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Sample records for activity high selectivity

  1. 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…

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

    SciTech Connect

    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.

  3. 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

  4. 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

  5. Highly active ozonides selected against drug resistant malaria.

    PubMed

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

    2016-06-07

    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.

  6. 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.

  7. Near-infrared light controlled photocatalytic activity of carbon quantum dots for highly selective oxidation reaction

    NASA Astrophysics Data System (ADS)

    Li, Haitao; Liu, Ruihua; Lian, Suoyuan; Liu, Yang; Huang, Hui; Kang, Zhenhui

    2013-03-01

    Selective oxidation of alcohols is a fundamental and significant transformation for the large-scale production of fine chemicals, UV and visible light driven photocatalytic systems for alcohol oxidation have been developed, however, the long wavelength near infrared (NIR) and infrared (IR) light have not yet fully utilized by the present photocatalytic systems. Herein, we reported carbon quantum dots (CQDs) can function as an effective near infrared (NIR) light driven photocatalyst for the selective oxidation of benzyl alcohol to benzaldehyde. Based on the NIR light driven photo-induced electron transfer property and its photocatalytic activity for H2O2 decomposition, this metal-free catalyst could realize the transformation from benzyl alcohol to benzaldehyde with high selectivity (100%) and conversion (92%) under NIR light irradiation. HO&z.rad; is the main active oxygen specie in benzyl alcohol selective oxidative reaction confirmed by terephthalic acid photoluminescence probing assay (TA-PL), selecting toluene as the substrate. Such metal-free photocatalytic system also selectively converts other alcohol substrates to their corresponding aldehydes with high conversion, demonstrating a potential application of accessing traditional alcohol oxidation chemistry.Selective oxidation of alcohols is a fundamental and significant transformation for the large-scale production of fine chemicals, UV and visible light driven photocatalytic systems for alcohol oxidation have been developed, however, the long wavelength near infrared (NIR) and infrared (IR) light have not yet fully utilized by the present photocatalytic systems. Herein, we reported carbon quantum dots (CQDs) can function as an effective near infrared (NIR) light driven photocatalyst for the selective oxidation of benzyl alcohol to benzaldehyde. Based on the NIR light driven photo-induced electron transfer property and its photocatalytic activity for H2O2 decomposition, this metal-free catalyst could realize

  8. Highly active chromium-based selective ethylene tri-/tetramerization catalysts supported by PNPO phosphazane ligands.

    PubMed

    Zhou, Yusheng; Wu, Hongfei; Xu, Sheng; Zhang, Xuejun; Shi, Min; Zhang, Jun

    2015-05-28

    Novel Cr(iii) catalysts supported by PNPO phosphazane ligands of the type Ph2PN(R)P(Ph)OAr have been prepared, all of which, upon activation with MMAO-3A, are highly active in ethylene tri-/tetramerization with considerable selectivity. The effect of ligand substitution on the catalytic performance has been examined. The Cr precatalyst supported by the PNPO phosphazane ligand with an N-cyclohexyl achieved high activity of 316.7 kg (g Cr h(-1))(-1) and a high total selectivity of 85.1% towards valuable 1-hexene (45.7%) and 1-octene (39.4%) using chlorobenzene as the solvent at 35 bar and 40 °C. In methylcyclohexane, the precatalyst supported by [Ph2PN((i)Pr)P(Ph)OPh] exhibited a higher 1-octene selectivity (54.0%) with a considerable activity of 73.3 kg (g Cr h(-1))(-1) at 35 bar and 40 °C. With the fine-tuned ligand backbone, such a PNPO phosphazane-based catalyst system provides a mode for precise understanding of the impact of ligand variations on catalytic performance.

  9. Highly Selective Salicylketoxime-Based Estrogen Receptor β Agonists Display Antiproliferative Activities in a Glioma Model

    PubMed Central

    2016-01-01

    Estrogen receptor β (ERβ) selective agonists are considered potential therapeutic agents for a variety of pathological conditions, including several types of cancer. Their development is particularly challenging, since differences in the ligand binding cavities of the two ER subtypes α and β are minimal. We have carried out a rational design of new salicylketoxime derivatives which display unprecedentedly high levels of ERβ selectivity for this class of compounds, both in binding affinity and in cell-based functional assays. An endogenous gene expression assay was used to further characterize the pharmacological action of these compounds. Finally, these ERβ-selective agonists were found to inhibit proliferation of a glioma cell line in vitro. Most importantly, one of these compounds also proved to be active in an in vivo xenograft model of human glioma, thus demonstrating the high potential of this type of compounds against this devastating disease. PMID:25559213

  10. Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists

    PubMed Central

    2015-01-01

    2-Aminooxazolines were discovered as a novel structural class of TAAR1 ligands. Starting from a known adrenergic compound 1, structural modifications were made to obtain highly potent and selective TAAR1 ligands such as 12 (RO5166017), 18 (RO5256390), 36 (RO5203648), and 48 (RO5263397). These compounds exhibit drug-like physicochemical properties, have good oral bioavailability, and display in vivo activity in a variety of animal models relevant for psychiatric diseases and addiction. PMID:26985297

  11. Biphasic catalysis using amphiphilic polyphenols-chelated noble metals as highly active and selective catalysts

    PubMed Central

    Mao, Hui; Yu, Hong; Chen, Jing; Liao, Xuepin

    2013-01-01

    In the field of catalysis, it is highly desired to develop novel catalysts that combine the advantages of both homogeneous and heterogeneous catalysts. Here we disclose that the use of plant pholyphenol as amphiphilic large molecule ligand/stabilizer allows for the preparation of noble metal complex and noble metal nanoparticle catalysts. These catalysts are found to be highly selective and active in aqueous-organic biphasic catalysis of cinnamaldehyde and quinoline, and can be reused at least 3 times without significant loss of activity. Moreover, the catalytic activity and reusability of the catalysts can be rationally controlled by simply adjusting the content of polyphenols in the catalysts. Our strategy may be extended to design a wide range of aqueous-organic biphasic catalysis system. PMID:23863916

  12. 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.

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

    PubMed

    Cui, Yuanyuan; Yang, Fan; Cao, Xu; Yarov-Yarovoy, Vladimir; Wang, KeWei; Zheng, Jie

    2012-04-01

    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.

  14. 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.

  15. 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.

  16. Discovery of highly selective 7-chloroquinoline-thiohydantoins with potent antimalarial activity.

    PubMed

    Raj, Raghu; Mehra, Vishu; Gut, Jiri; Rosenthal, Philip J; Wicht, Kathryn J; Egan, Timothy J; Hopper, Melissa; Wrischnik, Lisa A; Land, Kirkwood M; Kumar, Vipan

    2014-09-12

    A series of C-3 thiourea functionalized β-lactams, β-lactam-7-chloroquinoline conjugates and 7-chloroquinoline-thiohydantoin derivatives were prepared with the aim of probing antimalarial structure-activity relationships. 7-Chlorquinoline-thiohydantoin derivatives were found to be potent inhibitors of cultured Plasmodium falciparum, with the most potent and non-cytotoxic compound exhibiting an IC50 of 39.8 nM. Studies of β-hematin formation suggested that inhibition of haemozoin formation could be primary mechanism of action, with IC50 values comparable to those of chloroquine. Evaluation of cytotoxicity against HeLa cells demonstrated high selective indices.

  17. 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

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

    SciTech Connect

    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.

    2016-03-08

    Incorporating, a redox active organometallic molIncorporating, a redox active organometallic molecule within a porous matrix is a useful strategy to form redox active composite materials for emerging applications such as energy storage, electro-catalysis and electro-magnetic separation. Herein we report a new class of stable, redox active metal organic composites for oxygen/air separation with exceptional efficiency. In particular, Ferrocene impregnated in a thermally stable hierarchical porous framework showed a saturation uptake capacity of >51 mg/g for oxygen at a very low relative saturation pressure (P/Po) of 0.06. The material shows excellent O2 selectivity from air as evident from experimental and simulated breakthrough experiments. In detail structural analysis using 57Fe-Mössbauer, X-ray photoelectron spectroscopy (XPS) and pair distribution function (PDF) analysis show that of O2 adsorption affinity and selectivity originates by the formation Fe3+-O oxide due to the highly reactive nature of the organometallics imbedded in the porous matrix.

  19. 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.

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

    SciTech Connect

    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.

    2016-03-08

    A redox-active metal-organic composite material shows improved and selective O-2 adsorption over N-2 with respect to individual components (MIL-101 and ferrocene). The O-2 sensitivity of the composite material arises due to the formation of maghemite nanoparticles with the pore of the metal-organic framework material.

  1. 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

  2. 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

  3. Synthesis of Novel Hybrids of Thymoquinone and Artemisinin with High Activity and Selectivity Against Colon Cancer.

    PubMed

    Fröhlich, Tony; Ndreshkjana, Benardina; Muenzner, Julienne K; Reiter, Christoph; Hofmeister, Elisabeth; Mederer, Sandra; Fatfat, Maamoun; El-Baba, Chirine; Gali-Muhtasib, Hala; Schneider-Stock, Regine; Tsogoeva, Svetlana B

    2017-02-03

    Colorectal cancer causes 0.5 million deaths each year. To combat this type of cancer the development of new specific drug candidates is urgently needed. In the present work seven novel thymoquinone-artemisinin hybrids with different linkers were synthesized and tested for their in vitro anticancer activity against a panel of various tumor cell lines. The thymoquinone-artesunic acid hybrid 7 a, in which both subunits are connected via an ester bond, was found to be the most active compound and selectively decreased the viability of colorectal cancer cells with an IC50 value of 2.4 μm (HCT116) and 2.8 μm (HT29). Remarkably, hybrid 7 a was up to 20-fold more active than its parent compounds (thymoquinone and artesunic acid), while not affecting nonmalignant colon epithelial HCEC cells (IC50 >100 μm). Moreover, the activity of hybrid 7 a was superior to that of various 1:1 mixtures of thymoquinone and artesunic acid. Furthermore, hybrid 7 a was even more potent against both colon cancer cell lines than the clinically used drug 5-fluorouracil. These results are another excellent proof of the hybridization concept and confirm that the type and length of the linker play a crucial role for the biological activity of a hybrid drug. Besides an increase in reactive oxygen species (ROS), elevated levels of the DNA-damage marker γ-H2AX were observed. Both effects seem to be involved in the molecular mechanism of action for hybrid 7 a in colorectal cancer cells.

  4. 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)).

  5. 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.

  6. Novel highly potent and selective nonsteroidal aromatase inhibitors: synthesis, biological evaluation and structure-activity relationships investigation.

    PubMed

    Gobbi, Silvia; Zimmer, Christina; Belluti, Federica; Rampa, Angela; Hartmann, Rolf W; Recanatini, Maurizio; Bisi, Alessandra

    2010-07-22

    In further pursuing our search for potent and selective aromatase inhibitors, a new series of molecules was designed and synthesized, exploring possible structural modifications of a previously identified xanthone scaffold. Among them, highly potent compounds, with inhibitory activity in the low nanomolar range, were found. In particular, substitution of the heterocyclic oxygen atom in the xanthone core by a sulfur atom and/or increase in structure flexibility seemed to be favorable for the interaction with the enzyme.

  7. 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

  8. 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.

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

    PubMed

    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.

  10. Oxide-Nanotrap-Anchored Platinum Nanoparticles with High Activity and Sintering Resistance by Area-Selective Atomic Layer Deposition.

    PubMed

    Liu, Xiao; Zhu, Qianqian; Lang, Yun; Cao, Kun; Chu, Shengqi; Shan, Bin; Chen, Rong

    2017-02-01

    An area-selective atomic layer deposition (AS-ALD) method is described to construct oxide nanotraps to anchor Pt nanoparticles (NPs) on Al2 O3 supports. The as-synthesized catalysts have exhibited outstanding room-temperature CO oxidation activity, with a significantly lowered apparent activation energy (ca. 22.17 kJ mol(-1) ) that is half that of pure Pt catalyst with the same loading. Furthermore, the structure shows excellent sintering resistance with the high catalytic activity retention up to 600 °C calcination. The key feature of the oxide nanotraps lies in its ability to anchor Pt NPs via strong metal-oxide interactions while still leaving active metal facets exposed. Our reported method for forming such oxide structure with nanotraps shows great potential for the simultaneous enhancement of thermal stability and activity of precious metal NPs.

  11. 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.

  12. Highly active and selective catalysis of copper diphosphine complexes for the transformation of carbon dioxide into silyl formate.

    PubMed

    Motokura, Ken; Kashiwame, Daiki; Takahashi, Naoki; Miyaji, Akimitsu; Baba, Toshihide

    2013-07-22

    Copper diphosphine complexes have been found to be highly active and selective homogeneous catalysts for the hydrosilylation of CO2. The structure of the phosphine ligands strongly affects their catalytic activity. Turnover number (TON) reaches 70,000 after 24 hours with 1,2-bis(diisopropylphosphino)benzene as a ligand under 1 atmosphere of CO2. (1)H and (13)C NMR spectra, carried out under the reaction conditions, showed the reaction mechanism through insertion of CO2 into Cu-H to afford Cu/formate species.

  13. Histone deacetylase activators: N-acetylthioureas serve as highly potent and isozyme selective activators for human histone deacetylase-8 on a fluorescent substrate.

    PubMed

    Singh, Raushan K; Mandal, Tanmay; Balsubramanian, Narayanaganesh; Viaene, Tajae; Leedahl, Travis; Sule, Nitesh; Cook, Gregory; Srivastava, D K

    2011-10-01

    We report, for the first time, that certain N-acetylthiourea derivatives serve as highly potent and isozyme selective activators for the recombinant form of human histone deacetylase-8 in the assay system containing Fluor-de-Lys as a fluorescent substrate. The experimental data reveals that such activating feature is manifested via decrease in the K(m) value of the enzyme's substrate and increase in the catalytic turnover rate of the enzyme.

  14. Data-Driven Derivation of an "Informer Compound Set" for Improved Selection of Active Compounds in High-Throughput Screening.

    PubMed

    Paricharak, Shardul; IJzerman, Adriaan P; Jenkins, Jeremy L; Bender, Andreas; Nigsch, Florian

    2016-09-26

    Despite the usefulness of high-throughput screening (HTS) in drug discovery, for some systems, low assay throughput or high screening cost can prohibit the screening of large numbers of compounds. In such cases, iterative cycles of screening involving active learning (AL) are employed, creating the need for smaller "informer sets" that can be routinely screened to build predictive models for selecting compounds from the screening collection for follow-up screens. Here, we present a data-driven derivation of an informer compound set with improved predictivity of active compounds in HTS, and we validate its benefit over randomly selected training sets on 46 PubChem assays comprising at least 300,000 compounds and covering a wide range of assay biology. The informer compound set showed improvement in BEDROC(α = 100), PRAUC, and ROCAUC values averaged over all assays of 0.024, 0.014, and 0.016, respectively, compared to randomly selected training sets, all with paired t-test p-values <10(-15). A per-assay assessment showed that the BEDROC(α = 100), which is of particular relevance for early retrieval of actives, improved for 38 out of 46 assays, increasing the success rate of smaller follow-up screens. Overall, we showed that an informer set derived from historical HTS activity data can be employed for routine small-scale exploratory screening in an assay-agnostic fashion. This approach led to a consistent improvement in hit rates in follow-up screens without compromising scaffold retrieval. The informer set is adjustable in size depending on the number of compounds one intends to screen, as performance gains are realized for sets with more than 3,000 compounds, and this set is therefore applicable to a variety of situations. Finally, our results indicate that random sampling may not adequately cover descriptor space, drawing attention to the importance of the composition of the training set for predicting actives.

  15. 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.

  16. 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.

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

    SciTech Connect

    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

    2016-06-30

    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 are 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.

  18. 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

  19. Parallel synthesis and biological activity of a new class of high affinity and selective delta-opioid ligand.

    PubMed

    Barn, D R; Caulfield, W L; Cottney, J; McGurk, K; Morphy, J R; Rankovic, Z; Roberts, B

    2001-10-01

    A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogues of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimising a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulphonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physicochemical properties, notably aqueous solubility. The most active ligand had an affinity (IC(50)) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit 1 (IC(50) 98 nM). Compounds from this new series show good selectivity for the DOR over mu and kappa opioid receptors. However the most active and selective compounds had poor aqueous solubility. Improved aqueous solubility was obtained by replacing the phthalimide group in 1 by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to 1 was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test. In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, 46, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, respectively, at a dose of 10 mmol/kg i.v.).

  20. Enhanced natural killer activity and production of pro-inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax).

    PubMed

    Castoldi, Lindsey; Golim, Marjorie Assis; Filho, Orlando Garcia Ribeiro; Romagnoli, Graziela Gorete; Ibañez, Olga Célia Martinez; Kaneno, Ramon

    2007-03-01

    Strains of mice with maximal and minimal acute inflammatory responsiveness (AIRmax and AIRmin, respectively) were developed through selective breeding based on their high- or low-acute inflammatory responsiveness. Previous reports have shown that AIRmax mice are more resistant to the development of a variety of tumours than AIRmin mice, including spontaneous metastasis of murine melanoma. Natural killer activity is involved in immunosurveillance against tumour development, so we analysed the number and activity of natural killer cells (CD49b(+)), T-lymphocyte subsets and in vitro cytokine production by spleen cells of normal AIRmax and AIRmin mice. Analysis of lymphocyte subsets by flow cytometry showed that AIRmax mice had a higher relative number of CD49b(+) cells than AIRmin mice, as well as cytolytic activity against Yac.1 target cells. The number of CD3(+) CD8(+) cells was also higher in AIRmax mice. These findings were associated with the ability of spleen cells from AIRmax mice in vitro to produce higher levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin-12p40 and interferon-gamma but not the anti-inflammatory interleukin-10. Taken together, our data suggest that the selective breeding to achieve the AIRmax and AIRmin strains was able to polarize the genes associated with cytotoxic activity, which can be responsible for the antitumour resistance observed in AIRmax mice.

  1. 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.

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

    DOE PAGES

    Mistry, Hemma; Varela, Ana Sofia; Bonifacio, Cecile S.; ...

    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

  3. SKF-83959 is not a highly-biased functionally selective D1 dopamine receptor ligand with activity at phospholipase C.

    PubMed

    Lee, Sang-Min; Kant, Andrew; Blake, Daniel; Murthy, Vishakantha; Boyd, Kevin; Wyrick, Steven J; Mailman, Richard B

    2014-11-01

    SKF-83959 [6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine] is reported to be a functionally selective dopamine D1 receptor ligand with high bias for D1-mediated phospholipase C (PLC) versus D1-coupled adenylate cyclase signaling. This signaling bias is proposed to explain behavioral activity in both rat and primate Parkinson's disease models, and a D1-D2 heterodimer has been proposed as the underlying mechanism. We have conducted an in-depth pharmacological characterization of this compound in dopamine D1 and D2 receptors in both rat brain and heterologous systems expressing human D1 or D2 receptors. Contrary to common assumptions, SKF-83959 is similar to the classical, well-characterized partial agonist SKF38393 in all systems. It is a partial agonist (not an antagonist) at adenylate cyclase in vitro and ex vivo, and is a partial agonist in D1-mediated β-arrestin recruitment. Contrary to earlier reports, it does not have D1-mediated effects on PLC signaling in heterologous systems. Because drug metabolites can also contribute, its 3-N-demethylated analog also was synthesized and tested. As expected from the known structure-activity relationships of the benzazepines, this compound also had high affinity for the D1 receptor and somewhat higher intrinsic activity than the parent ligand, and also might contribute to in vivo effects of SKF-83959. Together, these data demonstrate that SKF-83959 is not a highly-biased functionally selective D1 ligand, and that its reported behavioral data can be explained solely by its partial D1 agonism in canonical signaling pathway(s). Mechanisms that have been proposed based on the purported signaling novelty of SKF-83959 at PLC should be reconsidered.

  4. Selective hydrogenation of lactic acid to 1,2-propanediol over highly active ruthenium-molybdenum oxide catalysts.

    PubMed

    Takeda, Yasuyuki; Shoji, Tomohiro; Watanabe, Hideo; Tamura, Masazumi; Nakagawa, Yoshinao; Okumura, Kazu; Tomishige, Keiichi

    2015-04-13

    Modification of Ru/C with a small amount of MoOx (RuMoOx /C) enhanced the catalytic activity in the hydrogenation of L-lactic acid to form 1,2-propanediol and maintained high selectivity. The turnover frequency based on the amount of Ru over the optimized RuMoOx /C catalyst (Mo/Ru molar ratio=1:16) was 114 h(-1) at 393 K, which was about 4 times higher than that over Ru/C. The same effect of MoOx was obtained over RuMoOx /SiO2 , although RuMoOx /SiO2 showed slightly lower activity than that of RuMoOx /C. RuMoOx /C achieved a high yield of 95 % in 18 h at 393 K and was applicable to various carboxylic acids to provide the corresponding alcohols in high yields. Modification with MoOx also brought about suppression of racemization and (S)-1,2-propanediol was obtained in high enantiomeric excess at 353 K. Based on kinetic analysis and characterization data, such as XRD, TEM, CO adsorption by a volumetric method, FTIR spectroscopy, and X-ray absorption spectroscopy, for RuMoOx /C and RuMoOx /SiO2 , the catalyst structure and reaction mechanism are proposed.

  5. γ Sulphate PNA (PNA S): highly selective DNA binding molecule showing promising antigene activity.

    PubMed

    Avitabile, Concetta; Moggio, Loredana; Malgieri, Gaetano; Capasso, Domenica; Di Gaetano, Sonia; Saviano, Michele; Pedone, Carlo; Romanelli, Alessandra

    2012-01-01

    Peptide Nucleic Acids (PNAs), nucleic acid analogues showing high stability to enzyme degradation and strong affinity and specificity of binding toward DNA and RNA are widely investigated as tools to interfere in gene expression. Several studies have been focused on PNA analogues with modifications on the backbone and bases in the attempt to overcome solubility, uptake and aggregation issues. γ PNAs, PNA derivatives having a substituent in the γ position of the backbone show interesting properties in terms of secondary structure and affinity of binding toward complementary nucleic acids. In this paper we illustrate our results obtained on new analogues, bearing a sulphate in the γ position of the backbone, developed to be more DNA-like in terms of polarity and charge. The synthesis of monomers and oligomers is described. NMR studies on the conformational properties of monomers and studies on the secondary structure of single strands and triplexes are reported. Furthermore the hybrid stability and the effect of mismatches on the stability have also been investigated. Finally, the ability of the new analogue to work as antigene, interfering with the transcription of the ErbB2 gene on a human cell line overexpressing ErbB2 (SKBR3), assessed by FACS and qPCR, is described.

  6. 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

  7. Selection of a Bacillus pumilus strain highly active against Ceratitis capitata (Wiedemann) larvae.

    PubMed

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

    2010-03-01

    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.

  8. Highly selective and active CO2 reduction electrocatalysts based on cobalt phthalocyanine/carbon nanotube hybrid structures

    PubMed Central

    Zhang, Xing; Wu, Zishan; Zhang, Xiao; Li, Liewu; Li, Yanyan; Xu, Haomin; Li, Xiaoxiao; Yu, Xiaolu; Zhang, Zisheng; Liang, Yongye; Wang, Hailiang

    2017-01-01

    Electrochemical reduction of carbon dioxide with renewable energy is a sustainable way of producing carbon-neutral fuels. However, developing active, selective and stable electrocatalysts is challenging and entails material structure design and tailoring across a range of length scales. Here we report a cobalt-phthalocyanine-based high-performance carbon dioxide reduction electrocatalyst material developed with a combined nanoscale and molecular approach. On the nanoscale, cobalt phthalocyanine (CoPc) molecules are uniformly anchored on carbon nanotubes to afford substantially increased current density, improved selectivity for carbon monoxide, and enhanced durability. On the molecular level, the catalytic performance is further enhanced by introducing cyano groups to the CoPc molecule. The resulting hybrid catalyst exhibits >95% Faradaic efficiency for carbon monoxide production in a wide potential range and extraordinary catalytic activity with a current density of 15.0 mA cm−2 and a turnover frequency of 4.1 s−1 at the overpotential of 0.52 V in a near-neutral aqueous solution. PMID:28272403

  9. Highly selective and active CO2 reduction electrocatalysts based on cobalt phthalocyanine/carbon nanotube hybrid structures.

    PubMed

    Zhang, Xing; Wu, Zishan; Zhang, Xiao; Li, Liewu; Li, Yanyan; Xu, Haomin; Li, Xiaoxiao; Yu, Xiaolu; Zhang, Zisheng; Liang, Yongye; Wang, Hailiang

    2017-03-08

    Electrochemical reduction of carbon dioxide with renewable energy is a sustainable way of producing carbon-neutral fuels. However, developing active, selective and stable electrocatalysts is challenging and entails material structure design and tailoring across a range of length scales. Here we report a cobalt-phthalocyanine-based high-performance carbon dioxide reduction electrocatalyst material developed with a combined nanoscale and molecular approach. On the nanoscale, cobalt phthalocyanine (CoPc) molecules are uniformly anchored on carbon nanotubes to afford substantially increased current density, improved selectivity for carbon monoxide, and enhanced durability. On the molecular level, the catalytic performance is further enhanced by introducing cyano groups to the CoPc molecule. The resulting hybrid catalyst exhibits >95% Faradaic efficiency for carbon monoxide production in a wide potential range and extraordinary catalytic activity with a current density of 15.0 mA cm(-2) and a turnover frequency of 4.1 s(-1) at the overpotential of 0.52 V in a near-neutral aqueous solution.

  10. Highly selective and active CO2 reduction electrocatalysts based on cobalt phthalocyanine/carbon nanotube hybrid structures

    NASA Astrophysics Data System (ADS)

    Zhang, Xing; Wu, Zishan; Zhang, Xiao; Li, Liewu; Li, Yanyan; Xu, Haomin; Li, Xiaoxiao; Yu, Xiaolu; Zhang, Zisheng; Liang, Yongye; Wang, Hailiang

    2017-03-01

    Electrochemical reduction of carbon dioxide with renewable energy is a sustainable way of producing carbon-neutral fuels. However, developing active, selective and stable electrocatalysts is challenging and entails material structure design and tailoring across a range of length scales. Here we report a cobalt-phthalocyanine-based high-performance carbon dioxide reduction electrocatalyst material developed with a combined nanoscale and molecular approach. On the nanoscale, cobalt phthalocyanine (CoPc) molecules are uniformly anchored on carbon nanotubes to afford substantially increased current density, improved selectivity for carbon monoxide, and enhanced durability. On the molecular level, the catalytic performance is further enhanced by introducing cyano groups to the CoPc molecule. The resulting hybrid catalyst exhibits >95% Faradaic efficiency for carbon monoxide production in a wide potential range and extraordinary catalytic activity with a current density of 15.0 mA cm-2 and a turnover frequency of 4.1 s-1 at the overpotential of 0.52 V in a near-neutral aqueous solution.

  11. Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist.

    PubMed Central

    Serradeil-Le Gal, C; Lacour, C; Valette, G; Garcia, G; Foulon, L; Galindo, G; Bankir, L; Pouzet, B; Guillon, G; Barberis, C; Chicot, D; Jard, S; Vilain, P; Garcia, C; Marty, E; Raufaste, D; Brossard, G; Nisato, D; Maffrand, J P; Le Fur, G

    1996-01-01

    SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2 receptor antagonist, has been characterized in several in vitro and in vivo models. This compound displayed highly competitive and selective affinity for V2 receptors in rat, bovine and human kidney (0.6 < or = Ki [nM] < or = 4.1). In this latter preparation, SR 121463A potently antagonized arginine vasopressin (AVP)-stimulated adenylyl cyclase activity (Ki = 0.26+/-0.04 nM) without any intrinsic agonistic effect. In autoradiographic experiments performed in rat kidney sections, SR 121463A displaced [3H]AVP labeling especially in the medullo-papillary region and confirmed that it is a suitable tool for mapping V2 receptors. In comparison, the nonpeptide V2 antagonist, OPC-31260, showed much lower affinity for animal and human renal V2 receptors and lower efficacy to inhibit vasopressin-stimulated adenylyl cyclase (Ki in the 10 nanomolar range). Moreover, OPC-31260 exhibited a poor V2 selectivity profile and can be considered as a V2/V1a ligand. In normally hydrated conscious rats, SR 121463A induced powerful aquaresis after intravenous (0.003-0.3 mg/kg) or oral (0.03-10 mg/kg) administration. The effect was dose-dependent and lasted about 6 hours at the dose of 3 mg/kg p.o. OPC-31260 had a similar aquaretic profile but with markedly lower oral efficacy. The action of SR 121463A was purely aquaretic with no changes in urine Na+ and K+ excretions unlike that of known diuretic agents such as furosemide or hydrochlorothiazide. In addition, no antidiuretic properties have been detected with SR 121463A in vasopressin-deficient Brattleboro rats. Thus, SR 121463A is the most potent and selective, orally active V2 antagonist yet described and could be a powerful tool for exploring V2 receptors and the therapeutical usefulness of V2 blocker aquaretic agents in water-retaining diseases. PMID:8981918

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

    DOE PAGES

    Book, Adam J.; Lewin, Gina R.; McDonald, Bradon 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

  13. 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.

  14. 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

  15. 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

  16. 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

    2014-01-07

    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

  17. Size-selective QD@MOF core-shell nanocomposites for the highly sensitive monitoring of oxidase activities.

    PubMed

    Wang, Ke; Li, Nan; Zhang, Jing; Zhang, Zhiqi; Dang, Fuquan

    2017-01-15

    In this work, we proposed a novel and facile method to monitor oxidase activities based on size-selective fluorescent quantum dot (QD)@metal-organic framework (MOF) core-shell nanocomposites (CSNCPs). The CSNCPs were synthesized from ZIF-8 and CdTe QDs in aqueous solution in 40min at room temperature with stirring. The prepared CdTe@ZIF-8 CSNCPs , which have excellent water dispersibility and stability, displays distinct fluorescence responses to hole scavengers of different molecular sizes (e.g., H2O2, substrate, and oxidase) due to the aperture limitation of the ZIF-8 shell. H2O2 can efficiently quench the fluorescence of CdTe@ZIF-8 CSNCPs over a linearity range of 1-100nM with a detection limit of 0.29nM, whereas large molecules such as substrate and oxidase have very little effect on its fluorescence. Therefore, the highly sensitive detection of oxidase activities was achieved by monitoring the fluorescence quenching of CdTe@ZIF-8 CSNCPs by H2O2 produced in the presence of substrate and oxidase, which is proportional to the oxidase activities. The linearity ranges of the uricase and glucose oxidase activity are 0.1-50U/L and 1-100U/L, respectively, and their detection limits are 0.024U/L and 0.26U/L, respectively. Therefore, the current QD@MOF CSNCPs based sensing system is a promising, widely applicable means of monitoring oxidase activities in biochemical research.

  18. Locus coeruleus galanin expression is enhanced after exercise in rats selectively bred for high capacity for aerobic activity.

    PubMed

    Murray, Patrick S; Groves, Jessica L; Pettett, Brett J; Britton, Steven L; Koch, Lauren G; Dishman, Rod K; Holmes, Philip V

    2010-12-01

    The neuropeptide galanin extensively coexists with norepinephrine in locus coeruleus (LC) neurons. Previous research in this laboratory has demonstrated that unlimited access to activity wheels in the home cage increases mRNA for galanin (GAL) in the LC, and that GAL mediates some of the beneficial effects of exercise on brain function. To assess whether capacity for aerobic exercise modulates this upregulation in galanin mRNA, three heterogeneous rat models were tested: rats selectively bred for (1) high intrinsic (untrained) aerobic capacity (High Capacity Runners, HCR) and (2) low intrinsic aerobic capacity (Low Capacity Runners, LCR) and (3) unselected Sprague-Dawley (SD) rats with and without free access to running wheels for 3 weeks. Following this exercise protocol, mRNA for tyrosine hydroxylase (TH) and GAL was measured in the LC. The wheel running distances between the three models were significantly different, and age contributed as a significant covariate. Both selection and wheel access condition significantly affected GAL mRNA expression, but not TH mRNA expression. GAL was elevated in exercising HCR and SD rats compared to sedentary rats while LCR rats did not differ between conditions. Overall running distance significantly correlated with GAL mRNA expression, but not with TH mRNA expression. No strain differences in GAL or TH gene expression were observed in sedentary rats. Thus, intrinsic aerobic running capacity influences GAL gene expression in the LC only insofar as actual running behavior is concerned; aerobic capacity does not influence GAL expression in addition to changes associated with running.

  19. Locus coeruleus galanin expression is enhanced after exercise in rats selectively bred for high capacity for aerobic activity

    PubMed Central

    Murray, Patrick S.; Groves, Jessica L.; Pettett, Brett J.; Britton, Steven L.; Koch, Lauren G.; Dishman, Rod K.

    2010-01-01

    The neuropeptide galanin extensively coexists with norepinephrine in locus coeruleus (LC) neurons. Previous research in this laboratory has demonstrated that unlimited access to activity wheels in the home cage increases mRNA for galanin (GAL) in the LC, and that GAL mediates some of the beneficial effects of exercise on brain function. To assess whether capacity for aerobic exercise modulates this upregulation in galanin mRNA, three heterogeneous rat models were tested: rats selectively bred for 1) high intrinsic (untrained) aerobic capacity (High Capacity Runners, HCR) and 2) low intrinsic aerobic capacity (Low Capacity Runners, LCR) and 3) unselected Sprague-Dawley (SD) rats with and without free access to running wheels for three weeks. Following this exercise protocol, mRNA for tyrosine hydroxylase (TH) and GAL was measured in the LC. The wheel-running distances between the three models were significantly different, and age contributed as a significant covariate. Both selection and wheel access condition significantly affected GAL mRNA expression, but not TH mRNA expression. GAL was elevated in exercising HCR and SD rats compared to sedentary rats while LCR rats did not differ between conditions. Overall running distance significantly correlated with GAL mRNA expression, but not with TH mRNA expression. No strain differences in GAL or TH gene expression were observed in sedentary rats. Thus, intrinsic aerobic running capacity influences GAL gene expression in the LC only insofar as actual running behavior is concerned; aerobic capacity does not influence GAL expression in addition to changes associated with running. PMID:20850488

  20. 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.

  1. 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.

  2. 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

  3. 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…

  4. Maximum cold-induced food consumption in mice selected for high locomotor activity: implications for the evolution of endotherm energy budgets.

    PubMed

    Koteja, P; Swallow, J G; Carter, P A; Garland, T

    2001-03-01

    We studied house mice (Mus domesticus) that had been artificially selected for high activity to test the hypothesis that a high capacity for energy assimilation in cold-exposed endotherms could evolve as a correlated response to selection for increased locomotor activity. After 10 generations of selection for increased voluntary wheel-running, mice from four selected lines ran 75 % more wheel revolutions per day than did mice from four random-bred, control lines. The maximum cold-induced rates of food consumption (C(max); mean 10.6 g day(-1)) and energy assimilation (A(max); mean 141 kJ day(-1)) were not significantly higher in the selected than in the control mice. However, in cold-exposure trials, mice from the selected lines maintained body mass better than did mice from the control lines. C(max) and A(max) were positively correlated with the amount of wheel-running activity measured before cold-exposure and also with the rates of food consumption measured when the mice had access to running wheels. In females at least, the correlation was significant not only among individuals but also among adjusted means of the replicate lines, which suggests the presence of a positive genetic correlation between the traits. Thus, despite the lack of a significant difference between the selected and control lines in maximum rate of food consumption, the remaining results conform to the hypothesis that a selection for increased locomotor activity could be a factor behind the evolution of the ability to sustain activity and maintain energy balance during prolonged cold-exposure, as occurred during the evolution of mammalian and avian endothermy.

  5. La-doped Al2O3 supported Au nanoparticles: highly active and selective catalysts for PROX under PEMFC operation conditions.

    PubMed

    Lin, Qingquan; Qiao, Botao; Huang, Yanqiang; Li, Lin; Lin, Jian; Liu, Xiao Yan; Wang, Aiqin; Li, Wen-Cui; Zhang, Tao

    2014-03-14

    La-doped γ-Al2O3 supported Au catalysts show high activity and selectivity for the PROX reaction under PEMFC operation conditions. The superior performance is attributed to the formation of LaAlO3, which suppresses H2 oxidation and strengthens CO adsorption on Au sites, thereby improving competitive oxidation of CO at elevated temperature.

  6. 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

  7. 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.

  8. High Specific Selectivity and Membrane-Active Mechanism of Synthetic Cationic Hybrid Antimicrobial Peptides Based on the Peptide FV7.

    PubMed

    Tan, Tingting; Wu, Di; Li, Weizhong; Zheng, Xin; Li, Weifen; Shan, Anshan

    2017-02-06

    Hybrid peptides integrating different functional domains of peptides have many advantages, such as remarkable antimicrobial activity, lower hemolysis and ideal cell selectivity, compared with natural antimicrobial peptides. FV7 (FRIRVRV-NH₂), a consensus amphiphilic sequence was identified as being analogous to host defense peptides. In this study, we designed a series of hybrid peptides FV7-LL-37 (17-29) (FV-LL), FV7-magainin 2 (9-21) (FV-MA) and FV7-cecropin A (1-8) (FV-CE) by combining the FV7 sequence with the small functional sequences LL-37 (17-29) (LL), magainin 2 (9-21) (MA) and cecropin A (1-8) (CE) which all come from well-described natural peptides. The results demonstrated that the synthetic hybrid peptides, in particular FV-LL, had potent antibacterial activities over a wide range of Gram-negative and Gram-positive bacteria with lower hemolytic activity than other peptides. Furthermore, fluorescent spectroscopy indicated that the hybrid peptide FV-LL exhibited marked membrane destruction by inducing outer and inner bacterial membrane permeabilization, while scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that FV-LL damaged membrane integrity by disrupting the bacterial membrane. Inhibiting biofilm formation assays also showed that FV-LL had similar anti-biofilm activity compared with the functional peptide sequence FV7. Synthetic cationic hybrid peptides based on FV7 could provide new models for combining different functional domains and demonstrate effective avenues to screen for novel antimicrobial agents.

  9. High Specific Selectivity and Membrane-Active Mechanism of Synthetic Cationic Hybrid Antimicrobial Peptides Based on the Peptide FV7

    PubMed Central

    Tan, Tingting; Wu, Di; Li, Weizhong; Zheng, Xin; Li, Weifen; Shan, Anshan

    2017-01-01

    Hybrid peptides integrating different functional domains of peptides have many advantages, such as remarkable antimicrobial activity, lower hemolysis and ideal cell selectivity, compared with natural antimicrobial peptides. FV7 (FRIRVRV-NH2), a consensus amphiphilic sequence was identified as being analogous to host defense peptides. In this study, we designed a series of hybrid peptides FV7-LL-37 (17–29) (FV-LL), FV7-magainin 2 (9–21) (FV-MA) and FV7-cecropin A (1–8) (FV-CE) by combining the FV7 sequence with the small functional sequences LL-37 (17–29) (LL), magainin 2 (9–21) (MA) and cecropin A (1–8) (CE) which all come from well-described natural peptides. The results demonstrated that the synthetic hybrid peptides, in particular FV-LL, had potent antibacterial activities over a wide range of Gram-negative and Gram-positive bacteria with lower hemolytic activity than other peptides. Furthermore, fluorescent spectroscopy indicated that the hybrid peptide FV-LL exhibited marked membrane destruction by inducing outer and inner bacterial membrane permeabilization, while scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that FV-LL damaged membrane integrity by disrupting the bacterial membrane. Inhibiting biofilm formation assays also showed that FV-LL had similar anti-biofilm activity compared with the functional peptide sequence FV7. Synthetic cationic hybrid peptides based on FV7 could provide new models for combining different functional domains and demonstrate effective avenues to screen for novel antimicrobial agents. PMID:28178190

  10. Highly sensitive and selective high-performance liquid chromatography method for bioequivalence study of cefpodoxime proxetil in rabbit plasma via fluorescence labeling of its active metabolite.

    PubMed

    Ahmed, Sameh; Abdel-Wadood, Hanaa M; Mohamed, Niveen A

    2013-09-01

    Cefpodoxime proxetil (CFP), a broad-spectrum third-generation cephalosporin, has been used most widely in the treatment of respiratory and urinary tract infections. For bioequivalence study of CFP in rabbit plasma, it was necessary to develop a highly sensitive and selective high-performance liquid chromatographic (HPLC) method with fluorescence (FL) detection. The pre-column labeling of cefpodoxime acid (CFA) (active metabolite) with an efficient benzofurazan type fluorogenic reagent, 4-N,N-dimethyl aminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F) was carried out in the present study in 100mM borate buffer (pH=8.5) at 50°C for 15min. The obtained fluorescent products were separated on C18 column with an isocratic elution of the mobile phase, which consists of 10mM phosphate buffer (pH=3.5)/CH3CN (70:30, v/v). The fluorescent product (DBD-CFA) was detected fluorimetrically at 556nm with an excitation wavelength of 430nm. Cefotaxime sodium was used as internal standard. The method was validated according to the requirements of US-FDA guidelines. The correlation coefficient of 0.999 was obtained in the concentration ranges of 10-1000ngmL(-1). The limits of detection and quantification (S/N=3) were 3 and 10ngmL(-1), respectively. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The proposed HPLC-FL method was successfully applied to study bioequivalence in rabbits for two formulations of different brands contained CFP (prodrug) in a randomized, two-way, single-dose, crossover study and all pharmacokinetic parameters for the two formulations were assessed.

  11. 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

    2016-07-03

    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.

  12. 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

  13. 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.

  14. One-Pot Synthesis of Mesoporous Ni-Ti-Al Ternary Oxides: Highly Active and Selective Catalysts for Steam Reforming of Ethanol.

    PubMed

    Gonçalves, Alexandre A S; Faustino, Patrícia B; Assaf, José M; Jaroniec, Mietek

    2017-02-22

    One-pot synthesis of nanostructured ternary oxides of Ni, Al, and Ti was designed and performed via evaporation induced self-assembly (EISA). For the purpose of comparison, analogous oxides were also prepared by the impregnation method. The resulting materials were applied in two catalytic reactions: steam reforming of ethanol (SRE) for H2 production (subjected to prior activation with H2) and ethanol dehydration (ED; used without prior activation), to in situ analyze carbon accumulation by ethylene depletion when ethanol interacts with acidic sites present on the support. Modification of Ni-Al mixed oxides with titania was shown to have several benefits. CO2, NH3, and propylamine sorption data indicate a decrease in the strength of acidic and basic sites after addition of titania, which in turn slowed down the carbon accumulation during the ED reaction. These changes in interactions between ethanol and byproducts with the support led to different reaction pathways in SRE, indicating that the catalysts obtained by EISA with titania addition showed higher ethylene selectivity and CO2/CO ratios. The opposite was observed for the impregnated catalysts, which were less coke-stable during ED reactions and showed no ethylene selectivity in SRE. Carbon formed during ED reactions was shown to be thermodynamically less favorable and easier to decompose in the presence of titania. All catalysts studied displayed similar and high selectivities (∼80%) and yields (∼5.3 molH2/molethanol) toward H2, which place them among the most active and selective catalysts for SRE. These results indicate the importance of tailoring the support surface acidity to achieve high reforming performance and higher selectivity toward SRE, one of the key processes to produce cleaner and efficient fuels. For an efficient reforming process, the yield of byproducts is low but still they affect the catalyst stability in the long-run, thus this work may impact future studies toward development of near

  15. High-Content pSTAT3/1 Imaging Assays to Screen for Selective Inhibitors of STAT3 Pathway Activation in Head and Neck Cancer Cell Lines

    PubMed Central

    Sen, Malabika; Hua, Yun; Camarco, Daniel; Shun, Tong Ying; Lazo, John S.; Grandis, Jennifer R.

    2014-01-01

    Abstract The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is hyperactivated in most cancers and represents a plausible therapeutic target. In the absence of STAT3-selective small-molecule inhibitors, we sought to develop pSTAT3/1 high-content imaging (HCS) assays to screen for selective inhibitors of STAT3 pathway activation in head and neck squamous cell carcinomas (HNSCC) tumor cell lines. Based on the expression of the interleukin-6 (IL-6)Rα and gp130 subunits of the IL-6 receptor complex and STAT3, we selected the Cal33 HNSCC cell line as our model. After developing image acquisition and analysis procedures, we rigorously investigated the cytokine activation responses to optimize the dynamic ranges of both assays and demonstrated that the pan-Janus kinase inhibitor pyridone 6 nonselectively inhibited pSTAT3 and pSTAT1 activation with 50% inhibition concentrations of 7.19±4.08 and 16.38±8.45 nM, respectively. The optimized pSTAT3 HCS assay performed very well in a pilot screen of 1,726 compounds from the Library of Pharmacologically Active Compounds and the National Institutes of Health clinical collection sets, and we identified 51 inhibitors of IL-6-induced pSTAT3 activation. However, only three of the primary HCS actives selectively inhibited STAT3 compared with STAT1. Our follow-up studies indicated that the nonselective inhibition of cytokine induced pSTAT3 and pSTAT1 activation by G-alpha stimulatory subunit-coupled G-protein-coupled receptor agonists, and forskolin was likely due to cyclic adenosine monophosphate-mediated up-regulation of suppressors of cytokine signaling 3. Azelastine, an H1 receptor antagonist approved for the treatment of seasonal allergic rhinitis, nonallergic vasomotor rhinitis, and ocular conjunctivitis, was subsequently confirmed as a selective inhibitor of IL-6-induced pSTAT3 activation that also reduced the growth of HNSCC cell lines. These data illustrate the power of a chemical

  16. Stimulation of food intake after central galanin is associated with arcuate nucleus activation and does not differ between genetically selected low and high body weight lines of chickens.

    PubMed

    Hagen, Christopher J; Newmyer, Brandon A; Webster, Rebekah I; Gilbert, Elizabeth R; Siegel, Paul B; Tachibana, Tetsuya; Cline, Mark A

    2013-08-01

    Galanin, a 29 residue peptide found in the hypothalamus, causes orexigenic effects in a variety of species. In the present study, we investigated appetite-associated effects of galanin in chicks from lines which have been selected from a common founder population for either low or high body weight. The low line consists of some anorexic individuals and there are obese individuals in the high line. Central galanin caused increased food intake in both lines with the magnitude of response similar in both lines. We also quantified the number of c-Fos immunoreactive cells in several hypothalamic nuclei that are associated with appetite. Only the arcuate nucleus had an increase in the number of reactive cells, a response that was similar for both lines. From these results we concluded that selection for body weight likely did not affect galanin function on induction of feeding in either lines, and that the effect of galanin is associated with arcuate nucleus activation in chicks.

  17. 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.

  18. Highly Efficient and Selective Hydrogenation of Aldehydes: A Well-Defined Fe(II) Catalyst Exhibits Noble-Metal Activity

    PubMed Central

    2016-01-01

    The synthesis and application of [Fe(PNPMe-iPr)(CO)(H)(Br)] and [Fe(PNPMe-iPr)(H)2(CO)] as catalysts for the homogeneous hydrogenation of aldehydes is described. These systems were found to be among the most efficient catalysts for this process reported to date and constitute rare examples of a catalytic process which allows selective reduction of aldehydes in the presence of ketones and other reducible functionalities. In some cases, TONs and TOFs of up to 80000 and 20000 h–1, respectively, were reached. On the basis of stoichiometric experiments and computational studies, a mechanism which proceeds via a trans-dihydride intermediate is proposed. The structure of the hydride complexes was also confirmed by X-ray crystallography. PMID:27660732

  19. 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

  20. 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.

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

    SciTech Connect

    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 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.

  2. Double-faced γ-Fe2O3||SiO2 nanohybrids: flame synthesis, in situ selective modification and highly interfacial activity

    NASA Astrophysics Data System (ADS)

    Li, Yunfeng; Hu, Yanjie; Jiang, Hao; Li, Chunzhong

    2013-05-01

    Double-faced γ-Fe2O3||SiO2 nanohybrids (NHs) and their in situ selective modification on silica faces with the 3-methacryloxypropyltrimethoxysilane molecules have been successfully prepared by a simple, rapid and scalable flame aerosol route. The double-faced NHs perfectly integrate magnetic hematite hemispheres and non-magnetic silica parts into an almost intact nanoparticle as a result of phase segregation during the preparation process. The unique feature allows us to easily manipulate these particles into one-dimensional chain-like nanostructures. On the other hand, in situ selectively modified double-faced γ-Fe2O3||SiO2 NHs possess excellent interfacial activities, which can assemble into many interesting architectures, such as interfacial film, magnetic responsive capsules, novel magnetic liquid marbles and so forth. The modified NHs prefer to assemble at the interface of water-oil or oil-water systems. It is believed that the highly interfacial active NHs are not only beneficial for the development of interface reaction in a miniature reactor, but also very promising functional materials for other smart applications.Double-faced γ-Fe2O3||SiO2 nanohybrids (NHs) and their in situ selective modification on silica faces with the 3-methacryloxypropyltrimethoxysilane molecules have been successfully prepared by a simple, rapid and scalable flame aerosol route. The double-faced NHs perfectly integrate magnetic hematite hemispheres and non-magnetic silica parts into an almost intact nanoparticle as a result of phase segregation during the preparation process. The unique feature allows us to easily manipulate these particles into one-dimensional chain-like nanostructures. On the other hand, in situ selectively modified double-faced γ-Fe2O3||SiO2 NHs possess excellent interfacial activities, which can assemble into many interesting architectures, such as interfacial film, magnetic responsive capsules, novel magnetic liquid marbles and so forth. The modified NHs

  3. High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus.

    PubMed

    Somogyi, Peter; Dalezios, Yannis; Luján, Rafael; Roberts, J David B; Watanabe, Masahiko; Shigemoto, Ryuichi

    2003-06-01

    The release of neurotransmitters is modulated by presynaptic metabotropic glutamate receptors (mGluRs), which show a highly selective expression and subcellular location in glutamatergic terminals in the hippocampus. Using immunocytochemistry, we investigated whether one of the receptors, mGluR7, whose level of expression is governed by the postsynaptic target, was present in GABAergic terminals and whether such terminals targeted particular cells. A total of 165 interneuron dendritic profiles receiving 466 synapses (82% mGluR7a-positive) were analysed. The presynaptic active zones of most GAD-(77%) or GABA-positive (94%) synaptic boutons on interneurons innervated by mGluR7a-enriched glutamatergic terminals (mGluR7a-decorated) were immunopositive for mGluR7a. GABAergic terminals on pyramidal cells and most other interneurons in str. oriens were mGluR7a-immunonegative. The mGluR7a-decorated cells were mostly somatostatin- and mGluR1alpha-immunopositive neurons in str. oriens and the alveus. Their GABAergic input mainly originated from VIP-positive terminals, 90% of which expressed high levels of mGluR7a in the presynaptic active zone. Parvalbumin-positive synaptic terminals were rare on mGluR7a-decorated cells, but on these neurons 73% of them were mGluR7a-immunopositive. Some type II synapses innervating interneurons were immunopositive for mGluR7b, as were some type I synapses. Because not all target cells of VIP-positive neurons are known it has not been possible to determine whether mGluR7 is expressed in a target-cell-specific manner in the terminals of single GABAergic cells. The activation of mGluR7 may decrease GABA release to mGluR7-decorated cells at times of high pyramidal cell activity, which elevates extracellular glutamate levels. Alternatively, the presynaptic receptor may be activated by as yet unidentified endogenous ligands released by the GABAergic terminals or the postsynaptic dendrites.

  4. New insights into selective heterogeneous nucleation of metal nanoparticles on oxides by microwave-assisted reduction: rapid synthesis of high-activity supported catalysts.

    PubMed

    Anumol, Erumpukuthickal Ashok; Kundu, Paromita; Deshpande, Parag Arvind; Madras, Giridhar; Ravishankar, Narayanan

    2011-10-25

    Microwave-based methods are widely employed to synthesize metal nanoparticles on various substrates. However, the detailed mechanism of formation of such hybrids has not been addressed. In this paper, we describe the thermodynamic and kinetic aspects of reduction of metal salts by ethylene glycol under microwave heating conditions. On the basis of this analysis, we identify the temperatures above which the reduction of the metal salt is thermodynamically favorable and temperatures above which the rates of homogeneous nucleation of the metal and the heterogeneous nucleation of the metal on supports are favored. We delineate different conditions which favor the heterogeneous nucleation of the metal on the supports over homogeneous nucleation in the solvent medium based on the dielectric loss parameters of the solvent and the support and the metal/solvent and metal/support interfacial energies. Contrary to current understanding, we show that metal particles can be selectively formed on the substrate even under situations where the temperature of the substrate is lower than that of the surrounding medium. The catalytic activity of the Pt/CeO(2) and Pt/TiO(2) hybrids synthesized by this method for H(2) combustion reaction shows that complete conversion is achieved at temperatures as low as 100 °C with Pt-CeO(2) catalyst and at 50 °C with Pt-TiO(2) catalyst. Our method thus opens up possibilities for rational synthesis of high-activity supported catalysts using a fast microwave-based reduction method.

  5. A quantitative structure-activity relationship (QSAR) study on a few series of potent, highly selective inhibitors of nitric oxide synthase.

    PubMed

    Bharti, Vishwa Deepak; Gupta, Satya P; Kumar, Harish

    2014-02-01

    QSAR study was performed on a series of 1,2-dihydro-4-quinazolinamines, 4,5-dialkylsubstituted-2-imino-1,3-thiazolidine derivatives and 4,5-disubstituted-1,3-oxazolidin-2-imine derivatives studied by Tinker et al. [J Med Chem (2003), 46, 913-916], Ueda et al. [Bioorg Med Chem (2004) 12, 4101-4116] and Ueda et al. [Bioorg Med Chem Lett (2004) 14, 313-316], respectively, as potent, highly selective inhibitors of inducible nitric oxide synthase (iNOS). The iNOS inhibition activity of the whole series of compounds was analyzed in relation to the physicochemical and molecular properties of the compounds. The QSAR analysis revealed that the inhibition potency of the compounds was controlled by a topological parameter 1chi(v) (Kier's first order valence molecular connectivity index), density (D), surface tension (St) and length (steric parameter) of a substituent. This suggested that the drug-receptor interaction predominantly involved the dispersion interaction, but the bulky molecule would face steric problem because of which the molecule may not completely fit in active sites of the receptor and thus may not have the optimum interaction.

  6. Plasma membrane Ca2+ release-activated Ca2+ channels with a high selectivity for Ca2+ identified by patch-clamp recording in rat liver cells.

    PubMed

    Rychkov, G; Brereton, H M; Harland, M L; Barritt, G J

    2001-04-01

    Repetitive waves of increased cytoplasmic Ca2+ concentration play a central role in the process by which hormones regulate liver function. Maintenance of these Ca2+ waves requires Ca2+ inflow through store-operated Ca2+ channels. The properties and mechanism(s) of activation of these channels are not well understood. Store-operated Ca2+ channels (SOCs) in the H4-IIE rat liver cell line were studied by whole-cell patch clamping. Depletion of Ca2+ in intracellular stores by intracellular perfusion with either inositol 1,4,5-trisphosphate (InsP(3)) or thapsigargin in the presence of 10 mmol/L ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid (EGTA), or with 10 mmol/L EGTA alone, activated an inward current that reversed at a membrane potential above +40 mV. In physiologic extracellular medium, this inward current was carried exclusively by Ca2+ and was blocked by a variety of di- and trivalent cations. In the absence of extracellular Ca2+ and Mg2+, the inward current was carried by monovalent cations. This current was 10 to 30 times larger than that observed in the presence of extracellular Ca2+, and permitted the detection of single-channel events that corresponded to a single-channel conductance of about 40 pS. Both the Ca2+ and Na+ inward currents were blocked by the calmodulin antagonist, N-(6-amino hexyl)-5-chloro-1-naphthalenesulphonamide (W7), but not by calmidazolium or calmodulin-dependent protein kinase II fragment 290-309. It is concluded that liver cells possess plasma membrane Ca2+ channels that have a high selectivity for Ca2+, are activated by a decrease in the concentration of Ca2+ in intracellular stores through a mechanism that is unlikely to involve calmodulin, and are involved in re-filling intracellular Ca2+ stores during Ca2+ signaling.

  7. Association between highly active antiretroviral therapy and selected cardiovascular disease risk factors in sub-Saharan Africa: a systematic review and meta-analysis protocol

    PubMed Central

    Dimala, Christian Akem; Blencowe, Hannah

    2017-01-01

    Introduction The increasing highly active antiretroviral therapy (HAART) coverage in sub-Saharan Africa (SSA) has been associated with increasing cardiovascular disease (CVD) incidence. However, the epidemiology of the association between HAART and CVD risk factors in SSA is sparse. We aim to assess the extent to which HAART is associated with selected cardiovascular risk factors (hypertension, diabetes, dyslipidaemia and metabolic syndrome) in SSA. Methods and analysis This will be a systematic review and meta-analysis of published studies on the association between HAART and CVD risk factors retrieved from Medline, Embase, Popline, Africa-Wide Information, African Index Medicus and the Cochrane library databases. Studies will be screened for eligibility according to the selection criteria by two independent reviewers. Eligible studies will be assessed for the quality of their evidence and risk of bias using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Health Institute and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, with respect to the measured outcomes (hypertension, diabetes, dyslipidaemia and metabolic syndrome). A data abstraction form will be produced on Epi info V.7 and data analysis done on STATA V.14 statistical software. Summary estimates of measures of effects for the association between HAART use and the outcomes will be derived. Random effects meta-analyses will be performed and I2 statistic used to assess for heterogeneity between studies with respect to measured parameters. Qualitative synthesis will be used where data is insufficient to produce quantitative synthesis. Ethics and dissemination The protocol has been reviewed by the Research Governance & Integrity Office of the Research Ethics Committee of the London School of Hygiene and Tropical Medicine and confirmed as not requiring ethical approval. The findings of this study will be made widely

  8. In-situ loading ultrafine AuPd particles on ceria: highly active catalyst for solvent-free selective oxidation of benzyl alcohol.

    PubMed

    Zhang, Hongye; Xie, Yun; Sun, Zhenyu; Tao, Ranting; Huang, Changliang; Zhao, Yanfei; Liu, Zhimin

    2011-02-01

    Ce(III) oxide was synthesized under the protection of nitrogen gas, which had strong ability to reduce noble metal ions (e.g., Au, Pd ions) into metallic forms under oxygen-free conditions. On the basis of the surface redox reaction between the Ce(III) oxide support and noble metal ions, an effective and novel approach was presented to prepare noble metal/CeO(2) nanocatalysts, and a series of AuPd/CeO(2) nanocomposites with different Au:Pd molar ratios and metal loadings were obtained in the absence of any extra reducing and protective agents. The resultant composites were characterized by different techniques including X-ray diffraction, transmission electron microspectroscopy, X-ray photoelectron microspectroscopy, and ICP-AES analysis. It was demonstrated that in the AuPd/CeO(2) composites the content of Ce(III) reached about 30%, and the AuPd bimetallic particles with average size of 2.6 or 3.3 nm and narrow size distribution were uniformly distributed on the CeO(2) nanorods. The AuPd/CeO(2) composites were found to be excellent heterogeneous nanocatalysts for the selective oxidation of benzyl alcohol under solvent-free conditions. It was shown that all the AuPd/CeO(2) catalysts exhibited good selectivity toward benzaldehyde; especially, the catalyst with Au:Pd = 1:5 and metal loading of 1.2 wt % displayed extremely high activity with a TOF = 30.1 s(-1) at 160 °C.

  9. Pharmacological evaluation of IQM-95,333, a highly selective CCKA receptor antagonist with anxiolytic-like activity in animal models

    PubMed Central

    Ballaz, Santiago; Barber, Ana; Fortuño, Ana; Del Río, Joaquín; Martín-Martínez, Mercedes; Gómez-Monterrey, Isabel; Herranz, Rosario; González-Muñiz, Rosario; García-López, Maria-Teresa

    1997-01-01

    The pyridopyrimidine derivative IQM-95,333 ((4aS,5R)-2-benzyl-5-[Nα-tert-butoxicarbonyl)L-tryptophyl]amino-1,3dioxoperhydropyrido[1,2-c]pyrimidine), a new non-peptide antagonist of cholecystokinin type A (CCKA) receptors, has been evaluated in vitro and in vivo in comparison with typical CCKA and CCKB receptor antagonists, such as devazepide, lorglumide, L-365,260 and PD-135,158. IQM-95,333 displaced [3H]-CCK-8S binding to CCKA receptors from rat pancreas with a high potency in the nanomolar range. Conversely, the affinity of this new compound at brain CCKB receptors was negligible (IC50>10 μM). IQM-95,333 was a more selective CCKA receptor ligand than devazepide and other CCKA receptor antagonists. Like devazepide, IQM-95,333 was a more potent antagonist of CCK-8S- than of CCK-4-induced contraction of the longitudinal muscle from guinea-pig ileum, suggesting selective antagonism at CCKA receptors. IQM-95,333 and devazepide were also potent inhibitors of CCK-8S-stimulated amylase release from isolated pancreatic acini, a CCKA receptor-mediated effect. The drug concentrations required (IC50s around 20 nM) were higher than in binding studies to pancreas homogenates. Low doses (50–100 μg kg−1, i.p.) of IQM-95,333 and devazepide, without any intrinsic effect on food intake or locomotion, blocked the hypophagia and the hypolocomotion induced by systemic administration of CCK-8S, two effects associated with stimulation of peripheral CCKA receptors. IQM-95,333 showed an anxiolytic-like profile in the light/dark exploration test in mice over a wide dose range (10–5,000 μg kg−1). Typical CCKA and CCKB antagonists, devazepide and L-365,260 respectively, were only effective within a more limited dose range. In a classical conflict paradigm for the study of anxiolytic drugs, the punished-drinking test, IQM-95,333, devazepide and L-365,260 were effective within a narrow dose range. The dose-response curve for the three drugs was biphasic, suggesting that

  10. 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.

  11. Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms

    PubMed Central

    Randall, Patrick A.; Lee, Christie A.; Podurgiel, Samantha J.; Hart, Evan; Yohn, Samantha E.; Jones, Myles; Rowland, Margaret; López-Cruz, Laura; Correa, Mercè

    2015-01-01

    Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans. PMID:25575584

  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. Selecting the Politically Active Social Studies Teacher

    ERIC Educational Resources Information Center

    O'Hanlon, James; Troshynski, Hugh

    1973-01-01

    This article outlines an innovative selection program to hire politically responsible social studies teachers. The objective is to produce aware and active citizens who know how to participate in the political process. (Editor)

  14. 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.

  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. 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

  17. 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.

  18. 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

    DOE PAGES

    Posada-Pérez, Sergio; Ramírez, Pedro J.; Evans, Jaime; ...

    2016-06-16

    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 impactmore » 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. Here, a control of the metal/carbon ratio paves the road for an efficient reutilization of this environmental harmful greenhouse gas.« less

  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

    SciTech Connect

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

    2016-06-16

    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. Here, a control of the metal/carbon ratio paves the road for an efficient reutilization of this environmental harmful greenhouse gas.

  20. Selectively deuterated and optically active cyclic ethers

    SciTech Connect

    Kawakami, Y.; Asai, T.; Umeyama, K.; Yamashita, Y.

    1982-08-27

    The synthesis of selectively deuterated epihalohydrins (F, Cl, Br, I) and 3,3-bis(chloromethyl)-d/sub 2/)oxetane and some observations on the stereochemistry of each transformation are reported. Further, the synthesis of optically active epihalohydrins, especially the optically active epifluorohydrin, from (S)-glycerol 1,2-acetonide ((S)-2), using mainly KX-18-CR-6 (X = F, Br, I), is reported. This is the first report on the synthesis of optically active epifluorohydrin. The direct halogenation of the presynthesized optically active epichlorohydrin with the same reagents gave the racemized products. The selectively deuterated or optically active compounds reported herein are expected to find a variety of uses in organic chemistry.

  1. Nylon-3 polymers with selective antifungal activity.

    PubMed

    Liu, Runhui; Chen, Xinyu; Hayouka, Zvi; Chakraborty, Saswata; Falk, Shaun P; Weisblum, Bernard; Masters, Kristyn S; Gellman, Samuel H

    2013-04-10

    Host-defense peptides inhibit bacterial growth but show little toxicity toward mammalian cells. A variety of synthetic polymers have been reported to mimic this antibacterial selectivity; however, achieving comparable selectivity for fungi is more difficult because these pathogens are eukaryotes. Here we report nylon-3 polymers based on a novel subunit that display potent antifungal activity (MIC = 3.1 μg/mL for Candida albicans ) and favorable selectivity (IC10 > 400 μg/mL for 3T3 fibroblast toxicity; HC10 > 400 μg/mL for hemolysis).

  2. 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

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

    PubMed

    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; Lindsley, Craig W

    2014-12-01

    Further chemical optimization of the halopemide-derived family of dual phospholipase D1/2 (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).

  4. Fluorinated analogues of marsanidine, a highly α2-AR/imidazoline I1 binding site-selective hypotensive agent. Synthesis and biological activities.

    PubMed

    Wasilewska, Aleksandra; Sączewski, Franciszek; Hudson, Alan L; Ferdousi, Mehnaz; Scheinin, Mika; Laurila, Jonne M; Rybczyńska, Apolonia; Boblewski, Konrad; Lehmann, Artur

    2014-11-24

    The aim of these studies was to establish the influence of fluorination of the indazole ring on the pharmacological properties of two selective α2-adrenoceptor (α2-AR) agonists: 1-[(imidazolidin-2-yl)imino]-1H-indazole (marsanidine, A) and its methylene analogue 1-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-1H-indazole (B). Introduction of fluorine into the indazole ring of A and B reduced both binding affinity and α2-AR/I1 imidazoline binding site selectivity. The most α2-AR-selective ligands were 6-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6c) and 7-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6d). The in vivo cardiovascular properties of fluorinated derivatives of A and B revealed that in both cases the C-7 fluorination leads to compounds with the highest hypotensive and bradycardic activities. The α2-AR partial agonist 6c was prepared as a potential lead compound for development of a radiotracer for PET imaging of brain α2-ARs.

  5. Estrogenic/antiestrogenic activity of selected selective serotonin reuptake inhibitors

    PubMed Central

    POP, ANCA; LUPU, DIANA IOANA; CHERFAN, JULIEN; KISS, BELA; LOGHIN, FELICIA

    2015-01-01

    Background and aims Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed classes of psychotropics. Even though the SSRI class consists of 6 molecules (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline), only fluoxetine was intensively studied for endocrine disruptive effects, while the other SSRIs received less attention. This study was designed to evaluate the estrogenic/antiestrogenic effect of fluoxetine, sertraline and paroxetine. Methods The in vitro (anti)estrogenic activity was assessed using a firefly luciferase reporter construct in the T47D-KBluc breast cancer cell line. These cells express nuclear estrogen receptors that can activate the transcription of the luciferase reporter gene upon binding of estrogen receptor agonists. Results All three compounds were found to interact with the estrogen receptor. Fluoxetine had dual properties, weak estrogenic at lower concentrations and antiestrogenic effect at higher concentrations. Sertraline shared the same properties with fluoxetine, but also increased the estradiol-mediated transcriptional activity. Paroxetine presented only one type of effect, the ability to increase the estradiol-mediated transcriptional activity. Conclusions Overall, our results indicate a possible interaction of SSRIs with the estrogen receptor. As SSRIs are being used by all categories of population, including pregnant women or children, establishing whether they can affect the endocrine mediated mechanisms should be a priority. PMID:26609273

  6. Paper-based fluorescent sensor for rapid naked-eye detection of acetylcholinesterase activity and organophosphorus pesticides with high sensitivity and selectivity.

    PubMed

    Chang, Jiafu; Li, Haiyin; Hou, Ting; Li, Feng

    2016-12-15

    Various strategies have been proposed for the sensing of acetylcholinesterase (AChE) activity and organophosphorus pesticides (OPs). However, the practical application of most methods is restricted by their intrinsic drawbacks such as complexity, long analysis time, and high cost. Thus, it is highly desirable to develop simple, fast and sensitive approaches for AChE activity and OPs detection. Herein, we reported a simple paper-based fluorescent sensor (PFS) based on the aggregation induced emission (AIE) effect of tetraphenylethylene (TPE) and the addition reaction capability of maleimide, which has been used as a powerful tool for rapid naked-eye detection of AChE activity and OPs. The introduction of TPE provides the probe with unique fluorescence property in solid state and is of great importance for improving the sensitivity of PFS. The hydrolysis product of acetylthiocholine catalyzed by AChE induced the maleimide ring destruction and activated the fluorescence performance of TPE. Given that AChE activity can be specifically inhibited by OPs, the as-proposed PFS can also be utilized for sensitive detection of OPs. Meanwhile, the variation of fluorescence signal can be readily detected by naked eyes, and low detection limits of 2.5mUmL(-1) and 0.5ngmL(-1) for AChE activity and OPs are obtained, respectively. Moreover, it has been successfully applied for AChE activity and OPs detection in diluted human serum samples, showing its great potential to be applied in real samples. Thus, this strategy possesses considerable advantages of simplicity, rapid detection, portability, cost efficiency and visualization.

  7. 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

    2015-07-07

    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.

  8. Stochastic cycle selection in active flow networks

    PubMed Central

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

    2016-01-01

    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

  9. Stochastic cycle selection in active flow networks

    NASA Astrophysics Data System (ADS)

    Woodhouse, Francis; Forrow, Aden; Fawcett, Joanna; Dunkel, Jorn

    2016-11-01

    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 non-equilibrium networks. By connecting concepts from lattice field theory, graph theory and transition rate theory, we show how topology controls dynamics in a generic model for actively driven flow on a network. Through theoretical and numerical analysis we identify symmetry-based rules to classify and predict the selection statistics of complex flow cycles from the network topology. Our conceptual framework is applicable to a broad class of biological and non-biological far-from-equilibrium networks, including actively controlled information flows, and establishes a new correspondence between active flow networks and generalized ice-type models.

  10. Active fragments-guided drug discovery and design of selective tropane alkaloids using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry coupled with virtual calculation and biological evaluation.

    PubMed

    Zhou, Mengge; Ma, Xiaoyao; Sun, Jixue; Ding, Guoyu; Cui, Qingxin; Miao, Yan; Hou, Yuanyuan; Jiang, Min; Bai, Gang

    2017-02-01

    Tropane alkaloids (TAs), rich in the plant of Physochlaina infundibularis Kuang, which is named Huashanshen (HSS) in China, showed good effects on types of spasms. However, no data were collected to explore the relationship between the specificity for muscarinic receptor subtypes and the structures of these TAs. To address this issue, an extracted ion chromatogram (EIC) strategy using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) based on the fragmentation behavior of the TA standards was established to rapidly capture the varied TAs from HSS. Based on the provided structural information of diagnostic ions or neutral loss, 29 TAs were efficiently profiled, especially some trace ingredients. In additional, via virtual validation combined with molecular dynamic simulation, approximately a dozen alkaloids were found with high selectivity for muscarinic receptors. In additional, N-acetyl convolicine was chosen for selectivity evaluation of M2 or M3 receptors through the use of a dual-luciferase reporter assay system at the cellular level and an ACh-induced constricted strip test in vitro. After summarizing the active fragments and the structure-activity relationship (SAR) information, a new modified TA that takes advantage of both the high affinity and high selectivity for M3 receptors was proposed and evaluated successfully. This study provided an effective approach for the discovery and design of natural products based on highly selective drugs by UPLC-Q/TOF-MS coupled with virtual calculation and biological evaluation. Graphical Abstract Active fragments-guided strategy for selective inhibitors from HSS.

  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. 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

  13. Antioxidant activity of selected Indian spices.

    PubMed

    Shobana, S; Naidu, K A

    2000-02-01

    Spices and vegetables possess antioxidant activity that can be applied for preservation of lipids and reduce lipid peroxidation in biological systems. The potential antioxidant activities of selected spices extracts (water and alcohol 1:1) were investigated on enzymatic lipid peroxidation. Water and alcoholic extract (1:1) of commonly used spices (garlic, ginger, onion, mint, cloves, cinnamon and pepper) dose-dependently inhibited oxidation of fatty acid, linoleic acid in presence of soybean lipoxygenase. Among the spices tested, cloves exhibited highest while onion showed least antioxidant activity. The relative antioxidant activities decreased in the order of cloves, cinnamon, pepper, ginger, garlic, mint and onion. Spice mix namely ginger, onion and garlic; onion and ginger; ginger and garlic showed cumulative inhibition of lipid peroxidation thus exhibiting their synergistic antioxidant activity. The antioxidant activity of spice extracts were retained even after boiling for 30 min at 100 degrees C, indicating that the spice constituents were resistant to thermal denaturation. The antioxidant activity of these dietary spices suggest that in addition to imparting flavor to the food, they possess potential health benefits by inhibiting the lipid peroxidation.

  14. Active Learning With Optimal Instance Subset Selection.

    PubMed

    Fu, Yifan; Zhu, Xingquan; Elmagarmid, A K

    2013-04-01

    Active learning (AL) traditionally relies on some instance-based utility measures (such as uncertainty) to assess individual instances and label the ones with the maximum values for training. In this paper, we argue that such approaches cannot produce good labeling subsets mainly because instances are evaluated independently without considering their interactions, and individuals with maximal ability do not necessarily form an optimal instance subset for learning. Alternatively, we propose to achieve AL with optimal subset selection (ALOSS), where the key is to find an instance subset with a maximum utility value. To achieve the goal, ALOSS simultaneously considers the following: 1) the importance of individual instances and 2) the disparity between instances, to build an instance-correlation matrix. As a result, AL is transformed to a semidefinite programming problem to select a k-instance subset with a maximum utility value. Experimental results demonstrate that ALOSS outperforms state-of-the-art approaches for AL.

  15. 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.

  16. ET-62HIGHLY SELECTIVE ACTIVITY OF MDM2 INHIBITOR RG7112 AGAINST MDM2-AMPLIFIED/TP53 WILD-TYPE GLIOBLASTOMAS

    PubMed Central

    Verreault, Maite; Levasseur, Camille; Schmitt, Charlotte; Guehennec, Jeremy; Labussiere, Marianne; Marie, Yannick; Haidar, Sam; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Ligon, Keith; Delattre, Jean-Yves; Idbaih, Ahmed

    2014-01-01

    Alteration of P53 pathway is one of the key molecular events involved in glioblastoma (GBM) biology. Genetic alterations which reduce TP53 function in GBM include MDM2 amplification (14% of patients), MDM4 amplification (7%), and TP53 gene mutations (35%), each of which is generally thought to be mutually exclusive. The study presented here aims to test the therapeutic activity of RG7112, a member of cis-imidazoline MDM2 inhibitors (Nutlins), in GBM cells according to their functional P53 pathway status. The effect of RG7112 was assessed in a panel of eleven GBM patient-derived cell lines (PDCLs) genetically selected to assess the drug response of the different alterations of P53 pathway. RG7112 was found to be able to induce cell death in all cell lines tested, with the highest cytotoxic efficacy against MDM2/MDM4-amplified GBM PDCL. Indeed, GBM cell lines carrying MDM2 or MDM4 gene amplification were 10 to 20 times more sensitive to the inhibitor than the other lines. TP53 mutant lines were the least sensitive lines. RG7112 treatment restored P53 and P21 protein levels in MDM2-amplified GBM cells. Most importantly, treatment of MDM2-amplified GBM orthotopic patient derived xenograft (PDX) bearing mice with 100 mg/kg RG7112 (Q5Dx3) reduced tumor growth rate and significantly increased survival duration compared to vehicle-treated mice. This data supports the research towards the development of RG7112 for clinical testing in MDM2/4-amplified glioblastoma patients. Studies assessing the capacity of RG7112 compound to cross the blood-brain barrier in healthy and GBM tumor tissue are currently ongoing.

  17. Porous carbon derived via KOH activation of a hypercrosslinked porous organic polymer for efficient CO{sub 2}, CH{sub 4}, H{sub 2} adsorptions and high CO{sub 2}/N{sub 2} selectivity

    SciTech Connect

    Modak, Arindam; Bhaumik, Asim

    2015-12-15

    Microporous carbon having Brunauer-Emmett-Teller (BET) surface area of 2186 m{sup 2} g{sup −1} and micropore volume of 0.85 cm{sup 3} g{sup −1} has been synthesized via KOH induced high temperature carbonization of a non-conjugated hypercrosslinked organic polymer. Owing to the templating and activation by KOH, we have succeeded in making a microporous carbon from this porous polymer and the resultant carbon material showed high uptake for CO{sub 2} (7.6 mmol g{sup −1}) and CH{sub 4} (2.4 mmol g{sup −1}) at 1 atm, 273 K together with very good selectivity for the CO{sub 2}/N{sub 2} (30.2) separation. Furthermore, low pressure (1 atm) H{sub 2} (2.6 wt%, 77 K) and water uptake (57.4 wt%, 298 K) ability of this polymer derived porous activated carbon is noteworthy. - Graphical abstract: Microporous carbon with BET surface area of 2186 m{sup 2} g{sup −1} has been synthesized via KOH activation of a porous organic polymer and it showed high uptake for CO{sub 2} (7.6 mmol g{sup −1}), CH{sub 4} (2.4 mmol g{sup −1}) and H{sub 2} (2.6 wt%) at 1 atm together with very good selectivity for CO{sub 2}. - Highlights: • Porous carbon from hypercrosslinked organic polymer. • KOH activated carbon with BET surface area 2186 m{sup 2} g{sup −1}. • High CO2 uptake (7.6 mmol g{sup −1}) and CO{sub 2}/N{sub 2} selectivity (30.2). • Porous carbon also showed high H{sub 2} (2.6 wt%) and H{sub 2}O (57.4 wt%) uptakes.

  18. 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.

  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. High-Molecular Compounds (Selected Articles).

    DTIC Science & Technology

    1987-10-30

    34 07 250 HIGH-MOLECULAR COMPOUNIDS (SELECTED ARTICLES)(U) FOREIGN Il TECNOLOGY DIV WIGT-PATTERtSON RFD ON 30 OCT 6? FTD-ID(RS)T- M 2-97 UNCLASSIFIED...one can see, Is quite small and corresponds to such low mobility of molecules, at which the NMR signal is not observed. 5 , - Introduction of...system, which is represented by curve 4 (Fig. 2), located near the axis of the ordinate. The mobility of molecules with this degree of plastification

  2. 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.

  3. 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.

  4. 1-[(Imidazolidin-2-yl)imino]indazole. Highly alpha 2/I1 selective agonist: synthesis, X-ray structure, and biological activity.

    PubMed

    Saczewski, Franciszek; Kornicka, Anita; Rybczyńska, Apolonia; Hudson, Alan L; Miao, Shu Sean; Gdaniec, Maria; Boblewski, Konrad; Lehmann, Artur

    2008-06-26

    Novel benzazole derivatives bearing a (imidazolidin-2-yl)imino moiety at position 1 or 2 were synthesized by reacting 1-amino- or 2-aminobenzazoles with N, N'-bis( tert-butoxycarbonyl)imidazolidine-2-thione in the presence of HgCl 2. Structures of 1-[(imidazolidin-2-yl)imino]indazole (marsanidine, 13a) and free base of the 4-Cl derivative 12e were confirmed by X-ray single crystal structure analysis. Compound 13a was found to be the selective alpha 2-adrenoceptor ligand with alpha 2-adrenoceptor/imidazoline I 1 receptor selectivity ratio of 3879, while 1-[(imidazolidin-2-yl)imino]-7-methylindazole ( 13k) proved to be a mixed alpha 2-adrenoceptor/imidazoline I 1 receptor agonist with alpha 2/I 1 selectivity ratio of 7.2. Compound 13k when administered intravenously to male Wistar rats induced a dose-dependent decrease in mean arterial blood pressure (ED50 = 0.6 microg/kg) and heart rate, which was attenuated following pretreatment with alpha 2A-adrenoceptor antagonist RX821002. Compound 13a may find a variety of medical uses ascribed to alpha 2-adrenoceptor agonists, and its 7-methyl derivative 13k is a good candidate for development as a centrally acting antihypertensive drug.

  5. An attempt to use selected strains of bacteria adapted to high concentrations of petroleum oil to increase the effective removal of petroleum products in excess activated sludge in laboratory conditions.

    PubMed

    Bieszkiewicz, E; Horoch, M; Boszczyk-Maleszak, H; Mycielski, R

    1998-01-01

    Forty two strains of bacteria were isolated from excess activated sludge from petroleum wastewater treatment plant. The strains were identified and classified to the following groups: Enterobacteriaceae (7 strains), Anitratum (3 strains), Pseudomonas (13 strains), Micrococcus (12 strains), Comamonas (2 strains), Xanthomonas (2 strains), Achromobacter (1 strain) and Vibrio-Aeromonas (1 strain). One of the isolates was found to be a yeast strain. Following preliminary selection ten strains, showing the best growth in medium with oil fraction as sole carbon source, were chosen for further studies. The selected strains belong to Pseudomonas (6 strains), Xanthomonas (2 strains), Micrococcus (1 strain) and Saccharomyces (1 strain). The strains were adapted to high oil concentration (500-2000 mg/L) and an attempt to use them to intensify removal of petroleum products from excess activated sludge was made. The sludge was inoculated with a mixture of the isolated strains. The experiment was carried out three times, each time with a fresh sample of the excess sludge. The obtained results show that the inoculation of activated sludge with the strains active against oil reduced the petroleum products content by 20% in 14 days. The greatest reduction of oil was observed in sludge with the lowest dry weight, that is with the greatest degree of hydration. The dry weight of the excess sludge did not significantly decrease during the course of the experiment, after having been inoculated with the mixture of strains.

  6. 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.

  7. 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...

  8. 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.

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

    PubMed Central

    Zheng, Shilong; Kaur, Gurpreet; Wang, Huanchen; Li, Minyong; Macnaughtan, Megan; Yang, Xiaochuan; Reid, Suazette; Prestegard, James; Wang, Binghe; Ke, Hengming

    2010-01-01

    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 IC50 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. PMID:19049349

  10. Anxiolytic and side-effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate receptors.

    PubMed

    Helton, D R; Tizzano, J P; Monn, J A; Schoepp, D D; Kallman, M J

    1998-02-01

    LY354740 is a conformationally constrained analog of glutamate which is a potent agonist for group II cAMP coupled metabotropic glutamate receptors (mGluRs). The discovery of this novel pharmacological agent has allowed the exploration of the functional consequences of activating group II mGluRs in vivo. In an effort to evaluate the clinical utility of LY354740 as an anxiolytic, we examined its effects in the fear potentiated startle and elevated plus maze models of anxiety and compared the results with the clinically prescribed anxiolytic diazepam. In the fear potentiated startle and elevated plus maze models, both LY354740 and diazepam produced significant anxiolytic activity (ED50 values of 0.3 and 0.4 mg/kg p. o. for fear potentiated startle and 0.2 and 0.5 mg/kg for the elevated plus maze, respectively). The duration of pharmacological effect for LY354740 in the efficacy models was 4 to 8 hr. In contrast to diazepam, acute administration of LY354740 did not produce sedation, cause deficits in neuromuscular coordination, interact with central nervous system depressants, produce memory impairment or change convulsive thresholds at doses 100- to 1000-fold the efficacious doses in animal models of anxiety. Thus, LY354740 has anxiolytic activity in animal models that are sensitive to benzodiazepines such as diazepam. However, at anxiolytic doses in these models, LY354740 produced none of the unwanted secondary pharmacology associated with diazepam. These data indicate a functional role for group II mGluRs in fear/anxiety responses in animals and suggest that compounds in this class may be beneficial in the treatment of anxiety-related disorders in humans without the side effects seen with currently prescribed medications.

  11. 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.

  12. Prion strain interactions are highly selective

    PubMed Central

    Nilsson, K. Peter R.; Joshi-Barr, Shivanjali; Winson, Olivia; Sigurdson, Christina J.

    2010-01-01

    Various misfolded and aggregated neuronal proteins commonly co-exist in neurodegenerative disease, but whether the proteins co-aggregate and alter the disease pathogenesis is unclear. Here we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. We tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound polythiophene acetic acid (PTAA), a conformation-sensitive fluorescent amyloid ligand. We found that prion strains interacted in a highly selective and strain-specific manner, with either (i) no interaction, (ii) hybrid plaque formation, or (iii) blockage of one strain by a second (interference). The hybrid plaques were maintained upon further passage in vivo and each strain seemed to maintain its original conformational properties, suggesting that one strain served only as a scaffold for aggregation of the second strain. These findings not only further our understanding of prion strain interactions, but also directly demonstrate interactions that may occur in other protein aggregate mixtures. PMID:20826672

  13. 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

  14. Active Batch Selection via Convex Relaxations with Guaranteed Solution Bounds.

    PubMed

    Chakraborty, Shayok; Balasubramanian, Vineeth; Sun, Qian; Panchanathan, Sethuraman; Ye, Jieping

    2015-10-01

    Active learning techniques have gained popularity to reduce human effort in labeling data instances for inducing a classifier. When faced with large amounts of unlabeled data, such algorithms automatically identify the exemplar instances for manual annotation. More recently, there have been attempts towards a batch mode form of active learning, where a batch of data points is simultaneously selected from an unlabeled set. In this paper, we propose two novel batch mode active learning (BMAL) algorithms: BatchRank and BatchRand. We first formulate the batch selection task as an NP-hard optimization problem; we then propose two convex relaxations, one based on linear programming and the other based on semi-definite programming to solve the batch selection problem. Finally, a deterministic bound is derived on the solution quality for the first relaxation and a probabilistic bound for the second. To the best of our knowledge, this is the first research effort to derive mathematical guarantees on the solution quality of the BMAL problem. Our extensive empirical studies on 15 binary, multi-class and multi-label challenging datasets corroborate that the proposed algorithms perform at par with the state-of-the-art techniques, deliver high quality solutions and are robust to real-world issues like label noise and class imbalance.

  15. 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...

  16. 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

    2016-08-03

    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.

  17. 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)

  18. Cyclic cholecystokinin analogues with high selectivity for central receptors.

    PubMed Central

    Charpentier, B; Pelaprat, D; Durieux, C; Dor, A; Reibaud, M; Blanchard, J C; Roques, B P

    1988-01-01

    Taking as a model the N-terminal folding of the cholecystokinin tyrosine-sulfated octapeptide [CCK-8; Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] deduced from conformational studies, two cyclic cholecystokinin (CCK) analogues were synthesized by conventional peptide synthesis: Boc-D-Asp-Tyr(SO3H)-Ahx-D-Lys-Trp-Ahx-Asp-Phe-NH2 [compound I (Ahx, 2-aminohexanoic acid)] and Boc-gamma-D-Glu-Tyr(SO3H)-Ahx-D-Lys-Trp-Ahx-Asp-Phe-NH2 (compound II). The binding characteristics of these peptides were investigated on brain cortex membranes and pancreatic acini of guinea pig. Compounds I and II were competitive inhibitors of [3H]Boc[Ahx28,31]CCK-(27-33) binding to central CCK receptors and showed a high degree of selectivity for these binding sites (compound I: Ki for pancreas/Ki for brain, 179; compound II: Ki for pancreas/Ki for brain, 1979). This high selectivity was associated with a high affinity for central CCK receptors (compound I: Ki, 5.1 nM; compound II: Ki, 0.49 nM). Similar affinities and selectivities were found when 125I Bolton-Hunter-labeled CCK-8 was used as a ligand. Moreover, these compounds were only weakly active in the stimulation of amylase release from guinea pig pancreatic acini (EC50 greater than 10,000 nM) and were unable to induce contractions in the guinea pig ileum (to 10(-6) M). The two cyclic CCK analogues, therefore, appear to be synthetic ligands exhibiting both high affinity and high selectivity for central CCK binding sites. These compounds could help clarify the respective role of central and peripheral receptors for various CCK-8-induced pharmacological effects. PMID:3162318

  19. Molluscicidal properties and selective toxicity of surface-active agents

    PubMed Central

    Visser, S. A.

    1965-01-01

    Of over 100 commercially produced surface-active agents tested against the bilharziasis vector snail Biomphalaria sudanica, 13 were found to possess considerable and highly selective molluscicidal properties at concentrations of less than 1 ppm for exposures of 48 hours. Against crustacea, fish, water plants, mosquito larvae, mice, and the eggs of B. sudanica, the toxicities of the 13 surfactants were slight. The chemicals did not appear to be absorbed by organic matter to any appreciable extent. It is thought that the toxicity to B. sudanica is of both a chemical and a physical nature. PMID:5294185

  20. Brain activity associated with selective attention, divided attention and distraction.

    PubMed

    Salo, Emma; Salmela, Viljami; Salmi, Juha; Numminen, Jussi; Alho, Kimmo

    2017-03-28

    Top-down controlled selective or divided attention to sounds and visual objects, as well as bottom-up triggered attention to auditory and visual distractors, has been widely investigated. However, no study has systematically compared brain activations related to all these types of attention. To this end, we used functional magnetic resonance imaging (fMRI) to measure brain activity in participants performing a tone pitch or a foveal grating orientation discrimination task, or both, distracted by novel sounds not sharing frequencies with the tones or by extrafoveal visual textures. To force focusing of attention to tones or gratings, or both, task difficulty was kept constantly high with an adaptive staircase method. A whole brain analysis of variance (ANOVA) revealed fronto-parietal attention networks for both selective auditory and visual attention. A subsequent conjunction analysis indicated partial overlaps of these networks. However, like some previous studies, the present results also suggest segregation of prefrontal areas involved in the control of auditory and visual attention. The ANOVA also suggested, and another conjunction analysis confirmed, an additional activity enhancement in the left middle frontal gyrus related to divided attention supporting the role of this area in top-down integration of dual task performance. Distractors expectedly disrupted task performance. However, contrary to our expectations, activations specifically related to the distractors were found only in the auditory and visual cortices. This suggests gating of the distractors from further processing perhaps due to strictly focused attention in the current demanding discrimination tasks.

  1. Alkoxide activation of aminoboranes towards selective amination.

    PubMed

    Solé, Cristina; Fernández, Elena

    2013-10-18

    Piece of the (inter)action: The interaction of alkoxides with the sp(2) Bpin (pin=pinacol) moiety in aminoboranes forms the in situ Lewis acid-base adduct [RO(-) →B(OR)2 N(R')2 ] which enables the amino moiety to react as a strong nucleophile with several electrophiles, thus providing amino alcohols, β-enamino esters, and β-hydroxy amides in a direct and remarkably selective way.

  2. 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

  3. Antiprotease activity of selected Slovak medicinal plants.

    PubMed

    Jedinak, A; Valachova, M; Maliar, T; Sturdik, E

    2010-02-01

    Fifty-six methanol extracts obtained from the barks, flowers, leaves and stems of 30 Slovak trees, bushes and herbs used in the traditional medicine of the Small Carpathians, Slovakia, have been screened for antiprotease (trypsin, thrombin and urokinase) activity using chromogenic bioassay. In this study, 14 extracts showed the strong inhibition activity to protease trypsin with IC50 values below 10 microg/mL. The highest inhibition activities were observed for methanol extracts of Acer platanoides IC50 = 1.8 microg/mL, Rhus typhina IC50 = 1.2 microg/mL and Tamarix gallica IC50 = 1.7 microg/mL. However, the results of extracts tested on thrombin were generally different from those observed for trypsin. The most marked inhibition activity to thrombin were estimated for extracts of Castanea sativa IC50 = 73.2 microg/mL, Larix decidua IC50 = 96.9 microg/mL and Rhus typhina IC50 = 20.5 microg/mL. In addition, Acer platanoides and Rhus typhina were the only extracts which showed inhibition activity to urokinase with IC50 = 171.1 microg/mL and IC50 = 38.3 microg/mL, respectively. In addition, Rhus typhina showed the broadest spectrum of inhibition activity to all tested serine proteases and seems to be a prospective new source of natural products as inhibitors of serine proteases.

  4. High Selective Performance of Designed Antibacterial and Anticancer Peptide Amphiphiles.

    PubMed

    Chen, Cuixia; Chen, Yucan; Yang, Cheng; Zeng, Ping; Xu, Hai; Pan, Fang; Lu, Jian Ren

    2015-08-12

    Short designed peptide amphiphiles are attractive at killing bacteria and inhibiting cancer cell growth, and the flexibility in their structural design offers a great potential for improving their potency and biocompatibility to mammalian host cells. Amino acid sequences such as G(IIKK)nI-NH2 (n≥3) have been shown to be membrane lytic, but terminal amino acid modifications could impose a huge influence on their performance. We report in this work how terminal amino acid modifications to G(IIKK)3I-NH2 influence its α-helical structure, membrane penetrating ability, and selective actions against different cell types. Deletion of an N-terminal Gly or a C-terminal Ile did not affect their antibacterial activity much, an observation consistent with their binding behavior to negatively charged membrane lipid monolayers. However, the cytotoxicity against mammalian cells was much worsened by the N-terminal Gly deletion, consistent with an increase in its helical content. Despite little impact on the antibacterial activity of G(IIKK)3I-NH2, deletion of both terminal amino acids greatly reduced its antitumor activity. Cholesterol present in tumor cell membrane-mimic was thought to constrain (IIKK)3-NH2 from penetrating into the cancerous membranes, evident from its lowest surface physical activity at penetrating model lipid membranes. On the other hand, its low toxicity to normal mammalian cells and high antibacterial activity in vitro and in vivo made it an attractive antibacterial agent. Thus, terminal modifications can help rebalance the different interactions involved and are highly effective at manipulating their selective membrane responses.

  5. Activity of selected phytochemicals against Plasmodium falciparum.

    PubMed

    Astelbauer, Florian; Gruber, Maria; Brem, Brigitte; Greger, Harald; Obwaller, Andreas; Wernsdorfer, Gunther; Congpuong, Kanungnit; Wernsdorfer, Walther H; Walochnik, Julia

    2012-08-01

    According to the WHO, in 2008, there were 247 million reported cases of malaria and nearly one million deaths from the disease. Parasite resistance against first-line drugs, including artemisinin and mefloquine, is increasing. In this study the plant-derived compounds aglafolin, rocaglamid, kokusaginine, arborine, arborinine and tuberostemonine were investigated for their anti-plasmodial activity in vitro. Fresh Plasmodium falciparum isolates were taken from patients in the area of Mae Sot, north-western Thailand in 2008 and the inhibition of schizont maturation was determined for the respective compounds. With inhibitory concentrations effecting 50%, 90% and 99% inhibition (IC(50), IC(90) and IC(99)) of 60.95 nM, 854.41 nM and 7351.49 nM, respectively, rocaglamid was the most active of the substances, closely followed by aglafoline with 53.49 nM, 864.55 nM and 8354.20 nM. The activity was significantly below that of artemisinin, but moderately higher than that of quinine. Arborine, arborinine, tuberostemonine and kokusaginine showed only marginal activity against P. falciparum characterized by IC(50) and IC(99) values higher than 350 nM and 180 μM, respectively, and regressions with relatively shallow slopes S>14.38. Analogues of rocaglamid and aglafoline merit further exploration of their anti-plasmodial activity.

  6. BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models.

    PubMed

    Liu, Ningshu; Rowley, Bruce R; Bull, Cathy O; Schneider, Claudia; Haegebarth, Andrea; Schatz, Christoph A; Fracasso, Paul R; Wilkie, Dean P; Hentemann, Martin; Wilhelm, Scott M; Scott, William J; Mumberg, Dominik; Ziegelbauer, Karl

    2013-11-01

    Because of the complexity derived from the existence of various phosphoinositide 3-kinase (PI3K) isoforms and their differential roles in cancers, development of PI3K inhibitors with differential pharmacologic and pharmacokinetic profiles would allow best exploration in different indications, combinations, and dosing regimens. Here, we report BAY 80-6946, a highly selective and potent pan-class I PI3K inhibitor with sub-nanomolar IC50s against PI3Kα and PI3Kδ. BAY 80-6946 exhibited preferential inhibition (about 10-fold) of AKT phosphorylation by PI3Kα compared with PI3Kβ in cells. BAY 80-6946 showed superior antitumor activity (>40-fold) in PIK3CA mutant and/or HER2 overexpression as compared with HER2-negative and wild-type PIK3CA breast cancer cell lines. In addition, BAY 80-6946 revealed potent activity to induce apoptosis in a subset of tumor cells with aberrant activation of PI3K as a single agent. In vivo, single intravenous administration of BAY 80-6946 exhibited higher exposure and prolonged inhibition of pAKT levels in tumors versus plasma. BAY 80-6946 is efficacious in tumors with activated PI3K when dosed either continuously or intermittently. Thus, BAY 80-6946 induced 100% complete tumor regression when dosed as a single agent every second day in rats bearing HER2-amplified and PIK3CA-mutated KPL4 breast tumors. In combination with paclitaxel, weekly dosing of BAY 80-6946 is sufficient to reach sustained response in all animals bearing patient-derived non-small cell lung cancer xenografts, despite a short plasma elimination half-life (1 hour) in mice. Thus, BAY 80-6946 is a promising agent with differential pharmacologic and pharmacokinetic properties for the treatment of PI3K-dependent human tumors.

  7. 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.

  8. Antimicrobial activity of selected herbal extracts.

    PubMed

    Gowthamarajan, K; Kulkarni, T Giriraj; Mahadevan, N; Santhi, K; Suresh, B

    2002-01-01

    METHANOLIC EXTRACT OF OLEORESINS OF ARAUCARIA BIDWILLI HOOK: and aerial parts of Cytisus scoparius Linn. Were screened for antimicrobial activity against two bacterial strains-Bacillus subtilis (Gram Positive) and Escherichia coli (Gem negative), and two fungal strains - Candida albicans and crytococcus neoformans by two-fold serial dilution technique. The results showed that all the microorganisms used were sensitive to the extracts. The minimum inhibitory concentrations (MIC) for A. bidwilli were found to be 31.25 μg/ml for Bacillus subtilis and 500 μg/ml for all other organisms used in the study. In case of C. Scoparius, the MIC values were 250 μg/ml for B. Subtilis and 500 μg/ml for allthe other strains used. However, in comparison the ampicillin (MIC: 62.5 μg/ml), and Amphotericin-B (MIC: 125 μg/ml ), the activities of both the extracts were less except A. bidwilli against B.Subtilis.

  9. High Electron Mobility Transistors (HEMT). Selected Papers

    DTIC Science & Technology

    2010-06-01

    phase shifts experienced by the incident electron aElectronic mail: linzhou@asu.edu. FIG. 1. Cross-sectional high-resolution TEM image recorded in 112...strongly diffracting condition and has a uniform potential through its projected thickness, then the relationship between the holographic phase shift ...of AFRL-RY-WP-TR-2010-1178. 15. SUBJECT TERMS microelectronics, heterostructure, holography , modeling/simulation 16. SECURITY CLASSIFICATION OF

  10. 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.

  11. Selective adsorption of flavor-active components on hydrophobic resins.

    PubMed

    Saffarionpour, Shima; Sevillano, David Mendez; Van der Wielen, Luuk A M; Noordman, T Reinoud; Brouwer, Eric; Ottens, Marcel

    2016-12-09

    This work aims to propose an optimum resin that can be used in industrial adsorption process for tuning flavor-active components or removal of ethanol for producing an alcohol-free beer. A procedure is reported for selective adsorption of volatile aroma components from water/ethanol mixtures on synthetic hydrophobic resins. High throughput 96-well microtiter-plates batch uptake experimentation is applied for screening resins for adsorption of esters (i.e. isoamyl acetate, and ethyl acetate), higher alcohols (i.e. isoamyl alcohol and isobutyl alcohol), a diketone (diacetyl) and ethanol. The miniaturized batch uptake method is adapted for adsorption of volatile components, and validated with column breakthrough analysis. The results of single-component adsorption tests on Sepabeads SP20-SS are expressed in single-component Langmuir, Freundlich, and Sips isotherm models and multi-component versions of Langmuir and Sips models are applied for expressing multi-component adsorption results obtained on several tested resins. The adsorption parameters are regressed and the selectivity over ethanol is calculated for each tested component and tested resin. Resin scores for four different scenarios of selective adsorption of esters, higher alcohols, diacetyl, and ethanol are obtained. The optimal resin for adsorption of esters is Sepabeads SP20-SS with resin score of 87% and for selective removal of higher alcohols, XAD16N, and XAD4 from Amberlite resin series are proposed with scores of 80 and 74% respectively. For adsorption of diacetyl, XAD16N and XAD4 resins with score of 86% are the optimum choice and Sepabeads SP2MGS and XAD761 resins showed the highest affinity towards ethanol.

  12. Biochemical approaches to selective antifungal activity. Focus on azole antifungals.

    PubMed

    Vanden Bossche, H; Marichal, P; Gorrens, J; Coene, M C; Willemsens, G; Bellens, D; Roels, I; Moereels, H; Janssen, P A

    1989-01-01

    Azole antifungals (e.g. the imidazoles: miconazole, clotrimazole, bifonazole, imazalil, ketoconazole, and the triazoles: diniconazole, triadimenol, propiconazole, fluconazole and itraconazole) inhibit in fungal cells the 14 alpha-demethylation of lanosterol or 24-methylenedihydrolanosterol. The consequent inhibition of ergosterol synthesis originates from binding of the unsubstituted nitrogen (N-3 or N-4) of their imidazole or triazole moiety to the heme iron and from binding of their N-1 substituent to the apoprotein of a cytochrome P-450 (P-450(14)DM) of the endoplasmic reticulum. Great differences in both potency and selectivity are found between the different azole antifungals. For example, after 16h of growth of Candida albicans in medium supplemented with [14C]-acetate and increasing concentrations of itraconazole, 100% inhibition of ergosterol synthesis is achieved at 3 x 10(-8) M. Complete inhibition of this synthesis by fluconazole is obtained at 10(-5) M only. The agrochemical imidazole derivative, imazalil, shows high selectivity, it has almost 80 and 98 times more affinity for the Candida P-450(s) than for those of the piglet testes microsomes and bovine adrenal mitochondria, respectively. However, the topically active imidazole antifungal, bifonazole, has the highest affinity for P-450(s) of the testicular microsomes. The triazole antifungal itraconazole inhibits at 10(-5) M the P-450-dependent aromatase by 17.9, whereas 50% inhibition of this enzyme is obtained at about 7.5 x 10(-6)M of the bistriazole derivative fluconazole. The overall results show that both the affinity for the fungal P-450(14)DM and the selectivity are determined by the nitrogen heterocycle and the hydrophobic N-1 substituent of the azole antifungals. The latter has certainly a greater impact. The presence of a triazole and a long hypdrophobic nonligating portion form the basis for itraconazole's potency and selectivity.

  13. Structure-activity relationship study of N⁶-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine analogues: development of highly selective D3 dopamine receptor agonists along with a highly potent D2/D3 agonist and their pharmacological characterization.

    PubMed

    Johnson, Mark; Antonio, Tamara; Reith, Maarten E A; Dutta, Aloke K

    2012-06-28

    In our effort to develop multifunctional drugs against Parkinson's disease, a structure-activity-relationship study was carried out based on our hybrid molecular template targeting D2/D3 receptors. Competitive binding with [(3)H]spiroperidol was used to evaluate affinity (K(i)) of test compounds. Functional activity of selected compounds in stimulating [(35)S]GTPγS binding was assessed in CHO cells expressing either human D2 or D3 receptors. Our results demonstrated development of highly selective compounds for D3 receptor (for (-)-40K(i), D3 = 1.84 nM, D2/D3 = 583.2; for (-)-45K(i), D3 = 1.09 nM, D2/D3 = 827.5). Functional data identified (-)-40 (EC(50), D2 = 114 nM, D3 = 0.26 nM, D2/D3 = 438) as one of the highest D3 selective agonists known to date. In addition, high affinity, nonselective D3 agonist (-)-19 (EC(50), D2 = 2.96 nM and D3 = 1.26 nM) was also developed. Lead compounds with antioxidant activity were evaluated using an in vivo PD animal model.

  14. 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.

  15. Yttrium phosphasalen initiators for rac-lactide polymerization: excellent rates and high iso-selectivities.

    PubMed

    Bakewell, Clare; Cao, Thi-Phuong-Anh; Long, Nicholas; Le Goff, Xavier F; Auffrant, Audrey; Williams, Charlotte K

    2012-12-26

    Highly active yttrium phosphasalen initiators for the stereocontrolled ring-opening polymerization of rac-lactide are reported. The initiators are coordinated by a new class of ancillary ligand: an iminophosphorane derivative of the popular "salen" ligand, termed "phosphasalen". Changing the phosphasalen structure enables access to high iso-selectivities (P(i) = 0.84) or hetero-selectivities (P(s) = 0.87). The initiators also show very high rates, excellent polymerization control, and tolerance to low loadings; furthermore, no chiral auxiliaries/ligands are needed for the stereocontrol. The combination of such high rates with high iso-selectivities is very unusual.

  16. Coupling Binding to Catalysis – Using Yeast Cell Surface Display to Select Enzymatic Activities

    PubMed Central

    Zhang, Keya; Bhuripanyo, Karan; Wang, Yiyang; Yin, Jun

    2015-01-01

    Summary We find yeast cell surface display can be used to engineer enzymes by selecting the enzyme library for high affinity binding to reaction intermediates. Here we cover key steps of enzyme engineering on the yeast cell surface including library design, construction, and selection based on magnetic and fluorescence activated cell sorting. PMID:26060080

  17. Coupling Binding to Catalysis: Using Yeast Cell Surface Display to Select Enzymatic Activities.

    PubMed

    Zhang, Keya; Bhuripanyo, Karan; Wang, Yiyang; Yin, Jun

    2015-01-01

    We find yeast cell surface display can be used to engineer enzymes by selecting the enzyme library for high affinity binding to reaction intermediates. Here we cover key steps of enzyme engineering on the yeast cell surface including library design, construction, and selection based on magnetic and fluorescence-activated cell sorting.

  18. Selective Early Retirement of Officers on an Active Duty List and the Reserve Active Status List and Selective Early Removal of Officers from the Reserve Active Status List,

    DTIC Science & Technology

    2007-11-02

    States Code, to update policies for the selective early retirement of commissioned officers and warrant officers from the Active Duty List, selective...early removal of commissioned officers from the Reserve Active Status List, and selective early retirement of officers in the Naval Reserve, serving in

  19. 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

  20. High-Activity Dealloyed Catalysts

    SciTech Connect

    Kongkanand, Anusorn

    2014-09-30

    Reduction of costly Pt usage in proton exchange membrane fuel cell electrodes is one of the major challenges towards development and commercialization of fuel cell vehicles. Although few have met the initial-kinetic activity requirements in a realistic fuel cell device, no catalyst material has ever met the demanding fuel cell durability targets set by DOE. In this project, a team of 4 universities and 2 companies came together to investigate a concept that appeared promising in preliminary non-fuel cell tests then to further develop the catalyst to a mature level ready for vehicle implementation. The team consists of academia with technical leadership in their respective areas, a catalyst supplier, and a fuel cell system integrator.The tightly collaborative project enabled development of a highly active and durable catalyst with performance that significantly exceeds that of previous catalysts and meets the DOE targets for the first time (Figure 1A). The catalyst was then further evaluated in full-active-area stack in a realistic vehicle operating condition (Figure 1B). This is the first public demonstration that one can realize the performance benefit and Pt cost reduction over a conventional pure Pt catalyst in a long-term realistic PEMFC system. Furthermore, systematic analyses of a range of catalysts with different performance after fuel cell testing allowed for correlation between catalyst microstructure and its electrocatalytic activity and durability. This will in turn aid future catalyst development.

  1. SPECTROSCOPICALLY SELECTED SPITZER 24 {mu}m ACTIVE GALACTIC NUCLEI

    SciTech Connect

    Choi, P. I.; Yan Lin; Helou, G.; Storrie-Lombardi, L. J.; Shim, H.; Fadda, D.; Im, M.

    2011-05-01

    We investigate the active galactic nucleus (AGN) sub-population of a 24 {mu}m flux-limited galaxy sample in the Spitzer Extragalactic First Look Survey. Using deep Keck optical spectroscopy and a series of emission-line diagnostics, we identify AGN-dominated systems over broad redshift 0 < z < 3.5 and luminosity 9 < log (L{sub TIR}) < 14 ranges, with sample means of (z) = 0.85 and (log (L{sub TIR})) = 11.5. We find that down to the flux limits of our Spitzer MIPS sample (f{sub 24} > 200 {mu}Jy), 15%-20% of sources exhibit strong AGN signatures in their optical spectra. At this flux limit, the AGN population accounts for as much as 25%-30% of the integrated 24 {mu}m flux. This corresponds to an MIR AGN contribution {approx}2-3 x greater than that found in ISOCAM 15 {mu}m studies that used X-ray AGN identifications. Based on our spectroscopically selected AGN sample, we also investigate the merits of Infrared Array Camera (IRAC) color selection for AGN identification. Our comparison reveals that although there is considerable overlap, a significant fraction of spectroscopic AGNs are not identifiable based on their MIR colors alone. Both the measured completeness and reliability of the IRAC color selections are found to be strongly dependent on the MIR flux limit. Finally, our spectroscopic AGN sample implies as much as a 3 x higher AGN surface density at high redshift (z > 1.2) than that of recent optical surveys at comparable optical flux limits, suggestive of a population of heavily obscured, optical/UV reddened AGNs.

  2. 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.

  3. 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.

  4. 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

  5. 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…

  6. Probes for narcotic receptor mediated phenomena. 44. Synthesis of an N-substituted 4-hydroxy-5-(3-hydroxyphenyl)morphan with high affinity and selective μ-antagonist activity

    PubMed Central

    Iyer, Malliga R.; Lee, Yong Sok; Deschamps, Jeffrey R.; Dersch, Christina M.; Rothman, Richard B.; Jacobson, Arthur E.; Rice, Kenner C.

    2012-01-01

    A simple three-step synthesis of 5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-4-ol (3a) was achieved using an osmium tetroxide mediated oxidation of the known intermediate 6. A pyrrolidine-ring variant of 3a (3-(7-(hydroxymethyl)-6-methyl-6-azabicyclo[3.2.1]octan-1-yl)phenol (5)) was isolated when other routes were used. The epimeric hydroxy analogue 4a was synthesized by simple inversion of the stereochemistry at C-4. Both N-methyl (3a and 4a) and N-phenethyl (3b and 4b) derivatives were synthesized. The compounds were examined for their opioid receptor affinity and the N-phenethyl analogue 3b was found to have relatively weak affinity for the μ-opioid receptor (Ki = 74 nM). However, the N-phenethyl analogue of the C-4 epimer, 4b, had about 15 fold higher affinity than 3b and was selective for the μ-opioid receptor (Ki = 4.6 nM). Compound 4b was a moderately potent μ-opioid antagonist (Ke = 12 nM), as determined by [35S]GTP-γ-S assays. Compounds 3b and 4b were energy minimized at the level of B3LYP/6-31G*, and then overlaid onto the 5-phenylmorphan, the (1R,5R,9S)-(−)-enantiomer of 2b (Fig. 1) with the α or β-OH group at the C-9 position. The spatial orientation of the hydroxyl moiety in 3b, 4b, 2a, and 2b is proposed to be the structural requirement for high μ-opioid receptor binding affinity and their agonist or antagonist activity. The modest change in spatial position of the hydroxyl moiety, and not the N-substituent, induced the change from potent agonist to an antagonist of moderate potency. PMID:22341895

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

    DOEpatents

    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.

  8. Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets

    PubMed Central

    Sadowska, Julita; Gębczyński, Andrzej K.; Konarzewski, Marek

    2017-01-01

    Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model—mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait. Males of each line type were divided into three groups and fed either a high fat, high carb or a control diet. They then spent 4 months in individual cages under conditions emulating human “sedentary lifestyle”, with SPA followed every month and measurements of metabolic risk indicators (body fat mass %, blood lipid profile, fasting blood glucose levels and oxidative damage in the livers, kidneys and hearts) taken at the end of study. Mice with genetically determined high BMR assimilated more energy and had higher SPA irrespective of type of diet. H-BMR individuals were characterized by lower dry body fat mass %, better lipid profile and lower fasting blood glucose levels, but higher oxidative damage in the livers and hearts. Genetically determined high BMR may be a protective factor against diet-induced obesity and most of the metabolic syndrome indicators. Elevated spontaneous activity is correlated with high BMR, and constitutes an important factor affecting individual capability to sustain energy balance even under energy dense diets. PMID:28235091

  9. Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets.

    PubMed

    Sadowska, Julita; Gębczyński, Andrzej K; Konarzewski, Marek

    2017-01-01

    Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model-mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait. Males of each line type were divided into three groups and fed either a high fat, high carb or a control diet. They then spent 4 months in individual cages under conditions emulating human "sedentary lifestyle", with SPA followed every month and measurements of metabolic risk indicators (body fat mass %, blood lipid profile, fasting blood glucose levels and oxidative damage in the livers, kidneys and hearts) taken at the end of study. Mice with genetically determined high BMR assimilated more energy and had higher SPA irrespective of type of diet. H-BMR individuals were characterized by lower dry body fat mass %, better lipid profile and lower fasting blood glucose levels, but higher oxidative damage in the livers and hearts. Genetically determined high BMR may be a protective factor against diet-induced obesity and most of the metabolic syndrome indicators. Elevated spontaneous activity is correlated with high BMR, and constitutes an important factor affecting individual capability to sustain energy balance even under energy dense diets.

  10. Carbon nanotube nanoweb-bioelectrode for highly selective dopamine sensing.

    PubMed

    Zhao, Jie; Zhang, Weimin; Sherrell, Peter; Razal, Joselito M; Huang, Xu-Feng; Minett, Andrew I; Chen, Jun

    2012-01-01

    A highly sensitive and selective dopamine sensor was fabricated with the unique 3D carbon nanotube nanoweb (CNT-N) electrode. The as-synthesised CNT-N was modified by oxygen plasma to graft functional groups in order to increase selective electroactive sites at the CNT sidewalls. This electrode was characterized physically and electrochemically using HRSEM, Raman, FT-IR, and cyclic voltammetry (CV). Our investigations indicated that the O(2)-plasma treated CNT-N electrode could serve as a highly sensitive biosensor for the selective sensing of dopamine (DA, 1 μM to 20 μM) in the presence of ascorbic acid (AA, 1000 μM).

  11. Catalytic Activation of Nitrogen Dioxide for Selective Synthesis of Nitroorganics

    DTIC Science & Technology

    2015-01-15

    AFRL-OSR-VA-TR-2015-0035 Catalytic activation of nitrogen dioxide for selective synthesis SETH BROWN UNIVERSITY OF NOTRE DAME DU LAC Final Report 01...8-98) v Prescribed by ANSI Std. Z39.18 12-01-2015 Final 15 Aug 2011 - 14 Aug 2014 Catalytic activation of nitrogen dioxide for selective synthesis...reductive elimination of the nitroarene has not. Nitrogen dioxide can be used as a source of the nitro group in reactions with arylboronic acids or their

  12. High Cytotoxic Activity of Phosphonium Salts and Their Complementary Selectivity towards HeLa and K562 Cancer Cells: Identification of Tri-n-butyl-n-hexadecylphosphonium bromide as a Highly Potent Anti-HeLa Phosphonium Salt

    PubMed Central

    Bachowska, Barbara; Kazmierczak-Baranska, Julia; Cieslak, Marcin; Nawrot, Barbara; Szczęsna, Dorota; Skalik, Joanna; Bałczewski, Piotr

    2012-01-01

    Quaternary ammonium and phosphonium salts have been screened for their toxic effect on HeLa and K562 cancer cell lines, as well as on normal HUVEC cells. Tri-n-butyl-n-hexadecylphosphonium bromide, the first phosphonium salt with a halogen anion tested against HeLa cells, was 12 times more potent (IC50 <5 μm after 24 and 48 h) than the clinically used reference compound cisplatin and 17 times more potent than tri-n-hexyltetradecylphosphonium bis(trifluoromethylsulfonyl)imide, which, to the best of our knowledge, is the first phosphonium salt to be evaluated in HeLa cells. However, it was inactive against K562 cells (24 and 48 h). According to a caspase-3/7 assay, its toxicity has not been connected with the induction of apoptosis. In contrast, triphenylalkylphosphonium iodides with shorter C1–5 alkyl chains were inactive against HeLa cells but very active against K562 cells (IC50=6–10 μm after 48 h). Phosphonium cations with halide counterions proved to be more potent than those with (CF3SO2)2N− as the anion, as in the anticancer agent NSC 747251, or other anions in molecules with similar alkyl chain lengths. On the other hand, a series of ammonium salts containing a short methylthiomethyl or methoxymethyl side chain revealed low cytotoxicity (IC50 >500 μm after 24 and 48 h) against both HeLa and K562 cancer cell lines as well as normal HUVEC cells, showing that the nontoxic N+CH2YMe (Y=S, O) structural motif in ammonium salts could be suitable for further optimization and development, especially in transfection experiments. PMID:24551490

  13. High Cytotoxic Activity of Phosphonium Salts and Their Complementary Selectivity towards HeLa and K562 Cancer Cells: Identification of Tri-n-butyl-n-hexadecylphosphonium bromide as a Highly Potent Anti-HeLa Phosphonium Salt.

    PubMed

    Bachowska, Barbara; Kazmierczak-Baranska, Julia; Cieslak, Marcin; Nawrot, Barbara; Szczęsna, Dorota; Skalik, Joanna; Bałczewski, Piotr

    2012-02-01

    Quaternary ammonium and phosphonium salts have been screened for their toxic effect on HeLa and K562 cancer cell lines, as well as on normal HUVEC cells. Tri-n-butyl-n-hexadecylphosphonium bromide, the first phosphonium salt with a halogen anion tested against HeLa cells, was 12 times more potent (IC50 <5 μm after 24 and 48 h) than the clinically used reference compound cisplatin and 17 times more potent than tri-n-hexyltetradecylphosphonium bis(trifluoromethylsulfonyl)imide, which, to the best of our knowledge, is the first phosphonium salt to be evaluated in HeLa cells. However, it was inactive against K562 cells (24 and 48 h). According to a caspase-3/7 assay, its toxicity has not been connected with the induction of apoptosis. In contrast, triphenylalkylphosphonium iodides with shorter C1-5 alkyl chains were inactive against HeLa cells but very active against K562 cells (IC50=6-10 μm after 48 h). Phosphonium cations with halide counterions proved to be more potent than those with (CF3SO2)2N(-) as the anion, as in the anticancer agent NSC 747251, or other anions in molecules with similar alkyl chain lengths. On the other hand, a series of ammonium salts containing a short methylthiomethyl or methoxymethyl side chain revealed low cytotoxicity (IC50 >500 μm after 24 and 48 h) against both HeLa and K562 cancer cell lines as well as normal HUVEC cells, showing that the nontoxic N(+)CH2YMe (Y=S, O) structural motif in ammonium salts could be suitable for further optimization and development, especially in transfection experiments.

  14. 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.

  15. Automated frame selection process for high-resolution microendoscopy

    PubMed Central

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

    2015-01-01

    Abstract. 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. PMID:25919426

  16. Transnitrosylation directs TRPA1 selectivity in N-nitrosamine activators.

    PubMed

    Kozai, Daisuke; Kabasawa, Yoji; Ebert, Maximilian; Kiyonaka, Shigeki; Otani, Yuko; Numata, Tomohiro; Takahashi, Nobuaki; Mori, Yasuo; Ohwada, Tomohiko

    2014-01-01

    S-Nitrosylation, the addition of a nitrosyl group to cysteine thiols, regulates various protein functions to mediate nitric oxide (NO) bioactivity. Recent studies have demonstrated that selectivity in protein S-nitrosylation signaling pathways is conferred through transnitrosylation, a transfer of the NO group, between proteins via interaction. We previously demonstrated that sensitivity to activation by synthetic NO-releasing agents via S-nitrosylation is a common feature of members of the transient receptor potential (TRP) family of Ca(2+)-permeable cation channels. However, strategies to confer subtype selectivity to nitrosylating agents targeted to TRP channels are yet to be developed. Here, we show selective activation of TRPA1 channels by novel NO donors derived from the ABBH (7-azabenzobicyclo[2.2.1]heptane) N-nitrosamines, which exhibit transnitrosylation reactivity to thiols without releasing NO. The NNO-ABBH1 (N-nitroso-2-exo,3-exo-ditrifluoromethyl-7-azabenzobicyclo[2.2.1]heptane) elicits S-nitrosylation of TRPA1 proteins, and dose-dependently induces robust Ca(2+) influx via both recombinant and native TRPA1 channels, but not via other NO-activated TRP channels. TRPA1 activation by NNO-ABBH1 is suppressed by specific cysteine mutations but not by NO scavenging, suggesting that cysteine transnitrosylation underlies the activation of TRPA1 by NNO-ABBH1. This is supported by the correlation of N-NO bond reactivity and TRPA1-activating potency in a congeneric series of ABBH N-nitrosamines. Interestingly, nonelectrophilic derivatives of ABBH also activate TRPA1 selectively, but less potently, compared with NNO-ABBH1. Thus, ABBH N-nitrosamines confer subtype selectivity on S-nitrosylation in TRP channels through synergetic effects of two chemical processes: cysteine transnitrosylation and molecular recognition of the nonelectrophilic moiety.

  17. 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

  18. 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.

  19. 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.

  20. Temperature selectivity in reversed-phase high performance liquid chromatography.

    PubMed

    Dolan, John W

    2002-08-02

    Column temperature plays two important roles in reversed-phase high-performance liquid chromatography (RP-HPLC): control of retention (k) and control of selectivity (a). While changes in retention as a function of temperature are ubiquitous, selectivity changes for any given solute pair are more pronounced for ionized samples and samples with more polar substituents. With many samples, column temperature can be selected in a manner that optimizes resolution. The selectivity effects observed for temperature changes in RP-HPLC generally are complementary to those observed for mobile phase strength changes, so it is often possible to improve resolution by simultaneous optimization of temperature and mobile phase percent organic or gradient steepness. Computer simulation is a powerful tool for such optimization experiments. This paper reviews the influence of temperature on chromatographic selectivity for RP-HPLC.

  1. 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.

  2. 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.

  3. Synergism of Selective Tumor Vascular Thrombosis and Protease Activated Prodrug

    DTIC Science & Technology

    2008-05-01

    cells of the hair follicles , and cells of the reproductive and digestive tracts. Chemotherapy can also cause nausea, vomiting, 14 W81XWH-07-1-0389......selected sites promises reduced toxicity and enhanced efficacy. We propose to investigate and validate a bipartite drug delivery-activation system that

  4. 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.

  5. In Vitro Selection of Cathepsin E-Activity-Enhancing Peptide Aptamers at Neutral pH

    PubMed Central

    Biyani, Madhu; Futakami, Masae; Kitamura, Koichiro; Kawakubo, Tomoyo; Suzuki, Miho; Yamamoto, Kenji; Nishigaki, Koichi

    2011-01-01

    The aspartic protease cathepsin E has been shown to induce apoptosis in cancer cells under physiological conditions. Therefore, cathepsin E-activity-enhancing peptides functioning in the physiological pH range are valuable potential cancer therapeutic candidates. Here, we have used a general in vitro selection method (evolutionary rapid panning analysis system (eRAPANSY)), based on inverse substrate-function link (SF-link) selection to successfully identify cathepsin E-activity-enhancing peptide aptamers at neutral pH. A successive enrichment of peptide activators was attained in the course of selection. One such peptide activated cathepsin E up to 260%, had a high affinity (KD; ∼300 nM), and had physiological activity as demonstrated by its apoptosis-inducing reaction in cancerous cells. This method is expected to be widely applicable for the identification of protease-activity-enhancing peptide aptamers. PMID:21527983

  6. Monopolar intracochlear pulse trains selectively activate the inferior colliculus.

    PubMed

    Schoenecker, Matthew C; Bonham, Ben H; Stakhovskaya, Olga A; Snyder, Russell L; Leake, Patricia A

    2012-10-01

    Previous cochlear implant studies using isolated electrical stimulus pulses in animal models have reported that intracochlear monopolar stimulus configurations elicit broad extents of neuronal activation within the central auditory system-much broader than the activation patterns produced by bipolar electrode pairs or acoustic tones. However, psychophysical and speech reception studies that use sustained pulse trains do not show clear performance differences for monopolar versus bipolar configurations. To test whether monopolar intracochlear stimulation can produce selective activation of the inferior colliculus, we measured activation widths along the tonotopic axis of the inferior colliculus for acoustic tones and 1,000-pulse/s electrical pulse trains in guinea pigs and cats. Electrical pulse trains were presented using an array of 6-12 stimulating electrodes distributed longitudinally on a space-filling silicone carrier positioned in the scala tympani of the cochlea. We found that for monopolar, bipolar, and acoustic stimuli, activation widths were significantly narrower for sustained responses than for the transient response to the stimulus onset. Furthermore, monopolar and bipolar stimuli elicited similar activation widths when compared at stimulus levels that produced similar peak spike rates. Surprisingly, we found that in guinea pigs, monopolar and bipolar stimuli produced narrower sustained activation than 60 dB sound pressure level acoustic tones when compared at stimulus levels that produced similar peak spike rates. Therefore, we conclude that intracochlear electrical stimulation using monopolar pulse trains can produce activation patterns that are at least as selective as bipolar or acoustic stimulation.

  7. 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.

  8. Mechanism of substrate selection by a highly specific CRISPR endoribonuclease.

    PubMed

    Sternberg, Samuel H; Haurwitz, Rachel E; Doudna, Jennifer A

    2012-04-01

    Bacteria and archaea possess adaptive immune systems that rely on small RNAs for defense against invasive genetic elements. CRISPR (clustered regularly interspaced short palindromic repeats) genomic loci are transcribed as long precursor RNAs, which must be enzymatically cleaved to generate mature CRISPR-derived RNAs (crRNAs) that serve as guides for foreign nucleic acid targeting and degradation. This processing occurs within the repetitive sequence and is catalyzed by a dedicated Cas6 family member in many CRISPR systems. In Pseudomonas aeruginosa, crRNA biogenesis requires the endoribonuclease Csy4 (Cas6f), which binds and cleaves at the 3' side of a stable RNA stem-loop structure encoded by the CRISPR repeat. We show here that Csy4 recognizes its RNA substrate with an ~50 pM equilibrium dissociation constant, making it one of the highest-affinity protein:RNA interactions of this size reported to date. Tight binding is mediated exclusively by interactions upstream of the scissile phosphate that allow Csy4 to remain bound to its product and thereby sequester the crRNA for downstream targeting. Substrate specificity is achieved by RNA major groove contacts that are highly sensitive to helical geometry, as well as a strict preference for guanosine adjacent to the scissile phosphate in the active site. Collectively, our data highlight diverse modes of substrate recognition employed by Csy4 to enable accurate selection of CRISPR transcripts while avoiding spurious, off-target RNA binding and cleavage.

  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. In Vitro Selection of pH-Activated DNA Nanostructures.

    PubMed

    Fong, Faye Yi; Oh, Seung Soo; Hawker, Craig J; Soh, H Tom

    2016-12-05

    We report the first in vitro selection of DNA nanostructures that switch their conformation when triggered by change in pH. Previously, most pH-active nanostructures were designed using known pH-active motifs, such as the i-motif or the triplex structure. In contrast, we performed de novo selections starting from a random library and generated nanostructures that can sequester and release Mipomersen, a clinically approved antisense DNA drug, in response to pH change. We demonstrate extraordinary pH-selectivity, releasing up to 714-fold more Mipomersen at pH 5.2 compared to pH 7.5. Interestingly, none of our nanostructures showed significant sequence similarity to known pH-sensitive motifs, suggesting that they may operate via novel structure-switching mechanisms. We believe our selection scheme is general and could be adopted for generating DNA nanostructures for many applications including drug delivery, sensors and pH-active surfaces.

  11. Perovskite for the highly selective enrichment of phosphopeptides.

    PubMed

    Li, Xiao-Shui; Chen, Xi; Sun, Huan; Yuan, Bi-Feng; Feng, Yu-Qi

    2015-01-09

    Selective and effective enrichment of phosphopeptides from complex samples is essential in phosphoproteome study by mass spectrometry (MS). In this work, we compared perovskites (MgTiO3, CaTiO3, SrTiO3, BaTiO3 and CaZrO3) with metal oxides (ZrO2 and TiO2) in their capability for the selective enrichment of phosphopeptides. It was found here that perovskites exhibited higher selectivity towards phosphopeptides than commonly used ZrO2 and TiO2, even though they all have high affinity to phosphopeptides. As for perovskites, CaTiO3 exhibited better selectivity for enrichment of phosphopeptides than SrTiO3, MgTiO3, BaTiO3 and CaZrO3, which might be ascribed to their crystal structures and electrophilic abilities. Moreover, to further confirm the performance of CaTiO3, CaTiO3 and TiO2 were applied to the enrichment of phosphopeptides from tryptic digest of proteins of human Jurkat-T cell lysate, respectively. The results showed CaTiO3 has much higher selectivity than TiO2 in the enrichment of phosphopeptides from the complex biological sample. Taken together, here we show that CaTiO3 is an excellent material for the highly selective enrichment of phosphopeptides and it could be potentially used in the large-scale phosphoproteome study.

  12. Controlling hydrogenation activity and selectivity of bimetallic surfaces and catalysts

    NASA Astrophysics Data System (ADS)

    Murillo, Luis E.

    Studies of bimetallic systems are of great interest in catalysis due to the novel properties that they often show in comparison with the parent metals. The goals of this dissertation are: (1) to expand the studies of self-hydrogenation and hydrogenation reactions on bimetallic surfaces under ultra high vacuum conditions (UHV) using different hydrocarbon as probe molecules; (2) to attempt to correlate the surface science findings with supported catalyst studies under more realistic conditions; and (3) to investigate the competitive hydrogenation of C=C versus C=O bonds on Pt(111) modified by different 3d transition metals. Hydrogenation studies using temperature programmed desorption (TPD) on Ni/Pt(111) bimetallic surfaces have demonstrated an enhancement in the low temperature hydrogenation activity relative to that of clean Pt(111). This novel hydrogenation pathway can be achieved under UHV conditions by controlling the structures of the bimetallic surfaces. A low temperature hydrogenation activity of 1-hexene and 1-butene has been observed on a Pt-Ni-Pt(111) subsurface structure, where Ni atoms are mainly present on the second layer of the Pt(111) single crystal. These results are in agreement with previous studies of self-hydrogenation and hydrogenation of cyclohexene. However, a much higher dehydrogenation activity is observed in the reaction of cyclohexene to produce benzene, demonstrating that the hydrocarbon structure has an effect on the reaction pathways. On the other hand, self-hydrogenation of 1-butene is not observed on the Pt-Ni-Pt(111) surface, indicating that the chain length (or molecular weight) has a significant effect on the selfhydrogenation activity. The gas phase reaction of cyclohexene on Ni/Pt supported on alumina catalysts has also shown a higher self-hydrogenation activity in comparison with the same reaction performed on supported monometallic catalysts. The effects of metal loading and impregnation sequence of the metal precursors are

  13. 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

    2012-03-05

    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.

  14. 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.

  15. Highly functionalized 7-azaindoles as selective PPAR gamma modulators.

    PubMed

    Debenham, Sheryl D; Chan, Audrey; Lau, Fiona Waiyu; Liu, Weiguo; Wood, Harold B; Lemme, Karen; Colwell, Lawrence; Habulihaz, Bahanu; Akiyama, Taro E; Einstein, Monica; Doebber, Thomas W; Sharma, Neelam; Wang, Chaunlin F; Wu, Margaret; Berger, Joel P; Meinke, Peter T

    2008-09-01

    A series of highly functionalized 3-aroyl and 3-phenoxy-2-methyl-7-azaindoles have been identified, which are potent selective PPARgamma modulators (SPPARgammaMs). Addition of substituents at the 6-position of the 7-azaindoles improves in vitro potency and pharmacokinetics. 7-Azaindoles have significantly improved off-target profiles compared to the parent indole series.

  16. High selectivity ZIF-93 hollow fiber membranes for gas separation.

    PubMed

    Cacho-Bailo, Fernando; Caro, Guillermo; Etxeberría-Benavides, Miren; Karvan, Oğuz; Téllez, Carlos; Coronas, Joaquín

    2015-06-30

    Zeolitic imidazolate framework-93 (ZIF-93) continuous membranes were synthesized on the inner side of P84 co-polyimide hollow fiber supports by microfluidics. MOFs and polymers showed high compatibility and the membrane exhibited H2-CH4 and CO2-CH4 separation selectivities of 97 (100 °C) and 17 (35 °C), respectively.

  17. High opportunity for postcopulatory sexual selection under field conditions.

    PubMed

    Turnell, Biz R; Shaw, Kerry L

    2015-08-01

    In polygamous systems, male fitness is determined not only by mating success but also by fertilization success. Despite the growing interest over the past several decades in postcopulatory sexual selection, its relative importance compared to precopulatory sexual selection remains a subject of debate. Here, we use extensive behavioral observations of a seminatural population of Hawaiian swordtail crickets, Laupala cerasina, and molecular paternity assignment to measure the opportunities for pre- and postcopulatory selection. Because postcopulatory selection has the potential to operate at multiple stages, we also separately attribute its effects to factors specific to mating events versus factors specific to males. We find that variance in postcopulatory success is over four times as great as variance in precopulatory success, with most of it unexplained by male mating order or the number of nuptial gifts given. Surprisingly, we also find that male singing effort is under postcopulatory selection, suggesting that males who sing more frequently also have more competitive ejaculates. Our results are consistent with the hypothesis that high polyandry levels promote greater relative postcopulatory selection. They also highlight the need for detailed behavioral observations under conditions as natural as possible when measuring mating and reproductive success.

  18. 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.

  19. 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.

  20. Novel 3-Oxazolidinedione-6-aryl-pyridinones as Potent, Selective, and Orally Active EP3 Receptor Antagonists.

    PubMed

    Jin, Jian; Morales-Ramos, Angel; Eidam, Patrick; Mecom, John; Li, Yue; Brooks, Carl; Hilfiker, Mark; Zhang, David; Wang, Ning; Shi, Dongchuan; Tseng, Pei-San; Wheless, Karen; Budzik, Brian; Evans, Karen; Jaworski, Jon-Paul; Jugus, Jack; Leon, Lisa; Wu, Charlene; Pullen, Mark; Karamshi, Bhumika; Rao, Parvathi; Ward, Emma; Laping, Nicholas; Evans, Christopher; Leach, Colin; Holt, Dennis; Su, Xin; Morrow, Dwight; Fries, Harvey; Thorneloe, Kevin; Edwards, Richard

    2010-10-14

    High-throughput screening and subsequent optimization led to the discovery of novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent and selective EP3 antagonists with excellent pharmacokinetic properties. Compound 2 was orally active and showed robust in vivo activities in overactive bladder models. To address potential bioactivation liabilities of compound 2, further optimization resulted in compounds 9 and 10, which maintained excellent potency, selectivity, and pharmacokinetic properties and showed no bioactivation liability in glutathione trapping studies. These highly potent, selective, and orally active EP3 antagonists are excellent tool compounds for investigating and validating potential therapeutic benefits from selectively inhibiting the EP3 receptor.

  1. Probing cathepsin K activity with a selective substrate spanning its active site.

    PubMed Central

    Lecaille, Fabien; Weidauer, Enrico; Juliano, Maria A; Brömme, Dieter; Lalmanach, Gilles

    2003-01-01

    The limited availability of highly selective cathepsin substrates seriously impairs studies designed to monitor individual cathepsin activities in biological samples. Among mammalian cysteine proteases, cathepsin K has a unique preference for a proline residue at P2, the primary determinant of its substrate specificity. Interestingly, congopain from Trypanosoma congolense also accommodates a proline residue in its S2 subsite. Analysis of a congopain model showed that amino acids forming its S2 subsite are identical with those of cathepsin K, except Leu67 which is replaced by a tyrosine residue in cathepsin K. Furthermore, amino acid residues of the congopain S2' binding pocket, which accepts a proline residue, are strictly identical with those of cathepsin K. Abz-HPGGPQ-EDN2ph [where Abz represents o-aminobenzoic acid and EDN2ph (=EDDnp) represents N -(2,4-dinitrophenyl)-ethylenediamine], a substrate initially developed for trypanosomal enzymes, was efficiently cleaved at the Gly-Gly bond by cathepsin K (kcat/ K(m)=426000 M(-1) x s(-1)). On the other hand, Abz-HPGGPQ-EDN2ph was resistant to hydrolysis by cathepsins B, F, H, L, S and V (20 nM enzyme concentration) and the Y67L (Tyr67-->Leu)/L205A cathepsin K mutant (20 nM), but still acted as a competitive inhibitor. Taken together, the selectivity of Abz-HPGGPQ-EDN2ph to cathepsin K primarily depends on the S2 and S2' subsite specificities of cathepsin K and the ionization state of histidine at P3. Whereas Abz-HPGGPQ-EDN2ph was hydrolysed by wild-type mouse fibroblast lysates, its hydrolysis was completely abolished in the cathepsin K-deficient samples, indicating that Abz-HPGGPQ-EDN2ph can be used to monitor selectively cathepsin K activity in physiological fluids and cell lysates. PMID:12837132

  2. 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.

  3. 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…

  4. Spatially Offset Active Galactic Nuclei. I. Selection and Spectroscopic Properties

    NASA Astrophysics Data System (ADS)

    Barrows, R. Scott; Comerford, Julia M.; Greene, Jenny E.; Pooley, David

    2016-09-01

    We present a sample of 18 optically selected and X-ray-detected spatially offset active galactic nuclei (AGNs) from the Sloan Digital Sky Survey (SDSS). In nine systems, the X-ray active galactic nucleus (AGN) is spatially offset from the galactic stellar core that is located within the 3″ diameter SDSS spectroscopic fiber. In 11 systems, the X-ray AGN is spatially offset from a stellar core that is located outside the fiber, with an overlap of two. To build the sample, we cross-matched Type II AGNs selected from the SDSS galaxy catalog with archival Chandra imaging and employed our custom astrometric and registration procedure. The projected angular (physical) offsets span a range of 0.″6 (0.8 kpc) to 17.″4 (19.4 kpc), with a median value of 2.″7 (4.6 kpc). The offset nature of an AGN is an unambiguous signature of a galaxy merger, and these systems can be used to study the properties of AGNs in galaxy mergers without the biases introduced by morphological merger selection techniques. In this paper (Paper I), we use our sample to assess the kinematics of AGN photoionized gas in galaxy mergers. We find that spectroscopic offset AGN selection may be up to {89}-16+7% incomplete due to small projected velocity offsets. We also find that the magnitude of the velocity offsets are generally larger than expected if our spatial selection introduces a bias toward face-on orbits, suggesting the presence of complex kinematics in the emission line gas of AGNs in galaxy mergers.

  5. Highly Z-Selective Metathesis Homocoupling of Terminal Olefins

    PubMed Central

    Jiang, Annie J.; Zhao, Yu; Schrock, Richard R.; Hoveyda, Amir H.

    2009-01-01

    Mo and W MonoAryloxide-Pyrrolide (MAP) olefin metathesis catalysts can couple terminal olefins to give as high as >98% Z-products in moderate to high yields with as little as 0.2% catalyst. Results are reported for 1-hexene, 1-octene, allylbenzene, allyltrimethylsilane, methyl-10-undecenoate, methyl-9-decenoate, allylB(pinacolate), allylOBenzyl, allylNHTosyl, and allylNHPh. It is proposed that high Z-selectivity is achieved because a large aryloxide only allows metallacyclobutanes to form that contain adjacent cis substituents and because isomerization of Z-product to E-product can be slow in that same steric environment. PMID:19919135

  6. Activity pattern of selected ungulates at Krau Wildlife Reserve

    NASA Astrophysics Data System (ADS)

    Sanusi, M. A. Mohd; Shukor, M. A.; Juliana, W. A. Wan; Traeholt, C.

    2013-11-01

    The study on ecology and feeding behaviour of selected wildlife species was carried out at the Krau Wildlife Reserve (KWR), Pahang. We aim to identify the wildlife species that present at KWR using camera traps, determine activity pattern ofungulates and study the feeding behaviour of selected herbivores including foraging time, method or behaviours and other individuals that are present during feeding. Camera trap data revealed a total of 19 wildlife species inhabiting the forest areas which include three species of ungulates namely Tapirus indicus, Sus scrofa and Muntiacus muntjak. The T. indicus was actively feeding between 2300 and 0500 hours, S. scrofa between 0600 and 1800 hours while M. muntjack 0600 and 1700 hours. Activity pattern of three ungulate species indicated that T. indicus is nocturnal, M. muntjak is diurnal and S. scrofais active both day and night. Each of the animal species inhabiting the study sites are able to compromise and did not compete among each other by foraging at different time and food resources.

  7. Antimicrobial activity of selected essential oils against cariogenic bacteria.

    PubMed

    Aguiar, G P; Carvalho, C E; Dias, H J; Reis, E B; Martins, M H G; Wakabayashi, K A L; Groppo, M; Martins, C H G; Cunha, W R; Crotti, A E M

    2013-01-01

    The antibacterial activity of nine selected essential oils (EOs) against a panel of oral pathogens was investigated in terms of their minimum inhibitory concentrations (MICs) by using the broth microdilution method. Most of the EOs displayed weak activity or were inactive against the selected oral pathogens, with MIC values ranging from 500 to 4000 μg/mL. However, the EO obtained from the leaves of Bidens sulphurea (Asteraceae) was found to display moderate activity against Streptococcus mutans (MIC = 250 μg/mL) and significant activity against Streptococcus mitis (MIC = 31.25 μg/mL). Germacrene D (38.3%), trans-caryophyllene (18.0%), β-elemene (13.9%) and bicyclogermacrene (13.1%) were identified as the main chemical components of this oil. 2,6-Di-tert-butyl-4-methylphenol, previously described as the major constituent in the EO from the flowers of B. sulphurea, was not detected in this study.

  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. 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.

  10. Selective glucocorticoid receptor-activating adjuvant therapy in cancer treatments

    PubMed Central

    Sundahl, Nora; Clarisse, Dorien; Bracke, Marc; Offner, Fritz; Berghe, Wim Vanden; Beck, Ilse M.

    2016-01-01

    Although adverse effects and glucocorticoid resistance cripple their chronic use, glucocorticoids form the mainstay therapy for acute and chronic inflammatory disorders, and play an important role in treatment protocols of both lymphoid malignancies and as adjuvant to stimulate therapy tolerability in various solid tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR), sets off a plethora of cell-specific events including therapeutically desirable effects, such as cell death, as well as undesirable effects, including chemotherapy resistance, systemic side effects and glucocorticoid resistance. In this context, selective GR agonists and modulators (SEGRAMs) with a more restricted GR activity profile have been developed, holding promise for further clinical development in anti-inflammatory and potentially in cancer therapies. Thus far, the research into the prospective benefits of selective GR modulators in cancer therapy limped behind. Our review discusses how selective GR agonists and modulators could improve the therapy regimens for lymphoid malignancies, prostate or breast cancer. We summarize our current knowledge and look forward to where the field should move to in the future. Altogether, our review clarifies novel therapeutic perspectives in cancer modulation via selective GR targeting. PMID:27713909

  11. High Frequency Performance of SiGeC HBTs with Selectively & Non-Selectively Grown Collector

    NASA Astrophysics Data System (ADS)

    Suvar, Erdal; Haralson, Erik; Radamson, Henry H.; Wang, Yong-Bin; Malm, B. Gunnar; Östling, Mikael

    2004-01-01

    Two high-frequency heterojunction bipolar transistor (HBT) architectures based on SiGeC have been fabricated and characterized. Different collector designs were applied either by using selective epitaxial growth doped with phosphorous or by nonselective epitaxial growth doped with arsenic. Both designs have a nonselectively deposited SiGeC base doped with boron and a poly-crystalline emitter doped with phosphorous. Both HBT designs exhibit similar electrical characteristics with a peak DC current gain of around 1600 and a BVCEO of 1.8V. The cut-off frequency (fT) and maximum frequency of oscillation (fmax) vary from 40 80GHz and 15 30GHz, respectively, depending on lateral design relations. Good high frequency performance for a device with a selectively grown collector is demonstrated for the first time.

  12. Synthesis of a selective HDAC6 inhibitor active in neuroblasts.

    PubMed

    Zwick, Vincent; Simões-Pires, Claudia A; Nurisso, Alessandra; Petit, Charlotte; Dos Santos Passos, Carolina; Randazzo, Giuseppe Marco; Martinet, Nadine; Bertrand, Philippe; Cuendet, Muriel

    2016-10-15

    In recent years, the role of HDAC6 in neurodegeneration has been partially elucidated, which led some authors to propose HDAC6 inhibitors as a therapeutic strategy to treat neurodegenerative diseases. In an effort to develop a selective HDAC6 inhibitor which can cross the blood brain barrier (BBB), a modified hydroxamate derivative (compound 3) was designed and synthetized. This compound was predicted to have potential for BBB penetration based on in silico and in vitro evaluation of passive permeability. When tested for its HDAC inhibitory activity, the IC50 value of compound 3 towards HDAC6 was in the nM range in both enzymatic and cell-based assays. Compound 3 showed a cell-based selectivity profile close to that of tubastatin A in SH-SY5Y human neuroblastoma cells, and a good BBB permeability profile.

  13. 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.

  14. Selecting Salient Features in High Feature to Exemplar Ratio Conditions

    DTIC Science & Technology

    2002-03-01

    We present an approach for identifying salient input features in high feature to exemplar ratio conditions. Basically we modify the SNR saliency...screening algorithm to improve the solution of the optimal salient feature subset problem. We propose that applying the SNR method to randomly selected...subsets (SRSS) has a superior potential to identify the salient features than the traditional SNR algorithm has. Two experimental studies are provided

  15. Subunit-selective proteasome activity profiling uncovers uncoupled proteasome subunit activities during bacterial infections.

    PubMed

    Misas-Villamil, Johana C; van der Burgh, Aranka M; Grosse-Holz, Friederike; Bach-Pages, Marcel; Kovács, Judit; Kaschani, Farnusch; Schilasky, Sören; Emon, Asif Emran Khan; Ruben, Mark; Kaiser, Markus; Overkleeft, Hermen S; van der Hoorn, Renier A L

    2017-01-24

    The proteasome is a nuclear - cytoplasmic proteolytic complex involved in nearly all regulatory pathways in plant cells. The three different catalytic activities of the proteasome can have different functions but tools to monitor and control these subunits selectively are not yet available in plant science. Here, we introduce subunit-selective inhibitors and dual-color fluorescent activity-based probes for studying two of the three active catalytic subunits of the plant proteasome. We validate these tools in two model plants and use this to study the proteasome during plant-microbe interactions. Our data reveals that Nicotiana benthamiana incorporates two different paralogs of each catalytic subunit into active proteasomes. Interestingly, both β1 and β5 activities are significantly increased upon infection with pathogenic Pseudomonas syringae pv. tomato DC3000 lacking hopQ1-1 (PtoDC3000(ΔhQ)) whilst the activity profile of the β1 subunit changes. Infection with wild-type PtoDC3000 causes proteasome activities that range from strongly induced β1 and β5 activities to strongly suppressed β5 activities, revealing that β1 and β5 activities can be uncoupled during bacterial infection. These selective probes and inhibitors are now available to the plant science community and can be widely and easily applied to study the activity and role of the different catalytic subunits of the proteasome in different plant species. This article is protected by copyright. All rights reserved.

  16. Highly selective bis(imino)pyridine iron-catalyzed alkene hydroboration.

    PubMed

    Obligacion, Jennifer V; Chirik, Paul J

    2013-06-07

    Bis(imino)pyridine iron dinitrogen complexes have been shown to promote the anti-Markovnikov catalytic hydroboration of terminal, internal, and geminal alkenes with high activity and selectivity. The isolated iron dinitrogen compounds offer distinct advantages in substrate scope and overall performance over known precious metal catalysts and previously reported in situ generated iron species.

  17. 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

  18. Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH

    PubMed Central

    Kirubakaran, Sivapriya; Gorla, Suresh Kumar; Sharling, Lisa; Zhang, Minjia; Liu, Xiaoping; Ray, Soumya S.; MacPherson, Iain S.; Striepen, Boris; Hedstrom, Lizbeth; Cuny, Gregory D.

    2012-01-01

    Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The C. parvum and C. hominis genomes indicate that the only route to guanine nucleotides is via inosine 5'-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro. PMID:22310229

  19. 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,…

  20. Discovery of Highly Potent and Selective α4β2-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonists Containing an Isoxazolylpyridine Ether Scaffold that Demonstrate Antidepressant-like Activity. Part II

    PubMed Central

    Yu, Li-Fang; Eaton, J. Brek; Fedolak, Allison; Zhang, Han-Kun; Hanania, Taleen; Brunner, Dani; Lukas, Ronald J.; Kozikowski, Alan P.

    2012-01-01

    In our continued efforts to develop α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure activity relationship (SAR) exploration of certain isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [3H]epibatidine binding studies together with functional assays based on 86Rb+ ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity, but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent promising lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics. PMID:23092294

  1. Discovery of highly potent and selective α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists containing an isoxazolylpyridine ether scaffold that demonstrate antidepressant-like activity. Part II.

    PubMed

    Yu, Li-Fang; Eaton, J Brek; Fedolak, Allison; Zhang, Han-Kun; Hanania, Taleen; Brunner, Dani; Lukas, Ronald J; Kozikowski, Alan P

    2012-11-26

    In our continued efforts to develop α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure-activity relationship (SAR) exploration of certain isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [(3)H]epibatidine binding studies together with functional assays based on (86)Rb(+) ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent promising lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics.

  2. 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.

  3. Face-selective activation in a congenital prosopagnosic subject.

    PubMed

    Hasson, Uri; Avidan, Galia; Deouell, Leon Y; Bentin, Shlomo; Malach, Rafael

    2003-04-01

    Congenital prosopagnosia is a severe impairment in face identification manifested from early childhood in the absence of any evident brain lesion. In this study, we used fMRI to compare the brain activity elicited by faces in a congenital prosopagnosic subject (YT) relative to a control group of 12 subjects in an attempt to shed more light on the nature of the brain mechanisms subserving face identification. The face-related activation pattern of YT in the ventral occipito-temporal cortex was similar to that observed in the control group on several parameters: anatomical location, activation profiles, and hemispheric laterality. In addition, using a modified vase-face illusion, we found that YT's brain activity in the face-related regions manifested global grouping processes. However, subtle differences in the degree of selectivity between objects and faces were observed in the lateral occipital cortex. These data suggest that face-related activation in the ventral occipito-temporal cortex, although necessary, might not be sufficient by itself for normal face identification.

  4. Select metal adsorption by activated carbon made from peanut shells.

    PubMed

    Wilson, Kermit; Yang, Hong; Seo, Chung W; Marshall, Wayne E

    2006-12-01

    Agricultural by-products, such as peanut shells, contribute large quantities of lignocellulosic waste to the environment each growing season; but few, if any, value-added uses exist for their disposal. The objective of this study was to convert peanut shells to activated carbons for use in adsorption of select metal ions, namely, cadmium (Cd2+), copper (Cu2+), lead (Pb2+), nickel (Ni2+) and zinc (Zn2+). Milled peanut shells were pyrolyzed in an inert atmosphere of nitrogen gas, and then activated with steam at different activation times. Following pyrolysis and activation, the carbons underwent air oxidation. The prepared carbons were evaluated either for adsorption efficiency or adsorption capacity; and these parameters were compared to the same parameters obtained from three commercial carbons, namely, DARCO 12x20, NORIT C GRAN and MINOTAUR. One of the peanut shell-based carbons had metal ion adsorption efficiencies greater than two of the three commercial carbons but somewhat less than but close to Minotaur. This study demonstrates that peanut shells can serve as a source for activated carbons with metal ion-removing potential and may serve as a replacement for coal-based commercial carbons in applications that warrant their use.

  5. 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.

  6. 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

  7. A primer on high-throughput computing for genomic selection.

    PubMed

    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

  8. Pathway-selective antagonism of proteinase activated receptor 2

    PubMed Central

    Suen, J Y; Cotterell, A; Lohman, R J; Lim, J; Han, A; Yau, M K; Liu, L; Cooper, M A; Vesey, D A; Fairlie, D P

    2014-01-01

    Background and Purpose Proteinase activated receptor 2 (PAR2) is a GPCR associated with inflammation, metabolism and disease. Clues to understanding how to block PAR2 signalling associated with disease without inhibiting PAR2 activation in normal physiology could be provided by studies of biased signalling. Experimental Approach PAR2 ligand GB88 was profiled for PAR2 agonist and antagonist properties by several functional assays associated with intracellular G-protein-coupled signalling in vitro in three cell types and with PAR2-induced rat paw oedema in vivo. Key Results In HT29 cells, GB88 was a PAR2 antagonist in terms of Ca2+ mobilization and PKC phosphorylation, but a PAR2 agonist in attenuating forskolin-induced cAMP accumulation, increasing ERK1/2 phosphorylation, RhoA activation, myosin phosphatase phosphorylation and actin filament rearrangement. In CHO-hPAR2 cells, GB88 inhibited Ca2+ release, but activated Gi/o and increased ERK1/2 phosphorylation. In human kidney tubule cells, GB88 inhibited cytokine secretion (IL6, IL8, GM-CSF, TNF-α) mediated by PAR2. A rat paw oedema induced by PAR2 agonists was also inhibited by orally administered GB88 and compared with effects of locally administered inhibitors of G-protein coupled pathways. Conclusions and Implications GB88 is a biased antagonist of PAR2 that selectively inhibits PAR2/Gq/11/Ca2+/PKC signalling, leading to anti-inflammatory activity in vivo, while being an agonist in activating three other PAR2-activated pathways (cAMP, ERK, Rho) in human cells. These findings highlight opportunities to design drugs to block specific PAR2-linked signalling pathways in disease, without blocking beneficial PAR2 signalling in normal physiology, and to dissect PAR2-associated mechanisms of disease in vivo. PMID:24821440

  9. Can programmed or self-selected physical activity affect physical fitness of adolescents?

    PubMed

    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

    2014-09-29

    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.

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

    PubMed

    Stompor, Monika; Żarowska, Barbara

    2016-05-11

    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.

  11. 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

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

    PubMed

    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.

  13. Enhanced activity and selectivity of carbon nanofiber supported Pd catalysts for nitrite reduction.

    PubMed

    Shuai, Danmeng; Choe, Jong Kwon; Shapley, John R; Werth, Charles J

    2012-03-06

    Pd-based catalyst treatment represents an emerging technology that shows promise to remove nitrate and nitrite from drinking water. In this work we use vapor-grown carbon nanofiber (CNF) supports in order to explore the effects of Pd nanoparticle size and interior versus exterior loading on nitrite reduction activity and selectivity (i.e., dinitrogen over ammonia production). Results show that nitrite reduction activity increases by 3.1-fold and selectivity decreases by 8.0-fold, with decreasing Pd nanoparticle size from 1.4 to 9.6 nm. Both activity and selectivity are not significantly influenced by Pd interior versus exterior CNF loading. Consequently, turnover frequencies (TOFs) among all CNF catalysts are similar, suggesting nitrite reduction is not sensitive to Pd location on CNFs nor Pd structure. CNF-based catalysts compare favorably to conventional Pd catalysts (i.e., Pd on activated carbon or alumina) with respect to nitrite reduction activity and selectivity, and they maintain activity over multiple reduction cycles. Hence, our results suggest new insights that an optimum Pd nanoparticle size on CNFs balances faster kinetics with lower ammonia production, that catalysts can be tailored at the nanoscale to improve catalytic performance for nitrite, and that CNFs hold promise as highly effective catalyst supports in drinking water treatment.

  14. 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.



  15. 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.

  16. 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.

  17. 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.

  18. Unconventional, highly selective CO2 adsorption in zeolite SSZ-13.

    PubMed

    Hudson, Matthew R; Queen, Wendy L; Mason, Jarad A; Fickel, Dustin W; Lobo, Raul F; Brown, Craig M

    2012-02-01

    Low-pressure adsorption of carbon dioxide and nitrogen was studied in both acidic and copper-exchanged forms of SSZ-13, a zeolite containing an 8-ring window. Under ideal conditions for industrial separations of CO(2) from N(2), the ideal adsorbed solution theory selectivity is >70 in each compound. For low gas coverage, the isosteric heat of adsorption for CO(2) was found to be 33.1 and 34.0 kJ/mol for Cu- and H-SSZ-13, respectively. From in situ neutron powder diffraction measurements, we ascribe the CO(2) over N(2) selectivity to differences in binding sites for the two gases, where the primary CO(2) binding site is located in the center of the 8-membered-ring pore window. This CO(2) binding mode, which has important implications for use of zeolites in separations, has not been observed before and is rationalized and discussed relative to the high selectivity for CO(2) over N(2) in SSZ-13 and other zeolites containing 8-ring windows.

  19. 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.

  20. 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

  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. 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

  3. 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.

  4. Mechanical stress-controlled tunable active frequency-selective surface

    NASA Astrophysics Data System (ADS)

    Huang, Bo-Cin; Hong, Jian-Wei; Lo, Cheng-Yao

    2017-01-01

    This study proposes a tunable active frequency-selective surface (AFSS) realized by mechanically expanding or contracting a split-ring resonator (SRR) array. The proposed AFSS transfers mechanical stress from its elastic substrate to the top of the SRR, thereby achieving electromagnetic (EM) modulation without the need for an additional external power supply, meeting the requirements for the target application: the invisibility cloak. The operating mechanism of the proposed AFSS differs from those of other AFSSs, supporting modulations in arbitrary frequencies in the target range. The proposed stress-controlled or strain-induced EM modulation proves the existence of an identical and linear relationship between the strain gradient and the frequency shift, implying its suitability for other EM modulation ranges and applications.

  5. Melittin selectively activates capsaicin-sensitive primary afferent fibers.

    PubMed

    Shin, Hong Kee; Kim, Jin Hyuk

    2004-08-06

    Whole bee venom (WBV)-induced pain model has been reported to be very useful for the study of pain. However, the major constituent responsible for the production of pain by WBV is not apparent. Intraplantar injection of WBV and melittin dramatically reduced mechanical threshold, and increased flinchings and paw thickness. In behavioral experiments, capsaicin pretreatment almost completely prevented WBV- and melittin-induced reduction of mechanical threshold and flinchings. Intraplantar injection of melittin increased discharge rate of dorsal horn neurons only with C fiber input from peripheral receptive field, which was completely blocked by topical application of capsaicin to sciatic nerve. These results suggest that both melittin and WBV induce nociceptive responses by selective activation of capsaicin-sensitive afferent fibers.

  6. Immunoglobulin octanucleotide: independent activity and selective interaction with enhancers

    SciTech Connect

    Parslow, T.G.; Jones, S.D.; Bond, B.; Yamamoto, K.R.

    1987-03-20

    The thymidine kinase (tk) promoter of herpes simplex virus includes an octanucleotide sequence motif (ATTTGCAT) that is also an essential component of immunoglobulin kappa gene promoters. In the absence of an enhancer, tk promoter derivatives that contain this element support a higher rate of transcription than those that lack it. The action of the kappa enhancer augments that of the octanucleotide in B lymphoid cells; when both elements are present, tk promoter activity is increased by more than an order of magnitude. In contrast, the presence of the octanucleotide in this promoter markedly reduces its response to a nonimmunoglobulin enhancer. These results suggest that the octanucleotide may mediate a selective interaction among promoters and enhancers.

  7. Selective fluorescence probes for dipeptidyl peptidase activity-fibroblast activation protein and dipeptidyl peptidase IV.

    PubMed

    Lai, Koon Siew; Ho, Nan-Hui; Cheng, Jonathan D; Tung, Ching-Hsuan

    2007-01-01

    Development of suitable tools to assess enzyme activity directly from their complex cellular environment has a dramatic impact on understanding the functional roles of proteins as well as on the discovery of new drugs. In this study, a novel fluorescence-based chemosensor strategy for the direct readout of dipeptidase activities within intact living cells is described. Selective activity-based probes were designed to sense two important type II transmembrane serine proteases, fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). These serine proteases have been implicated in diverse cellular activities, including blood coagulation, digestion, immune responses, wound healing, tumor growth, tumor invasion, and metastasis. Here, we validated that Ac-GPGP-2SBPO and GPGP-2SBPO probes are excellent reporters of both proteolytic activities. Furthermore, the novel probes can differentiate between FAP and DPP-IV proteolytic activities in cellular assay. Potentially, this assay platform is immediately useful for novel drug discovery.

  8. Selective Fluorescence Probes for Dipeptidyl Peptidase Activity - Fibroblast Activation Protein and Dipeptidyl Peptidase IV

    PubMed Central

    Lai, Koon Siew; Ho, Nan-Hui; Cheng, Jonathan D.; Tung, Ching-Hsuan

    2008-01-01

    Development of suitable tools to assess enzyme activity directly from their complex cellular environment has a dramatic impact on understanding the functional roles of proteins as well as on the discovery of new drugs. In this study, a novel fluorescence-based chemosensor strategy for the direct readout of dipeptidase activities within intact living cells is described. Selective activity-based probes were designed to sense two important type II transmembrane serine proteases, Fibroblast activation protein (FAP) and Dipeptidyl peptidase IV (DPP-IV). These serine proteases have been implicated in diverse cellular activities, including blood coagulation, digestion, immune responses, wound healing, tumor growth, tumor invasion and metastasis. We here validated that Ac-GPGP-2SBPO and GPGP-2SBPO probes are excellent reporters of both proteolytic activities. Furthermore, the novel probes can differentiate between FAP and DPP-IV proteolytic activities in cellular assay. Potentially, this assay platform is immediately useful for novel drug discovery. PMID:17489551

  9. Fabrication of highly selective tungsten oxide ammonia sensors

    SciTech Connect

    Llobet, E.; Molas, G.; Molinas, P.; Calderer, J.; Vilanova, X.; Brezmes, J.; Sueiras, J.E.; Correig, X.

    2000-02-01

    Tungsten oxide is shown to be a very promising material for the fabrication of highly selective ammonia sensors. Films of WO{sub 3} were deposited onto a silicon substrate by means of the drop-coating method. Then, the films were annealed in dry air at two different temperatures (300 and 400 C). X-ray photoelectron spectroscopy was used to investigate the composition of the films. Tungsten appeared both in WO{sub 2} and WO{sub 3} oxidation states, but the second state was clearly dominant. Scanning electron microscopy results showed that the oxide was amorphous or nanocrystalline. The WO{sub 3}-based devices were sensitive to ammonia vapors when operated between 250 and 350 C. The optimal operating temperature for the highest sensitivity to ammonia was 300 C. Furthermore, when the devices were operated at 300 C, their sensitivity to other reducing species such as ethanol, methane, toluene, and water vapor was significantly lower, and this resulted in a high selectivity to ammonia. A model for the sensing mechanisms of the fabricated sensors is proposed.

  10. A highly selective phosphorescence probe for histidine in living bodies.

    PubMed

    Gao, Quankun; Song, Bo; Ye, Zhiqiang; Yang, Liu; Liu, Ruoyang; Yuan, Jingli

    2015-11-14

    In this work, we designed and synthesized a heterobimetallic ruthenium(ii)-nickel(ii) complex, [Ru(bpy)2(phen-DPA)Ni](PF6)4 (Ru-Ni), as a highly selective phosphorescence probe for histidine. The probe exhibited weak emission at 603 nm because the phosphorescence of the Ru(ii) complex can be strongly quenched by the paramagnetic Ni(2+) ion. In the presence of histidine, reaction of Ru-Ni with histidine resulted in the release of nickel(ii) and an enhancement in the phosphorescence intensity at 603 nm. Ru-Ni showed high selectivity for histidine even in the presence of other amino acids and cellular abundant species. Cell imaging experimental results demonstrated that Ru-Ni is membrane permeable, and can be applied for visualizing histidine in live cells. More interestingly, Ru-Ni also can act as a novel reaction-based nuclear staining agent for visualizing exclusively the nuclei of living cells with a significant phosphorescence enhancement. In addition, the potential of the probe for biological applications was confirmed by employing it for phosphorescence imaging of histidine in larval zebrafish and Daphnia magna. These results demonstrated that Ru-Ni would be a useful tool for physiological and pathological studies involving histidine.

  11. 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.

  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. 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.

  14. A COMPARISON OF X-RAY AND MID-INFRARED SELECTION OF OBSCURED ACTIVE GALACTIC NUCLEI

    SciTech Connect

    Eckart, Megan E.; Harrison, Fiona A.; McGreer, Ian D.; Helfand, David J.; Stern, Daniel

    2010-01-01

    We compare the relative merits of active galactic nuclei (AGNs) selection at X-ray and mid-infrared wavelengths using data from moderately deep fields observed by both Chandra and Spitzer. The X-ray-selected AGN sample and associated photometric and spectroscopic optical follow-up are drawn from a subset of fields studied as part of the Serendipitous Extragalactic X-ray Source Identification (SEXSI) program. Mid-infrared data in these fields are derived from targeted and archival Spitzer imaging, and mid-infrared AGN selection is accomplished primarily through application of the Infrared Array Camera (IRAC) color-color AGN 'wedge' selection technique. Nearly all X-ray sources in these fields which exhibit clear spectroscopic signatures of AGN activity have mid-infrared colors consistent with IRAC AGN selection. These are predominantly the most luminous X-ray sources. X-ray sources that lack high-ionization and/or broad lines in their optical spectra are far less likely to be selected as AGNs by mid-infrared color selection techniques. The fraction of X-ray sources identified as AGNs in the mid-infrared increases monotonically as the X-ray luminosity increases. Conversely, only 22% of mid-infrared-selected AGNs are detected at X-ray energies in the moderately deep ((t{sub exp}) approx 100 ks) SEXSI Chandra data. We hypothesize that IRAC sources with AGN colors that lack X-ray detections are predominantly high-luminosity AGNs that are obscured and/or lie at high redshift. A stacking analysis of X-ray-undetected sources shows that objects in the mid-infrared AGN selection wedge have average X-ray fluxes in the 2-8 keV band 3 times higher than sources that fall outside the wedge. Their X-ray spectra are also harder. The hardness ratio of the wedge-selected stack is consistent with moderate intrinsic obscuration, but is not suggestive of a highly obscured, Compton-thick source population. It is evident from this comparative study that in order to create a complete

  15. 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 Central

    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

  16. Identification of highly active flocculant proteins in bovine blood.

    PubMed

    Piazza, George J; Nuñez, Alberto; Garcia, Rafael A

    2012-03-01

    Synthetic polymeric flocculants are used extensively for wastewater remediation, soil stabilization, and reduction in water leakage from unlined canals. Sources of highly active, inexpensive, renewable flocculants are needed to replace synthetic flocculants. High kaolin flocculant activity was documented for bovine blood (BB) and blood plasma with several anticoagulant treatments. BB serum also had high flocculant activity. To address the hypothesis that some blood proteins have strong flocculating activity, the BB proteins were separated by SEC. Then, the major proteins of the flocculant-active fractions were separated by SDS-PAGE. Identity of the major protein components was determined by tryptic digestion and peptide analysis by MALDI TOF MS. The sequence of selected peptides was confirmed using TOF/TOF-MS/MS fragmentation. Hemoglobin dimer (subunits α and β) was identified as the major protein component of the active fraction in BB; its high flocculation activity was confirmed by testing a commercial sample of hemoglobin. In the same manner, three proteins from blood plasma (fibrinogen, γ-globulin, α-2-macroglobulin) were found to be highly active flocculants, but bovine serum albumin, α-globulin, and β-globulin were not flocculants. On a mass basis, hemoglobin, γ-globulin, α-2-macroglobulin were as effective as anionic polyacrylamide (PAM), a widely used synthetic flocculant. The blood proteins acted faster than PAM, and unlike PAM, the blood proteins flocculants did not require calcium salts for their activity.

  17. Mechanism-Based Inhibitors of Serine Proteases with High Selectivity Through Optimization of S’ Subsite Binding

    PubMed Central

    Li, Yi; Dou, Dengfeng; He, Guijia; Lushington, Gerald H.; Groutas, William C.

    2009-01-01

    A series of mechanism-based inhibitors designed to interact with the S’ subsites of serine proteases was synthesized and their inhibitory activity toward the closely-related serine proteases human neutrophil elastase (HNE) and proteinase 3 (PR 3) was investigated. The compounds were found to be time-dependent inhibitors of HNE and were devoid of any inhibitory activity toward PR 3. The results suggest that highly selective inhibitors of serine proteases whose primary substrate specificity and active sites are similar can be identified by exploiting differences in their S’ subsites. The best inhibitor (compound 16) had a kinact/KI value of 4580 M−1 s−1. PMID:19394830

  18. 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…

  19. VARIABLE SELECTION AND PREDICTION WITH INCOMPLETE HIGH-DIMENSIONAL DATA1

    PubMed Central

    Liu, Ying; Wang, Yuanjia; Feng, Yang; Wall, Melanie M.

    2016-01-01

    We propose a Multiple Imputation Random Lasso (mirl) method to select important variables and to predict the outcome for an epidemiological study of Eating and Activity in Teens. In this study 80% of individuals have at least one variable missing. Therefore, using variable selection methods developed for complete data after listwise deletion substantially reduces prediction power. Recent work on prediction models in the presence of incomplete data cannot adequately account for large numbers of variables with arbitrary missing patterns. We propose MIRL to combine penalized regression techniques with multiple imputation and stability selection. Extensive simulation studies are conducted to compare MIRL with several alternatives. MIRL outperforms other methods in high-dimensional scenarios in terms of both reduced prediction error and improved variable selection performance, and it has greater advantage when the correlation among variables is high and missing proportion is high. MIRL is shown to have improved performance when comparing with other applicable methods when applied to the study of Eating and Activity in Teens for the boys and girls separately, and to a subgroup of low social economic status (ses) Asian boys who are at high risk of developing obesity. PMID:27213023

  20. The High-Redshift Clustering of Photometrically Selected Quasars

    NASA Astrophysics Data System (ADS)

    Timlin, John

    2017-01-01

    We present the data from the Spitzer IRAC Equatorial Survey (SpIES) along with our first high-redshift (2.9high-redshift quasars. Using the infrared data from SpIES and SHELA, and the deep optical data from SDSS, we employ the multi-dimensional Bayesian selection algorithm outlined in Richards et al. 2015 to identify ~5000 high-redshift quasar candidates in this field. We then combine these candidates with spectroscopically confirmed high-redshift quasars and measure the redshift space correlation function and the projected correlation function. Finally, using these results, we compute the linear bias to try to constrain quasar feedback models akin to those in Hopkins et al. 2007.

  1. Design and Synthesis of Potent and Highly Selective Orexin 1 Receptor Antagonists with a Morphinan Skeleton and Their Pharmacologies.

    PubMed

    Nagase, Hiroshi; Yamamoto, Naoshi; Yata, Masahiro; Ohrui, Sayaka; Okada, Takahiro; Saitoh, Tsuyoshi; Kutsumura, Noriki; Nagumo, Yasuyuki; Irukayama-Tomobe, Yoko; Ishikawa, Yukiko; Ogawa, Yasuhiro; Hirayama, Shigeto; Kuroda, Daisuke; Watanabe, Yurie; Gouda, Hiroaki; Yanagisawa, Masashi

    2017-02-09

    Nalfurafine, a κ-selective opioid receptor agonist, unexpectedly showed a selective antagonist activity toward the orexin 1 receptor (OX1R) (Ki = 250 nM). Modification of the 17-amino side chain of the opioid ligand to an arylsulfonyl group and the 6-furan acrylamide chain to 2-pyridyl acrylamide led to compound 71 with improvement of the antagonist activity (OX1R, Ki = 1.36 nM; OX2R, not active) without any detectable affinity for the opioid receptor. The dihydrosulfate salt of 71, freely soluble in water, attenuated the physical dependence of morphine. Furthermore, all of the active nalfurafine derivatives in this study had almost no activity for OX2R, which led to high OX1R selectivity. These results suggest that nalfurafine derivatives could be a useful series of lead compounds to develop highly selective OX1R antagonists.

  2. A Selective Review of Group Selection in High-Dimensional Models.

    PubMed

    Huang, Jian; Breheny, Patrick; Ma, Shuangge

    2012-01-01

    Grouping structures arise naturally in many statistical modeling problems. Several methods have been proposed for variable selection that respect grouping structure in variables. Examples include the group LASSO and several concave group selection methods. In this article, we give a selective review of group selection concerning methodological developments, theoretical properties and computational algorithms. We pay particular attention to group selection methods involving concave penalties. We address both group selection and bi-level selection methods. We describe several applications of these methods in nonparametric additive models, semiparametric regression, seemingly unrelated regressions, genomic data analysis and genome wide association studies. We also highlight some issues that require further study.

  3. Temporal selectivity in midbrain electrosensory neurons identified by modal variation in active sensing.

    PubMed

    Pluta, Scott R; Kawasaki, Masashi

    2010-07-01

    Mormyrid weakly electric fish actively sense their surroundings by continuously emitting discrete pulses of electricity separated by varying intervals of silence. The temporal pattern of this pulsing behavior is related to context. While resting in the absence of an overt stimulus, baseline interpulse intervals (IPIs) mostly range 200-450 ms, and sequential variation is relatively high. Spontaneously, or following the presentation of a novel stimulus, IPIs transiently shorten during the performance of an electromotor "burst" display. We made intracellular whole cell recordings in vivo from neurons in the lateral nucleus of the torus semicircularis while the fish's dynamic pulsing behavior modified the temporal pattern of stimulation. Stimulation was designed to simulate the spatial patterns of AM that occur during the electrolocation of a resistive object. We discovered that toral neurons selectively respond to stimulation during a particular mode of electromotor activity. Two types of temporally selective neurons were discovered: baseline-selective neurons that displayed significantly higher postsynaptic potential (PSP) amplitude and spike count per electric organ discharge (EOD) during baseline electromotor activity and burst-selective neurons that displayed significantly higher PSP amplitude and spike count per EOD during electromotor burst displays. Interval-dependent changes in the strength of excitation and inhibition contributed to their selectivity.

  4. 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.

  5. The role of surface reactions on the active and selective catalyst design for bioethanol steam reforming

    NASA Astrophysics Data System (ADS)

    Benito, M.; Padilla, R.; Serrano-Lotina, A.; Rodríguez, L.; Brey, J. J.; Daza, L.

    In order to study the role of surface reactions involved in bioethanol steam reforming mechanism, a very active and selective catalyst for hydrogen production was analysed. The highest activity was obtained at 700 °C, temperature at which the catalyst achieved an ethanol conversion of 100% and a selectivity to hydrogen close to 70%. It also exhibited a very high hydrogen production efficiency, higher than 4.5 mol H 2 per mol of EtOH fed. The catalyst was operated at a steam to carbon ratio (S/C) of 4.8, at 700 °C and atmospheric pressure. No by-products, such as ethylene or acetaldehyde were observed. In order to consider a further application in an ethanol processor, a long-term stability test was performed under the conditions previously reported. After 750 h, the catalyst still exhibited a high stability and selectivity to hydrogen production. Based on the intermediate products detected by temperature programmed desorption and reaction (TPD and TPR) experiments, a reaction pathway was proposed. Firstly, the adsorbed ethanol is dehydrogenated to acetaldehyde producing hydrogen. Secondly, the adsorbed acetaldehyde is transformed into acetone via acetic acid formation. Finally, acetone is reformed to produce hydrogen and carbon dioxide, which were the final reaction products. The promotion of such reaction sequence is the key to develop an active, selective and stable catalyst, which is the technical barrier for hydrogen production by ethanol reforming.

  6. Evaluation of JAK3 biology in autoimmune disease using a highly selective, irreversible JAK3 inhibitor.

    PubMed

    Elwood, Fiona; Witter, David; Piesvaux, Jennifer; Kraybill, Brian; Bays, Nathan; Alpert, Carla; Goldenblatt, Peter; Qu, Yujie; Ivanovska, Irena; Lee, Hyun-Hee; Chiu, Chi-Sung; Tang, Hao; Scott, Mark E; Deshmukh, Sujal; Zielstorff, Mark; Byford, Alan; Chakravarty, Kalyan; Dorosh, Lauren; Rivkin, Alexy; Klappenbach, Joel; Pan, Bo-Sheng; Kariv, Ilona; Dinsmore, Christopher; Slipetz, Deborah; Dandliker, Peter

    2017-02-13

    Reversible Janus kinase (JAK) inhibitors such as Tofacitinib(Changelian, et al., 2003;Flanagan, et al., 2010) and Decernotinib(Farmer, et al., 2015;Mahajan, et al., 2015) block cytokine signaling and are efficacious in treating autoimmune diseases (Kremer, et al., 2009;Fleischmann, et al., 2015;Fleischmann, et al., 2015;Krueger, et al., 2016;Sandborn, et al., 2012). However therapeutic doses are limited due to inhibition of other JAK/STAT pathways associated with hematopoiesis, lipid biogenesis, infection and immune responses(Kahn C, 2012). A selective JAK3 inhibitor may have a better therapeutic index, however, no compounds have been described that maintain JAK3 selectivity in cells, as well as against the kinome, with good physicochemical properties to test the JAK3 hypothesis in vivo. To quantify the biochemical basis for JAK isozyme selectivity, we determined that the apparent Km for each JAK isozyme ranged from 31.8 μM for JAK1 to 2.9 μM for JAK3. To confirm compound activity in cells, we developed a novel enzyme complimentation assay that read activity of single JAK isozymes in a cellular context. Reversible JAK3 inhibitors cannot achieve sufficient selectivity against other isozymes in the cellular context due to inherent differences in enzyme ATP Km values. Therefore, we developed irreversible JAK3 compounds that are potent and highly selective in vitro, in cells and against the kinome. Compound 2, a potent inhibitor of JAK3 (0.15 nM) was 4300-fold selective for JAK3 over JAK1 in enzyme assays, 67-fold (IL-2 vs. IL-6) or 140-fold (IL-2 vs. EPO or GMCSF) selective in cellular reporter assays and >35-fold selective in human PBMC assays (IL-7 vs. IL-6 or GMCSF). In vivo, selective JAK3 inhibition was sufficient to block the development of inflammation in a rat model of Rheumatoid Arthritis, while sparing hematopoiesis.

  7. Radio Selected Clusters of Galaxies at High Redshift

    NASA Astrophysics Data System (ADS)

    Wing, Joshua; Blanton, Elizabeth

    2010-08-01

    Previous studies have shown that three-component radio sources exhibiting some degree of bending between components are likely to be found in galaxy clusters. Often this radio emission is associated with a cD type galaxy at the center of a cluster. We have cross-correlated the Sloan Digital Sky Survey (SDSS) with samples selected from the Faint Images of the Radio Sky at Twenty Centimeters (FIRST) catalog and measured the richness of the cluster environments surrounding three- component sources exhibiting both bent and straight lobes. This has lead to the discovery and classification of a large number of galaxy clusters out to a redshift of z ~ 0.5. For both bent- and straight- lobed sources without an optical counterpart it is likely that the radio emission is associated with a galaxy fainter than m_r=22 (the limiting magnitude of the SDSS) and at a redshift higher than z~0.8. We propose to observe a small sub-sample of these sources with the FLAMINGOS instrument on the Mayall 4-m telescope in an attempt to discover if these sources are located in high redshift (z≳0.8) galaxy clusters. In our visually-selected bent radio source sample, 78% of sources with counterparts in the SDSS are associated with clusters.

  8. 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.

  9. Highly selective solar-driven methanol from CO2 by a photocatalyst/biocatalyst integrated system.

    PubMed

    Yadav, Rajesh K; Oh, Gyu Hwan; Park, No-Joong; Kumar, Abhishek; Kong, Ki-jeong; Baeg, Jin-Ook

    2014-12-03

    The successful development of a photocatalyst/biocatalyst integrated system that carries out selective methanol production from CO2 is reported herein. The fine-tuned system was derived from a judicious combination of graphene-based visible light active photocatalyst (CCG-IP) and sequentially coupled enzymes. The covalent attachment of isatin-porphyrin (IP) chromophore to chemically converted graphene (CCG) afforded newly developed CCG-IP photocatalyst for this research endeavor. The current work represents a new benchmark for carrying out highly selective methanol formation from CO2 in an environmentally benign manner.

  10. 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.

  11. 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

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

    PubMed

    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

    2015-02-12

    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.

  13. 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.

  14. (R)-(-)-10-methyl-11-hydroxyaporphine: a highly selective serotonergic agonist.

    PubMed

    Cannon, J G; Mohan, P; Bojarski, J; Long, J P; Bhatnagar, R K; Leonard, P A; Flynn, J R; Chatterjee, T K

    1988-02-01

    Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.

  15. Highly selective CNTFET based sensors using metal diversification methods

    NASA Astrophysics Data System (ADS)

    Bondavalli, P.; Gorintin, L.; Longnos, F.; Feugnet, G.

    2011-10-01

    This contribution deals with Carbon Nanotubes Field Effect transistors (CNTFETs) based gas sensors fabricated using a new dynamic spray based technique for SWCNTs deposition. This technique is compatible with large surfaces, flexible substrates and allows to fabricate high performances transistors exploiting the percolation effect of the SWCNTs networks achieved with extremely reproducible characteristics. Recently, we have been able to achieve extremely selective measurement of NO2 , NH3 and DMMP using four CNTFETS fabricated using different metals as electrodes (Pt, Au, Ti, Pd), exploiting the specific interaction between gas and metal/SWCNT junction. In this way we have identify a sort of electronic fingerprinting of the gas. The time response is evaluated at less than 30sec and the sensitivity can reach 20ppb for NO2, 100ppb for NH3 and 1ppm for DMMP (Di-Methyl-Methyl-Phosphonate).

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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…

  1. Identifying Luminous Active Galactic Nuclei in Deep Surveys: Revised IRAC Selection Criteria

    NASA Astrophysics Data System (ADS)

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

    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 2-10 keV(erg s-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 H (cm-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.

  2. 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.

  3. Abnormalities in auditory efferent activities in children with selective mutism.

    PubMed

    Muchnik, Chava; Ari-Even Roth, Daphne; Hildesheimer, Minka; Arie, Miri; Bar-Haim, Yair; Henkin, Yael

    2013-01-01

    Two efferent feedback pathways to the auditory periphery may play a role in monitoring self-vocalization: the middle-ear acoustic reflex (MEAR) and the medial olivocochlear bundle (MOCB) reflex. Since most studies regarding the role of auditory efferent activity during self-vocalization were conducted in animals, human data are scarce. The working premise of the current study was that selective mutism (SM), a rare psychiatric disorder characterized by consistent failure to speak in specific social situations despite the ability to speak normally in other situations, may serve as a human model for studying the potential involvement of auditory efferent activity during self-vocalization. For this purpose, auditory efferent function was assessed in a group of 31 children with SM and compared to that of a group of 31 normally developing control children (mean age 8.9 and 8.8 years, respectively). All children exhibited normal hearing thresholds and type A tympanograms. MEAR and MOCB functions were evaluated by means of acoustic reflex thresholds and decay functions and the suppression of transient-evoked otoacoustic emissions, respectively. Auditory afferent function was tested by means of auditory brainstem responses (ABR). Results indicated a significantly higher proportion of children with abnormal MEAR and MOCB function in the SM group (58.6 and 38%, respectively) compared to controls (9.7 and 8%, respectively). The prevalence of abnormal MEAR and/or MOCB function was significantly higher in the SM group (71%) compared to controls (16%). Intact afferent function manifested in normal absolute and interpeak latencies of ABR components in all children. The finding of aberrant efferent auditory function in a large proportion of children with SM provides further support for the notion that MEAR and MOCB may play a significant role in the process of self-vocalization.

  4. Two new iridoids from selected Penstemon species--antimicrobial activity.

    PubMed

    Zajdel, Sybilla M; Graikou, Konstantia; Sotiroudis, Georgios; Głowniak, Kazimierz; Chinou, Ioanna

    2013-01-01

    Eighteen secondary metabolites, belonging to three different chemical groups, were isolated from the methanolic extracts of the aerial parts of selected penstemon plants [Penstemon fruticosus (Pursh) Greene var. fruticosus, Penstemon palmeri Gray and Penstemon venustus Doug. ex Lindl.], and their structures were elucidated on the basis of spectral evidence. Six iridoid glucosides (1-6), three phenylpropanoid glucosides (13-15) and two acetophenone derivatives (16,17), obtained from P. fruticosus, five iridoids (2, 7-10), one phenylpropanoid glucoside (15) and two acetophenones (16, 18), isolated from P. palmeri while three iridoids (2, 11, 12) and three phenylpropanoids (13-15) were identified in P. venustus. Two of the iridoid glucosides (4, 5) from P. fruticosus are new natural products named accordingly as cis- and trans- forms of 10-O-p-methoxycinnamoylaucubin. All isolated compounds, as well as crude methanolic extracts, were evaluated for their antimicrobial activities against six Gram-positive and Gram-negative bacteria and three human pathogenic fungi.

  5. Anticancer activities of selected species of North American lichen extracts.

    PubMed

    Shrestha, Gajendra; El-Naggar, Atif M; St Clair, Larry L; O'Neill, Kim L

    2015-01-01

    Cancer is the second leading cause of human deaths in the USA. Despite continuous efforts to treat cancer over the past 50 years, human mortality rates have not decreased significantly. Natural products, such as lichens, have been good sources of anticancer drugs. This study reports the cytotoxic activity of crude extracts of 17 lichen species against Burkitt's lymphoma (Raji) cells. Out of the 17 lichen species, extracts from 14 species showed cytotoxicity against Raji cells. On the basis of IC50 values, we selected Xanthoparmelia chlorochroa and Tuckermannopsis ciliaris to study the mechanism of cell death. Viability of normal lymphocytes was not affected by the extracts of X. chlorochroa and T. ciliaris. We found that extracts from both lichens decreased proliferation, accumulated cells at the G0 /G1 stage, and caused apoptosis in a dose-dependent manner. Both lichen extracts also caused upregulation of p53. The T. ciliaris extract upregulated the expression of TK1 but X. chlorochroa did not. We also found that usnic, salazinic, constictic, and norstictic acids were present in the extract of X. chlorochroa, whereas protolichesterinic acid in T. ciliaris extracts. Our data demonstrate that lichen extracts merit further research as a potential source of anticancer drugs.

  6. Novel computational identification of highly selective biomarkers of pollutant exposure.

    PubMed

    Weisman, David; Liu, Hong; Redfern, Jessica; Zhu, Liya; Colón-Carmona, Adán

    2011-06-15

    The use of in vivo biosensors to acquire environmental pollution data is an emerging and promising paradigm. One major challenge is the identification of highly specific biomarkers that selectively report exposure to a target pollutant, while remaining quiescent under a diverse set of other, often unknown, environmental conditions. This study hypothesized that a microarray data mining approach can identify highly specific biomarkers, and, that the robustness property can generalize to unforeseen environmental conditions. Starting with Arabidopsis thaliana microarray data measuring responses to a variety of treatments, the study used the top scoring pair (TSP) algorithm to identify mRNA transcripts that respond uniquely to phenanthrene, a model polycyclic aromatic hydrocarbon. Subsequent in silico analysis with a larger set of microarray data indicated that the biomarkers remained robust under new conditions. Finally, in vivo experiments were performed with unforeseen conditions that mimic phenanthrene stress, and the biomarkers were assayed using qRT-PCR. In these experiments, the biomarkers always responded positively to phenanthrene, and never responded to the unforeseen conditions, thereby supporting the hypotheses. This data mining approach requires only microarray or next-generation RNA-seq data, and, in principle, can be applied to arbitrary biomonitoring organisms and chemical exposures.

  7. 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.

  8. 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.

  9. Barium ions selectively activate BK channels via the Ca2+-bowl site.

    PubMed

    Zhou, Yu; Zeng, Xu-Hui; Lingle, Christopher J

    2012-07-10

    Activation of Ca(2+)-dependent BK channels is increased via binding of micromolar Ca(2+) to two distinct high-affinity sites per BK α-subunit. One site, termed the Ca(2+) bowl, is embedded within the second RCK domain (RCK2; regulator of conductance for potassium) of each α-subunit, while oxygen-containing residues in the first RCK domain (RCK1) have been linked to a separate Ca(2+) ligation site. Although both sites are activated by Ca(2+) and Sr(2+), Cd(2+) selectively favors activation via the RCK1 site. Divalent cations of larger ionic radius than Sr(2+) are thought to be ineffective at activating BK channels. Here we show that Ba(2+), better known as a blocker of K(+) channels, activates BK channels and that this effect arises exclusively from binding at the Ca(2+)-bowl site. Compared with previous estimates for Ca(2+) bowl-mediated activation by Ca(2+), the affinity of Ba(2+) to the Ca(2+) bowl is reduced about fivefold, and coupling of binding to activation is reduced from ∼3.6 for Ca(2+) to about ∼2.8 for Ba(2+). These results support the idea that ionic radius is an important determinant of selectivity differences among different divalent cations observed for each Ca(2+)-binding site.

  10. Discovery and antiplatelet activity of a selective PI3Kβ inhibitor (MIPS-9922).

    PubMed

    Zheng, Zhaohua; Pinson, Jo-Anne; Mountford, Simon J; Orive, Stephanie; Schoenwaelder, Simone M; Shackleford, David; Powell, Andrew; Nelson, Erin M; Hamilton, Justin R; Jackson, Shaun P; Jennings, Ian G; Thompson, Philip E

    2016-10-21

    A series of amino-substituted triazines were developed and examined for PI3Kβ inhibition and anti-platelet function. Structural adaptations of a morpholine ring of the prototype pan-PI3K inhibitor ZSTK474 yielded PI3Kβ selective compounds, where the selectivity largely derives from an interaction with the non-conserved Asp862 residue, as shown by site directed mutagenesis. The most PI3Kβ selective inhibitor from the series was studied in detail through a series of in vitro and in vivo functional studies. MIPS-9922, 10 potently inhibited ADP-induced washed platelet aggregation. It also inhibited integrin αIIbβ3 activation and αIIbβ3 dependent platelet adhesion to immobilized vWF under high shear. It prevented arterial thrombus formation in the in vivo electrolytic mouse model of thrombosis without inducing prolonged bleeding or excess blood loss.

  11. Submillimetre observations of WISE-selected high-redshift, luminous AGN and their surrounding overdense environments

    NASA Astrophysics Data System (ADS)

    Jones, Suzy F.

    2016-08-01

    We present JCMT SCUBA-2 850 μm submillimetre (submm) observations of 10 mid-infrared (mid-IR) luminous active galactic nuclei (AGNs), detected by the Wide-field Infrared Survey Explorer (WISE) all-sky IR survey and 30 that have also been detected by the NVSS/FIRST radio survey. These rare sources are selected by their extremely red mid-IR spectral energy distributions (SEDs). Further investigations show that they are highly obscured, have abundant warm AGN-heated dust and are thought to be experiencing intense AGN feedback. When comparing the number of submm galaxies detected serendipitously in the surrounding 1.5 arcmin to those in blank-field submm surveys, there is a very significant overdensity, of order 3-5, but no sign of radial clustering centred at our primary objects. The WISE-selected AGN thus reside in 10-Mpc-scale overdense environments that could be forming in pre-viralized clusters of galaxies. WISE-selected AGNs appear to be the strongest signposts of high-density regions of active, luminous and dusty galaxies. SCUBA-2 850 μm observations indicate that their submm fluxes are low compared to many popular AGN SED templates, hence the WISE/radio-selected AGNs have either less cold and/or more warm dust emission than normally assumed for typical AGN. Most of the targets have total IR luminosities ≥1013 L⊙, with known redshifts of 20 targets between z ˜ 0.44-4.6.

  12. Synthesis and Biological Investigation of Oxazole Hydroxamates as Highly Selective Histone Deacetylase 6 (HDAC6) Inhibitors.

    PubMed

    Senger, Johanna; Melesina, Jelena; Marek, Martin; Romier, Christophe; Oehme, Ina; Witt, Olaf; Sippl, Wolfgang; Jung, Manfred

    2016-02-25

    Histone deacetylase 6 (HDAC6) catalyzes the removal of an acetyl group from lysine residues of several non-histone proteins. Here we report the preparation of thiazole-, oxazole-, and oxadiazole-containing biarylhydroxamic acids by a short synthetic procedure. We identified them as selective HDAC6 inhibitors by investigating the inhibition of recombinant HDAC enzymes and the protein acetylation in cells by Western blotting (tubulin vs histone acetylation). The most active compounds exhibited nanomolar potency and high selectivity for HDAC6. For example, an oxazole hydroxamate inhibits HDAC6 with an IC50 of 59 nM and has a selectivity index of >200 against HDAC1 and HDAC8. This is the first report showing that the nature of a heterocycle directly connected to a zinc binding group (ZBG) can be used to modulate subtype selectivity and potency for HDAC6 inhibitors to such an extent. We rationalize the high potency and selectivity of the oxazoles by molecular modeling and docking.

  13. 3-Amido-3-aryl-piperidines: A Novel Class of Potent, Selective, and Orally Active GlyT1 Inhibitors.

    PubMed

    Pinard, Emmanuel; Alberati, Daniela; Alvarez-Sanchez, Ruben; Brom, Virginie; Burner, Serge; Fischer, Holger; Hauser, Nicole; Kolczewski, Sabine; Lengyel, Judith; Mory, Roland; Saladin, Christian; Schulz-Gasch, Tanja; Stalder, Henri

    2014-04-10

    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.

  14. 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

  15. Melanogenesis and antityrosinase activity of selected South african plants.

    PubMed

    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 IC(50) 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 IC(50) 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.

  16. Highly selective medium for isolation of Listeria monocytogenes from food.

    PubMed

    al-Zoreky, N; Sandine, W E

    1990-10-01

    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.

  17. Highly selective inhibition of histone demethylases by de novo macrocyclic peptides.

    PubMed

    Kawamura, Akane; Münzel, Martin; Kojima, Tatsuya; Yapp, Clarence; Bhushan, Bhaskar; Goto, Yuki; Tumber, Anthony; Katoh, Takayuki; King, Oliver N F; Passioura, Toby; Walport, Louise J; Hatch, Stephanie B; Madden, Sarah; Müller, Susanne; Brennan, Paul E; Chowdhury, Rasheduzzaman; Hopkinson, Richard J; Suga, Hiroaki; Schofield, Christopher J

    2017-04-06

    The JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are current cancer targets; however, very few highly selective inhibitors for these are available. Here we report cyclic peptide inhibitors of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E isoforms. Crystal structures and biochemical analyses of one of the inhibitors (CP2) with KDM4A reveals that CP2 binds differently to, but competes with, histone substrates in the active site. Substitution of the active site binding arginine of CP2 to N-ɛ-trimethyl-lysine or methylated arginine results in cyclic peptide substrates, indicating that KDM4s may act on non-histone substrates. Targeted modifications to CP2 based on crystallographic and mass spectrometry analyses results in variants with greater proteolytic robustness. Peptide dosing in cells manifests KDM4A target stabilization. Although further development is required to optimize cellular activity, the results reveal the feasibility of highly selective non-metal chelating, substrate-competitive inhibitors of the JmjC KDMs.

  18. Beta-lactamase reporter system for selecting high-producing yeast clones.

    PubMed

    Hribar, Gorazd; Smilović, Vanja; Zupan, Ana Lenassi; Gaberc-Porekar, Vladka

    2008-04-01

    In modern production of protein biopharmaceuticals, a good screening and selection method of high-producing clones can dramatically influence the whole production process and lead to lower production costs. We have created a rapid, simple, and inexpensive method for selecting high-producing clones in the yeast Pichia pastoris that is based on the beta-lactamase reporter system. By integrating the reporter gene and the gene of interest into the same genome locus, it was possible to use beta-lactamase activity as a measure of the expression level of the protein of interest. A novel expression vector with two independent expression cassettes was designed and tested using green fluorescent protein (GFP) as a model. The first cassette contained the GFP gene under the control of a strong, inducible AOX1 promoter, while the second cassette consisted of the beta-lactamase reporter gene under the control of a weak constitutive YPT1 promotor. High-producing GFP clones were selected directly on the plates based on the color change after hydrolysis of the beta-lactamase substrate added to the medium. beta-lactamase activity was found to positively correlate with GFP fluorescence. The reporter system described is widely applicable-it can be easily applied to other, also pharmaceutically relevant proteins and to other yeast expression systems, such as Saccharomyces cerevisiae and Hansenula polymorpha.

  19. 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.

  20. Selection of Intracellularly Functional RNA Mimics of Green Fluorescent Protein Using Fluorescence-Activated Cell Sorting.

    PubMed

    Zou, Jiawei; Huang, Xin; Wu, Lei; Chen, Gangyi; Dong, Juan; Cui, Xin; Tang, Zhuo

    2015-12-01

    Fluorescence-activated cell sorting (FACS) was exploited to isolate Escherichia coli cells that were highly fluorescent due to the expression of RNA aptamers that induce fluorescence of 3,5-difluoro-4-hydroxybenzylidene imidazolinone. Two different aptamers, named ZT-26 and ZT-324, were identified by this method and compared to the fluorescence-signaling properties of Spinach, a previously reported RNA aptamer. Aptamer ZT-26 exhibits significantly enhanced fluorescence over Spinach only in vitro. However, aptamer ZT-324 is 36% brighter than Spinach when expressed in E. coli. The FACS-based selection strategy presented here is attractive for deriving fluorescent RNA aptamers that function in cells as it directly selects for cells with a high level of fluorescence due to the expression of the RNA aptamer.

  1. Surface display vectors for selective detection and isolation of high level antibody producing cells.

    PubMed

    Lang, Sabine; Drewello, Delia; Wichter, Johannes; Nommay, Audrey; Wilms, Burkhard; Knopf, Hans-Peter; Jostock, Thomas

    2016-11-01

    Cell line generation for production of biopharmaceuticals in mammalian cells usually involves intensive screening of clones to identify the rare high producers. In order to facilitate efficient and selective fluorescence activated cell sorting (FACS) based enrichment and cloning of antibody producing CHO cells, we developed a special vector setup by inserting a leaky translation termination signal between the heavy chain of an IgG antibody and an IgG transmembrane domain. Partial read-through during translation of the antibody heavy chain leads to display of a subset of the produced antibody on the surface of the expressing cell. We could show that the level of surface expression correlates well with the productivity. By applying FACS, high producing cells can be selectively enriched and cloned. Two sequential FACS enrichment cycles were performed which led to more than eightfold increased productivities of transfected and selected cell populations without cloning. The combination of selective FACS enrichment and FACS cloning with the new vector setup led to a sevenfold higher average productivity of the resulting clones as compared to a reference vector. Productivity and production stability assessment of clones generated with the new vector showed no negative impact of the co-expression of transmembrane antibody. Clone productivities of 4 g/L in a generic shake flask fed-batch model were achieved. Thus, this new vector setup facilitates fast and selective isolation of high producing production cell lines and allows significant reduction of clone screening efforts during cell line development for production cell lines. Additionally, the high productivity of FACS-enriched but non-clonal cell populations supports rapid, high yield, and cost efficient material production in early project phases. Biotechnol. Bioeng. 2016;113: 2386-2393. © 2016 Wiley Periodicals, Inc.

  2. High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2)

    PubMed Central

    2010-01-01

    Background Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching. Results In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus), a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella) possess proteins structurally similar to tachylectin-2. Conclusions Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1) part of Oculina's innate immunity repertoire, and 2) evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change. PMID:20482872

  3. CO2 copolymers from epoxides: catalyst activity, product selectivity, and stereochemistry control.

    PubMed

    Lu, Xiao-Bing; Ren, Wei-Min; Wu, Guang-Peng

    2012-10-16

    The use of carbon dioxide as a carbon source for the synthesis of organic chemicals can contribute to a more sustainable chemical industry. Because CO(2) is such a thermodynamically stable molecule, few effective catalysts are available to facilitate this transformation. Currently, the major industrial processes that convert CO(2) into viable products generate urea and hydroxybenzoic acid. One of the most promising new technologies for the use of this abundant, inexpensive, and nontoxic renewable resource is the alternating copolymerization of CO(2) and epoxides to provide biodegradable polycarbonates, which are highly valuable polymeric materials. Because this process often generates byproducts, such as polyether or ether linkages randomly dispersed within the polycarbonate chains and/or the more thermodynamically stable cyclic carbonates, the choice of catalyst is critical for selectively obtaining the expected product. In this Account, we outline our efforts to develop highly active Co(III)-based catalysts for the selective production of polycarbonates from the alternating copolymerization of CO(2) with epoxides. Binary systems consisting of simple (salen)Co(III)X and a nucleophilic cocatalyst exhibited high activity under mild conditions even at 0.1 MPa CO(2) pressure and afforded copolymers with >99% carbonate linkages and a high regiochemical control (∼95% head-to-tail content). Discrete, one-component (salen)Co(III)X complexes bearing an appended quaternary ammonium salt or sterically hindered Lewis base showed excellent activity in the selectively alternating copolymerization of CO(2) with both aliphatic epoxides and cyclohexene oxide at high temperatures with low catalyst loading and/or low pressures of CO(2). Binary or one-component catalysts based on unsymmetric multichiral Co(III) complexes facilitated the efficient enantioselective copolymerization of CO(2) with epoxides, providing aliphatic polycarbonates with >99% head-to-tail content. These

  4. 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.

  5. Antiviral activity and mode of action of propolis extracts and selected compounds.

    PubMed

    Schnitzler, Paul; Neuner, Annett; Nolkemper, Silke; Zundel, Christine; Nowack, Hans; Sensch, Karl Heinz; Reichling, Jürgen

    2010-01-01

    Aqueous and ethanol extracts of propolis were analysed phytochemically and examined for their antiviral activity in vitro. Different polyphenols, flavonoids and phenylcarboxylic acids were identified as major constituents. The antiviral effect of propolis extracts and selected constituents, e.g. caffeic acid (1), p-coumaric acid (2), benzoic acid (3), galangin (4), pinocembrin (5) and chrysin (6) against herpes simplex virus type 1 (HSV-1) was analysed in cell culture. The 50% inhibitory concentration (IC(50)) of aqueous and ethanol propolis extracts for HSV-1 plaque formation was determined at 0.0004% and 0.000035%, respectively. Both propolis extracts exhibited high levels of antiviral activity against HSV-1 in viral suspension tests, plaque formation was significantly reduced by >98%. In order to determine the mode of antiviral action of propolis, the extracts were added at different times during the viral infection cycle. Both propolis extracts exhibited high anti-HSV-1 activity when the viruses were pretreated with these drugs prior to infection. Among the analysed compounds, only galangin and chrysin displayed some antiviral activity. However, the extracts containing many different components exhibited significantly higher antiherpetic effects as well as higher selectivity indices than single isolated constituents. Propolis extracts might be suitable for topical application against herpes infection.

  6. 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.

  7. 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)

  8. 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…

  9. Chromatographic purification of highly active yeast ribosomes.

    PubMed

    Meskauskas, Arturas; Leshin, Jonathan A; Dinman, Jonathan D

    2011-10-24

    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.

  10. HIGH-RISK PROGRAM: Information on Selected High-Risk Areas.

    DTIC Science & Technology

    2007-11-02

    United States General Accounting Office GAO Information for House MajorityLeader Richard Armey and Representative Pete Sessions May 1997 GH-RISK ID...Information on Selected High-Risk Areas Corporate Author Or Publisher: General Accounting Office, GAO, Washington, DC 20548 Report Number: GAO/IHR-97-30 Report...Library: 000001 Record ID: 45053 GAO United States General Accounting OfficeWashington, D.C. 20548 Accounting and Information Management Division May

  11. 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.

  12. Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue.

    PubMed

    Del Lungo, Martina; Melchiorre, Michele; Guandalini, Luca; Sartiani, Laura; Mugelli, Alessandro; Koncz, Istvan; Szel, Tamas; Varro, Andras; Romanelli, Maria Novella; Cerbai, Elisabetta

    2012-05-01

    BACKGROUND AND PURPOSE Selective hyperpolarization activated, cyclic nucleotide-gated channel (HCN) blockers represent an important therapeutic goal due to the wide distribution and multiple functions of these proteins, representing the molecular correlate of f- and h-current (I(f) or I(h) ). Recently, new compounds able to block differentially the homomeric HCN isoforms expressed in HEK293 have been synthesized. In the present work, the electrophysiological and pharmacological properties of these new HCN blockers were characterized and their activities evaluated on native channels. EXPERIMENTAL APPROACH HEK293 cells expressing mHCN1, mHCN2 and hHCN4 isoforms were used to verify channel blockade. Selected compounds were tested on native guinea pig sinoatrial node cells and neurons from mouse dorsal root ganglion (DRG) by patch-clamp recordings and on dog Purkinje fibres by intracellular recordings. KEY RESULTS In HEK293 cells, EC18 was found to be significantly selective for HCN4 and MEL57A for HCN1 at physiological membrane potential. When tested on guinea pig sinoatrial node cells, EC18 (10 µM) maintained its activity, reducing I(f) by 67% at -120 mV, while MEL57A (3 µM) reduced I(f) by 18%. In contrast, in mouse DRG neurons, only MEL57A (30 and 100 µM) significantly reduced I(h) by 60% at -80 mV. In dog cardiac Purkinje fibres, EC18, but not MEL57A, reduced the amplitude and slowed the slope of the spontaneous diastolic depolarization. CONCLUSIONS Our results have identified novel and highly selective HCN isoform blockers, EC18 and MEL57A; the selectivity found in recombinant system was maintained in various tissues expressing different HCN isoforms.

  13. Use of a lag differential reinforcement contingency to increase varied selections of classroom activities.

    PubMed

    Cammilleri, Anthony P; Hanley, Gregory P

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

  14. Use of a Lag Differential Reinforcement Contingency to Increase Varied Selections of Classroom Activities

    ERIC Educational Resources Information Center

    Cammilleri, Anthony P.; Hanley, Gregory P.

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

  15. 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.

  16. Highly Efficient Selective Hydrogenation of Cinnamaldehyde to Cinnamyl Alcohol over Gold Supported on Zinc Oxide Materials

    DOE PAGES

    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

  17. MS-1020 is a novel small molecule that selectively inhibits JAK3 activity.

    PubMed

    Kim, Byung-Hak; Oh, Sei-Ryang; Yin, Chang-Hong; Lee, Sangku; Kim, Eun-Ah; Kim, Min-Seok; Sandoval, Claudio; Jayabose, Somasundaram; Bach, Erika A; Lee, Hyeong-Kyu; Baeg, Gyeong-Hun

    2010-01-01

    In order to identify Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling inhibitors, a cell-based high throughput screening was performed using a plant extract library that identified Nb-(alpha-hydroxynaphthoyl)serotonin called MS-1020 as a novel JAK3 inhibitor. MS-1020 potently inhibited persistently-active STAT3 in a cell type-specific manner. Further examination showed that MS-1020 selectively blocked constitutively-active JAK3 and consistently suppressed interleukin-2-induced JAK3/STAT5 signalling but not prolactin-induced JAK2/STAT5 signalling. Furthermore, MS-1020 affected cell viability only in cancer cells harbouring persistently-active JAK3/STATs, and in vitro kinase assays showed MS-1020 binds directly with JAK3, blocking its catalytic activity. Therefore, the present study suggested that this reagent selectively inhibits JAK3 and subsequently leads to a block in STAT signalling. Finally, MS-1020 decreased cell survival by inducing apoptosis via down-regulation of anti-apoptotic gene expression. These results suggest that MS-1020 may have therapeutic potential in the treatment of cancers harbouring aberrant JAK3 signalling.

  18. Selective targeting of the conserved active site cysteine of Mycobacterium tuberculosis methionine aminopeptidase with electrophilic reagents.

    PubMed

    Reddi, Ravikumar; Arya, Tarun; Kishor, Chandan; Gumpena, Rajesh; Ganji, Roopa J; Bhukya, Supriya; Addlagatta, Anthony

    2014-09-01

    Methionine aminopeptidases (MetAPs) cleave initiator methionine from ~ 70% of the newly synthesized proteins in every living cell, and specific inhibition or knockdown of this function is detrimental. MetAPs are metalloenzymes, and are broadly classified into two subtypes, type I and type II. Bacteria contain only type I MetAPs, and the active site of these enzymes contains a conserved cysteine. By contrast, in type II enzymes the analogous position is occupied by a conserved glycine. Here, we report the reactivity of the active site cysteine in a type I MetAP, MetAP1c, of Mycobacterium tuberculosis (MtMetAP1c) towards highly selective cysteine-specific reagents. The authenticity of selective modification of Cys105 of MtMetAP1c was established by using site-directed mutagenesis and crystal structure determination of covalent and noncovalent complexes. On the basis of these observations, we propose that metal ions in the active site assist in the covalent modification of Cys105 by orienting the reagents appropriately for a successful reaction. These studies establish, for the first time, that the conserved cysteine of type I MetAPs can be targeted for selective inhibition, and we believe that this chemistry can be exploited for further drug discovery efforts regarding microbial MetAPs.

  19. 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…

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. In Vitro Phytotoxicity and Antioxidant Activity of Selected Flavonoids

    PubMed Central

    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

  5. 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.

  6. 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

  7. New and highly active microbial phosphotriesterase sources.

    PubMed

    Santillan, Julia Y; Dettorre, Lucas A; Lewkowicz, Elizabeth S; Iribarren, Adolfo M

    2016-12-01

    Many toxic insecticides used worldwide as well as some chemical warfare agents are phosphotriester derivatives. Therefore, detoxification of organophosphorus compounds has become the subject of many studies and in particular bioremediation, based on the phosphotriesterase catalysed hydrolysis of these compounds, has shown to be an effective and ecological methodology. In order to identify new bacterial phosphotriesterases, a simple and sensitive fluorimetric screening method on solid media was employed that allowed the selection of six strains with phosphotriesterase activity. Since pH and temperature are important parameters for bioremediation of contaminated soils and waters, the influence of these variables on the rate of the enzymatic hydrolysis was assessed. This study afforded notable results, being the most remarkable one the increased activity exhibited by Nocardia asteroides and Streptomyces setonii strains at 50°C, 7 and 30 times higher than at 30°C, respectively. Compared with the results obtained with Brevundimonas diminuta, whose activity is usually considered as reference, an increase of 26 and 75 times is observed, respectively.

  8. Antibacterial Activity of Sirodesmin PL Phytotoxin: Application to the Selection of Phytotoxin-Deficient Mutants

    PubMed Central

    Boudart, Georges

    1989-01-01

    Sirodesmin PL, a phytotoxin and mycotoxin produced by Leptosphaeria maculans, the causal agent of stem-canker disease of crucifers, exhibited antibacterial activity against gram-positive bacteria and particularly Bacillus subtilis. The importance of the disulfide bridge of the molecule in antibacterial activity was demonstrated. A simple and reliable bioassay based on the antibacterial activity of the toxin was performed for screening sirodesmin PL-deficient mutants when grown on solid culture medium. A mutant was selected and found to produce 3,700-fold less toxin than did the wild-type strain. A sensitive procedure for quantification of the toxin by high-pressure liquid chromatography was developed. Levels of product as low as 100 ng could be detected by this procedure. Images PMID:16347949

  9. Molecular basis for agonist selectivity and activation of the orphan BRS-3-receptor

    PubMed Central

    Gonzalez, Nieves; Hocart, Simon J.; Portal-Nuñez, Sergio; Mantey, Samuel A.; Nakagawa, Tomoo; Zudaire, Enrique; Coy, David H.; Jensen, Robert T.

    2008-01-01

    Bombesin receptor subtype-3(BRS-3), a G protein-coupled orphan receptor, shares 51% identity with the mammalian bombesin(Bn) receptor for gastrin-releasing peptide(GRPR). There is increasing interest in BRS-3 because it is important in energy metabolism, glucose control,motility and tumor-growth. BRS-3 has low affinity for all Bn-related peptides, however, recently synthetic high-affinity agonists[D-Tyr6/D-Phe6,βAla11,Phe13,Nle14]Bn-(6–14) were described, but they are nonselective for BRS-3 over other Bn-receptors. Based on these peptides, three BRS-3 selective-ligands were developed: peptide#2,[D-Tyr6(R)-Apa11,Phe13,Nle14]Bn(6–14); peptide#3,[D-Tyr6,(R)-Apa11,4Cl-Phe13,Nle14]Bn(6–14); peptide #4,Ac-Phe-Trp-Ala-His(tBzl)-Nip-Gly-Arg-NH2. Their molecular determinants of selectivity/high affinity for BRS-3 are unknown. To address this we used a chimeric/site-mutagenesis approach. Substitution of extracellular domain2(EC2) of BRS-3 by the comparable GRPR domain decreased 26-,4,0-fold affinity for peptides#4,3,2. Substitution of EC3 decreased affinity 4-,11-,0-fold affinity for peptides#2,3,4. Ten point mutations in the EC2 and adjacent transmembrane regions (TM2) 2 and 3 of BRS-3 were made. His107(EC2-BRS-3) for lysine(H107K)(EC2-GRPR), decreased affinity(25-,0-fold) for peptide#4,1; however it could not be activated by either peptide. Its combination with Val101(TM2),Gly112(EC2),Arg127(TM3) resulted in complete loss-of-affinity of peptide#4. Receptor-modeling showed that each of these residues face inward and are within 4Å of the binding-pocket. These results demonstrate [Val101,His107,Gly112,Arg127] in the EC2/adjacent upper TMs of BRS-3 are critical for the high BRS3-selectivity of peptide#4. His107 in EC2 is essential for BRS-3 activation, suggesting amino-aromatic ligand/receptor interactions with peptide#4 are critical for both binding/ activation. Furthermore, these result demonstrate that even though these three BRS-3 selective agonists were developed

  10. Sensitive and selective colorimetric assay of alkaline phosphatase activity with Cu(II)-phenanthroline complex.

    PubMed

    Hu, Qiong; He, Minhui; Mei, Yaqi; Feng, Wenjie; Jing, Su; Kong, Jinming; Zhang, Xueji

    2017-01-15

    Alkaline phosphatase (ALP) plays a vital role in dephosphorylation- and phosphorylation-related cellular regulation and signaling processes. Accordingly, the development of efficient methods for ALP activity assay is of significant importance in clinical diagnosis. In this work, a simple and practical method is reported for the first time for the sensitive and selective colorimetric assay of ALP activity by exploiting a water-soluble Cu(II)-phenanthroline complex as the probe, on the basis of the distinctive metal-to-ligand charge-transfer (MLCT) properties. This method is simply built on a two-step chromogenic reaction: the enzymatic hydrolysis of the substrate ascorbic acid 2-phosphate to ascorbic acid (AA), followed by the reduction of the colorimetric probe Cu(BPDS)2(2-) (BPDS=bathophenanthroline disulfonate) by AA to its cuprous form. The latter process triggers a turn-on spectral absorption at 424nm and a striking color change of the solution from colorless to blackish-green. Needless of complicated protocols and instrumentation, this method allows a sensitive readout of ALP activity within a wide linear range of 0-200mUmL(-)(1), with a detection limit down to 1.25mUmL(-1). Results also reveal that it is highly selective and holds great potential in ALP inhibitor efficiency evaluation. In addition, quantitative analysis of ALP activity in spiked serum samples has been realized successfully in the linear range of 0-200mUmL(-1), with a detection limit of 1.75mUmL(-1). Advantages of simplicity, wide linear range, high sensitivity and selectivity, low cost, and little background interference render this method great potential in practical applications.

  11. Position paper - peer review and design verification of selected activities

    SciTech Connect

    Stine, M.D.

    1994-09-01

    Position Paper to develop and document a position on the performance of independent peer reviews on selected design and analysis components of the Title I (preliminary) and Title II (detailed) design phases of the Multi-Function Waste Tank Facility project.

  12. Optimizing the yield and selectivity of high purity nanoparticle clusters

    NASA Astrophysics Data System (ADS)

    Pease, Leonard F.

    2011-05-01

    Here we investigate the parameters that govern the yield and selectivity of small clusters composed of nanoparticles using a Monte Carlo simulation that accounts for spatial and dimensional distributions in droplet and nanoparticle density and size. Clustering nanoparticles presents a powerful paradigm with which to access properties not otherwise available using individual molecules, individual nanoparticles or bulk materials. However, the governing parameters that precisely tune the yield and selectivity of clusters fabricated via an electrospray droplet evaporation method followed by purification with differential mobility analysis (DMA) remain poorly understood. We find that the product of the electrospray droplet mean diameter to the third power and nanoparticle concentration governs the yield of individual clusters, while the ratio of the nanoparticle standard deviation to the mean diameter governs the selectivity. The resulting, easily accessible correlations may be used to minimize undesirable clustering, such as protein aggregation in the biopharmaceutical industry, and maximize the yield of a particular type of cluster for nanotechnology and energy applications.

  13. 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.

  14. 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.

  15. High-selectivity and high-deposition rate tungsten CVD freed from chamber cleaning

    SciTech Connect

    Maeda, Y.; Suzuki, H.; Sakoh, T.; Morita, K.; Morita, M.; Ohmi, T. )

    1994-02-01

    A chemical vapor deposition method for tungsten films using a chamber with a cold susceptor is proposed for attaining excellent selectivity and a cleaning-free process. High-rate selective deposition above 1.0 [mu]m/min using the reduction of tungsten hexafluoride by silane is achieved at a substrate temperature of 210 C by using a cold susceptor chilled by water at room temperature. No deposition of tungsten or by-products on the susceptor surface and the inner surface of the chamber is observed, indicating that the newly developed system is free from cleaning. The deposited tungsten film has the alpha-type structure. The lattice constant of the tungsten is changed by the deposition temperature and the flow ratio of silane to tungsten hexafluoride.

  16. Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity

    PubMed Central

    Dudhgaonkar, Shailesh; Ranade, Sourabh; Nagar, Jignesh; Subramani, Siva; Prasad, Durga Shiv; Karunanithi, Preethi; Srivastava, Ratika; Venkatesh, Kamala; Selvam, Sabariya; Krishnamurthy, Prasad; Mariappan, T. Thanga; Saxena, Ajay; Fan, Li; Stetsko, Dawn K.; Holloway, Deborah A.; Li, Xin; Zhu, Jun; Yang, Wen-Pin; Ruepp, Stefan; Nair, Satheesh; Santella, Joseph; Duncia, John; Hynes, John; McIntyre, Kim W.

    2017-01-01

    The serine/threonine kinase IL-1R–associated kinase (IRAK)4 is a critical regulator of innate immunity. We have identified BMS-986126, a potent, highly selective inhibitor of IRAK4 kinase activity that demonstrates equipotent activity against multiple MyD88-dependent responses both in vitro and in vivo. BMS-986126 failed to inhibit assays downstream of MyD88-independent receptors, including the TNF receptor and TLR3. Very little activity was seen downstream of TLR4, which can also activate an MyD88-independent pathway. In mice, the compound inhibited cytokine production induced by injection of several different TLR agonists, including those for TLR2, TLR7, and TLR9. The compound also significantly suppressed skin inflammation induced by topical administration of the TLR7 agonist imiquimod. BMS-986126 demonstrated robust activity in the MRL/lpr and NZB/NZW models of lupus, inhibiting multiple pathogenic responses. In the MRL/lpr model, robust activity was observed with the combination of suboptimal doses of BMS-986126 and prednisolone, suggesting the potential for steroid sparing activity. BMS-986126 also demonstrated synergy with prednisolone in assays of TLR7- and TLR9-induced IFN target gene expression using human PBMCs. Lastly, BMS-986126 inhibited TLR7- and TLR9-dependent responses using cells derived from lupus patients, suggesting that inhibition of IRAK4 has the potential for therapeutic benefit in treating lupus. PMID:28003376

  17. Squalyl Crown Ether Self-Assembled Conjugates: An Example of Highly Selective Artificial K(+) Channels.

    PubMed

    Sun, Zhanhu; Gilles, Arnaud; Kocsis, Istvan; Legrand, Yves-Marie; Petit, Eddy; Barboiu, Mihail

    2016-02-01

    The natural KcsA K(+) channel, one of the best-characterized biological pore structures, conducts K(+) cations at high rates while excluding Na(+) cations. The KcsA K(+) channel is of primordial inspiration for the design of artificial channels. Important progress in improving conduction activity and K(+) /Na(+) selectivity has been achieved with artificial ion-channel systems. However, simple artificial systems exhibiting K(+) /Na(+) selectivity and mimicking the biofunctions of the KcsA K(+) channel are unknown. Herein, an artificial ion channel formed by H-bonded stacks of squalyl crown ethers, in which K(+) conduction is highly preferred to Na(+) conduction, is reported. The K(+) -channel behavior is interpreted as arising from discreet stacks of dimers resulting in the formation of oligomeric channels, in which transport of cations occurs through macrocycles mixed with dimeric carriers undergoing dynamic exchange within the bilayer membrane. The present highly K(+) -selective macrocyclic channel can be regarded as a biomimetic alternative to the KcsA channel.

  18. 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

  19. 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.

  20. Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds.

    PubMed

    Riether, Doris; Zindell, Renee; Wu, Lifen; Betageri, Raj; Jenkins, James E; Khor, Someina; Berry, Angela K; Hickey, Eugene R; Ermann, Monika; Albrecht, Claudia; Ceci, Angelo; Gemkow, Mark J; Nagaraja, Nelamangala V; Romig, Helmut; Sauer, Achim; Thomson, David S

    2015-02-01

    Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.

  1. RADIOISOTOPE EXPERIMENTS IN HIGH SCHOOL BIOLOGY, AN ANNOTATED SELECTED BIBLIOGRAPHY.

    ERIC Educational Resources Information Center

    HURLBURT, EVELYN M.

    SELECTED REFERENCES ON THE USE OF RADIOISOTOPES IN BIOLOGY ARE CONTAINED IN THIS ANNOTATED BIBLIOGRAPHY FOR SECONDARY SCHOOL STUDENTS. MATERIALS INCLUDED WERE PUBLISHED AFTER 1960 AND DEAL WITH THE PROPERTIES OF RADIATION, SIMPLE RADIATION DETECTION PROCEDURES, AND TECHNIQUES FOR USING RADIOISOTOPES EXPERIMENTALLY. THE REFERENCES ARE LISTED IN…

  2. 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…

  3. 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

  4. Highly selective deuteration of pharmaceutically relevant nitrogen-containing heterocycles: a flow chemistry approach.

    PubMed

    Ötvös, Sándor B; Mándity, István M; Fülöp, Ferenc

    2011-08-01

    A simple and efficient flow-based technique is reported for the catalytic deuteration of several model nitrogen-containing heterocyclic compounds which are important building blocks of pharmacologically active materials. A continuous flow reactor was used in combination with on-demand pressure-controlled electrolytic D(2) production. The D(2) source was D(2)O, the consumption of which was very low. The experimental set-up allows the fine-tuning of pressure, temperature, and flow rate so as to determine the optimal conditions for the deuteration reactions. The described procedure lacks most of the drawbacks of the conventional batch deuteration techniques, and additionally is highly selective and reproducible.

  5. Analysis of high intensity activity in Premier League soccer.

    PubMed

    Di Salvo, V; Gregson, W; Atkinson, G; Tordoff, P; Drust, B

    2009-03-01

    The aim of the present investigation was to provide a detailed analysis of the high intensity running activity completed by elite soccer players during match-play. A further aim of the study was to evaluate the importance of high intensity running activity to overall team success. Observations on individual match performance measures were undertaken on 563 outfield players (median of 8 games per player; range=1-57) competing in the English Premier League from 2003/2004 to 2005/2006 using a computerised tracking system (Prozone, Leeds, England). High intensity activities selected for analysis included total high intensity running distance (THIR), total sprint distance (TSD) and the number and type of sprints undertaken. Total high intensity running distance in possession and without possession of the ball was also analysed. The THIR was dependant upon playing position with wide midfield (1,049+/-106 m) and central defenders (681+/-128 m) completing the highest and lowest distance respectively (p<0.001). High intensity activity was also related to team success with teams finishing in the bottom five (919+/-128 m) and middle ten (917+/-143 m) league positions completing significantly more THIR compared with teams in the top five (885+/-113 m) (p=0.003). The THIR and TSD also significantly declined during the 2nd half with the greatest decrements observed in wide midfield and attacking players (p<0.05). Both positional differences in high intensity activity and the observed change in activity throughout the game were also influenced by team success (p<0.05). The results of the present study indicate that high intensity activity in elite soccer match-play is influenced by both playing position and previous activity in the game. These activity patterns are also dependant upon success of the team. This may indicate that overall technical and tactical effectiveness of the team rather than high levels of physical performance per se are more important in determining success

  6. Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection.

    PubMed

    Ertelt, James M; Johanns, Tanner M; Mysz, Margaret A; Nanton, Minelva R; Rowe, Jared H; Aguilera, Marijo N; Way, Sing Sing

    2011-12-01

    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.

  7. Reversible Assembly of Graphitic Carbon Nitride 3D Network for Highly Selective Dyes Absorption and Regeneration.

    PubMed

    Zhang, Yuye; Zhou, Zhixin; Shen, Yanfei; Zhou, Qing; Wang, Jianhai; Liu, Anran; Liu, Songqin; Zhang, Yuanjian

    2016-09-27

    Responsive assembly of 2D materials is of great interest for a range of applications. In this work, interfacial functionalized carbon nitride (CN) nanofibers were synthesized by hydrolyzing bulk CN in sodium hydroxide solution. The reversible assemble and disassemble behavior of the as-prepared CN nanofibers was investigated by using CO2 as a trigger to form a hydrogel network at first. Compared to the most widespread absorbent materials such as active carbon, graphene and previously reported supramolecular gel, the proposed CN hydrogel not only exhibited a competitive absorbing capacity (maximum absorbing capacity of methylene blue up to 402 mg/g) but also overcame the typical deficiencies such as poor selectivity and high energy-consuming regeneration. This work would provide a strategy to construct a 3D CN network and open an avenue for developing smart assembly for potential applications ranging from environment to selective extraction.

  8. ACTIVE REGION MORPHOLOGIES SELECTED FROM NEAR-SIDE HELIOSEISMIC DATA

    SciTech Connect

    MacDonald, G. A.; McAteer, R. T. J.; Henney, C. J.; Arge, C. N.; Díaz Alfaro, M.; González Hernández, I.; Lindsey, C.

    2015-07-01

    We estimate the morphology of near-side active regions using near-side helioseismology. Active regions from two data sets, Air Force Data Assimilative Photospheric flux Transport synchronic maps and Global Oscillation Network Group near-side helioseismic maps, were matched and their morphologies compared. Our algorithm recognizes 382 helioseismic active regions between 2002 April 25 and 2005 December 31 and matches them to their corresponding magnetic active regions with 100% success. A magnetic active region occupies 30% of the area of its helioseismic signature. Recovered helioseismic tilt angles are in good agreement with magnetic tilt angles. Approximately 20% of helioseismic active regions can be decomposed into leading and trailing polarity. Leading polarity components show no discernible scaling relationship, but trailing magnetic polarity components occupy approximately 25% of the area of the trailing helioseismic component. A nearside phase-magnetic calibration is in close agreement with a previous far-side helioseismic calibration and provides confidence that these morphological relationships can be used with far-side helioseismic data. Including far-side active region morphology in synchronic maps will have implications for coronal magnetic topology predictions and solar wind forecasts.

  9. Active Region Morphologies Selected From Near-side Helioseismic Data

    NASA Astrophysics Data System (ADS)

    MacDonald, Gordon Andrew; Henney, Carl; Diaz Alfaro, Manuel; Gonzalez Hernandez, Irene; Arge, Nick; Lindsey, Charles; McAteer, James

    2015-04-01

    We estimate the morphology of near-side active regions using near-side helioseismology. Active regions from two data sets, ADAPT synchronic maps and GONG near-side helioseismic maps, were matched and their morphologies compared. Our algorithm recognizes 382 helioseismic active regions between 2002 April 25 and 2005 December 31 and matches them to their corresponding magnetic active regions with 100% success. A magnetic active region occupies 30% of the area of its helioseismic signature. Recovered helioseismic tilt angles are in good agreement with magnetic tilt angles. Approximately 20% of helioseismic active regions can be decomposed into leading and trailing polarity. Leading polarity components show no discernible scaling relationship, but trailing magnetic polarity components occupy approximately 25% of the area of the trailing helioseismic component. A nearside phase-magnetic calibration is in close agreement with a previous far-side helioseismic calibration and provides confidence that these morphological relationships can be used with far-side helioseismic data. Including far-side active region morphology in synchronic maps will have implications for coronal magnetic topology predictions and solar wind forecasts.

  10. Active Region Morphologies Selected from Near-side Helioseismic Data

    NASA Astrophysics Data System (ADS)

    MacDonald, G. A.; Henney, C. J.; Díaz Alfaro, M.; González Hernández, I.; Arge, C. N.; Lindsey, C.; McAteer, R. T. J.

    2015-07-01

    We estimate the morphology of near-side active regions using near-side helioseismology. Active regions from two data sets, Air Force Data Assimilative Photospheric flux Transport synchronic maps and Global Oscillation Network Group near-side helioseismic maps, were matched and their morphologies compared. Our algorithm recognizes 382 helioseismic active regions between 2002 April 25 and 2005 December 31 and matches them to their corresponding magnetic active regions with 100% success. A magnetic active region occupies 30% of the area of its helioseismic signature. Recovered helioseismic tilt angles are in good agreement with magnetic tilt angles. Approximately 20% of helioseismic active regions can be decomposed into leading and trailing polarity. Leading polarity components show no discernible scaling relationship, but trailing magnetic polarity components occupy approximately 25% of the area of the trailing helioseismic component. A nearside phase-magnetic calibration is in close agreement with a previous far-side helioseismic calibration and provides confidence that these morphological relationships can be used with far-side helioseismic data. Including far-side active region morphology in synchronic maps will have implications for coronal magnetic topology predictions and solar wind forecasts.

  11. High carotenoids content can enhance resistance of selected Pinctada fucata families to high temperature stress.

    PubMed

    Meng, Zihao; Zhang, Bo; Liu, Baosuo; Li, Haimei; Fan, Sigang; Yu, Dahui

    2017-02-01

    Carotenoids are a class of natural antioxidants widely found in aquatic, and they have significant effects on the growth, survival, and immunity of these organisms. To investigate the mechanisms of carotenoids in high temperature resistance, we observed the immune response of selected pearl oyster Pinctada fucata (Akoya pearl oyster) families with different carotenoids contents to high temperature stress. The results indicated that the survival rate (SR) of P. fucata decreased significantly with increase in temperature from 26 °C to 34 °C and with the decrease of total carotenoids content (TCC); when the TCC was higher, the SR tended to be higher. TCC and total antioxidant capacity (TAC) decreased significantly at 30 °C with increasing stress time. Correlation analysis indicated that TAC was positively and linearly correlated with TCC, and SR was S-type correlated with TCC and TAC. Immune analysis indicated that levels of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in selected families (with higher TCC) under temperature stress (at 30 °C) were generally significantly lower than in the control group (with lowest TCC) and from 0 to 96 h, the levels of each of these substances varied significantly. Levels of SOD, CAT, and MDA within each family first rose from 0 to 3 h, then decreased to their lowest point after 24 h, and then rose again to their highest levels at 96 h. When TCC was higher, the levels of SOD, CAT, and MDA tended to be lower. These findings indicated that carotenoids play an important role in improving survival rates of P. fucata under high temperature stress by enhancing animals' antioxidant system, and could serve as an index for breeding stress-resistant lines in selective breeding practices.

  12. Selective release of phosphorus and nitrogen from waste activated sludge with combined thermal and alkali treatment.

    PubMed

    Kim, Minwook; Han, Dong-Woo; Kim, Dong-Jin

    2015-08-01

    Selective release characteristics of phosphorus and nitrogen from waste activated sludge (WAS) were investigated during combined thermal and alkali treatment. Alkali (0.001-1.0N NaOH) treatment and combined thermal-alkali treatment were applied to WAS for releasing total P(T-P) and total nitrogen(T-N). Combined thermal-alkali treatment released 94%, 76%, and 49% of T-P, T-N, and COD, respectively. Release rate was positively associated with NaOH concentration, while temperature gave insignificant effect. The ratio of T-N and COD to T-P that released with alkali treatment ranged 0.74-0.80 and 0.39-0.50, respectively, while combined thermal-alkali treatment gave 0.60-0.90 and 0.20-0.60, respectively. Selective release of T-P and T-N was negatively associated with NaOH. High NaOH concentration created cavities on the surface of WAS, and these cavities accelerated the release rate, but reduced selectivity. Selective release of P and N from sludge has a beneficial effect on nutrient recovery with crystallization processes and it can also enhance methane production.

  13. Selective hyposmia in Parkinson disease: association with hippocampal dopamine activity.

    PubMed

    Bohnen, Nicolaas I; Gedela, Satyanarayana; Herath, Priyantha; Constantine, Gregory M; Moore, Robert Y

    2008-12-05

    Olfactory dysfunction is common in patients with Parkinson disease (PD) and has been attributed to early pathological deposition of Lewy bodies and Lewy neurites in primary olfactory centers. However, olfactory deficits do not always worsen over time despite progression of disease raising the possibility of additional pathobiological mechanisms contributing to olfactory functions in PD, such as changes in olfactory neurotransmitter functions. Neurotransmitter changes, such as altered dopaminergic status, may also better explain the selective nature of odor identification deficits in PD. Proper odor identification depends on higher order structures, such as the hippocampus, for olfactory cognitive or memory processing. Using the University of Pennsylvania Smell Identification Test (UPSIT), we previously identified three odors (banana, licorice, dill pickle, labeled as UPSIT-3) that PD subjects most frequently failed to recognize compared to age- and gender-matched controls. We also identified six odors that were equally successfully identified by controls and PD subjects (NPD-Olf6). A ratio of UPSIT-3 divided by NPD-Olf6 scores provides another descriptor of selective hyposmia in PD ("olfactory ratio"). In this study we investigated the pathophysiology of hyposmia in PD using dopamine transporter (DAT) PET. Twenty-nine PD patients (Hoehn and Yahr stages I-III; 7f/22m; age 60.2+/-10.8) underwent olfactory testing using the UPSIT and [(11)C]beta-CFT DAT PET. DAT binding potentials (BP) were assessed in the hippocampus, amygdala, ventral and dorsal striatum. We found that correlation coefficients between total UPSIT scores and regional brain DAT BP were highest for the hippocampus (Rs=0.54, P=0.002) and lower for the amygdala (Rs=0.44, P=0.02), ventral (Rs=0.48, P=0.008) and dorsal striatum (Rs=0.39, P=0.03). Correlations were most significant for the selective hyposmia measures and hippocampal DAT: UPSIT-3 (Rs=0.65, P=0.0001) and the olfactory ratio (Rs=0.74, P<0

  14. Locomotor activity and body temperature in selected mouse lines differing greatly in feed intake.

    PubMed

    Sojka, P A; Griess, R S; Nielsen, M K

    2013-08-01

    Locomotor activity, body temperature, feed intake, and BW were measured on 382 mature male mice sampled from lines previously selected (25 generations) for either high (MH) or low (ML) heat loss and an unselected control (MC). Animals were from all 3 independent replicates of the 3 lines and across 4 generations (68 through 71). Locomotor activity and body temperatures were obtained using implanted transmitters with data collection over 4 d following a 3-d postsurgery recovery period. Data were collected every minute and then averaged into 30-min periods, thus providing 192 data points for each mouse. Least-squares means for feed intake adjusted for BW (Feed/BW, feed·BW(-1)·d(-1), g/g) were 0.1586, 0.1234, and 0.1125 (±0.0022) for MH, MC, and ML, respectively, with line being a highly significant source of variation (P < 0.0003). Line effects for locomotor activity counts, transformed to the 0.25 power for analysis, were significantly different, with MH mice being 2.1 times more active than ML mice (P < 0.003); MC mice were intermediate. Differences in body temperature were significant for both line (P < 0.03) and day effects (P < 0.001), with a 0.32°C difference between the MH and ML lines. Fourier series analysis used the combined significant periodicities of 24, 18, 12, 9, 6, and 3 h to describe circadian cycles for activity and body temperature. All 3 lines expressed daily peaks in body temperature and locomotor activity ∼3 h into darkness and ∼2 h after lights were turned on. There was a stronger relationship between locomotor activity and Feed/BW (P < 0.0001) than between body temperature and Feed/BW (P < 0.01); differences between lines in locomotor activity and body temperature explained 17% and 3%, respectively, of differences between lines in Feed/BW. Thus, line differences in locomotor activity contribute to line differences in maintenance, but approximately 80% of the differences between the MH and ML selection lines in Feed/BW remains

  15. Novel Bifidobacterium promoters selected through microarray analysis lead to constitutive high-level gene expression.

    PubMed

    Wang, Yan; Kim, Jin Yong; Park, Myeong Soo; Ji, Geun Eog

    2012-08-01

    For the development of a food-grade expression system for Bifidobacterium, a strong promoter leading to high-level expression of cloned gene is a prerequisite. For this purpose, a promoter screening host-vector system for Bifidobacterium has been established using β-glucosidase from Bifidobacterium lactis as a reporter and Bifidobacterium bifidum BGN4 as a host, which is β-glucosidase negative strain. Seven putative promoters showing constitutive high-level expression were selected through microarray analysis based on the genome sequence of B. bifidum BGN4. They were cloned into upstream of β-glucosidase gene and transformed into Escherichia coli DH5α and B. bifidum BGN4. Promoter activities were analyzed both in E. coli and B. bifidum BGN4 by measuring β-glucosidase activity. β-Glucosidase activities in all of the transformants showed growth-associated characteristics. Among them, P919 was the strongest in B. bifidum BGN4 and showed maximum activity at 18 h, while P895 was the strongest in E. coli DH5α at 7 h. This study shows that novel strong promoters such as P919 can be used for high-level expression of foreign genes in Bifidobacterium and will be useful for the construction of an efficient food-grade expression system.

  16. 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.

  17. 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

  18. Intestinal first-pass glucuronidation activities of selected dihydroxyflavones.

    PubMed

    Wong, Yin Cheong; Zhang, Li; Lin, Ge; Zuo, Zhong

    2009-01-21

    Flavonoids have low bioavailabilities due to extensive intestinal first-pass metabolisms, especially glucuronidation. The present study aimed to evaluate the intestinal glucuronidation of dihydroxyflavones and provide more information on their structure-activity relationships. Seven dihydroxyflavones, namely 3,7-, 5,7-, 6,7-, 7,8-, 2',7-, 3',7-, and 4',7-dihydroxyflavone and a monohydroxyflavone, 7-hydroxyflavone, were investigated by incubating each hydroxyflavone at various concentrations with either human jejunum microsome or rat intestinal microsome. Two mono-glucuronides were identified for each dihydroxyflavone. For human jejunum microsome, most of the studied dihydroxyflavones demonstrated greater glucuronidation activities than that of 7-hydroxyflavone except for 3,7-dihydroxyflavone and 4',7-dihydroxyflavone. 3',7-dihydroxyflavone had the greatest intrinsic clearance which was at least seven times greater than that of all other dihydroxyflavones. In addition, species difference in glucuronidation activity was observed with human jejunum microsome higher than rat intestinal microsome for all hydroxyflavones except for 3,7-dihydroxyflavone. The results further demonstrated that the hydroxyl group positions do affect the intestinal glucuronidation activity of hydroxyflavones. Increasing the number of hydroxyl groups on A- or B-ring (except for 4'-OH) would enhance the glucuronidation activity of flavones, whereas adding a 3-OH on C-ring might not. Furthermore, existence of hydroxyl group at 3' position may enhance the glucuronidation activity of flavonoids.

  19. Hydrocarbon-stapled lipopeptides exhibit selective antimicrobial activity.

    PubMed

    Jenner, Zachary B; Crittenden, Christopher M; Gonzalez, Martín; Brodbelt, Jennifer S; Bruns, Kerry A

    2017-01-10

    Antimicrobial peptides (AMPs) occur widely in nature and have been studied for their therapeutic potential. AMPs are of interest due to the large number of possible chemical structural combinations using natural and unnatural amino acids, with varying effects on their biological activities. Using physicochemical properties from known naturally occurring amphipathic cationic AMPs, several hydrocarbon-stapled lipopeptides (HSLPs) were designed, synthesized, and tested for antimicrobial properties. Peptides were chemically modified by N-terminal acylation, C-terminal amidation, and some were hydrocarbon stapled by intramolecular olefin metathesis. The effects of peptide length, amphipathic character, and stapling on antimicrobial activity were tested against Escherichia coli, three species of Gram-positive bacteria (Staphylococcus aureus, Bacillus megaterium, and Enterococcus faecalis), and two strains of Candida albicans. Peptides were shown to disrupt liposomes of different phospholipid composition, as measured by leakage of a fluorescent compound from vesicles. Peptides with (S)-2-(4'-pentenyl)-alanine substituted for L-alanine in a reference peptide showed a marked increase in antimicrobial activity, hemolysis, and membrane disruption. Stapled peptides exhibited slightly higher antimicrobial potency; those with greatest hydrophobic character showed the greatest hemolysis and liposome leakage, but lower antimicrobial activity. The results support a model of HSLPs as membrane-disruptive AMPs with potent antimicrobial activity and relatively low hemolytic potential at biologically active peptide concentrations. This article is protected by copyright. All rights reserved.

  20. Highly stable antibacterial silver nanoparticles as selective fluorescent sensor for Fe³⁺ ions.

    PubMed

    Makwana, Bharat A; Vyas, Disha J; Bhatt, Keyur D; Jain, Vinod K; Agrawal, Yadvendra K

    2015-01-05

    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 Fe(3+) 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. Lipid selectivity in novel antimicrobial peptides: Implication on antimicrobial and hemolytic activity.

    PubMed

    Maturana, P; Martinez, M; Noguera, M E; Santos, N C; Disalvo, E A; Semorile, L; Maffia, P C; Hollmann, A

    2017-05-01

    Antimicrobial peptides (AMPs) are small cationic molecules that display antimicrobial activity against a wide range of bacteria, fungi and viruses. For an AMP to be considered as a therapeutic option, it must have not only potent antibacterial properties but also low hemolytic and cytotoxic activities [1]. Even though many studies have been conducted in order to correlate the antimicrobial activity with affinity toward model lipid membranes, the use of these membranes to explain cytotoxic effects (especially hemolysis) has been less explored. In this context, we studied lipid selectivity in two related novel AMPs, peptide 6 (P6) and peptide 6.2 (P6.2). Each peptide was designed from a previously reported AMP, and specific amino acid replacements were performed in an attempt to shift their hydrophobic moment or net charge. P6 showed no antimicrobial activity and high hemolytic activity, and P6.2 exhibited good antibacterial and low hemolytic activity. Using both peptides as a model we correlated the affinity toward membranes of different lipid composition and the antimicrobial and hemolytic activities. Our results from surface pressure and zeta potential assays showed that P6.2 exhibited a higher affinity and faster binding kinetic toward PG-containing membranes, while P6 showed this behavior for pure PC membranes. The final position and structure of P6.2 into the membrane showed an alpha-helix conversion, resulting in a parallel alignment with the Trps inserted into the membrane. On the other hand, the inability of P6 to adopt an amphipathic structure, plus its lower affinity toward PG-containing membranes seem to explain its poor antimicrobial activity. Regarding erythrocyte interactions, P6 showed the highest affinity toward erythrocyte membranes, resulting in an increased hemolytic activity. Overall, our data led us to conclude that affinity toward negatively charged lipids instead of zwitterionic ones seems to be a key factor that drives from hemolytic to

  2. 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

  3. Antibacterial activity of some selected medicinal plants of Pakistan

    PubMed Central

    2011-01-01

    Background Screening of the ethnobotenical plants is a pre-requisite to evaluate their therapeutic potential and it can lead to the isolation of new bioactive compounds. Methods The crude extracts and fractions of six medicinal important plants (Arisaema flavum, Debregeasia salicifolia, Carissa opaca, Pistacia integerrima, Aesculus indica, and Toona ciliata) were tested against three Gram positive and two Gram negative ATCC bacterial species using the agar well diffusion method. Results The crude extract of P. integerrima and A. indica were active against all tested bacterial strains (12-23 mm zone of inhibition). Other four plant's crude extracts (Arisaema flavum, Debregeasia salicifolia, Carissa opaca, and Toona ciliata) were active against different bacterial strains. The crude extracts showed varying level of bactericidal activity. The aqueous fractions of A. indica and P. integerrima crude extract showed maximum activity (19.66 and 16 mm, respectively) against B. subtilis, while the chloroform fractions of T. ciliata and D. salicifolia presented good antibacterial activities (13-17 mm zone of inhibition) against all the bacterial cultures tested. Conclusion The methanol fraction of Pistacia integerrima, chloroform fractions of Debregeasia salicifolia &Toona ciliata and aqueous fraction of Aesculus indica are suitable candidates for the development of novel antibacterial compounds. PMID:21718504

  4. 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.

  5. High temperature performance of high-efficiency, multi-layer solar selective coatings for tower applications

    DOE PAGES

    Gray, M. H.; Tirawat, R.; Kessinger, K. A.; ...

    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

  6. 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.

  7. 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.…

  8. 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.

  9. 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.

  10. Comparative anthelmintic activity investigation of selected ethno-medicinal weeds

    NASA Astrophysics Data System (ADS)

    Pueblos, Kirstin Rhys S.; Bajalla, Mark; Pacheco, Dixie; Ganot, Sheila; Paig, Daisy; Tapales, Radyn; Lagare, Jeanne; Quimque, Mark Tristan J.

    2017-01-01

    Helminth infections are one of the seriously neglected potent diseases in many parts of the world. The problems of parasitic helminthes becoming resistant to currently available anthelmintic drugs pose a challenge for the search - relying on natural products - for new and better anthelmintics. In this paper, four abundant Philippine weeds: Chrysopogon aciculatus Trin. Cyperus brevifolius Rottb., Ruellia tuberosa Linn. and Saccharum spontaneum Linn. were investigated for their anthelmintic activities to establish basis of their folkloric claim. The hexane-soluble and chloroform-soluble extracts were obtained through sequential solvent partitioning of the crude ethanolic extract of the air-dried aerial part of each plant sample. Meanwhile, the decoction was obtained from fresh aerial part of the plant samples. All extracts were then subjected to in vitro anthelmintic screening at different concentration as per method of Ghosh, et al. against African nightcrawler earthworms (Eudrillus euginiae) in which the activity of the extracts was determined by correlation with time. The anthelmintic bioassay results revealed a dose-dependent toxicity relationship. It indicated relatively low anthelmintic activities of the decoction of the four plant samples as compared to their corresponding crude ethanol extracts. Among the crude ethanol extracts, C. brevifolius (CBE) gave fastest time to bring about paralysis and death to the test organisms at all concentrations tested. For the hexane extracts, R. tuberosa (RTH) gave better activity among other plant samples. Lastly, among the chloroform-soluble extracts, both that of C. brevifolius (CBC) and R. tuberosa (RTC) comparably showed strongest anthelmintic activities at all tested concentrations, thus, exhibited best anthelmintic activity that is remarkably comparable to the positive control, Mebendazole at the highest concentration tested. In fact, CBC and RTC showed highest anthelmintic potential compared to all extracts tested in

  11. 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

  12. 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.

  13. Structural characterization of the GSK-3beta active site using selective and non-selective ATP-mimetic inhibitors.

    PubMed

    Bertrand, J A; Thieffine, S; Vulpetti, A; Cristiani, C; Valsasina, B; Knapp, S; Kalisz, H M; Flocco, M

    2003-10-17

    GSK-3beta is a regulatory serine/threonine kinase with a plethora of cellular targets. Consequently, selective small molecule inhibitors of GSK-3beta may have a variety of therapeutic uses including the treatment of neurodegenerative diseases, type II diabetes and cancer. In order to characterize the active site of GSK-3beta, we determined crystal structures of unphosphorylated GSK-3beta in complex with selective and non-selective ATP-mimetic inhibitors. Analysis of the inhibitors' interactions with GSK-3beta in the structures reveals how the enzyme can accommodate a number of diverse molecular scaffolds. In addition, a conserved water molecule near Thr138 is identified that can serve a functional role in inhibitor binding. Finally, a comparison of the interactions made by selective and non-selective inhibitors highlights residues on the edge of the ATP binding-site that can be used to obtain inhibitor selectivity. Information gained from these structures provides a promising route for the design of second-generation GSK-3beta inhibitors.

  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. 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

  16. Medium chain fatty acids are selective peroxisome proliferator activated receptor (PPAR) γ activators and pan-PPAR partial agonists.

    PubMed

    Liberato, Marcelo Vizoná; Nascimento, Alessandro S; 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.

  17. 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…

  18. Discovery of 2-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an active metabolite. A novel, potent and selective cannabinoid-1 receptor inverse agonist with high antiobesity efficacy in DIO mice.

    PubMed

    Wu, Chien-Huang; Hung, Ming-Shiu; Song, Jen-Shin; Yeh, Teng-Kuang; Chou, Ming-Chen; Chu, Cheng-Ming; Jan, Jiing-Jyh; Hsieh, Min-Tsang; Tseng, Shi-Liang; Chang, Chun-Ping; Hsieh, Wan-Ping; Lin, Yinchiu; Yeh, Yen-Nan; Chung, Wan-Ling; Kuo, Chun-Wei; Lin, Chin-Yu; Shy, Horng-Shing; Chao, Yu-Sheng; Shia, Kak-Shan

    2009-07-23

    By using the active metabolite 5 as an initial template, further structural modifications led to the identification of the titled compound 24 (BPR-890) as a highly potent CB1 inverse agonist possessing an excellent CB2/1 selectivity and remarkable in vivo efficacy in diet-induced obese mice with a minimum effective dose as low as 0.03 mg/kg (po qd) at the end of the 30-day chronic study. Current SAR studies along with those of many existing rimonabant-mimicking molecules imply that around the pyrazole C3-position, a rigid and deep binding pocket should exist for CB1 receptor. In addition, relative to the conventional carboxamide carbonyl, serving as a key hydrogen-bond acceptor during ligand-CB1 receptor interaction, the corresponding polarizable thione carbonyl might play a more critical role in stabilizing the Asp366-Lys192 salt bridge in the proposed CB1-receptor homology model and inducing significant selectivity for CB1R over CB2R.

  19. 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...

  20. 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...

  1. Molecular Determinant for Specific Ca/Ba Selectivity Profiles of Low and High Threshold Ca2+ Channels

    PubMed Central

    Cens, Thierry; Rousset, Matthieu; Kajava, Andrey; Charnet, Pierre

    2007-01-01

    Voltage-gated Ca2+ channels (VGCC) play a key role in many physiological functions by their high selectivity for Ca2+ over other divalent and monovalent cations in physiological situations. Divalent/monovalent selection is shared by all VGCC and is satisfactorily explained by the existence, within the pore, of a set of four conserved glutamate/aspartate residues (EEEE locus) coordinating Ca2+ ions. This locus however does not explain either the choice of Ca2+ among other divalent cations or the specific conductances encountered in the different VGCC. Our systematic analysis of high- and low-threshold VGCC currents in the presence of Ca2+ and Ba2+ reveals highly specific selectivity profiles. Sequence analysis, molecular modeling, and mutational studies identify a set of nonconserved charged residues responsible for these profiles. In HVA (high voltage activated) channels, mutations of this set modify divalent cation selectivity and channel conductance without change in divalent/monovalent selection, activation, inactivation, and kinetics properties. The CaV2.1 selectivity profile is transferred to CaV2.3 when exchanging their residues at this location. Numerical simulations suggest modification in an external Ca2+ binding site in the channel pore directly involved in the choice of Ca2+, among other divalent physiological cations, as the main permeant cation for VGCC. In LVA (low voltage activated) channels, this locus (called DCS for divalent cation selectivity) also influences divalent cation selection, but our results suggest the existence of additional determinants to fully recapitulate all the differences encountered among LVA channels. These data therefore attribute to the DCS a unique role in the specific shaping of the Ca2+ influx between the different HVA channels. PMID:17893194

  2. Highly selective receptive fields in mouse visual cortex.

    PubMed

    Niell, Cristopher M; Stryker, Michael P

    2008-07-23

    Genetic methods available in mice are likely to be powerful tools in dissecting cortical circuits. However, the visual cortex, in which sensory coding has been most thoroughly studied in other species, has essentially been neglected in mice perhaps because of their poor spatial acuity and the lack of columnar organization such as orientation maps. We have now applied quantitative methods to characterize visual receptive fields in mouse primary visual cortex V1 by making extracellular recordings with silicon electrode arrays in anesthetized mice. We used current source density analysis to determine laminar location and spike waveforms to discriminate putative excitatory and inhibitory units. We find that, although the spatial scale of mouse receptive fields is up to one or two orders of magnitude larger, neurons show selectivity for stimulus parameters such as orientation and spatial frequency that is near to that found in other species. Furthermore, typical response properties such as linear versus nonlinear spatial summation (i.e., simple and complex cells) and contrast-invariant tuning are also present in mouse V1 and correlate with laminar position and cell type. Interestingly, we find that putative inhibitory neurons generally have less selective, and nonlinear, responses. This quantitative description of receptive field properties should facilitate the use of mouse visual cortex as a system to address longstanding questions of visual neuroscience and cortical processing.

  3. Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor.

    PubMed

    Johnson, Douglas S; Stiff, Cory; Lazerwith, Scott E; Kesten, Suzanne R; Fay, Lorraine K; Morris, Mark; Beidler, David; Liimatta, Marya B; Smith, Sarah E; Dudley, David T; Sadagopan, Nalini; Bhattachar, Shobha N; Kesten, Stephen J; Nomanbhoy, Tyzoon K; Cravatt, Benjamin F; Ahn, Kay

    2011-02-10

    Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase that degrades the fatty acid amide family of signaling lipids, including the endocannabinoid anandamide. Genetic or pharmacological inactivation of FAAH leads to analgesic and anti-inflammatory phenotypes in rodents without showing the undesirable side effects observed with direct cannabinoid receptor agonists, indicating that FAAH may represent an attractive therapeutic target for the treatment of inflammatory pain and other nervous system disorders. Herein, we report the discovery and characterization of a highly efficacious and selective FAAH inhibitor PF-04457845 (23). Compound 23 inhibits FAAH by a covalent, irreversible mechanism involving carbamylation of the active-site serine nucleophile of FAAH with high in vitro potency (k(inact)/K(i) and IC(50) values of 40300 M(-1) s(-1) and 7.2 nM, respectively, for human FAAH). Compound 23 has exquisite selectivity for FAAH relative to other members of the serine hydrolase superfamily as demonstrated by competitive activity-based protein profiling. Oral administration of 23 at 0.1 mg/kg results in efficacy comparable to that of naproxen at 10 mg/kg in a rat model of inflammatory pain. Compound 23 is being evaluated in human clinical trials.

  4. Magnesium-Dependent Active-Site Conformational Selection in the Diels-Alderase Ribozyme

    SciTech Connect

    Berezniak, Tomasz; Zahran, Mai; Imhof, Petra; Jaeschke, Andres; Smith, Jeremy C

    2010-10-01

    The Diels-Alderase ribozyme, an in vitro-evolved ribonucleic acid enzyme, accelerates the formation of carbon-carbon bonds between an anthracene diene and a maleimide dienophile in a [4 + 2] cycloaddition, a reaction with broad application in organic chemistry. Here, the Diels-Alderase ribozyme is examined via molecular dynamics (MD) simulations in both crystalline and aqueous solution environments. The simulations indicate that the catalytic pocket is highly dynamic. At low Mg(2+) ion concentrations, inactive states with the catalytic pocket closed dominate. Stabilization of the enzymatically active, open state of the catalytic pocket requires a high concentration of Mg(2+) ions (e.g., 54 mM), with cations binding to specific phosphate sites on the backbone of the residues bridging the opposite strands of the pocket. The free energy profile for pocket opening at high Mg(2+) cation concentration exhibits a double minimum, with a barrier to opening of approximately 5.5 kJ/mol and the closed state approximately 3 kJ/mol lower than the open state. Selection of the open state on substrate binding leads to the catalytic activity of the ribozyme. The simulation results explain structurally the experimental observation that full catalytic activity depends on the Mg(2+) ion concentration

  5. Low-dose IL-2 selectively activates subsets of CD4+ Tregs and NK cells

    PubMed Central

    Hirakawa, Masahiro; Matos, Tiago; Liu, Hongye; Koreth, John; Kim, Haesook T.; Paul, Nicole E.; Murase, Kazuyuki; Whangbo, Jennifer; Alho, Ana C.; Nikiforow, Sarah; Cutler, Corey; Ho, Vincent T.; Armand, Philippe; Alyea, Edwin P.; Antin, Joseph H.; Blazar, Bruce R.; Lacerda, Joao F.; Soiffer, Robert J.

    2016-01-01

    CD4+ regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood. Using mass cytometry, we demonstrate that low concentrations of IL-2 selectively induce STAT5 phosphorylation in Helios+ CD4Tregs and CD56brightCD16– NK cells in vitro. Preferential activation and expansion of Helios+ CD4Tregs and CD56brightCD16– NK cells was also demonstrated in patients with chronic GVHD receiving low-dose IL-2. With prolonged IL-2 treatment for 48 weeks, phenotypic changes were also observed in Helios– CD4Tregs. The effects of low-dose IL-2 therapy on conventional CD4+ T cells and CD8+ T cells were limited to increased expression of PD-1 on effector memory T cells. These studies reveal the selective effects of low-dose IL-2 therapy on Helios+ CD4Tregs and CD56bright NK cells that constitutively express high-affinity IL-2 receptors as well as the indirect effects of prolonged exposure to low concentrations of IL-2 in vivo. PMID:27812545

  6. 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.

  7. 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.

  8. Electric Field-aided Selective Activation for Indium-Gallium-Zinc-Oxide Thin Film Transistors

    PubMed Central

    Lee, Heesoo; Chang, Ki Soo; Tak, Young Jun; Jung, Tae Soo; Park, Jeong Woo; Kim, Won-Gi; Chung, Jusung; Jeong, Chan Bae; Kim, Hyun Jae

    2016-01-01

    A new technique is proposed for the activation of low temperature amorphous InGaZnO thin film transistor (a-IGZO TFT) backplanes through application of a bias voltage and annealing at 130 °C simultaneously. In this ‘electrical activation’, the effects of annealing under bias are selectively focused in the channel region. Therefore, electrical activation can be an effective method for lower backplane processing temperatures from 280 °C to 130 °C. Devices fabricated with this method exhibit equivalent electrical properties to those of conventionally-fabricated samples. These results are analyzed electrically and thermodynamically using infrared microthermography. Various bias voltages are applied to the gate, source, and drain electrodes while samples are annealed at 130 °C for 1 hour. Without conventional high temperature annealing or electrical activation, current-voltage curves do not show transfer characteristics. However, electrically activated a-IGZO TFTs show superior electrical characteristics, comparable to the reference TFTs annealed at 280 °C for 1 hour. This effect is a result of the lower activation energy, and efficient transfer of electrical and thermal energy to a-IGZO TFTs. With this approach, superior low-temperature a-IGZO TFTs are fabricated successfully. PMID:27725695

  9. Electric Field-aided Selective Activation for Indium-Gallium-Zinc-Oxide Thin Film Transistors

    NASA Astrophysics Data System (ADS)

    Lee, Heesoo; Chang, Ki Soo; Tak, Young Jun; Jung, Tae Soo; Park, Jeong Woo; Kim, Won-Gi; Chung, Jusung; Jeong, Chan Bae; Kim, Hyun Jae

    2016-10-01

    A new technique is proposed for the activation of low temperature amorphous InGaZnO thin film transistor (a-IGZO TFT) backplanes through application of a bias voltage and annealing at 130 °C simultaneously. In this ‘electrical activation’, the effects of annealing under bias are selectively focused in the channel region. Therefore, electrical activation can be an effective method for lower backplane processing temperatures from 280 °C to 130 °C. Devices fabricated with this method exhibit equivalent electrical properties to those of conventionally-fabricated samples. These results are analyzed electrically and thermodynamically using infrared microthermography. Various bias voltages are applied to the gate, source, and drain electrodes while samples are annealed at 130 °C for 1 hour. Without conventional high temperature annealing or electrical activation, current-voltage curves do not show transfer characteristics. However, electrically activated a-IGZO TFTs show superior electrical characteristics, comparable to the reference TFTs annealed at 280 °C for 1 hour. This effect is a result of the lower activation energy, and efficient transfer of electrical and thermal energy to a-IGZO TFTs. With this approach, superior low-temperature a-IGZO TFTs are fabricated successfully.

  10. 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

  11. Characterization of rat hair follicle stem cells selected by vario magnetic activated cell sorting system.

    PubMed

    Huang, Enyi; Lian, Xiaohua; Chen, Wei; Yang, Tian; Yang, Li

    2009-10-30

    Hair follicle stem cells (HfSCs) play crucial roles in hair follicle morphogenesis and hair cycling. These stem cells are self-renewable and have the multi-lineage potential to generate epidermis, sebaceous glands, and hair follicle. The separation and identification of hair follicle stem cells are important for further research in stem cell biology. In this study, we report on the successful enrichment of rat hair follicle stem cells through vario magnetic activated cell sorting (Vario MACS) and the biological characteristics of the stem cells. We chose the HfSCs positive surface markers CD34, alpha 6-integrin and the negative marker CD71 to design four isolation strategies: positive selection with single marker of CD34, positive selection with single marker of alpha 6-integrin, CD71 depletion followed by CD34 positive selection, and CD71 depletion followed by alpha 6-integrin positive selection. The results of flow cytometry analysis showed that all four strategies had ideal effects. Specifically, we conducted a series of researches on HfSCs characterized by their high level of CD34, termed CD34(bri) cells, and low to undetectable expression of CD34, termed CD34(dim) cells. CD34(bri) cells had greater proliferative potential and higher colony-forming ability than CD34(dim) cells. Furthermore, CD34(bri) cells had some typical characteristics as progenitor cells, such as large nucleus, obvious nucleolus, large nuclear:cytoplasmic ratio and few cytoplasmic organelles. Our findings clearly demonstrated that HfSCs with high purity and viability could be successfully enriched with Vario MACS.

  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. 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

  14. Active focus stabilization for upright selective plane illumination microscopy

    PubMed Central

    Hedde, Per Niklas; Gratton, Enrico

    2015-01-01

    Due to its sectioning capability, large field of view, and minimal light exposure, selective plane illumination microscopy has become the preferred choice for 3D time lapse imaging. Single cells in a dish can be conveniently imaged using an upright/inverted configuration. However, for measurements on long time scales (hours to days), mechanical drift is a problem; especially for studies of mammalian cells that typically require heating to 37°C which causes a thermal gradient across the instrument. Since the light sheet diverges towards the edges of the field of view, such a drift leads to a decrease in axial resolution over time. Or, even worse, the specimen could move out of the imaging volume. Here, we present a simple, cost-effective way to stabilize the axial position using the microscope camera to track the sample position. Thereby, sample loss is prevented and an optimal axial resolution is maintained by keeping the sample at the position where the light sheet is at its thinnest. We demonstrate the virtue of our approach by measurements of the light sheet thickness and 3D time lapse imaging of a cell monolayer at physiological conditions. PMID:26072829

  15. Active focus stabilization for upright selective plane illumination microscopy.

    PubMed

    Hedde, Per Niklas; Gratton, Enrico

    2015-06-01

    Due to its sectioning capability, large field of view, and minimal light exposure, selective plane illumination microscopy has become the preferred choice for 3D time lapse imaging. Single cells in a dish can be conveniently imaged using an upright/inverted configuration. However, for measurements on long time scales (hours to days), mechanical drift is a problem; especially for studies of mammalian cells that typically require heating to 37°C which causes a thermal gradient across the instrument. Since the light sheet diverges towards the edges of the field of view, such a drift leads to a decrease in axial resolution over time. Or, even worse, the specimen could move out of the imaging volume. Here, we present a simple, cost-effective way to stabilize the axial position using the microscope camera to track the sample position. Thereby, sample loss is prevented and an optimal axial resolution is maintained by keeping the sample at the position where the light sheet is at its thinnest. We demonstrate the virtue of our approach by measurements of the light sheet thickness and 3D time lapse imaging of a cell monolayer at physiological conditions.

  16. 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

  17. 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

  18. 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.

  19. Highly selective indium mediated allylation of unprotected pentosylamines.

    PubMed

    Behr, Jean-Bernard; Hottin, Audrey; Ndoye, Alpha

    2012-03-16

    A straightforward functionalization of D-pentoses is reported, which affords homoallylaminopolyols in two steps and uses ion exchange chromatography as the only purification operation. The key indium-mediated allylation is effected on unprotected glycosylamines and occurs with good to excellent syn stereoselection. Validation of the synthetic utility of the method was exemplified by a 3-step synthesis of an optically active 1,2,3,6-tetrahydropyridine from D-xylose.

  20. Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression

    PubMed Central

    Paris, Robert M.; Petrovas, Constantinos; Ferrando-Martinez, Sara; Moysi, Eirini; Boswell, Kristin L.; Archer, Eva; Yamamoto, Takuya; Ambrozak, David; Casazza, Joseph P.; Haubrich, Richard; Connors, Mark; Ake, Julie; Kim, Jerome H.; Koup, Richard A.

    2015-01-01

    The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection. PMID:26678998

  1. Ice-active characteristics of soil bacteria selected by ice-affinity.

    PubMed

    Wilson, Sandra L; Kelley, Deborah L; Walker, Virginia K

    2006-10-01

    As an initial screen for microorganisms that produce ice-active macromolecules, ice-affinity was used to select microorganisms from soil consortia originating from three temperate regions. Once selected and subsequently purified to single colonies, these microbes were putatively identified by 16S ribosomal RNA sequencing and assayed for various ice-active properties. Ice-affinity selection appeared to select for bacteria with ice-associating activities: inhibition of ice recrystallization; ice nucleation; ice shaping. Although none of these activities were observed in Paenibacillus amyloliticus C8, others such as Chryseobacterium sp. GL8, demonstrated both ice recrystallization inhibition and ice-shaping activities. Pseudomonas borealis DL7 was classified as a type I ice nucleator, Flavobacterium sp. GL7, was identified as a type III ice nucleator and Acinetobacter radioresistens DL5 demonstrated ice recrystallization inhibition. In all, 19 different culturable bacteria were selected from the thousands of microbes in late-summer collected soil samples. Many of the selected microbes have been previously reported in glacial ice cores or polar sea ice, and of five isolates that were further characterized, four showed ice-associating activities. These results indicate the significant potential of ice-affinity selection even with temperate climate soils, suggesting that sampling in more extreme and remote areas is not required for the isolation of ice-active bacteria.

  2. Top-down suppression of incompatible motor activations during response selection under conflict.

    PubMed

    Klein, Pierre-Alexandre; Petitjean, Charlotte; Olivier, Etienne; Duque, Julie

    2014-02-01

    Top-down control is critical to select goal-directed actions in changeable environments, particularly when several options compete for selection. This control system is thought to involve a mechanism that suppresses activation of unwanted response representations. We tested this hypothesis, in humans, by measuring motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in a left finger muscle during motor preparation in an adapted Eriksen flanker task. Subjects reported, by a left or right button-press, the orientation of a left- or right-facing central arrow, flanked by two distractor arrows on each side. Central and peripheral arrows either pointed in the same (congruent trial) or in the opposite direction (incongruent trial). Top-down control was manipulated by changing the probability of congruent and incongruent trials in a given block. In the "mostly incongruent" (MI) blocks, 80% of trials were incongruent, producing a context in which subjects strongly anticipated that they would have to face conflict. In the "mostly congruent" (MC) blocks, 80% of trials were congruent and thus subjects barely anticipated conflict in that context. Thus, we assume that top-down control was stronger in the MI than in the MC condition. Accordingly, subjects displayed a lower error rate and shorter reaction times for the incongruent trials in the MI context than for similar trials in the MC context. More interestingly, we found that top-down control specifically reduced activation of the incompatible motor representation during response selection under high conflict. That is, when the central arrow specified a right hand response, left (non-selected) MEPs became smaller in the MI than in the MC condition, but only for incongruent trials, and this measure was positively correlated with performance. In contrast, MEPs elicited in the non-selected hand during congruent trials, or during all trials in which the left hand was selected, tended to increase

  3. Selected electrical properties of high ohmic thick-film resistors

    NASA Astrophysics Data System (ADS)

    DÄ browski, Arkadiusz; Tatar, Adam; Dziedzic, Andrzej

    2016-12-01

    Results of fabrication as well as electrical and stability characterization of thick-film high ohmic resistors are described in this paper. Five commercially available resistive compositions with sheet resistance of 1, 10, and 100 MΩ/sq were applied. The best properties were obtained for the lowest sheet resistance pastes, for which voltage coefficient of resistance (VCR) was lower than 3 ppm/V and hot temperature coefficient of resistance (HTCR) below 50 ppm/°C. Effect of resistor length on sheet resistance and impact of termination material were analyzed. High voltage pulse stress at 2 kV had negligible influence on resistors' properties.

  4. High yield sample preconcentration using a highly ion-conductive charge-selective polymer.

    PubMed

    Chun, Honggu; Chung, Taek Dong; Ramsey, J Michael

    2010-07-15

    The development and analysis of a microfluidic sample preconcentration system using a highly ion-conductive charge-selective polymer [poly-AMPS (2-acrylamido-2-methyl-1-propanesulfonic acid)] is reported. The preconcentration is based on the phenomenon of concentration polarization which develops at the boundaries of the poly-AMPS with buffer solutions. A negatively charged polymer, poly-AMPS, positioned between two microchannels efficiently extracts cations through its large cross section, resulting in efficient anion sample preconcentration. The present work includes the development of a robust polymer that is stable over a wide range of buffers with varying chemical compositions. The sample preconcentration effect remains linear to over 3 mM (0.15 pmol) and 500 microM (15 fmol) for fluorescein and TRITC-tagged albumin solutions, respectively. The system can potentially be used for concentrating proteins on microfluidic devices with subsequent analysis for proteomic applications.

  5. 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

  6. 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

  7. Strong transcriptional activators isolated from viral DNA by the 'activator trap', a novel selection system in mammalian cells.

    PubMed

    Gstaiger, M; Schaffner, W

    1994-10-11

    Transcription factors often contain activation domains that interact with the basic transcription machinery. We have developed a functional screening strategy in mammalian cells to selectively isolate activation domains from a library of random DNA inserts. For this, sonicated DNA fragments are cloned next to the DNA binding domain of GAL4 factor in a plasmid that also contains the SV40 origin of replication. Pools of fusion protein clones are transfected into CV-1-5GT monkey cells containing an SV40 T antigen gene under the control of a promoter with GAL4 binding sites. Plasmids that express functional transactivating fusion proteins activate the T antigen gene, thus promoting selective amplification of the plasmid in the mammalian host cell line. Using this method, we were able to select strong enhancer-type activation domains from the immediate early regions of two herpesviruses, namely pseudorabies virus and bovine herpesvirus 1. In both cases, the activation domains selected were homologues of the ICP4 regulatory protein of herpes simplex virus. The activation domain from pseudorabies virus is four times stronger than the activation domain of herpes simplex virus protein VP16 (Vmw65), making it the strongest activation domain characterized so far. This activator trap method should be useful for precisely localizing activation domain(s) in known factors, or to identify mammalian transcriptional adaptors that do not bind DNA and which may escape conventional detection methods.

  8. 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.

  9. 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

  10. 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.

  11. Wavelet Packet Feature Assessment for High-Density Myoelectric Pattern Recognition and Channel Selection toward Stroke Rehabilitation

    PubMed Central

    Wang, Dongqing; Zhang, Xu; Gao, Xiaoping; Chen, Xiang; Zhou, Ping

    2016-01-01

    This study presents wavelet packet feature assessment of neural control information in paretic upper limb muscles of stroke survivors for myoelectric pattern recognition, taking advantage of high-resolution time–frequency representations of surface electromyogram (EMG) signals. On this basis, a novel channel selection method was developed by combining the Fisher’s class separability index and the sequential feedforward selection analyses, in order to determine a small number of appropriate EMG channels from original high-density EMG electrode array. The advantages of the wavelet packet features and the channel selection analyses were further illustrated by comparing with previous conventional approaches, in terms of classification performance when identifying 20 functional arm/hand movements implemented by 12 stroke survivors. This study offers a practical approach including paretic EMG feature extraction and channel selection that enables active myoelectric control of multiple degrees of freedom with paretic muscles. All these efforts will facilitate upper limb dexterity restoration and improved stroke rehabilitation. PMID:27917149

  12. 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,…

  13. 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.

  14. 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)

  15. 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.

  16. High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition

    PubMed Central

    Dagne, Beza A; Sunay, Melis K; Cayla, Noëlie S; Ouyang, Yi-Bing; Knox, Susan J; Giffard, Rona G; Adler, John R.

    2017-01-01

    Studies on the effects of gamma radiation on brain tissue have produced markedly differing results, ranging from little effect to major pathology, following irradiation. The present study used control-matched animals to compare effects on a well characterized brain region following gamma irradiation. Male Sprague-Dawley rats were exposed to 60 Gy of whole brain gamma radiation and, after 24-hours, 48-hours, and one-week periods, hippocampal brain slices were isolated and measured for anatomical and physiological differences. There were no major changes observed in tissue appearance or evoked synaptic responses at any post-irradiation time point. However, exposure to 60 Gy of irradiation resulted in a small, but statistically significant (14% change; ANOVA p < 0.005; n = 9) reduction in synaptic inhibition seen at 100 ms, indicating a selective depression of the gamma-aminobutyric acid (GABAA) slow form of inhibition. Population spike (PS) amplitudes also transiently declined by ~ 10% (p < 0.005; n = 9) when comparing the 24-hour group to sham group. Effects on PS amplitude recovered to baseline 48 hour and one week later. There were no obvious negative pathological effects; however, a subtle depression in circuit level inhibition was observed and provides evidence for ‘radiomodulation’ of brain circuits.

  17. 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.

  18. Sensory Cortical Activity Is Related to the Selection of a Rhythmic Motor Action Pattern

    PubMed Central

    Li, Jennifer X.; Maier, Joost X.; Reid, Emily E.

    2016-01-01

    Rats produce robust, highly distinctive orofacial rhythms in response to taste stimuli—responses that aid in the consumption of palatable tastes and the ejection of aversive tastes, and that are sourced in a multifunctional brainstem central pattern generator. Several pieces of indirect evidence suggest that primary gustatory cortex (GC) may be a part of a distributed forebrain circuit involved in the selection of particular consumption-related rhythms, although not in the production of individual mouth movements per se. Here, we performed a series of tests of this hypothesis. We first examined the temporal relationship between GC activity and orofacial behaviors by performing paired single-neuron and electromyographic recordings in awake rats. Using a trial-by-trial analysis, we found that a subset of GC neurons shows a burst of activity beginning before the transition between nondistinct and taste-specific (i.e., consumption-related) orofacial rhythms. We further showed that shifting the latency of consumption-related behavior by selective cueing has an analogous impact on the timing of GC activity. Finally, we showed the complementary result, demonstrating that optogenetic perturbation of GC activity has a modest but significant impact on the probability that a specific rhythm will be produced in response to a strongly aversive taste. GC appears to be a part of a distributed circuit that governs the selection of taste-induced orofacial rhythms. SIGNIFICANCE STATEMENT In many well studied (typically invertebrate) sensorimotor systems, top-down modulation helps motor-control regions “select” movement patterns. Here, we provide evidence that gustatory cortex (GC) may be part of the forebrain circuit that performs this function in relation to oral behaviors (“gapes”) whereby a substance in the mouth is rejected as unpalatable. We show that GC palatability coding is well timed to play this role, and that the latency of these codes changes as the latency of

  19. Highly Selective H2 Separation Zeolite Membranes for Coal Gasification Membrane Reactor Applications

    SciTech Connect

    Mei Hong; Richard D. Noble; John L. Falconer

    2006-09-24

    Zeolite membranes are thermally, chemically, and mechanically stable. They also have tunable molecular sieving and catalytic ability. These unique properties make zeolite membrane an excellent candidate for use in catalytic membrane reactor applications related to coal conversion and gasification, which need high temperature and high pressure range separation in chemically challenging environment where existing technologies are inefficient or unable to operate. Small pore, good quality, and thin zeolite membranes are needed for highly selective H{sub 2} separation from other light gases (CO{sub 2}, CH{sub 4}, CO). However, zeolite membranes have not been successful for H{sub 2} separation from light gases because the zeolite pores are either too big or the membranes have a large number of defects. The objective of this study is to develop zeolite membranes that are more suitable for H{sub 2} separation. In an effort to tune the size of zeolite pores and/or to decrease the number of defects, medium-pore zeolite B-ZSM-5 (MFI) membranes were synthesized and silylated. Silylation on B-ZSM-5 crystals reduced MFI-zeolite pore volume, but had little effect on CO{sub 2} and CH{sub 4} adsorption. Silylation on B-ZSM-5 membranes increased H{sub 2} selectivity both in single component and in mixtures with CO{sub 2}CO{sub 2}, CH{sub 4}, or N2. Single gas and binary mixtures of H{sub 2}/CO{sub 2} and H{sub 2}/CH{sub 4} were separated through silylated B-ZSM-5 membranes at feed pressures up to 1.7 MPa and temperatures up to 773 K. For one BZSM-5 membrane after silylation, the H2/CO{sub 2} separation selectivity at 473 K increased from 1.4 to 37, whereas the H{sub 2}/CH{sub 4} separation selectivity increased from 1.6 to 33. Hydrogen permeance through a silylated B-ZSM-5 membrane was activated, but the CO{sub 2} and CH4 permeances decreased slightly with temperature in both single gas and in mixtures. Therefore, the H{sub 2} permeance and H{sub 2}/CO{sub 2} and H{sup 2} /CH{sub 4

  20. Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY‐876

    PubMed Central

    Siebeneicher, Holger; Cleve, Arwed; Rehwinkel, Hartmut; Neuhaus, Roland; Heisler, Iring; Müller, Thomas; Bauser, Marcus

    2016-01-01

    Abstract Despite the long‐known fact that the facilitative glucose transporter GLUT1 is one of the key players safeguarding the increase in glucose consumption of many tumor entities even under conditions of normal oxygen supply (known as the Warburg effect), only few endeavors have been undertaken to find a GLUT1‐selective small‐molecule inhibitor. Because other transporters of the GLUT1 family are involved in crucial processes, these transporters should not be addressed by such an inhibitor. A high‐throughput screen against a library of ∼3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N‐(1H‐pyrazol‐4‐yl)quinoline‐4‐carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure–activity relationship explorations, single‐digit nanomolar inhibitors with a selectivity factor of >100 against GLUT2, GLUT3, and GLUT4 were obtained. The most promising compound, BAY‐876 [N 4‐[1‐(4‐cyanobenzyl)‐5‐methyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐4‐yl]‐7‐fluoroquinoline‐2,4‐dicarboxamide], showed good metabolic stability in vitro and high oral bioavailability in vivo. PMID:27552707

  1. 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.

  2. 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

  3. 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

  4. Multisatellite constellation configuration selection for multiregional highly elliptical orbit constellations

    NASA Technical Reports Server (NTRS)

    Matossian, Mark G.

    1994-01-01

    The Archimedes Project is a joint effort of the European Space Agency (ESA) and the National Space Development Agency of Japan (NASDA). The primary goal of the Archimedes project is to perform a technical feasibility analysis and preliminary design of a highly inclined multisatellite constellation for direct broadcast and mobile communications services for Europe, Japan and much of North America. This report addresses one aspect of this project, specifically an analysis of continuous satellite coverage using multiregional highly elliptical orbits (M-HEO's). The analysis methodology and ensuing software tool, named SPIFF, were developed specifically for this project by the author during the summer of 1992 under the STA/NSF Summer Institute in Japan Program at Tsukuba Space Center.

  5. Operation and design selection of high temperature superconducting magnetic bearings

    NASA Astrophysics Data System (ADS)

    Werfel, F. N.; Floegel-Delor, U.; Riedel, T.; Rothfeld, R.; Wippich, D.; Goebel, B.

    2004-10-01

    Axial and radial high temperature superconducting (HTS) magnetic bearings are evaluated by their parameters. Journal bearings possess advantages over thrust bearings. High magnetic gradients in a multi-pole permanent magnet (PM) configuration, the surrounding melt textured YBCO stator and adequate designs are the key features for increasing the overall bearing stiffness. The gap distance between rotor and stator determines the specific forces and has a strong impact on the PM rotor design. We report on the designing, building and measuring of a 200 mm prototype 100 kg HTS bearing with an encapsulated and thermally insulated melt textured YBCO ring stator. The encapsulation requires a magnetically large-gap (4-5 mm) operation but reduces the cryogenic effort substantially. The bearing requires 3 l of LN2 for cooling down, and about 0.2 l LN2 h-1 under operation. This is a dramatic improvement of the efficiency and in the practical usage of HTS magnetic bearings.

  6. Rare Earth Doped High Temperature Ceramic Selective Emitters

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; Pal, AnnaMarie; Patton, Martin O.; Jenkins, Phillip P.

    1999-01-01

    As a result of their electron structure, rare earth ions in crystals at high temperature emit radiation in several narrow bands rather than in a continuous blackbody manner. This study develops a spectral emittance model for films of rare earth containing materials. Although there are several possible rare earth doped high temperature materials, this study was confined to rare earth aluminum garnets. Good agreement between experimental and theoretical spectral emittances was found for erbium, thulium and erbium-holmium aluminum garnets. Spectral emittances of these films are sensitive to temperature differences across the film. Emitter efficiency is also a sensitive function of temperature. For thulium aluminum garnet the efficiency is 0.38 at 1700 K but only 0.19 at 1262 K.

  7. Characterisation of novel modified active carbons and marine algal biomass for the selective adsorption of lead.

    PubMed

    Malik, D J; Strelko, V; Streat, M; Puziy, A M

    2002-03-01

    This paper discusses the sorption performance of novel materials for the removal of lead(II) and copper(II) from near-neutral aqueous solutions. Active carbons with surface heteroatoms of oxygen and phosphorus have been prepared. The surface functional groups display weakly acidic ion exchange characteristics. The optimum solution pH for maximum metal sorption is related to the pK values of the surface functional groups. In oxygenated active carbons, pK values are not distinct but can be obtained by describing proton binding to the heterogeneous adsorbent surface as a continuous proton affinity distribution. Information derived from zeta-potential measurements combined with knowledge of the pK distribution function and concentration of surface functional groups has been used to explain the selectivity of oxidised active carbons towards lead(lI) in the presence of copper(II) from multi-metal bearing solutions. Marine algal-based biosorbents have been challenged with lead(II) and copper(II)-bearing wastewater. The weakly acidic carboxyl groups of structural polysaccharides present within the algal matrix display high sorption capacity for both metals. The negative surface charge of algal particles results in electrostatic interactions as well as coordination between metal species and the adsorbent surface. Proton affinity for the algal surface lowers the negative surface potential at pH values around 2. The surface functional groups in algae unlike those in oxidised active carbons may be represented by discrete acid-dissociation constant values. The influence of conformational differences in uronic-acid segments upon metal ion selectivity is discussed.

  8. In vitro activity of RO363, a beta1-adrenoceptor selective agonist.

    PubMed Central

    Iakovidis, D.; Malta, E.; McPherson, G. A.; Raper, C.

    1980-01-01

    1 The beta-adrenoceptor stimulant effects of RO363 and (--)-isoprenaline have been compared in a variety of isolated tissue preparations. 2 RO363 is approximately half as potent as (--)-isoprenaline in tissues where actions are due to beta1-receptor activation (guinea-pig atrial and ileal preparations and ventricular strips from the rabbit, rat and guinea-pig. 3 In uterine and lung strip preparations from the guinea-pig, where responses are due to beta2-receptor stimulation. RO363 is 100 to 350 times less active than (--)-isoprenaline and has a low intrinsic activity. 4 In spontaneously contracted tracheal preparations from the guinea-pig, RO363 is a full agonist and is approximately half as potent as (--)-isoprenaline. These effects of RO363 are due to the activation of a population of beta1-receptors in the tissue since RO363 and (--)-isoprenaline have the same relative potencies in trachea, cardiac and ileal preparations. In addition the Kb values for practolol are similar in all these preparations when RO363 is used as the agonist. 5 The results show that RO363 is a potent and highly selective beta1-receptor agonist. PMID:6103722

  9. The Impact of the Non-Graded, Multi-Selective English Curriculum on High School Students.

    ERIC Educational Resources Information Center

    Gage, Thomas Evans

    Studies involving different populations were involved in this four-part evaluation of the impact of non-graded, multi-selective English on high school students. Study A involved students who consistently scored high or low in percentile gain in the four ability groups, to ascertain any pattern of courses selected, sequences of courses attended,…

  10. 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…

  11. 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

  12. Metal-Organic Frameworks for Highly Selective Separations

    SciTech Connect

    Omar M. Yaghi

    2009-09-28

    This grant was focused on the study of metal-organic frameworks with these specific objectives. (1) To examine the use of MOFs with well-defined open metal sites for binding of gases and small organics. (2) To develop a strategy for producing MOFs that combine large pore size with high surface area for their use in gas adsorption and separation of polycyclic organic compounds. (3) To functionalize MOFs for the storage of inert gases such as methane. A brief outline of our progress towards these objectives is presented here as it forms part of the basis for the ideas to be developed under the present proposal.

  13. 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.

  14. Utilizing Selected Di- and Trinucleotides of siRNA to Predict RNAi Activity

    PubMed Central

    Han, Ye; Liu, Yuanning; Zhang, Hao; He, Fei; Shu, Chonghe

    2017-01-01

    Small interfering RNAs (siRNAs) induce posttranscriptional gene silencing in various organisms. siRNAs targeted to different positions of the same gene show different effectiveness; hence, predicting siRNA activity is a crucial step. In this paper, we developed and evaluated a powerful tool named “siRNApred” with a new mixed feature set to predict siRNA activity. To improve the prediction accuracy, we proposed 2-3NTs as our new features. A Random Forest siRNA activity prediction model was constructed using the feature set selected by our proposed Binary Search Feature Selection (BSFS) algorithm. Experimental data demonstrated that the binding site of the Argonaute protein correlates with siRNA activity. “siRNApred” is effective for selecting active siRNAs, and the prediction results demonstrate that our method can outperform other current siRNA activity prediction methods in terms of prediction accuracy. PMID:28243313

  15. Di-substituted pyridinyl aminohydantoins as potent and highly selective human beta-secretase (BACE1) inhibitors.

    PubMed

    Malamas, Michael S; Barnes, Keith; Johnson, Matthew; Hui, Yu; Zhou, Ping; Turner, Jim; Hu, Yun; Wagner, Erik; Fan, Kristi; Chopra, Rajiv; Olland, Andrea; Bard, Jonathan; Pangalos, Menelas; Reinhart, Peter; Robichaud, Albert J

    2010-01-15

    The identification of highly selective small molecule di-substituted pyridinyl aminohydantoins as beta-secretase inhibitors is reported. The more potent and selective analogs demonstrate low nanomolar potency for the BACE1 enzyme as measured in a FRET assay, and exhibit comparable activity in a cell-based (ELISA) assay. In addition, these pyridine-aminohydantoins are highly selectivity (>500x) against the other structurally related aspartyl proteases BACE2, cathepsin D, pepsin and renin. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on the previously reported aminohydantoin 3a. We have taken advantage of the amino acid difference between the BACE1 and BACE2 at the S2' pocket (BACE1 Pro(70) changed to BACE2 Lys(86)) to build ligands with >500-fold selectivity against BACE2. The addition of large substituents on the targeted ligand at the vicinity of this aberration has generated a steric conflict between the ligand and these two proteins, thus impacting the ligand's affinity and selectivity. These ligands have also shown an exceptional selectivity against cathepsin D (>5000-fold) as well as the other aspartyl proteases mentioned. One of the more potent compounds (S)-39 displayed an IC(50) value for BACE1 of 10nM, and exhibited cellular activity with an EC(50) value of 130nM in the ELISA assay.

  16. 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...

  17. MCO Membranes: Enhanced Selectivity in High-Flux Class

    NASA Astrophysics Data System (ADS)

    Boschetti-de-Fierro, Adriana; Voigt, Manuel; Storr, Markus; Krause, Bernd

    2015-12-01

    Novel MCO high-flux membranes for hemodialysis have been developed with optimized permeability, allowing for filtration close to that of the natural kidney. A comprehensive in vitro characterization of the membrane properties by dextran filtration is presented. The sieving profile of pristine membranes, as well as that of membranes exposed to blood for 40 minutes, are described. The effective pore size (Stokes-Einstein radius) was estimated from filtration experiments before and after blood exposure, and results were compared to hydrodynamic radii of middle and large uremic toxins and essential proteins. The results indicate that the tailored pore sizes of the MCO membranes promote removal of large toxins while ensuring the retention of albumin.

  18. Coherent selection of invisible high-order electromagnetic excitations

    NASA Astrophysics Data System (ADS)

    Tseng, Ming Lun; Fang, Xu; Savinov, Vassili; Wu, Pin Chieh; Ou, Jun-Yu; Zheludev, Nikolay I.; Tsai, Din Ping

    2017-03-01

    Far-field spectroscopy and mapping of electromagnetic near-field distribution are the two dominant tools for analysis and characterization of the electromagnetic response in nanophotonics. Despite the widespread use, these methods can fail at identifying weak electromagnetic excitations masked by stronger neighboring excitations. This is particularly problematic in ultrafast nanophotonics, including optical sensing, nonlinear optics and nanolasers, where the broad resonant modes can overlap to a significant degree. Here, using plasmonic metamaterials, we demonstrate that coherent spectroscopy can conveniently isolate and detect such hidden high-order photonic excitations. Our results establish that the coherent spectroscopy is a powerful new tool. It complements the conventional methods for analysis of the electromagnetic response, and provides a new route to designing and characterizing novel photonic devices and materials.

  19. MCO Membranes: Enhanced Selectivity in High-Flux Class.

    PubMed

    Boschetti-de-Fierro, Adriana; Voigt, Manuel; Storr, Markus; Krause, Bernd

    2015-12-16

    Novel MCO high-flux membranes for hemodialysis have been developed with optimized permeability, allowing for filtration close to that of the natural kidney. A comprehensive in vitro characterization of the membrane properties by dextran filtration is presented. The sieving profile of pristine membranes, as well as that of membranes exposed to blood for 40 minutes, are described. The effective pore size (Stokes-Einstein radius) was estimated from filtration experiments before and after blood exposure, and results were compared to hydrodynamic radii of middle and large uremic toxins and essential proteins. The results indicate that the tailored pore sizes of the MCO membranes promote removal of large toxins while ensuring the retention of albumin.

  20. Coherent selection of invisible high-order electromagnetic excitations

    PubMed Central

    Tseng, Ming Lun; Fang, Xu; Savinov, Vassili; Wu, Pin Chieh; Ou, Jun-Yu; Zheludev, Nikolay I.; Tsai, Din Ping

    2017-01-01

    Far-field spectroscopy and mapping of electromagnetic near-field distribution are the two dominant tools for analysis and characterization of the electromagnetic response in nanophotonics. Despite the widespread use, these methods can fail at identifying weak electromagnetic excitations masked by stronger neighboring excitations. This is particularly problematic in ultrafast nanophotonics, including optical sensing, nonlinear optics and nanolasers, where the broad resonant modes can overlap to a significant degree. Here, using plasmonic metamaterials, we demonstrate that coherent spectroscopy can conveniently isolate and detect such hidden high-order photonic excitations. Our results establish that the coherent spectroscopy is a powerful new tool. It complements the conventional methods for analysis of the electromagnetic response, and provides a new route to designing and characterizing novel photonic devices and materials. PMID:28295021

  1. High throughput development of selective oxidation catalysts at Süd-Chemie.

    PubMed

    Mestl, Gerhard

    2012-02-01

    The Temkin reactor concept was successfully extended to the high throughput operation mode and it could be considerably improved as compared to the original design with respect to an optimized gas flow pattern over the full size beads. This improved parallel reactor design was successfully used for the high throughput optimization of an innovative new class of physically coated VAM shell catalysts. Exploiting this novel, improved Temkin reactor concept allowed Süd-Chemie not only to optimize the multiparameter compositional space of noble metal and promoter loadings on the support spheres but for the first time to combine this "chemical optimization" with the high throughput improvement of catalytically decisive parameters as the active shell thickness, the metal distribution cross the shell, the pore diameters, and the pore volumes. This new class of physically impregnated VA catalysts, called VAM²ax, impress by its exceptionally high VA selectivity of above 94% at 50% oxygen conversion and the very high space time yields of > 1000 g VAM/l*h which easily can be reached over these shell catalysts with optimized mass and heat transport properties.

  2. (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels.

    PubMed

    Akbulut, Yasemin; Gaunt, Hannah J; Muraki, Katsuhiko; Ludlow, Melanie J; Amer, Mohamed S; Bruns, Alexander; Vasudev, Naveen S; Radtke, Lea; Willot, Matthieu; Hahn, Sven; Seitz, Tobias; Ziegler, Slava; Christmann, Mathias; Beech, David J; Waldmann, Herbert

    2015-03-16

    Current therapies for common types of cancer such as renal cell cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal cancer cells through activation of calcium-permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (-)-englerin A. This compound was found to be a highly efficient, fast-acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high-affinity extracellular (-)-englerin A binding site may open up novel opportunities for drug discovery aimed at renal cancer.

  3. 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

  4. Cellular prion protein in the bovine mammary gland is selectively expressed in active lactocytes.

    PubMed

    Didier, Andrea; Dietrich, Richard; Steffl, Martin; Gareis, Manfred; Groschup, Martin H; Müller-Hellwig, Simone; Märtlbauer, Erwin; Amselgruber, Werner M

    2006-11-01

    The cellular prion protein (PrP(c)) is a highly conserved glycoprotein with a still enigmatic physiological function. It is mainly expressed in the central nervous system but accumulating data suggest that PrP(c) is also found in a broad spectrum of non-neuronal tissue. Here we investigated the cell-type-related PrP(c) expression in the bovine mammary gland by using immunohistochemistry (IHC), ELISA, Western blot, and real-time RT-PCR. Specific immunostaining of serial sections revealed that PrP(c) is selectively localized in mammary gland epithelial cells. Particularly strong expression was found at the basolateral surface of those cells showing active secretion. Results obtained by RT-PCR and ELISA complemented IHC findings. No correlation was found between the level of PrP(c) expression and other parameters such as age of the animals under study or stage of lactation.

  5. 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

  6. Palladium-catalyzed meta-selective C-H bond activation with a nitrile-containing template: computational study on mechanism and origins of selectivity.

    PubMed

    Yang, Yun-Fang; Cheng, Gui-Juan; Liu, Peng; Leow, Dasheng; Sun, Tian-Yu; Chen, Ping; Zhang, Xinhao; Yu, Jin-Quan; Wu, Yun-Dong; Houk, K N

    2014-01-08

    Density functional theory investigations have elucidated the mechanism and origins of meta-regioselectivity of Pd(II)-catalyzed C-H olefinations of toluene derivatives that employ a nitrile-containing template. The reaction proceeds through four major steps: C-H activation, alkene insertion, β-hydride elimination, and reductive elimination. The C-H activation step, which proceeds via a concerted metalation-deprotonation (CMD) pathway, is found to be the rate- and regioselectivity-determining step. For the crucial C-H activation, four possible active catalytic species-monomeric Pd(OAc)2, dimeric Pd2(OAc)4, heterodimeric PdAg(OAc)3, and trimeric Pd3(OAc)6-have been investigated. The computations indicated that the C-H activation with the nitrile-containing template occurs via a Pd-Ag heterodimeric transition state. The nitrile directing group coordinates with Ag while the Pd is placed adjacent to the meta-C-H bond in the transition state, leading to the observed high meta-selectivity. The Pd2(OAc)4 dimeric mechanism also leads to the meta-C-H activation product but with higher activation energies than the Pd-Ag heterodimeric mechanism. The Pd monomeric and trimeric mechanisms require much higher activation free energies and are predicted to give ortho products. Structural and distortion energy analysis of the transition states revealed significant effects of distortions of the template on mechanism and regioselectivity, which provided hints for further developments of new templates.

  7. AHEAD: Integrated Activities in the High Energy Astrophysics Domain

    NASA Astrophysics Data System (ADS)

    Piro, Luigi; Natalucci, Lorenzo; Ahead Consortium

    2015-09-01

    AHEAD (Integrated Activities in the High Energy Astrophysics Domain) is a forthcoming project approved in the framework of the European Horizon 2020 program (Research Infrastructures for High Energy Astrophysics). The overall objective of AHEAD is to integrate national efforts in high-energy Astrophysics and to promote the domain at the European level, to keep its community at the cutting edge of science and technology and ensure that space observatories for high-energy astrophysics, with particular regard to Athena, are at the state of the art. AHEAD will integrate key research infrastructures for on-ground test and calibration of space-based sensors and electronics and promote their coordinated use. In parallel, the best facilities for data analysis of high-energy astrophysical observatories will be made available to the European community. The technological development will focus on the improvement of selected critical technologies, background modeling, cross calibration, and feasibility studies of space-based instrumentation for the benefit of future high energy missions like Athena, and the best exploitation of existing observatories. AHEAD will support the community via grants for collaborative studies, dissemination of results, and promotion of workshops. A strong public outreach package will ensure that the domain is well publicized at national, European and International level. Networking, joint research activities and access to infrastructures as devised in AHEAD, will serve to establish strong connections between institutes and industry to create the basis for a more rapid advancement of high-energy astrophysical science, space oriented instrumentation and cutting-edge sensor technology in Europe. This enables the development of new technologies and the associated growth of the European technology market with a dedicated technology innovation package, as well as the creation of a new generation of researchers.

  8. Thermal Expansion Studies of Selected High Temperature Thermoelectric Materials

    NASA Technical Reports Server (NTRS)

    Ravi, Vilupanur; Firdosy, Samad; Caillat, Thierry; Brandon, Erik; Van Der Walde, Keith; Maricic, Lina; Sayir, Ali

    2008-01-01

    Radioisotope thermoelectric generators (RTGs) generate electrical power by converting the heat released from the nuclear decay of radioactive isotopes (typically plutonium-238) into electricity using a thermoelectric converter. RTGs have been successfully used to power a number of space missions and have demonstrated their reliability over an extended period of time (tens of years) and are compact, rugged, radiation resistant, scalable, and produce no noise, vibration or torque during operation. System conversion efficiency for state-of-practice RTGs is about 6% and specific power less than or equal to 5.1 W/kg. Higher specific power would result in more on-board power for the same RTG mass, or less RTG mass for the same on-board power. The Jet Propulsion Laboratory has been leading, under the advanced thermoelectric converter (ATEC) project, the development of new high-temperature thermoelectric materials and components for integration into advanced, more efficient RTGs. Thermoelectric materials investigated to date include skutterudites, the Yb14MnSb11 compound, and SiGe alloys. The development of long-lived thermoelectric couples based on some of these materials has been initiated and is assisted by a thermo-mechanical stress analysis to ensure that all stresses under both fabrication and operation conditions will be within yield limits for those materials. Several physical parameters are needed as input to this analysis. Among those parameters, the coefficient of thermal expansion (CTE) is critically important. Thermal expansion coefficient measurements of several thermoelectric materials under consideration for ATEC are described in this paper. The stress response at the interfaces in material stacks subjected to changes in temperature is discussed, drawing on work from the literature and project-specific tools developed here. The degree of CTE mismatch and the associated effect on the formation of stress is highlighted.

  9. Thermal Expansion Studies of Selected High-Temperature Thermoelectric Materials

    NASA Astrophysics Data System (ADS)

    Ravi, Vilupanur; Firdosy, Samad; Caillat, Thierry; Brandon, Erik; van der Walde, Keith; Maricic, Lina; Sayir, Ali

    2009-07-01

    Radioisotope thermoelectric generators (RTGs) generate electrical power by converting the heat released from the nuclear decay of radioactive isotopes (typically plutonium-238) into electricity using a thermoelectric converter. RTGs have been successfully used to power a number of space missions and have demonstrated their reliability over an extended period of time (tens of years) and are compact, rugged, radiation resistant, scalable, and produce no noise, vibration or torque during operation. System conversion efficiency for state-of-practice RTGs is about 6% and specific power ≤5.1 W/kg. A higher specific power would result in more onboard power for the same RTG mass, or less RTG mass for the same onboard power. The Jet Propulsion Laboratory has been leading, under the advanced thermoelectric converter (ATEC) project, the development of new high-temperature thermoelectric materials and components for integration into advanced, more efficient RTGs. Thermoelectric materials investigated to date include skutterudites, the Yb14MnSb11 compound, and SiGe alloys. The development of long-lived thermoelectric couples based on some of these materials has been initiated and is assisted by a thermomechanical stress analysis to ensure that all stresses under both fabrication and operation conditions will be within yield limits for those materials. Several physical parameters are needed as input to this analysis. Among those parameters, the coefficient of thermal expansion (CTE) is critically important. Thermal expansion coefficient measurements of several thermoelectric materials under consideration for ATEC are described in this paper. The stress response at the interfaces in material stacks subjected to changes in temperature is discussed, drawing on work from the literature and project-specific tools developed here. The degree of CTE mismatch and the associated effect on the formation of stress is highlighted.

  10. Characterization of a highly active promoter, PBbgpd, in Beauveria bassiana.

    PubMed

    Liao, Xing-gang; Fang, Wei-guo; Zhang, Yong-jun; Fan, Yan-hua; Wu, Xing-wei; Zhou, Qun; Pei, Yan

    2008-08-01

    The promoter of glyceraldehyde-3-phosphate dehydrogenase (gpd) gene from Aspergillus nidulans (PgpdA) is widely used to direct expression of target genes constitutively in fungi. However, in some species, a heterogeneous promoter is found to be of low efficiency. To obtain a high-efficiency promoter for transformation of Beauveria bassiana, an entomopathogenic fungus widely used as an mycoinsecticide, a glyceraldehyde-3-phosphate dehydrogenase gene (Bbgpd) promoter, was cloned and characterized. Four deletion constructs (-2118, -1153, -726, and -354) of the 5'-upstream sequence of Bbgpd linked to a bar::gus fusion gene (phosphinothricin-resistance::beta-glucuronidase fused gene), which were used as selected marker gene and report gene, respectively, were generated. GUS activities of transgenic strains harboring -726, -1153, and -2118 deletion constructs were much stronger than that of the promoter of Aspergillus nidulans gpdA (PgpdA), with a twofold to threefold increase over that in the PgpdA construct. The -726 fragment was necessary to direct GUS expression in B. bassiana. No -354 transgenic progenies were obtained, possibly because it failed to initiate the transcription of bar::gus fusion gene. A remarkable increase of GUS activity was found between the -1153 and -726 constructs, indicating that some active transcriptional elements were located in this region. With a high expression level and relatively short sequence, PBbgpd can be used to drive target genes in B. bassiana transgenic research.

  11. Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II.

    PubMed

    Tykvart, Jan; Schimer, Jiří; Jančařík, Andrej; Bařinková, Jitka; Navrátil, Václav; Starková, Jana; Šrámková, Karolína; Konvalinka, Jan; Majer, Pavel; Šácha, Pavel

    2015-05-28

    We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.

  12. Isolation and characterization of actinomycetes strains that produce phospholipase D having high transphosphatidylation activity.

    PubMed

    Nakazawa, Yozo; Uchino, Masataka; Sagane, Yoshimasa; Sato, Hiroaki; Takano, Katsumi

    2009-01-01

    The present study was conducted to screen microorganisms that produce phospholipase D (PLD), and we especially focused on the strains having high transphosphatidylation activity. Eighty bacterial strains were isolated from soil samples by a screening method utilizing a preliminary selection medium with phosphatidylcholine (PC) as the sole carbon source. The culture supernatants were then assayed for PLD activity. The finding of dual PLD activities in cultures revealed that the hydrolytic and transphosphatidylation activities were correlated. Consequently, six strains were selected as stably producing PLD enzyme(s) during continuous subcultures. The culture supernatants of selected strains synthesized phosphatidylglycerol, phosphatidylserine and phosphatidylethanolamine from PC with high conversion rates. These isolated strains will be made available to carry out phospholipid modification through the efficient transphosphatidylation activity of the PLD that they produce.

  13. Selectively lighting up two-photon photodynamic activity in mitochondria with AIE-active iridium(iii) complexes.

    PubMed

    Liu, Jiangping; Jin, Chengzhi; Yuan, Bo; Liu, Xingguo; Chen, Yu; Ji, Liangnian; Chao, Hui

    2017-02-07

    Herein a series of mitochondria-targeted AIE (aggregation-induced emission)-active Ir(iii) complexes were designed to selectively exert one-/two-photon photodynamic activities in mitochondria to address the issues which current PDT are confronted with (i.e., shallow penetration depth of routinely used irradiation; systematic toxicity associated with effective drug concentration; concentration-quenched photodynamic activity at the target, etc.).

  14. Green fluorescent protein retroviral vectors: low titer and high recombination frequency suggest a selective disadvantage.

    PubMed

    Hanazono, Y; Yu, J M; Dunbar, C E; Emmons, R V

    1997-07-20

    Green fluorescent protein (GFP) has been used as a reporter molecule for gene expression because it fluoresces green after blue-light excitation. Inclusion of this gene in a vector could allow rapid, nontoxic selection of successfully transduced cells. However, many attempts by our laboratory to isolate stable retroviral producer cell clones secreting biologically active vectors containing either the highly fluorescent S65T-GFP mutant or humanized GFP have failed. Vector plasmids containing various forms of GFP and the neomycin resistance gene were transfected into three different packaging cell lines and fluorescence was observed for several days, but stable clones selected with G418 no longer fluoresced. Using confocal microscopy, the brightest cells were observed to contract and die within a matter of days. RNA slot-blot analysis of retroviral producer supernatants showed no viral production from the GFP plasmid-transfected clones, although all clones derived after transfection with an identical retroviral construct not containing GFP produced virus. Genomic Southern analysis of the GFP-transduced clones showed a much higher probability of rearrangement of the priviral sequences than in the control non-GFP clones. Overall, 18/34 S65T-GFP clones and 17/33 humanized-GFP clones had rearrangements, whereas 2/15 control non-GFP clones had rearrangements. Hence, producer cells expressing high levels of these GFP genes seem to be selected against, with stable clones undergoing major rearrangements or other mutations that both abrogate GFP expression and prevent vector production. These observations indicate that GFP may not be an appropriate reporter gene for gene transfer applications in our vector/packaging system.

  15. Discovery of a Highly Selective, Brain-Penetrant Aminopyrazole LRRK2 Inhibitor.

    PubMed

    Chan, Bryan K; Estrada, Anthony A; Chen, Huifen; Atherall, John; Baker-Glenn, Charles; Beresford, Alan; Burdick, Daniel J; Chambers, Mark; Dominguez, Sara L; Drummond, Jason; Gill, Andrew; Kleinheinz, Tracy; Le Pichon, Claire E; Medhurst, Andrew D; Liu, Xingrong; Moffat, John G; Nash, Kevin; Scearce-Levie, Kimberly; Sheng, Zejuan; Shore, Daniel G; Van de Poël, Hervé; Zhang, Shuo; Zhu, Haitao; Sweeney, Zachary K

    2013-01-10

    The modulation of LRRK2 kinase activity by a selective small molecule inhibitor has been proposed as a potentially viable treatment for Parkinson's disease. By using aminopyrazoles as aniline bioisosteres, we discovered a novel series of LRRK2 inhibitors. Herein, we describe our optimization effort that resulted in the identification of a highly potent, brain-penetrant aminopyrazole LRRK2 inhibitor (18) that addressed the liabilities (e.g., poor solubility and metabolic soft spots) of our previously disclosed anilino-aminopyrimidine inhibitors. In in vivo rodent PKPD studies, 18 demonstrated good brain exposure and engendered significant reduction in brain pLRRK2 levels post-ip administration. The strategies of bioisosteric substitution of aminopyrazoles for anilines and attenuation of CYP1A2 inhibition described herein have potential applications to other drug discovery programs.

  16. Design and Synthesis of Phenylpyrrolidine Phenylglycinamides As Highly Potent and Selective TF-FVIIa Inhibitors

    PubMed Central

    2013-01-01

    Inhibitors of the Tissue Factor/Factor VIIa (TF-FVIIa) complex are promising novel anticoagulants that show excellent efficacy and minimal bleeding in preclinical models. On the basis of a zwitterionic phenylglycine acylsulfonamide 1, a phenylglycine benzylamide 2 was shown to possess improved permeability and oral bioavailability. Optimization of the benzylamide, guided by X-ray crystallography, led to a potent TF-FVIIa inhibitor 18i with promising oral bioavailability, but promiscuous activity in an in vitro safety panel of receptors and enzymes. Introducing an acid on the pyrrolidine ring, guided by molecular modeling, resulted in highly potent, selective, and efficacious TF-FVIIa inhibitors with clean in vitro safety profile. The pyrrolidine acid 20 showed a moderate clearance, low volume of distribution, and a short t1/2 in dog PK studies. PMID:24900796

  17. Metal-organic frameworks with high capacity and selectivity for harmful gases

    PubMed Central

    Britt, David; Tranchemontagne, David; Yaghi, Omar M.

    2008-01-01

    Benchmarks have been established for the performance of six metal-organic frameworks (MOFs) and isoreticular MOFs (IRMOFs, which have the same underlying topology as MOF-5), MOF-5, IRMOF-3, MOF-74, MOF-177, MOF-199, and IRMOF-62, as selective adsorbents for eight harmful gases: sulfur dioxide, ammonia, chlorine, tetrahydrothiophene, benzene, dichloromethane, ethylene oxide, and carbon monoxide. Kinetic breakthrough measurements are used to determine the calculated dynamic adsorption capacity of each “benchmark” MOF for each gas. The capacity of each MOF is compared to that of a sample of Calgon BPL activated carbon. We find that pore functionality plays a dominant role in determining the dynamic adsorption performance of MOFs. MOFs featuring reactive functionality outperform BPL carbon in all but one case and exhibit high dynamic adsorption capacities up to 35% by weight. PMID:18711128

  18. Highly sensitive and selective electrochemical dopamine sensing properties of multilayer graphene nanobelts

    NASA Astrophysics Data System (ADS)

    Karthick Kannan, Padmanathan; Moshkalev, Stanislav A.; Sekhar Rout, Chandra

    2016-02-01

    In the present study, we report the electrochemical sensing property of multi-layer graphene nanobelts (GNBs) towards dopamine (DA). GNBs are synthesized from natural graphite and characterized by using techniques like field-emission scanning electron microscopy, atomic force microscopy and Raman spectroscopy. An electrochemical sensor based on GNBs is developed for the detection of DA. From the cyclic voltammetry and amperometry studies, it is found that GNBs possess excellent electrocatalytic activity towards DA molecules. The developed DA sensor showed a sensitivity value of 0.95 μA μM-1 cm-2 with a linear range of 2 μM to 0.2 mM. The interference data exhibited that GNB is highly selective to DA even in the presence of common interfering species like ascorbic acid, uric acid, glucose and lactic acid.

  19. Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues.

    PubMed

    Ashton, M J; Cook, D C; Fenton, G; Karlsson, J A; Palfreyman, M N; Raeburn, D; Ratcliffe, A J; Souness, J E; Thurairatnam, S; Vicker, N

    1994-05-27

    The syntheses and biological activities of a number of benzamide derivatives, designed from rolipram, which are selective inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), are described. The effects of changes to the alkoxy groups, amide linkage, and benzamide N-phenyl ring on the inhibition of the cytosolic PDE IV from pig aorta have been investigated. As a result, some highly potent and selective PDE IV inhibitors have been identified. The most potent compounds have been further evaluated for their inhibitory potencies against PDE IV obtained from and superoxide O2- generation from guinea pig eosinophils in vitro. Selected compounds have also been examined for their activities in inhibiting histamine-induced bronchospasm in anaesthetized guinea pigs. 3-(Cyclopentyloxy)-N-(3,5-dichloro-4-pyridyl)-4-methoxybenzamide (15j) showed exceptional potency in all tests and may have therapeutic potential in the treatment of asthma.

  20. Carbonic anhydrase activators. The selective serotonin reuptake inhibitors fluoxetine, sertraline and citalopram are strong activators of isozymes I and II.

    PubMed

    Casini, Angela; Caccia, Silvio; Scozzafava, Andrea; Supuran, Claudiu T

    2003-08-18

    The selective serotonin reuptake inhibitors (SSRI) fluoxetine, sertraline and citalopram have been investigated for their ability to activate two carbonic anhydrase (CA) isozymes, hCA I and hCA II, in parallel with two standard activators for which the X-ray structure (in complex with isozyme II) has been resolved: histamine and phenylalanine. All three SSRI activated both isozymes with potencies comparable to that of the standards although the profile was different: for hCA I, best activators were fluoxetine and histamine, with citalopram and sertraline showing weaker activity. For hCA II, the best activators were phenylalanine and citalopram, and the weakest histamine and sertraline, whereas fluoxetine showed an intermediate behavior. These results suggest that SSRI efficacy in major depression complicating Alzheimer's disease may be partly due to their ability to activate CA isozymes and may lead to the development of potent activators for the therapy of diseases associated with significant decreases in brain CA activity.

  1. High-Throughput Analysis of Enzyme Activities

    SciTech Connect

    Lu, Guoxin

    2007-01-01

    High-throughput screening (HTS) techniques have been applied to many research fields nowadays. Robot microarray printing technique and automation microtiter handling technique allows HTS performing in both heterogeneous and homogeneous formats, with minimal sample required for each assay element. In this dissertation, new HTS techniques for enzyme activity analysis were developed. First, patterns of immobilized enzyme on nylon screen were detected by multiplexed capillary system. The imaging resolution is limited by the outer diameter of the capillaries. In order to get finer images, capillaries with smaller outer diameters can be used to form the imaging probe. Application of capillary electrophoresis allows separation of the product from the substrate in the reaction mixture, so that the product doesn't have to have different optical properties with the substrate. UV absorption detection allows almost universal detection for organic molecules. Thus, no modifications of either the substrate or the product molecules are necessary. This technique has the potential to be used in screening of local distribution variations of specific bio-molecules in a tissue or in screening of multiple immobilized catalysts. Another high-throughput screening technique is developed by directly monitoring the light intensity of the immobilized-catalyst surface using a scientific charge-coupled device (CCD). Briefly, the surface of enzyme microarray is focused onto a scientific CCD using an objective lens. By carefully choosing the detection wavelength, generation of product on an enzyme spot can be seen by the CCD. Analyzing the light intensity change over time on an enzyme spot can give information of reaction rate. The same microarray can be used for many times. Thus, high-throughput kinetic studies of hundreds of catalytic reactions are made possible. At last, we studied the fluorescence emission spectra of ADP and obtained the detection limits for ADP under three different

  2. Highly Selective H2 Separation Zeolite Membranes for Coal Gasification Membrane Reactor Applications

    SciTech Connect

    Mei Hong; Richard Noble; John Falconer

    2007-09-24

    Zeolite membranes are thermally, chemically, and mechanically stable. They also have tunable molecular sieving and catalytic ability. These unique properties make zeolite membrane an excellent candidate for use in catalytic membrane reactor applications related to coal conversion and gasification, which need high temperature and high pressure range separation in chemically challenging environment where existing technologies are inefficient or unable to operate. Small pore, good quality, and thin zeolite membranes are needed for highly selective H2 separation from other light gases (CO2, CH4, CO). However, current zeolite membranes have either too big zeolite pores or a large number of defects and have not been successful for H2 separation from light gases. The objective of this study is to develop zeolite membranes that are more suitable for H2 separation. In an effort to tune the size of zeolite pores and/or to decrease the number of defects, medium-pore zeolite B-ZSM-5 (MFI) membranes were synthesized and silylated. Silylation on B-ZSM-5 crystals reduced MFI-zeolite pore volume, but had little effect on CO2 and CH4 adsorption. Silylation on B-ZSM-5 membranes increased H2 selectivity both in single component and in mixtures with CO2, CH4, or N2. Single gas and binary mixtures of H2/CO2 and H2/CH4 were permeated through silylated B-ZSM-5 membranes at feed pressures up to 1.7 MPa and temperatures up to 773 K. For one B-ZSM-5 membrane after silylation, the H2/CO2 separation selectivity at 473 K increased from 1.4 to 37, whereas the H2/CH4 separation selectivity increased from 1.6 to 33. Hydrogen permeance through a silylated BZSM-5 membrane was activated with activation energy of {approx}10 kJ/mol, but the CO2 and CH4 permeances decreased slightly with temperature in both single gas and in mixtures. Therefore, the H2 permeance and H2/CO2 and H2/CH4 separation selectivities increased with temperature. At 673 K, the H2 permeance was 1.0x10-7 mol{center_dot}m-2{center

  3. One-Step Synthesis of Microporous Carbon Monoliths Derived from Biomass with High Nitrogen Doping Content for Highly Selective CO2 Capture

    PubMed Central

    Geng, Zhen; Xiao, Qiangfeng; Lv, Hong; Li, Bing; Wu, Haobin; Lu, Yunfeng; Zhang, Cunman

    2016-01-01

    The one-step synthesis method of nitrogen doped microporous carbon monoliths derived from biomass with high-efficiency is developed using a novel ammonia (NH3)-assisted activation process, where NH3 serves as both activating agent and nitrogen source. Both pore forming and nitrogen doping simultaneously proceed during the process, obviously superior to conventional chemical activation. The as-prepared nitrogen-doped active carbons exhibit rich micropores with high surface area and high nitrogen content. Synergetic effects of its high surface area, microporous structure and high nitrogen content, especially rich nitrogen-containing groups for effective CO2 capture (i.e., phenyl amine and pyridine-nitrogen) lead to superior CO2/N2 selectivity up to 82, which is the highest among known nanoporous carbons. In addition, the resulting nitrogen-doped active carbons can be easily regenerated under mild conditions. Considering the outstanding CO2 capture performance, low production cost, simple synthesis procedure and easy scalability, the resulting nitrogen-doped microporous carbon monoliths are promising candidates for selective capture of CO2 in industrial applications. PMID:27488268

  4. One-Step Synthesis of Microporous Carbon Monoliths Derived from Biomass with High Nitrogen Doping Content for Highly Selective CO2 Capture.

    PubMed

    Geng, Zhen; Xiao, Qiangfeng; Lv, Hong; Li, Bing; Wu, Haobin; Lu, Yunfeng; Zhang, Cunman

    2016-08-04

    The one-step synthesis method of nitrogen doped microporous carbon monoliths derived from biomass with high-efficiency is developed using a novel ammonia (NH3)-assisted activation process, where NH3 serves as both activating agent and nitrogen source. Both pore forming and nitrogen doping simultaneously proceed during the process, obviously superior to conventional chemical activation. The as-prepared nitrogen-doped active carbons exhibit rich micropores with high surface area and high nitrogen content. Synergetic effects of its high surface area, microporous structure and high nitrogen content, especially rich nitrogen-containing groups for effective CO2 capture (i.e., phenyl amine and pyridine-nitrogen) lead to superior CO2/N2 selectivity up to 82, which is the highest among known nanoporous carbons. In addition, the resulting nitrogen-doped active carbons can be easily regenerated under mild conditions. Considering the outstanding CO2 capture performance, low production cost, simple synthesis procedure and easy scalability, the resulting nitrogen-doped microporous carbon monoliths are promising candidates for selective capture of CO2 in industrial applications.

  5. One-Step Synthesis of Microporous Carbon Monoliths Derived from Biomass with High Nitrogen Doping Content for Highly Selective CO2 Capture

    NASA Astrophysics Data System (ADS)

    Geng, Zhen; Xiao, Qiangfeng; Lv, Hong; Li, Bing; Wu, Haobin; Lu, Yunfeng; Zhang, Cunman

    2016-08-01

    The one-step synthesis method of nitrogen doped microporous carbon monoliths derived from biomass with high-efficiency is developed using a novel ammonia (NH3)-assisted activation process, where NH3 serves as both activating agent and nitrogen source. Both pore forming and nitrogen doping simultaneously proceed during the process, obviously superior to conventional chemical activation. The as-prepared nitrogen-doped active carbons exhibit rich micropores with high surface area and high nitrogen content. Synergetic effects of its high surface area, microporous structure and high nitrogen content, especially rich nitrogen-containing groups for effective CO2 capture (i.e., phenyl amine and pyridine-nitrogen) lead to superior CO2/N2 selectivity up to 82, which is the highest among known nanoporous carbons. In addition, the resulting nitrogen-doped active carbons can be easily regenerated under mild conditions. Considering the outstanding CO2 capture performance, low production cost, simple synthesis procedure and easy scalability, the resulting nitrogen-doped microporous carbon monoliths are promising candidates for selective capture of CO2 in industrial applications.

  6. Surface free energy activated high-throughput cell sorting.

    PubMed

    Zhang, Xinru; Zhang, Qian; Yan, Tao; Jiang, Zeyi; Zhang, Xinxin; Zuo, Yi Y

    2014-09-16

    Cell sorting is an important screening process in microbiology, biotechnology, and clinical research. Existing methods are mainly based on single-cell analysis as in flow cytometric and microfluidic cell sorters. Here we report a label-free bulk method for sorting cells by differentiating their characteristic surface free energies (SFEs). We demonstrated the feasibility of this method by sorting model binary cell mixtures of various bacterial species, including Pseudomonas putida KT2440, Enterococcus faecalis ATCC 29212, Salmonella Typhimurium ATCC 14028, and Escherichia coli DH5α. This method can effectively separate 10(10) bacterial cells within 30 min. Individual bacterial species can be sorted with up to 96% efficiency, and the cell viability ratio can be as high as 99%. In addition to its capacity of sorting evenly mixed bacterial cells, we demonstrated the feasibility of this method in selecting and enriching cells of minor populations in the mixture (presenting at only 1% in quantity) to a purity as high as 99%. This SFE-activated method may be used as a stand-alone method for quickly sorting a large quantity of bacterial cells or as a prescreening tool for microbial discrimination. Given its advantages of label-free, high-throughput, low cost, and simplicity, this SFE-activated cell sorting method has potential in various applications of sorting cells and abiotic particles.

  7. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases

    PubMed Central

    Oprea, Tudor I.; Sklar, Larry A.; Agola, Jacob O.; Guo, Yuna; Silberberg, Melina; Roxby, Joshua; Vestling, Anna; Romero, Elsa; Surviladze, Zurab; Murray-Krezan, Cristina; Waller, Anna; Ursu, Oleg; Hudson, Laurie G.; Wandinger-Ness, Angela

    2015-01-01

    Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses—using the rotationally constrained carboxylate in R-naproxen—led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and

  8. Selective human endothelial cell activation by chemokines as a guide to cell homing.

    PubMed

    Crola Da Silva, Claire; Lamerant-Fayel, Nathalie; Paprocka, Maria; Mitterrand, Michèle; Gosset, David; Dus, Danuta; Kieda, Claudine

    2009-03-01

    An original model of organo-specific, immortalized and stabilized endothelial cell lines was used to delineate the part played by some chemokines (CCL21, CX3CL1, CCL5 and CXCL12) and their receptors in endothelium organo-specificity. Chemokine receptor expression and chemokine presentation were investigated on organo-specific human endothelial cell lines. Although the chemokines showed distinct binding patterns for the various endothelial cell lines, these were not correlated with the expression of the corresponding receptors (CX3CR1, CXCR4, CCR5 and CCR7). Experiments with CCL21 on peripheral lymph node endothelial cells demonstrated that the chemokine did not co-localize with its receptor but was associated with extracellular matrix components. The specific activity of chemokines was clearly shown to be related to the endothelial cell origin. Indeed, CX3CL1 and CCL21 promoted lymphocyte recruitment by endothelial cells from the appendix and peripheral lymph nodes, respectively, while CX3CL1 pro-angiogenic activity was restricted to endothelial cells from the appendix and skin. The high specificity of the chemokine/endothelium interaction allowed the design of a direct in vitro endothelial cell targeting assay. This unique cellular model demonstrated a fundamental role for chemokines in conferring on the endothelium its organo-specificity and its potential for tissue targeting through the selective binding, presentation and activation properties of chemokines.

  9. Biological Screening of Select Puerto Rican Plants for Cytotoxic and Antitumor Activities

    PubMed Central

    Campos, Karla Claudio; Rivera, Janibeth Hernández; Gutierrez, Jaymie Rivera; Rivera, Isamar Ortiz; Velez, Augusto Carvajal; Torres, Marianela Pérez; Ortiz, Mayra Pagán; Millán, Claudia A. Ospina

    2015-01-01

    Objective The objective of this study was to evaluate the cytotoxic and anticancer activities of extracts from 7 species of endemic and native plants from Puerto Rico. Methods The plant species selected for this study were Canella winterana, Croton discolor, Goetzea elegans, Guaiacum officinale, Pimenta racemosa, Simarouba tulae, and Thouinia striata. The dried plant material was extracted with a 1:1 mixture of CH2Cl2-MeOH. The resulting crude extract was suspended in water and extracted with solvents of different polarities. The extracts were evaluated for their cytotoxic effects against Artemia salina and 3 breast cancer cell lines. Results About 50% of the extracts evaluated against Artemia salina exhibited LC50 values of less than or equal to 200 µg/mL. The strongest activity was detected in the chloroform and ethyl acetate extracts of Guaiacum officinale, with lethality values below 10 µg/mL. The extracts were further evaluated for their bioactivity as possible inhibitors of several breast cancer cell lines, with the extracts from Simarouba tulae and Croton discolor showing the highest percentages of growth inhibition. The dose-effect data analysis for the crude extracts of the different plants also confirms the high cytotoxicities of Guaiacum officinale, Simarouba tulae, and Croton discolor. Conclusion Based on our results, we concluded that the Simarouba, Croton, and Guaiacum plant extracts show cytotoxic and anticancer activities that merit closer investigation in order to identify the chemical compounds responsible for these bioactivities. PMID:25856874

  10. Metabolic Activity of Bacteria at High Pressure

    NASA Astrophysics Data System (ADS)

    Picard, A.; Daniel, I.; Oger, P.

    2008-12-01

    Over the last 20 years, there has been increasing evidence for the presence of a large number of microbes in the oceanic subsurface. Such a habitat has a very low energy input because it is deprived of light. A few meters below the sediment surface, conditions are already anoxic in most cases, sulfate reduction and/or methanogenesis becoming thus the primary respiratory reactions of organic matter. Neither the fate of methanogenesis, nor the fate of Dissimilatory Metal-Reduction (DMR) has been investigated so far as a function of pressure. For this reason, we measured experimentally the pressure limits of microbial anaerobic energetic metabolism. In practice, we measured in situ the kinetics of selenite respiration by the bacterial model Shewanella oneidensis MR-1 under high hydrostatic pressure (HHP) between 0 and 150 MPa at 30°C. MR-1 stationary-phase cells were used in Luria-Bertani (LB) medium amended with lactate as an additional electron donor and sodium selenite as an electron acceptor. In situ measurements were performed by X- ray Absorption Near-Edge Structure (XANES) spectroscopy in both a diamond-anvil cell and an autoclave. A red precipitate of amorphous Se(0) was virtually observed at any pressure to 150 MPa. A progressive reduction of selenite Se(IV) into selenium Se(0) was also observed in the evolution of XANES spectra with time. All kinetics between 0.1 and 150 MPa can be adjusted to a first order kinetic law. MR-1 respires all available selenite up to 60 MPa. Above 60 MPa, the respiration yield decreases linearly as a function of pressure and reaches 0 at 155 ±5 MPa. This indicates that selenite respiration by Shewanella oneidensis MR-1 stops at about 155 MPa, whereas its growth is arrested at 50 MPa. Hence, the present results show that the respiration of selenium by the strain MR-1 occurs efficiently up to 60 MPa and 30°C, i.e. from the surface of a continental sediment to an equivalent depth of about 2 km, or beneath a 5-km water column and

  11. Wind selection and drift compensation optimize migratory pathways in a high-flying moth.

    PubMed

    Chapman, Jason W; Reynolds, Don R; Mouritsen, Henrik; Hill, Jane K; Riley, Joe R; Sivell, Duncan; Smith, Alan D; Woiwod, Ian P

    2008-04-08

    Numerous insect species undertake regular seasonal migrations in order to exploit temporary breeding habitats [1]. These migrations are often achieved by high-altitude windborne movement at night [2-6], facilitating rapid long-distance transport, but seemingly at the cost of frequent displacement in highly disadvantageous directions (the so-called "pied piper" phenomenon [7]). This has lead to uncertainty about the mechanisms migrant insects use to control their migratory directions [8, 9]. Here we show that, far from being at the mercy of the wind, nocturnal moths have unexpectedly complex behavioral mechanisms that guide their migratory flight paths in seasonally-favorable directions. Using entomological radar, we demonstrate that free-flying individuals of the migratory noctuid moth Autographa gamma actively select fast, high-altitude airstreams moving in a direction that is highly beneficial for their autumn migration. They also exhibit common orientation close to the downwind direction, thus maximizing the rectilinear distance traveled. Most unexpectedly, we find that when winds are not closely aligned with the moth's preferred heading (toward the SSW), they compensate for cross-wind drift, thus increasing the probability of reaching their overwintering range. We conclude that nocturnally migrating moths use a compass and an inherited preferred direction to optimize their migratory track.

  12. Highly Selective and Stable Reduction of CO2 to CO by a Graphitic Carbon Nitride/Carbon Nanotube Composite Electrocatalyst.

    PubMed

    Lu, Xunyu; Tan, Tze Hao; Ng, Yun Hau; Amal, Rose

    2016-08-16

    A stable and selective electrocatalyst for CO2 reduction was fabricated by covalently attaching graphitic carbon nitride onto multiwall carbon nanotubes (g-C3 N4 /MWCNTs). The as-prepared composite is able to reduce CO2 exclusively to CO with a maximum Faraday efficiency of 60 %, and no decay in the catalytic activity was observed even after 50 h of reaction. The enhanced catalytic activity towards CO2 reduction is attributed to the formation of active carbon-nitrogen bonds, high specific surface area, and improved material conductivity of the g-C3 N4 /MWCNT composite.

  13. Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors.

    PubMed

    Brullo, Chiara; Massa, Matteo; Villa, Carla; Ricciarelli, Roberta; Rivera, Daniela; Pronzato, Maria Adelaide; Fedele, Ernesto; Barocelli, Elisabetta; Bertoni, Simona; Flammini, Lisa; Bruno, Olga

    2015-07-01

    A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B2 and PDE4C2). Compound 3b, chosen among the synthesized compounds as the most promising in terms of inhibitory activity, selectivity and safety, showed an improved pharmacokinetic profile compared to its non fluorinated analogue. Spontaneous locomotor activity, assessed in an open field apparatus, showed that, differently from rolipram and diazepam, selective PDE4D inhibitors, such as compounds 3b, 5b and 7b, did not affect locomotion, whereas compound 1b showed a tendency to reduce the distance traveled and to prolong the immobility period, possibly due to a poor selectivity.

  14. Stress selectively and lastingly promotes learning of context-related high arousing information.

    PubMed

    Smeets, Tom; Wolf, Oliver T; Giesbrecht, Timo; Sijstermans, Kevin; Telgen, Sebastian; Joëls, Marian

    2009-09-01

    The secretion of adrenal stress hormones in response to acute stress is known to affect learning and memory, particularly for emotionally arousing memory material. Here, we investigated whether stress-induced modulation of learning and memory performance depends on (i) the conceptual relatedness between the material to be learned/remembered and the stressor and (ii) the timing of stress exposure versus learning phase. Participants learned stressor-related and stressor-unrelated words of varying arousal 1h prior to, immediately following, or 2h after exposure to the Trier Social Stress Test (all groups n=16). Twenty-four hours later, delayed free recall was assessed. Cortisol and alpha-amylase were sampled to evaluate if concurrent stress-induced raised glucocorticoid levels and high adrenergic activity are implicated in modulating learning performance. Our results demonstrate that immediate and delayed post-stress learning selectively enhanced the learning and delayed recall of stressor-related high arousing words. This enhancing effect was strongly associated with concurrent stress-induced cortisol and sympathetic activity. Our data suggest that when to-be-learned information is conceptually related to a stressor and considered important (i.e., arousing) by the individual, learning under stressful circumstances results in improved memorability afterwards.

  15. Highly selective PdCu/amorphous silica-alumina (ASA) catalysts for groundwater denitration.

    PubMed

    Xie, Yongbing; Cao, Hongbin; Li, Yuping; Zhang, Yi; Crittenden, John C

    2011-05-01

    Catalytic nitrate reduction is a promising technology in groundwater purification. In this study, PdCu bimetallic catalysts supported on an industrial amorphous silica-alumina (ASA) were synthesized and used to simulate catalytic removal of nitrate in groundwater. The catalysts exhibited very high activity and the highest catalytic selectivity toward N₂O and N₂ was 90.2%. The optimal Pd/Cu weight ratio was four. Relatively low reduction temperature was found benefit the catalytic stability and 300 °C was the appropriate reduction temperature during catalyst preparation. With an average particle size 5.4 nm, the metal particles were very uniformly distributed on the catalyst surface prepared with the codeposition method. This kept the catalyst more stable than the PdCu/Al₂O₂ catalyst with larger metal particles. According to XRD, TEM, and XPS results, the metals maintained zero-valence but aggregated by about 2 nm during the denitration reaction, which caused gradual deactivation of the catalysts. Little leaching of Cu and Pd from the catalyst might also have a slightly negative impact to the stability of the catalysts. A simple treatment was found to redistribute the particles on the deactivated catalysts, and high catalytic activity was recovered after this process.

  16. Associations between selected demographic, biological, school environmental and physical education based correlates, and adolescent physical activity.

    PubMed

    Hilland, Toni A; Ridgers, Nicola D; Stratton, Gareth; Fairclough, Stuart J

    2011-02-01

    The study investigated associations between selected physical activity correlates among 299 adolescents (90 boys, age 12-14 years) from 3 English schools. Physical activity was assessed by self-report and accelerometry. Correlates represented biological, predisposing, and demographic factors as described in the Youth Physical Activity Promotion Model. Boys engaged in more self-reported (p < .01) and accelerometer a