Sample records for forms potent contact

  1. Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens

    SciTech Connect

    Hagvall, Lina [Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, SE-412 96 Gothenburg (Sweden); Baron, Jens Malte [Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen (Germany); Boerje, Anna [Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, SE-412 96 Gothenburg (Sweden); Weidolf, Lars [Discovery DMPK and Bioanalytical Chemistry, AstraZeneca R and D Moelndal, SE-421 83 Moelndal (Sweden); Merk, Hans [Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen (Germany); Karlberg, Ann-Therese [Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, SE-412 96 Gothenburg (Sweden)], E-mail: karlberg@chem.gu.se

    2008-12-01

    Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktail consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol.

  2. Front contact solar cell with formed emitter

    DOEpatents

    Cousins, Peter John (Menlo Park, CA)

    2012-07-17

    A bipolar solar cell includes a backside junction formed by an N-type silicon substrate and a P-type polysilicon emitter formed on the backside of the solar cell. An antireflection layer may be formed on a textured front surface of the silicon substrate. A negative polarity metal contact on the front side of the solar cell makes an electrical connection to the substrate, while a positive polarity metal contact on the backside of the solar cell makes an electrical connection to the polysilicon emitter. An external electrical circuit may be connected to the negative and positive metal contacts to be powered by the solar cell. The positive polarity metal contact may form an infrared reflecting layer with an underlying dielectric layer for increased solar radiation collection.

  3. Contact sensitizer 2,4-dinitrochlorobenzene is a highly potent human TRPA1 agonist.

    PubMed

    Saarnilehto, M; Chapman, H; Savinko, T; Lindstedt, K; Lauerma, A I; Koivisto, A

    2014-10-01

    2,4-Dinitrochlorobenzene (DNCB) is widely used in human clinical studies and in experimental animal studies to evoke allergic contact dermatitis. 2,4-Dinitrochlorobenzene is a potent immunogen capable of inducing contact sensitization in all humans exposed. However, the mechanism by which DNCB evokes such symptoms is presently unknown. TRPA1 is a nonselective cation channel that is expressed in peptidergic sensory neurons and fibroblasts. TRPA1 activation was recently implicated in the pathophysiology of atopic dermatitis especially in transducing cutaneous itch signals. Here, we test the hypothesis that DNCB acts as a TRPA1 agonist and thereby evokes allergic symptoms. We found that DNCB activates human TRPA1 dose dependently in FLIPR experiments with an EC50 of 167 nM, an effect that was fully blocked by selective TRPA1 antagonists Chembridge-5861528 and A-967079. Similarly, DNCB activated nonselective TRPA1 current in patch clamp studies. Neutralization of 3 critical cysteines in TRPA1 resulted in a loss of DNCB agonism. PMID:25041656

  4. Ink-Jet Printer Forms Solar-Cell Contacts

    NASA Technical Reports Server (NTRS)

    Alexander, Paul, Jr.; Vest, R. W.; Binford, Don A.; Tweedell, Eric P.

    1988-01-01

    Contacts formed in controllable patterns with metal-based inks. System forms upper metal contact patterns on silicon photovoltaic cells. Uses metallo-organic ink, decomposes when heated, leaving behind metallic, electrically conductive residue in printed area.

  5. Method for forming thin films having superconductive contacts

    Microsoft Academic Search

    R. E. Joynson; C. A. Neugebauer; J. R. Rairden

    1970-01-01

    Superconductive contacts are formed on a thin film of niobium, tantalum and their alloys by the selective deposition of a superconductive contact metal atop the film within the chamber employed for the film deposition without breaching the vacuum of the chamber between depositions. Preferably metals forming a soft oxide layer, e.g. tin, are employed to form the contacts and the

  6. Systemic immunogenicity of para-Phenylenediamine and Diphenylcyclopropenone: two potent contact allergy-inducing haptens.

    PubMed

    Svalgaard, Jesper Dyrendom; Særmark, Carina; Dall, Morten; Buschard, Karsten; Johansen, Jeanne D; Engkilde, Kåre

    2014-01-01

    p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1% w/v or 0.01% w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1% PPD, 0.01% DPCP or 0.1% DPCP, compared with vehicle treatment, indicating that the mice were sensitized and that there was a local inflammation. Auricular lymph nodes, pancreatic lymph nodes, spleen, and liver showed changes in regulatory T-cell, B-cell, and NKT-cell frequencies, and increased activation of CD8(+) T cells and B cells. Intracellular cytokine profiling revealed an increase in the IFN-?- and IL-4-positive NKT cells present in the liver following treatment with both haptens. Moreover, we saw a tendency toward a systemic increase in IL-17A. We observed systemic immunological effects of PPD and DPCP. Furthermore, concentrations too low to increase ear thickness and cause clinical symptoms may still prime the immune system. These systemic immunological effects may potentially predispose individuals to certain diseases. PMID:24385090

  7. A reproducing kernel smooth contact formulation for metal forming simulations

    NASA Astrophysics Data System (ADS)

    Wang, Hui-Ping; Wu, Cheng-Tang; Chen, Jiun-Shyan

    2014-07-01

    This paper presents a meshfree smooth contact formulation for application to metal forming problems. The continuum-based contact formulation requires continuity in the approximation of contact surface geometry and displacement variables, which is difficult for the conventional finite elements. In this work, we introduce a reproducing kernel approximation to achieve arbitrary degree of smoothness for contact surface representation and displacement field approximation. This approach allows the employment of continuum-based contact formulation, leading to a continuous contact force vector and a consistent tangent particularly advantageous in the Newton iteration of contact analysis. The proposed meshfree smooth contact formulation has been applied to the simulation of metal forming processes and is shown to improve the convergence significantly in comparison with the finite element-based contact formulation.

  8. A new contact judgement method for sheet metal forming simulation

    Microsoft Academic Search

    Xu Weili; Yang Yuying; Z. R. Wang; Lin Zhongqin

    2000-01-01

    A new contact judgement method for sheet metal forming simulation is proposed. The method can overcome miss-judgement and error-judgement, and improve numerical stability and computational accuracy effectively. Based on the proposed contact judgement method, a static–implicit FE code is developed. Some typical sheet metal forming processes and the benchmark of NUMISHEET’93 are simulated, and satisfactory results being obtained.

  9. Protonated Form: The Potent Form of Potassium-Competitive Acid Blockers

    PubMed Central

    Luo, Hua-Jun; Deng, Wei-Qiao; Zou, Kun

    2014-01-01

    Potassium-competitive acid blockers (P-CABs) are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs. PMID:24845980

  10. Method of forming contacts for a back-contact solar cell

    DOEpatents

    Manning, Jane

    2013-07-23

    Methods of forming contacts for back-contact solar cells are described. In one embodiment, a method includes forming a thin dielectric layer on a substrate, forming a polysilicon layer on the thin dielectric layer, forming and patterning a solid-state p-type dopant source on the polysilicon layer, forming an n-type dopant source layer over exposed regions of the polysilicon layer and over a plurality of regions of the solid-state p-type dopant source, and heating the substrate to provide a plurality of n-type doped polysilicon regions among a plurality of p-type doped polysilicon regions.

  11. Autophagosomes form at ER-mitochondria contact sites.

    PubMed

    Hamasaki, Maho; Furuta, Nobumichi; Matsuda, Atsushi; Nezu, Akiko; Yamamoto, Akitsugu; Fujita, Naonobu; Oomori, Hiroko; Noda, Takeshi; Haraguchi, Tokuko; Hiraoka, Yasushi; Amano, Atsuo; Yoshimori, Tamotsu

    2013-03-21

    Autophagy is a tightly regulated intracellular bulk degradation/recycling system that has fundamental roles in cellular homeostasis. Autophagy is initiated by isolation membranes, which form and elongate as they engulf portions of the cytoplasm and organelles. Eventually isolation membranes close to form double membrane-bound autophagosomes and fuse with lysosomes to degrade their contents. The physiological role of autophagy has been determined since its discovery, but the origin of autophagosomal membranes has remained unclear. At present, there is much controversy about the organelle from which the membranes originate--the endoplasmic reticulum (ER), mitochondria and plasma membrane. Here we show that autophagosomes form at the ER-mitochondria contact site in mammalian cells. Imaging data reveal that the pre-autophagosome/autophagosome marker ATG14 (also known as ATG14L) relocalizes to the ER-mitochondria contact site after starvation, and the autophagosome-formation marker ATG5 also localizes at the site until formation is complete. Subcellular fractionation showed that ATG14 co-fractionates in the mitochondria-associated ER membrane fraction under starvation conditions. Disruption of the ER-mitochondria contact site prevents the formation of ATG14 puncta. The ER-resident SNARE protein syntaxin 17 (STX17) binds ATG14 and recruits it to the ER-mitochondria contact site. These results provide new insight into organelle biogenesis by demonstrating that the ER-mitochondria contact site is important in autophagosome formation. PMID:23455425

  12. 78 FR 23898 - Notice of Request for a New Information Collection (Accredited Laboratory Contact Update Form)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ...Information Collection (Accredited Laboratory Contact Update Form) AGENCY: Food Safety and...collection regarding the compilation of updated contact information for Accredited Laboratories...through Friday. FOR FURTHER INFORMATION CONTACT: Contact John O'Connell,...

  13. 75 FR 61245 - Proposed Collection; Comment Request for the EFTPS Primary Contact Information Change Form

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-04

    ...Comment Request for the EFTPS Primary Contact Information Change Form AGENCY: Internal...comments concerning the EFTPS Primary Contact Information Change Form. DATES: Written...Washington, DC 20224. FOR FURTHER INFORMATION CONTACT: Requests for additional...

  14. 78 FR 58608 - Proposed Collection; Comment Request for the EFTPS Primary Contact Information Change Form

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ...Comment Request for the EFTPS Primary Contact Information Change Form AGENCY: Internal...comments concerning the EFTPS Primary Contact Information Change Form. DATES: Written...Washington, DC 20224. FOR FURTHER INFORMATION CONTACT: Requests for additional...

  15. Contact-spring forming machine for flat conductor cable receptacles

    NASA Technical Reports Server (NTRS)

    Angele, W.; Martineck, H. G.

    1968-01-01

    Machine tool produces beryllium-copper contact springs for FCC /flat conductor cable/ feed-through receptacles. The springs are heat-treated and plated to impart the required electrical contact properties.

  16. Organic light-emitting diodes formed by soft contact lamination

    E-print Network

    Rogers, John A.

    against an electroluminescent organic. This method relies only on van der Waals interactions to establish, however, because they depend sensitively on complex chemical and physical interac- tions between the metal, 8, 9), provides a means for establishing electrical contacts at room temperature in ambient

  17. Thermal Contact Resistance Estimation: Influence of the Pressure Contact and the Coating Layer during a Hot Forming Process

    NASA Astrophysics Data System (ADS)

    Abdulhay, B.; Bourouga, B.; Dessain, C.

    2011-05-01

    The application of hot stamping in the automotive industry has experienced a fast growth due to the need for higher passive safety and weight reduction. Today, it is absolutely necessary to have reliable and accurate simulation predictions in order to assess the forming feasibility of a part as early as possible during the car design phase. In this paper, an original experimental procedure developed to estimate the thermal conductance at the Part-Tools interfaces during a hot stamping process, is presented. The tools set (punch and die) have been designed to form samples with an omega shape. Two types of material have been stamped: the Usibor 1500P® and the 22MnB5 galvanized steel. The object is to describe correctly the thermal boundary conditions at the Part-Tools interfaces; the adopted procedure consists in estimating accurately the thermal contact resistance TCR at different contact points for different contact pressure values.

  18. Contact

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > Contact Contact [1] For more information about the Office of Cancer Genomics, please contact: Office of Cancer Genomics National Cancer Institute 31 Center Drive, 10A07 Bethesda,

  19. Contact

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > Contact Contact [1] For more information about the Office of Cancer Genomics, please contact: Office of Cancer Genomics National Cancer Institute 31 Center Drive, 10A07 Bethesda,

  20. Forming reproducible non-lithographic nanocontacts to assess the effect of contact compressive strain in nanomaterials

    NASA Astrophysics Data System (ADS)

    Smith, Nathan A.; Lord, Alex M.; Evans, Jon E.; Barnett, Chris J.; Cobley, Richard J.; Wilks, S. P.

    2015-06-01

    The application of electrical nanoprobes to measure and characterize nanomaterials has become widely spread. However, the formation of quality electrical contacts using metallic probes on nanostructures has not been directly assessed. We investigate here the electrical behaviour of non-lithographically formed contacts to ZnO nanowires (NWs) and develop a method to reproducibly form Ohmic contacts for accurate electrical measurement of the nanostructures. The contacting method used in this work relies on an electrical feedback mechanism to determine the point of contact to the individual NWs, ensuring minimal compressive strain at the contact. This developed method is compared with the standard tip deflection contacting technique and shows a significant improvement in reproducibility. The effect of excessive compressive strain at the contact was investigated, with a change from rectifying to ohmic I–V behaviour observed as compressive strain at the contact was increased, leading to irreversible changes to the electrical properties of the NW. This work provides an ideal method for forming reproducible non-lithographic nanocontacts to a multitude of nanomaterials.

  1. FE-Analysis of the Sheet Metal Forming Processes using Continuous Contact Treatment

    SciTech Connect

    Kim, Tae-Jeong; Yang, Dong-Yol [Dept. of Mech. Eng., KAIST, Science Town, Daejeon, 305-701 (Korea, Republic of)

    2005-08-05

    In general, the sheet metal and die are described by finite elements for the simulation of the metal forming processes. Because the characteristics as continuum of the sheet metal are represented with triangles and rectangles, the errors occur inevitably in finite element analysis. Many contact schemes to describe the deformation modes exactly have been introduced in order to decrease these errors. In this study, a scheme for continuous contact treatment is proposed in order to consider the realistic behavior of contact phenomena during the forming process. The discrete mesh causes stepwise propagation of contact nodes of the sheet even though the contact region of the real forming process is altered very smoothly. It gives rise to convergence problem in case that the process, for example bending process, is sensitive to the contact between the sheet and the tools. For the verification of the proposed method, the compression forming of a tube is simulated and the contact pressures at each integration points are evaluated during deformation of the sheet. The analysis of hemi-spherical punch forming without blank holder is also presented in order to investigate the effects of the proposed algorithm.

  2. HeLa cells form focal contacts that are not fibronectin dependent.

    PubMed

    Morgan, J; Garrod, D

    1984-03-01

    HeLa cells cultured on glass substrata produce numerous prominent focal contacts, which reside at the termini of actin microfilament bundles. However, very few of the cells stain for fibronectin with specific anti-fibronectin antibody. Moreover, the cells form focal contacts in fibronectin-depleted medium, in the presence of high concentrations of anti-fibronectin immunoglobulin G and in the presence of monensin. No fibronectin synthesis can be detected by [35S]methionine-labelling and immunoprecipitation. The possibility that HeLa cell focal contacts are independent of fibronectin in their formation is discussed in relation to the controversy about the relationship between fibronectin and focal contacts. PMID:6746753

  3. Method of forming emitters for a back-contact solar cell

    DOEpatents

    Li, Bo; Cousins, Peter J; Smith, David D

    2014-12-16

    Methods of forming emitters for back-contact solar cells are described. In one embodiment, a method includes forming a first solid-state dopant source above a substrate. The first solid-state dopant source includes a plurality of regions separated by gaps. Regions of a second solid-state dopant source are formed above the substrate by printing.

  4. Measurement of contact angles of aqueous solutions on some rock forming minerals

    NASA Astrophysics Data System (ADS)

    Takakura, M.; Katsura, M.; Nakashima, S.

    2007-12-01

    Wetting properties of fluids on earth's materials are controlling fluid flows and dynamics of the geological systems. Although the wetting behavior of industrial materials have been widely examined often by contact angle measurements, contact angles of rock-forming materials have not been commonly measured. Therefore, we have been measuring contact angles of some representative rock-forming minerals. The surfaces of solid samples were polished successively by emery papers then by grinding powders (alumina: up to \\sharp3000: grain size about 5 micrometers). Water droplet from a micro-syringe needle are placed on solid surfaces by moving up the sample stage. Images of water drops on the solid surfaces are captured from the horizontal direction with a CCD camera. Contact angles can be determined from the height and the length of the images by assuming them to be parts of circles. Over 60 measurements of contact angles of pure water on (101) and (011) faces plates cut from a natural quartz single crystal were repeated. The average contact angles of pure water on (101) and (011) faces of quartz were 48 ± 5 degrees and 52 ± 3 degrees, respectively. Contact angles of pure water on a natural calcite single crystal was also measured in the same way to be 37 ± 8 degrees. Contact angles of various aqueous solutions such as NaCl and NaHCO3 on these minerals will also be measured in order to evaluate wetting properties of natural rock-water systems.

  5. UM Computer Science 2014-2015 Parent/Guardian Consent & Contact Form

    E-print Network

    Chu, Xi

    UM Computer Science 2014-2015 Parent/Guardian Consent & Contact Form Print Child's Name: __________ I/we give our son/daughter permission to participate in the UM Computer Science workshop to the provision of any necessary emergency treatment to my son/daughter during the program by UM Computer Science

  6. Front contact solar cell with formed electrically conducting layers on the front side and backside

    DOEpatents

    Cousins, Peter John

    2012-06-26

    A bipolar solar cell includes a backside junction formed by a silicon substrate and a first doped layer of a first dopant type on the backside of the solar cell. A second doped layer of a second dopant type makes an electrical connection to the substrate from the front side of the solar cell. A first metal contact of a first electrical polarity electrically connects to the first doped layer on the backside of the solar cell, and a second metal contact of a second electrical polarity electrically connects to the second doped layer on the front side of the solar cell. An external electrical circuit may be electrically connected to the first and second metal contacts to be powered by the solar cell.

  7. Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke

    Microsoft Academic Search

    Judy Huang; David B. Agus; Christopher J. Winfree; Szilard Kiss; William J. Mack; Ryan A. McTaggart; Tanvir F. Choudhri; Louis J. Kim; J. Mocco; David J. Pinsky; William D. Fox; Robert J. Israel; Thomas A. Boyd; David W. Golde; E. Sander Connolly Jr.

    2001-01-01

    Neuronal injury in ischemic stroke is partly mediated by cytotoxic reactive oxygen species. Although the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood-brain barrier (BBB), its oxidized form, dehydroascorbic acid (DHA), enters the brain by means of facilitative transport. We hypothesized that i.v. DHA would improve outcome after stroke because of its ability to cross the

  8. Effects of varying machine stiffness and contact area in UltraForm Finishing

    NASA Astrophysics Data System (ADS)

    Briggs, Dennis E.; Echaves, Samantha; Pidgeon, Brendan; Travis, Nathan; Ellis, Jonathan D.

    2013-09-01

    UltraForm Finishing (UFF) is a deterministic, subaperture, computer numerically controlled, grinding and polishing platform designed by OptiPro Systems. UFF is used to grind and polish a variety optics from simple spherical to fully freeform, and numerous materials from glasses to optical ceramics. The UFF system consists of an abrasive belt around a compliant wheel that rotates and contacts the part to remove material. This work aims to measure the stiffness variations in the system and how it can affect material removal rates. The stiffness of the entire system is evaluated using a triaxial load cell to measure forces and a capacitance sensor to measure deviations in height. Because the wheel is conformal and elastic, the shapes of contact areas are also of interest. For the scope of this work, the shape of the contact area is estimated via removal spot. The measured forces and removal spot area are directly related to material removal rate through Preston's equation. Using our current testing apparatus, we will demonstrate stiffness measurements and contact areas for a single UFF belt during different states of its lifecycle and assess the material removal function from spot diagrams as a function of wear. This investigation will ultimately allow us to make better estimates of Preston's coefficient and develop spot-morphing models in an effort to more accurately predict instantaneous material removal functions throughout the lifetime of a belt.

  9. Growth Law of the Oxide Film Formed on the Tin Plated Contact Surface and Its Contact Resistance Characteristic

    Microsoft Academic Search

    Yuuya Nabeta; Yasushi Saitoh; Shigeru Sawada; Yasuhiro Hattori; Terutaka Tamai

    2009-01-01

    Tin plating has been applied widely to electrical connectors to save the cost for electromechanical devices. However, the tin plated surface covered with oxide film is fundamentally different from gold plated surfaces. The oxide film prevents the surface from corrosion. When the film is interposed between contact interface, contact resistance increases. It is necessary to break down mechanically to obtain

  10. H-1B Visa Request Form (Contact & submit to PeiLei Chow, CBMG, 1119 Microbiology, pchow@umd.edu)

    E-print Network

    Gruner, Daniel S.

    H-1B Visa Request Form (Contact & submit to PeiLei Chow, CBMG, 1119 Microbiology, pchow@umd.edu) H1 Microbiology 3. Supporting letter on Univ. dept. letterhead 4. FRS #______________ for fees P.I. Name

  11. Ion Channel-Forming Alamethicin Is a Potent Elicitor of Volatile Biosynthesis and Tendril Coiling. Cross Talk between Jasmonate and Salicylate Signaling in Lima Bean1

    PubMed Central

    Engelberth, Jürgen; Koch, Thomas; Schüler, Göde; Bachmann, Nadine; Rechtenbach, Jana; Boland, Wilhelm

    2001-01-01

    Alamethicin (ALA), a voltage-gated, ion channel-forming peptide mixture from Trichoderma viride, is a potent elicitor of the biosynthesis of volatile compounds in lima bean (Phaseolus lunatus). Unlike elicitation with jasmonic acid or herbivore damage, the blend of substances emitted comprises only the two homoterpenes, 4,11-dimethylnona-1,3,7-triene and 4,8,12-trimethyltrideca-1,3,7,11-tetraene, and methyl salicylate. Inhibition of octadecanoid signaling by aristolochic acid and phenidone as well as mass spectrometric analysis of endogenous jasmonate demonstrate that ALA induces the biosynthesis of volatile compounds principally via the octadecanoid-signaling pathway (20-fold increase of jasmonic acid). ALA also up-regulates salicylate biosynthesis, and the time course of the production of endogenous salicylate correlates well with the appearance of the methyl ester in the gas phase. The massive up-regulation of the SA-pathway (90-fold) interferes with steps in the biosynthetic pathway downstream of 12-oxophytodienoic acid and thereby reduces the pattern of emitted volatiles to compounds previously shown to be induced by early octadecanoids. ALA also induces tendril coiling in various species like Pisum, Lathyrus, and Bryonia, but the response appears to be independent from octadecanoid biosynthesis, because inhibitors of lipoxygenase and phospholipase A2 do not prevent the coiling reaction. PMID:11154344

  12. Non-contact high precision measurement of surface form tolerances and central thickness for optical elements

    NASA Astrophysics Data System (ADS)

    Lou, Ying

    2010-10-01

    The traditional contact measuring methods could not satisfy the current optical elements measuring requirements. Noncontact high precision measuring theory, principle and instrument of the surface form tolerances and central thickness for optical elements were studied in the paper. In comparison with other types of interferometers, such as Twyman-Green and Mach-Zehnder, a Fizeau interferometer has the advantages of having fewer optical components, greater accuracy, and is easier to use. Some relations among the 3/A(B/C), POWER/PV and N/?N were studied. The PV with POWER removed can be the reference number of ?N. The chromatic longitudinal aberration of a special optical probe can be used for non-contanct central thickness measurement.

  13. Thermal Contact Resistance Estimation: Influence of the Pressure Contact and the Coating Layer during a Hot Forming Process

    Microsoft Academic Search

    B. Abdulhay; B. Bourouga; C. Dessain

    2011-01-01

    The application of hot stamping in the automotive industry has experienced a fast growth due to the need for higher passive safety and weight reduction. Today, it is absolutely necessary to have reliable and accurate simulation predictions in order to assess the forming feasibility of a part as early as possible during the car design phase. In this paper, an

  14. Rational Design of a Potent, Long-Lasting Form of Interferon:  A 40 kDa Branched Polyethylene Glycol-Conjugated Interferon ?-2a for the Treatment of Hepatitis C

    Microsoft Academic Search

    Pascal Bailon; Alicia Palleroni; Carol A. Schaffer; Cheryl L. Spence; Wen-Jian Fung; Jill E. Porter; George K. Ehrlich; Wen Pan; Zhi-Xin Xu; Marlene W. Modi; Adrienne Farid; Wolfgang Berthold; Mary Graves

    2001-01-01

    A potent, long-lasting form of interferon R-2a mono-pegylated with a 40 kilodalton branched poly- (ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon R-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon R-2a was found to be only 7% of the original activity. In contrast,

  15. Request for Animal Transfer for Imaging Completed form is to be forwarded to appropriate contact person at initiating Institute

    E-print Network

    Krovi, Venkat

    Request for Animal Transfer for Imaging Completed form is to be forwarded to appropriate contact Animal Transfer Information: Date of Arrival STRAIN No./Sex DOB Room/Rack/Cage Biohazard No Yes - Explain Protocol # Expiration Date MRI Scan Animal Information: Date of Arrival Strain: Number of Animals: Sex: Age

  16. Laser method for forming low-resistance ohmic contacts on semiconducting oxides

    DOEpatents

    Narayan, Jagdish (Knoxville, TN)

    1981-01-01

    This invention is a new method for the formation of high-quality ohmic contacts on wide-band-gap semiconducting oxides. As exemplified by the formation of an ohmic contact on n-type BaTiO.sub.3 containing a p-n junction, the invention entails depositing a film of a metallic electroding material on the BaTiO.sub.3 surface and irradiating the film with a Q-switched laser pulse effecting complete melting of the film and localized melting of the surface layer of oxide immediately underlying the film. The resulting solidified metallic contact is ohmic, has unusually low contact resistance, and is thermally stable, even at elevated temperatures. The contact does not require cleaning before attachment of any suitable electrical lead. This method is safe, rapid, reproducible, and relatively inexpensive.

  17. Basic investigations on boundary lubrication in metal forming processes by in situ observation of the real contact area

    Microsoft Academic Search

    S. Weidel; U. Engel; M. Merklein; M. Geiger

    2010-01-01

    In metal forming processes tribology plays a significant role for process feasibility and tool lifetime. Boundary and mixed\\u000a lubrication conditions are predominant in metal forming processes. Hence the appearing real contact area which is mainly influenced\\u000a by the topography of tool and workpiece has a major impact on friction conditions. For an improved understanding of friction\\u000a at the interface between

  18. Pt/Ti/n-InP nonalloyed ohmic contacts formed by rapid thermal processing

    NASA Astrophysics Data System (ADS)

    Katz, A.; Weir, B. E.; Chu, S. N. G.; Thomas, P. M.; Soler, M.; Boone, T.; Dautremont-Smith, W. C.

    1990-04-01

    Low resistance nonalloyed ohmic contacts of e-gun evaporated Pt/Ti to S doped n-InP 5×1017, 1×1018, and 5×1018 cm-3 have been fabricated by rapid thermal processing. The contacts to the lower doped substrates (5×1017 and 1×1018 cm-3) were rectifying as-deposited as well as after heat treatment at temperatures lower than 350 °C. Higher processing temperatures stimulated the Schottky to ohmic contact conversion with minimum specific contact resistance of 1.5×10-5 and 5×10-6 ? cm2, respectively, as a result of rapid thermal processing at 450 °C for 30 s. Heating at a temperature of 550 °C again yielded a Schottky contact. The contact to the 5×1018 cm-3 InP was ohmic as deposited with a specific contact resistance value of 1.1×10-4 ? cm2. Supplying heat treatment to the contact caused a decrease of the specific contact resistance to a minimum of 8×10-7 ? cm2 as a result of rapid thermal processing at 450 °C for 30 s. In all cases, this heat treatment caused a limited interfacial reactions between the Ti and the InP, and resulted in an almost abrupt interface. Heating at temperatures higher than 500 °C resulted in an interfacial intermixing and a mutual migration and reaction of the Ti and the semiconductor elements. The Pt/Ti bilayer structure was highly tensile as deposited (5×109 dyn cm-2) and became stress-free as a result of the interfacial reactions which took place while heating the samples to temperature of 400 °C or higher.

  19. Characterization of the metal–semiconductor interface of gold contacts on CdZnTe formed by electroless deposition

    NASA Astrophysics Data System (ADS)

    Bell, Steven J.; Baker, Mark A.; Duarte, Diana D.; Schneider, Andreas; Seller, Paul; Sellin, Paul J.; Veale, Matthew C.; Wilson, Matthew D.

    2015-06-01

    Fully spectroscopic x/?-ray imaging is now possible thanks to advances in the growth of wide-bandgap semiconductors. One of the most promising materials is cadmium zinc telluride (CdZnTe or CZT), which has been demonstrated in homeland security, medical imaging, astrophysics and industrial analysis applications. These applications have demanding energy and spatial resolution requirements that are not always met by the metal contacts deposited on the CdZnTe. To improve the contacts, the interface formed between metal and semiconductor during contact deposition must be better understood. Gold has a work function closely matching that of high resistivity CdZnTe and is a popular choice of contact metal. Gold contacts are often formed by electroless deposition however this forms a complex interface. The prior CdZnTe surface preparation, such as mechanical or chemo-mechanical polishing, and electroless deposition parameters, such as gold chloride solution temperature, play important roles in the formation of the interface and are the subject of the presented work. Techniques such as focused ion beam (FIB) cross section imaging, transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), x-ray photoelectron spectroscopy (XPS) and current?????voltage (I–V) analysis have been used to characterize the interface. It has been found that the electroless reaction depends on the surface preparation and for chemo-mechanically polished (1?1?1) CdZnTe, it also depends on the A/B face identity. Where the deposition occurred at elevated temperature, the deposited contacts were found to produce a greater leakage current and suffered from increased subsurface voiding due to the formation of cadmium chloride.

  20. INVESTIGATIONS ON THE MECHANISM BEHIND THE BENEFICIAL EFFECT OF A FORMING GAS ANNEAL ON SOLAR CELLS WITH SILVER THICK FILM CONTACTS

    Microsoft Academic Search

    G. Schubert; J. Horzel; S. Ohl

    In this contribution the beneficial effect of the forming gas anneal (FGA) on solar cells with silver thick film contacts is investigated regarding its application for contacting emitters with phosphorous surface concentrations below ND, surface = 1×10 20 cm-3. Measurements and simulations of silver - silicon contacts show that for emitters with ND, surface > 2×10 19 cm-3 the limiting

  1. EMERGENCY CONTACT AND MEDICAL INFORMATION FORM PLEASE MAIL OR FAX BEFORE MARCH 29, 2013

    E-print Network

    Saniie, Jafar

    by any of the foregoing parties seeking to secure me medical assistance: EMERGENCY CONTACT INFORMATION: _________________________________________________________________________ HEALTH INSURANCE INFORMATION Name of Health Insurance Company: ___________________________________________________________________ MEDICAL HEALTH INFORMATION Current Medication I Am Taking

  2. EMERGENCY CONTACT AND MEDICAL INFORMATION FORM PLEASE MAIL OR FAX BEFORE MARCH 31, 2014

    E-print Network

    Heller, Barbara

    by any of the foregoing parties seeking to secure me medical assistance: EMERGENCY CONTACT INFORMATION: ______________________________________________________________________________ Medical Conditions/Allergies I Have of Which Emergency Assistance Providers Should Be Aware to render assistance to me in the event of medical emergency. I have read this statement; I fully understand

  3. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics.

    PubMed

    Luz, John Gately; Antonysamy, Stephen; Kuklish, Steven L; Condon, Bradley; Lee, Matthew R; Allison, Dagart; Yu, Xiao-Peng; Chandrasekhar, Srinivasan; Backer, Ryan; Zhang, Aiping; Russell, Marijane; Chang, Shawn S; Harvey, Anita; Sloan, Ashley V; Fisher, Matthew J

    2015-06-11

    Microsomal prostaglandin E synthase 1 (mPGES-1) is an ?-helical homotrimeric integral membrane inducible enzyme that catalyzes the formation of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). Inhibition of mPGES-1 has been proposed as a therapeutic strategy for the treatment of pain, inflammation, and some cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the potential circumvention of cardiovascular risks associated with anti-inflammatory cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway downstream of PGH2 synthesis and avoiding suppression of antithrombotic prostacyclin production. We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to understand their structure-activity relationships and provide a framework for the rational design of improved molecules. In addition, we developed a light-scattering-based thermal stability assay to identify molecules for crystallographic studies. PMID:25961169

  4. Lithium fluoride injection layers can form quasi-Ohmic contacts for both holes and electrons

    NASA Astrophysics Data System (ADS)

    Bory, Benjamin F.; Rocha, Paulo R. F.; Janssen, René A. J.; Gomes, Henrique L.; De Leeuw, Dago M.; Meskers, Stefan C. J.

    2014-09-01

    Thin LiF interlayers are typically used in organic light-emitting diodes to enhance the electron injection. Here, we show that the effective work function of a contact with a LiF interlayer can be either raised or lowered depending on the history of the applied bias. Formation of quasi-Ohmic contacts for both electrons and holes is demonstrated by electroluminescence from symmetric LiF/polymer/LiF diodes in both bias polarities. The origin of the dynamic switching is charging of electrically induced Frenkel defects. The current density-electroluminescence-voltage characteristics can qualitatively be explained. The interpretation is corroborated by unipolar memristive switching and by bias dependent reflection measurements.

  5. Save the filled out contact form to your local disk. Send it as e-mail attachement to auslaenderbehoerde@tu-ilmenau.de

    E-print Network

    Knobloch,Jürgen

    Save the filled out contact form to your local disk. Send it as e-mail attachement information Telephone number E-mail address Herewith I would like to contact the Aliens Department for making Date of birth Nationality / citizenship Authorized representative if appropriate Address Optional

  6. Charge and discharge characteristics of a direct contact latent thermal energy storage unit using form-stable high-density polyethylene

    Microsoft Academic Search

    Y. Abe; M. Kamimoto; K. Kanari; T. Ozawa; R. Sakamoto; Y. Takahushi

    1984-01-01

    For solar thermal energy utilization in relatively low temperatures, a lab-scale direct contact, latent thermal energy storage unit using a form-stable high-density polyethylene (HDPE) was developed. The phase change material (PCM), the form-stable HDPE, does not fluidize nor adhere even after melting, and this particular property permits a direct contact heat transfer between the PCM and a heat transfer fluid

  7. Self-formed copper oxide contact interlayer for high-performance oxide thin film transistors

    SciTech Connect

    Gao, Xu, E-mail: GAO.Xu@nims.go.jp, E-mail: TSUKAGOSHI.Kazuhito@nims.go.jp; Aikawa, Shinya; Mitoma, Nobuhiko; Lin, Meng-Fang; Kizu, Takio; Tsukagoshi, Kazuhito, E-mail: GAO.Xu@nims.go.jp, E-mail: TSUKAGOSHI.Kazuhito@nims.go.jp [International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), Tsukuba, Ibaraki 305-0044 (Japan); Nabatame, Toshihide [MANA Foundry and MANA Advanced Device Materials Group, National Institute for Materials Science (NIMS), Tsukuba, Ibaraki 305-0044 (Japan)

    2014-07-14

    Oxide thin film transistor employing copper source/drain electrodes shows a small turn on voltage and reduced hysteresis. Cross-sectional high-resolution transmission electron microscopy image confirmed the formation of ?4?nm CuO{sub x} related interlayer. The lower bond-dissociation energy of Cu-O compared to Si-O and In-O suggests that the interlayer was formed by adsorbing oxygen molecules from surrounding environment instead of getting oxygen atoms from the semiconductor film. The formation of CuO{sub x} interlayer acting as an acceptor could suppress the carrier concentration in the transistor channel, which would be utilized to control the turn on voltage shifts in oxide thin film transistors.

  8. Effect of surface mechanical attrition treatment of titanium using alumina balls: surface roughness, contact angle and apatite forming ability

    NASA Astrophysics Data System (ADS)

    Jamesh, M.; Sankara Narayanan, T. S. N.; Chu, Paul K.; Park, Il Song; Lee, Min Ho

    2013-09-01

    The effect of surface mechanical attrition treatment (SMAT) of commercially pure titanium (CP-Ti) using 8mm Ø alumina balls was studied. SMAT induced plastic deformation, increased the surface roughness, reduced the grain size and decreased the contact angle (from 64° to 43°) with a corresponding increase in surface energy (from 32 to 53 mJ/m2). Untreated CP-Ti and those treated using alumina balls for 900 s reveals no apatite growth until the 28th day of immersion whereas those treated for 1800 and 2700 s exhibit apatite growth in selective areas and the extent of growth is increased with increase in immersion time in SBF. The study reveals that SMAT using alumina balls is beneficial in imparting the desired surface characteristics, provided the surface contamination is limited, which would otherwise decrease the apatite forming ability.

  9. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor.

    PubMed

    Finlay, M Raymond V; Anderton, Mark; Ashton, Susan; Ballard, Peter; Bethel, Paul A; Box, Matthew R; Bradbury, Robert H; Brown, Simon J; Butterworth, Sam; Campbell, Andrew; Chorley, Christopher; Colclough, Nicola; Cross, Darren A E; Currie, Gordon S; Grist, Matthew; Hassall, Lorraine; Hill, George B; James, Daniel; James, Michael; Kemmitt, Paul; Klinowska, Teresa; Lamont, Gillian; Lamont, Scott G; Martin, Nathaniel; McFarland, Heather L; Mellor, Martine J; Orme, Jonathon P; Perkins, David; Perkins, Paula; Richmond, Graham; Smith, Peter; Ward, Richard A; Waring, Michael J; Whittaker, David; Wells, Stuart; Wrigley, Gail L

    2014-10-23

    Epidermal growth factor receptor (EGFR) inhibitors have been used clinically in the treatment of non-small-cell lung cancer (NSCLC) patients harboring sensitizing (or activating) mutations for a number of years. Despite encouraging clinical efficacy with these agents, in many patients resistance develops leading to disease progression. In most cases, this resistance is in the form of the T790M mutation. In addition, EGFR wild type receptor inhibition inherent with these agents can lead to dose limiting toxicities of rash and diarrhea. We describe herein the evolution of an early, mutant selective lead to the clinical candidate AZD9291, an irreversible inhibitor of both EGFR sensitizing (EGFRm+) and T790M resistance mutations with selectivity over the wild type form of the receptor. Following observations of significant tumor inhibition in preclinical models, the clinical candidate was administered clinically to patients with T790M positive EGFR-TKI resistant NSCLC and early efficacy has been observed, accompanied by an encouraging safety profile. PMID:25271963

  10. Nanosulfur: A Potent Fungicide Against Food Pathogen, Aspergillus niger

    NASA Astrophysics Data System (ADS)

    Choudhury, Samrat Roy; Nair, Kishore K.; Kumar, Rajesh; Gogoi, Robin; Srivastava, Chitra; Gopal, Madhuban; Subhramanyam, B. S.; devakumar, C.; Goswami, Arunava

    2010-10-01

    Elemental sulfur (S0), man's oldest eco-friendly fungicide for curing fungal infections in plants and animals, is registered in India as a non-systemic and contact fungicide. However due to its high volume requirement, Indian agrochemical industry and farmers could not effectively use this product till date. We hypothesize that intelligent nanoscience applications might increase the visibility of nanosulfur in Indian agriculture as a potent and eco-safe fungicide. Sulfur nanoparticles (NPs) were synthesized bottom-up via a liquid synthesis method with average particle size in the range of 50-80 nm and the shapes of the NPs were spherical. A comparative study of elemental and nano-sulfur produced has been tested against facultative fungal food pathogen, Aspergillus niger. Results showed that nanosulfur is more efficacious than its elemental form.

  11. The comparison between two irrigation regimens on the dentine wettability for an epoxy resin based sealer by measuring its contact angle formed to the irrigated dentine

    PubMed Central

    Mohan, Rayapudi Phani; Pai, Annappa Raghavendra Vivekananda

    2015-01-01

    Aim: The aim was to assess the influence of two irrigation regimens having ethylenediaminetetraacetic acid (EDTA) and ethylenediaminetetraacetic acid with cetrimide (EDTAC) as final irrigants, respectively, on the dentine wettability for AH Plus sealer by comparing its contact angle formed to the irrigated dentine. Materials and Methods: Study samples were divided into two groups (n = 10). The groups were irrigated with 3% sodium hypochlorite (NaOCl) solution followed by either 17% EDTA or 17% EDTAC solution. AH Plus was mixed, and controlled volume droplet (0.1 mL) of the sealer was placed on the dried samples. The contact angle was measured using a Dynamic Contact Angle Analyzer and results were analyzed using SPSS 21.0 and 2 sample t-test. Results: There was a significant difference in the contact angle of AH Plus formed to the dentine irrigated with the above two regimens. AH Plus showed significantly lower contact angle with the regimen having EDTAC as a final irrigant than the one with EDTA (P < 0.05). Conclusion: An irrigation regimen consisting of NaOCl with either EDTA or EDTAC solution as a final irrigant influences the dentine wettability and contact angle of a sealer. EDTAC as a final irrigant facilitates better dentin wettability than EDTA for AH Plus to promote its better flow and adhesion.

  12. Modeling of contact theories for the manipulation of biological micro/nanoparticles in the form of circular crowned rollers based on the atomic force microscope

    NASA Astrophysics Data System (ADS)

    Korayem, M. H.; Khaksar, H.; Taheri, M.

    2013-11-01

    This article has dealt with the development and modeling of various contact theories for biological nanoparticles shaped as cylinders and circular crowned rollers for application in the manipulation of different biological micro/nanoparticles based on Atomic Force Microscope. First, the effective contact forces were simulated, and their impact on contact mechanics simulation was investigated. In the next step, the Hertz contact model was simulated and compared for gold and DNA nanoparticles with the three types of spherical, cylindrical, and circular crowned roller type contact geometries. Then by reducing the length of the cylindrical section in the circular crowned roller geometry, the geometry of the body was made to approach that of a sphere, and the results were compared for DNA nanoparticles. To anticipatory validate the developed theories, the results of the cylindrical and the circular crowned roller contacts were compared with the results of the existing spherical contact simulations. Following the development of these contact models for the manipulation of various biological micro/nanoparticles, the cylindrical and the circular crowned roller type contact theories were modeled based on the theories of Lundberg, Dowson, Nikpur, Heoprich, and Hertz for the manipulation of biological micro/nanoparticles. Then, for a more accurate validation, the results obtained from the simulations were compared with those obtained by the finite element method and with the experimental results available in previous articles. The previous research works on the simulation of nanomanipulation have mainly investigated the contact theories used in the manipulation of spherical micro/nanoparticles. However since in real biomanipulation situations, biological micro/nanoparticles of more complex shapes need to be displaced in biological environments, this article therefore has modeled and compared, for the first time, different contact theories for use in the biomanipulation of cylindrical and circular crowned roller shaped micro/nanoparticles. The results of models indicate that the contact model of Hertz achieves the largest amount of deformation for the DNA nanoparticle in cylindrical form and the contact model of Heoprich achieves the largest deformation for the circular crowned roller shaped DNA. Of course, this finding is not always true for the other nanoparticles; and considering the mechanical and environmental characteristics, different results can be obtained. Also, by comparing the deformations of different types of nanoparticles, it was determined that the platelet type nanoparticles display the highest degree of deformation in all the considered models, due to their particular mechanical characteristics.

  13. Modeling of contact theories for the manipulation of biological micro/nanoparticles in the form of circular crowned rollers based on the atomic force microscope

    SciTech Connect

    Korayem, M. H.; Khaksar, H.; Taheri, M. [Robotic Research Laboratory, Center of Excellence in Experimental Solid Mechanics and Dynamics, School of Mechanical Engineering, Iran University of Science and Technology, Tehran (Iran, Islamic Republic of)

    2013-11-14

    This article has dealt with the development and modeling of various contact theories for biological nanoparticles shaped as cylinders and circular crowned rollers for application in the manipulation of different biological micro/nanoparticles based on Atomic Force Microscope. First, the effective contact forces were simulated, and their impact on contact mechanics simulation was investigated. In the next step, the Hertz contact model was simulated and compared for gold and DNA nanoparticles with the three types of spherical, cylindrical, and circular crowned roller type contact geometries. Then by reducing the length of the cylindrical section in the circular crowned roller geometry, the geometry of the body was made to approach that of a sphere, and the results were compared for DNA nanoparticles. To anticipatory validate the developed theories, the results of the cylindrical and the circular crowned roller contacts were compared with the results of the existing spherical contact simulations. Following the development of these contact models for the manipulation of various biological micro/nanoparticles, the cylindrical and the circular crowned roller type contact theories were modeled based on the theories of Lundberg, Dowson, Nikpur, Heoprich, and Hertz for the manipulation of biological micro/nanoparticles. Then, for a more accurate validation, the results obtained from the simulations were compared with those obtained by the finite element method and with the experimental results available in previous articles. The previous research works on the simulation of nanomanipulation have mainly investigated the contact theories used in the manipulation of spherical micro/nanoparticles. However since in real biomanipulation situations, biological micro/nanoparticles of more complex shapes need to be displaced in biological environments, this article therefore has modeled and compared, for the first time, different contact theories for use in the biomanipulation of cylindrical and circular crowned roller shaped micro/nanoparticles. The results of models indicate that the contact model of Hertz achieves the largest amount of deformation for the DNA nanoparticle in cylindrical form and the contact model of Heoprich achieves the largest deformation for the circular crowned roller shaped DNA. Of course, this finding is not always true for the other nanoparticles; and considering the mechanical and environmental characteristics, different results can be obtained. Also, by comparing the deformations of different types of nanoparticles, it was determined that the platelet type nanoparticles display the highest degree of deformation in all the considered models, due to their particular mechanical characteristics.

  14. Structural and electrical characterization of silicided Ni/Au contacts formed at low temperature (<300 °C) on p-type [001] silicon

    NASA Astrophysics Data System (ADS)

    Alberti, A.; Badalà, P.; Pellegrino, G.; Santangelo, A.

    2011-12-01

    Silicided Ni/Au contacts with very low contact resistance were realized on p-type [001] silicon at low temperature by ex-situ or, alternatively, by in situ annealing processes. During the ex-situ annealing, performed at 200 °C for 10 s, a uniformly thin (14 nm) Ni2Si layer was formed having an extremely flat interface with silicon thanks to the trans-rotational structure of the silicide. During the in situ annealing, promoted by a sputter etch processing (T < 300 °C), a 44 nm-thick silicide layer was formed as a mixture of trans-rotational NiSi and epitaxial NiSi2, domains. In both cases, using a low thermal budget has guaranteed a limited consumption of silicon during the reaction process and a good adhesion with the substrate avoiding gold contaminations. As a consequence of the presence of trans-rotational domains, wherein a pseudo-epitaxial relationship between the silicide and the silicon lattices is established, an ohmic behavior was observed in a wide range of substrate doping (3.5 × 1018 ÷ 3 × 1019 B/cm3) for both annealing processes (in situ and ex-situ). On the other hand, conventional TiNiAu and CrNiAu contacts showed, in the same range of B doping concentration, a rectifying behavior with systematically higher specific contact resistance values (Rc) compared to those of the Ni silicided contacts.

  15. Ultraviolet band-pass Schottky barrier photodetectors formed by Al-doped ZnO contacts to n-GaN

    Microsoft Academic Search

    J. K. Sheu; M. L. Lee; C. J. Tun; S. W. Lin

    2006-01-01

    This work prepared Al-doped ZnO(AZO) films using dc sputtering to form Schottky contacts onto GaN films with low-temperature-grown GaN cap layer. Application of ultraviolet photodetector showed that spectral responsivity exhibits a narrow bandpass characteristic ranging from 345 to 375 nm. Moreover, unbiased peak responsivity was estimated to be around 0.12 A\\/W at 365 nm, which corresponds to a quantum efficiency

  16. Ultraviolet band-pass Schottky barrier photodetectors formed by Al-doped ZnO contacts to n-GaN

    Microsoft Academic Search

    J. K. Sheu; M. L. Lee; C. J. Tun; S. W. Lin

    2006-01-01

    This work prepared Al-doped ZnO(AZO) films using dc sputtering to form Schottky contacts onto GaN films with low-temperature-grown GaN cap layer. Application of ultraviolet photodetector showed that spectral responsivity exhibits a narrow bandpass characteristic ranging from 345 to 375 nm. Moreover, unbiased peak responsivity was estimated to be around 0.12 A?W at 365 nm, which corresponds to a quantum efficiency

  17. ATBC Study - Contact Us

    Cancer.gov

    Skip to Main Content Home Contact Us Links Study Details Questionnaires & Forms Current Projects ATBC Study Bibliography Study Investigators & Collaborators Proposal Review & Collaboration Research Consortium Projects Contact Us If you are seeking general

  18. Use of separate ZnTe interface layers to form OHMIC contacts to p-CdTe films

    DOEpatents

    Gessert, Timothy A. (Conifer, CO)

    1999-01-01

    A method of improving electrical contact to a thin film of a p-type tellurium-containing II-VI semiconductor comprising: depositing a first undoped layer of ZnTe on a thin film of p-type tellurium containing II-VI semiconductor with material properties selected to limit the formation of potential barriers at the interface between the p-CdTe and the undoped layer, to a thickness sufficient to control diffusion of the metallic-doped ZnTe into the p-type tellurim-containing II-VI semiconductor, but thin enough to minimize affects of series resistance; depositing a second heavy doped p-type ZnTe layer to the first layer using an appropriate dopant; and depositing an appropriate metal onto the outer-most surface of the doped ZnTe layer for connecting an external electrical conductor to an ohmic contact.

  19. Use of separate ZnTe interface layers to form ohmic contacts to p-CdTe films

    DOEpatents

    Gessert, T.A.

    1999-06-01

    A method of is disclosed improving electrical contact to a thin film of a p-type tellurium-containing II-VI semiconductor comprising: depositing a first undoped layer of ZnTe on a thin film of p-type tellurium containing II-VI semiconductor with material properties selected to limit the formation of potential barriers at the interface between the p-CdTe and the undoped layer, to a thickness sufficient to control diffusion of the metallic-doped ZnTe into the p-type tellurium-containing II-VI semiconductor, but thin enough to minimize affects of series resistance; depositing a second heavy doped p-type ZnTe layer to the first layer using an appropriate dopant; and depositing an appropriate metal onto the outer-most surface of the doped ZnTe layer for connecting an external electrical conductor to an ohmic contact. 11 figs.

  20. Voltammetric studies on the potent carcinogen, 7,12-dimethylbenz[ a]anthracene: Adsorptive stripping voltammetric determination in bulk aqueous forms and human urine samples and detection of DNA interaction on pencil graphite electrode

    Microsoft Academic Search

    Y. Yard?m; E. Keskin; A. Levent; M. Özsöz; Z. ?entürk

    2010-01-01

    7,12-Dimethylbenz[a]anthracene (DMBA), is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a very potent carcinogen. Initially, the electrochemical oxidation of DMBA at the glassy carbon and pencil graphite electrodes in non-aqueous media (dimethylsulphoxide with lithium perchlorate) was studied by cyclic voltammetry. DMBA was irreversibly oxidized in two steps at high positive potentials, resulting in the ill-resolved

  1. Contact Lenses

    MedlinePLUS

    ... Patients & Public > Caring for Your Vision > Contact Lenses Contact Lenses Eye See Tobacco Free Contact Lens Safety ... up visits over a specified time. Recommendations for Contact Lens Wearers from the American Optometric Association Always ...

  2. Surface preparation for Schottky metal - 4H-SiC contacts formed on plasma-etched SiC

    Microsoft Academic Search

    D. J. Morrison; A. J. Pidduck; V. Moore; P. J. Wilding; K. P. Hilton; M. J. Uren; C. M. Johnson; N. G. Wright; A. G. O'Neill

    2000-01-01

    Silicon-carbide-based devices frequently require a Schottky gate to be deposited on a plasma-etched surface. This paper considers the effectiveness of nine different pre-metallization surface preparation procedures in removing the etch damage. The surfaces were assessed by x-ray photoelectron spectroscopy and by current-voltage measurement of nickel Schottky diodes formed on both reactive-ion-etched and non-reactive-ion-etched silicon face 4H-SiC. The treatments included simple

  3. Staphylococcal alpha -toxin: Oligomerization of Hydrophilic Monomers to Form Amphiphilic Hexamers Induced through Contact with Deoxycholate Detergent Micelles

    Microsoft Academic Search

    Sucharit Bhakdi; Roswitha Fussle; Jorgen Tranum-Jensen

    1981-01-01

    Native staphylococcus aureus alpha -toxin is secreted as a hydrophilic polypeptide chain of Mr 34,000. The presence of deoxycholate above the critical micellar concentration induced the toxin monomers to self-associate, forming ring or cylindrical oligomers. The oligomers were amphiphilic and bound detergent. In deoxycholate solution, the protein-detergent complexes exhibited a sedimentation coefficient of 10.4 S. A Mr of 238,700 was

  4. Bullous contact dermatitis caused by self-applied crushed Paederus fuscipes for the treatment of vitiligo.

    PubMed

    You, Dong-O; Kang, Jung-Dae; Youn, Nyoung-Hoon; Park, Seok-Don

    2003-11-01

    Paederus dermatitis is a linear, blistering contact dermatitis caused by pederin, a potent vesicant agent that is contained in insects belonging to the genus Paederus. This form of dermatitis usually occurs accidentally in those who have contact with this insect during the summer season. We report a peculiar case of a patient developing severe chemical burnlike lesions after application to her skin of many crushed Paederus fuscipes that she collected from the soil of a riverbank in the early spring for the treatment of her vitiligo. PMID:14655779

  5. Abstract--At elevated temperatures Si reacts with SiO2 to form a volatile SiO. This process affects edges of contact windows in

    E-print Network

    Technische Universiteit Delft

    affects edges of contact windows in SiO2. In this paper a systematic analysis of the effect of a baking step on contact windows is presented. Formation of cavities at contact window edges and lateral widening of contact windows have been observed. Linear time dependence and temperature dependence according

  6. Texas A&M Identity Services One Time Data Request For help with completing this form, contact IT Infrastructure & Operations at idm-support@tamu.edu or the Identity Management Office at

    E-print Network

    Texas A&M Identity Services One Time Data Request For help with completing this form, contact IT Infrastructure & Operations at idm-support@tamu.edu or the Identity Management Office at 979.845.4300. Email the completed form to idm-support@tamu.edu, fax to 979.845.6090, or mail to Identity Management Office, MS 3374

  7. Curcumin analogs as potent aldose reductase inhibitors.

    PubMed

    Du, Zhi-Yun; Bao, Ya-Dan; Liu, Zhong; Qiao, Wei; Ma, Lin; Huang, Zhi-Shu; Gu, Lian-Quan; Chan, Albert S C

    2006-03-01

    In the present study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A(2)), 2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B(2)), 1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C(2)), and 3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D(2)) showed remarkably potent inhibitory effects on aldose reductase with IC(50) of 2.9 microM, 2.6 microM, 3.4 microM, and 4.9 microM, respectively. The structure-activity relationship revealed that the curcumin analogs with ortho-dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities. PMID:16528793

  8. Contact dermatitis

    MedlinePLUS

    Dermatitis - contact; Allergic dermatitis; Dermatitis - allergic ... There are two types of contact dermatitis. Irritant dermatitis: This is the most common type. It can be by contact with acids, alkaline materials such as soaps ...

  9. Making Contact. Generating Interethnic Contact for Multicultural Integration and Tolerance in Amsterdam

    ERIC Educational Resources Information Center

    Muller, Floris

    2012-01-01

    Interethnic contact is considered a potent tool for the generation of interethnic understanding and tolerance. This faith has engendered countless social projects that seek to stimulate contact between members of different ethnic groups under "optimal conditions". However, the academic literature does not stipulate how, if at all, these optimal…

  10. NCI-Frederick FACILITY - Contact

    Cancer.gov

      FACILITY Data Management Home System Overview How to Get Started Training User Information Forms Contact Information LASP Online Access System Administration Contact Information If you have questions, concerns, or suggestions regarding your use of

  11. TCGA Contacts

    Cancer.gov

    Home About TCGA People and Contacts TCGA Contacts TCGA Contacts For more information about The Cancer Genome Atlas Program, please contact: The Cancer Genome Atlas Program OfficeNational Cancer Institute at NIH31 Center DriveBldg. 31, Suite 3A20Bethesda,

  12. Design and Synthesis of Potent, Selective Inhibitors of Matriptase

    PubMed Central

    2012-01-01

    Matriptase is a member of the type II transmembrane serine protease family. Several studies have reported deregulated matriptase expression in several types of epithelial cancers, suggesting that matriptase constitutes a potential target for cancer therapy. We report herein a new series of slow, tight-binding inhibitors of matriptase, which mimic the P1–P4 substrate recognition sequence of the enzyme. Preliminary structure–activity relationships indicate that this benzothiazole-containing RQAR-peptidomimetic is a very potent inhibitor and possesses a good selectivity for matriptase versus other serine proteases. A molecular model was generated to elucidate the key contacts between inhibitor 1 and matriptase. PMID:24900505

  13. A Potent, Versatile Disulfide-Reducing Agent from Aspartic Acid John C. Lukesh, III,

    E-print Network

    Raines, Ronald T.

    , § Molecular & Cellular Pharmacology Graduate Training Program, and Department of Biochemistry, University a mixed disulfide by forming a six- membered ring.2a,5 DTT is a potent reducing agent (E° = -0.327 V),2g

  14. Contact Dermatitis

    MedlinePLUS

    ... happen immediately. Most take time to appear. Allergic contact dermatitis Some people have an allergic skin reaction. ... a few hours or days Latex gloves Irritant contact dermatitis This type is more common. It develops ...

  15. Contact Us

    Cancer.gov

    If you have any questions or need more information on federal legislation and congressional activity affecting cancer research, please contact us!  Be sure to include your e-mail address and office telephone number. Contact information National Cancer

  16. Investigation of montmorillonite alteration and form of iron corrosion products in compacted bentonite in contact with carbon steel for ten years

    NASA Astrophysics Data System (ADS)

    Ishidera, Takamitsu; Ueno, Kenichi; Kurosawa, Seiichi; Suyama, Tadahiro

    In high-level radioactive waste disposal, the alteration of montmorillonite due to the corrosion of carbon steel possibly affects the swelling and self-healing capacity of compacted bentonite used as a buffer material. The nature of the corrosion products in compacted bentonite is also important to evaluate not only the diffusion and sorption behavior of radionuclides but also the chemical composition and redox potential of pore water. In this study, the alteration of montmorillonite in compacted bentonite due to the interaction with carbon steel was analyzed by X-ray diffraction (XRD). The possibility of montmorillonite alteration was also investigated from the cation exchange capacity (CEC) of compacted bentonite and scanning electron microscopy (SEM) observation. The corrosion products distributed in the compacted bentonite were investigated by selective dissolution analysis, which can estimate the crystallinity of Fe-bearing compounds. The valence of Fe in the corrosion products was spectrophotometrically determined. From the XRD analysis, newly formed phyllosilicates resulting from the alteration of montmorillonite could not be identified in compacted bentonite. CEC of compacted bentonite adjacent to the carbon steel, in which high concentration of Fe was extracted, was hardly decreased. No significant differences of clay particles were observed with SEM. Thus, the alteration of montmorillonite was scarcely detected in compacted bentonite in contact with carbon steel for ten years. The selective dissolution and valence analyses suggest that most of the corrosion products of carbon steel existed in Kunipia F, which consists of over 95 wt% montmorillonite, was amorphous, non-crystalline or poorly ordered Fe(OH) 2. This means that Fe(OH) 2 distributed into compacted bentonite was scarcely crystallized within ten years at 80 oC. From the XRD analysis, small amount of green rust one containing Cl - at the interlayers (GR1(Cl -)) and lepidocrocite were also identified in Kunipia F. Therefore, under this experimental condition, Fe(OH) 2 formed in Kunipia F due to the corrosion of carbon steel was oxidized to GR1(Cl -) as intermediates, and then GR1(Cl -) was possibly oxidized to lepidocrocite. On the other hand, GR1(Cl -) was hardly detected in Kunigel V1, which contains 46-49 wt% montmorillonite, from the XRD analysis.

  17. A Potent Peptidomimetic Inhibitor of Botulinum Neurotoxin Serotype a Has a Very Different Conformation Than SNAP-25 Substrate

    SciTech Connect

    Zuniga, J.E.; Schmidt, J.J.; Fenn, T.; Burnett, J.C.; Arac, D.; Gussio, R.; Stafford, R.G.; Badie, S.S.; Bavari, S.; Brunger, A.T.

    2009-05-28

    Botulinum neurotoxin serotype A is the most lethal of all known toxins. Here, we report the crystal structure, along with SAR data, of the zinc metalloprotease domain of BoNT/A bound to a potent peptidomimetic inhibitor (Ki = 41 nM) that resembles the local sequence of the SNAP-25 substrate. Surprisingly, the inhibitor adopts a helical conformation around the cleavage site, in contrast to the extended conformation of the native substrate. The backbone of the inhibitor's P1 residue displaces the putative catalytic water molecule and concomitantly interacts with the 'proton shuttle' E224. This mechanism of inhibition is aided by residue contacts in the conserved S1' pocket of the substrate binding cleft, and the induction of new hydrophobic pockets, which are not present in the apo form, especially for the P2' residue of the inhibitor. Our inhibitor is specific for BoNT/A as it does not inhibit other BoNT serotypes or thermolysin.

  18. Thermal stability study of Cr/Au contact formed on n-type Ga-polar GaN, N-polar GaN, and wet-etched N-polar GaN surfaces

    NASA Astrophysics Data System (ADS)

    Choi, Yunju; Kim, Yangsoo; Ahn, Kwang-Soon; Kim, Hyunsoo

    2014-10-01

    The electrical characteristics and thermal stability of a Cr/Au contact formed on n-type Ga-polar (0 0 0 1) GaN, N-polar GaN, and wet-etched N-polar GaN were investigated. As-deposited Cr/Au showed a nearly ohmic contact behavior for all samples, i.e., the specific contact resistance was 3.2 × 10-3, 4.3 × 10-4, and 1.1 × 10-3 ? cm2 for the Ga-polar, flat N-polar, and roughened N-polar samples, respectively. However, thermal annealing performed at 250 °C for 1 min in a N2 ambient led to a significant degradation of contact, i.e., the contact resistance increased by 186, 3260, and 2030% after annealing for Ga-polar, flat N-polar, and roughened N-polar samples, respectively. This could be due to the different disruption degree of Cr/Au and GaN interface after annealing, i.e., the insignificant interfacial reaction occurred in the Ga-polar sample, while out-diffusion of Ga and N atoms was clearly observed in N-polar samples.

  19. Solar cell contact formation using laser ablation

    DOEpatents

    Harley, Gabriel; Smith, David D.; Cousins, Peter John

    2014-07-22

    The formation of solar cell contacts using a laser is described. A method of fabricating a back-contact solar cell includes forming a poly-crystalline material layer above a single-crystalline substrate. The method also includes forming a dielectric material stack above the poly-crystalline material layer. The method also includes forming, by laser ablation, a plurality of contacts holes in the dielectric material stack, each of the contact holes exposing a portion of the poly-crystalline materiat layer; and forming conductive contacts in the plurality of contact holes.

  20. Solar cell contact formation using laser ablation

    DOEpatents

    Harley, Gabriel; Smith, David; Cousins, Peter

    2012-12-04

    The formation of solar cell contacts using a laser is described. A method of fabricating a back-contact solar cell includes forming a poly-crystalline material layer above a single-crystalline substrate. The method also includes forming a dielectric material stack above the poly-crystalline material layer. The method also includes forming, by laser ablation, a plurality of contacts holes in the dielectric material stack, each of the contact holes exposing a portion of the poly-crystalline material layer; and forming conductive contacts in the plurality of contact holes.

  1. Potent Anti-Cancer Toxin

    Cancer.gov

    SKIP ALL NAVIGATION SKIP TO SUB MENU Search Site Standard Forms & Agreements Co-Development & Resources Careers & Training Intellectual Property & Inventions About TTC Overview Biomarkers Available Opportunities Resources Get Connected with TTC Complete

  2. Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors.

    PubMed

    Glunz, Peter W; Cheng, Xuhong; Cheney, Daniel L; Weigelt, Carolyn A; Wei, Anzhi; Luettgen, Joseph M; Wong, Pancras C; Wexler, Ruth R; Priestley, E Scott

    2015-05-15

    Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring forms key hydrophobic interactions with the S1' pocket. Exploration of phenylimidazole substitution led to the discovery of potent, selective and efficacious inhibitors of TF-FVIIa. PMID:25881820

  3. Contact electrification

    Microsoft Academic Search

    J. Lowell; A. C. Rose-Innes

    1980-01-01

    If two materials are brought into contact and then separated they are found to be charged; this is the phenomenon of `contact electrification'. The subject falls naturally into three divisions---electrification of metals by metals; of insulators by metals; and of insulators by insulators. The first of these is well understood; charge transfer between metals is such as to bring the

  4. Cross-contact chain

    NASA Technical Reports Server (NTRS)

    Lieneweg, Udo (Inventor)

    1988-01-01

    A system is provided for use with wafers that include multiple integrated circuits that include two conductive layers in contact at multiple interfaces. Contact chains are formed beside the integrated circuits, each contact chain formed of the same two layers as the circuits, in the form of conductive segments alternating between the upper and lower layers and with the ends of the segments connected in series through interfaces. A current source passes a current through the series-connected segments, by way of a pair of current tabs connected to opposite ends of the series of segments. While the current flows, voltage measurements are taken between each of a plurality of pairs of voltage tabs, the two tabs of each pair connected to opposite ends of an interface that lies along the series-connected segments. A plot of interface conductances on a normal probability chart, enables prediction of the yield of good integrated circuits from the wafer.

  5. Cross-contact chain

    NASA Technical Reports Server (NTRS)

    Lieneweg, U. (inventor)

    1986-01-01

    A system is provided for use with wafers that include multiple integrated circuits that include two conductive layers in contact at multiple interfaces. Contact chains are formed beside the integrated circuits, each contact chain formed of the same two layers as the circuits, in the form of conductive segments alternating between the upper and lower layers and with the ends of the segments connected in series through interfaces. A current source passes a current through the series-connected segments, by way of a pair of current tabs connected to opposite ends of the series of segments. While the current flows, voltage measurements are taken between each of a plurality of pairs of voltage tabs, the two tabs of each pair connected to opposite ends of an interface that lies along the series-connected segments. A plot of interface conductances on normal probability chart enables prediction of the yield of good integrated circuits from the wafer.

  6. Structures and mechanism for the design of highly potent glucocorticoids

    PubMed Central

    He, Yuanzheng; Yi, Wei; Suino-Powell, Kelly; Zhou, X Edward; Tolbert, W David; Tang, Xiaobo; Yang, Jing; Yang, Huaiyu; Shi, Jingjing; Hou, Li; Jiang, Hualiang; Melcher, Karsten; Xu, H Eric

    2014-01-01

    The evolution of glucocorticoid drugs was driven by the demand of lowering the unwanted side effects, while keeping the beneficial anti-inflammatory effects. Potency is an important aspect of this evolution as many undesirable side effects are associated with use of high-dose glucocorticoids. The side effects can be minimized by highly potent glucocorticoids that achieve the same treatment effects at lower doses. This demand propelled the continuous development of synthetic glucocorticoids with increased potencies, but the structural basis of their potencies is poorly understood. To determine the mechanisms underlying potency, we solved the X-ray structures of the glucocorticoid receptor (GR) ligand-binding domain (LBD) bound to its endogenous ligand, cortisol, which has relatively low potency, and a highly potent synthetic glucocorticoid, mometasone furoate (MF). The cortisol-bound GR LBD revealed that the flexibility of the C1-C2 single bond in the steroid A ring is primarily responsible for the low affinity of cortisol to GR. In contrast, we demonstrate that the very high potency of MF is achieved by its C-17? furoate group completely filling the ligand-binding pocket, thus providing additional anchor contacts for high-affinity binding. A single amino acid in the ligand-binding pocket, Q642, plays a discriminating role in ligand potency between MF and cortisol. Structure-based design led to synthesis of several novel glucocorticoids with much improved potency and efficacy. Together, these results reveal key structural mechanisms of glucocorticoid potency and provide a rational basis for developing novel highly potent glucocorticoids. PMID:24763108

  7. Structures and mechanism for the design of highly potent glucocorticoids.

    PubMed

    He, Yuanzheng; Yi, Wei; Suino-Powell, Kelly; Zhou, X Edward; Tolbert, W David; Tang, Xiaobo; Yang, Jing; Yang, Huaiyu; Shi, Jingjing; Hou, Li; Jiang, Hualiang; Melcher, Karsten; Xu, H Eric

    2014-06-01

    The evolution of glucocorticoid drugs was driven by the demand of lowering the unwanted side effects, while keeping the beneficial anti-inflammatory effects. Potency is an important aspect of this evolution as many undesirable side effects are associated with use of high-dose glucocorticoids. The side effects can be minimized by highly potent glucocorticoids that achieve the same treatment effects at lower doses. This demand propelled the continuous development of synthetic glucocorticoids with increased potencies, but the structural basis of their potencies is poorly understood. To determine the mechanisms underlying potency, we solved the X-ray structures of the glucocorticoid receptor (GR) ligand-binding domain (LBD) bound to its endogenous ligand, cortisol, which has relatively low potency, and a highly potent synthetic glucocorticoid, mometasone furoate (MF). The cortisol-bound GR LBD revealed that the flexibility of the C1-C2 single bond in the steroid A ring is primarily responsible for the low affinity of cortisol to GR. In contrast, we demonstrate that the very high potency of MF is achieved by its C-17? furoate group completely filling the ligand-binding pocket, thus providing additional anchor contacts for high-affinity binding. A single amino acid in the ligand-binding pocket, Q642, plays a discriminating role in ligand potency between MF and cortisol. Structure-based design led to synthesis of several novel glucocorticoids with much improved potency and efficacy. Together, these results reveal key structural mechanisms of glucocorticoid potency and provide a rational basis for developing novel highly potent glucocorticoids. PMID:24763108

  8. Types of Contact Lenses

    MedlinePLUS

    ... Consumer Devices Consumer Products Contact Lenses Types of Contact Lenses There are two general categories of contact ... Orthokeratology (Ortho-K) Decorative (Plano) Contact Lenses Soft Contact Lenses Soft contact lenses are made of soft, ...

  9. Cloning of regions required for contact hemolysis and entry into LLC-MK2 cells from Shigella sonnei form I plasmid: virF is a positive regulator gene for these phenotypes.

    PubMed Central

    Kato, J; Ito, K; Nakamura, A; Watanabe, H

    1989-01-01

    Two distinct regions required for both contact hemolysis and entry into LLC-MK2 cells were cloned into Escherichia coli from the Shigella sonnei form I plasmid, pSS120. The first region was cloned into an E. coli HB101 strain containing noninvasive Tn1 insertion mutants of the form I plasmid, and expression of ipa (invasion plasmid antigen) gene products was restored. The plasmid carrying the first region was then transformed into E. coli lacking the form I plasmid, and additional DNA fragments from the form I plasmid were cloned into the same recipient on compatible vectors. Five of these double transformants were found to be positive for contact hemolysis activity. Restriction analysis of these five clones indicated that the previously reported ipa locus and the invA locus were present on the second plasmid region. Only the strains carrying both of these regions were active in contact hemolysis and cell invasion assays. Several proteins, including the a, b, c, and d proteins encoded by the ipa genes, were detected in the double transformants by Western blot (immunoblot) analysis with serum of a monkey convalescing from shigellosis. A positive regulator was suggested to exist in the first region, since the amounts of most of these proteins were simultaneously increased in the presence of this region. Subcloning and nucleotide sequencing indicated that this positive regulator gene was virF. Product analysis of the virF gene with minicells showed that two peptides (30 and 21 kilodaltons) were synthesized and that at least the 30-kilodalton protein was essential for regulation of the ipa genes. Images PMID:2651305

  10. Allergic contact dermatitis

    Microsoft Academic Search

    Ian Kimber; David A Basketter; G. Frank Gerberick; Rebecca J Dearman

    2002-01-01

    Allergic contact dermatitis (ACD) is a common occupational and environmental health issue. In common with other forms of allergy the disease progresses in two stages; an initial phase during which sensitization is acquired, followed later (after subsequent exposure to the same chemical allergen) by elicitation of a cutaneous inflammatory reaction. The development of skin sensitization is associated with, and requires,

  11. Teachers Name Contact Number

    E-print Network

    South Australia, University of

    Teachers Name Contact Number Email School Year Level of Students Number of students attending Lakes on Thursday 19 September 2013, 1.00--3.30pm. Workshops are between 1.00 and 3.00pm, with a free Lakes campus Switch On: Mawson Lakes--Registration Form #12;

  12. Compact contacting device

    NASA Technical Reports Server (NTRS)

    Acharya, Arun (Inventor); Gottzmann, Christian F. (Inventor); Lockett, Michael J. (Inventor); Schneider, James S. (Inventor); Victor, Richard A. (Inventor); Zawierucha, Robert (Inventor)

    1994-01-01

    An apparatus comprising a rotatable mass of structured packing for mass or heat transfer between two contacting fluids of different densities wherein the packing mass is made up of corrugated sheets of involute shape relative to the axis of the packing mass and form a logarithmic spiral curved counter to the direction of rotation.

  13. Contact complete integrability

    NASA Astrophysics Data System (ADS)

    Khesin, B.; Tabachnikov, S.

    2010-10-01

    Complete integrability in a symplectic setting means the existence of a Lagrangian foliation leaf-wise preserved by the dynamics. In the paper we describe complete integrability in a contact set-up as a more subtle structure: a flag of two foliations, Legendrian and co-Legendrian, and a holonomy-invariant transverse measure of the former in the latter. This turns out to be equivalent to the existence of a canonical ? ? ? n-1 structure on the leaves of the co-Legendrian foliation. Further, the above structure implies the existence of n commuting contact fields preserving a special contact 1-form, thus providing the geometric framework and establishing equivalence with previously known definitions of contact integrability. We also show that contact completely integrable systems are solvable in quadratures. We present an example of contact complete integrability: the billiard system inside an ellipsoid in pseudo-Euclidean space, restricted to the space of oriented null geodesics. We describe a surprising acceleration mechanism for closed light-like billiard trajectories.

  14. Structures of potent anticancer compounds bound to tubulin.

    PubMed

    McNamara, Dan E; Senese, Silvia; Yeates, Todd O; Torres, Jorge Z

    2015-07-01

    Small molecules that bind to tubulin exert powerful effects on cell division and apoptosis (programmed cell death). Cell-based high-throughput screening combined with chemo/bioinformatic and biochemical analyses recently revealed a novel compound MI-181 as a potent mitotic inhibitor with heightened activity towards melanomas. MI-181 causes tubulin depolymerization, activates the spindle assembly checkpoint arresting cells in mitosis, and induces apoptotic cell death. C2 is an unrelated compound previously shown to have lethal effects on microtubules in tumorigenic cell lines. We report 2.60 Å and 3.75 Å resolution structures of MI-181 and C2, respectively, bound to a ternary complex of ??-tubulin, the tubulin-binding protein stathmin, and tubulin tyrosine ligase. In the first of these structures, our crystallographic results reveal a unique binding mode for MI-181 extending unusually deep into the well-studied colchicine-binding site on ?-tubulin. In the second structure the C2 compound occupies the colchicine-binding site on ?-tubulin with two chemical moieties recapitulating contacts made by colchicine, in combination with another system of atomic contacts. These insights reveal the source of the observed effects of MI-181 and C2 on microtubules, mitosis, and cultured cancer cell lines. The structural details of the interaction between tubulin and the described compounds may guide the development of improved derivative compounds as therapeutic candidates or molecular probes to study cancer cell division. PMID:25970265

  15. Systemic contact dermatitis Systemic contact dermatitis Systemic contact dermatitis Systemic contact dermatitis Systemic contact dermatitis

    Microsoft Academic Search

    A. K. Bajaj; A. Saraswat

    Systemic contact dermatitis (SCD), better termed systemically reactivated allergic contact dermatitis, is a type of contact hypersensitivity reaction in which ingestion or other systemic exposure to a contact allergen occurs in an already sensitized person. Although the initial sensitizing exposure is usually by topical application, re-exposure by the oral, intravenous or inhalation routes can cause SCD. Even percutaneous exposure through

  16. Formation Of Ohmic Gold Contacts On Epitaxial GaAs

    NASA Technical Reports Server (NTRS)

    Hecht, Michael H.; Bell, L. Doug; Kaiser, William J.

    1991-01-01

    New low-temperature procedure used to deposit ohmic gold contacts on gallium arsenide epitaxial films, forming ohmic electrical contacts. Keeping wafer in vacuum until metallization prevents formation of rectifying contacts.

  17. Contact Us

    Cancer.gov

    For more information, please contact: Office of Cancer Clinical Proteomics ResearchCenter for Strategic Scientific InitiativesOffice of the DirectorNational Cancer Institute31 Center Drive, MS 2580Bethesda, MD 20892-2580 Telephone: (301) 451-8883Email:

  18. Prioritized Contact Transport Stream

    NASA Technical Reports Server (NTRS)

    Hunt, Walter Lee, Jr. (Inventor)

    2015-01-01

    A detection process, contact recognition process, classification process, and identification process are applied to raw sensor data to produce an identified contact record set containing one or more identified contact records. A prioritization process is applied to the identified contact record set to assign a contact priority to each contact record in the identified contact record set. Data are removed from the contact records in the identified contact record set based on the contact priorities assigned to those contact records. A first contact stream is produced from the resulting contact records. The first contact stream is streamed in a contact transport stream. The contact transport stream may include and stream additional contact streams. The contact transport stream may be varied dynamically over time based on parameters such as available bandwidth, contact priority, presence/absence of contacts, system state, and configuration parameters.

  19. Low- and high-frequency C- V characteristics of the contacts formed by adding a solution of the nonpolymeric organic compound on p-type Si substrate

    NASA Astrophysics Data System (ADS)

    Ebeo?lu, M. A.; K?l?ço?lu, T.; Ayd?n, M. E.

    2007-05-01

    Al/quercetin/p-Si Schottky barrier diodes (SBDs) have been fabricated by adding a solution of the nonpolymeric organic compound quercetin in ethanol on top of p-Si substrate, and then evaporating the solvent. The quercetin/p-Si contact shows rectifying behaviour and the reverse curve exhibit a weak bias voltage dependence. Barrier height and ideality factor value of 0.86 and 1.06 eV, respectively, for the device have been determined from the forward bias current-voltage ( I-V) characteristics. The energy distribution of the interface state density located in the semiconductor band gap at quercetin/p-Si interface ranges from 2.12×10 12 cm -2 eV -1 in (0.680- Ev) eV to 4.68×10 11 cm -2 eV -1 in (0.813- Ev) eV have been determined from the I-V and the capacitance-voltage ( C-V) characteristics (high- and low frequency). The interface state density has an exponential rise with bias from the midgap towards the top of the valence band.

  20. Complete form and bring to Hawley Fitness Center, or mail to Janet Rochester, Dept AHS, Unit 1101. For information, contact Janet.Rochester@Uconn.edu, 6-5975.

    E-print Network

    Alpay, S. Pamir

    Complete form and bring to Hawley Fitness Center, or mail to Janet Rochester, Dept AHS, Unit 1101://cag.uconn.edu/ahs/hawley/ Class Size Limited! Are you ready for... Group Strength Training classes in Hawley Fitness Center conditioned fitness center in Hawley! Choose "The Basics" or "Advanced" levels Learn a variety of strength

  1. Sinterless Formation Of Contacts On Indium Phosphide

    NASA Technical Reports Server (NTRS)

    Weizer, Victor G.; Fatemi, Navid S.

    1995-01-01

    Improved technique makes it possible to form low-resistivity {nearly equal to 10(Sup-6) ohm cm(Sup2)} electrical contacts on indium phosphide semiconductor devices without damaging devices. Layer of AgP2 40 Angstrom thick deposited on InP before depositing metal contact. AgP2 interlayer sharply reduces contact resistance, without need for sintering.

  2. Contact dermatitis in children

    PubMed Central

    2010-01-01

    Contact dermatitis in pediatric population is a common but (previously) under recognized disease. It is usually divided into the allergic and the irritant forms. The diagnosis is usually obtained with the patch test technique after conducting a thorough medical history and careful physical examination but patch testing in infants may be particularly difficult, and false-positive reactions may occur. This study also provides an overview of the most common allergens in pediatric population and discusses various therapeutic modalities. PMID:20205907

  3. Design and Synthesis of Imidazopyrimidine Derivatives as Potent iNOS Dimerization Inhibitors

    PubMed Central

    Chu, Guo-Hua; Le Bourdonnec, Bertrand; Gu, Minghua; Ajello, Christopher W; Leister, Lara K; Sellitto, Ian; Cassel, Joel A; Tuthill, Paul A; O’ Hare, Heather; DeHaven, Robert N; Dolle, Roland E

    2009-01-01

    A series of imidazopyrimidine derivatives with the general formula I was synthesized and identified as potent inhibitors of iNOS dimer formation, a prerequisite for proper functioning of the enzyme. Stille and Negishi coupling reactions were used as key steps to form the carbon-carbon bond connecting the imidazopyrimidine core to the central cycloalkenyl, cycloalkyl and phenyl ring templates. PMID:19966921

  4. Chemistry and Biology of Deoxynyboquinone, a Potent Inducer of Cancer Cell Death

    E-print Network

    Hergenrother, Paul J.

    Chemistry and Biology of Deoxynyboquinone, a Potent Inducer of Cancer Cell Death Joseph S. Bair the mechanism by which DNQ induces death in cancer cells. DNQ was synthesized in seven linear steps through-oxidized by molecular oxygen, forming superoxide that induces cell death. Furthermore, global transcript profiling

  5. Identification of a Potent Endothelium-Derived Angiogenic Factor

    PubMed Central

    Jankowski, Vera; Tölle, Markus; Tran, Thi Nguyet Anh; van der Giet, Markus; Schuchardt, Mirjam; Lehmann, Kerstin; Janke, Doreen; Flick, Burkhard; Ortiz, Alberto Arduan; Sanchez, Niño Maria Dolores; Tepel, Martin; Zidek, Walter; Jankowski, Joachim

    2013-01-01

    The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N?=?6) were sufficient to induce angiogenic and proliferative effects (1.34±0.26 nmol L-1). In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor. PMID:23922657

  6. Texas A&M Identity Services Data Request For help with completing this form see http://infrastructure.tamu.edu/identity/access/form_help.html or contact IT Infrastructure & Operations at

    E-print Network

    Texas A&M Identity Services Data Request For help with completing this form see http://infrastructure.tamu.edu/identity-support@tamu.edu, fax to 979.845.6090, or mail to Director, IT Infrastructure & Operations, c/o Identity Management items 9-12. 9 Name and description of application or service that will use Texas A&M Identity Services

  7. Contact lens management of keratoconus.

    PubMed

    Downie, Laura E; Lindsay, Richard G

    2015-07-01

    Contact lenses are the primary form of visual correction for patients with keratoconus. Contemporary advances in contact lens designs and materials have significantly expanded the available fitting options for patients with corneal ectasia. Furthermore, imaging technology, such as corneal topography and anterior segment optical coherence tomography, can be applied to both gain insight into corneal microstructural changes and to guide contact lens fitting. This paper provides a comprehensive review of the range of contact lens modalities, including soft lenses, hybrid designs, rigid lenses, piggyback configurations, corneo-scleral, mini-scleral and scleral lenses that are currently available for the optical management of keratoconus. The review also discusses the importance of monitoring for disease progression in patients with keratoconus, in particular children, who tend to undergo more rapid progressive changes, so as to facilitate appropriate modification to contact lens fitting and/or potential referral for corneal collagen cross-linking treatment, as appropriate. PMID:26104589

  8. Contact Lens Risks

    MedlinePLUS

    ... Health and Consumer Devices Consumer Products Contact Lenses Contact Lens Risks Wearing contact lenses puts you at ... redness blurred vision swelling pain Serious Hazards of Contact Lenses Symptoms of eye irritation can indicate a ...

  9. EMERGENCY CONTACT CAMPUS DIRECTORY INFORMATION

    E-print Network

    Pilyugin, Sergei S.

    EMERGENCY CONTACT and CAMPUS DIRECTORY INFORMATION Please complete this form so that we have whether you wish to be included in the University of Florida Campus Directory. Submit completed form in the event of an emergency? (If yes, use space below) CAMPUS DIRECTORY Do you wish to have your home address

  10. Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization.

    PubMed

    Sköld, Maria; Börje, Anna; Harambasic, Elma; Karlberg, Ann-Therese

    2004-12-01

    Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an important fragrance chemical, frequently used in scented products because of its fresh, flowery odor. Linalool is an unsaturated hydrocarbon and is therefore susceptible to oxidation in the presence of air. The primary oxidation products, that is, hydroperoxides, formed in the autoxidation process, are reactive compounds that can be suspected to act as sensitizers. In the present investigation, we studied the autoxidation of linalool with emphasis on the formation of hydroperoxides. The oxidation products were isolated using flash chromatography and preparative HPLC and were identified with NMR and GC/MS, using synthesized reference compounds. Two hydroperoxides and several different secondary oxidation products were identified, among which some contain structural features that make them potential allergens. The amounts of linalool and the major oxidation products were quantified over time, using GC and an HPLC-method, suitable for the analysis of thermolabile primary oxidation products. The hydroperoxide 7-hydroperoxy-3,7-dimethylocta-1,5-diene-3-ol was found to be present in 15% in an oxidized sample. The local lymph node assay (LLNA) was used to investigate the sensitizing potential of pure linalool, two samples of air-exposed linalool, and oxidation products of linalool (an alpha,beta-unsaturated aldehyde, a mixture of two hydroperoxides, and an alcohol). Pure linalool showed no sensitizing potential. The air-exposed samples of linalool produced clearly positive responses, and the hydroperoxides were the strongest allergens of the tested oxidation products. The study demonstrates the importance of autoxidation on the sensitizing potential of linalool. We also conclude that the sensitizing potential differs with the composition of the oxidation mixture and thus with the air exposure time. PMID:15606147

  11. Semiconductor ohmic contact

    NASA Technical Reports Server (NTRS)

    Hawrylo, Frank Zygmunt (Inventor); Kressel, Henry (Inventor)

    1977-01-01

    A semiconductor device has one surface of P type conductivity material having a wide energy bandgap and a large crystal lattice parameter. Applied to the P type surface of the semiconductor device is a degenerate region of semiconductor material, preferably a group III-V semiconductor material, having a narrower energy bandgap. The degenerate region is doped with tin to increase the crystal lattice of the region to more closely approximate the crystal lattice of the one surface of the semiconductor device. The degenerate region is compensatingly doped with a P type conductivity modifier. An electrical contact is applied to one surface of the degenerate region forming an ohmic contact with the semiconductor device.

  12. Contact dermatitis.

    PubMed

    Christoforou, Mary

    2002-02-01

    Ted is a 38 year old service technician for a large chemical company servicing cooling towers at a car manufacturing plant. While blending a batch of chemicals, he accidentally splashed cooling tower fluid, Kathon, an isothiazolin-3 derivative, over his left forearm. He was wearing long sleeved overalls and safety glasses at the time. About 15 minutes later, Ted experienced some itchiness of his forearm and proceeded to wash the area. He did not change his uniform. Five hours later he experienced severe pain of the forearm. Inspection revealed a 5 cm dermal burn with obvious blistering over the left forearm. He sought medical treatment and was treated conservatively with routine burn dressings. The skin blistering healed after seven days. Ted returned to work undertaking full duties. When undertaking mixing of cooling tower chemicals he developed an itchy rash of the forearms that appeared to be spreading to his hand and shoulder areas. This skin irritation occurred even when there was no contact with cooling tower fluids. PMID:11936083

  13. Mechanistic basis for the potent anti-angiogenic activity of semaphorin 3F.

    PubMed

    Guo, Hou-Fu; Li, Xiaobo; Parker, Matthew W; Waltenberger, Johannes; Becker, Patrice M; Vander Kooi, Craig W

    2013-10-29

    Neuropilin-1 (Nrp1), an essential type I transmembrane receptor, binds two secreted ligand families, vascular endothelial growth factor (VEGF) and class III Semaphorin (Sema3). VEGF-A and Sema3F have opposing roles in regulating Nrp1 vascular function in angiogenesis. VEGF-A functions as one of the most potent pro-angiogenic cytokines, while Sema3F is a uniquely potent endogenous angiogenesis inhibitor. Sema3 family members require proteolytic processing by furin to allow competitive binding to Nrp1. We demonstrate that the furin-processed C-terminal domain of Sema3F (C-furSema) potently inhibits VEGF-A-dependent activation of endothelial cells. We find that this potent activity is due to unique heterobivalent engagement of Nrp1 by two distinct sites in the C-terminal domain of Sema3F. One of the sites is the C-terminal arginine, liberated by furin cleavage, and the other is a novel upstream helical motif centered on the intermolecular disulfide. Using a novel chimeric C-furSema, we demonstrate that combining a single C-terminal arginine with the helical motif is necessary and sufficient for potent inhibition of binding of VEGF-A to Nrp1. We further demonstrate that the multiple furin-processed variants of Sema3A, with the altered proximity of the two binding motifs, have dramatically different potencies. This suggests that furin processing not only switches Sema3 to an activated form but also, depending on the site processed, can also tune potency. These data establish the basis for potent competitive binding of Sema3 to Nrp1 and provide a basis for the design of bivalent Nrp inhibitors. PMID:24079887

  14. Orally Bioavailable Potent Soluble Epoxide Hydrolase Inhibitors

    PubMed Central

    Hwang, Sung Hee; Tsai, Hsing-Ju; Liu, Jun-Yan; Morisseau, Christophe; Hammock, Bruce D.

    2008-01-01

    A series of N,N?-disubstituted ureas having a conformationally restricted cis- or trans-1,4-cyclohexane ? to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activities against recombinant human sEH. Both isomers showed similar potencies, but the trans isomers were more metabolically stable in human hepatic microsomes. Furthermore, these new potent inhibitors show a greater metabolic stability in vivo than previously described sEH inhibitors. We demonstrated that trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid 13g (t-AUCB, IC50 = 1.3 ± 0.05 nM) had excellent oral bioavailability (98%, n = 2) and blood area under the curve in dogs and was effective in vivo to treat hypotension in lipopolysaccharide challenged murine models. PMID:17616115

  15. Strategies for preventing occupational exposure to potent compounds.

    PubMed

    Calhoun, Dean M; Coler, Angela B; Nieusma, Joe L

    2011-02-01

    Occupational exposure to active pharmaceutical ingredients in a manufacturing or laboratory environmental can cause unintended health effects in workers handling these compounds. Occupational health professionals in the pharmaceutical industry have responded to this hazard recognition by employing strategies for the risk evaluation and management of potent APIs, otherwise known by the term 'potent compounds'. The purpose of this paper is to provide an overview of the necessary strategy components for preventing occupational exposure to potent compounds. PMID:20507226

  16. On the nature of tribological contact in automotive brakes

    Microsoft Academic Search

    Mikael Eriksson; Filip Bergman; Staffan Jacobson

    2002-01-01

    The tribological contact in automotive brakes involves dry sliding contact at high speeds and high contact forces. The commonly used organic binder-type brake pad friction materials are extremely inhomogeneous and exhibit very low bulk strengths. Despite the low strength, the specific contact surfaces that form during the use render the pads very good friction and wear characteristics. This paper gives

  17. Yttrium hole-barrier contacts for germanium semiconductor detectors

    NASA Astrophysics Data System (ADS)

    Hull, Ethan L.; Pehl, Richard H.; Lathrop, James R.; Suttle, Bruce E.

    2011-01-01

    Sputtered yttrium metal forms a thin hole-barrier contact on both p- and n-type germanium semiconductor detectors. Yttrium contacts can provide a sufficiently high hole barrier to prevent measurable contact leakage current below ˜120 K. Detectors having yttrium contacts produce good gamma-ray spectroscopy data.

  18. Personal and Contact Information: APPLICATION FORM

    E-print Network

    Archer, Steven R.

    Grade Point Average Overall: Major: Age: Ethnicity: Female Male Phone Number with Area Code: Home: Cell Mailing Address Current Academic Record: Major: FreshmanStatus as of May 2013: Sophomore Junior Senior Phone: References: 1) Name: Phone Number: Email Address: 2) 3) Availability: Earliest available date

  19. Personal and Contact Information: APPLICATION FORM

    E-print Network

    Archer, Steven R.

    Grade Point Average Overall: Major: Age: Ethnicity: Female Male Phone Number with Area Code: Home: Cell Mailing Address Current Academic Record: Major: FreshmanStatus as of May 2012: Sophomore Junior Senior Phone: References: 1) Name: Phone Number: Email Address: 2) 3) Availability: Earliest available date

  20. Solution-Assisted Optical Contacting

    NASA Technical Reports Server (NTRS)

    Shaddock, Daniel; Abramovici, Alexander

    2004-01-01

    A modified version of a conventional optical-contact procedure has been found to facilitate alignment of optical components. The optical-contact procedure (called simply optical contacting in the art) is a standard means of bonding two highly polished and cleaned glass optical components without using epoxies or other adhesives. In its unmodified form, the procedure does not involve the use of any foreign substances at all: components to be optically contacted are dry. The main disadvantage of conventional optical contacting is that it is difficult or impossible to adjust the alignment of the components once they have become bonded. In the modified version of the procedure, a drop of an alcohol-based optical cleaning solution (isopropyl alcohol or similar) is placed at the interface between two components immediately before putting the components together. The solution forms a weak bond that gradually strengthens during a time interval of the order of tens of seconds as the alcohol evaporates. While the solution is present, the components can be slid, without loss of contact, to perform fine adjustments of their relative positions. After about a minute, most of the alcohol has evaporated and the optical components are rigidly attached to each other. If necessary, more solution can be added to enable resumption or repetition of the adjustment until the components are aligned to the required precision.

  1. EDITORIAL: Close contact Close contact

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-07-01

    The development of scanning probe techniques, such as scanning tunnelling microscopy [1], has often been touted as the catalyst for the surge in activity and progress in nanoscale science and technology. Images of nanoscale structural detail have served as an invaluable investigative resource and continue to fascinate with the fantastical reality of an intricate nether world existing all around us, but hidden from view of the naked eye by a disparity in scale. As is so often the case, the invention of the scanning tunnelling microscope heralded far more than just a useful new apparatus, it demonstrated the scope for exploiting the subtleties of electronic contact. The shrinking of electronic devices has been a driving force for research into molecular electronics, in which an understanding of the nature of electronic contact at junctions is crucial. In response, the number of experimental techniques in molecular electronics has increased rapidly in recent years. Scanning tunnelling microscopes have been used to study electron transfer through molecular films on a conducting substrate, and the need to monitor the contact force of scanning tunnelling electrodes led to the use of atomic force microscopy probes coated in a conducting layer as studied by Cui and colleagues in Arizona [2]. In this issue a collaboration of researchers at Delft University and Leiden University in the Netherlands report a new device architecture for the independent mechanical and electrostatic tuning of nanoscale charge transport, which will enable thorough studies of molecular transport in the future [3]. Scanning probes can also be used to pattern surfaces, such as through spatially-localized Suzuki and Heck reactions in chemical scanning probe lithography. Mechanistic aspects of spatially confined Suzuki and Heck chemistry are also reported in this issue by researchers in Oxford [4]. All these developments in molecular electronics fabrication and characterization provide alternative means to produce nanoscale device elements, such as carbon nanotube transistors [5] and high-density memory crossbar circuits [6]. Recently, the use of scanning tunnelling microscopes has broached a new field of research, which is currently attracting enormous interest—single molecule detection. In issue 25 of Nanotechnology researchers in Houston reported unprecedented sensitivities using localized surface plasmon resonance shifts of gold bipyramids to detect concentrations of substances down to the single molecule level [7]. In issue 26 a collaboration of researchers from the US and Czech Republic describe a different approach, namely tunnelling recognition. In their topical review they describe hydrogen-bond mediated tunnelling and the associated experimental methods that facilitate the detection of single molecules in a tunnel junction using chemically functionalized electrodes [8]. The nanoworld depicted by scanning probe microgaphs over 20 years ago may have looked as extraterrestrial as any science fiction generated alien terrain, but though study and analysis these nano-landscapes have become significantly less alien territory. The work so far to unveil the intricacies of electronic contact has been a story of progress in investigating this new territory and manipulating the mechanisms that govern it to formulate new devices and delve deeper into phenomena at the nanoscale. References [1] Binning G, Rohrer H, Gerber Ch and Weibel E 1982 Phys. Rev. Lett. 49 57-61 [2] X D Cui, X Zarate, J Tomfohr, O F Sankey, A Primak, A L Moore, T A Moore, D Gust, G~Harris and S M Lindsay 2002 Nanotechnology 13 5-14 [3] Martin C A, van Ruitenbeek J M and van der Zant S J H 2010 Nanotechnology 21 265201 [4] Davis J J and Hanyu Y 2010 Nanotechnology 21 265302 [5] Tans S J, Verschueren A R M and Dekker C 1998 Nature 393 49-52 [6] Chen Y, Jung G-Y, Ohlberg D A A, Li X, Stewart D R, Jeppesen J O, Nielsen K A, Stoddart J F and Williams R S 2003 Nanotechnology 14 462-8 [7] Mayer K M, Hao F, Lee S, Nordlander P and Hafner J H 2010 Nanotechnology 21 255503 [8] Lindsay S, He J, Sank

  2. Nanoscale roughness contact in a slider-disk interface.

    PubMed

    Hua, Wei; Liu, Bo; Yu, Shengkai; Zhou, Weidong

    2009-07-15

    The nanoscale roughness contact between molecularly smooth surfaces of a slider-disk interface in a hard disk drive is analyzed, and the lubricant behavior at very high shear rate is presented. A new contact model is developed to study the nanoscale roughness contact behavior by classifying various forms of contact into slider-lubricant contact, slider-disk elastic contact and plastic contact. The contact pressure and the contact probabilities of the three types of contact are investigated. The new contact model is employed to explain and provide insight to an interesting experimental result found in a thermal protrusion slider. The protrusion budget for head surfing in the lubricant, which is the ideal state for contact recording, is also discussed. PMID:19550006

  3. Buying Cosmetic Contact Lenses?

    MedlinePLUS

    ... Your Prescription Should Be Easy What Are Cosmetic Contacts? Whether you're planning to cap off a ... from blue to violet for the day, cosmetic contactscontact lenses meant to change the way your ...

  4. Contact Lens Care

    MedlinePLUS

    ... For Consumers Consumer Information by Audience For Women Contact Lens Care Print and Share (PDF 182KB) En ... 1088, www.fda.gov/medwatch Learn More about Contact Lens Care Other Tips on Contact Lenses Decorative ...

  5. Peptidomimetics as potent and selective PTP1B inhibitors.

    PubMed

    Patel, Dipam; Jain, Mukul; Shah, Shailesh R; Bahekar, Rajesh; Jadav, Pradip; Shah, Kiran; Joharapurkar, Amit; Shaikh, Mubeen; Sairam, Kalapatapu V V M

    2013-08-01

    A series of peptidomimetic containing bidentate pTyr mimetics (9a-w) are reported as potent and selective PTP1B inhibitors. Compounds (9p and 9q) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro), which confirms discovery of highly potent and selective PTP1B inhibitors. PMID:23030658

  6. Isolation of peptides of the brevinin-1 family with potent

    E-print Network

    Davidson, Carlos

    Isolation of peptides of the brevinin-1 family with potent candidacidal activity from the skin types of antifungal agents. Six peptides with antimicrobial activity were isolated from norepinephrine´l, T. & Rollins-Smith, L.A. Isolation of peptides of the brevinin-1 family with potent candidacidal

  7. Superstring amplitudes and contact interactions

    Microsoft Academic Search

    J. Greensite; F. R. Klinkhamer

    1988-01-01

    We show that scattering amplitudes computed from light-cone superstring field theory are divergent at tree level. The divergences can be eliminated, and supersymmetry restored, by the addition of certain counter terms to the light-cone hamiltonian. These counter terms have the form of local contact interactions, whose existence we had previously deduced on grounds of vacuum stability and closure of the

  8. Leptin: a potent inhibitor of insulin secretion.

    PubMed

    Fehmann, H C; Peiser, C; Bode, H P; Stamm, M; Staats, P; Hedetoft, C; Lang, R E; Göke, B

    1997-01-01

    The hormone leptin is expressed and secreted by the adipose tissue and impacts on the central nervous system. Leptin is involved in the regulation of energy balance, satiety, and body composition. The lack of active leptin results in obesity, high food intake, hyperglycemia, and hyperinsulinemia. We present data supporting effects of leptin on the endocrine pancreas. We found the leptin receptor to be expressed in insulin- and glucagon-secretin cells derived from mouse, hamster, and rat pancreas. In the isolated perfused rat pancreas leptin is a potent inhibitor of basal and glucose-induced insulin secretion, especially during the first phase of the insulin response. At isolated mouse islets and insulin-secreting INS-1 cells leptin reduced promptly and persistently the intracellular Ca2+ levels. Cytoplasmic Ca2+ oscillation amplitude was decreased and the oscillation frequency increased. These findings suggest functional active receptors for leptin on insulin-secreting B-cells. Therefore, leptin is a metabolic hormone and not only a signal to the brain indicating filled fat stores. Our data suggest that leptin is also a signal back to the endocrine pancreas that no more insulin is required to replenish fat stores. Thus, an "adipo-insular axis" operating with two arms exists: insulin and glucagon are signals to the adipocyte. This releases leptin, which could be the mediator of the respective feedback to the pancreas. A defective leptin suppression of insulin secretion could contribute to hyperinsulinemia and disturbances of glucose metabolism. PMID:9396072

  9. For questions, contact the Rice Alliance at 713.348.3443 Submit form with payment details via fax at 713.348.3110 or mail to: Rice Alliance for Technology and Entrepreneurship Rice University MS-531 P.O. Box 2932 Houston, TX 77252-2932

    E-print Network

    For questions, contact the Rice Alliance at 713.348.3443 · Submit form with payment details via fax at 713.348.3110 or mail to: Rice Alliance for Technology and Entrepreneurship · Rice University · MS-531 · P.O. Box 2932 · Houston, TX · 77252-2932 Rice Alliance Annual Corporate Underwriter Program 2012

  10. Contacts for wide bandgap semiconductor materials

    NASA Astrophysics Data System (ADS)

    Lamp, Thomas; Liu, Sam; Ramalingam, M. L.

    1997-01-01

    Several metal systems were evaluated to determine their ability to form electrical contacts on diamond and silicon carbide (SiC) materials. Experimental metal contacts were applied to doped samples of both diamond and SiC. The diamond contacts work reported herein focuses on the electrical and thermal stability properties of Au, Ni/W and Al/W contacts on p-type polycrystalline diamond films. These contacts on diamond exhibited perfect ohmic behavior in the as-deposited condition. Resistivities were on the order of 10-4 ohm-cm2. Although a number of ohmic contact systems on SiC were studied, the contact work reported herein specifically addresses the electrical performance and thermal stability of Ni/Cr/W on n-type 6H- and 4H-SiC. It was found that ohmic contacts are formed to both 6H- and 4H-SiC after annealing at 1273 K to 1323 K for 5 to 10 minutes. Contact resistivity ranges between 10-4 and 10-6 ohm-cm2 with excellent reproducibility. Testing of the SiC contact system at 923 K over a period of 3000 hours revealed no degradation in performance.

  11. Introduction Multi Market Contact

    E-print Network

    Bustamante, Fabián E.

    Introduction Multi Market Contact Formal Model Empirics The Competitive Eect of Multimarket Contact Arie, Sarit Markovich, Mauricio Varela Multi-Market Competition #12;Introduction Multi Market Contact Formal Model Empirics Hello Thanks for coming! What is multi-market contact? Why should we care? Prots

  12. Boundary element formulation for thermoelastohydrodynamic contact problems

    Microsoft Academic Search

    A. Gakwaya; D. Despres

    1991-01-01

    This paper presents a boundary element formulation and numerical solution of lubricated contact problems. It uses the full Navier-Stokes equation for thermoviscous incompressible lubricant fluid and the thermoelastic equations for the contacting solids. These equations form a coupled system that is written into equivalent boundary-domain integral equations which are then discretized using both conforming and nonconforming boundary elements. The resulting

  13. Sifuvirtide, a potent HIV fusion inhibitor peptide

    SciTech Connect

    Wang, Rui-Rui; Yang, Liu-Meng; Wang, Yun-Hua [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)] [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China); Pang, Wei [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China) [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China); Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Tam, Siu-Cheung [Department of Physiology, Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China)] [Department of Physiology, Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China); Tien, Po [Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China)] [Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Zheng, Yong-Tang, E-mail: zhengyt@mail.kiz.ac.cn [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)] [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)

    2009-05-08

    Enfuvirtide (ENF) is currently the only FDA approved HIV fusion inhibitor in clinical use. Searching for more drugs in this category with higher efficacy and lower toxicity seems to be a logical next step. In line with this objective, a synthetic peptide with 36 amino acid residues, called Sifuvirtide (SFT), was designed based on the crystal structure of gp41. In this study, we show that SFT is a potent anti-HIV agent with relatively low cytotoxicity. SFT was found to inhibit replication of all tested HIV strains. The effective concentrations that inhibited 50% viral replication (EC{sub 50}), as determined in all tested strains, were either comparable or lower than benchmark values derived from well-known anti-HIV drugs like ENF or AZT, while the cytotoxic concentrations causing 50% cell death (CC{sub 50}) were relatively high, rendering it an ideal anti-HIV agent. A GST-pull down assay was performed to confirm that SFT is a fusion inhibitor. Furthermore, the activity of SFT on other targets in the HIV life cycle was also investigated, and all assays showed negative results. To further understand the mechanism of action of HIV peptide inhibitors, resistant variants of HIV-1{sub IIIB} were derived by serial virus passage in the presence of increasing doses of SFT or ENF. The results showed that there was cross-resistance between SFT and ENF. In conclusion, SFT is an ideal anti-HIV agent with high potency and low cytotoxicity, but may exhibit a certain extent of cross-resistance with ENF.

  14. Allergic contact dermatitis from temporary henna tattoo.

    PubMed

    Jovanovic, Dragan L; Slavkovic-Jovanovic, Maja R

    2009-01-01

    Temporary henna tattooing has been very popular during recent years. Henna (Lawsonia inermis) is a plant from the Lythraceae family. For henna tattooing, henna dye is used. It is a dark green powder, made from the leaves of the plant, used for hair dyeing and body tattooing. Very often, para-phenylenediamine (PPD) is added to henna dye to make color blacker and to speed up dyeing. PPD may be a very potent contact sensitizer. We report a 9-year-old boy with allergic contact dermatitis due to temporary henna tattooing. Patch testing showed a positive reaction to PPD. After the treatment with topical corticosteroid and oral antihistamines, the lesion cleared with discrete residual hypopigmentation. PMID:19207440

  15. A Potent Lead Induces Apoptosis in Pancreatic Cancer Cells

    PubMed Central

    Zhao, Wenjing; Zheng, Xiliang; Wang, Jin; Wang, Erkang

    2012-01-01

    Pancreatic cancer is considered a lethal and treatment-refractory disease. To obtain a potent anticancer drug, the cytotoxic effect of 2-(benzo[d]oxazol-3(2H)-ylmethyl)- 5-((cyclohexylamino)methyl)benzene-1,4-diol, dihydrochloride (NSC48693) on human pancreatic cancer cells CFPAC-1, MiaPaCa-2, and BxPC-3 was assessed in vitro. The proliferation of CFPAC-1, MiaPaCa-2, and BxPC-3 is inhibited with IC50 value of 12.9±0.2, 20.6±0.3, and 6.2±0.6 µM at 48 h, respectively. This discovery is followed with additional analysis to demonstrate that NSC48693 inhibition is due to induction of apoptosis, including Annexin V staining, chromatins staining, and colony forming assays. It is further revealed that NSC48693 induces the release of cytochrome c, reduces mitochondrial membrane potential, generates reactive oxygen species, and activates caspase. These results collectively indicate that NSC48693 mainly induces apoptosis of CFPAC-1, MiaPaCa-2, and BxPC-3 cells by the mitochondrial-mediated apoptotic pathway. Excitingly, the study highlights an encouraging inhibition effect that human embryonic kidney (HEK-293) and liver (HL-7702) cells are more resistant to the antigrowth effect of NSC48693 compared to the three cancer cell lines. From this perspective, NSC48693 should help to open up a new opportunity for the treatment of patients with pancreatic cancer. PMID:22745658

  16. 76 FR 33031 - Agency Information Collection (Request for Contact Information) Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-07

    ...Agency Information Collection (Request for Contact Information) Activity Under OMB Review...correspondence. FOR FURTHER INFORMATION CONTACT: Denise McLamb, Enterprise Records Service...SUPPLEMENTARY INFORMATION: Title: Request for Contact Information, VA Form 21-30. OMB...

  17. Eutectic Contact Inks for Solar Cells

    NASA Technical Reports Server (NTRS)

    Ross, B.

    1985-01-01

    Low-resistance electrical contacts formed on solar cells by melting powders of eutectic composition of semiconductor and dopant. Process improves cell performance without subjecting cell to processing temperatures high enough to degrade other characteristics.

  18. Ohmic contacts to compound semiconductor transistors

    NASA Astrophysics Data System (ADS)

    Dormaier, Robert A., III

    This thesis addresses Ohmic contacts to InAlSb/InAs high electron mobility transistor (HEMT) heterostructures and InGaAs epilayers. Palladium-based contacts provide very low contact resistance to both materials, which helps minimize parasitic resistances in transistors. For Pd/Pt/Au and Pd/Ru/Au contacts to the HEMTs, lower contact resistances are correlated with increasing reaction between Pd (and Pt) and the semiconductor during annealing and aging at 175--200°C for 3 h or 1 week. Voids form in the Pt diffusion barrier layer when Pd/Pt/Au contacts are aged 1 week at 175°C and grow larger during aging at higher temperatures. The increase in contact resistance of Pd/Pt/Au contacts by more than a factor of 2 after a 1 week, 225°C aging cycle is discussed in light of the interfacial reactions that occur during aging. Alternatively, no reaction is observed between the Ru diffusion barrier and the semiconductor in Pd/Ru/Au contacts, which yield a contact resistance of 0.05 +/- 0.01 O mm after a 1 week, 225°C aging cycle that is comparable to the minimum value of 0.03 +/- 0.01 O mm yielded by Pd/Pt/Au contacts. Measurement artifacts associated with the transfer length method are identified and probe placements that mitigate the artifacts are used to reliably examine low specific contact resistance (rhoc) Ohmic contacts to InGaAs. Standardization of surface preparation procedures and a low relative humidity processing environment yield very low rhoc contacts to n-InGaAs. Examinations of wet etchants for oxide removal after UV/O 3 treatment demonstrate that BOE- and NH4OH-based etchants yield much lower rhoc values than HCl (5.0+/-0.6x10-9 and 5.7+/-1.4x10-9 versus 1.7+/-0.1x10 -8 O cm2). Palladium and Pt yield lower as-deposited and annealed rhoc values than Mo-, Ti-, and TiW-based contacts. Furthermore, collimated sputter-deposited contacts yield lower rho c values than electron-beam evaporated contacts. Several phenomena that may be responsible for the low rhoc values of Pd-based contacts are proposed and discussed. Ohmic contacts to p-InGaAs with a thin n-InGaAs cap are also examined: Pd/Ti multilayer contacts yield rhoc < 1x10-8 O cm2 after 2 hr at 270°C.

  19. Contact dermatitis to temporary tattoo.

    PubMed

    Tomljanovi?-Veselski, Mirna; Zilih-Ostoji?, Cecilija

    2006-01-01

    The development of contact hypersensitivity to temporary tattoos has been on an increase all over the world. Skin painting with henna is a traditional practice in the Moslems and Hindu, and has recently been increasingly used in western countries. Black henna is obtained by adding paraphenylenediamine to the natural occurring henna. The risk of sensitization increases with the length of contact and increase of the concentration. A case is presented of an 11-year-old boy who developed a severe reaction in the form of redness and edema accompanied by pruritus on the day following the application of a temporary tattoo. A year before, the patient had also developed a skin reaction following temporary tattooing, which had not been recognized as a contact dermatitis. Patch testing was positive for paraphenylenediamine and thiuram compounds. The patient was treated with medium-strength corticosteroids. PMID:17010265

  20. Structures of Potent Selective Peptide Mimetics Bound to Carboxypeptidase B

    SciTech Connect

    Adler, M.; Buckman, B.; Bryant, J.; Chang, Z.; Chu, K.; Emayan, K.; Hrvatin, P.; Islam, I.; Morser, J.; Sukovich, D.; West, C.; Yuan, S.; Whitlow, M.

    2009-05-11

    This article reports the crystal structures of inhibitors of the functional form of thrombin-activatable fibrinolysis inhibitor (TAFIa). In vivo experiments indicate that selective inhibitors of TAFIa would be useful in the treatment of heart attacks. Since TAFIa rapidly degrades in solution, the homologous protein porcine pancreatic carboxypeptidase B (pp-CpB) was used in these crystallography studies. Both TAFIa and pp-CpB are zinc-based exopeptidases that are specific for basic residues. The final development candidate, BX 528, is a potent inhibitor of TAFIa (2 nM) and has almost no measurable effect on the major selectivity target, carboxypeptidase N. BX 528 was designed to mimic the tripeptide Phe-Val-Lys. A sulfonamide replaces the Phe-Val amide bond and a phosphinate connects the Val and Lys groups. The phosphinate also chelates the active-site zinc. The electrostatic interactions with the protein mimic those of the natural substrate. The primary amine in BX 528 forms a salt bridge to Asp255 at the base of the S1 pocket. The carboxylic acid interacts with Arg145 and the sulfonamide is hydrogen bonded to Arg71. Isopropyl and phenyl groups replace the side chains of Val and Phe, respectively. A series of structures are presented here that illustrate the evolution of BX 528 from thiol-based inhibitors that mimic a free C-terminal arginine. The first step in development was the replacement of the thiol with a phosphinate. This caused a precipitous drop in binding affinity. Potency was reclaimed by extending the inhibitors into the downstream binding sites for the natural substrate.

  1. Herschel and Planck contacts STFC contact

    E-print Network

    Herschel and Planck contacts STFC contact Richard Holdaway Director STFC Space Science Director of Space Science & Exploration Tel: (0)1793 44 2174 mobile: 07901 514969 david. Christine Brockley-Blatt MSSL SPIRE Project Manager University College London Mullard Space Science

  2. Mixed formulation for frictionless contact problems

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Kim, Kyun O.

    1989-01-01

    Simple mixed finite element models and a computational precedure are presented for the solution of frictionless contact problems. The analytical formulation is based on a form of Reissner's large rotation theory of the structure with the effects of transverse shear deformation included. The contact conditions are incorporated into the formulation by using a perturbed Lagrangian approach with the fundamental unknowns consisting of the internal forces (stress resultants), the generalized displacements, and the Lagrange multipliers associated with the contact conditions. The element characteristic array are obtained by using a modified form of the two-field Hellinger-Reissner mixed variational principle. The internal forces and the Lagrange multipliers are allowed to be discontinuous at interelement boundaries. The Newton-Raphson iterative scheme is used for the solution of the nonlinear algebraic equations, and the determination of the contact area and the contact pressures.

  3. Potent and selective inhibitors of the proteasome: Dipeptidyl boronic acids

    Microsoft Academic Search

    Julian Adams; Mark Behnke; Shaowu Chen; Amy A. Cruickshank; Lawrence R. Dick; Louis Grenier; Janice M. Klunder; Yu-Ting Ma; Louis Plamondon; Ross L. Stein

    1998-01-01

    Potent and selective dipeptidyl boronic acid proteasome inhibitors are described. As compared to peptidyl aldehyde compounds, boronic acids in this series display dramatically enhanced potency. Compounds such as 15 are promising new therapeutics for treatment of cancer and inflammatory diseases.

  4. A diastereocontrolled synthesis of (+)-febrifugine: a potent antimalarial piperidine alkaloid.

    PubMed

    Taniguchi, T; Ogasawara, K

    2000-10-01

    A diastereocontrolled synthesis of (+)-febrifugine, a potent antimalarial piperidine alkaloid, has been achieved using a chiral block having a bicyclo[3.2.1]octane framework which exhibits inherent convex-face selectivity. PMID:11009379

  5. Quinoxalinediones: Potent Competitive Non-NMDA Glutamate Receptor Antagonists

    Microsoft Academic Search

    Tage Honore; Steve N. Davies; Jorgen Drejer; Elizabeth J. Fletcher; Poul Jacobsen; David Lodge; Flemming E. Nielsen

    1988-01-01

    The N-methyl-D-aspartate (NMDA)-subtype of glutamate receptors has been well described as a result of the early appearance of NMDA antagonists, but no potent antagonist for the ``non-NMDA'' glutamate receptors has been available. Quinoxalinediones have now been found to be potent and competitive antagonists at non-NMDA glutamate receptors. These compounds will be useful in the determination of the structure-activity relations of

  6. HL 752: A potent and long-acting antispasmodic agent

    Microsoft Academic Search

    Swati Bal-Tembe; Dilip N. Bhedi; Anil K. Mishra; Ramanujam Rajagopalan; Anil V. Ghate; Palakodety Subbarayan; Narayan S. Punekar; Anjali V. Kulkarni

    1997-01-01

    Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (2) were prepared with an aim to find a more potent and metabolically stable antispasmodic compound. The compounds were evaluated for their in vitro and in vivo antispasmodic activity, and stability to in vitro enzymatic hydrolysis. Of the compounds synthesised, HL 752 (21) showed the most potent and long-lasting antispasmodic activity and was selected

  7. HL 752: a potent and long-acting antispasmodic agent.

    PubMed

    Bal-Tembe, S; Bhedi, D N; Mishra, A K; Rajagopalan, R; Ghate, A V; Subbarayan, P; Punekar, N S; Kulkarni, A V

    1997-07-01

    Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (2) were prepared with an aim to find a more potent and metabolically stable antispasmodic compound. The compounds were evaluated for their in vitro and in vivo antispasmodic activity, and stability to in vitro enzymatic hydrolysis. Of the compounds synthesised, HL 752 (21) showed the most potent and long-lasting antispasmodic activity and was selected as the candidate for clinical development. PMID:9377098

  8. Discovery of a Potent And Selective Aurora Kinase Inhibitor

    SciTech Connect

    Oslob, J.D.; Romanowski, M.J.; Allen, D.A.; Baskaran, S.; Bui, M.; Elling, R.A.; Flanagan, W.M.; Fung, A.D.; Hanan, E.J.; Harris, S.; Heumann, S.A.; Hoch, U.; Jacobs, J.W.; Lam, J.; Lawrence, C.E.; McDowell, R.S.; Nannini, M.A.; Shen, W.; Silverman, J.A.; Sopko, M.M.; Tangonan, B.T.

    2009-05-21

    This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.

  9. 2-Methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 Potently Stimulates Gene-specific DNA Binding of the

    E-print Network

    Pike, J. Wesley

    of the Vitamin D Receptor in Osteoblasts* Received for publication, May 6, 2003, and in revised form, June 6,25-dihydroxyvitamin D3 (2MD) is a highly potent analog of 1,25-dihydroxyvita- min D3 (1,25(OH)2D3) whose actions at concentrations two logs lower than that for 1,25(OH)2D3. 2MD is also more potent in stimu- lating transfected

  10. Thermal contact resistance

    E-print Network

    Mikic, B. B.

    1966-01-01

    This work deals with phenomena of thermal resistance for metallic surfaces in contact. The main concern of the work is to develop reliable and practical methods for prediction of the thermal contact resistance for various ...

  11. Contact Name: Originator

    E-print Network

    Contact Name: Originator: Faculty & Department Contact Telephone: DIRECT DEPOSIT BANKING: Pay Frequency: Monthly: Biweekly: PREVIOUS BANK INFORMATION Name of Bank: Address of Bank: (street name, city, postal code) 3-digit Institution Number: 5-Digit Branch Number: Account Number: NEW BANK

  12. Glasses and Contact Lenses

    MedlinePLUS

    ... together the way they should. But eyeglasses or contact lenses, also called corrective lenses, can help most ... trouble, it's often a refractive problem. Glasses or contact lenses work so well because they can correct ...

  13. Buying Contact Lenses

    MedlinePLUS

    ... regulated by both the FDA and the Federal Trade Commission (FTC). Before you buy any contact lenses ... label contact lens, the name of the manufacturer, trade name of the private label brand, and if ...

  14. PARKING SERVICES SERVICE REQUEST FORM Form revised 21March 2011

    E-print Network

    PARKING SERVICES SERVICE REQUEST FORM Form revised 21March 2011 Request for (please check one): Contact Phone No. Fax No. __ Parking Scripts - __________ (specify quantity) Supv, Parking Services 24832 25386 __ Campus Maps - __________ (specify quantity) Supv Parking Services 24832 25386 __ Visitors

  15. Contact solution algorithms

    NASA Technical Reports Server (NTRS)

    Tielking, John T.

    1989-01-01

    Two algorithms for obtaining static contact solutions are described in this presentation. Although they were derived for contact problems involving specific structures (a tire and a solid rubber cylinder), they are sufficiently general to be applied to other shell-of-revolution and solid-body contact problems. The shell-of-revolution contact algorithm is a method of obtaining a point load influence coefficient matrix for the portion of shell surface that is expected to carry a contact load. If the shell is sufficiently linear with respect to contact loading, a single influence coefficient matrix can be used to obtain a good approximation of the contact pressure distribution. Otherwise, the matrix will be updated to reflect nonlinear load-deflection behavior. The solid-body contact algorithm utilizes a Lagrange multiplier to include the contact constraint in a potential energy functional. The solution is found by applying the principle of minimum potential energy. The Lagrange multiplier is identified as the contact load resultant for a specific deflection. At present, only frictionless contact solutions have been obtained with these algorithms. A sliding tread element has been developed to calculate friction shear force in the contact region of the rolling shell-of-revolution tire model.

  16. Lubrication of electrical contacts

    Microsoft Academic Search

    Bella H. Chudnovsky

    2005-01-01

    The paper presents a review of research data published during last 40-year period in the field of electrical contact lubrication. The paper examines the role of lubrication in corrosion protection as a barrier between contact surfaces and atmospheric pollutants. For effective long-term corrosion protection, it is important to properly choose and thoroughly qualify a lubrication product for a specific contact

  17. Coatings tribology—contact mechanisms and surface design

    Microsoft Academic Search

    Kenneth Holmberg; Allan Matthews; Helena Ronkainen

    1998-01-01

    The fundamentals of coating tribology are presented by using a generalised holistic approach to the friction and wear mechanisms of coated surfaces in dry sliding contacts. It is based on a classification of the tribological contact process into macromechanical, micromechanical, nanomechanical and tribochemical contact mechanisms, and material transfer. The important influence of thin tribo- and transfer layers formed during the

  18. From contact to connection: early events during synaptogenesis

    Microsoft Academic Search

    Philip G. Haydon; Pierre Drapeau

    1995-01-01

    When neuronal processes first come into contact, chemical synapses can form rapidly. Many neurons synthesize synaptic machinery through intrinsic programs before cell-cell interactions. During the formation of chemical synapses, contact with appropriate targets has been found to trigger intracellular signals that induce the assembly of pre-existing synaptic machinery. We propose that ‘promiscuous’ neurons secrete transmitter before contacting their targets, and

  19. MEDICAL AND EMERGENCY INFORMATION FORM

    E-print Network

    Rothman, Daniel

    MEDICAL AND EMERGENCY INFORMATION FORM Field Trip Name: __________________________ Trip Dates from information about your medical coverage that might be useful. Emergency Contact Information Emergency Personal;___________________________________________________________________________________ Please return completed form to the trip coordinator two weeks prior to departure. Known Medical

  20. Better Ohmic Contacts For InP Semiconductor Devices

    NASA Technical Reports Server (NTRS)

    Weizer, Victor G.; Fatemi, Navid S.

    1995-01-01

    Four design modifications enable fabrication of improved ohmic contacts on InP-based semiconductor devices. First modification consists of insertion of layer of gold phosphide between n-doped InP and metal or other overlayer of contact material. Second, includes first modification plus use of particular metal overlayer to achieve very low contact resistivities. Third, also involves deposition of Au(2)P(3) interlayer; in addition, refractory metal (W or Ta) deposited to form contact overlayer. In fourth, contact layer of Auln alloy deposited directly on InP. Improved contacts exhibit low electrical resistances and fabricated without exposing devices to destructive predeposition or postdeposition treatments.

  1. EMERGENCY CONTACTS for DOWNER LAB Contact Phone After Hours Purpose/Additional Info

    E-print Network

    Shvets, Gennady

    .utexas.edu/facilities/services for further information and non-emergency service request forms) Environmental Health & Safety 471-3511 911EMERGENCY CONTACTS for DOWNER LAB Contact Phone After Hours Purpose/Additional Info UT Police emergencies, call 911 or go to a local hospital emergency room. (see healthyhorns.utexas.edu/emergencies

  2. Dimeric 2G12 as a Potent Protection against HIV-1

    PubMed Central

    Luo, Xin M.; Lei, Margarida Y. Y.; Feidi, Rana A.; West, Anthony P.; Balazs, Alejandro Benjamin; Bjorkman, Pamela J.; Yang, Lili; Baltimore, David

    2010-01-01

    We previously showed that broadly neutralizing anti-HIV-1 antibody 2G12 (human IgG1) naturally forms dimers that are more potent than monomeric 2G12 in in vitro neutralization of various strains of HIV-1. In this study, we have investigated the protective effects of monomeric versus dimeric 2G12 against HIV-1 infection in vivo using a humanized mouse model. Our results showed that passively transferred, purified 2G12 dimer is more potent than 2G12 monomer at preventing CD4 T cell loss and suppressing the increase of viral load following HIV-1 infection of humanized mice. Using humanized mice bearing IgG “backpack” tumors that provided 2G12 antibodies continuously, we found that a sustained dimer concentration of 5–25 µg/ml during the course of infection provides effective protection against HIV-1. Importantly, 2G12 dimer at this concentration does not favor mutations of the HIV-1 envelope that would cause the virus to completely escape 2G12 neutralization. We have therefore identified dimeric 2G12 as a potent prophylactic reagent against HIV-1 in vivo, which could be used as part of an antibody cocktail to prevent HIV-1 infection. PMID:21187894

  3. X-ray structure of plasmepsin II complexed with a potent achiral inhibitor.

    PubMed

    Prade, Lars; Jones, Andrew F; Boss, Christoph; Richard-Bildstein, Sylvia; Meyer, Solange; Binkert, Christoph; Bur, Daniel

    2005-06-24

    The malaria parasite Plasmodium falciparum degrades host cell hemoglobin inside an acidic food vacuole during the blood stage of the infectious cycle. A number of aspartic proteinases called plasmepsins (PMs) have been identified to play important roles in this degradation process and therefore generated significant interest as new antimalarial targets. Several x-ray structures of PMII have been described previously, but thus far, structure-guided drug design has been hampered by the fact that only inhibitors comprising a statine moiety or derivatives thereof have been published. Our drug discovery efforts to find innovative, cheap, and easily synthesized inhibitors against aspartic proteinases yielded some highly potent non-peptidic achiral inhibitors. A highly resolved (1.6 A) x-ray structure of PMII is presented, featuring a potent achiral inhibitor in an unprecedented orientation, contacting the catalytic aspartates indirectly via the "catalytic" water. Major side chain rearrangements in the active site occur, which open up a new pocket and allow a new binding mode of the inhibitor. Moreover, a second inhibitor molecule could be located unambiguously in the active site of PMII. These newly obtained structural insights will further guide our attempts to improve compound properties eventually leading to the identification of molecules suitable as antimalarial drugs. PMID:15840589

  4. Contact lens in keratoconus

    PubMed Central

    Rathi, Varsha M; Mandathara, Preeji S; Dumpati, Srikanth

    2013-01-01

    Contact lenses are required for the visual improvement in patients with keratoconus. Various contact lens options, such as rigid gas permeable (RGP) lenses, soft and soft toric lenses, piggy back contact lenses (PBCL), hybrid lenses and scleral lenses are availble. This article discusses about selection of a lens depending on the type of keratoconus and the fitting philosophies of various contact lenses including the starting trial lens. A Medline search was carried out for articles in the English language with the keywords keratoconus and various contact lenses such as Rose k lens, RGP lens, hybrid lens, scleral lens and PBCL. PMID:23925325

  5. BISON Contact Improvements CASL FY14 Report

    SciTech Connect

    B. W. Spencer; J. D. Hales; D. R. Gaston; D. A. Karpeev; R. L. Williamson; S. R. Novascone; D. M. Perez; R. J. Gardner; K. A. Gamble

    2014-09-01

    The BISON code is the foundation for multiple fuel performance modeling efforts, and is cur- rently under heavy development. For a variety of fuel forms, the effects of heat conduction across a gap and mechanical contact between components of a fuel system are very significant. It is thus critical that BISON have robust capabilities for enforcement of thermal and mechanical contact. BISON’s solver robustness has generally been quite good before mechanical contact between the fuel and cladding occurs, but there have been significant challenges obtaining converged so- lutions once that contact occurs and the solver begins to enforce mechanical contact constraints. During the current year, significant development effort has been focused on the enforcement of mechanical contact to provide improved solution robustness. In addition to this work to improve mechanical contact robustness, an investigation into ques- tionable results attributable to thermal contact has been performed. This investigation found that the order of integration typically used on the surfaces involved in thermal contact was not suffi- ciently high. To address this problem, a new option was provided to permit the use of a different integration order for surfaces, and new usage recommendations were provided.

  6. Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat.

    PubMed Central

    Wilson, D K; Tarle, I; Petrash, J M; Quiocho, F A

    1993-01-01

    As the action of aldose reductase (EC 1.1.1.21) is believed to be linked to the pathogenesis of diabetic complications affecting the nervous, renal, and visual systems, the development of therapeutic agents has attracted intense effort. We report the refined 1.8 A x-ray structure of the human holoenzyme complexed with zopolrestat, one of the most potent noncompetitive inhibitors. The zopolrestat fits snugly in the hydrophobic active site pocket and induces a hinge-flap motion of two peptide segments that closes the pocket. Excellent complementarity and affinity are achieved on inhibitor binding by the formation of 110 contacts (< or = 4 A) with 15 residues (10 hydrophobic), 13 with the NADPH coenzyme and 9 with four water molecules. The structure is key to understanding the mode of action of this class of inhibitors and for rational design of better therapeutics. Images Fig. 1 Fig. 3 PMID:8234324

  7. The personal information requested on this form is collected under the authority of Section 33 (c) of the Alberta Freedom of Information and Protection of Privacy Act for the purpose of registering students, contacting students and tracking enrolment stat

    E-print Network

    MacMillan, Andrew

    , contacting students and tracking enrolment statistics. Questions concerning the collection, use or disposal of Alberta, Edmonton, AB T5J 4P6. Phone 780.492.5047. LEGAL FIRST NAME LEGAL MIDDLE NAME LEGAL LAST NAME FORMER LAST NAME (if Applicable) DATE OF BIRTH (mm-dd-yyyy) Male Female TELEPHONE Home Cell Work

  8. Contact Dermatitis: Signs and Symptoms

    MedlinePLUS

    ... treatments A - D Contact dermatitis Signs and symptoms Contact dermatitis: Signs and symptoms Allergic contact dermatitis : Testing ... these symptoms, you need immediate medical care. Allergic contact dermatitis This skin condition occurs when you have ...

  9. Benzofuran-derived benzylpyridinium bromides as potent acetylcholinesterase inhibitors.

    PubMed

    Baharloo, Farzaneh; Moslemin, Mohammad Hossein; Nadri, Hamid; Asadipour, Ali; Mahdavi, Mohammad; Emami, Saeed; Firoozpour, Loghman; Mohebat, Razieh; Shafiee, Abbas; Foroumadi, Alireza

    2015-03-26

    A series of benzofuran-based N-benzylpyridinium derivatives 5a-o were designed and synthesized as novel AChE inhibitors. The synthetic pathway of the compounds involved the preparation of 4-(benzofuran-2-yl)pyridine intermediates via the reaction of different salicylaldehyde derivatives and 4-(bromomethyl)pyridine, followed by intramolecular cyclization. Subsequently, the 4-(benzofuran-2-yl)pyridines were N-benzylated by using appropriate benzyl bromide to afford the final product 5a-o. The results of in vitro AChE activity evaluation of synthesized compounds revealed that all compound had potent anti-AChE activity comparable or more potent than standard drug donepezil. The N-(3,5-dimethylbenzyl) derivative 5e with IC50 value of 4.1 nM was the most active compound, being 7-fold more potent than donepezil. PMID:25681712

  10. Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors

    PubMed Central

    Ramos-Molina, Bruno; Lick, Adam N.; Nasrolahi Shirazi, Amir; Oh, Donghoon; Tiwari, Rakesh; El-Sayed, Naglaa Salem; Parang, Keykavous; Lindberg, Iris

    2015-01-01

    Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro and also inhibited intracellular convertases. Our finding that cationic cell-penetrating peptides exert potent effects on cellular convertase activity should be taken into account when biological effects are assessed. PMID:26110264

  11. Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 receptor antagonists.

    PubMed

    Hostetler, Greg; Dunn, Derek; McKenna, Beth Ann; Kopec, Karla; Chatterjee, Sankar

    2014-05-01

    Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists have been disclosed. One potent member from the lactam series, racemic compound 14 (Ki of 2.6 nM in binding assay, IC50 of 15 nM in functional cAMP antagonism assay) was separated into corresponding enantiomers that displayed the effect of chirality on binding potency (Ki of 1.6 nM and 3000 nM, respectively). The potent enantiomer displayed an IC50 of 8 nM in cAMP antagonism assay, selectivity against a number of family members as well as brain permeability in rats after 6h post oral administration. PMID:24704027

  12. Synthesis, molecular modeling, and biological evaluation of novel chiral thiosemicarbazone derivatives as potent anticancer agents.

    PubMed

    Ta?demir, Demet; Karaküçük-?yido?an, Ay?egül; Ula?li, Mustafa; Ta?kin-Tok, Tu?ba; Oruç-Emre, Em?ne Elç?n; Bayram, Hasan

    2015-02-01

    A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6??M) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3??M), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. PMID:25399965

  13. Contact dependent growth inhibition of E. coli O157:H7 by EC869 CDI system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Contact Dependent Growth Inhibition (CDI) is a recently discovered mechanism that microorganisms use to compete in various microecosystems. CDI systems express large cell surface exposed CdiA proteins with potent antimicrobial peptide tips. Many CDI systems also contain additional down...

  14. Contact changes near jamming

    NASA Astrophysics Data System (ADS)

    van Deen, Merlijn S.; Simon, Johannes; Zeravcic, Zorana; Dagois-Bohy, Simon; Tighe, Brian P.; van Hecke, Martin

    2014-08-01

    We probe the onset and effect of contact changes in soft harmonic particle packings which are sheared quasistatically. We find that the first contact changes are the creation or breaking of contacts on a single particle. We characterize the critical strain, statistics of breaking versus making a contact, and ratio of shear modulus before and after such events, and explain their finite size scaling relations. For large systems at finite pressure, the critical strain vanishes but the ratio of shear modulus before and after a contact change approaches one: linear response remains relevant in large systems. For finite systems close to jamming the critical strain also vanishes, but here linear response already breaks down after a single contact change.

  15. [Periorbital contact eczema].

    PubMed

    Worm, M; Sterry, W

    2005-11-01

    Periorbital contact eczema is most commonly the result of an allergic contact dermatitis whereas other eczematous skin diseases like atopic eczema or seborrheic eczema occur less frequently. Also, other diseases like autoimmune disorders or rosacea need to be considered. Allergic contact dermatitis is a T-cell-mediated immunological response towards ubiquitous contact allergens. Activated T-cells migrate through the vessels into the skin and produce several inflammatory mediators. Epicutaneous patch testing is an important tool for the diagnosis of contact allergy whereby the allergens are analysed in terms of their ability to induce eczematous skin reaction. Until now the short-term use of corticosteroids are is employed for the treatment of allergic contact eczema. Modern substances with an optimal therapeutic index should rather be used. PMID:16308815

  16. Characteristics of protein residue-residue contacts and their application in contact prediction.

    PubMed

    Wozniak, Pawel P; Kotulska, Malgorzata

    2014-11-01

    Contact sites between amino acids characterize important structural features of a protein. We investigated characteristics of contact sites in a representative set of proteins and their relations between protein class or topology. For this purpose, we used a non-redundant set of 5872 protein domains, identically categorized by CATH and SCOP databases. The proteins represented alpha, beta, and alpha+beta classes. Contact maps of protein structures were obtained for a selected set of physical distances in the main backbone and separations in protein sequences. For each set a dependency between contact degree and distance parameters was quantified. We indicated residues forming contact sites most frequently and unique amino acid pairs which created contact sites most often within each structural class. Contact characteristics of specific topologies were compared to the characteristics of their protein classes showing protein groups with a distinguished contact characteristic. We showed that our results could be used to improve the performance of recent top contact predictor - direct coupling analysis. Our work provides values of contact site propensities that can be involved in bioinformatic databases. PMID:25374390

  17. Non-contact measurement of contact wire

    NASA Astrophysics Data System (ADS)

    Yi, Yaxing; Ye, Xuemei; Li, Zhongke; Yue, Kaiduan

    2008-12-01

    The overhead contact system is the power supply unit of the electric locomotive. This article is to introduce our newly developed method to measure the height and pull out value of the contact wire. A carema dolly which can move on railway is applied to bear the weight of the measure equipment; two linear CCD cameras are installed on the dolly symmetrically about the midline of two rails. While the dolly move along the railway, two CCD cameras grasp the image synchronously, and a computer real-time process the images, the height and pull out value can be calculate out from the images.

  18. Optical contact micrometer

    DOEpatents

    Jacobson, Steven D.

    2014-08-19

    Certain examples provide optical contact micrometers and methods of use. An example optical contact micrometer includes a pair of opposable lenses to receive an object and immobilize the object in a position. The example optical contact micrometer includes a pair of opposable mirrors positioned with respect to the pair of lenses to facilitate viewing of the object through the lenses. The example optical contact micrometer includes a microscope to facilitate viewing of the object through the lenses via the mirrors; and an interferometer to obtain one or more measurements of the object.

  19. Composite electric contact materials

    NASA Astrophysics Data System (ADS)

    Senkara, J.; Kowalczyk, J.

    1985-12-01

    Two-phase composite materials, i.e., a high-melting component combined with a material exhibiting good electrical and thermal properties find a wide range of application for the manufacture of small- and medium-load relays and switches. Composite contacts can be used in air circuit-breakers (W-Ag, Ag-Ni), oil circuit-breakers (W-Cu, Mo-Cn), vacuum-type switches (W-CuSb, CuCr), and also switches operating in an atmosphere of SF sub 6 (W-Cu). Present-day trends aimed at increasing operating reliability and extending the service life of electrical equipment are finding their expression in efforts being made to modify the classical composites with a veiw to imparting new properties to them by suitably changing their composition and structure. These trends are also aimed at reducing the consumption of noble metals and of strategically important ones. Modern materials engineering and metallurgical technologies are being used, including isostatic sintering or explosive forming. Owing to the high activity of the constituents, all processes are conducted under high vacuum or in pure reducing atmospheres.

  20. Photoallergic contact dermatitis.

    PubMed

    Foti, C; Bonamonte, D; Cassano, N; Vena, G A; Angelini, G

    2009-10-01

    Photoallergic contact dermatitis (PCD) is a delayed-type hypersensitivity cutaneous reaction in response to a photoantigen applied to the skin in subjects previously sensitized to the same substance. For the development of PCD, irradiation with ultraviolet (UV) radiations, usually UVA, is required to create a complete antigen, and the culprit substance needs to be within the skin at the time of UVA exposure. The incidence of PCD in the general population is unknown and is considered uncommon. Epidemiological data have been obtained from studies performed using photo-patch tests in patients with suspected photodermatoses in tertiary care outpatient units. Prevalence of PCD over time has been also dependent on prescription and/or usage patterns of potential photosensitizers, and was particularly high in the past, causing mini-epidemics in some countries because of the widespread use of halogenated salicylanilides and other photosensitizing compounds. Many topical substances with photosensitizing properties are currently available, with the most important ones being sunscreen agents and nonsteroidal antiinflammatory drugs. The diagnosis of PCD, in patients with a history of photosensitivity and especially with an eczematous form of photodermatosis, should be confirmed by photo-patch testing. PMID:19834430

  1. Potent bradykinin B 1 receptor antagonists: 4-Substituted phenyl cyclohexanes

    Microsoft Academic Search

    Dai-Shi Su; John L. Lim; M. Kristine Markowitz; Bang-Lin Wan; Kathy L. Murphy; Duane R. Reiss; C. Meacham Harrell; Stacy S. O’Malley; Rick W. Ransom; Raymond S. L. Chang; Douglas J. Pettibone; Cuyue Tang; Thomayant Prueksaritanont; Roger M. Freidinger; Mark G. Bock

    2007-01-01

    Selective bradykinin (BK) B1 receptor antagonists have been shown to be antinociceptive in animal models and could be novel therapeutic agents for the treatment of pain and inflammation. Elucidation of the structure–activity relationships of the biphenyl moiety of the lead compound 1 provided a potent new structural class of BK B1 receptor antagonists.

  2. Statine based tripeptides as potent inhibitors of HIV-1 replication.

    PubMed

    Fehrentz, J A; Chomier, B; Bignon, E; Venaud, S; Chermann, J C; Nisato, D

    1992-10-30

    Starting from highly potent HIV-1 protease pepstatine analog inhibitors, we have tried to find the minimum consensus sequence which is necessary to conserve anti-protease potency and antiviral activity. We describe here some statine based tripeptides which exhibit high affinity for the protease and are able to inhibit the reproductive cycle of HIV-1 in MT-4-infected cells. PMID:1445328

  3. Extensive screening for herbal extracts with potent antioxidant properties

    PubMed Central

    Niwano, Yoshimi; Saito, Keita; Yoshizaki, Fumihiko; Kohno, Masahiro; Ozawa, Toshihiko

    2011-01-01

    This paper summarizes our research for herbal extracts with potent antioxidant activity obtained from a large scale screening based on superoxide radical (O2•?) scavenging activity followed by characterization of antioxidant properties. Firstly, scavenging activity against O2•? was extensively screened from ethanol extracts of approximately 1000 kinds of herbs by applying an electron spin resonance (ESR)-spin trapping method, and we chose four edible herbal extracts with prominently potent ability to scavenge O2•?. They are the extracts from Punica granatum (Peel), Syzygium aromaticum (Bud), Mangifera indica (Kernel), and Phyllanthus emblica (Fruit). These extracts were further examined to determine if they also scavenge hydroxyl radical (•OH), by applying the ESR spin-trapping method, and if they have heat resistance as a desirable characteristic feature. Experiments with the Fenton reaction and photolysis of H2O2 induced by UV irradiation demonstrated that all four extracts have potent ability to directly scavenge •OH. Furthermore, the scavenging activities against O2•? and •OH of the extracts of P. granatum (peel), M. indica (kernel) and P. emblica (fruit) proved to be heat-resistant. The results of the review might give useful information when choosing a potent antioxidant as a foodstuff. For instance, the four herbal extracts chosen from extensive screening possess desirable antioxidant properties. In particular, the extracts of the aforementioned three herbs are expected to be suitable for food processing in which thermal devices are used, because of their heat resistance. PMID:21297917

  4. Potent pyrrolidine- and piperidine-based BACE-1 inhibitors

    SciTech Connect

    Iserloh, U.; Wu, Y.; Cumming, J.N.; Pan, J.; Wang, L.Y.; Stamford, A.W.; Kennedy, M.E.; Kuvelkar, R.; Chen, X.; Parker, E.M.; Strickland, C.; Voigt, J. (Schering-Plough)

    2008-08-18

    Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. The discovery and development of novel BACE-1 inhibitors incorporating a cyclic amine scaffold is described.

  5. Potent Antioxidant Dendrimers Lacking Pro-oxidant Activity

    PubMed Central

    Lee, Choon Young; Sharma, Ajit; Uzarski, Rebecca L.; Cheong, Jae Eun; Xu, Hao; Held, Rich A.; Upadhaya, Samik K.; Nelson, Julie L.

    2010-01-01

    It is well known that antioxidants have protective effects against oxidative stress. Unfortunately, in the presence of transition metals, antioxidants including polyphenols with potent antioxidant activities may also exhibit pro-oxidant effects, which may irreversibly damage DNA. Therefore, antioxidants with strong free radical scavenging abilities and devoid of pro-oxidant effects would be of immense biological importance. We report two antioxidant dendrimers with a surface rich in multiple phenolic hydroxyl groups, benzylic hydrogens and electron donating ring substituents that contribute to their potent free radical quenching property. In order to minimize their pro-oxidant effects, the dendrimers were designed with a metal chelating tris(2-aminoethyl)amine (TREN) core. The dendritic antioxidants were prepared by attachment of six syringaldehyde or vanillin molecules to TREN by reductive amination. They exhibited potent radical scavenging properties: 5 times stronger than quercetin and 15 times more potent than Trolox according to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The antioxidant dendrimers also protected low-density lipoprotein, lysozyme and DNA against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced free radical damage. More importantly, unlike quercetin and Trolox, the two TREN antioxidant dendrimers did not damage DNA via their pro-oxidant effects when incubated with physiological amounts of copper ions. The dendrimers also showed no cytotoxicity towards Chinese hamster ovary cells. PMID:20977937

  6. Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors

    E-print Network

    reserved. Yersinia pestis, a Gram-negative bacillus, is the causa- tive agent of plague.1Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors Kyeong Lee,2 The pathogenicity of Yersinia re- lies on the activity of a bacterial virulence factor called YopH, a eukaryotic

  7. Identification of the first potent, selective and bioavailable PPAR? antagonist.

    PubMed

    Bravo, Yalda; Baccei, Christopher S; Broadhead, Alex; Bundey, Richard; Chen, Austin; Clark, Ryan; Correa, Lucia; Jacintho, Jason D; Lorrain, Daniel S; Messmer, Davorka; Stebbins, Karin; Prasit, Peppi; Stock, Nicholas

    2014-05-15

    The discovery and SAR of a novel series of potent and selective PPAR? antagonists are herein described. Exploration of replacements for the labile acyl sulfonamide linker led to a biaryl sulfonamide series of which compound 33 proved to be suitable for further profiling in vivo. Compound 33 demonstrated excellent potency, selectivity against other nuclear hormone receptors, and good pharmacokinetics in mouse. PMID:24745969

  8. Salicylanilides are Potent Inhibitors of Type III Secretion in Yersinia

    Microsoft Academic Search

    Anna M. KAUPPI; Roland Nordfelth; Ulrik Hägglund; Hans Wolf-Watz; Mikael Elofsson

    We have identified O-acyl salicylanilides as potent inhibitors of type III secretion in Y. pseudotuberculosis. These compounds can serve as a starting point for development of novel antibacterial agents that target virulence. Furthermore, compounds that affect bacterial virulence can be employed as chemical tools to study and further understand the processes involved in bacterial virulence. We now plan to use

  9. Original article Potent, orally available, selective COX-2 inhibitors based

    E-print Network

    Hammock, Bruce D.

    Original article Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core inhibitors. While the majority of the compounds prepared using an earlier developed imidazoline N-arylation methodology turned out to be inferior to the known COX-2 inhibitors, one lead compound displayed potency (300

  10. Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition

    E-print Network

    Lee, Keun Woo

    Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition Pterocarpan Sophora flavescens a b s t r a c t Pterocarpans (1­3) and flavanones (4­10) were isolated from Sophora flavescens and screened for their ability to inhibit neuraminidase (an enzyme crucial

  11. Language Contact: An Introduction.

    ERIC Educational Resources Information Center

    Thomason, Sarah G.

    This book surveys situations in which language contact arises and focuses on what happens to the languages themselves: sometimes nothing, sometimes the incorporation of new words, sometimes the spread of new sounds and sentence structures across many languages and wide swathes of territory. It outlines the origins and results of contact-induced…

  12. KNOT CONTACT HOMOLOGY TOBIAS EKHOLM, JOHN ETNYRE, LENHARD NG, AND MICHAEL SULLIVAN

    E-print Network

    Ng, Lenny

    ) homology, is a rich source of deformation invariants in contact topology. Legendrian homology associatesKNOT CONTACT HOMOLOGY TOBIAS EKHOLM, JOHN ETNYRE, LENHARD NG, AND MICHAEL SULLIVAN Abstract with contact structure equal to the kernel of the Liouville form. Knot contact homology, a topological link

  13. Can Imagined Interactions Produce Positive Perceptions?: Reducing Prejudice through Simulated Social Contact

    ERIC Educational Resources Information Center

    Crisp, Richard J.; Turner, Rhiannon N.

    2009-01-01

    The contact hypothesis states that, under the right conditions, contact between members of different groups leads to more positive intergroup relations. The authors track recent trends in contact theory to the emergence of extended, or indirect, forms of contact. These advances lead to an intriguing proposition: that simply imagining intergroup…

  14. TIGER FUND REQUEST FORM Organization Name

    E-print Network

    Bogaerts, Steven

    TIGER FUND REQUEST FORM Organization Name: President Name/contact: Treasurer Name/contact: Total Amount Organization is requesting: Tiger Fund hearing date your organization is attending: (Form must at time of request. #12;TIGER FUND GUIDELINES, PROCEDURES, AND REQUEST FORM I. Introduction The Tiger

  15. A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts

    PubMed Central

    Swarnkar, Gaurav; Sharan, Kunal; Siddiqui, Jawed A; Mishra, Jay Sharan; Khan, Kainat; Khan, Mohd Parvez; Gupta, Varsha; Rawat, Preeti; Maurya, Rakesh; Dwivedi, Anil K; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

    2012-01-01

    BACKGROUND AND PURPOSE Naringenin and its derivatives have been assessed in bone health for their oestrogen-‘like’ effects but low bioavailability impedes clinical potential. This study was aimed at finding a potent form of naringenin with osteogenic action. EXPERIMENTAL APPROACH Osteoblast cultures were harvested from mouse calvaria to study differentiation by naringenin, isosakuranetin, poncirin, phloretin and naringenin-6-C-glucoside (NCG). Balb/cByJ ovariectomized (OVx) mice without or with osteopenia were given naringenin, NCG, 17?-oestradiol (E2) or parathyroid hormone (PTH). Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labelling of bone. Plasma levels of NCG and naringenin were determined by HPLC. KEY RESULTS NCG stimulated osteoblast differentiation more potently than naringenin, while isosakuranetin, poncirin or phloretin had no effect. NCG had better oral bioavailability than naringenin. NCG increased the mRNA levels of oestrogen receptors (ERs) and bone morphogenetic protein (an ER responsive gene) in vivo, more than naringenin. In OVx mice, NCG treatment in a preventive protocol increased bone formation rate (BFR) and improved trabecular microarchitecture more than naringenin or E2. In osteopenic mice, NCG but not naringenin, in a therapeutic protocol, increased BFR and improved trabecular microarchitecture, comparable with effects of PTH treatment. Stimulatory effects of NCG on osteoblasts were abolished by an ER antagonist. NCG transactivated ER? but not ER?. NCG exhibited no uterine oestrogenicity unlike naringenin. CONCLUSIONS AND IMPLICATIONS NCG is a potent derivative of naringenin that has bone anabolic action through the activation of osteoblast ERs and exhibited substantial oral bioavailability. PMID:21864313

  16. Time domain contact model for tyre/road interaction including nonlinear contact stiffness due to small-scale roughness

    NASA Astrophysics Data System (ADS)

    Andersson, P. B. U.; Kropp, W.

    2008-11-01

    Rolling resistance, traction, wear, excitation of vibrations, and noise generation are all attributes to consider in optimisation of the interaction between automotive tyres and wearing courses of roads. The key to understand and describe the interaction is to include a wide range of length scales in the description of the contact geometry. This means including scales on the order of micrometres that have been neglected in previous tyre/road interaction models. A time domain contact model for the tyre/road interaction that includes interfacial details is presented. The contact geometry is discretised into multiple elements forming pairs of matching points. The dynamic response of the tyre is calculated by convolving the contact forces with pre-calculated Green's functions. The smaller-length scales are included by using constitutive interfacial relations, i.e. by using nonlinear contact springs, for each pair of contact elements. The method is presented for normal (out-of-plane) contact and a method for assessing the stiffness of the nonlinear springs based on detailed geometry and elastic data of the tread is suggested. The governing equations of the nonlinear contact problem are solved with the Newton-Raphson iterative scheme. Relations between force, indentation, and contact stiffness are calculated for a single tread block in contact with a road surface. The calculated results have the same character as results from measurements found in literature. Comparison to traditional contact formulations shows that the effect of the small-scale roughness is large; the contact stiffness is only up to half of the stiffness that would result if contact is made over the whole element directly to the bulk of the tread. It is concluded that the suggested contact formulation is a suitable model to include more details of the contact interface. Further, the presented result for the tread block in contact with the road is a suitable input for a global tyre/road interaction model that is also based on the presented contact formulation.

  17. RFI-641, a potent respiratory syncytial virus inhibitor.

    PubMed

    Huntley, Clayton C; Weiss, William J; Gazumyan, Anna; Buklan, Aron; Feld, Boris; Hu, William; Jones, Thomas R; Murphy, Timothy; Nikitenko, Antonia A; O'Hara, Bryan; Prince, Gregory; Quartuccio, Susan; Raifeld, Yuri E; Wyde, Philip; O'Connell, John F

    2002-03-01

    Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of acute upper and lower respiratory tract infections in infants, young children, and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo activity. RFI-641 is active against both RSV type A and B strains. The viral specificity and the large therapeutic window of RFI-641 (>100-fold) indicate that the antiviral activity of the compound is not due to adverse effects on normal cells. The potent in vitro activity of RFI-641 can be translated to efficacy in vivo: RFI-641 is efficacious when administered prophylactically by the intranasal route in mice, cotton rats, and African green monkeys. RFI-641 is also efficacious when administered therapeutically (24 h postinfection) in the monkey model. Mechanism of action studies indicate that RFI-641 blocks viral F protein-mediated fusion and cell syncytium formation. PMID:11850270

  18. RFI-641, a Potent Respiratory Syncytial Virus Inhibitor

    PubMed Central

    Huntley, Clayton C.; Weiss, William J.; Gazumyan, Anna; Buklan, Aron; Feld, Boris; Hu, William; Jones, Thomas R.; Murphy, Timothy; Nikitenko, Antonia A.; O'Hara, Bryan; Prince, Gregory; Quartuccio, Susan; Raifeld, Yuri E.; Wyde, Philip; O'Connell, John F.

    2002-01-01

    Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of acute upper and lower respiratory tract infections in infants, young children, and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo activity. RFI-641 is active against both RSV type A and B strains. The viral specificity and the large therapeutic window of RFI-641 (>100-fold) indicate that the antiviral activity of the compound is not due to adverse effects on normal cells. The potent in vitro activity of RFI-641 can be translated to efficacy in vivo: RFI-641 is efficacious when administered prophylactically by the intranasal route in mice, cotton rats, and African green monkeys. RFI-641 is also efficacious when administered therapeutically (24 h postinfection) in the monkey model. Mechanism of action studies indicate that RFI-641 blocks viral F protein-mediated fusion and cell syncytium formation. PMID:11850270

  19. Fragrance allergic contact dermatitis.

    PubMed

    Cheng, Judy; Zug, Kathryn A

    2014-01-01

    Fragrances are a common cause of allergic contact dermatitis in Europe and in North America. They can affect individuals at any age and elicit a spectrum of reactions from contact urticaria to systemic contact dermatitis. Growing recognition of the widespread use of fragrances in modern society has fueled attempts to prevent sensitization through improved allergen identification, labeling, and consumer education. This review provides an overview and update on fragrance allergy. Part 1 discusses the epidemiology and evaluation of suspected fragrance allergy. Part 2 reviews screening methods, emerging fragrance allergens, and management of patients with fragrance contact allergy. This review concludes by examining recent legislation on fragrances and suggesting potential additions to screening series to help prevent and detect fragrance allergy. PMID:25207685

  20. Contact Lens Solution Toxicity

    MedlinePLUS

    ... diseases: Allergic Contact Dermatitis Corneal Abrasion Corneal Foreign Body Pink Eye ... © 2006-2013 Logical Images, Inc. All rights reserved. Advertising Notice This Site and third parties who place ...

  1. Colored Contact Lens Dangers

    MedlinePLUS Videos and Cool Tools

    ... Without a Prescription It started as an impulsive buy from a souvenir shop, but 10 hours after ... are being sold illegally," Dr. Steinemann said. Never buy colored contact lenses from a retailer that does ...

  2. Language Contact in Qumul

    E-print Network

    Dwyer, Arienne M.

    1998-01-01

    At the eastern edge of China’s Xinjiang region, Qumul (Hami) has been a major gateway between Central Asia and inner China since at least the first century. This paper examines the effects of sustained language contact ...

  3. Grants Management Contacts

    Cancer.gov

    Please contact the grants management specialist assigned to your institution for questions regarding NCI grants. Institution Assigned Specialist FY 2015 3P Biotechnologies, INC. Scharf, Sarah Adheren, INC. Ward, Rosemary Alabama State University Young,

  4. Contacting My Donor Family

    MedlinePLUS

    ... Donor Family Newsroom Minorities Contacting My Donor Family Writing anything can be a challenge. Staring at a ... can take to get started. The process of writing your letter may take some time, but at ...

  5. Contact thermal lithography

    E-print Network

    Schmidt, Aaron Jerome, 1979-

    2004-01-01

    Contact thermal lithography is a method for fabricating microscale patterns using heat transfer. In contrast to photolithography, where the minimum achievable feature size is proportional to the wavelength of light used ...

  6. Total synthesis of valerenic acid, a potent GABAA receptor modulator.

    PubMed

    Ramharter, Jürgen; Mulzer, Johann

    2009-03-01

    The first total synthesis of the sesquiterpenoid valerenic acid, a constituent of Valeriana officinalis, is described. The compound is a potent modulator of the GABA(A) receptor and may thus be useful in the treatment of various dysfunctions of the central nervous system. The synthesis is enantio-, diastereo-, and regiocontrolled and utilizes an enyne-RCM, a metal-coordinated Diels-Alder reaction, a hydroxy-directed Crabtree hydrogenation, and a Negishi methylation as key steps. PMID:19178294

  7. Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors.

    PubMed

    Brasca, Maria Gabriella; Nesi, Marcella; Avanzi, Nilla; Ballinari, Dario; Bandiera, Tiziano; Bertrand, Jay; Bindi, Simona; Canevari, Giulia; Carenzi, Davide; Casero, Daniele; Ceriani, Lucio; Ciomei, Marina; Cirla, Alessandra; Colombo, Maristella; Cribioli, Sabrina; Cristiani, Cinzia; Della Vedova, Franco; Fachin, Gabriele; Fasolini, Marina; Felder, Eduard R; Galvani, Arturo; Isacchi, Antonella; Mirizzi, Danilo; Motto, Ilaria; Panzeri, Achille; Pesenti, Enrico; Vianello, Paola; Gnocchi, Paola; Donati, Daniele

    2014-09-01

    We report herein the discovery, structure guided design, synthesis and biological evaluation of a novel class of JAK2 inhibitors. Optimization of the series led to the identification of the potent and orally bioavailable JAK2 inhibitor 28 (NMS-P953). Compound 28 displayed significant tumour growth inhibition in SET-2 xenograft tumour model, with a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favourable pharmacokinetic and safety profile. PMID:25009002

  8. Dynorphin(1-13), an Extraordinarily Potent Opioid Peptide

    Microsoft Academic Search

    Avram Goldstein; S. Tachibana; L. I. Lowney; M. Hunkapiller; L. Hood

    1979-01-01

    We describe the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-terminal sequence of dynorphin, a novel porcine pituitary endorphin. It contains [Leu]enkephalin. In the guinea pig ileum longitudinal muscle preparation it is about 700 times more potent than [Leu]enkephalin. Its effects in this tissue are blocked completely by naloxone, but the apparent affinity of naloxone

  9. Species-Specific Detoxification Metabolism of Fenpyroximate, a Potent Acaricide

    Microsoft Academic Search

    Kazuhiko Motoba; Hideo Nishizawa; Takashi Suzuki; Hiroshi Hamaguchi; Matazaemon Uchida; Shunji Funayama

    2000-01-01

    The mode of selective toxicity of fenpyroximate (tert-butyl (E)-?-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy)-p-toluate), a potent acaricide, was studied with respect to its detoxification metabolism. Among its metabolites examined, only ester hydrolyzed metabolites completely lost the inhibitory activity toward NADH–ubiquinone oxidoreductase, which suggested that ester hydrolysis was the key step in detoxification. After a single oral administration of fenpyroximate to rats, two labile intermediates (metabolites

  10. Synthetic shRNAs as potent RNAi triggers

    Microsoft Academic Search

    Despina Siolas; Cara Lerner; Julja Burchard; Wei Ge; Peter S Linsley; Patrick J Paddison; Gregory J Hannon; Michele A Cleary

    2004-01-01

    Designing potent silencing triggers is key to the successful application of RNA interference (RNAi) in mammals. Recent studies suggest that the assembly of RNAi effector complexes is coupled to Dicer cleavage. Here we examine whether transfection of optimized Dicer substrates results in an improved RNAi response. Dicer cleavage of chemically synthesized short hairpin RNAs (shRNAs) with 29-base-pair stems and 2-nucleotide

  11. Diversity Against Adversity: How Adaptive Immune System Evolves Potent Antibodies

    NASA Astrophysics Data System (ADS)

    Heo, Muyoung; Zeldovich, Konstantin B.; Shakhnovich, Eugene I.

    2011-07-01

    Adaptive immunity is an amazing mechanism, whereby new protein functions—affinity of antibodies (Immunoglobulins) to new antigens—evolve through mutation and selection in a matter of a few days. Despite numerous experimental studies, the fundamental physical principles underlying immune response are still poorly understood. In considerable departure from past approaches, here, we propose a microscopic multiscale model of adaptive immune response, which consists of three essential players: The host cells, viruses, and B-cells in Germinal Centers (GC). Each moiety carries a genome, which encodes proteins whose stability and interactions are determined from their sequences using laws of Statistical Mechanics, providing an exact relationship between genomic sequences and strength of interactions between pathogens and antibodies and antibodies and host proteins (autoimmunity). We find that evolution of potent antibodies (the process known as Affinity Maturation (AM)) is a delicate balancing act, which has to reconcile the conflicting requirements of protein stability, lack of autoimmunity, and high affinity of antibodies to incoming antigens. This becomes possible only when antibody producing B cells elevate their mutation rates (process known as Somatic Hypermutation (SHM)) to fall into a certain range—not too low to find potency increasing mutations but not too high to destroy stable Immunoglobulins and/or already achieved affinity. Potent antibodies develop through clonal expansion of initial B cells expressing marginally potent antibodies followed by their subsequent affinity maturation through mutation and selection. As a result, in each GC the population of mature potent Immunoglobulins is monoclonal being ancestors of a single cell from initial (germline) pool. We developed a simple analytical theory, which provides further rationale to our findings. The model and theory reveal the molecular factors that determine the efficiency of affinity maturation, thereby providing insight into the variability of the immune response to cytopathic viruses (the direct response by germline antibodies) and poorly cytopathic viruses (a crucial role of SHM in the response).

  12. In search of potent 5-HT6 receptor inverse agonists.

    PubMed

    Hostetler, Greg; Dunn, Derek; McKenna, Beth Ann; Kopec, Karla; Chatterjee, Sankar

    2014-06-01

    A series of non-sulfonamide/non-sulfone derived potent 5-HT6 receptor inverse agonists has been disclosed. Representative compound 9 (Ki  = 14 nm) displayed selectivity against a set of family members as well as brain permeability 6 h post-oral administration. In addition, the separated enantiomers of compound 9 displayed difference in activity indicating the influence of chirality on potency. PMID:24406060

  13. Allergic contact dermatitis: cosmetics

    Microsoft Academic Search

    Anton C. de Groot; Carolus-Liduina Ziekenhuis

    \\u000a Cosmetics are frequent causes of allergic contact dermatitis. After metals, ingredients of cosmetic products are the most\\u000a common contact allergens identified. Even in the general population, some 2-3% may be allergic to substances that are present\\u000a in cosmetics and toiletries [1]. The recent introduction of mandatory ingredient labelling in the European Union [2] has greatly facilitated diagnostic procedures in patients

  14. Exploring the Nature of Contact Freezing

    NASA Astrophysics Data System (ADS)

    Kiselev, A. A.; Hoffmann, N.; Duft, D.; Leisner, T.

    2012-12-01

    The freezing of supercooled water droplets upon contact with aerosol particles (contact nucleation of ice) is the least understood mechanism of ice formation in atmospheric clouds. Although experimental evidences suggest that some aerosols can be better IN in the contact than in the immersion mode (that is, triggering ice nucleation at higher temperature), no final explanation of this phenomena currently exists. On the other hand, the contact freezing is believed to be responsible for the enhanced rate of secondary ice formation occasionally observed in LIDAR measurements in the cold mixed phase clouds. Recently we have been able to show that the freezing of supercooled droplets electrodynamically levitated in the laminar flow containing mineral dust particles (kaolinite) is a process solely governed by a rate of collisions between the supercooled droplet and the aerosol particles. We have shown that the probability of droplet freezing on a single contact with aerosol particle may differ over an order of magnitude for kaolinite particles having different genesis and morphology. In this presentation we extend the study of contact nucleation of ice and compare the IN efficiency measured for DMA-selected kaolinite, illite and hematite particles. We show that the freezing probability increases towards unity as the temperature decreases and discuss the functional form of this temperature dependence. We explore the size dependence of the contact freezing probability and show that it scales with the surface area of the particles, thus resembling the immersion freezing behavior. However, for all minerals investigated so far, the contact freezing has been shown to dominate over immersion freezing on the short experimental time scales. Finally, based on the combined ESEM and electron microprobe analysis, we discuss the significance of particle morphology and variability of chemical composition on its IN efficiency in contact mode.

  15. QUATERNIONIC CONTACT MANIFOLDS WITH A CLOSED FUNDAMENTAL STEFAN IVANOV AND DIMITER VASSILEV

    E-print Network

    Vassilev, Dimiter N.

    QUATERNIONIC CONTACT MANIFOLDS WITH A CLOSED FUNDAMENTAL 4-FORM STEFAN IVANOV AND DIMITER VASSILEV Abstract. We show that the fundamental 4-form on a quaternionic contact manifold of dimension at least. This condition characterizes quaternionic contact structures which are locally qc homothetic to 3-Sasakian

  16. Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid

    Microsoft Academic Search

    DINA SALEH; PIERRE ERNST; SAM LIM; PETER J. BARNES; ADEL GIAID

    Peroxynitrite is a potent oxidant formed by the rapid reaction of the free radicals ni- tric oxide (NO) and superoxide. It causes airway hy- perresponsiveness and airway epithelial damage, en- hances inflammatory cell recruitment, and inhibits pulmonary surfactant. Asthma is characterized by in- creased airway hyperresponsiveness, airway epithelial shedding, and inflammation. We examined the pro- duction of peroxynitrite and the

  17. Applying a multitarget rational drug design strategy: the first set of modulators with potent and balanced activity toward dopamine D3 receptor and fatty acid amide hydrolase.

    PubMed

    De Simone, Alessio; Ruda, Gian Filippo; Albani, Clara; Tarozzo, Glauco; Bandiera, Tiziano; Piomelli, Daniele; Cavalli, Andrea; Bottegoni, Giovanni

    2014-05-18

    Combining computer-assisted drug design and synthetic efforts, we generated compounds with potent and balanced activities toward both D3 dopamine receptor and fatty acid amide hydrolase (FAAH) enzyme. By concurrently modulating these targets, our compounds hold great potential toward exerting a disease-modifying effect on nicotine addiction and other forms of compulsive behavior. PMID:24691497

  18. Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity

    PubMed Central

    2010-01-01

    To identify a CCR5 antagonist as an HIV-1 entry inhibitor, we designed a novel series of indane derivatives based on conformational considerations. Modification on the indane ring led to the discovery of compound 22a (INCB9471) that exhibited high affinity for CCR5, potent anti-HIV-1 activity, high receptor selectivity, excellent oral bioavailability, and a tolerated safety profile. INCB9471 has entered human clinical trials. PMID:24900235

  19. Single point contact measurements of mechanical resonances

    Microsoft Academic Search

    C. P. Hsieh; B. T. Khuri-Yakub

    1992-01-01

    A technique for measuring the material properties of spherical objects is presented. The technique is also capable of detecting the presence of surface defects in these objects. Resonances of spheres are excited at both low and high frequencies. Resonances are generated by forming a one-point Hertzian contact between the sphere and a spherical depression in a buffer rod with a

  20. Pustular irritant contact dermatitis caused by dexpanthenol in a child.

    PubMed

    Gulec, Ali Ihsan; Albayrak, Hulya; Uslu, Esma; Ba?kan, Elife; Aliagaoglu, Cihangir

    2015-03-01

    Pustular irritant contact dermatitis is rare and unusual clinic form of contact dermatitis. Dexpanthenol is the stable alcoholic analogue of pantothenic acid. It is widely used in cosmetics and topical medical products for several purposes. We present the case of 8-year-old girl with pustules over erythematous and eczematous areas on the face and neck. To the best of our knowledge, this is the first case reported that is diagnosed as pustular irritant contact dermatitis caused by dexpanthenol. PMID:24506320

  1. Detection of microwave emission by means of SN point contacts

    Microsoft Academic Search

    Iu. G. Bevza; V. I. Karamushko; I. M. Dmitrenko

    1977-01-01

    The characteristics of microwave detection were studied for superconductor\\/normal metal (S-N) point contacts in the absence of a dc transport current. Nb-Sn, Nb-Cu, Cu-Nb, and Cu-Sn clamped contacts (the first element forming the point) were prepared in liquid helium and were tested in a rectangular microwave waveguide. The resistance of the contacts ranged from 1 to 100 ohms. The frequency

  2. Quaternionic contact Einstein structures and the quaternionic contact Yamabe problem

    E-print Network

    Vassilev, Dimiter N.

    Quaternionic contact Einstein structures and the quaternionic contact Yamabe problem Stefan Ivanov@math.unm.edu #12;#12;Contents Chapter 1. Introduction 1 Chapter 2. Quaternionic contact structures and the Biquard.2. The Curvature Tensor 18 Chapter 4. QC-Einstein quaternionic contact structures 23 4.1. The Bianchi identities 24

  3. Metrology Of Silicide Contacts For Future CMOS

    Microsoft Academic Search

    Stefan Zollner; Richard B. Gregory; M. L. Kottke; Victor Vartanian; Xiang-Dong Wang; David Theodore; P. L. Fejes; J. R. Conner; Mark Raymond; Xiaoyan Zhu; Dean Denning; Scott Bolton; Kyuhwan Chang; Ross Noble; Mohamad Jahanbani; Marc Rossow; Darren Goedeke; Stan Filipiak; Ricardo Garcia; Dharmesh Jawarani; Bill Taylor; Bich-Yen Nguyen; P. E. Crabtree; Aaron Thean

    2007-01-01

    Silicide materials (NiSi, CoSi2, TiSi2, etc) are used to form low-resistance contacts between the back-end (W plugs and Cu interconnects) and front-end portions (silicon source, drain, and gate regions) of integrated CMOS circuits. At the 65 nm node, a transition from CoSi2 to NiSi was necessary because of the unique capability of NiSi to form narrow silicide nanowires on active

  4. A unified model for insulator selection to form ultra-low resistivity metal-insulator-semiconductor contacts to n-Si, n-Ge, and n-InGaAs

    E-print Network

    Yener, Aylin

    A unified model for insulator selection to form ultra-low resistivity metal- insulator-semiconductor) heterostructure Appl. Phys. Lett. 101, 033505 (2012) Bipolar conductivity in nanocrystallized TiO2 Appl. Phys. Lett. 101, 032101 (2012) Determination of graphene work function and graphene-insulator-semiconductor

  5. Contact Dermatitis – Epidemiological Study

    PubMed Central

    STATESCU, Laura; BRANISTEANU, Daciana; DOBRE, C.; SOLOVASTRU, Laura Gheuca; VASILCA, A.; PETRESCU, Zenaida; AZOICAI, Doina

    2011-01-01

    ABSTRACT Aim: To evaluate the real incidence of contact dermatitis, to identify the most common allergens, the favoring factors, to establish the prophylaxis methods, the key for a correct management of the patient with contact dermatitis. Method: A retrospective study, on the patients that refers to the Dermatology Clinic, "St. Spiridon" Emergency Hospital Iasi, between 01.01.2006 and 31.12. 2009, based on demographic items, the type of contact dermatitis and the allergens implicated. Results: we enrolled 353 patients between 2006-2009, representing 3,89% from the hospitalized patients; the study reveals a higher incidence at women (60,27%), similar with data from literature; the majority of the patients was aged over 45, with the higher rate in the interval of 45-65 years old; the most frequent implicated allergens and irritants were plants (26,31% - 92 patients) and topical drugs and antiseptics (25,65% - 89 patients); the area most affected was the face (25%) and the hands (19,07%), from which almost 80-90% was occupational dermatitis. The distribution of cases depending on the type of contact dermatitis indicates an approximate percentage of those allergic to those irritant. Conclusions: The real prevalence of this disease is unknown, being frequently a missed diagnosis (other kinds of eczema), the key of the correct diagnose being a repeated, exhaustive anamnesis, revealing all the favoring conditions and possible contact allergens. PMID:22879841

  6. WELCOME .......................................................................................... 4 COSMOS CONTACTS............................................................................ 4

    E-print Network

    Guo, Ting

    .......................................................................................... 4 COSMOS CONTACTS............................................................................ 4 COSMOS OFFICE 4 STAFF 4 RESIDENCE HALL 4 AFTER HOURS EMERGENCY

  7. EMSL Sample Submission Form If you are sending Mass Spec samples, do not use this form.

    E-print Network

    EMSL Sample Submission Form If you are sending Mass Spec samples, do not use this form. Instead the form below after receiving approval from your EMSL Host or Point of Contact. User Information Name Email Address EMSL Proposal Number EMSL Point of Contact Sample Information Sample Type: Liquid Solid

  8. Contact and respiratory sensitization by chemical allergens: Uneasy relationships

    Microsoft Academic Search

    Ian Kimber

    1995-01-01

    A variety of chemicals are able to cause allergic disease in susceptible individuals. Chemical-induced allergy may take several forms, chief among them being skin sensitization or allergic contact dermatitis and respiratory hypersensitivity. It has been found that contact and respiratory chemical allergens induce in mice qualitatively divergent immune responses consistent with the preferential activation of discrete Thelper (Th) cell subpopulations,

  9. Adhesive strength of glass composite materials in the contact region

    Microsoft Academic Search

    B. S. Batalin; H. A. Pravina

    1992-01-01

    at a particular temperature. In this state the glass wets the surface particles of the two phases. The structure of the region of contact between the glass and the two phases is formed as a result of interactions between the glass and the two phases. For subsequent crystallization of the matrix this structure changes. The properties of the contact region

  10. Mixed complexes formed by lithioacetonitrile and chiral lithium amides: observation of (6)li,(15)N and (6)Li,(13)C couplings due to both C-Li and N-Li contacts.

    PubMed

    Sott, Richard; Granander, Johan; Hilmersson, Göran

    2004-06-01

    NMR spectroscopic studies have been performed on the mixed complexes formed by the lithium salt of acetonitrile (LiCH(2)CN) and the chiral lithium amides Li-(S)-N-(2-methoxybenzyl)-1-amino-1-phenyl-2-ethoxyethane (Li-1) and Li-(S)-N-isopropyl-2-amino-1-phenyl-3-methoxypropane (Li-2) in diethyl ether and tetrahydrofuran solvent. In diethyl ether Li-1 and LiCH(2)CN form a mixed dimeric (1:1) complex, while Li-2 and LiCH(2)CN form a mixed trimeric (2:1) complex. The dimer undergoes fast exchange between ketenimine and bridged structures. Both (1)J((15)N,(6)Li) and (1)J((13)C,(6)Li) couplings were observed for the respectively isotopically labeled compounds. In the trimeric complex the CH(2)CN anion also undergoes fast degenerate exchange between ketenimine and bridged structures, and the complex appears C(2)-symmetric on the NMR spectroscopy time scale. Both the dimer and trimer complexes have the bridged acetonitrile anion in common, as indicated by the highly shielded alpha-carbon (13)C NMR shifts (delta -6.1 and -7.4, respectively). In tetrahydrofuran only N-metalated mixed LiCH(2)CN dimers were observed for both Li-1 and Li-2 with the less shielded (13)C NMR shifts of delta -2.5 and -2.2 for the alpha-carbon of LiCH(2)CN of the complexes. PMID:15161308

  11. Contact sensitization in children.

    PubMed

    Manzini, B M; Ferdani, G; Simonetti, V; Donini, M; Seidenari, S

    1998-01-01

    Our study concerns contact sensitization in children, the frequency of which is still debated in the literature, even though specific reports are increasing. During a 7 year period (1988-1994) 670 patients, 6 months to 12 years of age, were patch tested with the European standard series, integrated with 24 haptens, at the same concentrations as for adults. We observed positive results in 42% of our patients. Thimerosal, nickel sulfate, Kathon CG, fragrance mix, neomycin, wool alcohols, and ammoniated mercury induced most of the positive responses. The highest sensitization rate was found in children from 0 to 3 years of age. Comments on main positive haptens are reported. Seventy-seven percent of our sensitized patients were atopics, suggesting that atopy represents a predisposing factor for contact hypersensitivity. Patch testing represents a useful diagnostic procedure for the definition of childhood eczematous dermatitis and for the identification of agents inducing contact sensitization which is frequently associated with atopic dermatitis. PMID:9496796

  12. Venison contact dermatitis.

    PubMed

    Reiche, Louise

    2002-02-01

    A 37-year-old meat inspector presented with a 5-month history of forearm eczema. His symptoms improved at weekends and over holidays but flared within a day of work. Scratch patch tests were strongly positive to fresh venison diaphragm and venison liver and weakly positive to venison hide and blood, and lamb blood. They were negative to other venison and lamb components. Type IV allergy tests with Standard European and fragrance batteries were negative. The eczema cleared with a change in work role, clobetasol-17-propionate cream, flucloxacillin and aqueous cream. He was then able to return to meat inspecting. Provided he was diligent about applying 'Dermashield' barrier foam and minimizing contact with irritants, his eczema has remained well controlled over the last 4 years. Attention to irritant contact dermatitis is important in the management of protein contact urticaria. PMID:11869215

  13. Shoe allergic contact dermatitis.

    PubMed

    Matthys, Erin; Zahir, Amir; Ehrlich, Alison

    2014-01-01

    Foot dermatitis is a widespread condition, affecting men and women of all ages. Because of the location, this condition may present as a debilitating problem to those who have it. Allergic contact dermatitis involving the feet is frequently due to shoes or socks. The allergens that cause shoe dermatitis can be found in any constituent of footwear, including rubber, adhesives, leather, dyes, metals, and medicaments. The goal of treatment is to identify and minimize contact with the offending allergen(s). The lack of product information released from shoe manufacturers and the continually changing trends in footwear present a challenge in treating this condition. The aim of this study is to review the current literature on allergic contact shoe dermatitis; clinical presentation, allergens, patch testing, and management will be discussed. PubMed and MEDLINE databases were used for the search, with a focus on literature updates from the last 15 years. PMID:25000234

  14. Design of potent substrate-analogue inhibitors of canine renin.

    PubMed

    Hui, K Y; Siragy, H M; Haber, E

    1992-08-01

    Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect. PMID:1446972

  15. Potent Small Molecule Suppression of Oxacillin Resistance in MRSA

    PubMed Central

    Harris, Tyler L.; Worthington, Roberta J.; Melander, Christian

    2013-01-01

    The use of adjuvant molecules that have the ability to restore the susceptibility of multi-drug resistant bacteria, such as MRSA, to clinically available antibiotics is a promising alternative to the development of novel antimicrobials. We report an extremely potent small molecule that, at sub-MIC levels, lowers the MIC of oxacillin against a number of MRSA strains by up to 512-fold. Preliminary mechanistic investigations indicate that the VraSR two-component system plays a role in the activity of this compound. PMID:23047322

  16. Synthesis and evaluation of bibenzyl glycosides as potent tyrosinase inhibitors.

    PubMed

    Tajima, Reiko; Oozeki, Hiromi; Muraoka, Seiichi; Tanaka, Saori; Motegi, Yukari; Nihei, Hiroyuki; Yamada, Yoichi; Masuoka, Noriyoshi; Nihei, Ken-ichi

    2011-04-01

    Bibenzyl glycosides 1-6 were synthesized from 2,4-dihydoxybenzaldehyde and xylose, glucose, cellobiose or maltose. The key steps in the synthesis were the Wittig reaction and trichloroacetimidate glycosylation. Tests for tyrosinase inhibitory activity showed that all were significantly active, indicating that they are unique hydrophilic tyrosinase inhibitors. Bibenzyl xyloside 2 is a particularly potent inhibitor (IC(50) = 0.43 ?M, 17 times higher than that of kojic acid). These results suggest that the hydrophilic cavity of tyrosinase might accommodate the bulky carbohydrate on the bibenzyl scaffold. PMID:21334791

  17. Synthesis of Novel Compounds as New Potent Tyrosinase Inhibitors

    PubMed Central

    Hamidian, Hooshang

    2013-01-01

    In the present paper, we report the synthesis and pharmacological evaluation of a new series of azo compounds with different groups (1-naphthol, 2-naphthol, and N,N-dimethylaniline) and trifluoromethoxy and fluoro substituents in the scaffold. All synthesized compounds (5a–5f) showed the most potent mushroom tyrosinase inhibition (IC50 values in the range of 4.39 ± 0.76–1.71 ± 0.49?µM), comparable to the kojic acid, as reference standard inhibitor. All the novel compounds were characterized by FT-IR, 1H NMR, 13C NMR, and elemental analysis. PMID:24260737

  18. Potent Protein Glycation Inhibition of Plantagoside in Plantago major Seeds

    PubMed Central

    Matsuura, Nobuyasu; Aradate, Tadashi; Kurosaka, Chihiro; Ubukata, Makoto; Kittaka, Shiho; Nakaminami, Yuri; Gamo, Kanae; Kojima, Hiroyuki; Ohara, Mitsuharu

    2014-01-01

    Plantagoside (5,7,4?,5?-tetrahydroxyflavanone-3?-O-glucoside) and its aglycone (5,7,3?,4?,5?-pentahydroxyflavanone), isolated from a 50% ethanol extract of Plantago major seeds (Plantaginaceae), were established to be potent inhibitors of the Maillard reaction. These compounds also inhibited the formation of advanced glycation end products in proteins in physiological conditions and inhibited protein cross-linking glycation. These results indicate that P. major seeds have potential therapeutic applications in the prevention of diabetic complications. PMID:24895551

  19. Discovery of Potent Dual PPAR? Agonists/CB1 Ligands

    PubMed Central

    2011-01-01

    This letter describes the synthesis and in vitro and in vivo evaluation of dual ligands targeting the cannabinoid and peroxisome proliferator-activated receptors (PPAR). These compounds were obtained from fusing the pharmacophores of fibrates and the diarylpyrazole rimonabant, a cannabinoid receptor antagonist. They are the first examples of dual compounds with nanomolar affinity for both PPAR? and cannabinoid receptors. Besides, lead compound 2 proved to be CB1 selective. Unexpectedly, the phenol intermediates tested were equipotent (compound 1 as compared to 2) or even more potent (compound 3 as compared with 4). This discovery opens the way to design new dual ligands. PMID:24936232

  20. Potent protein glycation inhibition of plantagoside in Plantago major seeds.

    PubMed

    Matsuura, Nobuyasu; Aradate, Tadashi; Kurosaka, Chihiro; Ubukata, Makoto; Kittaka, Shiho; Nakaminami, Yuri; Gamo, Kanae; Kojima, Hiroyuki; Ohara, Mitsuharu

    2014-01-01

    Plantagoside (5,7,4',5'-tetrahydroxyflavanone-3'-O-glucoside) and its aglycone (5,7,3',4',5'-pentahydroxyflavanone), isolated from a 50% ethanol extract of Plantago major seeds (Plantaginaceae), were established to be potent inhibitors of the Maillard reaction. These compounds also inhibited the formation of advanced glycation end products in proteins in physiological conditions and inhibited protein cross-linking glycation. These results indicate that P. major seeds have potential therapeutic applications in the prevention of diabetic complications. PMID:24895551

  1. Ohmic contacts to n-GaSb

    E-print Network

    Yang, Zhengchong

    1997-01-01

    RTA (Rapid Thermal Annealing) at 400'C for 10 seconds. More recently, Pd-based ohmic contacts to n-GaSb was investigated by Vogt and Hartnagal [10]. They developed PdSPd and PdGePd contacts on n-GaSb grown by molecular beam epitaxy which resulted... annealing (RTA) oven in flowing forming gas (12% Hz. g8% N&) ambient at different temperatures for electrical property evaluation and thermal stability assessment. In terms of thermal stability, since GaSb devices are processed at high temperature...

  2. Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone, and related analogues.

    PubMed

    Thaisrivongs, S; Pals, D T; Kati, W M; Turner, S R; Thomasco, L M; Watt, W

    1986-10-01

    Peptides that contain difluorostatine and difluorostatone residues have been shown to be potent inhibitors of the aspartyl protease renin. The readily hydrated fluoro ketone is proposed to mimic the tetrahedral intermediate that forms during the enzyme-catalyzed hydrolysis of a peptidic bond. It is suggested that the sp3-hybridized ketal acts as a transition-state analogue renin inhibitor. The fluoro ketone is shown to be a much more effective inhibitor than the corresponding nonfluorinated ketone, which acts as a pseudosubstrate. More lipophilic side chains at the P1 site can enhance the inhibitory potency of the difluorostatine analogue, but this cannot be demonstrated in the difluorostatone series. Additionally, high renin specificity has been shown for a difluorostatone-containing peptide. PMID:3531517

  3. Prefibrillar huntingtin oligomers isolated from HD brain potently seed amyloid formation.

    PubMed

    Morozova, Olga A; Gupta, Sharad; Colby, David W

    2015-07-01

    Many neurodegenerative diseases are associated with deposits of aggregated protein in the brain. The molecular pathways through which soluble proteins misfold to form amyloids and large protein aggregates often include diverse oligomeric species, only some of which progress to the amyloid state. Here we show that prefibrillar huntingtin (HTT) oligomers, isolated from Huntington's disease (HD) affected human brain samples or mouse models, stimulate polyglutamine amyloid formation. Fibrillar HTT oligomers have been shown to be unstable under denaturing conditions and appear not to lead to amyloid formation. Here we show that prefibrillar HTT oligomers are remarkably stable and are potent seeds of polyglutamine amyloid formation. Therefore, our findings help to dissect the complex molecular pathway of HTT misfolding. PMID:26037141

  4. Contact dermatitis from a presumed allergy to paraphenylenediamine.

    PubMed

    Hansen, Daniel; Voutsalath, Melissa

    2009-12-01

    Paraphenylenediamine (PPD) is a potent skin allergen found in permanent hair dye and temporary henna tattoo ink. Several cases of adverse skin reactions to PPD have been reported in the literature. Here we present a case involving a patient who acquired a temporary tattoo while vacationing in Mexico and subsequently developed contact dermatitis at the tattoo site. He provided a history of permanent hair dye use in the past with associated cutaneous reaction. Temporary tattoos have become increasingly popular with travelers and as a result so have reports of associated allergic contact dermatitis. Of concern is cross-reaction of PPD to related compounds, severe reactions in younger populations and sequelae including increased sensitization, permanent scarring, and persistent postinflammatory hyperpigmentation. PMID:19958436

  5. Solid-Contact Polymer Sensors Based on Composite Materials

    Microsoft Academic Search

    A. V. Legin; S. M. Makarychev-Mikhailov; D. O. Kirsanov; Yu. G. Vlasov

    2002-01-01

    Ammonium and nitrate polymer sensors with solid contact, based on composites formed by a mixture of a membrane cocktail with metallic silver and silver chloride, were developed and studied for the first time.

  6. Contact: Releasing the news

    NASA Astrophysics Data System (ADS)

    Pinotti, Roberto

    The problem of mass behavior after man's future contacts with other intelligences in the universe is not only a challenge for social scientists and political leaders all over the world, but also a cultural time bomb as well. In fact, since the impact of CETI (Contact with Extraterrestrial Intelligence) on human civilization, with its different cultures, might cause a serious socio-anthropological shock, a common and predetermined worldwide strategy is necessary in releasing the news after the contact, in order to keep possible manifestations of fear, panic and hysteria under control. An analysis of past studies in this field and of parallel historical situations as analogs suggests a definite "authority crisis" in the public as a direct consequence of an unexpected release of the news, involving a devastating "chain reaction" process (from both the psychological and sociological viewpoints) of anomie and maybe the collapse of today's society. The only way to prevent all this is to prepare the world's public opinion concerning contact before releasing the news, and to develop a long-term strategy through the combined efforts of scientists, political leaders, intelligence agencies and the mass media, in order to create the cultural conditions in which a confrontation with ETI won't affect mankind in a traumatic way. Definite roles and tasks in this multi-level model are suggested.

  7. Traffic Safety Research Contact

    E-print Network

    Latino Traffic Safety Initiative Research Contact: Katie Womack kwomack@tamu.edu tti will outnumber Caucasians in Texas by 2020. These converging realities underscore the need for a traffic safety for a traffic safety focus on the future majority population. · Motor vehicle traffic crashes are the leading

  8. Any Questions? Please contact

    E-print Network

    Rubin, Yoram

    ! To Donate To purchase a package and/or item(s), email Jessica Tran at jesstran@berkeley.edu and includeAny Questions? Please contact Name: Jessica Tran Phone Number: 805-587-7753 Email: jesstran Competition Team Cal's Seismic Team educates students on earthquakedesign of high rise buildings. Students

  9. Irritant Contact Dermatitis

    MedlinePLUS

    ... Terms of Use | Contact Us © 2006-2013 Logical Images, Inc. All rights reserved. Advertising Notice This Site and third parties who place ... practices and to make choices about online behavioral advertising, please click here . ... here . © Logical Images, Inc. All rights reserved. Use of this site ...

  10. Allergic Contact Dermatitis

    MedlinePLUS

    ... Terms of Use | Contact Us © 2006-2013 Logical Images, Inc. All rights reserved. Advertising Notice This Site and third parties who place ... practices and to make choices about online behavioral advertising, please click here . ... here . © Logical Images, Inc. All rights reserved. Use of this site ...

  11. Technology Advertising Contact Information

    E-print Network

    Peters, Richard

    Overview #12;Technology Advertising Contact Information Alex Sheath 8596 4063 asheath Overview Our online Technology section is geared towards an IT professional environment, reaching a range of technology enthusiasts from every day gadget consumers to business decision makers where enterprise solutions

  12. Plasticity in fretting contact

    Microsoft Academic Search

    J. M. Ambrico; M. R. Begley

    2000-01-01

    The fretting problem of a cyclically loaded cylinder on a flat elastic–plastic surface is analyzed under the assumption of plane strain. Severe fretting conditions are modeled by applying a constant normal load and a cyclic tangential load to the cylinder and describing the contact behavior using a Coulomb friction law. Detailed numerical results are presented for the evolution of plastic

  13. Multigrid contact detection method

    NASA Astrophysics Data System (ADS)

    He, Kejing; Dong, Shoubin; Zhou, Zhaoyao

    2007-03-01

    Contact detection is a general problem of many physical simulations. This work presents a O(N) multigrid method for general contact detection problems (MGCD). The multigrid idea is integrated with contact detection problems. Both the time complexity and memory consumption of the MGCD are O(N) . Unlike other methods, whose efficiencies are influenced strongly by the object size distribution, the performance of MGCD is insensitive to the object size distribution. We compare the MGCD with the no binary search (NBS) method and the multilevel boxing method in three dimensions for both time complexity and memory consumption. For objects with similar size, the MGCD is as good as the NBS method, both of which outperform the multilevel boxing method regarding memory consumption. For objects with diverse size, the MGCD outperform both the NBS method and the multilevel boxing method. We use the MGCD to solve the contact detection problem for a granular simulation system based on the discrete element method. From this granular simulation, we get the density property of monosize packing and binary packing with size ratio equal to 10. The packing density for monosize particles is 0.636. For binary packing with size ratio equal to 10, when the number of small particles is 300 times as the number of big particles, the maximal packing density 0.824 is achieved.

  14. Contact - Team Science Toolkit

    Cancer.gov

    The Team Science Toolkit was developed, and is maintained, by the Science of Team Science (SciTS) team at the National Cancer Institute, Division of Cancer Control and Population Science, Behavioral Research Program. To contact us, please email Dr. Kara L.

  15. Contact Efflorescence on Demand

    NASA Astrophysics Data System (ADS)

    Davis, R. D.; Lance, S.; Gordon, J. A.; Ushijima, S.; Tolbert, M. A.

    2014-12-01

    The phase state of atmospheric aerosols (liquid vs solid) plays an important role in particle growth, cloud formation, climate impact and visibility degradation. In the atmosphere, changes in relative humidity (RH) and temperature cause phase transitions in the atmospheric particulate. Efflorescence, the process of salt crystal nucleation from an aqueous electrolyte solution upon decreasing RH, often occurs at a lower RH than the reverse process of deliquescence. It has been shown that the efflorescence RH can occur at a higher RH in the presence of a heterogeneous surface immersed in a liquid particle. Here we present a new laboratory technique using optically levitated particles to study heterogeneous efflorescence initiated by contact with an external particle. In this work, collisions between aqueous microdroplets and heterogeneous nuclei are monitored in situ using scattered laser light to quantify the number of collisions and to detect phase transitions. We find that when contact initiates the phase transition, efflorescence occurs at a higher RH than when the same heterogeneous nucleus is immersed in the particle. The results of these experiments will be discussed in the context of understanding contact nucleation on a mechanistic level and predicting the relative importance of contact efflorescence in the atmosphere.

  16. CONTACT INFORMATION Sharon Smith

    E-print Network

    CONTACT INFORMATION Sharon Smith Director, Advanced Technology Lockheed Martin sharon of two respected leaders in industry and academia. Rice conducts an average of $30 million per year for materials, electronics, energy, security and defense. Through LANCER, Lockheed Martin engineers will pair

  17. Secure Core Contact Information

    E-print Network

    Secure Core Contact Information C. E. Irvine irvine@nps.edu 831-656-2461 Department of Computer for the secure management of local and/or remote information in multiple contexts. The SecureCore project Science Graduate School of Operations and Information Sciences www.cisr.nps.edu Project Description

  18. Contact Information Mustafa KRLI

    E-print Network

    Erdem, Erkut

    Contact Information Mustafa KÂRLI Turkish Air Forces Department of Comunications Electronics.hacettepe.edu.tr Business I have been working as an officer in Turkish Air Forces since 1996. I worked as software Forces Information System project. I am a SAP BASIS consultant as well. Education Ms.D. : Turkish Air

  19. Acridone alkaloids as potent inhibitors of cathepsin V.

    PubMed

    Severino, Richele P; Guido, Rafael V C; Marques, Emerson F; Brömme, Dieter; da Silva, M Fátima das G F; Fernandes, João B; Andricopulo, Adriano D; Vieira, Paulo C

    2011-02-15

    Cathepsin V is a lysosomal cysteine peptidase highly expressed in thymus, testis and corneal epithelium. Eleven acridone alkaloids were isolated from Swinglea glutinosa (Bl.) Merr. (Rutaceae), with eight of them being identified as potent and reversible inhibitors of cathepsin V (IC(50) values ranging from 1.2 to 3.9 ?M). Detailed mechanistic characterization of the effects of these compounds on the cathepsin V-catalyzed reaction showed clear competitive inhibition with respect to substrate, with dissociation constants (K(i)) in the low micromolar range (2, K(i)=1.2 ?M; 6, K(i)=1.0 ?M; 7, K(i)=0.2 ?M; and 11, K(i)=1.7 ?M). Molecular modeling studies provided important insight into the structural basis for binding affinity and enzyme inhibition. Experimental and computational approaches, including biological evaluation, mode of action assessment and modeling studies were successfully employed in the discovery of a small series of acridone alkaloid derivatives as competitive inhibitors of catV. The most potent inhibitor (7) has a K(i) value of 200 nM. PMID:21277783

  20. Potent inhibition of human phosphodiesterase-5 by icariin derivatives.

    PubMed

    Dell'Agli, Mario; Galli, Germana V; Dal Cero, Esther; Belluti, Federica; Matera, Riccardo; Zironi, Elisa; Pagliuca, Giampiero; Bosisio, Enrica

    2008-09-01

    Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium brevicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. brevicornum extract (80% inhibition at 50 microg/mL) and its active principle icariin (1) (IC50 5.9 microM) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development. PMID:18778098

  1. Potent Reversible Inhibition of Myeloperoxidase by Aromatic Hydroxamates*

    PubMed Central

    Forbes, Louisa V.; Sjögren, Tove; Auchère, Françoise; Jenkins, David W.; Thong, Bob; Laughton, David; Hemsley, Paul; Pairaudeau, Garry; Turner, Rufus; Eriksson, Håkan; Unitt, John F.; Kettle, Anthony J.

    2013-01-01

    The neutrophil enzyme myeloperoxidase (MPO) promotes oxidative stress in numerous inflammatory pathologies by producing hypohalous acids. Its inadvertent activity is a prime target for pharmacological control. Previously, salicylhydroxamic acid was reported to be a weak reversible inhibitor of MPO. We aimed to identify related hydroxamates that are good inhibitors of the enzyme. We report on three hydroxamates as the first potent reversible inhibitors of MPO. The chlorination activity of purified MPO was inhibited by 50% by a 5 nm concentration of a trifluoromethyl-substituted aromatic hydroxamate, HX1. The hydroxamates were specific for MPO in neutrophils and more potent toward MPO compared with a broad range of redox enzymes and alternative targets. Surface plasmon resonance measurements showed that the strength of binding of hydroxamates to MPO correlated with the degree of enzyme inhibition. The crystal structure of MPO-HX1 revealed that the inhibitor was bound within the active site cavity above the heme and blocked the substrate channel. HX1 was a mixed-type inhibitor of the halogenation activity of MPO with respect to both hydrogen peroxide and halide. Spectral analyses demonstrated that hydroxamates can act variably as substrates for MPO and convert the enzyme to a nitrosyl ferrous intermediate. This property was unrelated to their ability to inhibit MPO. We propose that aromatic hydroxamates bind tightly to the active site of MPO and prevent it from producing hypohalous acids. This mode of reversible inhibition has potential for blocking the activity of MPO and limiting oxidative stress during inflammation. PMID:24194519

  2. Things to Know about Cosmetic Contacts

    MedlinePLUS

    ... they decided to reclassify cosmetic lenses as cosmetics. Contacts are not Cosmetics Classifying cosmetic contact lenses in ... and soaking solutions. Things to Know About Cosmetic Contacts Things to Know About Cosmetic Contacts— Continued Contact ...

  3. 2-(4-aminophenyl) benzothiazole: a potent and selective pharmacophore with novel mechanistic action towards various tumour cell lines.

    PubMed

    Dubey, Raghvendra; Shrivastava, Prabhat K; Basniwal, Pawan K; Bhattacharya, Snehendu; Moorthy, Narayana S Hari Narayana

    2006-06-01

    2-(4-aminophenyl) benzothiazole (CJM -126) (Table 1 (1) and its analogues represent a potent and highly selective class of antitumor agents. These compounds in nanomolar range elicit potent growth inhibition in human-derived breast, colon, ovarian and renal tumour cell lines. Metabolism of benzothiazole plays a central role in its mode of action. Cytocrome P450 isoform, CYP1A1, biotransforms benzothiazoles, to active, as well as inactive metabolites. In vitro studies had confirmed that N-oxidation and N-acetylation (only 3' halogen congener) as main active metabolic transformation (generating cytotoxic electrophilic species), while C-6 oxidation and N-acetylation (except 3' halogen congener) as inactive metabolic transformation pathway. Generation of an inactive metabolite 2-(4-aminophenyl)-6-hydoxybenzothiazole [6-OH 126, (Table 1) (10)] is blocked by fluorinated analogue, substituted around benzothiazole nucleus, especially at 5-position. National Cancer Institute (NCI), USA, confirms this series as a unique mechanistic class distinct from clinically used chemotherapeutic agents. Benzothiazoles are potent aryl hydrocarbon receptor (AhR) agonists, binding to AhR results in induction of CYP1A1, causes generation of electrophilic reactive species which forms DNA adduct, ultimately resulting in cell death by activation of apoptotic machinery. To overcome the poor physiochemical and pharmaceutical properties (bioavailability problem) of this compounds, prodrug of benzothiazole derivatives were synthesized, which are introduced in clinical trails. PMID:16787373

  4. Asymmetric capillary bridges between contacting spheres.

    PubMed

    Farmer, Timothy P; Bird, James C

    2015-09-15

    When a drop of liquid wets two identical solid spheres, the liquid forms a capillary bridge between the spheres to minimize surface energy. In the absence of external forces, these bridges are typically assumed to be axisymmetric, and the shape that minimizes surface energy can be calculated analytically. However under certain conditions, the bridge is axisymmetrically unstable, and migrates to a non-axisymmetric configuration. The goal of this paper is to characterize these non-axisymmetric capillary bridges. Specifically, we numerically calculate the shape of the capillary bridge between two contacting spheres that minimizes the total surface energy for a given volume and contact angle and compare to experiments. When the bridge is asymmetric, finite element calculations demonstrate that the shape of the bridge is spherical. In general, the bridge shape depends on both volume and contact angle, yet we find the degree of asymmetry is controlled by a single parameter. PMID:26037268

  5. Microparticle assembly and contact line dynamics

    NASA Astrophysics Data System (ADS)

    Ghosh, Moniraj

    This thesis addresses three topics. First, microparticle assembly on solid surfaces from an evaporative suspension is studied. It is well known that microparticles collect near three phase contact lines owing to evaporative fluxes. In a dip coating configuration, if the evaporative flux and plate withdrawal velocity U are matched, large colloidal crystals form. Here, I investigate the consequences of varying the plate withdrawal rate, and find that periodic striped patterns emerge which depend strongly on U. The stripes form when three phase contact lines "jump", or recede rapidly, upon detaching from well-wet particle aggregates on less wet substrates. Stripe width, spacing and height change abruptly at a transition velocity which can be related to a Landau-Levich transition in the flow. The second part of my thesis is a numerical simulation of drop spreading and retraction as a function of drop scale. The drop moves over a thin liquid film, and drop motion is initiated by an impulsive change in surface wettability. Owing to the presence of the film, these simulations require no closure condition at the 'apparent' contact line. Rather, relationships emerge between the contact line velocity and the dynamic contact angle. For nanoscopic drops, molecular effects dominate the drop motion. For drops an order of magnitude larger than the thin film, regimes emerge in which drops move according to Tanner's law, a relationship derived for macroscopic drops. Drop retraction is considerably more rapid than spreading owing to rapid dewetting events near the contact line. This thesis concludes with a discussion of a technique for creating multifunctional surfaces presenting discrete patches of several proteins. The technique relies on microcontact printing (microCP) to define active regions, and the use of a microfluidics device to deliver proteins to those regions. The surfaces are used to capture cells from a suspension, to sort cells from a mixed suspension, and to study the shear-dependent cell adhesion. Potential applications include biosensors, fundamental studies of cell adhesion, and of stem cell differentiation.

  6. Contact Graph Routing

    NASA Technical Reports Server (NTRS)

    Burleigh, Scott C.

    2011-01-01

    Contact Graph Routing (CGR) is a dynamic routing system that computes routes through a time-varying topology of scheduled communication contacts in a network based on the DTN (Delay-Tolerant Networking) architecture. It is designed to enable dynamic selection of data transmission routes in a space network based on DTN. This dynamic responsiveness in route computation should be significantly more effective and less expensive than static routing, increasing total data return while at the same time reducing mission operations cost and risk. The basic strategy of CGR is to take advantage of the fact that, since flight mission communication operations are planned in detail, the communication routes between any pair of bundle agents in a population of nodes that have all been informed of one another's plans can be inferred from those plans rather than discovered via dialogue (which is impractical over long one-way-light-time space links). Messages that convey this planning information are used to construct contact graphs (time-varying models of network connectivity) from which CGR automatically computes efficient routes for bundles. Automatic route selection increases the flexibility and resilience of the space network, simplifying cross-support and reducing mission management costs. Note that there are no routing tables in Contact Graph Routing. The best route for a bundle destined for a given node may routinely be different from the best route for a different bundle destined for the same node, depending on bundle priority, bundle expiration time, and changes in the current lengths of transmission queues for neighboring nodes; routes must be computed individually for each bundle, from the Bundle Protocol agent's current network connectivity model for the bundle s destination node (the contact graph). Clearly this places a premium on optimizing the implementation of the route computation algorithm. The scalability of CGR to very large networks remains a research topic. The information carried by CGR contact plan messages is useful not only for dynamic route computation, but also for the implementation of rate control, congestion forecasting, transmission episode initiation and termination, timeout interval computation, and retransmission timer suspension and resumption.

  7. Electroless copper contacts for low concentration silicon solar cells

    NASA Astrophysics Data System (ADS)

    Janušonis, Julius; Galdikas, Algirdas; Juzumas, Valdemaras; JaraminÄ--, Lina; Lukštaraupis, Tomas; Andrijauskas, Darius; JanušonienÄ--, Vida; Janušonis, Darius; Ulbikas, Juras

    2012-10-01

    The purpose of this work was to form highly conductive and low cost copper contacts on shallow and hence optically thin p-n junctions (<0.4?m deep) on a randomly textured solar cells for low concentration PV (LCPV) module. At first, window formation process in SiNx by femtosecond UV laser pulse ablation on the textured surface was introduced. Then nickel silicide contacts were formed and subsequent contact thickening was performed by electroless copper plating in an industrially feasible way. Characteristics of finished solar cells were investigated in this work. The cells were successfully implemented into the low concentration (C=15x) PV module.

  8. /Au Back Contacts

    NASA Astrophysics Data System (ADS)

    Paudel, Naba R.; Compaan, Alvin D.; Yan, Yanfa

    2014-08-01

    We report on the fabrication and characterization of CdTe thin-film solar cells with Cu-free MoO3- x /Au back contacts. CdTe solar cells with sputtered CdTe absorbers of thicknesses from 0.5 to 1.75 ?m were fabricated on Pilkington SnO2:F/SnO2-coated soda-lime glasses coated with a 60- to 80-nm sputtered CdS layer. The MoO3- x /Au back contact layers were deposited by thermal evaporation. The incorporation of MoO3- x layer was found to improve the open circuit voltage ( V OC) but reduce the fill factor of the ultrathin CdTe cells. The V OC was found to increase as the CdTe thickness increased.

  9. Contact dynamics math model

    NASA Technical Reports Server (NTRS)

    Glaese, John R.; Tobbe, Patrick A.

    1986-01-01

    The Space Station Mechanism Test Bed consists of a hydraulically driven, computer controlled six degree of freedom (DOF) motion system with which docking, berthing, and other mechanisms can be evaluated. Measured contact forces and moments are provided to the simulation host computer to enable representation of orbital contact dynamics. This report describes the development of a generalized math model which represents the relative motion between two rigid orbiting vehicles. The model allows motion in six DOF for each body, with no vehicle size limitation. The rotational and translational equations of motion are derived. The method used to transform the forces and moments from the sensor location to the vehicles' centers of mass is also explained. Two math models of docking mechanisms, a simple translational spring and the Remote Manipulator System end effector, are presented along with simulation results. The translational spring model is used in an attempt to verify the simulation with compensated hardware in the loop results.

  10. Graphdiyne-metal contacts and graphdiyne transistors.

    PubMed

    Pan, Yuanyuan; Wang, Yangyang; Wang, Lu; Zhong, Hongxia; Quhe, Ruge; Ni, Zeyuan; Ye, Meng; Mei, Wai-Ning; Shi, Junjie; Guo, Wanlin; Yang, Jinbo; Lu, Jing

    2015-02-01

    Graphdiyne was prepared on a metal surface, and the preparation of devices using it inevitably involves its contact with metals. Using density functional theory with dispersion correction, we systematically studied, for the first time, the interfacial properties of graphdiyne that is in contact with a series of metals (Al, Ag, Cu, Au, Ir, Pt, Ni, and Pd). Graphdiyne forms an n-type Ohmic or quasi-Ohmic contact with Al, Ag, and Cu, while it forms a Schottky contact with Pd, Au, Pt, Ni, and Ir (at the source/drain-channel interface), with high Schottky barrier heights of 0.21, 0.46 (n-type), 0.30, 0.41, and 0.46 (p-type) eV, respectively. A graphdiyne field effect transistor (FET) with Al electrodes was simulated using quantum transport calculations. This device exhibits an on-off ratio up to 10(4) and a very large on-state current of 1.3 × 10(4) mA mm(-1) in a 10 nm channel length. Thus, a new prospect has opened up for graphdiyne in high performance nanoscale devices. PMID:25562182

  11. LANE MEDICAL COPORATE MEMBERSHIP FORM Print legibly and complete

    E-print Network

    Sonnenburg, Justin L.

    AND POLICIES Individuals representing a profit or non-profit company, or those who are self employed, may usLANE MEDICAL COPORATE MEMBERSHIP FORM Print legibly and complete Company Name: ______________________________________________________ Contact Person: ________________________Title of Contact Person: ________________________ Company Address

  12. Contact stress sensor

    DOEpatents

    Kotovsky, Jack

    2014-02-11

    A method for producing a contact stress sensor that includes one or more MEMS fabricated sensor elements, where each sensor element of includes a thin non-recessed portion, a recessed portion and a pressure sensitive element adjacent to the recessed portion. An electric circuit is connected to the pressure sensitive element. The circuit includes a pressure signal circuit element configured to provide a signal upon movement of the pressure sensitive element.

  13. Contact stress sensor

    DOEpatents

    Kotovsky, Jack (Oakland, CA)

    2012-02-07

    A contact stress sensor includes one or more MEMS fabricated sensor elements, where each sensor element of includes a thin non-recessed portion, a recessed portion and a pressure sensitive element adjacent to the recessed portion. An electric circuit is connected to the pressure sensitive element. The circuit includes a thermal compensator and a pressure signal circuit element configured to provide a signal upon movement of the pressure sensitive element.

  14. Occupational Contact Dermatitis: Hairdressers

    Microsoft Academic Search

    Heidi Søsted

    \\u000a Occupational contact dermatitis occurs in about half of all hairdressers and makes hairdressers susceptible to most skin diseases.\\u000a The clinical manifestations are typically seen as hand eczema. The hand eczema starts often at the time of hairdressing apprenticeship,\\u000a and protective gloves are very important for preventing eczema in this occupation. Persulfates are (almost) always used in\\u000a bleaching procedures in hairdressing

  15. Immediate Contact Reactions

    Microsoft Academic Search

    David Basketter; Arto Lahti

    \\u000a Immediate contact reactions comprise a diverse spectrum of inflammatory skin reactions of both immune and nonimmune origin\\u000a and involving several often poorly characterized mechanisms and which can be caused by an enormous variety of chemicals and\\u000a proteins. Reactions range from sensory effects through local weal and flare to a more generalized response, but all generally\\u000a characterized by a rapid onset

  16. Funeral Terms and Contact Information

    MedlinePLUS

    ... Site Planning Your Own Funeral Funeral Terms and Contact Information Related Items This article provides a glossary ... board that regulates the funeral industry. You may contact the board in your state for information or ...

  17. Guaiane sesquiterpenes from Biscogniauxia nummularia featuring potent antigerminative activity.

    PubMed

    Amand, Séverine; Langenfeld, Aude; Blond, Alain; Dupont, Joëlle; Nay, Bastien; Prado, Soizic

    2012-04-27

    Xylaranone, a previously unreported guaiane sesquiterpene along with the known terpenoid xylaranol B and the two mellein derivatives 3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin and 3,5-dimethyl-8-hydroxy-3,4-dihydroisocoumarin were isolated from Biscogniauxia nummularia. Pogostol was also isolated from this fungus, and in light of our spectroscopic data, its structure was revised and corrected. This fungus, which was isolated as an endophyte from the plum yew Cephalotaxus harringtonia, is also suspected of being a pathogen. Interestingly, we report here the potent antigerminative activity of xylaranone and xylaranol B against seeds of Raphanus sativus at concentrations comparable to glyphosate, a commonly used herbicide. This effect suggests a role for these metabolites in the latent fungal pathogenesis of B. nummularia. PMID:22486738

  18. Spinosad is a potent inhibitor of canine P-glycoprotein.

    PubMed

    Schrickx, Johannes A

    2014-04-01

    Inhibition of the drug transporter P-glycoprotein (P-gp) by the oral flea preventative spinosad has been suggested as the underlying cause of the drug-drug interaction with ivermectin. In this study, an in vitro model consisting of canine cells was validated to describe the inhibitory effect of drugs on canine P-gp. In this model, ivermectin, cyclosporin, verapamil, loperamide and ketoconazole inhibited P-gp function with IC50 values ranging from 0.1 to 3.7 ?mol/L. Spinosad was a potent inhibitor of canine P-gp with an IC50 value of 0.27 ?mol/L or 0.2 ?g/mL. The risk of spinosad causing P-gp related drug-drug interactions in the dog could be predicted by the IC50 value, the oral dosage and plasma concentrations. PMID:24582422

  19. Synthetic phenylethanoid glycoside derivatives as potent neuroprotective agents.

    PubMed

    Liu, Ying-Guo; Li, Xiaxi; Xiong, De-Cai; Yu, Binhan; Pu, Xiaoping; Ye, Xin-Shan

    2015-05-01

    Several phenylethanoid glycoside derivatives were designed and synthesized. Most of the synthetic compounds showed significant neuroprotective effects, including antioxidative and anti-apoptotic properties. Specifically, target compounds displayed potent effects against various toxicities such as H2O2 and 6-hydroxydopamine (6-OHDA) in PC12 cells. Among the synthetic derivatives, three compounds (5, 6, 8) exhibited much superior activities to the marketed drug Edaravone. The compounds were able to prevent the 6-OHDA-induced damage in PC12 cells in a dose-dependent manner. The anti-apoptotic effects could be observed via cell morphological changes. Moreover, the compounds significantly reduced the intracellular ROS increase resulting from 6-OHDA treatment. The preliminary structure-activity relationships were also explored. Compounds 5, 6, 8 may hold the potential as promising neuroprotective agents and new lead compounds for the treatment of neurodegenerative diseases or cerebral ischemia. PMID:25827400

  20. IRAS galaxies versus POTENT mass - Density fields, biasing, and Omega

    NASA Technical Reports Server (NTRS)

    Dekel, Avishai; Bertschinger, Edmund; Yahil, Amos; Strauss, Michael A.; Davis, Marc; Huchra, John P.

    1993-01-01

    A comparison of the galaxy density field extracted from a complete redshift survey of IRAS galaxies brighter than 1.936 Jy with the mass-density field reconstructed by the POTENT procedure from the observed peculiar velocities of 493 objects is presented. A strong correlation is found between the galaxy and mass-density fields; both feature the Great Attractor, part of the Perseus-Pisces supercluster, and the large void between them. Monte Carlo noise simulations show that the data are consistent with the hypotheses that the smoothed fluctuations of galaxy and mass densities at each point are proportional to each other with the 'biasing' factor of IRAS galaxies, b(I), and that the peculiar velocity field is related to the mass-density field as expected according to the gravitational instability theory. Under these hypotheses, the two density fields can be related by specifying b(I) and the cosmological density parameter, Omega.

  1. The Potent Oxidant Anticancer Activity of Organoiridium Catalysts**

    PubMed Central

    Liu, Zhe; Romero-Canelón, Isolda; Qamar, Bushra; Hearn, Jessica M; Habtemariam, Abraha; Barry, Nicolas P E; Pizarro, Ana M; Clarkson, Guy J; Sadler, Peter J

    2014-01-01

    Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(?5-Cpxbiph)Ir(phpy)(Cl)] (1-Cl), which contains ?-bonded biphenyltetramethylcyclopentadienyl (Cpxbiph) and C?N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(?5-Cpxbiph)Ir(phpy)(py)]+ (1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy. PMID:24616129

  2. Discovery of biaryl carboxylamides as potent ROR? inverse agonists.

    PubMed

    Chao, Jianhua; Enyedy, Istvan; Van Vloten, Kurt; Marcotte, Douglas; Guertin, Kevin; Hutchings, Richard; Powell, Noel; Jones, Howard; Bohnert, Tonika; Peng, Chi-Chi; Silvian, Laura; Hong, Victor Sukbong; Little, Kevin; Banerjee, Daliya; Peng, Liaomin; Taveras, Arthur; Viney, Joanne L; Fontenot, Jason

    2015-08-01

    ROR?t is a pivotal regulator of a pro-inflammatory gene expression program implicated in the pathology of several major human immune-mediated diseases. Evidence from mouse models demonstrates that genetic or pharmacological inhibition of ROR? activity can block the production of pathogenic cytokines, including IL-17, and convey therapeutic benefit. We have identified and developed a biaryl-carboxylamide series of ROR? inverse agonists via a structure based design approach. Co-crystal structures of compounds 16 and 48 supported the design approach and confirmed the key interactions with ROR? protein; the hydrogen bonding with His479 was key to the significant improvement in inverse agonist effect. The results have shown this is a class of potent and selective ROR? inverse agonists, with demonstrated oral bioavailability in rodents. PMID:26048806

  3. Development of a conformational search strategy for flexible ligands: a study of the potent mu-selective opioid analgesic fentanyl.

    PubMed

    Cometta-Morini, C; Loew, G H

    1991-08-01

    An extensive conformational search of the potent opioid analgesic, fentanyl, was performed using the semiempirical quantum mechanical method AM1 and the CHARMm potential energy function. A combination of two procedures was used to search the conformational space for fentanyl, which included nested dihedral scans, geometry optimization and molecular dynamics simulation at different temperatures. In addition, the effect of a continuum solvent environment was taken into account by use of appropriate values for the dielectric constant in the CHARMm computations. The results of the conformational search allowed the determination of the probable conformation of fentanyl in polar and nonpolar solvents and of three candidate conformers for its bioactive form. PMID:1665508

  4. Discovery of Potent Non-urea Inhibitors of Soluble Epoxide Hydrolase

    PubMed Central

    Xie, Yuli; Liu, Yidong; Gong, Gangli; Smith, Deborah H.; Yan, Fang; Rinderspacher, Alison; Feng, Yan; Zhu, Zhengxiang; Li, Xiangpo; Deng, Shi-Xian; Branden, Lars; Vidovi?, Dušica; Chung, Caty; Schürer, Stephan; Morisseau, Christophe; Hammock, Bruce D.; Landry, Donald W.

    2009-01-01

    Soluble epoxide hydrolase (sEH) is a novel target for the treatment of hypertension and vascular inflammation. A new class of potent non-urea sEH inhibitors was identified via high throughput screening (HTS) and chemical modification. IC50s of the most potent compounds range from micromolar to low nanomolar. A Class of potent non-Urea inhibitors of soluble epoxide hydrolase was discovered via high throughput screening and SARs-guided modification. PMID:19303288

  5. Are genotoxic carcinogens more potent than nongenotoxic carcinogens?

    PubMed Central

    Parodi, S; Malacarne, D; Romano, P; Taningher, M

    1991-01-01

    In this report we have raised the question whether genotoxic carcinogens are more potent than nongenotoxic carcinogens when studied in long-term carcinogenicity assays in rodents. To build a large database of compounds for which both carcinogenicity and genotoxicity had been investigated, we have used a database produced by Gold and co-workers for carcinogenic potency data (975 chemicals) and a database produced by Würgler for genotoxicity data (2834 chemicals). Considering compounds positive or negative in at least three short-term tests and in at least 75% of available tests, we could define 67 genotoxic carcinogens and 46 nongenotoxic carcinogens. Carcinogenic potency of genotoxic carcinogens was about 50 times higher than carcinogenic potency of nongenotoxic carcinogens. Our results are different from the results of Tennant et al.; their database (24 genotoxic carcinogens and 12 nongenotoxic carcinogens compatible with our definition) seems to suggest that there is practically no difference in potency between genotoxic and nongenotoxic carcinogens. The two databases have only four compounds in common and are also different in terms of number of elements for different chemical classes. Nitrosocompounds, nitrogen mustards, hydrazine derivatives, and polycyclic aromatic hydrocarbons are not represented in the database of Tennant. The overall impression from our analysis is that the usefulness of short-term tests of genotoxicity could be significantly better than what has been suggested by the previous work of Tennant et al. because these tests tend to detect, at least for many important chemical classes, the most potent carcinogens. This consideration may not be valid for certain classes of chemicals. PMID:1821372

  6. Determination of the Actual Contact Surface of a Brush Contact

    NASA Technical Reports Server (NTRS)

    Holm, Ragnar

    1944-01-01

    The number of partial contact surfaces of a brush-ring contact is measured by means of a statistical method. The particular brush is fitted with wicks - that is, insulated and cemented cylinders of brush material, terminating in the brush surface. The number of partial contact surfaces can be computed from the length of the rest periods in which such wicks remain without current. Resistance measurements enable the determination of the size of the contact surfaces. The pressure in the actual contact surface of a recently bedded brush is found to be not much lower than the Brinell hardness of the brush.

  7. RAM, an RGDS Analog, Exerts Potent Anti-Melanoma Effects In Vitro and In Vivo

    PubMed Central

    Aguzzi, Maria Simona; D'Arcangelo, Daniela; Giampietri, Claudia; Capogrossi, Maurizio C.; Facchiano, Antonio

    2011-01-01

    Peptides containing the RGD sequence are under continuous investigation given their ability to control cell adhesion and apoptosis. Since small peptides are quickly metabolized and degraded in vivo, developing analogs resistant to serum-induced degradation is a challenging task. RGD analogs developed so far are known as molecules mostly inhibiting cell adhesion; this feature may reduce cell proliferation and tumor development but may not induce regression of tumors or metastases already formed. In the current study, carried out in melanoma in vitro and in vivo models, we show that RAM, an RGD-non-peptide Analog-Molecule, strongly inhibits cells adhesion onto plastic, vitronectin, fibronectin, laminin and von Willebrand Factor while it does not inhibit cell adhesion onto collagen IV, similarly to the RGDS template peptide. It also strongly inhibits in vitro cell proliferation, migration and DNA-synthesis, increases melanoma cells apoptosis and reduces survivin expression. All such effects were observed in collagen IV seeded cells, therefore are most likely independent from the anti adhesive properties. Further, RAM is more stable than the template RGDS; in fact it maintains its anti-proliferation and anti-adhesion effects after long serum exposure while RGDS almost completely loses its effects upon serum exposure. In a mouse metastatic melanoma in vivo model, increasing doses of RAM significantly reduce up to about 80% lung metastases development, while comparable doses of RGDS are less potent. In conclusion these data show that RAM is a potent inhibitor of melanoma growth in vitro, strongly reduces melanoma metastases development in vivo and represents a novel candidate for further in vivo investigations in the cancer treatment field. PMID:21984914

  8. Multipurpose integrated active contact lenses

    Microsoft Academic Search

    Babak Parviz

    2009-01-01

    Over the last few decades, conventional contact lenses have been used to correct vision. Advances in manufacturing have changed the lens material: first from glass to the polymers used in gas-permeable contacts, and then to the current highly engineered hydrogels used in soft contact lenses. Recent ad- vances in nano and microfabrication—enabling the construction of exceedingly small electronic, photonic, and

  9. Correlation of contact deformation with contact electrification of identical materials

    NASA Astrophysics Data System (ADS)

    Xie, L.; He, P. F.; Zhou, J.; Lacks, D. J.

    2014-05-01

    We report an experimental study on the contact electrification produced by two chemically identical glass plates under different contact forces. For the given plate sizes, the mean value of the surface charge density is independent of the contact force, but the standard deviation of the surface charge density increases with increasing contact force, which indicates that the magnitude of charge transfer is enhanced with increasing contact force. The contact between plates of different sizes leads to the systematic transfer of charge in one direction. To understand this effect, finite element modelling was carried out, which shows that the contact between plates of different sizes leads to different in-plane strains developing in the two plates. The surface charge density from contact electrification correlates with the difference in the in-plane strain between the contacted plates. The results suggest that the in-plane strain difference between contact surfaces plays an essential role in contact electrification and may be a key driving force for the charge transfer between chemically identical surfaces.

  10. Test Scanning Request Form Please complete one form for each test and key.

    E-print Network

    Pantaleone, Jim

    Test Scanning Request Form Please complete one form for each test and key. This Section: Test Name: Contact Person: Email Regarding This Scan Date Received Time Initials Number of Tests Scored: / / : A.M. P

  11. Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.

    PubMed

    Lass, Christian; Vocanson, Marc; Wagner, Steffen; Schempp, Christoph M; Nicolas, Jean-Francois; Merfort, Irmgard; Martin, Stefan F

    2008-10-01

    Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice. PMID:18341569

  12. Nonlinear cyclical transport phenomena in copper point contacts

    NASA Astrophysics Data System (ADS)

    Kamarchuk, G. V.; Pospelov, A. P.; Savitskiy, A. V.; Koval, L. V.

    2014-10-01

    The method of recording the current-voltage characteristic was used to study the processes occurring at the surface of a point contact conductance channel. The transport characteristics of the point contact in a liquid medium are studied for the first time. The current states of the conductance channel corresponding to the reversible, transient, and irreversible regimes of charge transport in a point contact are studied and identified. In the irreversible range of bias voltage, the famous cyclical effect of electromechanical switching is observed on the contact, which governs the growth and dissolution of dendritic point contacts of the test sample. The electric resistance of the point-contact structure changes over time, going through stages of increase, decrease, and stabilization. Subsequently, the stages of this process are repeated multiple times, reflecting the cyclical nature of the changes in the physiochemical properties of the test object. The current-voltage characteristic of the point contact has a step structure, due to shell effects. Copper point contact conductance histograms, formed spontaneously in the electric field under the influence of the shell effect, are built using the obtained curves. There is a demonstrated presence of preferred current states for the conductance channel, serving as evidence of the quantum nature of conductance changes in the process of dendritic point contact formation.

  13. Contact Issue 7 

    E-print Network

    Multiple Contributors

    1981-01-01

    couldn't really feel where his feet were. The alien sat heavily on his legs, effectively pinning Kirk to the floor. Kirk felt the sharp sting of the needle going into his ankle, and the painful burn start as more of the drug went into his muscle... ealli9~phy (exee.pt p. 131) by CHERYL A. BOBBITT ? C:ONTACT 7 celebrates the Continuation of the Dream, a changing progression from the Old to the New. As we have followed the developing friendship between Kirk and Spock over the last eight years, we...

  14. Contact Issue 2 

    E-print Network

    Multiple Contributors

    1976-01-01

    Ublication and is not intended to infringe on the rights of Paramount, Norway Productions, N.B.C., or any other holders of STAR TREK copyrights. price: ~3.00 in person ~4.56 first class* $3030 book rate* *prices subject to change in postal rates. 1 2 CONTACT Dev...'t doing :l!?. any favors. l. don't want that from Spock. not .:lli!!1 way. 1 don't ~ charity, dammit. Wai t ~ minute. Charity ft2!ll ~ VulCan? -- !!lY. brains must be scrambled. 8 9 His nose was running, and he wiped it mindlessly, reaching...

  15. Adhesive Contact Sweeper

    NASA Technical Reports Server (NTRS)

    Patterson, Jonathan D.

    1993-01-01

    Adhesive contact sweeper removes hair and particles vacuum cleaner leaves behind, without stirring up dust. Also cleans loose rugs. Sweeper holds commercially available spools of inverted adhesive tape. Suitable for use in environments in which air kept free of dust; optics laboratories, computer rooms, and areas inhabited by people allergic to dust. For carpets, best used in tandem with vacuum cleaner; first pass with vacuum cleaner removes coarse particles, and second pass with sweeper extracts fine particles. This practice extends useful life of adhesive spools.

  16. A Prototype Antifungal Contact Lens

    PubMed Central

    Ciolino, Joseph B.; Hudson, Sarah P.; Mobbs, Ashley N.; Hoare, Todd R.; Iwata, Naomi G.; Fink, Gerald R.

    2011-01-01

    Purpose. To design a contact lens to treat and prevent fungal ocular infections. Methods. Curved contact lenses were created by encapsulating econazole-impregnated poly(lactic-co-glycolic) acid (PLGA) films in poly(hydroxyethyl methacrylate) (pHEMA) by ultraviolet photopolymerization. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. The contact lenses and their release media were tested in an antifungal assay against Candida albicans. Cross sections of the pre- and postrelease contact lenses were characterized by scanning electron microscopy and by Raman spectroscopy. Results. Econazole-eluting contact lenses provided extended antifungal activity against Candida albicans fungi. Fungicidal activity varied in duration and effectiveness depending on the mass of the econazole-PLGA film encapsulated in the contact lens. Conclusions. An econazole-eluting contact lens could be used as a treatment for fungal ocular infections. PMID:21527380

  17. Equilibrium contact angle or the most-stable contact angle?

    PubMed

    Montes Ruiz-Cabello, F J; Rodríguez-Valverde, M A; Cabrerizo-Vílchez, M A

    2014-04-01

    It is well-established that the equilibrium contact angle in a thermodynamic framework is an "unattainable" contact angle. Instead, the most-stable contact angle obtained from mechanical stimuli of the system is indeed experimentally accessible. Monitoring the susceptibility of a sessile drop to a mechanical stimulus enables to identify the most stable drop configuration within the practical range of contact angle hysteresis. Two different stimuli may be used with sessile drops: mechanical vibration and tilting. The most stable drop against vibration should reveal the changeless contact angle but against the gravity force, it should reveal the highest resistance to slide down. After the corresponding mechanical stimulus, once the excited drop configuration is examined, the focus will be on the contact angle of the initial drop configuration. This methodology needs to map significantly the static drop configurations with different stable contact angles. The most-stable contact angle, together with the advancing and receding contact angles, completes the description of physically realizable configurations of a solid-liquid system. Since the most-stable contact angle is energetically significant, it may be used in the Wenzel, Cassie or Cassie-Baxter equations accordingly or for the surface energy evaluation. PMID:24140073

  18. A Flexible Multibody Pantograph Model for the Analysis of the Catenary–Pantograph Contact

    Microsoft Academic Search

    Jorge Ambrósio; Frederico Rauter; João Pombo; Manuel S. Pereira

    \\u000a The pantograph–catenary system is still the most reliable form of collecting electric energy for running trains. This system\\u000a should ideally run with relatively low contact forces, in order to minimize wear and damage of the contacting elements but\\u000a without contact loss to avoid power supply interruption and electric arching. However, the quality of the pantograph–catenary\\u000a contact may be affected by

  19. A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor ? chains

    PubMed Central

    England, Bruce P.; Balasubramanian, Palaniappan; Uings, Iain; Bethell, Sue; Chen, Min-Jia; Schatz, Peter J.; Yin, Qun; Chen, Yao-Fen; Whitehorn, Erik A.; Tsavaler, Alexander; Martens, Christine L.; Barrett, Ronald W.; McKinnon, Murray

    2000-01-01

    Two series of peptides that specifically bind to the extracellular domain of the ? chain of the human interleukin-5 receptor (IL-5R?), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor ?/? heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor ? chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5R? extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R ? chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors. PMID:10823900

  20. A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor alpha chains.

    PubMed

    England, B P; Balasubramanian, P; Uings, I; Bethell, S; Chen, M J; Schatz, P J; Yin, Q; Chen, Y F; Whitehorn, E A; Tsavaler, A; Martens, C L; Barrett, R W; McKinnon, M

    2000-06-01

    Two series of peptides that specifically bind to the extracellular domain of the alpha chain of the human interleukin-5 receptor (IL-5Ralpha), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor alpha/beta heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor alpha chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5Ralpha extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R alpha chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors. PMID:10823900

  1. Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion.

    PubMed

    Abe, Masahiro; Hiura, Kenji; Wilde, Javier; Shioyasono, Atsushi; Moriyama, Keiji; Hashimoto, Toshihiro; Kido, Shinsuke; Oshima, Takashi; Shibata, Hironobu; Ozaki, Shuji; Inoue, Daisuke; Matsumoto, Toshio

    2004-10-15

    Multiple myeloma (MM) expands in the bone marrow and causes devastating bone destruction by enhancing osteoclastic bone resorption in its vicinity, suggesting a close interaction between MM cells and osteoclasts (OCs). Here, we show that peripheral blood mononuclear cell-derived OCs enhanced growth and survival of primary MM cells as well as MM cell lines more potently than stromal cells, and that OCs protected MM cells from apoptosis induced by serum depletion or doxorubicin. OCs produced osteopontin (OPN) and interleukin 6 (IL-6), and adhesion of MM cells to OCs increased IL-6 production from OCs. In addition, IL-6 and OPN in combination enhanced MM cell growth and survival. However, the effects of OCs on MM cell growth and survival were only partially suppressed by a simultaneous addition of anti-IL-6 and anti-OPN antibodies and were completely abrogated by inhibition of cellular contact between MM cells and OCs. These results demonstrate that OCs enhance MM cell growth and survival through a cell-cell contact-mediated mechanism that is partially dependent on IL-6 and OPN. It is suggested that interactions of MM cells with OCs augment MM growth and survival and, thereby, form a vicious cycle, leading to extensive bone destruction and MM cell expansion. PMID:15187021

  2. Transfer of cell membrane components via trogocytosis occurs in CD4+ Foxp3+ CD25+ regulatory T-cell contact-dependent suppression.

    PubMed

    Bahcheli, D; Hay, V; Nadeau, J L; Piccirillo, C A

    2011-12-01

    A key component of the immune system is its ability to establish and maintain peripheral tolerance. Naturally occurring CD4+ CD25+ Foxp3+ regulatory T (nTreg) cells represent an important means by which this is accomplished, through their potent ability to suppress the actions of both CD4+ and CD8+ effector (Teff) cells in vitro and in vivo. We hypothesized that direct contact between nTreg and Teff cells is sufficient for nTreg cell-contact suppression. We first show that nTreg cell suppression is independent of APCs and their derived co-stimulatory signals. We then used a two-colour, lipid dye labelling and quantification approach to formally demonstrate that nTreg cells specifically form cell conjugates with responding T (Tresp) cells only under TCR activating conditions. Strikingly, activated CD4+ nTreg cells undergo progressive trogocytosis, a process by which membrane fragments are transferred from one cell subset to another, with Tresp cells more readily than Teff cells. These results are the first to show that nTreg cell cognate interactions with Tresp cells leads to trogocytosis between the cells, and the first to relate the degree of trogocytosis with the level of nTreg-mediated suppression. PMID:21604971

  3. Allergic Contact Dermatitis

    PubMed Central

    Nelson, Jenny L.

    2010-01-01

    Epicutaneous patch testing is the gold standard method for the diagnosis of allergic contact dermatitis. Despite this knowledge, many clinical dermatologists do not offer patch testing in their offices or offer testing with only a limited number of allergens. Introduced in 1995, the Thin-Layer Rapid Use Epicutaneous Test originally contained 23 allergens and one control. In 2007, five additional allergens were added. This United States Food and Drug Administration-approved patch testing system made patch testing more convenient, and after its introduction, more dermatologists offered patch testing services. However, the number of allergens in the Thin-Layer Rapid Use Epicutaneous Test remains relatively low. Every two years, the North American Contact Dermatitis Group collects and reports the data from patch testing among its members to a standardized series of allergens. In 2005-2006, the Group used a series of 65 allergens. Of the top 30 allergens reported in 2005-2006, 10 were not included in the Thin-Layer Rapid Use Epicutaneous Test. Knowledge of and testing for additional allergens such as these may increase patch testing yield. PMID:20967194

  4. Seal for fluid forming tools

    DOEpatents

    Golovashchenko, Sergey Fedorovich (Beverly Hills, MI); Bonnen, John Joseph Francis (Milford, MI)

    2012-03-20

    An electro-hydraulic forming tool for forming a sheet metal blank in a one-sided die has first and second rigid rings that engage opposite sides of a sheet metal blank. The rigid rings are contained within slots on a die portion and a hydraulic force applicator portion of the forming tool. The seals are either resiliently biased by an elastomeric member or inherently resiliently biased into contact with the blank.

  5. Contact Information: First Name

    E-print Network

    Chapman, Michael S.

    the form, above. 2. If paying by credit card, fax the completed registration form to: 503-346-6826, Attn to OHSU Foundation Credit Card: Visa MasterCard American Express Discover Credit Card Number: Exp: / Name on card: Billing address (if different from above): Signature: Date: Registration: 1. Please sign

  6. Human graft-derived mesenchymal stromal cells potently suppress alloreactive T-cell responses.

    PubMed

    de Mare-Bredemeijer, Emmy L D; Mancham, Shanta; Verstegen, Monique M A; de Ruiter, Petra E; van Gent, Rogier; O'Neill, David; Tilanus, Hugo W; Metselaar, Herold J; de Jonge, Jeroen; Kwekkeboom, Jaap; Hall, Sean R R; van der Laan, Luc J W

    2015-06-15

    After organ transplantation, recipient T cells contribute to graft rejection. Mesenchymal stromal cells from the bone marrow (BM-MSCs) are known to suppress allogeneic T-cell responses, suggesting a possible clinical application of MSCs in organ transplantation. Human liver grafts harbor resident populations of MSCs (L-MSCs). We aimed to determine the immunosuppressive effects of these graft-derived MSCs on allogeneic T-cell responses and to compare these with the effects of BM-MSCs. BM-MSCs were harvested from aspirates and L-MSCs from liver graft perfusates. We cultured them for 21 days and compared their suppressive effects with the effects of BM-MSCs on allogeneic T-cell responses. Proliferation, cytotoxic degranulation, and interferon-gamma production of alloreactive T cells were more potently suppressed by L-MSCs than BM-MSCs. Suppression was mediated by both cell-cell contact and secreted factors. In addition, L-MSCs showed ex vivo a higher expression of PD-L1 than BM-MSCs, which was associated with inhibition of T-cell proliferation and cytotoxic degranulation in vitro. Blocking PD-L1 partly abrogated the inhibition of cytotoxic degranulation by L-MSCs. In addition, blocking indoleamine 2,3-dioxygenase partly abrogated the inhibitive effects of L-MSCs, but not BM-MSCs, on T-cell proliferation. In conclusion, liver graft-derived MSC suppression of allogeneic T-cell responses is stronger than BM-MSCs, which may be related to in situ priming and mobilization from the graft. These graft-derived MSCs may therefore be relevant in transplantation by promoting allohyporesponsiveness. PMID:25744002

  7. Evaluation and quantification of potent odorants of greek virgin olive oils

    Microsoft Academic Search

    G. Blekas; H. Guth

    1995-01-01

    The potent odorants of two Greek virgin olive olis differing in flavor were evaluated by aroma extract dilution analysis (AEDA) and quantitated by stable isotope dilution assay (SIDA). The odor activity values (OAVs) of these potent odorants were calculated by dividing their concentrations in the oil samples by the corresponding flavor threshold values, as an approach to objectify the flavor

  8. Synthesis and biological activities of novel indole derivatives as potent and selective PPARgamma modulators.

    PubMed

    Lamotte, Yann; Martres, Paul; Faucher, Nicolas; Laroze, Alain; Grillot, Didier; Ancellin, Nicolas; Saintillan, Yannick; Beneton, Véronique; Gampe, Robert T

    2010-02-15

    Starting from the structure of Telmisartan, a new series of potent and selective PPARgamma modulators was identified. The synthesis, in vitro and in vivo evaluation of the most potent compounds are reported and the X-ray structure of compound 7b bound to the PPARgamma ligand binding domain is described. PMID:20079636

  9. Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry.

    PubMed

    Cagide, F; Silva, T; Reis, J; Gaspar, A; Borges, F; Gomes, L R; Low, J N

    2015-02-18

    The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and chromone-3-carboxamide scaffolds. PMID:25579652

  10. Trifluoromethoxyl Substituted Phenylethylene Diamines as High Affinity Receptor Ligands with Potent Anti-Cocaine Actions

    E-print Network

    with Potent Anti-Cocaine Actions Trudy A. Smith, Xiaowen Yang, Huifang Wu, Buddy Pouw, Rae R. Matsumoto and with anti-cocaine actions that involve antagonism of 1 receptors. In order to increase the potency receptor affinity and represent the most potent anti-cocaine phenylethylene diamines yet described

  11. Healthy Contact Lens Wear and Care

    MedlinePLUS Videos and Cool Tools

    ... CDC.gov . Recommend on Facebook Tweet Share Compartir Water and Contact Lenses Don’t Mix May is ... Infections Eye infections related to contact lens wear... Water & Contact Lenses Keep contact lenses away from all ...

  12. Low contact resistivity of metals on nitrogen-doped cuprous oxide (Cu 2O) thin-films

    E-print Network

    Siah, Sin Cheng

    Forming low-resistivity contacts on cuprous oxide (Cu[subscript 2]O) is an essential step toward demonstrating its suitability as a candidate solar cell material. We measure the contact resistivity of three noble metals ...

  13. Hysteresis during contact angles measurement.

    PubMed

    Diaz, M Elena; Fuentes, Javier; Cerro, Ramon L; Savage, Michael D

    2010-03-15

    A theory, based on the presence of an adsorbed film in the vicinity of the triple contact line, provides a molecular interpretation of intrinsic hysteresis during the measurement of static contact angles. Static contact angles are measured by placing a sessile drop on top of a flat solid surface. If the solid surface has not been previously in contact with a vapor phase saturated with the molecules of the liquid phase, the solid surface is free of adsorbed liquid molecules. In the absence of an adsorbed film, molecular forces configure an advancing contact angle larger than the static contact angle. After some time, due to an evaporation/adsorption process, the interface of the drop coexists with an adsorbed film of liquid molecules as part of the equilibrium configuration, denoted as the static contact angle. This equilibrium configuration is metastable because the droplet has a larger vapor pressure than the surrounding flat film. As the drop evaporates, the vapor/liquid interface contracts and the apparent contact line moves towards the center of the drop. During this process, the film left behind is thicker than the adsorbed film and molecular attraction results in a receding contact angle, smaller than the equilibrium contact angle. PMID:20060981

  14. Organic light-emitting diodes formed by soft contact lamination

    Microsoft Academic Search

    Tae-Woo Lee; Jana Zaumseil; Zhenan Bao; Julia W. P. Hsu; John A. Rogers

    2004-01-01

    Although tremendous progress has been made in organic light-emitting diodes (OLEDs), with few exceptions they are fabricated in the standard way by sequentially depositing active layers and electrodes onto a substrate. Here we describe a different approach for building OLEDs, which is based on physical lamination of thin metal electrodes supported by an elastomeric layer against an electroluminescent organic. This

  15. Preplacement Screening Patient Contact Form UF Employee/Volunteer

    E-print Network

    Slatton, Clint

    Medications: doses and Frequency Visual loss (one or both eyes) Blindness Difficulty hearing/hearing or psychological conditions that you feel may prevent you from completely and safely performing the duties outlined

  16. Contact mechanics with adhesion: Interfacial separation and contact area

    E-print Network

    C. Yang; B. N. J. Persson; J. Israelachvili; K. Rosenberg

    2008-08-26

    We study the adhesive contact between elastic solids with randomly rough, self affine fractal surfaces. We present molecular dynamics (MD) simulation results for the interfacial stress distribution and the wall-wall separation. We compare the MD results for the relative contact area and the average interfacial separation, with the prediction of the contact mechanics theory of Persson. We find good agreement between theory and the simulation results. We apply the theory to the system studied by Benz et al. involving polymer in contact with polymer, but in this case the adhesion gives only a small modification of the interfacial separation as a function of the squeezing pressure.

  17. Xenoestrogens are potent activators of nongenomic estrogenic responses.

    PubMed

    Watson, Cheryl S; Bulayeva, Nataliya N; Wozniak, Ann L; Alyea, Rebecca A

    2007-02-01

    Studies of the nuclear transcriptional regulatory activities of non-physiological estrogens have not explained their actions in mediating endocrine disruption in animals and humans at the low concentrations widespread in the environment. However, xenoestrogens have rarely been tested for their ability to participate in the plethora of nongenomic steroid signaling pathways elucidated over the last several years. Here we review what is known about such responses in comparison to our recent evidence that xenoestrogens can rapidly and potently elicit signaling through nongenomic pathways culminating in functional endpoints. Both estradiol (E(2)) and compounds representing various classes of xenoestrogens (diethylstilbestrol, coumestrol, bisphenol A, DDE, nonylphenol, endosulfan, and dieldrin) act via a membrane version of the estrogen receptor-alpha on pituitary cells, and can provoke Ca(2+) influx via L-type channels, leading to prolactin (PRL) secretion. These hormones and mimetics can also cause the oscillating activation of extracellular regulated kinases (ERKs). However, individual estrogen mimetics differ in their potency and temporal phasing of these activations compared to each other and to E(2). It is perhaps in these ways that they disrupt some endocrine functions when acting in combination with physiological estrogens. Our quantitative assays allow comparison of these outcomes for each mimetic, and let us build a detailed picture of alternative signaling pathway usage. Such an understanding should allow us to determine the estrogenic or antiestrogenic potential of different types of xenoestrogens, and help us to develop strategies for preventing xenoestrogenic disruption of estrogen action in many tissues. PMID:17174995

  18. Plants from Brazilian Cerrado with Potent Tyrosinase Inhibitory Activity

    PubMed Central

    Souza, Paula Monteiro; Elias, Silvia Taveira; Simeoni, Luiz Alberto; de Paula, José Elias; Gomes, Sueli Maria; Guerra, Eliete Neves Silva; Fonseca, Yris Maria; Silva, Elton Clementino; Silveira, Dâmaris; Magalhães, Pérola Oliveira

    2012-01-01

    The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC50 value of 11.88 µg/mL, compared to kojic acid (IC50 value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC50 value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations. PMID:23173036

  19. Highly potent and specific inhibitors of human renin.

    PubMed

    Kokubu, T; Hiwada, K; Murakami, E; Imamura, Y; Matsueda, R; Yabe, Y; Koike, H; Iijima, Y

    1985-01-01

    Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors. PMID:2987128

  20. Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei.

    PubMed

    Ren, Yulin; Lantvit, Daniel D; Deng, Youcai; Kanagasabai, Ragu; Gallucci, Judith C; Ninh, Tran Ngoc; Chai, Hee-Byung; Soejarto, Djaja D; Fuchs, James R; Yalowich, Jack C; Yu, Jianhua; Swanson, Steven M; Kinghorn, A Douglas

    2014-06-27

    Two new (1 and 2) and four known arylnaphthalene lignan lactones (3-6) were isolated from different plant parts of Phyllanthus poilanei collected in Vietnam, with two further known analogues (7 and 8) being prepared from phyllanthusmin C (4). The structures of the new compounds were determined by interpretation of their spectroscopic data and by chemical methods, and the structure of phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis. Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29 human colon cancer cells, with compounds 1 and 7-O-[(2,3,4-tri-O-acetyl)-?-L-arabinopyranosyl)]diphyllin (7) found to be the most potent, exhibiting IC50 values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic effects by inducing tumor cell apoptosis through activation of caspase-3, but it did not inhibit DNA topoisomerase II? activity. PMID:24937209

  1. Development of potent inhibitors of the coxsackievirus 3C protease.

    PubMed

    Lee, Eui Seung; Lee, Won Gil; Yun, Soo-Hyeon; Rho, Seong Hwan; Im, Isak; Yang, Sung Tae; Sellamuthu, Saravanan; Lee, Yong Jae; Kwon, Sun Jae; Park, Ohkmae K; Jeon, Eun-Seok; Park, Woo Jin; Kim, Yong-Chul

    2007-06-22

    Coxsackievirus B3 (CVB3) 3C protease (3CP) plays essential roles in the viral replication cycle, and therefore, provides an attractive therapeutic target for treatment of human diseases caused by CVB3 infection. CVB3 3CP and human rhinovirus (HRV) 3CP have a high degree of amino acid sequence similarity. Comparative modeling of these two 3CPs revealed one prominent distinction; an Asn residue delineating the S2' pocket in HRV 3CP is replaced by a Tyr residue in CVB3 3CP. AG7088, a potent inhibitor of HRV 3CP, was modified by substitution of the ethyl group at the P2' position with various hydrophobic aromatic rings that are predicted to interact preferentially with the Tyr residue in the S2' pocket of CVB3 3CP. The resulting derivatives showed dramatically increased inhibitory activities against CVB3 3CP. In addition, one of the derivatives effectively inhibited the CVB3 proliferation in vitro. PMID:17485072

  2. Synthetic galactomannans with potent anti-HIV activity.

    PubMed

    Budragchaa, Davaanyam; Bai, Shiming; Kanamoto, Taisei; Nakashima, Hideki; Han, Shuqin; Yoshida, Takashi

    2015-10-01

    Ring-opening polymerization of a new 1,6-anhydro disaccharide monomer, 1, 6-anhydro-2, 3-di-O-benzyl-4-O-(2', 3', 4', 6'-tetra-O-benzyl-?-d-galactopyranosyl)-?-d-mannopyranose, was carried out using PF5 as a catalyst under high vacuum at -60°C to give galactose branched mannopyranan (synthetic galactomannan), 4-O-?-d-galactopyranosyl-(1?6)-?-d-mannopyranan, after debenzylation with Na in liquid NH3. The ring-opening copolymerization with 1, 6-anhydro-tri-O-benzyl-?-d-mannopyranose in various feeds was also performed to give synthetic galactomannans with various proportions of galactose branches. After sulfation, sulfated synthetic galactomannans were found to have anti-HIV activity and cytotoxicity as high and low as those of standard curdlan and dextran sulfates, respectively, which are potent anti-HIV sulfated polysaccharides with low cytotoxicity. The anti-HIV mechanism of sulfated synthetic galactomannans used by poly-l-lysine as a model peptide of the HIV surface protein was estimated by using SPR, DSL, and zeta potential measurements, revealing the electrostatic interaction between negatively charged sulfate groups and positively charged amino groups. PMID:26076622

  3. Vanadate: a potent inhibitor of multifunctional glucose-6-phosphatase.

    PubMed

    Singh, J; Nordlie, R C; Jorgenson, R A

    1981-12-18

    Vanadate has been found to be a potent inhibitor of both the hydrolytic and synthetic activities of the multifunctional enzyme glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9). The enzyme, when studied in both microsomal preparations and in situ using permeable isolated hepatocytes, is inhibited by micromolar concentrations of vanadate. The inhibition by vanadate is greater in detergent-treated than in untreated microsomes. In both the microsomal preparations and permeable hepatocytes, the inhibition by vanadate is competitive with the phosphate substrate and is greater for the phosphotransferase than the hydrolase activity of the enzyme. The Ki values of vanadate for carbamyl-phosphate : glucose phosphotransferase and glucose-6-phosphate phosphohydrolase determined with permeable hepatocytes are in good agreement with the values determined with detergent-dispersed microsomes. The previously described inhibition of glucose-6-phosphate phosphohydrolase by ATP (Nordlie, R.C., Hanson, T.L., Johns, P.T. and Lygre, D.G. (1968) Proc. Natl. Acad. Sci. USA 60, 590-597) can now be explained by the vanadium contamination of the commercially available ATP samples used. In contrast with glucose-6-phosphatase, hepatic glucokinase and hexokinase were not inhibited by vanadate. Physiological implications and utilitarian experimental applicability of vanadate as a selective metabolic probe, based on these observations, are suggested. PMID:6274421

  4. Small Molecule Anticonvulsant Agents with Potent In Vitro Neuroprotection

    PubMed Central

    Smith, Garry R.; Zhang, Yan; Du, Yanming; Kondaveeti, Sandeep K.; Zdilla, Michael J.; Reitz, Allen B.

    2012-01-01

    Severe seizure activity is associated with recurring cycles of excitotoxicity and oxidative stress that result in progressive neuronal damage and death. Intervention to halt these pathological processes is a compelling disease-modifying strategy for the treatment of seizure disorders. In the present study, a core small molecule with anticonvulsant activity has been structurally optimized for neuroprotection. Phenotypic screening of rat hippocampal cultures with nutrient medium depleted of antioxidants was utilized as a disease model. Increased cell death and decreased neuronal viability produced by acute treatment with glutamate or hydrogen peroxide were prevented by our novel molecules. The neuroprotection associated with this chemical series has marked structure activity relationships that focus on modification of the benzylic position of a 2-phenyl-2-hydroxyethyl sulfamide core structure. Complete separation between anticonvulsant activity and neuroprotective action was dependent on substitution at the benzylic carbon. Chiral selectivity was evident in that the S-enantiomer of the benzylic hydroxy group had neither neuroprotective nor anticonvulsant activity, while the R-enantiomer of the lead compound had full neuroprotective action at ?40 nM and antiseizure activity in three animal models. These studies indicate that potent, multifunctional neuroprotective anticonvulsants are feasible within a single molecular entity. PMID:22535312

  5. Potent Cytotoxic Arylnaphthalene Lignan Lactones from Phyllanthus poilanei

    PubMed Central

    2015-01-01

    Two new (1 and 2) and four known arylnaphthalene lignan lactones (3–6) were isolated from different plant parts of Phyllanthus poilanei collected in Vietnam, with two further known analogues (7 and 8) being prepared from phyllanthusmin C (4). The structures of the new compounds were determined by interpretation of their spectroscopic data and by chemical methods, and the structure of phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis. Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29 human colon cancer cells, with compounds 1 and 7-O-[(2,3,4-tri-O-acetyl)-?-l-arabinopyranosyl)]diphyllin (7) found to be the most potent, exhibiting IC50 values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic effects by inducing tumor cell apoptosis through activation of caspase-3, but it did not inhibit DNA topoisomerase II? activity. PMID:24937209

  6. 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors

    PubMed Central

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2015-01-01

    Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5-substituted 2-acetylphenol analogs (15) and related compounds (two) were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 µM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure–activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson’s disease.

  7. Potent Adjuvanticity of a Pure TLR7-Agonistic Imidazoquinoline Dendrimer

    PubMed Central

    Shukla, Nikunj M.; Salunke, Deepak B.; Balakrishna, Rajalakshmi; Mutz, Cole A.; Malladi, Subbalakshmi S.; David, Sunil A.

    2012-01-01

    Engagement of toll-like receptors (TLRs) serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. We synthesized a dendrimeric molecule bearing six units of a potent TLR7/TLR8 dual-agonistic imidazoquinoline to explore if multimerization of TLR7/8 would result in altered activity profiles. A complete loss of TLR8-stimulatory activity with selective retention of the TLR7-agonistic activity was observed in the dendrimer. This was reflected by a complete absence of TLR8-driven proinflammatory cytokine and interferon (IFN)-? induction in human PBMCs, with preservation of TLR7-driven IFN-? induction. The dendrimer was found to be superior to the imidazoquinoline monomer in inducing high titers of high-affinity antibodies to bovine ?-lactalbumin. Additionally, epitope mapping experiments showed that the dendrimer induced immunoreactivity to more contiguous peptide epitopes along the amino acid sequence of the model antigen. PMID:22952720

  8. A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis

    PubMed Central

    Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah; Franklin, Christopher C.; Genoux-Bastide, Estelle; Mahaffey, Gregory; Gauthier, Charlotte; Di Pietro, Attilio; Boumendjel, Ahcène

    2014-01-01

    Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2?,5?-dihydroxychalcone (2?,5?-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure–activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4?,6?-dimethoxy-2?-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements. PMID:22239485

  9. Potent antiviral flavone glycosides from Ficus benjamina leaves.

    PubMed

    Yarmolinsky, Ludmila; Huleihel, Mahmoud; Zaccai, Michele; Ben-Shabat, Shimon

    2012-03-01

    Crude ethanol extracts from Ficus benjamina leaves strongly inhibit Herpes Simplex Virus 1 and 2 (HSV-1/2) as well as Varicella Zoster Virus (VZV) cell infection in vitro. Bioassay-guided fractionation of the crude extract demonstrated that the most efficient inhibition of HSV-1 and HSV-2 was obtained with the flavonoid fraction. The present study was aimed to further isolate, purify and identify substances with potent antiviral activity from the flavonoid fraction of F. benjamina extracts. Flavonoids were collected from the leaf ethanol extracts through repeated purification procedure and HPLC analysis. The antiviral activity of each substance was then evaluated in cell culture. Three known flavone glycosides, (1) quercetin 3-O-rutinoside, (2) kaempferol 3-O-rutinoside and (3) kaempferol 3-O-robinobioside, showing highest antiviral efficiency were selected and their structure was determined by spectroscopic analyses including NMR and mass spectrometry (MS). These three flavones were highly effective against HSV-1 reaching a selectivity index (SI) of 266, 100 and 666 for compound 1, 2 and 3, respectively, while the SI of their aglycons, quercetin and kaempferol amounted only in 7.1 and 3.2, respectively. Kaempferol 3-O-robinobioside showed similar SI to that of acyclovir (ACV), the standard anti-HSV drug. Although highly effective against HSV-1 and HSV-2, these flavone glycosides did not show any significant activity against VZV. PMID:22155188

  10. A potent vasoactive cytolysin isolated from Scorpaena plumieri scorpionfish venom.

    PubMed

    Andrich, F; Carnielli, J B T; Cassoli, J S; Lautner, R Q; Santos, R A S; Pimenta, A M C; de Lima, M E; Figueiredo, S G

    2010-09-15

    A new vasoactive cytolytic toxin, referred to as Sp-CTx, has been purified from the venom of the scorpionfish Scorpaena plumieri by a combination of gel filtration and anion exchange chromatographies. An estimation of Sp-CTx native molecular mass, performed by size exclusion chromatography, demonstrated that it is a 121 kDa protein. Further physicochemical studies revealed its glycoproteic nature and dimeric constitution, comprising subunits of approximately 65 kDa (MALDI-TOF-MS). Such protein has proved to possess a potent hemolytic activity on washed rabbit erythrocytes (EC(50) 0.46 nM), whose effect was strongly reduced after treatment with antivenom raised against stonefish venom -Synanceja trachynis (SFAV). This cross-reactivity has been confirmed by western blotting. Like S. plumieri whole venom (100 microg/mL), Sp-CTx (1-50 nM) caused a biphasic response on phenylephrine pre-contracted rat aortic rings, characterized by an endothelium- and dose-dependent relaxation phase followed by a contractile phase. The vasorelaxant activity has been abolished by l-NAME, demonstrating the involvement of nitric oxide on the response. We report here the first isolation of a cytolytic/vasoactive protein from scorpionfish venom and the data provided suggest structural and functional similarities between Sp-CTx and previously published stonefish hemolytic toxins. PMID:20493199

  11. Novel Furin Inhibitors with Potent Anti-infectious Activity.

    PubMed

    Hardes, Kornelia; Becker, Gero L; Lu, Yinghui; Dahms, Sven O; Köhler, Susanne; Beyer, Wolfgang; Sandvig, Kirsten; Yamamoto, Hiroyuki; Lindberg, Iris; Walz, Lisa; von Messling, Veronika; Than, Manuel E; Garten, Wolfgang; Steinmetzer, Torsten

    2015-07-01

    New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4-guanidinomethyl-phenylacteyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) inhibits furin with a Ki value of 5.5?pM. The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI-1148 was crystallized in complex with human furin. Its N-terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short-term treatment of acute infectious diseases. PMID:25974265

  12. Prospects for introducing deferiprone as potent pharmaceutical antioxidant.

    PubMed

    Kontoghiorghes, George J

    2009-01-01

    Free radical formation is primarily initiated from metal catalytic centers involving iron and copper. Under certain conditions, free radical reactions can lead to free radical cascades and oxidative stress, which can cause biomolecular, cellular and tissue damage (FRD). The use of natural antioxidants to prevent FRD is in most cases not effective. Many chelators have been shown to inhibit free radical reactions and toxicity in experimental models of both in vitro and in vivo. Deferiprone (L1) has been shown to be effective and safe in the reversal of accelerating oxidative stress related tissue damage in iron loading and non iron loading conditions such as cardiomyopathy in thalassaemia, acute kidney disease and Friedreich ataxia. The selection of chelating drugs and their combinations could be used as new strategies for antioxidant therapies. In vitro, in vivo and clinical data suggest that L1 is the most potent drug antioxidant because of its high therapeutic index, ability to reach extracellular and intracellular compartments of many tissues and ability to inhibit both iron and copper catalysed free radical reactions. PMID:19482634

  13. Contact dermatitis in blacks.

    PubMed

    Berardesca, E; Maibach, H I

    1988-07-01

    Black skin is characterized by structural and functional differences such as increased stratum corneum cohesion, melanin content, and stratum corneum layers. These differences seem to make black skin difficult for irritants and light to penetrate, thus explaining the common opinion that skin in blacks is harder and develops contact dermatitis less frequently. The paucity of interpretable epidemiologic data and of clinical and experimental studies does not permit confirmation of this hypothesis, and the few data available are controversial. This article describes the main physiologic differences between black and white barrier function and reviews the literature on irritation, sensitization, and transcutaneous penetration. We found that the data are still too incomplete to generalize on the resistance, or lack thereof, of black skin (versus white skin) to chemical irritation, sensitization, and penetration. PMID:3048818

  14. The Effect of Contact Angle on the Depletion Layer when Water Meets a Hydrophobic Surface

    NASA Astrophysics Data System (ADS)

    Poynor, Adele

    2013-03-01

    By definition hydrophobic substances hate water. Water placed on a hydrophobic surface will form a drop in order to minimize its contact area. What happens when water is forced into contact with a hydrophobic surface? One theory is that an ultra-thin low-density depletion layer forms near the surface. We investigate the effect of contact angle on depletion layer formation using the surface sensitive technique of Surface Plasmon Resonance.

  15. Metrology Of Silicide Contacts For Future CMOS

    NASA Astrophysics Data System (ADS)

    Zollner, Stefan; Gregory, Richard B.; Kottke, M. L.; Vartanian, Victor; Wang, Xiang-Dong; Theodore, David; Fejes, P. L.; Conner, J. R.; Raymond, Mark; Zhu, Xiaoyan; Denning, Dean; Bolton, Scott; Chang, Kyuhwan; Noble, Ross; Jahanbani, Mohamad; Rossow, Marc; Goedeke, Darren; Filipiak, Stan; Garcia, Ricardo; Jawarani, Dharmesh; Taylor, Bill; Nguyen, Bich-Yen; Crabtree, P. E.; Thean, Aaron

    2007-09-01

    Silicide materials (NiSi, CoSi2, TiSi2, etc) are used to form low-resistance contacts between the back-end (W plugs and Cu interconnects) and front-end portions (silicon source, drain, and gate regions) of integrated CMOS circuits. At the 65 nm node, a transition from CoSi2 to NiSi was necessary because of the unique capability of NiSi to form narrow silicide nanowires on active (monocrystalline) and gate (polycrystalline) lines. Like its predecessors TiSi2 and CoSi2, NiSi is a mid-gap silicide, i.e., the Fermi level of the NiSi metal is pinned half-way between the conduction and valence band edges in silicon. This leads to a Schottky barrier between the silicide and silicon source-drain regions, which creates undesirable parasitic resistances. For future CMOS generations, band-edge silicides, such as PtSi for contacts to p-type or rare earth silicides for contacts to n-type Si will be needed. This paper reviews metrology and characterization techniques for NiSi process control for development and manufacturing, with special emphasis on x-ray reflectance and x-ray fluorescence. We also report measurement methods useful for development of a PtSi PMOS module.

  16. Fabrication of optically reflecting ohmic contacts for semiconductor devices

    DOEpatents

    Sopori, B.L.

    1995-07-04

    A method is provided to produce a low-resistivity ohmic contact having high optical reflectivity on one side of a semiconductor device. The contact is formed by coating the semiconductor substrate with a thin metal film on the back reflecting side and then optically processing the wafer by illuminating it with electromagnetic radiation of a predetermined wavelength and energy level through the front side of the wafer for a predetermined period of time. This method produces a thin epitaxial alloy layer between the semiconductor substrate and the metal layer when a crystalline substrate is used. The alloy layer provides both a low-resistivity ohmic contact and high optical reflectance. 5 figs.

  17. Fabrication of optically reflecting ohmic contacts for semiconductor devices

    DOEpatents

    Sopori, Bhushan L. (Denver, CO)

    1995-01-01

    A method is provided to produce a low-resistivity ohmic contact having high optical reflectivity on one side of a semiconductor device. The contact is formed by coating the semiconductor substrate with a thin metal film on the back reflecting side and then optically processing the wafer by illuminating it with electromagnetic radiation of a predetermined wavelength and energy level through the front side of the wafer for a predetermined period of time. This method produces a thin epitaxial alloy layer between the semiconductor substrate and the metal layer when a crystalline substrate is used. The alloy layer provides both a low-resistivity ohmic contact and high optical reflectance.

  18. Point contact readout for a quantum dot terahertz sensor

    NASA Astrophysics Data System (ADS)

    Pelling, S.; Davis, R.; Kulik, L.; Tzalenchuk, A.; Kubatkin, S.; Ueda, T.; Komiyama, S.; Antonov, V. N.

    2008-08-01

    We introduce a terahertz radiation sensor in which the photon-induced ionization state of a quantum dot is monitored by a point contact formed in the same semiconductor heterostructure. For comparison we used a readout based on a single electron transistor coupled to the same quantum dot. The experiments prove functionality of the point contact-based device with additional practical advantage of a higher operation temperature up to 1.5K and ease of nanofabrication.

  19. Contact dermatitis in a woodworker

    Microsoft Academic Search

    Christine E. Correale; James G. Marks

    2002-01-01

    Woods are capable of causing allergic or irritant contact dermatitis which typically occurs on the exposed areas of the arms, face, and neck. The allergens found in woods include quinones, stilbenes, phenols, and terpenes. We report an 84-year-old woodworker who developed allergic contact dermatitis from Bolivian rosewood and Cocobolo wood. The patient was patch-tested using the North American Contact Dermatitis

  20. Aurelia aurita (Cnidaria) Oocytes' Contact Plate Structure and Development

    PubMed Central

    Adonin, Leonid S.; Shaposhnikova, Tatyana G.; Podgornaya, Olga

    2012-01-01

    One of the A. aurita medusa main mesoglea polypeptides, mesoglein, has been described previously. Mesoglein belongs to ZP-domain protein family and therefore we focused on A.aurita oogenesis. Antibodies against mesoglein (AB RA47) stain the plate in the place where germinal epithelium contacts oocyte on the paraffin sections. According to its position, we named the structure found the “contact plate”. Our main instrument was AB against mesoglein. ZP-domain occupies about half of the whole amino acid sequence of the mesoglein. Immunoblot after SDS-PAGE and AU-PAGE reveals two charged and high Mr bands among the female gonad germinal epithelium polypeptides. One of the gonads' polypeptides Mr corresponds to that of mesogleal cells, the other ones' Mr is higher. The morphological description of contact plate formation is the subject of the current work. Two types of AB RA47 positive granules were observed during progressive oogenesis stages. Granules form the contact plate in mature oocyte. Contact plate of A.aurita oocyte marks its animal pole and resembles Zona Pellucida by the following features: (1) it attracts spermatozoids; (2) the material of the contact plate is synthesized by oocyte and stored in granules; (3) these granules and the contact plate itself contain ZP domain protein(s); (4) contact plate is an extracellular structure made up of fiber bundles similar to those of conventional Zona Pellucida. PMID:23185235

  1. Experimental study of friction in sheet metal forming

    Microsoft Academic Search

    L. Figueiredo; A. Ramalho; M. C. Oliveira; L. F. Menezes

    2011-01-01

    During deformation of the sheet metal over a tool, contact occurs only at the peak asperities of both surfaces. In the contact areas the processed material flows over the tool's surface, therefore all the models used to study forming processes must include a way to take into account the contact with friction phenomena. More widely used friction models are based

  2. HLö 7 dimethanesulfonate, a potent bispyridinium-dioxime against anticholinesterases.

    PubMed

    Eyer, P; Hagedorn, I; Klimmek, R; Lippstreu, P; Löffler, M; Oldiges, H; Spöhrer, U; Steidl, I; Szinicz, L; Worek, F

    1992-01-01

    HLö 7 dimethanesulfonate (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2,4-bis [(hydroxyimino)methyl]pyridinium dimethanesulfonate) is a broad-spectrum reactivator against highly toxic organophosphorus compounds. The compound was synthesized by a new route with the carcinogenic bis(chloromethyl)ether being substituted by the non-mutagenic bis(methylsulfonoxymethyl)ether. The very soluble dimethanesulfonate of obidoxime was also prepared by this way. HLö 7 dimethanesulfonate is the first water-soluble salt of HLö 7 that should be suitable for the wet/dry autoinjector technology, because aqueous solutions of HLö 7 are not very stable (calculated shelf-life 0.2 years when stored at 8 degrees C, 1 M solution, pH 2.5). The crystalline preparation contains 96% of the syn/syn-isomer, less than 2% of the syn/anti-isomer and some minor identified by-products. HLö 7 was very efficient in reactivating acetylcholinesterase (AChE) blocked by organophosphates as long as ageing did not prevent dephosphylation. HLö 7 was superior to HI 6 (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2- [(hydroxyimino)methyl]pyridinium dichloride) in reactivating soman and sarin-inhibited AChE from erythrocytes, and literature data indicate that HLö 7 exceeds HI 6 by far in reactivating tabun-inhibited AChE. In atropine-protected, soman-poisoned mice HLö 7 was three times more potent than HI 6 (protective ratio 5 versus 2.5), and in sarin-poisoned mice HLö 7 was 10 times more potent than HI 6 (protective ratio 8 for both oximes). In atropine-protected guinea-pigs HLö 7 was less effective than HI 6 (protective ratio: 2.3 versus 5.2 for soman; 5.2 versus 6.8 for sarin; 4.3 versus 3.8 for tabun). The mean survival time of anaesthetized guinea-pigs exposed to 5 LD50 soman (6.3 min) was increased by atropine (27 min) and atropine + HLö (57 min). HLö 7 alone did not prolong the survival. The most impressive effect of HLö 7 was on respiration: 3 min after i.v. injection of HLö 7 and atropine, the depressed respiration increased rapidly to 60% of control and remained at that level during the observation period (60 min). With atropine alone, respiration recovered only slowly. Behavioural and physiologic parameters were determined in atropine-protected mice exposed to a sublethal soman dose. The running performance was significantly improved by HLö 7. Even central symptoms, e.g. hypothermia and convulsions, were decreased markedly by HLö 7 (evaluation 60 min after poisoning). The pharmacokinetic data for HLö 7 in male beagle dogs are similar to those of HI 6.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1482283

  3. Discovery of Potent Broad Spectrum Antivirals Derived from Marine Actinobacteria

    PubMed Central

    Raveh, Avi; Delekta, Phillip C.; Dobry, Craig J.; Peng, Weiping; Schultz, Pamela J.; Blakely, Pennelope K.; Tai, Andrew W.; Matainaho, Teatulohi; Irani, David N.; Sherman, David H.; Miller, David J.

    2013-01-01

    Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable target for the continued development of broadly active antiviral compounds. PMID:24349254

  4. Potent and specific antitumor effect of CEA-targeted photoimmunotherapy.

    PubMed

    Shirasu, Naoto; Yamada, Hiromi; Shibaguchi, Hirotomo; Kuroki, Motomu; Kuroki, Masahide

    2014-12-01

    Conventional photodynamic therapy (PDT) for cancer is limited by the insufficient efficacy and specificity of photosensitizers. We herein describe a highly effective and selective tumor-targeted PDT using a near-infrared (NIR) photosensitizer, IRDye700DX, conjugated to a human monoclonal antibody (Ab) specific for carcinoembryonic antigen (CEA). The antitumor effects of this Ab-assisted PDT, called photoimmunotherapy (PIT), were investigated in vitro and in vivo. The Ab-IRDye conjugate induced potent cytotoxicity against CEA-positive tumor cells after NIR-irradiation, whereas CEA-negative cells were not affected at all, even in the presence of excess photoimmunoconjugate. We found an equivalent phototoxicity and a predominant plasma membrane localization of Ab-IRDye after both one and six hours of incubation. Either no or little caspase activation and membrane peroxidation were observed in PIT-treated cells and a panel of scavengers for reactive oxygen species showed only partial inhibition of the phototoxic effect. Strikingly, Ab-IRDye retained significant phototoxicity even under hypoxia. We established a xenograft model, which allowed us to sensitively investigate the therapeutic efficacy of PIT by non-invasive bioluminescence imaging. Luciferase-expressing MKN-45-luc human gastric carcinoma cells were subcutaneously implanted into both flanks of nude mice. NIR-irradiation was performed for only the tumor on one side. In vivo imaging and measurement of the tumor size revealed that a single PIT treatment, with intraperitoneal administration of Ab-IRDye and subsequent NIR-irradiation, caused rapid cell death and significant inhibition of tumor growth, but only on the irradiated side. Together, these data suggest that Ab-IRDye-mediated PIT has great potential as an anticancer therapeutics targeting CEA-positive tumors. PMID:24740257

  5. Dry Eye in Pediatric Contact Lens Wearers

    PubMed Central

    Greiner, Katie L.; Walline, Jeffrey J.

    2015-01-01

    Objectives To determine whether children who wear contact lenses truly have fewer dry eye complaints than adults. Methods Ninety-four pediatric contact lens wearers, ages 8 to 14 years, were recruited and given the Contact Lens Dry Eye Questionnaire (CLDEQ) short form. The survey is designed to diagnose dry eye syndrome by obtaining information on the frequency of dryness and light sensitivity and their corresponding intensity levels within the first two hours of putting in the lenses, in the middle of the day, and at the end of the day. The responses were scored by multiplying the frequency by the average intensity and a constant. A composite score was calculated by subtracting the photophobia score from the dryness score, and the results were compared to adult samples from the literature. The questionnaire also asked whether the subject thought he/she had dry eyes while wearing contact lenses. Subjects that thought they had dry eyes and had a CLDEQ composite score >0.03 were diagnosed with dry eye. Subjects who were unsure if they dry eye or said they did not have dry eye but scored >1.29 were also diagnosed with dry eye. Results The average (± SD) age of the sample was 11.7 ± 1.5 years, 56.4% were female, 59.6% were white, and 19.1% were black. The mean (± SD) CLDEQ composite score was 0.25 ±0.50 (range= -1.20 to 1.45). In the literature, the adult mean (± SD) CLDEQ composite score was 1.02 ±0.80 (range= -0.74 to 4.50). Of the 94 surveys collected, 4.3% of children were categorized with dry eye compared to 56.2% of adults who completed the CLDEQ survey in the adult study. Conclusions Pediatric contact lens wearers have fewer complaints about dry eyes than adult contact lens wearers, which may be due to improved tear film, differences in reporting of symptoms, or modality of contact lens wear. PMID:21060258

  6. Phenothiazine is a potent inhibitor of prostaglandin E2 production by Candida albicans biofilms.

    PubMed

    Ells, Ruan; Kemp, Gabré; Albertyn, Jacobus; Kock, Johan L F; Pohl, Carolina H

    2013-12-01

    Candida albicans is an important opportunistic yeast pathogen of humans and has the ability to form drug-resistant biofilms, with increased expression of multidrug ATP-binding cassette (ABC) transporters. These biofilms are also capable of secreting immune-modulating prostaglandin E2 (PGE2 ) from host-derived arachidonic acid (AA). Phenothiazine, an aromatic amine, and its derivatives display broad activity as inhibitors and antioxidants. These compounds have fungistatic and fungicidal activity against planktonic C. albicans and can inhibit ABC transporters of C. albicans. This study investigated the effect of phenothiazine on biofilm formation, ABC transporters and PGE2 production by C. albicans. This was carried out by growing C. albicans biofilms in the presence of AA and phenothiazine and measuring the biomass as well as reduction of 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5[(phenylamino) carbonyl]-2H tetrazolium hydroxide. The effect on ABC transporters was determined by rhodamine 6G efflux, and the concentration of PGE2 was determined by a monoclonal PGE2 enzyme-linked immunosorbent assay and LC/MS/MS. Our results indicate that phenothiazine can cause a reduction in both the metabolic activity and biomass of C. albicans biofilms, without affecting biofilm morphology or ABC transporters. However, it is a potent inhibitor of PGE2 production by C. albicans biofilms. PMID:24103090

  7. Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody.

    PubMed

    Freeman, Michael M; Seaman, Michael S; Rits-Volloch, Sophia; Hong, Xinguo; Kao, Chia-Ying; Ho, David D; Chen, Bing

    2010-12-01

    Ibalizumab is a humanized, anti-CD4 monoclonal antibody. It potently blocks HIV-1 infection and targets an epitope in the second domain of CD4 without interfering with immune functions mediated by interaction of CD4 with major histocompatibility complex (MHC) class II molecules. We report here the crystal structure of ibalizumab Fab fragment in complex with the first two domains (D1-D2) of CD4 at 2.2 Å resolution. Ibalizumab grips CD4 primarily by the BC-loop (residues 121-125) of D2, sitting on the opposite side of gp120 and MHC-II binding sites. No major conformational change in CD4 accompanies binding to ibalizumab. Both monovalent and bivalent forms of ibalizumab effectively block viral infection, suggesting that it does not need to crosslink CD4 to exert antiviral activity. While gp120-induced structural rearrangements in CD4 are probably minimal, CD4 structural rigidity is dispensable for ibalizumab inhibition. These results could guide CD4-based immunogen design and lead to a better understanding of HIV-1 entry. PMID:21134642

  8. Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody

    PubMed Central

    Freeman, Michael M.; Seaman, Michael S.; Rits-Volloch, Sophia; Hong, Xinguo; Kao, Chia-Ying; Ho, David D.; Chen, Bing

    2010-01-01

    Summary Ibalizumab is a humanized, anti-CD4 monoclonal antibody. It potently blocks HIV-1 infection and targets an epitope in the second domain of CD4 without interfering with immune functions mediated by interaction of CD4 with major histocompatibility complex (MHC) class II molecules. We report here the crystal structure of ibalizumab Fab fragment in complex with the first two domains (D1-D2) of CD4 at 2.2 Å resolution. Ibalizumab grips CD4 primarily by the BC-loop (residues 121-125) of D2, sitting on the opposite side of gp120 and MHC-II binding sites. No major conformational change in CD4 accompanies binding to ibalizumab. Both monovalent and bivalent forms of ibalizumab effectively block viral infection, suggesting that it does not need to crosslink CD4 to exert antiviral activity. While gp120-induced structural rearrangements in CD4 are probably minimal, CD4 structural rigidity is dispensable for ibalizumab inhibition. These results could guide CD4-based immunogen design and lead to a better understanding of HIV-1 entry. PMID:21134642

  9. Crystal Structure of HIV-1 Primary Receptor CD4 i Complex with a Potent Antiviral Antibody

    SciTech Connect

    Freeman, M.M.; Hong, X.; Seaman, M.S.; Rits-Vollock, S.p Kao, C.Y.; Ho, D.D.; Chen, B.

    2010-06-18

    Ibalizumab is a humanized, anti-CD4 monoclonal antibody. It potently blocks HIV-1 infection and targets an epitope in the second domain of CD4 without interfering with immune functions mediated by interaction of CD4 with major histocompatibility complex (MHC) class II molecules. We report here the crystal structure of ibalizumab Fab fragment in complex with the first two domains (D1-D2) of CD4 at 2.2 {angstrom} resolution. Ibalizumab grips CD4 primarily by the BC-loop (residues 121125) of D2, sitting on the opposite side of gp120 and MHC-II binding sites. No major conformational change in CD4 accompanies binding to ibalizumab. Both monovalent and bivalent forms of ibalizumab effectively block viral infection, suggesting that it does not need to crosslink CD4 to exert antiviral activity. While gp120-induced structural rearrangements in CD4 are probably minimal, CD4 structural rigidity is dispensable for ibalizumab inhibition. These results could guide CD4-based immunogen design and lead to a better understanding of HIV-1 entry.

  10. Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice

    PubMed Central

    Bhandarkar, Sulochana S.; Jaconi, Marisa; Fried, Levi E.; Bonner, Michael Y.; Lefkove, Benjamin; Govindarajan, Baskaran; Perry, Betsy N.; Parhar, Ravi; Mackelfresh, Jamie; Sohn, Allie; Stouffs, Michael; Knaus, Ulla; Yancopoulos, George; Reiss, Yvonne; Benest, Andrew V.; Augustin, Hellmut G.; Arbiser, Jack L.

    2009-01-01

    Hemangiomas are the most common type of tumor in infants. As they are endothelial cell–derived neoplasias, their growth can be regulated by the autocrine-acting Tie2 ligand angiopoietin 2 (Ang2). Using an experimental model of human hemangiomas, in which polyoma middle T–transformed brain endothelial (bEnd) cells are grafted subcutaneously into nude mice, we compared hemangioma growth originating from bEnd cells derived from wild-type, Ang2+/–, and Ang2–/– mice. Surprisingly, Ang2-deficient bEnd cells formed endothelial tumors that grew rapidly and were devoid of the typical cavernous architecture of slow-growing Ang2-expressing hemangiomas, while Ang2+/– cells were greatly impaired in their in vivo growth. Gene array analysis identified a strong downregulation of NADPH oxidase 4 (Nox4) in Ang2+/– cells. Correspondingly, lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreased Ang2 mRNA levels and greatly impaired hemangioma growth in vivo. Using a structure-based approach, we identified fulvenes as what we believe to be a novel class of Nox inhibitors. We therefore produced and began the initial characterization of fulvenes as potential Nox inhibitors, finding that fulvene-5 efficiently inhibited Nox activity in vitro and potently inhibited hemangioma growth in vivo. In conclusion, the present study establishes Nox4 as a critical regulator of hemangioma growth and identifies fulvenes as a potential class of candidate inhibitor to therapeutically interfere with Nox function. PMID:19620773

  11. Effects of secreted oligomers of amyloid ?-protein on hippocampal synaptic plasticity: a potent role for trimers

    PubMed Central

    Townsend, Matthew; Shankar, Ganesh M; Mehta, Tapan; Walsh, Dominic M; Selkoe, Dennis J

    2006-01-01

    The accumulation of amyloid ?-protein (A?) in brain regions serving memory and cognition is a central pathogenic feature of Alzheimer's disease (AD). We have shown that small soluble oligomers of human A? that are naturally secreted by cultured cells inhibit hippocampal long-term potentiation (LTP) in vitro and in vivo and transiently impair the recall of a complex learned behaviour in rats. These results support the hypothesis that diffusible oligomers of A? initiate a synaptic dysfunction that may be an early event in AD. We now report detailed electrophysiological analyses that define conditions under which acute application of soluble A? inhibits hippocampal synaptic plasticity in wild-type mice. To ascertain which A? assemblies contribute to the impairment of LTP, we fractionated oligomers by size-exclusion chromatography and found that A? trimers fully inhibit LTP, whereas dimers and tetramers have an intermediate potency. Natural A? oligomers are sensitive to heat denaturation, primarily inhibit the induction phase of LTP, and cause a sustained impairment of LTP even after extensive washout. We observed no effects of A? oligomers on presynaptic vesicle release. LTP in juvenile mice is resistant to the effects of A? oligomers, as is brain-derived-neurotrophic-factor-induced LTP in adult hippocampus. We conclude that specific assemblies, particularly timers, of naturally secreted A? oligomers are potent and selective inhibitors of certain forms of hippocampal LTP. PMID:16469784

  12. Characterization of a potent antimicrobial lipopeptide via coarse-grained molecular dynamics

    PubMed Central

    Horn, Joshua N.; Sengillo, Jesse D.; Lin, Dejun; Romo, Tod D.; Grossfield, Alan

    2013-01-01

    The prevalence of antibiotic-resistant pathogens is a major medical concern, prompting increased interest in the development of novel antimicrobial compounds. One such set of naturally occurring compounds, known as antimicrobial peptides (AMPs), have broad-spectrum activity, but come with many limitations for clinical use. Recent work has resulted in a set of antimicrobial lipopeptides (AMLPs) with micromolar minimum inhibitory concentrations and excellent selectivity for bacterial membranes. To characterize a potent, synthetic lipopeptide, C16-KGGK, we used multi-microsecond coarse-grained simulations with the MARTINI forcefield, with a total simulation time of nearly 46 microseconds. These simulations show rapid binding of C16-KGGK, which forms micelles in solution, to model bacterial lipid bilayers. Furthermore, upon binding to the surface of the bilayer, these lipopeptides alter the local lipid organization by recruiting negatively charged POPG lipids to the site of binding. It is likely that this drastic reorganization of the bilayer has major effects on bilayer dynamics and cellular processes that depend on specific bilayer compositions. By contrast, the simulations revealed no association between the lipopeptides and model mammalian bilayers. These simulations provide biophysical insights into lipopeptide selectivity and suggest a possible mechanism for antimicrobial action. PMID:21819964

  13. Glycosylated enfuvirtide: a long-lasting glycopeptide with potent anti-HIV activity.

    PubMed

    Cheng, Shuihong; Chang, Xuesong; Wang, Yan; Gao, George F; Shao, Yiming; Ma, Liying; Li, Xuebing

    2015-02-12

    Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (T1/2: 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and ?-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties. PMID:25594223

  14. Structural Basis of Potent and Broad HIV-1 Fusion Inhibitor CP32M*

    PubMed Central

    Yao, Xue; Chong, Huihui; Zhang, Chao; Qiu, Zonglin; Qin, Bo; Han, Ruiyun; Waltersperger, Sandro; Wang, Meitian; He, Yuxian; Cui, Sheng

    2012-01-01

    CP32M is a newly designed peptide fusion inhibitor possessing potent anti-HIV activity, especially against T20-resistant HIV-1 strains. In this study, we show that CP32M can efficiently inhibit a large panel of diverse HIV-1 variants, including subtype B?, CRF07_BC, and CRF01_AE recombinants and naturally occurring or induced T20-resistant viruses. To elucidate its mechanism of action, we determined the crystal structure of CP32M complexed with its target sequence. Differing from its parental peptide, CP621-652, the 621VEWNEMT627 motif of CP32M folds into two ?-helix turns at the N terminus of the pocket-binding domain, forming a novel layer in the six-helix bundle structure. Prominently, the residue Asn-624 of the 621VEWNEMT627 motif is engaged in the polar interaction with a hydrophilic ridge that borders the hydrophobic pocket on the N-terminal coiled coil. The original inhibitor design of CP32M provides several intra- and salt bridge/hydrogen bond interactions favoring the stability of the helical conformation of CP32M and its interactions with N-terminal heptad repeat (NHR) targets. We identified a novel salt bridge between Arg-557 on the NHR and Glu-648 of CP32M that is critical for the binding of CP32M and resistance against the inhibitor. Therefore, our data present important information for developing novel HIV-1 fusion inhibitors for clinical use. PMID:22679024

  15. Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor.

    PubMed

    Zha, R Helen; Sur, Shantanu; Boekhoven, Job; Shi, Heidi Y; Zhang, Ming; Stupp, Samuel I

    2015-01-01

    Aberrant angiogenesis plays a large role in pathologies ranging from tumor growth to macular degeneration. Anti-angiogenic proteins have thus come under scrutiny as versatile, potent therapeutics but face problems with purification and tissue retention. We report here on the synthesis of supramolecular nanostructures that mimic the anti-angiogenic activity of maspin, a class II tumor suppressor protein. These maspin-mimetic nanostructures are formed via self-assembly of small peptide amphiphiles containing the g-helix motif of maspin. Using tubulogenesis assays with human umbilical vein endothelial cells, we demonstrate that maspin-mimetic nanostructures show anti-angiogenic activity at concentrations that are significantly lower than those necessary for the g-helix peptide. Furthermore, in vivo assays in the chick chorioallantoic membrane show maspin-mimetic nanostructures to be effective over controls at inhibiting angiogenesis. Thus, the nanostructures investigated here offer an attractive alternative to the use of anti-angiogenic recombinant proteins in the treatment of cancer or other diseases involving abnormal blood vessel formation. PMID:25462852

  16. Structural basis of potent and broad HIV-1 fusion inhibitor CP32M.

    PubMed

    Yao, Xue; Chong, Huihui; Zhang, Chao; Qiu, Zonglin; Qin, Bo; Han, Ruiyun; Waltersperger, Sandro; Wang, Meitian; He, Yuxian; Cui, Sheng

    2012-08-01

    CP32M is a newly designed peptide fusion inhibitor possessing potent anti-HIV activity, especially against T20-resistant HIV-1 strains. In this study, we show that CP32M can efficiently inhibit a large panel of diverse HIV-1 variants, including subtype B', CRF07_BC, and CRF01_AE recombinants and naturally occurring or induced T20-resistant viruses. To elucidate its mechanism of action, we determined the crystal structure of CP32M complexed with its target sequence. Differing from its parental peptide, CP621-652, the (621)VEWNEMT(627) motif of CP32M folds into two ?-helix turns at the N terminus of the pocket-binding domain, forming a novel layer in the six-helix bundle structure. Prominently, the residue Asn-624 of the (621)VEWNEMT(627) motif is engaged in the polar interaction with a hydrophilic ridge that borders the hydrophobic pocket on the N-terminal coiled coil. The original inhibitor design of CP32M provides several intra- and salt bridge/hydrogen bond interactions favoring the stability of the helical conformation of CP32M and its interactions with N-terminal heptad repeat (NHR) targets. We identified a novel salt bridge between Arg-557 on the NHR and Glu-648 of CP32M that is critical for the binding of CP32M and resistance against the inhibitor. Therefore, our data present important information for developing novel HIV-1 fusion inhibitors for clinical use. PMID:22679024

  17. Posaconazole is a potent inhibitor of sterol 14alpha-demethylation in yeasts and molds.

    PubMed

    Munayyer, Hanan K; Mann, Paul A; Chau, Andrew S; Yarosh-Tomaine, Taisa; Greene, Jonathan R; Hare, Roberta S; Heimark, Larry; Palermo, Robert E; Loebenberg, David; McNicholas, Paul M

    2004-10-01

    Posaconazole (POS; SCH 56592) is a novel triazole that is active against a wide variety of fungi, including fluconazole-resistant Candida albicans isolates and fungi that are inherently less susceptible to approved azoles, such as Candida glabrata. In this study, we compared the effects of POS, itraconazole (ITZ), fluconazole (FLZ), and voriconazole (VOR) on sterol biosynthesis in strains of C. albicans (both azole-sensitive and azole-resistant strains), C. glabrata, Aspergillus fumigatus, and Aspergillus flavus. Following exposure to azoles, nonsaponifiable sterols were extracted and resolved by liquid chromatography and sterol identity was confirmed by mass spectroscopy. Ergosterol was the major sterol in all but one of the strains; C. glabrata strain C110 synthesized an unusual sterol in place of ergosterol. Exposure to POS led to a decrease in the total sterol content of all the strains tested. The decrease was accompanied by the accumulation of 14alpha-methylated sterols, supporting the contention that POS inhibits the cytochrome P450 14alpha-demethylase enzyme. The degree of sterol inhibition was dependent on both dose and the susceptibility of the strain tested. POS retained activity against C. albicans isolates with mutated forms of the 14alpha-demethylase that rendered these strains resistant to FLZ, ITZ, and VOR. In addition, POS was a more potent inhibitor of sterol synthesis in A. fumigatus and A. flavus than either ITZ or VOR. PMID:15388421

  18. Social & Educational Contact with MSU

    E-print Network

    Maxwell, Bruce D.

    About ARF Advocacy Social & Educational Contact with MSU Membership Issue of Concern Forthcoming, ARF also strives to foster the benefits, interests and well-being of retired faculty through social process and one is directed at improving social contact among retirees. A list of current project teams

  19. Creativity, Culture Contact, and Diversity

    Microsoft Academic Search

    Alfonso Montuori; Hillary Stephenson

    2010-01-01

    Recent trends in the understanding of culture contact, with concepts such as hybridization, cosmopolitanism, and cultural innovation, open up the possibility of a new understanding of human interaction. While the social imaginary is rich with images of conflict resulting from culture contact, images of creativity are far rarer. We propose the creation of an extensive research project to document cultural

  20. Cooperative autonomy for contact investigation

    Microsoft Academic Search

    Toby Schneider; Henrik Schmidt; Thomas Pastore; Michael Benjamin

    2010-01-01

    Autonomous surface and underwater vehicles present a safe and low-cost solution for various contact investigation tasks, such as harbor surveillance for potentially threatening small craft or submarines. Since such a task may involve many contacts of interest, such as all the normal boat traffic in a busy harbor, a single unmanned surface vehicle (USV) is unlikely to be able to

  1. Contact dermatitis with henna tattoo.

    PubMed

    Uzuner, Nevin; Olmez, Duygu; Babayigit, Arzu; Vayvada, Ozlem

    2009-05-01

    Allergic and irritant reactions to henna are rare. Para-phenylenediamine, which is sometimes added to obtain a dark, blackish henna, causes the majority of contact dermatitis reported related with tattoos. Allergic contact dermatitis due to temporary paint-on tattoo with black henna is described in two adolescents. PMID:19478355

  2. Interactions between contacting fibers

    NASA Astrophysics Data System (ADS)

    Petrich, Michael P.; Koch, Donald L.

    1998-08-01

    To investigate the nature of the forces involved in mechanical contact between fibers in a fluid, the interaction between a polymeric fiber settling under the influence of gravity and a fixed strand of the same material was observed. Initially after impact, the sedimenting fiber rotated about a fixed point. When the fiber came sufficiently close to vertical alignment so that the tangential component of gravity overcame the static friction, it slid along the surface of the fixed strand. The orientation of the fiber and its velocity were measured as a function of time, and compared to a simple model. The static coefficient of friction was found to be 0.38±0.06, in good agreement with published values. However, the velocity of the fiber after the onset of sliding was slower than that predicted by a theory incorporating friction and smooth cylinder lubrication, and an additional velocity-dependent resistance was required to model the fiber's sliding motion. A possible source of this resistance is the coupling of normal and tangential lubrication forces as roughness elements are forced to lift past each other.

  3. Discovery of potent, selective and orally bioavailable triaryl-sulfonamide based PTP1B inhibitors.

    PubMed

    Patel, Dipam; Jain, Mukul; Shah, Shailesh R; Bahekar, Rajesh; Jadav, Pradip; Joharapurkar, Amit; Dhanesha, Nirav; Shaikh, Mubeen; Sairam, Kalapatapu V V M; Kapadnis, Prashant

    2012-01-15

    A novel series of pTyr mimetics containing triaryl-sulfonamide derivatives (5a-r) are reported as potent and selective PTP1B inhibitors. Some of the test compounds (5o and 5p) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro). The lead compound 5o showed potent antidiabetic activity (in vivo), along with improved pharmacokinetic profile. These preliminary results confirm discovery of highly potent and selective PTP1B inhibitors for the treatment of T2DM. PMID:22189136

  4. Public Event Disability Access Accommodation Request Form

    E-print Network

    Chapman, Michael S.

    Public Event Disability Access Accommodation Request Form Event attendees with qualified. 11/06 Public Event Disability Access Accommodation Request Form Page 1 of 2 #12;How long have you Requesting Public Access Accommodation: Date Mail, fax or send this form by email to the department contact

  5. Applied Research Contact Information

    Cancer.gov

    Skip to Main Content at the National Institutes of Health | www.cancer.gov Print Page E-mail Page Search: Please wait while this form is being loaded.... Home Browse by Resource Type Browse by Area of Research Research Networks Funding Information About

  6. Method and apparatus for high-efficiency direct contact condensation

    DOEpatents

    Bharathan, Desikan (Lakewood, CO); Parent, Yves (Golden, CO); Hassani, A. Vahab (Golden, CO)

    1999-01-01

    A direct contact condenser having a downward vapor flow chamber and an upward vapor flow chamber, wherein each of the vapor flow chambers includes a plurality of cooling liquid supplying pipes and a vapor-liquid contact medium disposed thereunder to facilitate contact and direct heat exchange between the vapor and cooling liquid. The contact medium includes a plurality of sheets arranged to form vertical interleaved channels or passageways for the vapor and cooling liquid streams. The upward vapor flow chamber also includes a second set of cooling liquid supplying pipes disposed beneath the vapor-liquid contact medium which operate intermittently in response to a pressure differential within the upward vapor flow chamber. The condenser further includes separate wells for collecting condensate and cooling liquid from each of the vapor flow chambers. In alternate embodiments, the condenser includes a cross-current flow chamber and an upward flow chamber, a plurality of upward flow chambers, or a single upward flow chamber. The method of use of the direct contact condenser of this invention includes passing a vapor stream sequentially through the downward and upward vapor flow chambers, where the vapor is condensed as a result of heat exchange with the cooling liquid in the contact medium. The concentration of noncondensable gases in the resulting condensate-liquid mixtures can be minimized by controlling the partial pressure of the vapor, which depends in part upon the geometry of the vapor-liquid contact medium. In another aspect of this invention, the physical and chemical performance of a direct contact condenser can be predicted based on the vapor and coolant compositions, the condensation conditions. and the geometric properties of the contact medium.

  7. Method and apparatus for high-efficiency direct contact condensation

    DOEpatents

    Bharathan, D.; Parent, Y.; Hassani, A.V.

    1999-07-20

    A direct contact condenser having a downward vapor flow chamber and an upward vapor flow chamber, wherein each of the vapor flow chambers includes a plurality of cooling liquid supplying pipes and a vapor-liquid contact medium disposed thereunder to facilitate contact and direct heat exchange between the vapor and cooling liquid. The contact medium includes a plurality of sheets arranged to form vertical interleaved channels or passageways for the vapor and cooling liquid streams. The upward vapor flow chamber also includes a second set of cooling liquid supplying pipes disposed beneath the vapor-liquid contact medium which operate intermittently in response to a pressure differential within the upward vapor flow chamber. The condenser further includes separate wells for collecting condensate and cooling liquid from each of the vapor flow chambers. In alternate embodiments, the condenser includes a cross-current flow chamber and an upward flow chamber, a plurality of upward flow chambers, or a single upward flow chamber. The method of use of the direct contact condenser of this invention includes passing a vapor stream sequentially through the downward and upward vapor flow chambers, where the vapor is condensed as a result of heat exchange with the cooling liquid in the contact medium. The concentration of noncondensable gases in the resulting condensate-liquid mixtures can be minimized by controlling the partial pressure of the vapor, which depends in part upon the geometry of the vapor-liquid contact medium. In another aspect of this invention, the physical and chemical performance of a direct contact condenser can be predicted based on the vapor and coolant compositions, the condensation conditions, and the geometric properties of the contact medium. 39 figs.

  8. Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells

    SciTech Connect

    Shi, Lin [Department of Hematology, The Third Hospital, Peking University, 49 Huayuan North Road, Beijing 100191 (China)] [Department of Hematology, The Third Hospital, Peking University, 49 Huayuan North Road, Beijing 100191 (China); Song, Quansheng; Zhang, Yingmei [Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing 100191 (China) [Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing 100191 (China); Department of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191 (China); Lou, Yaxin [Peking University Medical and Health Analysis Center, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191 (China)] [Peking University Medical and Health Analysis Center, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191 (China); Wang, Yanfang [Department of Hematology, The Third Hospital, Peking University, 49 Huayuan North Road, Beijing 100191 (China)] [Department of Hematology, The Third Hospital, Peking University, 49 Huayuan North Road, Beijing 100191 (China); Tian, Linjie; Zheng, Yi; Ma, Dalong [Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing 100191 (China) [Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing 100191 (China); Department of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191 (China); Ke, Xiaoyan, E-mail: xiaoyank@yahoo.com [Department of Hematology, The Third Hospital, Peking University, 49 Huayuan North Road, Beijing 100191 (China)] [Department of Hematology, The Third Hospital, Peking University, 49 Huayuan North Road, Beijing 100191 (China); Wang, Ying, E-mail: yw@bjmu.edu.cn [Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing 100191 (China) [Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing 100191 (China); Department of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191 (China)

    2010-05-28

    Conventional chemotherapy is still frequently used. Programmed cell death 5 (PDCD5) enhances apoptosis of various tumor cells triggered by certain stimuli and is lowly expressed in leukemic cells from chronic myelogenous leukemia patients. Here, we describe for the first time that recombinant human PDCD5 protein (rhPDCD5) in combination with chemotherapy drugs has potent antitumor effects on chronic myelogenous leukemia K562 cells in vitro and in vivo. The antitumor efficacy of rhPDCD5 protein with chemotherapy drugs, idarubicin (IDR) or cytarabine (Ara-C), was examined in K562 cells in vitro and K562 xenograft tumor models in vivo. rhPDCD5 protein markedly increased the apoptosis rates and decreased the colony-forming capability of K562 cells after the combined treatment with IDR or Ara-C. rhPDCD5 protein by intraperitoneal administration dramatically improved the antitumor effects of IDR treatment in the K562 xenograft model. The tumor sizes and cell proliferation were significantly decreased; and TUNEL positive cells were significantly increased in the combined group with rhPDCD5 protein and IDR treatment compared with single IDR treatment groups. rhPDCD5 protein, in combination with IDR, has potent antitumor effects on chronic myelogenous leukemia K562 cells and may be a novel and promising agent for the treatment of chronic myelogenous leukemia.

  9. Fumagillin, a potent angiogenesis inhibitor, induces Kaposi sarcoma-associated herpesvirus replication in primary effusion lymphoma cells.

    PubMed

    Kanno, Takayuki; Uehara, Taeko; Osawa, Madori; Fukumoto, Hitomi; Mine, Sohtaro; Ueda, Keiji; Hasegawa, Hideki; Katano, Harutaka

    2015-08-01

    Kaposi sarcoma and primary effusion lymphoma cells are infected with Kaposi sarcoma-associated herpesvirus (KSHV), predominantly in the latent form, and KSHV replication is observed rarely. Angiogenesis plays a crucial role in the pathogenesis of both Kaposi sarcoma and primary effusion lymphoma. In this study, we found that fumagillin, a potent angiogenesis inhibitor, induced replication of KSHV in primary effusion lymphoma cell lines. The transcript and protein product of replication transcriptional activator (RTA) were induced by 1-10 ?M fumagillin at 24 and 48 h, respectively. Western blot analysis demonstrated that 10 ?M fumagillin induced not only RTA expression but also other KSHV-encoded lytic proteins. A real-time PCR array detecting KSHV gene expression demonstrated that the expression profiles of KSHV induced by fumagillin were similar to those induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), but the amounts of each transcript were lower than those induced by TPA. Finally, real-time PCR demonstrated an increase in that viral DNA copy number per cell in fumagillin-stimulated primary effusion lymphoma cell lines, indicating replication of KSHV. In addition to TPA, 10 ?M fumagillin resulted in growth inhibition of primary effusion lymphoma cell lines. These observations suggest that an angiogenesis inhibitor is an agent with potent effects on cell growth and KSHV reactivation in primary effusion lymphoma cells. PMID:26093300

  10. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface.

    PubMed

    Huang, Jinghe; Kang, Byong H; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A; Bailer, Robert T; Alam, Munir; Pugach, Pavel; Haynes, Barton F; Wyatt, Richard T; Sanders, Rogier W; Binley, James M; Ward, Andrew B; Mascola, John R; Kwong, Peter D; Connors, Mark

    2014-11-01

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 ?g ml(-1). The median IC50 of neutralized viruses was 0.033 ?g ml(-1), among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design. PMID:25186731

  11. THE SPINECARE FOUNDATION RESEARCH FUND APPLICATION FORM PhD 2014 THE SPINECARE FOUNDATION RESEARCH FUND APPLICATION FORM PhD 2014

    E-print Network

    THE SPINECARE FOUNDATION RESEARCH FUND APPLICATION FORM PhD 2014 THE SPINECARE FOUNDATIONCare Foundation will liaise with) Name Contact phone number Contact email address 4. The details of your Contact email address #12;THE SPINECARE FOUNDATION RESEARCH FUND APPLICATION FORM PhD 2014 6. Proposed

  12. CHTN :: Investigator Lead Submittal Form

    Cancer.gov

    If you are interested in obtaining human tissue samples from the CHTN, please complete the following form. Please provide a brief description of the type of tissues of interest in the description box below. A CHTN representative will contact you to discuss your research needs.

  13. 2,4-Dithiothymine as a potent UVA chemotherapeutic agent.

    PubMed

    Pollum, Marvin; Jockusch, Steffen; Crespo-Hernández, Carlos E

    2014-12-31

    Substitution of both oxygen atoms in the exocyclic carbonyl groups of the thymine chromophore by sulfur atoms results in a remarkable redshift of its absorption spectrum from an absorption maximum at 267 nm in thymidine to 363 nm in 2,4-dithiothymine (?E = 9905 cm(-1)). A single sulfur substitution of a carbonyl group in the thymine chromophore at position 2 or 4 results in a significantly smaller redshift in the absorption maximum, which depends sensitively on the position at which the sulfur atom is substituted, varying from 275 nm in 2-thiothymine to 335 nm in 4-thiothymidine. Femtosecond transient absorption spectroscopy reveals that excitation of 2,4-dithiothymine at 335 or 360 nm leads to the ultrafast population of the triplet state, with an intersystem crossing lifetime of 180 ± 40 fs—the shortest intersystem crossing lifetime of any DNA base derivative studied so far in aqueous solution. Surprisingly, the degree and position at which the sulfur atom is substituted have important effects on the magnitude of the intersystem crossing rate constant, showing a 1.2-, 3.2-, and 4.2-fold rate increases for 2-thiothymine, 4-thiothymidine, and 2,4-dithiothymine, respectively, relative to that of thymidine, whereas the triplet yield increases 60-fold to near unity, independent of the site of sulfur atom substitution. While the natural thymine monomers owe their high degree of photostability to ultrafast internal conversion to the ground state and low triplet yields, the near-unity triplet yields in the thiothymine series account for their potent photosensitization properties. Nanosecond time-resolved luminescence spectroscopy shows that 4-thiothymidine and 2,4-dithiothymine are efficient singlet oxygen generators, with singlet oxygen quantum yields of 0.42 ± 0.02 and 0.46 ± 0.02, respectively, in O2-saturated acetonitrile solution. Taken together, these photophysical measurements strongly suggest that 2,4-dithiothymine can act as a more effective UVA chemotherapeutic agent than the currently used 4-thiothymidine, especially in deeper-tissue chemotherapeutic applications. PMID:25506742

  14. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

    PubMed Central

    2011-01-01

    Background Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. Methods The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 ?g/mL (crude extract) and 1-10 ?g/mL (compound). Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue. In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3 cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. Results Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an ?-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an ?-methylene carboxylic acid. Cytotoxicity of EPD for normal fibroblasts at all time points IC50 was greater than 10 ?g/mL, whereas, for OVCAR3 cells at 48 hours IC50 was 5.3 ?g/mL (95% confidence interval 4.3 to 6.5 ?g/mL). Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 ?g/mL and 5 ?g/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects. Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly different, P = 0.13. Conclusions For the first time both crude plant extract from Calomeria amaranthoides and EPD have been shown to have potent anti-cancer effects against ovarian cancer. PMID:21401934

  15. 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP

    Microsoft Academic Search

    Richard Sulsky; Jeffrey A. Robl; Scott A. Biller; Thomas W. Harrity; John Wetterau; Fergal Connolly; Kern Jolibois; Lori Kunselman

    2004-01-01

    5-Carboxamido-1,3,2-dioxaphosphorinanes have been identified as potent inhibitors of microsomal triglyceride-transfer protein. The 1,3,2-dioxaphosphorine functionality acted as a neutral and stable replacement for piperidine and piperidine N-oxide.

  16. METHYLATION INACTIVATES PENTAVALENT ARSENIC SPECIES BUT ACTIVATES TRIVALENT ARSENIC SPECIES TO POTENT GENOTOXICANTS

    EPA Science Inventory

    Methylation Inactivates Pentavalent Arsenic Species but Activates Trivalent Arsenic Species to Potent Genotoxicants The sensitivity ofhumans to arsenic-induced cancer is thought to be related in part to the limited ability of humans to detoxify arsenic. Recently, methyl- ...

  17. Arylcarboxyamino-substituted diaryl ureas as potent and selective FLT3 inhibitors

    Microsoft Academic Search

    Hitesh K. Patel; Robert M. Grotzfeld; Andiliy G. Lai; Shamal A. Mehta; Zdravko V. Milanov; Qi Chao; Kelly G. Sprankle; Todd A. Carter; Anne Marie Velasco; Miles A. Fabian; Joyce James; Daniel K. Treiber; David J. Lockhart; Patrick P. Zarrinkar; Shripad S. Bhagwat

    2009-01-01

    A series of diaryl ureas with an amide substitution at the 4-position was prepared and found to be potent and selective FLT3 inhibitors with good oral bioavailability and efficacy in a tumor xenograft model.

  18. A review on cylindrospermopsin: The global occurrence, detection, toxicity and degradation of a potent cyanotoxin

    EPA Science Inventory

    Abstract: Cylindrospermopsin is now recognized as a potent cyanobacterial toxin found in water bodies worldwide. The ever-increasing and global occurrence of massive and prolonged blooms of cylindrospermopsin-producing cyanobacteria in freshwater poses a potential threat to both ...

  19. Pyridine-sugar conjugates as potent inhibitors of enzyme-catalysed glycoside hydrolysis.

    PubMed

    Nkansah, Peter A; Haines, Alan H; Stamford, N Patrick J

    2003-03-21

    A series of O- and N-linked pseudo-disaccharides incorporating simple functionalised pyridines were synthesized and demonstrated potent inhibition of the glucoamylase-catalysed reaction. PMID:12703822

  20. Discoipyrroles A-D: isolation, structure determination, and synthesis of potent migration inhibitors from Bacillus hunanensis

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > Discoipyrroles A-D: isolation, structure determination, and synthesis of potent migration inhibitors from Bacillus hunanensis Discoipyrroles A-D: isolation, structure determination,

  1. Discoipyrroles A-D: isolation, structure determination, and synthesis of potent migration inhibitors from Bacillus hunanensis

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > Discoipyrroles A-D: isolation, structure determination, and synthesis of potent migration inhibitors from Bacillus hunanensis Discoipyrroles A-D: isolation, structure determination,

  2. DOI: 10.1002/cbic.200900425 Potent Fluoro-oligosaccharide Probes of Adhesion in

    E-print Network

    Davis, Ben G.

    DOI: 10.1002/cbic.200900425 Potent Fluoro-oligosaccharide Probes of Adhesion in Toxoplasmosis Sarah including fluorinated oligosaccharide probes 2 and 4 that, despite unnatural constitution and substituents

  3. Potent achiral agonists of the ghrelin (growth hormone secretagogue) receptor. Part I: Lead identification

    Microsoft Academic Search

    Tom D. Heightman; Jackie S. Scott; Mark Longley; Vincent Bordas; David K. Dean; Richard Elliott; Gail Hutley; Jason Witherington; Lee Abberley; Barry Passingham; Manuela Berlanga; Maite de los Frailes; Alan Wise; Ben Powney; Alison Muir; Fiona McKay; Sharon Butler; Kim Winborn; Christopher Gardner; Jill Darton; Colin Campbell; Gareth Sanger

    2007-01-01

    High throughput screening combined with efficient datamining and parallel synthesis led to the discovery of a novel series of indolines showing potent in vitro ghrelin receptor agonist activity and acceleration of gastric emptying in rats.

  4. Hit-to-lead studies: the discovery of potent, orally bioavailable triazolethiol CXCR2 receptor antagonists.

    PubMed

    Baxter, Andrew; Bennion, Colin; Bent, Janice; Boden, Kerry; Brough, Steve; Cooper, Anne; Kinchin, Elizabeth; Kindon, Nicholas; McInally, Tom; Mortimore, Mike; Roberts, Bryan; Unitt, John

    2003-08-18

    A Hit-to-Lead optimisation programme was carried out on the high throughput screening hit, the triazolethiol 1, resulting in the discovery of the potent, orally bioavailable triazolethiol CXCR2 receptor antagonist 45. PMID:12873480

  5. Hit-to-Lead studies: the discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists.

    PubMed

    Baxter, Andrew; Cooper, Anne; Kinchin, Elizabeth; Moakes, Kerry; Unitt, John; Wallace, Alan

    2006-02-15

    A Hit-to-Lead optimisation programme was carried out on a high throughput screening hit, the thiazolopyrimidine 1, resulting in the discovery of the potent, orally bioavailable CXCR2 antagonist 29. PMID:16297626

  6. Hit-to-Lead studies: The discovery of potent, orally bioavailable triazolethiol CXCR2 receptor antagonists

    Microsoft Academic Search

    Andrew Baxter; Colin Bennion; Janice Bent; Kerry Boden; Steve Brough; Anne Cooper; Elizabeth Kinchin; Nicholas Kindon; Tom McInally; Mike Mortimore; Bryan Roberts; John Unitt

    2003-01-01

    A Hit-to-Lead optimisation programme was carried out on the high throughput screening hit, the triazolethiol 1, resulting in the discovery of the potent, orally bioavailable triazolethiol CXCR2 receptor antagonist 45.

  7. First principles study of metal contacts to monolayer black phosphorous

    NASA Astrophysics Data System (ADS)

    Chanana, Anuja; Mahapatra, Santanu

    2014-11-01

    Atomically thin layered black phosphorous (BP) has recently appeared as an alternative to the transitional metal dichalcogenides for future channel material in a metal-oxide-semiconductor transistor due to its lower carrier effective mass. Investigation of the electronic property of source/drain contact involving metal and two-dimensional material is essential as it impacts the transistor performance. In this paper, we perform a systematic and rigorous study to evaluate the Ohmic nature of the side-contact formed by the monolayer BP (mBP) and metals (gold, titanium, and palladium), which are commonly used in experiments. Employing the Density Functional Theory, we analyse the potential barrier, charge transfer and atomic orbital overlap at the metal-mBP interface in an optimized structure to understand how efficiently carriers could be injected from metal contact to the mBP channel. Our analysis shows that gold forms a Schottky contact with a higher tunnel barrier at the interface in comparison to the titanium and palladium. mBP contact with palladium is found to be purely Ohmic, where as titanium contact demonstrates an intermediate behaviour.

  8. Solar cell contact resistance - a review

    Microsoft Academic Search

    D. K. Schroder; D. L. Meier

    1984-01-01

    An overview of ohmic contacts on solar cells is presented. The fundamentals of metal-semiconductor contacts are reviewed, including the Schottky approach, Fermi level pinning by surface states, and the mechanisms of thermionic emission, thermionic\\/field emission, and tunneling for current transport. The concept of contact resistance is developed and contact resistance data for several different contact materials on both silicon and

  9. Solar cell with back side contacts

    DOEpatents

    Nielson, Gregory N; Okandan, Murat; Cruz-Campa, Jose Luis; Resnick, Paul J; Wanlass, Mark Woodbury; Clews, Peggy J

    2013-12-24

    A III-V solar cell is described herein that includes all back side contacts. Additionally, the positive and negative electrical contacts contact compoud semiconductor layers of the solar cell other than the absorbing layer of the solar cell. That is, the positive and negative electrical contacts contact passivating layers of the solar cell.

  10. Elastohydrodynamic lubrication of elliptical contacts

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.

    1981-01-01

    The determination of the minimum film thickness within contact is considered for both fully flooded and starved conditions. A fully flooded conjunction is one in which the film thickness is not significantly changed when the amount of lubricant is increased. The fully flooded results presented show the influence of contact geometry on minimum film thickness as expressed by the ellipticity parameter and the dimensionless speed, load, and materials parameters. These results are applied to materials of high elastic modulus (hard EHL), such as metal, and to materials of low elastic modulus(soft EHL), such as rubber. In addition to the film thickness equations that are developed, contour plots of pressure and film thickness are given which show the essential features of elastohydrodynamically lubricated conjunctions. The crescent shaped region of minimum film thickness, with its side lobes in which the separation between the solids is a minimum, clearly emerges in the numerical solutions. In addition to the 3 presented for the fully flooded results, 15 more cases are used for hard EHL contacts and 18 cases are used for soft EHL contacts in a theoretical study of the influence of lubricant starvation on film thickness and pressure. From the starved results for both hard and soft EHL contacts, a simple and important dimensionless inlet boundary distance is specified. This inlet boundary distance defines whether a fully flooded or a starved condition exists in the contact. Contour plots of pressure and film thickness in and around the contact are shown for conditions.

  11. Newton constant, contact terms and entropy

    E-print Network

    Solodukhin, Sergey N

    2015-01-01

    We discuss the renormalization of the Newton constant due to fields of various spin $s$. We first briefly review the cases of $s=0, \\, 1/2, \\, 1,\\, 3/2$ already discussed in the literature and notice the appearance of the well-known contact terms for the vector bosons. We then extend this discussion of the contact terms to massive vector fields, $p$-forms and to the case of spin $s=2$ particles (gravitons). We observe that, in general, the contact terms originate from the fields which mediate the interactions (such as vector gauge bosons and gravitons). We then discuss entanglement entropy and the conical entropy and their relation to the renormalized Newton constant. We address the puzzle of the non-analytic terms due to fields of spin $s=2$ and suggest that the resolution of this puzzle comes from the non-equivalence of the orbifold and $n$-fold cover constructions which are used in the entropy calculations. Finally, we propose a mechanism by which the Bekenstein-Hawking entropy is identified with entanglem...

  12. The discovery of potent and selective non-steroidal glucocorticoid receptor modulators, suitable for inhalation.

    PubMed

    Edman, Karl; Ahlgren, Ragnhild; Bengtsson, Malena; Bladh, Håkan; Bäckström, Stefan; Dahmén, Jan; Henriksson, Krister; Hillertz, Per; Hulikal, Vijakumar; Jerre, Anders; Kinchin, Liz; Kåse, Charlotte; Lepistö, Matti; Mile, Irene; Nilsson, Stinabritt; Smailagic, Amir; Taylor, John; Tjörnebo, Ann; Wissler, Lisa; Hansson, Thomas

    2014-06-01

    We report the discovery of highly potent and selective non-steroidal glucocorticoid receptor modulators with PK properties suitable for inhalation. A high throughput screen of the AstraZeneca compound collection identified sulfonamide 3 as a potent non-steroidal glucocorticoid receptor ligand. Further optimization of this lead generated indazoles 30 and 48 that were progressed to characterization in in vivo models. X-ray crystallography was used to gain further insight into the binding mode of selected ligands. PMID:24755427

  13. Discovery of Potent and Simplified Piperidinone-Based Inhibitors of the MDM2-p53 Interaction.

    PubMed

    Yu, Ming; Wang, Yingcai; Zhu, Jiang; Bartberger, Michael D; Canon, Jude; Chen, Ada; Chow, David; Eksterowicz, John; Fox, Brian; Fu, Jiasheng; Gribble, Michael; Huang, Xin; Li, Zhihong; Liu, Jiwen Jim; Lo, Mei-Chu; McMinn, Dustin; Oliner, Jonathan D; Osgood, Tao; Rew, Yosup; Saiki, Anne Y; Shaffer, Paul; Yan, Xuelei; Ye, Qiuping; Yu, Dongyin; Zhao, Xiaoning; Zhou, Jing; Olson, Steven H; Medina, Julio C; Sun, Daqing

    2014-08-14

    Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone-pyridine inhibitors 6, 7, 14, and 15 with improved pharmacokinetic properties in rats. Reducing structure complexity of the N-alkyl substituent led to the discovery of 23, a potent and simplified inhibitor of MDM2. Compound 23 exhibits excellent pharmacokinetic properties and substantial in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft mouse model. PMID:25147610

  14. Potent Hepatitis C Virus NS5A Inhibitors Containing a Benzidine Core

    PubMed Central

    2013-01-01

    Here we report the discovery of a series of potent hepatitis C virus (HCV) NS5A inhibitors based on the benzidine prolinamide backbone. Taking a simple synthetic route, we developed a novel inhibitor structure, which allows easy modification, and through optimization of the capping group, we identified compound 6 with highly potent anti-HCV activity. Compound 6 is nontoxic and is anticipated to be an effective HCV drug candidate. PMID:24900814

  15. Discovery of potent ?1L-adrenoceptor agonists: Design and synthesis of bicyclic derivatives.

    PubMed

    Suzuki, Shinya; Okano, Tsubasa; Horiuchi, Rie; Hareyama, Nana; Amikura, Kazutoshi; Yamamoto, Naoyoshi; Yoshizawa, Yoshitaka; Yagi, Mai; Serizawa, Kanako; Hayashi, Ryoji

    2015-08-15

    We aimed to create a novel and potent ?1L-adrenoceptor agonist because such agonists are possible drug candidates for stress urinary incontinence. We used ligand-based drug design and evaluated the ?1L-adrenoceptor agonist activity of the designed compounds. Among them, tetrahydroquinoline derivative 50 showed the most potent activity (ratio of noradrenaline half maximal effective concentration, 0.0028) and effectively induced contraction of rat bladder neck. PMID:26087939

  16. Potent and Selective Photo-inactivation of Proteins With Peptoid-Ruthenium Conjugates

    PubMed Central

    Lee, Jiyong; Udugamasooriya, D. Gomika; Lim, Hyun-Suk; Kodadek, Thomas

    2010-01-01

    Advances in high-throughput screening now enable the rapid discovery of bioactive small molecules, but these primary hits almost always exhibit modest potency. We report a strategy for the transformation of these hits into much more potent inhibitors without compound optimization. Appending a derivative of Ru(II)(tris-bipyridyl)2+, an efficient photosensitizer of singlet oxygen production, to synthetic protein-binding compounds results in highly potent and specific target protein inactivation upon irradiation with visible light. PMID:20228793

  17. Plasma contacting - An enabling technology

    NASA Technical Reports Server (NTRS)

    Williams, John D.; Wilbur, Paul J.

    1989-01-01

    An experimental study of plasma contacting with an emphasis on the electron collection mode of this process is described. Results illustrating variations in plasma property profiles and potential differences that develop at hollow cathode plasma contactors are presented. A model of the electron collection plasma contacting process that is consistent with experimentally measured results is reviewed. The shortcomings of laboratory results as direct predictors of contactor performance in space and their usefulness in validating numerical models of the contacting process, that can be used to predict such performance, are discussed.

  18. Allergic contact dermatitis from ketoconazole.

    PubMed

    Liu, Jing; Warshaw, Erin M

    2014-09-01

    Ketoconazole is a widely used imidazole antifungal agent. True contact allergy to topical ketoconazole is rare, and few cases of patients with contact allergy to ketoconazole have been reported. We present the case of a patient with a history of undiagnosed recurrent dermatitis who developed acute facial swelling and pruritus after using ketoconazole cream and shampoo for the treatment of seborrheic dermatitis. Patch testing revealed true contact allergy to ketoconazole without cross-reactivity to 4 other imidazole antifungals. Review of the patient's medical record suggested that prior incidences of dermatitis might have been due to ketoconazole exposure. When the patient avoided this imidazole agent, the dermatitis resolved. PMID:25279470

  19. Emerging magnetic order in platinum atomic contacts and chains.

    PubMed

    Strigl, Florian; Espy, Christopher; Bückle, Maximilian; Scheer, Elke; Pietsch, Torsten

    2015-01-01

    The development of atomic-scale structures revealing novel transport phenomena is a major goal of nanotechnology. Examples include chains of atoms that form while stretching a transition metal contact or the predicted formation of magnetic order in these chains, the existence of which is still debated. Here we report an experimental study of the magneto-conductance (MC) and anisotropic MC with atomic-size contacts and mono-atomic chains of the nonmagnetic metal platinum. We find a pronounced and diverse MC behaviour, the amplitude and functional dependence change when stretching the contact by subatomic distances. These findings can be interpreted as a signature of local magnetic order in the chain, which may be of particular importance for the application of atomic-sized contacts in spintronic devices of the smallest possible size. PMID:25649440

  20. Emerging magnetic order in platinum atomic contacts and chains

    PubMed Central

    Strigl, Florian; Espy, Christopher; Bückle, Maximilian; Scheer, Elke; Pietsch, Torsten

    2015-01-01

    The development of atomic-scale structures revealing novel transport phenomena is a major goal of nanotechnology. Examples include chains of atoms that form while stretching a transition metal contact or the predicted formation of magnetic order in these chains, the existence of which is still debated. Here we report an experimental study of the magneto-conductance (MC) and anisotropic MC with atomic-size contacts and mono-atomic chains of the nonmagnetic metal platinum. We find a pronounced and diverse MC behaviour, the amplitude and functional dependence change when stretching the contact by subatomic distances. These findings can be interpreted as a signature of local magnetic order in the chain, which may be of particular importance for the application of atomic-sized contacts in spintronic devices of the smallest possible size. PMID:25649440

  1. Contact Pressure and Shear Stress Analysis on Conforming Contact Problem

    NASA Astrophysics Data System (ADS)

    Nagatani, Haruo; Imou, Akitoshi

    Two methods to solve a conforming contact problem are proposed. First method is general and can be applicable to the contact case between elastic arbitrary shape bodies. For verification FEA is performed on the convex-concave sphere contact, and the result of this method is well corresponding to the FEA result. However, the accuracy deteriorates when the mesh aspect ratio is extremely large. This phenomenon is caused by the usage of numerical integration for the calculation of influence coefficient. The second method is devised to avoid this problem, while this improved method is applicable only to the case when the contact area can be considered to be on a cylinder surface. By using this method, the contact pressure can be obtained without the deterioration even in the case of edge load occurring between ball bearing race shoulder and ball. The results of the contact pressure and the shear stress that is necessary for bearing life estimation are compared with the FEA result, which showed well correspondence.

  2. Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating agent.

    PubMed

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Vasaitis, Tadas S; Bruno, Robert D; Gediya, Lalji K; Njar, Vincent C O

    2008-04-01

    The search for novel androgen receptor (AR) down-regulating agents by catalyst HipHop pharmacophore modeling led to the discovery of some lead molecules. Unexpectedly, the effect of these leads on human prostate cancer LNCaP cell viability did not correlate with the ability of the compounds to cause down-regulation of AR protein expression. Through rational synthetic optimization of the lead compound (BTB01434), we have discovered a series of novel substituted diaryl molecules as potent anti-prostate cancer agents. Some compounds (1-6) were shown to be extremely potent inhibitors of LNCaP cell viability with GI(50) values in the nanomolar range (1.45-83 nM). The most potent compound (4-methylphenyl)[(4-methylphenyl)sulfonyl]amine (5) with a GI(50) value of 1.45 nM is 27,000 times more potent than our lead compound BTB01434 (GI(50)=39.8 microM). In addition, some of the compounds exhibited modest anti-androgenic activities and one was also a potent inhibitor (GI(50)=850 nM) of PC-3 (AR-null) cell growth. A clear structure-activity relationship (SAR) has been established for activity against LNCaP cells, where potent molecules possess two substituted/unsubstituted aromatic rings connected through a sulfonamide linker. These novel compounds are strong candidates for development for the treatment of hormone-sensitive and importantly hormone-refractory prostate cancers in humans. PMID:18316193

  3. Formation of fire-through silver metal contacts on the porous silicon surface for silicon solar cells

    Microsoft Academic Search

    P. N. Vinod

    2008-01-01

    In the present study, the ohmic and microstructural properties of the fire-through Ag metal contacts formed on planar and thin layers of the porous silicon for the silicon solar cells are investigated. The SEM characterization of the Ag contacts shows that sintering of the contacts at high temperature enables to fire-through the applied Ag paste onto the etched porous silicon

  4. State Health Department Contacts for Hantavirus Information

    MedlinePLUS

    ... CDC.gov . Hantavirus Share Compartir State Health Department Contacts Click on a state for contact information, or ... address: Enter Email Address Submit Button What's this? Contact Us: Centers for Disease Control and Prevention Viral ...

  5. Healthy Contact Lens Wear and Care

    MedlinePLUS

    ... this? Submit Button Past Emails CDC Features Healthy Contact Lens Wear and Care Recommend on Facebook Tweet ... is essential to practice healthy habits. Spring Break Contact Lens Health Tips Proper contact lens wear and ...

  6. Mom, Can I Get Contact Lenses, Please?

    MedlinePLUS

    ... For Consumers Consumer Updates Mom, Can I Get Contact Lenses, Please? Search the Consumer Updates Section Go ... back to top What About Young Kids and Contacts? "Eye care professionals typically don't recommend contacts ...

  7. Contact Lens-Related Eye Infections

    MedlinePLUS

    ... Eye Health News Consumer Alerts Contact Lens-Related Eye Infections Tweet While contact lenses are safely used ... Video Caring For Your Contact Lenses Find An Eye M.D. Enter zip code here Search by ...

  8. Ohmic contacts for wide bandgap semiconductors: Processing, properties and mechanisms

    NASA Astrophysics Data System (ADS)

    Park, Mi-Ran

    Stable Ohmic contacts are essential for reliable operation of wide bandgap semiconductor electronic and optoelectronic devices. Such contacts have been made to molecular beam epitaxy (MBE) grown n-type and p-type ZnSe on (100) semi-insulating GaAs substrates and metalorganic chemical vapor deposition (MOCVD) grown p-type GaN on (0001) sapphire substrates. Various metals have been deposited by thermal evaporation and annealing techniques at different temperatures. Chemical etching and cleaning, plasma treatment using reactive ion etching (RIE), and cryogenic treatment in liquid nitrogen have been studied. Ion implantation was also performed to obtain highly doped materials. The electrical characteristics for the contacts were examined by the current versus voltage data and the specific contact resistance was determined by use of the transmission line method (TLM) for II-VI n-type and p-type ZnSe and the circular transmission line method (c-TLM) for III-V p-type GaN, respectively. Contacts formed by In/Au to n-type ZnSe and Cu/Au to p-type ZnSe showed the lowest specific contact resistance values of 1.04 x 10--2 Ocm2 and 1.67 x 10--1 Ocm 2, respectively. A nitrogen plasma treatment of the ZnSe surface prior to metallization was proven to lower the contact resistance to p-type ZnSe. Two different current flow mechanisms involving thermionic emission and thermionic field emission were shown for the Cu/Au contact to low doped p-ZnSe (1 x 1017 cm--3) and three involving thermionic emission, thermionic field emission, and tunneling for the Mg/Au contact to highly doped n-ZnSe (1.15 x 1019 cm--3). MOCVD grown p-type Mg-doped GaN with hole concentration of 1.41 x 1017 cm--3 was used to study Ohmic contacts to p-type GaN. The effects of the cryogenic process on improving Ohmic behavior (I-V linearity) and reducing the specific contact resistance were investigated and may result from a combination of the improved surface morphology and the recrystallizing of new compounds such as NiO and Au:Pd solid solution. The I-V-T measurement for both contacts had similar behavior and closely fit thermionic field emission current mechanisms with little deviation but dominant transport mechanisms were not clear since the contacts were practically Ohmic. (Abstract shortened by UMI.)

  9. Cooperative autonomy for contact investigation

    E-print Network

    Schmidt, Henrik

    Autonomous surface and underwater vehicles present a safe and low-cost solution for various contact investigation tasks, such as harbor surveillance for potentially threatening small craft or submarines. Since such a task ...

  10. Elastohydrodynamic lubrication of rectangular contacts

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.; Jacobson, B. O.

    1983-01-01

    An isothermal elastohydrodynamically lubricated rectangular contact was evaluated numerically. This required the simultaneous solution of the elasticity and Reynolds equations. In the elasticity analysis the contact zone was divided into equal rectangular areas, and it was assumed that a uniform pressure was applied over each area. The elastohydrodynamic lubrication theory thus developed was used to investigate the influence of the dimensionless speed, load, and materials parameters on minimum film thickness. Ten cases were used in obtaining the minimum film thickness formula. Plots are shown that indicate the details of the pressure distribution, film shape, and flow. The characteristic pressure spike is clearly in evidence as is the parallel film shape through the central portion of the contact, with a minimum film thickness occurring near the outlet of the contact.

  11. Contact Us: MedlinePlus

    MedlinePLUS

    ... indexrwd.cfm?lang=en Contact the U.S. National Library of Medicine Thank you for visiting MedlinePlus. We ... Sierra Leone Singapore Slovakia Slovenia Solomon Islands South Africa Spain Sri Lanka Sudan Suriname Sweden Switzerland Taiwan ...

  12. Contact Lens Use in Industry

    MedlinePLUS

    ... for updates. FS96 7/10 © 2010 Prevent Blindness America ® All rights reserved. According to the Contact Lens ... Occupational Safety and Health (NIOSH). Recommendations Prevent Blindness America makes the following recommendations to management that directs ...

  13. Racial Disparity in Police Contacts

    PubMed Central

    Crutchfield, Robert D.; Haggerty, Kevin P.; McGlynn, Anne; Catalano, Richard F.

    2013-01-01

    Criminologists agree the race disparity in arrests cannot be fully explained by differences in criminal behavior. We examine social environment factors that may lead to racial differences in police contact in early adolescence, including family, peers, school, and community. Data are from 331 8th-grade students. Blacks were almost twice as likely as Whites to report a police contact. Blacks reported more property crime but not more violent crime than Whites. Police contacts were increased by having a parent who had been arrested, a sibling involved in criminal activity, higher observed reward for negative behavior, having school disciplinary actions, and knowing adults who engaged in substance abuse or criminal behavior. Race differences in police contacts were partially attributable to more school discipline. PMID:24363956

  14. Contact | Office of Cancer Genomics

    Cancer.gov

    Skip to Main Content Email Updates Glossary Contact Search Programs CGCI Overview Research Publications Resources Projects Using CGCI Data CTD² Overview Research Publications Resources Centers Using CTD² Data CTD² Publication Guidelines TARGET Overview Research Collaborators Publications Resources Projects Using

  15. NCI: SBIR & STTR - Contact Us

    Cancer.gov

    Skip to main content Sign Up for Updates | Follow us on Twitter | Connect with us on LinkedIn | Contact Us | Site Map Search About Program Information Program Structure Goals Eligibility Criteria Employment Opportunities Meet the Team Funding Opportunities Find

  16. Racial Disparity in Police Contacts.

    PubMed

    Crutchfield, Robert D; Skinner, Martie L; Haggerty, Kevin P; McGlynn, Anne; Catalano, Richard F

    2012-07-01

    Criminologists agree the race disparity in arrests cannot be fully explained by differences in criminal behavior. We examine social environment factors that may lead to racial differences in police contact in early adolescence, including family, peers, school, and community. Data are from 331 8th-grade students. Blacks were almost twice as likely as Whites to report a police contact. Blacks reported more property crime but not more violent crime than Whites. Police contacts were increased by having a parent who had been arrested, a sibling involved in criminal activity, higher observed reward for negative behavior, having school disciplinary actions, and knowing adults who engaged in substance abuse or criminal behavior. Race differences in police contacts were partially attributable to more school discipline. PMID:24363956

  17. Pose and motion from contact

    SciTech Connect

    Jia, Y.B.; Erdmann, M. [Carnegie Mellon Univ., Pittsburgh, PA (United States). Robotics Inst.] [Carnegie Mellon Univ., Pittsburgh, PA (United States). Robotics Inst.

    1999-05-01

    In the absence of vision, grasping an object often relies on tactile feedback from the fingertips. As the finger pushes the object, the fingertip can feel the contact point move. If the object is known in advance, from this motion the finger may infer the location of the contact point on the object, and thereby, the object pose. This paper primarily investigates the problem of determining the pose (orientation and position) and motion (velocity and angular velocity) of a planar object with known geometry from such contact motion generated by pushing. A dynamic analysis of pushing yields a nonlinear system that relates through contact the object pose and motion to the finger motion. The contact motion on the fingertip thus encodes certain information about the object pose. Nonlinear observability theory is employed to show that such information is sufficient for the finger to observe not only the pose, but also the motion of the object. Therefore, a sensing strategy can be realized as an observer of the nonlinear dynamic system. Two observers are subsequently introduced. The first observer, based on the work of Gautheir, Hammouri, and Othman (1992), has its gain determined by the solution of a Lyapunov-like equation; it can be activated at any time instant during a push. The second observer, based on Newton`s method, solves for the initial (motionless) object pose from three intermediate contact points during a push. Under the Coulomb-friction model, the paper deals with support friction in the plane and/or contact friction between the finger and the object. Extensive simulations have been done to demonstrate the feasibility of the two observers. Preliminary experiments (with an Adept robot) have also been conducted. A contact sensor has been implemented using strain gauges.

  18. Method for lubricating contacting surfaces

    DOEpatents

    Dugger, Michael T. (Tijeras, NM); Ohlhausen, James A. (Albuquerque, NM); Asay, David B. (Boalsburg, PA); Kim, Seong H. (State College, PA)

    2011-12-06

    A method is provided for tribological lubrication of sliding contact surfaces, where two surfaces are in contact and in motion relative to each other, operating in a vapor-phase environment containing at least one alcohol compound at a concentration sufficiently high to provide one monolayer of coverage on at least one of the surfaces, where the alcohol compound continuously reacts at the surface to provide lubrication.

  19. Contact flows and integrable systems

    NASA Astrophysics Data System (ADS)

    Jovanovi?, Božidar; Jovanovi?, Vladimir

    2015-01-01

    We consider Hamiltonian systems restricted to the hypersurfaces of contact type and obtain a partial version of the Arnold-Liouville theorem: the system need not be integrable on the whole phase space, while the invariant hypersurface is foliated on an invariant Lagrangian tori. In the second part of the paper we consider contact systems with constraints. As an example, the Reeb flows on Brieskorn manifolds are considered.

  20. 2011 Regional Competitions *Please make a copy of the completed form for your records. If your team advances to the

    E-print Network

    Miami, University of

    .* Coach Confidential Medical Information and Emergency Notification Form Name Notification Information Emergency Contact: __________________________________________ Phone:_____________________ Relationship: ___________________________________________________________________________ Medical/Hospital

  1. Epitope Mapping of M36, a Human Antibody Domain with Potent and Broad HIV-1 Inhibitory Activity

    PubMed Central

    Chen, Weizao; Yuan, Xiaohui; Chong, Huihui; Prabakaran, Ponraj; Dimitrov, Dimiter S.; He, Yuxian

    2013-01-01

    M36 is the first member of a novel class of potent HIV-1 entry inhibitors based on human engineered antibody domains (eAds). It exhibits broad inhibitory activity suggesting that its CD4-induced epitope is highly conserved. Here, we describe fine mapping of its epitope by using several approaches. First, a panel of mimotopes was affinity-selected from a random peptide library and potential m36-binding residues were computationally predicted. Second, homology modeling of m36 and molecular docking of m36 onto gp120 revealed potentially important residues in gp120-m36 interactions. Third, the predicted contact residues were verified by site-directed mutagenesis. Taken together, m36 epitope comprising three discontinuous sites including six key gp120 residues (Site C1: Thr123 and Pro124; Site C3: Glu370 and Ile371; Site C4: Met426 and Trp427) were identified. In the 3D structure of gp120, the sites C1 and C4 are located in the bridging sheet and the site C3 is within the ?15-?3 excursion, which play essential roles for the receptor- and coreceptor-binding and are major targets of neutralizing antibodies. Based on these results we propose a precise localization of the m36 epitope and suggest a mechanism of its broad inhibitory activity which could help in the development of novel HIV-1 therapeutics based on eAds. PMID:23776690

  2. Crystal structures of multidrug-resistant HIV-1 protease in complex with two potent anti-malarial compounds

    SciTech Connect

    Yedidi, Ravikiran S.; Liu, Zhigang; Wang, Yong; Brunzelle, Joseph S.; Kovari, Iulia A.; Woster, Patrick M.; Kovari, Ladislau C.; Gupta, Deepak (LECOM); (WSI); (NWU); (MUSC); (WSU)

    2012-06-19

    Two potent inhibitors (compounds 1 and 2) of malarial aspartyl protease, plasmepsin-II, were evaluated against wild type (NL4-3) and multidrug-resistant clinical isolate 769 (MDR) variants of human immunodeficiency virus type-1 (HIV-1) aspartyl protease. Enzyme inhibition assays showed that both 1 and 2 have better potency against NL4-3 than against MDR protease. Crystal structures of MDR protease in complex with 1 and 2 were solved and analyzed. Crystallographic analysis revealed that the MDR protease exhibits a typical wide-open conformation of the flaps (Gly48 to Gly52) causing an overall expansion in the active site cavity, which, in turn caused unstable binding of the inhibitors. Due to the expansion of the active site cavity, both compounds showed loss of direct contacts with the MDR protease compared to the docking models of NL4-3. Multiple water molecules showed a rich network of hydrogen bonds contributing to the stability of the ligand binding in the distorted binding pockets of the MDR protease in both crystal structures. Docking analysis of 1 and 2 showed a decrease in the binding affinity for both compounds against MDR supporting our structure-function studies. Thus, compounds 1 and 2 show promising inhibitory activity against HIV-1 protease variants and hence are good candidates for further development to enhance their potency against NL4-3 as well as MDR HIV-1 protease variants.

  3. Stapled ??helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy

    PubMed Central

    Chang, Yong S.; Graves, Bradford; Guerlavais, Vincent; Tovar, Christian; Packman, Kathryn; To, Kwong-Him; Olson, Karen A.; Kesavan, Kamala; Gangurde, Pranoti; Mukherjee, Aditi; Baker, Theresa; Darlak, Krzysztof; Elkin, Carl; Filipovic, Zoran; Qureshi, Farooq Z.; Cai, Hongliang; Berry, Pamela; Feyfant, Eric; Shi, Xiangguo E.; Horstick, James; Annis, D. Allen; Manning, Anthony M.; Fotouhi, Nader; Nash, Huw; Vassilev, Lyubomir T.; Sawyer, Tomi K.

    2013-01-01

    Stapled ??helical peptides have emerged as a promising new modality for a wide range of therapeutic targets. Here, we report a potent and selective dual inhibitor of MDM2 and MDMX, ATSP-7041, which effectively activates the p53 pathway in tumors in vitro and in vivo. Specifically, ATSP-7041 binds both MDM2 and MDMX with nanomolar affinities, shows submicromolar cellular activities in cancer cell lines in the presence of serum, and demonstrates highly specific, on-target mechanism of action. A high resolution (1.7-Å) X-ray crystal structure reveals its molecular interactions with the target protein MDMX, including multiple contacts with key amino acids as well as a role for the hydrocarbon staple itself in target engagement. Most importantly, ATSP-7041 demonstrates robust p53-dependent tumor growth suppression in MDM2/MDMX-overexpressing xenograft cancer models, with a high correlation to on-target pharmacodynamic activity, and possesses favorable pharmacokinetic and tissue distribution properties. Overall, ATSP-7041 demonstrates in vitro and in vivo proof-of-concept that stapled peptides can be developed as therapeutically relevant inhibitors of protein–protein interaction and may offer a viable modality for cancer therapy. PMID:23946421

  4. Dermatitis, contact on the cheek (image)

    MedlinePLUS

    ... skin inflammation (dermatitis) on the cheek caused by contact with a substance that produced an allergic reaction (allergen). Contact dermatitis causes redness, itching, and small blisters (vesicles).

  5. Proteinaceous complexes from mitochondrial contact sites.

    PubMed

    Vyssokikh, M Y; Goncharova, N Y; Zhuravlyova, A V; Zorova, L D; Kirichenko, V V; Krasnikov, B F; Kuzminova, A E; Melikov, K C; Melik-Nubarov, N S; Samsonov, A V; Belousov, V V; Prischepova, A E; Zorov, D B

    1999-04-01

    A Triton X-100 extract from rat brain mitochondria was obtained using low detergent/protein ratio. From this extract a proteinaceous complex was purified; its molecular weight was as high as 880 kD. The complex contained both hexokinase and creatine kinase activity. When incorporated into phospholipid bilayer membranes, the complex formed a channel whose activity was different than the channel activity of purified porin isolated either by adsorption chromatography or by dissociation from protein complexes. A ligand of the mitochondrial benzodiazepine receptor (Ro5-4864) in submicromolar concentrations had an apparent influence on the kinetic behavior of enzymatic coupling of hexokinase and creatine kinase. It is suggested that the 880-kD complex is formed by mitochondrial contact sites. The role of the isolated protein complex in the formation of nonspecific permeability in mitochondria is discussed. PMID:10231591

  6. Partial slip in mesoscale contacts: dependence on contact size.

    PubMed

    Hanke, Sylvia; Petri, Judith; Johannsmann, Diethelm

    2013-09-01

    Using acoustic resonators, we have studied the occurrence and the magnitude of partial slip between glass spheres and polymer surfaces. The measurement relies on the shifts of resonance frequency and bandwidth, ?f and ??, induced by the contact as well as the dependence of ?f and ?? on the amplitude of oscillation. One often finds a decrease of ?f at elevated amplitudes, which goes back to partial slip (also "microslip"). Building on two different models of partial slip, we derive the frequency-amplitude relation from the force-displacement relation. In accordance with both models, the bandwidth is found to increase with amplitude in the partial slip regime. For the highest amplitudes and largest spheres investigated, one observes a decrease of bandwidth with amplitude, which is interpreted as a transition to gross slip. Deviating from both models of partial slip, ?f is sometimes found to be independent of amplitude in the low-amplitude range. Constant ?f implies linear force-displacement relations. The critical amplitude for the onset of partial slip depends on the contact radius, where partial slip is more pronounced for larger contacts. This finding can be explained by a smooth stress profile at the edge of the contact with no singularity. The stress at the edge might be lowered by nanoscale roughness, by capillary forces, or by the inability of the two surfaces to reestablish a sticking contact at the turning point of the oscillation. PMID:24125277

  7. Anti-AIDS Agents 78 †. Design, Synthesis, Metabolic Stability Assessment, and Antiviral Evaluation of Novel Betulinic Acid Derivatives as Potent Anti-Human Immunodeficiency Virus (HIV) Agents

    PubMed Central

    Qian, Keduo; Yu, Donglei; Chen, Chin-Ho; Huang, Li; Morris-Natschke, Susan L.; Nitz, Theodore J.; Salzwedel, Karl; Reddick, Mary; Allaway, Graham P.; Lee, Kuo-Hsiung

    2009-01-01

    In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives, as well as seven novel 3,28-disubstituted BA analogs were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21 showed an improved solubility and equal anti-HIV potency (EC50: 0.09 ?M), when compared to HIV entry inhibitors 3b (IC9564) and 4 (A43-D). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47 and 48 displayed potent anti-HIV activity with EC50 values of 0.007 ?M and 0.006 ?M, respectively. These results are slightly better than that of bevirimat (2), which is currently in Phase IIb clinical trials. Compounds 47 and 48 should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates. PMID:19388685

  8. Contact allergic potential of topical traditional Chinese medicaments in Singapore

    Microsoft Academic Search

    Yung-Hian Leow; See-Ket Ng; Wai-Kee Wong; Chee-Leok Goh

    1995-01-01

    Background: Western-based medication forms the basis of the health care system in Singapore. However, because Singapore is part of East Asia, there is still a high prevalence of use of topical traditional Chinese medicaments by the general population.Objective: This study was designed to determine the 10 most commonly used topical traditional Chinese medicaments by patients who were attending the Contact

  9. Comparison of the electric fields of electrophotography and contact electrography

    Microsoft Academic Search

    G Bartscher; S. O Cormier; R Lyness; L. B Schein

    2001-01-01

    In order to improve the quality of text and graphic printers, companies have increased the resolution and decreased the diameter of toner particles in powder marking technologies. We have been developing a new electrographic printing technology in which the latent image is formed by contacting a write head with many metal fingers to square metal pads on 50?m centers (500dpi)

  10. Back contacts for silicon-on-ceramic solar cells

    NASA Technical Reports Server (NTRS)

    Schuller, T. L.; Marquardt, S.

    1981-01-01

    Grooved substrate exposes back surface of photovoltaic cells, allowing dopant diffusion into surface and electrical contact. When substrate is coated successively with carbon and molten silicon, polycrystalline-silicon bridges form over grooves, but leave channels open. Best adhesion results when substrate grooves run perpendicular to direction of liquid-silicon layer and are closely spaced.

  11. Non-contact type seal device for turbocharger

    Microsoft Academic Search

    K. Washimi; M. Shibata; M. Ugajin

    1987-01-01

    A non-contact type seal device is described for a turbocharger, comprising: a retainer mounted in a compressor chamber of a housing of the turbocharger; a collar attached to a compressor wheel mounting portion of a rotor shaft of the turbocharger; and a ring provided on an inner peripheral surface of the retainer, an annular groove receiving the ring being formed

  12. Non-contacting techniques for plant drought stress detection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Non-contacting sensing techniques based on plant canopy temperature, plant leaf motion, and plant canopy reflectance were evaluated for drought stress detection using New Guinea Impatiens as a model plant. The performances of Crop Water Stress Index (CWSI), plant motion in the form of Covariance of ...

  13. Modeling and Learning Contact Dynamics in Human Motion

    Microsoft Academic Search

    Alessandro Bissacco

    2005-01-01

    We propose a simple model of human motion as a switching linear dynamical system where the switches cor- respond to contact forces with the ground. This significantly improves the modeling performance when compared to simpler linear systems, with only marginal increase in com- plexity. We introduce a novel closed-form (non-iterative) algorithm to estimate the switches and learn the model pa-

  14. Irritant bullous contact dermatitis caused by a rove beetle: an illustrated clinical course.

    PubMed

    McGrath, Lindsay; Piliouras, Peter; Robertson, Ivan

    2013-05-01

    A 26-year-old Australian female traveller in Sierra Leone presented with an irritant bullous contact dermatitis consistent with paederus dermatitis. The lesions were treated with a potent topical corticosteroid with good effect. The affected area resolved in 6?weeks and hyperpigmention persisted for months until complete resolution. This dermatitis occurs when beetles of the genus Paederus (rove beetles) are crushed on the skin, releasing pederin. The same dermatitis ensues with Australian Paederus species. Serial clinical photographs are presented which will aid Australian dermatologists in the diagnosis of this dermatitis, which presents in regional Australian patients and returned overseas travellers. PMID:23581998

  15. Investigating How Contact Angle Effects the Interaction between Water and a Hydrophobic Surface

    NASA Astrophysics Data System (ADS)

    Poynor, Adele; Neidig, Caitlyn

    2012-02-01

    By definition hydrophobic substances hate water. What happens when water is forced into contact with a hydrophobic surface? One theory is that an ultra-thin low-density region forms near the surface. Contact angle is a measure of how hydrophobic a surface is. We have employed an automated home-built Surface Plasmon Resonance (SPR) apparatus to investigate the effect of varying the contact angle on the depletion layer

  16. Humidity-induced room-temperature decomposition of Au contacted indium phosphide

    NASA Technical Reports Server (NTRS)

    Fatemi, Navid S.; Weizer, Victor G.

    1990-01-01

    It has been found that Au-contacted InP is chemically unstable at room temperature in a humid ambient due to the leaching action of indium nitrate islands that continually remove In from the contact metallization and thus, in effect, from the Inp substrate. While similar appearing islands form on Au-contacted GaAs, that system appears to be stable since leaching of the group III element does not take place.

  17. Copper inclusion and migration from the back contact in CdTe solar cells

    Microsoft Academic Search

    C. R. Corwine; A. O. Pudov; M. Gloeckler; S. H. Demtsu; J. R. Sites

    2004-01-01

    Metallic back contacts to CdS\\/CdTe solar cells will in general form Schottky barriers. Better performance is achieved with the inclusion of Cu in the back contact. This study uses current–voltage, capacitance–voltage, and laser beam induced current measurements to analyze as-deposited CdS\\/CdTe solar cells prepared with varying back-contact Cu amounts and to evaluate changes in cell performance following elevated-temperature stress. A

  18. Dynamic simulation of a contact-enhanced MEMS inertial switch in Simulink ®

    Microsoft Academic Search

    Zhuoqing Yang; Haogang Cai; Guifu Ding; Hong Wang; Xiaolin Zhao

    A novel contact-enhanced design of MEMS (micro-electro-mechanical system) inertial switch was proposed and modeled in Simulink®. The contact effect is improved by an easily realized modification on the traditional design, i.e. introducing a movable\\u000a contact point between the movable electrode (proof mass) and the stationary electrode, therefore forming a dual mass-spring\\u000a system. The focus of this paper is limited to

  19. IV Characterization of selected Contacts for CdS:In Thin Films

    Microsoft Academic Search

    Shadia J. Ikhmayies; Riyad N. Ahmad-Bitar

    An investigation of selected contacts for indium-doped cadmium sulphide (CdS:In) thin films was performed through the analysis of the I-V characteristics in the dark and room-light at room temperature. Indium, aluminum and silver were selected as contacts where two strips of each metal were vacuum- evaporated on the surface of the film. All of these metals could form ohmic contacts,

  20. In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase

    PubMed Central

    Kumar, Pasupuleti Santhosh; Kumar, Yellapu Nanda; Prasad, Uppu Venkateswara; Yeswanth, Sthanikam; Swarupa, Vimjam; Sowjenya, Gopal; Venkatesh, Katari; Srikanth, Lokanathan; Rao, Valasani Koteswara; Sarma, Potukuchi Venkata Gurunatha Krishna

    2014-01-01

    Background: The emergence of multidrug-resistant strains of Staphylococcus aureus, there is an urgent need for the development of new antimicrobials which are narrow and pathogen specific. Aim: In this context, the present study is aimed to have a control on the staphylococcal infections by targeting the unique and essential enzyme; porphobilinogen synthase (PBGS) catalyzes the condensation of two molecules of ?-aminolevulinic acid, an essential step in the tetrapyrrole biosynthesis. Hence developing therapeutics targeting PBGS will be the promising choice to control and manage the staphylococcal infections. 4,5-dioxovalerate (DV) is known to inhibit PBGS. Materials and Methods: In view of this, in this study, novel dioxovalerate derivatives (DVDs) molecules were designed so as to inhibit PBGS, a potential target of S. aureus and their inhibitory activity was predicted using molecular docking studies by molecular operating environment. The 3D model of PBGS was constructed using Chlorobium vibrioform (Protein Data Bank 1W1Z) as a template by homology modeling method. Results: The built structure was close to the crystal structure with Z score ? 8.97. Molecular docking of DVDs into the S. aureus PBGS active site revealed that they are showing strong interaction forming H-bonds with the active sites of K248 and R217. The ligand–receptor complex of DVD13 showed a best docking score of ? 14.4555 kcal/mol among DV and all its analogs while the substrate showed docking score of ? 13.0392 kcal/mol showing interactions with S199, K217 indicating that DVD13 can influence structural variations on the enzyme and thereby inhibiting the enzyme. Conclusion: The substrate analog DVD13 is showing significant interactions with active site of PBGS and it may be used as a potent inhibitor to control S. aureus infections. PMID:25035635

  1. Production of the Potent Antibacterial Polyketide Erythromycin C in Escherichia coli

    PubMed Central

    Peirú, Salvador; Menzella, Hugo G.; Rodríguez, Eduardo; Carney, John; Gramajo, Hugo

    2005-01-01

    An Escherichia coli strain capable of producing the potent antibiotic erythromycin C (Ery C) was developed by expressing 17 new heterologous genes in a 6-deoxyerythronolide B (6dEB) producer strain. The megalomicin gene cluster was used as the source for the construction of two artificial operons that contained the genes encoding the deoxysugar biosynthetic and tailoring enzymes necessary to convert 6dEB to Ery C. The reconstructed mycarose operon contained the seven genes coding for the enzymes that convert glucose-1-phosphate (G-1-P) to TDP-l-mycarose, a 6dEB mycarosyl transferase, and a 6dEB 6-hydroxylase. The activity of the pathway was confirmed by demonstrating conversion of exogenous 6dEB to 3-O-?-mycarosylerythronolide B (MEB). The reconstructed desosamine operon contained the six genes necessary to convert TDP-4-keto-6-deoxyglucose, an intermediate formed in the mycarose pathway, to TDP-d-desosamine, a desosamine transferase, a 6dEB 12-hydroxylase, and the rRNA methyltransferase ErmE; the last was required to confer resistance to the host cell upon production of mature macrolide antibiotics. The activity of this pathway was demonstrated by conversion of MEB to Ery C. When the mycarose and desosamine operons were expressed in an E. coli strain engineered to synthesize 6dEB, Ery C and Ery D were produced. The successful production of Ery C in E. coli shows the potentiality of this model microorganism to synthesize novel 6-deoxysugars and to produce bioactive glycosylated compounds and also establishes the basis for the future use of E. coli both in the production of new glycosylated polyketides and for the generation of novel bioactive compounds through combinatorial biosynthesis. PMID:15870344

  2. Potent cyclic enkephalin analogues for delta opioid receptors in the rat brain

    SciTech Connect

    Lui, G.; Kao, J.; Hruby, V.; Morelli, M.; Gulya, K.; Yamamura, H.I.

    1986-03-01

    (/sup 3/H) (D-Pen/sup 2/,D-Pen/sup 5/) enkephalin ((/sup 3/H)DPDPE) and (/sup 3/H) (D-Pen/sup 2/, L-Pen/sup 5/) enkephalin ((/sup 3/H)DPLPE) characterization studies showed high affinity binding of these radioligands to rat brain membranes with dissociation constants of 1.8 and 1.0 nM, respectively, while a similar number of receptor density was found with both radiolabeled ligands (77 fmoles/mg protein). Unlabeled DPDPE inhibited both radioligands with high affinity (IC50 = 7 nM0 while morphine (IC50 = 80 nM), DAGO (IC50 = 250 nM) and PLO17 (no inhibition at 1000 nM) were less effective in inhibiting the binding, thus, illustrating the selective action of these radiolabeled ligands at the delta opioid receptor. A series of conformationally restricted D-penicillamine containing cyclic enkephalin analogues were synthesized using standard solid phase methods and their ability to inhibit (/sup 3/H)DPDPE and (/sup 3/H)DPLPE were examined in rat brain radioreceptor assays. Substitutions in the DPDPE molecule were made in phe/sup 4/. These substitutions were pNO/sub 2/-phe/sup 4/, beta-methyl-phe/sup 4/, pNO/sub 2/-beta-methyl-phe/sub 4/, pNO/sub 2/-beta-methyl-phe/sup 4/ (three isomeric forms: A,B,D). The IC50 values for the above enkephalin analogues were 3.7, 16, 7, 7, 200 nM, respectively. Thus, these potent analogues of DPDPE should be useful in determining the structure activity relationships of the delta opioid receptor in rat brain.

  3. Potent infection reservoir of crayfish plague now permanently established in Norway.

    PubMed

    Vrålstad, Trude; Johnsen, Stein I; Fristad, Rosa Ferreira; Edsman, Lennart; Strand, David

    2011-11-01

    Noble crayfish Astacus astacus is threatened in Europe due to invasive crayfish carrying the crayfish plague agent Aphanomyces astaci. Norway is among the last countries in which the introduction of non-indigenous crayfish has been limited through strict legislation practices. However, North American signal crayfish Pacifastacus leniusculus were recently discovered in a water-course that has been repeatedly hit by the plague. We mapped the distribution and relative density (catch per unit effort) of signal crayfish within this lake, and performed agent-specific real-time PCR to estimate the prevalence of A. astaci in the population. The resulting length frequencies and relative density estimates clearly demonstrate a well-established signal crayfish population, in which 86.4% of the analysed individuals were confirmed carriers. The success of detection was significantly higher (84.1%) in the crayfish tailfan (i.e. uropods) than in the soft abdominal cuticle (38.4%), which is commonly used in prevalence studies. We therefore propose tailfan (uropods and telson) as the preferred tissue for studying A. astaci prevalence in signal crayfish populations. The likelihood of detecting an A. astaci-positive signal crayfish increased significantly with increasing crayfish length. Further, large female crayfish expressed significantly higher PCR-forming units values than large males. In surveys primarily exploring the presence of A. astaci-positive individuals in a population, large females should be selected for molecular analyses. Our study demonstrates that a potent crayfish plague infection reservoir, evidently originating from the illegal human introduction of signal crayfish, has permanently been established in Norway. PMID:22235597

  4. Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo

    PubMed Central

    Abbas, Atheir I.; Hedlund, Peter B.; Huang, Xi-Ping; Tran, Thuy B.; Meltzer, Herbert Y.; Roth, Bryan L.

    2010-01-01

    Rationale Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy. Amisulpride has also been demonstrated to be an antidepressant for patients with major depression in many clinical trials. In part because of the selective D2/D3 receptor antagonist properties of amisulpride, it has long been widely assumed that dopaminergic modulation is the proximal event responsible for mediating its antidepressant and antipsychotic properties. Objectives The purpose of these studies was to determine if amisulpride’s antidepressant actions are mediated by off-target interactions with other receptors. Materials and Methods We performed experiments that: (1) examined the pharmacological profile of amisulpride at a large number of CNS molecular targets and (2) after finding high potency antagonist affinity for human 5-HT7a serotonin receptors, characterized the actions of amisulpride as an antidepressant in wild-type and 5-HT7 receptor knock-out mice. Results We discovered that amisulpride was a potent competitive antagonist at 5-HT7a receptors and that interactions with no other molecular target investigated here could explain its antidepressant actions in vivo. Significantly, and in contrast to their wildtype littermates, 5-HT7 receptor knockout mice did not respond to amisulpride in a widely used rodent model of depression, the tail suspension test. Conclusions These results indicate that 5-HT7a receptor antagonism, and not D2/D3 receptor antagonism, likely underlies the antidepressant actions of amisulpride. PMID:19337725

  5. Imaging surface contacts: Power law contact distributions and contact stresses in quartz, calcite, glass and acrylic plastic

    USGS Publications Warehouse

    Dieterich, J.H.; Kilgore, B.D.

    1996-01-01

    A procedure has been developed to obtain microscope images of regions of contact between roughened surfaces of transparent materials, while the surfaces are subjected to static loads or undergoing frictional slip. Static loading experiments with quartz, calcite, soda-lime glass and acrylic plastic at normal stresses to 30 MPa yield power law distributions of contact areas from the smallest contacts that can be resolved (3.5 ??m2) up to a limiting size that correlates with the grain size of the abrasive grit used to roughen the surfaces. In each material, increasing normal stress results in a roughly linear increase of the real area of contact. Mechanisms of contact area increase are by growth of existing contacts, coalescence of contacts and appearance of new contacts. Mean contacts stresses are consistent with the indentation strength of each material. Contact size distributions are insensitive to normal stress indicating that the increase of contact area is approximately self-similar. The contact images and contact distributions are modeled using simulations of surfaces with random fractal topographies. The contact process for model fractal surfaces is represented by the simple expedient of removing material at regions where surface irregularities overlap. Synthetic contact images created by this approach reproduce observed characteristics of the contacts and demonstrate that the exponent in the power law distributions depends on the scaling exponent used to generate the surface topography.

  6. Part I: pathogenetic role of peroxynitrite in the development of diabetes and diabetic vascular complications: studies with FP15, a novel potent peroxynitrite decomposition catalyst.

    PubMed Central

    Szabó, Csaba; Mabley, Jon G.; Moeller, Suzanne M.; Shimanovich, Roman; Pacher, Pál; Virag, László; Soriano, Francisco G.; Van Duzer, John H.; Williams, William; Salzman, Andrew L.; Groves, John T.

    2002-01-01

    BACKGROUND: Peroxynitrite is a cytotoxic oxidant formed from nitric oxide (NO) and superoxide. Tyrosine nitration, a footprint of peroxynitrite, has been demonstrated in the pancreatic islets as well as in the cardiovascular system of diabetic subjects. Delineation of the pathogenetic role of peroxynitrite in disease conditions requires the use of potent, in vivo active peroxynitrite decomposition catalysts. The aim of the current work was to produce a potent peroxynitrite decomposition catalyst and to test its effects in rodent models of diabetes and its complications. METHODS: FP15 was synthesized and analyzed using standard chemical methods. Diabetes was triggered by the administration of streptozotocin. Tyrosine nitration was measured immunohistochemically. Cardiovascular and vascular measurements were conducted according to standard physiologic methods. RESULTS: FP15, a potent porphyrinic peroxynitrite decomposition catalyst, potently inhibited tyrosine nitration and peroxynitrite-induced cytotoxicity in vitro and in vivo. FP15 treatment (3-10 mg/kg/d) dose dependently and reduced the incidence and severity of diabetes mellitus in rats subjected to multiple low doses of streptozotocin, as well as in nonobese mice developing spontaneous autoimmune diabetes. Furthermore, treatment with FP15 protected against the development of vascular dysfunction (loss of endothelium-dependent relaxations) and the cardiac dysfunction (loss of myocardial contractility) in diabetic mice. FP15 treatment reduced tyrosine nitration in the diabetic pancreatic islets. CONCLUSIONS: The current results demonstrate the importance of endogenous peroxynitrite generation in the pathogenesis of autoimmune diabetes and diabetic cardiovascular complications. Peroxynitrite decomposition catalysts may be of therapeutic utility in diabetes and other pathophysiologic conditions. PMID:12477967

  7. Microdroplet evaporation with a forced pinned contact line.

    PubMed

    Gleason, Kevin; Putnam, Shawn A

    2014-09-01

    Experimental and numerical investigations of water microdroplet evaporation on heated, laser patterned polymer substrates are reported. The study is focused on both (i) controlling a droplet's contact line dynamics during evaporation to identifying how the contact line influences evaporative heat transfer and (ii) validating numerical simulations with experimental data. Droplets are formed on the polymer surface using a bottom-up methodology, where a computer-controlled syringe pump feeds water through a 200 ?m diameter fluid channel within the heated polymer substrate. This methodology facilitates precise control of the droplet's growth rate, size, and inlet temperature. In addition to this microchannel supply line, the substrate surfaces are laser patterned with a moatlike trench around the fluid-channel outlet, adding additional control of the droplet's contact line motion, area, and contact angle. In comparison to evaporation on a nonpatterned polymer surface, the laser patterned trench increases contact line pinning time by ?60% of the droplet's lifetime. Numerical simulations of diffusion controlled evaporation are compared the experimental data with a pinned contact line. These diffusion based simulations consistently over predict the droplet's evaporation rate. In efforts to improve this model, a temperature distribution along the droplet's liquid-vapor interface is imposed to account for the concentration distribution of saturated vapor along the interface, which yields improved predictions within 2-4% of the experimental data throughout the droplet's lifetime on heated substrates. PMID:25102248

  8. Contact electrification of insulating materials

    NASA Astrophysics Data System (ADS)

    Lacks, Daniel J.; Mohan Sankaran, R.

    2011-11-01

    The electrostatic charge that is generated when two materials are contacted or rubbed and then separated is a well-known physical process that has been studied for more than 2500 years. Contact electrification occurs in many contexts, both natural and technological. For example, in dust storms the collisions between particles lead to electrostatic charging and in extreme cases, extraordinary lightning displays. In electrophotography, toner particles are intentionally charged to guide their deposition in well-defined patterns. Despite such a long history and so many important consequences, a fundamental understanding of the mechanism behind contact electrification remains elusive. An open question is what type of species are transferred between the surfaces to generate charge—experiments suggest various species ranging from electrons to ions to nanoscopic bits of material, and theoretical work suggests that non-equilibrium states may play an important role. Another open question is the contact electrification that occurs when two insulating materials with identical physical properties touch—since there is no apparent driving force, it is not clear why charge transfer occurs. A third open question involves granular systems—models and experiments have shown that a particle-size dependence for the charging often exists. In this review, we discuss the fundamental aspects of contact electrification and highlight recent research efforts aimed at understanding these open questions.

  9. Heavy metal ions are potent inhibitors of protein folding

    SciTech Connect

    Sharma, Sandeep K. [Biochemisches Institut, Universitaet Zuerich, CH-8057 Zuerich (Switzerland); Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne (Switzerland); Goloubinoff, Pierre [Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne (Switzerland); Christen, Philipp [Biochemisches Institut, Universitaet Zuerich, CH-8057 Zuerich (Switzerland)], E-mail: christen@bioc.uzh.ch

    2008-07-25

    Environmental and occupational exposure to heavy metals such as cadmium, mercury and lead results in severe health hazards including prenatal and developmental defects. The deleterious effects of heavy metal ions have hitherto been attributed to their interactions with specific, particularly susceptible native proteins. Here, we report an as yet undescribed mode of heavy metal toxicity. Cd{sup 2+}, Hg{sup 2+} and Pb{sup 2+} proved to inhibit very efficiently the spontaneous refolding of chemically denatured proteins by forming high-affinity multidentate complexes with thiol and other functional groups (IC{sub 50} in the nanomolar range). With similar efficacy, the heavy metal ions inhibited the chaperone-assisted refolding of chemically denatured and heat-denatured proteins. Thus, the toxic effects of heavy metal ions may result as well from their interaction with the more readily accessible functional groups of proteins in nascent and other non-native form. The toxic scope of heavy metals seems to be substantially larger than assumed so far.

  10. Reliability of Semiautomated Computational Methods for Estimating Tibiofemoral Contact Stress in the Multicenter Osteoarthritis Study

    PubMed Central

    Anderson, Donald D.; Segal, Neil A.; Kern, Andrew M.; Nevitt, Michael C.; Torner, James C.; Lynch, John A.

    2012-01-01

    Recent findings suggest that contact stress is a potent predictor of subsequent symptomatic osteoarthritis development in the knee. However, much larger numbers of knees (likely on the order of hundreds, if not thousands) need to be reliably analyzed to achieve the statistical power necessary to clarify this relationship. This study assessed the reliability of new semiautomated computational methods for estimating contact stress in knees from large population-based cohorts. Ten knees of subjects from the Multicenter Osteoarthritis Study were included. Bone surfaces were manually segmented from sequential 1.0 Tesla magnetic resonance imaging slices by three individuals on two nonconsecutive days. Four individuals then registered the resulting bone surfaces to corresponding bone edges on weight-bearing radiographs, using a semi-automated algorithm. Discrete element analysis methods were used to estimate contact stress distributions for each knee. Segmentation and registration reliabilities (day-to-day and interrater) for peak and mean medial and lateral tibiofemoral contact stress were assessed with Shrout-Fleiss intraclass correlation coefficients (ICCs). The segmentation and registration steps of the modeling approach were found to have excellent day-to-day (ICC 0.93–0.99) and good inter-rater reliability (0.84–0.97). This approach for estimating compartment-specific tibiofemoral contact stress appears to be sufficiently reliable for use in large population-based cohorts. PMID:23097679

  11. Impact of fretting parameters on contact degradation

    Microsoft Academic Search

    Robert D. Malucci

    1996-01-01

    Two previously developed models, dealing with contact resistance and oxide build-up under fretting conditions, were refined and combined into a single analytical model. This model was used to predict the average effects of contact force and fretting amplitude on contact degradation. The results from fretting tests on specially prepared tin plated contacts were explained within the framework of this model.

  12. Advanced friction modeling for sheet metal forming

    Microsoft Academic Search

    J. Hol; M. V. Cid Alfaro; M. B. de Rooij; T. Meinders

    2011-01-01

    The Coulomb friction model is frequently used for sheet metal forming simulations. This model incorporates a constant coefficient of friction and does not take the influence of important parameters such as contact pressure or deformation of the sheet material into account. This article presents a more advanced friction model for large-scale forming simulations based on the surface changes on the

  13. UC Davis MIND Institute Donor Payment Form

    E-print Network

    Leistikow, Bruce N.

    UC Davis MIND Institute Donor Payment Form Contact Information: Name the need is greatest within MIND Institute (ND40567) ADHD (ADHDMND) Autism (AUTISM1) Chromosome 22q11: ____________________________ (Please Specify) Send the completed form to: c/o UC Davis MIND Institute Health Science Advancement 4900

  14. Elastic and plastic strains in Al\\/TiW\\/Si contacts during thermal cycles

    Microsoft Academic Search

    S. Berger

    2000-01-01

    Al\\/TiW\\/Si contacts are widely used in microelectronic devices. In spite of the thorough knowledge on the microstructure, composition and electrical properties of these contacts there is almost no knowledge on their elastic and plastic strains formed during and after thermal treatments. Such data is very valuable for optimization of the fabrication process and the operation conditions. This paper presents results

  15. For more information on E-Verify, please contact DHS at

    E-print Network

    For more information on E-Verify, please contact DHS at: 1-888-464-4218 We Participate in E of Homeland Security (DHS), with information from each applicant's Form I-9 to confirm work authorization to provide you written instructions and an opportunity to contact SSA and/or DHS before taking adverse action

  16. For more information on E-Verify, please contact DHS at

    E-print Network

    Bieber, Michael

    For more information on E-Verify, please contact DHS at: 1-888-464-4218 Participates in E, the Department of Homeland Security (DHS), with information from each new employee's Form I-9 to confirm work is required to provide you written instructions and an opportunity to contact SSA and/or DHS before taking

  17. Study of an Engineering Mixed Contact: Part I-Theoretical Analysis

    Microsoft Academic Search

    Yongbin Zhang

    2007-01-01

    The present study presents theoretical analysis of an engineering mixed lubrication contact in one-dimensional case between a deformable plane of regular roughness and an ideally smooth rigid plane. The roughness of the plane, respectively take the forms of triangle and truncated triangle ridges which are evenly distributed on the plane surface. The rough plane is assumed as elastic-plastic. The contact

  18. Bacterial interactions with contact lenses; effects of lens material, lens wear and microbial physiology

    Microsoft Academic Search

    M. D. P Willcox; N Harmis; B. A Cowell; T Williams; B. A Holden

    2001-01-01

    Contact lens wear is a successful form of vision correction. However, adverse responses can occur during wear. Many of these adverse responses are produced as a consequence of bacterial colonization of the lens. The present study demonstrated that during asymptomatic contact lens wear lenses are colonized by low levels of bacteria with gram-positive bacteria, such as coagulase negative staphylococci, predominating.

  19. EFFECT OF BACK-CONTACT COPPER CONCENTRATION ON CdTe CELL OPERATION

    E-print Network

    Sites, James R.

    EFFECT OF BACK-CONTACT COPPER CONCENTRATION ON CdTe CELL OPERATION A.O. Pudov, M. Gloeckler, S of Mechanical Engineering Colorado State University, Ft. Collins, CO 80523 ABSTRACT CdTe solar cells were Copper is commonly used to form low-barrier contacts to p-type CdTe absorbers. Copper, however, is a fast

  20. Contact pressure evolution at the die radius in sheet metal stamping

    Microsoft Academic Search

    Michael P. Pereira; John L. Duncan; Wenyi Yan; Bernard F. Rolfe

    2009-01-01

    The contact conditions at the die radius are of primary importance to the wear response for many sheet metal forming processes. In particular, a detailed understanding of the contact pressure at the wearing interface is essential for the application of representative wear tests, the use of wear resistant materials and coatings, the development of suitable wear models, and for the

  1. A survey of ohmic contacts to III-V compound semiconductors

    SciTech Connect

    Baca, A.G.; Zolper, J.C.; Briggs, R.D. [Sandia National Labs., Albuquerque, NM (United States); Ren, F. [Lucent Technologies, Murray Hill, NJ (United States); Pearton, S.J. [Univ. of Florida, Gainesville, FL (United States)

    1997-04-01

    A survey of ohmic contact materials and properties to GaAs, InP, GaN will be presented along with critical issues pertaining to each semiconductor material. Au-based alloys (e.g., GeAuNi for n-type GaAs) are the most commonly used contacts for GaAs and InP materials for both n- and p-type contacts due to the excellent contact resistivity, reliability, and usefulness over a wide range of doping levels. Research into new contacting schemes for these materials has focused on addressing limitations of the conventional Au-alloys in thermal stability, propensity for spiking, poor edge definition, and new approaches for a non-alloyed contact. The alternative contacts to GaAs and InP include alloys with higher temperature stability, contacts based on solid phase regrowth, and contacts that react with the substrate to form lower bandgap semiconductors alloys at the interface. A new area of contact studies is for the wide bandgap group III-Nitride materials. At present, low resistivity ohmic contact to p-type GaN has not been obtained primarily due to the large acceptor ionization energy and the resultant difficulty in achieving high free hole concentrations at room temperature. For n-type GaN, however, significant progress has been reported with reactive Ti-based metalization schemes or the use of graded InGaN layers. The present status of these approaches will be reviewed.

  2. Contact Bubble Bilayers with Flush Drainage

    PubMed Central

    Iwamoto, Masayuki; Oiki, Shigetoshi

    2015-01-01

    Planar lipid bilayers have been used to form stable bilayers into which membrane proteins are reconstituted for measurements of their function under an applied membrane potential. Recently, a lipid bilayer membrane is formed by the apposition of two monolayers that line an oil-electrolyte interface. Here, a bilayer membrane system is developed with picoliter bubbles under mechanically and chemically manipulable conditions. A water bubble lined with a phospholipid monolayer is blown from a glass pipette into an oil phase. Two blowing pipettes are manipulated, and bubbles (each with a diameter of ~ 50??m) are held side by side to form a bilayer, which is termed a contact bubble bilayer. With the electrode implemented in the blowing pipette, currents through the bilayer are readily measured. The intra-bubble pressure is varied with the pressure-controller, leading to various sizes of the bubble and the membrane area. A rapid solution exchange system is developed by introducing additional pressure-driven injection pipettes, and the blowing pipette works as a drain. The solution is exchanged within 20?ms. Also, an asymmetric membrane with different lipid composition of each leaflet is readily formed. Example applications of this versatile method are presented to characterize the function of ion channels. PMID:25772819

  3. Rolling Contact Force Energy Reconstruction

    NASA Astrophysics Data System (ADS)

    BRACCIALI, A.; CASCINI, G.

    2000-09-01

    Knowledge of the forces at the wheel-rail contact is fundamental to estimate the consequences in terms of noise and vibration. The traditional use of strain gauges mounted on the wheel web and axle is not capable of determining the high-frequency content of the contact force. Measurements made on the rail are characterized by the spatial variability of input-output transfer functions which makes it difficult to estimate the contact force by simple inversion of the point frequency response function. In this study the problem of rolling contact force reconstruction has been approached through the following steps: (i) the track has been characterized precisely for a finite length by the analysis of the time series of several impacts supplied with an instrumented hammer by using an ARMAX model that proved to be capable of modelling the vertical dynamics of the rail up to 5 kHz; (ii) the response of the rail has been simulated with a random force acting on the system, and the variability of the transfer function has been taken into account by distributing the force on adjacent elements; (iii) the simulated response has been compared with the rail acceleration measured for the passage of several trains; (iv) the wheel-rail contact force has been estimated with a closed-loop algorithm. It has thus been possible to reconstruct the13octave power spectrum of contact forces with a simple and stable iterative procedure. Forces reconstructed from different sensors were found to be practically the same for a given wheel; forces from nominally similar wheels are statistically examined and partial results of comparisons made on different rolling stock are shown.

  4. The Role of Contact Angle on the Depletion Layer when at the Interface Between Water and a Hydrophobic Surface

    NASA Astrophysics Data System (ADS)

    Poynor, Adele; Brown, Erin; Petersen, Shannon; McNany, Dylan

    2014-03-01

    By definition hydrophobic substances hate water. Water placed on a hydrophobic surface will form a drop in order to minimize its contact area. What happens when water is forced into contact with a hydrophobic surface? One theory is that an ultra-thin low-density depletion layer forms near the surface. We investigate the role of contact angle on depletion layer formation using the surface sensitive technique of Surface Plasmon Resonance

  5. The Role of Contact Angle on the Depletion Layer when at the Interface Between Water and a Hydrophobic Surface

    NASA Astrophysics Data System (ADS)

    Poynor, Adele; Petersen, Shannon; Ollander, Brooke

    2015-03-01

    By definition hydrophobic substances hate water. Water placed on a hydrophobic surface will form a drop in order to minimize its contact area. What happens when water is forced into contact with a hydrophobic surface? One theory is that an ultra-thin low-density depletion layer forms near the surface. We investigate the role of contact angle on depletion layer formation using the surface sensitive technique of Surface Plasmon Resonance.

  6. Contacts de langues et representations (Language Contacts and Representations).

    ERIC Educational Resources Information Center

    Matthey, Marinette, Ed.

    1997-01-01

    Essays on language contact and the image of language, entirely in French, include: "Representations 'du' contexte et representations 'en' contexte? Eleves et enseignants face a l'apprentissage de la langue" ("Representations 'of' Context or Representations 'in' Context? Students and Teachers Facing Language Learning" (Laurent Gajo); "Le crepuscule…

  7. Discovery and optimization of potent and selective triazolopyridazine series of c-Met inhibitors.

    PubMed

    Boezio, Alessandro A; Berry, Loren; Albrecht, Brian K; Bauer, David; Bellon, Steven F; Bode, Christiane; Chen, April; Choquette, Deborah; Dussault, Isabelle; Fang, Mei; Hirai, Satoko; Kaplan-Lefko, Paula; Larrow, Jay F; Lin, Min-Hwa Jasmine; Lohman, Julia; Potashman, Michele H; Qu, Yusheng; Rex, Karen; Santostefano, Michael; Shah, Kavita; Shimanovich, Roman; Springer, Stephanie K; Teffera, Yohannes; Yang, Yajing; Zhang, Yihong; Harmange, Jean-Christophe

    2009-11-15

    Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. We previously showed that O-linked triazolopyridazines can be potent inhibitors of c-Met. Herein, we report the discovery of a related series of N-linked triazolopyridazines which demonstrate nanomolar inhibition of c-Met kinase activity and display improved pharmacodynamic profiles. Specifically, the potent time-dependent inhibition of cytochrome P450 associated with the O-linked triazolopyridazines has been eliminated within this novel series of inhibitors. N-linked triazolopyridazine 24 exhibited favorable pharmacokinetics and displayed potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver PD model. Once-daily oral administration of 24 for 22days showed significant tumor growth inhibition in an NIH-3T3/TPR-Met xenograft mouse efficacy model. PMID:19819693

  8. Contacts of space--times

    SciTech Connect

    Maia, M.D.

    1981-03-01

    The concept of contact between manifolds is applied to space--times of general relativity. For a given background space--time a contact approximation of second order is defined and interpreted both from the point of view of a metric pertubation and of a higher order tangent manifold. In the first case, an application to the high frequency gravitational wave hypothesis is suggested. In the second case, a constant curvature tangent bundle is constructed and suggested as a means to define a ten parameter local space--time symmetry.

  9. Non- contacting capacitive diagnostic device

    DOEpatents

    Ellison, Timothy

    2005-07-12

    A non-contacting capacitive diagnostic device includes a pulsed light source for producing an electric field in a semiconductor or photovoltaic device or material to be evaluated and a circuit responsive to the electric field. The circuit is not in physical contact with the device or material being evaluated and produces an electrical signal characteristic of the electric field produced in the device or material. The diagnostic device permits quality control and evaluation of semiconductor or photovoltaic device properties in continuous manufacturing processes.

  10. Nanotechnology and Food Contact Materials

    NASA Astrophysics Data System (ADS)

    Papaspyrides, Constantine (Costas) D.

    2010-06-01

    The use of nanotechnology in food contact materials is highlighted in relation to novel applications and potential implications for consumer safety and regulatory controls. Nanotechnology applications are expected to bring a range of benefits to the food sector, including improved packaging, antimicrobial properties, traceability and security of food products. The toxicological nature of hazard, likelihood of exposure and risk to consumers from nanotechnology-derived food/food packaging are largely unknown and this work highlights the benefits of nanotechnology in food contact materials but also the gaps in knowledge regarding consumers safety that require further research.

  11. Stabilization of the potent odorant 2-acetyl-1-pyrroline and structural analogues by complexation with zinc halides.

    PubMed

    Fang, Ming-Chih; Cadwallader, Keith R

    2014-09-01

    2-Acetyl-1-pyrroline (2AP) and the structurally similar compounds 6-acetyl-2,3,4,5-tetrahydropyridine (ATHP, along with its tautomer 6-acetyl-1,2,3,4-tetrahydropyridine), 2-propionyl-1-pyrroline (2PP), and 2-acetyl-2-thiazoline (2A2T) are well-known potent odorants in various food products. However, due to the highly unstable nature of these compounds, especially 2AP and ATHP, they are scarcely used commercially in flavor formulations. A novel and attractive method for the stabilization of these potent odorants in dry powder form is presented. Coordination of 2AP, ATHP, 2PP, and 2A2T to zinc ions (ZnI2, ZnBr2, or ZnCl2) resulted in the formation in high yields of stable crystalline complexes, which upon hydration release the free odorant. Infrared spectroscopy was used to study the coordination complexes. 2AP contains donor atoms, which coordinate (with covalent character) through both the heterocyclic nitrogen and carbonyl oxygen atoms to the zinc ion. This is also the case for ATHP and 2PP, but not for 2A2T, because the sulfur group in 2A2T provides a third possible donor site. Stability studies showed that the 2AP-ZnI2 complex (with 14% loading) maintained >94% retention of 2AP after 3 months of storage at ambient temperature in a dry environment. Meanwhile, the ATHP-ZnI2 complex was similarly stable and retained 89% of the ATHP after 3 months of storage. This stabilization technology may enable the commercial use of this powerful aroma compound as a flavoring agent. PMID:25147956

  12. A novel bacteriophage Tail-Associated Muralytic Enzyme (TAME) from Phage K and its development into a potent antistaphylococcal protein

    PubMed Central

    2011-01-01

    Background Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. However, the rapid emergence of antibiotic resistance limits the choice of therapeutic options for treating infections caused by this organism. Muralytic enzymes from bacteriophages have recently gained attention for their potential as antibacterial agents against antibiotic-resistant gram-positive organisms. Phage K is a polyvalent virulent phage of the Myoviridae family that is active against many Staphylococcus species. Results We identified a phage K gene, designated orf56, as encoding the phage tail-associated muralytic enzyme (TAME). The gene product (ORF56) contains a C-terminal domain corresponding to cysteine, histidine-dependent amidohydrolase/peptidase (CHAP), which demonstrated muralytic activity on a staphylococcal cell wall substrate and was lethal to S. aureus cells. We constructed N-terminal truncated forms of ORF56 and arrived at a 16-kDa protein (Lys16) that retained antistaphylococcal activity. We then generated a chimeric gene construct encoding Lys16 and a staphylococcal cell wall-binding SH3b domain. This chimeric protein (P128) showed potent antistaphylococcal activity on global clinical isolates of S. aureus including methicillin-resistant strains. In addition, P128 was effective in decolonizing rat nares of S. aureus USA300 in an experimental model. Conclusions We identified a phage K gene that encodes a protein associated with the phage tail structure. The muralytic activity of the phage K TAME was localized to the C-terminal CHAP domain. This potent antistaphylococcal TAME was combined with an efficient Staphylococcus-specific cell-wall targeting domain SH3b, resulting in the chimeric protein P128. This protein shows bactericidal activity against globally prevalent antibiotic resistant clinical isolates of S. aureus and against the genus Staphylococcus in general. In vivo, P128 was efficacious against methicillin-resistant S. aureus in a rat nasal colonization model. PMID:21985151

  13. Synthetic analogues of the marine bisindole deoxytopsentin: potent selective inhibitors of MRSA pyruvate kinase.

    PubMed

    Veale, Clinton G L; Zoraghi, Roya; Young, Ryan M; Morrison, James P; Pretheeban, Manoja; Lobb, Kevin A; Reiner, Neil E; Andersen, Raymond J; Davies-Coleman, Michael T

    2015-03-27

    As part of an ongoing study to elucidate the SAR of bisindole alkaloid inhibitors against the evolutionary conserved MRSA pyruvate kinase (PK), we present here the synthesis and biological activity of six dihalogenated analogues of the naturally occurring sponge metabolite deoxytopsentin, including the naturally occurring dibromodeoxytopsentin. The most active compounds displayed potent low nanomolar inhibitory activity against MRSA PK with concomitant significant selectivity for MRSA PK over human PK orthologues. Computational studies suggest that these potent MRSA PK inhibitors occupy a region of the small interface of the enzyme tetramer where amino acid sequence divergence from common human PK orthologues may contribute to the observed selectivity. PMID:25372480

  14. Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants

    SciTech Connect

    Su, Dai-Shi; Lim, John J.; Tinney, Elizabeth; Wan, Bang-Lin; Young, Mary Beth; Anderson, Kenneth D.; Rudd, Deanne; Munshi, Vandna; Bahnck, Carolyn; Felock, Peter J.; Lu, Meiqing; Lai, Ming-Tain; Touch, Sinoeun; Moyer, Gregory; DiStefano, Daniel J.; Flynn, Jessica A.; Liang, Yuexia; Sanchez, Rosa; Prasad, Sridhar; Yan, Youwei; Perlow-Poehnelt, Rebecca; Torrent, Maricel; Miller, Mike; Vacca, Joe P.; Williams, Theresa M.; Anthony, Neville J.; Merck

    2010-09-27

    Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key elements of multidrug regimens, called HAART (Highly Active Antiretroviral Therapy), that are used to treat HIV-1 infections. Elucidation of the structure-activity relationships of the thiocarbamate moiety of the previous published lead compound 2 provided a series of novel tetrahydroquinoline derivatives as potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells. The SAR optimization, mutation profiles, preparation of compounds, and pharmacokinetic profile of compounds are described.

  15. Contact Analysis for the Critical Shoulder Height in Angular Contact Ball Bearing

    Microsoft Academic Search

    Jae Seob Kwak; Tae Wan Kim

    2011-01-01

    A method to determine the shoulder height in an angular contact ball bearing using a 3D contact analysis is proposed. The load analysis is performed by calculating the distributions of internal loads and contact angles for each rolling element. From the results of the bearing load analysis and the contact geometry between the ball and raceways, 3D contact analyses using

  16. Measurement of Contact Resistance Distribution in Fretting Corrosion Track for the Tin Plated Contacts

    Microsoft Academic Search

    Soushi Masui; Shigeru Sawada; Terutaka Tamai; Yasuhiro Hattori; Kazuo Iida

    2011-01-01

    It is observed that contact resistance of tin plated contact in automotive connectors increased due to fretting corrosion, which is originated from heat cycle or vibration. In this study, the measurement condition is established to obtain the contact resistance distribution on fretting corrosion trace of tin plated contact in order to clarify the relationship between contact resistance and oxide formation.

  17. Optical interferometry study of film formation in lubrication of sliding and/or rolling contacts

    NASA Technical Reports Server (NTRS)

    Stejskal, E. O.; Cameron, A.

    1972-01-01

    Seventeen fluids of widely varying physical properties and molecular structure were chosen for study. Film thickness and traction were measured simultaneously in point contacts by interferometry, from which a new theory of traction was proposed. Film thickness was measured in line contacts by interferometry and electrical capacitance to establish correlation between these two methods. An interferometric method for the absolute determination of refractive index in the contact zone was developed and applied to point contact fluid entrapments. Electrical capacitance was used to study the thickness and properties of the soft surface film which sometimes forms near a metal-fluid interface.

  18. Dual ohmic contact to N- and P-type silicon carbide

    NASA Technical Reports Server (NTRS)

    Okojie, Robert S. (Inventor)

    2013-01-01

    Simultaneous formation of electrical ohmic contacts to silicon carbide (SiC) semiconductor having donor and acceptor impurities (n- and p-type doping, respectively) is disclosed. The innovation provides for ohmic contacts formed on SiC layers having n- and p-doping at one process step during the fabrication of the semiconductor device. Further, the innovation provides a non-discriminatory, universal ohmic contact to both n- and p-type SiC, enhancing reliability of the specific contact resistivity when operated at temperatures in excess of 600.degree. C.

  19. Hydrogen sulfide as a potent cardiovascular protective agent.

    PubMed

    Yu, Xiao-Hua; Cui, Li-Bao; Wu, Kai; Zheng, Xi-Long; Cayabyab, Francisco S; Chen, Zhi-Wei; Tang, Chao-Ke

    2014-11-01

    Hydrogen sulfide (H2S) is a well-known toxic gas with the characteristic smell of rotten eggs. It is synthesized endogenously in mammals from the sulfur-containing amino acid l-cysteine by the action of several distinct enzymes: cystathionine-?-lyase (CSE), cystathionine-ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) along with cysteine aminotransferase (CAT). In particular, CSE is considered to be the major H2S-producing enzyme in the cardiovascular system. As the third gasotransmitter next to nitric oxide (NO) and carbon monoxide (CO), H2S plays an important role in the regulation of vasodilation, angiogenesis, inflammation, oxidative stress and apoptosis. Growing evidence has demonstrated that this gas exerts a significant protective effect against the progression of cardiovascular diseases by a number of mechanisms such as vasorelaxation, inhibition of cardiovascular remodeling and resistance to form foam cells. The aim of this review is to provide an overview of the physiological functions of H2S and its protection against several major cardiovascular diseases, and to explore its potential health and therapeutic benefits. A better understanding will help develop novel H2S-based therapeutic interventions for these diseases. PMID:25058799

  20. Characterization of Potent Fusion Inhibitors of Influenza Virus

    PubMed Central

    Rowse, Michael; Qiu, Shihong; Tsao, Jun; Xian, Tongmei; Khawaja, Sarah; Yamauchi, Yohei; Yang, Zhen; Wang, Guoxin; Luo, Ming

    2015-01-01

    New inhibitors of influenza viruses are needed to combat the potential emergence of novel human influenza viruses. We have identified a class of small molecules that inhibit replication of influenza virus at picomolar concentrations in plaque reduction assays. The compound also inhibits replication of vesicular stomatitis virus. Time of addition and dilution experiments with influenza virus indicated that an early time point of infection was blocked and that inhibitor 136 tightly bound to virions. Using fluorescently labeled influenza virus, inhibition of viral fusion to cellular membranes by blocked lipid mixing was established as the mechanism of action for this class of inhibitors. Stabilization of the neutral pH form of hemagglutinin (HA) was ruled out by trypsin digestion studies in vitro and with conformation specific HA antibodies within cells. Direct visualization of 136 treated influenza virions at pH 7.5 or acidified to pH 5.0 showed that virions remain intact and that glycoproteins become disorganized as expected when HA undergoes a conformational change. This suggests that exposure of the fusion peptide at low pH is not inhibited but lipid mixing is inhibited, a different mechanism than previously reported fusion inhibitors. We hypothesize that this new class of inhibitors intercalate into the virus envelope altering the structure of the viral envelope required for fusion to cellular membranes. PMID:25803288

  1. RISK FACTORS FOR CONTACT LENS INDUCED PAPILLARY CONJUNCTIVITIS ASSOCIATED WITH SILICONE HYDROGEL CONTACT LENS WEAR

    PubMed Central

    Tagliaferri, Angela; Love, Thomas E.; Szczotka-Flynn, Loretta

    2014-01-01

    BACKGROUND Contact lens induced papillary conjunctivitis (CLPC) continues to be a major cause of dropout during contact lens extended wear. This retrospective study explores risk factors for the development of CLPC during silicone hydrogel lens extended wear. METHODS Data from 205 subjects enrolled in the Longitudinal Analysis of Silicone Hydrogel Contact Lens (LASH) study wearing lotrafilcon A silicone hydrogel lenses for up to 30 days of continuous wear were used to determine risk factors for CLPC in this secondary analysis of the main cohort. The main covariates of interest included substantial lens-associated bacterial bioburden, and topographically determined lens base curve-to-cornea fitting relationships. Additional covariates of interest included history of prior adverse events, time of year, race, education level, gender and other subject demographics. Statistical analyses included univariate logistic regression to assess the impact of potential risk factors on the binary CLPC outcome, and Cox proportional hazards regression to describe the impact of those factors on time-to-CLPC diagnosis. RESULTS Across 12 months of follow-up, 52 subjects (25%) experienced CLPC. No associations were found between CLPC development and the presence of bacterial bioburden, lens-to-cornea fitting relationships, history of prior adverse events, gender or race. CLPC development followed the same seasonal trends as the local peaks in environmental allergans. CONCLUSIONS Lens fit and biodeposits, in the form of lens associated bacterial bioburden, were not associated with the development of CLPC during extended wear with lotrafilcon A silicone hydrogel lenses. PMID:24681609

  2. Interaction of a Contact Resonance of Microspheres with Surface Acoustic Waves

    E-print Network

    Boechler, Nicholas

    We study the interaction of surface acoustic waves (SAWs) with a contact-based vibrational resonance of 1???m silica microspheres forming a two-dimensional granular crystal adhered to a substrate. The laser-induced transient ...

  3. Orientation Honors Staff Contact Information

    E-print Network

    Mohaghegh, Shahab

    2014 New Student Orientation #12;Honors Staff Contact Information Dr. Ryan Claycomb Assistant Dean@mail.wvu.edu. Enjoy the rest of your summer and we'll see you in August! #12;Honors Orientation All students at West orientation courses required by academic departments for specific majors. You may be required by your

  4. Allergic contact dermatitis from aromatherapy

    Microsoft Academic Search

    Rochelle R. Weiss; William D. James

    1997-01-01

    Allergic contact dermatitis secondary to aromatherapy has been only rarely reported. We present 39-year-old woman who had used aromatherapy products for approximately 2 to 3 years who presented with an erythematous eruption on her face and chest. Patch testing showed a positive reaction to neomycin and fragrance mix. On cessation of her aromatherapy products, her eruption rapidly resolved. Aromatherapy products

  5. DISEASES CAUSED BY WATER CONTACT

    EPA Science Inventory

    Diseases associated with water contact are reviewed with respect to the sources of etiological agents, the types of diseases and the conditions under which they occur. The sources of disease agents fall into three general groups; point sources such as sewage treatment plants; dis...

  6. M Magazine Advertising Contact Information

    E-print Network

    Peters, Richard

    Overview #12;M Magazine Advertising Contact Information Call (03)8667 2000 or visit Adcentre they wear, where they go, what they do and therefore M covers fashion, food, health, the home, gardening-depth look at what's topical in the areas of culture, fashion, racing, food or travel. #12;John Mangan

  7. Patterns of Nonresident Father Contact

    PubMed Central

    CHEADLE, JACOB E.; AMATO, PAUL R.; KING, VALARIE

    2010-01-01

    We used the National Longitudinal Survey of Youth 1979 cohort (NLSY79) from 1979 to 2002 and the Children of the National Longitudinal Survey of Youth (CNLSY) from 1986 to 2002 to describe the number, shape, and population frequencies of U.S. nonresident father contact trajectories over a 14-year period using growth mixture models. The resulting four-category classification indicated that nonresident father involvement is not adequately characterized by a single population with a monotonic pattern of declining contact over time. Contrary to expectations, about two-thirds of fathers were consistently either highly involved or rarely involved in their children’s lives. Only one group, constituting approximately 23% of fathers, exhibited a clear pattern of declining contact. In addition, a small group of fathers (8%) displayed a pattern of increasing contact. A variety of variables differentiated between these groups, including the child’s age at father-child separation, whether the child was born within marriage, the mother’s education, the mother’s age at birth, whether the father pays child support regularly, and the geographical distance between fathers and children. PMID:20355691

  8. Interfacial closure of contacting surfaces

    NASA Astrophysics Data System (ADS)

    Rieutord, F.; Rauer, C.; Moriceau, H.

    2014-08-01

    Understanding the contact between solid surfaces is a long-standing problem which has a strong impact on the physics of many processes such as adhesion, friction, lubrication and wear. Experimentally, the investigation of solid/solid interfaces remains challenging today, due to the lack of experimental techniques able to provide sub-nanometer scale information on interfaces buried between millimeters of materials. Yet, a strong interest exists improving the modeling of contact mechanics of materials in order to adjust their interface properties (e.g., thermal transport, friction). We show here that the essential features of the residual gap between contacting surfaces can be measured using high energy X-ray synchrotron reflectivity. The presence of this nano-gap is general to the contact of solids. In some special case however, it can be removed when attractive forces take over repulsive contributions, depending on both height and wavelength of asperity distributions (roughness). A criterion for this instability is established in the standard case of van der Waals attractive forces and elastic asperity compression repulsive forces (Hertz model). This collapse instability is confirmed experimentally in the case of silicon direct bonding, using high-energy X-ray synchrotron reflectivity and adhesion energy measurements. The possibility to achieve fully closed interfaces at room temperature opens interesting perspectives to build stronger assemblies with smaller thermal budgets.

  9. Campus Contacts Titan Bookstore Cafe

    E-print Network

    de Lijser, Peter

    Campus Contacts Library Titan Bookstore Cafe Student A airs Susan M. Cooper Dean (657) 278 drawings) Pizza with the Dean April 18th , 5:30 p.m. - 6:30 p.m. IRVC-Lobby Stress Management Workshop with Student Affairs and Admissions, Registration, and Cashiering. Lunch with the Dean was followed

  10. Eugene Kiselev Office Contact Information

    E-print Network

    Snider, Barry B.

    South Street Waltham, Ma 02454 Personal Contact Information 180 B River Street, Apartment 3 Waltham, MA Research Associate, Russian State University of Oil and Gas, Moscow Russia (Telecommuting) June 2011 of geopolitics and international security - particularly on the energy security of Russia and Central Asia

  11. Ohmic contacts to semiconducting diamond

    NASA Astrophysics Data System (ADS)

    Zeidler, James R.; Taylor, M. J.; Zeisse, Carl R.; Hewett, C. A.; Delahoussaye, Paul R.

    1990-10-01

    Work was carried out to improve the electron beam evaporation system in order to achieve better deposited films. The basic system is an ion pumped vacuum chamber, with a three-hearth, single-gun e-beam evaporator. Four improvements were made to the system. The system was thoroughly cleaned and new ion pump elements, an e-gun beam adjust unit, and a more accurate crystal monitor were installed. The system now has a base pressure of 3 X 10(exp -9) Torr, and can easily deposit high-melting-temperature metals such as Ta with an accurately controlled thickness. Improved shadow masks were also fabricated for better alignment and control of corner contacts for electrical transport measurements. Appendices include: A Thermally Activated Solid State Reaction Process for Fabricating Ohmic Contacts to Semiconducting Diamond; Tantalum Ohmic Contacts to Diamond by a Solid State Reaction Process; Metallization of Semiconducting Diamond: Mo, Mo/Au, and Mo/Ni/Au; Specific Contact Resistance Measurements of Ohmic Contracts to Diamond; and Electrical Activation of Boron Implanted into Diamond.

  12. Carter Tribley Butts Contact Information

    E-print Network

    Loudon, Catherine

    Carter Tribley Butts Contact Information: · Work: Department of Sociology SSPA 2145 University of Panic in Belief," ASA Section on Mathematical Sociology, 1999 Grants and Fellowships: · Butts, Carter T #SES-1260798, NSF SBE, MMS. $15,140. · Anandkumar, Anima (PI) and Butts, Carter T. (Co-PI). (9

  13. Electrical contact tool set station

    DOEpatents

    Byers, M.E.

    1988-02-22

    An apparatus is provided for the precise setting to zero of electrically conductive cutting tools used in the machining of work pieces. An electrically conductive cylindrical pin, tapered at one end to a small flat, rests in a vee-shaped channel in a base so that its longitudinal axis is parallel to the longitudinal axis of the machine's spindle. Electronic apparatus is connected between the cylindrical pin and the electrically conductive cutting tool to produce a detectable signal when contact between tool and pin is made. The axes of the machine are set to zero by contact between the cutting tool and the sides, end or top of the cylindrical pin. Upon contact, an electrical circuit is completed, and the detectable signal is produced. The tool can then be set to zero for that axis. Should the tool contact the cylindrical pin with too much force, the cylindrical pin would be harmlessly dislodged from the vee-shaped channel, preventing damage either to the cutting tool or the cylindrical pin. 5 figs.

  14. Nanotechnology and Food Contact Materials

    Microsoft Academic Search

    2010-01-01

    The use of nanotechnology in food contact materials is highlighted in relation to novel applications and potential implications for consumer safety and regulatory controls. Nanotechnology applications are expected to bring a range of benefits to the food sector, including improved packaging, antimicrobial properties, traceability and security of food products. The toxicological nature of hazard, likelihood of exposure and risk to

  15. NASA Space Grant Contacts Directory

    NSDL National Science Digital Library

    This publication provides an overview of two NASA funding programs, the National Space Grant College and Fellowship Program (Space Grant) and the Experimental Program to Stimulate Competitive Research (EPSCOR). A listing of contacts for these programs in all 50 states (20 states for EPSCOR), the District of Columbia, and Puerto Rico is provided, as well as a link to the Space Grant homepage.

  16. Geothermal direct contact heat exchange

    Microsoft Academic Search

    A. V. Sims

    1977-01-01

    A glass direct contact heat exchange column was operated in the laboratory. The column was operated at atmospheric pressure using hot water and normal hexane. Column internals testing included an empty column, sieve trays, disk-and-doughnut trays, and two types of packing. Operation was very smooth in all cases and the minimum temperature approaches varied from less than 1 C for

  17. Tarnish-Resistant Contact Material

    Microsoft Academic Search

    TOSHITO HARA; K. Mano

    1969-01-01

    This paper suggests how tarnish-resistant contact material may be obtained. Of particular interest are those alloys made up of transition and nontransition metals that are able to resist corrosive gases and inhibit the formation of organic polymers. Such alloys can be identified by their physical properties, for example, magnetic susceptibility. The d electronic bands of transition metals are not normally

  18. Prosodic Change and Language Contact

    ERIC Educational Resources Information Center

    McMahon, April

    2004-01-01

    Using evidence from first-hand experimental work and existing studies, Colantoni and Gurlekian take a tentative but encouraging step towards exploring the role of contact in explaining intonational change. Their central question is whether Buenos Aires Spanish intonation is distinctive relative to other varieties of Spanish; and if so, whether…

  19. Contact dermatitis in hospital patients.

    PubMed

    Ancona, A; Arévalo, A; Macotela, E

    1990-01-01

    Contact dermatitis in hospital patients resulting from diagnostic and therapeutic procedures presents various causes and clinical aspects. Antiseptics are the most frequent cause of contact dermatitis in patients undergoing surgery. Thimerosal may cause allergic sensitization mainly in patients previously exposed to contact with different sources of these mercurials, such as tinctures and preservatives in other products. Iodine-containing solutions and quaternary ammonium compounds rarely sensitize. They may cause irritation under certain circumstances, however. Adhesive tapes formulated on a rubber and colophony base are rarely found nowadays in medical adhesives; however, some tapes and skin closures have still been found to contain them. Acrylate-based adhesives sensitize less frequently. Cardiology patients may present contact dermatitis from several different sources. Electrode gels and pastes may cause allergic contact dermatitis mainly from preservatives. Modern electrocardiographic equipment does not require the use of these products, so many of these problems are now easy to avoid. Adhesive-coated pregelled foam disks for holding long-term chest contacts may cause irritant dermatitis. Transdermal drug delivery systems such as nitroglycerin disks may cause irritation attributable to the acrylic adhesives. Silicone-based adhesive disks are a good alternative in this case. Sensitization to nitroglycerin itself is rare. Dermatitis originated from implantation of pacemakers is attributable either to epoxy resin or to the metal used for the casing of the pacemaker. Changing to a different material solves the problem. In other instances, the etiology remains unclear. Dermatoses in patients with stomas constitute an important problem not only because of their frequency but also because of the multiplicity of pictures involved. Irritant dermatitis from intestinal efflux in ileostomy patients is the most frequent problem. Allergic dermatitis may originate from the ostomy device, cementing materials, or topical medicaments. Individuals receiving hemodialysis have been reported to develop widespread dermatitis, probably secondary to rubber or metal components leached out from the hemodialysis apparatus. Systemic exposure to these compounds, although not certainly proved, seems to be the explanation. Allergic dermatitis at the puncture site on arteriovenous shunts has been demonstrated to be produced by epoxy resin adhesives present in catheters. Identification of the allergen allows one to find a safe alternative for these patients who depend on this procedure to survive. Contact dermatitis in hospital patients requires a precise diagnosis. Extensive patch testing is sometimes needed for establishing the cause, which in turn provides a more accurate prognosis and a rational treatment. PMID:2406065

  20. Potent antimalarial febrifugine analogues against the plasmodium malaria parasite.

    PubMed

    Kikuchi, Haruhisa; Tasaka, Hidehisa; Hirai, Shingo; Takaya, Yoshiaki; Iwabuchi, Yoshiharu; Ooi, Hidenori; Hatakeyama, Susumi; Kim, Hye-Sook; Wataya, Yusuke; Oshima, Yoshiteru

    2002-06-01

    Although febrifugine (1) and isofebrifugine (2), alkaloids isolated from roots of the Dichroa febrifuga plant, show powerful antimalarial activity against Plasmodium falciparum, strong side effects such as the emetic effect have precluded their clinical use against malaria. However, their antimalarial potency makes them attractive substances as leads for developing new types of chemotherapeutic antimalarial drugs. Thus, we have evaluated the in vitro antimalarial activity of the analogues of febrifugine (1) and isofebrifugine (2). The activities of the analogues derived from Df-1 (3) and Df-2 (4), condensation products of 1 and 2 with acetone, respectively, were also obtained. The 3' '-keto derivative (7, EC(50) = 2.0 x 10(-8) M) of 1 was found to exhibit potential antimalarial activity with high selectivity against P. falciparum in vitro. The in vitro activities of the reduction product (8, EC(50) = 2.0 x 10(-8) M) of 1 at C-2' and its cyclic derivatives 9 and 10 (EC(50) = 3.7 x 10(-9) and 8.6 x 10(-9) M, respectively) were found to be strongly active and selective. Additionally, the Dess-Martin oxidation product of 3 was found to be strongly active with high selectivity against P. falciparum. A structure-activity relationship study (SAR) demonstrates that the essential role played by the 4-quinazolinone ring in the appearance of activity and the presence of a 1' '-amino group and C-2', C-3' ' O-functionalities are crucial in the activity of 1. For 7, 8, and 9, prepared as racemic forms, an in vivo study has also been conducted. PMID:12036365