Science.gov

Sample records for forms potent contact

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

    SciTech Connect

    Hagvall, Lina; Baron, Jens Malte; Boerje, Anna; Weidolf, Lars; Merk, Hans; Karlberg, Ann-Therese

    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. Method for forming metal contacts

    DOEpatents

    Reddington, Erik; Sutter, Thomas C; Bu, Lujia; Cannon, Alexandra; Habas, Susan E; Curtis, Calvin J; Miedaner, Alexander; Ginley, David S; Van Hest, Marinus Franciscus Antonius Maria

    2013-09-17

    Methods of forming metal contacts with metal inks in the manufacture of photovoltaic devices are disclosed. The metal inks are selectively deposited on semiconductor coatings by inkjet and aerosol apparatus. The composite is heated to selective temperatures where the metal inks burn through the coating to form an electrical contact with the semiconductor. Metal layers are then deposited on the electrical contacts by light induced or light assisted plating.

  3. Contact degeneracies of closed 2-forms

    SciTech Connect

    Zot'ev, Dmitrii B

    2007-04-30

    Consider a closed 2-form that is degenerate at the points of a hypersurface and is non-degenerate outside it. In the neighbourhood of a singularity (which is called contact under certain natural conditions) the limit behaviour of Hamiltonian fields is investigated and a canonical form of the 2-form is found (Darboux's theorem). Connections with regular Lie structures are established. Properties of integrable structures on Liouville tori containing contact degeneracies are studied. Bibliography: 16 titles.

  4. 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.

  5. Front contact solar cell with formed emitter

    DOEpatents

    Cousins, Peter John

    2014-11-04

    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.

  6. Pion form factor from a contact interaction

    SciTech Connect

    Gutierrez-Guerrero, L. X.; Bashir, A.; Cloeet, I. C.; Roberts, C. D.

    2010-06-15

    In a Poincare-covariant vector-boson-exchange theory, the pion possesses components of pseudovector origin, which materially influence its observable properties. For a range of such quantities, we explore the consequences of a momentum-independent interaction, regularized in a symmetry-preserving manner. The contact interaction, while capable of describing pion static properties, produces a form factor whose evolution for Q{sup 2}>0.17 GeV{sup 2} disagrees markedly with experiment and whose asymptotic power-law behavior conflicts strongly with perturbative QCD.

  7. Pion form factor from a contact interaction.

    SciTech Connect

    Gutierrez-Guerrero, L. X.; Bashir, A.; Cloet, I. C.; Roberts, C. D.

    2010-01-01

    In a Poincare-covariant vector-boson-exchange theory, the pion possesses components of pseudovector origin, which materially influence its observable properties. For a range of such quantities, we explore the consequences of a momentum-independent interaction, regularized in a symmetry-preserving manner. The contact interaction, while capable of describing pion static properties, produces a form factor whose evolution for Q{sup 2} > 0.17 GeV{sup 2} disagrees markedly with experiment and whose asymptotic power-law behavior conflicts strongly with perturbative QCD.

  8. 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.

  9. "Car seat dermatitis": a newly described form of contact dermatitis.

    PubMed

    Ghali, Fred E

    2011-01-01

    Over the last several years, our clinic has documented an increasing trend of contact dermatitis presenting in areas that are in direct contact with certain types of car seats composed of a shiny, nylon-like material. Our practice has encountered these cases in both atopic and nonatopic infants, with a seasonal predilection for the warmer months. This brief report highlights some of the key features of this condition and alerts the clinician to this newly described form of contact dermatitis. PMID:20738797

  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. Organic light-emitting diodes formed by soft contact lamination

    E-print Network

    Rogers, John A.

    Organic light-emitting diodes formed by soft contact lamination Tae-Woo Lee* , Jana Zaumseil, 2003 (received for review July 5, 2003) Although tremendous progress has been made in organic light against an electroluminescent organic. This method relies only on van der Waals interactions to establish

  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. Contact resistance in organic transistors that use source and drain electrodes formed by soft contact lamination

    E-print Network

    Rogers, John A.

    Contact resistance in organic transistors that use source and drain electrodes formed by soft stamps against organic semiconductor films can yield high-performance organic transistors. This article by evaporation of gold electrodes directly on top of the organic semiconductors. These and other attractive

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

    DOEpatents

    Manning, Jane

    2015-10-20

    Methods of forming contacts for solar cells are described. In one embodiment, a method includes forming a silicon layer above a substrate, forming and patterning a solid-state p-type dopant source on the silicon layer, forming an n-type dopant source layer over exposed regions of the silicon 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 silicon regions among a plurality of p-type doped silicon regions.

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

    DOEpatents

    Manning, Jane

    2014-07-15

    Methods of forming contacts for solar cells are described. In one embodiment, a method includes forming a silicon layer above a substrate, forming and patterning a solid-state p-type dopant source on the silicon layer, forming an n-type dopant source layer over exposed regions of the silicon 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 silicon regions among a plurality of p-type doped silicon regions.

  16. 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...

  17. 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...

  18. Helicobacter pylori TlyA Forms Amyloid-like Aggregates with Potent Cytotoxic Activity.

    PubMed

    Lata, Kusum; Chattopadhyay, Kausik

    2015-06-16

    Helicobacter pylori is a potent human gastric pathogen. It is known to be associated with several gastroenteric disorders, including gastritis, peptic ulcer, and gastric cancer. The H. pylori genome encodes a gene product TlyA that has been shown to display potent membrane damaging properties and cytotoxic activity. On the basis of such properties, TlyA is considered as a potential virulence factor of H. pylori. In this study, we show that the H. pylori TlyA protein has a strong propensity to convert into the amyloid-like aggregated assemblies, upon exposure to elevated temperatures. Even at the physiological temperature of 37 °C, TlyA shows a strong amyloidogenic property. TlyA aggregates that are generated upon exposure at temperatures of ?37 °C show prominent binding to dyes like thioflavin T and Nile Red. Transmission electron microscopy also demonstrates the presence of typical amyloid-like fibrils in the TlyA aggregates generated at 37 °C. Conversion of TlyA into the amyloid-like aggregates is found to be associated with major alterations in the secondary and tertiary structural organization of the protein. Finally, our study shows that the preformed amyloid-like aggregates of TlyA are capable of exhibiting potent cytotoxic activities against human gastric adenocarcinoma cells. Altogether, such a propensity of H. pylori TlyA to convert into the amyloid-like aggregated assemblies with cytotoxic activity suggests potential implications for the virulence functionality of the protein. PMID:26015064

  19. 41 CFR 102-194.45 - Who should I contact about Standard and Optional forms?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 2010-07-01 false Who should I contact about Standard and Optional forms? ...PROGRAM § 102-194.45 Who should I contact about Standard and Optional forms? For Standard and Optional forms, you should contact the: Standard and Optional Forms...

  20. Process and structures for fabrication of solar cells with laser ablation steps to form contact holes

    DOEpatents

    Harley, Gabriel; Smith, David D; Dennis, Tim; Waldhauer, Ann; Kim, Taeseok; Cousins, Peter John

    2013-11-19

    Contact holes of solar cells are formed by laser ablation to accomodate various solar cell designs. Use of a laser to form the contact holes is facilitated by replacing films formed on the diffusion regions with a film that has substantially uniform thickness. Contact holes may be formed to deep diffusion regions to increase the laser ablation process margins. The laser configuration may be tailored to form contact holes through dielectric films of varying thickness.

  1. The soluble form of the tumor suppressor Lrig1 potently inhibits in vivo glioma growth irrespective of EGF receptor status

    PubMed Central

    Johansson, Mikael; Oudin, Anaïs; Tiemann, Katja; Bernard, Amandine; Golebiewska, Anna; Keunen, Olivier; Fack, Fred; Stieber, Daniel; Wang, Baofeng; Hedman, Håkan; Niclou, Simone P.

    2013-01-01

    Background Deregulated growth factor signaling is a major driving force in the initiation and progression of glioblastoma. The tumor suppressor and stem cell marker Lrig1 is a negative regulator of the epidermal growth factor receptor (EGFR) family. Here, we addressed the therapeutic potential of the soluble form of Lrig1 (sLrig1) in glioblastoma treatment and the mechanism of sLrig1-induced growth inhibition. Methods With use of encapsulated cells, recombinant sLrig1 was locally delivered in orthotopic glioblastoma xenografts generated from freshly isolated patient tumors. Tumor growth and mouse survival were evaluated. The efficacy of sLrig1 and the affected downstream signaling was studied in vitro and in vivo in glioma cells displaying variable expression of wild-type and/or a constitutively active EGFR mutant (EGFRvIII). Results Continuous interstitial delivery of sLrig1 in genetically diverse patient-derived glioma xenografts led to strong tumor growth inhibition. Glioma cell proliferation in vitro and tumor growth in vivo were potently inhibited by sLrig1, irrespective of EGFR expression levels. Of importance, tumor growth was also suppressed in EGFRvIII-driven glioma. sLrig1 induced cell cycle arrest without changing total receptor level or phosphorylation. Affected downstream effectors included MAP kinase but not AKT signaling. Of importance, local delivery of sLrig1 into established tumors led to a 32% survival advantage in treated mice. Conclusions To our knowledge, this is the first report demonstrating that sLrig1 is a potent inhibitor of glioblastoma growth in clinically relevant experimental glioma models and that this effect is largely independent of EGFR status. The potent anti-tumor effect of sLrig1, in combination with cell encapsulation technology for in situ delivery, holds promise for future treatment of glioblastoma. PMID:23723255

  2. 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

    ... Internal Revenue Service Proposed Collection; Comment Request for the EFTPS Primary Contact Information... the EFTPS Primary Contact Information Change Form. DATES: Written comments should be received on or.... FOR FURTHER INFORMATION CONTACT: Requests for additional information or copies of the form...

  3. 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

    ... Internal Revenue Service Proposed Collection; Comment Request for the EFTPS Primary Contact Information... the EFTPS Primary Contact Information Change Form. DATES: Written comments should be received on or.... FOR FURTHER INFORMATION CONTACT: Requests for additional information or copies of the form...

  4. Pixantrone can be activated by formaldehyde to generate a potent DNA adduct forming agent

    PubMed Central

    Evison, Ben J.; Mansour, Oula C.; Menta, Ernesto; Phillips, Don R.; Cutts, Suzanne M.

    2007-01-01

    Mitoxantrone is an anti-cancer agent used in the treatment of breast and prostate cancers. It is classified as a topoisomerase II poison, however can also be activated by formaldehyde to generate drug–DNA adducts. Despite identification of this novel form of mitoxantrone–DNA interaction, excessively high, biologically irrelevant drug concentrations are necessary to generate adducts. A search for mitoxantrone analogues that could potentially undergo this reaction with DNA more efficiently identified Pixantrone as an ideal candidate. An in vitro crosslinking assay demonstrated that Pixantrone is efficiently activated by formaldehyde to generate covalent drug–DNA adducts capable of stabilizing double-stranded DNA in denaturing conditions. Pixantrone–DNA adduct formation is both concentration and time dependent and the reaction exhibits an absolute requirement for formaldehyde. In a direct comparison with mitoxantrone–DNA adduct formation, Pixantrone exhibited a 10- to 100-fold greater propensity to generate adducts at equimolar formaldehyde and drug concentrations. Pixantrone–DNA adducts are thermally and temporally labile, yet they exhibit a greater thermal midpoint temperature and an extended half-life at 37°C when compared to mitoxantrone–DNA adducts. Unlike mitoxantrone, this enhanced stability, coupled with a greater propensity to form covalent drug–DNA adducts, may endow formaldehyde-activated Pixantrone with the attributes required for Pixantrone–DNA adducts to be biologically active. PMID:17483512

  5. Pixantrone can be activated by formaldehyde to generate a potent DNA adduct forming agent.

    PubMed

    Evison, Ben J; Mansour, Oula C; Menta, Ernesto; Phillips, Don R; Cutts, Suzanne M

    2007-01-01

    Mitoxantrone is an anti-cancer agent used in the treatment of breast and prostate cancers. It is classified as a topoisomerase II poison, however can also be activated by formaldehyde to generate drug-DNA adducts. Despite identification of this novel form of mitoxantrone-DNA interaction, excessively high, biologically irrelevant drug concentrations are necessary to generate adducts. A search for mitoxantrone analogues that could potentially undergo this reaction with DNA more efficiently identified Pixantrone as an ideal candidate. An in vitro crosslinking assay demonstrated that Pixantrone is efficiently activated by formaldehyde to generate covalent drug-DNA adducts capable of stabilizing double-stranded DNA in denaturing conditions. Pixantrone-DNA adduct formation is both concentration and time dependent and the reaction exhibits an absolute requirement for formaldehyde. In a direct comparison with mitoxantrone-DNA adduct formation, Pixantrone exhibited a 10- to 100-fold greater propensity to generate adducts at equimolar formaldehyde and drug concentrations. Pixantrone-DNA adducts are thermally and temporally labile, yet they exhibit a greater thermal midpoint temperature and an extended half-life at 37 degrees C when compared to mitoxantrone-DNA adducts. Unlike mitoxantrone, this enhanced stability, coupled with a greater propensity to form covalent drug-DNA adducts, may endow formaldehyde-activated Pixantrone with the attributes required for Pixantrone-DNA adducts to be biologically active. PMID:17483512

  6. Cleanroom After-Hours Request Form Personal Contact Information Date ___/___/___

    E-print Network

    . · For questions or comments, please contact Shaloma Malveaux (smalvea@lsu.edu). · Factors considered is required to be considered for After-Hours access. o Cooperation inside the cleanroom o Project requirements

  7. 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,

  8. 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,

  9. 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.

  10. Back contacted and small form factor GAAS solar cell.

    SciTech Connect

    Clews, Peggy Jane; Wanlass, Mark W.; Sanchez, Carlos A.; Pluym, Tammy; Cruz-Campa, Jose Luis; Okandan, Murat; Gupta, Vipin P.; Nielson, Gregory N.; Resnick, Paul James

    2010-06-01

    We present a newly developed microsystem enabled, back-contacted, shade-free GaAs solar cell. Using microsystem tools, we created sturdy 3 {micro}m thick devices with lateral dimensions of 250 {micro}m, 500 {micro}m, 1 mm, and 2 mm. The fabrication procedure and the results of characterization tests are discussed. The highest efficiency cell had a lateral size of 500 {micro}m and a conversion efficiency of 10%, open circuit voltage of 0.9 V and a current density of 14.9 mA/cm{sup 2} under one-sun illumination.

  11. Chronic, irritant contact dermatitis: Mechanisms, variables, and differentiation from other forms of contact dermatitis

    SciTech Connect

    Dahl, M.V. )

    1988-01-01

    Irritant dermatitis is an eczematous reaction to toxic chemicals contacting the skin. The mechanisms by which various chemicals elicit dermatitis are multiple. Strong irritants quickly elicit signs and symptoms of dermatitis, but weak irritants may not. Chronic cumulative exposure to weak irritants can elicit dermatitis which may mimic allergic contact dermatitis and mislead the physician and patient with respect to cause and preventative strategy. The skins of different people vary in susceptibilities to irritation. Susceptibility is also influenced by chemical properties, vehicles, concentrations, amounts applied to the skin surface, surface area, regional variations, length of exposure, method of exposure, age, sex, race, genetic background, environmental factors, hardening, concomitant disease, and the excited skin syndrome as well as treatment. Patch testing can help distinguish between allergens and irritants, but pitfalls may mislead.35 references.

  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

    ... Laboratory Contact Update Form) AGENCY: Food Safety and Inspection Service, USDA. ACTION: Notice and request... intention to request a new information collection regarding the compilation of updated contact information..., DC 20250-3700 between 8:00 a.m. and 4:30 p.m., Monday through Friday. FOR FURTHER INFORMATION...

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

    SciTech Connect

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

    2015-09-29

    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.

  14. 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.

  15. Method or forming emitters for a back-contact solar cell

    DOEpatents

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

    2014-08-12

    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.

  16. Tunnel oxide passivated contacts formed by ion implantation for applications in silicon solar cells

    NASA Astrophysics Data System (ADS)

    Reichel, Christian; Feldmann, Frank; Müller, Ralph; Reedy, Robert C.; Lee, Benjamin G.; Young, David L.; Stradins, Paul; Hermle, Martin; Glunz, Stefan W.

    2015-11-01

    Passivated contacts (poly-Si/SiOx/c-Si) doped by shallow ion implantation are an appealing technology for high efficiency silicon solar cells, especially for interdigitated back contact (IBC) solar cells where a masked ion implantation facilitates their fabrication. This paper presents a study on tunnel oxide passivated contacts formed by low-energy ion implantation into amorphous silicon (a-Si) layers and examines the influence of the ion species (P, B, or BF2), the ion implantation dose (5 × 1014 cm-2 to 1 × 1016 cm-2), and the subsequent high-temperature anneal (800 °C or 900 °C) on the passivation quality and junction characteristics using double-sided contacted silicon solar cells. Excellent passivation quality is achieved for n-type passivated contacts by P implantations into either intrinsic (undoped) or in-situ B-doped a-Si layers with implied open-circuit voltages (iVoc) of 725 and 720 mV, respectively. For p-type passivated contacts, BF2 implantations into intrinsic a-Si yield well passivated contacts and allow for iVoc of 690 mV, whereas implanted B gives poor passivation with iVoc of only 640 mV. While solar cells featuring in-situ B-doped selective hole contacts and selective electron contacts with P implanted into intrinsic a-Si layers achieved Voc of 690 mV and fill factor (FF) of 79.1%, selective hole contacts realized by BF2 implantation into intrinsic a-Si suffer from drastically reduced FF which is caused by a non-Ohmic Schottky contact. Finally, implanting P into in-situ B-doped a-Si layers for the purpose of overcompensation (counterdoping) allowed for solar cells with Voc of 680 mV and FF of 80.4%, providing a simplified and promising fabrication process for IBC solar cells featuring passivated contacts.

  17. Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites

    PubMed Central

    Verlinden, Bianca K.; de Beer, Marna; Pachaiyappan, Boobalan; Besaans, Ethan; Andayi, Warren A.; Reader, Janette; Niemand, Jandeli; van Biljon, Riette; Guy, Kiplin; Egan, Timothy; Woster, Patrick M.; Birkholtz, Lyn-Marie

    2015-01-01

    A new series of potent potent aryl/alkylated (bis)urea- and (bis)thiourea polyamine analogues were synthesized and evaluated in vitro for their antiplasmodial activity. Altering the carbon backbone and terminal substituents increased the potency of analogues in the compound library 3-fold, with the most active compounds, 15 and 16, showing half-maximal inhibitory concentrations (IC50 values) of 28 and 30 nM, respectively, against various Plasmodium falciparum parasite strains without any cross-resistance. In vitro evaluation of the cytotoxicity of these analogues revealed marked selectivity towards targeting malaria parasites compared to mammalian HepG2 cells (>5000-fold lower IC50 against the parasite). Preliminary biological evaluation of the polyamine analogue antiplasmodial phenotype revealed that (bis)urea compounds target parasite asexual proliferation, whereas (bis)thiourea compounds of the same series have the unique ability to block transmissible gametocyte forms of the parasite, indicating pluripharmacology against proliferative and non-proliferative forms of the parasite. In this manuscript, we describe these results and postulate a refined structure-activity relationship (SAR) model for antiplasmodial polyamine analogues. The terminally aryl/alkylated (bis)urea- and (bis)thiourea-polyamine analogues featuring a 3-5-3 or 3-6-3 carbon backbone represent a structurally novel and distinct class of potential antiplasmodials with activities in the low nanomolar range, and high selectivity against various lifecycle forms of P. falciparum parasites. PMID:25684422

  18. Process for forming pure silver ohmic contacts to N- and P-type gallium arsenide materials

    DOEpatents

    Hogan, S.J.

    1983-03-13

    Disclosed is an improved process for manufacturing gallium arsenide semiconductor devices having as its components a n-type gallium arsenide substrate layer and a p-type gallium arsenide diffused layer. The improved process comprises forming a pure silver ohmic contact to both the diffuse layer and the substrate layer wherein the n-type layer comprises a substantially low doping carrier concentration.

  19. 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

  20. Formulation of Contact Problems in Sheet Metal Forming Simulation Using Local Interpolation for Tool Surfaces

    NASA Astrophysics Data System (ADS)

    Hama, Takayuki; Takamura, Masato; Makinouchi, Akitake; Teodosiu, Cristian; Takuda, Hirohiko

    The treatment of contact between a sheet and tools is one of the most difficult problems to deal with in finite-element simulations of the sheet metal forming processes. In order to obtain more accurate tool models without increasing the number of elements, this paper describes new techniques for the contact problem using a local interpolation for tool surfaces proposed by Nagata. The Nagata patch enables the creation of tool models that are much more accurate in shape than those of the conventional polyhedral representations. Contact search algorithms between the sheet nodes and the interpolated tool surfaces and a consistent contact tangent stiffness matrix for the sliding sheet nodes were formulated. The proposed contact search algorithms allow robust and accurate contact analyses. The developed algorithms were introduced into the static-explicit elastoplastic finite-element method code STAMP3D. Simulations of a square-cup deep-drawing process with a very coarsely discretized punch model were carried out. The simulated results showed that the proposed algorithms yield the proper deformation process, thus demonstrating the validity of the proposed techniques.

  1. 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.

  2. Thin Film Solid-State Reactions Forming Carbides as Contact Materials for Carbon-Containing Semiconductors

    SciTech Connect

    Leroy,W.; Detavernier, C.; Van Meirhaeghe, R.; Lavoie, C.

    2007-01-01

    Metal carbides are good candidates to contact carbon-based semiconductors (SiC, diamond, and carbon nanotubes). Here, we report on an in situ study of carbide formation during the solid-state reaction between thin films. The solid-state reaction was examined between 11 transition metals (W, Mo, Fe, Cr, V, Nb, Mn, Ti, Ta, Zr, and Hf) and an amorphous carbon layer. Capping layers (C or TiN) of different thicknesses were applied to prevent oxidation. Carbide formation is evidenced for nine metals and the phases formed have been identified (for a temperature ranging from 100 to 1100 C). W first forms W{sub 2}C and then WC; Mo forms Mo{sub 2}C; Fe forms Fe{sub 3}C; Cr first forms metastable phases Cr{sub 2}C and Cr{sub 3}C{sub 2-x}, and finally forms Cr{sub 3}C{sub 2}; V forms VC{sub x}; Nb transforms into Nb{sub 2}C followed by NbC; Ti forms TiC; Ta first forms Ta{sub 2}C and then TaC; and Hf transforms into HfC. The activation energy for the formation of the various carbide phases has been obtained by in situ x-ray diffraction.

  3. Complex formation in aqueous solution and in the solid state of the potent insulin-enhancing V(IV)O2+ compounds formed by picolinate and quinolinate derivatives.

    PubMed

    Lodyga-Chruscinska, Elzbieta; Micera, Giovanni; Garribba, Eugenio

    2011-02-01

    The complexation of V(IV)O(2+) ion with 10 picolinate and quinolinate derivatives, provided with the donor set (N, COO(-)), was studied in aqueous solution and in the solid state through the combined application of potentiometric (pH-titrations), spectroscopic (EPR, UV/vis and IR spectroscopy), and computational (density functional theory (DFT) calculations) methods. Such derivatives, that form potent insulin-enhancing V(IV)O(2+) compounds, are picolinic (picH), 6-methylpicolinic (6-mepicH), 3-methylpicolinic (3-mepicH), 5-butylpicolinic or fusaric (fusarH), 6-methyl-2,3-pyridindicarboxylic (6-me-2,3-pdcH(2)), 2-pyridylacetic (2-pyacH), 2-quinolinecarboxylic or quinaldic (quinH), 4-hydroxyquinoline-2-carboxylic or kynurenic (kynurH), 1-isoquinolinecarboxylic (1-iqcH) and 3-isoquinolinecarboxylic (3-iqcH) acid. On the basis of the potentiometric, spectroscopic, and DFT results, they were divided into the classes A, B, and C. The ligands belonging to class A (3-mepicH, 1-iqcH, 2-pyacH) form square pyramidal complexes in aqueous solution and in the solid state, and those belonging to class B (picH, fusarH, 3-iqcH) form cis-octahedral species, in which the two ligands adopt an (equatorial-equatorial) and an (equatorial-axial) arrangement and one water molecule occupies an equatorial site in cis position with respect to the V?O bond. Class C ligands (6-mepicH, 6-me-2,3-pdcH(2), quinH, kynurH) yield bis chelated species, that in water are in equilibrium between the square pyramidal and trans-octahedral form, where both the ligand molecules adopt an (equatorial-equatorial) arrangement and one water is in trans position with respect to the V?O group. The trans-octahedral compounds are characterized by an anomalous electron paramagnetic resonance (EPR) response, with A(z) value being reduced by about 10% with respect to the prediction of the "additivity rule". DFT methods allow to calculate the structure, (51)V hyperfine coupling constant (A(z)), the stretching frequency of V?O bond (?(V?O)), the relative stability in aqueous solution, and the electronic structure and molecular orbital composition of bis chelated complexes. The results were used to explain the biotransformation of these potent insulin-enhancing compounds in blood serum. PMID:21226475

  4. Structure of Apo- and Monometalated Forms of NDM-1—A Highly Potent Carbapenem-Hydrolyzing Metallo-?-Lactamase

    PubMed Central

    Kim, Youngchang; Sacchettini, James; Joachimiak, Andrzej

    2011-01-01

    The New Delhi Metallo-?-lactamase (NDM-1) gene makes multiple pathogenic microorganisms resistant to all known ?-lactam antibiotics. The rapid emergence of NDM-1 has been linked to mobile plasmids that move between different strains resulting in world-wide dissemination. Biochemical studies revealed that NDM-1 is capable of efficiently hydrolyzing a wide range of ?-lactams, including many carbapenems considered as “last resort” antibiotics. The crystal structures of metal-free apo- and monozinc forms of NDM-1 presented here revealed an enlarged and flexible active site of class B1 metallo-?-lactamase. This site is capable of accommodating many ?-lactam substrates by having many of the catalytic residues on flexible loops, which explains the observed extended spectrum activity of this zinc dependent ?-lactamase. Indeed, five loops contribute “keg” residues in the active site including side chains involved in metal binding. Loop 1 in particular, shows conformational flexibility, apparently related to the acceptance and positioning of substrates for cleavage by a zinc-activated water molecule. PMID:21931780

  5. Structures of complexes formed by H5 influenza hemagglutinin with a potent broadly neutralizing human monoclonal antibody.

    PubMed

    Xiong, Xiaoli; Corti, Davide; Liu, Junfeng; Pinna, Debora; Foglierini, Mathilde; Calder, Lesley J; Martin, Stephen R; Lin, Yi Pu; Walker, Philip A; Collins, Patrick J; Monne, Isabella; Suguitan, Amorsolo L; Santos, Celia; Temperton, Nigel J; Subbarao, Kanta; Lanzavecchia, Antonio; Gamblin, Steven J; Skehel, John J

    2015-07-28

    H5N1 avian influenza viruses remain a threat to public health mainly because they can cause severe infections in humans. These viruses are widespread in birds, and they vary in antigenicity forming three major clades and numerous antigenic variants. The most important features of the human monoclonal antibody FLD194 studied here are its broad specificity for all major clades of H5 influenza HAs, its high affinity, and its ability to block virus infection, in vitro and in vivo. As a consequence, this antibody may be suitable for anti-H5 therapy and as a component of stockpiles, together with other antiviral agents, for health authorities to use if an appropriate vaccine was not available. Our mutation and structural analyses indicate that the antibody recognizes a relatively conserved site near the membrane distal tip of HA, near to, but distinct from, the receptor-binding site. Our analyses also suggest that the mechanism of infectivity neutralization involves prevention of receptor recognition as a result of steric hindrance by the Fc part of the antibody. Structural analyses by EM indicate that three Fab fragments are bound to each HA trimer. The structure revealed by X-ray crystallography is of an HA monomer bound by one Fab. The monomer has some similarities to HA in the fusion pH conformation, and the monomer's formation, which results from the presence of isopropanol in the crystallization solvent, contributes to considerations of the process of change in conformation required for membrane fusion. PMID:26170284

  6. Structures of complexes formed by H5 influenza hemagglutinin with a potent broadly neutralizing human monoclonal antibody

    PubMed Central

    Xiong, Xiaoli; Corti, Davide; Liu, Junfeng; Pinna, Debora; Foglierini, Mathilde; Calder, Lesley J.; Martin, Stephen R.; Lin, Yi Pu; Walker, Philip A.; Collins, Patrick J.; Monne, Isabella; Suguitan, Amorsolo L.; Santos, Celia; Temperton, Nigel J.; Subbarao, Kanta; Lanzavecchia, Antonio; Gamblin, Steven J.; Skehel, John J.

    2015-01-01

    H5N1 avian influenza viruses remain a threat to public health mainly because they can cause severe infections in humans. These viruses are widespread in birds, and they vary in antigenicity forming three major clades and numerous antigenic variants. The most important features of the human monoclonal antibody FLD194 studied here are its broad specificity for all major clades of H5 influenza HAs, its high affinity, and its ability to block virus infection, in vitro and in vivo. As a consequence, this antibody may be suitable for anti-H5 therapy and as a component of stockpiles, together with other antiviral agents, for health authorities to use if an appropriate vaccine was not available. Our mutation and structural analyses indicate that the antibody recognizes a relatively conserved site near the membrane distal tip of HA, near to, but distinct from, the receptor-binding site. Our analyses also suggest that the mechanism of infectivity neutralization involves prevention of receptor recognition as a result of steric hindrance by the Fc part of the antibody. Structural analyses by EM indicate that three Fab fragments are bound to each HA trimer. The structure revealed by X-ray crystallography is of an HA monomer bound by one Fab. The monomer has some similarities to HA in the fusion pH conformation, and the monomer’s formation, which results from the presence of isopropanol in the crystallization solvent, contributes to considerations of the process of change in conformation required for membrane fusion. PMID:26170284

  7. Chromium is proposed as an ideal metal to form contacts with monolayer MoS2 and WS2

    NASA Astrophysics Data System (ADS)

    Luo, B.; Liu, J.; Zhu, S. C.; Yi, L.

    2015-10-01

    In this paper, fifteen kinds of metal contacts to monolayer MoS2 and WS2 are investigated by first principles calculations. In a variety of metal contacts, the sixth subgroup metals (including Cr, Mo, W) show collective advantages in forming contacts with MoS2 or WS2. They have more favorable interface bonding, higher densities of states at the Fermi level, and lower potential barriers. Molybdenum (Mo) is one of the elements that form molybdenum disulphide (MoS2), and has been proved to form high quality contacts with MoS2. Similarly, tungsten (W) is one of the elements that form tungsten tellurium (WTe2), and is suggested to form favorable contacts with WTe2. The third metal in the sixth subgroup, chromium (Cr), is found here to be a superior metal compared with molybdenum and tungsten to form favorable contacts with molybdenum disulphide and tungsten disulphide. In all sixth subgroup metal contacts, Cr/MoS2 and Cr/WS2 show the best electronic transport properties and chromium has a lower melting point than molybdenum and tungsten, which lead to easier to process devices with transition-metal dichalcogenides.

  8. Ethanol Extract of Peanut Sprout Exhibits a Potent Anti-Inflammatory Activity in Both an Oxazolone-Induced Contact Dermatitis Mouse Model and Compound 48/80-Treated HaCaT Cells

    PubMed Central

    Choi, Da-In; Choi, Jee-Young; Kim, Young Jee; Lee, Jee-Bum; Kim, Sun-Ouck; Shin, Hyong-Taek

    2015-01-01

    Background We developed an ethanol extract of peanut sprouts (EPS), a peanut sprout-derived natural product, which contains a high level of trans-resveratrol (176.75 µg/ml) and was shown to have potent antioxidant activity. Objective We evaluated the potential anti-inflammatory activity of EPS by measuring its antioxidant potential in skin. Methods The anti-inflammatory activity of EPS was tested using two models of skin inflammation: oxazolone (OX)-induced contact dermatitis in mice and compound 48/80-treated HaCaT cells. As biomarkers of skin inflammation, cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) levels were measured. Results OX-induced contact dermatitis was suppressed markedly in mice that were treated with an ointment containing 5% EPS as evidenced by a decrease in the extent of scaling and thickening (p<0.05) and supported by a histological study. COX-2 (messenger RNA [mRNA] and protein) and NGF (mRNA) levels, which were upregulated in the skin of OX-treated mice, were suppressed markedly in the skin of OX+EPS-treated mice. Consistent with this, compound 48/80-induced expression of COX-2 (mRNA and protein) and NGF (mRNA) in HaCaT cells were suppressed by EPS treatment in a dose-dependent manner. As an inhibitor of NF-?B, I?B protein levels were dose-dependently upregulated by EPS. Fluorescence-activated cell sorting (FACS) analysis revealed that EPS scavenged compound 48/80-induced reactive oxygen species (ROS) in HaCaT cells. Conclusion EPS exerts a potent anti-inflammatory activity via its anti-oxidant activity in both mouse skin and compound 48/80-treated HaCaT cells in vitro. Compound 48/80-treated HaCaT cells are a useful new in vitro model of skin inflammation. PMID:25834352

  9. Ion channel-forming alamethicin is a potent elicitor of volatile biosynthesis and tendril coiling. Cross talk between jasmonate and salicylate signaling in lima bean.

    PubMed

    Engelberth, J; Koch, T; Schüler, G; Bachmann, N; Rechtenbach, J; Boland, W

    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 A(2) do not prevent the coiling reaction. PMID:11154344

  10. Drug resistance profile and biofilm forming potential of Pseudomonas aeruginosa isolated from contact lenses in Karachi-Pakistan

    PubMed Central

    2013-01-01

    Background The contaminated contact lens provides Pseudomonas aeruginosa an ideal site for attachment and biofilm production. Continuous contact of the eye to the biofilm-infested lens can lead to serious ocular diseases, such as keratitis (corneal ulcers). The biofilms also prevent effective penetration of the antibiotics, which increase the chances of antibiotic resistance. Methods For this study, 22 Pseudomonas aeruginosa isolates were obtained from 36 contact lenses and 14 contact lens protective fluid samples. These isolates were tested against eight commonly used antibiotics using Kirby-Bauer disk diffusion method. The biofilm forming potential of these isolates was also evaluated using various qualitative and quantitative techniques. Finally, a relationship between biofilm formation and antibiotic resistance was also examined. Results The isolates of Pseudomonas aeruginosa tested were found resistant to most of the antibiotics tested. Qualitative and quantitative biofilm analysis revealed that most of the isolates exhibited strong biofilm production. The biofilm production was significantly higher in isolates that were multi-drug resistant (p?forming Pseudomonas aeruginosa isolates are mainly involved in contact lens associated infections. This appears to be the first report from Pakistan, which analyzes both antibiotic resistance profile and biofilm forming potential of Pseudomonas aeruginosa isolates from contact lens of the patients with contact lens associated infections. PMID:24134792

  11. 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.

  12. Academic Petition Form Contact your graduate program office about completing this form. A change in status or registration may impact your

    E-print Network

    Academic Petition Form Contact your graduate program office about completing this form. A change in status or registration may impact your funding. Submit completed petition to your graduate program office status Note: All petitions must include a personal statement and required documentation. Please refer

  13. A nanorod polymer micro-array formed by micro-contact printing

    NASA Astrophysics Data System (ADS)

    Roche, Philip J. R.; Wang, Songzhe; Cheung, Maurice C. K.; Chodavarapu, Vamsy P.; Kirk, Andrew G.

    2012-03-01

    In previous work, we demonstrate a simple approach to creating a plasmonic polymer. Reflecting upon the need for greater spot density while still maintaining the objective of low cost analysis, the next generation of device is described where density up to 24000 sensing spots is achievable. A localized surface plasmon micro-array is described formed by single or multiple deposition of a nanorod plasmonic polymer by micro-contact printing. The structure of the polymer can be made micro-porous and thickness can be controlled by a cyclical deposition and rapid heat cure protocol. The consistency of feature deposition is assessed. The resulting micro-structure provides a large surface area for immobilization of biomolecules for assay development. Dark-field analysis of the polymer demonstrates complex microstructure and intense Mie Scattering as expected from gold nanorods. Using fluorescence confocal analysis images of the polymer demonstrates two independent photo-luminescent emission spectra. The two independent emission spectra are linked to the positions of the localized surface plasmons of the nanorods, using a pump source of 543nm excites the transverse plasmon (peak at 550nm)and it's commensurate emission, but doesn't excite the longer emission around 700nm that is linked to the longitudinal Plasmon around 737nm. The different emissions are demonstrated in the illumination of different portions of the polymer matrix under each pump source excitation. The potential for multiple spectroscopic biosensor analysis is discussed.

  14. 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.

  15. 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.

  16. 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.

  17. 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

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

    SciTech Connect

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

    2014-09-22

    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.

  19. UCSB Annual Income Tax Information Return Contacts To request missing forms

    E-print Network

    -877-467-3821 with additional questions. Nonresident Aliens o IRS Form 1042-S, Foreign Person's U.S. Source Income Subject Nonresident Aliens o California Form 592-B, Report of Tax Withheld at Source on Nonresidents

  20. Forming and breaking of contacts in jammed granular media by nonlinear acoustic waves

    NASA Astrophysics Data System (ADS)

    Wildenberg, S.; Yang, Y.; van Hecke, M.; Jia, X.

    2013-06-01

    We investigate the nonlinear response of pulsed sound transmission in weakly compressed granular materials, composed of glass beads and sand. Amplitude and velocity of longitudinal waves are simultaneously measured. We observe that weakly compressed packings can both exhibit strengthening and weakening of the sound velocity and transmission amplitude when excited by high amplitude sound. These effects are due to the changes of the contacts between the particles and although the effective medium theory qualitatively describes these effects it fails to quantitatively account for them.

  1. Influence of a deep-level-defect band formed in a heavily Mg-doped GaN contact layer on the Ni/Au contact to p-GaN

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Jing; Zhao, De-Gang; Jiang, De-Sheng; Chen, Ping; Zhu, Jian-Jun; Liu, Zong-Shun; Le, Ling-Cong; Yang, Jing; He, Xiao-Guang; Zhang, Li-Qun; Liu, Jian-Ping; Zhang, Shu-Ming; Yang, Hui

    2015-09-01

    The influence of a deep-level-defect (DLD) band formed in a heavily Mg-doped GaN contact layer on the performance of Ni/Au contact to p-GaN is investigated. The thin heavily Mg-doped GaN (p++-GaN) contact layer with DLD band can effectively improve the performance of Ni/Au ohmic contact to p-GaN. The temperature-dependent I-V measurement shows that the variable-range hopping (VRH) transportation through the DLD band plays a dominant role in the ohmic contact. The thickness and Mg/Ga flow ratio of p++-GaN contact layer have a significant effect on ohmic contact by controlling the Mg impurity doping and the formation of a proper DLD band. When the thickness of the p++-GaN contact layer is 25 nm thick and the Mg/Ga flow rate ratio is 10.29%, an ohmic contact with low specific contact resistivity of 6.97× 10- 4 ?·cm2 is achieved. Project supported by the National Natural Science Foundation of China (Grant Nos. 61474110, 61377020, 61376089, 61223005, and 61176126), the National Science Fund for Distinguished Young Scholars of China (Grant No. 60925017), One Hundred Person Project of the Chinese Academy of Sciences, and the Basic Research Project of Jiangsu Province, China (Grant No. BK20130362).

  2. Residual damage effects on gate contacts formed on SiC surfaces etched by using the amorphization technique

    NASA Astrophysics Data System (ADS)

    Alok, Dev; Makeshwar, K.; Jayant Baliga, B.

    1997-03-01

    A trench fabrication process has been proposed and experimentally demonstrated for silicon carbide using the amorphization technique. In the present work, the quality of gates [oxide for metal oxide semiconductor field-effect transistors (MOSFETs) and Schottky barrier contacts for metal semicondcutor field-effect transistors (MESFETs)] fabricated on the etched surfaces are compared with those formed on the as-grown silicon carbide surface. The resistivity and breakdown electric field of the thermal oxide grown on the etched surface was found to be comparable to that of thermal oxide grown on silicon. However, a large concentration of acceptor type interface states (0.5-1 x 1013 cm-2eV-1) was observed. This results in a large negative interface charge at room temperature and a significant shift in flat band voltage as a function of temperature, which makes the process unsuitable for formation of gates in UMOSFETs. Titanium Schottky contacts formed on the etched surface showed superior reverse current-voltage characteristics and higher breakdown voltages than the Schottky diodes formed on unetched surface with similar doping concentrations. This indicates that the argon implant process for trench formation is suitable for fabrication of gate regions in high voltage vertical MESFETs (or SITs).

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

    SciTech Connect

    Gao, Xu E-mail: TSUKAGOSHI.Kazuhito@nims.go.jp; Aikawa, Shinya; Mitoma, Nobuhiko; Lin, Meng-Fang; Kizu, Takio; Tsukagoshi, Kazuhito E-mail: TSUKAGOSHI.Kazuhito@nims.go.jp; Nabatame, Toshihide

    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.

  4. 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.

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

    SciTech Connect

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

    2010-10-04

    Elemental sulfur (S{sup 0}), 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.

  6. The Troy Microneedle: A Rapidly Separating, Dissolving Microneedle Formed by Cyclic Contact and Drying on the Pillar (CCDP)

    PubMed Central

    Kim, Miroo; Yang, Huisuk; Kim, Suyong; Lee, Chisong; Jung, Hyungil

    2015-01-01

    In dissolving microneedle (DMN)-mediated therapy, complete and rapid delivery of DMNs is critical for the desired efficacy. Traditional patch-based DMN delivery, however, may fail due to incomplete delivery from insufficient skin insertion or rapid separation of microneedles due to their strong bond to the backing film. Here, we introduce the Troy microneedle, which was created by cyclic contact and drying on the pillar (CCDP), and which enabled simultaneous complete and rapid delivery of DMN. This CCDP process could be flexibly repeated to achieve a specific desired drug dose in a DMN. We evaluated DMN separation using agarose gel, and the Troy microneedle achieved more complete and rapid separation than other, more deeply dipped DMN, primarily because of the Troy’s minimal junction between the DMN and pillar. When Troy microneedles were applied to pig cadaver skin, it took only 15 s for over 90% of encapsulated rhodamine B to be delivered, compared to 2 h with application of a traditional DMN patch. In vivo skin penetration studies demonstrated rapid DMN-separation of Troy microneedles still in solid form before dissolution. The Troy microneedle overcomes critical issues associated with the low penetration efficiency of flat patch-based DMN and provides an innovative route for DMN-mediated therapy, combining patient convenience with the desire drug efficacy. PMID:26308945

  7. 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.

    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.

  8. Ayu (Plecoglossus altivelis) in a contact zone between amphidromous and landlocked forms: genetic analyses of populations in the Yodo River system.

    PubMed

    Takeshima, Hirohiko; Lguchi, Kei'ichiro; Nishida, Mutsumi

    2009-08-01

    The migratory fish ayu, Plecoglossus altivelis, has two forms: an amphidromous form found throughout the Japanese islands and a landlocked form found in Lake Biwa. Because Lake Biwa is one of the sources of the Yodo River, which flows into Osaka Bay, it is likely that there has been contact between the two forms within the Yodo River system. To examine the effects of such contact, 573 ayu were collected from the Yodo River system and several other rivers and compared through an extensive investigation of microsatellite genotyping. Multivariate and individual admixture analyses of microsatellite data showed that samples of upstream migrants collected from the Yodo River in May 2003 included many individuals assigned to the amphidromous form, although fish collections in June and July 2003 were primarily composed of individuals of the landlocked form. Samples of drifting larvae, which we considered to be derived from eggs spawned in the Yodo River system, were mostly assigned to the amphidromous form. These results imply that an indigenous population of the amphidromous form exists and reproduces in the Yodo River system. it is likely that upstream migrants of the landlocked Lake Biwa form are supplied annually as well-developed larvae drifting out from Lake Biwa, but contribute very little to the next generation. PMID:19719405

  9. For more information contact the Computer Education Center at (860) 679-8870 Please send Website Request forms to: MC4003, attn: Computer Education Center or bensmith@uchc.edu

    E-print Network

    Oliver, Douglas L.

    For more information contact the Computer Education Center at (860) 679-8870 Please send Website Health Center Computer Education Center - Library STUDENT WEBSITE REQUEST FORM Contact Information: Name: Email: Phone Number: Graduation Date: How long will you be the website contact person? (ending date

  10. Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens.

    PubMed

    Karlberg, Ann-Therese; Börje, Anna; Duus Johansen, Jeanne; Lidén, Carola; Rastogi, Suresh; Roberts, David; Uter, Wolfgang; White, Ian R

    2013-12-01

    Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety. PMID:24107147

  11. Ohmic contacts on n-type layers formed in GaN/AlGaN/GaN by dual-energy Si ion implantation

    NASA Astrophysics Data System (ADS)

    Shiino, Tomohisa; Saitoh, Tomohiro; Nakamura, Tohru; Inada, Taroh

    2009-05-01

    Electrical properties of Si-implanted n-type GaN/AlGaN/GaN layers and contact resistances of ohmic electrodes (TiAl) formed on these layers have been examined. Experimental results have clearly shown that ohmic electrodes with a low specific-contact resistance of 1.4 × 10-7 ? cm2 can be fabricated on the n-type layer having a low sheet resistance of 145 ?/sq, which has been formed by the dual-energy Si ion implantation (80 keV:1.01 × 1015/cm2 + 30 keV:1.6 × 1014/cm2) and subsequent annealing at 1200 °C for 2 min using a Si3N4 layer as an encapsulant.

  12. Boron trichloride plasma treatment effect on ohmic contact resistance formed on GaN-based epitaxial structure

    NASA Astrophysics Data System (ADS)

    Kobelev, A. A.; Barsukov, Yu V.; Andrianov, N. A.; Smirnov, A. S.

    2015-01-01

    A BCl3 plasma treatment effect on GaN surface and reduction of ohmic contact resistance in GaN/AlGaN epitaxial structure with a GaN cap layer has been studied. The BCl3 plasma treatment was carried out by an inductively coupled plasma reactive ion etching (ICP RIE) system under conditions of low discharge power with zero external bias controlling power to prevent any recess etching of the GaN cap layer. The measured average contact resistances with and without plasma treatment were 1.8×10-5 and 1.05×10-5 ?·cm2 respectively. To study the BCl3 plasma treatment effect on GaN surface and explain the increasing of contact resistance, the elemental composition of GaN surface was measured using x-ray photoelectron spectroscopy. It was found that a Bx-Cly layer covered the GaN surface after the BCl3 plasma treatment. This can indicate that ion bombardment from plasma is inefficient to prevent deposition of BClx radicals on the GaN cap layer surface and subsequent formation of the Bx-Cly layer which is responsible for increase of ohmic contact resistance after the BCl3 plasma treatment.

  13. 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.

  14. 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.

  15. First-principles investigation on the electronic efficiency and binding energy of the contacts formed by graphene and poly-aromatic hydrocarbon anchoring groups

    SciTech Connect

    Li, Yang; Tu, Xingchen; Wang, Hao; Hou, Shimin; Sanvito, Stefano

    2015-04-28

    The electronic efficiency and binding energy of contacts formed between graphene electrodes and poly-aromatic hydrocarbon (PAH) anchoring groups have been investigated by the non-equilibrium Green’s function formalism combined with density functional theory. Our calculations show that PAH molecules always bind in the interior and at the edge of graphene in the AB stacking manner, and that the binding energy increases following the increase of the number of carbon and hydrogen atoms constituting the PAH molecule. When we move to analyzing the electronic transport properties of molecular junctions with a six-carbon alkyne chain as the central molecule, the electronic efficiency of the graphene-PAH contacts is found to depend on the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the corresponding PAH anchoring group, rather than its size. To be specific, the smaller is the HOMO-LUMO gap of the PAH anchoring group, the higher is the electronic efficiency of the graphene-PAH contact. Although the HOMO-LUMO gap of a PAH molecule depends on its specific configuration, PAH molecules with similar atomic structures show a decreasing trend for their HOMO-LUMO gap as the number of fused benzene rings increases. Therefore, graphene-conjugated molecule-graphene junctions with high-binding and high-conducting graphene-PAH contacts can be realized by choosing appropriate PAH anchor groups with a large area and a small HOMO-LUMO gap.

  16. First-principles investigation on the electronic efficiency and binding energy of the contacts formed by graphene and poly-aromatic hydrocarbon anchoring groups

    NASA Astrophysics Data System (ADS)

    Li, Yang; Tu, Xingchen; Wang, Hao; Sanvito, Stefano; Hou, Shimin

    2015-04-01

    The electronic efficiency and binding energy of contacts formed between graphene electrodes and poly-aromatic hydrocarbon (PAH) anchoring groups have been investigated by the non-equilibrium Green's function formalism combined with density functional theory. Our calculations show that PAH molecules always bind in the interior and at the edge of graphene in the AB stacking manner, and that the binding energy increases following the increase of the number of carbon and hydrogen atoms constituting the PAH molecule. When we move to analyzing the electronic transport properties of molecular junctions with a six-carbon alkyne chain as the central molecule, the electronic efficiency of the graphene-PAH contacts is found to depend on the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the corresponding PAH anchoring group, rather than its size. To be specific, the smaller is the HOMO-LUMO gap of the PAH anchoring group, the higher is the electronic efficiency of the graphene-PAH contact. Although the HOMO-LUMO gap of a PAH molecule depends on its specific configuration, PAH molecules with similar atomic structures show a decreasing trend for their HOMO-LUMO gap as the number of fused benzene rings increases. Therefore, graphene-conjugated molecule-graphene junctions with high-binding and high-conducting graphene-PAH contacts can be realized by choosing appropriate PAH anchor groups with a large area and a small HOMO-LUMO gap.

  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. Environmental Health & Safety Department -Chemical Storage and Distribution Facility (CSDF) Use this form if you would like the EH&S Department to ship DOT regulated materials. Contact the Chemical Hygiene

    E-print Network

    Hygiene Officer for clarification regarding whether or not your particular shipment will be considered? Contact the Chemical Hygiene Officer at the CSDF. (303) 273-3555 ShipHazmatForm2013a.PDF Additional

  19. Contact Dermatitis

    MedlinePLUS

    ... Z Diseases and treatments A - D Contact dermatitis Contact dermatitis Contact dermatitis : Many health care workers develop ... happen immediately. Most take time to appear. Allergic contact dermatitis Some people have an allergic skin reaction. ...

  20. Generation of a Potent Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Antagonist by Engineering a Stable Form of the Receptor-associated Protein (RAP) D3 Domain.

    PubMed

    Prasad, Joni M; Migliorini, Mary; Galisteo, Rebeca; Strickland, Dudley K

    2015-07-10

    The low density lipoprotein receptor-related protein 1 (LRP1) is a member of the low density lipoprotein receptor family and plays important roles in a number of physiological and pathological processes. Expression of LRP1 requires the receptor-associated protein (RAP), a molecular chaperone that binds LRP1 and other low density lipoprotein receptor family members in the endoplasmic reticulum and traffics with them to the Golgi where the acidic environment causes its dissociation. Exogenously added RAP is a potent LRP1 antagonist and binds to LRP1 on the cell surface, preventing ligands from binding. Following endocytosis, RAP dissociates in the acidic endosome, allowing LRP1 to recycle back to the cell surface. The acid-induced dissociation of RAP is mediated by its D3 domain, a relatively unstable three-helical bundle that denatures at pH <6.2 due to protonation of key histidine residues on helices 2 and 3. To develop an LRP1 inhibitor that does not dissociate at low pH, we introduced a disulfide bond between the second and third helices in the RAP D3 domain. By combining this disulfide bond with elimination of key histidine residues, we generated a stable RAP molecule that is resistant to both pH- and heat-induced denaturation. This molecule bound to LRP1 with high affinity at both neutral and acidic pH and proved to be a potent inhibitor of LRP1 function both in vitro and in vivo, suggesting that our stable RAP molecule may be useful in multiple pathological settings where LRP1 blockade has been shown to be effective. PMID:26013822

  1. DIMETHYLARSINE AND TRIMETHYLARSINE ARE POTENT GENOTOXINS IN VITRO.

    EPA Science Inventory

    Dimethylarsine and Trimethylarsine are potent genotoxins in vitro
    Andrewes, P; Kitchin, KT; and Wallace, KA

    Abstract
    The mechanism of arsenic carcinogenesis is unclear. A complicating factor receiving increasing attention is that arsenic is biomethylated to form vari...

  2. ORIGINAL PAPER Discovery of potent inhibitors for interleukin-2-inducible

    E-print Network

    Lee, Keun Woo

    ORIGINAL PAPER Discovery of potent inhibitors for interleukin-2-inducible T-cell kinase: structure Structure-based hypothesis PTK Protein tyrosine kinase PH Pleckstrin homology SH3 Src homology3 SH2 Src (cytoplasmic) kinases. Src and eight related molecules formed the largest family of cytoplasmic PTKs, while

  3. 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…

  4. Celebrity Patients, VIPs, and Potentates

    PubMed Central

    Groves, James E.; Dunderdale, Barbara A.; Stern, Theodore A.

    2002-01-01

    Background: During the second half of the 20th century, the literature on the doctor-patient relationship mainly dealt with the management of “difficult” (personality-disordered) patients. Similar problems, however, surround other types of “special” patients. Method: An overview and analysis of the literature were conducted. As a result, such patients can be subcategorized by their main presentations; each requires a specific management strategy. Results: Three types of “special” patients stir up irrational feelings in their caregivers. Sick celebrities threaten to focus public scrutiny on the private world of medical caregivers. VIPs generate awe in caregivers, with loss of the objectivity essential to the practice of scientific medicine. Potentates unearth narcissism in the caregiver-patient relationship, which triggers a struggle between power and shame. Pride, privacy, and the staff's need to be in control are all threatened by introduction of the special patient into medicine's closed culture. Conclusion: The privacy that is owed to sick celebrities should be extended to protect overexposed staff. The awe and loss of medical objectivity that VIPs generate are counteracted by team leadership dedicated to avoiding any deviation from standard clinical procedure. Moreover, the collective ill will surrounding potentates can be neutralized by reassuring them that they are “special”—and by caregivers mending their own vulnerable self-esteem. PMID:15014712

  5. 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,

  6. 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

  7. Hierarchical multicolor nano-pixel matrices formed by coordinating luminescent metal ions to a conjugated poly(4?-octyl-2?,6?-bispyrazoyl pyridine) film via contact printing

    PubMed Central

    Basak, Supratim; Mohiddon, Md Ahamad; Baumgarten, Martin; Müllen, Klaus; Chandrasekar, Rajadurai

    2015-01-01

    We introduce a cost-effective, yet feasible reactive printing approach namely, “coordination chemistry at the conjugated ligand polymer surface”. By using a contact printing technique we selectively fabricated high resolution nano-pixel configurations consisting of red, blue and green (R,G,B) colors arranged in a hierarchical three-dimensional fashion. For this, we have synthesized a novel blue emitting conjugated ligand polymer, [poly(4?-octyl-2?,6?-bispyrazoyl pyridine)] ( ~ 7–8?KDa) having a tridentate ligand in its repeating unit which forms a thin film prone of binding metal ions. On top of this ligand polymer film, a layer of high-resolution cross-stripes (width ca. 800?nm) was printed comprised of Eu and Tb ions over a large area ~ 100 × 100??m2. The final woodpile-like assembly produced a new pixel group consisting of B; BG; BR; and BGR (White) colors. The area of the white emitting square is ca. 0.64??m2. The patterned layers that make up the pixels are very thin and thus this new technique might find applications in flexible light emitting devices. PMID:25673007

  8. 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

  9. 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.

  10. Noneczematous Contact Dermatitis

    PubMed Central

    Foti, Caterina; Vestita, Michelangelo; Angelini, Gianni

    2013-01-01

    Irritant or allergic contact dermatitis usually presents as an eczematous process, clinically characterized by erythematoedematovesicous lesions with intense itching in the acute phase. Such manifestations become erythematous-scaly as the condition progresses to the subacute phase and papular-hyperkeratotic in the chronic phase. Not infrequently, however, contact dermatitis presents with noneczematous features. The reasons underlying this clinical polymorphism lie in the different noxae and contact modalities, as well as in the individual susceptibility and the various targeted cutaneous structures. The most represented forms of non-eczematous contact dermatitis include the erythema multiforme-like, the purpuric, the lichenoid, and the pigmented kinds. These clinical entities must obviously be discerned from the corresponding “pure” dermatitis, which are not associated with contact with exogenous agents. PMID:24109520

  11. 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

  12. Solar cell contact formation using laser ablation

    SciTech Connect

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

    2015-07-21

    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.

  13. 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.

  14. 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.

  15. ?-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists.

    PubMed

    Kim, Ho Shin; Jin, Mi-Kyoung; Kang, Sang-Uk; Lim, Ju-Ok; Tran, Phuong-Thao; Hoang, Van-Hai; Ann, Jihyae; Ha, Tae-Hwan; Pearce, Larry V; Pavlyukovets, Vladimir A; Blumberg, Peter M; Lee, Jeewoo

    2014-06-15

    A series of ?-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of ?-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant. PMID:24794110

  16. 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

  17. Potent antibacterial nanoparticles for pathogenic bacteria.

    PubMed

    Lai, Hong-Zheng; Chen, Wei-Yu; Wu, Ching-Yi; Chen, Yu-Chie

    2015-01-28

    Antibiotic-resistant bacteria have emerged because of the prevalent use of antibacterial agents. Thus, new antibacterial agents and therapeutics that can treat bacterial infections are necessary. Vancomycin is a potent antibiotic. Unfortunately, some bacterial strains have developed their resistance toward vancomycin. Nevertheless, it has been demonstrated that vancomycin-immobilized nanoparticles (NPs) are capable to be used in inhibition of the cell growth of vancomycin-resistant bacterial strains through multivalent interactions. However, multistep syntheses are usually necessary to generate vancomycin-immobilized NPs. Thus, maintaining the antibiotic activity of vancomycin when the drug is immobilized on the surface of NPs is challenging. In this study, a facile approach to generate vancomycin immobilized gold (Van-Au) NPs through one-pot stirring of vancomycin with aqueous tetrachloroauric acid at pH 12 and 25 °C for 24 h was demonstrated. Van-Au NPs (8.4 ± 1.3 nm in size) were readily generated. The generated Van-Au NPs maintained their antibiotic activities and inhibited the cell growth of pathogens, which included Gram-positive and Gram-negative bacteria as well as antibiotic-resistant bacterial strains. Furthermore, the minimum inhibitory concentration of the Van-Au NPs against bacteria was lower than that of free-form vancomycin. Staphylococcus aureus-infected macrophages were used as the model samples to examine the antibacterial activity of the Van-Au NPs. Macrophages have the tendency to engulf Van-Au NPs through endocytosis. The results showed that the cell growth of S. aureus in the macrophages was effectively inhibited, suggesting the potential of using the generated Van-Au NPs as antibacterial agents for bacterial infectious diseases. PMID:25584802

  18. 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.

  19. QS-21: a potent vaccine adjuvant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QS-21 is an potent adjuvant derived from the bark of a Chilean tree, Quillaja saponaria. One of the advantages of this adjuvant is that it promotes a balanced humoral and cell-mediaed immune response and can be widely applicable to a variety of vaccines. This adjuvant has used for some veterinary va...

  20. Chain Of Test Contacts For Integrated Circuits

    NASA Technical Reports Server (NTRS)

    Lieneweg, Udo

    1989-01-01

    Test structure forms chain of "cross" contacts fabricated together with large-scale integrated circuits. If necessary, number of such chains incorporated at suitable locations in integrated-circuit wafer for determination of fabrication yield of contacts. In new structure, resistances of individual contacts determined: In addition to making it possible to identify local defects, enables generation of statistical distributions of contact resistances for prediction of "parametric" contact yield of fabrication process.

  1. Last Updated Date: March, 2006 Instructions: Fill out Sections 1, 2, 3, and 4 only. All information is required. If you need assistance completing this form, please contact

    E-print Network

    Goodman, Robert M.

    Services at 732/445-4646. Completed and signed forms should be forwarded to Access Management, Enterprise: Financial / Budget / Procure To Pay (No Payroll) Data Access: Financial / Budget / Procure To Pay / Payroll

  2. Alternative Breaks Emergency Contact & Verification of Medical

    E-print Network

    Tipple, Brett

    Alternative Breaks Emergency Contact & Verification of Medical Insurance Form Participant Name: ___________________________ Emergency Contact/Medical Info Please list any allergies, medical conditions or medications you of Utah policy. Do you have personal medical health insurance? Yes No If Yes: I

  3. 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:

  4. Types of Contact Lenses

    MedlinePLUS

    ... Consumer Devices Consumer Products Contact Lenses Types of Contact Lenses Share Tweet Linkedin Pin it More sharing ... Orthokeratology (Ortho-K) Decorative (Plano) Contact Lenses Soft Contact Lenses Soft contact lenses are made of soft, ...

  5. 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.

  6. Reducing contact resistance in graphene devices through contact area patterning.

    PubMed

    Smith, Joshua T; Franklin, Aaron D; Farmer, Damon B; Dimitrakopoulos, Christos D

    2013-04-23

    Performance of graphene electronics is limited by contact resistance associated with the metal-graphene (M-G) interface, where unique transport challenges arise as carriers are injected from a 3D metal into a 2D-graphene sheet. In this work, enhanced carrier injection is experimentally achieved in graphene devices by forming cuts in the graphene within the contact regions. These cuts are oriented normal to the channel and facilitate bonding between the contact metal and carbon atoms at the graphene cut edges, reproducibly maximizing "edge-contacted" injection. Despite the reduction in M-G contact area caused by these cuts, we find that a 32% reduction in contact resistance results in Cu-contacted, two-terminal devices, while a 22% reduction is achieved for top-gated graphene transistors with Pd contacts as compared to conventionally fabricated devices. The crucial role of contact annealing to facilitate this improvement is also elucidated. This simple approach provides a reliable and reproducible means of lowering contact resistance in graphene devices to bolster performance. Importantly, this enhancement requires no additional processing steps. PMID:23473291

  7. High response Schottky ultraviolet photodetector formed by PEDOT:PSS transparent electrode contacts to Mg0.1Zn0.9O

    NASA Astrophysics Data System (ADS)

    Hu, Zuo-Fu; Wu, Huai-Hao; Lv, Yan-Wu; Zhang, Xi-Qing

    2015-10-01

    In this paper, we report a Schottky ultraviolet photodetector based on poly (3,4-ethylenedioxy-thiophene) poly(styrenesulfonate) (PEDOT:PSS) transparent electrode contacts to Mg0.1Zn0.9O. The I-V characteristic curves of the device are measured in the dark condition and under the illumination of a 340-nm UV light. The device shows a typical rectifying behavior with a current rectification ratio of 103 at ±2 V, which exhibits a good Schottky behavior. The photo-to-dark current ratio is high, which is 1×103 at -4 V. A peak response of 0.156 A/W at 340 nm is observed. The device also exhibits a wide response from 250 nm to 340 nm, with a response larger than 0.1 A/W. It covers the UV-B region (280 nm-320 nm), which makes the device very suitable for the detection of UV-B light. Project supported by the National Natural Science Foundation of China (Grant No. 50972007), the National Basic Research Program of China (Grant No. 2011CB932703), the National Natural Science Foundation for Distinguished Young Scholars of China (Grant No. 60825407), and the Opened Fund of the State Key Laboratory on Integrated Optoelectronics.

  8. 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.

  9. Quasi-Quantum Model of Potentization

    E-print Network

    Molski, Marcin

    2009-01-01

    Analytical time-dependent functions describing the change of the concentration of the solvent S(t) and the homeopathic active substance A(t) during the decimal and centesimal dilution are derived. The function S(t) is a special case of the West-Brown-Enquist curve describing the ontogenic growth, hence the increase in concentration of the solvent during potentization resembles the growth of biological systems. It is proven that the macroscopic S(t) function is the ground state solution of the microscopic non-local Horodecki-Feinberg equation for the time-dependent Hulthen potential at the critical screening. In consequence the potentization belongs to the class of quasi-quantum phenomena playing an important role both in the biological systems and homeopathy. A comparison of the model proposed with recently performed experiment on delayed luminescence of the homeopathic remedy will be also made.

  10. Quasi-Quantum Model of Potentization

    E-print Network

    Marcin Molski

    2009-11-23

    Analytical time-dependent functions describing the change of the concentration of the solvent S(t) and the homeopathic active substance A(t) during the decimal and centesimal dilution are derived. The function S(t) is a special case of the West-Brown-Enquist curve describing the ontogenic growth, hence the increase in concentration of the solvent during potentization resembles the growth of biological systems. It is proven that the macroscopic S(t) function is the ground state solution of the microscopic non-local Horodecki-Feinberg equation for the time-dependent Hulthen potential at the critical screening. In consequence the potentization belongs to the class of quasi-quantum phenomena playing an important role both in the biological systems and homeopathy. A comparison of the model proposed with recently performed experiment on delayed luminescence of the homeopathic remedy will be also made.

  11. Contact allergic dermatitis to dicyclohexylcarbodiimide used in protein synthesis.

    PubMed

    Hoffman, T E; Adams, R M

    1989-08-01

    Dicyclohexylcarbodiimide is a commonly used coupling agent found in protein synthesis. It is a potent allergic sensitizer found especially in the emerging industries involved in recombinant DNA synthesis. Chemists who work in research and development of this industry are especially at risk of development of contact dermatitis, unless they are careful and avoid skin contact. This report describes two chemists with allergic contact dermatitis from repeated contact with this compound in their work as research and development chemists. An appropriate concentration for patch testing is suggested. PMID:2526828

  12. Potent inhibition of tau fibrillization with a multivalent ligand

    SciTech Connect

    Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

    2007-11-09

    Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at {approx}80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors.

  13. Potent D-Peptide Inhibitors of HIV-1 Entry

    SciTech Connect

    Welch,B.; VanDemark, A.; Heroux, A.; Hill, C.; Kay, M.

    2007-01-01

    During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC50 = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS.

  14. 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.

  15. Potent complement C3a receptor agonists derived from oxazole amino acids: Structure-activity relationships.

    PubMed

    Singh, Ranee; Reed, Anthony N; Chu, Peifei; Scully, Conor C G; Yau, Mei-Kwan; Suen, Jacky Y; Durek, Thomas; Reid, Robert C; Fairlie, David P

    2015-12-01

    Potent ligands for the human complement C3a receptor (C3aR) were developed from the almost inactive tripeptide Leu-Ala-Arg corresponding to the three C-terminal residues of the endogenous peptide agonist C3a. The analogous Leu-Ser-Arg was modified by condensing the serine side chain with the leucine carbonyl with elimination of water to form leucine-oxazole-arginine. Subsequent elaboration with a variety of N-terminal amide capping groups produced agonists as potent as human C3a itself in stimulating Ca(2+) release from human macrophages. Structure-activity relationships are discussed. PMID:26522948

  16. Potent benzoazepinone ?-secretase modulators with improved bioavailability.

    PubMed

    Methot, Joey L; Fischer, Christian; Li, Chaomin; Rivkin, Alexey; Ahearn, Sean P; Brown, William Colby; Kattar, Sam; Kelley, Elizabeth; Mampreian, Dawn M; Schell, Adam; Rosenau, Andrew; Zhou, Hua; Ball, Richard; Deshmukh, Sujal V; Jeliazkova-Mecheva, Valentina V; Diaz, Damaris; Moy, Lily Y; Kenific, Candia M; Moxham, Chris; Shah, Sanjiv; Nuthall, Hugh; Szewczak, Alexander A; Hill, Armetta; Hughes, Bethany; Smotrov, Nadya; Munoz, Benito; Miller, Thomas A; Shearman, Mark S

    2015-09-01

    The triazolyl amide ?-secretase modulators are potent alternatives to the cinnamyl amides that have entered the clinic for the treatment of Alzheimer's disease. Herein we build on the lead benzoazepinones described in our prior communication with imidazomethoxyarene moiety alternatives that offer opportunities to fine tune physical properties as well as address hERG binding and PK. Both half-life and bioavailability were significantly improved, especially in dog, with robust brain A?42 lowering maintained in both transgenic mouse and rat. PMID:26142947

  17. 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

  18. Carvacrol as a potent natural acaricide against Dermanyssus gallinae.

    PubMed

    Tabari, Mohaddeseh Abouhosseini; Youssefi, Mohammad Reza; Barimani, Alireza; Araghi, Atefeh

    2015-10-01

    Resistance to conventional synthetic pesticides has been widely reported in Dermanyssus gallinae in poultry production systems. Introducing novel acaricides to poultry industry today is more urgent than ever. Research in this field recently focused on plants and plant-derived compounds as acaricides. In the present study, acaricidal activity of three plant bioactive components, carvacrol, thymol, and farnesol, was assessed against D. gallinae and compared with synthetic pesticide permethrin. Mode of acaricidal action was determined by contact toxicity and fumigant toxicity bioassays. Except farnesol which did not cause any mortality, carvacrol and thymol were found to be toxic to D. gallinae with LD50 values of 1 and 3.15 ?g/cm(3), respectively. Permethrin gave the LD50 value of 31.95 ?g/cm(3) which was less efficient than carvacrol and thymol. In fumigant toxicity bioassay, mortality rate in carvacrol- and thymol-treated groups in closed method was significantly higher than the open one. On the other hand, permethrin exhibited poor fumigant toxicity as there was no statistically significant difference between mortality rate in open and closed methods. These findings revealed that mechanism of acaricidal activity of carvacrol and thymol but not permethrin was mainly due to fumigant action. Results of the present study suggested that carvacrol and thymol, especially carvacrol, can be developed as a novel potent bioacaricide against D. gallinae. PMID:26143865

  19. Content uniformity of potent drugs in tablets.

    PubMed

    Orr, N A; Sallam, E A

    1978-12-01

    The type of distribution of low dosage drugs that occurs in batches of commercially available tablets has been examined. The uniformity of content of ethinyloestradiol tablets 10 micrograms B.P. from different sources, assessed by single tablet assay showed that three batches exhibited some positive skewness and one marked positive skewness. At the high level of dilution required, the mixing theory indicates that particles of drug must be very fine if acceptable content uniformity is to be obtained. Cohesion of particles impairs the efficiency of the mixing process. It is shown theoretically that unless the drug is dispersed into its component particles the shape of the distribution curve for the content of drug per tablet, in a batch of tablets, will be positively skewed. The relation between the tensile strength of the powdered drug and the degree of skewness of the drug content is also discussed. A positively skewed distribution for tablets containing a small amount of potent drug is unacceptable because this can lead to the presence of relatively large doses of drug in a single tablet. Where one unexpectedly high result occurs in the quality control of the content uniformity of tablets containing potent drugs it is suggested that sufficient single tablet assays be performed to allow the shape of the distribution curve to be assessed. A test for skewness should be included in compendial standards. PMID:32236

  20. Making eye contact without awareness.

    PubMed

    Rothkirch, Marcus; Madipakkam, Apoorva Rajiv; Rehn, Erik; Sterzer, Philipp

    2015-10-01

    Direct gaze is a potent non-verbal signal that establishes a communicative connection between two individuals, setting the course for further interactions. Although consciously perceived faces with direct gaze have been shown to capture attention, it is unknown whether an attentional preference for these socially meaningful stimuli exists even in the absence of awareness. In two experiments, we recorded participants' eye movements while they were exposed to faces with direct and averted gaze rendered invisible by interocular suppression. Participants' inability to correctly guess the occurrence of the faces in a manual forced-choice task demonstrated complete unawareness of the faces. However, eye movements were preferentially directed towards faces with direct compared to averted gaze, indicating a specific sensitivity to others' gaze directions even without awareness. This oculomotor preference suggests that a rapid and automatic establishment of mutual eye contact constitutes a biological advantage, which could be mediated by fast subcortical pathways in the human brain. PMID:26133642

  1. Highly potent fibrinolytic serine protease from Streptomyces.

    PubMed

    Uesugi, Yoshiko; Usuki, Hirokazu; Iwabuchi, Masaki; Hatanaka, Tadashi

    2011-01-01

    We introduce a highly potent fibrinolytic serine protease from Streptomyces omiyaensis (SOT), which belongs to the trypsin family. The fibrinolytic activity of SOT was examined using in vitro assays and was compared with those of known fibrinolytic enzymes such as plasmin, tissue-type plasminogen activator (t-PA), urokinase, and nattokinase. Compared to other enzymes, SOT showed remarkably higher hydrolytic activity toward mimic peptides of fibrin and plasminogen. The fibrinolytic activity of SOT is about 18-fold higher than that of plasmin, and is comparable to that of t-PA by fibrin plate assays. Furthermore, SOT had some plasminogen activator-like activity. Results show that SOT and nattokinase have very different fibrinolytic and fibrinogenolytic modes, engendering significant synergetic effects of SOT and nattokinase on fibrinolysis. These results suggest that SOT presents important possibilities for application in the therapy of thrombosis. PMID:22112764

  2. Potent antitrypanosomal triterpenoid saponins from Mussaenda luteola.

    PubMed

    Mohamed, Shaymaa M; Bachkeet, Enaam Y; Bayoumi, Soad A; Jain, Surendra; Cutler, Stephen J; Tekwani, Babu L; Ross, Samir A

    2015-12-01

    Five new triterpenoid saponins, heinsiagenin A 3-O-[?-l-rhamnopyranosyl-(1?2)-?-d-glucopyranosyl-(1?2)]-?-d-glucopyranoside (1), heinsiagenin A 3-O-[?-l-rhamnopyranosyl-(1?2)-?-d-glucopyranosyl-(1?2)]-[?-d-glucopyranosyl-(1?4)]-?-d-glucopyranoside (2), 2?-hydroxyheinsiagenin A 3-O-[?-l-rhamnopyranosyl-(1?2)-?-d-glucopyranosyl-(1?2)]-?-d-glucopyranoside (3), 2?-hydroxyheinsiagenin A 3-O-[?-d-glucopyranosyl-(1?2)]-[?-d-glucopyranosyl-(1?4)]-?-d-glucopyranoside (4) and N-(2S, 3R, 4R-3-methyl-4-pentanolid-2-yl)-18-hydroxylanosta-8 (9), 22E, 24E-trien-27-amide-3-O-[?-l-rhamnopyranosyl-(1?2)-?-d-glucopyranosyl-(1?2)]-[?-d-glucopyranosyl-(1?4)]-?-d-glucopyranoside (5) were isolated from the aerial parts of Mussaenda luteola Delile (Rubiaceae). Structural elucidation was based on the analysis of spectroscopic data (1D and 2D NMR) and HR-ESI-MS. Compound 1 showed potent antitrypanosomal activity with an IC50 value of 8.80?M. Compounds 2-4 showed highly potent antitrypanosomal activity with IC50 values ranging between (2.57-2.84?M) and IC90 values ranging between (3.36-4.35?M), which are 5 fold greater than the positive control DFMO (IC50 and IC90 values of 13.06 and 28.99?M, respectively). Compounds 1 and 2 showed moderate affinity to ?-opioid receptors with Ki values of 9.936?M and 0.872?M, respectively compared to a Ki value of 1.958nM for the positive control, naloxone HCl. PMID:26524249

  3. 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

  4. 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

  5. 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.

  6. Transition metal contacts to graphene

    NASA Astrophysics Data System (ADS)

    Politou, Maria; Asselberghs, Inge; Radu, Iuliana; Conard, Thierry; Richard, Olivier; Lee, Chang Seung; Martens, Koen; Sayan, Safak; Huyghebaert, Cedric; Tokei, Zsolt; De Gendt, Stefan; Heyns, Marc

    2015-10-01

    Achieving low resistance contacts to graphene is a common concern for graphene device performance and hybrid graphene/metal interconnects. In this work, we have used the circular Transfer Length Method (cTLM) to electrically characterize Ag, Au, Ni, Ti, and Pd as contact metals to graphene. The consistency of the obtained results was verified with the characterization of up to 72 cTLM structures per metal. Within our study, the noble metals Au, Ag and Pd, which form a weaker bond with graphene, are shown to result in lower contact resistance (Rc) values compared to the more reactive Ni and Ti. X-ray Photo Electron Spectroscopy and Transmission Electron Microscopy characterization for the latter have shown the formation of Ti and Ni carbides. Graphene/Pd contacts show a distinct intermediate behavior. The weak carbide formation signature and the low Rc values measured agree with theoretical predictions of an intermediate state of weak chemisorption of Pd on graphene.

  7. Contact Lens Risks

    MedlinePLUS

    ... Health and Consumer Devices Consumer Products Contact Lenses Contact Lens Risks Share Tweet Linkedin Pin it More ... redness blurred vision swelling pain Serious Hazards of Contact Lenses Symptoms of eye irritation can indicate a ...

  8. Contact Lens Care

    MedlinePLUS

    ... For Consumers Consumer Information by Audience For Women Contact Lens Care Share Tweet Linkedin Pin it More ... 1088, www.fda.gov/medwatch Learn More about Contact Lens Care Other Tips on Contact Lenses Decorative ...

  9. Irritant Contact Dermatitis

    MedlinePLUS

    newsletter | contact Share | Irritant Contact Dermatitis Information for adults A A A This image displays scaling bumps and slightly elevated lesions typical of dermatitis, with severe involvement ...

  10. Higher Education Mobility Agreement form

    E-print Network

    Greifswald, Ernst-Moritz-Arndt-Universität

    1 Higher Education Mobility Agreement form ......................................... STAFF MOBILITY/Department International Office Address Domstraße 8, 17489 Greifswald, Germany Country/ Country code5 DE Contact person name and position Sara Behr, ERASMUS Coordinator Contact person e-mail / phone sara

  11. N-naphthoyl-?-naltrexamine (NNTA), a highly selective and potent activator of ?/?-opioid heteromers

    PubMed Central

    Yekkirala, Ajay S.; Lunzer, Mary M.; McCurdy, Christopher R.; Powers, Michael D.; Kalyuzhny, Alexander E.; Roerig, Sandra C.; Portoghese, Philip S.

    2011-01-01

    Numerous G protein-coupled receptors (GPCRs) have been shown to form heteromeric receptors in cell-based assays. Among the many heteromers reported in the opioid receptor family are ?/?, ?/?, and ?/?. However, the in vivo physiological and behavioral relevance for the proposed heteromers have not yet been established. Here we report a unique example of a ligand, N-naphthoyl-?-naltrexamine (NNTA) that selectively activates heteromeric ?/?-opioid receptors in HEK-293 cells and induces potent antinociception in mice. NNTA was an exceptionally potent agonist in cells expressing ?/?-opioid receptors. Intriguingly, it was found to be a potent antagonist in cells expressing only ?-receptors. In the mouse tail-flick assay, intrathecal (i.t.) NNTA produced antinociception that was ~100-fold greater than by intracerebroventricular (i.c.v.) administration. The ?-antagonist, norBNI, decreased the i.t. potency, and the activity was virtually abolished in ?-opioid receptor knockout mice. No tolerance was induced i.t., but marginal tolerance (3-fold) was observed via the i.c.v. route. Moreover, NNTA produced neither significant physical dependence nor place preference in the ED50 dose range. Taken together, this work provides an important pharmacologic tool for investigating the in vivo functional relevance of heteromeric ?/?-opioid receptors and suggests an approach to potent analgesics with fewer deleterious side effects. PMID:21385944

  12. Potent effects of dioscin against liver fibrosis

    PubMed Central

    Zhang, Xiaoling; Han, Xu; Yin, Lianhong; Xu, Lina; Qi, Yan; Xu, Youwei; Sun, Huijun; Lin, Yuan; Liu, Kexin; Peng, Jinyong

    2015-01-01

    We previously reported the promising effects of dioscin against liver injury, but its effect on liver fibrosis remains unknown. The present work investigated the activities of dioscin against liver fibrosis and the underlying molecular mechanisms. Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2 and primary rat hepatic stellate cells (HSCs), but not hepatocytes. Furthermore, dioscin markedly increased peroxisome proliferator activated receptor-? (PPAR-?) expression and significantly reduced a-smooth muscle actin (?-SMA), transforming growth factor-?1 (TGF-?1), collagen ?1 (I) (COL1A1) and collagen ?1 (III) (COL3A1) levels in vitro. Notably, dioscin inhibited HSCs activation and induced apoptosis in activated HSCs. In vivo, dioscin significantly improved body weight and hydroxylproline, laminin, ?-SMA, TGF-?1, COL1A1 and COL3A1 levels, which were confirmed by histopathological assays. Dioscin facilitated matrix degradation, and exhibited hepatoprotective effects through the attenuation of oxidative stress and inflammation, in addition to exerting anti-fibrotic effects through the modulation of the TGF-?1/Smad, Wnt/?-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial signaling pathways, which triggered the senescence of activated HSCs. In conclusion, dioscin exhibited potent effects against liver fibrosis through the modulation of multiple targets and signaling pathways and should be developed as a novel candidate for the treatment of liver fibrosis in the future. PMID:25853178

  13. Chord diagrams, contact-topological quantum field theory, and contact categories

    NASA Astrophysics Data System (ADS)

    Mathews, Daniel

    In this thesis we study some interesting mathematics arising at the intersection of the studies of contact topology and sutured Floer homology. Although this work was originally motivated by the study of contact elements in sutured Floer homology, we also obtain results in pure contact topology. We consider contact elements in the sutured Floer homology of solid tori, as part of the (1+1)-dimensional topological quantum field theory defined by Honda-Kazez-Matic. We find that the Z2 sutured Floer homology of solid tori with longitudinal sutures forms a "categorification of Pascal's triangle", a triangle of vector spaces. Contact structures on solid tori with longitudinal sutures correspond bijectively to chord diagrams, which are sets of disjoint properly embedded arcs in the disc; these may in turn be identified with contact elements. The contact elements form distinguished subsets of the vector spaces in the categorified Pascal's triangle, of order given by the Narayana numbers. We find natural "creation and annihilation operators" which allow us to define a QFT-type basis of each SFH vector space, consisting of contact elements. We show that sutured Floer homology in this case reduces to the combinatorics of chord diagrams. We prove that contact elements are in bijective correspondence with comparable pairs of basis elements with respect to a certain partial order, and in a natural and explicit way. We also prove numerous results about the structure of contact elements and investigate various algebraic structures which arise. Our main theorem, describing how contact elements lie in sutured Floer homology, has a purely combinatorial interpretation, as a statement about chords on discs subject to a certain surgery and a single addition relation. The algebraic and combinatorial structures which naturally arise in this description have intrinsic contact-topological meaning. In particular, the QFT-type basis of sutured Floer homology, and its partial order, have a natural interpretation in pure contact topology, related to the contact category of a disc: the partial order enables us to tell when the sutured solid cylinder obtained by "stacking" two chord diagrams has a tight contact structure. This leads us to extend Honda's notion of contact category to a "bounded" contact category, containing chord diagrams and contact structures which occur within a given contact solid cylinder. We compute this bounded contact category in certain cases. Moreover, the decomposition of a contact element into basis elements naturally gives a triple of contact structures on solid cylinders which we regard as a type of "distinguished triangle" in the contact category. We also use the algebraic structures arising among contact elements to extend the notion of contact category to a 2-category.

  14. EMERGENCY CONTACT CAMPUS DIRECTORY INFORMATION

    E-print Network

    Ma, Lena

    whether you wish to be included in the University of Florida Campus Directory. Submit completed form: ( ) ext: Home/evening phone: ( ) In the event the above person cannot be reached, please contact: Name in the event of an emergency? (If yes, use space below) CAMPUS DIRECTORY Do you wish to have your home address

  15. Sifuvirtide, a potent HIV fusion inhibitor peptide

    SciTech Connect

    Wang, Rui-Rui; Yang, Liu-Meng; Wang, Yun-Hua; Pang, Wei; Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 ; Tam, Siu-Cheung; Tien, Po; Zheng, Yong-Tang

    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.

  16. Immunologic contact urticaria.

    PubMed

    McFadden, John

    2014-02-01

    The wheal and flare reaction from direct contact with a chemical or protein agent is known as contact urticaria. Contact urticaria can be either nonimmunologic (no sensitization required) or immunologic (sensitization required). Immunologic contact urticaria often gives a more aggravated response and has the potential to spread from the local vicinity. Skin testing in immunologic contact urticaria gives a quicker response compared with skin testing in nonimmunologic contact urticaria. There are a wide variety of agents that can cause immunologic contact urticaria, and they can be either low-molecular-weight chemicals (haptens) or proteins. PMID:24262696

  17. Graded contact manifolds and contact Courant algebroids

    E-print Network

    Janusz Grabowski

    2013-02-06

    We develop a systematic approach to contact and Jacobi structures on graded supermanifolds. In this framework, contact structures are interpreted as symplectic principal GL(1,R)-bundles. Gradings compatible with the GL(1,R)-action lead to the concept of a graded contact manifold, in particular a linear (more generally, n-linear) contact structure. Linear contact structures are proven to be exactly the canonical contact structures on first jets of line bundles. They provide linear Kirillov (or Jacobi) brackets and give rise to the concept of a Kirillov algebroid, an analog of a Lie algebroid, for which the corresponding cohomology operator is represented not by a vector field (de Rham derivative) but a first-order differential operator. It is shown that one can view Kirillov or Jacobi brackets as homological Hamiltonians on linear contact manifolds. Contact manifolds of degree 2 are studied, as well as contact analogs of Courant algebroids. We define lifting procedures that provide us with constructions of canonical examples of the structures in question.

  18. 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.

  19. The alkynylphosphonate analogue of calcitriol EM1 has potent anti-metastatic effects in breast cancer.

    PubMed

    Ferronato, María J; Obiol, Diego J; Fermento, María E; Gandini, Norberto A; Alonso, Eliana N; Salomón, Débora G; Vitale, Cristian; Mascaró, Evangelina; Fall, Yagamare; Raimondi, Ana R; Curino, Alejandro C; Facchinetti, María M

    2015-11-01

    The active form of vitamin D3, calcitriol, plays a major role in maintaining calcium/phosphate homeostasis. In addition, it is a potent antiproliferative and prodifferentiating agent. However, when effective antitumor doses of calcitriol are employed, hypercalcemic effects are observed, thus precluding its therapeutic application. To overcome this problem, structural analogues have been designed with the aim at retaining or even increasing the antitumor effects while decreasing its calcemic activity. This report shows the biological evaluation of an alkynylphosphonate vitamin D less-calcemic analogue in a murine model of breast cancer. We demonstrate that this compound has potent anti-metastatic effects through its action over cellular migration and invasion likely mediated through the up-regulation of E-cadherin expression. Based on the current in vitro and in vivo results, EM1 is a promising candidate as a therapeutic agent in breast cancer. PMID:26365558

  20. Vitamin D analogue: potent antiproliferative effects on cancer cell lines and lack of hypercalcemic activity.

    PubMed

    Ferronato, María Julia; Salomón, Débora Gisele; Fermento, María Eugenia; Gandini, Norberto Ariel; López Romero, Alejandro; Rivadulla, Marcos Lois; Pérez-García, Xenxo; Gómez, Generosa; Pérez, Manuel; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2015-05-01

    The active form of vitamin D3, 1?,25(OH)2D3, plays a major role in maintaining calcium/phosphate homeostasis. In addition, it is a potent antiproliferative and pro-differentiating agent. Unfortunately, it usually causes hypercalcemia in vivo when effective antitumour doses are used. It has therefore been found necessary to synthesise new analogues that retain or even increase the antitumour effects but preclude hypercalcemia. This report presents the synthesis of a novel Gemini vitamin D analogue (UVB1) and its biological evaluation. We demonstrate that this compound has potent antitumoural effects over a wide panel of tumour cell lines while showing lack of hypercalcemic activity and toxicity effects in in vivo assays. PMID:25864390

  1. Synthetic studies of the potent marine toxin, (-)-gymnodimine 

    E-print Network

    Yang, Ju

    1999-01-01

    The enantioselective synthesis of the tetrahydrofuran fragment of (-)-gymnodimine, a potent marine neurotoxin, has been achieved in 13% overall yield and 16 steps from 1,3-propanediol. Key features of the convergent synthesis include a chiral...

  2. Chemistry and Biology of Deoxynyboquinone, a Potent Anticancer Compound

    E-print Network

    Hergenrother, Paul J.

    S1 Chemistry and Biology of Deoxynyboquinone, a Potent Anticancer Compound Joseph S. Bair, Rahul Biotechnology. Anti-HSP70 monoclonal mouse antibody (SPA-810) and anti-HMOX-1 rabbit polyclonal antibody (SPA

  3. Development of a potent and selective cell penetrant Legumain inhibitor.

    PubMed

    Ness, Kerry A; Eddie, Sharon L; Higgins, Catherine A; Templeman, Amy; D'Costa, Zenobia; Gaddale, Kishore K D; Bouzzaoui, Samira; Jordan, Linda; Janssen, Dominic; Harrison, Timothy; Burkamp, Frank; Young, Andrew; Burden, Roberta; Scott, Christopher J; Mullan, Paul B; Williams, Rich

    2015-12-01

    This Letter describes the continued SAR exploration of small molecule Legumain inhibitors with the aim of developing a potent and selective in vitro tool compound. Work continued in this Letter explores the use of alternative P2-P3 linker units and the P3 group SAR which led to the identification of 10t, a potent, selective and cellularly active Legumain inhibitor. We also demonstrate that 10t has activity in both cancer cell viability and colony formation assays. PMID:26522952

  4. 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...

  5. 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.

  6. Cosmic Contact Censorship

    E-print Network

    Vaidya, P G

    2007-01-01

    Till date we have not made Contact with any Extraterrestrial civilizations. The Fermi Paradox remains a paradox - the Great Silence prevails. In the light of the Rare Earth hypothesis, it seems that advanced life is exceedingly rare in the universe. Also, if there does exist some Extraterrestrial civilizations then still achieving Contact is extremely difficult as the very nature of the universe discourages Contact. It's as if there is a Cosmic Contact Censorship in place.

  7. Cosmic Contact Censorship

    E-print Network

    Pushkar Ganesh Vaidya

    2007-02-20

    Till date we have not made Contact with any Extraterrestrial civilizations. The Fermi Paradox remains a paradox - the Great Silence prevails. In the light of the Rare Earth hypothesis, it seems that advanced life is exceedingly rare in the universe. Also, if there does exist some Extraterrestrial civilizations then still achieving Contact is extremely difficult as the very nature of the universe discourages Contact. It's as if there is a Cosmic Contact Censorship in place.

  8. CONTACT URTICARIA: PRESENT SCENARIO

    PubMed Central

    Bhatia, Ruchi; Alikhan, Ali; Maibach, Howard I

    2009-01-01

    Immunological contact urticaria is a hypersensitivity reaction that appears on the skin following contact with an eliciting substance. Recent advances in our understanding of the molecular mechanism and pathogenesis of this reaction have altered its classification, diagnosis, and treatment. We discuss classification, epidemiology, diagnosis, testing, and treatment options that are available to patients with contact urticaria. PMID:20161861

  9. 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

  10. Extensive screening for edible herbal extracts with potent scavenging activity against superoxide anions.

    PubMed

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

    2008-06-01

    To search for edible herbal extracts with potent antioxidant activity, we conducted a large scale screening based on the superoxide scavenging activity. That is, scavenging activity against superoxide anions were extensively screened from ethanol extracts of approximately 1,000 kinds of herbs by applying an electron spin resonance (ESR)-spin trapping method. Among them we chose four edible herbal extracts with prominently potent ability to reduce the signal intensity of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OOH, a spin adduct formed by DMPO and superoxide anion. They are the extracts from Punica granatum (Peel), Syzygium aromaticum (Bud), Mangifera indica (Kernel), and Phyllanthus emblica (Fruit), and are allowed to be used as foodstuffs according to the Japanese legal regulation. The ESR-spin trapping method coupled with steady state kinetic analysis showed that all of the four extracts directly scavenge superoxide anions, and that the superoxide scavenging potential of any of the extracts was comparable to that of L-ascorbic acid. Furthermore, polyphenol determination indicates that the activity is at least in part attributable to polyphenols. These results with such large scale screening might give useful information when choosing a potent antioxidant as a foodstuff. PMID:18236159

  11. Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A

    PubMed Central

    Lu, Yingying; Dong, Shichen; Hao, Baixia; Li, Chang; Zhu, Kaiyuan; Guo, Wenjing; Wang, Qian; Cheung, King-Ho; Wong, Connie WM; Wu, Wu-Tian; Markus, Huss; Yue, Jianbo

    2014-01-01

    Autophagy is a catabolic lysosomal degradation process essential for cellular homeostasis and cell survival. Dysfunctional autophagy has been associated with a wide range of human diseases, e.g., cancer and neurodegenerative diseases. A large number of small molecules that modulate autophagy have been widely used to dissect this process and some of them, e.g., chloroquine (CQ), might be ultimately applied to treat a variety of autophagy-associated human diseases. Here we found that vacuolin-1 potently and reversibly inhibited the fusion between autophagosomes and lysosomes in mammalian cells, thereby inducing the accumulation of autophagosomes. Interestingly, vacuolin-1 was less toxic but at least 10-fold more potent in inhibiting autophagy compared with CQ. Vacuolin-1 treatment also blocked the fusion between endosomes and lysosomes, resulting in a defect in general endosomal-lysosomal degradation. Treatment of cells with vacuolin-1 alkalinized lysosomal pH and decreased lysosomal Ca2+ content. Besides marginally inhibiting vacuolar ATPase activity, vacuolin-1 treatment markedly activated RAB5A GTPase activity. Expression of a dominant negative mutant of RAB5A or RAB5A knockdown significantly inhibited vacuolin-1-induced autophagosome-lysosome fusion blockage, whereas expression of a constitutive active form of RAB5A suppressed autophagosome-lysosome fusion. These data suggest that vacuolin-1 activates RAB5A to block autophagosome-lysosome fusion. Vacuolin-1 and its analogs present a novel class of drug that can potently and reversibly modulate autophagy. PMID:25483964

  12. Promoter Activation by CII, a Potent Transcriptional Activator from Bacteriophage 186*

    PubMed Central

    Murchland, Iain; Ahlgren-Berg, Alexandra; Priest, David G.; Dodd, Ian B.; Shearwin, Keith E.

    2014-01-01

    The lysogeny promoting protein CII from bacteriophage 186 is a potent transcriptional activator, capable of mediating at least a 400-fold increase in transcription over basal activity. Despite being functionally similar to its counterpart in phage ?, it shows no homology at the level of protein sequence and does not belong to any known family of transcriptional activators. It also has the unusual property of binding DNA half-sites that are separated by 20 base pairs, center to center. Here we investigate the structural and functional properties of CII using a combination of genetics, in vitro assays, and mutational analysis. We find that 186 CII possesses two functional domains, with an independent activation epitope in each. 186 CII owes its potent activity to activation mechanisms that are dependent on both the ?70 and ? C-terminal domain (?CTD) components of RNA polymerase, contacting different functional domains. We also present evidence that like ? CII, 186 CII is proteolytically degraded in vivo, but unlike ? CII, 186 CII proteolysis results in a specific, transcriptionally inactive, degradation product with altered self-association properties. PMID:25294872

  13. 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

  14. Promoter activation by CII, a potent transcriptional activator from bacteriophage 186.

    PubMed

    Murchland, Iain; Ahlgren-Berg, Alexandra; Priest, David G; Dodd, Ian B; Shearwin, Keith E

    2014-11-14

    The lysogeny promoting protein CII from bacteriophage 186 is a potent transcriptional activator, capable of mediating at least a 400-fold increase in transcription over basal activity. Despite being functionally similar to its counterpart in phage ?, it shows no homology at the level of protein sequence and does not belong to any known family of transcriptional activators. It also has the unusual property of binding DNA half-sites that are separated by 20 base pairs, center to center. Here we investigate the structural and functional properties of CII using a combination of genetics, in vitro assays, and mutational analysis. We find that 186 CII possesses two functional domains, with an independent activation epitope in each. 186 CII owes its potent activity to activation mechanisms that are dependent on both the ?(70) and ? C-terminal domain (?CTD) components of RNA polymerase, contacting different functional domains. We also present evidence that like ? CII, 186 CII is proteolytically degraded in vivo, but unlike ? CII, 186 CII proteolysis results in a specific, transcriptionally inactive, degradation product with altered self-association properties. PMID:25294872

  15. Potent inhibitors precise to S1' loop of MMP-13, a crucial target for osteoarthritis.

    PubMed

    Kalva, Sukesh; Saranyah, K; Suganya, P Rathi; Nisha, M; Saleena, Lilly M

    2013-07-01

    Matrix metalloproteinase-13 (MMP-13) is the primary MMP involved in cartilage degradation through its particular ability to cleave type-II collagen. This protein is expressed by chondrocytes and synovial cells in human osteoarthritis and rheumatoid arthritis; hence, it is an attractive target for the treatment of arthritic diseases. Currently available inhibitors lack specificity for metalloproteinase because of a common Zn binding site in MMPs; thus, there is a need to identify selective MMP-13 inhibitors for osteoarthritis therapy. Because selectivity is the major concern, both ligand-based and protein-based pharmacophore methodologies were used to identity potent and selective MMP-13 inhibitors. Different hypotheses were validated, and the best hypothesis was used to screen Zinc (natural and chemical) databases to seek novel scaffolds as MMP-13 inhibitors. The identified hits were validated using different strategies, such as Glide Standard precision, extra precision, E-model energies and receiver operating curve (ROC). In addition, potent inhibitors were selected based on two criteria: a similar binding mode as that of the active site PB3 crystal ligand and crucial amino acid interactions that are catalytically important for the function of MMP-13. The candidate potent inhibitors ZINC 02535232, ZINC 08399795, ZINC 12419118 and ZINC 00624580 nearly reproduced the H-bond interactions formed in the crystal structure of 1XUC with reasonable RMSD values exhibiting a novel interaction pattern that was not previously observed in MMP-13 inhibitors. The identified potent hits with diverse chemical scaffolds may be useful in designing new MMP-13 inhibitors. PMID:23938376

  16. Human placenta is a potent hematopoietic niche containing hematopoietic stem and progenitor cells throughout development

    PubMed Central

    Robin, Catherine; Bollerot, Karine; Mendes, Sandra; Haak, Esther; Crisan, Mihaela; Cerisoli, Francesco; Lauw, Ivoune; Kaimakis, Polynikis; Jorna, Ruud; Vermeulen, Mark; Kayser, Manfred; van der Linden, Reinier; Imanirad, Parisa; Verstegen, Monique; Nawaz-Yousaf, Humaira; Papazian, Natalie; Steegers, Eric; Cupedo, Tom; Dzierzak, Elaine

    2009-01-01

    Hematopoietic stem cells (HSC) are responsible for the life-long production of the blood system and are pivotal cells in hematologic transplantation therapies. During mouse and human development, the first HSCs are produced in the aorta-gonad-mesonephros region. Subsequent to this emergence, HSCs are found in other anatomical sites of the mouse conceptus. While the mouse placenta contains abundant HSCs at midgestation, little is known concerning whether HSCs or hematopoietic progenitors are present and supported in the human placenta during development. In this study we show, over a range of developmental times including term, that the human placenta contains hematopoietic progenitors and HSCs. Moreover, stromal cell lines generated from human placenta at several developmental time points are pericyte-like cells and support human hematopoiesis. Immunostaining of placenta sections during development localizes hematopoietic cells in close contact with pericytes/perivascular cells. Thus, the human placenta is a potent hematopoietic niche throughout development. PMID:19796619

  17. 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.

  18. ATBC Study - Questionnaires and Forms

    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 Questionnaires & Forms Baseline

  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. Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors.

    PubMed

    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

  1. 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

  2. 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 ...

  3. Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain.

    PubMed

    Fujii, Naoaki; Mallari, Jeremy P; Hansell, Elizabeth J; Mackey, Z; Doyle, Patricia; Zhou, Y M; Gut, Jiri; Rosenthal, Philip J; McKerrow, James H; Guy, R Kiplin

    2005-01-01

    Herein we report the synthesis and evaluation of a series of thiosemicarbazones as potential inhibitors of cysteine proteases relevant to parasitic diseases. Derivatives of thiosemicarbazone 1 were discovered to be potent inhibitors of cruzain and rhodesain, crucial proteases in the life cycles of Trypanosoma cruzi and T. brucei rhodesiense, the organisms causing Chagas' disease and sleeping sickness. However, the entire series had only modest potency against falcipain-2, an essential protease for Plasmodium falciparum, the organism causing malaria. Among the active inhibitors, several potently inhibited proliferation of cultures of T. brucei. However, only modest activity was observed in inhibition of proliferation of T. cruzi or P. falciparum. PMID:15582423

  4. 9-Benzoyl 9-deazaguanines as potent xanthine oxidase inhibitors.

    PubMed

    Rodrigues, Marili V N; Barbosa, Alexandre F; da Silva, Júlia F; Dos Santos, Deborah A; Vanzolini, Kenia L; de Moraes, Marcela C; Corrêa, Arlene G; Cass, Quezia B

    2016-01-15

    A novel potent xanthine oxidase inhibitor, 3-nitrobenzoyl 9-deazaguanine (LSPN451), was selected from a series of 10 synthetic derivatives. The enzymatic assays were carried out using an on-flow bidimensional liquid chromatography (2D LC) system, which allowed the screening¸ the measurement of the kinetic inhibition constant and the characterization of the inhibition mode. This compound showed a non-competitive inhibition mechanism with more affinity for the enzyme-substrate complex than for the free enzyme, and inhibition constant of 55.1±9.80nM, about thirty times more potent than allopurinol. Further details of synthesis and enzymatic studies are presented herein. PMID:26712096

  5. 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

  6. Adhesive rough contacts near complete contact

    E-print Network

    M. Ciavarella

    2015-05-01

    Recently, there has been some debate over the effect of adhesion on the contact of rough surfaces. Classical asperity theories predict, in agreement with experimental observations, that adhesion is always destroyed by roughness except if the amplitude of the same is extremely small, and the materials are particularly soft. This happens for all fractal dimensions. However, these theories are limited due to the geometrical simplification, which may be particularly strong in conditions near full contact. We introduce therefore a simple model for adhesion, which aims at being rigorous near full contact, where we postulate there are only small isolated gaps between the two bodies. The gaps can be considered as "pressurized cracks" by using Ken Johnson's idea of searching a corrective solution to the full contact solution. The solution is an extension of the adhesive-less solution proposed recently by Xu, Jackson, and Marghitu (XJM model) (2014). This process seems to confirm recent theories using the JKR theory, namely that the effect of adhesion depends critically on the fractal dimension. For D2.5, seems for large enough magnifications that a full fractal roughness completely destroys adhesion. These results are partly paradoxical since strong adhesion is not observed in nature except in special cases. A possible way out of the paradox may be that the conclusion is relevant for the near full contact regime, where the strong role of flaws at the interfaces, and of gaps full of contaminant, trapped air or liquid in pressure, needs to be further explored. If conditions near full contact are not achieved on loading, probably the conclusions of classical asperity theories may be confirmed.

  7. 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.

  8. 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...

  9. Optical contact micrometer

    SciTech Connect

    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.

  10. Hazardous Materials Alert Departmental Contact(s)

    E-print Network

    Hickman, Mark

    VATE If it is a "gAs" or "HAzArDOUs MATEriAl AlErT", shout a warning, pass the alarm by word of mouth. If able of material involved. 4. COnTAin Don't risk contact with material or allow spread. Do not smell, touch

  11. Relaxation damping in oscillating contacts

    NASA Astrophysics Data System (ADS)

    Popov, M.; Popov, V. L.; Pohrt, R.

    2015-11-01

    If a contact of two purely elastic bodies with no sliding (infinite coefficient of friction) is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears, that is not dependent on friction or dissipation in the material. We call this effect “relaxation damping”. The rate of energy dissipation due to relaxation damping is calculated in a closed analytic form for arbitrary axially-symmetric contacts. In the case of equal frequency of normal and tangential oscillations, the dissipated energy per cycle is proportional to the square of the amplitude of tangential oscillation and to the absolute value of the amplitude of normal oscillation, and is dependent on the phase shift between both oscillations. In the case of low frequency tangential oscillations with superimposed high frequency normal oscillations, the dissipation is proportional to the ratio of the frequencies. Generalization of the results for macroscopically planar, randomly rough surfaces as well as for the case of finite friction is discussed.

  12. Extensive screening for herbal extracts with potent antioxidant properties.

    PubMed

    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 (O(2) (•-)) scavenging activity followed by characterization of antioxidant properties. Firstly, scavenging activity against O(2) (•-) 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 O(2) (•-). 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 H(2)O(2) induced by UV irradiation demonstrated that all four extracts have potent ability to directly scavenge (•)OH. Furthermore, the scavenging activities against O(2) (•-) 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

  13. 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.

    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.

  14. Potent Antibody Protection against an Emerging Alphavirus Threat.

    PubMed

    Kielian, Margaret; Saphire, Erica Ollmann

    2015-11-19

    Chikungunya virus recently caused large outbreaks world-wide. In this issue of Cell, Fox et al. describe several potently neutralizing antibodies against multiple alphaviruses. The structure of the virus in complex with one of the antibodies reveals the antibody-induced rearrangement and crosslinking of the viral surface proteins that result in neutralization. PMID:26590413

  15. 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

  16. 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

  17. Shear strength of metal-sapphire contacts

    NASA Technical Reports Server (NTRS)

    Pepper, S. V.

    1976-01-01

    The shear strength of polycrystalline Ag, Cu, Ni, and Fe contacts on clean (0001) sapphire has been studied in ultrahigh vacuum. Both clean metal surfaces and surfaces exposed to O2, Cl2, and C2H4 were used. The results indicate that there are two sources of strength of Al2O3-metal contacts: an intrinsic one that depends on the particular clean metal in contact with Al2O3 and an additional one due to intermediate films. The shear strength of the clean metal contacts correlated directly with the free energy of oxide formation for the lowest metal oxide, in accord with the hypothesis that a chemical bond is formed between metal cations and oxygen anions in the sapphire surface. Contacts formed by metals exposed to chlorine exhibited uniformly low shear strength indicative of van der Waals bonding between chlorinated metal surfaces and sapphire. Contacts formed by metals exposed to oxygen exhibited enhanced shear strength, in accord with the hypothesis that an intermediate oxide layer increases interfacial strength.

  18. Contact Lens Solution Toxicity

    MedlinePLUS

    ... A large percentage of contact lens wearers experience reactions to contact lens solutions at some time. Most often, this occurs when there has been ... used it, and how quickly you reacted. Toxic reactions can start out slow and mild the first time, but when you try the same product again, ...

  19. Enhancing Intergenerational Contact.

    ERIC Educational Resources Information Center

    Ralston, Penny A.; And Others

    This document is a curriculum module designed to assist secondary school home economic teachers in teaching students about aging. The three major purposes of this module are to provide data-based information on aging related to needs of students to enhance intergenerational contact; to facilitate the expansion of intergenerational contacts by…

  20. Electrical Contacts to Nanomaterials.

    PubMed

    Bandaru, P R; Faraby, H; DiBattista, M

    2015-12-01

    The efficient passage of electrical current from an external contact to a nanomaterial is necessary for harnessing characteristics unique to the nanoscale, such as those relevant to energy quantization. However, an intrinsic resistance pertinent to dimensionality crossover and the presence of impurities precludes optimal electrical contact formation. In this review, we first discuss the relevant principles and contact resistance measurement methodologies, with modifications necessary for the nanoscale. Aspects related to the deposition of the contact material are deemed to be crucial. Consequently, the use of focused ion beam (FIB) based deposition, which relies on the ion-induced decomposition of a metallorganic precursor, and which has been frequently utilized for nanoscale contacts is considered in detail. PMID:26682353

  1. Identifying the causes of contact dermatitis.

    PubMed

    Jones, Ruth; Horn, Helen M

    2014-06-01

    Contact dermatitis results from skin contact with an exogenous substance. It can be caused by direct contact, airborne particles, vapours or light. Individuals of any age can be affected. The two most common variants are irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD is more common and has a worse prognosis. Other less common forms of contact dermatitis include photocontact allergy and, in food handlers, protein contact dermatitis. ICD is a form of eczema and is induced by direct inflammatory pathways without prior sensitisation. Classical ACD is mediated by type 4 cell-mediated immunity. Sensitisation occurs within 5 to 16 days of skin contact with a potential allergen but at this first exposure there is no inflammation. Frequent exposure and high concentrations of potential allergens increase the risk of sensitisation. If eczema is recurrent/persistent, or occurs in an individual with no previous history of eczema, contact dermatitis should be considered. Dorsal aspects of the hands are most often affected by ICD, usually with involvement of the finger webs. Cumulative effects of water, soaps and detergents are the most common cause of ICD which affects the hands more often than any other site. Nickel, fragrances, rubber accelerators and biocides are the most common sensitisers in ACD. Patients with leg ulcers and stasis eczema are at especially high risk of developing allergies to ingredients of their topical treatments, dressings and bandages. If ACD is suspected the patient should be referred to secondary care for patch testing. Age should not be a deterrent to patch testing. Accurate diagnosis, avoidance of identified allergens and protection from irritants are the key to successful treatment. PMID:25102574

  2. 77 FR 12903 - 60-Day Notice of Proposed Information Collection: DS-158, Contact Information and Work History...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... Notice of Proposed Information Collection: DS-158, Contact Information and Work History for Nonimmigrant... of Information Collection: Contact Information and Work History for Nonimmigrant Visa Applicant. OMB... collection: This form collects contact information, current employment information, and previous...

  3. Contact Interface Verification for DYNA3D Scenario 1: Basic Contact

    SciTech Connect

    McMichael, L D

    2006-05-10

    A suite of test problems has been developed to examine contact behavior within the nonlinear, three-dimensional, explicit finite element analysis (FEA) code DYNA3D (Lin, 2005). The test problems address the basic functionality of the contact algorithms, including the behavior of various kinematic, penalty, and Lagrangian enforcement formulations. The results from the DYNA3D analyses are compared to closed form solutions to verify the contact behavior. This work was performed as part of the Verification and Validation efforts of LLNL W Program within the NNSA's Advanced Simulation and Computing (ASC) Program. DYNA3D models the transient dynamic response of solids and structures including the interactions between disjoint bodies (parts). A wide variety of contact surfaces are available to represent the diverse interactions possible during an analysis, including relative motion (sliding), separation and gap closure (voids), and fixed relative position (tied). The problem geometry may be defined using a combination of element formulations, including one-dimensional beam and truss elements, two-dimensional shell elements, and three-dimensional solid elements. Consequently, it is necessary to consider various element interactions for each contact algorithm being verified. Most of the contact algorithms currently available in DYNA3D are examined; the exceptions are the Type 4--Single Surface Contact and Type 11--SAND algorithms. It is likely that these algorithms will be removed since their functionality is embodied in other, more robust, contact algorithms. The automatic contact algorithm is evaluated using the Type 12 interface. Two other variations of automatic contact, Type 13 and Type 14, offer additional means to adapt the interface domain, but share the same search and restoration algorithms as Type 12. The contact algorithms are summarized in Table 1. This report and associated test problems examine the scenario where one contact surface exists between two disjoint bodies. These test problems focus on whether a particular contact algorithm properly represents the interactions along the interface. A companion report (McMichael, 2006) and test problems address the multi-contact scenario in which multiple bodies interact with each other via multiple interfaces. The multi-contact test problems examine whether any ordering issues exist in the contact logic. The test problems are analyzed using version 5.2 (compiled on 12/22/2005) of DYNA3D. The analytical results are used to form baseline solutions for subsequent regression testing.

  4. Lithium-drifted silicon detector with segmented contacts

    DOEpatents

    Tindall, Craig S.; Luke, Paul N.

    2006-06-13

    A method and apparatus for creating both segmented and unsegmented radiation detectors which can operate at room temperature. The devices include a metal contact layer, and an n-type blocking contact formed from a thin layer of amorphous semiconductor. In one embodiment the material beneath the n-type contact is n-type material, such as lithium compensated silicon that forms the active region of the device. The active layer has been compensated to a degree at which the device may be fully depleted at low bias voltages. A p-type blocking contact layer, or a p-type donor material can be formed beneath a second metal contact layer to complete the device structure. When the contacts to the device are segmented, the device is capable of position sensitive detection and spectroscopy of ionizing radiation, such as photons, electrons, and ions.

  5. Optical contacting of quartz

    NASA Technical Reports Server (NTRS)

    Payne, L. L.

    1982-01-01

    The strength of the bond between optically contacted quartz surfaces was investigated. The Gravity Probe-B (GP-B) experiment to test the theories of general relativity requires extremely precise measurements. The quartz components of the instruments to make these measurements must be held together in a very stable unit. Optical contacting is suggested as a possible method of joining these components. The fundamental forces involved in optical contacting are reviewed and relates calculations of these forces to the results obtained in experiments.

  6. Telescopic vision contact lens

    NASA Astrophysics Data System (ADS)

    Tremblay, Eric J.; Beer, R. Dirk; Arianpour, Ashkan; Ford, Joseph E.

    2011-03-01

    We present the concept, optical design, and first proof of principle experimental results for a telescopic contact lens intended to become a visual aid for age-related macular degeneration (AMD), providing magnification to the user without surgery or external head-mounted optics. Our contact lens optical system can provide a combination of telescopic and non-magnified vision through two independent optical paths through the contact lens. The magnified optical path incorporates a telescopic arrangement of positive and negative annular concentric reflectors to achieve 2.8x - 3x magnification on the eye, while light passing through a central clear aperture provides unmagnified vision.

  7. A silver nanocomposite biomaterial for blood-contacting implants.

    PubMed

    de Mel, Achala; Chaloupka, Karla; Malam, Yogeshkumar; Darbyshire, Arnold; Cousins, Brian; Seifalian, Alexander M

    2012-09-01

    Cardiovascular implants must resist infection and thrombosis. A nanocomposite polymeric material [polyhedral-oligomeric-silsesquioxane-poly(carbonate-urea)urethane; POSS-PCU] demonstrates ideal properties for cardiovascular applications. Silver nanoparticles or nanosilver (NS) are recognized for efficient antibacterial properties. This study aims to determine the influence of NS integrated POSS-PCU on thrombogenicity. Silver nitrate was reduced with dimethylformamide and stabilized by the inclusion of fumed silica nanoparticles to prevent aggregation of NS and were incorporated into POSS-PCU to form a range of POSS-PCU-NS concentrations (by weight); 0.20% (NS16), 0.40% (NS32), 0.75% (NS64), and 1.50% (NS128). Surface wettability was determined with sessile-drop water contact angles. Platelets were introduced onto test samples and Alamar Blue (AB), mitochondrial-activity assay, quantified the degree of platelet adhesion whilst platelet-factor-4 (PF4) ELISA quantified the degree of platelet activation. Thromboelastography (TEG) determined the profiles of whole blood kinetics while hemolysis assay demonstrated the degree of blood compatibility. Increasing levels of NS induced greater hydrophilicity. A concentration dependant decrease in platelet adhesion and activation was observed with AB and PF4 readings, respectively. TEG demonstrated that the antithrombogenic properties of POSS-PCU were retained with POSS-PCU-NS16, and enhanced with POSS-PCU-NS32, but was reduced with POSS-PCU-NS64 and POSS-PCU-NS128. POSS-PCU-NS64 and POSS-PCU-NS128 demonstrated a hemolytic tendency, but no hemolysis was observed with POSS-PCU-NS16 and POSS-PCU-NS32. Overall, POSS-PCU-NS32 rendered potent antithrombogenic properties. PMID:22528182

  8. Electrophilic Peroxisome Proliferator–Activated Receptor-? Ligands Have Potent Antifibrotic Effects in Human Lung Fibroblasts

    PubMed Central

    Ferguson, Heather E.; Kulkarni, Ajit; Lehmann, Geniece M.; Garcia-Bates, Tatiana M.; Thatcher, Thomas H.; Huxlin, Krystel R.; Phipps, Richard P.; Sime, Patricia J.

    2009-01-01

    Pulmonary fibrosis is a progressive scarring disease with no effective treatment. Transforming growth factor (TGF)-? is up-regulated in fibrotic diseases, where it stimulates differentiation of fibroblasts to myofibroblasts and production of excess extracellular matrix. Peroxisome proliferator–activated receptor (PPAR) ? is a transcription factor that regulates adipogenesis, insulin sensitization, and inflammation. We report here that a novel PPAR? ligand, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), is a potent inhibitor of TGF-?–stimulated differentiation of human lung fibroblasts to myofibroblasts, and suppresses up-regulation of ?–smooth muscle actin, fibronectin, collagen, and the novel myofibroblast marker, calponin. The inhibitory concentration causing a 50% decrease in aSMA for CDDO was 20-fold lower than the endogenous PPAR? ligand, 15-deoxy-?12,14-prostaglandin J2 (15 d-PGJ2), and 400-fold lower than the synthetic ligand, rosiglitazone. Pharmacologic and genetic approaches were used to demonstrate that CDDO mediates its activity via a PPAR?-independent pathway. CDDO and 15 d-PGJ2 contain an ?/? unsaturated ketone, which acts as an electrophilic center that can form covalent bonds with cellular proteins. Prostaglandin A1 and diphenyl diselenide, both strong electrophiles, also inhibit myofibroblast differentiation, but a structural analog of 15 d-PGJ2 lacking the electrophilic center is much less potent. CDDO does not alter TGF-?–induced Smad or AP-1 signaling, but does inhibit acetylation of CREB binding protein/p300, a critical coactivator in the transcriptional regulation of TGF-?–responsive genes. Overall, these data indicate that certain PPAR? ligands, and other small molecules with electrophilic centers, are potent inhibitors of critical TGF-?–mediated profibrogenic activities through pathways independent of PPAR?. As the inhibitory concentration causing a 50% decrease in aSMA for CDDO is 400-fold lower than that in rosiglitazone, the translational potential of CDDO for treatment of fibrotic diseases is high. PMID:19286977

  9. Identification of potent inhibitors of the chicken soluble epoxide hydrolase.

    PubMed

    Shihadih, Diyala S; Harris, Todd R; Yang, Jun; Merzlikin, Oleg; Lee, Kin Sing S; Hammock, Bruce D; Morisseau, Christophe

    2015-01-15

    In vertebrates, soluble epoxide hydrolase (sEH) hydrolyzes natural epoxy-fatty acids (EpFAs), which are chemical mediators modulating inflammation, pain, and angiogenesis. Chick embryos are used to study angiogenesis, particularly its role in cardiovascular biology and pathology. To find potent and bio-stable inhibitors of the chicken sEH (chxEH) a library of human sEH inhibitors was screened. Derivatives of 1(adamantan-1-yl)-3-(trans-4-phenoxycyclohexyl) urea were found to be very potent tight binding inhibitors (KI <150pM) of chxEH while being relatively stable in chicken liver microsomes, suggesting their usefulness to study the role of EpFAs in chickens. PMID:25479771

  10. 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

  11. Potent Urea and Carbamate Inhibitors of Soluble Epoxide Hydrolases

    NASA Astrophysics Data System (ADS)

    Morisseau, Christophe; Goodrow, Marvin H.; Dowdy, Deanna; Zheng, Jiang; Greene, Jessica F.; Sanborn, James R.; Hammock, Bruce D.

    1999-08-01

    The soluble epoxide hydrolase (sEH) plays a significant role in the biosynthesis of inflammation mediators as well as xenobiotic transformations. Herein, we report the discovery of substituted ureas and carbamates as potent inhibitors of sEH. Some of these selective, competitive tightbinding inhibitors with nanomolar Ki values interacted stoichiometrically with the homogenous recombinant murine and human sEHs. These inhibitors enhance cytotoxicity of trans-stilbene oxide, which is active as the epoxide, but reduce cytotoxicity of leukotoxin, which is activated by epoxide hydrolase to its toxic diol. They also reduce toxicity of leukotoxin in vivo in mice and prevent symptoms suggestive of acute respiratory distress syndrome. These potent inhibitors may be valuable tools for testing hypotheses of involvement of diol and epoxide lipids in chemical mediation in vitro or in vivo systems.

  12. Potent CXCR4 Antagonists Containing Amidine Type Peptide Bond Isosteres

    PubMed Central

    2011-01-01

    A series of FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] analogues containing amidine type peptide bond isosteres were synthesized as selective CXC chemokine receptor type 4 (CXCR4) antagonists. An isosteric amidine substructure was constructed by a macrocyclization process using nitrile oxide-mediated C?N bond formation. All of the amidine-containing FC131 analogues exhibited potent SDF-1 binding inhibition to CXCR4. The Nal-Gly-substituted analogue was characterized as one of the most potent cyclic pentapeptide-based CXCR4 antagonists reported to date. The improved activity against human immunodeficiency virus (HIV) type-1 X4 strains suggested that addition of another basic amidine group to the peptide backbone effectively increases the selective binding of the peptides to CXCR4 receptor. PMID:24900333

  13. Contact Information-OCCAM

    Cancer.gov

    Contact Us | Sitemap CAM at the NCI NCI CAM History Highlights of NCI CAM Activities NCI CAM Annual Report Research Funding Opportunities Grant Application Information Research Resources Funded Research Research Results Training Opportunities FAQ's

  14. Grants Management Contacts

    Cancer.gov

    Please contact the grants management specialist assigned to your institution for questions regarding NCI grants. Institution Assigned Specialist FY 2016 ACOUSTIC MEDSYSTEMS, INC. GASTLEY, KERRY ALABAMA STATE UNIVERSITY YOUNG, ESTHER ALASKA

  15. 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 ...

  16. Admission Requirements Contact/ Information

    E-print Network

    Fernandez, Eduardo

    Restoration, Invasive Species in Terrestrial and Aquatic Ecosystems, and Ecological Modeling. #12;Admission Requirements Contact/ Information Graduate Programs Cynthia Berman-Gruen Charles E, letters of recommendation, and/or portfolios should be submitted directly to your graduate program

  17. 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

  18. Benzoxazinones as potent positive allosteric AMPA receptor modulators: part I.

    PubMed

    Mueller, Rudolf; Li, Yong-Xin; Hampson, Aidan; Zhong, Sheng; Harris, Clayton; Marrs, Christopher; Rachwal, Stanislaw; Ulas, Jolanta; Nielsson, Lena; Rogers, Gary

    2011-07-01

    AMPA receptors (AMPARs) are an increasingly important therapeutic target in the CNS. Aniracetam, the first identified potentiator of AMPARs, led to the rigid and more potent CX614. This lead molecule was optimized in order to increase affinity towards the AMPA receptor. The substitution of the dioxine with a benzoxazinone ring system increased the activity and allowed further investigation of the sidechain SAR. PMID:21636275

  19. 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).

  20. Frictional contact between 3D beams

    NASA Astrophysics Data System (ADS)

    Litewka, P.; Wriggers, P.

    The paper deals with frictional contact between 3D beams with rectangular cross-sections. In the analysis large displacements and small strains are allowed. Hence the cross-section behaves like a rigid body undergoing displacement and rotations. Contact between the beams is assumed to be point-wise between their edges. For the friction the simple non-associated Coulomb law is adopted. The analogy to rigid plasticity is used where stick and slip conditions are considered and backward Euler scheme is applied whenever the yield condition is violated. Contact constraints for normal and tangential part are introduced using the active set strategy and the penalty method. A consistent linearisation of both contact contributions is derived and expressed in suitable matrix form, easy to use in FEM approximations. Several numerical examples including the comparison to the full 3D-solid analysis depict the efficiency of the presented approach.

  1. 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…

  2. Contact Lenses for Vision Correction

    MedlinePLUS

    ... Eye Health News Consumer Alerts Contact Lenses for Vision Correction Tweet What are contacts? Contact lenses are ... on the surface of the eye. They correct vision like eyeglasses do and are safe when used ...

  3. 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.

  4. The bioreduction of a series of benzoquinone ansamycins by NAD(P)H:quinone oxidoreductase 1 to more potent heat shock protein 90 inhibitors, the hydroquinone ansamycins.

    PubMed

    Guo, Wenchang; Reigan, Philip; Siegel, David; Zirrolli, Joseph; Gustafson, Daniel; Ross, David

    2006-10-01

    We have previously evaluated the role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the bioreductive metabolism of 17-(allylamino)-demethoxygeldanamycin (17AAG) to the corresponding hydroquinone, a more potent 90-kDa heat shock protein (Hsp90) inhibitor. Here, we report an extensive study with a series of benzoquinone ansamycins, which includes gel-danamycin, 17-(amino)-17-demethoxygeldanamycin, and 17-demethoxy-17-[[2-(dimethylamino)ethyl]amino]-geldanamycin. The reduction of these benzoquinone ansamycins by recombinant human NQO1 to the corresponding hydroquinone ansamycins was monitored by high-performance liquid chromatography (HPLC) and confirmed by liquid chromatography/mass spectrometry. Inhibition of purified yeast Hsp90 ATPase activity was augmented in the presence of NQO1 and abrogated by 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl-]indole-4,7-dione (ES936), a mechanism-based inhibitor of NQO1, showing that the hydroquinone ansamycins were more potent Hsp90 inhibitors than their parent quinones. An isogenic pair of human breast cancer cell lines, MDA468 and MDA468/NQ16, differing in expression of NQO1, was used, and HPLC analysis showed that hydroquinone ansamycins were formed by the MDA468/NQ16 cells, which could be prevented by ES936 pretreatment. The MDA468/NQ16 cells were more sensitive to growth inhibition after treatment with the benzoquinone ansamycins compared with the MDA468 cells; this increased sensitivity could be reduced by ES936 pretreatment. The increased duration of benzoquinone ansamycin exposure showed increased potency and -fold inhibition in MDA468/NQ16 cells relative to the parental MDA468 cells. Computational-based molecular modeling studies displayed additional contacts between yeast Hsp90 and the hydroquinone ansamycins, which translated to greater interaction energies compared with the corresponding benzoquinone ansamycins. In conclusion, these studies show that the reduction of this series of benzoquinone ansamycins by NQO1 generates the corresponding hydroquinone ansamycins, which exhibit enhanced Hsp90 inhibition. PMID:16825487

  5. Searching the Sequence Space for Potent Aptamers Using SELEX in Silico.

    PubMed

    Zhou, Qingtong; Xia, Xiaole; Luo, Zhaofeng; Liang, Haojun; Shakhnovich, Eugene

    2015-12-01

    To isolate functional nucleic acids that bind to defined targets with high affinity and specificity, which are known as aptamers, the systematic evolution of ligands by exponential enrichment (SELEX) methodology has emerged as the preferred approach. Here, we propose a computational approach, SELEX in silico, that allows the sequence space to be more thoroughly explored regarding binding of a certain target. Our approach consists of two steps: (i) secondary structure-based sequence screening, which aims to collect the sequences that can form a desired RNA motif as an enhanced initial library, followed by (ii) sequence enrichment regarding target binding by molecular dynamics simulation-based virtual screening. Our SELEX in silico method provided a practical computational solution to three key problems in aptamer sequence searching: design of nucleic acid libraries, knowledge of sequence enrichment, and identification of potent aptamers. Six potent theophylline-binding aptamers, which were isolated by SELEX in silico from a sequence space containing 4(13) sequences, were experimentally verified to bind theophylline with high affinity: Kd ranging from 0.16 to 0.52 ?M, compared with the dissociation constant of the original aptamer-theophylline, 0.32 ?M. These results demonstrate the significant potential of SELEX in silico as a new method for aptamer discovery and optimization. PMID:26642994

  6. the GaAlAs layer. Zn diffusion is performed at 600C for 15 min to form a low resistance ohmic base contact. Ni-AuGe is

    E-print Network

    Pal, Sankar Kumar

    the GaAlAs layer. Zn diffusion is performed at 600°C for 15 min to form a low resistance ohmic base doping level. Current gains hfe ranging from 20 to 300 indicate an electron diffusion length of about 5, Le = l' nH (bonding wire length of 1 mm with its diameter of 20

  7. This form should only be used by individuals who received a Ph.D. in the Biomedical Sciences. For medical school transcripts, please contact 718-430-2102 (phone), 718-430-4123 (fax)

    E-print Network

    Emmons, Scott

    -430-8655 or Mail to Einstein Graduate Programs in the Biomedical Sciences Albert Einstein College of Medicine 1300: Please complete form, then download and E-mail to sgregistrar@einstein.yu.edu or Fax to 718 OF ATTENDANCE: BANNER ID#: CELLPHONE NUMBER: LAB EXT. (If Current Student): PERMANENT E-MAIL (not Einstein e

  8. GENERAL STORES UPS PICK UP FORM

    E-print Network

    Clayton, Dale H.

    GENERAL STORES UPS PICK UP FORM DATE:____________ TIME:____________ DEPT NAME DATE ______________________________ ____________________ PICKED UP BY DATE ANY UPS SHIPPER NUMBER #_______________________________ EMERGENCY CONTACT NUMBER

  9. AUTHORIZATION TO INVOICE FORM Student Name

    E-print Network

    Martin, Jeff

    AUTHORIZATION TO INVOICE FORM Student Name: (as on birth certificate) ___________________________ ______________________________ Last Name First Name Date of Birth: (as on birth certificate: _______________________________________________________________________ Contact Person's Name & Title

  10. Experimental investigation on the electrical contact behavior of rolling contact connector.

    PubMed

    Chen, Junxing; Yang, Fei; Luo, Kaiyu; Zhu, Mingliang; Wu, Yi; Rong, Mingzhe

    2015-12-01

    Rolling contact connector (RCC) is a new technology utilized in high performance electric power transfer systems with one or more rotating interfaces, such as radars, satellites, wind generators, and medical computed tomography machines. Rolling contact components are used in the RCC instead of traditional sliding contacts to transfer electrical power and/or signal. Since the requirement of the power transmission is increasing in these years, the rolling electrical contact characteristics become more and more important for the long-life design of RCC. In this paper, a typical form of RCC is presented. A series of experimental work are carried out to investigate the rolling electrical contact characteristics during its lifetime. The influence of a variety of factors on the electrical contact degradation behavior of RCC is analyzed under both vacuum and air environment. Based on the surface morphology and elemental composition changes in the contact zone, which are assessed by field emission scanning electron microscope and confocal laser scanning microscope, the mechanism of rolling electrical contact degradation is discussed. PMID:26724076

  11. Electrical contacts for a thin-film semiconductor device

    DOEpatents

    Carlson, David E. (Yardley, PA); Dickson, Charles R. (Pennington, NJ); D'Aiello, Robert V. (East Brunswick, NJ)

    1989-08-08

    A method of fabricating spaced-apart back contacts on a thin film of semiconductor material by forming strips of buffer material on top of the semiconductor material in locations corresponding to the desired dividing lines between back contacts, forming a film of metal substantially covering the semiconductor material and buffer strips, and scribing portions of the metal film overlying the buffer strips with a laser without contacting the underlying semiconductor material to separate the metal layer into a plurality of back contacts. The buffer material serves to protect the underlying semiconductor material from being damaged during the laser scribing. Back contacts and multi-cell photovoltaic modules incorporating such back contacts also are disclosed.

  12. Contacting the Government among College Students

    ERIC Educational Resources Information Center

    Yaghi, Abdulfattah

    2009-01-01

    The literature on political participation indicates that initiating contacts with the government is a vital form of civic engagement. Using this criterion to define participation, some researchers claim that students in general are apathetic about government and have poor efficacy about public affairs. The present study examines this assumption by…

  13. [Contact dermatitis: an approach used by a medical officer].

    PubMed

    Vologzhanin, D A; Bozhchenko, A A; Bala, A M

    2012-01-01

    The article deals with contact dermatitis issues, that are of interest not only for dermatologists and specialists in professional pathology, but as well as for general practitioners. Issues of contact dermatitis classification, pathogenic peculiarities of the disease main forms and their basic causes are discussed. Clinical manifestations of irritative and allergic contact dermatitis are described in detail, aspects of differential diagnostics analysed. A detailed consideration is given to allergic diagnostics of contact dermatitis using application test-systems with the most common contact allergens. Main principles of contact dermatitis treatment are outlined in the article. The necessity of a complex approach to this disease therapy that requires not only external therapy, but the compliance with an appropriate treatment regimen, diet as well as application of a particular system therapy is shown. Recommendations for contact dermatitis prophylaxis are given. PMID:22545447

  14. CTEP — Forms, Templates and Documents

    Cancer.gov

    Skip to Content Home | Investigator Resources | Protocol Development | Initiatives/Programs/Collaborations | Links to More Resources | Funding Opportunities | About CTEP Home | Sitemap | Contact CTEP Search this site Forms, Templates and Documents CTEP

  15. Spa contact dermatitis.

    PubMed

    Yankura, Jessica A; Marks, James G; Anderson, Bryan E; Adams, David R

    2008-01-01

    Potassium monopersulfate (MPS) is widely used in spa and pool "shock" treatments, yet contact dermatitis associated with MPS has been rarely reported. A patient presented with a generalized scattered dermatitis from the neck down that worsened after spa use. Patch testing elicited a ++ reaction to ammonium persulfate. Contact with ammonium persulfate was ruled out; however, MPS, which can cross-react with ammonium persulfate, was found to be the active ingredient in the patient's spa shock treatments. The dermatitis cleared after the patient switched to a hydrogen peroxide-based shock treatment. PMID:18413112

  16. Switchable telescopic contact lens.

    PubMed

    Tremblay, Eric J; Stamenov, Igor; Beer, R Dirk; Arianpour, Ashkan; Ford, Joseph E

    2013-07-01

    We present design and first demonstration of optics for a telescopic contact lens with independent optical paths for switching between normal and magnified vision. The magnified optical path incorporates a telescopic arrangement of positive and negative annular concentric reflectors to achieve 2.8 x magnification on the eye, while light passing through a central clear aperture provides unmagnified vision. We present an experimental demonstration of the contact lens mounted on a life-sized optomechanical model eye and, using a pair of modified commercial 3D television glasses, demonstrate electrically operated polarization switching between normal and magnified vision. PMID:23842384

  17. 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

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    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.

  19. Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR

    SciTech Connect

    Mitchell, Charlotte J.; Ballantine, Stuart P.; Coe, Diane M.; Cook, Caroline M.; Delves, Christopher J.; Dowle, Mike D.; Edlin, Chris D.; Hamblin, J. Nicole; Holman, Stuart; Johnson, Martin R.; Jones, Paul S.; Keeling, Sue E.; Kranz, Michael; Lindvall, Mika; Lucas, Fiona S.; Neu, Margarete; Solanke, Yemisi E.; Somers, Don O.; Trivedi, Naimisha A.; Wiseman, Joanne O.

    2012-05-03

    Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-{alpha} production from isolated human peripheral blood mononuclear cells.

  20. Repromicin derivatives with potent antibacterial activity against Pasteurella multocida.

    PubMed

    McFarland, J W; Hecker, S J; Jaynes, B H; Jefson, M R; Lundy, K M; Vu, C B; Glazer, E A; Froshauer, S A; Hayashi, S F; Kamicker, B J; Reese, C P; Olson, J A

    1997-03-14

    Reductive amination of repromicin with polyfunctional amines has led to new macrolide antibacterial agents, some of which are highly potent against the Gram-negative pathogen Pasteurella multocida both in vitro and in a mouse infection model. A key element in this discovery was the recognition that among certain known macrolides increasing lipophilicity results in diminished in vivo activity. One repromicin derivative, 20-[N-[3-(dimethylamino)-propyl]-N-L-alanylamino]-20-deoxorepro micin (35), was selected for advanced evaluation. At 5 mg/kg, a single subcutaneous dose was found to control induced pasteurellosis in swine and induced respiratory disease in cattle. PMID:9083494

  1. Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists

    SciTech Connect

    Zuercher, William J.; Buckholz?, Richard G.; Campobasso, Nino; Collins, Jon L.; Galardi, Cristin M.; Gampe, Robert T.; Hyatt, Stephen M.; Merrihew, Susan L.; Moore, John T.; Oplinger, Jeffrey A.; Reid, Paul R.; Spearing, Paul K.; Stanley, Thomas B.; Stewart, Eugene L.; Willson, Timothy M.

    2010-08-12

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  2. Discovery of benzamides as potent human ?3 adrenergic receptor agonists.

    PubMed

    Zhu, Cheng; Kar, Nam F; Li, Bing; Costa, Melissa; Dingley, Karen H; Di Salvo, Jerry; Ha, Sookhee N; Hurley, Amanda L; Li, Xiaofang; Miller, Randy R; Salituro, Gino M; Struthers, Mary; Weber, Ann E; Hale, Jeffrey J; Edmondson, Scott D

    2016-01-01

    The paper will describe the synthesis and SAR studies that led to the discovery of benzamide (reverse amide) as potent and selective human ?3-adrenergic receptor agonist. Based on conformationally restricted pyrrolidine scaffold we discovered earlier, pyrrolidine benzoic acid intermediate 22 was synthesized. From library synthesis and further optimization efforts, several structurally diverse reverse amides such as 24c and 24i were found to have excellent human ?3-adrenergic potency and good selectivity over the ?1 and ?2 receptors. In addition to human ?1, ?2, ?3 and hERG data, PK of selected compounds will be described. PMID:26590100

  3. Donation Form DONOR INFORMATION

    E-print Network

    Montréal, Université de

    Donation Form DONOR INFORMATION First and Last Names: Organization Name: Address: Contact Name: Email: ONE DONATION, 5 WAYS TO MAKE A DIFFERENCE 1. Support students in their educational needs for student scholarships. This will be ensured through the placement of 80% of all donations

  4. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact...processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer...

  5. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact...processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer...

  6. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact...processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer...

  7. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact...processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer...

  8. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact...processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer...

  9. 2-(Hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors.

    PubMed

    Saeed, Aamer; Imran, Aqeel; Channar, Pervaiz A; Shahid, Mohammad; Mahmood, Wajahat; Iqbal, Jamshed

    2015-02-01

    A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 ?M. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637). PMID:24938644

  10. Drug screen targeted at Plasmodium liver stages identifies a potent multistage antimalarial drug.

    PubMed

    da Cruz, Filipa P; Martin, Cécilie; Buchholz, Kathrin; Lafuente-Monasterio, Maria J; Rodrigues, Tiago; Sönnichsen, Birte; Moreira, Rui; Gamo, Francisco-Javier; Marti, Matthias; Mota, Maria M; Hannus, Michael; Prudêncio, Miguel

    2012-04-15

    Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host's liver cells before they are able to infect erythrocytes and cause malaria symptoms. To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore, decoquinate kills the parasite's replicative blood stages and is active against developing gametocytes, the forms responsible for transmission. The drug acts by selectively and specifically inhibiting the parasite's mitochondrial bc(1) complex, with little cross-resistance with the antimalarial drug atovaquone. Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compound. PMID:22396598

  11. Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug

    PubMed Central

    da Cruz, Filipa P.; Martin, Cécilie; Buchholz, Kathrin; Lafuente-Monasterio, Maria J.; Rodrigues, Tiago; Sönnichsen, Birte; Moreira, Rui; Gamo, Francisco-Javier; Marti, Matthias; Mota, Maria M.; Hannus, Michael

    2012-01-01

    Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host’s liver cells before they are able to infect erythrocytes and cause malaria symptoms. To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore, decoquinate kills the parasite’s replicative blood stages and is active against developing gametocytes, the forms responsible for transmission. The drug acts by selectively and specifically inhibiting the parasite’s mitochondrial bc1 complex, with little cross-resistance with the antimalarial drug atovaquone. Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compound. PMID:22396598

  12. Aurones: A Promising Heterocyclic Scaffold for the Development of Potent Antileishmanial Agents

    PubMed Central

    Roussaki, Marina; Costa Lima, Sofia; Kypreou, Anna-Maria; Kefalas, Panagiotis; Cordeiro da Silva, Anabela; Detsi, Anastasia

    2012-01-01

    A series of (Z)-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety of substituents on rings A and B were synthesized and evaluated for their antiparasitic activity against the intracellular amastigote form of Leishmania infantum and their cytotoxicity against human THP1-differentiated macrophages. In general, aurones bearing no substituents on ring A (compounds 4a–4f) exhibit higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g–4l). Among the latter, two aurones possessing a 2?-methoxy or a 2?-methyl group (compounds 4i and 4j) exhibit potent antileishmanial activity (IC50 = 1.3 ± 0.1??M and IC50 = 1.6 ± 0.2??M, resp.), comparable to the activity of the reference drug Amphotericin B, whereas they present significantly lower cytotoxicity than Amphotericin B as deduced by the higher selectivity index. PMID:25374683

  13. 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

  14. Thermal Contact Conductance

    NASA Technical Reports Server (NTRS)

    Salerno, Louis J.; Kittel, Peter

    1997-01-01

    The performance of cryogenic instruments is often a function of their operating temperature. Thus, designers of cryogenic instruments often are required to predict the operating temperature of each instrument they design. This requires accurate thermal models of cryogenic components which include the properties of the materials and assembly techniques used. When components are bolted or otherwise pressed together, a knowledge of the thermal performance of such joints are also needed. In some cases, the temperature drop across these joints represents a significant fraction of the total temperature difference between the instrument and its cooler. While extensive databases exist on the thermal properties of bulk materials, similar databases for pressed contacts do not. This has often lead to instrument designs that avoid pressed contacts or to the over-design of such joints at unnecessary expense. Although many people have made measurements of contact conductances at cryogenic temperatures, this data is often very narrow in scope and even more often it has not been published in an easily retrievable fashion, if published at all. This paper presents a summary of the limited pressed contact data available in the literature.

  15. 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

  16. Traffic Safety Research Contact

    E-print Network

    Latino Traffic Safety Initiative Research Contact: Katie Womack kwomack@tamu.edu tti lower restraint use rates (use of child safety seats, booster seats, and seat belts) than non Americans) among all four types of road users: drivers, passengers, pedestrians, and cyclists. · Hispanic

  17. UNDER REVIEW CONTACT ACCOUNTING

    E-print Network

    UNDER REVIEW CONTACT ACCOUNTING UNIVERSITY OF CALIFORNIA, SANTA BARBARA Accounting Office ALIEN@ucsbuxa.ucsb.edu. Last Modified By: HMW, 5/21/97 Page 1 of 25145 Payments to Aliens (Attachment B) 9/17/2007http to Aliens (Attachment B) 9/17/2007http://www.policy.ucsb.edu/vcas/accounting/5145_attach_b.html #12;

  18. Quantitative Finance CONTACT INFORMATION

    E-print Network

    Arnold, Elizabeth A.

    Quantitative Finance CONTACT INFORMATION Pamela Peterson Drake, PhD Department Head, Finance of Finance College of Business ZSH 325 (540) 568-8107 finkjd@jmu.edu Michelle Duncan, Advisor Academic Services Center College of Business ZSH 205 (540) 568-3078 duncanml@jmu.edu What is a quantitative finance

  19. Religious Allergic Contact Dermatitis.

    PubMed

    Goldenberg, Alina; Matiz, Catalina; Eichenfield, Lawrence F

    2015-01-01

    Henna, derived from a combination of natural leaves and coloring additives, is a common decorative dye traditionally used in many Islamic religious celebrations. Para-phenylenediamine (PPD), a major component of black henna tattoo, is a strong sensitizer and common allergen. We report a case of severe connubial allergic contact dermatitis after black henna heterotransfer in a girl. PMID:25968562

  20. 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.

  1. 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.

  2. Multilingual Contacts in Brussels.

    ERIC Educational Resources Information Center

    Universite Libre de Bruxelles (Belgium). Institut de Phonetique.

    This article attempts to present an exhaustive, fully-documented discussion of recent and current work around the world on questions related to French/Dutch multilingual contact in Brussels. An attempt has been made to go beyond mere bibliographical listing to an evaluation of everything of importance written around this topic, primarily in the…

  3. Have Confidence in Contact

    ERIC Educational Resources Information Center

    Crisp, Richard J.; Turner, Rhiannon N.

    2010-01-01

    In an article in the May-June 2009 "American Psychologist," we discussed a new approach to reducing prejudice and encouraging more positive intergroup relations (Crisp & Turner, 2009). We named the approach imagined intergroup contact and defined it as "the mental simulation of a social interaction with a member or members of an outgroup category"…

  4. [Contact allergies in musicians].

    PubMed

    Gasenzer, E R; Neugebauer, E A M

    2012-12-01

    During the last years, the problem of allergic diseases has increased. Allergies are errant immune responses to a normally harmless substance. In musicians the allergic contact dermatitis to exotic woods is a special problem. Exotic rosewood contains new flavonoids, which trigger an allergic reaction after permanent contact with the instrument. High quality woodwind instruments such as baroque flute or clarinets are made in ebony or palisander because of its great sound. Today instruments for non-professional players are also made in these exotic materials and non-professionals may have the risk to develop contact dermatitis, too. Brass-player has the risk of an allergic reaction to the different metals contained in the metal sheets of modern flutes and brass instruments. Specially nickel and brass alloys are used to product flute tubes or brass instruments. Special problem arises in children: patients who are allergic to plants or foods have a high risk to develop contact dermatitis. Parents don't know the materials of low-priced instruments for beginners. Often unknown cheap woods from exotic areas are used. Low-priced brass instruments contain high amount of brass and other cheap metals. Physicians should advice musician-patients or parents about the risks of the different materials and look for the reason of eczema on mouth, face, or hands. PMID:23233303

  5. Cyclic alpha-conotoxin peptidomimetic chimeras as potent GLP-1R agonists.

    PubMed

    Swedberg, Joakim E; Schroeder, Christina I; Mitchell, Justin M; Durek, Thomas; Fairlie, David P; Edmonds, David J; Griffith, David A; Ruggeri, Roger B; Derksen, David R; Loria, Paula M; Liras, Spiros; Price, David A; Craik, David J

    2015-10-20

    Type 2 diabetes mellitus (T2DM) results from compromised pancreatic ?-cell function, reduced insulin production, and lowered insulin sensitivity in target organs resulting in hyperglycemia. The GLP-1 hormone has two biologically active forms, GLP-1-(7-37) and GLP-1-(7-36)amide, which are equipotent at the glucagon-like peptide-1 receptor (GLP-1R). These peptides are central both to normal glucose metabolism and dysregulation in T2DM. Several structurally modified GLP-1 analogues are now approved drugs, and a number of other analogues are in clinical trials. None of these compounds is orally bioavailable and all require parenteral delivery. Recently, a number of smaller peptidomimetics containing 11-12 natural and unnatural amino acids have been identified that have similar insulin regulating profiles as GLP-1. The ?-conotoxins are a class of disulfide rich peptide venoms isolated from cone snails, and are known for their highly constrained structures and resistance to enzymatic degradation. In this study, we examined whether 11-residue peptidomimetics incorporated into ?-conotoxin scaffolds, forming monocyclic or bicyclic compounds constrained by disulfide bonds and/or backbone cyclization, could activate the GLP-1 receptor (GLP-1R). Several compounds showed potent (nanomolar) agonist activity at GLP-1R, as evaluated via cAMP signaling. In addition, HPLC retention times and in silico calculations suggested that mono- and bicyclic compounds had more favorable n-octanol/water partition coefficients according to the virtual partition coefficient model (vLogP), while maintaining a smaller radius of gyration compared to corresponding uncyclized peptidomimetics. Our findings suggest that cyclic peptidomimetics provide a potential avenue for future design of potent, compact ligands targeting GLP-1R and possessing improved physicochemical properties. PMID:26352676

  6. Analogues of ethionamide, a drug used for multidrug-resistant tuberculosis, exhibit potent inhibition of tyrosinase.

    PubMed

    Choi, Joonhyeok; Park, Sung-Jean; Jee, Jun-Goo

    2015-12-01

    Tyrosinase catalyzes two distinct sequential reactions in melanin biosynthesis: the hydroxylation of tyrosine to DOPA followed by the oxidation of DOPA to dopaquinone. The central roles of melanin in living species have motivated researchers to maintain constant efforts to discover new agents that modulate tyrosinase activity. In this study, we report on the inhibition of tyrosinase by ethionamide and its analogues. Ethionamide, 2-ethylpyridine-4-carbothioamide, is a second-line antituberculosis drug used for the treatment of multidrug-resistant tuberculosis. The chemical similarity of ethionamide to phenylthiourea, a well-known tyrosinase inhibitor, led us to investigate its inhibitory effects on mushroom tyrosinase and the IC50 was calculated as 4 ?M. Five analogues of ethionamide, including another antituberculosis drug, prothionamide, were also inhibitory, with values for IC50 in the range of 3-43 ?M. Fluorescence quenching experiments supported a mechanism of direct binding. In contrast, isoniazid, a structural analogue and first-line antituberculosis drug, was a poor inhibitor of tyrosinase. We also tested the effects of ethionamide and its analogues on melanin content in B16F10 cells. At a concentration of 50 ?M, the molecules, pyridine-2-carbothioamide and thiobenzamide substantially decreased the melanin content by 44% and 37%, respectively. In addition to identifying other interactions, docking simulations showed that the carbothioamide groups of the molecules make essential contacts with the catalytic di-copper atoms. Our results suggest that carbothioamide can be a central moiety for the development of new and potent tyrosinase inhibitors. PMID:26544630

  7. The effectiveness of potent dental adhesives on the viability of LPS challenged human gingival fibroblasts.

    PubMed

    Garner, Angelia D; Tucci, Michelle A; Benghuzzi, Hamed A

    2014-01-01

    Dental adhesives are necessary for the retention of specific dental restorations utilized to repair the anatomy of the tooth after dental decay is removed. Adhesives come into contact with healthy and diseased periodontal tissues. Porphyromonas gingivalis is a gram negative bacterial pathogen, and lipopolysaccharide (LPS-PG) is an endotoxin found in gingival connective tissues of patients who suffer from periodontal disease. The presence of the endotoxin causes inflammation. This study aims to evaluate the effectiveness of potent dental adhesives when human gingival fibroblasts are challenged with LPS-PG. The fibroblasts were exposed to the dental adhesives polymethly methacrylate (PMMA), OptiBond®, and Prime & Bond® which were purchased from Patterson Dental, a national dental materials supplier. The human gingival fibroblasts (HGF-1, ATCC® CRL-2014?) were purchased from American Type Culture Collection (ATCC). The porphyromonas gingival lipopolysaccharide (LPS-PG) was purchased from Fisher Scientific (Pittsburg, PA). No significant differences in metabolic behavior was detected among the groups (p<0.132). While the glutathione assay determined that there was not any significant increase in oxidative stress levels; the lactate dehydrogenase assay identified significant cellular damage in the group exposed to combinations of the Prime & Bond® adhesives and LPS-PG at 48 hour intervals (p<0.003). No significant changes were noted in cellular morphology at any phases, and all cells demonstrated typical fibroblast spindle shape. PMID:25405402

  8. Potent Inhibitors of Plasmodium Phospholipid Metabolism with a Broad Spectrum of In Vitro Antimalarial Activities

    PubMed Central

    Ancelin, Marie L.; Calas, Michèle; Vidal-Sailhan, Valérie; Herbuté, Serge; Ringwald, Pascal; Vial, Henri J.

    2003-01-01

    We characterized the potent in vitro antimalarial activity and biologic assessment of 13 phospholipid polar head analogs on a comparative basis. There was a positive relationship between the abilities of the drugs to inhibit parasite growth in culture and their abilities to specifically inhibit phosphatidylcholine biosynthesis of Plasmodium falciparum-infected erythrocytes. Maximal activity of G25 was observed for the trophozoite stage of the 48-h erythrocytic cycle (50% inhibitory concentration, 0.75 nM), whereas the schizont and ring stages were 12- and 213-fold less susceptible. The compounds exerted a rapid nonreversible cytotoxic effect, with complete clearance of parasitemia after 5 h of contact with the mature stages. The compounds were highly specific against P. falciparum, with much lower toxicity against three other mammalian cell lines, and the in vitro therapeutic indices ranged from 300 to 2,500,000. Finally, the monoquaternary ammonium E10 and two bis-ammonium salts, G5 and G25, were similarly active against multiresistant strains and fresh isolates of P. falciparum. This impressive selective in vitro toxicity against P. falciparum strongly highlights the clinical potential of these quaternary ammonium salts for malarial chemotherapy. PMID:12878524

  9. Relaxation damping in oscillating contacts.

    PubMed

    Popov, M; Popov, V L; Pohrt, R

    2015-01-01

    If a contact of two purely elastic bodies with no sliding (infinite coefficient of friction) is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears, that is not dependent on friction or dissipation in the material. We call this effect "relaxation damping". The rate of energy dissipation due to relaxation damping is calculated in a closed analytic form for arbitrary axially-symmetric contacts. In the case of equal frequency of normal and tangential oscillations, the dissipated energy per cycle is proportional to the square of the amplitude of tangential oscillation and to the absolute value of the amplitude of normal oscillation, and is dependent on the phase shift between both oscillations. In the case of low frequency tangential oscillations with superimposed high frequency normal oscillations, the dissipation is proportional to the ratio of the frequencies. Generalization of the results for macroscopically planar, randomly rough surfaces as well as for the case of finite friction is discussed. PMID:26549011

  10. Obituary--rigid contact lenses.

    PubMed

    Efron, Nathan

    2010-10-01

    Scleral and corneal rigid lenses represented 100 per cent of the contact lens market immediately prior to the invention of soft lenses in the mid-1960s. In the United Kingdom today, rigid lenses comprise 2 per cent of all new lens fits. Low rates of rigid lens fitting are also apparent in 27 other countries which have recently been surveyed. Thus, the 1998 prediction of the author that rigid lenses--also referred to as 'rigid gas permeable' (RGP) lenses or 'gas permeable' (GP) lenses--would be obsolete by the year 2010 has essentially turned out to be correct. In this obituary, the author offers 10 reasons for the demise of rigid lens fitting: initial rigid lens discomfort; intractable rigid lens-induced corneal and lid pathology; extensive soft lens advertising; superior soft lens fitting logistics; lack of rigid lens training opportunities; redundancy of the rigid lens 'problem solver' function; improved soft toric and bifocal/varifocal lenses; limited uptake of orthokeratology; lack of investment in rigid lenses; and the emergence of aberration control soft lenses. Rigid lenses are now being fitted by a minority of practitioners with specialist skills/training. Certainly, rigid lenses can no longer be considered as a mainstream form of contact lens correction. May their dear souls (bulk properties) rest in peace. PMID:20674469

  11. Relaxation damping in oscillating contacts

    PubMed Central

    Popov, M.; Popov, V.L.; Pohrt, R.

    2015-01-01

    If a contact of two purely elastic bodies with no sliding (infinite coefficient of friction) is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears, that is not dependent on friction or dissipation in the material. We call this effect “relaxation damping”. The rate of energy dissipation due to relaxation damping is calculated in a closed analytic form for arbitrary axially-symmetric contacts. In the case of equal frequency of normal and tangential oscillations, the dissipated energy per cycle is proportional to the square of the amplitude of tangential oscillation and to the absolute value of the amplitude of normal oscillation, and is dependent on the phase shift between both oscillations. In the case of low frequency tangential oscillations with superimposed high frequency normal oscillations, the dissipation is proportional to the ratio of the frequencies. Generalization of the results for macroscopically planar, randomly rough surfaces as well as for the case of finite friction is discussed. PMID:26549011

  12. The development of potent and selective bisarylmaleimide GSK3 inhibitors.

    PubMed

    Engler, Thomas A; Malhotra, Sushant; Burkholder, Timothy P; Henry, James R; Mendel, David; Porter, Warren J; Furness, Kelly; Diefenbacher, Clive; Marquart, Angela; Reel, Jon K; Li, Yihong; Clayton, Joshua; Cunningham, Brian; McLean, Johnathan; O'toole, John C; Brozinick, Joseph; Hawkins, Eric; Misener, Elizabeth; Briere, Daniel; Brier, Richard A; Wagner, Jill R; Campbell, Robert M; Anderson, Bryan D; Vaughn, Renee; Bennett, Donald B; Meier, Timothy I; Cook, James A

    2005-02-15

    Many 3-aryl-4-(1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl)maleimides exhibit potent GSK3 inhibitory activity (<100 nM IC(50)), although few show significant selectivity (>100x) versus CDK2, CDK4, or PKCbetaII. However, combining 3-(imidazo[1,2-a]pyridin-3-yl), 3-(pyrazolo[1,5-a]pyridin-3-yl) or aza-analogs with a 4-(2-acyl-(1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl)) group on the maleimide resulted in very potent inhibitors of GSK3 (160 to >10,000-fold selectivity versus CDK2/4 and PKCbetaII. These compounds also inhibited tau phosphorylation in cells and were effective in lowering plasma glucose in a rat model of type 2 diabetes (ZDF rat). PMID:15686883

  13. 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

  14. Potent Inhibition of HIV-1 Replication by a Tat Mutant

    PubMed Central

    Major, Lee; Suhrbier, Andreas; Harrich, David

    2009-01-01

    Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection. PMID:19901984

  15. Dual contact pogo pin assembly

    DOEpatents

    Hatch, Stephen McGarry

    2015-01-20

    A contact assembly includes a base and a pair of electrical contacts supported by the base. A first end of the first electrical contact corresponds to a first end of the base and is configured to engage a first external conductive circuit element. A first end of the second electrical contact also corresponds to the first end of the base and is configured to engage a second external conductive circuit element. The first contact and the second contact are electrically isolated from one another and configured to compress when engaging an external connector element. The base includes an aperture positioned on a second end of the base outboard of a second end of the first and second electrical contacts. The aperture presents a narrowing shape with a wide mouth distal the electrical contacts and a narrow internal through-hole proximate the electrical contacts.

  16. 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.

  17. Development of a potent and selective GPR7 (NPBW1) agonist: a systematic structure-activity study of neuropeptide B.

    PubMed

    Kanesaka, Maki; Matsuda, Masao; Hirano, Atsushi; Tanaka, Kenichi; Kanatani, Akio; Tokita, Shigeru

    2007-06-01

    Neuropeptide B (NPB) has been recently identified as an endogenous ligand for GPR7 (NPBW1) and GPR8 (NPBW2) and has been shown to possess a relatively high selectivity for GPR7. In order to identify useful experimental tools to address physiological roles of GPR7, we synthesized a series of NPB analogs based on modification of an unbrominated form of 23 amino acids with amidated C-terminal, Br(-)NPB-23-NH(2). We confirmed that truncation of the N-terminal Trp residue resulted in almost complete loss of the binding affinity of NPB for GPR7 and GPR8, supporting the special importance of this residue for binding. Br(-)NPB-23-NH2 analogs in which each amino acid in positions 4, 5, 7, 8, 9, 10, 12 and 21 was replaced with alanine or glycine exhibited potent binding affinity comparable to the parent peptide. In contrast, replacement of Tyr(11) with alanine reduced the binding affinity for both GPR7 and GPR8 four fold. Of particular interest, several NPB analogs in which the consecutive amino acids from Pro4 to Val(13) were replaced with several units of 5-aminovaleric acid (Ava) linkers retained their potent affinity for GPR7. Furthermore, these Ava-substituted NPB analogs exhibited potent agonistic activities for GPR7 expressed in HEK293 cells. Among the Ava-substituted NPB analogs, analog 15 (Ava-5) and 17 (Ava-3) exhibited potency comparable to the parent peptide for GPR7 with significantly reduced activity for GPR8, resulting in high selectivity for GPR7. These highly potent and selective NPB analogs may be useful pharmacological tools to investigate the physiological and pharmacological roles of GPR7. PMID:17486669

  18. Metal Silicides: Active elements of ULSI contacts

    NASA Astrophysics Data System (ADS)

    Osburn, C. M.; Tsai, J. Y.; Sun, J.

    1996-11-01

    As device dimensions scale to the 0.1 urn regime, the self-aligned suicide (SALICIDE) contact technology increasingly becomes an integral part of both the ultra-shallow junction and the metal oxide semiconductor field-effect transistor device itself. This paper will discuss the effect of suicide materials and formation processes on suicide stability, junction consumption, the ability to accurately profile shallow junctions, and contact resistance in series with the channel. The use of suicides as diffusion sources (SADS) provides an important pathway toward optimization of suicide technology. Diffusion of boron and arsenic from nearly epitaxial layers of CoSi2, formed from bilayers of Ti and Co, offer good suicide stability, ultra-shallow, low-leakage junctions, and low contact resistance.

  19. Contact Sensing: A Sequential Decision Approach to Sensing Manipulation Contact

    E-print Network

    Eberman, Brian Scott

    1995-05-01

    This paper describes a new statistical, model-based approach to building a contact state observer. The observer uses measurements of the contact force and position, and prior information about the task encoded in a ...

  20. /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.

  1. 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.

  2. 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.

  3. 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.

  4. Language Contact in Qumul

    E-print Network

    Dwyer, Arienne M.

    1998-01-01

    during the Tang dynasty, and far away from the Qaraqanid presence in the southern Tarim Basin. Like other languages in contact situations that are isolated from the main group, Qumul Uyghur has both preserved older Eastern Turkic features now lost...-179. 34 Uyghur dialects and vernaculars (Osmanov 1990): North (Ürümchi, Ghulja [Y«lí]) Central East (Turfan, Qumul) South (Kucha and the Tarim vernaculars, Aqsu, Kashghar, Atush) Southern/Hotän (Hotän, Keriye...

  5. Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity

    PubMed Central

    Cortes, Leonel A.; Castro, Lorena; Pesce, Bárbara; Maya, Juan D.; Ferreira, Jorge; Castro-Castillo, Vicente; Parra, Eduardo; Jara, José A.; López-Muñoz, Rodrigo

    2015-01-01

    Chagas disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate group linked to a triphenylphosphonium (TPP+) moiety (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP+-C8, TPP+-C10, TPP+-C11, and TPP+-C12, respectively). We analyzed parasite viability in isolated parasites (by MTT reduction and flow cytometry) and infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four derivatives, TPP+-C10 and TPP+-C12 were the most potent in both models, with EC50 values (in isolated parasites) of 1.0 ± 0.6 and 1.0 ± 0.7 ?M, respectively, and were significantly more potent than nifurtimox (EC50 = 4.1 ± 0.6 ?M). At 1 ?M, TPP+-C10 and TPP+-C12 induced markers of cell death, such as phosphatidylserine exposure and propidium iodide permeabilization. In addition, at 1 ?M, TPP+-C10 and TPP+-C12 significantly decreased the number of intracellular amastigotes (TPP+-C10: 24.3%, TPP+-C12: 19.0% of control measurements, as measured by DAPI staining) and the parasite’s DNA load (C10: 10%, C12: 13% of control measurements, as measured by qPCR). Based on the previous mode of action described for these compounds in cancer cells, we explored their mitochondrial effects in isolated trypomastigotes. TPP+-C10 and TPP+-C12 were the most potent compounds, significantly altering mitochondrial membrane potential at 1 ?M (measured by JC-1 fluorescence) and inducing mitochondrial transition pore opening at 5 ?M. Taken together, these results indicate that the TPP+-C10 and TPP+-C12 derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity. PMID:26317199

  6. Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity.

    PubMed

    Cortes, Leonel A; Castro, Lorena; Pesce, Bárbara; Maya, Juan D; Ferreira, Jorge; Castro-Castillo, Vicente; Parra, Eduardo; Jara, José A; López-Muñoz, Rodrigo

    2015-01-01

    disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate group linked to a triphenylphosphonium (TPP(+)) moiety (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP(+)-C8, TPP(+)-C10, TPP(+)-C11, and TPP(+)-C12, respectively). We analyzed parasite viability in isolated parasites (by MTT reduction and flow cytometry) and infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four derivatives, TPP(+)-C10 and TPP(+)-C12 were the most potent in both models, with EC50 values (in isolated parasites) of 1.0 ± 0.6 and 1.0 ± 0.7 ?M, respectively, and were significantly more potent than nifurtimox (EC50 = 4.1 ± 0.6 ?M). At 1 ?M, TPP(+)-C10 and TPP(+)-C12 induced markers of cell death, such as phosphatidylserine exposure and propidium iodide permeabilization. In addition, at 1 ?M, TPP(+)-C10 and TPP(+)-C12 significantly decreased the number of intracellular amastigotes (TPP(+)-C10: 24.3%, TPP(+)-C12: 19.0% of control measurements, as measured by DAPI staining) and the parasite's DNA load (C10: 10%, C12: 13% of control measurements, as measured by qPCR). Based on the previous mode of action described for these compounds in cancer cells, we explored their mitochondrial effects in isolated trypomastigotes. TPP(+)-C10 and TPP(+)-C12 were the most potent compounds, significantly altering mitochondrial membrane potential at 1 ?M (measured by JC-1 fluorescence) and inducing mitochondrial transition pore opening at 5 ?M. Taken together, these results indicate that the TPP(+)-C10 and TPP(+)-C12 derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity. PMID:26317199

  7. Functional modular contact lens

    NASA Astrophysics Data System (ADS)

    Shum, Angela J.; Cowan, Melissa; Lähdesmäki, Ilkka; Lingley, Andrew; Otis, Brian; Parviz, Babak A.

    2009-08-01

    Tear fluid offers a potential route for non-invasive sensing of physiological parameters. Utilization of this potential depends on the ability to manufacture sensors that can be placed on the surface of the eye. A contact lens makes a natural platform for such sensors, but contact lens polymers present a challenge for sensor fabrication. This paper describes a microfabrication process for constructing sensors that can be integrated into the structure of a functional contact lens in the future. To demonstrate the capabilities of the process, an amperometric glucose sensor was fabricated on a polymer substrate. The sensor consists of platinum working and counter electrodes, as well as a region of indium-tin oxide (ITO) for glucose oxidase immobilization. An external silver-silver chloride electrode was used as the reference electrode during the characterization experiments. Sensor operation was validated by hydrogen peroxide measurements in the 10- 20 ?M range and glucose measurements in the 0.125-20 mM range.

  8. Models for ohmic contacts on graded crystalline or amorphous heterojunctions

    NASA Astrophysics Data System (ADS)

    Sebestyen, T.

    1982-07-01

    A one-dimensional model for sandwich-type graded heterojunctions is presented to explain the formation of contacts that cannot be based on highly doped contact layers, such as indium contacts to GaAs and GaSb. In this model a hyperbolic dependence on distance for the permittivity and a constant space charge density owing to filled interferance states is assumed. Algebraic solutions have been obtained for the barrier height and capacitance of a wide variety of heterojunctions. The conditions for zero barrier height, i.e. ohmic contacts, are discussed. The graded heterojunction model is also applied to heterojunctions formed by an amorphous and a crystalline semiconductor to explain the formation of ohmic contacts in cases where neither doping nor crystalline heterojunction effects can be assumed, such as Au, Ag, InAu, InAg and AuNi metal contacts to GaAs, GaSb or GaP.

  9. Antistiction technique using elastomer contact structure in woven electronic textiles

    NASA Astrophysics Data System (ADS)

    Yamashita, Takahiro; Takamatsu, Seiichi; Miyake, Koji; Itoh, Toshihiro

    2014-01-01

    In this paper, we present an antistiction technique using an elastomer contact structure in woven electronic textiles (e-textiles). A coating of poly(3,4-ethylenedioxythiophene):poly(4-styrene sulfonate) (PEDOT:PSS) in the form of a solid conductive film on a hemispherical silicone elastomer structure is employed in creating an electrical circuit embedded into the fabric of a woven e-textile, where the contact structure reduces the contact area and capillary force generated by the moisture in air between weft and warp ribbons. Stiction occurs between a weft and a warp without the contact structure under an RH of 80%, and the detachment of the stuck ribbon requires a delamination load of about 0.2 N. On the other hand, in the case of contact between the contact structure and the ribbon coated with plain PEDOT:PSS, stiction does not occur as the relative humidity increases from 20 to 80%.

  10. Policy on Media Contacts Regarding Athletes Policy on Media Contacts

    E-print Network

    Sridhar, Srinivas

    Policy on Media Contacts Regarding Athletes 9/1/2013 Policy on Media Contacts Regarding Athletics I-athletes and the media and other contacts related to public relations matters. The Office of Athletic Communications-athletes, coaches, and administrators, and the media. The office provides coverage of athletic programs

  11. 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

  12. Prodrugs of bisthiazolium salts are orally potent antimalarials

    PubMed Central

    Vial, Henri J.; Wein, Sharon; Farenc, Christine; Kocken, Clemens; Nicolas, Olivier; Ancelin, Marie Laure; Bressolle, Francoise; Thomas, Alan; Calas, Michèle

    2004-01-01

    We created neutral antimalarial prodrugs that deliver bisthiazolium compounds with antimalarial activity in the nanomolar range. These drugs primarily affect early intraerythrocytic stages through rapid, nonreversible cytotoxicity. The compounds are suitable for both parenteral and oral use and plasma promotes rapid conversion of the prodrug into the drug. We demonstrate that very low doses offer protection in a murine model of malaria. The drugs show great potential for curing high parasitemia with short-course treatments. Oral administration of the TE3 prodrug completely cures Plasmodium cynomolgi infection in rhesus monkeys. The drugs specifically accumulate inside infected erythrocytes, block phosphatidylcholine biosynthesis, and interact with hemozoin. To our knowledge, this class of compounds represents one of the most potent antimalarials tested to date. These unique properties signal a promising future for this class of antimalarial. PMID:15492221

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

    SciTech Connect

    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 . E-mail: wjpark@gist.ac.kr; Kim, Yong-Chul . E-mail: yongchul@gist.ac.kr

    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.

  14. A Potent and Site-Selective Agonist of TRPA1.

    PubMed

    Takaya, Junichiro; Mio, Kazuhiro; Shiraishi, Takuya; Kurokawa, Tatsuki; Otsuka, Shinya; Mori, Yasuo; Uesugi, Motonari

    2015-12-23

    TRPA1 is a member of the transient receptor potential (TRP) cation channel family that is expressed primarily on sensory neurons. This chemosensor is activated through covalent modification of multiple cysteine residues with a wide range of reactive compounds including allyl isothiocyanate (AITC), a spicy component of wasabi. The present study reports on potent and selective agonists of TRPA1, discovered through screening 1657 electrophilic molecules. In an effort to validate the mode of action of hit molecules, we noted a new TRPA1-selective agonist, JT010 (molecule 1), which opens the TRPA1 channel by covalently and site-selectively binding to Cys621 (EC50 = 0.65 nM). The results suggest that a single modification of Cys621 is sufficient to open the TRPA1 channel. The TRPA1-selective probe described herein might be useful for further mechanistic studies of TRPA1 activation. PMID:26630251

  15. Pseudosaccharin amines as potent and selective KV1.5 blockers.

    PubMed

    Lloyd, John; Finlay, Heather J; Kover, Alexander; Johnson, James; Pi, Zulan; Jiang, Ji; Neels, James; Cavallaro, Cullen; Wexler, Ruth; Conder, Mary Lee; Shi, Hong; Li, Danshi; Sun, Huabin; Chimalakonda, Anjaneya; Huang, Christine; Salvati, Mark; Levesque, Paul

    2015-11-01

    Phenethyl aminoheterocycles like compound 1 were known to be potent IKur blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent KV1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects. PMID:25801931

  16. Potent anti-seizure effects of D-leucine.

    PubMed

    Hartman, Adam L; Santos, Polan; O'Riordan, Kenneth J; Stafstrom, Carl E; Marie Hardwick, J

    2015-10-01

    There are no effective treatments for millions of patients with intractable epilepsy. High-fat ketogenic diets may provide significant clinical benefit but are challenging to implement. Low carbohydrate levels appear to be essential for the ketogenic diet to work, but the active ingredients in dietary interventions remain elusive, and a role for ketogenesis has been challenged. A potential antiseizure role of dietary protein or of individual amino acids in the ketogenic diet is understudied. We investigated the two exclusively ketogenic amino acids, L-leucine and L-lysine, and found that only L-leucine potently protects mice when administered prior to the onset of seizures induced by kainic acid injection, but not by inducing ketosis. Unexpectedly, the D-enantiomer of leucine, which is found in trace amounts in the brain, worked as well or better than L-leucine against both kainic acid and 6Hz electroshock-induced seizures. However, unlike L-leucine, D-leucine potently terminated seizures even after the onset of seizure activity. Furthermore, D-leucine, but not L-leucine, reduced long-term potentiation but had no effect on basal synaptic transmission in vitro. In a screen of candidate neuronal receptors, D-leucine failed to compete for binding by cognate ligands, potentially suggesting a novel target. Even at low doses, D-leucine suppressed ongoing seizures at least as effectively as diazepam but without sedative effects. These studies raise the possibility that D-leucine may represent a new class of anti-seizure agents, and that D-leucine may have a previously unknown function in eukaryotes. PMID:26054437

  17. Polyoxometalates--potent and selective ecto-nucleotidase inhibitors.

    PubMed

    Lee, Sang-Yong; Fiene, Amelie; Li, Wenjin; Hanck, Theodor; Brylev, Konstantin A; Fedorov, Vladimir E; Lecka, Joanna; Haider, Ali; Pietzsch, Hans-Jürgen; Zimmermann, Herbert; Sévigny, Jean; Kortz, Ulrich; Stephan, Holger; Müller, Christa E

    2015-01-15

    Polyoxometalates (POMs) are inorganic cluster metal complexes that possess versatile biological activities, including antibacterial, anticancer, antidiabetic, and antiviral effects. Their mechanisms of action at the molecular level are largely unknown. However, it has been suggested that the inhibition of several enzyme families (e.g., phosphatases, protein kinases or ecto-nucleotidases) by POMs may contribute to their pharmacological properties. Ecto-nucleotidases are cell membrane-bound or secreted glycoproteins involved in the hydrolysis of extracellular nucleotides thereby regulating purinergic (and pyrimidinergic) signaling. They comprise four distinct families: ecto-nucleoside triphosphate diphosphohydrolases (NTPDases), ecto-nucleotide pyrophosphatases/phosphodiesterases (NPPs), alkaline phosphatases (APs) and ecto-5'-nucleotidase (eN). In the present study, we evaluated the inhibitory potency of a series of polyoxometalates as well as chalcogenide hexarhenium cluster complexes at a broad range of ecto-nucleotidases. [Co4(H2O)2(PW9O34)2](10-) (5, PSB-POM142) was discovered to be the most potent inhibitor of human NTPDase1 described so far (Ki: 3.88 nM). Other investigated POMs selectively inhibited human NPP1, [TiW11CoO40](8-) (4, PSB-POM141, Ki: 1.46 nM) and [NaSb9W21O86](18-) (6, PSB-POM143, Ki: 4.98 nM) representing the most potent and selective human NPP1 inhibitors described to date. [NaP5W30O110](14-) (8, PSB-POM144) strongly inhibited NTPDase1-3 and NPP1 and may therefore be used as a pan-inhibitor to block ATP hydrolysis. The polyoxoanionic compounds displayed a non-competitive mechanism of inhibition of NPPs and eN, but appeared to be competitive inhibitors of TNAP. Future in vivo studies with selected inhibitors identified in the current study are warranted. PMID:25449596

  18. Solar cell with improved electrical contacts

    SciTech Connect

    Cavicchi, B.T.; Dill, H.G.; Zemmrich, D.K.

    1987-10-06

    A solar cell is described comprising: a first layer of semiconductor material of a first conductivity type; a second layer of semiconductor material of a second opposite conductivity type disposed on the first layer forming a semiconductor junction therebetween. The first and second layers having first and second major essentially parallel surfaces, respectively, essentially parallel to the semiconductor junction; a layer of aluminum gallium arsenide semiconductor material of the second conductivity type disposed on the second major surface and having an exposed front major surface essentially parallel to the second major surface and further having grooves extending vertically to the second layer; electrically conductive material filling the grooves and electrically contacting the second layer to form metallic contact lines; a flat conductive bar transversely disposed on the exposed front major surface across the grooves and making electrical contact ot the electrically conductive material in the grooves; an electrically conductive flat strip disposed on the exposed major surface and spaced apart from the conductive bar; and at least one electrically conductive bridge electrically coupling the conductive bar to the contact strip.

  19. Circumbinary Components of Contact Binaries

    NASA Astrophysics Data System (ADS)

    Demircan, O.; Bulut, ?.

    2015-07-01

    Period changes in contact binaries obtained by the analysis of times of eclipse are often found to be chaotic in nature. However, they may be representable by a few cyclic changes superposed on a secular change. The cyclic changes are most likely caused by third components revolving around the contact binaries. This contribution shows some typical examples of the period changes in contact binaries.

  20. Contact position sensor using constant contact force control system

    NASA Technical Reports Server (NTRS)

    Sturdevant, Jay (Inventor)

    1995-01-01

    A force control system (50) and method are provided for controlling a position contact sensor (10) so as to produce a constant controlled contact force therewith. The system (50) includes a contact position sensor (10) which has a contact probe (12) for contacting the surface of a target to be measured and an output signal (V.sub.o) for providing a position indication thereof. An actuator (30) is provided for controllably driving the contact position sensor (10) in response to an actuation control signal (I). A controller (52) receives the position indication signal (V.sub.o) and generates in response thereto the actuation control signal (I) so as to provide a substantially constant selective force (F) exerted by the contact probe (12). The actuation drive signal (I) is generated further in response to substantially linear approximation curves based on predetermined force and position data attained from the sensor (10) and the actuator (30).

  1. Contact dermatitis to methylisothiazolinone*

    PubMed Central

    Scherrer, Maria Antonieta Rios; Rocha, Vanessa Barreto; Andrade, Ana Regina Coelho

    2015-01-01

    Methylisothiazolinone (MI) is a preservative found in cosmetic and industrial products. Contact dermatitis caused by either methylchloroisothiazolinone/methylisothiazolinone (MCI/MI or Kathon CG) or MI has shown increasing frequency. The latter is preferably detected through epicutaneous testing with aqueous MI 2000 ppm, which is not included in the Brazilian standard tray. We describe a series of 23 patients tested using it and our standard tray. A case with negative reaction to MCI/MI and positive to MI is emphasized. PMID:26734880

  2. Producing thin film photovoltaic modules with high integrity interconnects and dual layer contacts

    DOEpatents

    Jansen, Kai W. (Lawrenceville, NJ); Maley, Nagi (Exton, PA)

    2000-01-01

    High performance photovoltaic modules are produced with improved interconnects by a special process. Advantageously, the photovoltaic modules have a dual layer back (rear) contact and a front contact with at least one layer. The front contact and the inner layer of the back contact can comprise a transparent conductive oxide. The outer layer of the back contact can comprise a metal or metal oxide. The front contact can also have a dielectric layer. In one form, the dual layer back contact comprises a zinc oxide inner layer and an aluminum outer layer and the front contact comprises a tin oxide inner layer and a silicon dioxide dielectric outer layer. One or more amorphous silicon-containing thin film semiconductors can be deposited between the front and back contacts. The contacts can be positioned between a substrate and an optional superstrate. During production, the transparent conductive oxide layer of the front contact is scribed by a laser, then the amorphous silicon-containing semiconductors and inner layer of the dual layer back contact are simultaneously scribed and trenched (drilled) by the laser and the trench is subsequently filled with the same metal as the outer layer of the dual layer back contact to provide a superb mechanical and electrical interconnect between the front contact and the outer layer of the dual layer back contact. The outer layer of the dual layer back contact can then be scribed by the laser. For enhanced environmental protection, the photovoltaic modules can be encapsulated.

  3. Producing thin film photovoltaic modules with high integrity interconnects and dual layer contacts

    DOEpatents

    Jansen, Kai W. (Lawrenceville, NJ); Maley, Nagi (Exton, PA)

    2001-01-01

    High performance photovoltaic modules are produced with improved interconnects by a special process. Advantageously, the photovoltaic modules have a dual layer back (rear) contact and a front contact with at least one layer. The front contact and the inner layer of the back contact can comprise a transparent conductive oxide. The outer layer of the back contact can comprise a metal or metal oxide. The front contact can also have a dielectric layer. In one form, the dual layer back contact comprises a zinc oxide inner layer and an aluminum outer layer and the front contact comprises a tin oxide inner layer and a silicon dioxide dielectric outer layer. One or more amorphous silicon-containing thin film semiconductors can be deposited between the front and back contacts. The contacts can be positioned between a substrate and an optional superstrate. During production, the transparent conductive oxide layer of the front contact is scribed by a laser, then the amorphous silicon-containing semiconductors and inner layer of the dual layer back contact are simultaneously scribed and trenched (drilled) by the laser and the trench is subsequently filled with the same metal as the outer layer of the dual layer back contact to provide a superb mechanical and electrical interconnect between the front contact and the outer layer of the dual layer back contact. The outer layer of the dual layer back contact can then be scribed by the laser. For enhanced environmental protection, the photovoltaic modules can be encapsulated.

  4. Radiation Therapy Immunity Status Form

    E-print Network

    Radiation Therapy Immunity Status Form Students are required to supply evidence of their immunity/her contact details in the allocated spaces on the form below. Please note: · OnlyImmunity B surface antigen Negative Positive Hepatitis B surface antibody Immune Not Immune Hepatitis C

  5. TOPIC PRIMARY CONTACT SECONDARY CONTACT(S) Accident Reports Marybeth Wilcox Steve Marley

    E-print Network

    Chen, Yiling

    Reclassification Steve Marley Marybeth Wilcox Posting Student Jobs Christie Gilliland Steve Marley or MarybethTOPIC PRIMARY CONTACT SECONDARY CONTACT(S) Accident Reports Marybeth Wilcox Steve Marley Agency Temps Christie Gilliland Steve Marley or Marybeth Wilcox ASPIRE - Hiring Procedures - Posting a Position

  6. Metallization options and annealing temperatures for low contact resistance ohmic contacts to n-type GaSb

    NASA Astrophysics Data System (ADS)

    Ikossi, K.; Goldenberg, M.; Mittereder, J.

    2002-10-01

    With GaSb emerging as one of the crucial material for 6.1 Å based electronic devices, low contact resistivity ohmic contacts suitable for nano-electronic and high-speed device operation are desirable. The surface of GaSb is believed to exhibit Fermi level pinning near the valence band making ohmic contact formation to n-type GaSb challenging. MBE GaSb, doped n-type with GaTe and grown on semi-insulating GaAs, is examined. The semi-insulating substrate allows mesa isolation and accurate ohmic contact evaluation by Transmission Line Model (TLM) measurements. A variety of metallization schemes and alloy temperatures are examined with lowest contact resistances observed for Pd containing ohmic contacts. A Pd/Ge/Pd/In/Pd metallization on GaSb:Te doped to 5.6×10 17 cm -3 alloyed at 350 °C for 60 s exhibited a specific contact resistivity as low as 1.4×10 -6?-cm 2 and contact resistance of 0.068 ?-mm. Pd/Ge/Pd metallization on GaSb:Te doped at 1.8×10 18 cm -3 exhibited specific contact resistivities of 3.8×10 -6?-cm 2 and contact resistances of 0.058 ?-mm after a 400 °C/60 s alloy. During the alloy cycle a solid phase reaction and regrowth is taking place forming a new interface compound responsible for the low contact resistances. At this time these results represent the lowest reported contact resistivity ohmic contacts to n-type GaSb.

  7. Contact Dermatitis: Diagnosis, Treatment, and Outcome

    MedlinePLUS

    ... A - D Contact dermatitis Diagnosis, treatment, and outcome Contact dermatitis: Diagnosis, treatment, and outcome How dermatologists diagnose contact dermatitis To diagnose this common skin condition, dermatologists: ...

  8. Point contacts in encapsulated graphene

    NASA Astrophysics Data System (ADS)

    Handschin, Clevin; Fülöp, Bálint; Makk, Péter; Blanter, Sofya; Weiss, Markus; Watanabe, Kenji; Taniguchi, Takashi; Csonka, Szabolcs; Schönenberger, Christian

    2015-11-01

    We present a method to establish inner point contacts with dimensions as small as 100 nm on hexagonal boron nitride (hBN) encapsulated graphene heterostructures by pre-patterning the top-hBN in a separate step prior to dry-stacking. 2- and 4-terminal field effect measurements between different lead combinations are in qualitative agreement with an electrostatic model assuming point-like contacts. The measured contact resistances are 0.5-1.5 k? per contact, which is quite low for such small contacts. By applying a perpendicular magnetic field, an insulating behaviour in the quantum Hall regime was observed, as expected for inner contacts. The fabricated contacts are compatible with high mobility graphene structures and open up the field for the realization of several electron optical proposals.

  9. 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

  10. Close Contact Fluctuations: Time of Contact

    E-print Network

    Daniel R. Bush; Amit K. Chattopadhyay

    2014-12-03

    The letter resolves the long standing debate as to the proper time scale ($$) of the onset of the immunological synapse (IS) bond, the non-covalent chemical bond defining the immune pathways involving T-cells and antigen presenting cells (APC). Results from our model calculations show $$ to be of the order of seconds instead of minutes. Close to the linearly stable regime, we show that in between the two critical spatial thresholds defined by the integrin:ligand pair ($\\Delta_2\\sim$ 40-45 nm) and the T cell receptor (TCR):pMHC bond ($\\Delta_1\\sim$ 14-15 nm), $$ grows monotonically with increasing co-receptor bond length separation $\\delta$ (= $\\Delta_2-\\Delta_1\\sim$ 26-30 nm) while $$ decays with $\\Delta_1$ for fixed $\\Delta_2$. The non-universal $\\delta$-dependent power-law structure of the probability density function (PDF) further explains why only the TCR:pMHC bond is a likely candidate to form a stable synapse.

  11. FOR REGISTRAR RELATED INQUIRIES CONTACT: Registrar@nps.edu IF APPLYING FOR A DEGREE PROGRAM AT NPS CONTACT: Grad-Ed@nps.edu

    E-print Network

    FOR REGISTRAR RELATED INQUIRIES CONTACT: Registrar@nps.edu IF APPLYING FOR A DEGREE PROGRAM AT NPS CONTACT: Grad-Ed@nps.edu STAFF/EMPLOYEE ENROLLMENT REQUEST FORM Please Read Instructions Below Fill information, visit www.nps.edu/Technology/Security/CAC-guide.pdf Please deliver completed form to: Naval

  12. 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 AGENCY... correspondence. FOR FURTHER INFORMATION CONTACT: Denise McLamb, Enterprise Records Service (005R1B), Department... INFORMATION: Title: Request for Contact Information, VA Form 21-30. OMB Control Number: 2900-0660. Type...

  13. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... contact cooling and heating water subcategory. 463.10 Section 463.10 Protection of Environment... FORMING POINT SOURCE CATEGORY Contact Cooling and Heating Water Subcategory § 463.10 Applicability; description of the contact cooling and heating water subcategory. This subpart applies to discharges...

  14. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... contact cooling and heating water subcategory. 463.10 Section 463.10 Protection of Environment... FORMING POINT SOURCE CATEGORY Contact Cooling and Heating Water Subcategory § 463.10 Applicability; description of the contact cooling and heating water subcategory. This subpart applies to discharges...

  15. 40 CFR 463.10 - Applicability; description of the contact cooling and heating water subcategory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... contact cooling and heating water subcategory. 463.10 Section 463.10 Protection of Environment... FORMING POINT SOURCE CATEGORY Contact Cooling and Heating Water Subcategory § 463.10 Applicability; description of the contact cooling and heating water subcategory. This subpart applies to discharges...

  16. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses

    NASA Astrophysics Data System (ADS)

    Moon, James J.; Suh, Heikyung; Bershteyn, Anna; Stephan, Matthias T.; Liu, Haipeng; Huang, Bonnie; Sohail, Mashaal; Luo, Samantha; Ho Um, Soong; Khant, Htet; Goodwin, Jessica T.; Ramos, Jenelyn; Chiu, Wah; Irvine, Darrell J.

    2011-03-01

    Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.

  17. SST3-selective potent peptidic somatostatin receptor antagonists

    PubMed Central

    Reubi, Jean Claude; Schaer, Jean-Claude; Wenger, Sandra; Hoeger, Carl; Erchegyi, Judit; Waser, Beatrice; Rivier, Jean

    2000-01-01

    A family of octapeptide derivatives of somatostatin cyclized via a disulfide bridge (des-AA1,2,4,5,12,13[d-2Nal8]-somatostatin-14, ODN-8) was identified that has high affinity and selectivity for the human sst3 somatostatin receptor subtype transfected in CCL39 cells. The binding affinity of carbamoyl-des-AA1,2,4,5,12,13[d-Cys3,Tyr7,d-Agl8(Me,2-naphthoyl)]-somatostatin-14 (sst3-ODN-8) is equal to that of somatostatin-28 for sst3 and less than one-thousandth that for the other four somatostatin receptor subtypes. Compound sst3-ODN-8 potently reverses the somatostatin-28-induced inhibition of forskolin-stimulated cAMP production (pKB = 9.07) and reverses the somatostatin-28-induced stimulation of phospholipase C activity (pKi = 9.22) in sst3-transfected CCL39 cells. [125I-Tyr7]sst3-ODN-8 selectively labels sst3-expressing cells with subnanomolar binding affinity (KD = 0.27 nM). With the use of this radioligand, sst3-expressing human tumors, particularly inactive pituitary adenomas, can be identified with receptor autoradiography; moreover, areas of the human lymphoreticular system express sst3 binding sites selectively displaced by nanomolar concentrations of sst3-ODN-8. Based on the structure–activity relationship of selected analogs substituted at positions 3, 7, and 8, we hypothesize that the basis for sst3 selectivity, high affinity, and possibly antagonism resides in the ring size of the analog and the unique conformational and structural character of the N-methylated amino-2-naphthoyl side chain of aminoglycine at position 8 and not in the Tyr7 substitution or in the d-configuration at position 3. The family of labeled and unlabeled sst3-ODN-8 analogs represents highly innovative, potent, and specific sst3-selective antagonist tools for the study of sst3-mediated physiological and pathophysiological conditions that may suggest novel clinical applications. PMID:11095748

  18. Method for forming materials

    DOEpatents

    Tolle, Charles R. (Idaho Falls, ID); Clark, Denis E. (Idaho Falls, ID); Smartt, Herschel B. (Idaho Falls, ID); Miller, Karen S. (Idaho Falls, ID)

    2009-10-06

    A material-forming tool and a method for forming a material are described including a shank portion; a shoulder portion that releasably engages the shank portion; a pin that releasably engages the shoulder portion, wherein the pin defines a passageway; and a source of a material coupled in material flowing relation relative to the pin and wherein the material-forming tool is utilized in methodology that includes providing a first material; providing a second material, and placing the second material into contact with the first material; and locally plastically deforming the first material with the material-forming tool so as mix the first material and second material together to form a resulting material having characteristics different from the respective first and second materials.

  19. Wireless Measurement of Contact and Motion Between Contact Surfaces

    NASA Technical Reports Server (NTRS)

    Woodard, Stanley E.; Taylor, Bryant D.

    2007-01-01

    This method uses a magnetic-field- response contact sensor that is designed to identify surface contact and motion between contact locations. The sensor has three components: (1) a capacitor-inductor circuit with two sets of electrical contact pads, (2) a capacitor with a set of electrical contact pads, and (3) an inductor with a set of electrical contact pads. A unique feature of this sensor is that it is inherently multifunctional. Information can be derived from analyzing such sensor response attributes as amplitude, frequency, and bandwidth. A change in one attribute can be due to a change in a physical property of a system. A change in another attribute can be due to another physical property, which has no relationship to the first one.

  20. Modeling contact tracing in outbreaks with application to Ebola.

    PubMed

    Browne, Cameron; Gulbudak, Hayriye; Webb, Glenn

    2015-11-01

    Contact tracing is an important control strategy for containing Ebola epidemics. From a modeling perspective, explicitly incorporating contact tracing with disease dynamics presents challenges, and population level effects of contact tracing are difficult to determine. In this work, we formulate and analyze a mechanistic SEIR type outbreak model which considers the key features of contact tracing, and we characterize the impact of contact tracing on the effective reproduction number, Re, of Ebola. In particular, we determine how relevant epidemiological properties such as incubation period, infectious period and case reporting, along with varying monitoring protocols, affect the efficacy of contact tracing. In the special cases of either perfect monitoring of traced cases or perfect reporting of all cases, we derive simple formulae for the critical proportion of contacts that need to be traced in order to bring the effective reproduction number Re below one. Also, in either case, we show that Re can be expressed completely in terms of observable reported case/tracing quantities, namely Re=k((1-q)/q)+km where k is the number of secondary traced infected contacts per primary untraced reported case, km is the number of secondary traced infected contacts per primary traced reported case and (1-q)/q is the odds that a reported case is not a traced contact. These formulae quantify contact tracing as both an intervention strategy that impacts disease spread and a probe into the current epidemic status at the population level. Data from the West Africa Ebola outbreak is utilized to form real-time estimates of Re, and inform our projections of the impact of contact tracing, and other control measures, on the epidemic trajectory. PMID:26297316

  1. Preplacement Screening Patient Contact Form UF Employee/Volunteer

    E-print Network

    Slatton, Clint

    abuse/alcoholism Drug abuse/addiction Immunosuppression Latex allergy or other skin sensitivities/hearing aides Deafness Allergic rhinitis Hepatitis (type) Other liver disease (type) Diabetes (type pathogens and communicable diseases. You have an ethical and legal obligation to disclose any chronic

  2. Long-chain carboxychromanols, metabolites of vitamin E, are potent inhibitors of cyclooxygenases

    PubMed Central

    Jiang, Qing; Yin, Xinmin; Lill, Markus A.; Danielson, Matthew L.; Freiser, Helene; Huang, Jianjie

    2008-01-01

    Cyclooxygenase (COX-1/COX-2)-catalyzed eicosanoid formation plays a key role in inflammation-associated diseases. Natural forms of vitamin E are recently shown to be metabolized to long-chain carboxychromanols and their sulfated counterparts. Here we find that vitamin E forms differentially inhibit COX-2-catalyzed prostaglandin E2 in IL-1?-stimulated A549 cells without affecting COX-2 expression, showing the relative potency of ?-tocotrienol ? ?-tocopherol > ?-tocopherol ? ?- or ?-tocopherol. The cellular inhibition is partially diminished by sesamin, which blocks the metabolism of vitamin E, suggesting that their metabolites may be inhibitory. Consistently, conditioned media enriched with long-chain carboxychromanols, but not their sulfated counterparts or vitamin E, reduce COX-2 activity in COX-preinduced cells with 5 ?M arachidonic acid as substrate. Under this condition, 9?- or 13?-carboxychromanol, the vitamin E metabolites that contain a chromanol linked with a 9- or 13-carbon-length carboxylated side chain, inhibits COX-2 with an IC50 of 6 or 4 ?M, respectively. But 13?-carboxychromanol inhibits purified COX-1 and COX-2 much more potently than shorter side-chain analogs or vitamin E forms by competitively inhibiting their cyclooxygenase activity with Ki of 3.9 and 10.7 ?M, respectively, without affecting the peroxidase activity. Computer simulation consistently indicates that 13?-carboxychromanol binds more strongly than 9?-carboxychromanol to the substrate-binding site of COX-1. Therefore, long-chain carboxychromanols, including 13?-carboxychromanol, are novel cyclooxygenase inhibitors, may serve as anti-inflammation and anticancer agents, and may contribute to the beneficial effects of certain forms of vitamin E. PMID:19074288

  3. Potent production of capsaicinoids and capsinoids by Capsicum peppers.

    PubMed

    Kobata, Kenji; Sugawara, Mai; Mimura, Makoto; Yazawa, Susumu; Watanabe, Tatsuo

    2013-11-20

    The fundamental structure of capsinoids is a fatty acid ester with vanillyl alcohol, whereas in capsaicinoids, a fatty acid amide is linked to vanillylamine. To clarify the relationship between their biosynthesis in Capsicum plants, we carried out an in vivo tracer experiment using stable isotopically labeled putative precursors. Liquid chromatography-tandem mass spectrometry was used to measure the uptake of isotopes into metabolites after injection of the labeled precursors into intact fruits of a pungent cultivar, Peru, and a non-pungent cultivar, CH-19 Sweet. Labeled vanillylamine was incorporated into capsaicinoids in both cultivars. While labeled vanillyl alcohol was incorporated into capsinoids in both cultivars, the accumulation of intact capsaicinoids in Peru was suppressed by over 60% after administration of vanillyl alcohol. In Peru, labeled vanillin was converted to both vanillylamine and, in 5-fold excess, vanillyl alcohol. Moreover, labeled vanillin was converted exclusively to vanillyl alcohol in CH-19 Sweet. These data are consistent with the incorporation of labeled vanillin into capsaicinoids and capsinoids in both cultivars. We conclude that pungent cultivars are highly potent producers of vanillyl alcohol that is incorporated into capsinoids and that biosynthesis of capsinoids is catalyzed by capsaicin synthase. PMID:24147886

  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. Small molecule anticonvulsant agents with potent in vitro neuroprotection.

    PubMed

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

    2012-06-01

    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

  6. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

    PubMed

    Haj, Christeene G; Sumariwalla, Percy F; Hanuš, Lumír; Kogan, Natalya M; Yektin, Zhana; Mechoulam, Raphael; Feldmann, Mark; Gallily, Ruth

    2015-10-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to ?(9)-tetrahydrocannabinol (?(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-?, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive ?(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a ?(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-? production by macrophages); in vivo it led to suppression of production of TNF-? and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause ?(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. PMID:26272937

  7. 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. PMID:26203229

  8. Potent Agonists of the Protease Activated Receptor 2 (PAR2)

    PubMed Central

    Boitano, Scott; Flynn, Andrea N.; Schulz, Stephanie M.; Hoffman, Justin; Price, Theodore J.; Vagner, Josef

    2011-01-01

    Novel peptidomimetic pharmacophores to PAR2 were designed based on the known activating peptide SLIGRL-NH2. A set of 15 analogues was evaluated with a model cell line (16HBE14o-) that highly expresses PAR2. Cells exposed to the PAR2 activating peptide with N-terminal 2-furoyl modification (2-furoyl-LIGRLO-NH2) initiated increases in intracellular calcium concentration ([Ca2+]i EC50 = 0.84 ?M) and in vitro physiological responses as measured by the xCELLigence real time cell analyzer (RTCA EC50 = 138 nM). We discovered two selective PAR2 agonists with comparable potency: compound 1 (2-aminothiazol-4-yl; Ca2+ EC50 = 1.77 ?M, RTCA EC50 = 142 nM) and compound 2 (6-aminonicotinyl; Ca2+ EC50 = 2.60 ?M, RTCA EC50 = 311 nM). Unlike the previously described agonist, these novel agonists are devoid of the metabolically unstable 2-furoyl modification and thus provide potential advantages for PAR2 peptide design for in vitro and in vivo studies. The novel compounds described herein also serve as a starting point for structure–activity relationship (SAR) design and are, for the first time, evaluated via a unique high throughput in vitro physiological assay. Together these will lead to discovery of more potent agonists and antagonists of PAR2. PMID:21294569

  9. 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

  10. 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

  11. Acetone Extract from Rhodomyrtus tomentosa: A Potent Natural Antioxidant

    PubMed Central

    Lavanya, Goodla; Voravuthikunchai, Supayang Piyawan; Towatana, Nongporn Hutadilok

    2012-01-01

    Rhodomyrtus tomentosa (Myrtaceae) has been employed in traditional Thai medicine to treat colic diarrhoea, dysentery, abscesses, haemorrhage, and gynaecopathy. In addition, it has been used to formulate skin-whitening, anti-aging and skin beautifying agents. Ethnomedical activities of this plant may be due its antioxidant property. Hence, the aim of this study was to evaluate both in vitro and in vivo antioxidant activities of R. tomentosa leaf extract. In vitro antioxidant activity of the extract was assessed by lipid peroxidation inhibition capacity, ferric reducing antioxidant power, and metal chelating activity. R. tomentosa extract demonstrated its free radical scavenging effects in concentration dependent manner. In vivo antioxidant activity of the extract was conducted in Swiss Albino mice. Levels of thio-barbituric acid reactive substances (TBARS), glutathione (GSH), and the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in blood, liver, and kidney were analyzed using microtitre plate photometer. Administration of CCl4 caused significant increase in TBARS and decrease in GSH, SOD, CAT and GPx levels. In contrast, R. tomentosa extract (0.8?g/kg) effectively prevented these alterations and maintained the antioxidant status. The results suggest that R. tomentosa extract can serve as a potent antioxidant. PMID:23125869

  12. Potent and selective nonpeptidic inhibitors of procollagen C-proteinase.

    PubMed

    Fish, Paul V; Allan, Gillian A; Bailey, Simon; Blagg, Julian; Butt, Richard; Collis, Michael G; Greiling, Doris; James, Kim; Kendall, Jackie; McElroy, Andrew; McCleverty, Dawn; Reed, Charlotte; Webster, Robert; Whitlock, Gavin A

    2007-07-26

    6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux. Sulfonamide 56 had excellent PCP enzyme activity when measured with a peptide substrate (Ki 8.7 nM) or with the endogenous substrate procollagen (IC50 3.4 nM) and demonstrates excellent selectivity over MMPs involved in wound healing (>10 000-fold). In the fibroplasia model, 56 inhibited deposition of insoluble collagen by 76 +/- 2% at 10 microM and was very effective at penetrating human skin in vitro with a TED flux of 1.5 microg/cm2/h, which compares favorably with values for agents that are known to penetrate skin well in vivo. Based on this profile, 56 (UK-421,045) was selected as a candidate for further preclinical evaluation as a topically applied, dermal anti-scarring agent. PMID:17591762

  13. Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses.

    PubMed

    Makarov, Vadim A; Braun, Heike; Richter, Martina; Riabova, Olga B; Kirchmair, Johannes; Kazakova, Elena S; Seidel, Nora; Wutzler, Peter; Schmidtke, Michaela

    2015-10-01

    There are currently no drugs available for the treatment of enterovirus (EV)-induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well-tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC50 values between 0.04 and 0.64??M for viruses resistant to pleconaril, a known capsid-binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3-(4-trifluoromethylphenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine (OBR-5-340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3-induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR-5-340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing. PMID:26260222

  14. 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

  15. 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

  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. 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

  18. 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

  19. Predictive models for moving contact line flows

    NASA Technical Reports Server (NTRS)

    Rame, Enrique; Garoff, Stephen

    2003-01-01

    Modeling flows with moving contact lines poses the formidable challenge that the usual assumptions of Newtonian fluid and no-slip condition give rise to a well-known singularity. This singularity prevents one from satisfying the contact angle condition to compute the shape of the fluid-fluid interface, a crucial calculation without which design parameters such as the pressure drop needed to move an immiscible 2-fluid system through a solid matrix cannot be evaluated. Some progress has been made for low Capillary number spreading flows. Combining experimental measurements of fluid-fluid interfaces very near the moving contact line with an analytical expression for the interface shape, we can determine a parameter that forms a boundary condition for the macroscopic interface shape when Ca much les than l. This parameter, which plays the role of an "apparent" or macroscopic dynamic contact angle, is shown by the theory to depend on the system geometry through the macroscopic length scale. This theoretically established dependence on geometry allows this parameter to be "transferable" from the geometry of the measurement to any other geometry involving the same material system. Unfortunately this prediction of the theory cannot be tested on Earth.

  20. A single-pixel wireless contact lens display

    NASA Astrophysics Data System (ADS)

    Lingley, A. R.; Ali, M.; Liao, Y.; Mirjalili, R.; Klonner, M.; Sopanen, M.; Suihkonen, S.; Shen, T.; Otis, B. P.; Lipsanen, H.; Parviz, B. A.

    2011-12-01

    We present the design, construction and in vivo rabbit testing of a wirelessly powered contact lens display. The display consists of an antenna, a 500 × 500 µm2 silicon power harvesting and radio integrated circuit, metal interconnects, insulation layers and a 750 × 750 µm2 transparent sapphire chip containing a custom-designed micro-light emitting diode with peak emission at 475 nm, all integrated onto a contact lens. The display can be powered wirelessly from ~1 m in free space and ~2 cm in vivo on a rabbit. The display was tested on live, anesthetized rabbits with no observed adverse effect. In order to extend display capabilities, design and fabrication of micro-Fresnel lenses on a contact lens are presented to move toward a multipixel display that can be worn in the form of a contact lens. Contact lenses with integrated micro-Fresnel lenses were also tested on live rabbits and showed no adverse effect.

  1. Graphite-Graphene Contact Resistance

    NASA Astrophysics Data System (ADS)

    Chari, Tarun; Dean, Cory; Meric, Inanc; Wang, Lei; Shepard, Ken

    2013-03-01

    Exploiting the exceptional electronic properties of graphene has been attempted in several applications. However, graphene based applications still lag behind conventional electronics due, in part, to the highly resistive metal-graphene junction. For example, graphene based RF transistors suffer a diminished fmax due to highly resistive source-drain contacts (> 200 ? - ?m). Reducing this paracistic resistance can yield substantial improvement in device performance for transistors and many other applications. To achieve this, we create an electrical contact to graphene using mesoscopic, exfoliated graphite (10 - 20 nm thick). We fabricate graphite-graphene contacts by transferring pre-defined graphite contacts to graphene on silicon dioxide. Experimental measurement has shown the contact resistance to be < 50 ? - ?m , a four-fold improvement over conventional contacts to graphene. Columbia Energy Frontier Research Council

  2. 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.

  3. Contact Interface Verification for DYNA3D Scenario 2: Multi-Surface Contact

    SciTech Connect

    McMichael, L D

    2006-05-10

    A suite of test problems has been developed to examine contact behavior within the nonlinear, three-dimensional, explicit finite element analysis (FEA) code DYNA3D (Lin, 2005). The test problems use multiple interfaces and a combination of enforcement methods to assess the basic functionality of the contact algorithms. The results from the DYNA3D analyses are compared to closed form solutions to verify the contact behavior. This work was performed as part of the Verification and Validation efforts of LLNL W Program within the NNSA's Advanced Simulation and Computing (ASC) Program. DYNA3D models the transient dynamic response of solids and structures including the interactions between disjoint bodies (parts). A wide variety of contact surfaces are available to represent the diverse interactions possible during an analysis, including relative motion (sliding), separation and gap closure (voids), and fixed relative position (tied). The problem geometry may be defined using a combination of element formulations, including one-dimensional beam and truss elements, two-dimensional shell elements, and three-dimensional solid elements. Consequently, it is necessary to consider various element interactions during contact. This report and associated test problems examine the scenario where multiple bodies interact with each other via multiple interfaces. The test problems focus on whether any ordering issues exist in the contact logic by using a combination of interface types, contact enforcement options (i.e., penalty, Lagrange, and kinematic), and element interactions within each problem. The influence of rigid materials on interface behavior is also examined. The companion report (McMichael, 2006) and associated test problems address the basic contact scenario where one contact surface exists between two disjoint bodies. The test problems are analyzed using version 5.2 (compiled on 12/22/2005) of DYNA3D. The analytical results are used to form baseline solutions for subsequent regression testing. In section 2, the test problems are presented, and the static solution is developed for two idealized systems. Section 3 describes the finite element representation of the generic problem, including the interface combinations considered. The verification criteria and expected results are presented next in section 4. Section 5 discusses the numerical results obtained from each test problem. Finally, section 6 summarizes the observed interface behavior.

  4. 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 ...

  5. Structural influence on radical formation and sensitizing capacity of alkylic limonene hydroperoxide analogues in allergic contact dermatitis.

    PubMed

    Johansson, Staffan G H; Emilsson, Katarina; Grøtli, Morten; Börje, Anna

    2010-03-15

    Hydroperoxides are known to be strong contact allergens and a common cause of contact allergy. They are easily formed by the autoxidation of, for example, fragrance terpenes, compounds that are common in perfumes, cosmetics, and household products. A requirement of the immunological mechanisms of contact allergy is the formation of an immunogenic hapten-protein complex. For hydroperoxides, a radical mechanism is postulated for this formation. In our previous investigations of allylic limonene hydroperoxides, we found that the formation of carbon- and oxygen-centered radicals, as well as the sensitizing capacity, is influenced by the structure of the hydroperoxides. The aim of the present work was to further investigate the connection between structure, radical formation, and sensitizing capacity by studying alkylic analogues of the previously investigated allylic limonene hydroperoxides. The radical formation was studied in radical-trapping experiments employing 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride as an initiator and 1,1,3,3-tetramethylisoindolin-2-yloxyl as a radical trapper. We found that the investigated hydroperoxides initially form carbon- and oxygen-centered radicals that subsequently form alcohols and ketones. Trapped carbon-centered radicals and nonradical products were isolated and identified. Small changes in structure, like the omission of the endocyclic double bond or the addition of a methyl group, resulted in large differences in radical formation. The results indicate that alkoxyl radicals seem to be more important than carbon-centered radicals in the immunogenic complex formation. The sensitizing capacities were studied in the murine local lymph node assay (LLNA), and all hydroperoxides tested were found to be potent sensitizers. For two of the hydroperoxides investigated, the recently suggested thiol-ene reaction is a possible mechanism for the formation of immunogenic complexes. For the third investigated, fully saturated, hydroperoxide, the thiol-ene mechanism is not possible for immunogenic complex formation. This strongly indicates that several radical reaction pathways for immunogenic complex formation of limonene hydroperoxides are active in parallel. PMID:20163165

  6. Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis

    PubMed Central

    Pisithkul, Tippapha; Jacobson, Tyler B.; O'Brien, Thomas J.; Stevenson, David M.

    2015-01-01

    An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using 13C-labeled sugars and [15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. PMID:26070680

  7. 5% CO2 is a potent, fast acting inhalation anticonvulsant

    PubMed Central

    Tolner, Else A.; Hochman, Daryl W.; Hassinen, Pekka; Otáhal, Jakub; Gaily, Eija; Haglund, Michael M.; Kubová, Hana; Schuchmann, Sebastian; Vanhatalo, Sampsa; Kaila, Kai

    2010-01-01

    Purpose CO2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO2 can be used to suppress seizures in epilepsy patients. The effect of CO2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and a non-human primate and based on these data, preliminary tests were carried out in humans. Methods In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. 5% CO2 was applied for 5 minutes, 3 minutes before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG and received 5% CO2 in medical carbogen shortly after electrographic seizure onset. Results In rats, 5% CO2 strongly suppressed cortical afterdischarges, by ca. 75%, while responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO2 from 37 to 44-45 mmHg (corresponding to inhalation of 5% CO2 or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced epileptiform spikes by ca. 25%. In a pilot trial carried out in 7 patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO2 was started after seizure generalization. Conclusions 5% CO2 has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO2 can be used for acute treatment to suppress seizures in epilepsy patients. PMID:20887367

  8. 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

  9. Potent antioxidant role of pirfenidone in experimental cirrhosis.

    PubMed

    Salazar-Montes, Adriana; Ruiz-Corro, Luis; López-Reyes, Alberto; Castrejón-Gómez, Eugenio; Armendáriz-Borunda, Juan

    2008-10-24

    Three important features must be considered when proposing therapeutic strategies in liver cirrhosis: inflammation, oxidative stress and fibrogenesis. Pirfenidone is a synthetic molecule which oxidative action has not been tested in cirrhosis. Cirrhosis was induced in rats by ligation of the common bile duct or carbon tetrachloride (CCl(4)) chronic intoxication and treated with pirfenidone or diphenyleneiodonium (a potent known antioxidant) for the last two weeks for bile duct ligation model or for the last three weeks for CCl(4) chronic intoxication. A 60% reduction in fibrosis index for bile duct ligation model and 42% for CCl(4) along with reduced inflammation was observed. Considerable reduction on hepatic enzymes and total and direct bilirubins were detected with pirfenidone in both models. Pirfenidone antioxidant capacity rendered a 28% and 30% reduction in nitrites and malonyldealdehide concentration in bile duct ligation and 52% and 38% in CCl(4). With respect to gene expression, fibrotic genes like transforming growth factor-beta (TGF-beta) and collagen Ialpha (Col-1alpha) were down-regulated by pirfenidone and increased expression of regenerative genes like hepatocyte growth factor (HGF) and c-met . Superoxide dismutase (SOD), catalase (CAT) and inducible nitric oxide synthase (iNOS) gene expression were importantly down-regulated where nuclear factor kappa B (NF-kappaB) binding activity also decreased with pirfenidone treatment. Also, SOD and CAT functional activity decreased after pirfenidone action. On the other hand, diphenyleneiodonium induced a drop in oxidative stress similar in extent to pirfenidone, but it was not as effective as pirfenidone in reducing fibrosis. In this work, we showed antioxidant properties of pirfenidone beyond its well-known antifibrotic effect. These features make pirfenidone an attractive drug for trying fibrotic diseases accompanied by oxidative stress processes. PMID:18652820

  10. Design of Contact Filters To Serve 10,000 People

    E-print Network

    Pleasant, Carl

    1911-06-01

    the sewage from a population of ten thousand people. The sewage is assumed to be ordinary house sewage, unaffected by a considerable volume of trade waste. The quantity of the sewage is estimated on an assum­ ed average rate of water consumption of one..., THE DESIGN OP A SERIES OF CONTACT FILTERS TO SERVE TEN THOUSAND PEOPLE. THESIS PRESENTED FOR THE DEGREE OF MASTER OF SCIENCE by Carl Pleasant June, 191Sewage Purification at Columbus 1905* A New Form of Primary Contact Beds...

  11. Creating, Varying, and Growing Single-Site Molecular Contacts

    NASA Astrophysics Data System (ADS)

    Siaj, Mohamed; McBreen, Peter H.

    2005-07-01

    The known range of chemisorption bonds forms the toolbox for the design of electrical contacts in molecular electronics devices. Double-bond contacts to technologically relevant materials would be attractive for a number of reasons. They are truly single-site, bonding to a single surface atom. They obviate the need for a thiol linkage, and they may be amenable to further modification through olefin-metathesis methodologies. We report olefin-metathesis methods for establishing, varying, and growing thermally stable double-bond contacts to molybdenum carbide, a conducting material.

  12. Dynamic enhancer-gene body contacts during transcription elongation.

    PubMed

    Lee, Kiwon; Hsiung, Chris C-S; Huang, Peng; Raj, Arjun; Blobel, Gerd A

    2015-10-01

    Enhancers govern transcription through multiple mechanisms, including the regulation of elongation by RNA polymerase II (RNAPII). We characterized the dynamics of looped enhancer contacts during synchronous transcription elongation. We found that many distal enhancers form stable contacts with their target promoters during the entire interval of elongation. Notably, we detected additional dynamic enhancer contacts throughout the gene bodies that track with elongating RNAPII and the leading edge of RNA synthesis. These results support a model in which the gene body changes its position relative to a stable enhancer-promoter complex, which has broad ramifications for enhancer function and architectural models of transcriptional elongation. PMID:26443845

  13. Modeling receding contact lines on superhydrophobic surfaces.

    PubMed

    Mognetti, B M; Yeomans, J M

    2010-12-01

    We use mesoscale simulations to study the depinning of a receding contact line on a superhydrophobic surface patterned by a regular array of posts. For the simulations to be feasible, we introduce a novel geometry where a column of liquid dewets a capillary bounded by a superhydrophobic plane that faces a smooth hydrophilic wall of variable contact angle. We present results for the dependence of the depinning angle on the shape and spacing of the posts and discuss the form of the meniscus at depinning. We find, in agreement with ref 17 , that the local post concentration is a primary factor in controlling the depinning angle and show that the numerical results agree well with recent experiments. We also present two examples of metastable pinned configurations where the posts are partially wet. PMID:21067143

  14. High effectiveness contour matching contact heat exchanger

    SciTech Connect

    Blakely, R.L.; Roebelen, G.J. Jr.; Davenport, A.K.; Hartland, E.

    1988-08-09

    A high effectiveness contour matching contact heat exchanger is described having substantial manufacturing and physical distortion tolerance, comprising: (a) opposing shell members, (b) heat transfer pins extending between the shell members, each pin having a base and an outer end opposite the base, and each of the pins being attached at its respective base to a predetermined one of the shell members, and (c) means forming a close fitting receptacle for receiving the portion of each pin at the outer end thereof in the opposing shell member and closely contacting the sides of each pin thereat while providing for relative movement between each pin and its corresponding receptacle, for efficiently transfering heat between the pins and the shell members notwithstanding variations in the inter-shell spacing as much as substantially the depth of the receptacles.

  15. Modelling receding contact lines on superhydrophobic surfaces

    E-print Network

    B. M. Mognetti; J. M. Yeomans

    2010-10-23

    We use mesoscale simulations to study the depinning of a receding contact line on a superhydrophobic surface patterned by a regular array of posts. In order that the simulations are feasible, we introduce a novel geometry where a column of liquid dewets a capillary bounded by a superhydrophobic plane which faces a smooth hydrophilic wall of variable contact angle. We present results for the dependence of the depinning angle on the shape and spacing of the posts, and discuss the form of the meniscus at depinning. We find, in agreement with [17], that the local post concentration is a primary factor in controlling the depinning angle, and show that the numerical results agree well with recent experiments. We also present two examples of metastable pinned configurations where the posts are partially wet.

  16. 'Contact' in Space Leads to New Lenses

    NASA Technical Reports Server (NTRS)

    2004-01-01

    While gravity has its advantages in keeping us balanced and grounded here on Earth, scientists often find that they are at a disadvantage when trying to conduct research under its powerful, pulling influence. In these instances, the scientists prefer performing their studies in the weightless atmosphere of microgravity, where gravity is greatly reduced and solids, liquids, and gases behave differently. In 1993, Paragon Vision Sciences, Inc., of Mesa, Arizona, participated in a research project with NASA's Langley Research Center to perfect a process for developing contact lenses. The project called for three experiments that would fly onboard the Space Shuttle over the course of three separate missions, from 1993 to 1996. By unleashing contact lens materials to the microgravity settings of space, scientists from NASA and Paragon hoped to better understand how polymers - large molecules that make up plastics - are formed.

  17. 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

  18. Wearable telescopic contact lens.

    PubMed

    Arianpour, Ashkan; Schuster, Glenn M; Tremblay, Eric J; Stamenov, Igor; Groisman, Alex; Legerton, Jerry; Meyers, William; Amigo, Goretty Alonso; Ford, Joseph E

    2015-08-20

    We describe the design, fabrication, and testing of a 1.6 mm thick scleral contact lens providing both 1× and 2.8× magnified vision paths, intended for use as a switchable eye-borne telescopic low-vision aid. The F/9.7 telescopic vision path uses an 8.2 mm diameter annular entrance pupil and 4 internal reflections in a polymethyl methacrylate precision optic. This gas-impermeable insert is contained inside a smooth outer casing of rigid gas-permeable polymer, which also provides achromatic correction for refraction at the curved lens face. The unmagnified F/4.1 vision path is through the central aperture of the lens, with additional transmission between the annular telescope rings to enable peripheral vision. We discuss potential solutions for providing oxygenation for an extended wear version of the lens. The prototype lenses were characterized using a scale-model human eye, and telescope functionality was confirmed in a small-scale clinical (nondispensed) demonstration. PMID:26368753

  19. 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

  20. Role of membrane contact sites in protein import into mitochondria.

    PubMed

    Horvath, Susanne E; Rampelt, Heike; Oeljeklaus, Silke; Warscheid, Bettina; van der Laan, Martin; Pfanner, Nikolaus

    2015-03-01

    Mitochondria import more than 1,000 different proteins from the cytosol. The proteins are synthesized as precursors on cytosolic ribosomes and are translocated by protein transport machineries of the mitochondrial membranes. Five main pathways for protein import into mitochondria have been identified. Most pathways use the translocase of the outer mitochondrial membrane (TOM) as the entry gate into mitochondria. Depending on specific signals contained in the precursors, the proteins are subsequently transferred to different intramitochondrial translocases. In this article, we discuss the connection between protein import and mitochondrial membrane architecture. Mitochondria possess two membranes. It is a long-standing question how contact sites between outer and inner membranes are formed and which role the contact sites play in the translocation of precursor proteins. A major translocation contact site is formed between the TOM complex and the presequence translocase of the inner membrane (TIM23 complex), promoting transfer of presequence-carrying preproteins to the mitochondrial inner membrane and matrix. Recent findings led to the identification of contact sites that involve the mitochondrial contact site and cristae organizing system (MICOS) of the inner membrane. MICOS plays a dual role. It is crucial for maintaining the inner membrane cristae architecture and forms contacts sites to the outer membrane that promote translocation of precursor proteins into the intermembrane space and outer membrane of mitochondria. The view is emerging that the mitochondrial protein translocases do not function as independent units, but are embedded in a network of interactions with machineries that control mitochondrial activity and architecture. PMID:25514890

  1. Divalent cations modulate membrane binding and pore formation of a potent antibiotic peptide analog of alamethicin.

    PubMed

    Aquila, Marco; Benedusi, Mascia; Koch, Karl-Wilhelm; Dell'Orco, Daniele; Rispoli, Giorgio

    2013-03-01

    The Ca(2+) modulation of pore formation (and disaggregation) kinetics of a synthetic analog of alamethicin F50/5 ([l-Glu(OMe)(7,18,19)]), a potent antibiotic peptide, was investigated in situ and in vitro. The in situ experiments consisted in whole-cell recording from isolated retinal rod outer segments (OS), because once blocking the only OS endogenous conductance with saturating light, the current flows entirely through the (exogenous) channels formed by the peptide. The kinetics of current change induced by peptide application and removal (in ?50ms) on the OS extracellular side was measured in the presence of divalent cations at different concentrations. The in vitro experiments consisted on the divalent cations modulation of [l-Glu(OMe)(7,18,19)] binding to a mimetic OS membrane immobilized on a sensor chip surface, employing surface plasmon resonance spectroscopy (SPR). The presence of even low mM Ca(2+) or Mg(2+) sufficed to increase the [l-Glu(OMe)(7,18,19)] apparent affinity for the mimetic OS membrane up to ?4-fold, which accelerated the activation of the peptide-induced current in OS by ?10-fold with respect to low Ca(2+). In situ and in vitro experiments indicate that high concentrations of divalent cations increased also membrane rigidity, contrasting their effect on increasing the pore formation rate. PMID:23261317

  2. Purification and characterization of the potent endonuclease in extracts of bovine heart mitochondria.

    PubMed

    Cummings, O W; King, T C; Holden, J A; Low, R L

    1987-02-15

    A potent endonuclease identified in a crude fraction of soluble proteins from bovine heart mitochondria has been purified 2500-fold and partially characterized. Physical studies of the enzyme indicate a Stokes radius of 30.3 A and a sedimentation coefficient, S20 degrees, w, of 4.1 yielding a native molecule weight of 59,000 and a frictional coefficient of 1.2. Analysis of extensively purified fractions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals a major band at 29,000 Da accounting for 50% of the total protein and suggesting a dimeric subunit structure. The endonuclease maintains two distinct pH optima: pH 5.1-5.5 and 7-8. Both acid and neutral activities nick supercoiled M13 circular double-stranded replicative form I DNA and fragment single-stranded DNA templates to generate 5'-phosphoryl-3'-hydroxyl breaks. The endonuclease requires a divalent cation (preferring Mn2+ over Mg2+) and is sensitive to N-ethylmaleimide and moderate levels of salt. Analysis of the digestion products of double-stranded DNA after prolonged nuclease treatment yields a mixture of oligonucleotides, 13% of which are di- and trinucleotides. Despite the enzyme's ability to degrade DNA to oligonucleotides under some conditions, a strikingly nonrandom pattern of cleavage is observed when a restriction fragment composed of bovine D-loop DNA is used as a template. In this case, a strong preference for guanine tracts is seen. PMID:3818585

  3. Potent 19-norvitamin D analogs for prostate and liver cancer therapy

    PubMed Central

    Kittaka, Atsushi; Yoshida, Akihiro; Chiang, Kun-Chun; Takano, Masashi; Sawada, Daisuke; Sakaki, Toshiyuki; Chen, Tai C

    2013-01-01

    The active form of vitamin D3, 1?,25(OH)2D3 or calcitriol, is known to inhibit the proliferation and invasiveness of many types of cancer cells, including prostate and liver cancer cells. These findings support the use of 1?,25(OH)2D3 for prostate and liver cancer therapy. However, 1?,25(OH)2D3 can cause hypercalcemia, thus, analogs of 1?,25(OH)2D3 that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. We have developed 2?-functional group substituted 19-norvitamin D3 analogs with and without 14-epimerization. Among them, 2?- and 2?-(3-hydroxypropyl)-1?,25-dihydroxy-19-norvitamin D3 (MART-10 and -11, respectively) and 14-epi-2?- and 14-epi-2?-(3-hydroxypropyl)-1?,25-dihydroxy-19-norvitamin D3 (14-epi-MART-10 and 14-epi-MART-11, respectively) were found to be the most promising. In this review, we discuss the synthesis of this unique class of vitamin D analogs, the molecular mechanism of anticancer actions of vitamin D, and the biological evaluation of these analogs for potential application to the prevention and treatment of prostate and liver cancer. PMID:23157238

  4. Na?-K?-ATPase, a potent neuroprotective modulator against Alzheimer disease.

    PubMed

    Zhang, Li-Nan; Sun, Yong-Jun; Pan, Shuo; Li, Jun-Xia; Qu, Yin-E; Li, Yao; Wang, Yong-Li; Gao, Zi-Bin

    2013-02-01

    Alzheimer disease (AD) is a neurodegenerative disorder clinically characterized by progressive cognitive and memory dysfunction, which is the most common form of dementia. Although the pathogenesis of neuronal injury in AD is not clear, recent evidences suggest that Na?-K?-ATPase plays an important role in AD, and may be a potent neuroprotective modulator against AD. This review aims to provide readers with an in-depth understanding of Na?-K?-ATPase in AD through these modulations of some factors that are as follows, which leads to the change of learning and memory in the process of AD. 1. The deficiency in Na?, K?-ATPase ?1, ?2 and ?3 isoform genes induced learning and memory deficits, and ? isoform was evidently changed in AD, revealing that Na?, K?-ATPase ? isoform genes may play an important role in AD. 2. Some factors, such as ?-amyloid, cholinergic and oxidative stress, can modulate learning and memory in AD through the mondulation of Na?-K?-ATPase activity. 3. Some substances, such as Zn, s-Ethyl cysteine, s-propyl cysteine, citicoline, rivastigmine, Vit E, memantine, tea polyphenol, curcumin, caffeine, Alpinia galanga (L.) fractions, and Bacopa monnieri could play a role in improving memory performance and exert protective effects against AD by increasing expression or activity of Na?, K?-ATPase. PMID:23033963

  5. 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.

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

    PubMed

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

    2012-02-01

    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?s. 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. This article is part of a Special Issue entitled: Membrane protein structure and function. PMID:21819964

  7. Contact modeling for robotics applications

    SciTech Connect

    Lafarge, R.A.; Lewis, C.

    1998-08-01

    At Sandia National Laboratories (SNL), the authors are developing the ability to accurately predict motions for arbitrary numbers of bodies of arbitrary shapes experiencing multiple applied forces and intermittent contacts. In particular, the authors are concerned with the simulation of systems such as part feeders or mobile robots operating in realistic environments. Preliminary investigation of commercial dynamics software packages led them to the conclusion that they could use commercial software to provide everything they needed except for the contact model. They found that ADAMS best fit their needs for a simulation package. To simulate intermittent contacts, they need collision detection software that can efficiently compute the distances between non-convex objects and return the associated witness features. They also require a computationally efficient contact model for rapid simulation of impact, sustained contact under load, and transition to and from contact conditions. This paper provides a technical review of a custom hierarchical distance computation engine developed at Sandia, called the C-Space Toolkit (CSTk). In addition, they describe an efficient contact model using a non-linear damping term developed by SNL and Ohio State. Both the CSTk and the non-linear damper have been incorporated in a simplified two-body testbed code, which is used to investigate how to correctly model the contact using these two utilities. They have incorporated this model into the ADAMS software using the callable function interface. An example that illustrates the capabilities of the 9.02 release of ADAMS with their extensions is provided.

  8. Effect of flow field and geometry on the dynamic contact angle A. V. Lukyanov1

    E-print Network

    Lukyanov, Alex

    contact angle formed by an advancing liquid-gas interface with a solid substrate depends on the flow field is whether, for a given gas-liquid-solid system, the dynamic contact angle formed by an advancing free of formation of a new liquid-solid interface newly "wetted" solid surface and hence should be considered

  9. Design and Synthesis of Potent Macrocyclic HIV-1 Protease Inhibitors Involving P1-P2 Ligands

    PubMed Central

    Ghosh, Arun K.; Schiltz, Gary E.; Rusere, Linah N.; Osswald, Heather L.; Walters, D. Eric; Amano, Masayuki; Mitsuya, Hiroaki

    2014-01-01

    A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings between a Nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to respective unsaturated derivatives. Compound 8a containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity. PMID:25050776

  10. Novel, nonpeptidic cyanamides as potent and reversible inhibitors of human cathepsins K and L.

    PubMed

    Falgueyret, J P; Oballa, R M; Okamoto, O; Wesolowski, G; Aubin, Y; Rydzewski, R M; Prasit, P; Riendeau, D; Rodan, S B; Percival, M D

    2001-01-01

    Compounds containing a 1-cyanopyrrolidinyl ring were identified as potent and reversible inhibitors of cathepsins K and L. The original lead compound 1 inhibits cathepsins K and L with IC(50) values of 0. 37 and 0.45 M, respectively. Modification of compound 1 by replacement of the quinoline moiety led to the synthesis of N-(1-cyano-3-pyrrolidinyl)benzenesulfonamide (2). Compound 2 was found to be a potent inhibitor of cathepsins K and L with a K(i) value of 50 nM for cathepsin K. Replacement of the 1-cyanopyrrolidine of compound 2 by a 1-cyanoazetidine increased the potency of the inhibitor by 10-fold. This increase in potency is probably due to an enhanced chemical reactivity of the compound toward the thiolate of the active site of the enzyme. This is demonstrated when the assay is performed in the presence of glutathione at pH 7.0 which favors the formation of a GSH thiolate anion. Under these assay conditions, there is a loss of potency in the 1-cyanoazetidine series due to the formation of an inactive complex between the GSH thiolate and the 1-cyanoazetidine inhibitors. 1-Cyanopyrrolidinyl inhibitors exhibited time-dependent inhibition which allowed us to determine the association and dissociation rate constants with human cathepsin K. The kinetic data obtained showed that the increase of potency observed between different 1-cyanopyrrolidinyl inhibitors is due to an increase of k(on) values and that the association of the compound with the enzyme fits an apparent one-step mechanism. (13)C NMR experiments performed with the enzyme papain showed that compound 2 forms a covalent isothiourea ester adduct with the enzyme. As predicted by the kinetic analysis, the addition of the irreversible inhibitor E64 to the enzyme-cyanopyrrolidinyl complex totally abolished the signal of the isothiourea bond as observed by (13)C NMR, thereby demonstrating that the formation of the covalent bond with the active site cysteine residue is reversible. Finally, compound 2 inhibits bone resorption in an in vitro assay involving rabbit osteoclasts and bovine bone with an IC(50) value of 0.7 M. 1-Cyanopyrrolidine represents a new class of nonpeptidic compounds that inhibit cathepsin K and L activity and proteolysis of bone collagen. PMID:11141092

  11. Potent Neutralization of Hendra and Nipah Viruses by Human Monoclonal Antibodies

    PubMed Central

    Zhu, Zhongyu; Dimitrov, Antony S.; Bossart, Katharine N.; Crameri, Gary; Bishop, Kimberly A.; Choudhry, Vidita; Mungall, Bruce A.; Feng, Yan-Ru; Choudhary, Anil; Zhang, Mei-Yun; Feng, Yang; Wang, Lin-Fa; Xiao, Xiaodong; Eaton, Bryan T.; Broder, Christopher C.; Dimitrov, Dimiter S.

    2006-01-01

    Hendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 ?g/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 ?g/ml, and 98% neutralization required only 1.6 ?g/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines. PMID:16378991

  12. Influence of potent antioxidant leguminosae family plant extracts on growth and antioxidant defense system of Hep2 cancer cell line.

    PubMed

    Spanou, Chrysoula; Stagos, Dimitrios; Aligiannis, Nektarios; Kouretas, Demetrios

    2010-02-01

    Legumes are considered to be a very good source of polyphenolic compounds that may act as chemopreventive agents, especially by their antioxidant properties. However, many of the chemopreventive properties may depend on the concentrations of the phytochemical compounds because potent antioxidant polyphenolic compounds may have pro-oxidant properties and negatively affect cell growth and viability. Thus, the aim of the present study was to assess the possible effect of two potent antioxidant Greek Leguminosae family plant extracts on the growth of a specific cancer cell line and its antioxidant defense cell system. Aqueous extracts of aerial parts of Lathyrus laxiflorus and Phaseolus vulgaris plants were initially examined for their cytotoxicity on the Hep2 cancer cell line at concentrations that possess potent antioxidant properties (100, 400, and 800 microg/mL). After a 24-hour incubation with the extracts, only L. laxiflorus plant extract exhibited the ability to inhibit the cell growth at 400 and 800 microg/mL by 57% and 74%, respectively, whereas P. vulgaris extract had no effect on cell growth at any of the tested concentrations. Noncytotoxic concentrations, 100 microg/mL L. laxiflorus and 800 microg/mL P. vulgaris extract, were used for 2-, 12-, and 24-hour incubation of the cells. The influence of the extracts on the antioxidant defense system of the cells was assessed by measuring the total antioxidant capacity (TAC) of the cells, the catalase (CAT) activity, and the concentrations of reduced glutathione, the oxidized form of glutathione, and thiobarbituric-reactive substances (TBARS) in all times of incubation with the cells. From the results obtained, it seems that only L. laxiflorus extract induces oxidative stress in the cells by reducing TAC and CAT activity and by inducing TBARS, especially with 2 and 12 hours of incubation. P. vulgaris extract reduced only TAC at 2 hours of incubation, indicating also a mild induction of oxidative stress. These results imply that potent antioxidant extracts, beyond a critical concentration, may induce oxidative stress even with no apparent cytotoxicity in cells. PMID:20136449

  13. End-bonded contacts for carbon nanotube transistors with low, size-independent resistance.

    PubMed

    Cao, Qing; Han, Shu-Jen; Tersoff, Jerry; Franklin, Aaron D; Zhu, Yu; Zhang, Zhen; Tulevski, George S; Tang, Jianshi; Haensch, Wilfried

    2015-10-01

    Moving beyond the limits of silicon transistors requires both a high-performance channel and high-quality electrical contacts. Carbon nanotubes provide high-performance channels below 10 nanometers, but as with silicon, the increase in contact resistance with decreasing size becomes a major performance roadblock. We report a single-walled carbon nanotube (SWNT) transistor technology with an end-bonded contact scheme that leads to size-independent contact resistance to overcome the scaling limits of conventional side-bonded or planar contact schemes. A high-performance SWNT transistor was fabricated with a sub-10-nanometer contact length, showing a device resistance below 36 kilohms and on-current above 15 microampere per tube. The p-type end-bonded contact, formed through the reaction of molybdenum with the SWNT to form carbide, also exhibited no Schottky barrier. This strategy promises high-performance SWNT transistors, enabling future ultimately scaled device technologies. PMID:26430114

  14. End-bonded contacts for carbon nanotube transistors with low, size-independent resistance

    NASA Astrophysics Data System (ADS)

    Cao, Qing; Han, Shu-Jen; Tersoff, Jerry; Franklin, Aaron D.; Zhu, Yu; Zhang, Zhen; Tulevski, George S.; Tang, Jianshi; Haensch, Wilfried

    2015-10-01

    Moving beyond the limits of silicon transistors requires both a high-performance channel and high-quality electrical contacts. Carbon nanotubes provide high-performance channels below 10 nanometers, but as with silicon, the increase in contact resistance with decreasing size becomes a major performance roadblock. We report a single-walled carbon nanotube (SWNT) transistor technology with an end-bonded contact scheme that leads to size-independent contact resistance to overcome the scaling limits of conventional side-bonded or planar contact schemes. A high-performance SWNT transistor was fabricated with a sub-10-nanometer contact length, showing a device resistance below 36 kilohms and on-current above 15 microampere per tube. The p-type end-bonded contact, formed through the reaction of molybdenum with the SWNT to form carbide, also exhibited no Schottky barrier. This strategy promises high-performance SWNT transistors, enabling future ultimately scaled device technologies.

  15. Potent drugs that attenuate anti-Candida albicans activity of fluconazole and their possible mechanisms of action.

    PubMed

    Urai, Makoto; Kaneko, Yukihiro; Niki, Mamiko; Inoue, Manabu; Tanabe, Koichi; Umeyama, Takashi; Fukazawa, Hidesuke; Ohno, Hideaki; Miyazaki, Yoshitsugu

    2014-10-01

    Fluconazole (FLCZ) is a first-line drug for treating Candida albicans infections, but clinical failure due to reduced sensitivity is a growing concern. Our previous study suggested that certain drug combinations pose a particular challenge in potently reducing FLCZ's anti-C. albicans activity, and cyclooxygenase inhibitors formed the major group of these attenuating drugs in combination with FLCZ. In this study, we examined the effects of diclofenac sodium (DFNa) and related compounds in combination with FLCZ against C. albicans, and investigated their possible mechanisms of interaction. DFNa, ibuprofen, and omeprazole elevated the minimum inhibitory concentration (MIC) of FLCZ by 8-, 4-, and 4-fold, respectively; however, loxoprofen sodium and celecoxib did not. An analogue of DFNa, 2,6-dichlorodiphenylamine, also elevated the MIC by 4-fold. Gene expression analysis revealed that diclofenac sodium induced CDR1 efflux pump activity, but not CDR2 activity. In addition, an efflux pump CDR1 mutant, which was manipulated to not be induced by DFNa, showed less elevation of MIC compared to that shown by the wild type. Therefore, DFNa and related compounds are potent factors for reducing the sensitivity of C. albicans to FLCZ partly via induction of an efflux pump. Although it is not known whether such antagonism is relevant to the clinical treatment failure observed, further investigation of the molecular mechanisms underlying the reduction of FLCZ's anti-C. albicans activity is expected to promote safer and more effective use of the drug. PMID:25009090

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

    SciTech Connect

    Shi, Lin; Song, Quansheng; Zhang, Yingmei; Department of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191 ; Lou, Yaxin; Wang, Yanfang; Tian, Linjie; Zheng, Yi; Ma, Dalong; Department of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191 ; Ke, Xiaoyan; Wang, Ying; Department of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191

    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.

  17. The nature of electrical interaction of Schottky contacts

    SciTech Connect

    Torkhov, N. A.

    2011-08-15

    Electrical interaction between metal-semiconductor contacts combined in a diode matrix with a Schottky barrier manifests itself in an appreciable variation in their surface potentials and static current-volt-characteristics. The necessary condition for appearance of electrical interaction between such contacts consists in the presence of a peripheral electric field (a halo) around them; this field propagates to a fairly large distances (<30 {mu}m). The sufficient condition is the presence of regions where the above halos overlap. It has been shown that variation in the surface potential and the current-voltage characteristics of contacts occurs under the effect of the intrinsic electric field of the contact's periphery and also under the effect of an electric field at matrix periphery; the latter field is formed as a result of superposition of electric fields of halos which form its contacts. The degree of the corresponding effect is governed by the distance between contacts and by the total charge of the space charge regions for all contacts of the matrix: their number, sizes (diameter D{sub i,j}), concentration of doping impurities in the semiconductor N{sub D}, and physical nature of a metal-semiconductor system with a Schottky barrier (with the barrier height {phi}{sub b}). It is established that bringing the contacts closer leads to a relative decrease in the threshold value of the 'dead' zone in the forward current-voltage characteristics, an increase in the effective height of the barrier, and an insignificant increase in the nonideality factor. An increase in the total area of contacts (a total electric charge in the space charge region) in the matrix brings about an increase in the threshold value of the 'dead' zone, a relative decrease in the effective barrier height, and an insignificant increase in the ideality factor.

  18. Potent anti-muscarinic activity in a novel series of quinuclidine derivatives.

    PubMed

    Starck, Jean-Philippe; Talaga, Patrice; Quéré, Luc; Collart, Philippe; Christophe, Bernard; Lo Brutto, Patrick; Jadot, Sophie; Chimmanamada, Dinesh; Zanda, Matteo; Wagner, Alain; Mioskowski, Charles; Massingham, Roy; Guyaux, Michel

    2006-01-15

    The synthesis and biological evaluation of a novel family of M(3) muscarinic antagonists are described. A systematic modification of the substituents to a novel alkyne-quinuclidine scaffold yielded original compounds displaying potent in vitro anticholinergic properties. PMID:16275087

  19. Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates

    E-print Network

    Dong, Yizhou

    siRNA therapeutics have promise for the treatment of a wide range of genetic disorders. Motivated by lipoproteins, we report lipopeptide nanoparticles as potent and selective siRNA carriers with a wide therapeutic index. ...

  20. Multivalent Antibiotics via Metal Complexes: Potent Divalent Vancomycins against Vancomycin-Resistant Enterococci

    E-print Network

    Xing, Bengang

    Multivalent Antibiotics via Metal Complexes: Potent Divalent Vancomycins against Vancomycin-Resistant than that of Van itself) against vancomycin- resistant enterococci (VRE). The result suggests inhibitors. Introduction Drug resistance1 of bacteria poses a serious public health threat and demands

  1. 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,

  2. 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,

  3. 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 ...

  4. Is Glyoxylate, a Glycine-derived Ketoacid, a Potent Detoxifier of ROS in Pseudomonas fluorescens?

    E-print Network

    Appanna, Vasu

    1 Is Glyoxylate, a Glycine-derived Ketoacid, a Potent Detoxifier of ROS in Pseudomonas fluorescens as an ROS scavenger by Pseudomonas fluorescens. Metabolomic analysis revealed oxalate and formate, two

  5. Structural characterization of more potent alternatives to HAMLET, a tumoricidal complex of ?-lactalbumin and oleic acid.

    PubMed

    Nemashkalova, Ekaterina L; Kazakov, Alexei S; Khasanova, Leysan M; Permyakov, Eugene A; Permyakov, Sergei E

    2013-09-10

    HAMLET is a complex of human ?-lactalbumin (hLA) with oleic acid (OA) that kills various tumor cells and strains of Streptococcus pneumoniae. More potent protein-OA complexes were previously reported for bovine ?-lactalbumin (bLA) and ?-lactoglobulin (bLG), and pike parvalbumin (pPA), and here we explore their structural features. The concentration dependencies of the tryptophan fluorescence of hLA, bLA, and bLG complexes with OA reveal their disintegration at protein concentrations below the micromolar level. Chemical cross-linking experiments provide evidence that association with OA shifts the distribution of oligomeric forms of hLA, bLA, bLG, and pPA toward higher-order oligomers. This effect is confirmed for bLA and bLG using the dynamic light scattering method, while pPA is shown to associate with OA vesicles. Like hLA binding, OA binding increases the affinity of bLG for small unilamellar dipalmitoylphosphatidylcholine vesicles, while pPA efficiently binds to the vesicles irrespective of OA binding. The association of OA with bLG and pPA increases their ?-helix and cross-?-sheet content and resistance to enzymatic proteolysis, which is indicative of OA-induced protein structuring. The lack of excess heat sorption during melting of bLG and pPA in complex with OA and the presence of a cooperative thermal transition at the level of their secondary structure suggest that the OA-bound forms of bLG and pPA lack a fixed tertiary structure but exhibit a continuous thermal transition. Overall, despite marked differences, the HAMLET-like complexes that were studied exhibit a common feature: a tendency toward protein oligomerization. Because OA-induced oligomerization has been reported for other proteins, this phenomenon is inherent to many proteins. PMID:23947814

  6. 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.

  7. 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.

  8. Formation of Catalytic Metal-Molecule Contacts

    NASA Astrophysics Data System (ADS)

    Tulevski, George S.; Myers, Matt B.; Hybertsen, Mark S.; Steigerwald, Michael L.; Nuckolls, Colin

    2005-07-01

    We describe a new strategy for the in situ growth of molecular wires predicated on the synthesis of a trifunctional ``primed'' contact formed from metal-carbon multiple bonds. The ruthenium-carbon ? bond provides structural stability to the molecular linkages under ambient conditions, and density functional calculations indicate the formation of an efficient conduit for charge carriers to pass between the metal and the molecule. Moreover, the metal-carbon ? bond provides a chemically reactive site from which a conjugated molecular wire can be grown in situ through an olefin metathesis reaction.

  9. Contact Eczema Caused by True Teak (Tectona Grandis)

    PubMed Central

    Krogh, H. K.

    1962-01-01

    An epidemiological study of occupational contact eczema in a furniture factory is presented. The localization, distribution, and clinical features of the skin lesions were characteristic of contact eczema caused by a sensitizing or irritating dust. True teak—Tectona grandis—was the cause of the skin condition. That teak is a fairly potent sensitizer and also contains primary irritants is fully confirmed by the present study. About half the employees who were heavily exposed to teak dust suffered from eczema and/or severe itching. Only 8% of those with slight exposure to teak dust experienced skin symptoms. Patch tests with native teak dust moistened with water were applied on 10 “controls” and 112 workers who were exposed to teak in various working procedures. Moistened teak dust produced toxic reactions in 20·5%, while native teak dust did not have primary irritant effects and was, therefore, considered to be the substance of choice for patch testing; 18·7% of the workers showed an allergic skin reaction to native teak dust. The diagnosis of allergic contact eczema was made in 12·5%, and 6·2% were considered to have latent allergy. Primary irritant (contact) eczema was considered to be present in four individuals who had experienced acute, transitory, eczematous eruptions during the hot part of the summer when they perspired freely. In these cases the patch test to native teak dust was negative. Desensitization or “hardening” was observed in four workers. In most cases the skin lesions were not severe enough to cause sickness absence. The cause of the relatively high percentage of sensitization to teak among the workers in the factory is discussed. The importance of suitable prophylactic measures is stressed. PMID:14459786

  10. Environmental Health and Safety Training Confirmation Form

    E-print Network

    Environmental Health and Safety Training Confirmation Form The purpose of this form is to document this form and viewing a specific safety training module contact Environmental Health and Safety at x2723 to Environmental Health and Safety, Mail Mode 3930, via campus mail. The address is located at the bottom

  11. Public Event Disability Access Accommodation Request Form

    E-print Network

    Chapman, Michael S.

    Public Event Disability Access Accommodation Request Form Event attendees with qualified disabilities may use this form to request a reasonable accommodation for an OHSU sponsored event. Submit the completed form to the event contact person at least five business days prior to the event. If appropriate

  12. 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

  13. 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.

  14. 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.

  15. Measuring The Contact Resistances Of Photovoltaic Cells

    NASA Technical Reports Server (NTRS)

    Burger, D. R.

    1985-01-01

    Simple method devised to measure contact resistances of photovoltaic solar cells. Method uses readily available equipment and applicable at any time during life of cell. Enables evaluation of cell contact resistance, contact-end resistance, contact resistivity, sheet resistivity, and sheet resistivity under contact.

  16. 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

  17. Back contact buffer layer for thin-film solar cells

    DOEpatents

    Compaan, Alvin D.; Plotnikov, Victor V.

    2014-09-09

    A photovoltaic cell structure is disclosed that includes a buffer/passivation layer at a CdTe/Back contact interface. The buffer/passivation layer is formed from the same material that forms the n-type semiconductor active layer. In one embodiment, the buffer layer and the n-type semiconductor active layer are formed from cadmium sulfide (CdS). A method of forming a photovoltaic cell includes the step of forming the semiconductor active layers and the buffer/passivation layer within the same deposition chamber and using the same material source.

  18. Using Tutte polynomials to characterize sexual contact networks

    NASA Astrophysics Data System (ADS)

    Cadavid Muñoz, Juan José

    2014-06-01

    Tutte polynomials are used to characterize the dynamic and topology of the sexual contact networks, in which pathogens are transmitted as an epidemic. Tutte polynomials provide an algebraic characterization of the sexual contact networks and allow the projection of spread control strategies for sexual transmission diseases. With the usage of Tutte polynomials, it allows obtaining algebraic expressions for the basic reproductive number of different pathogenic agents. Computations are done using the computer algebra software Maple, and it's GraphTheory Package. The topological complexity of a contact network is represented by the algebraic complexity of the correspondent polynomial. The change in the topology of the contact network is represented as a change in the algebraic form of the associated polynomial. With the usage of the Tutte polynomials, the number of spanning trees for each contact network can be obtained. From the obtained results in the polynomial form, it can be said that Tutte polynomials are of great importance for designing and implementing control measures for slowing down the propagation of sexual transmitted pathologies. As a future research line, the analysis of weighted sexual contact networks using weighted Tutte polynomials is considered.

  19. 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.

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

    SciTech Connect

    Chanana, Anuja; Mahapatra, Santanu

    2014-11-28

    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.

  1. 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.

  2. Wireless Device Request Form Department

    E-print Network

    Wireless Device Request Form Department: Employee ID #: St. Francis Xavier University TSG Contact Centre Angus L. MacDonald Library Main Entrance Phone: 902-867-2356 email: tsg@stfx.ca http Date: Part II - Employee Agreement I agree and acknowledge that I have read the Wireless Communications

  3. Morphology and the Strength of Intermolecular Contact in Protein Crystals

    NASA Technical Reports Server (NTRS)

    Matsuura, Yoshiki; Chernov, Alexander A.

    2002-01-01

    The strengths of intermolecular contacts (macrobonds) in four lysozyme crystals were estimated based on the strengths of individual intermolecular interatomic interaction pairs. The periodic bond chain of these macrobonds accounts for the morphology of protein crystals as shown previously. Further in this paper, the surface area of contact, polar coordinate representation of contact site, Coulombic contribution on the macrobond strength, and the surface energy of the crystal have been evaluated. Comparing location of intermolecular contacts in different polymorphic crystal modifications, we show that these contacts can form a wide variety of patches on the molecular surface. The patches are located practically everywhere on this surface except for the concave active site. The contacts frequently include water molecules, with specific intermolecular hydrogen-bonds on the background of non-specific attractive interactions. The strengths of macrobonds are also compared to those of other protein complex systems. Making use of the contact strengths and taking into account bond hydration we also estimated crystal-water interfacial energies for different crystal faces.

  4. 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

  5. 02/23/2011 CONTACT

    E-print Network

    Hoffman, Andrew J.

    02/23/2011 CONTACT: Pam Sturner, Leopold Leadership Program: 650) 723-9296, mshwartz@stanford.edu [Subject line:] STANFORD: 2011 Leopold Leadership researchers selected as 2011 Leopold Leadership fellows [Summary:] Twenty

  6. 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

  7. 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

  8. Contact Kinetics in Fractal Macromolecules

    NASA Astrophysics Data System (ADS)

    Dolgushev, Maxim; Guérin, Thomas; Blumen, Alexander; Bénichou, Olivier; Voituriez, Raphaël

    2015-11-01

    We consider the kinetics of first contact between two monomers of the same macromolecule. Relying on a fractal description of the macromolecule, we develop an analytical method to compute the mean first contact time for various molecular sizes. In our theoretical description, the non-Markovian feature of monomer motion, arising from the interactions with the other monomers, is captured by accounting for the nonequilibrium conformations of the macromolecule at the very instant of first contact. This analysis reveals a simple scaling relation for the mean first contact time between two monomers, which involves only their equilibrium distance and the spectral dimension of the macromolecule, independently of its microscopic details. Our theoretical predictions are in excellent agreement with numerical stochastic simulations.

  9. Patrick J. Bartlein CONTACT INFORMATION

    E-print Network

    Roering, Joshua J.

    Patrick J. Bartlein CONTACT INFORMATION Department of Geography, University of Oregon, Eugene Letters, DOI: 10.1002/grl.50350 #12;Patrick J. Bartlein -- April 2, 2014 Page 2 Marlon, J.R. P.J. Bartlein

  10. 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 ...

  11. Contact Kinetics in Fractal Macromolecules.

    PubMed

    Dolgushev, Maxim; Guérin, Thomas; Blumen, Alexander; Bénichou, Olivier; Voituriez, Raphaël

    2015-11-13

    We consider the kinetics of first contact between two monomers of the same macromolecule. Relying on a fractal description of the macromolecule, we develop an analytical method to compute the mean first contact time for various molecular sizes. In our theoretical description, the non-Markovian feature of monomer motion, arising from the interactions with the other monomers, is captured by accounting for the nonequilibrium conformations of the macromolecule at the very instant of first contact. This analysis reveals a simple scaling relation for the mean first contact time between two monomers, which involves only their equilibrium distance and the spectral dimension of the macromolecule, independently of its microscopic details. Our theoretical predictions are in excellent agreement with numerical stochastic simulations. PMID:26613478

  12. Advertising Contact Information Laura Langthorne

    E-print Network

    Peters, Richard

    Overview #12;Money Advertising Contact Information Laura Langthorne 02 8596 2957 llangthorne to personal finance including tax strategies, savings, share market strategies, superannuation and property. Profile* Why Advertise* · Our audience have a combined total of $900 billion in investments · 388

  13. First total synthesis of (+)-Vedelianin, a potent antiproliferative agent

    PubMed Central

    Topczewski, Joseph J.; Wiemer, David F.

    2011-01-01

    The total synthesis of (+)-vedelianin has been accomplished in 18 steps from vanillin. Preparation of a key intermediate in nonracemic form through a Shi epoxidation has allowed determination of the absolute stereochemistry of the natural product as the (2S, 3R, 4aR, 9aR)-isomer. PMID:22053119

  14. 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

  15. Water on a Hydrophobic Surface: Contact Angle vs. Depletion Layer

    NASA Astrophysics Data System (ADS)

    Neidig, Caitlyn; Brezinsky, Jacob; Zhou, Mengjue; Poynor, Adele

    2012-02-01

    Hydrophobic surfaces repel water. When this occurs, a depletion layer is formed between the water and the hydrophobic surface. We will be studying the effects from the contact angle, the angle at which the water droplet meets the surface, on the depletion layer. Larger contact angles create thicker depletion layers, which has lead us to determine if there is a direct relationship between the contact angle and depletion layer. In order to do this, we will be coating gold slides with a hydrophobic ODT solution, a hydrophilic Mercapto solution, and various mixtures of both of these solutions to create a large range of contact angles. We will be using Surface Plasmon Resonance to study to any depletion layer created by water on these surfaces.

  16. Emerging magnetic order in platinum atomic contacts and chains

    NASA Astrophysics Data System (ADS)

    Strigl, Florian; Espy, Christopher; Bückle, Maximilian; Scheer, Elke; Pietsch, Torsten

    2015-02-01

    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.

  17. 78 FR 14549 - National Contact Center; Information Collection; National Contact Center Customer Evaluation Survey

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-06

    ... ADMINISTRATION National Contact Center; Information Collection; National Contact Center Customer Evaluation Survey AGENCY: Contact Center Services, Federal Citizen Information Center, Office of Citizen Services... requirement regarding the National Contact Center customer evaluation surveys. In this request, the...

  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. Pose and motion from contact

    SciTech Connect

    Jia, Y.B.; Erdmann, M.

    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.

  20. Prescriptions for Eye Glasses and Contact Lenses

    MedlinePLUS

    ... esta página en español Prescriptions for Eyeglasses and Contact Lenses Related Items The Basics of LASIK Eye Surgery Buying Cosmetic Contact Lenses? Millions of Americans wear glasses or contact ...

  1. SARS Patients and Their Close Contacts

    MedlinePLUS

    ... Fact Sheet for SARS Patients and Their Close Contacts Format: Select one PDF [256 KB] Recommend on ... that are not now known. What does "close contact" mean? In the context of SARS, close contact ...

  2. 5 CFR 2600.102 - Contact information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Contact information. 2600.102 Section 2600...OF GOVERNMENT ETHICS § 2600.102 Contact information. (a) Address. ...Persons who are deaf or speech impaired may contact OGE at the following TDD...

  3. Mechanisms of rolling contact spalling

    NASA Technical Reports Server (NTRS)

    Kumar, A. M.; Kulkarni, S. M.; Bhargava, V.; Hahn, G. T.; Rubin, C. A.

    1987-01-01

    The results of a study aimed at analyzing the mechanical material interactions responsible for rolling contact spalling of the 440 C steel, high pressure oxygen turbopump bearings are presented. A coupled temperature displacement finite element analysis of the effects of friction heating under the contact is presented. The contact is modelled as a stationary, heat generating, 2 dimensional indent in an elastic perfectly plastic half-space with heat fluxes up to 8.6 x 10000 KW/m sq comparable to those generated in the bearing. Local temperatures in excess of 1000 C are treated. The calculations reveal high levels of residual tension after the contact is unloaded and cools. Efforts to promote Mode 2/Mode 3 fatigue crack growth under cyclic torsion in hardened 440 C steel are described. Spalls produced on 440 C steel by a 3 ball/rod rolling contact testing machine were studied with scanning microscopy. The shapes of the cyclic, stress strain hysteresis loops displayed by hardened 440 C steel in cyclic torsion at room temperature are defined for the plastic strain amplitudes encountered in rolling/sliding contact. Results of these analyses are discussed in detail.

  4. Crane-Load Contact Sensor

    NASA Technical Reports Server (NTRS)

    Youngquist, Robert; Mata, Carlos; Cox, Robert

    2005-01-01

    An electronic instrument has been developed as a prototype of a portable crane-load contact sensor. Such a sensor could be helpful in an application in which the load rests on a base in a horizontal position determined by vertical alignment pins (see Figure 1). If the crane is not positioned to lift the load precisely vertically, then the load can be expected to swing once it has been lifted clear of the pins. If the load is especially heavy, large, and/or fragile, it could hurt workers and/or damage itself and nearby objects. By indicating whether the load remains in contact with the pins when it has been lifted a fraction of the length of the pins, the crane-load contact sensor helps the crane operator determine whether it is safe to lift the load clear of the pins: If there is contact, then the load is resting against the sides of the pins and, hence, it may not be safe to lift; if contact is occasionally broken, then the load is probably not resting against the pins, so it should be safe to lift. It is assumed that the load and base, or at least the pins and the surfaces of the alignment holes in the load, are electrically conductive, so the instrument can use electrical contact to indicate mechanical contact. However, DC resistance cannot be used as an indicator of contact for the following reasons: The load and the base are both electrically grounded through cables (the load is grounded through the lifting cable of the crane) to prevent discharge of static electricity. In other words, the DC resistance between the load and the pins is always low, as though they were always in direct contact. Therefore, instead of DC resistance, the instrument utilizes the AC electrical impedance between the pins and the load. The signal frequency used in the measurement is high enough (.1 MHz) that the impedance contributed by the cables and the electrical ground network of the building in which the crane and the base are situated is significantly greater than the contact impedance between the pins and the load. The instrument includes a signal generator and voltage-measuring circuitry, and is connected to the load and the base as shown in Figure 2. The output of the signal generator (typically having amplitude of the order of a volt) is applied to the load via a 50-resistor, and the voltage between the load and the pins is measured. When the load and the pins are not in contact, the impedance between them is relatively high, causing the measured voltage to exceed a threshold value. When the load and the pins are in contact, the impedance between them falls to a much lower value, causing the voltage to fall below the threshold value. The voltage-measuring circuitry turns on a red light-emitting diode (LED) to indicate the lower-voltage/ contact condition. Whenever the contact has been broken and the non-contact/higher-voltage condition has lasted for more than 2 ms, the voltage-measuring circuitry indicates this condition by blinking a green LED.

  5. 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

  6. 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

    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.

  7. Crystal structures of multidrug-resistant HIV-1 protease in complex with two potent anti-malarial compounds

    PubMed Central

    Yedidi, Ravikiran S.; Liu, Zhigang; Wang, Yong; Brunzelle, Joseph S.; Kovari, Iulia A.; Woster, Patrick M.; Kovari, Ladislau C.; Gupta, Deepak

    2012-01-01

    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. PMID:22469467

  8. Ferromagnetic tunnel contacts to graphene: Contact resistance and spin signal

    SciTech Connect

    Cubukcu, M.; Laczkowski, P.; Vergnaud, C.; Marty, A.; Attané, J.-P.; Notin, L.; Vila, L. Jamet, M.; Martin, M.-B.; Seneor, P.; Anane, A.; Deranlot, C.; Fert, A.; Auffret, S.; Ducruet, C.

    2015-02-28

    We report spin transport in CVD graphene-based lateral spin valves using different magnetic contacts. We compared the spin signal amplitude measured on devices where the cobalt layer is directly in contact with the graphene to the one obtained using tunnel contacts. Although a sizeable spin signal (up to ?2 ?) is obtained with direct contacts, the signal is strongly enhanced (?400 ?) by inserting a tunnel barrier. In addition, we studied the resistance-area product (R.A) of a variety of contacts on CVD graphene. In particular, we compared the R.A products of alumina and magnesium oxide tunnel barriers grown by sputtering deposition of aluminum or magnesium and subsequent natural oxidation under pure oxygen atmosphere or by plasma. When using an alumina tunnel barrier on CVD graphene, the R.A product is high and exhibits a large dispersion. This dispersion can be highly reduced by using a magnesium oxide tunnel barrier, as for the R.A value. This study gives insight in the material quest for reproducible and efficient spin injection in CVD graphene.

  9. 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).

  10. A Novel Bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI), GRL-98065, Is Potent Against Mulutiple-PI-Resistant Human Immunodeficiency Virus in Vitro

    SciTech Connect

    Amano,M.; Koh, Y.; Das, D.; Li, J.; Leschenko, S.; Wang, Y.; Boross, P.; Weber, I.; Ghosh, A.; Mitsuya, H.

    2007-01-01

    We designed, synthesized, and identified GRL-98065, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF), and a sulfonamide isostere, which is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC{sub 50}], 0.0002 to 0.0005 {mu}M) with minimal cytotoxicity (50% cytotoxicity, 35.7 {mu}M in CD4{sup +} MT-2 cells). GRL-98065 blocked the infectivity and replication of each of the HIV-1{sub NL4-3} variants exposed to and selected by up to a 5 {mu}M concentration of saquinavir, indinavir, nelfinavir, or ritonavir and a 1 {mu}M concentration of lopinavir or atazanavir (EC{sub 50}, 0.0015 to 0.0075 {mu}M), although it was less active against HIV-1{sub NLV4-3} selected by amprenavir (EC{sub 50}, 0.032 {mu}M). GRL-98065 was also potent against multiple-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents, HIV-1 isolates of various subtypes, and HIV-2 isolates examined. Structural analyses revealed that the close contact of GRL-98065 with the main chain of the protease active-site amino acids (Asp29 and Asp30) is important for its potency and wide-spectrum activity against multiple-PI-resistant HIV-1 variants. The present data demonstrate that the privileged nonpeptide P2 ligand, bis-THF, is critical for the binding of GRL-98065 to the HIV protease substrate binding site and that this scaffold can confer highly potent antiviral activity against a wide spectrum of HIV isolates.

  11. Single mode Lamb wave excitation in thin plates by Hertzian contacts F. Levent Degertekin and Butrus T. KhuriYakub

    E-print Network

    Khuri-Yakub, Butrus T. "Pierre"

    Single mode Lamb wave excitation in thin plates by Hertzian contacts F. Levent Degertekin Lamb wave excitation in thin plates by Hertzian contacts F. Levent Degertekina) and Butrus T. Khuri symmetric (So) and antisymmetric (Ao) Lamb wave modes in thin solid plates. Hertzian contacts are formed

  12. 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.

  13. 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

  14. On the structure of contact binaries. I - The contact discontinuity

    NASA Technical Reports Server (NTRS)

    Shu, F. H.; Lubow, S. H.; Anderson, L.

    1976-01-01

    The problem of the interior structure of contact binaries is reviewed, and a simple resolution of the difficulties which plague the theory is suggested. It is proposed that contact binaries contain a contact discontinuity between the lower surface of the common envelope and the Roche lobe of the cooler star. This discontinuity is maintained against thermal diffusion by fluid flow, and the transition layer is thin to the extent that the dynamical time scale is short in comparison with the thermal time scale. The idealization that the transition layer has infinitesimal thickness allows a simple formulation of the structure equations which are closed by appropriate jump conditions across the discontinuity. The further imposition of the standard boundary conditions suffices to define a unique model for the system once the chemical composition, the masses of the two stars, and the orbital separation are specified.

  15. Vocalizations associated with pectoral fin contact in bottlenose dolphins (Tursiops truncatus).

    PubMed

    Evans-Wilent, J; Dudzinski, K M

    2013-11-01

    Pectoral fin contact in bottlenose dolphins represents one form of tactile communication. Acoustic communication associated with pectoral fin contact is an additional level of communication that may change or enhance the tactile message between two individuals. In this study, we examine vocalization types associated with pectoral fin contact in a group of captive bottlenose dolphins (Tursiops truncatus). From 2006 to 2009, vocalizations potentially associated with 748 pectoral fin contacts were examined: whistles, click trains and overlap of whistles and click trains were documented when associated with fin contact. Dolphins were also documented not vocalizing when exchanging pectoral fin contacts. Call type associated with pectoral fin contact was compared for the proportion of the type of pectoral fin contact, vocalizer sex, initiator and receiver roles, and gender pair. Overall, vocalizations differed significantly by vocalizer role as rubber or rubbee, initiator, and sex. Receivers and rubbees clicked and used overlap vocalizations more frequently, and males produced overlap vocalizations more frequently. These results suggest that whistles may be used to initiate pectoral fin contact or show preference for a particular partner, while click trains may be used to show disinterest in pectoral fin contact or to signal the end of a contact. Examining vocalizations produced in conjunction with tactile contact is a relatively new approach in the study of individual dolphin behavior and may be useful for understanding dolphin social alliances and social preferences for various individuals within a population. PMID:23954831

  16. Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors

    PubMed Central

    Florence, Gordon J.; Fraser, Andrew L.; Gould, Eoin R.; King, Elizabeth F.; Menzies, Stefanie K.; Morris, Joanne C.; Tulloch, Lindsay B.; Smith, Terry K.

    2015-01-01

    A series of novel bis-tetrahydropyran 1,4-triazole analogues based on the acetogenin framework display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness. A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure activity relationship studies. PMID:25145275

  17. Method for manufacturing electrical contacts for a thin-film semiconductor device

    DOEpatents

    Carlson, David E. (Yardley, PA); Dickson, Charles R. (Pennington, NJ); D'Aiello, Robert V. (East Brunswick, NJ)

    1988-11-08

    A method of fabricating spaced-apart back contacts on a thin film of semiconductor material by forming strips of buffer material on top of the semiconductor material in locations corresponding to the desired dividing lines between back contacts, forming a film of metal substantially covering the semiconductor material and buffer strips, and scribing portions of the metal film overlying the buffer strips with a laser without contacting the underlying semiconductor material to separate the metal layer into a plurality of back contacts. The buffer material serves to protect the underlying semiconductor material from being damaged during the laser scribing. Back contacts and multi-cell photovoltaic modules incorporating such back contacts also are disclosed.

  18. 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.

  19. 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.

  20. [Safety of food contact materials].

    PubMed

    Wölfle, D; Pfaff, K

    2010-06-01

    For materials and articles intended to come in contact with food - particularly for substances from plastics (e.g., monomers, additives) - there are comprehensive European regulations based on toxicological evaluations. Other food contact materials, e.g., paper and rubber, are covered by resolutions established by the European Council without additional evaluations, while in Germany substances from these materials are toxicologically evaluated by the Federal Institute for Risk Assessment (BfR) and are included in the "BfR recommendations". Some further areas of food contact materials are not regulated by European or by national regulations (e.g., substances from printing inks). Recently, new European regulations for recycled plastics intended for food contact and for active and intelligent materials and articles have been released. Future challenges are the risk assessment of contaminants and reaction products from the production of food contact substances, which may migrate into the food in only tiny amounts, and of complex mixtures of substances, e.g., of hormone-like substances (endocrine disruptors). PMID:20449553

  1. Method and apparatus for producing co-current fluid contact

    DOEpatents

    Trutna, W.R.

    1997-12-09

    An improved packing system and method are disclosed wherein a packing section includes a liquid distributor and a separator placed above the distributor so that gas rising through the liquid distributor contacts liquid in the distributor, forming a gas-liquid combination which rises in co-current flow to the separator. Liquid is collected in the separator, from which gas rises. 13 figs.

  2. Method and apparatus for producing co-current fluid contact

    DOEpatents

    Trutna, William R. (6 Postwood, Austin, TX 78738-1503)

    1997-01-01

    An improved packing system and method are disclosed wherein a packing section includes a liquid distributor and a separator placed above the distributor so that gas rising through the liquid distributor contacts liquid in the distributor, forming a gas-liquid combination which rises in co-current flow to the separator. Liquid is collected in the separator, from which gas rises.

  3. Contact the Canadian Anti-Fraud Centre (CAFC)

    E-print Network

    Boonstra, Rudy

    Contact the Canadian Anti-Fraud Centre (CAFC) Report the theft to the Canadian Anti- Fraud Center agency in Canada that collects information and criminal intelligence on all forms of mass marketing fraud, including advance fee fraud letters (e.g. West African fraud letters), Internet fraud, identity theft

  4. 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 ...

  5. Heavy metal ions are potent inhibitors of protein folding

    SciTech Connect

    Sharma, Sandeep K.; Goloubinoff, Pierre; Christen, Philipp

    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.

  6. Contact Kinetics in Fractal Macromolecules

    E-print Network

    Dolgushev, Maxim; Blumen, Alexander; Bénichou, Olivier; Voituriez, Raphaël

    2015-01-01

    We consider the kinetics of first contact between two monomers of the same macromolecule. Relying on a fractal description of the macromolecule, we develop an analytical method to compute the Mean First Contact Time (MFCT) for various molecular sizes. In our theoretical description, the non-Markovian feature of monomer motion, arising from the interactions with the other monomers, is captured by accounting for the non-equilibrium conformations of the macromolecule at the very instant of first contact. This analysis reveals a simple scaling relation for the MFCT between two monomers, which involves only their equilibrium distance and the spectral dimension of the macromolecule, independently of its microscopic details. Our theoretical predictions are in excellent agreement with numerical stochastic simulations.

  7. The influence of surface dents and grooves on traction in sliding EHD point contacts

    NASA Technical Reports Server (NTRS)

    Cusano, C.; Wedeven, L. D.

    1982-01-01

    Changes in traction, caused by dents and grooves on a highly polished ball,are investigated as these defects approach and go through sliding elastohydrodynamic point contacts. The contacts are formed with the ball loading against a transparent disk. The ball and thus the topographical features are held stationary at various locations in the vicinity and within the contact while the disk is rotating. These topographical features can cause substantial changes in the traction when compared to traction obtained with smooth surfaces.

  8. Heat transfer at nanoscale contacts investigated with scanning thermal microscopy

    NASA Astrophysics Data System (ADS)

    Assy, Ali; Gomès, Séverine

    2015-07-01

    This article investigates heat transfer at nanoscale contacts through scanning thermal microscopy (SThM) under vacuum conditions. Measurements were performed using two types of resistive SThM probes operating in active mode on germanium and silicon samples. The experiments measure the heat transfer through the nanoscale point contacts formed between the probe apex, platinum-rhodium alloy, or silicon nitride depending on the probe used, and the samples. The thermal resistance at the probe apex-sample interface becomes extremely important as the contact size becomes smaller or comparable to the phonon mean free path within the materials in contact. This resistance is derived from the measurements using a nanoconstriction model. Consistent to what is expected, the interfacial thermal resistance is found to be dependent on the tip and sample. Assuming perfect interfaces, the thermal boundary resistance Rb is determined for the different contacts. Results obtained for Rb range from 10-9 m2 K W-1 up to 14 × 10-9 m2 K W-1 and have the same order of magnitude of values previously published for other materials. The determination of the averaged phonon transmission coefficient t from the data is discussed, and coefficients t for the Si3N4/Ge and Si3N4/Si contacts are estimated based on the diffuse mismatch model (tSi3N4/Ge = 0.5 and tSi3N4/Si = 0.9).

  9. Process for fabricating a wraparound contact solar cell

    SciTech Connect

    Minahan, J.A.; Ralph, E.L.; Dill, H.G.

    1986-09-09

    A process is described for fabricating a wraparound contact solar cell comprising: (a) providing a silicon substrate of a chosen size and shape having first and second opposed major surfaces, (b) forming openings in the substrate and extending through the substrate form the first major surface thereof to the second major surface and spaced apart by a desired lateral dimension of a solar cell, (c) processing the substrate to form a p-n junction therein and between the openings, whereby the vertical walls of the substrate defining the openings are exposed for oxidation, photolithography, and junction-forming steps, (d) utilizing these steps in paragraph (c) above to also form p-region and n-region contacts on the major surfaces of the substrate and extending to a single one of the first and second major surfaces thereof through the openings where they are electrically isolated for bonding to a common solar cell support member, and (e) forming grid lines on one major surface of the substrate for interconnection to one of the p- or n-region contacts for deriving a solar cell output voltage resulting from charge carriers generated at the p-n junction.

  10. 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.

  11. 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.

  12. Permission Forms

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2005-01-01

    The prevailing practice in public schools is to routinely require permission or release forms for field trips and other activities that pose potential for liability. The legal status of such forms varies, but they are generally considered to be neither rock-solid protection nor legally valueless in terms of immunity. The following case and the…

  13. 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

  14. Electrophilic peroxisome proliferator-activated receptor-gamma ligands have potent antifibrotic effects in human lung fibroblasts.

    PubMed

    Ferguson, Heather E; Kulkarni, Ajit; Lehmann, Geniece M; Garcia-Bates, Tatiana M; Thatcher, Thomas H; Huxlin, Krystel R; Phipps, Richard P; Sime, Patricia J

    2009-12-01

    Pulmonary fibrosis is a progressive scarring disease with no effective treatment. Transforming growth factor (TGF)-beta is up-regulated in fibrotic diseases, where it stimulates differentiation of fibroblasts to myofibroblasts and production of excess extracellular matrix. Peroxisome proliferator-activated receptor (PPAR) gamma is a transcription factor that regulates adipogenesis, insulin sensitization, and inflammation. We report here that a novel PPARgamma ligand, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), is a potent inhibitor of TGF-beta-stimulated differentiation of human lung fibroblasts to myofibroblasts, and suppresses up-regulation of alpha-smooth muscle actin, fibronectin, collagen, and the novel myofibroblast marker, calponin. The inhibitory concentration causing a 50% decrease in aSMA for CDDO was 20-fold lower than the endogenous PPARgamma ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15 d-PGJ(2)), and 400-fold lower than the synthetic ligand, rosiglitazone. Pharmacologic and genetic approaches were used to demonstrate that CDDO mediates its activity via a PPARgamma-independent pathway. CDDO and 15 d-PGJ(2) contain an alpha/beta unsaturated ketone, which acts as an electrophilic center that can form covalent bonds with cellular proteins. Prostaglandin A(1) and diphenyl diselenide, both strong electrophiles, also inhibit myofibroblast differentiation, but a structural analog of 15 d-PGJ(2) lacking the electrophilic center is much less potent. CDDO does not alter TGF-beta-induced Smad or AP-1 signaling, but does inhibit acetylation of CREB binding protein/p300, a critical coactivator in the transcriptional regulation of TGF-beta-responsive genes. Overall, these data indicate that certain PPARgamma ligands, and other small molecules with electrophilic centers, are potent inhibitors of critical TGF-beta-mediated profibrogenic activities through pathways independent of PPARgamma. As the inhibitory concentration causing a 50% decrease in aSMA for CDDO is 400-fold lower than that in rosiglitazone, the translational potential of CDDO for treatment of fibrotic diseases is high. PMID:19286977

  15. Spin analysis of concentrated traction contacts

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.

    1983-01-01

    Spin, the result of a mismatch in contact radii on either side of the point of rolling, has a detrimental effect on traction contact performance. It occurs in concentrated contacts having conical or contoured rolling elements, such as those in traction drives or angular contact bearings, and is responsible for an increase in contact heating and power loss. The kinematics of spin producing contact geometries and the subsequent effect on traction and power loss are investigated. The influence of lubricant traction characteristics and contact geometries that minimize spin are also addressed.

  16. Spin analysis of concentrated traction contacts

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.

    1986-01-01

    Spin, the result of a mismatch in contact radii on either side of the point of rolling, has a detrimental effect on traction contact performance. It occurs in concentrated contacts having conical or contoured rolling elements, such as those in traction drives or angular contact bearings, and is responsible for an increase in contact heating and power loss. The kinematics of spin producing contact geometries and the subsequent effect on traction and power loss are investigated. The influence of lubricant traction characteristics and contact geometries that minimize spin are also addressed.

  17. Graded contact manifolds and principal Courant algebroids

    E-print Network

    Grabowski, Janusz

    2011-01-01

    A systematic approach to contact and Jacobi structures on graded supermanifolds is developed. In this framework contact structures are interpreted as symplectic principal $\\R^x$-bundles. Gradings compatible with the $\\R^x$-action lead to the concept of a graded contact manifold, in particular n-linear contact structures. Linear contact structures are proven to be exactly the canonical contact structures on first jets of line bundles. They give rise to linear Kirillov (or Jacobi) brackets and the concept of a principal Lie algebroid, a contact analog of a Lie algebroid. The corresponding cohomology operator is represented not by a vector field (the de Rham derivative) but a first-order differential operator. It is shown that one can view Kirillov or Jacobi brackets as homological Hamiltonians on linear contact manifolds. Contact manifolds of degree 2 are also studied as well as contact analogs of Courant algebroids. Lifting procedures to tangent and cotangent bundles are proposed that leads to constructions of...

  18. Improved Electrical Contact For Dowhhole Drilling Networks

    DOEpatents

    Hall, David R. (Provo, UT); Hall, Jr., H. Tracy (Provo, UT); Pixton, David S. (Lehi, UT); Dahlgren, Scott (Provo, UT); Fox, Joe (Spanish Fork, UT); Sneddon, Cameron (Provo, UT)

    2005-08-16

    An electrical contact system for transmitting information across tool joints while minimizing signal reflections that occur at the tool joints includes a first electrical contact comprising an annular resilient material. An annular conductor is embedded within the annular resilient material and has a surface exposed from the annular resilient material. A second electrical contact is provided that is substantially equal to the first electrical contact. Likewise, the second electrical contact has an annular resilient material and an annular conductor. The two electrical contacts configured to contact one another such that the annular conductors of each come into physical contact. The annular resilient materials of each electrical contact each have dielectric characteristics and dimensions that are adjusted to provide desired impedance to the electrical contacts.

  19. Mutations at Beta N265 in ?-Aminobutyric Acid Type A Receptors Alter Both Binding Affinity and Efficacy of Potent Anesthetics

    PubMed Central

    Stewart, Deirdre S.; Pierce, David W.; Hotta, Mayo; Stern, Alex T.; Forman, Stuart A.

    2014-01-01

    Etomidate and propofol are potent general anesthetics that act via GABAA receptor allosteric co-agonist sites located at transmembrane ?+/?? inter-subunit interfaces. Early experiments in heteromeric receptors identified ?N265 (M2-15?) on ?2 and ?3 subunits as an important determinant of sensitivity to these drugs. Mechanistic analyses suggest that substitution with serine, the ?1 residue at this position, primarily reduces etomidate efficacy, while mutation to methionine eliminates etomidate sensitivity and might prevent drug binding. However, the ?N265 residue has not been photolabeled with analogs of either etomidate or propofol. Furthermore, substituted cysteine modification studies find no propofol protection at this locus, while etomidate protection has not been tested. Thus, evidence of contact between ?N265 and potent anesthetics is lacking and it remains uncertain how mutations alter drug sensitivity. In the current study, we first applied heterologous ?1?2N265C?2L receptor expression in Xenopus oocytes, thiol-specific aqueous probe modification, and voltage-clamp electrophysiology to test whether etomidate inhibits probe reactions at the ?-265 sidechain. Using up to 300 µM etomidate, we found both an absence of etomidate effects on ?1?2N265C?2L receptor activity and no inhibition of thiol modification. To gain further insight into anesthetic insensitive ?N265M mutants, we applied indirect structure-function strategies, exploiting second mutations in ?1?2/3?2L GABAA receptors. Using ?1M236C as a modifiable and anesthetic-protectable site occupancy reporter in ?+/?? interfaces, we found that ?N265M reduced apparent anesthetic affinity for receptors in both resting and GABA-activated states. ?N265M also impaired the transduction of gating effects associated with ?1M236W, a mutation that mimics ?+/?? anesthetic site occupancy. Our results show that ?N265M mutations dramatically reduce the efficacy/transduction of anesthetics bound in ?+/?? sites, and also significantly reduce anesthetic affinity for resting state receptors. These findings are consistent with a role for ?N265 in anesthetic binding within the ?+/?? transmembrane sites. PMID:25347186

  20. 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.

  1. Plasmepsin Inhibitory Activity and Structure-Guided Optimization of a Potent Hydroxyethylamine-Based Antimalarial Hit

    PubMed Central

    2014-01-01

    Antimalarial hit 1SR (TCMDC-134674) identified in a GlaxoSmithKline cell based screening campaign was evaluated for inhibitory activity against the digestive vacuole plasmepsins (Plm I, II, and IV). It was found to be a potent Plm IV inhibitor with no selectivity over Cathepsin D. A cocrystal structure of 1SR bound to Plm II was solved, providing structural insight for the design of more potent and selective analogues. Structure-guided optimization led to the identification of structurally simplified analogues 17 and 18 as low nanomolar inhibitors of both, plasmepsin Plm IV activity and P. falciparum growth in erythrocytes. PMID:24900843

  2. Selective Inhibitors of Methionyl-tRNA Synthetase Have Potent Activity against Trypanosoma brucei Infection in Mice?†

    PubMed Central

    Shibata, Sayaka; Gillespie, J. Robert; Kelley, Angela M.; Napuli, Alberto J.; Zhang, Zhongsheng; Kovzun, Kuzma V.; Pefley, Ranae M.; Lam, Jocelyn; Zucker, Frank H.; Van Voorhis, Wesley C.; Merritt, Ethan A.; Hol, Wim G. J.; Verlinde, Christophe L. M. J.; Fan, Erkang; Buckner, Frederick S.

    2011-01-01

    Human African trypanosomiasis continues to be an important public health threat in extensive regions of sub-Saharan Africa. Treatment options for infected patients are unsatisfactory due to toxicity, difficult administration regimes, and poor efficacy of available drugs. The aminoacyl-tRNA synthetases were selected as attractive drug targets due to their essential roles in protein synthesis and cell survival. Comparative sequence analysis disclosed differences between the trypanosome and mammalian methionyl-tRNA synthetases (MetRSs) that suggested opportunities for selective inhibition using drug-like molecules. Experiments using RNA interference on the single MetRS of Trypanosoma brucei demonstrated that this gene product was essential for normal cell growth. Small molecules (diaryl diamines) similar to those shown to have potent activity on prokaryotic MetRS enzymes were synthesized and observed to have inhibitory activity on the T. brucei MetRS (50% inhibitory concentration, <50 nM) and on bloodstream forms of T. brucei cultures (50% effective concentration, as low as 4 nM). Twenty-one compounds had a close correlation between enzyme binding/inhibition and T. brucei growth inhibition, indicating that they were likely to be acting on the intended target. The compounds had minimal effects on mammalian cell growth at 20 ?M, demonstrating a wide therapeutic index. The most potent compound was tested in the murine model of trypanosomiasis and demonstrated profound parasite suppression and delayed mortality. A homology model of the T. brucei MetRS based on other MetRS structures was used to model binding of the lead diaryl diamine compounds. Future studies will focus on improving the pharmacological properties of the MetRS inhibitors. PMID:21282428

  3. Selective inhibitors of methionyl-tRNA synthetase have potent activity against Trypanosoma brucei Infection in Mice.

    PubMed

    Shibata, Sayaka; Gillespie, J Robert; Kelley, Angela M; Napuli, Alberto J; Zhang, Zhongsheng; Kovzun, Kuzma V; Pefley, Ranae M; Lam, Jocelyn; Zucker, Frank H; Van Voorhis, Wesley C; Merritt, Ethan A; Hol, Wim G J; Verlinde, Christophe L M J; Fan, Erkang; Buckner, Frederick S

    2011-05-01

    Human African trypanosomiasis continues to be an important public health threat in extensive regions of sub-Saharan Africa. Treatment options for infected patients are unsatisfactory due to toxicity, difficult administration regimes, and poor efficacy of available drugs. The aminoacyl-tRNA synthetases were selected as attractive drug targets due to their essential roles in protein synthesis and cell survival. Comparative sequence analysis disclosed differences between the trypanosome and mammalian methionyl-tRNA synthetases (MetRSs) that suggested opportunities for selective inhibition using drug-like molecules. Experiments using RNA interference on the single MetRS of Trypanosoma brucei demonstrated that this gene product was essential for normal cell growth. Small molecules (diaryl diamines) similar to those shown to have potent activity on prokaryotic MetRS enzymes were synthesized and observed to have inhibitory activity on the T. brucei MetRS (50% inhibitory concentration, <50 nM) and on bloodstream forms of T. brucei cultures (50% effective concentration, as low as 4 nM). Twenty-one compounds had a close correlation between enzyme binding/inhibition and T. brucei growth inhibition, indicating that they were likely to be acting on the intended target. The compounds had minimal effects on mammalian cell growth at 20 ?M, demonstrating a wide therapeutic index. The most potent compound was tested in the murine model of trypanosomiasis and demonstrated profound parasite suppression and delayed mortality. A homology model of the T. brucei MetRS based on other MetRS structures was used to model binding of the lead diaryl diamine compounds. Future studies will focus on improving the pharmacological properties of the MetRS inhibitors. PMID:21282428

  4. 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

  5. MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential.

    PubMed

    Chiang, Kun-Chun; Kuo, Sheng-Fong; Chen, Chih-Hung; Ng, Sohching; Lin, Shu-Fu; Yeh, Chun-Nan; Chen, Li-Wei; Takano, Masashi; Chen, Tai C; Juang, Horng-Heng; Kittaka, Atsushi; Lin, Jen-Der; Pang, Jong-Hwei S

    2015-12-01

    The survival rate of anaplastic thyroid cancer (ATC) is still very poor due to its fast growth and high metastatic potential. Currently, no effective treatment is available. The active form of vitamin D3, 1?,25(OH)2D3, has been shown to have a anti-metastatic effect in pre-clinical studies, however induction of hypercalcemia hampered its clinical application. The new class of less-calcemic vitamin D analog, 19-nor-2?-(3-hydroxypropyl)-1?,25-dihydroxyvitamin D3 (MART-10), is much more potent than 1?,25(OH)2D3 to repress cancer growth and metastasis in a variety of cancers. In this study, we demonstrated that both 1?,25(OH)2D3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, 8305C and 8505C, with MART-10 much more potent than 1?,25(OH)2D3. The anti-metastatic effect of 1?,25(OH)2D3 and MART-10 on ATC cells is mediated by reversal of cadherin switch (upregulation of E-cadherin and downregulation of N-cadherin), which led to the attenuation of EMT process, and decrease of F-actin formation. We further showed that the expressions of Slug, the EMT-related transcriptional factor, and MMP-9 were inhibited by 1?,25(OH)2D3 and MART-10 in 8505C cells, but not in 8303C cells. Since metastasis is the important cause of ATC-related death, our results strongly encourage the further in vivo study of MART-10 application against ATC. PMID:26282787

  6. The Russians Are Coming, the Russians are Dead: Myth and Historical Consciousness in Two Contact Narratives.

    ERIC Educational Resources Information Center

    Ruppert, James

    This research paper examines hidden cultural patterns establishing the expression of historical thought in Native Alaskan narratives which describe first contact with Russians. Historical consciousness in oral contact stories is always mythic in form, as well as in content. Native American oral cultures understood new events by "troping," or…

  7. Using Contact Work in Interactions with Adults with Learning Disabilities and Autistic Spectrum Disorders

    ERIC Educational Resources Information Center

    Brooks, Sharon; Paterson, Gail

    2011-01-01

    This article describes a project about using contact work with people with learning disabilities and autistic spectrum disorder. People with learning disabilities and additional autistic spectrum disorder are at risk of becoming socially isolated because of their difficulties in interacting with others. Contact work is a form of Pre-Therapy, which…

  8. Animal Contact Occupational Health & Safety

    E-print Network

    Feig, Andrew

    Animal Contact Occupational Health & Safety Program (AniCon) 2014 Office of Environmental Health & Safety www.oehs.wayne.edu #12;2 AniCon Program Overview A Board Certified Occupational Health Nurse guidelines set forth in the National Research Council's publication Occupational Health and Safety

  9. 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.

  10. 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.

  11. NATHAN I. HAMMER CONTACT INFORMATION

    E-print Network

    Tchumper, Gregory S.

    ) Chemistry 662, Theory of Molecular Structure, Spectroscopy, 29 students (2009, 2012) Chemistry 797NATHAN I. HAMMER CONTACT INFORMATION Department of Chemistry and Biochemistry Voice: (662) 915 38677, USA Internet: http://www.thehammerlab.com EDUCATION Ph. D. Physical Chemistry 2003 University

  12. Barrier/Cu contact resistivity

    SciTech Connect

    Reid, J.S.; Nicolet, M.A.; Angyal, M.S.; Lilienfeld, D.; Shacham-Diamand, Y.; Smith, P.M.

    1995-10-17

    The specific contact resistivity of Cu with ({alpha} + {beta})-Ta, TiN, {alpha}-W, and amorphous-Ta{sub 36}Si{sub 14}N{sub 50} barrier films is measured using a novel four-point-probe approach. Geometrically, the test structures consist of colinear sets of W-plugs to act as current and voltage probes that contact the bottom of a planar Cu/barrier/Cu stack. Underlying Al interconnects link the plugs to the current source and voltmeter. The center-to-center distance of the probes ranges from 3 to 200 {micro}m. Using a relation developed by Vu et al., a contact resistivity of roughly 7 {times} 10{sup {minus}9} {Omega} cm{sup 2} is obtained for all tested barrier/Cu combinations. By reflective-mode small-angle X-ray scattering, the similarity in contact resistivity among the barrier films may be related to interfacial impurities absorbed from the deposition process.

  13. Contact Symmetries and Hamiltonian Thermodynamics

    E-print Network

    A. Bravetti; C. S. Lopez-Monsalvo; F. Nettel

    2015-02-22

    It has been shown that contact geometry is the proper framework underlying classical thermodynamics and that thermodynamic fluctuations are captured by an additional metric structure related to Fisher's Information Matrix. In this work we analyze several unaddressed aspects about the application of contact and metric geometry to thermodynamics. We consider here the Thermodynamic Phase Space and start by investigating the role of gauge transformations and Legendre symmetries for metric contact manifolds and their significance in thermodynamics. Then we present a novel mathematical characterization of first order phase transitions as equilibrium processes on the Thermodynamic Phase Space for which the Legendre symmetry is broken. Moreover, we use contact Hamiltonian dynamics to represent thermodynamic processes in a way that resembles the classical Hamiltonian formulation of conservative mechanics and we show that the relevant Hamiltonian coincides with the irreversible entropy production along thermodynamic processes. Therefore, we use such property to give a geometric definition of thermodynamically admissible fluctuations according to the Second Law of thermodynamics. Finally, we show that the length of a curve describing a thermodynamic process measures its entropy production.

  14. Contact Information University of Houston

    E-print Network

    Glasser, Adrian

    committed to the future success of all of its students. Leonard M. Baynes Dean and Professor of Law 3 #122015 #12;Contact Information University of Houston Law Center 100 Law Center Houston, TX 77204-6060 law.uh.edu Dean Leonard M. Baynes lawdean@uh.edu Office of Admissions 713.743.2280 lawadmissions

  15. John J. Stachowicz Contact Information

    E-print Network

    Stachowicz, Jay

    into ecology, evolution and biogeography. Sinauer Press, Sunderland MA. 495pp. Refereed papers Tomas-Nash F., JJohn J. Stachowicz Contact Information Department of Evolution and Ecology (and Center;Publications Books Sax, D.F., J.J. Stachowicz, and S.D. Gaines (editors). 2005. Species invasions: insights

  16. Assessing Measures of Contact Theory.

    ERIC Educational Resources Information Center

    Brown, William R.; Patchen, Martin

    This paper consolidates findings from two related studies: William Brown's research on the predictive ability of measures of early and non-high school interracial contact/opportunities that appear to affect interracial attitudes and behaviors in high school; and Martin Patchen's investigation in Indianapolis, Indiana high schools analyzing the…

  17. Good Weekend Advertising Contact Information

    E-print Network

    Peters, Richard

    #12;Good Weekend Advertising Contact Information Lauren McIntyre: 9282 1064 lauren Saturday Good Weekend connects Australians with the world around them. Stories that move, provoke and amuse.1 million Australians each week Good Weekend offers advertisers the opportunity to connect with readers

  18. Characterization of potent fusion inhibitors of influenza virus.

    PubMed

    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

  19. 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

  20. A survey of ohmic contacts to III-V compound semiconductors

    SciTech Connect

    Baca, A.G.; Zolper, J.C.; Briggs, R.D.; Ren, F.; Pearton, S.J.

    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.

  1. Occupational allergic contact dermatitis caused by exposure to acrylates during work with dental prostheses.

    PubMed

    Kanerva, L; Estlander, T; Jolanki, R; Tarvainen, K

    1993-05-01

    Between 1974 and 1992, we were consulted by 4 patients (an orthodontist, 2 dental technicians and a dental worker trained in-house) who had developed occupational allergic contact dermatitis from working with dental prostheses. All patients had positive allergic patch test reactions to methyl methacrylate (MMA), the acrylate which is the most widely used in work with prostheses. All but the orthodontist also reacted to dimethacrylates, which are used in cross-linked dental prostheses. The last patient, investigated in 1992, had been exposed mainly to light-cured acrylics, which are similar in composition to dental composite resins. These acrylics, only recently introduced into prosthetic work, contain more potent acrylic sensitizers than MMA. Accordingly, dental personnel working with prostheses may face a higher risk of sensitization than previously. To detect cases of occupational allergic contact dermatitis, we suggest that patients working with dental prostheses should be patch tested with MMA, 2-hydroxyethyl methacrylate, dimethacrylates, epoxy acrylates and urethane acrylates. PMID:8365125

  2. 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

  3. TREAS OPS FORM REQUEST FOR ACCESS

    E-print Network

    Pittendrigh, Barry

    TREAS OPS FORM 8/2009 REQUEST FOR ACCESS BANK DATA Please complete the following and return to Treasury Operations/FREH. Use one request form for each applicant. If you have any questions, please contact the Office of Treasury Operations 49-49453. Date Access Requested: ______________ New Delete

  4. JMU Event Approval Form Outdoor Addendum

    E-print Network

    Arnold, Elizabeth A.

    JMU Event Approval Form Outdoor Addendum Completion of this form does not guarantee space availability or event approval. Event Reference #: Org./Dept. Name: Event Date: Start Time: End Time: Title of Event: Location: Attendance: Requestor/On-site Contact: Email/Phone: Event Description

  5. CSDF Chemical Requisition Form CSDF Only Please

    E-print Network

    is required annually to maintain eligibility. Please contact the EH&S Department's Environmental Health from the CSDF. -- All requestors are responsible for proper transportation, storage, use, and disposal completed form with a different name before attaching to email. Email completed form to: CSDF@Mines

  6. Nonlinear dynamic intertwining of rods with self-contact

    E-print Network

    Sachin Goyal; N. C. Perkins; Christopher L. Lee

    2007-01-06

    Twisted marine cables on the sea floor can form highly contorted three-dimensional loops that resemble tangles. Such tangles or hockles are topologically equivalent to the plectomenes that form in supercoiled DNA molecules. The dynamic evolution of these intertwined loops is studied herein using a computational rod model that explicitly accounts for dynamic self-contact. Numerical solutions are presented for an illustrative example of a long rod subjected to increasing twist at one end. The solutions reveal the dynamic evolution of the rod from an initially straight state, through a buckled state in the approximate form of a helix, through the dynamic collapse of this helix into a near-planar loop with one site of self-contact, and the subsequent intertwining of this loop with multiple sites of self-contact. This evolution is controlled by the dynamic conversion of torsional strain energy to bending strain energy or, alternatively by the dynamic conversion of twist (Tw) to writhe (Wr). KEY WORDS Rod Dynamics, Self-contact, Intertwining, DNA Supercoiling, Cable Hockling

  7. Good form.

    PubMed

    Sorrel, Amy Lynn

    2015-03-01

    New standardized prior authorization forms for health care services and prescription drugs released by the Texas Department of Insurance promise to alleviate administrative busy work and its related costs. PMID:25761070

  8. 78 FR 13897 - Final Revision and Publication of the 2012 Form M-1, Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-01

    ...under ERISA. FOR FURTHER INFORMATION CONTACT: For inquiries regarding the Form M-1 filing requirement, contact Allison Goodman or Suzanne Bach, Office of Health Plan Standards and Compliance Assistance, at (202) 693-8335. This is not a...

  9. Diphenylthiourea, a common rubber chemical, is bioactivated to potent skin sensitizers.

    PubMed

    Samuelsson, Kristin; Bergström, Moa Andresen; Jonsson, Charlotte A; Westman, Gunnar; Karlberg, Ann-Therese

    2011-01-14

    Diphenylthiourea (DPTU) is a known skin sensitizer commonly used as a vulcanization accelerator in the production of synthetic rubber, for example, neoprene. The versatile usage of neoprene is due to the multifaceted properties of the material; for example, it is stretchable, waterproof, and chemical- and abrasion-resistant. The wide application of neoprene has resulted in numerous case reports of dermatitis patients allergic to DPTU. The mechanism by which DPTU works as a contact allergen has not been described; thus, the aim of the present study was to investigate if DPTU is a prohapten that can be activated by skin metabolism. The metabolic activation and covalent binding of (14)C-labeled DPTU to proteins were tested using a skinlike cytochrome P450 (P450) cocktail containing the five most abundant P450s found in human skin (CYP1A1, 1B1, 2B6, 2E1, and 3A5) and human liver microsomes. The incubations were carried out in the presence or absence of the metabolite trapping agents glutathione, methoxylamine, and benzylamine. The metabolism mixtures were analyzed by LC-radiochromatography, LC-MS, and LC-MS/MS. DPTU was mainly metabolically activated to reactive sulfoxides resulting in desulfurated adducts in both enzymatic systems used. Also, phenylisothiocyanate and phenylisocyanate were found to be metabolites of DPTU. The sensitizing capacity of the substrate (DPTU) and three metabolites was tested in the murine local lymph node assay. Two out of three metabolites tested were strong skin sensitizers, whereas DPTU itself, as previously known, was negative using this mouse model. In conclusion, DPTU forms highly reactive metabolites upon bioactivation by enzymes present in the skin. These metabolites are able to induce skin sensitization and are probable causes for DPTU allergy. To increase the possibilities of diagnosing contact allergy to DPTU-containing items, we suggest that suitable metabolites of DPTU should be used for screening testing. PMID:21073181

  10. Implicit Multibody Penalty-BasedDistributed Contact.

    PubMed

    Hongyi Xu; Yili Zhao; Barbic, Jernej

    2014-09-01

    The penalty method is a simple and popular approach to resolving contact in computer graphics and robotics. Penalty-based contact, however, suffers from stability problems due to the highly variable and unpredictable net stiffness, and this is particularly pronounced in simulations with time-varying distributed geometrically complex contact. We employ semi-implicit integration, exact analytical contact gradients, symbolic Gaussian elimination and a SVD solver to simulate stable penalty-based frictional contact with large, time-varying contact areas, involving many rigid objects and articulated rigid objects in complex conforming contact and self-contact. We also derive implicit proportional-derivative control forces for real-time control of articulated structures with loops. We present challenging contact scenarios such as screwing a hexbolt into a hole, bowls stacked in perfectly conforming configurations, and manipulating many objects using actively controlled articulated mechanisms in real time. PMID:26357376

  11. Contact structure for use in catalytic distillation

    DOEpatents

    Jones, Jr., Edward M. (Friendswood, TX)

    1985-01-01

    A method and apparatus for conducting catalytic chemical reactions and fractionation of the reaction mixture, comprising and feeding reactants into a distillation column reactor contracting said reactant in a liquid phase with a fixed bed catalyst in the form of a contact catalyst structure, consisting of closed porous containers containing the catalyst for the reaction and a clip means to hold and support said containers, which are disposed above, i.e., on the distillation trays in the tower. The trays have weir means to provide a liquid level on the trays to substantially cover the containers. In other words, the trays function in their ordinary manner with the addition thereto of the catalyst. The reaction mixture is concurrently fractionated in the column.

  12. Contact structure for use in catalytic distillation

    DOEpatents

    Jones, E.M. Jr.

    1985-08-20

    A method and apparatus are disclosed for conducting catalytic chemical reactions and fractionation of the reaction mixture, comprising and feeding reactants into a distillation column reactor contracting said reactant in a liquid phase with a fixed bed catalyst in the form of a contact catalyst structure, consisting of closed porous containers containing the catalyst for the reaction and a clip means to hold and support said containers, which are disposed above, i.e., on the distillation trays in the tower. The trays have weir means to provide a liquid level on the trays to substantially cover the containers. In other words, the trays function in their ordinary manner with the addition thereto of the catalyst. The reaction mixture is concurrently fractionated in the column. 7 figs.

  13. Contact structure for use in catalytic distillation

    DOEpatents

    Jones, Jr., Edward M. (Friendswood, TX)

    1984-01-01

    A method for conducting catalytic chemical reactions and fractionation of the reaction mixture comprising feeding reactants into a distillation column reactor contracting said reactant in liquid phase with a fixed bed catalyst in the form of a contact catalyst structure consisting of closed porous containers containing the catatlyst for the reaction and a clip means to hold and support said containers, which are disposed above, i.e., on the distillation trays in the tower. The trays have weir means to provide a liquid level on the trays to substantially cover the containers. In other words, the trays function in their ordinary manner with the addition thereto of the catalyst. The reaction mixture is concurrently fractionated in the column.

  14. Contact structure for use in catalytic distillation

    DOEpatents

    Jones, E.M. Jr.

    1984-03-27

    A method is described for conducting catalytic chemical reactions and fractionation of the reaction mixture comprising feeding reactants into a distillation column reactor, contracting said reactant in liquid phase with a fixed bed catalyst in the form of a contact catalyst structure consisting of closed porous containers containing the catalyst for the reaction and a clip means to hold and support said containers, which are disposed above, i.e., on the distillation trays in the tower. The trays have weir means to provide a liquid level on the trays to substantially cover the containers. In other words, the trays function in their ordinary manner with the addition thereto of the catalyst. The reaction mixture is concurrently fractionated in the column. 7 figs.

  15. An improved In-based ohmic contact to n-GaSb

    NASA Astrophysics Data System (ADS)

    Robinson, J. A.; Mohney, S. E.

    2004-09-01

    A Pd/In/Pd/Pt/Au ohmic contact to n-GaSb is presented with a specific contact resistance of 2.4 × 10 -6 ? cm 2. The annealing temperature range over which the specific contact resistance drops to a minimum, while maintaining a suitable surface morphology, is at least twice that of previously reported ohmic contacts to n-GaSb. Materials characterization using cross-sectional transmission electron microscopy confirms that Ga xIn 1- xSb forms at the metal/semiconductor interface, and its formation is believed to be responsible for ohmic behavior.

  16. 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.

  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. Improvement of Electrical Contact Reliability by Conductive Polymer Coated Elastomer Structure in Woven Electronic Textiles

    NASA Astrophysics Data System (ADS)

    Yamashita, Takahiro; Takamatsu, Seiichi; Miyake, Koji; Itoh, Toshihiro

    2012-12-01

    This article presents an improvement in the stability and durability of the electrical contacts employed in flexible devices. A coating of poly(3,4-ethylenedioxythiophene): poly(4-styrenesulfonate) in form of a solid conductive layer on a silicone elastomer structure is employed in creating an electrical circuit embedded into the fabric of a woven electronic textile, where the coating serves as an electrical contact between weft and warp ribbons. When the contact load increases to 1 mN, then, due to the flexibility of the structure, an electric current begins to flow through the circuit. The structure can sextuplicate the life of the electrical contact.

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

    E-print Network

    compounds, known as antimicrobial peptides (AMPs), have broad-spectrum activity, but come with manyCharacterization of a potent antimicrobial lipopeptide via coarse-grained molecular dynamics 2011 Accepted 16 July 2011 Available online 28 July 2011 Keywords: Antimicrobial peptides Lipopeptides

  20. Synthesis of proline analogues as potent and selective cathepsin S inhibitors.

    PubMed

    Kim, Mira; Jeon, Jiyoung; Song, Jiyeon; Suh, Kwee Hyun; Kim, Young Hoon; Min, Kyung Hoon; Lee, Kwang-Ok

    2013-06-01

    Cathepsin S is a potential target of autoimmune disease. A series of proline derived compounds were synthesized and evaluated as cathepsin S inhibitors. We discovered potent cathepsin S inhibitors through structure-activity relationship studies of proline analogues. In particular, compound 19-(S) showed promising in vitro/vivo pharmacological activities and properties as a selective cathepsin S inhibitor. PMID:23639544

  1. Maltodextrin-binding proteins from diverse bacteria and archaea are potent solubility enhancers

    E-print Network

    Maltodextrin-binding proteins from diverse bacteria and archaea are potent solubility enhancers Je published online 29 January 2003 Edited by Takashi Gojobori Abstract Escherichia coli maltose bacteria and archaea. In the present study, we compared the ability of MBPs from six diverse microorganisms

  2. Characterization of typical potent odorants in cola-flavored carbonated beverages by aroma extract dilution analysis.

    PubMed

    Lorjaroenphon, Yaowapa; Cadwallader, Keith R

    2015-01-28

    The aroma-active compounds in typical cola-flavored carbonated beverages were characterized using gas chromatography-olfactometry and gas chromatography-mass spectrometry. The potent odorants in the top three U.S. brands of regular colas were identified by aroma extract dilution analysis (AEDA). Among the numerous odorants identified, eugenol (spicy, clovelike, sweet) and coumarin (sweet, herbaceous) were predominant in all colas. Other predominant odorants in at least one brand included guaiacol (smoky) and linalool (floral, sweet), while 1,8-cineole (minty, eucalyptus-like) was a moderately potent odorant in all colas. Determination of the enantiomeric compositions indicated that (R)-(-)-linalool (34.5%) was a more potent odorant than the (S)-(+)-enantiomer (65.6%) due to its much lower odor detection threshold. In addition, lemon-lime and cooling attributes determined by sensory descriptive analysis had the highest odor intensities among the eight sensory descriptors. The aroma profiles of the three colas were in good agreement with the potent odorants identified by AEDA. PMID:25528884

  3. Discovery of potent, selective, and orally bioavailable inhibitors of interleukin-1 receptor-associate kinase-4.

    PubMed

    Wang, Zhulun; Sun, Daqing; Johnstone, Sheree; Cao, Zhaodan; Gao, Xiong; Jaen, Juan C; Liu, Jingqian; Lively, Sarah; Miao, Shichang; Sudom, Athena; Tomooka, Craig; Walker, Nigel P C; Wright, Matthew; Yan, Xuelei; Ye, Qiuping; Powers, Jay P

    2015-12-01

    In this Letter, we report the continued optimization of the N-acyl-2-aminobenzimidazole series, focusing in particular on the N-alkyl substituent and 5-position of the benzimidazole based on the binding mode and the early SAR. These efforts led to the discovery of 16, a highly potent, selective, and orally bioavailable inhibitor of IRAK-4. PMID:26526214

  4. Design, Synthesis, Molecular Docking, and Antibacterial Evaluation of Some Novel Flouroquinolone Derivatives as Potent Antibacterial Agent

    PubMed Central

    Patel, Mehul M.; Patel, Laxman J.

    2014-01-01

    Objective. Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. Methods. A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl)-2-(substituted)-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT) by Schrodinger's Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. Results. Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. Conclusion. This investigation identified the potent antibacterial agents against certain infections. PMID:25574496

  5. Urolithins, Intestinal Microbial Metabolites of Pomegranate Ellagitannins, Exhibit Potent Antioxidant Activity in Cell-Based Assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many health benefits of pomegranate products have been attributed to the potent antioxidant action of their tannin components, mainly punicalagins and ellagic acid. While moving through the intestines, ellagitannins are metabolized by gut bacteria into urolithins that readily enter systemic circulat...

  6. Structure-activity relationship investigations of a potent and selective benzodiazepine oxytocin antagonist.

    PubMed

    Wyatt, P G; Allen, M J; Chilcott, J; Hickin, G; Miller, N D; Woollard, P M

    2001-05-21

    We have investigated the structure-activity relationships of the 1- and 3-substituents and replacements of the 5-phenyl group of GW405212X 1, a potent selective oxytocin antagonist. The effect of these modifications on oxytocin binding antagonism and on pharmacokinetic parameters is reported. PMID:11392542

  7. ORIGINAL RESEARCH Theoretical approaches to identify the potent scaffold for human

    E-print Network

    Lee, Keun Woo

    statistical parameters including total accuracy: 0.98 and positive recalls: 0.95. Additionally, BM1 showed good predictive power for the test set (total accuracy: 0.87 and positive recall: 0.87). In addition and potent SIRT1 activators, and will benefit medicinal chemists focused on designing novel lead compounds

  8. Draft Genome Sequence of Pedobacter sp. Strain NL19, a Producer of Potent Antibacterial Compounds

    PubMed Central

    2015-01-01

    Here, we report the draft genome sequence of Pedobacter sp. strain NL19. The genome has 5.99 Mbp and a G+C content of 39.0%. NL19 was isolated from sludge from an abandoned uranium mine in the north of Portugal, and it produces potent antibacterials against Gram-positive and Gram-negative bacteria. PMID:25814603

  9. Peptides 26 (2005) 737743 Peptide Tyrosine Arginine, a potent immunomodulatory peptide

    E-print Network

    Richter, Stephen C.

    2005-01-01

    Peptides 26 (2005) 737­743 Peptide Tyrosine Arginine, a potent immunomodulatory peptide isolated sequencing using high-resolution mass spectrometry (Q-TOF MS). The peptide, named peptide Tyrosine Arginine (pYR) shares 77.8% homology with peptide Leucine Arginine (pLR). The effects of the natural amidated

  10. Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate.

    PubMed Central

    Lazarowski, E. R.; Watt, W. C.; Stutts, M. J.; Boucher, R. C.; Harden, T. K.

    1995-01-01

    1. The human P2U-purinoceptor was stably expressed in 1321N1 human astrocytoma cells and the pharmacological selectivity of the expressed receptor was studied by measurement of inositol lipid hydrolysis. 2. High basal levels of inositol phosphates occurred in P2U-purinoceptor-expressing cells. This phenomenon was shown to be due to release of large amounts of ATP from 1321N1 cells, and could be circumvented by adoption of an assay protocol that did not involve medium changes. 3. UTP, ATP and ATP gamma S were full and potent agonists for activation of phospholipase C with EC50 values of 140 nM, 230 nM, and 1.72 microM, respectively. 5BrUTP, 2C1ATP and 8BrATP were also full agonists although less potent than their natural congeners. Little or no effect was observed with the selective P2Y-, P2X-, and P2T-purinoceptor agonists, 2MeSATP, alpha,beta-MeATP, and 2MeSADP, respectively. 4. Diadenosine tetraphosphate, Ap4A, was a surprisingly potent agonist at the expressed P2U-purinoceptor with an EC50 (720 nM) in the range of the most potent P2U-purinoceptor agonists. Ap4A may be a physiologically important activator of P2U-purinoceptors. PMID:8564228

  11. Application of Potent Potential Functions in Eye/Head Movement Bijoy K. Ghosh and Indika Wijayasinghe

    E-print Network

    Ghosh, Bijoy K.

    Application of Potent Potential Functions in Eye/Head Movement Control Bijoy K. Ghosh and Indika Wijayasinghe Abstract-- In this paper we study the human eye movement and the head movement system as a simple mechanical control system. Most of the time, eye movements obey Listing's con- straint, which states

  12. 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 a route employing three palladium-mediated coupling reactions. Experiments performed on cancer cells grown

  13. Total Synthesis of ?12-Prostaglandin J3, a Highly Potent and Selective Antileukemic Agent**

    PubMed Central

    Heretsch, Philipp; ElMarrouni, Abdelatif; Hale, Christopher R. H.; Pulukuri, Kiran K.; Kudva, Avinash K.; Narayan, Vivek; Sandeep Prabhu, K.

    2014-01-01

    A catalytic asymmetric total synthesis of the potent and selective antileukemic ?12-prostaglandin J3 (?12-PGJ3) is described. The convergent synthesis proceeded through intermediates 2 and 3, constructed enantioselectively from readily available starting materials and coupled through an aldol reaction followed by dehydration to afford stereoselectively the cyclopentenone alkylidene structural motif of the molecule. PMID:25098181

  14. 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- ...

  15. The potent pharmacological effects of opiates have been recognized by humans since ancient times. Today,

    E-print Network

    Barr, Gordon A.

    The potent pharmacological effects of opiates have been recognized by humans since ancient times. Today, opiates are still used in medical settings for their analgesic virtue and abused as `street'drugs for their recreational properties. Chronic exposure to opiates leadstodramaticbehavioralandneuralchangesknown

  16. Synthesis and SAR of potent LXR agonists containing an indole pharmacophore

    SciTech Connect

    Washburn, David G.; Hoang, Tram H.; Campobasso, Nino; Smallwood, Angela; Parks, Derek J.; Webb, Christine L.; Frank, Kelly A.; Nord, Melanie; Duraiswami, Chaya; Evans, Christopher; Jaye, Michael; Thompson, Scott K.

    2009-03-27

    A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXR{alpha} will be disclosed.

  17. The structureactivity relationships of mansonone F, a potent anti-MRSA sesquiterpenoid quinone: SAR studies

    E-print Network

    Suh, Young-Ger

    The structure­activity relationships of mansonone F, a potent anti-MRSA sesquiterpenoid quinone on mansonone F, a series of C6 and C9 analogs of mansonone F have been synthesized and their anti-MRSA activities were evaluated. Most of the analogs exhibited good or excellent anti-MRSA activities

  18. Synthesis of the ester side chains of some potently antileukemic harringtonia alkaloids from chiral citrates.

    PubMed

    Ancliff, Rachael A; Russell, Andrew T; Sanderson, Adam J

    2006-08-14

    The selective reduction of one of the three carboxyl groups of two chiral citric acid derivatives to the corresponding aldehydes, under Rosenmund conditions, are reported together with the application of these aldehydes to the syntheses of the ester side chains of some potently antileukemic Cephalotaxus alkaloids e.g. anhydroharringtonine. PMID:17028757

  19. The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2.

    PubMed

    Boyd, H F; Hammond, B; Hickey, D M; Ife, R J; Leach, C A; Lewis, V A; Macphee, C H; Milliner, K J; Pinto, I L; Smith, S A; Stansfield, I G; Theobald, C J; Whittaker, C M

    2001-03-12

    Modification of the pyrimidone 5-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, lipophilic inhibitors of lipoprotein-associated phospholipase A2, has given inhibitors of nanomolar potency and improved physicochemical properties. Compound 23 was identified as a potent, highly water soluble. CNS penetrant inhibitor suitable for intravenous administration. PMID:11266173

  20. Spectroscopic characterization of the chemical composition of the potent sweetener Vartamil

    NASA Astrophysics Data System (ADS)

    Kolosova, T. E.; Prokhodchenko, L. K.; Pilipenko, V. V.; Suboch, V. P.

    2008-03-01

    The chemical composition of the potent sweetener Vartamil was characterized using spectral methods. It was demonstrated that Vartamil is a mixture of saccharose chloro derivatives, the main one of which is 4,1',6'-trichloro-4,1',6'-trideoxygalactosaccharose (Sucralose).