silica gel column chromatography. The purity of each analog was confirmed by spectroscopic methods (1H, 13C NMR and LC/MS). Among these analogs, the compound AA9 showed the best toxic activity on L. major (LD50 = 3.34 μM), which represents a 9 fold higher lethality as compared with its parental AA1 (Fer-1) compound (LD50 = 28.75 μM). In addition, AA9 showed no significant toxicity at 80 μM on U20S Human Osteoblasts, Raw 264.7 Macrophages or intraperitoneal macrophages. In summary, our combined SAR study and biological evaluation data of AA1-AA27 compounds allow the identification of novel arylalkylamine compound AA9 that exhibits potent cytotoxicity against L. major promastigote with minimum toxic effect on human cells. PMID:26410073

  18. High energy activation data library (HEAD-2009)

    SciTech Connect

    Mashnik, Stepan G; Korovin, Yury A; Natalenko, Anatoly A; Konobeyev, Alexander Yu; Stankovskiy, A Yu

    2010-01-01

    A proton activation data library for 682 nuclides from 1 H to 210Po in the energy range from 150 MeV up to 1 GeV was developed. To calculate proton activation data, the MCNPX 2.6.0 and CASCADE/INPE codes were chosen. Different intranuclear cascade, preequilibrium, and equilibrium nuclear reaction models and their combinations were used. The optimum calculation models have been chosen on the basis of statistical correlations for calculated and experimental proton data taken from the EXFOR library of experimental nuclear data. All the data are written in ENDF-6 format. The library is called HEPAD-2008 (High-Energy Proton Activation Data). A revision of IEAF-2005 neutron activation data library has been performed. A set of nuclides for which the cross-section data can be (and were) updated using more modern and improved models is specified, and the corresponding calculations have been made in the present work. The new version of the library is called IEAF-2009. The HEPAD-2008 and IEAF-2009 are merged to the final HEAD-2009 library.

  19. High energy activation data library (HEAD-2009)

    NASA Astrophysics Data System (ADS)

    Korovin, Yu. A.; Natalenko, A. A.; Stankovskiy, A. Yu.; Mashnik, S. G.; Konobeyev, A. Yu.

    2010-12-01

    A proton activation data library for 682 nuclides from 1H to 210Po in the energy range from 150 MeV up to 1 GeV was developed. To calculate proton activation data, the MCNPX 2.6.0 and CASCADE/INPE codes were chosen. Different intranuclear cascade, preequilibrium, and equilibrium nuclear reaction models and their combinations were used. The optimum calculation models have been chosen on the basis of statistical correlations for calculated and experimental proton data taken from the EXFOR library of experimental nuclear data. All the data are written in ENDF-6 format. The library is called HEPAD-2008 (High-Energy Proton Activation Data). A revision of IEAF-2005 neutron activation data library has been performed. A set of nuclides for which the cross-section data can be (and were) updated using more modern and improved models is specified, and the corresponding calculations have been made in the present work. The new version of the library is called IEAF-2009. The HEPAD-2008 and IEAF-2009 are merged to the final HEAD-2009 library.

  20. Highly stable antibacterial silver nanoparticles as selective fluorescent sensor for Fe3+ ions

    NASA Astrophysics Data System (ADS)

    Makwana, Bharat A.; Vyas, Disha J.; Bhatt, Keyur D.; Jain, Vinod K.; Agrawal, Yadvendra K.

    2015-01-01

    Calix[4]resorcinarene polyhydrazide (CPH) protected water dispersible fluorescent silver nanaoparticles (AgNps) were prepared by one-pot method using water soluble CPH and AgNO3. (CPH) bearing hydrazide group on its periphery acts as a reducing agent and its web type of structure as a stabilizing agent for the formation of calix protected silver nanoparticles (CPH-AgNps). CPH-AgNps were found to be highly stable over 120 days at room temperature and at varied pH. CPH-AgNps were characterized by UV/Vis-spectroscopy, particle size analyzer (PSA), transmission electron microscopy (TEM) and Energy dispersive X-ray analysis (EDX). Duly characterized nanoparticles were explored for their application as sensitive and selective fluorescent chemosensors for various metal ions. It was found that nanoparticles were selective and sensitive only for Fe3+ ions with the linear range of detection from 0.1 μM to 10 μM. CPH-AgNps were also found to exhibit good antimicrobial activity when compared with standard Chloramphenicol. The selectivity and antimicrobial activity of CPH-AgNps suggests its potential use as a sensor for Fe(III) ions in ecosystems prone to industrial pollution and as an antimicrobial agent in biological applications.

  1. Selective activation of functional suppressor cells by human seminal fluid.

    PubMed Central

    Witkin, S S

    1986-01-01

    The ability of seminal fluid (SF) to induce suppressor cell activity from peripheral blood mononuclear cells (PBMN) was examined. PBMN were incubated with SF for 48 h, washed to remove SF components, treated with mitomycin C (mit C) and co-cultured with Raji cells, a lymphoblastoid cell line. Raji cell proliferation was inhibited by SF-treated PBMN proportionally to SF concentration. SF (50-200 micrograms), mit C-treated Raji cells or mit C-treated PBMN pre-incubated with phytohaemagglutinin were without effect on Raji cell growth. Suppressor T lymphocytes generated by incubation of PBMN with concanavalin A inhibited Raji cells to the same extent as did SF-treated PBMN. All activity was lost following heating at 56 degrees C for 30 min; freezing and thawing reduced the ability of SF to induce suppression by 50%. Dialysis of SF or treatment with antibody to prostaglandin E2 led to a 50% reduction in suppression. PMID:2943541

  2. Improving upon Nature: Active site remodeling produces highly efficient aldolase activity towards hydrophobic electrophilic substrates

    PubMed Central

    Cheriyan, Manoj; Toone, Eric J.; Fierke, Carol A.

    2012-01-01

    Substrate specificity of enzymes is frequently narrow and constrained by multiple interactions, limiting the use of natural enzymes in biocatalytic applications. Aldolases have important synthetic applications, but the usefulness of these enzymes is hampered by their narrow reactivity profile with unnatural substrates. To explore the determinants of substrate selectivity and alter the specificity of E. coli 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, we employed structure-based mutagenesis coupled with library screening of mutant enzymes localized to the bacterial periplasm. We identified two active site mutations (T161S/S184L) that work additively to enhance the substrate specificity of this aldolase to include catalysis of retro-aldol cleavage of (4S)-2-keto-4-hydroxy-4-(2′-pyridyl)butyrate (S-KHPB). These mutations improve the value of kcat/KMS-KHPB by >450-fold, resulting in a catalytic efficiency that is comparable to that of the wild-type enzyme with the natural substrate while retaining high stereoselectivity. Moreover, the value of kcatS-KHPB for this mutant enzyme, a parameter critical for biocatalytic applications, is 3-fold higher than the maximum value achieved by the natural aldolase with any substrate. This mutant also possesses high catalytic efficiency for the retro-aldol cleavage of the natural substrate, KDPG, and a >50-fold improved activity for cleavage of 2-keto-4-hydroxy-octonoate (KHO), a non-functionalized hydrophobic analog. These data suggest a substrate binding mode that illuminates the origin of facial selectivity in aldol addition reactions catalyzed by KDPG and 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) aldolases. Furthermore, targeting mutations to the active site provides marked improvement in substrate selectivity, demonstrating that structure-guided active site mutagenesis combined with selection techniques can efficiently identify proteins with characteristics that compare favorably to naturally occurring enzymes. PMID

  3. Transient Receptor Potential Canonical 7 (TRPC7): A Diacylglycerol-Activated Non-Selective Cation Channel

    PubMed Central

    Zhang, Xuexin

    2016-01-01

    Transient receptor potential canonical 7 (TRPC7) channel is the seventh member of the mammalian TRPC channel family. TRPC7 mRNA, protein and channel activity have been detected in many tissues and organs from mouse, rat and human. TRPC7 has high sequence homology with TRPC3 and TRPC6 and all three channels are activated by membrane receptors that couple to isoforms of phospholipase C (PLC) and mediate non-selective cation currents. TRPC7, along with TRPC3 and TRPC6 can be activated by direct exogenous application of diacylglycerol (DAG) analogs and by pharmacological maneuvers that increase endogenous DAG in cells. TRPC7 shows distinct properties of activation, such as constitutive activity, susceptibility to negative regulation by extracellular Ca2+ and by protein kinase C. TRPC7 can form heteromultimers with TRPC3 and TRPC6. Although TRPC7 remains one of the least studied TRPC channel, its role in various cell types and physiological and pathophysiological conditions is begining to emerge. PMID:24756707

  4. Antioxidant and anticancer activities of selected persian gulf algae.

    PubMed

    Namvar, F; Baharara, J; Mahdi, A A

    2014-01-01

    In the present study, the effect of red (Gracillaria corticata), green (Ulva fasciata) and brown (Sargassum ilicifolium) seaweeds alcoholic extract, against five important human cancer cell lines (MCF-7, MDA-MB-231, HeLa, HepG2, and HT-29) proliferation, apoptosis and cell cycle arrest were evaluated. The reducing activity and total polyphenol content were also investigated. MTT assay was used for cytotoxicity test. Morphological alterations were examined using phase contrast, fluorescent and electron microscopy. All the extracts were antiproliferative against all the cancer cell lines, dose-dependently, with G. corticata methanol extract (GCME) having the greatest inhibition activity against MCF-7 cell line. The percentage of apoptosis increased from 18 to 78 %. The cell cycle analysis also showed that GCME can induce apoptosis which confirm by TEM. Algal extract reducing activities were as follows: G. corticata > S. ilicifolium > U. fasciata. The GCME is a good source of potential complementary and alternative functional food for prevention and treatment of cancer. PMID:24478544

  5. A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.

    PubMed

    Liu, Yan; Wang, Yubin; Zhu, Guoqi; Sun, Jiandong; Bi, Xiaoning; Baudry, Michel

    2016-06-01

    While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation. PMID:26907807

  6. Evaluation of Antileishmanial Activity of Selected Brazilian Plants and Identification of the Active Principles

    PubMed Central

    Filho, Valdir Cechinel; Meyre-Silva, Christiane; Niero, Rivaldo; Bolda Mariano, Luisa Nathália; Gomes do Nascimento, Fabiana; Vicente Farias, Ingrid; Gazoni, Vanessa Fátima; dos Santos Silva, Bruna; Giménez, Alberto; Gutierrez-Yapu, David; Salamanca, Efrain; Malheiros, Angela

    2013-01-01

    This study evaluated extracts, fractions, and isolated compounds from some selected Brazilian medicinal plants against strains of promastigotes of Leishmania amazonensis and L. brasiliensis in vitro. The cell viability was determined, comparing the results with reference standards. The dichloromethane fractions of the roots, stems, and leaves of Allamanda schottii showed IC50 values between 14.0 and 2.0 μg/mL. Plumericin was the main active compound, with IC50 of 0.3 and 0.04 μg/mL against the two species of Leishmania analyzed. The hexane extract of Eugenia umbelliflora fruits showed IC50 of 14.3 and 5.7 μg/mL against L. amazonensis and L. brasiliensis, respectively. The methanolic extracts of the seeds of Garcinia achachairu and guttiferone A presented IC50 values of 35.9 and 10.4 μg/mL, against L. amazonensis, respectively. The ethanolic extracts of the stem barks of Rapanea ferruginea and the isolated compound, myrsinoic acid B, presented activity against L. brasiliensis with IC50 of 24.1 and 6.1 μg/mL. Chloroform fraction of Solanum sisymbriifolium exhibited IC50 of 33.8 and 20.5 μg/mL, and cilistol A was the main active principle, with IC50 of 6.6 and 3.1 μg/mL against L. amazonensis and L. brasiliensis, respectively. It is concluded that the analyzed plants are promising as new and effective antiparasitic agents. PMID:23840252

  7. Evaluation of antileishmanial activity of selected brazilian plants and identification of the active principles.

    PubMed

    Filho, Valdir Cechinel; Meyre-Silva, Christiane; Niero, Rivaldo; Bolda Mariano, Luisa Nathália; Gomes do Nascimento, Fabiana; Vicente Farias, Ingrid; Gazoni, Vanessa Fátima; Dos Santos Silva, Bruna; Giménez, Alberto; Gutierrez-Yapu, David; Salamanca, Efrain; Malheiros, Angela

    2013-01-01

    This study evaluated extracts, fractions, and isolated compounds from some selected Brazilian medicinal plants against strains of promastigotes of Leishmania amazonensis and L. brasiliensis in vitro. The cell viability was determined, comparing the results with reference standards. The dichloromethane fractions of the roots, stems, and leaves of Allamanda schottii showed IC50 values between 14.0 and 2.0  μ g/mL. Plumericin was the main active compound, with IC50 of 0.3 and 0.04  μ g/mL against the two species of Leishmania analyzed. The hexane extract of Eugenia umbelliflora fruits showed IC50 of 14.3 and 5.7  μ g/mL against L. amazonensis and L. brasiliensis, respectively. The methanolic extracts of the seeds of Garcinia achachairu and guttiferone A presented IC50 values of 35.9 and 10.4  μ g/mL, against L. amazonensis, respectively. The ethanolic extracts of the stem barks of Rapanea ferruginea and the isolated compound, myrsinoic acid B, presented activity against L. brasiliensis with IC50 of 24.1 and 6.1  μ g/mL. Chloroform fraction of Solanum sisymbriifolium exhibited IC50 of 33.8 and 20.5  μ g/mL, and cilistol A was the main active principle, with IC50 of 6.6 and 3.1  μ g/mL against L. amazonensis and L. brasiliensis, respectively. It is concluded that the analyzed plants are promising as new and effective antiparasitic agents. PMID:23840252

  8. Quiescent Fibroblasts Exhibit High Metabolic Activity

    PubMed Central

    Lemons, Johanna M. S.; Feng, Xiao-Jiang; Bennett, Bryson D.; Legesse-Miller, Aster; Johnson, Elizabeth L.; Raitman, Irene; Pollina, Elizabeth A.; Rabitz, Herschel A.; Rabinowitz, Joshua D.; Coller, Hilary A.

    2010-01-01

    Many cells in mammals exist in the state of quiescence, which is characterized by reversible exit from the cell cycle. Quiescent cells are widely reported to exhibit reduced size, nucleotide synthesis, and metabolic activity. Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes. In contrast, we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition. By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data, we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells, with greater overflow flux from the pentose phosphate pathway back to glycolysis. Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts. By feeding the cells labeled glutamine, we also detected a “backwards” flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis. The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid, and in part toward excretion of extracellular matrix proteins. Thus, reduced metabolic activity is not a hallmark of the quiescent state. Quiescent fibroblasts, relieved of the biosynthetic requirements associated with generating progeny, direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole. PMID:21049082

  9. Highly selective luminescent nanostructures for mitochondrial imaging and targeting

    NASA Astrophysics Data System (ADS)

    Fanizza, E.; Iacobazzi, R. M.; Laquintana, V.; Valente, G.; Caliandro, G.; Striccoli, M.; Agostiano, A.; Cutrignelli, A.; Lopedota, A.; Curri, M. L.; Franco, M.; Depalo, N.; Denora, N.

    2016-02-01

    Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents.Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino

  10. High efficiency in mode-selective frequency conversion.

    PubMed

    Quesada, Nicolás; Sipe, J E

    2016-01-15

    Frequency conversion (FC) is an enabling process in many quantum information protocols. Recently, it has been observed that upconversion efficiencies in single-photon, mode-selective FC are limited to around 80%. In this Letter, we argue that these limits can be understood as time-ordering corrections (TOCs) that modify the joint conversion amplitude of the process. Furthermore, using a simple scaling argument, we show that recently proposed cascaded FC protocols that overcome the aforementioned limitations act as "attenuators" of the TOCs. This observation allows us to argue that very similar cascaded architectures can be used to attenuate TOCs in photon generation via spontaneous parametric downconversion. Finally, by using the Magnus expansion, we argue that the TOCs, which are usually considered detrimental for FC efficiency, can also be used to increase the efficiency of conversion in partially mode-selective FC. PMID:26766715

  11. Highly Selective Phosphinylphosphination of Alkenes with Tetraphenyldiphosphine Monoxide.

    PubMed

    Sato, Yuki; Kawaguchi, Shin-Ichi; Nomoto, Akihiro; Ogawa, Akiya

    2016-08-01

    In sharp contrast to tetraphenyldiphosphine, which does not add to carbon-carbon double bonds efficiently, its monoxide, [Ph2 P(O)PPh2 ] can engage in a radical addition to various alkenes, thus affording the corresponding 1-phosphinyl-2-phosphinoalkanes regioselectively, and they can be converted into their sulfides by treatment with elemental sulfur. The phosphinylphosphination proceeds by the homolytic cleavage of the P(V) (O)-P(III) single bond of Ph2 P(O)PPh2 , followed by selective attack of the phosphinyl radical at the terminal position of the alkenes, and selective trapping of the resulting carbon radical by the phosphino group. Furthermore, the phosphinylphosphination product could be converted directly into its platinum complex with a hemilabile P,O chelation. PMID:27374767

  12. Discovery of a Selective Inhibitor of Oncogenic B-Raf Kinase With Potent Antimelanoma Activity

    SciTech Connect

    Tsai, J.; Lee, J.T.; Wang, W.; Zhang, J.; Cho, H.; Mamo, S.; Bremer, R.; Gillette, S.; Kong, J.; Haass, N.K.; Sproesser, K.; Li, L.; Smalley, K.S.M.; Fong, D.; Zhu, Y.-L.; Marimuthu, A.; Nguyen, H.; Lam, B.; Liu, J.; Cheung, I.; Rice, J.

    2009-05-26

    BRAF{sup V600E} is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting 'active' protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf{sup V600E} with an IC{sub 50} of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf{sup V600E} kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf{sup V600E}-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf{sup V600E}-positive cells. In B-Raf{sup V600E}-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf{sup V600E}-driven tumors.

  13. Most Common Types of Physical Activity Self-Selected by People with Multiple Sclerosis

    PubMed Central

    Weikert, Madeline; Dlugonski, Deirdre; Balantrapu, Swathi

    2011-01-01

    The promotion of physical activity for people with multiple sclerosis (MS) would benefit from information about the common types of physical activity self-selected by this population. This study examined the most frequent types of physical activity self-reported by a large sample of people with MS. The data were collected as part of the baseline assessment of a longitudinal investigation of physical activity in relapsing-remitting MS (RRMS). The participants (N = 272) were sent a battery of questionnaires through the US Postal Service that included the Modifiable Activity Questionnaire for assessing types of physical activity performed during the previous year. Walking was ranked number 1 for both the first and second most common types of physical activity self-selected by people with MS, and it was ranked number 4 as the third most common type of self-selected physical activity. Collectively, 79% of the sample reported walking as a frequent form of self-selected physical activity in the previous year. Other notable types of physical activities self-selected by people with MS were gardening (44%), weight training (34%), bicycling (30%), and calisthenics (20%). This information may assist clinicians and practitioners in the development of physical activity programs and recommendations for people with MS. PMID:24453701

  14. The selective catalytic cracking of Fischer-Tropsch liquids to high value transportation fuels. Final report

    SciTech Connect

    Schwartz, M.M.; Reagon, W.J.; Nicholas, J.J.; Hughes, R.D.

    1994-11-01

    Amoco Oil Company, investigated a selective catalytic cracking process (FCC) to convert the Fischer-Tropsch (F-T) gasoline and wax fractions to high value transportation fuels. The primary tasks of this contract were to (1) optimize the catalyst and process conditions of the FCC process for maximum conversion of F-T wax into reactive olefins for later production of C{sub 4}{minus}C{sub 8} ethers, and (2) use the olefin-containing light naphtha obtained from FCC processing of the F-T wax as feedstock for the synthesis of ethers. The catalytic cracking of F-T wax feedstocks gave high conversions with low activity catalysts and low process severities. HZSM-5 and beta zeolite catalysts gave higher yields of propylene, isobutylene, and isoamylenes but a lower gasoline yield than Y zeolite catalysts. Catalyst selection and process optimization will depend on product valuation. For a given catalyst and process condition, Sasol and LaPorte waxes gave similar conversions and product selectivities. The contaminant iron F-T catalyst fines in the LaPorte wax caused higher coke and hydrogen yields.

  15. CHP REGIONAL APPLICATION CENTERS: ACTIVITIES AND SELECTED RESULTS

    SciTech Connect

    Schweitzer, Martin

    2010-08-01

    Between 2001 and 2005, the U.S. Department of Energy (DOE) created a set of eight Regional Application Centers (RACs) to facilitate the development and deployment of Combined Heat and Power (CHP) technologies. By utilizing the thermal energy that is normally wasted when electricity is produced at central generating stations, Combined Heat and Power installations can save substantial amounts of energy compared to more traditional technologies. In addition, the location of CHP facilities at or near the point of consumption greatly reduces or eliminates electric transmission and distribution losses. The regional nature of the RACs allows each one to design and provide services that are most relevant to the specific economic and market conditions in its particular geographic area. Between them, the eight RACs provide services to all 50 states and the District of Columbia. Through the end of the federal 2009 fiscal year (FY 2009), the primary focus of the RACs was on providing CHP-related information to targeted markets, encouraging the creation and adoption of public policies and incentives favorable to CHP, and providing CHP users and prospective users with technical assistance and support on specific projects. Beginning with the 2010 fiscal year, the focus of the regional centers broadened to include district energy and waste heat recovery and these entities became formally known as Clean Energy Application Centers, as required by the Energy Independence and Security Act (EISA) of 2007. In 2007, ORNL led a cooperative effort to establish metrics to quantify the RACs accomplishments. That effort began with the development of a detailed logic model describing RAC operations and outcomes, which provided a basis for identifying important activities and accomplishments to track. A data collection spreadsheet soliciting information on those activities for FY 2008 and all previous years of RAC operations was developed and sent to the RACs in the summer of 2008. This

  16. Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    2016-01-01

    We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells. PMID:27144688

  17. Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis.

    PubMed

    Gold, Ben; Smith, Robert; Nguyen, Quyen; Roberts, Julia; Ling, Yan; Lopez Quezada, Landys; Somersan, Selin; Warrier, Thulasi; Little, David; Pingle, Maneesh; Zhang, David; Ballinger, Elaine; Zimmerman, Matthew; Dartois, Véronique; Hanson, Paul; Mitscher, Lester A; Porubsky, Patrick; Rogers, Steven; Schoenen, Frank J; Nathan, Carl; Aubé, Jeffrey

    2016-07-14

    We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells. PMID:27144688

  18. High temperature size selective membranes. Final report, September 1992--March 1995

    SciTech Connect

    1996-02-01

    Availability of a high temperature size selective membrane capable of separating hydrogen from carbon dioxide and other gases is seen as highly desirable from an economic perspective. Preparation of such a membrane is technically very difficult due to the limitations that the high temperature places on materials selection. We have prepared high temperature membranes as thin film composites of a porous Blackglas{trademark} support and a carbon molecular sieve selective film. Porous Blackglail{trademark} supports have been prepared by pyrolysis of a formed mixture of Blackglas{trademark} B-staged precursor and short Carbon fibers. Such supports have the necessary smoothness for use as a membrane support, good mechanical properties, and an appropriate pore size distribution. These supports can be made either in flat sheet form or in a tubular configuration. A carbon molecular sieve layer can be added to the support by repeated coating/pyrolysis with a dilute solution of precursor polymer. The preferred precursors are polyimide or polyamic acid. Crack formation is observed after the first pyrolyses, but these cracks are repaired during later pyrolyses. The final membrane thickness is only 2.5 {mu}m. The permeation flux of the membrane for hydrogen ranges from 8.1 x 10{sup -5} at room temperature to 3.0 x 10{sup -3} cm{sup 3} (STP) cm{sup -2} sec{sup -1} cmHg{sup -1} at 717{degrees}C, and the selectivity for hydrogen over nitrogen from 2.8 to 3.8, and a selectivity for hydrogen over carbon dioxide of 2.4. This selectivity is close to the Knudsen diffusion limit. In a companion study, unsupported carbon molecular sieve films were also prepared under pyrolysis conditions similar to those used for the supported film. Hydrogen adsorption porosimetry at 19.7{degrees}K was used to show that, under appropriate activation or pyrolysis conditions, such films can be prepared which adsorb hydrogen to a much greater extent than carbon dioxide.

  19. Experimental determination of the temperature dependence of water activities for a selection of aqueous organic solutions

    NASA Astrophysics Data System (ADS)

    Ganbavale, G.; Marcolli, C.; Krieger, U. K.; Zuend, A.; Stratmann, G.; Peter, T.

    2014-09-01

    This work presents experimental data of the temperature dependence of water activity in aqueous organic solutions relevant for tropospheric conditions (200-273 K). Water activity (aw) at low temperatures (T) is a crucial parameter for predicting homogeneous ice nucleation. We investigated temperature-dependent water activities, ice freezing and melting temperatures of solutions, and vapour pressures of a selection of atmospherically relevant aqueous organic systems. To measure aw over a wide composition range and with a focus on low temperatures, we use various aw measurement techniques and instruments: a dew point water activity meter, an electrodynamic balance (EDB), differential scanning calorimetry (DSC), and a setup to measure the total gas phase pressure at equilibrium over aqueous solutions. Water activity measurements were performed for aqueous multicomponent and multifunctional organic mixtures containing the functional groups typically found in atmospheric organic aerosols, such as hydroxyl, carboxyl, ketone, ether, ester, and aromatic groups. The aqueous organic systems studied at several fixed compositions over a considerable temperature range differ significantly in their temperature dependence. Aqueous organic systems of 1,4-butanediol and methoxyacetic acid show a moderate decrease in aw with decreasing temperature. The aqueous M5 system (a multicomponent system containing five different dicarboxylic acids) and aqueous 2-(2-ethoxyethoxy)ethanol solutions both show a strong increase of water activity with decreasing temperature at high solute concentrations for T < 270 K and T < 260 K, respectively. These measurements show that the temperature trend of aw can be reversed at low temperatures and that linear extrapolations of high-temperature data may lead to erroneous predictions. To avoid this, experimentally determined aw at low temperature are needed to improve thermodynamic models towards lower temperatures and for improved predictions of the ice

  20. Experimental determination of the temperature dependence of water activities for a selection of aqueous organic solutions

    NASA Astrophysics Data System (ADS)

    Ganbavale, G.; Marcolli, C.; Krieger, U. K.; Zuend, A.; Stratmann, G.; Peter, T.

    2014-05-01

    This work presents experimental data of the temperature dependence of water activity in aqueous organic solutions relevant for tropospheric conditions (200-273 K). Water activity (aw) at low temperatures (T) is a crucial parameter for predicting homogeneous ice nucleation. We investigated temperature dependent water activities, ice freezing and melting temperatures of solutions, and vapour pressures of a selection of atmospherically relevant aqueous organic systems. To measure aw over a wide composition range and with a focus on low temperatures, we use various aw measurement techniques and instruments: a dew point water activity meter, an electrodynamic balance (EDB), differential scanning calorimetry (DSC), and a setup to measure the total gas phase pressure at equilibrium over aqueous solutions. Water activity measurements were performed for aqueous multicomponent and multifunctional organic mixtures containing the functional groups typically found in atmospheric organic aerosols, such as hydroxyl, carboxyl, ketone, ether, ester, and aromatic groups. The aqueous organic systems studied at several fixed compositions over a considerable temperature range differ significantly in their temperature dependence. Aqueous organic systems of 1,4-butanediol and methoxyacetic acid show a moderate decrease in aw with decreasing temperature. The aqueous M5 system (a multicomponent system containing five different dicarboxylic acids) and aqueous 2-(2-ethoxyethoxy)ethanol solutions both show a strong increase of water activity with decreasing temperature at high solute concentrations for T<270 K and T<260 K, respectively. These measurements show that the temperature trend of aw can be reversed at low temperatures and that linear extrapolations of high temperature data may lead to erroneous predictions. To avoid this, experimentally determined aw at low temperature are needed to improve thermodynamic models towards lower temperatures and for improved predictions of the ice

  1. Selective activity of butyrylcholinesterase in serum by a chemiluminescent assay.

    PubMed

    Yavo, B; Brunetti, I L; da Fonseca, L M; Catalani, L H; Campa, A

    2001-01-01

    In a previous study, we showed that purified commercial esterase activity can be detected in a chemiluminescent assay based on the hydrolysis of 2-methyl-1-propenylbenzoate (MPB) to 2-methyl-1-propenol, which is subsequently oxidized by the horseradish peroxidase (HRP)-H(2)O(2) system. The purpose of this study was to verify the applicability of this assay to human serum. The existence of an esterase activity capable of hydrolysing MPB is indicated by the fact that the MPB-serum-HRP-H(2)O(2) system consumes oxygen and emits light. Both signals were abolished by prior serum heat inactivation and were preserved when serum was stored at < or =4 degrees C. Addition of aliesterase inhibitors, such as fluoride ion and trichlorfon or the cholinesterase inhibitor eserine, totally prevents light emission. The butyrylcholinesterase-specific substrate benzoylcholine causes a delay in both O(2) uptake and light emission, while the specific acetylcholinesterase substrate, acetyl-beta-methylcholine, had practically no effect. Purified butyrylcholinesterase, but not acetylcholinesterase, triggered light emission. The finding that butyrylcholinesterase is responsible for the hydrolysis of MPB in serum should serve as the basis for the development of a specific chemiluminescent assay for this enzyme. PMID:11590700

  2. Foot posture influences the electromyographic activity of selected lower limb muscles during gait

    PubMed Central

    2009-01-01

    Background Some studies have found that flat-arched foot posture is related to altered lower limb muscle function compared to normal- or high-arched feet. However, the results from these studies were based on highly selected populations such as those with rheumatoid arthritis. Therefore, the objective of this study was to compare lower limb muscle function of normal and flat-arched feet in people without pain or disease. Methods Sixty adults aged 18 to 47 years were recruited to this study. Of these, 30 had normal-arched feet (15 male and 15 female) and 30 had flat-arched feet (15 male and 15 female). Foot posture was classified using two clinical measurements (the arch index and navicular height) and four skeletal alignment measurements from weightbearing foot x-rays. Intramuscular fine-wire electrodes were inserted into tibialis posterior and peroneus longus under ultrasound guidance, and surface EMG activity was recorded from tibialis anterior and medial gastrocnemius while participants walked barefoot at their self-selected comfortable walking speed. Time of peak amplitude, peak and root mean square (RMS) amplitude were assessed from stance phase EMG data. Independent samples t-tests were performed to assess for significant differences between the normal- and flat-arched foot posture groups. Results During contact phase, the flat-arched group exhibited increased activity of tibialis anterior (peak amplitude; 65 versus 46% of maximum voluntary isometric contraction) and decreased activity of peroneus longus (peak amplitude; 24 versus 37% of maximum voluntary isometric contraction). During midstance/propulsion, the flat-arched group exhibited increased activity of tibialis posterior (peak amplitude; 86 versus 60% of maximum voluntary isometric contraction) and decreased activity of peroneus longus (RMS amplitude; 25 versus 39% of maximum voluntary isometric contraction). Effect sizes for these significant findings ranged from 0.48 to 1.3, representing moderate to

  3. Estimation of active pharmaceutical ingredients content using locally weighted partial least squares and statistical wavelength selection.

    PubMed

    Kim, Sanghong; Kano, Manabu; Nakagawa, Hiroshi; Hasebe, Shinji

    2011-12-15

    Development of quality estimation models using near infrared spectroscopy (NIRS) and multivariate analysis has been accelerated as a process analytical technology (PAT) tool in the pharmaceutical industry. Although linear regression methods such as partial least squares (PLS) are widely used, they cannot always achieve high estimation accuracy because physical and chemical properties of a measuring object have a complex effect on NIR spectra. In this research, locally weighted PLS (LW-PLS) which utilizes a newly defined similarity between samples is proposed to estimate active pharmaceutical ingredient (API) content in granules for tableting. In addition, a statistical wavelength selection method which quantifies the effect of API content and other factors on NIR spectra is proposed. LW-PLS and the proposed wavelength selection method were applied to real process data provided by Daiichi Sankyo Co., Ltd., and the estimation accuracy was improved by 38.6% in root mean square error of prediction (RMSEP) compared to the conventional PLS using wavelengths selected on the basis of variable importance on the projection (VIP). The results clearly show that the proposed calibration modeling technique is useful for API content estimation and is superior to the conventional one. PMID:22001843

  4. Anion selective optodes: development of a fluorescent fiber optic sensor for the determination of nitrite activity

    NASA Astrophysics Data System (ADS)

    Barker, Susan L. R.; Shortreed, Michael R.; Kopelman, Raoul

    1996-12-01

    The response of state of the art anion optodes often cannot be described in a thermodynamically exact manner because the ionic strength within the membrane phase of such optodes changes during the course of a titration. Incorporating lipophilic charge sites in the anion optode membranes provides a constant ionic strength in the membrane phase, the ability to measure anion activities, and a more thermodynamically describable system. This configuration has been used to create a micrometer-sized nitrite-selective optode. Recent elucidation of the many biological roles of nitric oxide (NO) has spurred interest in sensitive and selective detection of this molecule. In biological systems NO is converted to NO2- within 30 sec and the biological concentration of NO2- is normally on the micromolar level. The optode we have prepared contains a selective vitamin B12 derivative ionophore, a fluorescent chromoionophore (ETH 2439 or ETH 5350), and lipophilic charge sites. These components are entrapped in a highly plasticized PVC matrix which is placed on the distal end of the fiber. Sensor characteristics such as limit of detection and reversibility are presented.

  5. High temperature performance of high-efficiency, multi-layer solar selective coatings for tower applications

    SciTech Connect

    Gray, M. H.; Tirawat, R.; Kessinger, K. A.; Ndione, P. F.

    2015-05-01

    The roadmap to next-generation concentrating solar power plants anticipates a progression to central towers with operating temperatures in excess of 650°C. These higher temperatures are required to drive higher power-cycle efficiencies, resulting in lower cost energy. However, these conditions also place a greater burden on the materials making up the receiver. Any novel absorber material developed for next-generation receivers must be stable in air, cost effective, and survive thousands of heating and cooling cycles. The collection efficiency of a power tower plant can be increased if the energy absorbed by the receiver is maximized while the heat loss from the receiver to the environment is minimized. Thermal radiation losses can be significant (>7% annual energy loss) with receivers at temperatures above 650°C. We present progress toward highly efficient and durable solar selective absorbers (SSAs) intended for operating temperatures from 650°C to 1000°C. Selective efficiency (ηsel) is defined as the energy retained by the absorber, accounting for both absorptance and emittance, relative to the energy incident on the surface. The low emittance layers of multilayer SSAs are binary compounds of refractory metals whose material properties indicate that coatings formed of these materials should be oxidation resistant in air to 800-1200°C. On this basis, we initially developed a solar selective coating for parabolic troughs. This development has been successfully extended to meet the absorptance and emittance objectives for the more demanding, high temperature regime. We show advancement in coating materials, processing and designs resulting in the initial attainment of target efficiencies ηsel > 0.91 for proposed tower conditions. Additionally, spectral measurements show that these coatings continue to perform at targeted levels after cycling to temperatures of 1000°C in environments of nitrogen and forming gas.

  6. High temperature performance of high-efficiency, multi-layer solar selective coatings for tower applications

    DOE PAGESBeta

    Gray, M. H.; Tirawat, R.; Kessinger, K. A.; Ndione, P. F.

    2015-05-01

    The roadmap to next-generation concentrating solar power plants anticipates a progression to central towers with operating temperatures in excess of 650°C. These higher temperatures are required to drive higher power-cycle efficiencies, resulting in lower cost energy. However, these conditions also place a greater burden on the materials making up the receiver. Any novel absorber material developed for next-generation receivers must be stable in air, cost effective, and survive thousands of heating and cooling cycles. The collection efficiency of a power tower plant can be increased if the energy absorbed by the receiver is maximized while the heat loss from themore » receiver to the environment is minimized. Thermal radiation losses can be significant (>7% annual energy loss) with receivers at temperatures above 650°C. We present progress toward highly efficient and durable solar selective absorbers (SSAs) intended for operating temperatures from 650°C to 1000°C. Selective efficiency (ηsel) is defined as the energy retained by the absorber, accounting for both absorptance and emittance, relative to the energy incident on the surface. The low emittance layers of multilayer SSAs are binary compounds of refractory metals whose material properties indicate that coatings formed of these materials should be oxidation resistant in air to 800-1200°C. On this basis, we initially developed a solar selective coating for parabolic troughs. This development has been successfully extended to meet the absorptance and emittance objectives for the more demanding, high temperature regime. We show advancement in coating materials, processing and designs resulting in the initial attainment of target efficiencies ηsel > 0.91 for proposed tower conditions. Additionally, spectral measurements show that these coatings continue to perform at targeted levels after cycling to temperatures of 1000°C in environments of nitrogen and forming gas.« less

  7. Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations

    NASA Astrophysics Data System (ADS)

    Ikegami, Tohru; Tanaka, Nobuo

    2016-06-01

    Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics.

  8. Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations.

    PubMed

    Ikegami, Tohru; Tanaka, Nobuo

    2016-06-12

    Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics. PMID:27306311

  9. Influence of time and length size feature selections for human activity sequences recognition.

    PubMed

    Fang, Hongqing; Chen, Long; Srinivasan, Raghavendiran

    2014-01-01

    In this paper, Viterbi algorithm based on a hidden Markov model is applied to recognize activity sequences from observed sensors events. Alternative features selections of time feature values of sensors events and activity length size feature values are tested, respectively, and then the results of activity sequences recognition performances of Viterbi algorithm are evaluated. The results show that the selection of larger time feature values of sensor events and/or smaller activity length size feature values will generate relatively better results on the activity sequences recognition performances. PMID:24075148

  10. Active tectonics in the Moroccan High Atlas

    NASA Astrophysics Data System (ADS)

    Sébrier, Michel; Siame, Lionel; Zouine, El Mostafa; Winter, Thierry; Missenard, Yves; Leturmy, Pascale

    2006-01-01

    Review of seismological and structural data coupled with new data on topographical, geomorphology, and Quaternary geology allows delineating the major active faults of the High Atlas. These are the North and South border faults of which fault segmentations correspond to Mw ranging between 6.1 and 6.4. Detail active tectonics analyses were performed on the South Atlas Fault Zone in the Souss and Ouarzazate basins, where deformed Quaternary levels permit to estimate slip rates on individual faults in the order of 0.1 mm yr -1. Such low slip rates imply that large observational time-window is needed to analyze active deformation in low-seismicity regions. However, the complex 3D geometry of reverse or thrust faults may cause difficulty to relate surface observations with the deeper faults that have the potential to nucleate big earthquakes. Further studies are necessary to interpret the Anti Atlas seismicity. To cite this article: M. Sebrier et al., C. R. Geoscience 338 (2006).

  11. Neuroprotective effects of high affinity sigma 1 receptor selective compounds

    PubMed Central

    Luedtke, Robert R.; Perez, Evelyn; Yang, Shao-Hua; Liu, Ran; Vangveravong, Suwanna; Tu, Zhude; Mach, Robert H.; Simpkins, James W.

    2014-01-01

    We previously reported that the antipsychotic drug haloperidol, a multifunctional D2-like dopamine and sigma receptor subtype antagonist, has neuroprotective properties. In this study we further examined the association between neuroprotection and receptor antagonism by evaluating a panel of novel compounds with varying affinity at sigma and D2-like dopamine receptors. These compounds were evaluated using an in vitro cytotoxicity assay that utilizes a hippocampal-derived cell line, HT-22, in the presence or absence of varying concentrations (5 to 20 mM) of glutamate. While haloperidol was found to be a potent neuroprotective agent in this in vitro cell assay, the prototypic sigma 1 receptor agonist (+)-pentazocine was found not to be neuroprotective. Subsequently, the potency for the neuroprotection of HT-22 cells was evaluated for a) three SV series indoles which have nMolar affinity at D2-like receptors but varying affinity at sigma 1 receptor and b) two benzyl phenylacetamides sigma 1 receptor selective compounds which bind with low affinity at D2-like receptors but have nMolar affinity for the sigma 1 receptor. We observed that cytoprotection correlated with the affinity of the compounds for sigma 1 receptors. Based upon results from the HT-22 cell-based in vitro assay, two phenylacetamides, LS-127 and LS-137, were further evaluated in vivo using a transient middle cerebral artery occlusion (t-MCAO) model of stroke. At a dose of 100 µg/kg, both LS-127 and LS-137 attenuated infarct volume by approximately 50%. These studies provide further evidence that sigma 1 receptor selective compounds can provide neuroprotection in cytotoxic situations. These results also demonstrate that sigma 1 receptor selective benzyl phenylacetamides are candidate pharmacotherapeutic agents that could be used to minimize neuronal death after a stroke or head trauma. PMID:22285434

  12. High-Spatial-Resolution Imaging Combining High-Order Adaptive Optics, Frame Selection, and Speckle Masking Reconstruction

    NASA Astrophysics Data System (ADS)

    Denker, Carsten; Mascarinas, Dulce; Xu, Yan; Cao, Wenda; Yang, Guo; Wang, Haimin; Goode, Philip R.; Rimmele, Thomas

    2005-04-01

    We present, for the first time, high-spatial-resolution observations combining high-order adaptive optics (AO), frame selection, and post-facto image correction via speckle masking. The data analysis is based on observations of solar active region NOAA 10486 taken with the Dunn Solar Telescope (DST) at the Sacramento Peak Observatory (SPO) of the National Solar Observatory (NSO) on 29 October 2003. The high Strehl ratio encountered in AO corrected short-exposure images provides highly improved signal-to-noise ratios leading to a superior recovery of the object’s Fourier phases. This allows reliable detection of small-scale solar features near the diffraction limit of the telescope. Speckle masking imaging provides access to high-order wavefront aberrations, which predominantly originate at high atmospheric layers and are only partially corrected by the AO system. In addition, the observations provided qualitative measures of the image correction away from the lock point of the AO system. We further present a brief inspection of the underlying imaging theory discussing the limitations and prospects of this multi-faceted image reconstruction approach in terms of the recovery of spatial information, photometric accuracy, and spectroscopic applications.

  13. A Comparison of Athletes and Non-Athletes at Highly Selective Colleges: Academic Performance and Personal Development

    ERIC Educational Resources Information Center

    Aries, Elizabeth; McCarthy, Danielle; Salovey, Peter; Banaji, Mahzarin R.

    2004-01-01

    Student-athletes were studied over 4 years at a highly selective liberal arts college and an Ivy League university. Students spending 10 or more hours per week in athletic activities had lower entering academic credentials and academic self-assessments than non-athletes, but the academic performance of athletes was not below what would be expected…

  14. Highly selective catalytic process for synthesizing 1-hexene from ethylene

    DOEpatents

    Sen, Ayusman; Murtuza, Shahid; Harkins, Seth B.; Andes, Cecily

    2002-01-01

    Ethylene is trimerized to form 1-hexene, at a selectivity of up to about 99 mole percent, by contacting ethylene, at an ethylene pressure of from about 200-1500 psig and at a reaction temperature of from about 0.degree. C. to about 100.degree. C., with a catalyst comprising a tantalum compound (e.g., TaCl.sub.5) and a alkylating component comprising a metal hydrocarbyl compound or a metal hydrocarbyl halide compound (e.g., Sn(CH.sub.3).sub.4).

  15. Donor-acceptor organo-imido polyoxometalates: high transparency, high activity redox-active NLO chromophores.

    PubMed

    Al-Yasari, Ahmed; Van Steerteghem, Nick; El Moll, Hani; Clays, Koen; Fielden, John

    2016-02-21

    We show that polyoxometalates (POMs) are an excellent redox-active acceptor on which to base high performance 2(nd) order non-linear optical (NLO) chromophores. This is demonstrated through three new organoimido-Lindqvist derivatives with HRS β0-values exceeding those of any dipolar organic system with comparable donor, π-system and absorption profile. Thus, organoimido POMs may provide a new generation of high performance, high transparency, and potentially redox-switchable NLO materials. PMID:26815652

  16. Active cooling for downhole instrumentation: Preliminary analysis and system selection

    SciTech Connect

    Bennett, G.A.

    1988-03-01

    A feasibility study and a series of preliminary designs and analyses were done to identify candidate processes or cycles for use in active cooling systems for downhole electronic instruments. A matrix of energy types and their possible combinations was developed and the energy conversion process for each pari was identified. The feasibility study revealed conventional as well as unconventional processes and possible refrigerants and identified parameters needing further clarifications. A conceptual design or series od oesigns for each system was formulated and a preliminary analysis of each design was completed. The resulting coefficient of performance for each system was compared with the Carnot COP and all systems were ranked by decreasing COP. The system showing the best combination of COP, exchangeability to other operating conditions, failure mode, and system serviceability is chosen for use as a downhole refrigerator. 85 refs., 48 figs., 33 tabs.

  17. Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons.

    PubMed

    Shlosberg, Dan; Buskila, Yossi; Abu-Ghanem, Yasmin; Amitai, Yael

    2012-01-01

    Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300-400 μm from the stimulation, but not when inhibition was non-selectively weakened with the GABA(A) blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity. PMID:22347168

  18. Delayed cerebrospinal fluid sterilization, in vitro bactericidal activities, and side effects of selected beta-lactams.

    PubMed

    Dajani, A S; Pokowski, L H

    1990-01-01

    Ampicillin (or penicillin G) plus chloramphenicol, cefuroxime, ceftriaxone, and cefotaxime have been used in the treatment of bacterial meningitis beyond the neonatal period. Review of recent data from the USA and Europe indicates that delayed CSF sterilization occurs significantly more often with ampicillin/chloramphenicol and cefuroxime than with ceftriaxone and cefotaxime. Delayed CSF sterilization is associated with an increased morbidity and neurological complications. Previously reported in vitro interactions between chloramphenicol and various beta-lactam antibiotics indicate that for bacteria where chloramphenicol is only bacteriostatic, the combination of chloramphenicol with beta-lactams is antagonistic. Killing rates of various beta-lactams were compared against a number of gram-positive and gram-negative bacteria. Cidal activity of some beta-lactams was inoculum dependent. There was a good correlation between in vitro activity and ability to sterilize CSF. Ceftriaxone is highly protein bound and its use in newborns is discouraged. Diarrhea occurs significantly more often after cefriaxone use than after the use of other agents. Ceftriaxone is uniquely associated with a high frequency of biliary pseudolithiasis which may be symptomatic and can cause measureable morbidity. In selecting the "proper" antimicrobial agent for the treatment of bacterial meningitis considerations should be given to proven clinical efficacy, prompt CSF sterilization, rapid in vitro cidal activity, safety and cost. We recommend cefotaxime as the agent of choice in the treatment of bacterial meningitis. PMID:2091255

  19. Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate.

    PubMed Central

    Lazarowski, E. R.; Watt, W. C.; Stutts, M. J.; Boucher, R. C.; Harden, T. K.

    1995-01-01

    1. The human P2U-purinoceptor was stably expressed in 1321N1 human astrocytoma cells and the pharmacological selectivity of the expressed receptor was studied by measurement of inositol lipid hydrolysis. 2. High basal levels of inositol phosphates occurred in P2U-purinoceptor-expressing cells. This phenomenon was shown to be due to release of large amounts of ATP from 1321N1 cells, and could be circumvented by adoption of an assay protocol that did not involve medium changes. 3. UTP, ATP and ATP gamma S were full and potent agonists for activation of phospholipase C with EC50 values of 140 nM, 230 nM, and 1.72 microM, respectively. 5BrUTP, 2C1ATP and 8BrATP were also full agonists although less potent than their natural congeners. Little or no effect was observed with the selective P2Y-, P2X-, and P2T-purinoceptor agonists, 2MeSATP, alpha,beta-MeATP, and 2MeSADP, respectively. 4. Diadenosine tetraphosphate, Ap4A, was a surprisingly potent agonist at the expressed P2U-purinoceptor with an EC50 (720 nM) in the range of the most potent P2U-purinoceptor agonists. Ap4A may be a physiologically important activator of P2U-purinoceptors. PMID:8564228

  20. Resistance to selective BRAF inhibition can be mediated by modest upstream pathway activation.

    PubMed

    Su, Fei; Bradley, William D; Wang, Qiongqing; Yang, Hong; Xu, Lizhong; Higgins, Brian; Kolinsky, Kenneth; Packman, Kathryn; Kim, Min Jung; Trunzer, Kerstin; Lee, Richard J; Schostack, Kathleen; Carter, Jade; Albert, Thomas; Germer, Soren; Rosinski, Jim; Martin, Mitchell; Simcox, Mary Ellen; Lestini, Brian; Heimbrook, David; Bollag, Gideon

    2012-02-15

    A high percentage of patients with BRAF(V600E) mutant melanomas respond to the selective RAF inhibitor vemurafenib (RG7204, PLX4032) but resistance eventually emerges. To better understand the mechanisms of resistance, we used chronic selection to establish BRAF(V600E) melanoma clones with acquired resistance to vemurafenib. These clones retained the V600E mutation and no second-site mutations were identified in the BRAF coding sequence. Further characterization showed that vemurafenib was not able to inhibit extracellular signal-regulated kinase phosphorylation, suggesting pathway reactivation. Importantly, resistance also correlated with increased levels of RAS-GTP, and sequencing of RAS genes revealed a rare activating mutation in KRAS, resulting in a K117N change in the KRAS protein. Elevated levels of CRAF and phosphorylated AKT were also observed. In addition, combination treatment with vemurafenib and either a MAP/ERK kinase (MEK) inhibitor or an AKT inhibitor synergistically inhibited proliferation of resistant cells. These findings suggest that resistance to BRAF(V600E) inhibition could occur through several mechanisms, including elevated RAS-GTP levels and increased levels of AKT phosphorylation. Together, our data implicate reactivation of the RAS/RAF pathway by upstream signaling activation as a key mechanism of acquired resistance to vemurafenib, in support of clinical studies in which combination therapy with other targeted agents are being strategized to combat resistance. PMID:22205714

  1. Water-soluble Co(III) complexes of substituted phenanthrolines with cell selective anticancer activity.

    PubMed

    Jagadeesan, Sivaraman; Balasubramanian, Vimalkumar; Baumann, Patric; Neuburger, Markus; Häussinger, Daniel; Palivan, Cornelia G

    2013-11-01

    Transition metal complexes with substituted phenanthrolines as ligands represent potential anticancer products without the drawbacks of platinum complexes that are currently marketed. Here, we report the synthesis and cell selective anticancer activity of five new water-soluble Co(III) complexes with methyl substituted phenanthroline ligands. The complexes were characterized by elemental analysis, NMR, FAB-mass spectrometry, FTIR, electronic spectroscopy, and single crystal X-ray diffraction. Possible interaction of these complexes with DNA was assessed by a combination of circular dichroism, UV-vis spectroscopy titration, and ethidium bromide displacement assay, and the results indicated that DNA interaction is weak for these complexes. Cellular uptake and cytotoxicity of complexes at low concentrations were assessed by flow cytometry on PC-3 cells, while their effect on intracellular mitochondrial function was measured by MTS assay on HeLa and PC-3 cell lines. These complexes showed selective cytotoxicity with a significantly higher effect on intracellular mitochondrial function in PC-3 cells than in HeLa cells. At low concentrations, complex 2 had the highest cytotoxic effect on PC-3 cells, inducing around 38% cell death, and the correlation of cytotoxicity of these complexes to their hydrophobicity indicates that an appropriate value of the hydrophobicity is essential for high antitumor activity. PMID:24127683

  2. Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons

    PubMed Central

    Canetta, Sarah; Bolkan, Scott; Padilla-Coreano, Nancy; Song, LouJin; Sahn, Ryan; Harrison, Neil; Gordon, Joshua A.; Brown, Alan; Kellendonk, Christoph

    2015-01-01

    Summary Abnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

  3. Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes.

    PubMed

    Nardid, Oleg A; Schetinskey, Miroslav I; Kucherenko, Yuliya V

    2013-03-01

    Dimethyl sulfoxide (DMSO), a by-product of the pulping industry, is widely used in biological research, cryobiology and medicine. On cellular level DMSO was shown to suppress NMDA-AMPA channels activation, blocks Na+ channel activation and attenuates Ca2+ influx (Lu and Mattson 2001). In the present study we explored the whole-cell patch-clamp to examine the acute effect of high concentrations of DMSO (0.1-2 mol/l) on cation channels activity in human erythrocytes. Acute application of DMSO (0.1-2 mol/l) dissolved in Cl--containing saline buffer solution significantly inhibited cation conductance in human erythrocytes. Inhibition was concentration-dependent and had an exponential decay profile. DMSO (2 mol/l) induced cation inhibition in Cl-- containing saline solutions of: 40.3 ± 3.9% for K+, 35.4 ± 3.1% for Ca2+ and 47.4 ± 1.9% for NMDG+. Substitution of Cl- with gluconate- increased the inhibitory effect of DMSO on the Na+ current. Inhibitory effect of DMSO was neither due to high permeability of erythrocytes to DMSO nor to an increased tonicity of the bath media since no effect was observed in 2 mol/l glycerol solution. In conclusion, we have shown that high concentrations of DMSO inhibit the non-selective cation channels in human erythrocytes and thus protect the cells against Na+ and Ca2+ overload. Possible mechanisms of DMSO effect on cation conductance are discussed. PMID:23531832

  4. A Novel Ion - selective Polymeric Membrane Sensor for Determining Thallium(I) With High Selectivity

    NASA Astrophysics Data System (ADS)

    Kassim, Anuar; Rezayi, Majid; Ahmadzadeh, Saeid; Rounaghi, Gholamhossein; Mohajeri, Masoomeh; Azah Yusof, Noor; Tee, Tan Wee; Yook Heng, Lee; Halim Abdullah, Abd

    2011-02-01

    Thallium is a toxic metal that introduced into the environment mainly as a waste from the production of zinc, cadmium, and lead and by combustion of coal. Thallium causes gastrointestinal irritation and nerve damage when people are exposed to it for relatively short period of time. For long term, thallium has the potential to cause the following effects: change in blood chemistry, damage to liver, kidney, intestinal and testicular tissue, and hair loss. In this work a membrane was prepared by use of 4'-nitrobenzo -18-crown-6 (4'NB18C6) as an ion carrier, polyvinylchloride (PVC) as a matrix, and diocthylphetalate (DOP) as a plasticizer for making an ion selective electrode for measurement of Tl+ cation in solutions. The amount of 4'-nitrobenzo-18C6 and polyvinylchloride were optimized in the preparation of the membrane. The response of the electrode was Nernstian within the concentration range 1.0 × 10-8 to 1.0 × 10-1M. This sensor displays a drift in Nernstian response for this cation with increasing the amount of ionophore and decreasing the amount of polyvinylchloride.The results of potentiometric measurements showed that, this electrode also responses to Cu2+ Ni2+ and Pb2+ cations, but the electrode has a wider dynamic range and a lower detection limit to Tl+ cation. The effects of various parameters such as pH, different cations interferences, effect of the amount of ionophore and polyvinylchloride and time on response of the coated ion selective electrode were investigated. Finally the constructed electrode was used in complexometric and precipitation titrations of Tl+ cation with EDTA and KBr, respectively. The response of the fabricated electrode at concentration range from 1.0 × 10-8 to 1.0 × 10-1M is linear with a Nernstian slope of 57.27 mV.

  5. "XSEL" Virtual Selective High School Provision: Delivering Academically Selective Secondary Curriculum in Regional, Rural and Remote NSW

    ERIC Educational Resources Information Center

    Furney, Ann-Marie; McDiarmid, Carole

    2014-01-01

    This paper describes the development and implementation of the "xsel" program in Western NSW. The program supports identified high school students from regional, rural and remote communities to access the study of English, maths and science at an academically selective level. A program review was undertaken during 2012 using a structured…

  6. Repellent activity of selected essential oils against Aedes aegypti.

    PubMed

    Choochote, W; Chaithong, U; Kamsuk, K; Jitpakdi, A; Tippawangkosol, P; Tuetun, B; Champakaew, D; Pitasawat, B

    2007-07-01

    Essential oils extracted from ten plant species were screened for repellency against Aedes aegypti mosquitoes. Three oils; Zanthoxylum piperitum, Anethum graveolens and Kaempferia galanga, exerted protection against A. aegypti, with median complete-protection times of 1, 0.5 and 0.25 h, respectively. The protection times were increased significantly by incorporating 10% vanillin. The highest potential was established from Z. piperitum oil +10% vanillin (2.5 h, range=1-2.5 h). Mixtures from pairs of the effective oils possessed slight repellency that ranged from 0-0.5 h. None of the oil combinations repelled A. aegypti for longer than their constituent oil alone. With vanillin added, however, each oil mixture provided improved protection, which was approximately equal to oil on its own. GC/MS analysis revealed that the main component of Z. piperitum fruit oil was limonene (37.99%), with minor amounts of sabinene (13.30%) and beta-myrcene (7.17%). Repellent testing of stored samples of Z. piperitum fruit oil against A. aegypti demonstrated that repellent activity of those kept at -20 degrees C or 4 degrees C was present for a period of at least 3 months. Therefore, the essential oil of Z. piperitum fruit may prove useful in the development of mosquito repellents as an effective personal protection measure against mosquito bites. PMID:17512681

  7. Spatial Correlation Function of the Chandra Selected Active Galactic Nuclei

    NASA Technical Reports Server (NTRS)

    Yang, Y.; Mushotzky, R. F.; Barger, A. J.; Cowie, L. L.

    2006-01-01

    two groups. We have also found that the correlation between X-ray luminosity and clustering amplitude is weak, which, however, is fully consistent with the expectation using the simplest relations between X-ray luminosity, black hole mass, and dark halo mass. We study the evolution of the AGN clustering by dividing the samples into 4 redshift bins over 0.1 Mpc< z <3.0 Mpc. We find a very mild evolution in the clustering amplitude, which show the same evolution trend found in optically selected quasars in the 2dF survey. We estimate the evolution of the bias, and find that the bias increases rapidly with redshift (b(z = 0.45) = 0.95 +/- 0.15 and b(z = 2.07) = 3.03 +/- 0.83): The typical mass of the dark matter halo derived from the bias estimates show little change with redshift. The average halo mass is found to be log (M(sub halo)/M(sun))approximates 12.1. Subject headings: cosmology: observations - large-scale structure of the universe - x-rays: diffuse background - galaxies: nuclei

  8. Highly selective hydrogenation of phenol and derivatives over a Pd@carbon nitride catalyst in aqueous media.

    PubMed

    Wang, Yong; Yao, Jia; Li, Haoran; Su, Dangsheng; Antonietti, Markus

    2011-03-01

    Cyclohexanone is an important intermediate in the manufacture of polyamides in chemical industry, but direct selective hydrogenation of phenol to cyclohexanone under mild conditions is a challenge. We report here a catalyst made of Pd nanoparticles supported on a mesoporous graphitic carbon nitride, Pd@mpg-C(3)N(4), which was shown to be highly active and promoted the selective formation of cyclohexanone under atmospheric pressure of hydrogen in aqueous media without additives. Conversion of 99% and a selectivity higher than 99% were achieved within 2 h at 65 °C. The reaction can be accelerated at higher temperature, but even at room temperature, 99% conversion and 96% selectivity could still be obtained. The generality of the Pd@mpg-C(3)N(4) catalyst for this reaction was demonstrated by selective hydrogenation of other hydroxylated aromatic compounds with similar performance. PMID:21294506

  9. A new hydroxynaphthyl benzothiazole derived fluorescent probe for highly selective and sensitive Cu(2+) detection.

    PubMed

    Tang, Lijun; He, Ping; Zhong, Keli; Hou, Shuhua; Bian, Yanjiang

    2016-12-01

    A new reactive probe, 1-(benzo[d]thiazol-2-yl)naphthalen-2-yl-picolinate (BTNP), was designed and synthesized. BTNP acts as a highly selective probe to Cu(2+) in DMSO/H2O (7/3, v/v, Tris-HCl 10mM, pH=7.4) solution based on Cu(2+) catalyzed hydrolysis of the picolinate ester moiety in BTNP, which leads to the formation of an ESIPT active product with dual wavelength emission enhancement. The probe also possesses the advantages of simple synthesis, rapid response and high sensitivity. The pseudo-first-order reaction rate constant was calculated to be 0.205min(-1). Moreover, application of BTNP to Cu(2+) detection in living cells and real water samples was also explored. PMID:27391231

  10. A new hydroxynaphthyl benzothiazole derived fluorescent probe for highly selective and sensitive Cu2 + detection

    NASA Astrophysics Data System (ADS)

    Tang, Lijun; He, Ping; Zhong, Keli; Hou, Shuhua; Bian, Yanjiang

    2016-12-01

    A new reactive probe, 1-(benzo[d]thiazol-2-yl)naphthalen-2-yl-picolinate (BTNP), was designed and synthesized. BTNP acts as a highly selective probe to Cu2 + in DMSO/H2O (7/3, v/v, Tris-HCl 10 mM, pH = 7.4) solution based on Cu2 + catalyzed hydrolysis of the picolinate ester moiety in BTNP, which leads to the formation of an ESIPT active product with dual wavelength emission enhancement. The probe also possesses the advantages of simple synthesis, rapid response and high sensitivity. The pseudo-first-order reaction rate constant was calculated to be 0.205 min- 1. Moreover, application of BTNP to Cu2 + detection in living cells and real water samples was also explored.

  11. Characteristic interactivity of landiolol, an ultra-short-acting highly selective β1-blocker, with biomimetic membranes: Comparisons with β1-selective esmolol and non-selective propranolol and alprenolol

    PubMed Central

    Tsuchiya, Hironori; Mizogami, Maki

    2013-01-01

    Although β1-blockers have been perioperatively used to reduce the cardiac disorders associated with general anesthesia, little is known about the mechanistic characteristics of ultra-short-acting highly selective β1-blocker landiolol. We studied its membrane-interacting property in comparison with other selective and non-selective β1-blockers. Biomimetic membranes prepared with phospholipids and cholesterol of varying compositions were treated with β1-selective landiolol and esmolol and non-selective propranolol and alprenolol at 0.5–200 μM. The membrane interactivity and the antioxidant activity were determined by measuring fluorescence polarization and by peroxidizing membrane lipids with peroxynitrite, respectively. Non-selective β1-blockers, but not selective ones, intensively acted on 1,2-dipalmitoylphosphatidylcholine (DPPC) liposomal membranes and cardiomyocyte-mimetic membranes to increase the membrane fluidity. Landiolol and its inactive metabolite distinctively decreased the fluidity of DPPC liposomal membranes, suggesting that a membrane-rigidifying effect is attributed to the morpholine moiety in landiolol structure but unlikely to clinically contribute to the β1-blocking effect of landiolol. Propranolol and alprenolol interacted with lipid raft model membranes, whereas neither landiolol nor esmolol. All drugs fluidized mitochondria-mimetic membranes and inhibited the membrane lipid peroxidation with the potency correlating to their membrane interactivity. Landiolol is characterized as a drug devoid of the interactivity with membrane lipid rafts relating to β2-adrenergic receptor blockade. The differentiation between β1-blocking selectivity and non-selectivity is compatible with that between membrane non-interactivity and interactivity. The mitochondrial membrane fluidization by landiolol independent of blocking β1-adrenergic receptors is responsible for the antioxidant cardioprotection common to non-selective and selective β1-blockers

  12. Characteristic interactivity of landiolol, an ultra-short-acting highly selective β1-blocker, with biomimetic membranes: Comparisons with β1-selective esmolol and non-selective propranolol and alprenolol.

    PubMed

    Tsuchiya, Hironori; Mizogami, Maki

    2013-01-01

    Although β1-blockers have been perioperatively used to reduce the cardiac disorders associated with general anesthesia, little is known about the mechanistic characteristics of ultra-short-acting highly selective β1-blocker landiolol. We studied its membrane-interacting property in comparison with other selective and non-selective β1-blockers. Biomimetic membranes prepared with phospholipids and cholesterol of varying compositions were treated with β1-selective landiolol and esmolol and non-selective propranolol and alprenolol at 0.5-200 μM. The membrane interactivity and the antioxidant activity were determined by measuring fluorescence polarization and by peroxidizing membrane lipids with peroxynitrite, respectively. Non-selective β1-blockers, but not selective ones, intensively acted on 1,2-dipalmitoylphosphatidylcholine (DPPC) liposomal membranes and cardiomyocyte-mimetic membranes to increase the membrane fluidity. Landiolol and its inactive metabolite distinctively decreased the fluidity of DPPC liposomal membranes, suggesting that a membrane-rigidifying effect is attributed to the morpholine moiety in landiolol structure but unlikely to clinically contribute to the β1-blocking effect of landiolol. Propranolol and alprenolol interacted with lipid raft model membranes, whereas neither landiolol nor esmolol. All drugs fluidized mitochondria-mimetic membranes and inhibited the membrane lipid peroxidation with the potency correlating to their membrane interactivity. Landiolol is characterized as a drug devoid of the interactivity with membrane lipid rafts relating to β2-adrenergic receptor blockade. The differentiation between β1-blocking selectivity and non-selectivity is compatible with that between membrane non-interactivity and interactivity. The mitochondrial membrane fluidization by landiolol independent of blocking β1-adrenergic receptors is responsible for the antioxidant cardioprotection common to non-selective and selective β1-blockers. PMID

  13. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity

    PubMed Central

    Tsai, James; Lee, John T.; Wang, Weiru; Zhang, Jiazhong; Cho, Hanna; Mamo, Shumeye; Bremer, Ryan; Gillette, Sam; Kong, Jun; Haass, Nikolas K.; Sproesser, Katrin; Li, Ling; Smalley, Keiran S. M.; Fong, Daniel; Zhu, Yong-Liang; Marimuthu, Adhirai; Nguyen, Hoa; Lam, Billy; Liu, Jennifer; Cheung, Ivana; Rice, Julie; Suzuki, Yoshihisa; Luu, Catherine; Settachatgul, Calvin; Shellooe, Rafe; Cantwell, John; Kim, Sung-Hou; Schlessinger, Joseph; Zhang, Kam Y. J.; West, Brian L.; Powell, Ben; Habets, Gaston; Zhang, Chao; Ibrahim, Prabha N.; Hirth, Peter; Artis, Dean R.; Herlyn, Meenhard; Bollag, Gideon

    2008-01-01

    BRAFV600E is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting “active” protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-RafV600E with an IC50 of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-RafV600E kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-RafV600E-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-RafV600E-positive cells. In B-RafV600E-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-RafV600E-driven tumors. PMID:18287029

  14. GAS PHASE SELECTIVE PHOTOXIDATION OF ALCOHOLS USING LIGHT-ACTIVATED TITANIUM DIOXIDE AND MOLECULAR OXYGEN

    EPA Science Inventory

    Gas Phase Selective Oxidation of Alcohols Using Light-Activated Titanium Dioxide and Molecular Oxygen

    Gas phase selective oxidations of various primary and secondary alcohols are studied in an indigenously built stainless steel up-flow photochemical reactor using ultravi...

  15. GENETIC ACTIVITY PROFILES AND PATTERN RECOGNITION IN TEST BATTERY SELECTION (JOURNAL VERSION)

    EPA Science Inventory

    Computer-generated genetic activity profiles and pairwise matching procedures may aid in the selection of the most appropriate short-term bioassays to be used in test batteries for the evaluation of the genotoxicity of a given chemical or group of chemicals. Selection of test bat...

  16. Highly Tunable Selectivity for Syngas-Derived Alkenes over Zinc and Sodium-Modulated Fe5 C2 Catalyst.

    PubMed

    Zhai, Peng; Xu, Cong; Gao, Rui; Liu, Xi; Li, Mengzhu; Li, Weizhen; Fu, Xinpu; Jia, Chunjiang; Xie, Jinglin; Zhao, Ming; Wang, Xiaoping; Li, Yong-Wang; Zhang, Qianwen; Wen, Xiao-Dong; Ma, Ding

    2016-08-16

    Zn- and Na-modulated Fe catalysts were fabricated by a simple coprecipitation/washing method. Zn greatly changed the size of iron species, serving as the structural promoter, while the existence of Na on the surface of the Fe catalyst alters the electronic structure, making the catalyst very active for CO activation. Most importantly, the electronic structure of the catalyst surface suppresses the hydrogenation of double bonds and promotes desorption of products, which renders the catalyst unexpectedly reactive toward alkenes-especially C5+ alkenes (with more than 50% selectivity in hydrocarbons)-while lowering the selectivity for undesired products. This study enriches C1 chemistry and the design of highly selective new catalysts for high-value chemicals. PMID:27445106

  17. Directing reaction pathways by catalyst active-site selection using self-assembled monolayers.

    PubMed

    Pang, Simon H; Schoenbaum, Carolyn A; Schwartz, Daniel K; Medlin, J Will

    2013-01-01

    One key route for controlling reaction selectivity in heterogeneous catalysis is to prepare catalysts that exhibit only specific types of sites required for desired product formation. Here we show that alkanethiolate self-assembled monolayers with varying surface densities can be used to tune selectivity to desired hydrogenation and hydrodeoxygenation products during the reaction of furfural on supported palladium catalysts. Vibrational spectroscopic studies demonstrate that the selectivity improvement is achieved by controlling the availability of specific sites for the hydrogenation of furfural on supported palladium catalysts through the selection of an appropriate alkanethiolate. Increasing self-assembled monolayer density by controlling the steric bulk of the organic tail ligand restricts adsorption on terrace sites and dramatically increases selectivity to desired products furfuryl alcohol and methylfuran. This technique of active-site selection simultaneously serves both to enhance selectivity and provide insight into the reaction mechanism. PMID:24025780

  18. An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase

    PubMed Central

    Deacon, Sean W.; Beeser, Alexander; Fukui, Jami A.; Rennefahrt, Ulrike E. E.; Myers, Cynthia; Chernoff, Jonathan; Peterson, Jeffrey R.

    2015-01-01

    SUMMARY Autoregulatory domains found within kinases may provide more unique targets for chemical inhibitors than the conserved ATP-binding pocket targeted by most inhibitors. The kinase Pak1 contains an autoinhibitory domain that suppresses the catalytic activity of its kinase domain. Pak1 activators relieve this autoinhibition and initiate conformational rearrangements and autophosphorylation events leading to kinase activation. We developed a screen for allosteric inhibitors targeting Pak1 activation and identified the inhibitor IPA-3. Remarkably, pre-activated Pak1 is resistant to IPA-3. IPA-3 also inhibits activation of related Pak isoforms regulated by autoinhibition, but not more distantly related Paks, nor >200 other kinases tested. Pak1 inhibition by IPA-3 in live cells supports a critical role for Pak in PDGF-stimulated Erk activation. These studies illustrate a novel strategy for kinase inhibition and introduce a highly selective, cell-permeable chemical inhibitor of Pak. PMID:18420139

  19. Selection and Physical Properties of High-redshift Galaxies

    NASA Astrophysics Data System (ADS)

    Fang, G. W.

    2014-09-01

    that the fraction of OGs and DGs in our sample (COSMOS) is similar, about 52% of them are DGs, and the other 48% are OGs. For 24 EROs in the UDF, 16 fall into DGs, while 8 are OGs. To reduce the redundancy of these three different classification methods, we perform a principal component analysis on the measurements of EROs, and find that the nonparametric measures and SEDs are efficient in segregating DGs and OGs. We investigate the dependence of the fraction of EROs on their observational properties, and the results suggest that DGs become increasingly important toward fainter magnitudes, redder colors, and higher redshifts. Moreover, we find that the clustering of EROs is much stronger than that of full K-limited samples of galaxies; and the clustering amplitude of OGs is a factor of ˜2 larger than DGs. In Chapter 3, we pick out 1609 star-forming galaxies (sgzKs: gzK=(z-K)_{AB}-1.4(g-z)_{AB}≥ 0.2) and 422 passively evolving galaxies (pgzKs: gzK<0.2 and (z-K)_{AB}>2.7) at z˜2 in the AEGIS field (K_{AB} < 22.0). The number counts of pgzKs in our sample turn over at K_{AB} ˜ 21.0, and both the number of faint and bright objects (including sgzKs and pgzKs) exceed the predictions of a recent semi-analytic model of galaxy formation. A more successful model is needed to explain this diversity. It is also found that the star formation rate (SFR) and specific SFR (sSFR) of sgzKs increase with redshift at all masses, implying that star-forming galaxies were much more active on average in the past. Moreover, the sSFR of massive galaxies is lower at all redshifts, suggesting that the mass growth of low-mass galaxies is more attributed to the star formation while comparing with high-mass galaxies. From the HST WFC3/F160W imaging data, we find that gzKs not only have diffuse structures, but also have single-object morphologies, implying that there are morphological variety and different formation processes for these galaxies at z˜2. In addition, we also find ˜ 10% of 828 gz

  20. Calcium-activated non-selective cation currents are involved in generation of tonic and bursting activity in dopamine neurons of the substantia nigra pars compacta.

    PubMed

    Mrejeru, Ana; Wei, Aguan; Ramirez, Jan Marino

    2011-05-15

    Nigral dopamine neurons are transiently activated by high frequency glutamatergic inputs relaying reward-predicting sensory information. The tonic firing pattern of dopamine cells responds to these inputs with a transient burst of spikes that requires NMDA receptors. Here, we show that NMDA receptor activation further excites the cell by recruiting a calcium-activated non-selective cation current (ICAN) capable of generating a plateau potential. Burst firing in vitro is eliminated after blockade of ICAN with flufenamic acid, 9-phenanthrol, or intracellular BAPTA. ICAN is likely to be mediated by a transient receptor potential (TRP) channel, and RT-PCR was used to confirm expression of TRPM2 and TRPM4mRNA in substantia nigra pars compacta.We propose that ICAN is selectively activated during burst firing to boost NMDA currents and allow plateau potentials. This boost mechanism may render DA cells vulnerable to excitotoxicity. PMID:21486760

  1. Discovery of a Highly Potent, Selective, and Orally Bioavailable Macrocyclic Inhibitor of Blood Coagulation Factor VIIa-Tissue Factor Complex.

    PubMed

    Zhang, Xiaojun; Glunz, Peter W; Johnson, James A; Jiang, Wen; Jacutin-Porte, Swanee; Ladziata, Vladimir; Zou, Yan; Phillips, Monique S; Wurtz, Nicholas R; Parkhurst, Brandon; Rendina, Alan R; Harper, Timothy M; Cheney, Daniel L; Luettgen, Joseph M; Wong, Pancras C; Seiffert, Dietmar; Wexler, Ruth R; Priestley, E Scott

    2016-08-11

    Inhibitors of the tissue factor (TF)/factor VIIa complex (TF-FVIIa) are promising novel anticoagulants which show excellent efficacy and minimal bleeding in preclinical models. Starting with an aminoisoquinoline P1-based macrocyclic inhibitor, optimization of the P' groups led to a series of highly potent and selective TF-FVIIa inhibitors which displayed poor permeability. Fluorination of the aminoisoquinoline reduced the basicity of the P1 group and significantly improved permeability. The resulting lead compound was highly potent, selective, and achieved good pharmacokinetics in dogs with oral dosing. Moreover, it demonstrated robust antithrombotic activity in a rabbit model of arterial thrombosis. PMID:27455395

  2. Selective Reduction in Neural Responses to High Calorie Foods Following Gastric Bypass Surgery

    PubMed Central

    Ochner, Christopher N.; Kwok, Yolande; Conceição, Eva; Pantazatos, Spiro P.; Puma, Lauren M.; Carnell, Susan; Teixeira, Julio; Hirsch, Joy; Geliebter, Allan

    2011-01-01

    Objective To investigate changes in neural activation and desire to eat in response to appetitive cues from pre- to postbariatric surgery for obesity. Background Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure. However, the mechanisms of action in RYGB are not well understood. A significant proportion of the resulting reduction in caloric intake is unaccounted for by the restrictive and malabsorptive mechanisms and is thought to be mediated by neuroendocrine function. Numerous investigations of postsurgical changes in gut peptides have resulted; however, changes in neural activation after RYGB surgery have not been previously investigated. Methods Functional magnetic resonance imaging and verbal rating scales were used to assess brain activation and desire to eat in response to high-and low-calorie food cues in 10 female patients 1-month pre- and post-RYGB surgery. Results Postsurgical reductions in brain activation were found in key areas within the mesolimbic reward pathway, which were significantly more pronounced in response to food cues that were high (vs. low) in caloric density. These changes mirrored concurrent postsurgical reductions in desire to eat, which were also greater in response to food cues that were high versus low in caloric density (P = 0.007). Conclusions Findings support the contention that RYGB surgery leads to substantial changes in neural responses to food cues encountered in the environment, provide a potential mechanism for the selective reduction in preferences for high-calorie foods, and suggest partial neural mediation of changes in caloric intake seen after RYGB surgery. PMID:21169809

  3. Electrochemical plasmonic sensing system for highly selective multiplexed detection of biomolecules based on redox nanoswitches.

    PubMed

    Dallaire, Anne-Marie; Patskovsky, Sergiy; Vallée-Bélisle, Alexis; Meunier, Michel

    2015-09-15

    In this paper, we present the development of a nanoswitch-based electrochemical surface plasmon resonance (eSPR) transducer for the multiplexed and selective detection of DNA and other biomolecules directly in complex media. To do so, we designed an experimental set-up for the synchronized measurements of electrochemical and electro-plasmonic responses to the activation of multiple electrochemically labeled structure-switching biosensors. As a proof of principle, we adapted this strategy for the detection of DNA sequences that are diagnostic of two pathogens (drug-resistant tuberculosis and Escherichia coli) by using methylene blue-labeled structure-switching DNA stem-loop. The experimental sensitivity of the switch-based eSPR sensor is estimated at 5 nM and target detection is achieved within minutes. Each sensor is reusable several times with a simple 8M urea washing procedure. We then demonstrated the selectivity and multiplexed ability of these switch-based eSPR by simultaneously detecting two different DNA sequences. We discuss the advantages of the proposed eSPR approach for the development of highly selective sensor devices for the rapid and reliable detection of multiple molecular markers in complex samples. PMID:25889347

  4. Progress in site selection for China`s high-level radioactive waste repository

    SciTech Connect

    Xu, G.; Wang, J.; Jin, Y.; Chen, W.

    1995-12-31

    In 1985, the China National Nuclear Corporation (CNNC) worked out an R and D program called DG program for the deep geological disposal of high-level radioactive waste in China. The site selection process for China`s HLW repository has been carried out since then according to this program. Granite is considered as the candidate host rock for the repository. The general siting criteria are based on the principle that, under the effect of natural and human activities, the long term (100,000 years) safety of the repository can be reasonably obtained and the disposed radioactive waste can be avoided from entering the biosphere and harming human beings. During siting, two types of factors are considered: (1) social factors, including the nuclear industry distribution population, economic potential and environmental protection etc.; (2) natural factors, including geographic, meteorological and geological (crustal stability, host rocks, hydrogeology, engineering geology). The site selection process is divided into 4 stages: (1) nationwide screening, (2) regional screening; (3) district screening; and (4) site screening. During the first stage (1985--1986) the following were considered as potential regions: (1) southwest China, (2) Guangdong area, (3) Inner Mongolia, (4) east China and (5) northwest China. During the second stage (1986--1988), 21 districts were selected for further investigation. Since 1989 most efforts have been focused on the Beishan area, Gansu province, northwest China, which is considered as the most potential district for the repository.

  5. Potent, Highly Selective, and Orally Bioavailable Gem-Difluorinated Monocationic Inhibitors of Neuronal Nitric Oxide Synthase

    PubMed Central

    Xue, Fengtian; Li, Huiying; Delker, Silvia L.; Fang, Jianguo; Martásek, Pavel; Roman, Linda J.; Poulos, Thomas L.; Silverman, Richard B.

    2010-01-01

    In our efforts to discover neuronal isoform selective nitric oxide synthase (NOS) inhibitors we have developed a series of compounds containing a pyrrolidine ring with two stereogenic centers. The enantiomerically pure compounds, (S,S) vs. (R,R), exhibited two different binding orientations, with (R,R) inhibitors showing much better potency and selectivity. To improve the bioavailability of these inhibitors we have introduced a CF2 moiety geminal to an amino group in the long tail of one of these inhibitors, which reduced its basicity, resulting in compounds with monocationic character under physiological pH conditions. Biological evaluations have led to a nNOS inhibitor with a Ki of 36 nM and high selectivity for nNOS over eNOS (3800-fold) and iNOS (1400-fold). MM-PBSA calculations indicated that the low pKa NH is, at least, partially protonated when bound to the active site. A comparison of rat oral bioavailability of the difluorinated compound to the parent molecule shows 22% for the difluorinated compound versus essentially no oral bioavailability for the parent compound. This indicates that the goal of this research to make compounds with only one protonated nitrogen atom at physiological pH to allow for membrane permeability, but which can become protonated when bound to NOS, has been accomplished. PMID:20843082

  6. Conformational Restriction Leading to a Selective CB2 Cannabinoid Receptor Agonist Orally Active Against Colitis

    PubMed Central

    2014-01-01

    The CB2 cannabinoid receptor has been implicated in the regulation of intestinal inflammation. Following on from the promising activity of a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide, we developed constrained analogues based on a 2H-pyrazolo[4,3-c]quinolin-3(5H)-one scaffold, with improved affinity for the hCB2 receptor and had very high selectivity over the hCB1 receptor. Importantly, the lead of this series (26, hCB2: Ki = 0.39 nM, hCB1: Ki > 3000 nM) was found to protect mice against experimental colitis after oral administration. PMID:25699149

  7. Selective Heterogeneous C-H Activation/Halogenation Reactions Catalyzed by Pd@MOF Nanocomposites.

    PubMed

    Pascanu, Vlad; Carson, Fabian; Solano, Marta Vico; Su, Jie; Zou, Xiaodong; Johansson, Magnus J; Martín-Matute, Belén

    2016-03-01

    A directed heterogeneous C-H activation/halogenation reaction catalyzed by readily synthesized Pd@MOF nanocatalysts was developed. The heterogeneous Pd catalysts used were a novel and environmentally benign Fe-based metal-organic framework (MOF) (Pd@MIL-88B-NH2 (Fe)) and the previously developed Pd@MIL-101-NH2 (Cr). Very high conversions and selectivities were achieved under very mild reaction conditions and in short reaction times. A wide variety of directing groups, halogen sources, and substitution patterns were well tolerated, and valuable polyhalogenated compounds were synthesized in a controlled manner. The synthesis of the Pd-functionalized Fe-based MOF and the recyclability of the two catalysts are also presented. PMID:26481867

  8. Directed Evolution of RebH for Site Selective Halogenation of Large, Biologically Active Molecules**

    PubMed Central

    Payne, James T.; Poor, Catherine B.

    2015-01-01

    We recently characterized the substrate scope of wild-type RebH and evolved variants of this enzyme with improved stability for biocatalysis. The substrate scopes of both RebH and the stabilized variants, however, are limited primarily to compounds similar in size to tryptophan. We have now used a substrate walking approach to further evolve RebH variants with expanded substrate scope. Two particularly notable variants were identified: 3-SS, which provides high conversion of tricyclic tryptoline derivatives; and 4-V, which accepts a broad range of large indoles and carbazoles. This constitutes the first reported use of directed evolution to enable functionalization of substrates not accepted by wild-type RebH and demonstrates the utility of RebH variants for site-selective halogenation of biologically active compounds. PMID:25678465

  9. Differential Classical Conditioning Selectively Heightens Response Gain of Neural Population Activity in Human Visual Cortex

    PubMed Central

    Song, Inkyung; Keil, Andreas

    2015-01-01

    Neutral cues, after being reliably paired with noxious events, prompt defensive engagement and amplified sensory responses. To examine the neurophysiology underlying these adaptive changes, we quantified the contrast-response function of visual cortical population activity during differential aversive conditioning. Steady-state visual evoked potentials (ssVEPs) were recorded while participants discriminated the orientation of rapidly flickering grating stimuli. During each trial, luminance contrast of the gratings was slowly increased and then decreased. Right-tilted gratings (CS+) were paired with loud white noise but left-tilted gratings (CS−) were not. The contrast-following waveform envelope of ssVEPs showed selective amplification of the CS+ only during the high-contrast stage of the viewing epoch. Findings support the notion that motivational relevance, learned in a time frame of minutes, affects vision through a response gain mechanism. PMID:24981277

  10. High Temperature Ultrasonic Transducers : Material Selection and Testing

    NASA Technical Reports Server (NTRS)

    Bar-Cohen, Yoseph; Bruno, Alessandro

    2012-01-01

    The task of my two-months internship was to test different materials to be used to build an high temperature transducer, to develop some prototypes and to test their performance, to assess the reliability of commercial product rated for such a temperature, as well as to collaborate in developing the signal processing code to measure the condensed water levels.

  11. An Inexpensive, Very High Impedance Digital Voltmeter for Selective Electrodes.

    ERIC Educational Resources Information Center

    Caceci, Marco S.

    1984-01-01

    Describes a compact, digital voltmeter which exceeds, both in accuracy and input impedance, most commercial pH meters and potentiometers. The instrument consists of two parts: a very high impedance hybrid operational amplifier used as a voltage follower (ICH8500/A, Intersil) and a four and one-half digits LED display panel meter (RP-4500,…

  12. How Selected High School Newspapers Covered the Persian Gulf War.

    ERIC Educational Resources Information Center

    Peterson, Jane W.; Maronn, Michelle

    1995-01-01

    Discusses the many ways in which high school newspapers covered the Persian Gulf War, ranging from a serious analysis to satire in the form of a Cliff Notes summary. Compares two editorials from "The Little Hawk" (Iowa City, Iowa), one supporting the war and the other against. (PA)

  13. Particle impactor assembly for size selective high volume air sampler

    DOEpatents

    Langer, Gerhard

    1988-08-16

    Air containing entrained particulate matter is directed through a plurality of parallel, narrow, vertically oriented impactor slots of an inlet element toward an adjacently located, relatively large, dust impaction surface preferably covered with an adhesive material. The air flow turns over the impaction surface, leaving behind the relatively larger particles according to the human thoracic separation system and passes through two elongate exhaust apertures defining the outer bounds of the impaction collection surface to pass through divergent passages which slow down and distribute the air flow, with entrained smaller particles, over a fine filter element that separates the fine particles from the air. The elongate exhaust apertures defining the impaction collection surface are spaced apart by a distance greater than the lengths of elongate impactor slots in the inlet element and are oriented to be normal thereto. By appropriate selection of dimensions and the number of impactor slots air flow through the inlet element is provided a nonuniform velocity distribution with the lower velocities being obtained near the center of the impactor slots, in order to separate out particles larger than a certain predetermined size on the impaction collection surface. The impaction collection surface, even in a moderately sized apparatus, is thus relatively large and permits the prolonged sampling of air for periods extending to four weeks.

  14. Production of high specific activity silicon-32

    DOEpatents

    Phillips, Dennis R.; Brzezinski, Mark A.

    1994-01-01

    A process for preparation of silicon-32 is provide and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  15. Production of high specific activity silicon-32

    SciTech Connect

    Phillips, D.R.; Brzezinski, M.A.

    1994-09-13

    A process for the preparation of silicon-32 is provided and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  16. Active coloration with flexible high contrast metastructures

    NASA Astrophysics Data System (ADS)

    Zhu, Li; Kapraun, Jonas; Ferrara, James; Chang-Hasnain, Connie J.

    2015-02-01

    The ability to actively control the perceived color of objects is highly desirable for a variety of applications, such as camouflage, sensing, and displays. Such a phenomenon can be readily found in nature - the chameleon is an excellent example. However, the capability to change color at-will has yet to be reproduced by humans. Ultra-thin dielectric high contrast metastructures (HCMs) have been shown to exhibit unique versatility to manipulate light. In this work, we report a completely new flexible HCM structure whose color can be varied by stretching the membrane. This is accomplished with a novel HCM design that annihilates the 0th order diffraction in a grating while enhancing the -1st order. The color perception of the HCM, determined by the -1st diffraction order, is thus easily changed with the variation of its period. The ultra-thin HCM is patterned on a silicon-on-insulator wafer and transferred onto a flexible membrane. We measure more than 15 times stronger intensity in the -1st order diffraction than the 0th order, in excellent agreement with theoretical results. We experimentally demonstrate brilliant colors and change the color of a 1 cm×1 cm sample from green to orange (39 nm wavelength change) with a stretch of 4.9% (25 nm period change). The same effect can be used for steering a laser beam. We demonstrate more than 40 resolvable beam spots.

  17. Survival of selected bacterial species in sterilized activated carbon filters and biological activated carbon filters.

    PubMed Central

    Rollinger, Y; Dott, W

    1987-01-01

    The survival of selected hygienically relevant bacterial species in activated carbon (AC) filters on a bench scale was investigated. The results revealed that after inoculation of the test strains the previously sterilized AC absorbed all bacteria (10(6) to 10(7)). After a period of 6 to 13 days without countable bacteria in the effluent, the numbers of Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas putida increased up to 10(4) to 10(5) CFU/ml of effluent and 10(6) to 10(7) CFU/g of AC. When Klebsiella pneumoniae and Streptococcus faecalis were used, no growth in filters could be observed. The numbers of E. coli, P. aeruginosa, and P. putida, however, decreased immediately and showed no regrowth in nonsterile AC from a filter which had been continuously connected to running tap water for 2 months. Under these conditions an autochthonous microflora developed on the carbon surface which could be demonstrated by scanning electron microscopy and culturing methods (heterotrophic plate count). These bacteria reduced E. coli, P. aeruginosa, and P. putida densities in the effluent by a factor of more than 10(5) within 1 to 5 days. The hypothesis that antagonistic substances of the autochthonous microflora were responsible for the elimination of the artificial contamination could not be confirmed because less than 1% of the isolates of the autochthonous microflora were able to produce such substances as indicated by in vitro tests. Competition for limiting nutrients was thought to be the reason for the observed effects. PMID:3579281

  18. HOST GALAXY PROPERTIES OF THE SWIFT BAT ULTRA HARD X-RAY SELECTED ACTIVE GALACTIC NUCLEUS

    SciTech Connect

    Koss, Michael; Mushotzky, Richard; Veilleux, Sylvain; Winter, Lisa M.; Baumgartner, Wayne; Tueller, Jack; Gehrels, Neil; Valencic, Lynne

    2011-10-01

    We have assembled the largest sample of ultra hard X-ray selected (14-195 keV) active galactic nucleus (AGN) with host galaxy optical data to date, with 185 nearby (z < 0.05), moderate luminosity AGNs from the Swift BAT sample. The BAT AGN host galaxies have intermediate optical colors (u - r and g - r) that are bluer than a comparison sample of inactive galaxies and optically selected AGNs from the Sloan Digital Sky Survey (SDSS) which are chosen to have the same stellar mass. Based on morphological classifications from the RC3 and the Galaxy Zoo, the bluer colors of BAT AGNs are mainly due to a higher fraction of mergers and massive spirals than in the comparison samples. BAT AGNs in massive galaxies (log M{sub *} >10.5) have a 5-10 times higher rate of spiral morphologies than in SDSS AGNs or inactive galaxies. We also see enhanced far-infrared emission in BAT AGN suggestive of higher levels of star formation compared to the comparison samples. BAT AGNs are preferentially found in the most massive host galaxies with high concentration indexes indicative of large bulge-to-disk ratios and large supermassive black holes. The narrow-line (NL) BAT AGNs have similar intrinsic luminosities as the SDSS NL Seyferts based on measurements of [O III] {lambda}5007. There is also a correlation between the stellar mass and X-ray emission. The BAT AGNs in mergers have bluer colors and greater ultra hard X-ray emission compared to the BAT sample as a whole. In agreement with the unified model of AGNs, and the relatively unbiased nature of the BAT sources, the host galaxy colors and morphologies are independent of measures of obscuration such as X-ray column density or Seyfert type. The high fraction of massive spiral galaxies and galaxy mergers in BAT AGNs suggest that host galaxy morphology is related to the activation and fueling of local AGN.

  19. Active interrogation of highly enriched uranium

    NASA Astrophysics Data System (ADS)

    Fairrow, Nannette Lea

    Safeguarding special nuclear material (SNM) in the Department of Energy Complex is vital to the national security of the United States. Active and passive nondestructive assays are used to confirm the presence of SNM in various configurations ranging from waste to nuclear weapons. Confirmation measurements for nuclear weapons are more challenging because the design complicates the detection of a distinct signal for highly enriched uranium. The emphasis of this dissertation was to investigate a new nondestructive assay technique that provides an independent and distinct signal to confirm the presence of highly enriched uranium (HEU). Once completed and tested this assay method could be applied to confirmation measurements of nuclear weapons. The new system uses a 14-MeV neutron source for interrogation and records the arrival time of neutrons between the pulses with a high efficiency detection system. The data is then analyzed by the Feynman reduced variance method. The analysis determined the amount of correlation in the data and provided a unique signature of correlated fission neutrons. Measurements of HEU spheres were conducted at Los Alamos with the new system. Then, Monte Carlo calculations were performed to verify hypothesis made about the behavior of the neutrons in the experiment. Comparisons of calculated counting rates by the Monte Carlo N-Particle Transport Code (MCNP) were made with the experimental data to confirm that the measured response reflected the desired behavior of neutron interactions in the highly enriched uranium. In addition, MCNP calculations of the delayed neutron build-up were compared with the measured data. Based on the results obtained from this dissertation, this measurement method has the potential to be expanded to include mass determinations of highly enriched uranium. Although many safeguards techniques exist for measuring special nuclear material, the number of assays that can be used to confirm HEU in shielded systems is

  20. Select Novice Elementary Teachers' Perceived Knowledge and Implementation of High-Quality Reading Instruction

    ERIC Educational Resources Information Center

    Bumstead, Stacey

    2012-01-01

    The purpose of this mixed methods study was to examine select novice teachers' perceived knowledge of high-quality reading instruction, explore the extent that select novice teachers implemented high-quality reading instruction into their own classrooms, and to investigate any factors that explain the similarities and differences between…