Insecticidal and acetylcholine esterase inhibition activity of Asteraceae plant essential oils and their constituents against adults of the German cockroach (Blattella germanica).

PubMed

Yeom, Hwa-Jeong; Jung, Chan-Sik; Kang, Jaesoon; Kim, Junheon; Lee, Jae-Hyeon; Kim, Dong-Soo; Kim, Hyun-Seok; Park, Pil-Sun; Kang, Kyu-Suk; Park, Il-Kwon

2015-03-04

The fumigant and contact toxicities of 16 Asteraceae plant essential oils and their constituents against adult male and female Blattella germanica were examined. In a fumigant toxicity test, tarragon oil exhibited 100% and 90% fumigant toxicity against adult male German cockroaches at 5 and 2.5 mg/filter paper, respectively. Fumigant toxicities of Artemisia arborescens and santolina oils against adult male German cockroaches were 100% at 20 mg/filter paper, but were reduced to 60% and 22.5% at 10 mg/filter paper, respectively. In contact toxicity tests, tarragon and santolina oils showed potent insecticidal activity against adult male German cockroaches. Components of active oils were analyzed using gas chromatography, gas chromatography-mass spectrometry, or nuclear magnetic resonance spectrometer. Among the identified compounds from active essential oils, estragole demonstrated potent fumigant and contact toxicity against adult German cockroaches. β-Phellandrene exhibited inhibition of male and female German cockroach acetylcholinesterase activity with IC50 values of 0.30 and 0.28 mg/mL, respectively.

Revealing the drug-resistant mechanism for diarylpyrimidine analogue inhibitors of HIV-1 reverse transcriptase.

PubMed

Zhang, Hao; Qin, Fang; Ye, Wei; Li, Zeng; Ma, Songyao; Xia, Yan; Jiang, Yi; Zhu, Jiayi; Li, Yixue; Zhang, Jian; Chen, Hai-Feng

2011-09-01

Diaryltriazine (DATA) and diarylpyrimidine (DAPY) were two category inhibitors with highly potent activity for wild type (wt) and four principal mutant types (L100I, K103N, Y181C and Y188L) of HIV-1 reverse transcriptase (RT). We had revealed the drug-resistant mechanism of DATA analogue inhibitors with molecular dynamics simulation and three-dimensional quantitative structure-activity relationship (3D-QSAR) methods. In this work, we investigated the drug-resistant mechanism of DAPY analogue inhibitors. It was found that DAPY analogue inhibitors form more hydrogen bonds and hydrophobic contacts with wild type and mutants of HIV-1 RT than DATA inhibitors. This could explain that DAPY analogue inhibitors are more potent than DATA for the wild type and mutants of HIV-1 RT. Then, 3D-QSAR models were constructed for these inhibitors of wild type and four principal mutant types HIV-1 RT and evaluated by test set compounds. These combined models can be used to design new chemical entities and make quantitative prediction of the bioactivities for HIV-1 RT inhibitors before resorting to in vitro and in vivo experiment. © 2011 John Wiley & Sons A/S.

Optimization of protease-inhibitor interactions by randomizing adventitious contacts

PubMed Central

Komiyama, Tomoko; VanderLugt, Bryan; Fugère, Martin; Day, Robert; Kaufman, Randal J.; Fuller, Robert S.

2003-01-01

Polypeptide protease inhibitors are often found to inhibit targets with which they did not coevolve, as in the case of high-affinity inhibition of bacterial subtilisin by the leech inhibitor eglin c. Two kinds of contacts exist in such complexes: (i) reactive site loop-active site contacts and (ii) interactions outside of these that form the broader enzyme-inhibitor interface. We hypothesized that the second class of “adventitious” contacts could be optimized to generate significant increases in affinity for a target enzyme or discrimination of an inhibitor for closely related target proteases. We began with a modified eglin c, Arg-42–Arg-45–eglin, in which the reactive site loop had been optimized for subtilisin-related processing proteases of the Kex2/furin family. We randomized 10 potential adventitious contact residues and screened for inhibition of soluble human furin. Substitutions at one of these sites, Y49, were also screened against yeast Kex2 and human PC7. These screens identified not only variants that exhibited increased affinity (up to 20-fold), but also species that exhibited enhanced selectivity, that is, increased discrimination between the target enzymes (up to 41-fold for furin versus PC7 and 20-fold for PC7 versus furin). One variant, Asp-49–Arg-42–Arg-45–eglin, exhibited a Ki of 310 pM for furin and blocked furin-dependent processing of von Willebrand factor in COS-1 cells when added to the culture medium of the cells. The exploitation of adventitious contact sites may provide a versatile technique for developing potent, selective inhibitors for newly discovered proteases and could in principle be applied to optimize numerous protein–protein interactions. PMID:12832612

Infection-induced regulation of natural killer cells by macrophages and collagen at the lymph node subcapsular sinus.

PubMed

Coombes, Janine L; Han, Seong-Ji; van Rooijen, Nico; Raulet, David H; Robey, Ellen A

2012-07-26

Infection leads to heightened activation of natural killer (NK) cells, a process that likely involves direct cell-to-cell contact, but how this occurs in vivo is poorly understood. We have used two-photon laser-scanning microscopy in conjunction with Toxoplasma gondii mouse infection models to address this question. We found that after infection, NK cells accumulated in the subcapsular region of the lymph node, where they formed low-motility contacts with collagen fibers and CD169(+) macrophages. We provide evidence that interactions with collagen regulate NK cell migration, whereas CD169(+) macrophages increase the activation state of NK cells. Interestingly, a subset of CD169(+) macrophages that coexpress the inflammatory monocyte marker Ly6C had the most potent ability to activate NK cells. Our data reveal pathways through which NK cell migration and function are regulated after infection and identify an important accessory cell population for activation of NK cell responses in lymph nodes. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Highly potent silver-organoalkoxysilane antimicrobial porous nanomembrane

NASA Astrophysics Data System (ADS)

Umar, Sirajo; Liu, Yuanfeng; Wu, Yiguang; Li, Guangtao; Ding, Jiabo; Xiong, Runsong; Chen, Jinchun

2013-04-01

We used a simple electrospinning technique to fabricate a highly potent silver-organoalkoxysilane antimicrobial composite from AgNO3-polyvinylpyrrolidone (PVP)/3-aminopropyltrimethoxysilane (APTMS)/tetraethoxysilane (TEOS) solution. Spectroscopic and microscopic analyses of the composite showed that the fibers contain an organoalkoxysilane `skeleton,' 0.18 molecules/nm2 surface amino groups, and highly dispersed and uniformly distributed silver nanoparticles (5 nm in size). Incorporation of organoalkoxysilanes is highly beneficial to the antimicrobial mat as (1) amino groups of APTMS are adhesive and biocidal to microorganisms, (2) polycondensation of APTMS and TEOS increases the membrane's surface area by forming silicon bonds that stabilize fibers and form a composite mat with membranous structure and high porosity, and (3) the organoalkoxysilanes are also instrumental to the synthesis of the very small-sized and highly dispersed silver metal particles in the fiber mat. Antimicrobial property of the composite was evaluated by disk diffusion, minimum inhibition concentration (MIC), kinetic, and extended use assays on bacteria (Escherichia coli, Bacillus anthracis, Staphylococcus aureus, and Brucella suis), a fungus (Aspergillus niger), and the Newcastle disease virus. The membrane shows quick and sustained broad-spectrum antimicrobial activity. Only 0.3 mg of fibers is required to achieve MIC against all the test organisms. Bacteria are inhibited within 30 min of contact, and the fibers can be used repeatedly. The composite is silver efficient and environment friendly, and its membranous structure is suitable for many practical applications as in air filters, antimicrobial linen, coatings, bioadhesives, and biofilms.

Myxococcus xanthus induces actinorhodin overproduction and aerial mycelium formation by Streptomyces coelicolor

PubMed Central

Pérez, Juana; Muñoz‐Dorado, José; Braña, Alfredo F.; Shimkets, Lawrence J.; Sevillano, Laura; Santamaría, Ramón I.

2011-01-01

Summary Interaction of the predatory myxobacterium Myxococcus xanthus with the non‐motile, antibiotic producer Streptomyces coelicolor was examined using a variety of experimental approaches. Myxococcus xanthus cells prey on S. coelicolor, forming streams of ordered cells that lyse the S. coelicolor hyphae in the contact area between the two colonies. The interaction increases actinorhodin production by S. coelicolor up to 20‐fold and triggers aerial mycelium production. Other bacteria are also able to induce these processes in S. coelicolor though to a lesser extent. These studies offer new clues about the expression of genes that remain silent or are expressed at low level in axenic cultures and open the possibility of overproducing compounds of biotechnological interest by using potent inducers synthesized by other bacteria. PMID:21342463

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heaslet, H.; Rosenfeld, R.; Giffin, M.

The crystal structures of wild-type HIV protease (HIV PR) in the absence of substrate or inhibitor in two related crystal forms at 1.4 and 2.15 {angstrom} resolution are reported. In one crystal form HIV PR adopts an 'open' conformation with a 7.7 {angstrom} separation between the tips of the flaps in the homodimer. In the other crystal form the tips of the flaps are 'curled' towards the 80s loop, forming contacts across the local twofold axis. The 2.3 {angstrom} resolution crystal structure of a sixfold mutant of HIV PR in the absence of substrate or inhibitor is also reported. Themore » mutant HIV PR, which evolved in response to treatment with the potent inhibitor TL-3, contains six point mutations relative to the wild-type enzyme (L24I, M46I, F53L, L63P, V77I, V82A). In this structure the flaps also adopt a 'curled' conformation, but are separated and not in contact. Comparison of the apo structures to those with TL-3 bound demonstrates the extent of conformational change induced by inhibitor binding, which includes reorganization of the packing between twofold-related flaps. Further comparison with six other apo HIV PR structures reveals that the 'open' and 'curled' conformations define two distinct families in HIV PR. These conformational states include hinge motion of residues at either end of the flaps, opening and closing the entire {beta}-loop, and translational motion of the flap normal to the dimer twofold axis and relative to the 80s loop. The alternate conformations also entail changes in the {beta}-turn at the tip of the flap. These observations provide insight into the plasticity of the flap domains, the nature of their motions and their critical role in binding substrates and inhibitors.« less

Prevalence of potent skin sensitizers in oxidative hair dye products in Korea.

PubMed

Kim, Hyunji; Kim, Kisok

2016-09-01

The objective of the present study was to elucidate the prevalence of potent skin sensitizers in oxidative hair dye products manufactured by Korean domestic companies. A database on hair dye products made by domestic companies and selling in the Korean market in 2013 was used to obtain information on company name, brand name, quantity of production, and ingredients. The prevalence of substances categorized as potent skin sensitizers was calculated using the hair dye ingredient database, and the pattern of concomitant presence of hair dye ingredients was analyzed using network analysis software. A total of 19 potent skin sensitizers were identified from a database that included 99 hair dye products manufactured by Korean domestic companies. Among 19 potent skin sensitizers, the four most frequent were resorcinol, m-aminophenol, p-phenylenediamine (PPD), and p-aminophenol; these four skin-sensitizing ingredients were found in more than 50% of the products studied. Network analysis showed that resorcinol, m-aminophenol, and PPD existed together in many hair dye products. In 99 products examined, the average product contained 4.4 potent sensitizers, and 82% of the products contained four or more skin sensitizers. The present results demonstrate that oxidative hair dye products made by Korean domestic manufacturers contain various numbers and types of potent skin sensitizers. Furthermore, these results suggest that some hair dye products should be used with caution to prevent adverse effects on the skin, including allergic contact dermatitis.

[Toxic contact dermatitis from poison ivy in a private garden in Germany].

PubMed

Schauder, S; Callauch, R; Hausen, B M

2006-07-01

A couple suffered for 5 years from recurrent eruptions with vesicles and bullae after contact with an unknown "climbing weed" in their private garden in Germany. After this plant was identified as poison ivy and eradicated, their skin problems were solved. This is the first report of poison ivy in this setting. Urushiols in poison ivy are not only strong allergens but also potent irritants. Negative patch tests in the husband suggest that the bullous dermatitis was a toxic reaction.

Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension.

PubMed

Su, Hao; Yan, Ji; Xu, Jian; Fan, Xi-Zhen; Sun, Xian-Lin; Chen, Kang-Yu

2015-08-01

Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho-kinase (ROCK) pathway plays a central role in the pathologic progression of PH and thus the Rho kinase, an essential effector of the ROCK pathway, is considered as a potential therapeutic target to attenuate PH. In the current study, a synthetic pipeline is used to discover new potent Rho inhibitors from various natural products. In the pipeline, the stepwise high-throughput virtual screening, quantitative structure-activity relationship (QSAR)-based rescoring, and kinase assay were integrated. The screening was performed against a structurally diverse, drug-like natural product library, from which six identified compounds were tested to determine their inhibitory potencies agonist Rho by using a standard kinase assay protocol. With this scheme, we successfully identified two potent Rho inhibitors, namely phloretin and baicalein, with activity values of IC50 = 0.22 and 0.95 μM, respectively. Structural examination suggested that complicated networks of non-bonded interactions such as hydrogen bonding, hydrophobic forces, and van der Waals contacts across the complex interfaces of Rho kinase are formed with the screened compounds.

77 FR 24487 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

... INFORMATION CONTACT: Sally Rand, Climate Change Division, Office of Atmospheric Programs (6207J... are very potent greenhouse gases with global warming potentials several thousand times that of carbon....regulations.gov as EPA receives them and without change, unless the comment contains copyrighted material...

[Acaricidal activity of clove bud oil against Dermatophagoides farinae (Acari: Pyroglyphidae)].

PubMed

Li, Jing; Wu, Hai-Qiang; Liu, Zhi-Gang

2009-12-01

Volatile oil from the clove bud was extracted by petroleum ether using Soxhlet Extractor. The acaricidal activity was examined using direct contact and vapour phase toxicity bioassays. In a filter paper contact toxicity bio-assay, at 2.5 h after treatment, clove bud oil at a dose of 12.20 microg/cm2 killed all dust mites. As judged by 24-h LD50 values, potent fumigant action was observed with clove bud oil (12.20 microg/cm2), showing an adequate acaricidal activity against indoor Dermatophagoides farinae.

Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chruszcz, Maksymilian; Pomés, Anna; Glesner, Jill

2012-07-11

House dust mites produce potent allergens, Der p 1 and Der f 1, that cause allergic sensitization and asthma. Der p 1 and Der f 1 are cysteine proteases that elicit IgE responses in 80% of mite-allergic subjects and have proinflammatory properties. Their antigenic structure is unknown. Here, we present crystal structures of natural Der p 1 and Der f 1 in complex with a monoclonal antibody, 4C1, which binds to a unique cross-reactive epitope on both allergens associated with IgE recognition. The 4C1 epitope is formed by almost identical amino acid sequences and contact residues. Mutations of the contactmore » residues abrogate mAb 4C1 binding and reduce IgE antibody binding. These surface-exposed residues are molecular targets that can be exploited for development of recombinant allergen vaccines.« less

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...

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.

Conformational flexibility in the flap domains of ligand-free HIV protease.

PubMed

Heaslet, Holly; Rosenfeld, Robin; Giffin, Mike; Lin, Ying Chuan; Tam, Karen; Torbett, Bruce E; Elder, John H; McRee, Duncan E; Stout, C David

2007-08-01

The crystal structures of wild-type HIV protease (HIV PR) in the absence of substrate or inhibitor in two related crystal forms at 1.4 and 2.15 A resolution are reported. In one crystal form HIV PR adopts an 'open' conformation with a 7.7 A separation between the tips of the flaps in the homodimer. In the other crystal form the tips of the flaps are 'curled' towards the 80s loop, forming contacts across the local twofold axis. The 2.3 A resolution crystal structure of a sixfold mutant of HIV PR in the absence of substrate or inhibitor is also reported. The mutant HIV PR, which evolved in response to treatment with the potent inhibitor TL-3, contains six point mutations relative to the wild-type enzyme (L24I, M46I, F53L, L63P, V77I, V82A). In this structure the flaps also adopt a 'curled' conformation, but are separated and not in contact. Comparison of the apo structures to those with TL-3 bound demonstrates the extent of conformational change induced by inhibitor binding, which includes reorganization of the packing between twofold-related flaps. Further comparison with six other apo HIV PR structures reveals that the 'open' and 'curled' conformations define two distinct families in HIV PR. These conformational states include hinge motion of residues at either end of the flaps, opening and closing the entire beta-loop, and translational motion of the flap normal to the dimer twofold axis and relative to the 80s loop. The alternate conformations also entail changes in the beta-turn at the tip of the flap. These observations provide insight into the plasticity of the flap domains, the nature of their motions and their critical role in binding substrates and inhibitors.

Solar cell contact formation using laser ablation

DOEpatents

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.

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.

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.

Deficient Repair of Particulate Hexavalent chromium-Induced DNA Double Strand Breaks Leads To Neoplastic Transformation

PubMed Central

Xie, Hong; Wise, Sandra S.; Wise, John. P.

2008-01-01

Hexavalent chromium (Cr(VI)) is a potent respiratory toxicant and carcinogen. The most carcinogenic forms of Cr(VI) are the particulate salts such as lead chromate, which deposit and persist in the respiratory tract after inhalation. We demonstrate here that particulate chromate induces DNA double strand breaks in human lung cells with 0.1, 0.5, and 1 ug/cm2 lead chromate inducing 1.5, 2 and 5 relative increases in the percent of DNA in the comet tail, respectively. These lesions are repaired within 24 h and require Mre11 expression for their repair. Particulate chromate also caused Mre11 to co-localize with gamma-H2A.X and ATM. Failure to repair these breaks with Mre11 induced neoplastic transformation including loss of cell contact inhibition and anchorage independent growth. A 5-day exposure to lead chromate induced loss of cell contact inhibition in a concentration-dependent manner with 0, 0.1, 0.5 and 1 ug/cm2 lead chromate inducing 1, 78 and 103 foci in 20 dishes, respectively. These data indicate that Mre11 is critical to repairing particulate Cr(VI)-induced double strand breaks and preventing Cr(VI)-induced neoplastic transformation. PMID:18023605

Acrylate Systemic Contact Dermatitis.

PubMed

Sauder, Maxwell B; Pratt, Melanie D

2015-01-01

Acrylates, the 2012 American Contact Dermatitis Society allergen of the year, are found in a range of products including the absorbent materials within feminine hygiene pads. When fully polymerized, acrylates are nonimmunogenic; however, if not completely cured, the monomers can be potent allergens.A 28-year-old woman is presented, who had her teeth varnished with Isodan (Septodont, Saint-Maur-des-Fossés, France) containing HEMA (2-hydroxyethyl methacrylate) with no initial reaction. Approximately 1 month later, the patient developed a genital dermatitis secondary to her feminine hygiene pads. The initial reaction resolved, but 5 months later, the patient developed a systemic contact dermatitis after receiving a second varnishing.The patient was dramatically patch test positive to many acrylates. This case demonstrates a reaction to likely unpolymerized acrylates within a feminine hygiene pad, as well as broad cross-reactivity or cosensitivity to acrylates, and possibly a systemic contact dermatitis with systemic re-exposure to unpolymerized acrylates.

Method to fabricate micro and nano diamond devices

DOEpatents

Morales, Alfredo M.; Anderson, Richard J.; Yang, Nancy Y. C.; Skinner, Jack L.; Rye, Michael J.

2017-04-11

A method including forming a diamond material on the surface of a substrate; forming a first contact and a separate second contact; and patterning the diamond material to form a nanowire between the first contact and the second contact. An apparatus including a first contact and a separate second contact on a substrate; and a nanowire including a single crystalline or polycrystalline diamond material on the substrate and connected to each of the first contact and the second contact.

Method to fabricate micro and nano diamond devices

DOEpatents

Morales, Alfredo M; Anderson, Richard J; Yang, Nancy Y. C.; Skinner, Jack L; Rye, Michael J

2014-10-07

A method including forming a diamond material on the surface of a substrate; forming a first contact and a separate second contact; and patterning the diamond material to form a nanowire between the first contact and the second contact. An apparatus including a first contact and a separate second contact on a substrate; and a nanowire including a single crystalline or polycrystalline diamond material on the substrate and connected to each of the first contact and the second contact.

Fabricating solar cells with silicon nanoparticles

DOEpatents

Loscutoff, Paul; Molesa, Steve; Kim, Taeseok

2014-09-02

A laser contact process is employed to form contact holes to emitters of a solar cell. Doped silicon nanoparticles are formed over a substrate of the solar cell. The surface of individual or clusters of silicon nanoparticles is coated with a nanoparticle passivation film. Contact holes to emitters of the solar cell are formed by impinging a laser beam on the passivated silicon nanoparticles. For example, the laser contact process may be a laser ablation process. In that case, the emitters may be formed by diffusing dopants from the silicon nanoparticles prior to forming the contact holes to the emitters. As another example, the laser contact process may be a laser melting process whereby portions of the silicon nanoparticles are melted to form the emitters and contact holes to the emitters.

PlyC, a bacteriophage endolysin that is internalized by epithelial cells and retains bacteriolytic activity against intracellular streptococci

USDA-ARS?s Scientific Manuscript database

PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial...

Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yedidi, Ravikiran S.; Muhuhi, Joseck M.; Liu, Zhigang

Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC{sub 50}: 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the {sup 15}N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded activemore » site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC{sub 50}: 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of {sup 15}N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV.« less

Preparation and evaluation of a new releasable PEGylated tumor necrosis factor-α (TNF-α) conjugate for therapeutic application.

PubMed

Dai, ChuanYun; Fu, Ya; Chen, ShaoCheng; Li, Biao; Yao, Bo; Liu, WanHong; Zhu, LiQing; Chen, Nan; Chen, Ji; Zhang, Qiang

2013-01-01

To design a releasable PEGylated TNF-α (rPEG-TNF-α), a cathepsin B-sensitive dipeptide (Val-Cit moiety) was inserted into conventional PEG-modified TNF-α (PEG-TNF-α), facilitating its clinical use for anti-tumor therapy. Comparative pharmacokinetic and pharmacodynamic studies showed that the half-lives of both PEGylated forms of TNF-α were ∼60-fold greater than that of unmodified TNF-α. In addition, the in vitro bioactivity of rPEG-TNF-α was greater than that of PEG-TNF-α with the same degree of PEG modification. Release of TNF-α from rPEG-TNF-α in vitro was dependent on the presence of cathepsin B and was inhibited by a cathepsin B inhibitor. Despite the potent cytotoxicity of unmodified TNF-α against normal cells, its PEGylated forms at higher TNF-α concentrations showed low cytotoxic activity against these cells. In contrast, both forms of PEGylated TNF-α showed potent cytotoxic activity against the B16 and L929 cell lines, with rPEG-TNF-α being 5- and 9-fold more potent, respectively, than PEG-TNF-α. Moreover, rPEG-TNF-α was a more potent in vivo antitumor agent than PEG-TNF-α.

Patch testing with hair cosmetic series in Europe: a critical review and recommendation.

PubMed

Uter, Wolfgang; Bensefa-Colas, Lynda; Frosch, Peter; Giménez-Arnau, Ana; John, Swen M; Lepoittevin, Jean-Pierre; Lidén, Carola; White, Ian R; Duus Johansen, Jeanne

2015-08-01

Many key ingredients of hair cosmetics (in particular, dyes, bleaches, and hair-styling agents) are potent (strong to extreme) contact allergens. Some heterogeneity is apparent from published results concerning the range of allergens for which patch testing is important. The objective of the present review was to collect information on the current practice of using 'hair cosmetic series', and discuss this against the background of evidence concerning consumer/professional exposure and regulatory aspects to finally derive a recommendation for a 'European hair cosmetic series'. The methods involved (i) a survey targeting all members of the COST action 'StanDerm' (TD1206) consortium, (ii) analysis of data in the database of the European Surveillance System on Contact Allergies (ESSCA), and (iii) literature review. Information from 19 European countries was available, partly from national networks, and partly from one or several departments of dermatology or, occasionally, occupational medicine. Apart from some substances being tested only in single departments, a broad overlap regarding 'important' allergens was evident. Some of the substances are no longer permitted for use in cosmetics (Annex II of the Cosmetics Regulation). An up-to-date 'European hair cosmetics series', as recommended in the present article, should (i) include broadly used and/or potent contact allergens, (ii) eliminate substances of only historical concern, and (iii) be continually updated as new evidence emerges. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

... EFTPS Primary Contact Information Change Form AGENCY: Internal Revenue Service (IRS), Treasury. ACTION..., the IRS is soliciting comments concerning the EFTPS Primary Contact Information Change Form. DATES... Constitution Avenue NW., Washington, DC 20224. FOR FURTHER INFORMATION CONTACT: Requests for additional...

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

... EFTPS Primary Contact Information Change Form AGENCY: Internal Revenue Service (IRS), Treasury. ACTION..., the IRS is soliciting comments concerning the EFTPS Primary Contact Information Change Form. DATES... Constitution Avenue, NW., Washington, DC 20224. FOR FURTHER INFORMATION CONTACT: Requests for additional...

Laser processing of solar cells with anti-reflective coating

DOEpatents

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

2016-02-16

Contact holes of solar cells are formed by laser ablation to accommodate 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 thicknesses.

Laser process and corresponding structures for fabrication of solar cells with shunt prevention dielectric

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harley, Gabriel; Smith, David D.; Dennis, Tim

Contact holes of solar cells are formed by laser ablation to accommodate 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 thicknesses.

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

PubMed

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

2008-10-01

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

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.

Dimethyl fumarate contact dermatitis of the foot: an increasingly widespread disease.

PubMed

D'Erme, Angelo Massimiliano; Bassi, Andrea; Lotti, Torello; Gola, Massimo

2012-01-01

Dimethyl fumarate (DMF) has been recognized as an extremely potent irritant and sensitizer found in sachets inside furniture. The first skin manifestations were correlated to contact with sofas, chairs, and other furniture. In these last years, some papers have reported a development of allergic contact dermatitis on the foot caused by DMF present in high concentration in shoes made in China. We report the case of a 37-year-old woman who presented with severe eczema on the foot shortly after having bought a new pair of shoes. The diagnosis was performed by patch tests with DMF in several dilutions, with pieces of internal and external parts of the shoes, and by chemical analysis of the shoes. In the last three years, goods containing DMF increased diffusely despite the augmentation on global preventive measures by Europe. Therefore, new cases of contact dermatitis could be dependent on DMF, and it is of note that this allergen is not included in most series for patch testing. © 2011 The International Society of Dermatology.

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.

High voltage semiconductor devices and methods of making the devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matocha, Kevin; Chatty, Kiran; Banerjee, Sujit

A multi-cell MOSFET device including a MOSFET cell with an integrated Schottky diode is provided. The MOSFET includes n-type source regions formed in p-type well regions which are formed in an n-type drift layer. A p-type body contact region is formed on the periphery of the MOSFET. The source metallization of the device forms a Schottky contact with an n-type semiconductor region adjacent the p-type body contact region of the device. Vias can be formed through a dielectric material covering the source ohmic contacts and/or Schottky region of the device and the source metallization can be formed in the vias.more » The n-type semiconductor region forming the Schottky contact and/or the n-type source regions can be a single continuous region or a plurality of discontinuous regions alternating with discontinuous p-type body contact regions. The device can be a SiC device. Methods of making the device are also provided.« less

High voltage semiconductor devices and methods of making the devices

DOEpatents

Matocha, Kevin; Chatty, Kiran; Banerjee, Sujit

2017-02-28

A multi-cell MOSFET device including a MOSFET cell with an integrated Schottky diode is provided. The MOSFET includes n-type source regions formed in p-type well regions which are formed in an n-type drift layer. A p-type body contact region is formed on the periphery of the MOSFET. The source metallization of the device forms a Schottky contact with an n-type semiconductor region adjacent the p-type body contact region of the device. Vias can be formed through a dielectric material covering the source ohmic contacts and/or Schottky region of the device and the source metallization can be formed in the vias. The n-type semiconductor region forming the Schottky contact and/or the n-type source regions can be a single continuous region or a plurality of discontinuous regions alternating with discontinuous p-type body contact regions. The device can be a SiC device. Methods of making the device are also provided.

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

... Request for a New Information Collection (Accredited Laboratory Contact Update Form) AGENCY: Food Safety... compilation of updated contact information for Accredited Laboratories. DATES: Comments on this notice must be... FURTHER INFORMATION CONTACT: Contact John O'Connell, Paperwork Reduction Act Coordinator, Food Safety and...

GRID and docking analyses reveal a molecular basis for flavonoid inhibition of Src family kinase activity.

PubMed

Wright, Bernice; Watson, Kimberly A; McGuffin, Liam J; Lovegrove, Julie A; Gibbins, Jonathan M

2015-11-01

Flavonoids reduce cardiovascular disease risk through anti-inflammatory, anti-coagulant and anti-platelet actions. One key flavonoid inhibitory mechanism is blocking kinase activity that drives these processes. Flavonoids attenuate activities of kinases including phosphoinositide-3-kinase, Fyn, Lyn, Src, Syk, PKC, PIM1/2, ERK, JNK and PKA. X-ray crystallographic analyses of kinase-flavonoid complexes show that flavonoid ring systems and their hydroxyl substitutions are important structural features for their binding to kinases. A clearer understanding of structural interactions of flavonoids with kinases is necessary to allow construction of more potent and selective counterparts. We examined flavonoid (quercetin, apigenin and catechin) interactions with Src family kinases (Lyn, Fyn and Hck) applying the Sybyl docking algorithm and GRID. A homology model (Lyn) was used in our analyses to demonstrate that high-quality predicted kinase structures are suitable for flavonoid computational studies. Our docking results revealed potential hydrogen bond contacts between flavonoid hydroxyls and kinase catalytic site residues. Identification of plausible contacts indicated that quercetin formed the most energetically stable interactions, apigenin lacked hydroxyl groups necessary for important contacts and the non-planar structure of catechin could not support predicted hydrogen bonding patterns. GRID analysis using a hydroxyl functional group supported docking results. Based on these findings, we predicted that quercetin would inhibit activities of Src family kinases with greater potency than apigenin and catechin. We validated this prediction using in vitro kinase assays. We conclude that our study can be used as a basis to construct virtual flavonoid interaction libraries to guide drug discovery using these compounds as molecular templates. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

Drug Abuse: The Crack Cocaine Epidemic Health Consequences and Treatment.

DTIC Science & Technology

1991-01-01

addicts . Buackground Once considered to be nonaddictive, recent studies show that cocaine is one of the most potent drugs of abuse. Cocaine is a...responsibility for addiction prevention and treatment programs. The agencies we contacted include NIDA, the Alcohol, Drug Abuse, and Mental Health Administration...heroin addicts for Treating Crack are being used to treat many crack addicts . Meanwhile, drug treatment Addicts researchers are experimenting with new

Combined therapy in vulvar lichen sclerosus: does topical tretinoin improve the efficacy of mometasone furoate?

PubMed

Borghi, Alessandro; Minghetti, Sara; Toni, Giulia; Virgili, Annarosa; Corazza, Monica

2017-09-01

Abstrract Purpose: To assess efficacy and safety profile of combining a potent corticosteroid with a retinoid in the treatment of vulvar lichen sclerosus (VLS). We retrospectively compared 21 VLS patients treated with tretinoin (T) in short-contact therapy and mometasone furoate (MMF) (group A) and 20 treated with cold cream (CC) and MMF (group B) for 5 consecutive days/week for 12 weeks. The efficacy parameters were the response rate, the percentage of patients achieving an improvement from baseline of ≥75% in subjective and objective scores and the mean reduction in subjective and objective scores. Thirteen patients (75.2%) were considered as responders in group A and 15 (78.9%) in group B; 50% and 61.1% of patients in group A and 100% and 63.1% in group B achieved an improvement of at least 75% in subjective and objective scores, respectively. The scheme combining MMF and CC was better tolerated than the combination of MMF and T. The combination with a topical retinoid did not enhance the effectiveness of a potent corticosteroid in the treatment of VLS. Either the scarce efficacy of the short-contact therapy regimen or a less favorable safety profile of such combination may account for these findings.

Reliability of semiautomated computational methods for estimating tibiofemoral contact stress in the Multicenter Osteoarthritis Study.

PubMed

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.

New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents.

PubMed

Nakajima, Tadashi; Matsugi, Takeshi; Goto, Wakana; Kageyama, Masaaki; Mori, Nobuaki; Matsumura, Yasushi; Hara, Hideaki

2003-12-01

To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive effects with minimal side effects, we evaluated the agonistic activities of newly synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor both in vitro and in vivo. The iris constrictions induced by the derivatives and their effects on melanin content were examined using cat isolated iris sphincters and cultured B16 melanoma cells, respectively. The effects of derivative ester forms on miosis and intraocular pressure (IOP) were evaluated in cats and cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost (100 microM) significantly increased the melanin content of cultured B16 melanoma cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not. Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005% latanoprost (for at least 8 h). These findings indicate that 15,15-difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may be worthy of further evaluation as an ocular-hypotensive agent.

Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment.

PubMed

Friis, Ulrik F; Menné, Torkil; Schwensen, Jakob F; Flyvholm, Mari-Ann; Bonde, Jens P E; Johansen, Jeanne D

2014-12-01

Irritant contact dermatitis (ICD) is a common diagnosis in patients with occupational contact dermatitis (OCD). Studies are lacking on the usefulness of material safety data sheets (MSDSs) in making the diagnosis of ICD. To characterize irritant exposures leading to the diagnosis of occupational ICD (OICD), and to evaluate the occurrence of concomitant exposures to contact allergens. We included 316 patients with suspected occupational hand dermatitis, referred to the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark during January 2010-August 2011, in a programme consisting of a clinical examination, exposure assessment, and extensive patch/prick testing. OCD was diagnosed in 228 patients. Of these patients, 118 were diagnosed with OICD. The main irritant exposures identified were wet work (n = 64), gloves (n = 45), mechanical traumas (n = 19), and oils (n = 15). Exposure to specific irritant chemicals was found in 9 patients, and was identified from MSDSs/ingredients labelling in 8 of these patients. Review of MSDSs and ingredients labelling showed that 41 patients were exposed to 41 moderate to potent contact allergens, and 18 patients were exposed to 25 weak workplace contact allergens. In the present study, the systematic exposure assessment did not reveal any new irritants. MSDSs have a limited role in the investigation of ICD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.

PubMed

Möller, L

1994-10-01

During incomplete combustion of organic matter, nitro-polycyclic aromatic hydrocarbons (nitro-PAHs), are formed in a reaction that is catalyzed by a low pH. 2-Nitrofluorene (NF), a marker for nitro-PAHs, is metabolized in vivo by two different routes. After inhalation, potent mutagenic metabolites, hydroxylated nitrofluorenes (OH-NFs), are formed. The metabolites are distributed by systemic circulation. After oral administration, NF is reduced to the corresponding amine, a reaction mediated by the intestinal microflora. This metabolite is acetylated to 2-acetylaminofluorene (AAF), a potent carcinogen. Further ring-hydroxylation of AAF leads to detoxification and excretion. Induction of cytochrome P450s affects the metabolism, and more OH-NFs are formed. As a consequence, more mutagenic metabolites are found in the circulation. OH-NFs are excreted in the bile as, in terms of mutagenicity, totally harmless glucuronide conjugates. When these conjugates are excreted via the bile, intestinal beta-glucuronidase can liberate direct-acting mutagens in the intestine. Thus, inhalation of NF can lead to formation of potent mutagens in the intestine. NF is a direct-acting mutagen in bacterial assays and an initiator and promoter of the carcinogenic process, and gives rise to DNA adduct formation in laboratory animals.

Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

PubMed

Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

2012-01-01

Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

[Levitra (oral dispersible tablet)--an innovative drug for the treatment of patients with erectile dysfunction].

PubMed

Korneev, I A

2013-01-01

The arsenal of professionals providing assistance to men with erectile dysfunction includes a new, mouth dissolving dosage form of the vardenafil--levitra ODT. This form is effective, safe, and has a higher bioavailability as compared to vardenafil in the form of coated tablets. POTENT I and POTENT II studies revealed that levitra ODT equally successfully corrects erectile dysfunction in men younger and older than 65 years regardless of concomitant diseases and metabolic disorders: hypertension, diabetes, dyslipidemia. In addition, it was found that this drug helped to successfully carry out sexual intercourse in the first 15 minutes after dosing in 62.5% of patients. This allows to widely recommend levitra ODT for the treatment of erectile dysfunction in young men and older men.

Direct contact as a moderator of extended contact effects: cross-sectional and longitudinal impact on outgroup attitudes, behavioral intentions, and attitude certainty.

PubMed

Christ, Oliver; Hewstone, Miles; Tausch, Nicole; Wagner, Ulrich; Voci, Alberto; Hughes, Joanne; Cairns, Ed

2010-12-01

Cross-group friendships (the most effective form of direct contact) and extended contact (i.e., knowing ingroup members who have outgroup friends) constitute two of the most important means of improving outgroup attitudes. Using cross-sectional and longitudinal samples from different intergroup contexts, this research demonstrates that extended contact is most effective when individuals live in segregated neighborhoods having only few, or no, direct friendships with outgroup members. Moreover, by including measures of attitudes and behavioral intentions the authors showed the broader impact of these forms of contact, and, by assessing attitude certainty as one dimension of attitude strength, they tested whether extended contact can lead not only to more positive but also to stronger outgroup orientations. Cross-sectional data showed that direct contact was more strongly related to attitude certainty than was extended contact, but longitudinal data showed both forms of contact affected attitude certainty in the long run.

Occupational Criteria for Chemical Agent VX

DTIC Science & Technology

1988-09-01

nervous system in mild exposures may include tension, anxiety, jitteriness, restlessness, m insomnia , or excessive dreaming. Higher exposures may cause ...toxic substance which can cause death at very low doses. It is both an inhalation and a skin contact hazard. Despite its low vapor m pressure, a...hen and cat can a syndrome similar to that in humans be induced (Gordon et al. 1983, Johnson 1975a). Abou-Donia (1981) states that potent cholin

Method of manufacturing a hybrid emitter all back contact solar cell

DOEpatents

Loscutoff, Paul; Rim, Seung

2017-02-07

A method of manufacturing an all back contact solar cell which has a hybrid emitter design. The solar cell has a thin dielectric layer formed on a backside surface of a single crystalline silicon substrate. One emitter of the solar cell is made of doped polycrystalline silicon that is formed on the thin dielectric layer. A second emitter of the solar cell is formed in the single crystalline silicon substrate and is made of doped single crystalline silicon. The method further includes forming contact holes that allow metal contacts to connect to corresponding emitters.

Influence of Asymmetric Contact Form on Contact Resistance and Schottky Barrier, and Corresponding Applications of Diode.

PubMed

Zhao, Yudan; Xiao, Xiaoyang; Huo, Yujia; Wang, Yingcheng; Zhang, Tianfu; Jiang, Kaili; Wang, Jiaping; Fan, Shoushan; Li, Qunqing

2017-06-07

We have fabricated carbon nanotube and MoS 2 field-effect transistors with asymmetric contact forms of source-drain electrodes, from which we found the current directionality of the devices and different contact resistances under the two current directions. By designing various structures, we can conclude that the asymmetric electrical performance was caused by the difference in the effective Schottky barrier height (Φ SB ) caused by the different contact forms. A detailed temperature-dependent study was used to extract and compare the Φ SB for both contact forms of CNT and MoS 2 devices; we found that the Φ SB for the metal-on-semiconductor form was much lower than that of the semiconductor-on-metal form and is suitable for all p-type, n-type, or ambipolar semiconductors. This conclusion is meaningful with respect to the design and application of nanomaterial electronic devices. Additionally, using the difference in barrier height caused by the contact forms, we have also proposed and fabricated Schottky barrier diodes with a current ratio up to 10 4 ; rectifying circuits consisting of these diodes were able to work in a wide frequency range. This design avoided the use of complex chemical doping or heterojunction methods to achieve fundamental diodes that are relatively simple and use only a single material; these may be suitable for future application in nanoelectronic radio frequency or integrated circuits.

A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells.

PubMed

Ito, Akihiko; Morita, Nobuyoshi; Miura, Daisaku; Koma, Yu-Ichiro; Kataoka, Tatsuki R; Yamasaki, Hiroshi; Kitamura, Yukihiko; Kita, Yasuyuki; Nojima, Hiroshi

2004-10-01

We reported previously that the abnormally augmented expression of connexin 26 (Cx26) is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells, and that the exogenous expression of a dominant negative form of Cx26 inhibits the spontaneous metastasis of BL6. Here we show that daily intraperitoneal (i.p.) injections of oleamide, a sleep-inducing lipid hormone, weakly inhibited the spontaneous metastasis of BL6 cells. To obtain a more effective reagent, 19 oleamide derivatives were chemically synthesized and tested for their ability to inhibit the gap junction-mediated intercellular communications (GJIC) that are formed between HeLa cells by the ectopic expression of Cx26 or Cx43. One of these, denoted metastasis inhibitor-18 (MI-18), inhibited the GJIC formed by Cx26 as well as oleamide but unlike oleamide, which is a non-selective inhibitor of connexin, it did not inhibit the GJIC formed by Cx43. Daily i.p. injections of MI-18 potently blocked the spontaneous metastasis of BL6 cells down to 15% of that in the untreated control mice. MI-18 was safe because even after >7 weeks of daily injections, the survival rate of the mice was 93%. We propose that MI-18 may serve as a novel and clinically important prototype of a potent inhibitor of spontaneous metastasis.

Hybrid emitter all back contact solar cell

DOEpatents

Loscutoff, Paul; Rim, Seung

2016-04-12

An all back contact solar cell has a hybrid emitter design. The solar cell has a thin dielectric layer formed on a backside surface of a single crystalline silicon substrate. One emitter of the solar cell is made of doped polycrystalline silicon that is formed on the thin dielectric layer. The other emitter of the solar cell is formed in the single crystalline silicon substrate and is made of doped single crystalline silicon. The solar cell includes contact holes that allow metal contacts to connect to corresponding emitters.

Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

PubMed Central

Schanz, Merle; Reynell, Lucy; Günthard, Huldrych F.; Rusert, Peter; Trkola, Alexandra

2012-01-01

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo. PMID:22496655

Limonene hydroperoxide analogues show specific patch test reactions.

PubMed

Christensson, Johanna Bråred; Hellsén, Staffan; Börje, Anna; Karlberg, Ann-Therese

2014-05-01

The fragrance terpene R-limonene is a very weak sensitizer, but forms allergenic oxidation products upon contact with air. The primary oxidation products of oxidized limonene, the hydroperoxides, have an important impact on the sensitizing potency of the oxidation mixture. One analogue, limonene-1-hydroperoxide, was experimentally shown to be a significantly more potent sensitizer than limonene-2-hydroperoxide in the local lymph node assay with non-pooled lymph nodes. To investigate the pattern of reactivity among consecutive dermatitis patients to two structurally closely related limonene hydroperoxides, limonene-1-hydroperoxide and limonene-2-hydroperoxide. Limonene-1-hydroperoxide, limonene-2-hydroperoxide, at 0.5% in petrolatum, and oxidized limonene 3.0% pet. were tested in 763 consecutive dermatitis patients. Of the tested materials, limonene-1-hydroperoxide gave most reactions, with 2.4% of the patients showing positive patch test reactions. Limonene-2-hydroperoxide and oxidized R-limonene gave 1.7% and 1.2% positive patch test reactions, respectively. Concomitant positive patch test reactions to other fragrance markers in the baseline series were frequently noted. The results are in accordance with the experimental studies, as limonene-1-hydroperoxide gave more positive patch test reactions in the tested patients than limonene-2-hydroperoxide. Furthermore, the results support the specificity of the allergenic activity of the limonene hydroperoxide analogues and the importance of oxidized limonene as a cause of contact allergy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fish allergy in childhood.

PubMed

Pascual, Cristina Y; Reche, Marta; Fiandor, Ana; Valbuena, Teresa; Cuevas, Teresa; Esteban, Manuel Martin

2008-11-01

Fish and its derived products play an important role in human nutrition, but they may also be a potent food allergen. Fish can be an ingested, contact, and inhalant allergen. Gad c I, a Parvalbumin, the major allergen in codfish, is considered as fish and amphibian pan-allergen. Prevalence of fish allergy appears to depend on the amount of fish eaten in the local diet. In Europe, the highest consumption occurs in Scandinavian countries, Spain and Portugal. In Spain, fish is the third most frequent allergen in children under 2 yr of age after egg and cow's milk. An adverse reaction to fish may be of non-allergic origin, due to food contamination or newly formed toxic products, but the most frequent type of adverse reactions to fish are immunologic-mediated reactions (allergic reactions). Such allergic reactions may be both IgE-mediated and non-IgE-mediated. Most cases are IgE-mediated, due to ingestion or contact with fish or as a result of inhalation of cooking vapors. Some children develop non-IgE-mediated type allergies such as food protein induced enterocolitis syndrome. The clinical symptoms related to IgE-mediated fish allergy are most frequently acute urticaria and angioedema as well as mild oral symptoms, worsening of atopic dermatitis, respiratory symptoms such as rhinitis or asthma, and gastrointestinal symptoms such as nausea and vomiting. Anaphylaxis may also occur. Among all the species studied, those from the Tunidae and Xiphiidae families appear to be the least allergenic.

75 FR 70335 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... Mail Contacts, and Form G-40, on Electronic Mail Contacts November 12, 2010. Pursuant to Section 19(b... agency''); (iv) amendments to Rule G-40, on electronic mail contacts, by municipal advisors; and (v) amendments to Form G-40, on electronic mail contacts. The proposed rule change is effective immediately upon...

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.

Immunological and Toxinological Responses to Jellyfish Stings

PubMed Central

Tibballs, James; Yanagihara, Angel A.; Turner, Helen C.; Winkel, Ken

2013-01-01

Just over a century ago, animal responses to injections of jellyfish extracts unveiled the phenomenon of anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact, jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by prominent species of jellyfish including Physalia sp. (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically, both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier therapy. The current challenge for immunotoxinologists is to deconstruct the actions of venom components to target therapeutic modalities for sting treatment. PMID:21824077

Identification of the HIV-1 Vif and Human APOBEC3G Protein Interface.

PubMed

Letko, Michael; Booiman, Thijs; Kootstra, Neeltje; Simon, Viviana; Ooms, Marcel

2015-12-01

Human cells express natural antiviral proteins, such as APOBEC3G (A3G), that potently restrict HIV replication. As a counter-defense, HIV encodes the accessory protein Vif, which binds A3G and mediates its proteasomal degradation. Our structural knowledge on how Vif and A3G interact is limited, because a co-structure is not available. We identified specific points of contact between Vif and A3G by using functional assays with full-length A3G, patient-derived Vif variants, and HIV forced evolution. These anchor points were used to model and validate the Vif-A3G interface. The resultant co-structure model shows that the negatively charged β4-α4 A3G loop, which contains primate-specific variation, is the core Vif binding site and forms extensive interactions with a positively charged pocket in HIV Vif. Our data present a functional map of this viral-host interface and open avenues for targeted approaches to block HIV replication by obstructing the Vif-A3G interaction. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Selectivity Mechanism of ATP-Competitive Inhibitors for PKB and PKA.

PubMed

Wu, Ke; Pang, Jingzhi; Song, Dong; Zhu, Ying; Wu, Congwen; Shao, Tianqu; Chen, Haifeng

2015-07-01

Protein kinase B (PKB) acts as a central node on the PI3K kinase pathway. Constitutive activation and overexpression of PKB have been identified to involve in various cancers. However, protein kinase A (PKA) sharing high homology with PKB is essential for metabolic regulation. Therefore, specific targeting on PKB is crucial strategy in drug design and development for antitumor. Here, we had revealed the selectivity mechanism for PKB inhibitors with molecular dynamics simulation and 3D-QSAR methods. Selective inhibitors of PKB could form more hydrogen bonds and hydrophobic contacts with PKB than those with PKA. This could explain that selective inhibitor M128 is more potent to PKB than to PKA. Then, 3D-QSAR models were constructed for these selective inhibitors and evaluated by test set compounds. 3D-QSAR model comparison of PKB inhibitors and PKA inhibitors reveals possible methods to improve the selectivity of inhibitors. These models can be used to design new chemical entities and make quantitative prediction of the specific selective inhibitors before resorting to in vitro and in vivo experiment. © 2014 John Wiley & Sons A/S.

5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms.

PubMed

Orban, Oliver C F; Korn, Ricarda S; Benítez, Diego; Medeiros, Andrea; Preu, Lutz; Loaëc, Nadège; Meijer, Laurent; Koch, Oliver; Comini, Marcelo A; Kunick, Conrad

2016-08-15

Trypanothione synthetase is an essential enzyme for kinetoplastid parasites which cause highly disabling and fatal diseases in humans and animals. Inspired by the observation that N(5)-substituted paullones inhibit the trypanothione synthetase from the related parasite Leishmania infantum, we designed and synthesized a series of new derivatives. Although none of the new compounds displayed strong inhibition of Trypanosoma brucei trypanothione synthetase, several of them caused a remarkable growth inhibition of cultivated Trypanosoma brucei bloodstream forms. The most potent congener 3a showed antitrypanosomal activity in double digit nanomolar concentrations and a selectivity index of three orders of magnitude versus murine macrophage cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

Une formulation variationnelle du problème de contact avec frottement de Coulomb

NASA Astrophysics Data System (ADS)

Le van, Anh; Nguyen, Tai H. T.

2008-07-01

A variational relationship is proposed as the weak form of the large deformation contact problem with Coulomb friction. It is a mixed relationship involving both the displacements and the multipliers; the weighting functions are the virtual displacements and the virtual multipliers. It is shown that the proposed weak form is equivalent to the strong form of the initial/boundary value contact problem and the multipliers are equal to the contact tractions. To cite this article: A. Le van, T.H.T. Nguyen, C. R. Mecanique 336 (2008).

In-vitro and in-vivo anti-Trichophyton activity of essential oils by vapour contact.

PubMed

Inouye, S; Uchida, K; Yamaguchi, H

2001-05-01

The minimum inhibitory doses (MIDs) of essential oils by vapour contact to inhibit the growth of Trichophyton mentagrophytes and Trichophyton rubrum on agar medium were determined using airtight boxes. Among seven essential oils examined, cinnamon bark oil showed the least MID, followed by lemongrass, thyme and perilla oils. Lavender and tea tree oils showed moderate MID, and citron oil showed the highest MID, being 320 times higher than that of cinnamon bark oil. The MID values were less than the minimum inhibitory concentration (MIC) values determined by agar dilution assay. Furthermore, the minimum agar concentration (MAC) of essential oils absorbed from vapour was determined at the time of MID determination as the second antifungal measure. The MAC value by vapour contact was 1.4 to 4.7 times less than the MAC remaining in the agar at the time of MIC determination by agar dilution assay. Using selected essential oils, the anti-Trichophyton activity by vapour contact was examined in more detail. Lemongrass, thyme and perilla oils killed the conidia, inhibited germination and hyphal elongation at 1-4 micrograms ml-1 air, whereas lavender oil was effective at 40-160 micrograms ml-1 air. The in-vivo efficacy of thyme and perilla oils by vapour contact was shown against an experimental tinea pedis in guinea pigs infected with T. mentagrophytes. These results indicated potent anti-Trichophyton action of essential oils by vapour contact.

Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

PubMed

Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

2018-06-11

Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers

PubMed Central

Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

2012-01-01

Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid–ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids. PMID:25755991

The wide spectrum high biocidal potency of Bioxy formulation when dissolved in water at different concentrations

PubMed Central

Dagher, Fadi

2017-01-01

Traditional surface disinfectants that have long been applied in medicine, animal husbandry, manufacturing and institutions are inconvenient at best and dangerous at worst. Moreover, some of these substances have adverse environmental impacts: for example, quaternary ammonium compounds (“quats”) are reproductive toxicants in both fish and mammals. Halogens are corrosive both to metals and living tissues, are highly reactive, can be readily neutralized by metals, and react with organic matter to form toxic, persistent by-products such as dioxins and furans. Aldehydes may be carcinogenic to both human and animals upon repeated exposures, are corrosive, cross-link living tissues and many synthetic materials, and may lose efficacy when pathogens enzymatically adapt to them. Alcohols are flammable and volatile and can be enzymatically degraded by certain bacterial pathogens. Quats are highly irritating to mucous membranes and over time can induce pathogen resistance, especially if they are not alternated with functionally different disinfectants. In contrast, peracetic acid (PAA), a potent oxidizer, liberates hydrogen peroxide (itself a disinfectant), biodegrades to carbon dioxide, water and oxygen, and is at least as efficacious as contact biocides e.g., halogens and aldehydes. Nevertheless, the standard form of liquid PAA is highly corrosive, is neutralized by metals and organic matter, gives off noxious odours and must be stored in vented containers. For the reasons stated above, Bioxy formulations were developed, a series of powder forms of PAA, which are odourless, stable in storage and safe to transport and handle. They generate up to 10% PAA in situ when dissolved in water. A 0.2% aqueous solution of Bioxy (equivalent to 200 ppm PAA) effected a 6.76 log reduction in Methicillin-resistant Staphylococcus aureus (MRSA) within 2 minutes after application. A 5% aqueous solution of Bioxy achieved a 3.93 log reduction in the bovine tuberculosis bacillus Mycobacterium bovis, within 10 minutes after contact. A 1% solution of Bioxy reduced vancomycin-resistant enterococci (VRE) and Pseudomonas aeruginosa by 6.31 and 7.18 logs, respectively, within 3 minutes after application. A 0.5% solution of Bioxy inactivated porcine epidemic diarrhea virus (PEDV) within 15 minutes of contact, and a 5% solution of Bioxy realized a 5.36 log reduction in the spores of Clostridium difficile within 10 minutes of application. In summary, Bioxy is safe and easy to transport and store, poses negligible human, animal and environmental health risks, shows high levels of pathogen control efficacy and does not induce microbial resistance. Further investigations are recommended to explore its use as an industrial biocide. PMID:28207828

The wide spectrum high biocidal potency of Bioxy formulation when dissolved in water at different concentrations.

PubMed

Dagher, Dori; Ungar, Ken; Robison, Richard; Dagher, Fadi

2017-01-01

Traditional surface disinfectants that have long been applied in medicine, animal husbandry, manufacturing and institutions are inconvenient at best and dangerous at worst. Moreover, some of these substances have adverse environmental impacts: for example, quaternary ammonium compounds ("quats") are reproductive toxicants in both fish and mammals. Halogens are corrosive both to metals and living tissues, are highly reactive, can be readily neutralized by metals, and react with organic matter to form toxic, persistent by-products such as dioxins and furans. Aldehydes may be carcinogenic to both human and animals upon repeated exposures, are corrosive, cross-link living tissues and many synthetic materials, and may lose efficacy when pathogens enzymatically adapt to them. Alcohols are flammable and volatile and can be enzymatically degraded by certain bacterial pathogens. Quats are highly irritating to mucous membranes and over time can induce pathogen resistance, especially if they are not alternated with functionally different disinfectants. In contrast, peracetic acid (PAA), a potent oxidizer, liberates hydrogen peroxide (itself a disinfectant), biodegrades to carbon dioxide, water and oxygen, and is at least as efficacious as contact biocides e.g., halogens and aldehydes. Nevertheless, the standard form of liquid PAA is highly corrosive, is neutralized by metals and organic matter, gives off noxious odours and must be stored in vented containers. For the reasons stated above, Bioxy formulations were developed, a series of powder forms of PAA, which are odourless, stable in storage and safe to transport and handle. They generate up to 10% PAA in situ when dissolved in water. A 0.2% aqueous solution of Bioxy (equivalent to 200 ppm PAA) effected a 6.76 log reduction in Methicillin-resistant Staphylococcus aureus (MRSA) within 2 minutes after application. A 5% aqueous solution of Bioxy achieved a 3.93 log reduction in the bovine tuberculosis bacillus Mycobacterium bovis, within 10 minutes after contact. A 1% solution of Bioxy reduced vancomycin-resistant enterococci (VRE) and Pseudomonas aeruginosa by 6.31 and 7.18 logs, respectively, within 3 minutes after application. A 0.5% solution of Bioxy inactivated porcine epidemic diarrhea virus (PEDV) within 15 minutes of contact, and a 5% solution of Bioxy realized a 5.36 log reduction in the spores of Clostridium difficile within 10 minutes of application. In summary, Bioxy is safe and easy to transport and store, poses negligible human, animal and environmental health risks, shows high levels of pathogen control efficacy and does not induce microbial resistance. Further investigations are recommended to explore its use as an industrial biocide.

Enhanced End-Contacts by Helium Ion Bombardment to Improve Graphene-Metal Contacts

PubMed Central

Jia, Kunpeng; Su, Yajuan; Zhan, Jun; Shahzad, Kashif; Zhu, Huilong; Zhao, Chao; Luo, Jun

2016-01-01

Low contact resistance between graphene and metals is of paramount importance to fabricate high performance graphene-based devices. In this paper, the impact of both defects induced by helium ion (He+) bombardment and annealing on the contact resistance between graphene and various metals (Ag, Pd, and Pt) were systematically explored. It is found that the contact resistances between all metals and graphene are remarkably reduced after annealing, indicating that not only chemically adsorbed metal (Pd) but also physically adsorbed metals (Ag and Pt) readily form end-contacts at intrinsic defect locations in graphene. In order to further improve the contact properties between Ag, Pd, and Pt metals and graphene, a novel method in which self-aligned He+ bombardment to induce exotic defects in graphene and subsequent thermal annealing to form end-contacts was proposed. By using this method, the contact resistance is reduced significantly by 15.1% and 40.1% for Ag/graphene and Pd/graphene contacts with He+ bombardment compared to their counterparts without He+ bombardment. For the Pt/graphene contact, the contact resistance is, however, not reduced as anticipated with He+ bombardment and this might be ascribed to either inappropriate He+ bombardment dose, or inapplicable method of He+ bombardment in reducing contact resistance for Pt/graphene contact. The joint efforts of as-formed end-contacts and excess created defects in graphene are discussed as the cause responsible for the reduction of contact resistance. PMID:28335286

40 CFR 463.11 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... AND STANDARDS (CONTINUED) PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact Cooling and... one plastics molding and forming process that uses contact cooling and heating water is the sum of the... heating water process and comes in contact with the plastic product over a period of one year. ...

40 CFR 463.11 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... AND STANDARDS (CONTINUED) PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact Cooling and... one plastics molding and forming process that uses contact cooling and heating water is the sum of the... heating water process and comes in contact with the plastic product over a period of one year. ...

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

PubMed

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

2015-08-15

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inefficacy of marketed contact lens disinfection solutions against keratitis-causing Acanthamoeba castellanii belonging to the T4 genotype.

PubMed

Lakhundi, Sahreena; Khan, Naveed Ahmed; Siddiqui, Ruqaiyyah

2014-06-01

The aim of this study was to assess the anti-amoebic effects of marketed contact lens disinfecting solutions. Using amoebistatic, amoebicidal, and cysticidal assays, nine different contact lens solutions were tested including: ReNu MultiPlus, DuraPlus, Ultimate Plus, OptiFree Replenish, OptiFree Express, Kontex Clean, Kontex Normal, Kontex Multisol extra+, Kontex Soak. In vitro growth inhibition (amoebistatic) assays were performed by incubating Acanthamoeba castellanii with aforementioned contact lens disinfection solutions as per manufacturer's instructions in the growth medium for up to 48h at 30°C. To determine amoebicidal and cysticidal effects, amoebae were incubated with contact lens solutions in phosphate buffered saline for 24h and viability was determined by haemocytometer counting as well as re-inoculating them in the growth medium. For controls, solutions were tested against bacterial corneal pathogen, Pseudomonas aeruginosa, as well as amoebae were incubated with the solvent alone. Of the nine contact lens solutions tested, none of them showed potent amoebicidal effects. Only DuraPlus and OptiFree Replenish exhibited trophozoite lysis of 85.3% and 73.7% respectively. In contrast, all contact lens disinfection solutions except Kontex Clean, Kontex Normal, Kontex Multisol extra+, tested showed amoebistatic effects. Importantly, none of the contact lens disinfection solutions exhibited cysticidal effects using qualitative assays, i.e., cysts treated with aforementioned solutions re-emerged as viable amoebae upon inoculation in the growth medium. However, more than 3-log reduction was observed when ReNu MultiPlus, DuraPlus and OptiFree Express were tested against P. aeruginosa which is in accordance with the ISO Stand-Alone Primary acceptance criteria. These findings are of great concern for contact lens users. Copyright © 2014 Elsevier Inc. All rights reserved.

Increased resistance of contact lens related bacterial biofilms to antimicrobial activity of soft contact lens care solutions

PubMed Central

Szczotka-Flynn, Loretta B.; Imamura, Yoshifumi; Chandra, Jyotsna; Yu, Changping; Mukherjee, Pranab K.; Pearlman, Eric; Ghannoum, Mahmoud A.

2014-01-01

PURPOSE To determine if clinical and reference strains of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus form biofilms on silicone hydrogel contact lenses, and ascertain antimicrobial activities of contact lens care solutions. METHODS Clinical and American Type Culture Collection (ATCC) reference strains of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus were incubated with lotrafilcon A lenses under conditions that facilitate biofilm formation. Biofilms were quantified by quantitative culturing (colony forming units, CFUs), and gross morphology and architecture were evaluated using scanning electron microscopy (SEM) and confocal microscopy. Susceptibilities of the planktonic and biofilm growth phases of the bacteria to five common multipurpose contact lens care solutions and one hydrogen peroxide care solution were assessed. RESULTS P. aeruginosa, S. marcescens, and S. aureus reference and clinical strains formed biofilms on lotrafilcon A silicone hydrogel contact lenses, as dense networks of cells arranged in multiple layers with visible extracellular matrix. The biofilms were resistant to commonly used biguanide preserved multipurpose care solutions. P. aeruginosa and S. aureus biofilms were susceptible to a hydrogen peroxide and a polyquaternium preserved care solution, whereas S. marcescens biofilm was resistant to a polyquaternium preserved care solution but susceptible to hydrogen peroxide disinfection. In contrast, the planktonic forms were always susceptible. CONCLUSIONS P. aeruginosa, S. marcescens, and S. aureus form biofilms on lotrafilcon A contact lenses, which in contrast to planktonic cells, are resistant to the antimicrobial activity of several soft contact lens care products. PMID:19654521

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

DOEpatents

Carlson, David E.; Dickson, Charles R.; D'Aiello, Robert V.

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.

Electrical contacts for a thin-film semiconductor device

DOEpatents

Carlson, David E.; Dickson, Charles R.; D'Aiello, Robert V.

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.

Antiallergic activity of unripe Citrus hassaku fruits extract and its flavanone glycosides on chemical substance-induced dermatitis in mice.

PubMed

Itoh, Kimihisa; Masuda, Megumi; Naruto, Shunsuke; Murata, Kazuya; Matsuda, Hideaki

2009-10-01

Oral administration of a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits collected in July exhibited a potent dose-dependent inhibition of IgE (immunoglobulin E)-mediated triphasic cutaneous reaction at 1 h [immediate phase response (IPR)], 24 h [late phase response (LPR)] and 8 days [very late phase response (vLPR)] after dinitrofluorobenzene challenge in mice. Naringin, a major flavanone glycoside component of CH-ext, showed a potent dose-dependent inhibition against IPR, LPR and vLPR. Neohesperidin, another major glycoside component of CH-ext, showed an inhibition against vLPR. The effect of CH-ext on type IV allergic reaction was examined by determining inhibitory activity against ear swelling in mice by using the picryl chloride-induced contact dermatitis (PC-CD) model. Oral administration (p.o.) of CH-ext and subcutaneous administration (s.c.) of prednisolone inhibited ear swelling during the induction phase of PC-CD. The inhibitory activities of combinations of CH-ext (p.o.) and prednisolone (s.c.) against PC-CD in mice were more potent than those of CH-ext alone and prednisolone alone, without enhancing the adverse effects. Other combinations of prednisolone (s.c.) and flavanone glycoside (p.o.) components of CH-ext, i.e. naringin and neohesperidin, exerted similar synergistic effects.

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.

Nanoscale electro-structural characterisation of ohmic contacts formed on p-type implanted 4H-SiC

NASA Astrophysics Data System (ADS)

Frazzetto, Alessia; Giannazzo, Filippo; Lo Nigro, Raffaella; di Franco, Salvatore; Bongiorno, Corrado; Saggio, Mario; Zanetti, Edoardo; Raineri, Vito; Roccaforte, Fabrizio

2011-12-01

This work reports a nanoscale electro-structural characterisation of Ti/Al ohmic contacts formed on p-type Al-implanted silicon carbide (4H-SiC). The morphological and the electrical properties of the Al-implanted layer, annealed at 1700°C with or without a protective capping layer, and of the ohmic contacts were studied using atomic force microscopy [AFM], transmission line model measurements and local current measurements performed with conductive AFM. The characteristics of the contacts were significantly affected by the roughness of the underlying SiC. In particular, the surface roughness of the Al-implanted SiC regions annealed at 1700°C could be strongly reduced using a protective carbon capping layer during annealing. This latter resulted in an improved surface morphology and specific contact resistance of the Ti/Al ohmic contacts formed on these regions. The microstructure of the contacts was monitored by X-ray diffraction analysis and a cross-sectional transmission electron microscopy, and correlated with the electrical results.

High gain photoconductive semiconductor switch having tailored doping profile zones

DOEpatents

Baca, Albert G.; Loubriel, Guillermo M.; Mar, Alan; Zutavern, Fred J; Hjalmarson, Harold P.; Allerman, Andrew A.; Zipperian, Thomas E.; O'Malley, Martin W.; Helgeson, Wesley D.; Denison, Gary J.; Brown, Darwin J.; Sullivan, Charles T.; Hou, Hong Q.

2001-01-01

A photoconductive semiconductor switch with tailored doping profile zones beneath and extending laterally from the electrical contacts to the device. The zones are of sufficient depth and lateral extent to isolate the contacts from damage caused by the high current filaments that are created in the device when it is turned on. The zones may be formed by etching depressions into the substrate, then conducting epitaxial regrowth in the depressions with material of the desired doping profile. They may be formed by surface epitaxy. They may also be formed by deep diffusion processes. The zones act to reduce the energy density at the contacts by suppressing collective impact ionization and formation of filaments near the contact and by reducing current intensity at the contact through enhanced current spreading within the zones.

Poison Ivy Treatment

MedlinePlus

... skin reactions. These skin reactions are forms of contact dermatitis. Treatment Treating reactions to poison ivy—the most frequent of these forms of contact dermatitis—is a straightforward matter. Prevention is the best ...

Structure-based design of oxygen-linked macrocyclic kinase inhibitors: discovery of SB1518 and SB1578, potent inhibitors of Janus kinase 2 (JAK2) and Fms-like tyrosine kinase-3 (FLT3)

NASA Astrophysics Data System (ADS)

Poulsen, Anders; William, Anthony; Blanchard, Stéphanie; Lee, Angeline; Nagaraj, Harish; Wang, Haishan; Teo, Eeling; Tan, Evelyn; Goh, Kee Chuan; Dymock, Brian

2012-04-01

Macrocycles from our Aurora project were screened in a kinase panel and were found to be active on other kinase targets, mainly JAKs, FLT3 and CDKs. Subsequently these compounds became leads in our JAK2 project. Macrocycles with a basic nitrogen in the linker form a salt bridge with Asp86 in CDK2 and Asp698 in FLT3. This residue is conserved in most CDKs resulting in potent pan CDK inhibition. One of the main project objectives was to achieve JAK2 potency with 100-fold selectivity against CDKs. Macrocycles with an ether linker have potent JAK2 activity with the ether oxygen forming a hydrogen bond to Ser936. A hydrogen bond to the equivalent residues of JAK3 and most CDKs cannot be formed resulting in good selectivity for JAK2 over JAK3 and CDKs. Further optimization of the macrocyclic linker and side chain increased JAK2 and FLT3 activity as well as improving DMPK properties. The selective JAK2/FLT3 inhibitor 11 (Pacritinib, SB1518) has successfully finished phase 2 clinical trials for myelofibrosis and lymphoma. Another selective JAK2/FLT3 inhibitor, 33 (SB1578), has entered phase 1 clinical development for the non-oncology indication rheumatoid arthritis.

Functionalizing aluminum substrata by quaternary ammonium for antifouling performances

NASA Astrophysics Data System (ADS)

He, Xiaoyan; Suo, Xinkun; Bai, Xiuqin; Yuan, Chengqing; Li, Hua

2018-05-01

Due to the great loss induced by biofouling, developing new strategies for combating biofouling has attracted extensive attention. Quaternary ammonium salts are potent cationic antimicrobials used in consumer products and their use for surface immobilization could create a contact-active antimicrobial layer. Here we report the facile preparation of a contact-active antifouling coating by tethering polyethyleneimine (PEI) onto flat/nanostructured aluminum surface by hydrogen bonding between PEI and AlOOH. Quaternized PEI (QPEI) is obtained through quaternization reactions. Biofouling testing suggests excellent antifouling performances of the samples by declining the adhesion of 95% Phaeodactylum tricornutum and 98% of Chlorella pyrenoidosa. The antifouling properties of PEI/QPEI are attributed predominately to their hydrophilic and antimicrobial nature. The technical route of PEI/QPEI surface grafting shows great potential for modifying marine infrastructures for enhanced antifouling performances.

Regulation of cutaneous allergic reaction by odorant inhalation.

PubMed

Hosoi, J; Tsuchiya, T

2000-03-01

Olfactory stimuli modulate emotional conditions and the whole body immune system. Effects of odorant inhalation on cutaneous immune reaction were examined. Contact hypersensitivity to 2,4, 6-trinitrochlorobenzene was elicited in C57BL/6 mice. The reaction was suppressed at both the induction and elicitation phases by exposure to an odorant, citralva. Topical application of citralva or lyral/lilial did not affect the reaction. The suppressive effect of citralva was more potent than that of another odorant, lyral/lilial. Citralva decreased the number of epidermal Langerhans cells, whereas lyral/lilial had a weak effect. Citralva but not lyral/lilial induced plasma corticosterone. Glucocorticoid receptor antagonist abrogated the suppressive effect of citralva on contact hypersensitivity. Serum interleukin-12 was downregulated by exposure to citralva or lyral/lilial. These data demonstrate that olfactory stimuli regulate the cutaneous immune system.

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 < 0.0001). Conclusion Our study indicates that multi-drug resistant, biofilm 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

Method of forming emitters for a back-contact solar cell

DOEpatents

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.

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.

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.

Integration Of Heat Transfer Coefficient In Glass Forming Modeling With Special Interface Element

NASA Astrophysics Data System (ADS)

Moreau, P.; César de Sá, J.; Grégoire, S.; Lochegnies, D.

2007-05-01

Numerical modeling of the glass forming processes requires the accurate knowledge of the heat exchange between the glass and the forming tools. A laboratory testing is developed to determine the evolution of the heat transfer coefficient in different glass/mould contact conditions (contact pressure, temperature, lubrication…). In this paper, trials are performed to determine heat transfer coefficient evolutions in experimental conditions close to the industrial blow-and-blow process conditions. In parallel of this work, a special interface element is implemented in a commercial Finite Element code in order to deal with heat transfer between glass and mould for non-meshing meshes and evolutive contact. This special interface element, implemented by using user subroutines, permits to introduce the previous heat transfer coefficient evolutions in the numerical modelings at the glass/mould interface in function of the local temperatures, contact pressures, contact time and kind of lubrication. The blow-and-blow forming simulation of a perfume bottle is finally performed to assess the special interface element performance.

Combining Multiple Forms Of Visual Information To Specify Contact Relations In Spatial Layout

NASA Astrophysics Data System (ADS)

Sedgwick, Hal A.

1990-03-01

An expert system, called Layout2, has been described, which models a subset of available visual information for spatial layout. The system is used to examine detailed interactions between multiple, partially redundant forms of information in an environment-centered geometrical model of an environment obeying certain rather general constraints. This paper discusses the extension of Layout2 to include generalized contact relations between surfaces. In an environment-centered model, the representation of viewer-centered distance is replaced by the representation of environmental location. This location information is propagated through the representation of the environment by a network of contact relations between contiguous surfaces. Perspective information interacts with other forms of information to specify these contact relations. The experimental study of human perception of contact relations in extended spatial layouts is also discussed. Differences between human results and Layout2 results reveal limitations in the human ability to register available information; they also point to the existence of certain forms of information not yet formalized in Layout2.

78 FR 19464 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... identifiers or contact information. Any associated form(s) for this collection may be located within this same... number, and title. FOR FURTHER INFORMATION CONTACT: To request more information on this proposed... Public Outreach at (703) 695- 3845. Title; Associated Form; and OMB Number: Request for Armed Forces...

Apparent contact angle and contact angle hysteresis on liquid infused surfaces.

PubMed

Semprebon, Ciro; McHale, Glen; Kusumaatmaja, Halim

2016-12-21

We theoretically investigate the apparent contact angle and contact angle hysteresis of a droplet placed on a liquid infused surface. We show that the apparent contact angle is not uniquely defined by material parameters, but also has a dependence on the relative size between the droplet and its surrounding wetting ridge formed by the infusing liquid. We derive a closed form expression for the contact angle in the limit of vanishing wetting ridge, and compute the correction for small but finite ridge, which corresponds to an effective line tension term. We also predict contact angle hysteresis on liquid infused surfaces generated by the pinning of the contact lines by the surface corrugations. Our analytical expressions for both the apparent contact angle and contact angle hysteresis can be interpreted as 'weighted sums' between the contact angles of the infusing liquid relative to the droplet and surrounding gas phases, where the weighting coefficients are given by ratios of the fluid surface tensions.

Compact vacuum insulation embodiments

DOEpatents

Benson, D.K.; Potter, T.F.

1992-04-28

An ultra-thin compact vacuum insulation panel is comprised of two hard, but bendable metal wall sheets closely spaced apart from each other and welded around the edges to enclose a vacuum chamber. Glass or ceramic spacers hold the wall sheets apart. The spacers can be discrete spherical beads or monolithic sheets of glass or ceramic webs with nodules protruding therefrom to form essentially point' or line' contacts with the metal wall sheets. In the case of monolithic spacers that form line' contacts, two such spacers with the line contacts running perpendicular to each other form effectively point' contacts at the intersections. Corrugations accommodate bending and expansion, tubular insulated pipes and conduits, and preferred applications are also included. 26 figs.

Compact vacuum insulation

DOEpatents

Benson, D.K.; Potter, T.F.

1993-01-05

An ultra-thin compact vacuum insulation panel is comprised of two hard, but bendable metal wall sheets closely spaced apart from each other and welded around the edges to enclose a vacuum chamber. Glass or ceramic spacers hold the wall sheets apart. The spacers can be discrete spherical beads or monolithic sheets of glass or ceramic webs with nodules protruding therefrom to form essentially point'' or line'' contacts with the metal wall sheets. In the case of monolithic spacers that form line'' contacts, two such spacers with the line contacts running perpendicular to each other form effectively point'' contacts at the intersections. Corrugations accommodate bending and expansion, tubular insulated pipes and conduits, and preferred applications are also included.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, Dong-Kyun; Medpelli, Dinesh; Ladd, Danielle

A product formed from a first material including a geopolymer resin material, a geopolymer material, or a combination thereof by contacting the first material with a fluid and removing at least some of the fluid to yield a product. The first material may be formed by heating and/or aging an initial geopolymer resin material to yield the first material before contacting the first material with the fluid. In some cases, contacting the first material with the fluid breaks up or disintegrates the first material (e.g., in response to contact with the fluid and in the absence of external mechanical stress),more » thereby forming particles having an external dimension in a range between 1 nm and 2 cm.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, Dong-Kyun; Medpelli, Dinesh; Ladd, Danielle

A product formed from a first material including a geopolymer resin material, a geopolymer resin, or a combination thereof by contacting the first material with a fluid and removing at least some of the fluid to yield a product. The first material may be formed by heating and/or aging an initial geopolymer resin material to yield the first material before contacting the first material with the fluid. In some cases, contacting the first material with the fluid breaks up or disintegrates the first material (e.g., in response to contact with the fluid and in the absence of external mechanical stress),more » thereby forming particles having an external dimension in a range between 1 nm and 2 cm.« less

Compact vacuum insulation

DOEpatents

Benson, David K.; Potter, Thomas F.

1993-01-01

An ultra-thin compact vacuum insulation panel is comprised of two hard, but bendable metal wall sheets closely spaced apart from each other and welded around the edges to enclose a vacuum chamber. Glass or ceramic spacers hold the wall sheets apart. The spacers can be discrete spherical beads or monolithic sheets of glass or ceramic webs with nodules protruding therefrom to form essentially "point" or "line" contacts with the metal wall sheets. In the case of monolithic spacers that form "line" contacts, two such spacers with the line contacts running perpendicular to each other form effectively "point" contacts at the intersections. Corrugations accommodate bending and expansion, tubular insulated pipes and conduits, and preferred applications are also included.

Compact vacuum insulation embodiments

DOEpatents

Benson, David K.; Potter, Thomas F.

1992-01-01

An ultra-thin compact vacuum insulation panel is comprised of two hard, but bendable metal wall sheets closely spaced apart from each other and welded around the edges to enclose a vacuum chamber. Glass or ceramic spacers hold the wall sheets apart. The spacers can be discrete spherical beads or monolithic sheets of glass or ceramic webs with nodules protruding therefrom to form essentially "point" or "line" contacts with the metal wall sheets. In the case of monolithic spacers that form "line" contacts, two such spacers with the line contacts running perpendicular to each other form effectively "point" contacts at the intersections. Corrugations accommodate bending and expansion, tubular insulated pipes and conduits, and preferred applications are also included.

Secondary treatment of films of colloidal quantum dots for optoelectronics and devices produced thereby

DOEpatents

Semonin, Octavi Escala; Luther, Joseph M; Beard, Matthew C; Chen, Hsiang-Yu

2014-04-01

A method of forming an optoelectronic device. The method includes providing a deposition surface and contacting the deposition surface with a ligand exchange chemical and contacting the deposition surface with a quantum dot (QD) colloid. This initial process is repeated over one or more cycles to form an initial QD film on the deposition surface. The method further includes subsequently contacting the QD film with a secondary treatment chemical and optionally contacting the surface with additional QDs to form an enhanced QD layer exhibiting multiple exciton generation (MEG) upon absorption of high energy photons by the QD active layer. Devices having an enhanced QD active layer as described above are also disclosed.

Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Jinghe; Kang, Byong H.; Ishida, Elise

Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permittedmore » it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.« less

The use of docking-based comparative intermolecular contacts analysis to identify optimal docking conditions within glucokinase and to discover of new GK activators

NASA Astrophysics Data System (ADS)

Taha, Mutasem O.; Habash, Maha; Khanfar, Mohammad A.

2014-05-01

Glucokinase (GK) is involved in normal glucose homeostasis and therefore it is a valid target for drug design and discovery efforts. GK activators (GKAs) have excellent potential as treatments of hyperglycemia and diabetes. The combined recent interest in GKAs, together with docking limitations and shortages of docking validation methods prompted us to use our new 3D-QSAR analysis, namely, docking-based comparative intermolecular contacts analysis (dbCICA), to validate docking configurations performed on a group of GKAs within GK binding site. dbCICA assesses the consistency of docking by assessing the correlation between ligands' affinities and their contacts with binding site spots. Optimal dbCICA models were validated by receiver operating characteristic curve analysis and comparative molecular field analysis. dbCICA models were also converted into valid pharmacophores that were used as search queries to mine 3D structural databases for new GKAs. The search yielded several potent bioactivators that experimentally increased GK bioactivity up to 7.5-folds at 10 μM.

Disruption of Contact Lens–Associated Pseudomonas aeruginosa Biofilms Formed in the Presence of Neutrophils

PubMed Central

Parks, Quinn M.; Young, Robert L.; Kret, Jennifer; Poch, Katie R.; Malcolm, Kenneth C.; Nichols, David P.; Nichols, Michelle; Zhu, Meifang; Cavanagh, H. Dwight; Nick, Jerry A.

2011-01-01

Purpose. To evaluate the capacity of neutrophils to enhance biofilm formation on contact lenses by an infectious Pseudomonas aeruginosa (PA) corneal isolate. Agents that target F-actin and DNA were tested as a therapeutic strategy for disrupting biofilms formed in the setting of neutrophils in vitro and for limiting the infectious bioburden in vivo. Methods. Biofilm formation by infectious PA strain 6294 was assessed in the presence of neutrophils on a static biofilm plate and on unworn etafilcon A soft contact lenses. A d-isomer of poly(aspartic acid) was used alone and with DNase to reduce biofilm formation on test contact lenses. The gentamicin survival assay was used to determine the effectiveness of the test compound in reducing subsequent intracellular bacterial load in the corneal epithelium in a contact lens infection model in the rabbit. Results. In a static reactor and on hydrogel lenses, PA biofilm density was enhanced 30-fold at 24 hours in the presence of neutrophils (P < 0.0001). The combination of DNase and anionic poly(aspartic acid) reduced the PA biofilms formed in the presence of activated neutrophils by 79.2% on hydrogel contact lenses (P < 0.001). An identical treatment resulted in a 41% reduction in internalized PA in the rabbit corneal epithelium after 24 hours (P = 0.03). Conclusions. These results demonstrate that PA can exploit the presence of neutrophils to form biofilm on contact lenses within a short time. Incorporation of F-actin and DNA represent a mechanism for neutrophil-induced biofilm enhancement and are targets for available agents to disrupt pathogenic biofilms formed on contact lenses and as a treatment for established corneal infections. PMID:21245396

Disarming Fungal Pathogens: Bacillus safensis Inhibits Virulence Factor Production and Biofilm Formation by Cryptococcus neoformans and Candida albicans

PubMed Central

2017-01-01

ABSTRACT Bacteria interact with each other in nature and often compete for limited nutrient and space resources. However, it is largely unknown whether and how bacteria also interact with human fungal pathogens naturally found in the environment. Here, we identified a soil bacterium, Bacillus safensis, which potently blocked several key Cryptococcus neoformans virulence factors, including formation of the antioxidant pigment melanin and production of the antiphagocytic polysaccharide capsule. The bacterium also inhibited de novo cryptococcal biofilm formation but had only modest inhibitory effects on already formed biofilms or planktonic cell growth. The inhibition of fungal melanization was dependent on direct cell contact and live bacteria. B. safensis also had anti-virulence factor activity against another major human-associated fungal pathogen, Candida albicans. Specifically, dual-species interaction studies revealed that the bacterium strongly inhibited C. albicans filamentation and biofilm formation. In particular, B. safensis physically attached to and degraded candidal filaments. Through genetic and phenotypic analyses, we demonstrated that bacterial chitinase activity against fungal cell wall chitin is a factor contributing to the antipathogen effect of B. safensis. PMID:28974618

Fatty Acid-binding Proteins Interact with Comparative Gene Identification-58 Linking Lipolysis with Lipid Ligand Shuttling*

PubMed Central

Hofer, Peter; Boeszoermenyi, Andras; Jaeger, Doris; Feiler, Ursula; Arthanari, Haribabu; Mayer, Nicole; Zehender, Fabian; Rechberger, Gerald; Oberer, Monika; Zimmermann, Robert; Lass, Achim; Haemmerle, Guenter; Breinbauer, Rolf; Zechner, Rudolf; Preiss-Landl, Karina

2015-01-01

The coordinated breakdown of intracellular triglyceride (TG) stores requires the exquisitely regulated interaction of lipolytic enzymes with regulatory, accessory, and scaffolding proteins. Together they form a dynamic multiprotein network designated as the “lipolysome.” Adipose triglyceride lipase (Atgl) catalyzes the initiating step of TG hydrolysis and requires comparative gene identification-58 (Cgi-58) as a potent activator of enzyme activity. Here, we identify adipocyte-type fatty acid-binding protein (A-Fabp) and other members of the fatty acid-binding protein (Fabp) family as interaction partners of Cgi-58. Co-immunoprecipitation, microscale thermophoresis, and solid phase assays proved direct protein/protein interaction between A-Fabp and Cgi-58. Using nuclear magnetic resonance titration experiments and site-directed mutagenesis, we located a potential contact region on A-Fabp. In functional terms, A-Fabp stimulates Atgl-catalyzed TG hydrolysis in a Cgi-58-dependent manner. Additionally, transcriptional transactivation assays with a luciferase reporter system revealed that Fabps enhance the ability of Atgl/Cgi-58-mediated lipolysis to induce the activity of peroxisome proliferator-activated receptors. Our studies identify Fabps as crucial structural and functional components of the lipolysome. PMID:25953897

Status of wraparound contact solar cells and arrays

NASA Technical Reports Server (NTRS)

Baraona, C. R.; Young, L. E.

1978-01-01

Solar cells with wraparound contacts provide the following advantages in array assembly: (1) eliminate the need for discretely formed, damage susceptible series tabs; (2) eliminate the n gap problem by allowing the use of uniform covers over the entire cell surface; (3) allow a higher packing factor by reducing the additional series spacing formly required for forming, and routing the series tab; and (4) allow the cell bonding to the interconnect system to be a single-side function wherein series contacts can be made at the same time parallel contracts are made.

Intravascular laser therapy in different forms of lung diseases

NASA Astrophysics Data System (ADS)

Kirillov, M. N.; Reshetnikov, V. A.; Kazhekin, O. A.; Shepelenko, A. F.

1993-06-01

The potentions of laser intravascular therapy in elimination of pyogenic and inflammatory intoxication in cases of acute pneumonia, pyo-destructive diseases (including posttraumatic diseases) of the lungs are studied clinically.

The influence of rail surface irregularities on contact forces and local stresses

NASA Astrophysics Data System (ADS)

Andersson, Robin; Torstensson, Peter T.; Kabo, Elena; Larsson, Fredrik

2015-01-01

The effect of initial rail surface irregularities on promoting further surface degradation is investigated. The study concerns rolling contact fatigue formation, in particular in the form of the so-called squats. The impact of surface irregularities in the form of dimples is quantified by peak magnitudes of dynamic contact stresses and contact forces. To this end simulations of two-dimensional (later extended to three-dimensional) vertical dynamic vehicle-track interaction are employed. The most influencing parameters are identified. It is shown that even very shallow dimples might have a large impact on local contact stresses. Peak magnitudes of contact forces and stresses due to the influence of rail dimples are shown to exceed those due to rail corrugation.

Periodic nanostructures formed on a poly-methyl methacrylate surface with a femtosecond laser for biocompatibility improvement

NASA Astrophysics Data System (ADS)

Takenaka, Keisuke; Tsukamoto, Masahiro; Sato, Yuji; Ooga, Takahiro; Asai, Satoru; Murai, Kensuke

2018-06-01

Poly(methyl methacrylate) (PMMA) is widely used as a biomaterial. The formation of periodic nanostructures on the surface is necessary to improve the biocompatibility. A method was proposed and developed to form periodic nanostructures on a PMMA surface. A PMMA plate was placed on titanium (Ti) plate, and then the Ti plate was irradiated with a laser through the PMMA plate. We try to effectively produce periodic nanostructures on PMMA with a femtosecond laser at a fundamental wavelength by increasing the contact pressure and using titanium (Ti) plate. The contact pressure between PMMA and Ti required to form a periodic nanostructure is 300 kPa, and for a contact pressure of 2400 kPa, periodic nanostructures are formed in 62% of the laser-irradiated area on the PMMA surface. These results suggest that the formation efficiency of the periodic nanostructure depends on the laser conditions and the contact pressure.

Integration Of Heat Transfer Coefficient In Glass Forming Modeling With Special Interface Element

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreau, P.; Gregoire, S.; Lochegnies, D.

2007-05-17

Numerical modeling of the glass forming processes requires the accurate knowledge of the heat exchange between the glass and the forming tools. A laboratory testing is developed to determine the evolution of the heat transfer coefficient in different glass/mould contact conditions (contact pressure, temperature, lubrication...). In this paper, trials are performed to determine heat transfer coefficient evolutions in experimental conditions close to the industrial blow-and-blow process conditions. In parallel of this work, a special interface element is implemented in a commercial Finite Element code in order to deal with heat transfer between glass and mould for non-meshing meshes and evolutivemore » contact. This special interface element, implemented by using user subroutines, permits to introduce the previous heat transfer coefficient evolutions in the numerical modelings at the glass/mould interface in function of the local temperatures, contact pressures, contact time and kind of lubrication. The blow-and-blow forming simulation of a perfume bottle is finally performed to assess the special interface element performance.« less

Synthesis and disulfide bond connectivity-activity studies of a kalata B1-inspired cyclopeptide against dengue NS2B-NS3 protease.

PubMed

Gao, Yaojun; Cui, Taian; Lam, Yulin

2010-02-01

Kalata B1 is a plant protein with remarkable thermal, chemical and enzymatic stability. Its potential applications could be centered on the possibility of using its cyclic structure and cystine knot motif as a scaffold for the design of stable pharmaceuticals. To discover potent dengue NS2B-NS3 protease inhibitors, we have prepared various kalata B1 analogues by varying the amino acid sequence. Mass spectrometric and biochemical investigations of these analogues revealed a cyclopeptide whose two fully oxidized forms are substrate-competitive inhibitors of the dengue viral NS2B-NS3 protease. Both oxidized forms showed potent inhibition with K(i) of 1.39+/-0.35 and 3.03+/-0.75 microM, respectively. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

The Role of Regular Eating and Self-Monitoring in the Treatment of Bulimia Nervosa: A Pilot Study of an Online Guided Self-Help CBT Program.

PubMed

Barakat, Sarah; Maguire, Sarah; Surgenor, Lois; Donnelly, Brooke; Miceska, Blagica; Fromholtz, Kirsty; Russell, Janice; Hay, Phillipa; Touyz, Stephen

2017-06-26

Background : Despite cognitive behavioural therapy (CBT) being regarded as the first-line treatment option for bulimia nervosa (BN), barriers such as its time-consuming and expensive nature limit patient access. In order to broaden treatment availability and affordability, the efficacy and convenience of CBT could be improved through the use of online treatments and selective emphasis on its most 'potent' components of which behavioural techniques form the focus. Method: Twenty-six individuals with BN were enrolled in an online CBT-based self-help programme and 17 completed four weeks of regular eating and food-monitoring using the online Food Diary tool. Participants were contacted for a weekly check-in phone call and had their bulimic symptom severity assessed at five time points (baseline and weeks 1-4). Results : There was a significant decrease in the frequency of self-reported objective binge episodes, associated loss of control and objective binge days reported between pre- and post-treatment measures. Significant improvements were also observed in most subscales of the Eating Disorder Examination-Questionnaire. Conclusion : This study provides encouraging preliminary evidence of the potential of behavioural techniques of online CBT in the treatment of BN. Online therapy with this focus is potentially a viable and practical form of treatment delivery in this illness group. These preliminary findings support the need for larger studies using control groups.

Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3)

PubMed Central

Koymans, Kirsten J.; Feitsma, Louris J.; Brondijk, T. Harma C.; Aerts, Piet C.; Lukkien, Eddie; Lössl, Philip; van Kessel, Kok P. M.; de Haas, Carla J. C.; van Strijp, Jos A. G.; Huizinga, Eric G.

2015-01-01

Toll-like receptors (TLRs) are crucial in innate recognition of invading micro-organisms and their subsequent clearance. Bacteria are not passive bystanders and have evolved complex evasion mechanisms. Staphylococcus aureus secretes a potent TLR2 antagonist, staphylococcal superantigen-like protein 3 (SSL3), which prevents receptor stimulation by pathogen-associated lipopeptides. Here, we present crystal structures of SSL3 and its complex with TLR2. The structure reveals that formation of the specific inhibitory complex is predominantly mediated by hydrophobic contacts between SSL3 and TLR2 and does not involve interaction of TLR2–glycans with the conserved LewisX binding site of SSL3. In the complex, SSL3 partially covers the entrance to the lipopeptide binding pocket in TLR2, reducing its size by ∼50%. We show that this is sufficient to inhibit binding of agonist Pam2CSK4 effectively, yet allows SSL3 to bind to an already formed TLR2–Pam2CSK4 complex. The binding site of SSL3 overlaps those of TLR2 dimerization partners TLR1 and TLR6 extensively. Combined, our data reveal a robust dual mechanism in which SSL3 interferes with TLR2 activation at two stages: by binding to TLR2, it blocks ligand binding and thus inhibits activation. Second, by interacting with an already formed TLR2–lipopeptide complex, it prevents TLR heterodimerization and downstream signaling. PMID:26283364

Molecularly Imprinted Polymers: Novel Discovery for Drug Delivery.

PubMed

Dhanashree, Surve; Priyanka, Mohite; Manisha, Karpe; Vilasrao, Kadam

2016-01-01

Molecularly imprinted polymers (MIP) are novel carriers synthesized by imprinting of a template over a polymer. This paper presents the recent application of MIP for diagnostic and therapeutic drug delivery. MIP owing to their 3D polymeric structures and due to bond formation with the template serves as a reservoir of active causing stimuli sensitive, enantioselective, targetted and/or controlled release. The review elaborates about key factors for optimization of MIP, controlled release by MIP for various administration routes various forms like patches, contact lenses, nanowires along with illustrations. To overcome the limitation of organic solvent usage causing increased cost, water compatible MIP and use of supercritical fluid technology for molecular imprinting were developed. Novel methods for developing water compatible MIP like pickering emulsion polymerization, co-precipitation method, cyclodextrin imprinting, surface grafting, controlled/living radical chain polymerization methods are described with illustration in this review. Various protein imprinting methods like bulk, epitope and surface imprinting are described along with illustrations. Further, application of MIP in microdevices as biomimetic sensing element for personalized therapy is elaborated. Although development and application of MIP in drug delivery is still at its infancy, constant efforts of researchers will lead to a novel intelligent drug delivery with commercial value. Efforts should be directed in developing solid oral dosage forms consisting of MIP for therapeutic protein and peptide delivery and targeted release of potent drugs addressing life threatening disease like cancer. Amalgamation of bio-engineering and pharmaceutical techniques can make these future prospects into reality.

Dual mTORC2/mTORC1 targeting results in potent suppressive effects on acute myeloid leukemia (AML) progenitors*

PubMed Central

Altman, Jessica K.; Sassano, Antonella; Kaur, Surinder; Glaser, Heather; Kroczynska, Barbara; Redig, Amanda J.; Russo, Suzanne; Barr, Sharon; Platanias, Leonidas C.

2011-01-01

Purpose To determine whether mTORC2 and RI-mTORC1 complexes are present in AML cells and to examine the effects of dual mTORC2/mTORC1 inhibition on primitive AML leukemic progenitors. Experimental Design Combinations of different experimental approaches were used, including immunoblotting to detect phosphorylated/activated forms of elements of the mTOR pathway in leukemic cell lines and primary AML blasts; cell proliferation assays; direct assessment of mRNA translation in polysomal fractions of leukemic cells; and clonogenic assays in methylcellulose to evaluate leukemic progenitor colony formation. Results mTORC2 complexes are active in AML cells and play critical roles in leukemogenesis. Rapamycin insensitive (RI) mTORC1 complexes are also formed and regulate the activity of the translational repressor 4E-BP1 in AML cells. OSI-027, blocks mTORC1 and mTORC2 activities and suppresses mRNA translation of cyclin D1 and other genes that mediate proliferative responses in AML cells. Moreover, OSI-027 acts as a potent suppressor of primitive leukemic precursors from AML patients and is much more effective than rapamycin in eliciting antileukemic effects in vitro. Conclusions Dual targeting of mTORC2 and mTORC1 results in potent suppressive effects on primitive leukemic progenitors from AML patients. Inhibition of the mTOR catalytic site with OSI-027 results in suppression of both mTORC2 and RI-mTORC1 complexes and elicits much more potent antileukemic responses than selective mTORC1 targeting with rapamycin. PMID:21415215

Process for Nitrogen Oxide Waste Conversion to Fertilizer

NASA Technical Reports Server (NTRS)

Lueck, Dale E. (Inventor); Parrish, Clyde F. (Inventor)

2003-01-01

The present invention describes a process for converting vapor streams from sources containing at least one nitrogen-containing oxidizing agent therein to a liquid fertilizer composition comprising the steps of: a) directing a vapor stream containing at least one nitrogen-containing oxidizing agent to a first contact zone; b) contacting said vapor stream with water to form nitrogen oxide(s) from said at least one nitrogen-containing oxidizing agent; c) directing said acid(s) as a second stream to a second contact zone; d) exposing said second stream to hydrogen peroxide which is present within said second contact zone in a relative amount of at least 0.1% by weight of said second stream within said second contact zone to convert at least some of any nitrogen oxide species or ions other than in the nitrate form present within said second stream to nitrate ion; e) sampling said stream within said second contact zone to determine the relative amount of hydrogen peroxide within said second contact zone; f) adding hydrogen peroxide to said second contact zone when a level of hydrogen peroxide less than 0.1 % by weight in said second stream is determined by said sampling; g) adding a solution comprising potassium hydroxide to said second stream to maintain a pH between 6.0 and 11.0 within said second stream within said second contact zone to form a solution of potassium nitrate; and h) removing said solution of potassium nitrate from said second contact zone.

Process and Equipment for Nitrogen Oxide Waste Conversion to Fertilizer

NASA Technical Reports Server (NTRS)

Lueck, Dale E. (Inventor); Parrish, Clyde F. (Inventor)

2000-01-01

The present invention describes a process for converting vapor streams from sources containing at least one nitrogen-containing oxidizing agent therein to a liquid fertilizer composition comprising the steps of: (1) directing a vapor stream containing at least nitrogen-containing oxidizing agent to a first contact zone; (2) contacting said vapor stream with water to form nitrogen oxide(s) from said at least one nitrogen- containing oxidizing agent; (3) directing said acid(s) as a second stream to a second contact zone; (4) exposing said second stream to hydrogen peroxide which is present within said second contact zone in a relative amount of at least 0.1% by weight of said second stream within said second contact zone to convert at least some of any nitrogen oxide species or ions other than in the nitrite form present within said second stream to nitrate ion; (5) sampling said stream within said second contact zone to determine the relative amount of hydrogen peroxide within said second contact zone; (6) adding hydrogen peroxide to said second contact zone when a level on hydrogen peroxide less than 0.1% by weight in said second stream is determined by said sampling; (7) adding a solution comprising potassium hydroxide to said second stream to maintain a pH between 6.0 and 11.0 within said second stream within said second contact zone to form a solution of potassium nitrate; and (8) removing sais solution of potassium nitrate from said second contact zone.

1,2,3-Triazolyl ester of Ketorolac: A "Click Chemistry"-based highly potent PAK1-blocking cancer-killer.

PubMed

Nguyen, Binh Cao Quan; Takahashi, Hideaki; Uto, Yoshihiro; Shahinozzaman, M D; Tawata, Shinkichi; Maruta, Hiroshi

2017-01-27

An old anti-inflammatory/analgesic drug called Toradol is a racemic form of Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2 (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form and of COX-2 by the S-form, eventually down-regulating the production of prostaglandins. However, due to its COOH moiety which is clearly repulsive to negatively-charged phospholipid-based plasma membrane, its cell-permeability is rather poor (the IC 50 against the growth of human cancer cells such as A549 is around 13 μM). In an attempt to boost its anti-cancer activity, hopefully by increasing its cell-permeability through abolishing the negative charge, yet keeping its water-solubility, here we synthesized a 1,2,3-triazolyl ester of Toradol through "Click Chemistry". The resultant water-soluble "azo" derivative called "15K" was found to be over 500 times more potent than Toradol with the IC 50 around 24 nM against the PAK1-dependent growth of A549 cancer cells, inactivating PAK1 in cell culture with the apparent IC 50 around 65 nM, and inhibiting COX-2 in vitro with the IC 50 around 6 nM. Furthermore, the Click Chemistry boosts the anti-cancer activity of Ketorolac by 5000 times against the PAK1-independent growth of B16F10 melanoma cells. Using a multi-drug-resistant (MDR) cancer cell line (EMT6), we found that the esterization of Ketorolac boosts its cell-permeability by at least 10 folds. Thus, the Click Chemistry dramatically boosts the anti-cancer activity of Ketorolac, at least in three ways: increasing its cell-permeability, the anti-PAK1 activity of R-form and anti-COX-2 activity of S-form. The resultant "15K" is so far among the most potent PAK1-blockers, and therefore would be potentially useful for the therapy of many different PAK1-dependent diseases/disorders such as cancers. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Regulatory T cells and type 2 innate lymphoid cell-dependent asthma.

PubMed

Aron, J L; Akbari, O

2017-08-01

Group 2 innate lymphoid cells (ILC2s) are a recently identified group of cells with the potent capability to produce Th2-type cytokines such as interleukin (IL)-5 and IL-13. Several studies suggest that ILC2s play an important role in the development of allergic diseases and asthma. Activation of pulmonary ILC2s in murine models lacking T and B cells induces eosinophilia and airway hyper-reactivity (AHR), which are cardinal features of asthma. More importantly, numerous recent studies have highlighted the role of ILC2s in asthma persistence and exacerbation among human subjects, and thus, regulation of pulmonary ILC2s is a major area of investigation aimed at curbing allergic lung inflammation and exacerbation. Emerging evidence reveals that a group of regulatory T cells, induced Tregs (iTregs), effectively suppress the production of ILC2-driven, pro-inflammatory cytokines IL-5 and IL-13. The inhibitory effects of iTregs are blocked by preventing direct cellular contact or by inhibiting the ICOS-ICOS-ligand (ICOSL) pathway, suggesting that both direct contact and ICOS-ICOSL interaction are important in the regulation of ILC2 function. Also, cytokines such as IL-10 and TGF-β1 significantly reduce cytokine secretion by ILC2s. Altogether, these new findings uncover iTregs as potent regulators of ILC2 activation and implicate their utility as a therapeutic approach for the treatment of ILC2-mediated allergic asthma and respiratory disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amano, Masayuki; Miguel Salcedo-Gómez, Pedro; Yedidi, Ravikiran S.

We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014–0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2ROD. Under the selection condition, where HIV-1NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no variants highly resistant against GRL-09510more » emerged over long-term in vitro passage of the virus. Crystallographic analysis demonstrated that the Crwn-THF moiety of GRL-09510 forms strong hydrogen-bond-interactions with HIV-1 protease (PR) active-site amino acids and is bulkier with a larger contact surface, making greater van der Waals contacts with PR than the bis-THF moiety of darunavir. The present data demonstrate that GRL-09510 has favorable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants, that the newly generated P2-Crwn-THF moiety confers highly desirable anti-HIV-1 potency. The use of the novel Crwn-THF moiety sheds lights in the design of novel PIs.« less

Transition Metal Free C-N Bond Forming Dearomatizations and Aryl C-H Aminations by in Situ Release of a Hydroxylamine-Based Aminating Agent.

PubMed

Farndon, Joshua J; Ma, Xiaofeng; Bower, John F

2017-10-11

We outline a simple protocol that accesses directly unprotected secondary amines by intramolecular C-N bond forming dearomatization or aryl C-H amination. The method is dependent on the generation of a potent electrophilic aminating agent released by in situ deprotection of O-Ts activated N-Boc hydroxylamines.

Tumor cell-derived microparticles: a new form of cancer vaccine.

PubMed

Zhang, Huafeng; Huang, Bo

2015-08-01

For cancer vaccines, tumor antigen availability is currently not an issue due to technical advances. However, the generation of optimal immune stimulation during vaccination is challenging. We have recently demonstrated that tumor cell-derived microparticles (MP) can function as a new form of potent cancer vaccine by efficiently activating type I interferon pathway in a cGAS/STING dependent manner.

Silicon carbide semiconductor device fabrication and characterization

NASA Technical Reports Server (NTRS)

Davis, R. F.; Das, K.

1990-01-01

A number of basic building blocks i.e., rectifying and ohmic contacts, implanted junctions, MOS capacitors, pnpn diodes and devices, such as, MESFETs on both alpha and beta SiC films were fabricated and characterized. Gold forms a rectifying contact on beta SiC. Since Au contacts degrade at high temperatures, these are not considered to be suitable for high temperature device applications. However, it was possible to utilize Au contact diodes for electrically characterizing SiC films. Preliminary work indicates that sputtered Pt or Pt/Si contacts on beta SiC films are someways superior to Au contacts. Sputtered Pt layers on alpha SiC films form excellent rectifying contacts, whereas Ni layers following anneal at approximately 1050 C provide an ohmic contact. It has demonstrated that ion implantation of Al in substrates held at 550 C can be successfully employed for the fabrication of rectifying junction diodes. Feasibility of fabricating pnpn diodes and platinum gated MESFETs on alpha SiC films was also demonstrated.

Voltage Controlled Hot Carrier Injection Enables Ohmic Contacts Using Au Island Metal Films on Ge.

PubMed

Ganti, Srinivas; King, Peter J; Arac, Erhan; Dawson, Karl; Heikkilä, Mikko J; Quilter, John H; Murdoch, Billy; Cumpson, Peter; O'Neill, Anthony

2017-08-23

We introduce a new approach to creating low-resistance metal-semiconductor ohmic contacts, illustrated using high conductivity Au island metal films (IMFs) on Ge, with hot carrier injection initiated at low applied voltage. The same metallization process simultaneously allows ohmic contact to n-Ge and p-Ge, because hot carriers circumvent the Schottky barrier formed at metal/n-Ge interfaces. A 2.5× improvement in contact resistivity is reported over previous techniques to achieve ohmic contact to both n- and p- semiconductor. Ohmic contacts at 4.2 K confirm nonequilibrium current transport. Self-assembled Au IMFs are strongly orientated to Ge by annealing near the Au/Ge eutectic temperature. Au IMF nanostructures form, provided the Au layer is below a critical thickness. We anticipate that optimized IMF contacts may have applicability to many material systems. Optimizing this new paradigm for metal-semiconductor contacts offers the prospect of improved nanoelectronic systems and the study of voltage controlled hot holes and electrons.

Two M-T hook residues greatly improve the antiviral activity and resistance profile of the HIV-1 fusion inhibitor SC29EK

PubMed Central

2014-01-01

Background Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1 gp41 such as T20 (Enfuvirtide) and C34 are potent viral fusion inhibitors. We have recently found that two N-terminal residues (Met115 and Thr116) of CHR peptides form a unique M-T hook structure that can greatly enhance the binding and anti-HIV activity of inhibitors. Here, we applied two M-T hook residues to optimize SC29EK, an electrostatically constrained peptide inhibitor with a potent anti-HIV activity. Results The resulting peptide MT-SC29EK showed a dramatically increased binding affinity and could block the six-helical bundle (6-HB) formation more efficiently. As expected, MT-SC29EK potently inhibited HIV-1 entry and infection, especially against those T20- and SC29EK-resistant HIV-1 variants. More importantly, MT-SC29EK and its short form (MT-SC22EK) suffered from the difficulty to induce HIV-1 resistance during the in vitro selection, suggesting their high genetic barriers to the development of resistance. Conclusions Our studies have verified the M-T hook structure as a vital strategy to design novel HIV-1 fusion inhibitors and offered an ideal candidate for clinical development. PMID:24884671

Phorbol Ester Effects on Neurotransmission: Interaction with Neurotransmitters and Calcium in Smooth Muscle

NASA Astrophysics Data System (ADS)

Baraban, Jay M.; Gould, Robert J.; Peroutka, Stephen J.; Snyder, Solomon H.

1985-01-01

Stimulation of the phosphatidylinositol cycle by neurotransmitters generates diacylglycerol, an activator of protein kinase C, which may regulate some forms of neurotransmission. Phorbol esters, potent inflammatory and tumorpromoting compounds, also activate protein kinase C. We demonstrate potent and selective effects of phorbol esters on smooth muscle, indicating a role for protein kinase C in neurotransmission. In rat vas deferens and dog basilar artery, phorbol esters synergize with calcium to mimic the contractile effects of neurotransmitters that act through the phosphatidylinositol cycle. In guinea pig ileum and rat uterus, phorbol esters block contractions produced by these neurotransmitters.

Selling brand MD.

PubMed

Hudson, T

1999-08-01

Health care is more than local, of course: It's personal. Recognizing the connections between doctors and patients as a potent form of brand loyalty, health systems are looking for ways to leverage those bonds--and encourage new ones--with special marketing campaigns.

Canine bombesin-like gastrin releasing peptides stimulate gastrin release and acid secretion in the dog.

PubMed Central

Bunnett, N W; Clark, B; Debas, H T; Del Milton, R C; Kovacs, T O; Orloff, M S; Pappas, T N; Reeve, J R; Rivier, J E; Walsh, J H

1985-01-01

The synthetic mammalian bombesin-like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose-dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml-1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency. PMID:3839849

Large-scale unassisted smoking cessation over 50 years: lessons from history for endgame planning in tobacco control.

PubMed

Chapman, Simon; Wakefield, Melanie A

2013-05-01

In the 50 years since the twentieth century's smoking epidemic began to decline from the beginning of the 1960s, hundreds of millions of smokers around the world have stopped smoking permanently. Overwhelmingly, most stopped without any formal assistance in the form of medication or professional assistance, including many millions of former heavy smokers. Nascent discussion about national and global tobacco endgame scenarios is dominated by an assumption that transitioning from cigarettes to alternative forms of potent, consumer-acceptable forms of nicotine will be essential to the success of endgames. This appears to uncritically assume (1) the hardening hypothesis: that as smoking prevalence moves toward and below 10%, the remaining smokers will be mostly deeply addicted, and will be largely unable to stop smoking unless they are able to move to other forms of 'clean' nicotine addiction such as e-cigarettes and more potent forms of nicotine replacement; and (2) an overly medicalised view of smoking cessation that sees unassisted cessation as both inefficient and inhumane. In this paper, we question these assumptions. We also note that some vanguard nations which continue to experience declining smoking prevalence have long banned smokeless tobacco and non-therapeutic forms of nicotine delivery. We argue that there are potentially risky consequences of unravelling such bans when history suggests that large-scale cessation is demonstrably possible.

Large-scale unassisted smoking cessation over 50 years: lessons from history for endgame planning in tobacco control

PubMed Central

Chapman, Simon; Wakefield, Melanie A

2013-01-01

In the 50 years since the twentieth century's smoking epidemic began to decline from the beginning of the 1960s, hundreds of millions of smokers around the world have stopped smoking permanently. Overwhelmingly, most stopped without any formal assistance in the form of medication or professional assistance, including many millions of former heavy smokers. Nascent discussion about national and global tobacco endgame scenarios is dominated by an assumption that transitioning from cigarettes to alternative forms of potent, consumer-acceptable forms of nicotine will be essential to the success of endgames. This appears to uncritically assume (1) the hardening hypothesis: that as smoking prevalence moves toward and below 10%, the remaining smokers will be mostly deeply addicted, and will be largely unable to stop smoking unless they are able to move to other forms of ‘clean’ nicotine addiction such as e-cigarettes and more potent forms of nicotine replacement; and (2) an overly medicalised view of smoking cessation that sees unassisted cessation as both inefficient and inhumane. In this paper, we question these assumptions. We also note that some vanguard nations which continue to experience declining smoking prevalence have long banned smokeless tobacco and non-therapeutic forms of nicotine delivery. We argue that there are potentially risky consequences of unravelling such bans when history suggests that large-scale cessation is demonstrably possible. PMID:23591504

Explosive bulk charge

DOEpatents

Miller, Jacob Lee

2015-04-21

An explosive bulk charge, including: a first contact surface configured to be selectively disposed substantially adjacent to a structure or material; a second end surface configured to selectively receive a detonator; and a curvilinear side surface joining the first contact surface and the second end surface. The first contact surface, the second end surface, and the curvilinear side surface form a bi-truncated hemispherical structure. The first contact surface, the second end surface, and the curvilinear side surface are formed from an explosive material. Optionally, the first contact surface and the second end surface each have a substantially circular shape. Optionally, the first contact surface and the second end surface consist of planar structures that are aligned substantially parallel or slightly tilted with respect to one another. The curvilinear side surface has one of a smooth curved geometry, an elliptical geometry, and a parabolic geometry.

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.

Pronounced Photovoltaic Response from Multi-layered MoTe2 Phototransistor with Asymmetric Contact Form.

PubMed

Liu, Junku; Guo, Nan; Xiao, Xiaoyang; Zhang, Kenan; Jia, Yi; Zhou, Shuyun; Wu, Yang; Li, Qunqing; Xiao, Lin

2017-11-22

In this study, we fabricate air-stable p-type multi-layered MoTe 2 phototransistor using Au as electrodes, which shows pronounced photovoltaic response in off-state with asymmetric contact form. By analyzing the spatially resolved photoresponse using scanning photocurrent microscopy, we found that the potential steps are formed in the vicinity of the electrodes/MoTe 2 interface due to the doping of the MoTe 2 by the metal contacts. The potential step dominates the separation of photoexcited electron-hole pairs in short-circuit condition or with small V sd biased. Based on these findings, we infer that the asymmetric contact cross-section between MoTe 2 -source and MoTe 2 -drain electrodes is the reason to form non-zero net current and photovoltaic response. Furthermore, MoTe 2 phototransistor shows a faster response in short-circuit condition than that with higher biased V sd within sub-millisecond, and its spectral range can be extended to the infrared end of 1550 nm.

Defect-free erbium silicide formation using an ultrathin Ni interlayer.

PubMed

Choi, Juyun; Choi, Seongheum; Kang, Yu-Seon; Na, Sekwon; Lee, Hoo-Jeong; Cho, Mann-Ho; Kim, Hyoungsub

2014-08-27

An ultrathin Ni interlayer (∼1 nm) was introduced between a TaN-capped Er film and a Si substrate to prevent the formation of surface defects during thermal Er silicidation. A nickel silicide interfacial layer formed at low temperatures and incurred uniform nucleation and the growth of a subsequently formed erbium silicide film, effectively inhibiting the generation of recessed-type surface defects and improving the surface roughness. As a side effect, the complete transformation of Er to erbium silicide was somewhat delayed, and the electrical contact property at low annealing temperatures was dominated by the nickel silicide phase with a high Schottky barrier height. After high-temperature annealing, the early-formed interfacial layer interacted with the growing erbium silicide, presumably forming an erbium silicide-rich Er-Si-Ni mixture. As a result, the electrical contact property reverted to that of the low-resistive erbium silicide/Si contact case, which warrants a promising source/drain contact application for future high-performance metal-oxide-semiconductor field-effect transistors.

Pronounced Photovoltaic Response from Multi-layered MoTe2 Phototransistor with Asymmetric Contact Form

NASA Astrophysics Data System (ADS)

Liu, Junku; Guo, Nan; Xiao, Xiaoyang; Zhang, Kenan; Jia, Yi; Zhou, Shuyun; Wu, Yang; Li, Qunqing; Xiao, Lin

2017-11-01

In this study, we fabricate air-stable p-type multi-layered MoTe2 phototransistor using Au as electrodes, which shows pronounced photovoltaic response in off-state with asymmetric contact form. By analyzing the spatially resolved photoresponse using scanning photocurrent microscopy, we found that the potential steps are formed in the vicinity of the electrodes/MoTe2 interface due to the doping of the MoTe2 by the metal contacts. The potential step dominates the separation of photoexcited electron-hole pairs in short-circuit condition or with small V sd biased. Based on these findings, we infer that the asymmetric contact cross-section between MoTe2-source and MoTe2-drain electrodes is the reason to form non-zero net current and photovoltaic response. Furthermore, MoTe2 phototransistor shows a faster response in short-circuit condition than that with higher biased V sd within sub-millisecond, and its spectral range can be extended to the infrared end of 1550 nm.

Magnitude and nature of carbohydrate-aromatic interactions in fucose-phenol and fucose-indole complexes: CCSD(T) level interaction energy calculations.

PubMed

Tsuzuki, Seiji; Uchimaru, Tadafumi; Mikami, Masuhiro

2011-10-20

The CH/π contact structures of the fucose-phenol and fucose-indole complexes and the stabilization energies by formation of the complexes (E(form)) were studied by ab initio molecular orbital calculations. The three types of interactions (CH/π and OH/π interactions and OH/O hydrogen bonds) were compared and evaluated in a single molecular system and at the same level of theory. The E(form) calculated for the most stable CH/π contact structure of the fucose-phenol complex at the CCSD(T) level (-4.9 kcal/mol) is close to that for the most stable CH/π contact structure of the fucose-benzene complex (-4.5 kcal/mol). On the other hand the most stable CH/π contact structure of the fucose-indole complex has substantially larger E(form) (-6.5 kcal/mol). The dispersion interaction is the major source of the attraction in the CH/π contact structures of the fucose-phenol and fucose-indole complexes as in the case of the fucose-benzene complex. The electrostatic interactions in the CH/π contact structures are small (less than 1.5 kcal/mol). The nature of the interactions between the nonpolar surface of the carbohydrate and aromatic rings is completely different from that of the conventional hydrogen bonds where the electrostatic interaction is the major source of the attraction. The distributed multipole analysis and DFT-SATP analysis show that the dispersion interactions in the CH/π contact structure of fucose-indole complex are substantially larger than those in the CH/π contact structures of fucose-benzene and fucose-phenol complexes. The large dispersion interactions are responsible for the large E(form) for the fucose-indole complex.

Contact formation and gettering of precipitated impurities by multiple firing during semiconductor device fabrication

DOEpatents

Sopori, Bhushan

2014-05-27

Methods for contact formation and gettering of precipitated impurities by multiple firing during semiconductor device fabrication are provided. In one embodiment, a method for fabricating an electrical semiconductor device comprises: a first step that includes gettering of impurities from a semiconductor wafer and forming a backsurface field; and a second step that includes forming a front contact for the semiconductor wafer, wherein the second step is performed after completion of the first step.

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT... heating water subcategory are processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer during plastics molding and forming. ...

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT... heating water subcategory are processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer during plastics molding and forming. ...

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.

Where the lake meets the sea: strong reproductive isolation is associated with adaptive divergence between lake resident and anadromous three-spined sticklebacks.

PubMed

Ravinet, Mark; Hynes, Rosaleen; Poole, Russell; Cross, Tom F; McGinnity, Phil; Harrod, Chris; Prodöhl, Paulo A

2015-01-01

Contact zones between divergent forms of the same species are often characterised by high levels of phenotypic diversity over small geographic distances. What processes are involved in generating such high phenotypic diversity? One possibility is that introgression and recombination between divergent forms in contact zones results in greater phenotypic and genetic polymorphism. Alternatively, strong reproductive isolation between forms may maintain distinct phenotypes, preventing homogenisation by gene flow. Contact zones between divergent freshwater-resident and anadromous stickleback (Gasterosteus aculeatus L.) forms are numerous and common throughout the species distribution, offering an opportunity to examine these contrasting hypotheses in greater detail. This study reports on an interesting new contact zone located in a tidally influenced lake catchment in western Ireland, characterised by high polymorphism for lateral plate phenotypes. Using neutral and QTL-linked microsatellite markers, we tested whether the high diversity observed in this contact zone arose as a result of introgression or reproductive isolation between divergent forms: we found strong support for the latter hypothesis. Three phenotypic and genetic clusters were identified, consistent with two divergent resident forms and a distinct anadromous completely plated population that migrates in and out of the system. Given the strong neutral differentiation detected between all three morphotypes (mean FST = 0.12), we hypothesised that divergent selection between forms maintains reproductive isolation. We found a correlation between neutral genetic and adaptive genetic differentiation that support this. While strong associations between QTL linked markers and phenotypes were also observed in this wild population, our results support the suggestion that such associations may be more complex in some Atlantic populations compared to those in the Pacific. These findings provide an important foundation for future work investigating the dynamics of gene flow and adaptive divergence in this newly discovered stickleback contact zone.

Where the Lake Meets the Sea: Strong Reproductive Isolation Is Associated with Adaptive Divergence between Lake Resident and Anadromous Three-Spined Sticklebacks

PubMed Central

Ravinet, Mark; Hynes, Rosaleen; Poole, Russell; Cross, Tom F.; McGinnity, Phil; Harrod, Chris; Prodöhl, Paulo A.

2015-01-01

Contact zones between divergent forms of the same species are often characterised by high levels of phenotypic diversity over small geographic distances. What processes are involved in generating such high phenotypic diversity? One possibility is that introgression and recombination between divergent forms in contact zones results in greater phenotypic and genetic polymorphism. Alternatively, strong reproductive isolation between forms may maintain distinct phenotypes, preventing homogenisation by gene flow. Contact zones between divergent freshwater-resident and anadromous stickleback (Gasterosteus aculeatus L.) forms are numerous and common throughout the species distribution, offering an opportunity to examine these contrasting hypotheses in greater detail. This study reports on an interesting new contact zone located in a tidally influenced lake catchment in western Ireland, characterised by high polymorphism for lateral plate phenotypes. Using neutral and QTL-linked microsatellite markers, we tested whether the high diversity observed in this contact zone arose as a result of introgression or reproductive isolation between divergent forms: we found strong support for the latter hypothesis. Three phenotypic and genetic clusters were identified, consistent with two divergent resident forms and a distinct anadromous completely plated population that migrates in and out of the system. Given the strong neutral differentiation detected between all three morphotypes (mean FST = 0.12), we hypothesised that divergent selection between forms maintains reproductive isolation. We found a correlation between neutral genetic and adaptive genetic differentiation that support this. While strong associations between QTL linked markers and phenotypes were also observed in this wild population, our results support the suggestion that such associations may be more complex in some Atlantic populations compared to those in the Pacific. These findings provide an important foundation for future work investigating the dynamics of gene flow and adaptive divergence in this newly discovered stickleback contact zone. PMID:25874617

Footwear contact dermatitis from dimethyl fumarate.

PubMed

Švecová, Danka; Šimaljakova, Maria; Doležalová, Anna

2013-07-01

Dimethyl fumarate (DMF) is an effective inhibitor of mold growth. In very low concentrations, DMF is a potent sensitizer that can cause severe allergic contact dermatitis (ACD). It has been identified as the agent responsible for furniture contact dermatitis in Europe. The aim of this study was to evaluate patients in Slovakia with footwear ACD associated with DMF, with regard to clinical manifestations, patch test results, and results of chemical analysis of their footwear. Nine patients with suspected footwear contact dermatitis underwent patch testing with the following allergens: samples of their own footwear, commercial DMF, the European baseline, shoe screening, textile and leather dye screening, and industrial biocides series. The results were recorded according to international guidelines. The content of DMF in footwear and anti-mold sachets was analyzed using gas chromatography and mass spectrometry. Acute ACD was observed in nine Caucasian female patients. All patients developed delayed sensitization, as demonstrated by positive patch testing using textile footwear lining. Seven patients were patch tested with 0.1% DMF, and all seven were positive. Chemical analysis of available footwear showed that DMF was present in very high concentrations (25-80 mg/Kg). Dimethyl fumarate is a new footwear allergen and was responsible for severe ACD in our patients. To avoid an increase in the number of cases, the already approved European preventive measures should be accepted and commonly employed. © 2013 The International Society of Dermatology.

Stereoselective Effects of Abused “Bath Salt” Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation

PubMed Central

Gannon, Brenda M.; Williamson, Adrian; Suzuki, Masaki; Rice, Kenner C.

2016-01-01

3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit “bath salts” products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(−)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(−)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(−)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(−)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(−)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse. PMID:26769917

Immunization With Fc-Based Recombinant Epstein–Barr Virus gp350 Elicits Potent Neutralizing Humoral Immune Response in a BALB/c Mice Model

PubMed Central

Zhao, Bingchun; Zhang, Xiao; Krummenacher, Claude; Song, Shuo; Gao, Ling; Zhang, Haojiong; Xu, Miao; Feng, Lin; Feng, Qisheng; Zeng, Musheng; Xu, Yuting; Zeng, Yixin

2018-01-01

Epstein–Barr virus (EBV) was the first human virus proved to be closely associated with tumor development, such as lymphoma, nasopharyngeal carcinoma, and EBV-associated gastric carcinoma. Despite many efforts to develop prophylactic vaccines against EBV infection and diseases, no candidates have succeeded in effectively blocking EBV infection in clinical trials. Previous investigations showed that EBV gp350 plays a pivotal role in the infection of B-lymphocytes. Nevertheless, using monomeric gp350 proteins as antigens has not been effective in preventing infection. Multimeric forms of the antigen are more potently immunogenic than monomers; however, the multimerization elements used in previous constructs are not approved for human clinical trials. To prepare a much-needed EBV prophylactic vaccine that is potent, safe, and applicable, we constructed an Fc-based form of gp350 to serve as a dimeric antigen. Here, we show that the Fc-based gp350 antigen exhibits dramatically enhanced immunogenicity compared with wild-type gp350 protein. The complete or partial gp350 ectodomain was fused with the mouse IgG2a Fc domain. Fusion with the Fc domain did not impair gp350 folding, binding to a conformation-dependent neutralizing antibody (nAb) and binding to its receptor by enzyme-linked immunosorbent assay and surface plasmon resonance. Specific antibody titers against gp350 were notably enhanced by immunization with gp350-Fc dimers compared with gp350 monomers. Furthermore, immunization with gp350-Fc fusion proteins elicited potent nAbs against EBV. Our data strongly suggest that an EBV gp350 vaccine based on Fc fusion proteins may be an efficient candidate to prevent EBV infection in clinical applications. PMID:29765376

Stereoselective Effects of Abused "Bath Salt" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation.

PubMed

Gannon, Brenda M; Williamson, Adrian; Suzuki, Masaki; Rice, Kenner C; Fantegrossi, William E

2016-03-01

3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit "bath salts" products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(-)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(-)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(-)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(-)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(-)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse. U.S. Government work not protected by U.S. copyright.

Peptide fragments of a beta-defensin derivative with potent bactericidal activity.

PubMed

Reynolds, Natalie L; De Cecco, Martin; Taylor, Karen; Stanton, Chloe; Kilanowski, Fiona; Kalapothakis, Jason; Seo, Emily; Uhrin, Dusan; Campopiano, Dominic; Govan, John; Macmillan, Derek; Barran, Perdita; Dorin, Julia R

2010-05-01

Beta-defensins are known to be both antimicrobial and able to chemoattract various immune cells. Although the sequences of paralogous genes are not highly conserved, the core defensin structure is retained. Defb14-1C(V) has bactericidal activity similar to that of its parent peptide (murine beta-defensin Defb14) despite all but one of the canonical six cysteines being replaced with alanines. The 23-amino-acid N-terminal half of Defb14-1C(V) is a potent antimicrobial while the C-terminal half is not. Here, we use a library of peptide derivatives to demonstrate that the antimicrobial activity can be localized to a particular region. Overlapping fragments of the N-terminal region were tested for their ability to kill Gram-positive and Gram-negative bacteria. We demonstrate that the most N-terminal fragments (amino acids 1 to 10 and 6 to 17) are potent antimicrobials against Gram-negative bacteria whereas fragments based on sequence more C terminal than amino acid 13 have very poor activity against both Gram-positive and -negative types. We further test a series of N-terminal deletion peptides in both their monomeric and dimeric forms. We find that bactericidal activity is lost against both Gram types as the deletion region increases, with the point at which this occurs varying between bacterial strains. The dimeric form of the peptides is more resistant to the peptide deletions, but this is not due just to increased charge. Our results indicate that the primary sequence, together with structure, is essential in the bactericidal action of this beta-defensin derivative peptide and importantly identifies a short fragment from the peptide that is a potent bactericide.

Peptide Fragments of a β-Defensin Derivative with Potent Bactericidal Activity ▿

PubMed Central

Reynolds, Natalie L.; De Cecco, Martin; Taylor, Karen; Stanton, Chloe; Kilanowski, Fiona; Kalapothakis, Jason; Seo, Emily; Uhrin, Dusan; Campopiano, Dominic; Govan, John; Macmillan, Derek; Barran, Perdita; Dorin, Julia R.

2010-01-01

β-Defensins are known to be both antimicrobial and able to chemoattract various immune cells. Although the sequences of paralogous genes are not highly conserved, the core defensin structure is retained. Defb14-1CV has bactericidal activity similar to that of its parent peptide (murine β-defensin Defb14) despite all but one of the canonical six cysteines being replaced with alanines. The 23-amino-acid N-terminal half of Defb14-1CV is a potent antimicrobial while the C-terminal half is not. Here, we use a library of peptide derivatives to demonstrate that the antimicrobial activity can be localized to a particular region. Overlapping fragments of the N-terminal region were tested for their ability to kill Gram-positive and Gram-negative bacteria. We demonstrate that the most N-terminal fragments (amino acids 1 to 10 and 6 to 17) are potent antimicrobials against Gram-negative bacteria whereas fragments based on sequence more C terminal than amino acid 13 have very poor activity against both Gram-positive and -negative types. We further test a series of N-terminal deletion peptides in both their monomeric and dimeric forms. We find that bactericidal activity is lost against both Gram types as the deletion region increases, with the point at which this occurs varying between bacterial strains. The dimeric form of the peptides is more resistant to the peptide deletions, but this is not due just to increased charge. Our results indicate that the primary sequence, together with structure, is essential in the bactericidal action of this β-defensin derivative peptide and importantly identifies a short fragment from the peptide that is a potent bactericide. PMID:20176896

Coated semiconductor devices for neutron detection

DOEpatents

Klann, Raymond T.; McGregor, Douglas S.

2002-01-01

A device for detecting neutrons includes a semi-insulated bulk semiconductor substrate having opposed polished surfaces. A blocking Schottky contact comprised of a series of metals such as Ti, Pt, Au, Ge, Pd, and Ni is formed on a first polished surface of the semiconductor substrate, while a low resistivity ("ohmic") contact comprised of metals such as Au, Ge, and Ni is formed on a second, opposed polished surface of the substrate. In one embodiment, n-type low resistivity pinout contacts comprised of an Au/Ge based eutectic alloy or multi-layered Pd/Ge/Ti/Au are also formed on the opposed polished surfaces and in contact with the Schottky and ohmic contacts. Disposed on the Schottky contact is a neutron reactive film, or coating, for detecting neutrons. The coating is comprised of a hydrogen rich polymer, such as a polyolefin or paraffin; lithium or lithium fluoride; or a heavy metal fissionable material. By varying the coating thickness and electrical settings, neutrons at specific energies can be detected. The coated neutron detector is capable of performing real-time neutron radiography in high gamma fields, digital fast neutron radiography, fissile material identification, and basic neutron detection particularly in high radiation fields.

Composite drill pipe and method for forming same

DOEpatents

Leslie, James C; Leslie, II, James C; Heard, James; Truong, Liem V; Josephson, Marvin

2012-10-16

A lightweight and durable drill pipe string capable of short radius drilling formed using a composite pipe segment formed to include tapered wall thickness ends that are each defined by opposed frustoconical surfaces conformed for self-aligning receipt and intimate bonding contact within an annular space between corresponding surfaces of a coaxially nested set of metal end pieces and a set of nonconductive sleeves. The distal peripheries of the nested end pieces and sleeves are then welded to each other and the sandwiched and bonded portions are radially pinned. The composite segment may include imbedded conductive leads and the axial end portions of the end pieces are shaped to form a threaded joint with the next pipe assembly that includes contact rings in the opposed surfaces of the pipe joint for contact together.

Nanoscale roughness contact in a slider-disk interface.

PubMed

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

2009-07-15

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

Binding regularities in complexes of transcription factors with operator DNA: homeodomain family.

PubMed

Chirgadze, Yu N; Zheltukhin, E I; Polozov, R V; Sivozhelezov, V S; Ivanov, V V

2009-06-01

In order to disclose general regularities of binding in homeodomain-DNA complexes we considered five of them and extended the observed regularities over the entire homeodomain family. The five complexes have been selected by similarity of protein structures and patterns of contacting residues. Their long range interactions and interfaces were compared. The long-range stage of the recognition process was characterized by electrostatic potentials about 5 Angstrom away from molecular surfaces of protein or DNA. For proteins, clear positive potential is displayed only at the side contacting the DNA. The double-chained DNA molecule displays a rather strong negative potential, especially in their grooves. Thus, a functional role of electrostatics is a guiding of the protein into the DNA major groove, so the protein and DNA could form a loose non-specific complex. At the close-range stage, neutralization of the phosphate charges by positively charged residues is necessary for decreasing the strong electrostatic potential of DNA, allowing nucleotide bases to participate in the formation of protein-DNA atomic contacts in the interface. The recognizing alpha-helix of protein was shown to form both invariant and variable groups of contacts with DNA by means of certain specific side groups. The invariant contacts included highly specific protein-DNA hydrogen bonds between asparagine and adenine, nonpolar contacts of hydrophobic amino acids serving as a stereochemical barrier for fixing the protein factor on DNA, and an interface cluster of water molecules providing local conformational mobility necessary for the dissociation process. There is a unique water molecule within the interface that is conservative and located at the interface center. Invariant contacts of the proteins are mostly formed with the TAAT motif of the promoter DNA forward strand. While the invariant contacts specify the family of homeodomains, the variable contacts that are formed with the reverse strand of DNA provide specificity of individual complexes within the homeodomain family.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Socha, Aaron; Singh, Seema; Simmons, Blake A.

Methods and compositions are provided for synthesizing ionic liquids from lignin derived compounds comprising: contacting a starting material comprising lignin with a depolymerization agent to depolymerize the lignin and form a mixture of aldehyde containing compounds; contacting the mixture of aldehyde containing compounds with an amine under conditions suitable to convert the mixture of aldehyde containing compounds to a mixture of amine containing compounds; and contacting the mixture of amine containing compounds with an acid under conditions suitable to form an ammonium salt, thereby preparing the ionic liquid.

TWISTED RIBBON FUEL ELEMENT

DOEpatents

Breden, C.R.; Schultz, A.B.

1961-06-01

A reactor core formed of bundles of parallel fuel elements in the form of ribbons is patented. The fuel ribbons are twisted about their axes so as to have contact with one another at regions spaced lengthwise of the ribbons and to be out of contact with one another at locations between these spaced regions. The contact between the ribbons is sufficient to allow them to be held together in a stable bundle in a containing tube without intermediate support, while permitting enough space between the ribbon for coolant flowing.

Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation.

PubMed

Danquah, Welbeck; Meyer-Schwesinger, Catherine; Rissiek, Björn; Pinto, Carolina; Serracant-Prat, Arnau; Amadi, Miriam; Iacenda, Domenica; Knop, Jan-Hendrik; Hammel, Anna; Bergmann, Philine; Schwarz, Nicole; Assunção, Joana; Rotthier, Wendy; Haag, Friedrich; Tolosa, Eva; Bannas, Peter; Boué-Grabot, Eric; Magnus, Tim; Laeremans, Toon; Stortelers, Catelijne; Koch-Nolte, Friedrich

2016-11-23

Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β). To further explore its function, we generated and characterized nanobodies against mouse P2X7 that effectively blocked (13A7) or potentiated (14D5) gating of the channel. Systemic injection of nanobody 13A7 in mice blocked P2X7 on T cells and macrophages in vivo and ameliorated experimental glomerulonephritis and allergic contact dermatitis. We also generated nanobody Dano1, which specifically inhibited human P2X7. In endotoxin-treated human blood, Dano1 was 1000 times more potent in preventing IL-1β release than small-molecule P2X7 antagonists currently in clinical development. Our results show that nanobody technology can generate potent, specific therapeutics against ion channels, confirm P2X7 as a therapeutic target for inflammatory disorders, and characterize a potent new drug candidate that targets P2X7. Copyright © 2016, American Association for the Advancement of Science.

Transition metal sensing by Toll-like receptor-4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators.

PubMed

Rachmawati, Dessy; Bontkes, Hetty J; Verstege, Marleen I; Muris, Joris; von Blomberg, B Mary E; Scheper, Rik J; van Hoogstraten, Ingrid M W

2013-06-01

Nickel was recently identified as a potent activator of dendritic cells through ligating with human Toll-like receptor (TLR)-4. Here, we studied an extended panel of transition metals neighbouring nickel in the periodic table of elements, for their capacity to activate human monocyte-derived dendritic cells (MoDCs). The panel included chromium, cobalt, and palladium, all of which are known to be frequent clinical sensitizers. MoDC activation was monitored by assessment of release of the pro-inflammatory mediator interleukin (IL)-8, a major downstream result of TLR ligation. Results The data obtained in the present study show that cobalt and palladium also have potent MoDC-activating capacities, whereas copper and zinc, but not iron and chromium, have low but distinct MoDC-activating potential. Involvement of endotoxin contamination in MoDC activation was excluded by Limulus assays and consistent stimulation in the presence of polymyxin B. The critical role of TLR4 in nickel-induced, cobalt-induced and palladium-induced activation was confirmed by essentially similar stimulatory patterns obtained in an HEK293 TLR4/MD2 transfectant cell line. Given the adjuvant role of costimulatory danger signals, the development of contact allergies to the stimulatory metals may be facilitated by signals from direct TLR4 ligation, whereas other metal sensitizers, such as chromium, may rather depend on microbial or tissue-derived cofactors to induce clinical sensitization. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cross-contact chain

NASA Technical Reports Server (NTRS)

Lieneweg, Udo (Inventor)

1988-01-01

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

Cross-contact chain

NASA Technical Reports Server (NTRS)

Lieneweg, U. (Inventor)

1986-01-01

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

[Dry hands (irritative contact dermatitis) in housewives which is not alleviated on cessation of domestic work: clinical varieties].

PubMed

Grimalt, F; Romaguera, C; Vilaplana, J; Mascaro, J

1988-01-01

There are three types of hand dermatitis in housewives. The most usual are cured when housework is stopped. Another type is that of housewife contact dermatitis which appears on pre-existing endogenous lesions such as dyshidrosis or nummular eczema. The third form is housewife hand contact dermatitis which appears, or coexists with, localized endogenous lesions of the hands. The last two forms are not cured when housework is stopped. In some cases the three forms may coexist or appear one after another. It is not usual for a person suffering from typical flexural atopic dermatitis to present with one of the described three forms of hand dermatitis. Nevertheless, without having some relationship to atopic diathesis no woman could suffer from any of these three forms of dermatitis. In spite of the lack of analytical data, everyday clinical facts (one example being these different forms of housewife hand dermatitis) suggest the need to accept a subgroup of cutaneous atopic diathesis.

The molecular basis of peanut allergy

USDA-ARS?s Scientific Manuscript database

Peanut allergens can trigger a potent and sometimes dangerous immune response in an increasing number of people. The molecular structures of these allergens form the basis for understanding this response. This review describes the currently known peanut allergen structures, and discusses how modif...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chanana, Anuja; Mahapatra, Santanu, E-mail: santanu@dese.iisc.ernet.in

Investigation of a transition metal dichalcogenide (TMD)-metal interface is essential for the effective functioning of monolayer TMD based field effect transistors. In this work, we employ the Density Functional Theory calculations to analyze the modulation of the electronic structure of monolayer WS{sub 2} with chlorine doping and the relative changes in the contact properties when interfaced with gold and palladium. We initially examine the atomic and electronic structures of pure and doped monolayer WS{sub 2} supercell and explore the formation of midgap states with band splitting near the conduction band edge. Further, we analyze the contact nature of the puremore » supercell with Au and Pd. We find that while Au is physiosorbed and forms n-type contact, Pd is chemisorped and forms p-type contact with a higher valence electron density. Next, we study the interface formed between the Cl-doped supercell and metals and observe a reduction in the Schottky barrier height (SBH) in comparison to the pure supercell. This reduction found is higher for Pd in comparison to Au, which is further validated by examining the charge transfer occurring at the interface. Our study confirms that Cl doping is an efficient mechanism to reduce the n-SBH for both Au and Pd, which form different types of contact with WS{sub 2}.« less

NASA interdisciplinary collaboration in tribology. A review of oxidational wear

NASA Technical Reports Server (NTRS)

Quinn, T. F. J.

1983-01-01

An in-depth review of oxidational wear of metals is presented. Special emphasis is given to a description of the concept of oxidational wear and the formulation of an Oxidational Wear Theory. The parallelism between the formation of an oxide film for dry contact conditions and the formation of other surface films for a lubricated contact is discussed. The description of oxidational wear is prefaced with a unification of wear modes into two major classes of mild and severe wear including both lubricated and dry contacts. Oxidational wear of metals is a class of mild wear where protective oxide films are formed at real areas of contact and during the time of contact at temperataure T sub c. When the oxide reaches a critical thickness, frequently in the range of 1 to 3 microns, the oxide breaks up and eventually appears as a wear particle. These oxides are preferentially formed on plateaux which alternately carry the load as they reach their critical thickness and are removed. If the system is operated at elevated temperatures, thick oxides can form both out of contact and between the plateaux. Temperature is important in determining the structure of the oxide film present. Spinel oxide (Fe3O4) which forms above 300 C is more protective than the lower temperature rhomobohedral (alpha-Fe2O3) oxide which is abrasive. An Oxidational Wear Theory is derived using a modified Archard wear law expressed in terms of activation energy (Qp) and Arrhenius constant (Ap).

Seal assembly

DOEpatents

Johnson, Roger Neal; Longfritz, William David

2001-01-01

A seal assembly that seals a gap formed by a groove comprises a seal body, a biasing element, and a connection that connects the seal body to the biasing element to form the seal assembly. The seal assembly further comprises a concave-shaped center section and convex-shaped contact portions at each end of the seal body. The biasing element is formed from an elastic material and comprises a convex-shaped center section and concave-shaped biasing zones that are opposed to the convex-shaped contact portions. The biasing element is adapted to be compressed to change a width of the seal assembly from a first width to a second width that is smaller than the first width. In the compressed state, the seal assembly can be disposed in the groove. After release of the compressing force, the seal assembly expands. The contact portions will move toward a surface of the groove and the biasing zones will move into contact with another surface of the groove. The biasing zones will bias the contact portions of the seal body against the surface of the groove.

Comparison of the surfaces and interfaces formed for sputter and electroless deposited gold contacts on CdZnTe

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.

2018-01-01

Cadmium zinc telluride (CdZnTe) is a leading sensor material for spectroscopic X/γ-ray imaging in the fields of homeland security, medical imaging, industrial analysis and astrophysics. The metal-semiconductor interface formed during contact deposition is of fundamental importance to the spectroscopic performance of the detector and is primarily determined by the deposition method. A multi-technique analysis of the metal-semiconductor interface formed by sputter and electroless deposition of gold onto (111) aligned CdZnTe is presented. Focused ion beam (FIB) cross section imaging, X-ray photoelectron spectroscopy (XPS) depth profiling and current-voltage (IV) analysis have been applied to determine the structural, chemical and electronic properties of the gold contacts. In a novel approach, principal component analysis has been employed on the XPS depth profiles to extract detailed chemical state information from different depths within the profile. It was found that electroless deposition forms a complicated, graded interface comprised of tellurium oxide, gold/gold telluride particulates, and cadmium chloride. This compared with a sharp transition from surface gold to bulk CdZnTe observed for the interface formed by sputter deposition. The electronic (IV) response for the detector with electroless deposited contacts was symmetric, but was asymmetric for the detector with sputtered gold contacts. This is due to the electroless deposition degrading the difference between the Cd- and Te-faces of the CdZnTe (111) crystal, whilst these differences are maintained for the sputter deposited gold contacts. This work represents an important step in the optimisation of the metal-semiconductor interface which currently is a limiting factor in the development of high resolution CdZnTe detectors.

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

PubMed

Mohan, Rayapudi Phani; Pai, Annappa Raghavendra Vivekananda

2015-01-01

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

Selective photooxidation of hydrocarbons in zeolites by oxygen

DOEpatents

Frei, Heinz; Blatter, Fritz; Sun, Hai

1998-01-01

A selective photooxidation process for the conversion of hydrocarbon molecules to partially oxygenated derivatives, which comprises the steps of adsorbing a hydrocarbon and oxygen onto a dehydrated zeolite support matrix to form a hydrocarbon-oxygen contact pair, and subsequently exposing the hydrocarbon-oxygen contact pair to visible light, thereby forming a partially oxygenated derivative.

Passivated contact formation using ion implantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, David L.; Stradins, Pauls; Nemeth, William

2018-05-29

Methods for forming passivated contacts include implanting compound-forming ions into a substrate to about a first depth below a surface of the substrate, and implanting dopant ions into the substrate to about a second depth below the surface. The second depth may be shallower than the first depth. The methods also include annealing the substrate.

Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses.

PubMed

Samarasekera, E J; Sawyer, L; Wonderling, D; Tucker, R; Smith, C H

2013-05-01

The majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta-analyses of randomized trial data of U.K.-licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta-analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22,028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice- and once-daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long-term efficacy and safety data available on topical interventions used for psoriasis. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Terminalia ferdinandiana Exell. Extracts inhibit the growth of body odour-forming bacteria.

PubMed

McManus, K; Wood, A; Wright, M H; Matthews, B; Greene, A C; Cock, I E

2017-10-01

Terminalia ferdinandiana extracts are potent growth inhibitors of many bacterial pathogens. They may also inhibit the growth of malodour-producing bacteria and thus be useful deodorant components, although this is yet to be tested. Terminalia ferdinandiana fruit and leaf solvent extracts were investigated by disc diffusion and liquid dilution MIC assays against the most significant bacterial contributors to axillary and plantar malodour formation. Toxicity was determined using the Artemia franciscana nauplii bioassay. Non-targeted HPLC separation of the methanolic leaf extract coupled to high-resolution time-of-flight (TOF) mass spectroscopy was used for the identification and characterization of individual components in the extract. The T. ferdinandiana leaf extracts were the most potent bacterial growth inhibitors. The leaf methanolic extract was particularly potent, with low MIC values against C. jeikeium (233 μg mL -1 ), S. epidermidis (220 μg mL -1 ), P. acnes (625 μg mL -1 ) and B. linens (523 μg mL -1 ). The aqueous and ethyl acetate leaf extracts were also potent growth inhibitors of C. jeikeium and S. epidermidis (MICs < 1000 μg mL -1 ). In comparison, the fruit extracts were substantially less potent antibacterial agents, although still with MIC values indicative of moderate growth inhibitory activity. All T. ferdinandiana leaf extracts were non-toxic in the Artemia franciscana bioassay. Non-biased phytochemical analysis of the methanolic leaf extract revealed the presence of high levels of and high diversity of tannins and high levels of the flavone luteolin. The low toxicity of the T. ferdinandiana leaf extracts and their potent growth inhibition of axillary and plantar malodour-producing bacteria indicate their potential as deodorant components. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Vps39 Interacts with Tom40 to Establish One of Two Functionally Distinct Vacuole-Mitochondria Contact Sites.

PubMed

González Montoro, Ayelén; Auffarth, Kathrin; Hönscher, Carina; Bohnert, Maria; Becker, Thomas; Warscheid, Bettina; Reggiori, Fulvio; van der Laan, Martin; Fröhlich, Florian; Ungermann, Christian

2018-06-04

The extensive subcellular network of membrane contact sites plays central roles in organelle biogenesis and communication, yet the precise contributions of the involved machineries remain largely enigmatic. The yeast vacuole forms a membrane contact site with mitochondria, called vacuolar and mitochondrial patch (vCLAMP). Formation of vCLAMPs involves the vacuolar Rab GTPase Ypt7 and the Ypt7-interacting Vps39 subunit of the HOPS tethering complex. Here, we uncover the general preprotein translocase of the outer membrane (TOM) subunit Tom40 as the direct binding partner of Vps39 on mitochondria. We identify Vps39 mutants defective in TOM binding, but functional for HOPS. Cells that cannot form vCLAMPs show reduced growth under stress conditions and impaired survival upon starvation. Unexpectedly, our mutant analysis revealed the existence of two functionally independent vacuole-mitochondria MCSs: one formed by the Ypt7-Vps39-Tom40 tether and a second one by Vps13-Mcp1, which is redundant with ER-mitochondrial contacts formed by ERMES. Copyright © 2018 Elsevier Inc. All rights reserved.

Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation.

PubMed

Dernedde, Jens; Rausch, Alexandra; Weinhart, Marie; Enders, Sven; Tauber, Rudolf; Licha, Kai; Schirner, Michael; Zügel, Ulrich; von Bonin, Arne; Haag, Rainer

2010-11-16

Adhesive interactions of leukocytes and endothelial cells initiate leukocyte migration to inflamed tissue and are important for immune surveillance. Acute and chronic inflammatory diseases show a dysregulated immune response and result in a massive efflux of leukocytes that contributes to further tissue damage. Therefore, targeting leukocyte trafficking may provide a potent form of anti-inflammatory therapy. Leukocyte migration is initiated by interactions of the cell adhesion molecules E-, L-, and P-selectin and their corresponding carbohydrate ligands. Compounds that efficiently address these interactions are therefore of high therapeutic interest. Based on this rationale we investigated synthetic dendritic polyglycerol sulfates (dPGS) as macromolecular inhibitors that operate via a multivalent binding mechanism mimicking naturally occurring ligands. dPGS inhibited both leukocytic L-selectin and endothelial P-selectin with high efficacy. Size and degree of sulfation of the polymer core determined selectin binding affinity. Administration of dPGS in a contact dermatitis mouse model dampened leukocyte extravasation as effectively as glucocorticoids did and edema formation was significantly reduced. In addition, dPGS interacted with the complement factors C3 and C5 as was shown in vitro and reduced C5a levels in a mouse model of complement activation. Thus, dPGS represent an innovative class of a fully synthetic polymer therapeutics that may be used for the treatment of inflammatory diseases.

Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation

PubMed Central

Dernedde, Jens; Rausch, Alexandra; Weinhart, Marie; Enders, Sven; Tauber, Rudolf; Licha, Kai; Schirner, Michael; Zügel, Ulrich; von Bonin, Arne; Haag, Rainer

2010-01-01

Adhesive interactions of leukocytes and endothelial cells initiate leukocyte migration to inflamed tissue and are important for immune surveillance. Acute and chronic inflammatory diseases show a dysregulated immune response and result in a massive efflux of leukocytes that contributes to further tissue damage. Therefore, targeting leukocyte trafficking may provide a potent form of anti-inflammatory therapy. Leukocyte migration is initiated by interactions of the cell adhesion molecules E-, L-, and P-selectin and their corresponding carbohydrate ligands. Compounds that efficiently address these interactions are therefore of high therapeutic interest. Based on this rationale we investigated synthetic dendritic polyglycerol sulfates (dPGS) as macromolecular inhibitors that operate via a multivalent binding mechanism mimicking naturally occurring ligands. dPGS inhibited both leukocytic L-selectin and endothelial P-selectin with high efficacy. Size and degree of sulfation of the polymer core determined selectin binding affinity. Administration of dPGS in a contact dermatitis mouse model dampened leukocyte extravasation as effectively as glucocorticoids did and edema formation was significantly reduced. In addition, dPGS interacted with the complement factors C3 and C5 as was shown in vitro and reduced C5a levels in a mouse model of complement activation. Thus, dPGS represent an innovative class of a fully synthetic polymer therapeutics that may be used for the treatment of inflammatory diseases. PMID:21041668

Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.

PubMed

Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2014-07-01

Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering. © 2013 Wiley Periodicals, Inc.

Nuclear magnetic resonance and restrained molecular dynamics studies of the interaction of an epidermal growth factor-derived peptide with protein tyrosine phosphatase 1B.

PubMed

Glover, N R; Tracey, A S

1999-04-20

The epidermal growth factor-derived (EGFR988) fluorophosphonate peptide, DADE(F2Pmp)L, is a potent (30 pM) inhibitor of the protein tyrosine phosphatase PTP1B. Nuclear magnetic resonance (NMR) transferred nuclear Overhauser effect (nOe) experiments have been used to determine the conformation of DADE(F2Pmp)L while bound in the active site of PTP1B. When bound, the peptide adopts an extended beta-strand conformation. Molecular modeling and molecular dynamics simulations allowed the elucidation of the sources of many of the interactions leading to binding of this inhibitor. Electrostatic, hydrophobic, and hydrogen-bonding interactions were all found to contribute significantly to its binding. However, despite the overall tight binding of this inhibitor, the N-terminal and adjacent residue of the peptide were virtually unrestrained in their motion. The major contributions to binding arose from hydrophobic interactions at the leucine and at the aromatic center, hydrogen bonding to the pro-R fluorine of the fluorophosphonomethyl group, and electrostatic interactions involving the carboxylate functionalities of the aspartate and glutamate residues. These latter two residues were found to form tight contacts with surface recognition elements (arginine and lysine) situated near the active-site cleft.

A complex study of 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate: A new low-molecular-weight immune response modifier

NASA Astrophysics Data System (ADS)

Ryng, Stanisław; Zimecki, Michał; Jezierska-Mazzarello, Aneta; Panek, Jarosław J.; Mączyński, Marcin; Głowiak, Tadeusz; Sawka-Dobrowolska, Wanda; Koll, Aleksander

2011-07-01

A new potential lead structure with immunological activity, 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate, was synthesized. A detailed description of synthesis is presented together with X-ray structural analysis. In vitro assays showed that the compound had a potent immunosuppressive activity. Next, Density Functional Theory (DFT) was employed to shed a light on molecular properties of the investigated isoxazole derivative. The molecular modeling part included geometric as well as electronic structure descriptions: (i) the conformational analysis was performed to localize the most appropriate conformation; (ii) the coordination energy and Basis Set Superposition Error (BSSE) were estimated for the complex of the isoxazole derivative interacting with water molecule; (iii) the potential energy distribution was used to assign molecular vibrations, and NBO population analysis served to describe the electronic structure; (iv) the electrostatic potential map was generated to provide the graphical presentation of regions exposed for intermolecular interactions. The contacts between the water molecule and the nitrogen atom of the isoxazole ring edge were present in the solid phase. On the other hand, the theoretical DFT prediction was that the oxygen atom of the edge should form a more stable complex with the water molecule.

Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites

DOE PAGES

Winarski, Katie L.; Thornburg, Natalie J.; Yu, Yingchun; ...

2015-07-13

Antigenic drift of circulating seasonal influenza viruses necessitates an international vaccine effort to reduce the impact on human health. A critical feature of the seasonal vaccine is that it stimulates an already primed immune system to diversify memory B cells to recognize closely related, but antigenically distinct, influenza glycoproteins (hemagglutinins). Influenza pandemics arise when hemagglutinins to which no preexisting adaptive immunity exists acquire the capacity to infect humans. Hemagglutinin 5 is one subtype to which little preexisting immunity exists and is only a few acquired mutations away from the ability to transmit efficiently between ferrets, and possibly humans. In thismore » paper, we describe the structure and molecular mechanism of neutralization by H5.3, a vaccine-elicited antibody that neutralizes hemagglutinin 5 viruses and variants with expanded host range. H5.3 binds in the receptor-binding site, forming contacts that recapitulate many of the sialic acid interactions, as well as multiple peripheral interactions, yet is not sensitive to mutations that alter sialic acid binding. H5.3 is highly specific for a subset of H5 strains, and this specificity arises from interactions to the periphery of the receptor-binding site. Finally, H5.3 is also extremely potent, despite retaining germ line-like conformational flexibility.« less

Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winarski, Katie L.; Thornburg, Natalie J.; Yu, Yingchun

Antigenic drift of circulating seasonal influenza viruses necessitates an international vaccine effort to reduce the impact on human health. A critical feature of the seasonal vaccine is that it stimulates an already primed immune system to diversify memory B cells to recognize closely related, but antigenically distinct, influenza glycoproteins (hemagglutinins). Influenza pandemics arise when hemagglutinins to which no preexisting adaptive immunity exists acquire the capacity to infect humans. Hemagglutinin 5 is one subtype to which little preexisting immunity exists and is only a few acquired mutations away from the ability to transmit efficiently between ferrets, and possibly humans. In thismore » paper, we describe the structure and molecular mechanism of neutralization by H5.3, a vaccine-elicited antibody that neutralizes hemagglutinin 5 viruses and variants with expanded host range. H5.3 binds in the receptor-binding site, forming contacts that recapitulate many of the sialic acid interactions, as well as multiple peripheral interactions, yet is not sensitive to mutations that alter sialic acid binding. H5.3 is highly specific for a subset of H5 strains, and this specificity arises from interactions to the periphery of the receptor-binding site. Finally, H5.3 is also extremely potent, despite retaining germ line-like conformational flexibility.« less

Two-step deposition of Al-doped ZnO on p-GaN to form ohmic contacts.

PubMed

Su, Xi; Zhang, Guozhen; Wang, Xiao; Chen, Chao; Wu, Hao; Liu, Chang

2017-12-01

Al-doped ZnO (AZO) thin films were deposited directly on p-GaN substrates by using a two-step deposition consisting of polymer assisted deposition (PAD) and atomic layer deposition (ALD) methods. Ohmic contacts of the AZO on p-GaN have been formed. The lowest sheet resistance of the two-step prepared AZO films reached to 145 Ω/sq, and the specific contact resistance reduced to 1.47 × 10 -2 Ω·cm 2 . Transmittance of the AZO films remained above 80% in the visible region. The combination of PAD and ALD technique can be used to prepare p-type ohmic contacts for optoelectronics.

Two-step deposition of Al-doped ZnO on p-GaN to form ohmic contacts

NASA Astrophysics Data System (ADS)

Su, Xi; Zhang, Guozhen; Wang, Xiao; Chen, Chao; Wu, Hao; Liu, Chang

2017-07-01

Al-doped ZnO (AZO) thin films were deposited directly on p-GaN substrates by using a two-step deposition consisting of polymer assisted deposition (PAD) and atomic layer deposition (ALD) methods. Ohmic contacts of the AZO on p-GaN have been formed. The lowest sheet resistance of the two-step prepared AZO films reached to 145 Ω/sq, and the specific contact resistance reduced to 1.47 × 10-2 Ω·cm2. Transmittance of the AZO films remained above 80% in the visible region. The combination of PAD and ALD technique can be used to prepare p-type ohmic contacts for optoelectronics.

Electrode Arrangement As Substitute Bottom For An Electrothermic Slag Smelting Furnace.

DOEpatents

Aune, Jan Arthur; Brinch, Jon Christian; Johansen, Kai

2005-12-27

The electrode arrangement uses vertically oriented electrodes with side wall contacts for an electrothermic smelting furnace for aluminum production. The side wall contacts are radially moveable into the furnace to compensate for wear on the contacts. The side wall contacts can be hollow to allow a slag forming charge to be fed to the furnace.

Features of Protein-Protein Interactions that Translate into Potent Inhibitors: Topology, Surface Area and Affinity

PubMed Central

Smith, Matthew C.; Gestwicki, Jason E.

2013-01-01

Protein-protein interactions (PPIs) control the assembly of multi-protein complexes and, thus, these contacts have enormous potential as drug targets. However, the field has produced a mix of both exciting success stories and frustrating challenges. Here, we review known examples and explore how the physical features of a PPI, such as its affinity, hotspots, off-rates, buried surface area and topology, may influence the chances of success in finding inhibitors. This analysis suggests that concise, tight binding PPIs are most amenable to inhibition. However, it is also clear that emerging technical methods are expanding the repertoire of “druggable” protein contacts and increasing the odds against difficult targets. In particular, natural product-like compound libraries, high throughput screens specifically designed for PPIs and approaches that favor discovery of allosteric inhibitors appear to be attractive routes. The first group of PPI inhibitors has entered clinical trials, further motivating the need to understand the challenges and opportunities in pursuing these types of targets. PMID:22831787

Fluorinated tin oxide back contact for AZTSSe photovoltaic devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gershon, Talia S.; Gunawan, Oki; Haight, Richard A.

A photovoltaic device includes a substrate, a back contact comprising a stable low-work function material, a photovoltaic absorber material layer comprising Ag.sub.2ZnSn(S,Se).sub.4 (AZTSSe) on a side of the back contact opposite the substrate, wherein the back contact forms an Ohmic contact with the photovoltaic absorber material layer, a buffer layer or Schottky contact layer on a side of the absorber layer opposite the back contact, and a top electrode on a side of the buffer layer opposite the absorber layer.

MICROBIAL SEQUESTRATION OF LEAD AND OTHER HEAVY METALS

EPA Science Inventory

Human activity resulting in heavy metal contamination is a worldwide concern. Lead is a potent neurotoxin that can cause heart problems, kidney damage, and mental retardation. Mercury causes toxicity based on its form and route of exposure. Effects range from allergic reactions t...

Educating Savages.

ERIC Educational Resources Information Center

Morris, Richard

1997-01-01

Examines different narratives of Native American education. Discusses the narrative about the nature and consequences of rhetorical and cultural transformation. Argues that rhetoric generated by Native Americans who have experienced dominant educational efforts in the United States reveals a form of mimesis that serves as a potent strategy for…

Trail-marking substance of the Texas leaf-cutting ant: source and potency

Treesearch

John C. Moser; Murray S. Blum

1963-01-01

The trail-marking substance of Atta texana (Buckley) is formed in the true poison gland and deposited by the sting. This attractant is initially produced by teneral workers. The substance obtained from mature, large workers is the most potent.

Method for formation of high quality back contact with screen-printed local back surface field

DOEpatents

Rohatgi, Ajeet; Meemongkolkiat, Vichai

2010-11-30

A thin silicon solar cell having a back dielectric passivation and rear contact with local back surface field is described. Specifically, the solar cell may be fabricated from a crystalline silicon wafer having a thickness from 50 to 500 micrometers. A barrier layer and a dielectric layer are applied at least to the back surface of the silicon wafer to protect the silicon wafer from deformation when the rear contact is formed. At least one opening is made to the dielectric layer. An aluminum contact that provides a back surface field is formed in the opening and on the dielectric layer. The aluminum contact may be applied by screen printing an aluminum paste having from one to 12 atomic percent silicon and then applying a heat treatment at 750 degrees Celsius.

Fabricating and using a micromachined magnetostatic relay or switch

NASA Technical Reports Server (NTRS)

Tai, Yu-Chong (Inventor); Wright, John A. (Inventor)

2001-01-01

A micromachined magnetostatic relay or switch includes a springing beam on which a magnetic actuation plate is formed. The springing beam also includes an electrically conductive contact. In the presence of a magnetic field, the magnetic material causes the springing beam to bend, moving the electrically conductive contact either toward or away from another contact, and thus creating either an electrical short-circuit or an electrical open-circuit. The switch is fabricated from silicon substrates and is particularly useful in forming a MEMs commutation and control circuit for a miniaturized DC motor.

Multiple piece turbine blade/vane

DOEpatents

Kimmel, Keith D

2013-02-05

An air cooled turbine blade or vane of a spar and shell construction with the shell made from a high temperature resistant material that must be formed from an EDM process. The shell and the spar both have a number of hooks extending in a spanwise direction and forming a contact surface that is slanted such that a contact force increases as the engaging hooks move away from one another. The slanted contact surfaces on the hooks provides for an better seal and allows for twisting between the shell and the spar while maintaining a tight fit.

EMIIM Wetting Properties & Their Effect on Electrospray Thruster Design

DTIC Science & Technology

2012-03-01

tension and contact or “wetting" angle formed when a liquid droplet comes in contact with a solid surface. Ideally this angle is a function of the...3 3 Picture of a Taylor cone formed at AFRL, note bubbles present. . . . . . . 3 4 Titanium electrode grids in use at AFRL...cone formed using an internally wetted emitter and the ionic liquid BMI-BG4 is shown in Figure 3.[7] Emitters are precisely aligned with openings

Potent D-peptide inhibitors of HIV-1 entry

PubMed Central

Welch, Brett D.; VanDemark, Andrew P.; Heroux, Annie; Hill, Christopher P.; Kay, Michael S.

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. PMID:17942675

Suppression of tumor cell invasiveness by hydrolyzable tannins (plant polyphenols) via the inhibition of matrix metalloproteinase-2/-9 activity.

PubMed

Tanimura, Susumu; Kadomoto, Ryoji; Tanaka, Takashi; Zhang, Ying-Jun; Kouno, Isao; Kohno, Michiaki

2005-05-20

Elevated expression of matrix metalloproteinases (MMPs), especially that of MMP-2 and MMP-9, is associated with increased metastatic potential in many tumor cells. Recently, green tea polyphenol epigallocatechin-3-O-gallate (EGCG) has been shown to inhibit the MMP-2/-9 activity as well as the invasiveness of tumor cells. In this study, we have examined the inhibitory effect of hydrolyzable tannins (plant polyphenols) on the tumor cell invasion. Our results demonstrate that beta-d-glucose whose hydroxy groups are substituted entirely with galloyl group and further some of them are cross-linked to form hexahydroxydiphenoyl group, for example, suppresses the invasiveness of tumor cells much more potently than EGCG via direct inhibition of the MMP-2/-9 activity. Among those examined, 1,2,4-tri-O-galloyl-3,6-hexahydroxydiphenoyl-beta-d-glucose (punicafolin) inhibits the invasion of HT1080 fibrosarcoma cells most potently. These hydrolyzable tannins would provide new leads for the development of potent inhibitors against tumor metastasis.

Investigations on the 4-Quinolone-3-Carboxylic Acid Motif. 5. Modulation of the Physicochemical Profile of a Set of Potent and Selective Cannabinoid-2 Receptor Ligands through a Bioisosteric Approach

PubMed Central

Nocerino, Stefania; Pedani, Valentina; Pasquini, Serena; Tafi, Andrea; De Chiaro, Maria; Bellucci, Luca; Valoti, Massimo; Guida, Francesca; Luongo, Livio; Dragoni, Stefania; Ligresti, Alessia; Rosenberg, Avraham; Bolognini, Daniele; Cascio, Maria Grazia; Pertwee, Roger G.; Moaddel, Ruin; Maione, Sabatino; Di Marzo, Vincenzo

2012-01-01

Three heterocyclic systems were selected as potential surrogates of the amide linker for a series of 1,6-disubstituted-4-quinolone-3-carboxamides, potent and selective CB2 ligands exhibiting scarce water solubility, with the aim of improving their physicochemical profile and also of clarifying properties of importance for amide bond mimicry. Among the newly synthesized compounds, the 1,2,3-triazole derivative 11 emerged as the most promising in terms of both physicochemical and pharmacodynamic properties. When assayed in vitro, 11 exhibited inverse agonist activity, whereas, in vivo, in the formalin test in mice, it produced analgesic effects antagonized by a well established inverse agonist. Metabolic studies allowed the identification of the side chain hydroxylated derivative 32 as its only metabolite which, in its racemic form, showed still appreciable CB2 selectivity, but was 150-fold less potent than the parent compound. PMID:22383251

Treatment of electrochemical cell components with lithium tetrachloroaluminate (LiAlCl.sub.4) to promote electrolyte wetting

DOEpatents

Eberhart, James G.; Battles, James E.

1980-01-01

Electrochemical cell components such as interelectrode separators, retaining screens and current collectors are contacted with lithium tetrachloroaluminate prior to contact with molten electrolytic salt to improve electrolyte wetting. The LiAlCl.sub.4 can be applied in powdered, molten or solution form but, since this material has a lower melting point than the electrolytic salt used in high-temperature cells, the powdered LiAlCl.sub.4 forms a molten flux prior to contact by the molten electrolyte when both materials are initially provided in solid form. Components of materials such as boron nitride and other materials which are difficult to wet with molten salts are advantageously treated by this process.

Strong Fermi-Level Pinning at Metal/n-Si(001) Interface Ensured by Forming an Intact Schottky Contact with a Graphene Insertion Layer.

PubMed

Yoon, Hoon Hahn; Jung, Sungchul; Choi, Gahyun; Kim, Junhyung; Jeon, Youngeun; Kim, Yong Soo; Jeong, Hu Young; Kim, Kwanpyo; Kwon, Soon-Yong; Park, Kibog

2017-01-11

We report the systematic experimental studies demonstrating that a graphene layer inserted at metal/n-Si(001) interface is efficient to explore interface Fermi-level pinning effect. It is confirmed that an inserted graphene layer prevents atomic interdiffusion to form an atomically abrupt Schottky contact. The Schottky barriers of metal/graphene/n-Si(001) junctions show a very weak dependence on metal work-function, implying that the metal Fermi-level is almost completely pinned at charge neutrality level close to the valence band edge of Si. The atomically impermeable and electronically transparent properties of graphene can be used generally to form an intact Schottky contact for all semiconductors.

Via Method for Lithography Free Contact and Preservation of 2D Materials.

PubMed

Telford, Evan J; Benyamini, Avishai; Rhodes, Daniel; Wang, Da; Jung, Younghun; Zangiabadi, Amirali; Watanabe, Kenji; Taniguchi, Takashi; Jia, Shuang; Barmak, Katayun; Pasupathy, Abhay N; Dean, Cory R; Hone, James

2018-02-14

Atomically thin 2D materials span the common components of electronic circuits as metals, semiconductors, and insulators, and can manifest correlated phases such as superconductivity, charge density waves, and magnetism. An ongoing challenge in the field is to incorporate these 2D materials into multilayer heterostructures with robust electrical contacts while preventing disorder and degradation. In particular, preserving and studying air-sensitive 2D materials has presented a significant challenge since they readily oxidize under atmospheric conditions. We report a new technique for contacting 2D materials, in which metal via contacts are integrated into flakes of insulating hexagonal boron nitride, and then placed onto the desired conducting 2D layer, avoiding direct lithographic patterning onto the 2D conductor. The metal contacts are planar with the bottom surface of the boron nitride and form robust contacts to multiple 2D materials. These structures protect air-sensitive 2D materials for months with no degradation in performance. This via contact technique will provide the capability to produce "atomic printed circuit boards" that can form the basis of more complex multilayer heterostructures.

Influence and evolution mechanism of different sharpness contact forms to mechanical property of cortical bone by nanoindentation

NASA Astrophysics Data System (ADS)

Sun, Xingdong; Guo, Yue; Li, Lijia; Liu, Zeyang; Wu, Di; Shi, Dong; Zhao, Hongwei; Zhang, Shizhong

2018-03-01

Based on different damage forms of various contact forms to bone, the mechanical response and mechanism were investigated by nanoindentation under different sharpness contact forms. For the purpose of simulating the different sharpness contact forms, two kinds of indenters were used in experiments and finite elements simulations. Through nanoindentation experiments, it was concluded that the residual depth of sharp indenter was bigger than that of blunt indenter with small penetration depth. However, the contrary law was obtained with bigger penetration depth. There was a turning point of transition from blunt tendency to sharp tendency. By calculation, it was concluded that the sharper the indenter was, the bigger the proportion of plastic energy in total energy was. Basically, results of finite elements simulation could correspond with the experimental conclusions. By the observation of FE-SEM, the surface of cortical bone compressed was more seriously directly below the blunt indenter than the lateral face. For the berkovich indenter, the surface of indentation compressed was less directly below the indenter, but seriously on three lateral faces. This research may provide some new references to the studies of bone fracture mechanism in different load patterns in the initial press-in stage and offer new explanation for bone trauma diagnosis in clinical treatment and criminal investigation.

Sterol-recognition ability and membrane-disrupting activity of Ornithogalum saponin OSW-1 and usual 3-O-glycosyl saponins.

PubMed

Malabed, Raymond; Hanashima, Shinya; Murata, Michio; Sakurai, Kaori

2017-12-01

OSW-1 is a structurally unique steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, and has exhibited highly potent and selective cytotoxicity in tumor cell lines. This study aimed to investigate the molecular mechanism for the membrane-permeabilizing activity of OSW-1 in comparison with those of other saponins by using various spectroscopic approaches. The membrane effects and hemolytic activity of OSW-1 were markedly enhanced in the presence of membrane cholesterol. Binding affinity measurements using fluorescent cholestatrienol and solid-state NMR spectroscopy of a 3-d-cholesterol probe suggested that OSW-1 interacts with membrane cholesterol without forming large aggregates while 3-O-glycosyl saponin, digitonin, forms cholesterol-containing aggregates. The results suggest that OSW-1/cholesterol interaction is likely to cause membrane permeabilization and pore formation without destroying the whole membrane integrity, which could partly be responsible for its highly potent cell toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

m1A and m1G Potently Disrupt A-RNA Structure Due to the Intrinsic Instability of Hoogsteen Base Pairs

PubMed Central

Zhou, Huiqing; Kimsey, Isaac J.; Nikolova, Evgenia N.; Sathyamoorthy, Bharathwaj; Grazioli, Gianmarc; McSally, James; Bai, Tianyu; Wunderlich, Christoph H.; Kreutz, Christoph; Andricioaei, Ioan; Al-Hashimi, Hashim M.

2016-01-01

The B-DNA double helix can dynamically accommodate G–C and A–T base pairs in either Watson-Crick or Hoogsteen configurations. Here, we show that G–C+ and A–U Hoogsteen base pairs are strongly disfavored in A-RNA. As a result, N1-methyl adenosine and N1-methyl guanosine, which occur in DNA as a form of alkylation damage, and in RNA as a posttranscriptional modification, have dramatically different consequences. They create G–C+ and A–U Hoogsteen base pairs in duplex DNA that maintain the structural integrity of the double helix, but block base pairing all together and induce local duplex melting in RNA, providing a mechanism for potently disrupting RNA structure through posttranscriptional modifications. The markedly different propensities to form Hoogsteen base pairs in B-DNA and A-RNA may help meet the opposing requirements of maintaining genome stability on one hand, and dynamically modulating the structure of the epitranscriptome on the other. PMID:27478929

Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus

PubMed Central

Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel M. L.; Lok, Laurence S. C.; Monie, Tom; van Wigcheren, Glenn; Raisen, Claire; Ba, Xiaoliang; Gleadall, Nicholas; Hadjirin, Nazreen; Timmerman, Arjen J.; Wagenaar, Jaap A.; Klunder, Heleen M.; Fitzgerald, J. Ross; Zadoks, Ruth; Paterson, Gavin K.; Torres, Carmen; Waller, Andrew S.; Loeffler, Anette; Loncaric, Igor; Hoet, Armando E.; Bergström, Karin; De Martino, Luisa; Pomba, Constança; de Lencastre, Hermínia; Ben Slama, Karim; Gharsa, Haythem; Richardson, Emily J.; Chilvers, Edwin R.; de Haas, Carla; van Kessel, Kok; van Strijp, Jos A. G.; Harrison, Ewan M.; Holmes, Mark A.

2017-01-01

Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S. aureus leukocidin; LukPQ. LukPQ is encoded on a 45 kb prophage (ΦSaeq1) found in six different clonal lineages, almost exclusively in strains cultured from equids. We show that LukPQ is a potent and specific killer of equine neutrophils and identify equine-CXCRA and CXCR2 as its target receptors. Although the S-component (LukP) is highly similar to the S-component of LukED, the species specificity of LukPQ and LukED differs. By forming non-canonical toxin pairs, we identify that the F-component contributes to the observed host tropism of LukPQ, thereby challenging the current paradigm that leukocidin specificity is driven solely by the S-component. PMID:28106142

On contact modelling in isogeometric analysis

NASA Astrophysics Data System (ADS)

Cardoso, R. P. R.; Adetoro, O. B.

2017-11-01

IsoGeometric Analysis (IGA) has proved to be a reliable numerical tool for the simulation of structural behaviour and fluid mechanics. The main reasons for this popularity are essentially due to: (i) the possibility of using higher order polynomials for the basis functions; (ii) the high convergence rates possible to achieve; (iii) the possibility to operate directly on CAD geometry without the need to resort to a mesh of elements. The major drawback of IGA is the non-interpolatory characteristic of the basis functions, which adds a difficulty in handling essential boundary conditions and makes it particularly challenging for contact analysis. In this work, the IGA is expanded to include frictionless contact procedures for sheet metal forming analyses. Non-Uniform Rational B-Splines (NURBS) are going to be used for the modelling of rigid tools as well as for the modelling of the deformable blank sheet. The contact methods developed are based on a two-step contact search scheme, where during the first step a global search algorithm is used for the allocation of contact knots into potential contact faces and a second (local) contact search scheme where point inversion techniques are used for the calculation of the contact penetration gap. For completeness, elastoplastic procedures are also included for a proper description of the entire IGA of sheet metal forming processes.

Role of membrane contact sites in protein import into mitochondria

PubMed Central

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

2015-01-01

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

Fabrication of contacts for silicon solar cells including printing burn through layers

DOEpatents

Ginley, David S; Kaydanova, Tatiana; Miedaner, Alexander; Curtis, Calvin J; Van Hest, Marinus Franciscus Antonius Maria

2014-06-24

A method for fabricating a contact (240) for a solar cell (200). The method includes providing a solar cell substrate (210) with a surface that is covered or includes an antireflective coating (220). For example, the substrate (210) may be positioned adjacent or proximate to an outlet of an inkjet printer (712) or other deposition device. The method continues with forming a burn through layer (230) on the coating (220) by depositing a metal oxide precursor (e.g., using an inkjet or other non-contact printing method to print or apply a volume of liquid or solution containing the precursor). The method includes forming a contact layer (240) comprising silver over or on the burn through layer (230), and then annealing is performed to electrically connect the contact layer (240) to the surface of the solar cell substrate (210) through a portion of the burn through layer (230) and the coating (220).

Compliant sleeve for ceramic turbine blades

DOEpatents

Cai, Hongda; Narasimhan, Dave; Strangman, Thomas E.; Easley, Michael L.; Schenk, Bjoern

2000-01-01

A compliant sleeve for attaching a ceramic member to a metal member is comprised of a superalloy substrate having a metal contacting side and a ceramic contacting side. The ceramic contacting side is plated with a layer of nickel followed by a layer of platinum. The substrate is then oxidized to form nickel oxide scale on the ceramic contacting side and a cobalt oxide scale on the metal contacting side. A lubricious coating of boron nitride is then applied over the metal contacting side, and a shear-stress limiting gold coating is applied over the ceramic contacting side.

Surface hole gas enabled transparent deep ultraviolet light-emitting diode

NASA Astrophysics Data System (ADS)

Zhang, Jianping; Gao, Ying; Zhou, Ling; Gil, Young-Un; Kim, Kyoung-Min

2018-07-01

The inherent deep-level nature of acceptors in wide-band-gap semiconductors makes p-ohmic contact formation and hole supply difficult, impeding progress for short-wavelength optoelectronics and high-power high-temperature bipolar electronics. We provide a general solution by demonstrating an ultrathin rather than a bulk wide-band-gap semiconductor to be a successful hole supplier and ohmic contact layer. Free holes in this ultrathin semiconductor are assisted to activate from deep acceptors and swept to surface to form hole gases by a large electric field, which can be provided by engineered spontaneous and piezoelectric polarizations. Experimentally, a 6 nm thick AlN layer with surface hole gas had formed p-ohmic contact to metals and provided sufficient hole injection to a 280 nm light-emitting diode, demonstrating a record electrical-optical conversion efficiency exceeding 8.5% at 20 mA (55 A cm‑2). Our approach of forming p-type wide-band-gap semiconductor ohmic contact is critical to realizing high-efficiency ultraviolet optoelectronic devices.

Non-Dissipative Structural Evolutions in Granular Materials

NASA Astrophysics Data System (ADS)

Pouragha, Mehdi; Wan, Richard

2017-06-01

The structure of the contact network in granular assemblies can evolve due to either dissipative mechanisms such as sliding at contact points, or non-dissipative mechanisms through the phenomenon of contact gain and loss. Being associated with negligible deformations, non-dissipative mechanisms is actually active even in the small strain range of 10-3, especially in the case of densely packed assemblies. Hence, from a constitutive modelling point of view, it is crucial to be able to estimate such non-dissipative evolutions since both elastic and plastic properties of granular assemblies highly depend on contact network characteristics. The current study proposes an analytical scheme that allows us to estimate the non-dissipative contact gain/loss regime in terms of directional changes in the average contact force. The probability distribution of contact forces is used to compute the number of lost contact for each direction. Similarly, the number of newly formed contacts is estimated by considering the probability distribution of the gap between neighbouring particles. Based on the directional contact gain/loss computed, the changes in coordination number and fabric anisotropy can be found which, together with statistical treatments of Love-Weber stress expression, form a complete system of equations describing the evolution of other controlling microvariables. Finally, the results of the calculations have been compared with DEM simulations which verify the accuracy of the proposed scheme.

Methylisothiazolinone testing at 2000 ppm: a prevalent sensitizer for allergic contact dermatitis.

PubMed

Ham, Kaiya; Posso-De Los Rios, Claudia J; Gooderham, Melinda

2015-01-01

Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) have been identified as potent allergens. The optimal MI concentration for patch testing for reaction to these agents has not yet been identified, but it has been suggested that testing MI at 2000 ppm may reduce false-negative reactions. The aim of this study was to report allergic reactions to MI and MCI/MI detected in a community dermatology practice setting in Ontario, Canada. The patch test records of patients with suspected allergic contact dermatitis seen between October 2007 and June 2014 were reviewed. We compared positive patch testing before and after December 2011 when a higher MI concentration was used (2000 ppm aqueous) in addition to the baseline series MCI/MI at 100 ppm. A total of 794 patient records were reviewed. There were 38 true-positive reactions to MI or MCI/MI. Of these 38 patients, 26 (68%) were female. We detected an overall increase in the rate of positive patch testing to MCI/MI, MI alone, or both from 3.13% to 7.45% when MI concentration was introduced at 2000 ppm aqueous. Occupational differences existed between sexes. The addition of MI at 2000 ppm to our screening series effectively increased the detection of MI-induced allergic contact dermatitis.

Arterial thrombosis is accelerated in mice deficient in histidine-rich glycoprotein

PubMed Central

Vu, Trang T.; Zhou, Ji; Leslie, Beverly A.; Stafford, Alan R.; Fredenburgh, James C.; Ni, Ran; Qiao, Shengjun; Vaezzadeh, Nima; Jahnen-Dechent, Willi; Monia, Brett P.; Gross, Peter L.; Weitz, Jeffrey I.

2015-01-01

Factor (F) XII, a key component of the contact system, triggers clotting via the intrinsic pathway, and is implicated in propagating thrombosis. Although nucleic acids are potent activators, it is unclear how the contact system is regulated to prevent uncontrolled clotting. Previously, we showed that histidine-rich glycoprotein (HRG) binds FXIIa and attenuates its capacity to trigger coagulation. To investigate the role of HRG as a regulator of the intrinsic pathway, we compared RNA- and DNA-induced thrombin generation in plasma from HRG-deficient and wild-type mice. Thrombin generation was enhanced in plasma from HRG-deficient mice, and accelerated clotting was restored to normal with HRG reconstitution. Although blood loss after tail tip amputation was similar in HRG-deficient and wild-type mice, carotid artery occlusion after FeCl3 injury was accelerated in HRG-deficient mice, and HRG administration abrogated this effect. To confirm that HRG modulates the contact system, we used DNase, RNase, and antisense oligonucleotides to characterize the FeCl3 model. Whereas DNase or FVII knockdown had no effect, carotid occlusion was abrogated with RNase or FXII knockdown, confirming that FeCl3-induced thrombosis is triggered by RNA in a FXII-dependent fashion. Therefore, in a nucleic acid–driven model, HRG inhibits thrombosis by modulating the intrinsic pathway of coagulation. PMID:25691157

Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse.

PubMed

Reichardt, Peter; Dornbach, Bastian; Rong, Song; Beissert, Stefan; Gueler, Faikah; Loser, Karin; Gunzer, Matthias

2007-09-01

Naive B cells are ineffective antigen-presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell-dendritic-cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell-primed regulatory T cells, "bTregs," as a useful approach for therapeutic intervention in adverse adaptive immune responses.

EMIIM Wetting Properties of & Their Effect on Electrospray Thruster Design

DTIC Science & Technology

2012-03-21

materials can be characterized using the surface tension and contact or “wetting" angle formed when a liquid droplet comes in contact with a solid surface...Illustration of the instantaneous dipole formed by electron motion in a hy- drogen atom(left) and how these instantaneous dipoles can attract each other...the extractor grid and of like charge to the emitter. A Taylor cone formed using an internally wetted emitter and the ionic liquid BMI-BG4 is shown in

Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents.

PubMed

Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Buchman, Marek; Shah, Akshay A; Cen, Nicholas; McCurry, Megan D; Beabout, Kathryn; Shamoo, Yousif

2017-11-08

An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

75 FR 75186 - Proposed Information Collection Activity: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-02

... a form that the NTSB plans to use to obtain the contact information of family members and friends of... accidents, and/or victims' family members and friends. The NTSB's purpose in proposing to use the form is to ensure that the NTSB has correct contact information for family members and friends of victims and/or...

PRODUCTION OF HAFNIUM METAL

DOEpatents

Elger, G.W.; Boubel, R.W.

1963-01-01

This patent deals with a process of producing pure Hf metal from oxygen- contaminated gaseous Hf chloride. The oxygen compounds in the chioride gas are halogenated by contacting the gas at elevated temperature with Cl/sub 2/ in the presence of C. The Hf chloride, still in gaseous form, is contacted with molten Mg whereby Hf metal is formed and condensed on the Mg. (AEC)

Curriculum as a Moral Educator.

ERIC Educational Resources Information Center

Wynne, Edward A.; Ryan, Kevin

1993-01-01

Explores issues of curriculum as a moral educator, examining moral values conveyed by the hidden curriculum. Greater emphasis on moral education and character formation is a rediscovery of curriculum's core intention. Teachers can find their most potent instrument for moral education in the form and substance of the curriculum. (SLD)

The Interaction of Nitrites with Food, Drugs, and Contaminants.

ERIC Educational Resources Information Center

Greenland, Sander

1978-01-01

Nitrites commonly occur in food and drinking water as additives, contaminants, or products of biological processes. These highly reactive substances combine with other commonly ingested substances to form potent carcinogens. Controls are needed on levels of nitrites and reactive contaminants in food and drinking water. (RE)

Spanish in Four Continents: Studies in Language Contact and Bilingualism.

ERIC Educational Resources Information Center

Silva-Corvalan, Carmen, Ed.

Papers on Spanish bilingualism and Spanish in contact with other languages include: "The Study of Language Contact: An Overview of the Issues" (Carmen Silva-Corvalan); "Language Mixture: Ordinary Processes, Extraordinary Results" (Sarah G. Thomason); "The Impact of Quichua on Verb Forms Used in Spanish Requests in Otavalo,…

76 FR 5207 - Agency Information Collection Activities: Reinstatement With Change of a Previously Approved...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

...: Comments Requested Action: 60-Day Notice of Information Collection Under Review: Police Public Contact... instrument with instructions or additional information, please contact Christine Eith, (202) 305-4559, Bureau... Contact Survey. (3) The agency form number, if any, and the applicable component of the Department...

Liftoff process for exfoliation of thin film photovoltaic devices and back contact formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haight, Richard A.; Hannon, James B.; Oida, Satoshi

A method for forming a back contact on an absorber layer in a photovoltaic device includes forming a two dimensional material on a first substrate. An absorber layer including Cu--Zn--Sn--S(Se) (CZTSSe) is grown over the first substrate on the two dimensional material. A buffer layer is grown on the absorber layer on a side opposite the two dimensional material. The absorber layer is exfoliated from the two dimensional material to remove the first substrate from a backside of the absorber layer opposite the buffer layer. A back contact is deposited on the absorber layer.

FORMING PROTECTIVE FILMS ON METAL

DOEpatents

Gurinsky, D.H.; Kammerer, O.F.; Sadofsky, J.; Weeks, J.R.

1958-12-16

Methods are described of inhibiting the corrosion of ferrous metal by contact with heavy liquid metals such as bismuth and gallium at temperatures above 500 icient laborato C generally by bringing nltrogen and either the metal zirconium, hafnium, or titanium into reactlve contact with the ferrous metal to form a thin adherent layer of the nitride of the metal and thereafter maintaining a fractional percentage of the metal absorbed in the heavy liquid metal in contact with the ferrous metal container. The general purpose for uslng such high boiling liquid metals in ferrous contalners would be as heat transfer agents in liquid-metal-fueled nuclear reactors.

Perforation patterned electrical interconnects

DOEpatents

Frey, Jonathan

2014-01-28

This disclosure describes systems and methods for increasing the usable surface area of electrical contacts within a device, such as a thin film solid state device, through the implementation of electrically conductive interconnects. Embodiments described herein include the use of a plurality of electrically conductive interconnects that penetrate through a top contact layer, through one or more multiple layers, and into a bottom contact layer. The plurality of conductive interconnects may form horizontal and vertical cross-sectional patterns. The use of lasers to form the plurality of electrically conductive interconnects from reflowed layer material further aids in the manufacturing process of a device.

Method of fabricating a back-contact solar cell and device thereof

DOEpatents

Li, Bo; Smith, David; Cousins, Peter

2014-07-29

Methods of fabricating back-contact solar cells and devices thereof are described. A method of fabricating a back-contact solar cell includes forming an N-type dopant source layer and a P-type dopant source layer above a material layer disposed above a substrate. The N-type dopant source layer is spaced apart from the P-type dopant source layer. The N-type dopant source layer and the P-type dopant source layer are heated. Subsequently, a trench is formed in the material layer, between the N-type and P-type dopant source layers.

Method of fabricating a back-contact solar cell and device thereof

DOEpatents

Li, Bo; Smith, David; Cousins, Peter

2016-08-02

Methods of fabricating back-contact solar cells and devices thereof are described. A method of fabricating a back-contact solar cell includes forming an N-type dopant source layer and a P-type dopant source layer above a material layer disposed above a substrate. The N-type dopant source layer is spaced apart from the P-type dopant source layer. The N-type dopant source layer and the P-type dopant source layer are heated. Subsequently, a trench is formed in the material layer, between the N-type and P-type dopant source layers.

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

Mental health service use among high school students exposed to interpersonal violence

PubMed Central

Johnson, Renee M.; Dunn, Erin C.; Lindsey, Michael; Xuan, Ziming; Zaslavsky, Alan M.

2013-01-01

BACKGROUND Violence-exposed youth rarely receive mental health services, even though exposure increases risk for academic and psychosocial problems. This study examines the association between violence exposure and mental health service contact. The four forms of violence exposure were peer, family, sexual, and witnessing. METHODS Data are from 1,534 Boston public high school students who participated in a 2008 self-report survey of violence exposure and its correlates. Multivariate logistic regressions estimated associations between each form of violence with service contact, then examined whether associations persisted when controlling for suicidality and self-injurious behaviors. RESULTS In unadjusted models, violence-exposed students more often reported service contact than their peers. However, in multivariate models, only exposure to family (OR=1.69, CI=1.23–2.31) and sexual violence (OR=2.34, CI=1.29–4.20) were associated with service contact. Associations attenuated when controlling for suicidality and self-injurious behaviors, indicating they were largely explained by self-harm. Sexual violence alone remained associated with mental health service contact in fully adjusted models, but only for girls (OR=3.32, CI=1.30–8.45), suggesting gender-specific pathways. CONCLUSIONS Associations between adolescent violence exposure and mental health service contact vary by form of exposure. Outreach to a broader set of exposed youth may reduce the impact of violence and its consequences for vulnerable students. PMID:25099429

Selected important fragrance sensitizers in perfumes--current exposures.

PubMed

Rastogi, Suresh Chandra; Johansen, Jeanne Duus; Bossi, Rossana

2007-04-01

Contact allergy to fragrance ingredients is frequent. Recommendations and regulations of some of the most frequent and potent fragrance allergens have recently been introduced. To investigate current exposures to 4 important fragrance allergens in hydroalcoholic cosmetic products. 25 popular perfume products of Danish as well as international brands were purchased from the Danish retail market. Contents of 4 important fragrance allergens, isoeugenol, hydroxy-iso-hexyl 3-cyclohexene carboxaldehyde (HICC, Lyral), were determined by gas chromatography-mass spectrometry, and atranol and chloro-atranol were determined by liquid chromatography-tandem mass spectrometry. Isoeugenol was found in 56%, HICC in 72%, atranol in 59%, and chloro-atranol in 36% of the 22 eau de toilette/eau de parfum products. The concentrations of isoeugenol were, in all products, below the recommended maximum concentration of 0.02%. HICC reached a maximum of 0.2%, which is 10-fold higher than maximum tolerable concentration considered safe by the EU Scientific Committee. The median concentrations of atranol and chloro-atranol in the investigated products were similar to those found in similar products in 2003. A significant decrease in the frequency of presence of chloro-atranol in the products was observed. There is still a wide-spread exposure to potent fragrance allergens in perfumes.

The profile and progress of neglected and abused children in long-term foster care.

PubMed

Barber, James G; Delfabbro, Paul H

2009-07-01

This study compared the profile of neglected and abused children in the Australian foster care system as well as differences between maltreatment types in relation to parental contact, reunification and psychosocial progress in care. The case files of 235 children entering foster care were examined and their social workers were administered standardised questionnaires at the point of intake. All measures were repeated for those remaining in care 1 year and then again 2 years later. Neglected children were younger than non-neglected children, more likely to have a physical or mental disability, more likely to experience multiple forms of maltreatment and less likely to pose conduct problems for carers. Neglected children were more likely than non-neglected children to experience a decline in parental contact over time, and were less likely to be reunified with their families of origin. There was minimal difference between neglected and non-neglected in their psychosocial progress while in care. Aboriginal children were more likely to be reunified than non-Aboriginal children when neglect was attributable to transient factors (parental incapacity) but the reverse was true for non-neglected children. The fact that neglected children more often require a second form of maltreatment before being removed from home suggests that children's services workers are less inclined to remove children for neglect than for other forms of maltreatment. As a consequence, those neglected children who are in care tend to come from more dysfunctional families than non-neglected children do, as evidenced by the relatively poorer parental contact and reunification results of neglected children. Neglected children differ systematically from non-neglected children and suffer relative disadvantage in relation to multiple forms of maltreatment, parental contact, and reunification. The fact that declines in parental contact among neglected children in care occurred only when indirect contact was provided suggests that, wherever possible, care plans should include face-to-face visits and overnight stays rather than being restricted to less direct forms of contact. The difference in the success of reunification according to type of neglect (chronic or transient) also suggests that parental intervention programs need to focus their efforts on chronic factors rather than transient parental factors.

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.

Microstructural Control via Copious Nucleation Manipulated by In Situ Formed Nucleants: Large-Sized and Ductile Metallic Glass Composites.

PubMed

Song, Wenli; Wu, Yuan; Wang, Hui; Liu, Xiongjun; Chen, Houwen; Guo, Zhenxi; Lu, Zhaoping

2016-10-01

A novel strategy to control the precipitation behavior of the austenitic phase, and to obtain large-sized, transformation-induced, plasticity-reinforced bulk metallic glass matrix composites, with good tensile properties, is proposed. By inducing heterogeneous nucleation of the transformable reinforcement via potent nucleants formed in situ, the characteristics of the austenitic phase are well manipulated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Contacts to Semiconductor Nanowires

DTIC Science & Technology

2009-10-03

SiNW diameters and the amount of metal deposited, or alternatively, the atomic ratio between Pt and Si. The uniformity of the silicided NWs was...program. The Schottky contact is a metal silicide formed by rapid thermal annealing of the deposited contact metal . The θ- Ni2Si/n-Si NW Schottky...decision. unless so designated by other documentation. 14. ABSTRACT Metal contacts to semiconductor nanowires share similarities with their thin-film

Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

PubMed

Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

2018-04-18

Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

Surface Stresses and a Force Balance at a Contact Line.

PubMed

Liang, Heyi; Cao, Zhen; Wang, Zilu; Dobrynin, Andrey V

2018-06-26

Results of the coarse-grained molecular dynamics simulations are used to show that the force balance analysis at the triple-phase contact line formed at an elastic substrate has to include a quartet of forces: three surface tensions (surface free energies) and an elastic force per unit length. In the case of the contact line formed by a droplet on an elastic substrate an elastic force is due to substrate deformation generated by formation of the wetting ridge. The magnitude of this force f el is proportional to the product of the ridge height h and substrate shear modulus G. Similar elastic line force should be included in the force analysis at the triple-phase contact line of a solid particle in contact with an elastic substrate. For this contact problem elastic force obtained from contact angles and surface tensions is a sum of the elastic forces acting from the side of a solid particle and an elastic substrate. By considering only three line forces acting at the triple-phase contact line, one implicitly accounts the bulk stress contribution as a part of the resultant surface stresses. This "contamination" of the surface properties by a bulk contribution could lead to unphysically large values of the surface stresses in soft materials.

Cd1-xZnxTe photodetectors with transparent conductive ZnO contacts

NASA Astrophysics Data System (ADS)

Tang, Ke; Huang, Jian; Lu, Yuanxi; Hu, Yan; Shen, Yibin; Zhang, Jijun; Gu, Qingmiao; Wang, Linjun; Lu, Yicheng

2018-03-01

High quality Cd1-xZnxTe (CZT) films were prepared using the close-spaced sublimation (CSS) technique. CZT film UV (ultraviolet) photodetectors were fabricated with B and Ga co-doped ZnO (BGZO) transparent conductive interdigitated contacts. The contact properties of BGZO/CZT were investigated by the transmission line model (TLM). The results indicate that a good ohmic contact is formed between BGZO and CZT with a very low contact resistivity of about 0.26 Ω·cm2. Compared with CZT photodetectors with Au contacts, the detectors with BGZO contacts show a higher value of UV photo response.

Better Ohmic Contacts For InP Semiconductor Devices

NASA Technical Reports Server (NTRS)

Weizer, Victor G.; Fatemi, Navid S.

1995-01-01

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

State-Of-The-Science Review: Everything NanoSilver and More

EPA Science Inventory

Silver has been known to be a potent antibacterial, antifungal and antiviral agent, but in recent years, the use of silver as a biocide in solution, suspension, and especially in nano-particulate form has experienced a dramatic revival. Due to the properties of silver at the nano...

Detoxification of nitric oxide by Fusarium verticillioides is linked to denitrification

USDA-ARS?s Scientific Manuscript database

Nitric oxide (NO) is a potent cellular signaling molecule and a byproduct of nitrogen metabolism. High concentrations of NO are a form of nitrosative stress, and to alleviate this stress, organisms utilize flavohemoglobins to convert NO into nontoxic nitrate ions. We have investigated the capacity o...

Bench-Scale Evaluation of Peracetic Acid and Twin Oxide ™ as Disinfectants in Drinking Water

EPA Science Inventory

Chlorine is widely used as an inexpensive and potent disinfectant in the United States for drinking water. However, chlorine has the potential for forming carcinogenic and mutagenic disinfection by-products (DBPs). In this study, bench scale experiments were conducted at the U.S...

DETERMINATION OF OPTIMAL TOXICANT LOADING FOR BIOLOGICAL CLOSURE OF A HAZARDOUS WASTE SITE

EPA Science Inventory

Information on Phase I and Phase Il of a multitask effort to achieve biological closure of an abandoned hazardous waste site. aste materials, in the form of buried sludges and lagoon wastes, were examined. ptimal loading levels were evaluated on the basis of biodegradative potent...

75 FR 38829 - Renewal of Approved Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

... contact Barbara Gamble at 202- 912-7148. Persons who use a telecommunication device for the deaf (TDD) may call the Federal Information Relay Service (FIRS) on 1-800-877- 8339, to contact Ms. Gamble. You may also contact Ms. Gamble to obtain a copy, at no cost, of the regulations and forms that require this...

14 CFR 243.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... control over an aircraft, by force or violence or threat of force or violence, or by any other form of... piracy. Contact means a person not on the covered flight or an entity that should be contacted in case of an aviation disaster. The contact need not have any particular relationship to a passenger. Covered...

14 CFR 243.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... control over an aircraft, by force or violence or threat of force or violence, or by any other form of... piracy. Contact means a person not on the covered flight or an entity that should be contacted in case of an aviation disaster. The contact need not have any particular relationship to a passenger. Covered...

14 CFR 243.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... control over an aircraft, by force or violence or threat of force or violence, or by any other form of... piracy. Contact means a person not on the covered flight or an entity that should be contacted in case of an aviation disaster. The contact need not have any particular relationship to a passenger. Covered...

14 CFR 243.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... control over an aircraft, by force or violence or threat of force or violence, or by any other form of... piracy. Contact means a person not on the covered flight or an entity that should be contacted in case of an aviation disaster. The contact need not have any particular relationship to a passenger. Covered...

14 CFR 243.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... control over an aircraft, by force or violence or threat of force or violence, or by any other form of... piracy. Contact means a person not on the covered flight or an entity that should be contacted in case of an aviation disaster. The contact need not have any particular relationship to a passenger. Covered...

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…

The Politics of Educational Innovation.

ERIC Educational Resources Information Center

House, Ernest R.

This book is developed on the theme that most innovation is dependent on face-to-face personal contacts and that these contacts condition the occurrence and frequency of innovation. Chapter 1 presents the substance, basis, and implications of this reasoning. Chapter 2 shows the influence of personal contacts in the form of population centers on…

ComplexContact: a web server for inter-protein contact prediction using deep learning.

PubMed

Zeng, Hong; Wang, Sheng; Zhou, Tianming; Zhao, Feifeng; Li, Xiufeng; Wu, Qing; Xu, Jinbo

2018-05-22

ComplexContact (http://raptorx2.uchicago.edu/ComplexContact/) is a web server for sequence-based interfacial residue-residue contact prediction of a putative protein complex. Interfacial residue-residue contacts are critical for understanding how proteins form complex and interact at residue level. When receiving a pair of protein sequences, ComplexContact first searches for their sequence homologs and builds two paired multiple sequence alignments (MSA), then it applies co-evolution analysis and a CASP-winning deep learning (DL) method to predict interfacial contacts from paired MSAs and visualizes the prediction as an image. The DL method was originally developed for intra-protein contact prediction and performed the best in CASP12. Our large-scale experimental test further shows that ComplexContact greatly outperforms pure co-evolution methods for inter-protein contact prediction, regardless of the species.

Thin film photovoltaic device

DOEpatents

Catalano, Anthony W.; Bhushan, Manjul

1982-01-01

A thin film photovoltaic solar cell which utilizes a zinc phosphide semiconductor is of the homojunction type comprising an n-type conductivity region forming an electrical junction with a p-type region, both regions consisting essentially of the same semiconductor material. The n-type region is formed by treating zinc phosphide with an extrinsic dopant such as magnesium. The semiconductor is formed on a multilayer substrate which acts as an opaque contact. Various transparent contacts may be used, including a thin metal film of the same chemical composition as the n-type dopant or conductive oxides or metal grids.

Process for the enhanced capture of heavy metal emissions

DOEpatents

Biswas, Pratim; Wu, Chang-Yu

2001-01-01

This invention is directed to a process for forming a sorbent-metal complex. The process includes oxidizing a sorbent precursor and contacting the sorbent precursor with a metallic species. The process further includes chemically reacting the sorbent precursor and the metallic species, thereby forming a sorbent-metal complex. In one particular aspect of the invention, at least a portion of the sorbent precursor is transformed into sorbent particles during the oxidation step. These sorbent particles then are contacted with the metallic species and chemically reacted with the metallic species, thereby forming a sorbent-metal complex. Another aspect of the invention is directed to a process for forming a sorbent metal complex in a combustion system. The process includes introducing a sorbent precursor into a combustion system and subjecting the sorbent precursor to an elevated temperature sufficient to oxidize the sorbent precursor and transform the sorbent precursor into sorbent particles. The process further includes contacting the sorbent particles with a metallic species and exposing the sorbent particles and the metallic species to a complex-forming temperature whereby the metallic species reacts with the sorbent particles thereby forming a sorbent-metal complex under UV irradiation.

High-efficiency photovoltaic cells

DOEpatents

Yang, H.T.; Zehr, S.W.

1982-06-21

High efficiency solar converters comprised of a two cell, non-lattice matched, monolithic stacked semiconductor configuration using optimum pairs of cells having bandgaps in the range 1.6 to 1.7 eV and 0.95 to 1.1 eV, and a method of fabrication thereof, are disclosed. The high band gap subcells are fabricated using metal organic chemical vapor deposition (MOCVD), liquid phase epitaxy (LPE) or molecular beam epitaxy (MBE) to produce the required AlGaAs layers of optimized composition, thickness and doping to produce high performance, heteroface homojunction devices. The low bandgap subcells are similarly fabricated from AlGa(As)Sb compositions by LPE, MBE or MOCVD. These subcells are then coupled to form a monolithic structure by an appropriate bonding technique which also forms the required transparent intercell ohmic contact (IOC) between the two subcells. Improved ohmic contacts to the high bandgap semiconductor structure can be formed by vacuum evaporating to suitable metal or semiconductor materials which react during laser annealing to form a low bandgap semiconductor which provides a low contact resistance structure.

Humidity-induced room-temperature decomposition of Au contacted indium phosphide

NASA Technical Reports Server (NTRS)

Fatemi, Navid S.; Weizer, Victor G.

1990-01-01

It has been found that Au-contacted InP is chemically unstable at room temperature in a humid ambient due to the leaching action of indium nitrate islands that continually remove In from the contact metallization and thus, in effect, from the Inp substrate. While similar appearing islands form on Au-contacted GaAs, that system appears to be stable since leaching of the group III element does not take place.

Investigating How Contact Angle Effects the Interaction between Water and a Hydrophobic Surface

NASA Astrophysics Data System (ADS)

Poynor, Adele; Neidig, Caitlyn

2012-02-01

By definition hydrophobic substances hate water. What happens when water is forced into contact with a hydrophobic surface? One theory is that an ultra-thin low-density region forms near the surface. Contact angle is a measure of how hydrophobic a surface is. We have employed an automated home-built Surface Plasmon Resonance (SPR) apparatus to investigate the effect of varying the contact angle on the depletion layer

The topological pressure-temperature phase diagram and crystal structures of the dimorphic system spiperone.

PubMed

Robert, B; Perrin, M-A; Coquerel, G; Céolin, R; Rietveld, I B

2016-03-01

The topological pressure-temperature phase diagram for the dimorphism of spiperone, a potent neuroleptic drug, has been constructed using literature data and improved crystal structures obtained with new crystallographic data from single-crystal X-ray diffraction at various temperatures. It is inferred that form II, which is the more dense form and exhibits the lower melting temperature, becomes the more stable phase under pressure. Under ambient conditions, form I is more stable. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Hair dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation.

PubMed

Lee, Hye-Young; Jeong, Young-Il; Choi, Ki-Choon

2011-01-01

p-Phenylenediamine (PDA) or its related chemicals are used more extensively than oxidative hair dyes. However, permanent hair dyes such as PDA are known to have potent contact allergy reactions in humans, and severe allergic reactions are problematic. PDA-incorporated nanoparticles were prepared based on ion-complex formation between the cationic groups of PDA and the anionic groups of poly(γ-glutamic acid) (PGA). To reinforce PDA/PGA ion complexes, glycol chitosan (GC) was added. PDA-incorporated nanoparticles were characterized using field-emission scanning electron microscopy, Fourier- transform infrared (FT-IR) spectroscopy, dynamic light scattering, and powder X-ray diffractometry (XRD). Nanoparticles were formed by ion-complex formation between the amine groups of PDA and the carboxyl groups of PGA. PDA-incorporated nanoparticles are small in size (<100 nm), and morphological observations showed spherical shapes. FT-IR spectra results showed that the carboxylic acid peak of PGA decreased with increasing PDA content, indicating that the ion complexes were formed between the carboxyl groups of PGA and the amine groups of PDA. Furthermore, the intrinsic peak of the carboxyl groups of PGA was also decreased by the addition of GC. Intrinsic crystalline peaks of PDA were observed by XRD. This crystalline peak of PDA was completely nonexistent when nanoparticles were formed by ion complex between PDA, PGA, and GC, indicating that PDA was complexed with PGA and no free drug existed in the formulation. During the drug-release experiment, an initial burst release of PDA was observed, and then PDA was continuously released over 1 week. Cytotoxicity testing against HaCaT human skin keratinocyte cells showed PDA-incorporated nanoparticles had lower toxicity than PDA itself. Furthermore, PDA-incorporated nanoparticles showed reduced apoptosis and necrosis reaction at HaCaT cells. The authors suggest that these microparticles are ideal candidates for a vehicle for decreasing side effects of hair dye.

Contact-dependent killing by Caulobacter crescentus via cell surface-associated, glycine zipper proteins.

PubMed

García-Bayona, Leonor; Guo, Monica S; Laub, Michael T

2017-03-21

Most bacteria are in fierce competition with other species for limited nutrients. Some bacteria can kill nearby cells by secreting bacteriocins, a diverse group of proteinaceous antimicrobials. However, bacteriocins are typically freely diffusible, and so of little value to planktonic cells in aqueous environments. Here, we identify an atypical two-protein bacteriocin in the α-proteobacterium Caulobacter crescentus that is retained on the surface of producer cells where it mediates cell contact-dependent killing. The bacteriocin-like proteins CdzC and CdzD harbor glycine-zipper motifs, often found in amyloids, and CdzC forms large, insoluble aggregates on the surface of producer cells. These aggregates can drive contact-dependent killing of other organisms, or Caulobacter cells not producing the CdzI immunity protein. The Cdz system uses a type I secretion system and is unrelated to previously described contact-dependent inhibition systems. However, Cdz-like systems are found in many bacteria, suggesting that this form of contact-dependent inhibition is common.

Development of a conformational search strategy for flexible ligands: A study of the potent μ-selective opioid analgesic fentanyl

NASA Astrophysics Data System (ADS)

Cometta-Morini, Chiara; Loew, Gilda H.

1991-08-01

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

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.

The (in)stability of 21st century orthopedic patient contact information and its implications on clinical research: a cross-sectional study

PubMed Central

London, Daniel A; Stepan, Jeffrey G; Goldfarb, Charles A; Boyer, Martin I; Calfee, Ryan P

2016-01-01

Background In clinical research, minimizing patients lost to follow-up is essential for data validity. Researchers can employ better methodology to prevent patient loss. We examined how orthopedic surgery patients’ contact information changes over time to optimize data collection for long-term outcomes research. Methods Patients presenting to orthopedic outpatient clinics completed questionnaires regarding methods of contact: home phone, cell phone, mailing address, and e-mail address. They reported currently available methods of contact, if they changed in the past five and ten years, and when they changed. Differences in the rates of change amongst methods were assessed via Fisher exact tests. Whether participants changed any of their contact information in the past five and ten years was determined via multivariate modeling, controlling for demographic variables. Results Among 152 patients, 51% changed at least one form of contact information within 5 years, and 66% changed at least one form within 10 years. The rate of change for each contact method was similar over five (15-28%) and ten years (26-41%). One patient changed all 4 methods of contact within the past five years, and seven within the past ten years. Females and younger patients were more likely to change some type of contact information. Conclusions The type of contact information least likely to change over five to ten years is influenced by demographic factors such as sex and age, with females and younger participants more likely to change some aspect of their contact information. Collecting all contact methods appears necessary to minimize patients lost to follow-up, especially as technological norms evolve. PMID:28359191

The (in)stability of 21st century orthopedic patient contact information and its implications on clinical research: A cross-sectional study.

PubMed

London, Daniel A; Stepan, Jeffrey G; Goldfarb, Charles A; Boyer, Martin I; Calfee, Ryan P

2017-04-01

In clinical research, minimizing patients lost to follow-up is essential for data validity. Researchers can employ better methodology to prevent patient loss. We examined how orthopedic surgery patients' contact information changes over time to optimize data collection for long-term outcomes research. Patients presenting to orthopedic outpatient clinics completed questionnaires regarding methods of contact: home phone, cell phone, mailing address, and e-mail address. They reported currently available methods of contact, if they changed in the past 5 and 10 years, and when they changed. Differences in the rates of change among methods were assessed via Fisher's exact tests. Whether participants changed any of their contact information in the past 5 and 10 years was determined via multivariate modeling, controlling for demographic variables. Among 152 patients, 51% changed at least one form of contact information within 5 years, and 66% changed at least one form within 10 years. The rate of change for each contact method was similar over 5 (15%-28%) and 10 years (26%-41%). One patient changed all four methods of contact within the past 5 years and seven within the past 10 years. Females and younger patients were more likely to change some type of contact information. The type of contact information least likely to change over 5-10 years is influenced by demographic factors such as sex and age, with females and younger participants more likely to change some aspect of their contact information. Collecting all contact methods appears necessary to minimize patients lost to follow-up, especially as technological norms evolve.

Probing the Allosteric Modulator Binding Site of GluR2 with Thiazide Derivatives

PubMed Central

Ptak, Christopher P.; Ahmed, Ahmed H.; Oswald, Robert E.

2009-01-01

Ionotropic glutamate receptors mediate the majority of vertebrate excitatory synaptic transmission and are therapeutic targets for cognitive enhancement and treatment of schizophrenia. The binding domains of these tetrameric receptors consist of two dimers, and the dissociation of the dimer interface of the ligand-binding domain leads to desensitization in the continued presence of agonist. Positive allosteric modulators act by strengthening the dimer interface and reducing desensitization, thereby increasing steady-state activation. Removing the desensitized state for simplified analysis of receptor activation is commonly achieved using cyclothiazide (CTZ), the most potent modulator of the benzothiadiazide class, with the flip form of the AMPA receptor subtype. IDRA-21, the first benzothiadiazide to have an effect in behavioral tests, is an important lead compound in clinical trials for cognitive enhancement as it can cross the blood-brain barrier. Intermediate structures between CTZ and IDRA-21 show reduced potency suggesting that these two compounds have different contact points associated with binding. To understand how benzothiadiazides bind to the pocket bridging the dimer interface, we generated a series of crystal structures of the GluR2 ligand-binding domain complexed with benzothiadiazide derivatives (IDRA-21, hydroflumethiazide, hydrochlorothiazide, chlorothiazide, trichlormethiazide, and althiazide) for comparison with an existing structure for cyclothiazide. The structures detail how changes in the substituents in the 3- and 7-positions of the hydrobenzothiadiazide ring shift the orientation of the drug in the binding site and, in some cases, change the stoichiometry of binding. All derivatives maintain a hydrogen bond with the Ser754 hydroxyl, affirming the partial selectivity of the benzothiadiazides for the flip form of AMPA receptors. PMID:19673491

Crystal Structure of Crataeva tapia Bark Protein (CrataBL) and Its Effect in Human Prostate Cancer Cell Lines

PubMed Central

Ferreira, Joana Gasperazzo; Silva, Mariana Cristina Cabral; Silva-Lucca, Rosemeire Aparecida; Mentele, Reinhard; Paredes-Gamero, Edgar Julian; Bertolin, Thiago Carlos; dos Santos Correia, Maria Tereza; Paiva, Patrícia Maria Guedes; Gustchina, Alla; Wlodawer, Alexander; Oliva, Maria Luiza Vilela

2013-01-01

A protein isolated from the bark of Crataeva tapia (CrataBL) is both a Kunitz-type plant protease inhibitor and a lectin. We have determined the amino acid sequence and three-dimensional structure of CrataBL, as well as characterized its selected biochemical and biological properties. We found two different isoforms of CrataBL isolated from the original source, differing in positions 31 (Pro/Leu); 92 (Ser/Leu); 93 (Ile/Thr); 95 (Arg/Gly) and 97 (Leu/Ser). CrataBL showed relatively weak inhibitory activity against trypsin (Kiapp = 43 µM) and was more potent against Factor Xa (Kiapp = 8.6 µM), but was not active against a number of other proteases. We have confirmed that CrataBL contains two glycosylation sites and forms a dimer at high concentration. The high-resolution crystal structures of two different crystal forms of isoform II verified the β-trefoil fold of CrataBL and have shown the presence of dimers consisting of two almost identical molecules making extensive contacts (∼645 Å2). The structure differs from those of the most closely related proteins by the lack of the N-terminal β-hairpin. In experiments aimed at investigating the biological properties of CrataBL, we have shown that addition of 40 µM of the protein for 48 h caused maximum growth inhibition in MTT assay (47% of DU145 cells and 43% of PC3 cells). The apoptosis of DU145 and PC3 cell lines was confirmed by flow cytometry using Annexin V/FITC and propidium iodide staining. Treatment with CrataBL resulted in the release of mitochondrial cytochrome c and in the activation of caspase-3 in DU145 and PC3 cells. PMID:23823708

Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations.

PubMed

Subbotina, Julia; Yarov-Yarovoy, Vladimir; Lees-Miller, James; Durdagi, Serdar; Guo, Jiqing; Duff, Henry J; Noskov, Sergei Yu

2010-11-01

The hERG1 gene (Kv11.1) encodes a voltage-gated potassium channel. Mutations in this gene lead to one form of the Long QT Syndrome (LQTS) in humans. Promiscuous binding of drugs to hERG1 is known to alter the structure/function of the channel leading to an acquired form of the LQTS. Expectably, creation and validation of reliable 3D model of the channel have been a key target in molecular cardiology and pharmacology for the last decade. Although many models were built, they all were limited to pore domain. In this work, a full model of the hERG1 channel is developed which includes all transmembrane segments. We tested a template-driven de-novo design with ROSETTA-membrane modeling using side-chain placements optimized by subsequent molecular dynamics (MD) simulations. Although backbone templates for the homology modeled parts of the pore and voltage sensors were based on the available structures of KvAP, Kv1.2 and Kv1.2-Kv2.1 chimera channels, the missing parts are modeled de-novo. The impact of several alignments on the structure of the S4 helix in the voltage-sensing domain was also tested. Herein, final models are evaluated for consistency to the reported structural elements discovered mainly on the basis of mutagenesis and electrophysiology. These structural elements include salt bridges and close contacts in the voltage-sensor domain; and the topology of the extracellular S5-pore linker compared with that established by toxin foot-printing and nuclear magnetic resonance studies. Implications of the refined hERG1 model to binding of blockers and channels activators (potent new ligands for channel activations) are discussed. © 2010 Wiley-Liss, Inc.

Structural Basis for Reversible and Irreversible Inhibition of Human Cathepsin L by their Respective dipeptidyl glyoxal and diazomethylketone Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

R Shenoy; J Sivaraman

Cathepsin L plays a key role in many pathophysiological conditions including rheumatoid arthritis, tumor invasion and metastasis, bone resorption and remodeling. Here we report the crystal structures of two analogous dipeptidyl inhibitor complexes which inhibit human cathepsin L in reversible and irreversible modes, respectively. To-date, there are no crystal structure reports of complexes of proteases with their glyoxal inhibitors or complexes of cathepsin L and their diazomethylketone inhibitors. These two inhibitors - inhibitor 1, an {alpha}-keto-{beta}-aldehyde and inhibitor 2, a diazomethylketone, have different groups in the S1 subsite. Inhibitor 1 [Z-Phe-Tyr (OBut)-COCHO], with a Ki of 0.6 nM, is themore » most potent, reversible, synthetic peptidyl inhibitor of cathepsin L reported to-date. The structure of the inhibitor 1 complex was refined up to 2.2 {angstrom} resolution. The structure of the complex of the inhibitor 2 [Z-Phe-Tyr (t-Bu)-diazomethylketone], an irreversible inhibitor that can inactivate cathepsin L at {micro}M concentrations, was refined up to 1.76 {angstrom} resolution. These two inhibitors have substrate-like interactions with the active site cysteine (Cys25). Inhibitor 1 forms a tetrahedral hemithioacetal adduct, whereas the inhibitor 2 forms a thioester with Cys25. The inhibitor 1 {beta}-aldehyde group is shown to make a hydrogen bond with catalytic His163, whereas the ketone carbonyl oxygen of the inhibitor 2 interacts with the oxyanion hole. tert-Butyl groups of both inhibitors are found to make several non-polar contacts with S' subsite residues of cathepsin L. These studies, combined with other complex structures of cathepsin L, reveal the structural basis for their potency and selectivity.« less

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

PubMed

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

2006-06-01

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

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.

PEGylated bilirubin nanoparticle as an anti-oxidative and anti-inflammatory demulcent in pancreatic islet xenotransplantation.

PubMed

Kim, Min Jun; Lee, Yonghyun; Jon, Sangyong; Lee, Dong Yun

2017-07-01

Transplanted islets suffer hypoxic stress, which leads to nonspecific inflammation. This is the major cause of islet graft failure during the early stage of intrahepatic islet transplantation. Although bilirubin has shown potent anti-oxidative and anti-inflammatory functions, its clinical applications have been limited due to its insolubility and short half-life. To overcome this problem, novel amphiphilic bilirubin nanoparticles are designed. Hydrophilic poly(ethylene glycol) (PEG) is conjugated to the hydrophobic bilirubin molecule. Then, the PEG-bilirubin conjugates form nanoparticles via self-assembly, i.e., so-called to BRNPs. BRNPs can protect islet cells not only from chemically induced oxidative stress by scavenging reactive oxygen species molecules, but also from activated macrophages by suppressing cytokine release. Importantly, in vivo experiments demonstrate that BRNP treatment can dramatically and significantly prolong islet graft survival compared to bilirubin treatment. In addition, immunohistochemical analysis shows BRNPs have potent anti-oxidative and anti-inflammatory capabilities. Collectively, novel BRNPs can be a new potent remedy for successful islet transplantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rational Design of a Highly Potent and Selective Peptide Inhibitor of PACE4 by Salt Bridge Interaction with D160 at Position P3.

PubMed

Dianati, Vahid; Shamloo, Azar; Kwiatkowska, Anna; Desjardins, Roxane; Soldera, Armand; Day, Robert; Dory, Yves L

2017-08-08

PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH 2 . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal. Moreover, the β-branched nature of the new P3 residue favors the extended β-sheet conformation usually associated with substrates of proteases. This work provides new insight for better understanding of β-sheet backbone-backbone interactions between serine proteases and their peptidic ligands. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Yan; Li, Fengling; Babault, Nicolas

G9a-like protein (GLP) and G9a are highly homologous protein lysine methyltransferases (PKMTs) sharing approximately 80% sequence identity in their catalytic domains. GLP and G9a form a heterodimer complex and catalyze mono- and dimethylation of histone H3 lysine 9 and nonhistone substrates. Although they are closely related, GLP and G9a possess distinct physiological and pathophysiological functions. Thus, GLP or G9a selective small-molecule inhibitors are useful tools to dissect their distinct biological functions. We previously reported potent and selective G9a/GLP dual inhibitors including UNC0638 and UNC0642. Here we report the discovery of potent and selective GLP inhibitors including 4 (MS0124) and 18more » (MS012), which are >30-fold and 140-fold selective for GLP over G9a and other methyltransferases, respectively. The cocrystal structures of GLP and G9a in the complex with either 4 or 18 displayed virtually identical binding modes and interactions, highlighting the challenges in structure-based design of selective inhibitors for either enzyme.« less

A New Class of Antibody-Drug Conjugates with Potent DNA Alkylating Activity.

PubMed

Miller, Michael L; Fishkin, Nathan E; Li, Wei; Whiteman, Kathleen R; Kovtun, Yelena; Reid, Emily E; Archer, Katie E; Maloney, Erin K; Audette, Charlene A; Mayo, Michele F; Wilhelm, Alan; Modafferi, Holly A; Singh, Rajeeva; Pinkas, Jan; Goldmacher, Victor; Lambert, John M; Chari, Ravi V J

2016-08-01

The promise of tumor-selective delivery of cytotoxic agents in the form of antibody-drug conjugates (ADC) has now been realized, evidenced by the approval of two ADCs, both of which incorporate highly cytotoxic tubulin-interacting agents, for cancer therapy. An ongoing challenge remains in identifying potent agents with alternative mechanisms of cell killing that can provide ADCs with high therapeutic indices and favorable tolerability. Here, we describe the development of a new class of potent DNA alkylating agents that meets these objectives. Through chemical design, we changed the mechanism of action of our novel DNA cross-linking agent to a monofunctional DNA alkylator. This modification, coupled with linker optimization, generated ADCs that were well tolerated in mice and demonstrated robust antitumor activity in multiple tumor models at doses 1.5% to 3.5% of maximally tolerated levels. These properties underscore the considerable potential of these purpose-created, unique DNA-interacting conjugates for broadening the clinical application of ADC technology. Mol Cancer Ther; 15(8); 1870-8. ©2016 AACR. ©2016 American Association for Cancer Research.

A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells.

PubMed

Fuwa, Haruhiko; Sato, Mizuho

2017-10-20

Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells.

A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells

PubMed Central

Sato, Mizuho

2017-01-01

Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells. PMID:29053565

A nodally condensed SUPG formulation for free-surface computation of steady-state flows constrained by unilateral contact - Application to rolling

NASA Astrophysics Data System (ADS)

Arora, Shitij; Fourment, Lionel

2018-05-01

In the context of the simulation of industrial hot forming processes, the resultant time-dependent thermo-mechanical multi-field problem (v →,p ,σ ,ɛ ) can be sped up by 10-50 times using the steady-state methods while compared to the conventional incremental methods. Though the steady-state techniques have been used in the past, but only on simple configurations and with structured meshes, and the modern-days problems are in the framework of complex configurations, unstructured meshes and parallel computing. These methods remove time dependency from the equations, but introduce an additional unknown into the problem: the steady-state shape. This steady-state shape x → can be computed as a geometric correction t → on the domain X → by solving the weak form of the steady-state equation v →.n →(t →)=0 using a Streamline Upwind Petrov Galerkin (SUPG) formulation. There exists a strong coupling between the domain shape and the material flow, hence, a two-step fixed point iterative resolution algorithm was proposed that involves (1) the computation of flow field from the resolution of thermo-mechanical equations on a prescribed domain shape and (2) the computation of steady-state shape for an assumed velocity field. The contact equations are introduced in the penalty form both during the flow computation as well as during the free-surface correction. The fact that the contact description is inhomogeneous, i.e., it is defined in the nodal form in the former, and in the weighted residual form in the latter, is assumed to be critical to the convergence of certain problems. Thus, the notion of nodal collocation is invoked in the weak form of the surface correction equation to homogenize the contact coupling. The surface correction algorithm is tested on certain analytical test cases and the contact coupling is tested with some hot rolling problems.

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.

Method for cleaning a solar cell surface opening made with a solar etch paste

DOEpatents

Rohatgi, Ajeet; Meemongkolkiat, Vichai

2010-06-22

A thin silicon solar cell having a back dielectric passivation and rear contact with local back surface field is described. Specifically, the solar cell may be fabricated from a crystalline silicon wafer having a thickness from 50 to 500 micrometers. A barrier layer and a dielectric layer are applied at least to the back surface of the silicon wafer to protect the silicon wafer from deformation when the rear contact is formed. At least one opening is made to the dielectric layer. An aluminum contact that provides a back surface field is formed in the opening and on the dielectric layer. The aluminum contact may be applied by screen printing an aluminum paste having from one to 12 atomic percent silicon and then applying a heat treatment at 750 degrees Celsius.

Planar varactor frequency multiplier devices with blocking barrier

NASA Technical Reports Server (NTRS)

Lieneweg, Udo (Inventor); Frerking, Margaret A. (Inventor); Maserjian, Joseph (Inventor)

1994-01-01

The invention relates to planar varactor frequency multiplier devices with a heterojunction blocking barrier for near millimeter wave radiation of moderate power from a fundamental input wave. The space charge limitation of the submillimeter frequency multiplier devices of the BIN(sup +) type is overcome by a diode structure comprising an n(sup +) doped layer of semiconductor material functioning as a low resistance back contact, a layer of semiconductor material with n-type doping functioning as a drift region grown on the back contact layer, a delta doping sheet forming a positive charge at the interface of the drift region layer with a barrier layer, and a surface metal contact. The layers thus formed on an n(sup +) doped layer may be divided into two isolated back-to-back BNN(sup +) diodes by separately depositing two surface metal contacts. By repeating the sequence of the drift region layer and the barrier layer with the delta doping sheet at the interfaces between the drift and barrier layers, a plurality of stacked diodes is formed. The novelty of the invention resides in providing n-type semiconductor material for the drift region in a GaAs/AlGaAs structure, and in stacking a plurality of such BNN(sup +) diodes stacked for greater output power with and connected back-to-back with the n(sup +) GaAs layer as an internal back contact and separate metal contact over an AlGaAs barrier layer on top of each stack.

Discovery of a diazo-forming enzyme in cremeomycin biosynthesis.

PubMed

Waldman, Abraham J; Balskus, Emily P

2018-05-17

The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N-N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology and enable genome-based discovery of new diazo-containing metabolites.

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…

Hemin as a generic and potent protein misfolding inhibitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yanqin; Carver, John A.; Ho, Lam H.

2014-11-14

Highlights: • Hemin prevents Aβ42, α-synuclein and RCM-κ-casein forming amyloid fibrils. • Hemin inhibits the β-sheet structure formation of Aβ42. • Hemin reduces the cell toxicity caused by fibrillar Aβ42. • Hemin dissociates partially formed Aβ42 fibrils. • Hemin prevents amorphous aggregation by ADH, catalase and γs-crystallin. - Abstract: Protein misfolding causes serious biological malfunction, resulting in diseases including Alzheimer’s disease, Parkinson’s disease and cataract. Molecules which inhibit protein misfolding are a promising avenue to explore as therapeutics for the treatment of these diseases. In the present study, thioflavin T fluorescence and transmission electron microscopy experiments demonstrated that hemin preventsmore » amyloid fibril formation of kappa-casein, amyloid beta peptide and α-synuclein by blocking β-sheet structure assembly which is essential in fibril aggregation. Further, inhibition of fibril formation by hemin significantly reduces the cytotoxicity caused by fibrillar amyloid beta peptide in vitro. Interestingly, hemin degrades partially formed amyloid fibrils and prevents further aggregation to mature fibrils. Light scattering assay results revealed that hemin also prevents protein amorphous aggregation of alcohol dehydrogenase, catalase and γs-crystallin. In summary, hemin is a potent agent which generically stabilises proteins against aggregation, and has potential as a key molecule for the development of therapeutics for protein misfolding diseases.« less

Clay Nanoparticles Elicit Long-Term Immune Responses by Forming Biodegradable Depots for Sustained Antigen Stimulation.

PubMed

Chen, Weiyu; Zuo, Huali; Li, Bei; Duan, Chengcheng; Rolfe, Barbara; Zhang, Bing; Mahony, Timothy J; Xu, Zhi Ping

2018-05-01

Nanomaterials have been widely tested as new generation vaccine adjuvants, but few evoke efficient immunoreactions. Clay nanoparticles, for example, layered double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent adjuvanticity in generating effective and durable immune responses. However, the mechanism by which clay nanoadjuvants stimulate the immune system is not well understood. Here, it is demonstrated that LDH and HEC-antigen complexes form loose agglomerates in culture medium/serum. They also form nodules with loose structures in tissue after subcutaneous injection, where they act as a depot for up to 35 d. More importantly, clay nanoparticles actively and continuously recruit immune cells into the depot for up to one month, and stimulate stronger immune responses than FDA-approved adjuvants, Alum and QuilA. Sustained antigen release is also observed in clay nanoparticle depots, with 50-60% antigen released after 35 d. In contrast, Alum-antigen complexes show minimal antigen release from the depot. Importantly, LDH and HEC are more effective than QuilA and Alum in promoting memory T-cell proliferation. These findings suggest that both clay nanoadjuvants can serve as active vaccine platforms for sustained and potent immune responses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antibiofilm Effect of DNase against Single and Mixed Species Biofilm

PubMed Central

Sharma, Komal

2018-01-01

Biofilms are aggregates of microorganisms that coexist in socially coordinated micro-niche in a self-produced polymeric matrix on pre-conditioned surfaces. The biofilm matrix reduces the efficacy of antibiofilm strategies. DNase degrades the extracellular DNA (e-DNA) present in the matrix, rendering the matrix weak and susceptible to antimicrobials. In the current study, the effect of DNase I was evaluated during biofilm formation (pre-treatment), on preformed biofilms (post-treatment) and both (dual treatment). The DNase I pre-treatment was optimized for P. aeruginosa PAO1 (model biofilm organism) at 10 µg/mL and post-treatment at 10 µg/mL with 15 min of contact duration. Inclusion of Mg2+ alongside DNase I post-treatment resulted in 90% reduction in biofilm within only 5 min of contact time (irrespective of age of biofilm). On extension of these findings, DNase I was found to be less effective against mixed species biofilm than individual biofilms. DNase I can be used as potent antibiofilm agent and with further optimization can be effectively used for biofilm prevention and reduction in situ. PMID:29562719

Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

PubMed Central

Sawada, Yu; Hanakawa, Sho; Nakamizo, Satoshi; Murata, Teruasa; Ueharaguchi-Tanada, Yuri; Ono, Sachiko; Amano, Wataru; Nakajima, Saeko; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Kitoh, Akihiko; Dainichi, Teruki; Ogawa, Narihito; Kobayashi, Yuichi; Yokomizo, Takehiko; Arita, Makoto; Nakamura, Motonobu; Miyachi, Yoshiki

2015-01-01

Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID:26438363

HTLV-1-induced leukotriene B4 secretion by T cells promotes T cell recruitment and virus propagation

PubMed Central

Percher, Florent; Curis, Céline; Pérès, Eléonore; Artesi, Maria; Rosewick, Nicolas; Jeannin, Patricia; Gessain, Antoine; Gout, Olivier; Mahieux, Renaud; Ceccaldi, Pierre-Emmanuel; Van den Broeke, Anne; Duc Dodon, Madeleine; Afonso, Philippe V.

2017-01-01

The human T-lymphotropic virus type 1 (HTLV-1) is efficiently transmitted through cellular contacts. While the molecular mechanisms of viral cell-to-cell propagation have been extensively studied in vitro, those facilitating the encounter between infected and target cells remain unknown. In this study, we demonstrate that HTLV-1-infected CD4 T cells secrete a potent chemoattractant, leukotriene B4 (LTB4). LTB4 secretion is dependent on Tax-induced transactivation of the pla2g4c gene, which encodes the cytosolic phospholipase A2 gamma. Inhibition of LTB4 secretion or LTB4 receptor knockdown on target cells reduces T-cell recruitment, cellular contact formation and virus propagation in vitro. Finally, blocking the synthesis of LTB4 in a humanized mouse model of HTLV-1 infection significantly reduces proviral load. This results from a decrease in the number of infected clones while their expansion is not impaired. This study shows the critical role of LTB4 secretion in HTLV-1 transmission both in vitro and in vivo. PMID:28639618

The glutaminase activity of l-asparaginase is not required for anticancer activity against ASNS-negative cells

PubMed Central

Chan, Wai Kin; Lorenzi, Philip L.; Anishkin, Andriy; Purwaha, Preeti; Rogers, David M.; Sukharev, Sergei; Rempe, Susan B.; Weinstein, John N.

2014-01-01

l-Asparaginase (l-ASP) is a key component of therapy for acute lymphoblastic leukemia. Its mechanism of action, however, is still poorly understood, in part because of its dual asparaginase and glutaminase activities. Here, we show that l-ASP’s glutaminase activity is not always required for the enzyme’s anticancer effect. We first used molecular dynamics simulations of the clinically standard Escherichia coli l-ASP to predict what mutated forms could be engineered to retain activity against asparagine but not glutamine. Dynamic mapping of enzyme substrate contacts identified Q59 as a promising mutagenesis target for that purpose. Saturation mutagenesis followed by enzymatic screening identified Q59L as a variant that retains asparaginase activity but shows undetectable glutaminase activity. Unlike wild-type l-ASP, Q59L is inactive against cancer cells that express measurable asparagine synthetase (ASNS). Q59L is potently active, however, against ASNS-negative cells. Those observations indicate that the glutaminase activity of l-ASP is necessary for anticancer activity against ASNS-positive cell types but not ASNS-negative cell types. Because the clinical toxicity of l-ASP is thought to stem from its glutaminase activity, these findings suggest the hypothesis that glutaminase-negative variants of l-ASP would provide larger therapeutic indices than wild-type l-ASP for ASNS-negative cancers. PMID:24659632

Total Synthesis of (+)- and (±)-Hosieine A.

PubMed

Huang, Yu-Wen; Kong, Ke; Wood, John

2018-05-03

Described here is a concise total synthesis of the highly potent nicotinic acetylcholine receptor antagonist hosieine A in racemic ((±)-2) and enantioenriched ((+)-2) forms. The synthesis requires only 7-steps and features a telescoped reaction sequence initiated by a gold-catalyzed Rautenstrauch reaction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity

USDA-ARS?s Scientific Manuscript database

Botulinum neurotoxins (BoNTs) are highly potent oral poisons produced by Clostridium botulinum. BoNTs are secreted along with several auxiliary proteins forming progenitor toxin complexes (PTC). Here, we report the structure of a ~760 kDa 14-subunit PTC using a combination of X-ray crystallography a...

Recurrent selection to alter grain phytic acid concentration and iron bioavailability

USDA-ARS?s Scientific Manuscript database

Most of the phosphorus (P) in cereal grains is in the form of phytic acid, a potent inhibitor of iron absorption that cannot be digested by monogastric livestock or humans. High phytate content in staple crops contributes to the high incidence of iron deficiency in developing countries. Low phytic a...

Dynamics of solid dispersions in oil during the lubrication of point contacts. Part 1: Graphite

NASA Technical Reports Server (NTRS)

Cusano, C.; Sliney, H. E.

1981-01-01

A Hertzian contact was lubricated with dispersed graphite in mineral oils under boundary lubrication conditions. The contact was optically observed under pure rolling, combined rolling and sliding, and pure sliding conditions. The contact was formed with a steel ball on the flat surface of a glass disk. Photomicrographs are presented which show the distribution of the graphite in and around the contact. Friction and surface damage are also shown for conditions when the base oils are used alone and when graphite is added to the base oils. Under pure rolling and combined rolling and sliding conditions, it is found that, for low speeds, a graphite film can form which will separate the contacting surfaces. Under pure sliding conditions, graphite accumulates at the inlet and sweeps around the contact, but very little of the graphite passes through the contact. The accumulated graphite appears to act as a barrier which reduces the supply of oil available to the contact for boundary lubrication. Friction data show no clear short term beneficial or detrimental effect caused by addition of graphite to the base oil. However, during pure sliding, more abrasion occurs on the polished balls lubricated with the dispersion than on those lubricated with the base oil alone. All observations were for the special case of a highly-polished ball on a glass surface and may not be applicable to other geometries and materials, or to rougher surfaces.

D-enantiomeric peptides that eradicate wild-type and multi-drug resistant biofilms and protect against lethal Pseudomonas aeruginosa infections

PubMed Central

de la Fuente-Núñez, César; Reffuveille, Fany; Mansour, Sarah C.; Reckseidler-Zenteno, Shauna L.; Hernández, Diego; Brackman, Gilles; Coenye, Tom; Hancock, Robert E.W.

2015-01-01

SUMMARY In many infections, bacteria form surface-associated communities known as biofilms that are substantially more resistant to antibiotics than their planktonic counterparts. Based on the design features of active anti-biofilm peptides, we made a series of related 12-amino acid L-, D- and retro-inverso derivatives. Specific D-enantiomeric peptides were the most potent at inhibiting biofilm development and eradicating pre-formed biofilms of seven species of wild-type and multiply antibiotic resistant Gram-negative pathogens. Moreover, these peptides showed strong synergy with conventional antibiotics, reducing the antibiotic concentrations required for complete biofilm inhibition by up to 64-fold. As shown previously for 1018, these D-amino acid peptides targeted the intracellular stringent response signal (p)ppGpp. The most potent peptides DJK-5 and DJK-6 protected invertebrates from lethal P. aeruginosa infections, and were considerably more active than a previously described L-amino acid peptide 1018. Thus, the protease resistant peptides produced here were more effective both in vitro and in vivo. PMID:25699603

The effect of oxidant on resputtering of Bi from Bi-Sr-Ca-Cu-O films

NASA Astrophysics Data System (ADS)

Grace, J. M.; McDonald, D. B.; Reiten, M. T.; Olson, J.; Kampwirth, R. T.; Gray, K. E.

1991-09-01

The type and partial pressure of oxidant mixed with argon can affect the selective resputtering of Bi in composite-target, magnetron-sputtered Bi-Sr-Ca-Cu-O films. Comparative studies using oxygen and ozone show that ozone is a more potent oxidant, as well as a more potent source of resputterers, than is oxygen. Severe resputtering from ozone is significantly reduced by a -40 V potential on the sample block. We suggest that oxygen causes resputtering by forming O2(+)p , which interacts with the target to produce energetic O(-). In contrast, ozone may form lower-energy O(-) by electron impact in the dark space. Negative oxygen ions from the target itself may be responsible for a background resputtering effect. Our results and those found for Y-Ba-Cu-O by others are comparable. Bi in Bi-Sr-Ca-Cu-O behaves as Ba in Y-Ba-Cu-O, with regard to selective resputtering; furthermore, the response of Sr, Ca, and Cu to oxygen in sputtered Bi-Sr-Ca-Cu-O is similar to what is observed for Cu in Y-Ba-Cu-O.

Direct effects of manganese compounds on dopamine and its metabolite Dopac: an in vitro study

PubMed Central

Sistrunk, Shannon C.; Ross, Matthew K.; Filipov, Nikolay M.

2007-01-01

Following combustion of fuel containing the additive methylcyclopentadienyl-manganese-tricarbonyl (MMT), manganese phosphate (MnPO4) and manganese sulfate (MnSO4) are emitted in the atmosphere. Manganese chloride (MnCl2), another Mn2+ species, is widely used experimentally. Using rat striatal slices, we found that MnPO4 decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl2 or MnSO4; antioxidants were partially protective. Also, both MnCl2 and MnPO4 (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO4 will be more potent in forming aminochrome than MnCl2 or MnSO4 which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO4 in particular, is the generation of reactive DA intermediates. PMID:18449324

Caustic ulcers caused by cement aqua: report of a case.

PubMed

Machovcova, Alena

2010-01-01

Chromium is widely used in various industries including construction sector. Skin contact with cement has been associated with allergic or irritant contact dermatitis. Contact dermatitis is one of the most frequently reported health problems among construction workers. Irritant contact dermatitis from cement ranges from cement burns to cumulative irritant contact dermatitis. Cement burns are rarely reported and are considered a severe form of acute irritant contact dermatitis. They are associated with amateur user working in a short ready-mix time-frame with poor protective measures. They usually result in significant morbidity and initially are associated with minimal discomfort. We report a typical case.

Exposure of T lymphocytes to leflunomide but not to dexamethasone favors the production by monocytic cells of interleukin-1 receptor antagonist and the tissue-inhibitor of metalloproteinases-1 over that of interleukin-1beta and metalloproteinases.

PubMed

Déage, V; Burger, D; Dayer, J M

1998-12-01

On direct cell-cell contact, stimulated T lymphocytes potently trigger the production of pro-inflammatory factors such as interleukin-1beta (IL-1beta) and matrix metalloproteinases (MMP-1 and MMP-9), as well as anti-inflammatory factors such as IL-1 receptor antagonist (IL-1Ra) and the tissue inhibitor of metalloproteinases (TIMP-1) in peripheral blood monocytes and the monocytic cell line THP-1. Such mechanisms might play an important part in many inflammatory diseases where tissue destruction occurs. To assess whether anti-inflammatory agents such as dexamethasone (DEX) and leflunomide (LF) would affect contact-activation of monocytic cells, T lymphocytes were stimulated by PMA and PHA in the presence or absence of increasing concentrations of drug. LF and DEX (10- 4 M) inhibited the ability of stimulated T lymphocytes to activate monocytic cells by 66-97% and 43-70%, respectively, depending on the readout product. Upon contact with T lymphocytes stimulated in the presence of 10- 5 M LF, the molar ratio of IL-1Ra/IL-1beta and TIMP-1/MMP-1 produced by THP-1 cells was enhanced 3.6- and 1.9-fold, respectively, whereas it was enhanced only 1.3- and 1.4-fold upon contact with T lymphocytes stimulated in the presence of 10- 4 M DEX. Therefore, LF tends to favor the inhibition of pro-inflammatory and matrix-destructive factors over that of anti-inflammatory factors and metalloproteinase inhibitors, thus interfering with both inflammation and tissue destruction. These experiments indicate that LF and DEX have the potential to affect the capacity of stimulated T lymphocytes to activate, on direct cell-cell contact, monocytic cells. Furthermore, flow cytometric analysis revealed that surface molecules of T lymphocytes that were partially involved in contact-signaling of monocytes (i.e., CD69 and CD11) were not modulated by either LF or DEX, suggesting that factors which remain to be identified were mainly involved in the activation of monocytes on direct cell-cell contact.

Contact Us About Managing the Quality of Environmental Information

EPA Pesticide Factsheets

The contact us form for the EPA Quality Program regarding quality management activities for all environmental data collection and environmental technology programs performed by or for the Agency and the EPA Information Quality Guidelines.

Contacting passengers after exposure to measles on an international flight: Implications for responding to new disease threats and bioterrorism.

PubMed

Lasher, Lara E; Ayers, Tracy L; Amornkul, Pauli N; Nakatab, Michele N; Effler, Paul V

2004-01-01

On May 21, 2000, a passenger with measles traveled from Japan to Hawai'i on a seven-hour flight. When the flight landed, the U.S. Public Health Service (USPHS) Quarantine Station in Honolulu alerted passengers that a suspected case of measles had been identified, but they were not detained. The next day, to offer appropriate post-exposure prophylaxis, the Hawai'i Department of Health (HDOH) attempted to contact all passengers from the flight using information from the airline, U.S. Customs declaration forms, and tour agencies. Of 335 total passengers, 270 (81%) were successfully reached and provided complete information. The mean time from exposure to contact for all respondents was 61 hours (95% confidence interval 57, 66). A total of 202 (75%) of the responding passengers were contacted within 72 hours after exposure, the time period during which administration of measles vaccine would have provided protection for susceptible individuals. The time-to-contact was significantly longer for passengers who did not stay in hotels than for hotel guests. Customs forms proved to be of limited utility in contacting international travelers. This experience highlights the need for more complete and timely methods of contacting passengers potentially exposed to infectious agents aboard flights.

Method to protect charge recombination in the back-contact dye-sensitized solar cell.

PubMed

Yoo, Beomjin; Kim, Kang-Jin; Lee, Doh-Kwon; Kim, Kyungkon; Ko, Min Jae; Kim, Yong Hyun; Kim, Won Mok; Park, Nam-Gyu

2010-09-13

We prepared a back-contact dye-sensitized solar cell and investigated effect of the sputter deposited thin TiO₂ film on the back-contact ITO electrode on photovoltaic property. The nanocrystalline TiO₂ layer with thickness of about 11 μm formed on a plain glass substrate in the back-contact structure showed higher optical transmittance than that formed on an ITO-coated glass substrate, which led to an improved photocurrent density by about 6.3%. However, photovoltage was found to decrease from 817 mV to 773 mV. The photovoltage recovered after deposition of a 35 nm-thick thin TiO₂ film on the surface of the back-contact ITO electrode. Little difference in time constant for electron transport was found for the back-contact ITO electrodes with and without the sputter deposited thin TiO₂ film. Whereas, time constant for charge recombination increased after introduction of the thin TiO₂ film, indicating that such a thin TiO₂ film protected back electron transfer, associated with the recovery of photovoltage. As the result of the improved photocurrent density without deterioration of photovoltage, the back-contact dye-sensitized solar cell exhibited 13.6% higher efficiency than the ITO-coated glass substrate-based dye-sensitized solar cell.

Contacting passengers after exposure to measles on an international flight: Implications for responding to new disease threats and bioterrorism.

PubMed Central

Lasher, Lara E.; Ayers, Tracy L.; Amornkul, Pauli N.; Nakatab, Michele N.; Effler, Paul V.

2004-01-01

On May 21, 2000, a passenger with measles traveled from Japan to Hawai'i on a seven-hour flight. When the flight landed, the U.S. Public Health Service (USPHS) Quarantine Station in Honolulu alerted passengers that a suspected case of measles had been identified, but they were not detained. The next day, to offer appropriate post-exposure prophylaxis, the Hawai'i Department of Health (HDOH) attempted to contact all passengers from the flight using information from the airline, U.S. Customs declaration forms, and tour agencies. Of 335 total passengers, 270 (81%) were successfully reached and provided complete information. The mean time from exposure to contact for all respondents was 61 hours (95% confidence interval 57, 66). A total of 202 (75%) of the responding passengers were contacted within 72 hours after exposure, the time period during which administration of measles vaccine would have provided protection for susceptible individuals. The time-to-contact was significantly longer for passengers who did not stay in hotels than for hotel guests. Customs forms proved to be of limited utility in contacting international travelers. This experience highlights the need for more complete and timely methods of contacting passengers potentially exposed to infectious agents aboard flights. PMID:15313108

A novel aromatic oil compound inhibits microbial overgrowth on feet: a case study.

PubMed

Misner, Bill D

2007-07-13

Athlete's Foot (Tinea pedis) is a form of ringworm associated with highly contagious yeast-fungi colonies, although they look like bacteria. Foot bacteria overgrowth produces a harmless pungent odor, however, uncontrolled proliferation of yeast-fungi produces small vesicles, fissures, scaling, and maceration with eroded areas between the toes and the plantar surface of the foot, resulting in intense itching, blisters, and cracking. Painful microbial foot infection may prevent athletic participation. Keeping the feet clean and dry with the toenails trimmed reduces the incidence of skin disease of the feet. Wearing sandals in locker and shower rooms prevents intimate contact with the infecting organisms and alleviates most foot-sensitive infections. Enclosing feet in socks and shoes generates a moisture-rich environment that stimulates overgrowth of pungent both aerobic bacteria and infectious yeast-fungi. Suppression of microbial growth may be accomplished by exposing the feet to air to enhance evaporation to reduce moistures' growth-stimulating effect and is often neglected. There is an association between yeast-fungi overgrowths and disabling foot infections. Potent agents virtually exterminate some microbial growth, but the inevitable presence of infection under the nails predicts future infection. Topical antibiotics present a potent approach with the ideal agent being one that removes moisture producing antibacterial-antifungal activity. Severe infection may require costly prescription drugs, salves, and repeated treatment. A 63-y female volunteered to enclose feet in shoes and socks for 48 hours. Aerobic bacteria and yeast-fungi counts were determined by swab sample incubation technique (1) after 48-hours feet enclosure, (2) after washing feet, and (3) after 8-hours socks-shoes exposure to a aromatic oil powder-compound consisting of arrowroot, baking soda, basil oil, tea tree oil, sage oil, and clove oil. Application of this novel compound to the external surfaces of feet completely inhibited both aerobic bacteria and yeast-fungi-mold proliferation for 8-hours in spite of being in an enclosed environment compatible to microbial proliferation. Whether topical application of this compound prevents microbial infections in larger populations is not known. This calls for more research collected from subjects exposed to elements that may increase the risk of microbial-induced foot diseases.

Performance comparison of small-pixel CdZnTe radiation detectors with gold contacts formed by sputter and electroless deposition

NASA Astrophysics Data System (ADS)

Bell, S. J.; Baker, M. A.; Duarte, D. D.; Schneider, A.; Seller, P.; Sellin, P. J.; Veale, M. C.; Wilson, M. D.

2017-06-01

Recent improvements in the growth of wide-bandgap semiconductors, such as cadmium zinc telluride (CdZnTe or CZT), has enabled spectroscopic X/γ-ray imaging detectors to be developed. These detectors have applications covering homeland security, industrial analysis, space science and medical imaging. At the Rutherford Appleton Laboratory (RAL) a promising range of spectroscopic, position sensitive, small-pixel Cd(Zn)Te detectors have been developed. The challenge now is to improve the quality of metal contacts on CdZnTe in order to meet the demanding energy and spatial resolution requirements of these applications. The choice of metal deposition method and fabrication process are of fundamental importance. Presented is a comparison of two CdZnTe detectors with contacts formed by sputter and electroless deposition. The detectors were fabricated with a 74 × 74 array of 200 μm pixels on a 250 μm pitch and bump-bonded to the HEXITEC ASIC. The X/γ-ray emissions from an 241Am source were measured to form energy spectra for comparison. It was found that the detector with contacts formed by electroless deposition produced the best uniformity and energy resolution; the best pixel produced a FWHM of 560 eV at 59.54 keV and 50% of pixels produced a FWHM better than 1.7 keV . This compared with a FWHM of 1.5 keV for the best pixel and 50% of pixels better than 4.4 keV for the detector with sputtered contacts.

Phosphorylation of Ser136 is critical for potent bone sialoprotein-mediated nucleation of hydroxyapatite crystals.

PubMed

Baht, Gurpreet S; O'Young, Jason; Borovina, Antonia; Chen, Hong; Tye, Coralee E; Karttunen, Mikko; Lajoie, Gilles A; Hunter, Graeme K; Goldberg, Harvey A

2010-05-27

Acidic phosphoproteins of mineralized tissues such as bone and dentin are believed to play important roles in HA (hydroxyapatite) nucleation and growth. BSP (bone sialoprotein) is the most potent known nucleator of HA, an activity that is thought to be dependent on phosphorylation of the protein. The present study identifies the role phosphate groups play in mineral formation. Recombinant BSP and peptides corresponding to residues 1-100 and 133-205 of the rat sequence were phosphorylated with CK2 (protein kinase CK2). Phosphorylation increased the nucleating activity of BSP and BSP-(133-205), but not BSP-(1-100). MS analysis revealed that the major site phosphorylated within BSP-(133-205) was Ser136, a site adjacent to the series of contiguous glutamate residues previously implicated in HA nucleation. The critical role of phosphorylated Ser136 in HA nucleation was confirmed by site-directed mutagenesis and functional analyses. Furthermore, peptides corresponding to the 133-148 sequence of rat BSP were synthesized with or without a phosphate group on Ser136. As expected, the phosphopeptide was a more potent nucleator. The mechanism of nucleation was investigated using molecular-dynamics simulations analysing BSP-(133-148) interacting with the {100} crystal face of HA. Both phosphorylated and non-phosphorylated sequences adsorbed to HA in extended conformations with alternating residues in contact with and facing away from the crystal face. However, this alternating-residue pattern was more pronounced when Ser136 was phosphorylated. These studies demonstrate a critical role for Ser136 phosphorylation in BSP-mediated HA nucleation and identify a unique mode of interaction between the nucleating site of the protein and the {100} face of HA.

An aspirin-triggered lipoxin A4 stable analog displays a unique topical anti-inflammatory profile.

PubMed

Schottelius, Arndt J; Giesen, Claudia; Asadullah, Khusru; Fierro, Iolanda M; Colgan, Sean P; Bauman, John; Guilford, William; Perez, Hector D; Parkinson, John F

2002-12-15

Lipoxins and 15-epi-lipoxins are counter-regulatory lipid mediators that modulate leukocyte trafficking and promote the resolution of inflammation. To assess the potential of lipoxins as novel anti-inflammatory agents, a stable 15-epi-lipoxin A(4) analog, 15-epi-16-p-fluorophenoxy-lipoxin A(4) methyl ester (ATLa), was synthesized by total organic synthesis and examined for efficacy relative to a potent leukotriene B(4) (LTB(4)) receptor antagonist (LTB(4)R-Ant) and the clinically used topical glucocorticoid methylprednisolone aceponate. In vitro, ATLa was 100-fold more potent than LTB(4)R-Ant for inhibiting neutrophil chemotaxis and trans-epithelial cell migration induced by fMLP, but was approximately 10-fold less potent than the LTB(4)R-Ant in blocking responses to LTB(4). A broad panel of cutaneous inflammation models that display pathological aspects of psoriasis, atopic dermatitis, and allergic contact dermatitis was used to directly compare the topical efficacy of ATLa with that of LTB(4)R-Ant and methylprednisolone aceponate. ATLa was efficacious in all models tested: LTB(4)/Iloprost-, calcium ionophore-, croton oil-, and mezerein-induced inflammation and trimellitic anhydride-induced allergic delayed-type hypersensitivity. ATLa was efficacious in mouse and guinea pig skin inflammation models, exhibiting dose-dependent effects on edema, neutrophil or eosinophil infiltration, and epidermal hyperproliferation. We conclude that the LXA(4) and aspirin-triggered LXA(4) pathways play key anti-inflammatory roles in vivo. Moreover, these results suggest that ATLa and related LXA(4) analogs may have broad therapeutic potential in inflammatory disorders and could provide an alternative to corticosteroids in certain clinical settings.

7 CFR 622.20 - Application.

Code of Federal Regulations, 2010 CFR

2010-01-01

... forms for Federal assistance or other approved forms may be obtained from NRCS State, area, or field offices. These forms should be submitted to the Single Point of Contact in accordance with the State...

Monolithic integration of a MOSFET with a MEMS device

DOEpatents

Bennett, Reid; Draper, Bruce

2003-01-01

An integrated microelectromechanical system comprises at least one MOSFET interconnected to at least one MEMS device on a common substrate. A method for integrating the MOSFET with the MEMS device comprises fabricating the MOSFET and MEMS device monolithically on the common substrate. Conveniently, the gate insulator, gate electrode, and electrical contacts for the gate, source, and drain can be formed simultaneously with the MEMS device structure, thereby eliminating many process steps and materials. In particular, the gate electrode and electrical contacts of the MOSFET and the structural layers of the MEMS device can be doped polysilicon. Dopant diffusion from the electrical contacts is used to form the source and drain regions of the MOSFET. The thermal diffusion step for forming the source and drain of the MOSFET can comprise one or more of the thermal anneal steps to relieve stress in the structural layers of the MEMS device.

A novel head-neck cooling device for concussion injury in contact sports

PubMed Central

Wang, Huan; Wang, Bonnie; Jackson, Kevin; Miller, Claire M.; Hasadsri, Linda; Llano, Daniel; Rubin, Rachael; Zimmerman, Jarred; Johnson, Curtis; Sutton, Brad

2015-01-01

Emerging research on the long-term impact of concussions on athletes has allowed public recognition of the potentially devastating effects of these and other mild head injuries. Mild traumatic brain injury (mTBI) is a multifaceted disease for which management remains a clinical challenge. Recent pre-clinical and clinical data strongly suggest a destructive synergism between brain temperature elevation and mTBI; conversely, brain hypothermia, with its broader, pleiotropic effects, represents the most potent neuro-protectant in laboratory studies to date. Although well-established in selected clinical conditions, a systemic approach to accomplish regional hypothermia has failed to yield an effective treatment strategy in traumatic brain injury (TBI). Furthermore, although systemic hypothermia remains a potentially valid treatment strategy for moderate to severe TBIs, it is neither practical nor safe for mTBIs. Therefore, selective head-neck cooling may represent an ideal strategy to provide therapeutic benefits to the brain. Optimizing brain temperature management using a National Aeronautics and Space Administration (NASA) spacesuit spinoff head-neck cooling technology before and/or after mTBI in contact sports may represent a sensible, practical, and effective method to potentially enhance recover and minimize post-injury deficits. In this paper, we discuss and summarize the anatomical, physiological, preclinical, and clinical data concerning NASA spinoff head-neck cooling technology as a potential treatment for mTBIs, particularly in the context of contact sports. PMID:28123788

Arterial thrombosis is accelerated in mice deficient in histidine-rich glycoprotein.

PubMed

Vu, Trang T; Zhou, Ji; Leslie, Beverly A; Stafford, Alan R; Fredenburgh, James C; Ni, Ran; Qiao, Shengjun; Vaezzadeh, Nima; Jahnen-Dechent, Willi; Monia, Brett P; Gross, Peter L; Weitz, Jeffrey I

2015-04-23

Factor (F) XII, a key component of the contact system, triggers clotting via the intrinsic pathway, and is implicated in propagating thrombosis. Although nucleic acids are potent activators, it is unclear how the contact system is regulated to prevent uncontrolled clotting. Previously, we showed that histidine-rich glycoprotein (HRG) binds FXIIa and attenuates its capacity to trigger coagulation. To investigate the role of HRG as a regulator of the intrinsic pathway, we compared RNA- and DNA-induced thrombin generation in plasma from HRG-deficient and wild-type mice. Thrombin generation was enhanced in plasma from HRG-deficient mice, and accelerated clotting was restored to normal with HRG reconstitution. Although blood loss after tail tip amputation was similar in HRG-deficient and wild-type mice, carotid artery occlusion after FeCl3 injury was accelerated in HRG-deficient mice, and HRG administration abrogated this effect. To confirm that HRG modulates the contact system, we used DNase, RNase, and antisense oligonucleotides to characterize the FeCl3 model. Whereas DNase or FVII knockdown had no effect, carotid occlusion was abrogated with RNase or FXII knockdown, confirming that FeCl3-induced thrombosis is triggered by RNA in a FXII-dependent fashion. Therefore, in a nucleic acid-driven model, HRG inhibits thrombosis by modulating the intrinsic pathway of coagulation. © 2015 by The American Society of Hematology.

Contact toxicity and repellency of the essential oil from Mentha haplocalyx Briq. against Lasioderma serricorne.

PubMed

Zhang, Wen-Juan; Yang, Kai; You, Chun-Xue; Wang, Cheng-Fang; Geng, Zhu-Feng; Su, Yang; Wang, Ying; Du, Shu-Shan; Deng, Zhi-Wei

2015-05-01

The chemical composition of the essential oil obtained by hydrodistillation from the aerial parts of Mentha haplocalyx was investigated by GC-FID and GC/MS analyses. In sum, 23 components, representing 92.88% of the total oil composition, were identified, and the main compounds were found to be menthol (59.71%), menthyl acetate (7.83%), limonene (6.98%), and menthone (4.44%). By bioassay-guided fractionation (contact toxicity), three compounds were obtained from the essential oil and identified as menthol, menthyl acetate, and limonene. The essential oil and the three isolated compounds exhibited potent contact toxicity against Lasioderma serricorne adults, with LD50 values of 16.5, 7.91, 5.96, and 13.7 μg/adult, respectively. Moreover, the oil and its isolated compounds also exhibited strong repellency against L. serricorne adults. At the lower concentrations tested and at 2 h after exposure, menthol showed even significantly stronger repellency than the positive control DEET. The study revealed that the bioactivity properties of the essential oil can be attributed to the synergistic effects of its diverse major and minor components, which indicates that the M. haplocalyx oil and its isolated compounds have potential for the development as natural insecticides and/or repellents to control insects in stored grains and traditional Chinese medicinal materials. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

Thin film photovoltaic device

DOEpatents

Catalano, A.W.; Bhushan, M.

1982-08-03

A thin film photovoltaic solar cell which utilizes a zinc phosphide semiconductor is of the homojunction type comprising an n-type conductivity region forming an electrical junction with a p-type region, both regions consisting essentially of the same semiconductor material. The n-type region is formed by treating zinc phosphide with an extrinsic dopant such as magnesium. The semiconductor is formed on a multilayer substrate which acts as an opaque contact. Various transparent contacts may be used, including a thin metal film of the same chemical composition as the n-type dopant or conductive oxides or metal grids. 5 figs.

Method for forming metallic silicide films on silicon substrates by ion beam deposition

DOEpatents

Zuhr, Raymond A.; Holland, Orin W.

1990-01-01

Metallic silicide films are formed on silicon substrates by contacting the substrates with a low-energy ion beam of metal ions while moderately heating the substrate. The heating of the substrate provides for the diffusion of silicon atoms through the film as it is being formed to the surface of the film for interaction with the metal ions as they contact the diffused silicon. The metallic silicide films provided by the present invention are contaminant free, of uniform stoichiometry, large grain size, and exhibit low resistivity values which are of particular usefulness for integrated circuit production.

Reusable vibration resistant integrated circuit mounting socket

DOEpatents

Evans, Craig N.

1995-01-01

This invention discloses a novel form of socket for integrated circuits to be mounted on printed circuit boards. The socket uses a novel contact which is fabricated out of a bimetallic strip with a shape which makes the end of the strip move laterally as temperature changes. The end of the strip forms a barb which digs into an integrated circuit lead at normal temperatures and holds it firmly in the contact, preventing loosening and open circuits from vibration. By cooling the contact containing the bimetallic strip the barb end can be made to release so that the integrated circuit lead can be removed from the socket without damage either to the lead or to the socket components.

Composite drill pipe

DOEpatents

Leslie, James C [Fountain Valley, CA; Leslie, II, James C.; Heard, James [Huntington Beach, CA; Truong, Liem , Josephson; Marvin, Neubert [Huntington Beach, CA; Hans, [Anaheim, CA

2008-12-02

A composite pipe segment is formed to include tapered in wall thickness ends that are each defined by opposed frustoconical surfaces conformed for self centering receipt and intimate bonding contact within an annular space between corresponding surfaces of a coaxially nested set of metal end pieces. The distal peripheries of the nested end pieces are then welded to each other and the sandwiched and bonded portions are radially pinned. The composite segment may include imbedded conductive leads and the axial end portions of the end pieces are shaped to form a threaded joint with the next pipe assembly that includes a contact ring in one pipe assembly pierced by a pointed contact in the other to connect the corresponding leads across the joint.

Die Deformation Measurement System during Sheet Metal Forming

NASA Astrophysics Data System (ADS)

Funada, J.; Takahashi, S.; Fukiharu, H.

2011-08-01

In order to reduce affection to the earth environment, it is necessary to lighten the vehicles. For this purpose, high tensile steels are applied. Because of high strength, high forming force is required for producing automotive sheet metal parts. In this situation, since the dies are elastic, they are deformed during forming parts. For reducing die developing period, sheet metal forming simulation is widely applied. In the numerical simulation, rigid dies are usually used for shortening computing time. It means that the forming conditions in the actual forming and the simulation are different. It will make large errors in the results between actual forming and simulation. It can be said that if contact pressure between dies and a sheet metal in the simulation can be reproduced in the actual forming, the differences of forming results between them can also been reduced. The basic idea is to estimate die shape which can produce the same distribution as computed from simulation with rigid dies. In this study, die deformation analyses with Finite Element Method as basic technologies are evaluated. For example, simple shape and actual dies elastic contact problems were investigated. The contact width between simple shape dies was investigated. The computed solutions were in good agreement with experimental results. The one case of the actual dies in two cases was also investigated. Bending force was applied to the blank holder with a mechanical press machine. The methodology shown with applying inductive displacement sensor for measuring die deformation during applying force was also proposed.

46 CFR 148.11 - Hazardous or potentially dangerous characteristics.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Contact with water may cause evolution of flammable gases, which may form explosive mixtures with air. 3 Contact with water may cause evolution of toxic gases. 4 If involved in a fire, will greatly intensify the...

46 CFR 148.11 - Hazardous or potentially dangerous characteristics.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Contact with water may cause evolution of flammable gases, which may form explosive mixtures with air. 3 Contact with water may cause evolution of toxic gases. 4 If involved in a fire, will greatly intensify the...

46 CFR 148.11 - Hazardous or potentially dangerous characteristics.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Contact with water may cause evolution of flammable gases, which may form explosive mixtures with air. 3 Contact with water may cause evolution of toxic gases. 4 If involved in a fire, will greatly intensify the...

46 CFR 148.11 - Hazardous or potentially dangerous characteristics.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Contact with water may cause evolution of flammable gases, which may form explosive mixtures with air. 3 Contact with water may cause evolution of toxic gases. 4 If involved in a fire, will greatly intensify the...

Increasing light coupling in a photovoltaic film by tuning nanoparticle shape with substrate surface energy

NASA Astrophysics Data System (ADS)

Kataria, Devika; Krishnamoorthy, Kothandam; Iyer, S. Sundar Kumar

2017-08-01

Tuning metal nanoparticle (MNP) contact angle on the surface it is formed can help maximise the useful optical coupling in photovoltaic films by localized surface plasmon (LSP) resonance—opening up the possibility of building improved photovoltaic cells. In this work experimental demonstration of optical absorption increase in copper phthalocyanine (CuPc) films by tuning silver MNP shape by changing its contact angles with substrate has been reported. Thin films of poly3,4 ethylenedioxythiophene: sodium dodecycl sulphate (PEDOT:SDS) with different surface energies were formed on indium tin oxide (ITO) coated glass by electro-deposition. Silver MNPs thermally evaporated directly on ozonised ITO as well as on the PEDOT:SDS films showed contact angles ranging from 60° to 125°. The CuPc layer was deposited on top of the MNPs. For the samples studied, best optical absorption in the CuPc layer was for a contact angle of 110°.

Planarized arrays of aligned, untangled multiwall carbon nanotubes with Ohmic back contacts

DOE PAGES

Rochford, C.; Limmer, S. J.; Howell, S. W.; ...

2014-11-26

Vertically aligned, untangled planarized arrays of multiwall carbon nanotubes (MWNTs) with Ohmic back contacts were grown in nanopore templates on arbitrary substrates. The templates were prepared by sputter depositing Nd-doped Al films onto W-coated substrates, followed by anodization to form an aluminum oxide nanopore array. The W underlayer helps eliminate the aluminum oxide barrier that typically occurs at the nanopore bottoms by instead forming a thin WO 3 layer. The WO 3 can be selectively etched to enable electrodeposition of Co catalysts with control over the Co site density. This led to control of the site density of MWNTs grownmore » by thermal chemical vapor deposition, with the W also serving as a back electrical contact. As a result, Ohmic contact to MWNTs was confirmed, even following ultrasonic cutting of the entire array to a uniform height.« less

Intermediate view synthesis for eye-gazing

NASA Astrophysics Data System (ADS)

Baek, Eu-Ttuem; Ho, Yo-Sung

2015-01-01

Nonverbal communication, also known as body language, is an important form of communication. Nonverbal behaviors such as posture, eye contact, and gestures send strong messages. In regard to nonverbal communication, eye contact is one of the most important forms that an individual can use. However, lack of eye contact occurs when we use video conferencing system. The disparity between locations of the eyes and a camera gets in the way of eye contact. The lock of eye gazing can give unapproachable and unpleasant feeling. In this paper, we proposed an eye gazing correction for video conferencing. We use two cameras installed at the top and the bottom of the television. The captured two images are rendered with 2D warping at virtual position. We implement view morphing to the detected face, and synthesize the face and the warped image. Experimental results verify that the proposed system is effective in generating natural gaze-corrected images.

Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity.

PubMed

Williard, Robin L; Middaugh, Lawrence D; Zhu, Hao-Jie B; Patrick, Kennerly S

2007-02-01

Ethylphenidate is formed by metabolic transesterification of methylphenidate and ethanol. Study objectives were to (a) establish that ethylphenidate is formed in C57BL/6 (B6) mice; (b) compare the stimulatory effects of ethylphenidate and methylphenidate enantiomers; (c) determine methylphenidate and ethylphenidate plasma and brain distribution and (d) establish in-vitro effects of methylphenidate and ethylphenidate on monoamine transporter systems. Experimental results were that: (a) coadministration of ethanol with the separate methylphenidate isomers enantioselectively produced l-ethylphenidate; (b) d and dl-forms of methylphenidate and ethylphenidate produced dose-responsive increases in motor activity with stimulation being less for ethylphenidate; (c) plasma and whole-brain concentrations were greater for ethylphenidate than methylphenidate and (d) d and DL-methylphenidate and ethylphenidate exhibited comparably potent low inhibition of the dopamine transporter, whereas ethylphenidate was a less potent norepinephrine transporter inhibitor. These experiments establish the feasibility of the B6 mouse model for examining the interactive effects of ethanol and methylphenidate. As reported for humans, concurrent exposure of B6 mice to methylphenidate and ethanol more readily formed l-ethylphenidate than d-ethylphenidate, and the l-isomers of both methylphenidate and ethylphenidate were biologically inactive. The observed reduced stimulatory effect of d-ethylphenidate relative to d-methylphenidate appears not to be the result of brain dispositional factors, but rather may be related to its reduced inhibition of the norepinephrine transporter, perhaps altering the interaction of dopaminergic and noradrenergic neural systems.

Pustular irritant contact dermatitis caused by dexpanthenol in a child.

PubMed

Gulec, Ali Ihsan; Albayrak, Hulya; Uslu, Esma; Başkan, Elife; Aliagaoglu, Cihangir

2015-03-01

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

Health effects of coal mining and combustion: carcinogens and cofactors.

PubMed Central

Falk, H L; Jurgelski, W

1979-01-01

Some polynuclear aromatics (PNA) have been found to be potent carcinogens for all tissues and organs of experimental animals that have been exposed to them, but different dose levels are needed for these effects. They have been known for decades to cause cancer at the site of application but also at certain sites distant from the area of contact. Although some hydrocarbons are potent and complete carcinogens, the majority of related hydrocarbons was originally found to be inactive. Since they generally appear together, it was important to know more about their interaction, particularly whether they would synergize, or antagonize. The polycyclic hydrocarbons have been studied by subcutaneous injection, where they prove very potent carcinogens. They are also very active on the skin of mice where they produce cancer on prolonged application. Inhalation studies, require larger doses yielded negative results until particulate matter was introduced which facilitated the development of lung tumors. Although iron oxide dust was used initially, other dusts were also capable of enhancing the response of the tissue to benzo(a)pyrene carcinogenesis. This point is of importance, particularly since the inhalation of PNA in situations of air pollution or coal mining involves particulates, although of a different type. Soot is not a homogenous substance and several factors determine its properties. Soots will lose some of the absorbed chemicals during their residence in air, but they retain their PNAs for long periods of time when they reach the soil. The carcinogenicity of PNAs in the adsorbed state may be completely absent, depending on particle size of the soot and availability of eluting capability of the tissues or cells in contact with the soot. Whenever the carcinogenic polynuclear aromatics can be eluted they will be active in producing cancer if their residence is adequate. There seems to be no reason to assume that a large increase in coal combustion in the future will by necessity lead to greater risks of cancer to the coal miners or the general urban dweller, because activities to be started now can take into consideration the requirements necessary for control of air pollution in mines as well as in cities. If new uses of coal will be developed, it will be a completely different situation, and statements about the carcinogenic risk from coal utilization do not apply there. Although some of the same carcinogenic PNAs are involved in the health hazards from those processes, other carcinogens and also cocarcinogens will be present, and the exposed workers will not have the apparent benefits of adsorption of PNAs on soot. PMID:540618

Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells

PubMed Central

Hillaire, Marine L. B.; Dejnirattisai, Wanwisa; Mongkolsapaya, Juthathip; Screaton, Gavin R.; Davidson, Andrew D.; Dreux, Marlène

2014-01-01

Dengue virus (DENV) is the leading cause of mosquito-borne viral illness and death in humans. Like many viruses, DENV has evolved potent mechanisms that abolish the antiviral response within infected cells. Nevertheless, several in vivo studies have demonstrated a key role of the innate immune response in controlling DENV infection and disease progression. Here, we report that sensing of DENV infected cells by plasmacytoid dendritic cells (pDCs) triggers a robust TLR7-dependent production of IFNα, concomitant with additional antiviral responses, including inflammatory cytokine secretion and pDC maturation. We demonstrate that unlike the efficient cell-free transmission of viral infectivity, pDC activation depends on cell-to-cell contact, a feature observed for various cell types and primary cells infected by DENV, as well as West Nile virus, another member of the Flavivirus genus. We show that the sensing of DENV infected cells by pDCs requires viral envelope protein-dependent secretion and transmission of viral RNA. Consistently with the cell-to-cell sensing-dependent pDC activation, we found that DENV structural components are clustered at the interface between pDCs and infected cells. The actin cytoskeleton is pivotal for both this clustering at the contacts and pDC activation, suggesting that this structural network likely contributes to the transmission of viral components to the pDCs. Due to an evolutionarily conserved suboptimal cleavage of the precursor membrane protein (prM), DENV infected cells release uncleaved prM containing-immature particles, which are deficient for membrane fusion function. We demonstrate that cells releasing immature particles trigger pDC IFN response more potently than cells producing fusion-competent mature virus. Altogether, our results imply that immature particles, as a carrier to endolysosome-localized TLR7 sensor, may contribute to regulate the progression of dengue disease by eliciting a strong innate response. PMID:25340500

Rac regulates vascular endothelial growth factor stimulated motility.

PubMed

Soga, N; Connolly, J O; Chellaiah, M; Kawamura, J; Hruska, K A

2001-01-01

During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood. Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF. These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent. VEGF stimulated chemotaxis, is critically dependent on Rac activation. Osteopontin was a potent matrix activator of motility, and perhaps one explanation for the absence of a VEGF plus osteopontin effect is that osteopontin stimulated motility was inhibitory to the Rac pathway.

Ultrastructure of the central subnucleus of the nucleus tractus solitarii and the esophageal afferent terminals in the rat.

PubMed

Hayakawa, Tetsu; Takanaga, Akinori; Tanaka, Koichi; Maeda, Seishi; Seki, Makoto

2003-03-01

The central subnucleus of the nucleus tractus solitarii (ceNTS) receives afferent projections from the esophageal wall and projects to the nucleus ambiguus, thus serving as a relay nucleus for peristalsis of the esophagus. Here we examine the synaptic organization of the ceNTS, and its esophageal afferents by using transganglionic anterograde transport of cholera toxin-conjugated horseradish peroxidase (CT-HRP). When CT-HRP was injected into the subdiaphragmatic esophagus, many anterogradely labeled terminals were found only in the ceNTS. The ceNTS was composed of round or oval-shaped, small neurons (14.7x8.7 micro m) containing sparse organelles and an irregularly shaped nucleus. The average number of axosomatic terminals was only 1.3 per section cut through the nucleolus. Most of them (92%) contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), and a few (8%) contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). All anterogradely labeled terminals contacted dendrites but not the neuronal somata. The labeled terminals were large (2.55+/-0.07 micro m) and exclusively Gray's type I. More than half of them (60%) contacted small dendrites (less than 1 micro m in diameter), and contained dense-cored vesicles. More than 40% of the labeled terminals contacted two to four dendrites, thus forming a synaptic glomerulus. Sometimes a labeled terminal that contacted an unlabeled terminal by an adherent junction was found within the glomerulus. The large terminals and these complex synaptic relations appeared to characterize the esophageal afferent projections in the ceNTS.

Understanding the operational parameters affecting NDMA formation at Advanced Water Treatment Plants.

PubMed

Farré, Maria José; Döderer, Katrin; Hearn, Laurence; Poussade, Yvan; Keller, Jurg; Gernjak, Wolfgang

2011-01-30

N-nitrosodimethylamine (NDMA) can be formed when secondary effluents are disinfected by chloramines. By means of bench scale experiments this paper investigates operational parameters than can help Advanced Water Treatment Plants (AWTPs) to reduce the formation of NDMA during the production of high quality recycled water. The formation of NDMA was monitored during a contact time of 24h using dimethylamine as NDMA model precursor and secondary effluent from wastewater treatment plants. The three chloramine disinfection strategies tested were pre-formed and in-line formed monochloramine, and pre-formed dichloramine. Although the latter is not employed on purpose in full-scale applications, it has been suggested as the main contributing chemical generating NDMA during chloramination. After 24h, the NDMA formation decreased in both matrices tested in the order: pre-formed dichloramine>in-line formed monochloramine≫pre-formed monochloramine. The most important parameter to consider for the inhibition of NDMA formation was the length of contact time between disinfectant and wastewater. Formation of NDMA was initially inhibited for up to 6h with concentrations consistently <10 ng/L during these early stages of disinfection, regardless of the disinfection strategy. The reduction of the contact time was implemented in Bundamba AWTP (Queensland, Australia), where NDMA concentrations were reduced by a factor of 20 by optimizing the disinfection strategy. Copyright © 2010 Elsevier B.V. All rights reserved.

Response of jammed packings to thermal fluctuations

NASA Astrophysics Data System (ADS)

Wu, Qikai; Bertrand, Thibault; Shattuck, Mark D.; O'Hern, Corey S.

2017-12-01

We focus on the response of mechanically stable (MS) packings of frictionless, bidisperse disks to thermal fluctuations, with the aim of quantifying how nonlinearities affect system properties at finite temperature. In contrast, numerous prior studies characterized the structural and mechanical properties of MS packings of frictionless spherical particles at zero temperature. Packings of disks with purely repulsive contact interactions possess two main types of nonlinearities, one from the form of the interaction potential (e.g., either linear or Hertzian spring interactions) and one from the breaking (or forming) of interparticle contacts. To identify the temperature regime at which the contact-breaking nonlinearities begin to contribute, we first calculated the minimum temperatures Tc b required to break a single contact in the MS packing for both single- and multiple-eigenmode perturbations of the T =0 MS packing. We find that the temperature required to break a single contact for equal velocity-amplitude perturbations involving all eigenmodes approaches the minimum value obtained for a perturbation in the direction connecting disk pairs with the smallest overlap. We then studied deviations in the constant volume specific heat C¯V and deviations of the average disk positions Δ r from their T =0 values in the temperature regime TC ¯V100 for linear spring interactions is independent of system size. This result emphasizes that contact-breaking nonlinearities are dominant over form nonlinearities in the low-temperature range Tc b

Metamorphic assemblages and the direction of flow of metamorphic fluids in four instances of serpentinization

USGS Publications Warehouse

Barnes, I.; Rapp, J.B.; O'Neil, J.R.; Sheppard, R.A.; Gude, A.J.

1972-01-01

Fluids related to Serpentinization are of at least three types. The first reported (Barnes and O'Neil, 1969) is a fluid of local meteoric origin, the chemical and thermodynamic properties of which are entirely controlled by olivine, orthopyroxene, brucite, and serpentine reactions. It is a Ca+2-OH-1 type and is shown experimentally to be capable of reacting with albite to yield calcium hydroxy silicates. Rodingites may form where the Ca+2-OH-1 type waters flow across the ultramafic contact and react with siliceous country rock. The second type of fluid has its chemical composition largely controlled before it enters the ultramafic rocks, but reactions within the ultramafic rocks fix the thermodynamic properties by reactions of orthopyroxene, olivine, calcite, brucite, and serpentine. The precipitation of brucite from this fluid clearly shows that fluid flow allows reaction products to be deposited at a distance from the point of solution. Thus, textural evidence for volume relations during Serpentinization may not be valid. The third type of fluid has its chemical properties fixed in part before the reactions with ultramafic rocks, in part by the reactions of orthopyroxene, olivine, and serpentine and in part by reactions with siliceous country rock at the contact. The reactions of the ultramafic rock and country rock with the fluid must be contemporaneous and require flow to be along the contact. This third type of fluid is grossly supersaturated with talc and tremolite, both found along the contact. The occurrence of magadiite, kenyaite, mountainite, and rhodesite along the contact is probably due to a late stage low-temperature reaction of fluids of the same thermodynamic properties as those that formed the talc and tremolite at higher temperatures. Oxygen isotope analyses of some of these minerals supports this conclusion. Rodingites form from Ca+2-rich fluids flowing across the contact; talc and tremolite form from silica-rich fluids flowing along the contact. Isotopic analyses of the fluids indicate varied origins including unaltered local meteoric water and connate water. Complexion Spring water may be a sample of only slightly altered Jurassic or Cretaceous sea water. ?? 1972 Springer-Verlag.

Method development and validation of potent pyrimidine derivative by UV-VIS spectrophotometer.

PubMed

Chaudhary, Anshu; Singh, Anoop; Verma, Prabhakar Kumar

2014-12-01

A rapid and sensitive ultraviolet-visible (UV-VIS) spectroscopic method was developed for the estimation of pyrimidine derivative 6-Bromo-3-(6-(2,6-dichlorophenyl)-2-(morpolinomethylamino) pyrimidine4-yl) -2H-chromen-2-one (BT10M) in bulk form. Pyrimidine derivative was monitored at 275 nm with UV detection, and there is no interference of diluents at 275 nm. The method was found to be linear in the range of 50 to 150 μg/ml. The accuracy and precision were determined and validated statistically. The method was validated as a guideline. The results showed that the proposed method is suitable for the accurate, precise, and rapid determination of pyrimidine derivative. Graphical Abstract Method development and validation of potent pyrimidine derivative by UV spectroscopy.

The Danger of Using Tap Water with Contact Lenses

EPA Pesticide Factsheets

Acanthamoeba is a microbe that is very common in tap water. It has two forms: the trophozoite and the cyst. These trophozoites and cysts can stick to the surface of your contact lenses and then infect your eye.

Deposition of bi-dispersed particles in inkjet-printed evaporating colloidal drops

NASA Astrophysics Data System (ADS)

Sun, Ying; Joshi, Abhijit; Chhasatia, Viral

2010-11-01

In this study, the deposition behaviors of inkjet-printed evaporating colloidal drops consisting of bi-dispersed micro and nano-sized particles are investigated by fluorescence microscopy and SEM. The results on hydrophilic glass substrates show that, evaporatively-driven outward flow drives the nanoparticles to deposit close to the pinned contact line while an inner ring deposition is formed by microparticles. This size-induced particle separation is consistent with the existence of a wedge-shaped drop edge near the contact line region of an evaporating drop on a hydrophilic substrate. The replenishing evaporatively-driven flow assembles nanoparticles closer to the pinned contact line forming an outer ring of nanoparticles and this particle jamming further enhances the contact line pinning. Microparticles are observed to form an inner ring inside the nano-sized deposits. This size-induced particle separation presents a new challenge to the uniformity of functional materials in bioprinting applications where nanoparticles and micro-sized cells are mixed together. On the other hand, particle self-assembly based on their sizes provides enables easy and well-controlled pattern formation. The effects of particle size contrast, particle volume fraction, substrate surface energy, and relative humidity of the printing environment on particle separation are examined in detail.

Protecting Your Child's Personal Information at School

ERIC Educational Resources Information Center

Federal Trade Commission, 2012

2012-01-01

Back to school--an annual ritual that includes buying new notebooks, packing lunches, coordinating transportation, and filling out forms: registration forms, health forms, permission slips, and emergency contact forms, to name a few. Many school forms require personal and, sometimes, sensitive information. In the wrong hands, this information can…

Steel refining with an electrochemical cell

DOEpatents

Blander, M.; Cook, G.M.

1988-05-17

Apparatus is described for processing a metallic fluid containing iron oxide, container for a molten metal including an electrically conductive refractory disposed for contact with the molten metal which contains iron oxide, an electrolyte in the form of a basic slag on top of the molten metal, an electrode in the container in contact with the slag electrically separated from the refractory, and means for establishing a voltage across the refractory and the electrode to reduce iron oxide to iron at the surface of the refractory in contact with the iron oxide containing fluid. A process is disclosed for refining an iron product containing not more than about 10% by weight oxygen and not more than about 10% by weight sulfur, comprising providing an electrolyte of a slag containing one or more of calcium oxide, magnesium oxide, silica or alumina, providing a cathode of the iron product in contact with the electrolyte, providing an anode in contact with the electrolyte electrically separated from the cathode, and operating an electrochemical cell formed by the anode, the cathode and the electrolyte to separate oxygen or sulfur present in the iron product therefrom. 2 figs.

Contact-dependent killing by Caulobacter crescentus via cell surface-associated, glycine zipper proteins

PubMed Central

García-Bayona, Leonor; Guo, Monica S; Laub, Michael T

2017-01-01

Most bacteria are in fierce competition with other species for limited nutrients. Some bacteria can kill nearby cells by secreting bacteriocins, a diverse group of proteinaceous antimicrobials. However, bacteriocins are typically freely diffusible, and so of little value to planktonic cells in aqueous environments. Here, we identify an atypical two-protein bacteriocin in the α-proteobacterium Caulobacter crescentus that is retained on the surface of producer cells where it mediates cell contact-dependent killing. The bacteriocin-like proteins CdzC and CdzD harbor glycine-zipper motifs, often found in amyloids, and CdzC forms large, insoluble aggregates on the surface of producer cells. These aggregates can drive contact-dependent killing of other organisms, or Caulobacter cells not producing the CdzI immunity protein. The Cdz system uses a type I secretion system and is unrelated to previously described contact-dependent inhibition systems. However, Cdz-like systems are found in many bacteria, suggesting that this form of contact-dependent inhibition is common. DOI: http://dx.doi.org/10.7554/eLife.24869.001 PMID:28323618

Micromachine friction test apparatus

DOEpatents

deBoer, Maarten P.; Redmond, James M.; Michalske, Terry A.

2002-01-01

A microelectromechanical (MEM) friction test apparatus is disclosed for determining static or dynamic friction in MEM devices. The friction test apparatus, formed by surface micromachining, is based on a friction pad supported at one end of a cantilevered beam, with the friction pad overlying a contact pad formed on the substrate. A first electrostatic actuator can be used to bring a lower surface of the friction pad into contact with an upper surface of the contact pad with a controlled and adjustable force of contact. A second electrostatic actuator can then be used to bend the cantilevered beam, thereby shortening its length and generating a relative motion between the two contacting surfaces. The displacement of the cantilevered beam can be measured optically and used to determine the static or dynamic friction, including frictional losses and the coefficient of friction between the surfaces. The test apparatus can also be used to assess the reliability of rubbing surfaces in MEM devices by producing and measuring wear of those surfaces. Finally, the friction test apparatus, which is small in size, can be used as an in situ process quality tool for improving the fabrication of MEM devices.

Universal diffusion-limited injection and the hook effect in organic thin-film transistors

NASA Astrophysics Data System (ADS)

Liu, Chuan; Huseynova, Gunel; Xu, Yong; Long, Dang Xuan; Park, Won-Tae; Liu, Xuying; Minari, Takeo; Noh, Yong-Young

2016-07-01

The general form of interfacial contact resistance was derived for organic thin-film transistors (OTFTs) covering various injection mechanisms. Devices with a broad range of materials for contacts, semiconductors, and dielectrics were investigated and the charge injections in staggered OTFTs was found to universally follow the proposed form in the diffusion-limited case, which is signified by the mobility-dependent injection at the metal-semiconductor interfaces. Hence, real ohmic contact can hardly ever be achieved in OTFTs with low carrier concentrations and mobility, and the injection mechanisms include thermionic emission, diffusion, and surface recombination. The non-ohmic injection in OTFTs is manifested by the generally observed hook shape of the output conductance as a function of the drain field. The combined theoretical and experimental results show that interfacial contact resistance generally decreases with carrier mobility, and the injection current is probably determined by the surface recombination rate, which can be promoted by bulk-doping, contact modifications with charge injection layers and dopant layers, and dielectric engineering with high-k dielectric materials.

Universal diffusion-limited injection and the hook effect in organic thin-film transistors.

PubMed

Liu, Chuan; Huseynova, Gunel; Xu, Yong; Long, Dang Xuan; Park, Won-Tae; Liu, Xuying; Minari, Takeo; Noh, Yong-Young

2016-07-21

The general form of interfacial contact resistance was derived for organic thin-film transistors (OTFTs) covering various injection mechanisms. Devices with a broad range of materials for contacts, semiconductors, and dielectrics were investigated and the charge injections in staggered OTFTs was found to universally follow the proposed form in the diffusion-limited case, which is signified by the mobility-dependent injection at the metal-semiconductor interfaces. Hence, real ohmic contact can hardly ever be achieved in OTFTs with low carrier concentrations and mobility, and the injection mechanisms include thermionic emission, diffusion, and surface recombination. The non-ohmic injection in OTFTs is manifested by the generally observed hook shape of the output conductance as a function of the drain field. The combined theoretical and experimental results show that interfacial contact resistance generally decreases with carrier mobility, and the injection current is probably determined by the surface recombination rate, which can be promoted by bulk-doping, contact modifications with charge injection layers and dopant layers, and dielectric engineering with high-k dielectric materials.

In vitro reestablishment of cell-cell contacts in adult rat cardiomyocytes. Functional role of transmembrane components in the formation of new intercalated disk-like cell contacts.

PubMed

Eppenberger, H M; Zuppinger, C

1999-01-01

Primary adult rat cardiomyocytes (ARC)in culture are shown to be a model system for cardiac cell hypertrophy in vitro. ARC undergo a process of morphological transformation and grow only by increase in cell size, however, without loss of the cardiac phenotype. The isolated cells spread and establish new cell-cell contacts, eventually forming a two-dimensional heart tissue-like synchronously beating cell sheet. The reformation of specific cell contacts (intercalated disks) is shown also between ventricular and atrial cardiomyocytes by using antibodies against the gap junction protein connexin-43 and after microinjection into ARC of N-cadherin cDNA fused to reporter green fluorescent protein (GFP) cDNA. The expressed fusion protein allowed the study of live cell cultures and of the dynamics of the adherens junction protein N-cadherin during the formation of new cell-cell contacts. The possible use of the formed ARC cell-sheet cells under microgravity conditions as a test system for the reformation of the cytoskeleton of heart muscle cells is proposed.

Steel refining with an electrochemical cell

DOEpatents

Blander, M.; Cook, G.M.

1985-05-21

Disclosed is an apparatus for processing a metallic fluid containing iron oxide, container for a molten metal including an electrically conductive refractory disposed for contact with the molten metal which contains iron oxide, an electrolyte in the form of a basic slag on top of the molten metal, an electrode in the container in contact with the slag electrically separated from the refractory, and means for establishing a voltage across the refractory and the electrode to reduce iron oxide to iron at the surface of the refractory in contact with the iron oxide containing fluid. A process is disclosed for refining an iron product containing not more than about 10% by weight sulfur, comprising providing an electrolyte of a slag containing one or more of calcium oxide, magnesium oxide, silica or alumina, providing a cathode of the iron product in contact with the electrolyte, providing an anode in contact with the electrolyte electrically separated from the cathode, and operating an electrochemical cell formed by the anode, the cathode and the electrolyte to separate oxygen or sulfur present in the iron product therefrom.

Universal diffusion-limited injection and the hook effect in organic thin-film transistors

PubMed Central

Liu, Chuan; Huseynova, Gunel; Xu, Yong; Long, Dang Xuan; Park, Won-Tae; Liu, Xuying; Minari, Takeo; Noh, Yong-Young

2016-01-01

The general form of interfacial contact resistance was derived for organic thin-film transistors (OTFTs) covering various injection mechanisms. Devices with a broad range of materials for contacts, semiconductors, and dielectrics were investigated and the charge injections in staggered OTFTs was found to universally follow the proposed form in the diffusion-limited case, which is signified by the mobility-dependent injection at the metal-semiconductor interfaces. Hence, real ohmic contact can hardly ever be achieved in OTFTs with low carrier concentrations and mobility, and the injection mechanisms include thermionic emission, diffusion, and surface recombination. The non-ohmic injection in OTFTs is manifested by the generally observed hook shape of the output conductance as a function of the drain field. The combined theoretical and experimental results show that interfacial contact resistance generally decreases with carrier mobility, and the injection current is probably determined by the surface recombination rate, which can be promoted by bulk-doping, contact modifications with charge injection layers and dopant layers, and dielectric engineering with high-k dielectric materials. PMID:27440253

Steel refining with an electrochemical cell

DOEpatents

Blander, Milton; Cook, Glenn M.

1988-01-01

Apparatus for processing a metallic fluid containing iron oxide, container for a molten metal including an electrically conductive refractory disposed for contact with the molten metal which contains iron oxide, an electrolyte in the form of a basic slag on top of the molten metal, an electrode in the container in contact with the slag electrically separated from the refractory, and means for establishing a voltage across the refractory and the electrode to reduce iron oxide to iron at the surface of the refractory in contact with the iron oxide containing fluid. A process is disclosed for refining an iron product containing not more than about 10% by weight oxygen and not more than about 10% by weight sulfur, comprising providing an electrolyte of a slag containing one or more of calcium oxide, magnesium oxide, silica or alumina, providing a cathode of the iron product in contact with the electrolyte, providing an anode in contact with the electrolyte electrically separated from the cathode, and operating an electrochemical cell formed by the anode, the cathode and the electrolyte to separate oxygen or sulfur present in the iron product therefrom.

Anti-Toxoplasma activity and impact evaluation of lyophilization, hot molding process, and gamma-irradiation techniques on CLH-PLGA intravitreal implants.

PubMed

Fernandes-Cunha, Gabriella M; Rezende, Cíntia M F; Mussel, Wagner N; da Silva, Gisele R; de L Gomes, Elionai C; Yoshida, Maria I; Fialho, Sílvia L; Goes, Alfredo M; Gomes, Dawison A; de Almeida Vitor, Ricardo W; Silva-Cunha, Armando

2016-01-01

Intraocular delivery systems have been developed to treat many eye diseases, especially those affecting the posterior segment of the eye. However, ocular toxoplasmosis, the leading cause of infectious posterior uveitis in the world, still lacks an effective treatment. Therefore, our group developed an intravitreal polymeric implant to release clindamycin, a potent anti-Toxoplasma antibiotic. In this work, we used different techniques such as differential scanning calorimetry, thermogravimetry, X-ray diffraction, scanning electron microscopy, and fourier-transform infrared spectroscopy to investigate drug/polymer properties while manufacturing the delivery system. We showed that the lyophilization, hot molding process, and sterilization by gamma irradiation did not change drug/polymer physical-chemistry properties. The drug was found to be homogeneously dispersed into the poly lactic-co-glycolic acid (PLGA) chains and the profile release was characterized by an initial burst followed by prolonged release. The drug profile release was not modified after gamma irradiation and non-covalent interaction was found between the drug and the PLGA. We also observed the preservation of the drug activity by showing the potent anti-Toxoplasma effect of the implant, after 24-72 h in contact with cells infected by the parasite, which highlights this system as an alternative to treat toxoplasmic retinochoroiditis.

Current data regarding the structure-toxicity relationship of boron-containing compounds.

PubMed

Farfán-García, E D; Castillo-Mendieta, N T; Ciprés-Flores, F J; Padilla-Martínez, I I; Trujillo-Ferrara, J G; Soriano-Ursúa, M A

2016-09-06

Boron is ubiquitous in nature, being an essential element of diverse cells. As a result, humans have had contact with boron containing compounds (BCCs) for a long time. During the 20th century, BCCs were developed as antiseptics, antibiotics, cosmetics and insecticides. Boric acid was freely used in the nosocomial environment as an antiseptic and sedative salt, leading to the death of patients and an important discovery about its critical toxicology for humans. Since then the many toxicological studies done in relation to BCCs have helped to establish the proper limits of their use. During the last 15 years, there has been a boom of research on the design and use of new, potent and efficient boron containing drugs, finding that the addition of boron to some known drugs increases their affinity and selectivity. This mini-review summarizes two aspects of BCCs: toxicological data found with experimental models, and the scarce but increasing data about the structure-activity relationship for toxicity and therapeutic use. As is the case with boron-free compounds, the biological activity of BCCs is related to their chemical structure. We discuss the use of new technology to discover potent and efficient BCCs for medicinal therapy by avoiding toxic effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.

PubMed

Baker, David A; Stewart, Lindsay B; Large, Jonathan M; Bowyer, Paul W; Ansell, Keith H; Jiménez-Díaz, María B; El Bakkouri, Majida; Birchall, Kristian; Dechering, Koen J; Bouloc, Nathalie S; Coombs, Peter J; Whalley, David; Harding, Denise J; Smiljanic-Hurley, Ela; Wheldon, Mary C; Walker, Eloise M; Dessens, Johannes T; Lafuente, María José; Sanz, Laura M; Gamo, Francisco-Javier; Ferrer, Santiago B; Hui, Raymond; Bousema, Teun; Angulo-Barturén, Iñigo; Merritt, Andy T; Croft, Simon L; Gutteridge, Winston E; Kettleborough, Catherine A; Osborne, Simon A

2017-09-05

To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC 50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC 50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P. falciparum SCID mouse model. The series targets both merozoite egress and erythrocyte invasion, but crucially, also blocks transmission of mature P. falciparum gametocytes to Anopheles stephensi mosquitoes. A co-crystal structure of PvPKG bound to ML10, reveals intimate molecular contacts that explain the high levels of potency and selectivity we have measured. The properties of this series warrant consideration for further development to produce an antimalarial drug.Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes.

Toxins and bioactive compounds from cyanobacteria and their implications on human health.

PubMed

Rao, P V Lakshmana; Gupta, Nidhi; Bhaskar, A S B; Jayaraj, R

2002-07-01

Many species of cyanobacteria (blue-green algae) produce secondary metabolites with potent biotoxic or cytotoxic properties. These metabolites differ from the intermediates and cofactor compounds that are essential for cell structural synthesis and energy transduction. The mass growth of cyanobacteria which develop in fresh, brackish and, marine waters commonly contain potent toxins. Cyanobacterial toxins or cyanotoxins are responsible for or implicated in animal poisoning, human gastroenteritis, dermal contact irritations and primary liver cancer in humans. These toxins (microcystins, nodularins, saxitoxins, anatoxin-a, anatoxin-a(s), cylindrospermopsin) are structurally diverse and their effects range from liver damage, including liver cancer to neurotoxicity. Several incidents of human illness and more recently, the death of 60 haemodialysis patients in Caruaru, Brazil, have been linked to the presence of microcystins in water. In response to the growing concern about the non-lethal acute and chronic effects of microcystins, World Health Organization has recently set a new provisional guideline value for microcystin-LR of 1.0 microg/L in drinking water. Cyanobacteria including microcystin-producing strains produce a large number of peptide compounds, e.g. micropeptins, cyanopeptolins, microviridin, circinamide, aeruginosin, with varying bioactivities and potential pharmacological application. This article discusses briefly cyanobacterial toxins and their implications on human health.

Stapled α−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 α−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

A Review of the Current Research Trends in the Application of Medicinal Plants as a Source for Novel Therapeutic Agents Against Acanthamoeba Infections

PubMed Central

Niyyati, Maryam; Dodangeh, Samira; Lorenzo-Morales, Jacob

2016-01-01

Acanthamoeba keratitis (AK) is a sight-threating infection of the cornea that mostly affects contact lens wearers. Until now, AK treatment remains very difficult due to the existence of a highly resistant cyst stage in the life cycle of Acanthamoeba which is extremely resistant to most of the available anti-amoebic compounds. Moreover, current treatment of AK is usually based in the combination of various therapeutic agents such as polyhexamethylene biguanide or chlorhexidine and propamidine isethionate. However, all the mentioned compounds have also showed toxic side effects on human keratocytes and presented poor cysticidal effect at the concentrations currently used in the established AK treatments. Nowadays, the elucidation of novel compounds with antimicrobial and anticancer properties from plant and herbs with medicinal properties have encouraged researchers to evaluate plants as a source of new molecules with anti-trophozoite and cysticidal effects. Thus, in recent years, many natural products have been reported to present potent anti-Acanthamoeba properties with good selectivity and minimal toxic effects. Therefore, the chemical drugs currently used for AK treatment, their drawbacks as well as the current research in medicinal plants as a source of potent anti-Acanthamoeba compounds are described in this review. PMID:28243287

Superconductor-normal-superconductor with distributed Sharvin point contacts

DOEpatents

Holcomb, Matthew J.; Little, William A.

1994-01-01

A non-linear superconducting junction device comprising a layer of high transient temperature superconducting material which is superconducting at an operating temperature, a layer of metal in contact with the layer of high temperature superconducting material and which remains non-superconducting at the operating temperature, and a metal material which is superconducting at the operating temperature and which forms distributed Sharvin point contacts with the metal layer.

Transcriptional responses to cantharidin a protein phosphatase inhibitor in Arabidopsis thaliana reveal the involvement of multiple signal transduction pathways

USDA-ARS?s Scientific Manuscript database

Cantharidin is a natural compound isolated from the blister beetle (Epicauta spp.). It is a very potent inhibitor of serine/threonine protein phosphatases PPP, especially PP2A and PP4. Protein phosphatases and kinases maintain a sensitive balance between phosphorylated and dephosphorylated forms of ...

Disease Risk Mitigation: The Equivalence of Two Selective Mixing Strategies on Aggregate Contact Patterns & Resulting Epidemic Spread☆

PubMed Central

Morin, Benjamin R; Perrings, Charles; Levin, Simon; Kinzig, Ann

2014-01-01

The personal choices affecting the transmission of infectious diseases include the number of contacts an individual makes, and the risk-characteristics of those contacts. We consider whether these different choices have distinct implications for the course of an epidemic. We also consider whether choosing contact mitigation (how much to mix) and affinity mitigation (with whom to mix) strategies together has different epidemiological effects than choosing each separately. We use a set of differential equation compartmental models of the spread of disease, coupled with a model of selective mixing. We assess the consequences of varying contact or affinity mitigation as a response to disease risk. We do this by comparing disease incidence and dynamics under varying contact volume, contact type, and both combined across several different disease models. Specifically, we construct a change of variables that allows one to transition from contact mitigation to affinity mitigation, and vice versa. In the absence of asymptomatic infection we find no difference in the epidemiological impacts of the two forms of disease risk mitigation. Furthermore, since models that include both mitigation strategies are under-determined, varying both results in no outcome that could not be reached by choosing either separately. Which strategy is actually chosen then depends not on their epidemiological consequences, but on the relative cost of reducing contact volume versus altering contact type. Although there is no fundamental epidemiological difference between the two forms of mitigation, the social cost of alternative strategies can be very different. From a social perspective, therefore, whether one strategy should be promoted over another depends on economic not epidemiological factors. PMID:25150459

Disease risk mitigation: the equivalence of two selective mixing strategies on aggregate contact patterns and resulting epidemic spread.

PubMed

Morin, Benjamin R; Perrings, Charles; Levin, Simon; Kinzig, Ann

2014-12-21

The personal choices affecting the transmission of infectious diseases include the number of contacts an individual makes, and the risk-characteristics of those contacts. We consider whether these different choices have distinct implications for the course of an epidemic. We also consider whether choosing contact mitigation (how much to mix) and affinity mitigation (with whom to mix) strategies together has different epidemiological effects than choosing each separately. We use a set of differential equation compartmental models of the spread of disease, coupled with a model of selective mixing. We assess the consequences of varying contact or affinity mitigation as a response to disease risk. We do this by comparing disease incidence and dynamics under varying contact volume, contact type, and both combined across several different disease models. Specifically, we construct a change of variables that allows one to transition from contact mitigation to affinity mitigation, and vice versa. In the absence of asymptomatic infection we find no difference in the epidemiological impacts of the two forms of disease risk mitigation. Furthermore, since models that include both mitigation strategies are underdetermined, varying both results in no outcome that could not be reached by choosing either separately. Which strategy is actually chosen then depends not on their epidemiological consequences, but on the relative cost of reducing contact volume versus altering contact type. Although there is no fundamental epidemiological difference between the two forms of mitigation, the social cost of alternative strategies can be very different. From a social perspective, therefore, whether one strategy should be promoted over another depends on economic not epidemiological factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

[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.

6,7-Dimorpholinoalkoxy quinazoline derivatives as potent EGFR inhibitors with enhanced antiproliferative activities against tumor cells.

PubMed

Zhang, Yaling; Chen, Li; Xu, Hongjiang; Li, Xiabing; Zhao, Lijun; Wang, Wei; Li, Baolin; Zhang, Xiquan

2018-03-10

A series of novel 6,7-dimorpholinoalkoxy quinazoline derivatives was designed, synthesized and evaluated as potent EGFR inhibitors. Most of synthesized derivatives exhibited moderate to excellent antiproliferative activities against five human tumor cell lines. Compound 8d displayed the most remarkable inhibitory activities against tumor cells expressing wild type (A431, A549 and SW480 cells) or mutant (HCC827 and NCI-H1975 cells) epidermal growth factor receptor (EGFR) (with IC 50 values in the range of 0.37-4.87 μM), as well as more potent inhibitory effects against recombinant EGFR tyrosine kinase (EGFR-TK, wt or T790M) (with the IC 50 values of 7.0 and 9.3 nM, respectively). Molecular docking showed that 8d can form four hydrogen bonds with EGFR, and two of them were located in the Asp855-Phe856-Gly857 (DFG) motif of EGFR. Meanwhile, 8d can significantly block EGF-induced EGFR activation and the phosphorylation of its downstream proteins such as Akt and Erk1/2 in human NSCLC cells. Also, 8d mediated cell apoptosis and the prolongation of cell cycle progression in G0/G1-phase in A549 cells. The work would have remarkable implications for further design and development of more potent EGFR tyrosine kinase inhibitors (TKIs). Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pituitary adenylate cyclase-activating polypeptide is a potent broad-spectrum antimicrobial peptide: Structure-activity relationships.

PubMed

Starr, Charles G; Maderdrut, Jerome L; He, Jing; Coy, David H; Wimley, William C

2018-06-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally occurring cationic peptide with potent immunosuppressant and cytoprotective activities. We now show that full length PACAP38 and to a lesser extent, the truncated form PACAP27, and the closely related vasoactive intestinal peptide (VIP) and secretin had antimicrobial activity against the Gram-negative bacteria Escherichia coli in the radial diffusion assay. PACAP38 was more potent than either the bovine neutrophil antimicrobial peptide indolicidin or the synthetic antimicrobial peptide ARVA against E. coli. PACAP38 also had activity against the Gram-positive bacteria Staphylococcus aureus in the same assay with comparable potency to indolicidin and ARVA. In the more stringent broth dilution assay, PACAP38 had moderate sterilizing activity against E. coli, and potent sterilizing activity against the Gram-negative bacteria Pseudomonas aeruginosa. PACAP27, VIP and secretin were much less active than PACAP38 in this assay. PACAP38 also had some activity against the Gram-positive bacteria Bacillus cereus in the broth dilution assay. Many exopeptidase-resistant analogs of PACAP38, including both receptor agonists and antagonists, had antimicrobial activities equal to, or better than PACAP38, in both assays. PACAP38 made the membranes of E. coli permeable to SYTOX Green, suggesting a classical membrane lytic mechanism. These data suggest that analogs of PACPAP38 with a wide range of useful biological activities can be made by judicious substitutions in the sequence. Copyright © 2018 Elsevier Inc. All rights reserved.

Apparent and microscopic dynamic contact angles in confined flows

NASA Astrophysics Data System (ADS)

Omori, Takeshi; Kajishima, Takeo

2017-11-01

An abundance of empirical correlations between a dynamic contact angle and a capillary number representing a translational velocity of a contact line have been provided for the last decades. The experimentally obtained dynamic contact angles are inevitably apparent contact angles but often undistinguished from microscopic contact angles formed right on the wall. As Bonn et al. ["Wetting and spreading," Rev. Mod. Phys. 81, 739-805 (2009)] pointed out, however, most of the experimental studies simply report values of angles recorded at some length scale which is quantitatively unknown. It is therefore hard to evaluate or judge the physical validity and the generality of the empirical correlations. The present study is an attempt to clear this clutter regarding the dynamic contact angle by measuring both the apparent and the microscopic dynamic contact angles from the identical data sets in a well-controlled manner, by means of numerical simulation. The numerical method was constructed so that it reproduced the fine details of the flow with a moving contact line predicted by molecular dynamics simulations [T. Qian, X. Wang, and P. Sheng, "Molecular hydrodynamics of the moving contact line in two-phase immiscible flows," Commun. Comput. Phys. 1, 1-52 (2006)]. We show that the microscopic contact angle as a function of the capillary number has the same form as Blake's molecular-kinetic model [T. Blake and J. Haynes, "Kinetics of liquid/liquid displacement," J. Colloid Interface Sci. 30, 421-423 (1969)], regardless of the way the flow is driven, the channel width, the mechanical properties of the receding fluid, and the value of the equilibrium contact angle under the conditions where the Reynolds and capillary numbers are small. We have also found that the apparent contact angle obtained by the arc-fitting of the interface behaves surprisingly universally as claimed in experimental studies in the literature [e.g., X. Li et al., "An experimental study on dynamic pore wettability," Chem. Eng. Sci. 104, 988-997 (2013)], although the angle deviates significantly from the microscopic contact angle. It leads to a practically important point that it suffices to measure arc-fitted contact angles to make formulae to predict flow rates in capillary tubes.

Glycoconjugates and methods

DOEpatents

Bertozzi, Carolyn C [Albany, CA; Yarema, Kevin J [Albany, CA; Mahal, Lara K [Berkeley, CA

2008-04-01

Methods for making the functionalized glycoconjugates include (a) contacting a cell with a first monosaccharide, and (b) incubating the cell under conditions whereby the cell (i) internalizes the first monosaccharide, (ii) biochemically processes the first monosaccharide into a second saccharide, (iii) conjugates the saccharide to a carrier to form a glycoconjugate, and (iv) extracellularly expresses the glycoconjugate to form an extracellular glycoconjugate comprising a selectively reactive functional group. Methods for forming products at a cell further comprise contacting the functional group of the extracellularly expressed glycoconjugate with an agent which selectively reacts with the functional group to form a product. Subject compositions include cyto-compatible monosaccharides comprising a nitrogen or ether linked functional group selectively reactive at a cell surface and compositions and cells comprising such saccharides.

Investigation of Proposed Process Sequence for the Array Automated Assembly Task, Phase 2. [low cost silicon solar array fabrication

NASA Technical Reports Server (NTRS)

Mardesich, N.; Garcia, A.; Bunyan, S.; Pepe, A.

1979-01-01

The technological readiness of the proposed process sequence was reviewed. Process steps evaluated include: (1) plasma etching to establish a standard surface; (2) forming junctions by diffusion from an N-type polymeric spray-on source; (3) forming a p+ back contact by firing a screen printed aluminum paste; (4) forming screen printed front contacts after cleaning the back aluminum and removing the diffusion oxide; (5) cleaning the junction by a laser scribe operation; (6) forming an antireflection coating by baking a polymeric spray-on film; (7) ultrasonically tin padding the cells; and (8) assembling cell strings into solar circuits using ethylene vinyl acetate as an encapsulant and laminating medium.

Interconnect assembly for an electronic assembly and assembly method therefor

DOEpatents

Gerbsch, Erich William

2003-06-10

An interconnect assembly and method for a semiconductor device, in which the interconnect assembly can be used in lieu of wirebond connections to form an electronic assembly. The interconnect assembly includes first and second interconnect members. The first interconnect member has a first surface with a first contact and a second surface with a second contact electrically connected to the first contact, while the second interconnect member has a flexible finger contacting the second contact of the first interconnect member. The first interconnect member is adapted to be aligned and registered with a semiconductor device having a contact on a first surface thereof, so that the first contact of the first interconnect member electrically contacts the contact of the semiconductor device. Consequently, the assembly method does not require any wirebonds, but instead merely entails aligning and registering the first interconnect member with the semiconductor device so that the contacts of the first interconnect member and the semiconductor device make electrically contact, and then contacting the second contact of the first interconnect member with the flexible finger of the second interconnect member.

Approximate stresses in 2-D flat elastic contact fretting problems

NASA Astrophysics Data System (ADS)

Urban, Michael Rene

Fatigue results from the cyclic loading of a solid body. If the body subject to fatigue is in contact with another body and relative sliding motion occurs between these two bodies, then rubbing surface damage can accelerate fatigue failure. The acceleration of fatigue failure is especially important if the relative motion between the two bodies results in surface damage without excessive surface removal via wear. The situation just described is referred to as fretting fatigue. Understanding of fretting fatigue is greatly enhanced if the stress state associated with fretting can be characterized. For Hertzian contact, this can readily be done. Unfortunately, simple stress formulae are not available for flat body contact. The primary result of the present research is the development of a new, reasonably accurate, approximate closed form expression for 2-dimensional contact stresses which has been verified using finite element modeling. This expression is also combined with fracture mechanics to provide a simple method of determining when a crack is long enough to no longer be affected by the contact stress field. Lower bounds on fatigue life can then easily be calculated using fracture mechanics. This closed form expression can also be used to calculate crack propagation within the contact stress field. The problem of determining the cycles required to generate an initial crack and what to choose as an initial crack size is unresolved as it is in non-fretting fatigue.

76 FR 16802 - Extension of Approval of Information Collection, OMB Control Number 1004-0196

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

...'' regardless of the form of your comments. FOR FURTHER INFORMATION CONTACT: Barbara Gamble, Division of Fluid... Federal Information Relay Service (FIRS) at 1-800-877-8339, to contact Ms. Gamble. You may also review the...

Topical treatments for chronic plaque psoriasis.

PubMed

Mason, Anne R; Mason, James; Cork, Michael; Dooley, Gordon; Edwards, Gladys

2009-04-15

Chronic plaque psoriasis is the most common type of psoriasis and is characterised by redness, thickness and scaling. First line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and topical retinoids. To compare the effectiveness, tolerability and safety of topical treatments for chronic plaque psoriasis with placebo; to compare vitamin D analogues with other topical treatments. The Cochrane Skin Group's Trials Register was searched (2004/12). To update an unpublished 2002 review we also searched CENTRAL in The Cochrane Library (Issue 1,2005); MEDLINE (to 2005/02); EMBASE (to 2005/08); Science Citation Index (to 2005); Biosis (to 2005); Dissertation Abstracts (all publication years); Inside Conferences (all publication years); SIGLE (to 2005); National Research Register (all projects with a start date of 2001 to 2005); metaRegister of Current Controlled Trials. Randomised trials comparing treatments against placebo or against vitamin D analogues in people with chronic plaque psoriasis. One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted triallists and companies for missing data. We extracted data on withdrawals and adverse events. The review included 131 RCTs with 21,448 participants. Vitamin D was significantly more effective than placebo, although there was a wide variation in effect size with the standardised mean difference (SMD) ranging from -0.82 (95% CI -1.34 to -0.29) to -1.90 (95% CI -2.09 to -1.71). With one exception, all corticosteroids performed better than placebo, with potent corticosteroids (SMD: -0.95 (95% CI: -1.11 to -0.80; I(2): 61.1%; 17 studies; 2386 participants)) having smaller benefits than very potent corticosteroids (SMD: -1.29 (95% CI: -1.45 to -1.13; I(2): 53.2%; 11 studies; 1571 participants)). Dithranol and tazarotene performed better than placebo. Head-to-head comparisons of vitamin D against potent or very potent corticosteroids found no significant differences. However, combined treatment with vitamin D /corticosteroid performed significantly better than either vitamin D alone or corticosteroid alone. Vitamin D performed better than coal tar, but findings relative to dithranol were mixed. Potent corticosteroids were less likely than vitamin D to cause local adverse events. No comparison of topical agents found a significant difference in systemic adverse effects. Corticosteroids perform as well as vitamin D analogues and are associated with a lower incidence of local adverse events. Further research is required to inform long-term maintenance treatment.

BUTIMBA: Intensifying the Hunt for Child TB in Swaziland through Household Contact Tracing

PubMed Central

Alonso Ustero, Pilar; Golin, Rachel; Anabwani, Florence; Mzileni, Bulisile; Sikhondze, Welile; Stevens, Robert

2017-01-01

Background Limited data exists to inform contact tracing guidelines in children and HIV-affected populations. We evaluated the yield and additionality of household contact and source case investigations in Swaziland, a TB/HIV high-burden setting, while prioritizing identification of childhood TB. Methods In partnership with 7 local TB clinics, we implemented standardized contact tracing of index cases (IC) receiving TB treatment. Prioritizing child contacts and HIV-affected households, screening officers screened contacts for TB symptoms and to identify risk factors associated with TB. We ascertained factors moderating the yield of contact tracing and measured the impact of our program by additional notifications. Results From March 2013 to November 2015, 3,258 ICs (54% bacteriologically confirmed; 70% HIV-infected; 85% adults) were enrolled leading to evaluation of 12,175 contacts (median age 18 years, IQR 24–42; 45% children; 9% HIV-infected). Among contacts, 196 TB cases (56% bacteriologically confirmed) were diagnosed resulting in a program yield of 1.6% for all forms of TB. The number needed to screen (NNS) to identify a bacteriologically confirmed TB case or all forms TB case traced from a child IC <5 years was respectively 62% and 40% greater than the NNS for tracing from an adult IC. In year one, we demonstrated a 32% increase in detection of bacteriologically confirmed child TB. Contacts were more likely to have TB if <5 years (OR = 2.0), HIV-infected (OR = 4.9), reporting ≥1 TB symptoms (OR = 7.7), and sharing a bed (OR = 1.7) or home (OR = 1.4) with the IC. There was a 1.4 fold increased chance of detecting a TB case in households known to be HIV-affected. Conclusion Contact tracing prioritizing children is not only feasible in a TB/HIV high-burden setting but contributes to overall case detection. Our findings support WHO guidelines prioritizing contact tracing among children and HIV-infected populations while highlighting potential to integrate TB and HIV case finding. PMID:28107473

Inhibitory effect of chalcone derivatives on recombinant human aldose reductase.

PubMed

Iwata, S; Nagata, N; Omae, A; Yamaguchi, S; Okada, Y; Shibata, S; Okuyama, T

1999-03-01

More than fifty chalcone derivatives were synthesized to examine structure-activity relationships against human aldose reductase. Certain 2',4'-dihydroxychalcone derivatives inhibited human aldose reductase activities, and 2',4',2, 4-tetrahydroxychalcone and 2',4',2-trihydroxychalcone showed potent inhibitory activity with IC50 values of 7.4x10(-9) M and 1.6x10(-7) M, respectively. On the other hand, cis-form chalcones, which were isomerized from the original trans-forms by irradiation of daylight in methanol solution, promoted the activity of human aldose reductase.

Reusable vibration resistant integrated circuit mounting socket

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, C.N.

1993-12-31

This invention discloses a novel form of socket for integrated circuits to be mounted on printed circuit boards. The socket uses a novel contact which is fabricated out of a bimetallic strip with a shape which makes the end of the strip move laterally as temperature changes. The end of the strip forms a barb which digs into an integrated circuit lead at normal temperatures and hold it firmly in the contact, preventing loosening and open circuits from vibration. By cooling the contact containing the bimetallic strip the barb end can be made to release so that the integrated circuitmore » lead can be removed from the socket without damage either to the lead or to the socket components.« less

Reusable vibration resistant integrated circuit mounting socket

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, C.N.

1995-08-29

This invention discloses a novel form of socket for integrated circuits to be mounted on printed circuit boards. The socket uses a novel contact which is fabricated out of a bimetallic strip with a shape which makes the end of the strip move laterally as temperature changes. The end of the strip forms a barb which digs into an integrated circuit lead at normal temperatures and holds it firmly in the contact, preventing loosening and open circuits from vibration. By cooling the contact containing the bimetallic strip the barb end can be made to release so that the integrated circuitmore » lead can be removed from the socket without damage either to the lead or to the socket components. 11 figs.« less

18O 16O ratios in cherts associated with the saline lake deposits of East Africa

USGS Publications Warehouse

O'Neil, J.R.; Hay, R.L.

1973-01-01

The cherts formed from sodium silicate precursors in East African saline, alkaline lakes have ??18O values ranging from 31.1 to 44.1. The ??18O values correlate in general with lake salinities as inferred from geologic evidence, indicating that most chert was formed from its precursor in contact with lake water trapped at the time of deposition. A few of the analyzed cherts probably formed in contact with dilute meteoric water. From the widely varying ??18O values we conclude that precursors were transformed to chert in fluids of widely varying salinity and aNa+/aH+ ratio. ?? 1973.

Grafted functional groups on expanded tetrafluoroethylene (ePTFE) support for fuel cell and water transport membranes

DOEpatents

Fuller, Timothy J.; Jiang, Ruichun

2017-01-24

A method for forming a modified solid polymer includes a step of contacting a solid fluorinated polymer with a sodium sodium-naphthalenide solution to form a treated fluorinated solid polymer. The treated fluorinated solid polymer is contacted with carbon dioxide, sulfur dioxide, or sulfur trioxide to form a solid grafted fluorinated polymer. Characteristically, the grafted fluorinated polymer includes appended CO.sub.2H or SO.sub.2H or SO.sub.3H groups. The solid grafted fluorinated polymer is advantageously incorporated into a fuel cell as part of the ion-conducting membrane or a water transport membrane in a humidifier.

Method for making hydrogen rich gas from hydrocarbon fuel

DOEpatents

Krumpelt, M.; Ahmed, S.; Kumar, R.; Doshi, R.

1999-07-27

A method of forming a hydrogen rich gas from a source of hydrocarbon fuel in which the hydrocarbon fuel contacts a two-part catalyst comprising a dehydrogenation portion and an oxide-ion conducting portion at a temperature not less than about 400 C for a time sufficient to generate the hydrogen rich gas while maintaining CO content less than about 5 volume percent. There is also disclosed a method of forming partially oxidized hydrocarbons from ethanes in which ethane gas contacts a two-part catalyst comprising a dehydrogenation portion and an oxide-ion conducting portion for a time and at a temperature sufficient to form an oxide. 4 figs.

Method for making hydrogen rich gas from hydrocarbon fuel

DOEpatents

Krumpelt, Michael; Ahmed, Shabbir; Kumar, Romesh; Doshi, Rajiv

1999-01-01

A method of forming a hydrogen rich gas from a source of hydrocarbon fuel in which the hydrocarbon fuel contacts a two-part catalyst comprising a dehydrogenation portion and an oxide-ion conducting portion at a temperature not less than about 400.degree. C. for a time sufficient to generate the hydrogen rich gas while maintaining CO content less than about 5 volume percent. There is also disclosed a method of forming partially oxidized hydrocarbons from ethanes in which ethane gas contacts a two-part catalyst comprising a dehydrogenation portion and an oxide-ion conducting portion for a time and at a temperature sufficient to form an oxide.

Effect of surface ionization on wetting layers

NASA Technical Reports Server (NTRS)

Kayser, R. F.

1986-01-01

A surface ionization model due to Langmuir is generalized to liquid mixtures of polar and nonpolar components in contact with ionizable substrates. When a predominantly nonpolar mixture is near a miscibility gap, thick wetting layers of the conjugate polar phase form on the substrate. Such charged layers can be much thicker than similar wetting layers stabilized by dispersion forces. This model may explain the 0.4- to 0.6-micron-thick wetting layers formed in stirred mixtures of nitromethane and carbon disulfide in contact with glass.

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.

Utilizing technology for longitudinal communication with homeless youth.

PubMed

Bender, Kimberly; Begun, Stephanie; DePrince, Anne; Haffejee, Badiah; Kaufmann, Sarah

2014-10-01

The current study investigated forms of technology (phone calls, texts, email and Facebook) for maintaining contact with homeless youth over baseline, 1-week, 6-week, and 3-month follow-up interviews. The study combined quantitative tracking of youths' response patterns and open-ended interviews regarding youths' preferred methods of communication. Results indicate that maintaining communication with homeless youth requires persistence, including frequent contact attempts over several days. Cell phone contacts (calls or texts) were most successful in communicating with youth, with e-mail and Facebook messaging useful when phones were lost or stolen. Youth who maintained contact were strikingly similar to youth who discontinued contact.

An Epoxyisoprostane is a Major Regulator of Endothelial Cell Function

PubMed Central

Zhong, Wei; Springstead, James R.; Al-Mubarak, Ramea; Lee, Sangderk; Li, Rongsong; Emert, Benjamin; Berliner, Judith A.; Jung, Michael E.

2014-01-01

The goal of these studies was to determine the effect of 5,6-epoxyisoprostane, EI, on human aortic endothelial cells (HAEC). EI can form as a phospholipase product of 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine, PEIPC, a pro-inflammatory molecule that accumulates in sites of inflammation where phospholipases are also increased. To determine the effect of EI on HAEC, we synthesized several stereoisomers of EI using a convergent approach from the individual optically pure building blocks, the epoxyaldehydes 5 and 6 and the bromoenones 14 and 16. The desired stereoisomer of EI can be prepared from these materials in only six operations and thus large amounts of the product can be obtained. The trans/trans isomers had the most potent activity, suggesting specificity in the interaction of EI with the cell surface. EI has potent anti-inflammatory effects in HAEC. EI strongly inhibits the production of MCP-1, a major monocyte chemotactic factor, and either decreases or minimally increases the levels of ten pro-inflammatory molecules increased by PEIPC. EI also strongly downregulates the inflammatory effects of IL-1β, a major inflammatory cytokine. Thus EI, a hydrolytic product of PEIPC, has potent anti-inflammatory function. PMID:24117045

Discovery of a Potent BTK Inhibitor with a Novel Binding Mode by Using Parallel Selections with a DNA-Encoded Chemical Library.

PubMed

Cuozzo, John W; Centrella, Paolo A; Gikunju, Diana; Habeshian, Sevan; Hupp, Christopher D; Keefe, Anthony D; Sigel, Eric A; Soutter, Holly H; Thomson, Heather A; Zhang, Ying; Clark, Matthew A

2017-05-04

We have identified and characterized novel potent inhibitors of Bruton's tyrosine kinase (BTK) from a single DNA-encoded library of over 110 million compounds by using multiple parallel selection conditions, including variation in target concentration and addition of known binders to provide competition information. Distinct binding profiles were observed by comparing enrichments of library building block combinations under these conditions; one enriched only at high concentrations of BTK and was competitive with ATP, and another enriched at both high and low concentrations of BTK and was not competitive with ATP. A compound representing the latter profile showed low nanomolar potency in biochemical and cellular BTK assays. Results from kinetic mechanism of action studies were consistent with the selection profiles. Analysis of the co-crystal structure of the most potent compound demonstrated a novel binding mode that revealed a new pocket in BTK. Our results demonstrate that profile-based selection strategies using DNA-encoded libraries form the basis of a new methodology to rapidly identify small molecule inhibitors with novel binding modes to clinically relevant targets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-120 interface

PubMed Central

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

2014-01-01

The isolation of human monoclonal antibodies (mAbs) is providing important insights regarding the specificities that underlie broad neutralization of HIV-1 (reviewed in1). Here we report a broad and extremely potent HIV-specific mAb, termed 35O22, which binds novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with an IC50<50 μg/ml. The median IC50 of neutralized viruses was 0.033 μg/ml, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed it to bind a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current mAb-based approaches to immunotherapies, prophylaxis, and vaccine design. PMID:25186731

Quercetin derivatives as non-nucleoside inhibitors for dengue polymerase: molecular docking, molecular dynamics simulation, and binding free energy calculation.

PubMed

Anusuya, Shanmugam; Gromiha, M Michael

2017-10-01

Dengue is an important public health problem in tropical and subtropical regions of the world. Neither vaccine nor an antiviral medication is available to treat dengue. This insists the need of drug discovery for dengue. In order to find a potent lead molecule, RNA-dependent RNA polymerase which is essential for dengue viral replication is chosen as a drug target. As Quercetin showed antiviral activity against several viruses, quercetin derivatives developed by combinatorial library synthesis and mined from PubChem databases were screened for a potent anti-dengue viral agent. Our study predicted Quercetin 3-(6″-(E)-p-coumaroylsophoroside)-7-rhamnoside as a dengue polymerase inhibitor. The results were validated by molecular dynamics simulation studies which reveal water bridges and hydrogen bonds as major contributors for the stability of the polymerase-lead complex. Interactions formed by this compound with residues Trp795, Arg792 and Glu351 are found to be essential for the stability of the polymerase-lead complex. Our study demonstrates Quercetin 3-(6″-(E)-p-coumaroylsophoroside)-7-rhamnoside as a potent non-nucleoside inhibitor for dengue polymerase.

Dichotomous roles of leptin and adiponectin as enforcers against lipotoxicity during feast and famine.

PubMed

Unger, Roger H; Scherer, Philipp E; Holland, William L

2013-10-01

Science is marked by the death of dogmas; the discovery that adipocytes are more than just lipid-storing cells but rather produce potent hormones is one such example that caught physiologists by surprise and reshaped our views of metabolism. While we once considered the adipocyte as a passive storage organ for efficient storage of long-term energy reserves in the form of triglyceride, we now appreciate the general idea (once a radical one) that adipocytes are sophisticated enough to have potent endocrine functions. Over the past two decades, the discoveries of these adipose-derived factors ("adipokines") and their mechanistic actions have left us marveling at and struggling to understand the role these factors serve in physiology and the pathophysiology of obesity and diabetes. These hormones may serve an integral role in protecting nonadipose tissues from lipid-induced damage during nutrient-deprived or replete states. As such, adipocytes deliver not only potentially cytotoxic free fatty acids but, along with these lipids, antilipotoxic adipokines such as leptin, adiponectin, and fibroblast growth factor 21 that potently eliminate excessive local accumulation of these lipids or their conversion to unfavorable sphingolipid intermediates.

Persistence of increased Eotaxin-1 (CCL11) level in tears of patients wearing contact lenses: a long-term follow-up study.

PubMed

Tran, H V; Eperon, S; Guex-Crosier, Y

2011-04-01

Eotaxin-1 (CCL11) is a potent eosinophil chemotactic and activating peptide that may be implicated in the pathogenesis of chronic allergic eye disease and has been associated with the wearing of contact lenses (CL) in patients with contact lens papillary conjunctivitis (CLPC). The purpose of this study was to study eotaxin-1 expression in the tears of long-term CL wearers. Tears were collected with glass capillaries from 15 patients (2 male, 13 female) with various degree of CLPC at 2-year intervals. CLPC severity was graded from 0 to 4 with reference to standard slit-lamp photographs of the superior tarsal conjunctiva. The eotaxin-1 level in the tears was measured by an ELISA, using mouse anti-human eotaxin monoclonal antibodies. The mean age was 32.5 ± 13.3 years (range: 17 - 69 years). The mean interval between the tear collections was 30 ± 4.8 months. The mean concentration of eotaxin was 2150 ± 477 pg/mL and 2486 ± 810 pg/mL for the first and second series, respectively. The difference was not statistically significant (paired Wilcoxon/Kruskal-Wallis, p = 0.803). The mean score of papilla grade was 1.26 ± 0.18 for the first sample and 1.40 ± 0.19 two years later. There was no significant difference of grading between the two time periods (paired Wilcoxon/Kruskal-Wallis, p = 0.751). the eotaxin-1 level remains up-regulated over a long time period in patients wearing CL, most of them with chronic CLPC. Eotaxin may play a role in the pathogenesis of contact lens intolerance. © Georg Thieme Verlag KG Stuttgart · New York.

The tobacco carcinogen NNK is stereoselectively reduced by human pancreatic microsomes and cytosols.

PubMed

Trushin, Neil; Leder, Gerhard; El-Bayoumy, Karam; Hoffmann, Dietrich; Beger, Hans G; Henne-Bruns, Doris; Ramadani, Marco; Prokopczyk, Bogdan

2008-07-01

Cigarette smoking increases the risk of cancer of the pancreas. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the only known environmental compound that induces pancreatic cancer in laboratory animals. Concentrations of NNK are significantly higher in the pancreatic juice of smokers than in that of nonsmokers. The chiral NNK metabolite, (R,S)-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is itself a potent pancreatic carcinogen in rats. The carcinogenicity of NNAL is related to its stereochemistry; (S)-NNAL is a more potent lung tumorigen in the A/J mouse than is (R)-NNAL. In this study, we determined the potential of the human pancreas to convert NNK into NNAL. Human pancreatic microsomes and cytosols were incubated with [5-(3)H]NNK, and the metabolic products were determined by high-performance liquid chromatography (HPLC). (S)-NNAL was the predominant isomer formed in all cytosolic incubations. In ten microsomal samples, NNAL was formed at an average rate of 3.8 +/- 1.6 pmol/mg/min; (R)-NNAL was the predominant isomer in this group. The average rate of NNAL formation in 18 other microsomal samples was significantly lower, 0.13 +/- 0.12 pmol/mg/min (p < 0.001); (S)-NNAL was the predominant isomer formed in this group. In human pancreatic tissues, there is intraindividual variability regarding the capacity for, and stereoselectivity of, carbonyl reduction of NNK.

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.

Allergic manifestations of contact lens wearing.

PubMed

Solomon, Abraham

2016-10-01

Contact lens-induced papillary conjunctivitis (CLPC) is a common ocular allergic disease in contact lens wearers. In its more severe form, it can cause giant papillary conjunctivitis, resulting in contact lens intolerance and the need to discontinue the use of contact lenses. This review presents the pathogenesis, clinical manifestations and management guidelines of this common disorder. Different types of contact lenses are associated with differences in the severity of CLPC. Refitting patients with silicone hydrogel contact lenses or with daily disposable contact lenses may improve the signs and symptoms of CLPC. The recent introduction of the topical immunomodulatory agent tacrolimus in other severe allergic eye diseases may apply in suppressing the allergic inflammation in CLPC as well. CLPC is a common ocular disorder in contact lens wearers, with a significant impact on the quality of vision. It should be promptly recognized by healthcare practitioners and managed by modifications of the types and wearing schedules of contact lenses, as well as novel treatment options with topical immunomodulators.

Solvent Orange 60 is a potent contact sensitizer in occupational and everyday life.

PubMed

Linauskienė, Kotryna; Zimerson, Erik; Antelmi, Annarita; Bruze, Magnus; Hagvall, Lina; Hamnerius, Nils; Hauksson, Inese; Ryberg, Kristina; Isaksson, Marléne

2018-05-30

Solvent Orange (SO) 60 is a perinone-type dye that is often used in plastic materials such as spectacle frames and has been shown to cause contact allergy. The first case of SO 60 allergic contact dermatitis caused by spectacle frames was reported in 1999, and the second in 2011. We have recently seen 10 patients, of whom 6 developed dermatitis in the retroauricular/temporal area after wearing plastic spectacles. To report the cause of the dermatitis in the 10 patients and to describe our first case with occupational SO 60 contact allergy. In this retrospective study, patch test results of 10 patients, tested with the Swedish baseline series and our specific spectacle and/or plastic series, including SO 60 1.0% pet., in 2011-2017, were analysed and compared with data published earlier. Ten patients, 2 males and 8 females, aged 43 to 71 years, reacted positively to SO 60 1.0% pet., namely, 4 pensioners, 2 nurses, 1 office worker, 1 teacher, 1 shop assistant, and 1 unemployed person. Four of the patients had an atopic history. Patch test reactions varied from + to +++; some had spread >20 cm outside the test area, and consisted of erythematous, infiltrated skin with papules. Retesting of patient no. 1 with serial dilutions of SO 60 in acetone to pinpoint his level of reactivity showed positive reactions down to 1 ppm. Three patients reacted to the extracts of their earpieces. Gas chromatography-mass spectrometry was used to confirm the presence of SO 60 in 2 earpieces. SO 60 should be included in any spectacle patch test series that may be used. If there is a strong suspicion of contact allergy to SO 60 before patch testing, lowering the test concentration from 1.0% to 0.01% should be considered. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Carrier Selective, Passivated Contacts for High Efficiency Silicon Solar Cells based on Transparent Conducting Oxides

DOE PAGES

Young, David L.; Nemeth, William; Grover, Sachit; ...

2014-01-01

We describe the design, fabrication and results of passivated contacts to n-type silicon utilizing thin SiO 2 and transparent conducting oxide layers. High temperature silicon dioxide is grown on both surfaces of an n-type wafer to a thickness <50 Å, followed by deposition of tin-doped indium oxide (ITO) and a patterned metal contacting layer. As deposited, the thin-film stack has a very high J0, contact, and a non-ohmic, high contact resistance. However, after a forming gas anneal, the passivation quality and the contact resistivity improve significantly. The contacts are characterized by measuring the recombination parameter of the contact (J0, contact)more » and the specific contact resistivity (ρ contact) using a TLM pattern. The best ITO/SiO 2 passivated contact in this study has J 0,contact = 92.5 fA/cm 2 and ρ contact = 11.5 mOhm-cm 2. These values are placed in context with other passivating contacts using an analysis that determines the ultimate efficiency and the optimal area fraction for contacts for a given set of (J0, contact, ρ contact) values. The ITO/SiO 2 contacts are found to have a higher J0, contact, but a similar ρ contact compared to the best reported passivated contacts.« less

The Influence of Multiple Host Contacts on the Acquisition and Transmission of Dengue-2 Virus

DTIC Science & Technology

1993-01-01

5500 Stanoard Form 298 (Rev 2-89) PIs~~ bv AtI %t .34-| II Best Available Copy ABSTRACT Title of Dissertation: THE INFLUENCE OF MULTIPLE HOST CONTACTS...ABSTRACT Title of the Dissertaton: THE INFLUENCE OF MULTIPLE HOST CONTACTS ON THE ACQUISITION AND TRANSMISSION OF DENGUE-2 VIRUS BY A=DISAEX2 . John L...virus does not alter the feeding behavior of An. n•ngy~i. THE INFLUENCE OF MULTIPLE HOST CONTACTS ON THE ACQUISITION AND TRANSMISSION OF DENGUE-2 VIRUS BY

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.

Vanadium-based Ohmic contacts to n-AlGaN in the entire alloy composition

NASA Astrophysics Data System (ADS)

France, Ryan; Xu, Tao; Chen, Papo; Chandrasekaran, R.; Moustakas, T. D.

2007-02-01

The authors report on the formation and evaluation of V-based Ohmic contacts to n-AlGaN films in the entire alloy composition. The films were produced by plasma assisted molecular beam epitaxy and doped n-type with Si. The conductivity of the films was determined to vary from 103to10-2(Ωcm )-1 as the AlN mole fraction increases from 0% to 100%. Ohmic contacts were formed by e-beam evaporation of V(15nm )/Al(80nm)/V(20nm)/Au(100nm). These contacts were rapid thermal annealed in N2 for 30s at various temperatures. The optimum annealing temperature for this contact scheme to n-GaN is about 650°C and increases monotonically to about 1000°C for 95%-100% AlN mole fraction. The specific contact resistivity was found to be about 10-6Ωcm2 for all films up to 70% AlN mole fraction and then increases to 0.1-1Ωcm2 for films from 95%-100% AlN mole fraction. These results were accounted for by hypothesizing that vanadium, upon annealing, interacts with the nitride film and forms vanadium nitride, which is consistent with reports that it is a metal with low work function.

Continuity tester screens out faulty socket connections

NASA Technical Reports Server (NTRS)

Golding, G.

1964-01-01

A device, used before and after assembly, tests the continuity of an electrical circuit through each pin and socket of multiple connector sockets. Electrically insulated except at the contact area, a test probe is dimensioned to make contact only in properly formed sockets.

75 FR 60433 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... Form, and OMB Number: Personal Information Questionnaire; OMB Control Number 0703-0012. Needs and Uses... Personal Information Questionnaire is used to provide Headquarters, U.S. Marine Corps with a standardized... without change, including any personal identifiers or contact information. FOR FURTHER INFORMATION CONTACT...

Porous body infiltrating method

DOEpatents

Corman, Gregory Scot

2002-01-01

A mixture is formed that comprises at least some to about 10 wt % boron nitride and silicon. A body comprising a component that is wetted by or reacts with silicon is contacted with the mixture and the contacted body is infiltrated with silicon from the mixture.

Heterodimerization with the β1 subunit directs the α2 subunit of nitric oxide-sensitive guanylyl cyclase to calcium-insensitive cell-cell contacts in HEK293 cells: Interaction with Lin7a.

PubMed

Hochheiser, Julia; Haase, Tobias; Busker, Mareike; Sömmer, Anne; Kreienkamp, Hans-Jürgen; Behrends, Sönke

2016-12-15

Nitric oxide-sensitive guanylyl cyclase is a heterodimeric enzyme consisting of an α and a β subunit. Two different α subunits (α 1 and α 2 ) give rise to two heterodimeric enzymes α 1 /β 1 and α 2 /β 1 . Both coexist in a wide range of tissues including blood vessels and the lung, but expression of the α 2 /β 1 form is generally much lower and approaches levels similar to the α 1 /β 1 form in the brain only. In the present paper, we show that the α 2 /β 1 form interacts with Lin7a in mouse brain synaptosomes based on co-precipitation analysis. In HEK293 cells, we found that the overexpressed α 2 /β 1 form, but not the α 1 /β 1 form is directed to calcium-insensitive cell-cell contacts. The isolated PDZ binding motif of an amino-terminally truncated α 2 subunit was sufficient for cell-cell contact localization. For the full length α 2 subunit with the PDZ binding motif this was only the case in the heterodimer configuration with the β 1 subunit, but not as isolated α 2 subunit. We conclude that the PDZ binding motif of the α 2 subunit is only accessible in the heterodimer conformation of the mature nitric oxide-sensitive enzyme. Interaction with Lin7a, a small scaffold protein important for synaptic function and cell polarity, can direct this complex to nectin based cell-cell contacts via MPP3 in HEK293 cells. We conclude that heterodimerization is a prerequisite for further protein-protein interactions that direct the α 2 /β 1 form to strategic sites of the cell membrane with adjacent neighbouring cells. Drugs increasing the nitric oxide-sensitivity of this specific form may be particularly effective. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of titanium aluminide in n-gallium nitride ohmic contact technology

NASA Astrophysics Data System (ADS)

Pelto, Christopher M.

Ohmic contacts are essential to the realization of efficient and affordable nitride-based electronic and optoelectronic devices. Currently, the most successful ohmic contact schemes to n-GaN are based on the Al/Ti bilayer structure, although the mechanism responsible for the low resistance in these contacts is not sufficiently understood. In this work, the intermetallic TiAl3 has been employed both as a model ohmic contact system to help understand the essential features of the Al/Ti standard contact, as well as a thermally stable oxidation cap for the bilayer structure. A quaternary isotherm of the Al-Ti-Ga-N system was calculated at 600°C, which showed that a sufficient phase topology was present to apply the exchange mechanism to the TiAl 3/GaN couple. The exchange mechanism rationalized the selection of the TiAl3 intermetallic by predicting that an Al-rich AlGaN layer will form at the metal/semiconductor interface. As part of the investigation of these novel contact systems, a thorough characterization was undertaken on both a standard Al/Ti and Au/Ni/Al/Ti contact to n-GaN in which the essential processing parameters and metallurgical properties were identified. The TiAl 3 contact was found to exhibit inferior electrical behavior compared to the Al/Ti bilayer, requiring significantly higher annealing temperatures to achieve comparable specific contact resistance. It is conjectured that this is due to the early formation of a TiN layer at the metal/semiconductor interface of the bilayer contact, even though both contacts are suspected to form the Al-rich nitride layer at higher temperature. As an oxidation cap, the TiAl3 metallization was found to provide much improved performance characteristics compared to the four-layer Au/Al/Ni/Ti standard. The TiAl 3/Al/Ti contact proved to achieve optimal performance at a much lower temperature than the standard, and furthermore showed complete insensitivity to the oxidation content of the annealing ambient. Reaction mechanisms for the TiAl3-capped and the four-layer contact metallizations are suggested that account for both the morphology and the expected interfacial phases of each system.

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

Analysis of Electrowetting Dynamics with Level Set Method

NASA Astrophysics Data System (ADS)

Park, Jun Kwon; Hong, Jiwoo; Kang, Kwan Hyoung

2009-11-01

Electrowetting is a versatile tool to handle tiny droplets and forms a backbone of digital microfluidics. Numerical analysis is necessary to fully understand the dynamics of electrowetting, especially in designing electrowetting-based liquid lenses and reflective displays. We developed a numerical method to analyze the general contact-line problems, incorporating dynamic contact angle models. The method was applied to the analysis of spreading process of a sessile droplet for step input voltages in electrowetting. The result was compared with experimental data and analytical result which is based on the spectral method. It is shown that contact line friction significantly affects the contact line motion and the oscillation amplitude. The pinning process of contact line was well represented by including the hysteresis effect in the contact angle models.

Restricted-Access Al-Mediated Material Transport in Al Contacting of PureGaB Ge-on-Si p + n Diodes

NASA Astrophysics Data System (ADS)

Sammak, Amir; Qi, Lin; Nanver, Lis K.

2015-12-01

The effectiveness of using nanometer-thin boron (PureB) layers as interdiffusion barrier to aluminum (Al) is studied for a contacting scheme specifically developed for fabricating germanium-on-silicon (Ge-on-Si) p + n photodiodes with an oxide-covered light entrance window. Contacting is achieved at the perimeter of the Ge-island anode directly to an Al interconnect metallization. The Ge is grown in oxide windows to the Si wafer and covered by a B and gallium (Ga) layer stack (PureGaB) composed of about a nanometer of Ga for forming the p + Ge region and 10 nm of B as an interdiffusion barrier to the Al. To form contact windows, the side-wall oxide is etched away, exposing a small tip of the Ge perimeter to Al that from this point travels about 5 μm into the bulk Ge crystal. In this process, Ge and Si materials are displaced, forming Ge-filled V-grooves at the Si surface. The Al coalesces in grains. This process is studied here by high-resolution cross-sectional transmission electron microscopy and energy dispersive x-ray spectroscopy that confirm the purities of the Ge and Al grains. Diodes are fabricated with different geometries and statistical current-voltage characterization reveals a spread that can be related to across-the-wafer variations in the contact processing. The I- V behavior is characterized by low dark current, low contact resistance, and breakdown voltages that are suitable for operation in avalanching modes. The restricted access to the Ge of the Al inducing the Ge and Si material transport does not destroy the very good electrical characteristics typical of PureGaB Ge-on-Si diodes.

Self-Sorting of Bidispersed Colloidal Particles Near Contact Line of an Evaporating Sessile Droplet.

PubMed

Patil, Nagesh D; Bhardwaj, Rajneesh; Sharma, Atul

2018-06-13

Here, we investigate deposit patterns and associated morphology formed after the evaporation of an aqueous droplet containing mono- and bidispersed colloidal particles. In particular, the combined effect of substrate heating and particle diameter is investigated. We employ high-speed visualization, optical microscopy, and scanning electron microscopy to characterize the evaporating droplets, particle motion, and deposit morphology, respectively. In the context of monodispersed colloidal particles, an inner deposit and a typical ring form for smaller and larger particles, respectively, on a nonheated surface. The formation of the inner deposit is attributed to early depinning of the contact line, explained by a mechanistic model based on the balance of several forces acting on a particle near the contact line. At larger substrate temperature, a thin ring with inner deposit forms, explained by the self-pinning of the contact line and advection of the particles from the contact line to the center of the droplet due to the Marangoni flow. In the context of bidispersed colloidal particles, self-sorting of the colloidal particles within the ring occurs at larger substrate temperature. The smaller particles deposit at the outermost edge compared to the larger particles, and this preferential deposition in a stagnation region near the contact line is due to the spatially varying height of the liquid-gas interface above the substrate. The sorting occurs at a smaller ratio of the diameters of the smaller and larger particles. At larger substrate temperature and larger ratio, the particles do not get sorted and mix into each other. Our measurements show that there exists a critical substrate temperature as well as a diameter ratio to achieve the sorting. We propose regime maps on substrate temperature-particle diameter and substrate temperature-diameter ratio plane for mono- and bidispersed solutions, respectively.

Gelation of Oil upon Contact with Water: A Bioinspired Scheme for the Self-Repair of Oil Leaks from Underwater Tubes.

PubMed

Oh, Hyuntaek; Yaraghi, Nicholas; Raghavan, Srinivasa R

2015-05-19

Molecular organogelators convert oils into gels by forming self-assembled fibrous networks. Here, we demonstrate that such gelation can be activated by contacting the oil with an immiscible solvent (water). Our gelator is dibenzylidene sorbitol (DBS), which forms a low-viscosity sol when added to toluene containing a small amount of dimethyl sulfoxide (DMSO). Upon contact with water, DMSO partitions into the water, activating gelation of DBS in the toluene. The gel grows from the oil/water interface and slowly envelops the oil phase. We have exploited this effect for the self-repair of oil leaks from underwater tubes. When a DBS/toluene/DMSO solution flows through the tube, it forms a gel selectively at the leak point, thereby plugging the leak and restoring flow. Our approach is reminiscent of wound-sealing via blood-clotting: there also, inactive gelators in blood are activated at the wound site into a fibrous network, thereby plugging the wound and restoring blood flow.

Numerical analysis of deposition frequency for successive droplets coalescence dynamics

NASA Astrophysics Data System (ADS)

Cheng, Xiaoding; Zhu, Yunlong; Zhang, Lei; Zhang, Dingyi; Ku, Tao

2018-04-01

A pseudopotential based multi-relaxation-time lattice Boltzmann model is employed to investigate the dynamic behaviors of successive droplets' impact and coalescence on a solid surface. The effects of deposition frequency on the morphology of the formed line are investigated with a zero receding contact angle by analyzing the droplet-to-droplet coalescence dynamics. Two collision modes (in-phase mode and out-of-phase mode) between the pre-deposited bead and the subsequent droplet are identified depending on the deposition frequency. A uniform line can be obtained at the optimal droplet spacing in the in-phase mode (Δt* < 1.875). However, a scalloped line pattern is formed in the out-of-phase mode (Δt* > 1.875). It is found that decreasing the droplet spacing or advancing contact angle can improve the smoothness of line in the out-of-phase mode. Furthermore, the effects of deposition frequency on the morphology of the formed lines are validated to be applicable to cases with a finite receding contact angle.

Media Effects in Youth Exposed to Terrorist Incidents: a Historical Perspective.

PubMed

Pfefferbaum, Betty; Tucker, Phebe; Pfefferbaum, Rose L; Nelson, Summer D; Nitiéma, Pascal; Newman, Elana

2018-03-05

This paper reviews the evidence on the relationship between contact with media coverage of terrorist incidents and psychological outcomes in children and adolescents while tracing the evolution in research methodology. Studies of recent events in the USA have moved from correlational cross-sectional studies examining primarily television coverage and posttraumatic stress reactions to longitudinal studies that address multiple media forms and a range of psychological outcomes including depression and anxiety. Studies of events in the USA-the 1995 Oklahoma City bombing, the September 11 attacks, and the 2013 Boston Marathon bombing-and elsewhere have used increasingly sophisticated research methods to document a relationship between contact with various media forms and adverse psychological outcomes in children with different event exposures. Although adverse outcomes are associated with reports of greater contact with terrorism coverage in cross-sectional studies, there is insufficient evidence at this time to assume a causal relationship. Additional research is needed to investigate a host of issues such as newer media forms, high-risk populations, and contextual factors.

Form and function of cnidarian spirocysts. III. Ultrastructure of the thread and the function of spirocysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mariscal, R.N.; McLean, R.B.; Hand, C.

1977-01-01

Unlike most nematocysts, undischarged spirocyst threads bear hollow tubules rather than spines. The undischarged tubules are interconnected in hexagonal arrays and appear to be arranged in bundles along the length of the thread. Although the wall of the thread is folded in length and width, the tubules are not. Upon discharge and contact with sea water, the tubules solubilize and adhere to various substrates and prey. Traction between such objects and the everting thread causes the tubules to spin out into a web or meshwork of fine microfibrillae. Lack of contact of the everting thread with objects results in themore » tubules forming small droplets of partially solubilized material, some of which appear to be arranged in a helical pattern around the thread. The web or meshwork formed by the solubilized tubules in contact with various substrates probably serves to increase significantly the surface area and adhesive properties of the everted spirocyst thread.« less

Interaction of the alpha-subunit of Escherichia coli RNA polymerase with DNA: rigid body nature of the protein-DNA contact.

PubMed

Heyduk, E; Baichoo, N; Heyduk, T

2001-11-30

The alpha-subunit of Escherichia coli RNA polymerase plays an important role in the activity of many promoters by providing a direct protein-DNA contact with a specific sequence (UP element) located upstream of the core promoter sequence. To obtain insight into the nature of thermodynamic forces involved in the formation of this protein-DNA contact, the binding of the alpha-subunit of E. coli RNA polymerase to a fluorochrome-labeled DNA fragment containing the rrnB P1 promoter UP element sequence was quantitatively studied using fluorescence polarization. The alpha dimer and DNA formed a 1:1 complex in solution. Complex formation at 25 degrees C was enthalpy-driven, the binding was accompanied by a net release of 1-2 ions, and no significant specific ion effects were observed. The van't Hoff plot of temperature dependence of binding was linear suggesting that the heat capacity change (Deltac(p)) was close to zero. Protein footprinting with hydroxyradicals showed that the protein did not change its conformation upon protein-DNA contact formation. No conformational changes in the DNA molecule were detected by CD spectroscopy upon protein-DNA complex formation. The thermodynamic characteristics of the binding together with the lack of significant conformational changes in the protein and in the DNA suggested that the alpha-subunit formed a rigid body-like contact with the DNA in which a tight complementary recognition interface between alpha-subunit and DNA was not formed.

Homeopathic potentization based on nanoscale domains.

PubMed

Czerlinski, George; Ypma, Tjalling

2011-12-01

The objectives of this study were to present a simple descriptive and quantitative model of how high potencies in homeopathy arise. The model begins with the mechanochemical production of hydrogen and hydroxyl radicals from water and the electronic stabilization of the resulting nanodomains of water molecules. The life of these domains is initially limited to a few days, but may extend to years when the electromagnetic characteristic of a homeopathic agent is copied onto the domains. This information is transferred between the original agent and the nanodomains, and also between previously imprinted nanodomains and new ones. The differential equations previously used to describe these processes are replaced here by exponential expressions, corresponding to simplified model mechanisms. Magnetic stabilization is also involved, since these long-lived domains apparently require the presence of the geomagnetic field. Our model incorporates this factor in the formation of the long-lived compound. Numerical simulation and graphs show that the potentization mechanism can be described quantitatively by a very simplified mechanism. The omitted factors affect only the fine structure of the kinetics. Measurements of pH changes upon absorption of different electromagnetic frequencies indicate that about 400 nanodomains polymerize to form one cooperating unit. Singlet excited states of some compounds lead to dramatic changes in their hydrogen ion dissociation constant, explaining this pH effect and suggesting that homeopathic information is imprinted as higher singlet excited states. A simple description is provided of the process of potentization in homeopathic dilutions. With the exception of minor details, this simple model replicates the results previously obtained from a more complex model. While excited states are short lived in isolated molecules, they become long lived in nanodomains that form coherent cooperative aggregates controlled by the geomagnetic field. These domains either slowly emit biophotons or perform specific biochemical work at their target.

Multi-target screening mines hesperidin as a multi-potent inhibitor: Implication in Alzheimer's disease therapeutics.

PubMed

Chakraborty, Sandipan; Bandyopadhyay, Jaya; Chakraborty, Sourav; Basu, Soumalee

2016-10-04

Alzheimer's disease (AD) is the most frequent form of neurodegenerative disorder in elderly people. Involvement of several pathogenic events and their interconnections make this disease a complex disorder. Therefore, designing compounds that can inhibit multiple toxic pathways is the most attractive therapeutic strategy in complex disorders like AD. Here, we have designed a multi-tier screening protocol combining ensemble docking to mine BACE1 inhibitor, as well as 2-D QSAR models for anti-amyloidogenic and antioxidant activities. An in house developed phytochemical library of 200 phytochemicals has been screened through this multi-target procedure which mine hesperidin, a flavanone glycoside commonly found in citrus food items, as a multi-potent phytochemical in AD therapeutics. Steady-state and time-resolved fluorescence spectroscopy reveal that binding of hesperidin to the active site of BACE1 induces a conformational transition of the protein from open to closed form. Hesperidin docks close to the catalytic aspartate residues and orients itself in a way that blocks the cavity opening thereby precluding substrate binding. Hesperidin is a high affinity BACE1 inhibitor and only 500 nM of the compound shows complete inhibition of the enzyme activity. Furthermore, ANS and Thioflavin-T binding assay show that hesperidin completely inhibits the amyloid fibril formation which is further supported by atomic force microscopy. Hesperidin exhibits moderate ABTS(+) radical scavenging assay but strong hydroxyl radical scavenging ability, as evident from DNA nicking assay. Present study demonstrates the applicability of a novel multi-target screening procedure to mine multi-potent agents from natural origin for AD therapeutics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

pH triggered controlled drug delivery from contact lenses: Addressing the challenges of drug leaching during sterilization and storage.

PubMed

Maulvi, Furqan A; Choksi, Harsh H; Desai, Ankita R; Patel, Akanksha S; Ranch, Ketan M; Vyas, Bhavin A; Shah, Dinesh O

2017-09-01

In the present work a novel cyclosporine-loaded Eudragit S100 (pH-sensitive) nanoparticles-laden contact lenses were designed to provide sustained release of cyclosporine at therapeutic rates, without leaching of drug during sterilization and storage period (shelf life). The nanoparticles were prepared by Quasi-emulsion solvent diffusion technique using different weight ratios of cyclosporine to Eudragit S100. The contact lenses with direct drug entrapment were also fabricated (DL-50) for comparison. The percentage swelling and optical transparency of nanoparticles-laden contact lenses were improved in comparison to DL-50 lenses. The nanoparticles-laden contact lenses showed sustained drug release profiles, with inverse relationship to the amount of nanoparticles loaded in the contact lenses. It was interesting to note that nanoparticles form nanochannels/cavities after dissolution of Eudragit S 100 in tear fluid pH=7.4 (in vitro release study). This followed the precipitation of drug in hydrogel matrix of contact lenses. As the amount of nanoparticles loading increased, more number of cavities were formed, which caused the formation of large cavities in contact lens matrix. This in turn precipitated the drug. The nanoparticles-laden contact lenses with 1:1 (drug: Eudragit) weight ratio showed the most promising results of sustaining the drug release up to 156h, without affecting optical and physical properties of contact lenses. Packaging study confirmed that the drug was not leached in packaging solution (buffer, pH=6.5) from nanoparticles-laden lenses during shelf life period. In-vivo study in rabbit tear fluid showed sustained release up to 14days. The study revealed the application of pH-sensitive nanoparticles-laden contact lenses for controlled release of cyclosporine without altering the optical and physical properties of lens material. Copyright © 2017 Elsevier B.V. All rights reserved.

Carrier Transport of Silver Nanowire Contact to p-GaN and its Influence on Leakage Current of LEDs

NASA Astrophysics Data System (ADS)

Oh, Munsik; Kang, Jae-Wook; Kim, Hyunsoo

2018-03-01

The authors investigated the silver nanowires (AgNWs) contact formed on p-GaN. Transmission line model applied to the AgNWs contact to p-GaN produced near ohmic contact with a specific contact resistance (ρ sc) of 10-1˜10-4 Ω·cm2. Noticeably, the contact resistance had a strong bias-voltage (or current-density) dependence associated with a local joule heating effect. Current-voltage-temperature (I-V-T) measurement revealed a strong temperature dependence with respect to ρ sc, indicating that the temperature played a key role of an enhanced carrier transport. The local joule heating at AgNW/GaN interface, however, resulted in a generation of leakage current of light-emitting diodes (LEDs) caused by degradation of AgNW contact.

Metagenomics: A Call for Bringing a New Science into the Classroom (While It's Still New)

ERIC Educational Resources Information Center

Jurkowski, Anne; Reid, Ann H.; Labov, Jay B.

2007-01-01

This article describes the emerging field of metagenomics, a potent new tool that vastly expands the ability of scientists to study the myriad capabilities of microbial communities and the as yet unrecognized relationships and interactions of microbes with other forms of life and the environment. The birth of this exciting new field provides the…

Determination of the aflatoxin M1 (AFM1) from milk by direct analysis in real time - mass spectrometry (DART-MS)

USDA-ARS?s Scientific Manuscript database

Certain fungi that grow on crops can produce aflatoxins, which are highly carcinogenic. One of these, aflatoxin B1 can be metabolized by mammals to aflatoxin M1, a form that retains potent carcinogenicity and which can be excreted into milk. Direct analysis in real time (DART) ionization coupled to ...

Geometry Three Ways: An fMRI Investigation of Geometric Information Processing during Reorientation

ERIC Educational Resources Information Center

Sutton, Jennifer E.; Twyman, Alexandra D.; Joanisse, Marc F.; Newcombe, Nora S.

2012-01-01

The geometry formed by the walls of a room is known to be a potent cue in reorientation, yet little is known about the use of geometric information gleaned from other contexts. We used functional magnetic resonance imaging to examine neural activity in adults while reorienting in 3 different environments: the typical rectangular walled room, a…

40 CFR 463.11 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Contact Cooling and Heating Water... process operates. The “average process water usage flow rate” for a plant with more than one plastics... process and comes in contact with the plastic product over a period of one year. ...

Novel 3-Nitro-1H-1,2,4-triazole-based Amides and Sulfonamides as Potential anti-Trypanosomal Agents

PubMed Central

Papadopoulou, Maria V.; Bloomer, William D.; Rosenzweig, Howard S.; Chatelain, Eric; Kaiser, Marcel; Wilkinson, Shane R.; McKenzie, Caroline; Ioset, Jean-Robert

2012-01-01

A series of novel 3-nitro-1H-1,2,4-triazole-(and in some cases 2-nitro-1H-imidazole)-based amides and sulfonamides were characterized for their in vitro anti-trypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1H-1,2,4-triazoles) displayed significant activity against T. cruzi intracellular amastigotes (IC50 ranging from 28 nM to 3.72 μM) without concomitant toxicity to L6 host cells (selectivity 66 to 2782). Twenty three of these active compounds were more potent (up to 58 fold) than the reference drug benznidazole, tested in parallel. In addition, 9 nitrotriazoles which were moderately active (0.5 μM ≤ IC50 < 6.0 μM) against T. b. rhodesiense trypomastigotes, were 5 to 31 fold more active against bloodstream-form T. b. brucei trypomastigotes engineered to overexpress NADH-dependent nitroreductase (TbNTR). Finally, 3 nitrotriazoles displayed a moderate activity against the axenic form of Leishmania donovani. Therefore, 3-nitro-1H-1,2,4-triazole-based amides and sulfonamides are potent anti-trypanosomal agents. PMID:22550999

Candidacidal activity of synthetic peptides based on the antimicrobial domain of the neutrophil-derived protein, CAP37

PubMed Central

Pereira, H. Anne; Tsyshevskaya-Hoover, Irina; Hinsley, Heather; Logan, Sreemathi; Nguyen, Melissa; Nguyen, Thuy-Trang; Pohl, Jan; Wozniak, Karen; Fidel, Paul L.

2009-01-01

The primary bactericidal domain of CAP37, a cationic antimicrobial protein with potent activity against Gram-negative organisms was previously shown to reside between amino acids 20 through 44 (NQGRHFCGGALIHARFVMTAASCFQ) of the native protein. In this study, we explored the efficacy of four synthetic CAP37 peptide analogs, based on this sequence, against various Candida species including fluconazole-sensitive and -resistant isolates of C. albicans. Three of the peptides demonstrated strong antifungal activity for C. albicans, including fluconazole-resistant isolates of C. albicans and were active against C. guilliermondii, C. tropicalis, C. pseudotropicalis, C. parapsilosis, and C. dubliniensis. The peptides were ineffective against C. glabrata, C. krusei, and Saccharomyces cerevisiae. For C. albicans isolates, the peptides had relatively greater activity against blastoconidia than hyphal forms, although strong antifungal activity was observed with pseudohyphal forms of the various Candida species tested. Kinetic studies demonstrated fungicidal rather than fungistatic activity. These findings indicate that synthetic peptides based on the antimicrobial domain of CAP37 also have activity against eukaryotic organisms suggesting a broader range of activity than originally demonstrated and show for the first time their potent fungicidal activity. PMID:19626550

The HIV glycan shield as a target for broadly neutralizing antibodies.

PubMed

Doores, Katie J

2015-12-01

The HIV envelope glycoprotein (Env) is the sole target for HIV broadly neutralizing antibodies (bnAbs). HIV Env is one of the most heavily glycosylated proteins known, with approximately half of its mass consisting of host-derived N-linked glycans. The high density of glycans creates a shield that impedes antibody recognition but, critically, some of the most potent and broadly active bnAbs have evolved to recognize epitopes formed by these glycans. Although the virus hijacks the host protein synthesis and glycosylation machinery to generate glycosylated HIV Env, studies have shown that HIV Env glycosylation diverges from that typically observed on host-derived glycoproteins. In particular, the high density of glycans leads to a nonself motif of underprocessed oligomannose-type glycans that forms the target of some of the most broad and potent HIV bnAbs. This review discusses the changing perception of the HIV glycan shield, and summarizes the protein-directed and cell-directed factors controlling HIV Env glycosylation that impact on HIV bnAb recognition and HIV vaccine design strategies. © The Author. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Environmental change and the conversion of permanently frozen ground to wetlands

NASA Astrophysics Data System (ADS)

Neumann, R. B.; Moorberg, C.; Turner, J.; Wong, A.; Waldrop, M. P.; Euskirchen, E. S.; Edgar, C.; Turetsky, M. R.

2017-12-01

Much of the land around the arctic is permanently frozen, even in the summer. However, because the world is getting warmer, this frozen ground, known as permafrost, is thawing. When permafrost thaws, the ground collapses and sinks, and often a wetland forms within the collapsed area. This conversion of a permanently frozen landscape to a wetland changes the exchange of greenhouse gases between the land and atmosphere, which can, in turn, impact global temperatures and environmental conditions. Wetlands pull carbon dioxide out of the atmosphere because they support the growth of many plants. This uptake of atmospheric carbon dioxide by wetlands helps reduce global warming. However, wetlands also release methane into the atmosphere, which is a potent greenhouse gas — more potent than carbon dioxide. The net effect on global temperatures and environmental conditions depends on the balance between wetland uptake of atmospheric carbon dioxide and release of methane. We are measuring the exchange of these two greenhouse gases between the land and atmosphere in a wetland that formed after permafrost thawed so we can know how global temperatures and environmental conditions will change as northern landscapes continue to thaw.

Chronic Exposure to Zinc Chromate Induces Centrosome Amplification and Spindle Assembly Checkpoint Bypass in Human Lung Fibroblasts

PubMed Central

Holmes, Amie L.; Wise, Sandra S.; Pelsue, Stephen C.; Aboueissa, AbouEl-Makarim; Lingle, Wilma; Salisbury, Jeffery; Gallagher, Jamie; Wise, John Pierce

2010-01-01

Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen, however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no increase in aneuploidy after a 24 hour exposure to zinc chromate, but with more chronic exposures, zinc chromate induced concentration- and time-dependent increases in aneuploidy in the form of hypodiploidy, hyperdiploidy and tetraploidy. Zinc chromate also induced centrosome amplification in a concentration- and time-dependent manner in both interphase and mitotic cells after chronic exposure, producing cells with centriolar defects. Further, chronic exposure to zinc chromate induced concentration- and time-dependent increases in spindle assembly checkpoint bypass with increases in centromere spreading, premature centromere division and premature anaphase. Lastly, we found that chronic exposure to zinc chromate induced a G2 arrest. All together, these data indicate that zinc chromate can induce chromosome instability after prolonged exposures. PMID:20030412

Interactions of p-Nitrobenzene Diazonium Fluoroborate and Analogs with the Active Sites of Acetylcholine-Receptor and -Esterase*

PubMed Central

Mautner, Henry G.; Bartels, Eva

1970-01-01

p-Nitrobenzene diazonium fluoroborate (NDF) is a potent inhibitor of the carbamylcholine-induced depolarization of the electroplax and of acetylcholinesterase. It probably forms covalent bonds with the acetylcholine-receptor and -esterase at the active site of the proteins. Its inhibitory strength is at least the same as that of trimethylammonium diazonium fluoroborate (TDF). The p-acetoxy analog, with its weaker electron-withdrawing group, is about ten times weaker as an inhibitor than the trimethylammonium or p-nitro analogs, both of which have strong electron-withdrawing groups. After treatment of the electroplax preparation with dithiothreitol, NDF remains an irreversible receptor-inhibitor, while TDF becomes a potent reversible receptor-activator. TDF is self-inhibitory: applied before reduction, it no longer depolarizes. Although the first observations on TDF suggested that the compound labels both proteins by virtue of the steric complementary of its trimethylammonium group to a negative subsite in the proteins, the present study indicates that it is the positively charged diazonium group that reacts with the active sites of the proteins to form a covalent bond with an appropriate amino-acid residue. PMID:5272331

The formation of ordered nanoclusters controls cadherin anchoring to actin and cell–cell contact fluidity

PubMed Central

Strale, Pierre-Olivier; Duchesne, Laurence; Peyret, Grégoire; Montel, Lorraine; Nguyen, Thao; Png, Evelyn; Tampé, Robert; Troyanovsky, Sergey; Hénon, Sylvie; Ladoux, Benoit

2015-01-01

Oligomerization of cadherins could provide the stability to ensure tissue cohesion. Cadherins mediate cell–cell adhesion by forming trans-interactions. They form cis-interactions whose role could be essential to stabilize intercellular junctions by shifting cadherin clusters from a fluid to an ordered phase. However, no evidence has been provided so far for cadherin oligomerization in cellulo and for its impact on cell–cell contact stability. Visualizing single cadherins within cell membrane at a nanometric resolution, we show that E-cadherins arrange in ordered clusters, providing the first demonstration of the existence of oligomeric cadherins at cell–cell contacts. Studying the consequences of the disruption of the cis-interface, we show that it is not essential for adherens junction formation. Its disruption, however, increased the mobility of junctional E-cadherin. This destabilization strongly affected E-cadherin anchoring to actin and cell–cell rearrangement during collective cell migration, indicating that the formation of oligomeric clusters controls the anchoring of cadherin to actin and cell–cell contact fluidity. PMID:26195669

Genome contact map explorer: a platform for the comparison, interactive visualization and analysis of genome contact maps

PubMed Central

Kumar, Rajendra; Sobhy, Haitham

2017-01-01

Abstract Hi-C experiments generate data in form of large genome contact maps (Hi-C maps). These show that chromosomes are arranged in a hierarchy of three-dimensional compartments. But to understand how these compartments form and by how much they affect genetic processes such as gene regulation, biologists and bioinformaticians need efficient tools to visualize and analyze Hi-C data. However, this is technically challenging because these maps are big. In this paper, we remedied this problem, partly by implementing an efficient file format and developed the genome contact map explorer platform. Apart from tools to process Hi-C data, such as normalization methods and a programmable interface, we made a graphical interface that let users browse, scroll and zoom Hi-C maps to visually search for patterns in the Hi-C data. In the software, it is also possible to browse several maps simultaneously and plot related genomic data. The software is openly accessible to the scientific community. PMID:28973466

Making a Back-Illuminated Imager with Back-Side Contact and Alignment Markers

NASA Technical Reports Server (NTRS)

Pain, Bedabrata

2008-01-01

A design modification and a fabrication process that implements the modification have been conceived to solve two problems encountered in the development of back-illuminated, back-sidethinned complementary metal oxide/ semiconductor (CMOS) image-detector integrated circuits. The two problems are (1) how to form metal electrical-contact pads on the back side that are electrically connected through the thickness in proper alignment with electrical contact points on the front side and (2) how to provide alignment keys on the back side to ensure proper registration of backside optical components (e.g., microlenses and/or color filters) with the front-side pixel pattern. The essence of the design modification is to add metal plugs that extend from the desired front-side locations through the thickness and protrude from the back side of the substrate. The plugs afford the required front-to-back electrical conduction, and the protrusions of the plugs serve as both the alignment keys and the bases upon which the back-side electrical-contact pads can be formed.

Exploring the role of internal friction in the dynamics of unfolded proteins using simple polymer models.

PubMed

Cheng, Ryan R; Hawk, Alexander T; Makarov, Dmitrii E

2013-02-21

Recent experiments showed that the reconfiguration dynamics of unfolded proteins are often adequately described by simple polymer models. In particular, the Rouse model with internal friction (RIF) captures internal friction effects as observed in single-molecule fluorescence correlation spectroscopy (FCS) studies of a number of proteins. Here we use RIF, and its non-free draining analog, Zimm model with internal friction, to explore the effect of internal friction on the rate with which intramolecular contacts can be formed within the unfolded chain. Unlike the reconfiguration times inferred from FCS experiments, which depend linearly on the solvent viscosity, the first passage times to form intramolecular contacts are shown to display a more complex viscosity dependence. We further describe scaling relationships obeyed by contact formation times in the limits of high and low internal friction. Our findings provide experimentally testable predictions that can serve as a framework for the analysis of future studies of contact formation in proteins.

Engineering parvovirus-like particles for the induction of B-cell, CD4(+) and CTL responses.

PubMed

Rueda, P; Martínez-Torrecuadrada, J L; Sarraseca, J; Sedlik, C; del Barrio, M; Hurtado, A; Leclerc, C; Casal, J I

1999-09-01

An antigen delivery system based on hybrid recombinant parvovirus-like particles (VLPs) formed by the self-assembly of the capsid VP2 protein of porcine (PPV) or canine parvovirus (CPV) expressed in insect cells with the baculovirus system has been developed. PPV:VLPs containing a CD8(+) epitope from the LCMV nucleoprotein evoked a potent CTL response and were able to protect mice against a lethal infection with the virus. Also, PPV:VLPs containing the C3:T epitope from poliovirus elicited a CD4(+)3 log(10) units) against poliovirus. The possibility of combining different types of epitopes in different positions of a single particle to stimulate different branches of the immune system paves the way to the production of more potent vaccines in a simple and cheap way.

Potent haloperidol derivatives covalently binding to the dopamine D2 receptor.

PubMed

Schwalbe, Tobias; Kaindl, Jonas; Hübner, Harald; Gmeiner, Peter

2017-10-01

The dopamine D 2 receptor (D 2 R) is a common drug target for the treatment of a variety of neurological disorders including schizophrenia. Structure based design of subtype selective D 2 R antagonists requires high resolution crystal structures of the receptor and pharmacological tools promoting a better understanding of the protein-ligand interactions. Recently, we reported the development of a chemically activated dopamine derivative (FAUC150) designed to covalently bind the L94C mutant of the dopamine D 2 receptor. Using FAUC150 as a template, we elaborated the design and synthesis of irreversible analogs of the potent antipsychotic drug haloperidol forming covalent D 2 R-ligand complexes. The disulfide- and Michael acceptor-functionalized compounds showed significant receptor affinity and an irreversible binding profile in radioligand depletion experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

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 μM. 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). © 2014 John Wiley & Sons A/S.

Efficient generation of endothelial cells from human pluripotent stem cells and characterization of their functional properties.

PubMed

Song, Wei; Kaufman, Dan S; Shen, Wei

2016-03-01

Although endothelial cells (ECs) have been derived from human pluripotent stem cells (hPSCs), large-scale generation of hPSC-ECs remains challenging and their functions are not well characterized. Here we report a simple and efficient three-stage method that allows generation of approximately 98 and 9500 ECs on day 16 and day 34, respectively, from each human embryonic stem cell (hESC) input. The functional properties of hESC-ECs derived in the presence and absence of a TGFβ-inhibitory molecule SB431542 were characterized and compared with those of human umbilical vein endothelial cells (HUVECs). Confluent monolayers formed by SB431542 + hESC-ECs, SB431542 - hESC-ECs, and HUVECs showed similar permeability to 10,000 Da dextran, but these cells exhibited striking differences in forming tube-like structures in 3D fibrin gels. The SB431542 + hESC-ECs were most potent in forming tube-like structures regardless of whether VEGF and bFGF were present in the medium; less potent SB431542 - hESC-ECs and HUVECs responded differently to VEGF and bFGF, which significantly enhanced the ability of HUVECs to form tube-like structures but had little impact on SB431542 - hESC-ECs. This study offers an efficient approach to large-scale hPSC-EC production and suggests that the phenotypes and functions of hPSC-ECs derived under different conditions need to be thoroughly examined before their use in technology development. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 678-687, 2016. © 2015 Wiley Periodicals, Inc.

Novel ciprofloxacin hybrids using biology oriented drug synthesis (BIODS) approach: Anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis, topoisomerase II inhibition, and antibacterial activity.

PubMed

Kassab, Asmaa E; Gedawy, Ehab M

2018-04-25

As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC 50 values against the most sensitive cancer cell lines. In vitro results showed that the five compounds exhibited potent anticancer activity against test cell lines in nanomolar to micromolar range, with IC 50 values between 0.72 and 4.92 μM, which was 9 to1.5 folds more potent than doxorubicin. In this study, two promising potent anticancer CP hybrids, 3f and 3o, were identified. The anti-proliferative activity of these compounds appears to correlate well with their ability to inhibit Topo II (IC 50  = 0.58 and 0.86 μM). It is worth mentioning that compound 3f was 6 folds more potent than doxorubicin, 5 folds more potent than amsacrine and 1.5 folds more potent than etoposide. At the same time, compound 3o showed 4 folds more inhibitory activity against Topo II than doxorubicin, 3 folds more potent than amsacrine and almost equipotent activity to etoposide. Activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Moreover, compounds 3f and 3o showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the level of active caspase-3 compared to control. This observation may indicate that both CP hybrids can chelate with zinc, a powerful inhibitor of procaspase-3 enzymatic activity, so procaspase-3 may process itself to the active form. The synthesized CP derivatives were tested for their in vitro antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa strains. The results proved that all of the test compounds have shown good to excellent antibacterial activity, as compared to its parent molecule ciprofloxacin. Compounds 2, 3b, 3k, 3l, 3m, 3p, 5a, 5b, 5d and 5e exhibited equipotent or comparable activity to ciprofloxacin against the test strains. Compounds 3p and 5a were more potent than ciprofloxacin against Pseudomonas aeruginosa, a common organism causing infections in granulocytopenic cancer patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Laser-fired contact formation on metallized and passivated silicon wafers under short pulse durations

NASA Astrophysics Data System (ADS)

Raghavan, Ashwin S.

The objective of this work is to develop a comprehensive understanding of the physical processes governing laser-fired contact (LFC) formation under microsecond pulse durations. Primary emphasis is placed on understanding how processing parameters influence contact morphology, passivation layer quality, alloying of Al and Si, and contact resistance. In addition, the research seeks to develop a quantitative method to accurately predict the contact geometry, thermal cycles, heat and mass transfer phenomena, and the influence of contact pitch distance on substrate temperatures in order to improve the physical understanding of the underlying processes. Finally, the work seeks to predict how geometry for LFCs produced with microsecond pulses will influence fabrication and performance factors, such as the rear side contacting scheme, rear surface series resistance and effective rear surface recombination rates. The characterization of LFC cross-sections reveals that the use of microsecond pulse durations results in the formation of three-dimensional hemispherical or half-ellipsoidal contact geometries. The LFC is heavily alloyed with Al and Si and is composed of a two-phase Al-Si microstructure that grows from the Si wafer during resolidification. As a result of forming a large three-dimensional contact geometry, the total contact resistance is governed by the interfacial contact area between the LFC and the wafer rather than the planar contact area at the original Al-Si interface within an opening in the passivation layer. By forming three-dimensional LFCs, the total contact resistance is significantly reduced in comparison to that predicted for planar contacts. In addition, despite the high energy densities associated with microsecond pulse durations, the passivation layer is well preserved outside of the immediate contact region. Therefore, the use of microsecond pulse durations can be used to improve device performance by leading to lower total contact resistances while preserving the passivation layer. A mathematical model was developed to accurately predict LFC geometry over a wide range of processing parameters by accounting for transient changes in Al and Si alloy composition within the LFC. Since LFC geometry plays a critical role in device performance, an accurate method to predict contact geometry is an important tool that can facilitate further process development. Dimensionless analysis was also conducted to evaluate the relative importance of heat and mass transfer mechanisms. It is shown that convection plays a dominant role in the heat and mass transfer within the molten pool. Due to convective mass transfer, the contacts are heavily doped with Al and Si within 10 is after contact formation, which contributes to the entire resolidified region behaving as the electrically active LFC. The validated model is also used to determine safe operating regimes during laser processing to avoid excessively high operating temperatures. By maintaining processing temperatures below a critical temperature threshold, the onset of liquid metal expulsion and loss of alloying elements can be avoided. The process maps provide a framework that can be used to tailor LFC geometry for device fabrication. Finally, using various geometric relationships for the rear side contacting scheme for photovoltaic devices, it is shown that by employing hemispherical contacts, the number of LFCs required on the rear side can be reduced 75% while doubling the pitch distance and increasing the passivation fraction. Reducing the number of backside contacts required can have a noteworthy impact of manufacturing throughput. In addition, the analytical models suggest that device performance can be maintained at levels comparable to those achieved for planar contacts when producing three-dimensional contacts. The materials and electrical characterization results, device simulations, and design considerations presented in this thesis indicate that by forming three-dimensional LFCs, performance levels of Si-based photovoltaic devices can be maintained while greatly enhancing manufacturing efficiency. The research lays a solid foundation for future development of the LFC process with microsecond pulse durations and indicates that device fabrication employing this method is a critical step moving forward.

URANIUM EXTRACTION

DOEpatents

Harrington, C.D.; Opie, J.V.

1958-07-01

The recovery of uranium values from uranium ore such as pitchblende is described. The ore is first dissolved in nitric acid, and a water soluble nitrate is added as a salting out agent. The resulting feed solution is then contacted with diethyl ether, whereby the bulk of the uranyl nitrate and a portion of the impurities are taken up by the ether. This acid ether extract is then separated from the aqueous raffinate, and contacted with water causing back extractioa of the uranyl nitrate and impurities into the water to form a crude liquor. After separation from the ether extract, this crude liquor is heated to about 118 deg C to obtain molten uranyl nitrate hexahydratc. After being slightly cooled the uranyl nitrate hexahydrate is contacted with acid free diethyl ether whereby the bulk of the uranyl nitrate is dissolved into the ethcr to form a neutral ether solution while most of the impurities remain in the aqueous waste. After separation from the aqueous waste, the resultant ether solution is washed with about l0% of its volume of water to free it of any dissolved impurities and is then contacted with at least one half its volume of water whereby the uranyl nitrate is extracted into the water to form an aqueous product solution.

Scouts in Contact: Tactical Vignettes for Cavalry Leaders

DTIC Science & Technology

2016-12-01

comprehension of those core fundamentals that must be mastered by all scout leaders and cavalry officers. These core fundamentals are intended to... listening post (LP) as an inferior force and maneuver the platoon to destroy the outpost with multiple forms of contact. If the platoon leader chooses a...leader now has to react to the contact. ○○○○ Cavalry leadership dilemma: The platoon leader must assess that this observation post (OP)/ listening

Activation of nitrite. [Interaction of amino compounds to form carcinogenic N-nitroso compounds in digestive tract of animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lijinsky, W.

At low doses dietary nitrite has no obvious deleterious effect, even when ingested for long periods, and nitrites have been used for a long time as flavoring and coloring additives to meat and fish and as preservatives in food in which there is a danger of botulism. In recent years there has been increasing concern that one form of activation of nitrite might be related to cancer. That is the property of interaction with amino compounds to form N-nitroso compounds, which are potent chemical carcinogens. Results are reported from studies on the carcinogenic effects of nitrite and amines in rats.more » (CH)« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reichel, Christian, E-mail: christian.reichel@ise.fraunhofer.de; National Renewable Energy Laboratory; Feldmann, Frank

Passivated contacts (poly-Si/SiO{sub x}/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 BF{sub 2}), the ion implantation dose (5 × 10{sup 14 }cm{sup −2} to 1 × 10{sup 16 }cm{sup −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.more » 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 (iV{sub oc}) of 725 and 720 mV, respectively. For p-type passivated contacts, BF{sub 2} implantations into intrinsic a-Si yield well passivated contacts and allow for iV{sub oc} of 690 mV, whereas implanted B gives poor passivation with iV{sub oc} 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 V{sub oc} of 690 mV and fill factor (FF) of 79.1%, selective hole contacts realized by BF{sub 2} 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 V{sub oc} of 680 mV and FF of 80.4%, providing a simplified and promising fabrication process for IBC solar cells featuring passivated contacts.« less

Occupational carprofen photoallergic contact dermatitis.

PubMed

Kerr, A C; Muller, F; Ferguson, J; Dawe, R S

2008-12-01

The nonsteroidal anti-inflammatory drug carprofen was used in humans in the 1980s, before its withdrawal due to adverse effects. It re-emerged for veterinary uses, for which it is still widely prescribed, in the 1990s. There has been one previous report published of photoallergic contact dermatitis (PACD) in a pharmaceutical factory worker exposed to carprofen. Investigation of carprofen as a cause of PACD in pharmaceutical factory workers presenting with facial dermatitis. Photopatch testing to carprofen dilutions in two pharmaceutical factory workers and three healthy volunteer controls using the European consensus methodology. This was followed by testing of eight further employees, referred by occupational health services, in the same factory. The index patient suspected a problem with carprofen and was found to have PACD to carprofen. The second patient presented with a widespread, although especially photoexposed site, dermatitis and was initially labelled as having an 'unclassified dermatitis'. Only subsequently was her exposure (indirect; she did not work in the packaging section of the factory like the first patient) to carprofen recognized and testing confirmed both contact allergy and PACD to carprofen. One of three healthy volunteer controls had an active photoallergy sensitization event to carprofen starting 10 days after photopatch testing. Three of eight factory employees subsequently referred because of skin problems had carprofen PACD. Carprofen is a potent photoallergen. These cases emphasize the importance of photopatch testing, and considering agents not included in standard series, when investigating patients presenting with a photoexposed site dermatitis.

Method for laser welding a fin and a tube

DOEpatents

Fuerschbach, Phillip W.; Mahoney, A. Roderick; Milewski, John O

2001-01-01

A method of laser welding a planar metal surface to a cylindrical metal surface is provided, first placing a planar metal surface into approximate contact with a cylindrical metal surface to form a juncture area to be welded, the planar metal surface and cylindrical metal surface thereby forming an acute angle of contact. A laser beam, produced, for example, by a Nd:YAG pulsed laser, is focused through the acute angle of contact at the juncture area to be welded, with the laser beam heating the juncture area to a welding temperature to cause welding to occur between the planar metal surface and the cylindrical metal surface. Both the planar metal surface and cylindrical metal surface are made from a reflective metal, including copper, copper alloys, stainless steel alloys, aluminum, and aluminum alloys.

Recent advancements in low cost solar cell processing

NASA Technical Reports Server (NTRS)

Ralph, E. L.

1975-01-01

A proof-of-concept solar cell process has been developed that is adaptable to automation. This involved the development of a new contact system, a new antireflection coating system, a drift field cell design and a new contoured surface treatment. All these processes are performed without the use of vacuum chambers and expensive masking techniques, thus providing the possibility of reduced costs by automation using conventional semiconductor processing machinery. The contacts were printed on the cells by conventional silk screen machinery. The P(+) back field was formed by diffusing in aluminum from a printed aluminum back contact. The antireflection coating was formed by spinning on and baking a TiO2-SiO2 glass film. Air-mass-zero efficiencies of over 10% were achieved using this completely vacuum-free process.

Low inductance busbar assembly

DOEpatents

Holbrook, Meghan Ann

2010-09-21

A busbar assembly for electrically coupling first and second busbars to first and second contacts, respectively, on a power module is provided. The assembly comprises a first terminal integrally formed with the first busbar, a second terminal integrally formed with the second busbar and overlapping the first terminal, a first bridge electrode having a first tab electrically coupled to the first terminal and overlapping the first and second terminals, and a second tab electrically coupled to the first contact, a second bridge electrode having a third tab electrically coupled to the second terminal, and overlapping the first and second terminals and the first tab, and a fourth tab electrically coupled to the second contact, and a fastener configured to couple the first tab to the first terminal, and the third tab to the second terminal.

Microstructural Characterization of Base Metal Alloys with Conductive Native Oxides for Electrical Contact Applications

NASA Astrophysics Data System (ADS)

Senturk, Bilge Seda

Metallic contacts are a ubiquitous method of connecting electrical and electronic components/systems. These contacts are usually fabricated from base metals because they are inexpensive, have high bulk electrical conductivities and exhibit excellent formability. Unfortunately, such base metals oxidize in air under ambient conditions, and the characteristics of the native oxide scales leads to contact resistances orders of magnitude higher than those for mating bare metal surface. This is a critical technological issue since the development of unacceptably high contact resistances over time is now by far the most common cause of failure in electrical/electronic devices and systems. To overcome these problems, several distinct approaches are developed for alloying base metals to promote the formation of self-healing inherently conductive native oxide scales. The objective of this dissertation study is to demonstrate the viability of these approaches through analyzing the data from Cu-9La (at%) and Fe-V binary alloy systems. The Cu-9 La alloy structure consists of eutectic colonies tens of microns in diameter wherein a rod-like Cu phase lies within a Cu6La matrix phase. The thin oxide scale formed on the Cu phase was found to be Cu2O as expected while the thicker oxide scale formed on the Cu6La phase was found to be a polycrystalline La-rich Cu2O. The enhanced electrical conductivity in the native oxide scale of the Cu-9La alloy arises from heavy n-type doping of the Cu2O lattice by La3+. The Fe-V alloy structures consist of a mixture of large elongated and equiaxed grains. A thin polycrystalline Fe3O4 oxide scale formed on all of the Fe-V alloys. The electrical conductivities of the oxide scales formed on the Fe-V alloys are higher than that formed on pure Fe. It is inferred that this enhanced conductivity arises from doping of the magnetite with V+4 which promotes electron-polaron hopping. Thus, it has been demonstrated that even in simple binary alloy systems one can obtain a dramatic reduction in the contact resistances of alloy oxidized surfaces as compared with those of the pure base metals.

Topical treatments for chronic plaque psoriasis.

PubMed

Mason, Anne R; Mason, James; Cork, Michael; Dooley, Gordon; Hancock, Helen

2013-03-28

Chronic plaque psoriasis is the most common type of psoriasis, and it is characterised by redness, thickness, and scaling. First-line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid, and topical retinoids. To compare the effectiveness, tolerability, and safety of topical treatments for chronic plaque psoriasis, relative to placebo, and to similarly compare vitamin D analogues (used alone or in combination) with other topical treatments. We updated our searches of the following databases to February 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 2), MEDLINE (from 1948), EMBASE (from 1980), Science Citation Index (from 2008), Conference Proceedings Citation Index - Science (from 2008), BIOSIS (from 1993), Dissertation Abstracts via DialogClassic (all publication years), and Inside Conferences (all publication years).We identified ongoing and unpublished studies from the UK Clinical Research Network Study Portfolio and the metaRegister of Controlled Trials. We checked the bibliographies of published studies and reviews for further references to relevant trials, and we contacted trialists and companies for information about newly published studies.A separate search for adverse effects was undertaken in February 2011 using MEDLINE and EMBASE (from 2005).Final update searches for both RCTs and adverse effects were undertaken in August 2012. Although it has not been possible to incorporate RCTs and adverse effects studies identified through these final searches within this review, we will incorporate these into the next update. Randomised trials comparing active topical treatments against placebo or against vitamin D analogues (used alone or in combination) in people with chronic plaque psoriasis. One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted trialists and companies for missing data. We also extracted data on withdrawals and on local and systemic adverse events. We defined long-term trials as those with a duration of at least 24 weeks. This update added 48 trials and provided evidence on 7 new active treatments. In total, the review included 177 randomised controlled trials, with 34,808 participants, including 26 trials of scalp psoriasis and 6 trials of inverse psoriasis, facial psoriasis, or both. The number of included studies counted by Review Manager (RevMan) is higher than these figures (190) because we entered each study reporting a placebo and an active comparison into the 'Characteristics of included studies' table as 2 studies.When used on the body, most vitamin D analogues were significantly more effective than placebo, with the standardised mean difference (SMD) ranging from -0.67 (95% CI -1.04 to -0.30; 1 study, 119 participants) for twice-daily becocalcidiol to SMD -1.66 (95% CI -2.66 to -0.67; 1 study, 11 participants) for once-daily paricalcitol. On a 6-point global improvement scale, these effects translate into 0.8 and 1.9 points, respectively. Most corticosteroids also performed better than placebo; potent corticosteroids (SMD -0.89; 95% CI -1.06 to -0.72; I² statistic = 65.1%; 14 studies, 2011 participants) had smaller benefits than very potent corticosteroids (SMD -1.56; 95% CI -1.87 to -1.26); I² statistic = 81.7%; 10 studies, 1264 participants). On a 6-point improvement scale, these benefits equate to 1.0 and 1.8 points, respectively. Dithranol, combined treatment with vitamin D/corticosteroid, and tazarotene all performed significantly better than placebo.Head-to-head comparisons of vitamin D for psoriasis of the body against potent or very potent corticosteroids had mixed findings. For both body and scalp psoriasis, combined treatment with vitamin D and corticosteroid performed significantly better than vitamin D alone or corticosteroid alone. Vitamin D generally performed better than coal tar, but findings relative to dithranol were mixed. When applied to psoriasis of the scalp, vitamin D was significantly less effective than both potent corticosteroids and very potent corticosteroids. Indirect evidence from placebo-controlled trials supported these findings.For both body and scalp psoriasis, potent corticosteroids were less likely than vitamin D to cause local adverse events, such as burning or irritation. Combined treatment with vitamin D/corticosteroid on either the body or the scalp was tolerated as well as potent corticosteroids, and significantly better than vitamin D alone. Only 25 trials assessed clinical cutaneous dermal atrophy; few cases were detected, but trials reported insufficient information to determine whether assessment methods were robust. Clinical measurements of dermal atrophy are insensitive and detect only the most severe cases. No comparison of topical agents found a significant difference in systemic adverse effects. Corticosteroids perform at least as well as vitamin D analogues, and they are associated with a lower incidence of local adverse events. However, for people with chronic plaque psoriasis receiving long-term treatment with corticosteroids, there remains a lack of evidence about the risk of skin dermal atrophy. Further research is required to inform long-term maintenance treatment and provide appropriate safety data.

Determination of the Contact Angle Based on the Casimir Effect

NASA Technical Reports Server (NTRS)

Mazuruk, Konstantin; Volz, Martin P.

2015-01-01

On a macroscopic scale, a nonreactive liquid partially covering a homogeneous solid surface will intersect the solid at an angle called the contact angle. For molten metals and semiconductors, the contact angle is materially dependent upon both the solid and liquid and typical values fall in the range 80-170 deg, depending on the crucible material. On a microscopic scale, there does not exist a precise and sharp contact angle but rather the liquid and solid surfaces merge smoothly and continuously. Consider the example of the so called detached Bridgman crystal growth process. In this technique, a small gap is formed between the growing crystal and the crucible. At the crystal/melt interface, a meniscus ring is formed. Its width can be in the range of a few micrometers, approaching a microscopic scale. It then becomes questionable to describe the shape of this meniscus by the contact angle. A more advanced treatment of the interface is needed and here we propose such a refined model. The interaction of the liquid surface with the solid can be calculated by considering two forces: a short-range repulsive force and a longer range (up to a few micrometers) Casimir or van der Waals force.

Influence of Amphibian Antimicrobial Peptides and Short Lipopeptides on Bacterial Biofilms Formed on Contact Lenses

PubMed Central

Maciejewska, Magdalena; Bauer, Marta; Neubauer, Damian; Kamysz, Wojciech; Dawgul, Malgorzata

2016-01-01

The widespread use of contact lenses is associated with several complications, including ocular biofilm-related infections. They are very difficult to manage with standard antimicrobial therapies, because bacterial growth in a biofilm is associated with an increased antibiotic resistance. The principal aim of this study was to evaluate the efficacy of antimicrobial peptides (AMPs) in eradication of bacterial biofilms formed on commercially available contact lenses. AMPs were synthesized according to Fmoc/tBu chemistry using the solid-phase method. Minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of the compounds were determined. Anti-biofilm activity of the antimicrobial peptides determined at different temperatures (25 °C and 37 °C) were compared with the effectiveness of commercially available contact lens solutions. All of the tested compounds exhibited stronger anti-biofilm properties as compared to those of the tested lens solutions. The strongest activity of AMPs was noticed against Gram-positive strains at a temperature of 25 °C. Conclusions: The results of our experiments encourage us toward further studies on AMPs and their potential application in the prophylaxis of contact lens-related eye infections. PMID:28773992

Fire-through Ag contact formation for crystalline Si solar cells using single-step inkjet printing.

PubMed

Kim, Hyun-Gang; Cho, Sung-Bin; Chung, Bo-Mook; Huh, Joo-Youl; Yoon, Sam S

2012-04-01

Inkjet-printed Ag metallization is a promising method of forming front-side contacts on Si solar cells due to its non-contact printing nature and fine grid resolution. However, conventional Ag inks are unable to punch through the SiN(x) anti-reflection coating (ARC) layer on emitter Si surfaces. In this study, a novel formulation of Ag ink is examined for the formation of fire-through contacts on a SiN(x)-coated Si substrate using the single-step printing of Ag ink, followed by rapid thermal annealing at 800 degrees C. In order to formulate Ag inks with fire-through contact formation capabilities, a liquid etching agent was first formulated by dissolving metal nitrates in an organic solvent and then mixing the resulting solution with a commercial Ag nanoparticle ink at various volume ratios. During the firing process, the dissolved metal nitrates decomposed into metal oxides and acted in a similar manner to the glass frit contained in Ag pastes for screen-printed Ag metallization. The newly formulated ink with a 1 wt% loading ratio of metal oxides to Ag formed finely distributed Ag crystallites on the Si substrate after firing at 800 degrees C for 1 min.

Whiskerless Schottky diode

NASA Technical Reports Server (NTRS)

Bishop, William L. (Inventor); Mcleod, Kathleen A. (Inventor); Mattauch, Robert J. (Inventor)

1991-01-01

A Schottky diode for millimeter and submillimeter wave applications is comprised of a multi-layered structure including active layers of gallium arsenide on a semi-insulating gallium arsenide substrate with first and second insulating layers of silicon dioxide on the active layers of gallium arsenide. An ohmic contact pad lays on the silicon dioxide layers. An anode is formed in a window which is in and through the silicon dioxide layers. An elongated contact finger extends from the pad to the anode and a trench, preferably a transverse channel or trench of predetermined width, is formed in the active layers of the diode structure under the contact finger. The channel extends through the active layers to or substantially to the interface of the semi-insulating gallium arsenide substrate and the adjacent gallium arsenide layer which constitutes a buffer layer. Such a structure minimizes the effect of the major source of shunt capacitance by interrupting the current path between the conductive layers beneath the anode contact pad and the ohmic contact. Other embodiments of the diode may substitute various insulating or semi-insulating materials for the silicon dioxide, various semi-conductors for the active layers of gallium arsenide, and other materials for the substrate, which may be insulating or semi-insulating.

Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies.

PubMed

Rudolph, Michael J; Vance, David J; Cheung, Jonah; Franklin, Matthew C; Burshteyn, Fiana; Cassidy, Michael S; Gary, Ebony N; Herrera, Cristina; Shoemaker, Charles B; Mantis, Nicholas J

2014-08-26

Ricin is a select agent toxin and a member of the RNA N-glycosidase family of medically important plant and bacterial ribosome-inactivating proteins. In this study, we determined X-ray crystal structures of the enzymatic subunit of ricin (RTA) in complex with the antigen binding domains (VHH) of five unique single-chain monoclonal antibodies that differ in their respective toxin-neutralizing activities. None of the VHHs made direct contact with residues involved in RTA's RNA N-glycosidase activity or induced notable allosteric changes in the toxin's subunit. Rather, the five VHHs had overlapping structural epitopes on the surface of the toxin and differed in the degree to which they made contact with prominent structural elements in two folding domains of the RTA. In general, RTA interactions were influenced most by the VHH CDR3 (CDR, complementarity-determining region) elements, with the most potent neutralizing antibody having the shortest and most conformationally constrained CDR3. These structures provide unique insights into the mechanisms underlying toxin neutralization and provide critically important information required for the rational design of ricin toxin subunit vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Triflumuron Effects on the Physiology and Reproduction of Rhodnius prolixus Adult Females

PubMed Central

Henriques, Bianca Santos; Mello, Cícero Brasileiro; Silva, Lucas Rangel; Codogno, Thaís Franco; Oliveira, Alyne F. R.; Marinho, Lourena Pinheiro; Lima, José Bento Pereira; Feder, Denise; Gonzalez, Marcelo Salabert; Azambuja, Patricia

2016-01-01

We evaluated the efficacy of the growth regulator triflumuron (TFM) in inducing mortality and disrupting both oviposition and egg hatching in Rhodnius prolixus adult females. TFM was administered via feeding, topically or by continuous contact with impregnated surfaces. Feeding resulted in mild biological effects compared with topical and impregnated surfaces. One day after treatment, the highest mortality levels were observed with topical surface and 30 days later both topical and impregnated surfaces induced higher mortalities than feeding. Oral treatment inhibited oviposition even at lower doses, and hatching of eggs deposited by treated females was similarly affected by the three delivery modes. Topical treatment of eggs deposited by nontreated females significantly reduced hatching. However, treatment per contact of eggs oviposited by untreated females did not disrupt eclosion. Additionally, oral treatment increased the number of immature oocytes per female, and topical treatment reduced the mean size of oocytes. TFM also affected carcass chitin content, diuresis, and innate immunity of treated insects. These results suggest that TFM acts as a potent growth inhibitor of R. prolixus adult females and has the potential to be used in integrated vector control programs against hematophagous triatomine species. PMID:27822479

Triflumuron Effects on the Physiology and Reproduction of Rhodnius prolixus Adult Females.

PubMed

Henriques, Bianca Santos; Genta, Fernando Ariel; Mello, Cícero Brasileiro; Silva, Lucas Rangel; Codogno, Thaís Franco; Oliveira, Alyne F R; Marinho, Lourena Pinheiro; Valle, Denise; Lima, José Bento Pereira; Feder, Denise; Gonzalez, Marcelo Salabert; Azambuja, Patricia

2016-01-01

We evaluated the efficacy of the growth regulator triflumuron (TFM) in inducing mortality and disrupting both oviposition and egg hatching in Rhodnius prolixus adult females. TFM was administered via feeding, topically or by continuous contact with impregnated surfaces. Feeding resulted in mild biological effects compared with topical and impregnated surfaces. One day after treatment, the highest mortality levels were observed with topical surface and 30 days later both topical and impregnated surfaces induced higher mortalities than feeding. Oral treatment inhibited oviposition even at lower doses, and hatching of eggs deposited by treated females was similarly affected by the three delivery modes. Topical treatment of eggs deposited by nontreated females significantly reduced hatching. However, treatment per contact of eggs oviposited by untreated females did not disrupt eclosion. Additionally, oral treatment increased the number of immature oocytes per female, and topical treatment reduced the mean size of oocytes. TFM also affected carcass chitin content, diuresis, and innate immunity of treated insects. These results suggest that TFM acts as a potent growth inhibitor of R. prolixus adult females and has the potential to be used in integrated vector control programs against hematophagous triatomine species.

Recombinant α1-Antitrypsin Pittsburgh Attenuates Experimental Gram-Negative Septicemia

PubMed Central

Colman, Robert W.; Flores, Daniel N.; De La Cadena, Raul A.; Scott, Cheryl F.; Cousens, Laurence; Barr, Philip J.; Hoffman, Ian B.; Kueppers, Friedrich; Fisher, Donald; Idell, Steven; Pisarello, Jorge

1988-01-01

Alpha1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met → Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 108 CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia. PMID:3257651

Technique for microswitch manufacture

NASA Technical Reports Server (NTRS)

Kitamura, T.; Kiyoyama, S.

1983-01-01

A five-step technique for microswitch manufacture is described: (1) A clad board is inlaid with a precious metal and the board is pressed. (2) One end of the fixed contact containing a precious metal inlay section is curved, and this edge of the precious metal inlay section becomes a fixed contact. (3) Inserts are formed in the unit body and terminal strips are placed through the top and bottom of the base and held. (4) The unit body is held by the base and the sequential contact strips are cut off. (5) Movable stripes are attached to the support of the terminal strips on the movable side and movable contacts are placed opposite the fixed contacts.

Three tooth kinematic coupling

DOEpatents

Hale, Layton C.

2000-01-01

A three tooth kinematic coupling based on having three theoretical line contacts formed by mating teeth rather than six theoretical point contacts. The geometry requires one coupling half to have curved teeth and the other coupling half to have flat teeth. Each coupling half has a relieved center portion which does not effect the kinematics, but in the limit as the face width approaches zero, three line contacts become six point contacts. As a result of having line contact, a three tooth coupling has greater load capacity and stiffness. The kinematic coupling has application for use in precision fixturing for tools or workpieces, and as a registration device for a work or tool changer or for optics in various products.

Comparison of nickel silicide and aluminium ohmic contact metallizations for low-temperature quantum transport measurements.

PubMed

Polley, Craig M; Clarke, Warrick R; Simmons, Michelle Y

2011-10-03

We examine nickel silicide as a viable ohmic contact metallization for low-temperature, low-magnetic-field transport measurements of atomic-scale devices in silicon. In particular, we compare a nickel silicide metallization with aluminium, a common ohmic contact for silicon devices. Nickel silicide can be formed at the low temperatures (<400°C) required for maintaining atomic precision placement in donor-based devices, and it avoids the complications found with aluminium contacts which become superconducting at cryogenic measurement temperatures. Importantly, we show that the use of nickel silicide as an ohmic contact at low temperatures does not affect the thermal equilibration of carriers nor contribute to hysteresis in a magnetic field.

40 CFR 463.2 - General definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... final plastic product. It includes water used in both the detergent wash and rinse cycles of a cleaning... blended, molded, formed, or otherwise processed into intermediate or final products. (b) “Process water” is any raw, service, recycled, or reused water that contacts the plastic product or contacts shaping...

40 CFR 463.2 - General definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... final plastic product. It includes water used in both the detergent wash and rinse cycles of a cleaning... blended, molded, formed, or otherwise processed into intermediate or final products. (b) “Process water” is any raw, service, recycled, or reused water that contacts the plastic product or contacts shaping...

40 CFR 463.2 - General definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... final plastic product. It includes water used in both the detergent wash and rinse cycles of a cleaning... blended, molded, formed, or otherwise processed into intermediate or final products. (b) “Process water” is any raw, service, recycled, or reused water that contacts the plastic product or contacts shaping...

40 CFR 463.2 - General definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY General Provisions § 463.2 General definitions... part: (a) “Plastics molding and forming” is a manufacturing process in which plastic materials are...” is any raw, service, recycled, or reused water that contacts the plastic product or contacts shaping...

Antimicrobial activity of synthetic cationic peptides and lipopeptides derived from human lactoferricin against Pseudomonas aeruginosa planktonic cultures and biofilms.

PubMed

Sánchez-Gómez, Susana; Ferrer-Espada, Raquel; Stewart, Philip S; Pitts, Betsey; Lohner, Karl; Martínez de Tejada, Guillermo

2015-07-07

Infections by Pseudomonas aeruginosa constitute a serious health threat because this pathogen -particularly when it forms biofilms - can acquire resistance to the majority of conventional antibiotics. This study evaluated the antimicrobial activity of synthetic peptides based on LF11, an 11-mer peptide derived from human lactoferricin against P. aeruginosa planktonic and biofilm-forming cells. We included in this analysis selected N-acylated derivatives of the peptides to analyze the effect of acylation in antimicrobial activity. To assess the efficacy of compounds against planktonic bacteria, microdilution assays to determine the minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill studies were conducted. The anti-biofilm activity of the agents was assessed on biofilms grown under static (on microplates) and dynamic (in a CDC-reactor) flow regimes. The antimicrobial activity of lipopeptides differed from that of non-acylated peptides in their killing mechanisms on planktonic and biofilm-forming cells. Thus, acylation enhanced the bactericidal activity of the parental peptides and resulted in lipopeptides that were uniformly bactericidal at their MIC. In contrast, acylation of the most potent anti-biofilm peptides resulted in compounds with lower anti-biofilm activity. Both peptides and lipopeptides displayed very rapid killing kinetics and all of them required less than 21 min to reduce 1,000 times the viability of planktonic cells when tested at 2 times their MBC. The peptides, LF11-215 (FWRIRIRR) and LF11-227 (FWRRFWRR), displayed the most potent anti-biofilm activity causing a 10,000 fold reduction in cell viability after 1 h of treatment at 10 times their MIC. At that concentration, these two compounds exhibited low citotoxicity on human cells. In addition to its bactericidal activity, LF11-227 removed more that 50 % of the biofilm mass in independent assays. Peptide LF11-215 and two of the shortest and least hydrophobic lipopeptides, DI-MB-LF11-322 (2,2-dimethylbutanoyl-PFWRIRIRR) and DI-MB-LF11-215, penetrated deep into the biofilm structure and homogenously killed biofilm-forming bacteria. We identified peptides derived from human lactoferricin with potent antimicrobial activity against P. aeruginosa growing either in planktonic or in biofilm mode. Although further structure-activity relationship analyses are necessary to optimize the anti-biofilm activity of these compounds, the results indicate that lactoferricin derived peptides are promising anti-biofilm agents.

Silicide Nanowires for Low-Resistance CMOS Transistor Contacts.

NASA Astrophysics Data System (ADS)

Zollner, Stefan

2007-03-01

Transition metal (TM) silicide nanowires are used as contacts for modern CMOS transistors. (Our smallest wires are ˜20 nm thick and ˜50 nm wide.) While much research on thick TM silicides was conducted long ago, materials perform differently at the nanoscale. For example, the usual phase transformation sequences (e.g., Ni, Ni2Si, NiSi, NiSi2) for the reaction of thick metal films on Si no longer apply to nanostructures, because the surface and interface energies compete with the bulk energy of a given crystal structure. Therefore, a NiSi film will agglomerate into hemispherical droplets of NiSi by annealing before it reaches the lowest-energy (NiSi2) crystalline structure. These dynamics can be tuned by addition of impurities (such as Pt in Ni). The Si surface preparation is also a more important factor for nanowires than for silicidation of thick TM films. Ni nanowires formed on Si surfaces that were cleaned and amorphized by sputtering with Ar ions have a tendency to form NiSi2 pyramids (``spikes'') even at moderate temperatures (˜400^oC), while similar Ni films formed on atomically clean or hydrogen-terminated Si form uniform NiSi nanowires. Another issue affecting TM silicides is the barrier height between the silicide contact and the silicon transistor. For most TM silicides, the Fermi level of the silicide is aligned with the center of the Si band gap. Therefore, silicide contacts experience Schottky barrier heights of around 0.5 eV for both n-type and p-type Si. The resulting contact resistance becomes a significant term for the overall resistance of modern CMOS transistors. Lowering this contact resistance is an important goal in CMOS research. New materials are under investigation (for example PtSi, which has a barrier height of only 0.3 eV to p-type Si). This talk will describe recent results, with special emphasis on characterization techniques and electrical testing useful for the development of silicide nanowires for CMOS contacts. In collaboration with: P. Grudowski, D. Jawarani, R. Garcia, M.L. Kottke, R.B. Gregory, X.-D. Wang, D. Theodore, P. Fejes, W.J. Taylor, B.Y. Nguyen, C. Capasso, M. Raymond, D. Denning, K. Chang, R. Noble, M. Jahanbani, S. Bolton, P. Crabtree, D. Goedeke, M. Rossow, M. Chowdhury, H. Desjardins, A.Thean.

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

DOEpatents

Narayan, Jagdish

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.

Method for forming low-resistance ohmic contacts on semiconducting oxides

DOEpatents

Narayan, J.

1979-10-01

The invention provides 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 temmperatures. The contact does not require cleaning before attachment of any suitable electrical lead. This method is safe, rapid, reproducible, and relatively inexpensive.

Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7

NASA Astrophysics Data System (ADS)

Gunzburg, Menachem J.; Kulkarni, Ketav; Watson, Gabrielle M.; Ambaye, Nigus D.; Del Borgo, Mark P.; Brandt, Rebecca; Pero, Stephanie C.; Perlmutter, Patrick; Wilce, Matthew C. J.; Wilce, Jacqueline A.

2016-06-01

The design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we report the crystal structure of a stapled bicyclic peptide inhibitor G7-B1 in complex with the Grb7-SH2 domain. This revealed an unexpected binding mode of the peptide, in which the staple forms an alternative contact with the surface of the target protein. Based on this structural information, we designed a new series of bicyclic G7 peptides that progressively constrain the starting peptide, to arrive at the G7-B4 peptide that binds with an approximately 2-fold enhanced affinity to the Grb7-SH2 domain (KD = 0.83 μM) compared to G7-B1 and shows low affinity binding to Grb2-, Grb10- and Grb14-SH2 domains (KD > 100 μM). Furthermore, we determined the structure of the G7-B4 bicyclic peptide in complex with the Grb7-SH2 domain, both before and after ring closing metathesis to show that the closed staple is essential to the target interaction. The G7-B4 peptide represents an advance in the development of Grb7 inhibitors and is a classical example of structure aided inhibitor development.

Immobilization of alginate-encapsulated Bacillus thuringiensis var. israelensis containing different multivalent counterions for mosquito control.

PubMed

Prabakaran, G; Hoti, S L

2008-08-01

Immobilized techniques have been used widely for the controlled release formulation of mosquitoes. Among the microbial formulations, polymeric matrices play an important role in the controlled release of microbial pesticide at rates sufficiently effective to kill mosquitoes in the field. The advantage of these matrices is that they enhance the stability of both spores and toxin against pH, temperature variations, and UV irradiation. The disadvantage of using calcium alginate beads is that they are unstable upon contact with phosphate of potassium or sodium ions rich in the mosquito habitats. To overcome these problems, attempts were made to encapsulate Bacillus thuringiensis var. israelensis within alginate by using different multivalent counterions, namely, calcium chloride, zinc sulfate, copper sulfate, cobalt chloride, and ferric chloride, and the beads formed were tested for its mosquito larvicidal activity. Among all the beads tested, zinc alginate beads resulted in maximum larvicidal activity of 98% (+/-1.40 SE) against Culex quinquefasciatus IIIrd instar larvae and maximum spore count of 3.36 x 10(5) (+/-5291.50 SE) CFU/ml. Zinc alginate beads maintained their structure for up to 48 h when shaken vigorously on a rotary shaker at 180 rpm in the presence of 10 mM potassium phosphate buffer (pH 6.8 +/- 0.1). In conclusion, our results suggest that the use of zinc sulfate as counterions to encapsulate B. thuringiensis var. israelensis within alginate may be a potent mosquito control program in the habitats where more phosphate ions are present.

Molecular Recognition of Corticotropin releasing Factor by Its G protein-coupled Receptor CRFR1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pioszak, Augen A.; Parker, Naomi R.; Suino-Powell, Kelly

2009-01-15

The bimolecular interaction between corticotropin-releasing factor (CRF), a neuropeptide, and its type 1 receptor (CRFR1), a class B G-protein-coupled receptor (GPCR), is crucial for activation of the hypothalamic-pituitary-adrenal axis in response to stress, and has been a target of intense drug design for the treatment of anxiety, depression, and related disorders. As a class B GPCR, CRFR1 contains an N-terminal extracellular domain (ECD) that provides the primary ligand binding determinants. Here we present three crystal structures of the human CRFR1 ECD, one in a ligand-free form and two in distinct CRF-bound states. The CRFR1 ECD adopts the alpha-beta-betaalpha fold observedmore » for other class B GPCR ECDs, but the N-terminal alpha-helix is significantly shorter and does not contact CRF. CRF adopts a continuous alpha-helix that docks in a hydrophobic surface of the ECD that is distinct from the peptide-binding site of other class B GPCRs, thereby providing a basis for the specificity of ligand recognition between CRFR1 and other class B GPCRs. The binding of CRF is accompanied by clamp-like conformational changes of two loops of the receptor that anchor the CRF C terminus, including the C-terminal amide group. These structural studies provide a molecular framework for understanding peptide binding and specificity by the CRF receptors as well as a template for designing potent and selective CRFR1 antagonists for therapeutic applications.« less

Cutin monomers and surface wax constituents elicit H2O2 in conditioned cucumber hypocotyl segments and enhance the activity of other H2O2 elicitors

PubMed

Fauth; Schweizer; Buchala; Markstadter; Riederer; Kato; Kauss

1998-08-01

Hypocotyls from etiolated cucumber (Cucumis sativus L.) seedlings were gently abraded at their epidermal surface and cut segments were conditioned to develop competence for H2O2 elicitation. Alkaline hydrolysates of cutin from cucumber, tomato, and apple elicited H2O2 in such conditioned segments. The most active constituent of cucumber cutin was identified as dodecan-1-ol, a novel cutin monomer capable of forming hydrophobic terminal chains. Additionally, the cutin hydrolysates enhanced the activity of a fungal H2O2 elicitor, similar to cucumber surface wax, which contained newly identified alkan-1,3-diols. The specificity of elicitor and enhancement activity was further elaborated using some pure model compounds. Certain saturated hydroxy fatty acids were potent H2O2 elicitors as well as enhancers. Some unsaturated epoxy and hydroxy fatty acids were also excellent H2O2 elicitors but inhibited the fungal elicitor activity. Short-chain alkanols exhibited good elicitor and enhancer activity, whereas longer-chain alkan-1-ols were barely active. The enhancement effect was also observed for H2O2 elicitation by ergosterol and chitosan. The physiological significance of these observations might be that once the cuticle is degraded by fungal cutinase, the cutin monomers may act as H2O2 elicitors. Corrosion of cutin may also bring surface wax constituents in contact with protoplasts and enhance elicitation.

On the stability and instantaneous velocity of grasped frictionless objects

NASA Technical Reports Server (NTRS)

Trinkle, Jeffrey C.

1992-01-01

A quantitative test for form closure valid for any number of contact points is formulated as a linear program, the optimal objective value of which provides a measure of how far a grasp is from losing form closure. Another contribution of the study is the formulation of a linear program whose solution yields the same information as the classical approach. The benefit of the formulation is that explicit testing of all possible combinations of contact interactions can be avoided by the algorithm used to solve the linear program.

Spring loaded compliant seal for high temperature use

DOEpatents

Memmen, Robert L; Fedock, John A; Downs, James P

2013-10-15

A flexible seal having an X-shaped cross section that forms four contact points on four contact surfaces of two opposed seal slots. The flexible seal is used for a component in which the two seal slots undergo a large deflection such that the opposed slots are not aligned and a rigid seal will not form an adequate seal. The flexible seal can be used in a component of a combustor or a turbine in a gas turbine engine where opposed seal slots undergo the large deflection during operation.

Apparatus and process for ultrasonic seam welding stainless steel foils

DOEpatents

Leigh, Richard W.

1992-01-01

An ultrasonic seam welding apparatus having a head which is rotated to form contact, preferably rolling contact, between a metallurgically inert coated surface of the head and an outside foil of a plurality of layered foils or work materials. The head is vibrated at an ultrasonic frequency, preferably along a longitudinal axis of the head. The head is constructed to transmit vibration through a contacting surface of the head into each of the layered foils. The contacting surface of the head is preferably coated with aluminum oxide to prevent the head from becoming welded to layered stainless steel foils.

Preparation of hydrophobic coatings

DOEpatents

Branson, Eric D [Albuquerque, NM; Shah, Pratik B [Albuquerque, NM; Singh, Seema [Rio Rancho, NM; Brinker, C Jeffrey [Albuquerque, NM

2009-02-03

A method for preparing a hydrophobic coating by preparing a precursor sol comprising a metal alkoxide, a solvent, a basic catalyst, a fluoroalkyl compound and water, depositing the precursor sol as a film onto a surface, such as a substrate or a pipe, heating, the film and exposing the film to a hydrophobic silane compound to form a hydrophobic coating with a contact angle greater than approximately 150.degree.. The contact angle of the film can be controlled by exposure to ultraviolet radiation to reduce the contact angle and subsequent exposure to a hydrophobic silane compound to increase the contact angle.

Ultra Thin Poly-Si Nanosheet Junctionless Field-Effect Transistor with Nickel Silicide Contact

PubMed Central

Lin, Yu-Ru; Tsai, Wan-Ting; Wu, Yung-Chun; Lin, Yu-Hsien

2017-01-01

This study demonstrated an ultra thin poly-Si junctionless nanosheet field-effect transistor (JL NS-FET) with nickel silicide contact. For the nickel silicide film, two-step annealing and a Ti capping layer were adopted to form an ultra thin uniform nickel silicide film with low sheet resistance (Rs). The JL NS-FET with nickel silicide contact exhibited favorable electrical properties, including a high driving current (>107A), subthreshold slope (186 mV/dec.), and low parasitic resistance. In addition, this study compared the electrical characteristics of JL NS-FETs with and without nickel silicide contact. PMID:29112139

Ultra Thin Poly-Si Nanosheet Junctionless Field-Effect Transistor with Nickel Silicide Contact.

PubMed

Lin, Yu-Ru; Tsai, Wan-Ting; Wu, Yung-Chun; Lin, Yu-Hsien

2017-11-07

This study demonstrated an ultra thin poly-Si junctionless nanosheet field-effect transistor (JL NS-FET) with nickel silicide contact. For the nickel silicide film, two-step annealing and a Ti capping layer were adopted to form an ultra thin uniform nickel silicide film with low sheet resistance (Rs). The JL NS-FET with nickel silicide contact exhibited favorable electrical properties, including a high driving current (>10⁷A), subthreshold slope (186 mV/dec.), and low parasitic resistance. In addition, this study compared the electrical characteristics of JL NS-FETs with and without nickel silicide contact.

A multidisciplinary study of 3-(β-d-glucopyranosyl)-5-substituted-1,2,4-triazole derivatives as glycogen phosphorylase inhibitors: Computation, synthesis, crystallography and kinetics reveal new potent inhibitors.

PubMed

Kun, Sándor; Begum, Jaida; Kyriakis, Efthimios; Stamati, Evgenia C V; Barkas, Thomas A; Szennyes, Eszter; Bokor, Éva; Szabó, Katalin E; Stravodimos, George A; Sipos, Ádám; Docsa, Tibor; Gergely, Pál; Moffatt, Colin; Patraskaki, Myrto S; Kokolaki, Maria C; Gkerdi, Alkistis; Skamnaki, Vassiliki T; Leonidas, Demetres D; Somsák, László; Hayes, Joseph M

2018-03-10

3-(β-d-Glucopyranosyl)-5-substituted-1,2,4-triazoles have been revealed as an effective scaffold for the development of potent glycogen phosphorylase (GP) inhibitors but with the potency very sensitive to the nature of the alkyl/aryl 5-substituent (Kun et al., Eur. J. Med. Chem. 2014, 76, 567). For a training set of these ligands, quantum mechanics-polarized ligand docking (QM-PLD) demonstrated good potential to identify larger differences in potencies (predictive index PI = 0.82) and potent inhibitors with K i 's < 10 μM (AU-ROC = 0.86). Accordingly, in silico screening of 2335 new analogues exploiting the ZINC docking database was performed and nine predicted candidates selected for synthesis. The compounds were prepared in O-perbenzoylated forms by either ring transformation of 5-β-d-glucopyranosyl tetrazole by N-benzyl-arenecarboximidoyl chlorides, ring closure of C-(β-d-glucopyranosyl)formamidrazone with aroyl chlorides, or that of N-(β-d-glucopyranosylcarbonyl)arenethiocarboxamides by hydrazine, followed by deprotections. Kinetics experiments against rabbit muscle GPb (rmGPb) and human liver GPa (hlGPa) revealed five compounds as potent low μM inhibitors with three of these on the submicromolar range for rmGPa. X-ray crystallographic analysis sourced the potency to a combination of favorable interactions from the 1,2,4-triazole and suitable aryl substituents in the GP catalytic site. The compounds also revealed promising calculated pharmacokinetic profiles. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Activation of polyphenol oxidase in extracts of bran from several wheat (Triticum aestivum) cultivars using organic solvents, detergents, and chaotropes.

PubMed

Okot-Kotber, Moses; Liavoga, Allan; Yong, Kwon-Joong; Bagorogoza, Katherine

2002-04-10

Polyphenol oxidase (PPO), known to induce browning in wheat-based products, has been shown to be activatable in wheat (Triticum aestivum) bran extracts by chemical compounds. The activity in the extracts could be increased to varying degrees with acetone, methanol, ethanol, 2-propanol, and n-butanol as additives in the extraction buffer. The most potent alcoholic activator was n-butanol (about a 3-fold increase), followed by 2-propanol and ethanol, whereas methanol had the least effect. Ionic detergents in the extraction buffer were also good activators, with sodium dodecyl sulfate (SDS) being more potent (3-fold increase) than cetyltrimethylammonium bromide (CTAB) that had only half as much effect, whereas the nonionic detergent, Triton X-114, was ineffective. The chaotropes, urea and guanidine x HCl (GND), were the most potent activators of all, increasing the activity over 4-fold. Of the two chaotropes, GND was more effective at lower concentrations (<6 M) than urea. However, the enzyme activity lessened at a higher concentration of GND (6 M), while there was a further increase in the activity with 6 M urea treatment. The activity lessened with higher concentration of GND presumably as a result of extensive denaturation of the enzyme, as GND is known to be a more potent denaturant than urea. It is hypothesized that in wheat PPO exists in an inactive form which may be activated by the presence of activators, hitherto unknown, similar in effect to that elicited by the chemical denaturants in this study.

Surface morphology and nanomechanical properties of tribological antiwear films derived from zinc dialkyl dithiophosphate compounds

NASA Astrophysics Data System (ADS)

Aktary, Mirwais

The protection of mechanical equipment from wear is of significant economic interest. It has been estimated that up to half of a percent of the gross domestic product of industrialized countries goes to replacing mechanical components that have lost compliance due to wear. Antiwear additives are key ingredients in lubrication oils that assist in protecting components from wear during high loads. These agents form sacrificial films on metal parts that limit the adhesion between the contacting surfaces and reduce the wear rate considerably. One of the most common classes of compounds employed as an antiwear agent is zinc dialkyldithiophosphates (ZDDP). This work will explore the formation, structure, and mechanical properties of ZDDP derived antiwear films on the nanoscale. These studies are important because the macroscopic performance of antiwear coatings is dictated by their nanoscale surface properties. As a first study, scanning force microscopy (SFM) is employed to track the formation of films formed from the thermooxidative decomposition of ZDDP on gold substrates. The SFM analysis is correlated with infrared spectroscopy to relate surface structure to chemical composition. The morphology and mechanical strength of ZDDP tribofilms formed at the interface of sliding stainless steel contacts is also investigated. The tribofilms evolve morphologically with contact time and are characterized by distinct segregated islands at low times that transforms to a full film at longer times. The nanomechanical properties of the tribofilms are evaluated by nanoindentation analysis. It is found that the films are mechanically softer than the underlying steel substrate. SFM and nanoindentation analyses reveal that calcium sulphonate detergents promote the formation of ZDDP tribofilms and impart to them greater mechanical stability. By contrast succinimide dispersants reduce the capacity of ZDDP to form effective antiwear films. The first application of SFM and nanoindentation to the study of automotive engine components obtained directly from vehicles is demonstrated. The wear zone on a rocker arm bridge from a diesel engine is shown to contain a tribofilm at the periphery of contact where the contact load is less. SFM images also reveal wear damage at the center of the wear zone where the contact load is expected to be higher.

77 FR 54806 - Adoption of Updated EDGAR Filer Manual

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... that qualify either under the JOBS Act or the Division of Corporate Finance's foreign private issuer... Corporation Finance, for questions on Confidential Registration Statement, Form ID, and Forms D contact...

Wilson Disease: Frequently Asked Questions

MedlinePlus

... Are Wilson's Wilson's Warriors WDA Publications Back Downloads Corporate Sponsorship Forms Membership Forms Resources The Big WOW ... Help Donate Become a Member The Big WOW Corporate Sponsorship Marketplace Contact Us Search Our Site About ...

30 CFR 1210.201 - How do I submit Form MMS-4430, Solid Minerals Production and Royalty Report?

Code of Federal Regulations, 2012 CFR

2012-07-01

... submitting Form MMS-4430 are available on our Internet reporting web site or you may contact us toll free at... submit Form MMS-4430 electronically using our Internet reporting web site unless you meet the conditions...

77 FR 63924 - Proposed Collection; Comment Request for Form 8633

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-17

... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Form 8633 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY... 20224. FOR FURTHER INFORMATION CONTACT: Requests for additional information or copies of the form and...

The Mathematical and Computer Aided Analysis of the Contact Stress of the Surface With 4th Order

NASA Astrophysics Data System (ADS)

Huran, Liu

Inspired from some gears with heavy power transmission in practical usage after serious plastic deformation in metallurgical industry, we believe that there must existed some kind of gear profile which is most suitable in both the contact and bending fatigue strength. From careful analysis and deep going investigation, we think that it is the profile of equal conjugate curvature with high order of contact, and analyzed the forming principle of this kind of profile. Based on the second curve and comparative analysis of fourth order curves, combined with Chebyshev polynomial terms of higher order contact with tooth contact stress formula derived. Note high exposure in the case of two extreme points of stress and extreme positions and the derived extreme contact stress formula. Finally, a pair of conjugate gear tooth profile curvature provides specific contact stress calculation.

ER-PM Contacts Define Actomyosin Kinetics for Proper Contractile Ring Assembly.

PubMed

Zhang, Dan; Bidone, Tamara C; Vavylonis, Dimitrios

2016-03-07

The cortical endoplasmic reticulum (ER), an elaborate network of tubules and cisternae [1], establishes contact sites with the plasma membrane (PM) through tethering machinery involving a set of conserved integral ER proteins [2]. The physiological consequences of forming ER-PM contacts are not fully understood. Here, we reveal a kinetic restriction role of ER-PM contacts over ring compaction process for proper actomyosin ring assembly in Schizosaccharomyces pombe. We show that fission yeast cells deficient in ER-PM contacts exhibit aberrant equatorial clustering of actin cables during ring assembly and are particularly susceptible to compromised actin filament crosslinking activity. Using quantitative image analyses and computer simulation, we demonstrate that ER-PM contacts function to modulate the distribution of ring components and to constrain their compaction kinetics. We propose that ER-PM contacts have evolved as important physical modulators to ensure robust ring assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PLASTICS MOLDING AND... cooling and heating water subcategory are processes where process water comes in contact with plastic materials or plastic products for the purpose of heat transfer during plastics molding and forming. ...

GLCF: Services

Science.gov Websites

Services Contact Site Map Go Services GLCF General Services Contact us with the online form. Answer classification Special Group Services Special workspaces for groups accessing datasets Data Ordering Services Click here to proceed to Data Ordering Service Hard Media Orders Metrics Services ESDS Metrics

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…

Seating and Grouping Choices: A Chance for Making Contact

ERIC Educational Resources Information Center

Lin, Isadora Jung-Hsiu

2015-01-01

This paper discusses how international students negotiated their chances for making contact with other students in higher education and how such effort affected their educational experiences in Australia. In the past few decades, international students have formed part of the increasingly diverse multicultural student population in Australian…

40 CFR 463.20 - Applicability; description of the cleaning water subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Cleaning... the cleaning water subcategory are processes where water comes in contact with the plastic product for... equipment, such as molds and mandrels, that contact the plastic material for the purpose of cleaning the...