10 CFR 33.13 - Requirements for the issuance of a Type A specific license of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of broad scope. 33.13 Section 33.13 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.13 Requirements for the issuance of a Type A specific license of broad scope. An application for a Type A specific license of broad...

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of broad scope. 33.15 Section 33.15 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.15 Requirements for the issuance of a Type C specific license of broad scope. An application for a Type C specific license of broad...

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of broad scope. 33.15 Section 33.15 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.15 Requirements for the issuance of a Type C specific license of broad scope. An application for a Type C specific license of broad...

10 CFR 33.13 - Requirements for the issuance of a Type A specific license of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of broad scope. 33.13 Section 33.13 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.13 Requirements for the issuance of a Type A specific license of broad scope. An application for a Type A specific license of broad...

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols.

PubMed

Ye, Chen-Xi; Melcamu, Yared Yohannes; Li, Heng-Hui; Cheng, Jiang-Tao; Zhang, Tian-Tian; Ruan, Yuan-Ping; Zheng, Xiao; Lu, Xin; Huang, Pei-Qiang

2018-01-29

Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman-Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N'-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).

Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products.

PubMed

Ghislieri, Diego; Green, Anthony P; Pontini, Marta; Willies, Simon C; Rowles, Ian; Frank, Annika; Grogan, Gideon; Turner, Nicholas J

2013-07-24

The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine.

Photoinduced Miyaura Borylation by a Rare Earth Photoreductant: the Hexachlorocerate(III) Anion.

PubMed

Qiao, Yusen; Yang, Qiaomu; Schelter, Eric

2018-05-12

The first photoinduced sp2 carbon-heteroatom bond forming reaction by a rare earth photoreductant, a Miyaura borylation, has been achieved. This simple, scalable, and novel borylation method that makes use of the hexachlorocerate(III) anion, [CeIIICl6]3-, has a broad substrate scope and functional group tolerance and can be conducted at room temperature. Combined with Suzuki-Miyaura cross-coupling, the methodology is applicable to the synthesis of various biaryl products, including through the use of aryl chloride substrates. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper-catalyzed oxidative homo- and cross-coupling of Grignard reagents using diaziridinone.

PubMed

Zhu, Yingguang; Xiong, Tao; Han, Wenyong; Shi, Yian

2014-12-05

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)-C(sp(3)) coupling.

(3+3)-Annulation of Donor-Acceptor Cyclopropanes with Diaziridines.

PubMed

Trushkov, Igor V; Chagarovskiy, Alexey O; Vasin, Vladimir S; Kuznetsov, Vladimir V; Ivanova, Olga A; Rybakov, Victor B; Shumsky, Alexey N; Makhova, Nina N

2018-06-23

The first example of (3+3)-annulation of two different three-membered rings is reported herein. Donor-acceptor cyclopropanes in reaction with diaziridines were found to afford perhydropyridazine derivatives in high yields and diastereoselectivity under mild Lewis acid catalysis. The disclosed reaction is applicable for the broad substrate scope and exhibits an excellent functional group tolerance. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rhodium(III)-catalyzed vinylic sp2 C-H bond functionalization: efficient synthesis of pyrido[1,2-α]benzimidazoles and imidazo[1,2-α]pyridines.

PubMed

Dong, Lin; Huang, Ji-Rong; Qu, Chuan-Hua; Zhang, Qian-Ru; Zhang, Wei; Han, Bo; Peng, Cheng

2013-09-28

A simple approach for synthesis of novel aza-fused scaffolds such as pyrido[1,2-α]benzimidazoles and imidazo[1,2-α]pyridines was developed by Rh(III)-catalyzed direct oxidative coupling between alkenes and unactivated alkynes without an extra directing group. The method would allow a broad substrate scope, providing fused heterocycles with potential biological properties.

Copper-catalyzed aerobic decarboxylative sulfonylation of cinnamic acids with sodium sulfinates: stereospecific synthesis of (E)-alkenyl sulfones.

PubMed

Jiang, Qing; Xu, Bin; Jia, Jing; Zhao, An; Zhao, Yu-Rou; Li, Ying-Ying; He, Na-Na; Guo, Can-Cheng

2014-08-15

A copper-catalyzed aerobic decarboxylative sulfonylation of alkenyl carboxylic acids with sodium sulfinates is developed. This study offers a new and expedient strategy for stereoselective synthesis of (E)-alkenyl sulfones that are widely present in biologically active natural products and therapeutic agents. Moreover, the transformation is proposed to proceed via a radical process and exhibits a broad substrate scope and good functional group tolerance.

Copper-Catalyzed Oxidative Homo- and Cross-Coupling of Grignard Reagents Using Diaziridinone

PubMed Central

2015-01-01

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)–C(sp3) coupling. PMID:25420218

Rhodium(III)-catalyzed three-component reaction of imines, alkynes, and aldehydes through C-H activation.

PubMed

Huang, Ji-Rong; Song, Qiang; Zhu, Yu-Qin; Qin, Liu; Qian, Zhi-Yong; Dong, Lin

2014-12-15

An efficient rhodium(III)-catalyzed tandem three-component reaction of imines, alkynes and aldehydes through CH activation has been developed. High stereo- and regioselectivity, as well as good yields were obtained in most cases. The simple and atom-economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Pang, Haobo; Gallou, Fabrice; Sohn, Hyuntae

A remarkable synergistic effect has been uncovered between ppm levels of Pd and Ni embedded within iron nanoparticles that leads to mild and selective catalytic reductions of nitro-containing aromatics and heteroaromatics in water at room temperature. NaBH4 serves as the source of inexpensive hydride. Broad substrate scope is documented, along with several other features including: low catalyst loading, low residual metal in the products, and recycling of the catalyst and reaction medium, highlight the green nature of this new technology.

Selective reduction of carboxylic acids to aldehydes with hydrosilane via photoredox catalysis.

PubMed

Zhang, Muliang; Li, Nan; Tao, Xingyu; Ruzi, Rehanguli; Yu, Shouyun; Zhu, Chengjian

2017-09-12

The direct reduction of carboxylic acids to aldehydes with hydrosilane was achieved through visible light photoredox catalysis. The combination of both single electron transfer and hydrogen atom transfer steps offers a novel and convenient approach to selective reduction of carboxylic acids to aldehydes. The method also features mild conditions, high yields, broad substrate scope, and good functional group tolerance, such as alkyne, ester, ketone, amide and amine groups.

10 CFR 33.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL § 33.1 Purpose and scope. This part prescribes requirements for the issuance of specific licenses of broad scope for byproduct material (“broad licenses”) and certain regulations governing holders of such licenses. The...

10 CFR 33.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL § 33.1 Purpose and scope. This part prescribes requirements for the issuance of specific licenses of broad scope for byproduct material (“broad licenses”) and certain regulations governing holders of such licenses. The...

10 CFR 33.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL § 33.1 Purpose and scope. This part prescribes requirements for the issuance of specific licenses of broad scope for byproduct material (“broad licenses”) and certain regulations governing holders of such licenses. The...

10 CFR 33.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL § 33.1 Purpose and scope. This part prescribes requirements for the issuance of specific licenses of broad scope for byproduct material (“broad licenses”) and certain regulations governing holders of such licenses. The...

10 CFR 33.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL § 33.1 Purpose and scope. This part prescribes requirements for the issuance of specific licenses of broad scope for byproduct material (“broad licenses”) and certain regulations governing holders of such licenses. The...

GO-Cu7S4 catalyzed ortho-aminomethylation of phenol derivatives with N,N-dimethylbenzylamines: site-selective oxidative CDC.

PubMed

Gupta, Sonu; Chandna, Nisha; Dubey, Pooja; Singh, Ajai K; Jain, Nidhi

2018-06-21

Copper chalcogenide nanoparticles (Cu7S4) supported on graphene oxide (GO) have been synthesized for the first time from Cu2S, and used as highly efficient heterogeneous catalysts for oxidative ortho-selective C-H aminomethylation of phenols with N,N-dimethylbenzylamines. The NPs (30-80 nm) have been characterized by HRTEM, SEM-EDX, PXRD, FTIR, Raman, ICP-AES and XPS analyses. The NP catalyzed sp2-sp3 cross dehydrogenative coupling (CDC) features a broad substrate scope, excellent functional group tolerance, high yields, use of an inexpensive and reusable copper catalyst, mild conditions, and no need for pre-functionalization of substrates.

Discovery of a metalloenzyme-like cooperative catalytic system of metal nanoclusters and catechol derivatives for the aerobic oxidation of amines.

PubMed

Yuan, Hao; Yoo, Woo-Jin; Miyamura, Hiroyuki; Kobayashi, Shū

2012-08-29

We have discovered a new class of cooperative catalytic system, consisting of heterogeneous polymer-immobilized bimetallic Pt/Ir alloyed nanoclusters (NCs) and 4-tert-butylcatechol, for the aerobic oxidation of amines to imines under ambient conditions. After optimization, the desired imines were obtained in good to excellent yields with broad substrate scope. The reaction rate was determined to be first-order with respect to the substrate and catechol and zero-order for the alloyed Pt/Ir NC catalyst. Control studies revealed that both the heterogeneous NC catalyst and 4-tert-butylcatechol are essential and act cooperatively to facilitate the aerobic oxidation under mild conditions.

Scope and mechanism in palladium-catalyzed isomerizations of highly substituted allylic, homoallylic, and alkenyl alcohols.

PubMed

Larionov, Evgeny; Lin, Luqing; Guénée, Laure; Mazet, Clément

2014-12-03

Herein we report the palladium-catalyzed isomerization of highly substituted allylic alcohols and alkenyl alcohols by means of a single catalytic system. The operationally simple reaction protocol is applicable to a broad range of substrates and displays a wide functional group tolerance, and the products are usually isolated in high chemical yield. Experimental and computational mechanistic investigations provide complementary and converging evidence for a chain-walking process consisting of repeated migratory insertion/β-H elimination sequences. Interestingly, the catalyst does not dissociate from the substrate in the isomerization of allylic alcohols, whereas it disengages during the isomerization of alkenyl alcohols when additional substituents are present on the alkyl chain.

Chiral poly-rare earth metal complexes in asymmetric catalysis

PubMed Central

Shibasaki, Masakatsu

2006-01-01

Asymmetric catalysis is a powerful component of modern synthetic organic chemistry. To further broaden the scope and utility of asymmetric catalysis, new basic concepts for the design of asymmetric catalysts are crucial. Because most chemical reactions involve bond-formation between two substrates or moieties, high enantioselectivity and catalyst activity should be realized if an asymmetric catalyst can activate two reacting substrates simultaneously at defined positions. Thus, we proposed the concept of bifunctional asymmetric catalysis, which led us to the design of new asymmetric catalysts containing two functionalities (e.g. a Lewis acid and a Brønsted base or a Lewis acid and a Lewis base). These catalysts demonstrated broad reaction applicability with excellent substrate generality. Using our catalytic asymmetric reactions as keys steps, efficient total syntheses of pharmaceuticals and their biologically active lead natural products were achieved. PMID:25792774

Concise copper-catalyzed synthesis of tricyclic biaryl ether-linked aza-heterocyclic ring systems.

PubMed

Mestichelli, Paola; Scott, Matthew J; Galloway, Warren R J D; Selwyn, Jamie; Parker, Jeremy S; Spring, David R

2013-11-01

A new method for the synthesis of tricyclic biaryl ether-linked ring systems incorporating seven-, eight-, and nine-membered ring amines is presented. In the presence of catalytic quantities of copper(I), readily accessible acyclic precursors undergo an intramolecular carbon-oxygen bond-forming reaction facilitated by a "templating" chelating nitrogen atom. The methodology displays a broad substrate scope, is practical, and generates rare and biologically interesting tricyclic heteroaromatic products that are difficult to access by other means.

Preparation of Benzo[c]carbazol-6-amines via Manganese-Catalyzed Enaminylation of 1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Oxidative Cyclization.

PubMed

Zhou, Xiaorong; Li, Zhenmin; Zhang, Zhiyin; Lu, Ping; Wang, Yanguang

2018-03-02

Manganese-catalyzed C 2 -H enaminylation of 1-(pyrimidin-2-yl)-1H-indoles with ketenimines is reported. The reaction provided 2-enaminylated indole derivatives in moderate to excellent yields with a broad substrate scope. A migration of the directing group pyrimidinyl occurred during this process. The synthesized 2-enaminyl indoles could be conveniently converted into 5-aryl-7H-benzo[c]carbazol-6-amines.

Construction of Pyrrolo[1,2-a]indoles via Cobalt(III)-Catalyzed Enaminylation of 1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Base-Promoted Cyclization.

PubMed

Zhou, Xiaorong; Fan, Zili; Zhang, Zhiyin; Lu, Ping; Wang, Yanguang

2016-09-16

A cobalt(III)-catalyzed cross-coupling reaction of 1-(pyrimidin-2-yl)-1H-indoles with ketenimines is reported. The reaction provided 2-enaminylated indole derivatives in moderate to excellent yields with a broad substrate scope. The prepared 2-enaminylated indoles could be conveniently converted into pyrrolo[1,2-a]indoles, which are an important class of compounds in medicinal chemistry.

A dehydrogenative cross-coupling reaction between aromatic aldehydes or ketones and dialkyl H-phosphonates for formyl or acylphenylphosphonates.

PubMed

Huang, Xing-Fen; Wu, Qing-Lai; He, Jian-Shi; Huang, Zhi-Zhen

2015-04-21

A novel DCC reaction between aromatic aldehydes or ketones and H-phosphonates has been developed for the synthesis of p-formyl or p-acylphenylphosphonates. The synthetic method has excellent para regioselectivities, good yields, and broad substrate scopes and is more benign to the environment. The DCC reaction also tolerates many functional groups, and results in a series of new p-formyl and p-acylphenylphosphonates, which should be important building blocks for the synthesis of versatile arylphosphonate derivatives.

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

PubMed

Meng, Guangrong; Szostak, Michal

2016-06-15

The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined ().

10 CFR 33.16 - Application for other specific licenses.

Code of Federal Regulations, 2011 CFR

2011-01-01

....16 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.16 Application for other specific licenses. An application filed pursuant to part 30 of this chapter for a specific license other than one of broad scope will be...

10 CFR 33.16 - Application for other specific licenses.

Code of Federal Regulations, 2010 CFR

2010-01-01

....16 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.16 Application for other specific licenses. An application filed pursuant to part 30 of this chapter for a specific license other than one of broad scope will be...

10 CFR 33.16 - Application for other specific licenses.

Code of Federal Regulations, 2013 CFR

2013-01-01

....16 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.16 Application for other specific licenses. An application filed pursuant to part 30 of this chapter for a specific license other than one of broad scope will be...

10 CFR 33.16 - Application for other specific licenses.

Code of Federal Regulations, 2012 CFR

2012-01-01

....16 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.16 Application for other specific licenses. An application filed pursuant to part 30 of this chapter for a specific license other than one of broad scope will be...

10 CFR 33.16 - Application for other specific licenses.

Code of Federal Regulations, 2014 CFR

2014-01-01

....16 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.16 Application for other specific licenses. An application filed pursuant to part 30 of this chapter for a specific license other than one of broad scope will be...

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.15 Requirements for the... this chapter; and (b) The applicant submits a statement that byproduct material will be used only by... bachelor level, or equivalent training and experience, in the physical or biological sciences or in...

Access to Diosgenyl Glycoconjugates via Gold(I)-Catalyzed Etherification of Diosgen-3-yl ortho-Hexynylbenzoate.

PubMed

Zhang, Li; Li, Linfeng; Bai, Shujin; Zhou, Xin; Wang, Peng; Li, Ming

2016-12-02

An efficient protocol for the synthesis of diverse diosgen-3-yl glycoconjugates, a class of novel synthetic analogs of natural saponins of biological significance, has been developed. The method relies on gold(I)-catalyzed etherification of diosgen-3-yl ortho-hexynylbenzoate with stoichiometric sugar alcohols to afford the corresponding glycoconjugates in 38%-99% yields. The reaction involves the preferential attack of hydroxyl groups to the C3 position of homoallylic carbocation intermediate and displays a broad substrate scope and a good functional group tolerance.

Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines.

PubMed

Sakamoto, Ryu; Sakurai, Shunya; Maruoka, Keiji

2017-07-06

The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of stilbene derivatives via visible-light-induced cross-coupling of aryl diazonium salts with nitroalkenes using -NO2 as a leaving group.

PubMed

Zhang, Na; Quan, Zheng-Jun; Zhang, Zhang; Da, Yu-Xia; Wang, Xi-Cun

2016-12-06

The straightforward visible-light-induced synthesis of stilbene compounds via the cross-coupling of nitroalkenes and diazonium tetrafluoroborates under transition-metal-free conditions is described. The protocol uses green LEDs as light sources and eosin Y as an organophotoredox catalyst. Broad substrate scope and exclusive selectivity for the (E)-configuration of stilbenes are observed. This protocol proceeds via a radical pathway, with nitroalkenes serving as the radical acceptor, and the nitro group is cleaved during the process.

Family Medicine Department Chairs' Opinions Regarding Scope of Practice.

PubMed

Peterson, Lars E; Blackburn, Brenna; Phillips, Robert L; Mainous, Arch G

2015-12-01

Family physicians are trained broadly to provide the majority of health care across multiple settings; however, their scope of practice has narrowed. Department chairs' role modeling of a broad scope of practice may set the tone for faculty and trainees. In 2013, the authors surveyed family medicine department chairs about their scope of practice, personal and department characteristics, and attitudes and beliefs about scope of practice and role modeling. They used descriptive statistics and bivariate analyses to test for associations between scope of practice, personal and department characteristics, and attitudes and beliefs. They created a Scope of Practice Index by summing the number of services each respondent provided to compare scope of practice across chairs. Of 146 chairs, 88 responded (60.3% response rate); 85 were included in the final analysis. Sixty-five (77.4%) respondents were male; 73 (86.9%) were 51 years or older. Respondents spent a mean of 19.7% of their time in direct patient care and had a mean Scope of Practice Index of 11.9. Fifty-three (62.4%) disagreed that the scope of practice of family medicine was too broad for practicing physicians to keep up in all areas, and 56 (65.9%) believed that faculty should role model the full scope of practice to learners. Responses generally did not vary by respondents' personal scope of practice. Family medicine department chairs believe that role modeling a broad scope of practice increases students' interest in family medicine and encourages residency graduates to provide a wide range of services.

A method to restrain the charging effect on an insulating substrate in high energy electron beam lithography

NASA Astrophysics Data System (ADS)

Mingyan, Yu; Shirui, Zhao; Yupeng, Jing; Yunbo, Shi; Baoqin, Chen

2014-12-01

Pattern distortions caused by the charging effect should be reduced while using the electron beam lithography process on an insulating substrate. We have developed a novel process by using the SX AR-PC 5000/90.1 solution as a spin-coated conductive layer, to help to fabricate nanoscale patterns of poly-methyl-methacrylate polymer resist on glass for phased array device application. This method can restrain the influence of the charging effect on the insulating substrate effectively. Experimental results show that the novel process can solve the problems of the distortion of resist patterns and electron beam main field stitching error, thus ensuring the accuracy of the stitching and overlay of the electron beam lithography system. The main characteristic of the novel process is that it is compatible to the multi-layer semiconductor process inside a clean room, and is a green process, quite simple, fast, and low cost. It can also provide a broad scope in the device development on insulating the substrate, such as high density biochips, flexible electronics and liquid crystal display screens.

Chiral Brønsted Acid-Catalyzed Allylboration of Aldehydes

PubMed Central

Jain, Pankaj; Antilla, Jon C.

2010-01-01

The catalytic enantioselective allylation of aldehydes is a long-standing problem with considerable interest to the chemical community. We wish to disclose a new high yielding and highly enantioselective chiral Brønsted acid-catalyzed allylboration of aldehydes. The reaction is shown to be highly general, with broad substrate scope that covers aryl, heteroaryl, α,β-unsaturated, and aliphatic aldehydes. The reaction conditions were also shown to be effective for the catalytic enantioselective crotylation of aldehydes. We believe that the high reactivity of the allyl boronate is due to protonation of the boronate oxygen by the chiral phosphoric acid catalyst. PMID:20690662

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes.

PubMed

Wang, Hao; Chen, Cui; Liu, Weibing; Zhu, Zhibo

2017-01-01

We developed a direct vicinal difunctionalization of alkenes with iodine and TBHP at room temperature. This iodination and peroxidation in a one-pot synthesis produces 1-( tert -butylperoxy)-2-iodoethanes, which are inaccessible through conventional synthetic methods. This method generates multiple radical intermediates in situ and has excellent regioselectivity, a broad substrate scope and mild conditions. The iodine and peroxide groups of 1-( tert -butylperoxy)-2-iodoethanes have several potential applications and allow further chemical modifications, enabling the preparation of synthetically valuable molecules.

Rhodium/Silver-Cocatalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles with Vinyl Azides: Divergent Synthesis of Pyrroles and 2 H-Pyrazines.

PubMed

Zhang, Lin; Sun, Ge; Bi, Xihe

2016-11-07

The first cyclization reaction between vinyl azides and N-sulfonyl-1,2,3-triazoles is reported. A Rh/Ag binary metal catalyst system proved to be necessary for the successful cyclization. By varying the structure of vinyl azides, such reaction allows the divergent synthesis of pyrroles and 2H-pyrazines. The cyclization reactions feature a broad substrate scope, good functional group tolerance, high reaction efficiency, and good to high product yields. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: expansion of substrate scope and mechanistic studies.

PubMed

Lee, Doris; Williamson, Caitlin L; Chan, Lina; Taylor, Mark S

2012-05-16

Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.

Using the written description requirement to limit broad patent scope, allow competition, and encourage innovation in biotechnology.

PubMed

Mull, William C

2004-01-01

The biotechnology research and development process is extremely expensive and companies must attract investors to this high-risk industry to pay for these costs. Biotechnology companies rely on their ability to exclude others from exploiting the benefits of their research through patent protection to attract these investors. Consequently, they seek strong patent protection for their inventions by claiming a broad scope of patent protection for their inventions. Biotechnology is an industry where the scope of protection should be limited. Science-based technologies exploit the perceived technological opportunities from recent scientific developments, concentrating the attention of many inventors on the same areas. This poses several unique problems. First, only the first of several inventors will receive a patent to the invention. Second, due to publicly available, basic techniques, the actual contribution made by the inventor may be relatively small. Finally, there is a significant risk that permitting an overbroad patent scope may permit original patentees to control a variety of improvements and a number of applications. Additionally, a broad scope of protection for an invention tends to cause underutilization of many potential inventions or improvements. By limiting the scope of protection, one allows competitors to utilize these potential inventions or improvements and encourages the advancement of the technology. Traditionally, courts have used the scope of the disclosure to limit a patent with an overly broad scope of protection. The Federal Circuit is correctly applying the written description requirement as part of the disclosure to limit broad claim scope in biotechnology patents. The written description requirement is separate from the enablement requirement and applies to all claims. By requiring a written description to allow a PHOSITA to determine the structural characteristics of the claimed invention, the Federal Circuit is able limit biotechnology patents with overly broad patent scope. Recognizing that particular technologies will become more established as biotechnology matures giving rise to different issues in setting the appropriate level of patent scope, the court allowed the written description requirement to mature in tandem with advances in biotechnology to meet these new developments.

Weak coordination as a powerful means for developing broadly useful C-H functionalization reactions.

PubMed

Engle, Keary M; Mei, Tian-Sheng; Wasa, Masayuki; Yu, Jin-Quan

2012-06-19

Reactions that convert carbon-hydrogen (C-H) bonds into carbon-carbon (C-C) or carbon-heteroatom (C-Y) bonds are attractive tools for organic chemists, potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. Despite extensive inorganic and organometallic study of the insertion of homogeneous metal species into unactivated C-H bonds, practical applications of this technology in organic chemistry are still rare. Only in the past decade have metal-catalyzed C-H functionalization reactions become more widely utilized in organic synthesis. Research in the area of homogeneous transition metal-catalyzed C-H functionalization can be broadly grouped into two subfields. They reflect different approaches and goals and thus have different challenges and opportunities. One approach involves reactions of completely unfunctionalized aromatic and aliphatic hydrocarbons, which we refer to as "first functionalization". Here the substrates are nonpolar and hydrophobic and thus interact very weakly with polar metal species. To overcome this weak affinity and drive metal-mediated C-H cleavage, chemists often use hydrocarbon substrates in large excess (for example, as solvent). Because highly reactive metal species are needed in first functionalization, controlling the chemoselectivity to avoid overfunctionalization is often difficult. Additionally, because both substrates and products are comparatively low-value chemicals, developing cost-effective catalysts with exceptionally high turnover numbers that are competitive with alternatives (including heterogeneous catalysts) is challenging. Although an exciting field, first functionalization is beyond the scope of this Account. The second subfield of C-H functionalization involves substrates containing one or more pre-existing functional groups, termed "further functionalization". One advantage of this approach is that the existing functional group (or groups) can be used to chelate the metal catalyst and position it for selective C-H cleavage. Precoordination can overcome the paraffin nature of C-H bonds by increasing the effective concentration of the substrate so that it need not be used as solvent. From a synthetic perspective, it is desirable to use a functional group that is an intrinsic part of the substrate so that extra steps for installation and removal of an external directing group can be avoided. In this way, dramatic increases in molecular complexity can be accomplished in a single stroke through stereo- and site-selective introduction of a new functional group. Although reactivity is a major challenge (as with first functionalization), the philosophy in further functionalization differs; the major challenge is developing reactions that work with predictable selectivity in intricately functionalized contexts on commonly occurring structural motifs. In this Account, we focus on an emergent theme within the further functionalization literature: the use of commonly occurring functional groups to direct C-H cleavage through weak coordination. We discuss our motivation for studying Pd-catalyzed C-H functionalization assisted by weakly coordinating functional groups and chronicle our endeavors to bring reactions of this type to fruition. Through this approach, we have developed reactions with a diverse range of substrates and coupling partners, with the broad scope likely stemming from the high reactivity of the cyclopalladated intermediates, which are held together through weak interactions.

Weak Coordination as a Powerful Means for Developing Broadly Useful C–H Functionalization Reactions

PubMed Central

Engle, Keary M.; Mei, Tian-Sheng; Wasa, Masayuki

2011-01-01

Conspectus Reactions that convert carbon–hydrogen (C–H) bonds into carbon–carbon (C–C) or carbon–heteroatom (C–Y) bonds are attractive tools for organic chemists, potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. Despite extensive inorganic and organometallic study of the insertion of homogeneous metal species into unactivated C–H bonds, practical applications of this technology in organic chemistry are still rare. Only in the past decade have metal-catalyzed C–H functionalization reactions become more widely utilized in organic synthesis. Research in the area of homogeneous transition metal–catalyzed C–H functionalization can be broadly grouped into two subfields. They reflect different approaches and goals and thus have different challenges and opportunities. One approach involves reactions of completely unfunctionalized aromatic and aliphatic hydrocarbons, which we refer to as “first functionalization.” Here the substrates are nonpolar and hydrophobic and thus interact very weakly with polar metal species. To overcome this weak affinity and drive metal-mediated C–H cleavage, chemists often use hydrocarbon substrates in large excess (for example, as solvent). Because highly reactive metal species are needed in first functionalization, controlling the chemoselectivity to avoid over-functionalization is often difficult. Additionally, because both substrates and products are comparatively low-value chemicals, developing cost-effective catalysts with exceptionally high turnover numbers that are competitive with alternatives (including heterogeneous catalysts) is challenging. Although an exciting field, first functionalization is beyond the scope of this Account. The second subfield of C–H functionalization involves substrates containing one or more pre-existing functional groups, termed “further functionalization.” One advantage of this approach is that the existing functional group (or groups) can be used to chelate the metal catalyst and position it for selective C–H cleavage. Precoordination can overcome the paraffin nature of C–H bonds by increasing the effective concentration of the substrate so that it needn't be used as solvent. From a synthetic perspective, it is desirable to use a functional group that is an intrinsic part of the substrate so that extra steps for installation and removal of an external directing group can be avoided. In this way, dramatic increases in molecular complexity can be accomplished in a single stroke through stereo- and site-selective introduction of a new functional group. Although reactivity is a major challenge (as with first functionalization), the philosophy in further functionalization differs—the major challenge is developing reactions that work with predictable selectivity in intricately functionalized contexts on commonly occurring structural motifs. In this Account, we focus on an emergent theme within the further functionalization literature: the use of commonly occurring functional groups to direct C–H cleavage through weak coordinations. We discuss our motivation for studying Pd-catalyzed C–H functionalization assisted by weakly coordinating functional groups and chronicle our endeavors to bring reactions of this type to fruition. Through this approach, we have developed reactions with a diverse range of substrates and coupling partners, with the broad scope likely stemming from higher reactivity of the less stable cyclopalladated intermediates held in place by weak coordinations. PMID:22166158

Enantioselective Cyanation of Benzylic C–H Bonds via Copper-Catalyzed Radical Relay

PubMed Central

Zhang, Wen; Wang, Fei; McCann, Scott D.; Wang, Dinghai; Chen, Pinhong; Stahl, Shannon; Liu, Guosheng

2017-01-01

Direct methods for stereoselective functionalization of C(sp3)–H bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C–H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp3)–CN bond upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90-99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C–H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways. PMID:27701109

Halogenase engineering and its utility in medicinal chemistry.

PubMed

Fraley, Amy E; Sherman, David H

2018-06-15

Halogenation is commonly used in medicinal chemistry to improve the potency of pharmaceutical leads. While synthetic methods for halogenation present selectivity and reactivity challenges, halogenases have evolved over time to perform selective reactions under benign conditions. The optimization of halogenation biocatalysts has utilized enzyme evolution and structure-based engineering alongside biotransformation in a variety of systems to generate stable site-selective variants. The recent improvements in halogenase-catalyzed reactions has demonstrated the utility of these biocatalysts for industrial purposes, and their ability to achieve a broad substrate scope implies a synthetic tractability with increasing relevance in medicinal chemistry. Copyright © 2018 Elsevier Ltd. All rights reserved.

10 CFR 33.8 - Information collection requirements: OMB approval.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

10 CFR 33.8 - Information collection requirements: OMB approval.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

10 CFR 33.8 - Information collection requirements: OMB approval.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

10 CFR 33.8 - Information collection requirements: OMB approval.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

10 CFR 33.8 - Information collection requirements: OMB approval.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

When lithography meets self-assembly: a review of recent advances in the directed assembly of complex metal nanostructures on planar and textured surfaces

NASA Astrophysics Data System (ADS)

Hughes, Robert A.; Menumerov, Eredzhep; Neretina, Svetlana

2017-07-01

One of the foremost challenges in nanofabrication is the establishment of a processing science that integrates wafer-based materials, techniques, and devices with the extraordinary physicochemical properties accessible when materials are reduced to nanoscale dimensions. Such a merger would allow for exacting controls on nanostructure positioning, promote cooperative phenomenon between adjacent nanostructures and/or substrate materials, and allow for electrical contact to individual or groups of nanostructures. With neither self-assembly nor top-down lithographic processes being able to adequately meet this challenge, advancements have often relied on a hybrid strategy that utilizes lithographically-defined features to direct the assembly of nanostructures into organized patterns. While these so-called directed assembly techniques have proven viable, much of this effort has focused on the assembly of periodic arrays of spherical or near-spherical nanostructures comprised of a single element. Work directed toward the fabrication of more complex nanostructures, while still at a nascent stage, has nevertheless demonstrated the possibility of forming arrays of nanocubes, nanorods, nanoprisms, nanoshells, nanocages, nanoframes, core-shell structures, Janus structures, and various alloys on the substrate surface. In this topical review, we describe the progress made in the directed assembly of periodic arrays of these complex metal nanostructures on planar and textured substrates. The review is divided into three broad strategies reliant on: (i) the deterministic positioning of colloidal structures, (ii) the reorganization of deposited metal films at elevated temperatures, and (iii) liquid-phase chemistry practiced directly on the substrate surface. These strategies collectively utilize a broad range of techniques including capillary assembly, microcontact printing, chemical surface modulation, templated dewetting, nanoimprint lithography, and dip-pen nanolithography and employ a wide scope of chemical processes including redox reactions, alloying, dealloying, phase separation, galvanic replacement, preferential etching, template-mediated reactions, and facet-selective capping agents. Taken together, they highlight the diverse toolset available when fabricating organized surfaces of substrate-supported nanostructures.

Scope and limitations of carbohydrate hydrolysis for de novo glycan sequencing using a hydrogen peroxide/metallopeptide-based glycosidase mimetic.

PubMed

Peng, Tianyuan; Wooke, Zachary; Pohl, Nicola L B

2018-03-22

Acidic hydrolysis is commonly used as a first step to break down oligo- and polysaccharides into monosaccharide units for structural analysis. While easy to set up and amenable to mass spectrometry detection, acid hydrolysis is not without its drawbacks. For example, ring-destruction side reactions and degradation products, along with difficulties in optimizing conditions from analyte to analyte, greatly limits its broad utility. Herein we report studies on a hydrogen peroxide/CuGGH metallopeptide-based glycosidase mimetic design for a more efficient and controllable carbohydrate hydrolysis. A library of methyl glycosides consisting of ten common monosaccharide substrates, along with oligosaccharide substrates, was screened with the artificial glycosidase for hydrolytic activity in a high-throughput format with a robotic liquid handling system. The artificial glycosidase was found to be active towards most screened linkages, including alpha- and beta-anomers, thus serving as a potential alternative method for traditional acidic hydrolysis approaches of oligosaccharides. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mono- and tri-ester hydrogenolysis using tandem catalysis. Scope and mechanism.

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

Lohr, Tracy L.; Li, Zhi; Assary, Rajeev S.

The scope and mechanism of thermodynamically leveraged ester RC(O)O-R' bond hydrogenolysis by tandem metal triflate + supported Pd catalysts are investigated both experimentally and theoretically by DFT and energy span analysis. This catalytic system has a broad scope, with relative cleavage rates scaling as, tertiary 4 secondary 4 primary ester at 1 bar H-2, yielding alkanes and carboxylic acids with high conversion and selectivity. Benzylic and allylic esters display the highest activity. The rate law is nu = k[M(OTf )(n)](1)[ester](0)[H-2](0) with an H/D kinetic isotope effect = 6.5 +/- 0.5, implying turnover-limiting C-H scission following C-O cleavage, in agreement withmore » theory. Intermediate alkene products are then rapidly hydrogenated. Applying this approach with the very active Hf(OTf)(4) catalyst to bio-derived triglycerides affords near-quantitative yields of C-3 hydrocarbons rather than glycerol. From model substrates, it is found that RC(O)O-R' cleavage rates are very sensitive to steric congestion and metal triflate identity. For triglycerides, primary/external glyceryl CH2-O cleavage predominates over secondary/internal CH-O cleavage, with the latter favored by less acidic or smaller ionic radius metal triflates, raising the diester selectivity to as high as 48% with Ce(OTf)(3).« less

From ketones to esters by a Cu-catalyzed highly selective C(CO)-C(alkyl) bond cleavage: aerobic oxidation and oxygenation with air.

PubMed

Huang, Xiaoqiang; Li, Xinyao; Zou, Miancheng; Song, Song; Tang, Conghui; Yuan, Yizhi; Jiao, Ning

2014-10-22

The Cu-catalyzed aerobic oxidative esterification of simple ketones via C-C bond cleavage has been developed. Varieties of common ketones, even inactive aryl long-chain alkyl ketones, are selectively converted into esters. The reaction tolerates a wide range of alcohols, including primary and secondary alcohols, chiral alcohols with retention of the configuration, electron-deficient phenols, as well as various natural alcohols. The usage of inexpensive copper catalyst, broad substrate scope, and neutral and open air conditions make this protocol very practical. (18)O labeling experiments reveal that oxygenation occurs during this transformation. Preliminary mechanism studies indicate that two novel pathways are mainly involved in this process.

Reaction of Donor-Acceptor Cyclobutanes with Indoles: A General Protocol for the Formal Total Synthesis of (±)-Strychnine and the Total Synthesis of (±)-Akuammicine.

PubMed

Feng, Liang-Wen; Ren, Hai; Xiong, Hu; Wang, Pan; Wang, Lijia; Tang, Yong

2017-03-06

A ligand-promoted catalytic [4+2] annulation reaction using indole derivatives and donor-acceptor (D-A) cyclobutanes is reported, thus providing an efficient and atom-economical access to versatile cyclohexa-fused indolines with excellent levels of diastereoselectivity and a broad substrate scope. In the presence of a chiral SaBOX ligand, excellent enantioselectivity was realized with up to 94 % ee. This novel synthetic method is applied as a general protocol for the total synthesis of (±)-akuammicine and the formal total synthesis of (±)-strychnine from the same common-core scaffold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regioconvergent and Enantioselective Rhodium-Catalyzed Hydroamination of Internal and Terminal Alkynes: A Highly Flexible Access to Chiral Pyrazoles.

PubMed

Haydl, Alexander M; Hilpert, Lukas J; Breit, Bernhard

2016-05-04

The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with internal and terminal alkynes features an utmost chemo-, regio-, and enantioselective access to enantiopure allylic pyrazoles, readily available for incorporation in small-molecule pharmaceuticals. This methodology is distinguished by a broad substrate scope, resulting in a remarkable compatability with a variety of different functional groups. It furthermore exhibits an intriguing case of regio-, position-, and enantioselectivity in just one step, underscoring the sole synthesis of just one out of up to six possible products in a highly flexible approach to allylated pyrazoles by emanating from various internal and terminal alkynes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carboxylic acid reductase enzymes (CARs).

PubMed

Winkler, Margit

2018-04-01

Carboxylate reductases (CARs) are emerging as valuable catalysts for the selective one-step reduction of carboxylic acids to their corresponding aldehydes. The substrate scope of CARs is exceptionally broad and offers potential for their application in diverse synthetic processes. Two major fields of application are the preparation of aldehydes as end products for the flavor and fragrance sector and the integration of CARs in cascade reactions with aldehydes as the key intermediates. The latest applications of CARs are dominated by in vivo cascades and chemo-enzymatic reaction sequences. The challenge to fully exploit product selectivity is discussed. Recent developments in the characterization of CARs are summarized, with a focus on aspects related to the domain architecture and protein sequences of CAR enzymes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lesions of the Broad Ligament: A Review.

PubMed

Heller, Debra S

2015-01-01

The differential diagnosis of lesions arising in the broad ligament is quite large. Many of these lesions can be clinically interpreted before surgery as adnexal or uterine neoplasms. Although some lesions are similar to those arising in other müllerian sites, there are unique lesions as well. The lesions are uncommon and may prove challenging to clinicians. The purpose was to review the scope of lesions affecting the broad ligament. A literature review was conducted. A Medline search was performed using the terms broad ligament, mesosalpinx, and mesovarium. A review of the scope of broad ligament lesions is presented to assist in developing a differential diagnosis if a patient with such a lesion is encountered. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

NASA aerospace database subject scope: An overview

NASA Technical Reports Server (NTRS)

1993-01-01

Outlined here is the subject scope of the NASA Aerospace Database, a publicly available subset of the NASA Scientific and Technical (STI) Database. Topics of interest to NASA are outlined and placed within the framework of the following broad aerospace subject categories: aeronautics, astronautics, chemistry and materials, engineering, geosciences, life sciences, mathematical and computer sciences, physics, social sciences, space sciences, and general. A brief discussion of the subject scope is given for each broad area, followed by a similar explanation of each of the narrower subject fields that follow. The subject category code is listed for each entry.

Beyond D-luciferin: Expanding the Scope of Bioluminescence Imaging in vivo

PubMed Central

Adams, Spencer T.; Miller, Stephen C.

2014-01-01

The light-emitting chemical reaction catalyzed by the enzyme firefly luciferase is widely used for noninvasive imaging in live mice. However, photon emission from the luciferase is critically dependent on the chemical properties of its substrate, D-luciferin. In this review, we describe recent work to replace the natural luciferase substrate with synthetic analogs that extend the scope of bioluminescence imaging. PMID:25078002

Mild and selective base-free C–H arylation of heteroarenes: experiment and computation† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc02595a Click here for additional data file.

PubMed Central

Gemoets, Hannes P. L.; Kalvet, Indrek; Nyuchev, Alexander V.; Erdmann, Nico; Hessel, Volker

2017-01-01

A mild and selective C–H arylation strategy for indoles, benzofurans and benzothiophenes is described. The arylation method engages aryldiazonium salts as arylating reagents in equimolar amounts. The protocol is operationally simple, base free, moisture tolerant and air tolerant. It utilizes low palladium loadings (0.5 to 2.0 mol% Pd), short reaction times, green solvents (EtOAc/2-MeTHF or MeOH) and is carried out at room temperature, providing a broad substrate scope (47 examples) and excellent selectivity (C-2 arylation for indoles and benzofurans, C-3 arylation for benzothiophenes). Mechanistic experiments and DFT calculations support a Heck–Matsuda type coupling mechanism. PMID:28451243

Suzuki–Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

PubMed Central

Quasdorf, Kyle W.; Antoft-Finch, Aurora; Liu, Peng; Silberstein, Amanda L.; Komaromi, Anna; Blackburn, Tom; Ramgren, Stephen D.; Houk, K. N.; Snieckus, Victor; Garg, Neil K.

2011-01-01

The first Suzuki–Miyaura cross-coupling reactions of the synthetically versatile O-aryl carbamate and O-sulfamate groups is described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups (EDGs, EWGs) are tolerated, in addition to those that possess ortho substitutents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative additions with carbamates and sulfamates occur via a five-centered transition state, resulting in the exclusive cleavage of the Ar–O bond. Water is found to stabilize the Ni–carbamate catalyst resting state, and thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest. PMID:21456551

Substrate scope of a dehydrogenase from Sphingomonas species A1 and its potential application in the synthesis of rare sugars and sugar derivatives.

PubMed

Beer, Barbara; Pick, André; Döring, Manuel; Lommes, Petra; Sieber, Volker

2018-07-01

Rare sugars and sugar derivatives that can be obtained from abundant sugars are of great interest to biochemical and pharmaceutical research. Here, we describe the substrate scope of a short-chain dehydrogenase/reductase from Sphingomonas species A1 (SpsADH) in the oxidation of aldonates and polyols. The resulting products are rare uronic acids and rare sugars respectively. We provide insight into the substrate recognition of SpsADH using kinetic analyses, which show that the configuration of the hydroxyl groups adjacent to the oxidized carbon is crucial for substrate recognition. Furthermore, the specificity is demonstrated by the oxidation of d-sorbitol leading to l-gulose as sole product instead of a mixture of d-glucose and l-gulose. Finally, we applied the enzyme to the synthesis of l-gulose from d-sorbitol in an in vitro system using a NADH oxidase for cofactor recycling. This study shows the usefulness of exploring the substrate scope of enzymes to find new enzymatic reaction pathways from renewable resources to value-added compounds. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Management Prerogatives and the Scope of Public School Bargaining.

ERIC Educational Resources Information Center

Baldwin, Grover H.

Examination of the scope of management prerogatives in negotiation raises the question of available guidelines for school boards. State legislation indicates that the scope of bargaining ranges from narrow restrictions to broad capabilities. Management prerogatives include the power to oversee budgets and hire and dismiss employees. School…

A survey of wellness management strategies used by Canadian doctors of chiropractic.

PubMed

Stainsby, Brynne E; Porr, Jason T C; Kim, Peter; Collinge, Ashley M; Hunter, Julie C

2011-01-01

The purpose of this study was to investigate if Canadian doctors of chiropractic consider using wellness strategies after functional recovery in acute and chronic conditions. This study also attempted to determine if there is a difference in the use of wellness management strategies between broad and narrow scope practitioners. Forty-one practicing, licensed chiropractors were recruited to complete an interview survey regarding 2 mock clinical case presentations. Interviews were recorded, and influential words or word pairings were identified. Investigators formulated criteria to divide practitioners into broad scope (mixers) and narrow scope (straights). Data were analyzed using Crawdad Analysis Software (version 1.2). All subjects indicated that they would provide information regarding public health and wellness strategies to a patient after functional resolution of the presenting chronic or acute complaints. The responses of broad scope (mixer) chiropractors appeared to be focused on the patient specifically, whereas narrow scope (straight) responses appeared to be more varied when analyzed for noun and noun-pair influence. This study of practicing, licensed Canadian chiropractors suggests that wellness strategies may be commonly considered in practice. All subjects in this study reported a number of strategies to educate patients regarding wellness after functional recovery of a complaint. Copyright © 2011 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

A One-Pot/Single-Analysis Approach to Substrate Scope Investigations Using Comprehensive Two-Dimensional Gas Chromatography (GC×GC).

PubMed

O'Neil, Gregory W; Nelson, Robert K; Wright, Alicia M; Reddy, Christopher M

2016-05-06

A representative substrate scope investigation for an enantioselective catalytic ketone-reduction has been performed as a single reaction on a mixture containing equimolar amounts of nine (9) prototypical compounds. The resulting analyte pool containing 18 potential products from nine different reactions could all be completely resolved in a single chromatographic injection using comprehensive two-dimensional gas chromatography (GC×GC) with time-of-flight mass spectrometry, allowing for simultaneous determination of percent conversion and enantiomeric excess for each substrate. The results obtained for an enantioselective iron-catalyzed asymmetric transfer hydrogenation using this one-pot/single-analysis approach were similar to those reported for the individualized reactions, demonstrating the utility of this strategy for streamlining substrate scope investigations. Moreover, for this particular catalyst, activity and selectivity were not greatly affected by the presence of other ketones or enantioenriched reduced products. This approach allows for faster and greener analyses that are central to new reaction development, as well as an opportunity to gain further insights into other established transformations.

Quantitative Comparison of Protein Adsorption and Conformational Changes on Dielectric-Coated Nanoplasmonic Sensing Arrays.

PubMed

Ferhan, Abdul Rahim; Jackman, Joshua A; Sut, Tun Naw; Cho, Nam-Joon

2018-04-22

Nanoplasmonic sensors are a popular, surface-sensitive measurement tool to investigate biomacromolecular interactions at solid-liquid interfaces, opening the door to a wide range of applications. In addition to high surface sensitivity, nanoplasmonic sensors have versatile surface chemistry options as plasmonic metal nanoparticles can be coated with thin dielectric layers. Within this scope, nanoplasmonic sensors have demonstrated promise for tracking protein adsorption and substrate-induced conformational changes on oxide film-coated arrays, although existing studies have been limited to single substrates. Herein, we investigated human serum albumin (HSA) adsorption onto silica- and titania-coated arrays of plasmonic gold nanodisks by localized surface plasmon resonance (LSPR) measurements and established an analytical framework to compare responses across multiple substrates with different sensitivities. While similar responses were recorded on the two substrates for HSA adsorption under physiologically-relevant ionic strength conditions, distinct substrate-specific behavior was observed at lower ionic strength conditions. With decreasing ionic strength, larger measurement responses occurred for HSA adsorption onto silica surfaces, whereas HSA adsorption onto titania surfaces occurred independently of ionic strength condition. Complementary quartz crystal microbalance-dissipation (QCM-D) measurements were also performed, and the trend in adsorption behavior was similar. Of note, the magnitudes of the ionic strength-dependent LSPR and QCM-D measurement responses varied, and are discussed with respect to the measurement principle and surface sensitivity of each technique. Taken together, our findings demonstrate how the high surface sensitivity of nanoplasmonic sensors can be applied to quantitatively characterize protein adsorption across multiple surfaces, and outline broadly-applicable measurement strategies for biointerfacial science applications.

14 CFR 1216.314 - Tiering.

Code of Federal Regulations, 2011 CFR

2011-01-01

... are the subject of an environmental impact statement and which represents projects of broad scope may... “Tiering” (§ 1508.28 of the CEQ Regulations) of environmental impact statements to relate such broad and...

14 CFR 1216.314 - Tiering.

Code of Federal Regulations, 2010 CFR

2010-01-01

... are the subject of an environmental impact statement and which represents projects of broad scope may... “Tiering” (§ 1508.28 of the CEQ Regulations) of environmental impact statements to relate such broad and...

14 CFR 1216.314 - Tiering.

Code of Federal Regulations, 2012 CFR

2012-01-01

... are the subject of an environmental impact statement and which represents projects of broad scope may... “Tiering” (§ 1508.28 of the CEQ Regulations) of environmental impact statements to relate such broad and...

A Haloalkane Dehalogenase from a Marine Microbial Consortium Possessing Exceptionally Broad Substrate Specificity.

PubMed

Buryska, Tomas; Babkova, Petra; Vavra, Ondrej; Damborsky, Jiri; Prokop, Zbynek

2018-01-15

The haloalkane dehalogenase enzyme DmmA was identified by marine metagenomic screening. Determination of its crystal structure revealed an unusually large active site compared to those of previously characterized haloalkane dehalogenases. Here we present a biochemical characterization of this interesting enzyme with emphasis on its structure-function relationships. DmmA exhibited an exceptionally broad substrate specificity and degraded several halogenated environmental pollutants that are resistant to other members of this enzyme family. In addition to having this unique substrate specificity, the enzyme was highly tolerant to organic cosolvents such as dimethyl sulfoxide, methanol, and acetone. Its broad substrate specificity, high overexpression yield (200 mg of protein per liter of cultivation medium; 50% of total protein), good tolerance to organic cosolvents, and a broad pH range make DmmA an attractive biocatalyst for various biotechnological applications. IMPORTANCE We present a thorough biochemical characterization of the haloalkane dehalogenase DmmA from a marine metagenome. This enzyme with an unusually large active site shows remarkably broad substrate specificity, high overexpression, significant tolerance to organic cosolvents, and activity under a broad range of pH conditions. DmmA is an attractive catalyst for sustainable biotechnology applications, e.g., biocatalysis, biosensing, and biodegradation of halogenated pollutants. We also report its ability to convert multiple halogenated compounds to corresponding polyalcohols. Copyright © 2018 American Society for Microbiology.

Application of Stable Isotope-Assisted Metabolomics for Cell Metabolism Studies

PubMed Central

You, Le; Zhang, Baichen; Tang, Yinjie J.

2014-01-01

The applications of stable isotopes in metabolomics have facilitated the study of cell metabolisms. Stable isotope-assisted metabolomics requires: (1) properly designed tracer experiments; (2) stringent sampling and quenching protocols to minimize isotopic alternations; (3) efficient metabolite separations; (4) high resolution mass spectrometry to resolve overlapping peaks and background noises; and (5) data analysis methods and databases to decipher isotopic clusters over a broad m/z range (mass-to-charge ratio). This paper overviews mass spectrometry based techniques for precise determination of metabolites and their isotopologues. It also discusses applications of isotopic approaches to track substrate utilization, identify unknown metabolites and their chemical formulas, measure metabolite concentrations, determine putative metabolic pathways, and investigate microbial community populations and their carbon assimilation patterns. In addition, 13C-metabolite fingerprinting and metabolic models can be integrated to quantify carbon fluxes (enzyme reaction rates). The fluxome, in combination with other “omics” analyses, may give systems-level insights into regulatory mechanisms underlying gene functions. More importantly, 13C-tracer experiments significantly improve the potential of low-resolution gas chromatography-mass spectrometry (GC-MS) for broad-scope metabolism studies. We foresee the isotope-assisted metabolomics to be an indispensable tool in industrial biotechnology, environmental microbiology, and medical research. PMID:24957020

29 CFR 1630.1 - Purpose, applicability, and construction.

Code of Federal Regulations, 2012 CFR

2012-07-01

... programs. (4) Broad coverage. The primary purpose of the ADAAA is to make it easier for people with... broad scope of protection under the ADA, the definition of “disability” in this part shall be construed...

Synthesis of a Bicyclic Azetidine with In Vivo Antimalarial Activity Enabled by Stereospecific, Directed C(sp3)-H Arylation.

PubMed

Maetani, Micah; Zoller, Jochen; Melillo, Bruno; Verho, Oscar; Kato, Nobutaka; Pu, Jun; Comer, Eamon; Schreiber, Stuart L

2017-08-16

The development of new antimalarial therapeutics is necessary to address the increasing resistance to current drugs. Bicyclic azetidines targeting Plasmodium falciparum phenylalanyl-tRNA synthetase comprise one promising new class of antimalarials, especially due to their activities against three stages of the parasite's life cycle, but a lengthy synthetic route to these compounds may affect the feasibility of delivering new therapeutic agents within the cost constraints of antimalarial drugs. Here, we report an efficient synthesis of antimalarial compound BRD3914 (EC 50 = 15 nM) that hinges on a Pd-catalyzed, directed C(sp 3 )-H arylation of azetidines at the C3 position. This newly developed protocol exhibits a broad substrate scope and provides access to valuable, stereochemically defined building blocks. BRD3914 was evaluated in P. falciparum-infected mice, providing a cure after four oral doses.

A broad scope knowledge based model for optimization of VMAT in esophageal cancer: validation and assessment of plan quality among different treatment centers.

PubMed

Fogliata, Antonella; Nicolini, Giorgia; Clivio, Alessandro; Vanetti, Eugenio; Laksar, Sarbani; Tozzi, Angelo; Scorsetti, Marta; Cozzi, Luca

2015-10-31

To evaluate the performance of a broad scope model-based optimisation process for volumetric modulated arc therapy applied to esophageal cancer. A set of 70 previously treated patients in two different institutions, were selected to train a model for the prediction of dose-volume constraints. The model was built with a broad-scope purpose, aiming to be effective for different dose prescriptions and tumour localisations. It was validated on three groups of patients from the same institution and from another clinic not providing patients for the training phase. Comparison of the automated plans was done against reference cases given by the clinically accepted plans. Quantitative improvements (statistically significant for the majority of the analysed dose-volume parameters) were observed between the benchmark and the test plans. Of 624 dose-volume objectives assessed for plan evaluation, in 21 cases (3.3 %) the reference plans failed to respect the constraints while the model-based plans succeeded. Only in 3 cases (<0.5 %) the reference plans passed the criteria while the model-based failed. In 5.3 % of the cases both groups of plans failed and in the remaining cases both passed the tests. Plans were optimised using a broad scope knowledge-based model to determine the dose-volume constraints. The results showed dosimetric improvements when compared to the benchmark data. Particularly the plans optimised for patients from the third centre, not participating to the training, resulted in superior quality. The data suggests that the new engine is reliable and could encourage its application to clinical practice.

29 CFR 783.21 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... that Congress intended the Fair Labor Standards Act to be broad in its scope (Helena Glendale Ferry Co... exemptions in this Act have been made preclude their enlargement by implication” and “no matter how broad the... broad objectives for which the Act was passed (Phillips v. Walling, 324 U.S. 490; Mitchell v. Kentucky...

29 CFR 783.21 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... that Congress intended the Fair Labor Standards Act to be broad in its scope (Helena Glendale Ferry Co... exemptions in this Act have been made preclude their enlargement by implication” and “no matter how broad the... broad objectives for which the Act was passed (Phillips v. Walling, 324 U.S. 490; Mitchell v. Kentucky...

29 CFR 783.21 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... that Congress intended the Fair Labor Standards Act to be broad in its scope (Helena Glendale Ferry Co... exemptions in this Act have been made preclude their enlargement by implication” and “no matter how broad the... broad objectives for which the Act was passed (Phillips v. Walling, 324 U.S. 490; Mitchell v. Kentucky...

29 CFR 783.21 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... that Congress intended the Fair Labor Standards Act to be broad in its scope (Helena Glendale Ferry Co... exemptions in this Act have been made preclude their enlargement by implication” and “no matter how broad the... broad objectives for which the Act was passed (Phillips v. Walling, 324 U.S. 490; Mitchell v. Kentucky...

29 CFR 783.21 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... that Congress intended the Fair Labor Standards Act to be broad in its scope (Helena Glendale Ferry Co... exemptions in this Act have been made preclude their enlargement by implication” and “no matter how broad the... broad objectives for which the Act was passed (Phillips v. Walling, 324 U.S. 490; Mitchell v. Kentucky...

Structural basis of the broad substrate tolerance of the antibody 7B9-catalyzed hydrolysis of p-nitrobenzyl esters.

PubMed

Miyamoto, Naoki; Yoshimura, Miho; Okubo, Yuji; Suzuki-Nagata, Kayo; Tsumuraya, Takeshi; Ito, Nobutoshi; Fujii, Ikuo

2018-05-01

Catalytic antibody 7B9, which was elicited against p-nitrobenzyl phosphonate transition-state analogue (TSA) 1, hydrolyzes a wide range of p-nitrobenzyl monoesters and thus shows broad substrate tolerance. To reveal the molecular basis of this substrate tolerance, the 7B9 Fab fragment complexed with p-nitrobenzyl ethylphosphonate 2 was crystallized and the three-dimensional structure was determined. The crystal structure showed that the strongly antigenic p-nitrobenzyl moiety occupied a relatively shallow antigen-combining site and therefore the alkyl moiety was located outside the pocket. These results support the observed broad substrate tolerance of 7B9 and help rationalize how 7B9 can catalyze various p-nitrobenzyl ester derivatives. The crystal structure also showed that three amino acid residues (Asn H33 , Ser H95 , and Arg L96 ) were placed in key positions to form hydrogen bonds with the phosphonate oxygens of the transitions-state analogue. In addition, the role of these amino acid residues was examined by site-directed mutagenesis to alanine: all mutants (Asn H33 Ala, Ser H95 Ala, and Arg L96 Ala) showed no detectable catalytic activity. Coupling the findings from our structural studies with these mutagenesis results clarified the structural basis of the observed broad substrate tolerance of antibody 7B9-catalyzed hydrolyses. Our findings provide new strategies for the generation of catalytic antibodies that accept a broad range of substrates, aiding their practical application in synthetic organic chemistry. Copyright © 2017 Elsevier Ltd. All rights reserved.

29 CFR 779.101 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to be broad in its scope. “Breadth of coverage is vital to its mission.” (Powell v. U.S. Cartridge Co... exemptions is necessary to carry out the broad objectives for which the Act was passed. (Phillips v. Walling...

29 CFR 779.101 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... to be broad in its scope. “Breadth of coverage is vital to its mission.” (Powell v. U.S. Cartridge Co... exemptions is necessary to carry out the broad objectives for which the Act was passed. (Phillips v. Walling...

29 CFR 779.101 - Guiding principles for applying coverage and exemption provisions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... to be broad in its scope. “Breadth of coverage is vital to its mission.” (Powell v. U.S. Cartridge Co... exemptions is necessary to carry out the broad objectives for which the Act was passed. (Phillips v. Walling...

HealthScope: a model for a low cost health education program using commercial television.

PubMed Central

Braun, K L; Conybeare, C R

1995-01-01

HealthScope is a health education based on the Health Belief Model that uses television and print materials. It was designed for a number of agendas--(a) a desire by health educators to provide health information to a broad audience at a reasonable cost (b) a desire by the local medical association to promote its role in prevention and primary care, and (c) a desire by commercial television to expand its coverage of local health issues in a cost-effective way. In its summer series, HealthScope included 10 weekly television programs that focused on various aspects of disease prevention and health promotion and answered viewers' questions on the air. Each program was followed by a bank of physicians answering questions on the telephone for 90 minutes. Corresponding fact sheets were distributed through a local pharmacy chain. A "healthy weekend" sweepstakes contest also was held. Intermediate outcome measures indicated that HealthScope had a broad reach and stimulated viewers to seek additional information about health. At the same time, the program generated revenue for the commercial television station. PMID:7638337

Development of a Memory Game to Improve Knowledge Retention in Preparation for Broad Scope Exams in an Introductory Earth Science Course

NASA Astrophysics Data System (ADS)

Cook, H. M.; Bilsley, N. A.

2015-12-01

As the demand for introductory earth science classes rises at educational institutions, large class sizes place strain on the educator's time and ability to offer extensive project-based assignments. As a result, exams covering a broad spectrum of material are more heavily weighted in students' grades. Students often struggle on the first exam, as they attempt to retain a large amount of information from several different topics, while having no exposure to the type of questions that will be asked. This frequently leads to a large dropout rate early in the academic term, or at least a sense of discouragement and stress among struggling students. To better prepare students for a broad scope exam, a review activity modelled after the traditional Milton Bradley "Memory" game was developed to remind students of what would be covered on the exam, prepare them for the style of questions that may be asked, as well as provide a fun, interactive, and educational activity. The Earth Science Memory Game was developed to have interchangeable sets to cover a broad range of topics and thus also be reusable for the duration of the course. Example games sets presented include, but are not limited to, the scientific method, minerals, rocks, topographic maps, tectonics, geologic structures, volcanoes, and weather. The Earth Science Memory Game not only provides an effective review tool to improve success rates on broad scope exams, but is also customizable by the instructor, reusable, and easily constructed by common office supplies.

Three-Dimensional Multiscale, Multistable, and Geometrically Diverse Microstructures with Tunable Vibrational Dynamics Assembled by Compressive Buckling.

PubMed

Ning, Xin; Wang, Heling; Yu, Xinge; Soares, Julio A N T; Yan, Zheng; Nan, Kewang; Velarde, Gabriel; Xue, Yeguang; Sun, Rujie; Dong, Qiyi; Luan, Haiwen; Lee, Chan Mi; Chempakasseril, Aditya; Han, Mengdi; Wang, Yiqi; Li, Luming; Huang, Yonggang; Zhang, Yihui; Rogers, John

2017-04-11

Microelectromechanical systems remain an area of significant interest in fundamental and applied research due to their wide ranging applications. Most device designs, however, are largely two-dimensional and constrained to only a few simple geometries. Achieving tunable resonant frequencies or broad operational bandwidths requires complex components and/or fabrication processes. The work presented here reports unusual classes of three-dimensional (3D) micromechanical systems in the form of vibratory platforms assembled by controlled compressive buckling. Such 3D structures can be fabricated across a broad range of length scales and from various materials, including soft polymers, monocrystalline silicon, and their composites, resulting in a wide scope of achievable resonant frequencies and mechanical behaviors. Platforms designed with multistable mechanical responses and vibrationally de-coupled constituent elements offer improved bandwidth and frequency tunability. Furthermore, the resonant frequencies can be controlled through deformations of an underlying elastomeric substrate. Systematic experimental and computational studies include structures with diverse geometries, ranging from tables, cages, rings, ring-crosses, ring-disks, two-floor ribbons, flowers, umbrellas, triple-cantilever platforms, and asymmetric circular helices, to multilayer constructions. These ideas form the foundations for engineering designs that complement those supported by conventional, microelectromechanical systems, with capabilities that could be useful in systems for biosensing, energy harvesting and others.

Expanding Water/Base Tolerant Frustrated Lewis Pair Chemistry to Alkylamines Enables Broad Scope Reductive Aminations

PubMed Central

Fasano, Valerio

2017-01-01

Abstract Lower Lewis acidity boranes demonstrate greater tolerance to combinations of water/strong Brønsted bases than B(C6F5)3, this enables Si−H bond activation by a frustrated Lewis pair (FLP) mechanism to proceed in the presence of H2O/alkylamines. Specifically, BPh3 has improved water tolerance in the presence of alkylamines as the Brønsted acidic adduct H2O–BPh3 does not undergo irreversible deprotonation with aliphatic amines in contrast to H2O–B(C6F5)3. Therefore BPh3 is a catalyst for the reductive amination of aldehydes and ketones with alkylamines using silanes as reductants. A range of amines inaccessible using B(C6F5)3 as catalyst, were accessible by reductive amination catalysed by BPh3 via an operationally simple methodology requiring no purification of BPh3 or reagents/solvent. BPh3 has a complementary reductive amination scope to B(C6F5)3 with the former not an effective catalyst for the reductive amination of arylamines, while the latter is not an effective catalyst for the reductive amination of alkylamines. This disparity is due to the different pK a values of the water–borane adducts and the greater susceptibility of BPh3 species towards protodeboronation. An understanding of the deactivation processes occurring using B(C6F5)3 and BPh3 as reductive amination catalysts led to the identification of a third triarylborane, B(3,5‐Cl2C6H3)3, that has a broader substrate scope being able to catalyse the reductive amination of both aryl and alkyl amines with carbonyls. PMID:27977048

Using scoping as a design process

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

Mulvihill, P.R.; Jacobs, P.

1998-07-01

Skillful use of the scoping phase of environment assessment (EA) is critical in cases involving a wide diversity of stakeholders and perspectives. Scoping can exert a strong influence in shaping a relevant impact assessment and increasing the probability of a process that satisfies stakeholders. This article explores key challenges facing scoping processes conducted in highly pluralistic settings. Elements of a notable case study--the scoping process conducted in 1992 for the proposed Great Whale Hydroelectric project in Northern Quebec--are discussed to illustrate innovative approaches. When used as a design process, scoping can ensure that EA reflects the different value sets andmore » cultures that are at play, particularly where diverse knowledge systems and ways of describing environmental components and impacts exist. As it sets the stage for subsequent steps in the EA process, scoping needs to be a sufficiently broad umbrella that accommodates diverse approaches to identifying, classifying, and assessing impacts.« less

Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes

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

Key, Hanna M.; Dydio, Paweł; Liu, Zhennan

Enzymes catalyze organic transformations with exquisite levels of selectivity, including chemoselectivity, stereoselectivity, and substrate selectivity, but the types of reactions catalyzed by enzymes are more limited than those of chemical catalysts. Thus, the convergence of chemical catalysis and biocatalysis can enable enzymatic systems to catalyze abiological reactions with high selectivity. Recently, we disclosed artificial enzymes constructed from the apo form of heme proteins and iridium porphyrins that catalyze the insertion of carbenes into a C-H bond. Here, we postulated that the same type of Ir(Me)-PIX enzymes could catalyze the cyclopropanation of a broad range of alkenes with control of multiplemore » modes of selectivity. Here, we report the evolution of artificial enzymes that are highly active and highly stereoselective for the addition of carbenes to a wide range of alkenes. These enzymes catalyze the cyclopropanation of terminal and internal, activated and unactivated, electron-rich and electron-deficient, conjugated and nonconjugated alkenes. In particular, Ir(Me)-PIX enzymes derived from CYP119 catalyze highly enantio- and diastereoselective cyclopropanations of styrene with ±98% ee, > 70:1 dr, > 75% yield, and ~10,000 turnovers (TON), as well as 1,2-disubstituted styrenes with up to 99% ee, 35:1 dr, and 54% yield. Moreover, Ir(Me)-PIX enzymes catalyze cyclopropanation of internal, unactivated alkenes with up to 99% stereoselectivity, 76% yield, and 1300 TON. They also catalyze cyclopropanation of natural products with diastereoselectivities that are complementary to those attained with standard transition metal catalysts. Finally, Ir(Me)-PIX P450 variants react with substrate selectivity that is reminiscent of natural enzymes; they react preferentially with less reactive internal alkenes in the presence of more reactive terminal alkenes. Altogether, the studies reveal the suitability of Ir-containing P450s to combine the broad reactivity and substrate scope of transition metal catalysts with the exquisite selectivity of enzymes, generating catalysts that enable reactions to occur with levels and modes of activity and selectivity previously unattainable with natural enzymes or transition metal complexes alone.« less

Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes

DOE PAGES

Key, Hanna M.; Dydio, Paweł; Liu, Zhennan; ...

2017-04-01

Enzymes catalyze organic transformations with exquisite levels of selectivity, including chemoselectivity, stereoselectivity, and substrate selectivity, but the types of reactions catalyzed by enzymes are more limited than those of chemical catalysts. Thus, the convergence of chemical catalysis and biocatalysis can enable enzymatic systems to catalyze abiological reactions with high selectivity. Recently, we disclosed artificial enzymes constructed from the apo form of heme proteins and iridium porphyrins that catalyze the insertion of carbenes into a C-H bond. Here, we postulated that the same type of Ir(Me)-PIX enzymes could catalyze the cyclopropanation of a broad range of alkenes with control of multiplemore » modes of selectivity. Here, we report the evolution of artificial enzymes that are highly active and highly stereoselective for the addition of carbenes to a wide range of alkenes. These enzymes catalyze the cyclopropanation of terminal and internal, activated and unactivated, electron-rich and electron-deficient, conjugated and nonconjugated alkenes. In particular, Ir(Me)-PIX enzymes derived from CYP119 catalyze highly enantio- and diastereoselective cyclopropanations of styrene with ±98% ee, > 70:1 dr, > 75% yield, and ~10,000 turnovers (TON), as well as 1,2-disubstituted styrenes with up to 99% ee, 35:1 dr, and 54% yield. Moreover, Ir(Me)-PIX enzymes catalyze cyclopropanation of internal, unactivated alkenes with up to 99% stereoselectivity, 76% yield, and 1300 TON. They also catalyze cyclopropanation of natural products with diastereoselectivities that are complementary to those attained with standard transition metal catalysts. Finally, Ir(Me)-PIX P450 variants react with substrate selectivity that is reminiscent of natural enzymes; they react preferentially with less reactive internal alkenes in the presence of more reactive terminal alkenes. Altogether, the studies reveal the suitability of Ir-containing P450s to combine the broad reactivity and substrate scope of transition metal catalysts with the exquisite selectivity of enzymes, generating catalysts that enable reactions to occur with levels and modes of activity and selectivity previously unattainable with natural enzymes or transition metal complexes alone.« less

Remote C-H Activation of Quinolines through Copper-Catalyzed Radical Cross-Coupling.

PubMed

Xu, Jun; Shen, Chao; Zhu, Xiaolei; Zhang, Pengfei; Ajitha, Manjaly J; Huang, Kuo-Wei; An, Zhongfu; Liu, Xiaogang

2016-03-18

Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a formidable challenge in organic chemistry. Herein, we report a novel approach to activating remote C-H bonds at the C5 position of 8-aminoquinoline through copper-catalyzed sulfonylation under mild conditions. Our strategy shows high conversion efficiency, a broad substrate scope, and good toleration with different functional groups. Furthermore, our mechanistic investigations suggest that a single-electron-transfer process plays a vital role in generating sulfonyl radicals and subsequently initiating C-S cross-coupling. Importantly, our copper-catalyzed remote functionalization protocol can be expanded for the construction of a variety of chemical bonds, including C-O, C-Br, C-N, C-C, and C-I. These findings provide a fundamental insight into the activation of remote C-H bonds, while offering new possibilities for rational design of drug molecules and optoelectronic materials requiring specific modification of functional groups. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A metalloenzyme-like catalytic system for the chemoselective oxidative cross-coupling of primary amines to imines under ambient conditions.

PubMed

Largeron, Martine; Fleury, Maurice-Bernard

2015-02-23

The direct oxidative cross-coupling of primary amines is a challenging transformation as homocoupling is usually preferred. We report herein the chemoselective preparation of cross-coupled imines through the synergistic combination of low loadings of Cu(II) metal-catalyst and o-iminoquinone organocatalyst under ambient conditions. This homogeneous cooperative catalytic system has been inspired by the reaction of copper amine oxidases, a family of metalloenzymes with quinone organic cofactors that mediate the selective oxidation of primary amines to aldehydes. After optimization, the desired cross-coupled imines are obtained in high yields with broad substrate scope through a transamination process that leads to the homocoupled imine intermediate, followed by dynamic transimination. The ability to carry out the reactions at room temperature and with ambient air, rather than molecular oxygen as the oxidant, and equimolar amounts of each coupling partner is particularly attractive from an environmentally viewpoint. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium

NASA Astrophysics Data System (ADS)

Feng, Zhang; Min, Qiao-Qiao; Fu, Xia-Ping; An, Lun; Zhang, Xingang

2017-09-01

Difluoromethylated aromatic compounds are of increasing importance in pharmaceuticals, agrochemicals and materials. Chlorodifluoromethane (ClCF2H), an inexpensive, abundant and widely used industrial raw material, represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF2H) from ClCF2H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF2H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate scope, including heteroarylboronic acids, and was used for difluoromethylation of a range of pharmaceuticals and biologically active compounds. Preliminary mechanistic studies revealed that a palladium difluorocarbene intermediate is involved in the reaction. Although numerous metal-difluorocarbene complexes have been prepared, the catalytic synthesis of difluoromethylated or difluoromethylenated compounds involving metal-difluorocarbene complexes has not received much attention. This new reaction therefore also opens the door to understand metal-difluorocarbene complex catalysed reactions.

Mn-Catalyzed Highly Efficient Aerobic Oxidative Hydroxyazidation of Olefins: A Direct Approach to β-Azido Alcohols.

PubMed

Sun, Xiang; Li, Xinyao; Song, Song; Zhu, Yuchao; Liang, Yu-Feng; Jiao, Ning

2015-05-13

An efficient Mn-catalyzed aerobic oxidative hydroxyazidation of olefins for synthesis of β-azido alcohols has been developed. The aerobic oxidative generation of azido radical employing air as the terminal oxidant is disclosed as the key process for this transformation. The reaction is appreciated by its broad substrate scope, inexpensive Mn-catalyst, high efficiency, easy operation under air, and mild conditions at room temperature. This chemistry provides a novel approach to high value-added β-azido alcohols, which are useful precursors of aziridines, β-amino alcohols, and other important N- and O-containing heterocyclic compounds. This chemistry also provides an unexpected approach to azido substituted cyclic peroxy alcohol esters. A DFT calculation indicates that Mn catalyst plays key dual roles as an efficient catalyst for the generation of azido radical and a stabilizer for peroxyl radical intermediate. Further calculation reasonably explains the proposed mechanism for the control of C-C bond cleavage or for the formation of β-azido alcohols.

A broadly applicable [18F]trifluoromethylation of aryl and heteroaryl iodides for PET imaging

NASA Astrophysics Data System (ADS)

Huiban, Mickael; Tredwell, Matthew; Mizuta, Satoshi; Wan, Zehong; Zhang, Xiaomin; Collier, Thomas Lee; Gouverneur, Véronique; Passchier, Jan

2013-11-01

Molecules labelled with the unnatural isotope fluorine-18 are used for positron emission tomography. Currently, this molecular imaging technology is not exploited at its full potential because many 18F-labelled probes are inaccessible or notoriously difficult to produce. Typical challenges associated with 18F radiochemistry are the short half-life of 18F (<2 h), the use of sub-stoichiometric amounts of 18F, relative to the precursor and other reagents, as well as the limited availability of parent 18F sources of suitable reactivity ([18F]F- and [18F]F2). There is a high-priority demand for general methods allowing access to [18F]CF3-substituted molecules for application in pharmaceutical discovery programmes. We report the development of a process for the late-stage [18F]trifluoromethylation of (hetero)arenes from [18F]fluoride using commercially available reagents and (hetero)aryl iodides. This [18F]CuCF3-based protocol benefits from a large substrate scope and is characterized by its operational simplicity.

EarthChem and SESAR: Data Resources and Interoperability for EarthScope Cyberinfrastructure

NASA Astrophysics Data System (ADS)

Lehnert, K. A.; Walker, D.; Block, K.; Vinay, S.; Ash, J.

2008-12-01

Data management within the EarthScope Cyberinfrastructure needs to pursue two goals in order to advance and maximize the broad scientific application and impact of the large volumes of observational data acquired by EarthScope facilities: (a) to provide access to all data acquired by EarthScope facilities, and to promote their use by broad audiences, and (b) to facilitate discovery of, access to, and integration of multi-disciplinary data sets that complement EarthScope data in support of EarthScope science. EarthChem and SESAR, the System for Earth Sample Registration, are two projects within the Geoinformatics for Geochemistry program that offer resources for EarthScope CI. EarthChem operates a data portal that currently provides access to >13 million analytical values for >600,000 samples, more than half of which are from North America, including data from the USGS and all data from the NAVDAT database, a web-accessible repository for age, chemical and isotopic data from Mesozoic and younger igneous rocks in western North America. The new EarthChem GEOCHRON database will house data collected in association with GeoEarthScope, storing and serving geochronological data submitted by participating facilities. The EarthChem Deep Lithosphere Dataset is a compilation of petrological data for mantle xenoliths, initiated in collaboration with GeoFrame to complement geophysical endeavors within EarthScope science. The EarthChem Geochemical Resource Library provides a home for geochemical and petrological data products and data sets. Parts of the digital data in EarthScope CI refer to physical samples such as drill cores, igneous rocks, or water and gas samples, collected, for example, by SAFOD or by EarthScope science projects and acquired through lab-based analysis. Management of sample-based data requires the use of global unique identifiers for samples, so that distributed data for individual samples generated in different labs and published in different papers can be unambiguously linked and integrated. SESAR operates a registry for Earth samples that assigns and administers the International GeoSample Numbers (IGSN) as a global unique identifier for samples. Registration of EarthScope samples with SESAR and use of the IGSN will ensure their unique identification in publications and data systems, thus facilitating interoperability among sample-based data relevant to EarthScope CI and globally. It will also make these samples visible to global audiences via the SESAR Global Sample Catalog.

Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

PubMed Central

Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

2012-01-01

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

Development and Comparison of the Substrate Scope of Pd-Catalysts for the Aerobic Oxidation of Alcohols

PubMed Central

Schultz, Mitchell J.; Hamilton, Steven S.; Jensen, David R.; Sigman, Matthew S.

2009-01-01

Three catalysts for aerobic oxidation of alcohols are discussed and the effectiveness of each is evaluated for allylic, benzylic, aliphatic, and functionalized alcohols. Additionally, chiral nonracemic substrates as well as chemoselective and diastereoselective oxidations are investigated. In this study, the most convenient system for the Pd-catalyzed aerobic oxidation of alcohols is Pd(OAc)2 in combination with triethylamine. This system functions effectively for the majority of alcohols tested and uses mild conditions (3 to 5 mol % of catalyst, room temperature). Pd(IiPr)(OAc)2(H2O) (1) also successfully oxidizes the majority of alcohols evaluated. This system has the advantage of significantly lowering catalyst loadings but requires higher temperatures (0.1 to 1 mol % of catalyst, 60 °C). A new catalyst is also disclosed, Pd(IiPr)(OPiv)2 (2). This catalyst operates under very mild conditions (1 mol %, room temperature, and air as the O2 source) but with a more limited substrate scope. PMID:15844968

Laccase versus Laccase-Like Multi-Copper Oxidase: A Comparative Study of Similar Enzymes with Diverse Substrate Spectra

PubMed Central

Reiss, Renate; Ihssen, Julian; Richter, Michael; Eichhorn, Eric; Schilling, Boris; Thöny-Meyer, Linda

2013-01-01

Laccases (EC 1.10.3.2) are multi-copper oxidases that catalyse the one-electron oxidation of a broad range of compounds including substituted phenols, arylamines and aromatic thiols to the corresponding radicals. Owing to their broad substrate range, copper-containing laccases are versatile biocatalysts, capable of oxidizing numerous natural and non-natural industry-relevant compounds, with water as the sole by-product. In the present study, 10 of the 11 multi-copper oxidases, hitherto considered to be laccases, from fungi, plant and bacterial origin were compared. A substrate screen of 91 natural and non-natural compounds was recorded and revealed a fairly broad but distinctive substrate spectrum amongst the enzymes. Even though the enzymes share conserved active site residues we found that the substrate ranges of the individual enzymes varied considerably. The EC classification is based on the type of chemical reaction performed and the actual name of the enzyme often refers to the physiological substrate. However, for the enzymes studied in this work such classification is not feasible, even more so as their prime substrates or natural functions are mainly unknown. The classification of multi-copper oxidases assigned as laccases remains a challenge. For the sake of simplicity we propose to introduce the term “laccase-like multi-copper oxidase” (LMCO) in addition to the term laccase that we use exclusively for the enzyme originally identified from the sap of the lacquer tree Rhus vernicifera. PMID:23755261

A scoping review of scoping reviews: advancing the approach and enhancing the consistency.

PubMed

Pham, Mai T; Rajić, Andrijana; Greig, Judy D; Sargeant, Jan M; Papadopoulos, Andrew; McEwen, Scott A

2014-12-01

The scoping review has become an increasingly popular approach for synthesizing research evidence. It is a relatively new approach for which a universal study definition or definitive procedure has not been established. The purpose of this scoping review was to provide an overview of scoping reviews in the literature. A scoping review was conducted using the Arksey and O'Malley framework. A search was conducted in four bibliographic databases and the gray literature to identify scoping review studies. Review selection and characterization were performed by two independent reviewers using pretested forms. The search identified 344 scoping reviews published from 1999 to October 2012. The reviews varied in terms of purpose, methodology, and detail of reporting. Nearly three-quarter of reviews (74.1%) addressed a health topic. Study completion times varied from 2 weeks to 20 months, and 51% utilized a published methodological framework. Quality assessment of included studies was infrequently performed (22.38%). Scoping reviews are a relatively new but increasingly common approach for mapping broad topics. Because of variability in their conduct, there is a need for their methodological standardization to ensure the utility and strength of evidence. © 2014 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd.

Proceedings from the Digital Innovation in Mental Health Conference, London, 2017

PubMed Central

Inkster, Becky

2018-01-01

Aims and Scope: The conference aims were two-fold: (1) to explore how digital technology is implemented into personalized and/or group mental health interventions and (2) to promote digital equality through developing culturally sensitive ways of bringing technological innovation to disadvantaged groups. A broad scope of perspectives were welcomed and encouraged, from lived experience, academic, clinical, media, the arts, policy-making, tech innovation, and other perspectives. PMID:29623001

Broadly tunable terahertz difference-frequency generation in quantum cascade lasers on silicon

NASA Astrophysics Data System (ADS)

Jung, Seungyong; Kim, Jae Hyun; Jiang, Yifan; Vijayraghavan, Karun; Belkin, Mikhail A.

2018-01-01

We report broadly tunable terahertz (THz) sources based on intracavity Cherenkov difference-frequency generation in quantum cascade lasers transfer-printed on high-resistivity silicon substrates. Spectral tuning from 1.3 to 4.3 THz was obtained from a 2-mm long laser chip using a modified Littrow external cavity setup. The THz power output and the midinfrared-to-THz conversion efficiency of the devices transferred on silicon are dramatically enhanced, compared with the devices on a native semi-insulating InP substrate. Enhancement is particularly significant at higher THz frequencies, where the tail of the Reststrahlen band results in a strong absorption of THz light in the InP substrate.

Unmanned Aircraft Systems Demand Forecast Study

NASA Technical Reports Server (NTRS)

Hackenberg, Davis L.

2017-01-01

UAS demand slides discuss the purpose, scope, and assumptions of the UAS Demand Forecast Study. It discusses some operational environments and market research study, this information is broad knowledge in the UAS community.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

PubMed Central

Feng, Pengju; Ngai, Ming-Yu

2016-01-01

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 °C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials. PMID:26862864

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

Goldsmith, Steven Y.; Spires, Shannon V.

There are currently two proposed standards for agent communication languages, namely, KQML (Finin, Lobrou, and Mayfield 1994) and the FIPA ACL. Neither standard has yet achieved primacy, and neither has been evaluated extensively in an open environment such as the Internet. It seems prudent therefore to design a general-purpose agent communications facility for new agent architectures that is flexible yet provides an architecture that accepts many different specializations. In this paper we exhibit the salient features of an agent communications architecture based on distributed metaobjects. This architecture captures design commitments at a metaobject level, leaving the base-level design and implementationmore » up to the agent developer. The scope of the metamodel is broad enough to accommodate many different communication protocols, interaction protocols, and knowledge sharing regimes through extensions to the metaobject framework. We conclude that with a powerful distributed object substrate that supports metaobject communications, a general framework can be developed that will effectively enable different approaches to agent communications in the same agent system. We have implemented a KQML-based communications protocol and have several special-purpose interaction protocols under development.« less

Substrate Specificity of Human Protein Arginine Methyltransferase 7 (PRMT7)

PubMed Central

Feng, You; Hadjikyriacou, Andrea; Clarke, Steven G.

2014-01-01

Protein arginine methyltransferase 7 (PRMT7) methylates arginine residues on various protein substrates and is involved in DNA transcription, RNA splicing, DNA repair, cell differentiation, and metastasis. The substrate sequences it recognizes in vivo and the enzymatic mechanism behind it, however, remain to be explored. Here we characterize methylation catalyzed by a bacterially expressed GST-tagged human PRMT7 fusion protein with a broad range of peptide and protein substrates. After confirming its type III activity generating only ω-NG-monomethylarginine and its distinct substrate specificity for RXR motifs surrounded by basic residues, we performed site-directed mutagenesis studies on this enzyme, revealing that two acidic residues within the double E loop, Asp-147 and Glu-149, modulate the substrate preference. Furthermore, altering a single acidic residue, Glu-478, on the C-terminal domain to glutamine nearly abolished the activity of the enzyme. Additionally, we demonstrate that PRMT7 has unusual temperature dependence and salt tolerance. These results provide a biochemical foundation to understanding the broad biological functions of PRMT7 in health and disease. PMID:25294873

Kinetic and dynamic kinetic resolution of secondary alcohols with ionic-surfactant-coated Burkholderia cepacia lipase: substrate scope and enantioselectivity.

PubMed

Kim, Cheolwoo; Lee, Jusuk; Cho, Jeonghun; Oh, Yeonock; Choi, Yoon Kyung; Choi, Eunjeong; Park, Jaiwook; Kim, Mahn-Joo

2013-03-15

Forty-four different secondary alcohols, which can be classified into several types (II-IX), were tested as the substrates of ionic surfactant-coated Burkholderia cepacia lipase (ISCBCL) to see its substrate scope and enantioselectivity in kinetic and dynamic kinetic resolution (KR and DKR). They include 6 boron-containing alcohols, 24 chiral propargyl alcohols, and 14 diarylmethanols. The results from the studies on KR indicate that ISCBCL accepted most of them with high enantioselectivity at ambient temperature and with useful to high enantioselectivity at elevated temperatures. In particular, ISCBCL displayed high enantioselectivity toward sterically demanding secondary alcohols (types VIII and IX) which have two bulky substituents at the hydroxymethine center. DKR reactions were performed by the combination of ISCBCL with a ruthenium-based racemization catalyst at 25-60 °C. Forty-one secondary alcohols were tested for DKR. About half of them were transformed into their acetates of high enantiopurity (>90% ee) with good yields (>80%). It is concluded that ISCBCL appears to be a superb enzyme for the KR and DKR of secondary alcohols.

A scoping review of scoping reviews: advancing the approach and enhancing the consistency

PubMed Central

Pham, Mai T; Rajić, Andrijana; Greig, Judy D; Sargeant, Jan M; Papadopoulos, Andrew; McEwen, Scott A

2014-01-01

Background The scoping review has become an increasingly popular approach for synthesizing research evidence. It is a relatively new approach for which a universal study definition or definitive procedure has not been established. The purpose of this scoping review was to provide an overview of scoping reviews in the literature. Methods A scoping review was conducted using the Arksey and O'Malley framework. A search was conducted in four bibliographic databases and the gray literature to identify scoping review studies. Review selection and characterization were performed by two independent reviewers using pretested forms. Results The search identified 344 scoping reviews published from 1999 to October 2012. The reviews varied in terms of purpose, methodology, and detail of reporting. Nearly three-quarter of reviews (74.1%) addressed a health topic. Study completion times varied from 2 weeks to 20 months, and 51% utilized a published methodological framework. Quality assessment of included studies was infrequently performed (22.38%). Conclusions Scoping reviews are a relatively new but increasingly common approach for mapping broad topics. Because of variability in their conduct, there is a need for their methodological standardization to ensure the utility and strength of evidence. © 2014 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. PMID:26052958

A Measure of the Broad Substrate Specificity of Enzymes Based on ‘Duplicate’ Catalytic Residues

PubMed Central

Chakraborty, Sandeep; Ásgeirsson, Bjarni; Rao, Basuthkar J.

2012-01-01

The ability of an enzyme to select and act upon a specific class of compounds with unerring precision and efficiency is an essential feature of life. Simultaneously, these enzymes often catalyze the reaction of a range of similar substrates of the same class, and also have promiscuous activities on unrelated substrates. Previously, we have established a methodology to quantify promiscuous activities in a wide range of proteins. In the current work, we quantitatively characterize the active site for the ability to catalyze distinct, yet related, substrates (BRASS). A protein with known structure and active site residues provides the framework for computing ‘duplicate’ residues, each of which results in slightly modified replicas of the active site scaffold. Such spatial congruence is supplemented by Finite difference Poisson Boltzmann analysis which filters out electrostatically unfavorable configurations. The congruent configurations are used to compute an index (BrassIndex), which reflects the broad substrate profile of the active site. We identify an acetylhydrolase and a methyltransferase as having the lowest and highest BrassIndex, respectively, from a set of non-homologous proteins extracted from the Catalytic Site Atlas. The acetylhydrolase, a regulatory enzyme, is known to be highly specific for platelet-activating factor. In the methyltransferase (PDB: 1QAM), various combinations of glycine (Gly38/40/42), asparagine (Asn101/11) and glutamic acid (Glu59/36) residues having similar spatial and electrostatic profiles with the specified scaffold (Gly38, Asn101 and Glu59) exemplifies the broad substrate profile such an active site may provide. ‘Duplicate’ residues identified by relaxing the spatial and/or electrostatic constraints can be the target of directed evolution methodologies, like saturation mutagenesis, for modulating the substrate specificity of proteins. PMID:23166637

Space transfer concepts and analysis for exploration missions

NASA Technical Reports Server (NTRS)

1991-01-01

A broad scoped and systematic study was made of space transfer concepts for human Lunar and Mars missions. Relevant space transportation studies were initiated to lead to further detailed activities in the following study period.

Direct Displacement of Alkoxy Groups of Vinylogous Esters by Grignard Reagents

PubMed Central

Brockway, Anthony J.; González-López, Marcos; Fettinger, James C.

2011-01-01

The direct displacement of alkoxy groups from the beta position of aromatic and unsaturated esters and ketones is described. The reaction is chemo- and regioselective, displaying wide substrate scope. PMID:21446670

A taxonomy of accountable care organizations for policy and practice.

PubMed

Shortell, Stephen M; Wu, Frances M; Lewis, Valerie A; Colla, Carrie H; Fisher, Elliott S

2014-12-01

To develop an exploratory taxonomy of Accountable Care Organizations (ACOs) to describe and understand early ACO development and to provide a basis for technical assistance and future evaluation of performance. Data from the National Survey of Accountable Care Organizations, fielded between October 2012 and May 2013, of 173 Medicare, Medicaid, and commercial payer ACOs. Drawing on resource dependence and institutional theory, we develop measures of eight attributes of ACOs such as size, scope of services offered, and the use of performance accountability mechanisms. Data are analyzed using a two-step cluster analysis approach that accounts for both continuous and categorical data. We identified a reliable and internally valid three-cluster solution: larger, integrated systems that offer a broad scope of services and frequently include one or more postacute facilities; smaller, physician-led practices, centered in primary care, and that possess a relatively high degree of physician performance management; and moderately sized, joint hospital-physician and coalition-led groups that offer a moderately broad scope of services with some involvement of postacute facilities. ACOs can be characterized into three distinct clusters. The taxonomy provides a framework for assessing performance, for targeting technical assistance, and for diagnosing potential antitrust violations. © Health Research and Educational Trust.

Aerobic scope measurements of fishes in an era of climate change: respirometry, relevance and recommendations.

PubMed

Clark, Timothy D; Sandblom, Erik; Jutfelt, Fredrik

2013-08-01

Measurements of aerobic scope [the difference between minimum and maximum oxygen consumption rate ( and , respectively)] are increasing in prevalence as a tool to address questions relating to fish ecology and the effects of climate change. However, there are underlying issues regarding the array of methods used to measure aerobic scope across studies and species. In an attempt to enhance quality control before the diversity of issues becomes too great to remedy, this paper outlines common techniques and pitfalls associated with measurements of , and aerobic scope across species and under different experimental conditions. Additionally, we provide a brief critique of the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis, a concept that is intricately dependent on aerobic scope measurements and is spreading wildly throughout the literature despite little evidence for its general applicability. It is the intention of this paper to encourage transparency and accuracy in future studies that measure the aerobic metabolism of fishes, and to highlight the fundamental issues with assuming broad relevance of the OCLTT hypothesis.

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... shall not: (1) Conduct tracer studies in the environment involving direct release of byproduct material... required; or (4) Add or cause the addition of byproduct material to any food, beverage, cosmetic, drug, or...

Direct displacement of alkoxy groups of vinylogous esters by Grignard reagents.

PubMed

Brockway, Anthony J; González-López, Marcos; Fettinger, James C; Shaw, Jared T

2011-05-06

The direct displacement of alkoxy groups from the β position of aromatic and unsaturated esters and ketones is described. The reaction is chemo- and regioselective, displaying wide substrate scope. © 2011 American Chemical Society

The Evolution of Pd0/PdII-Catalyzed Aromatic Fluorination

PubMed Central

2016-01-01

Conspectus Aromatic fluorides are prevalent in both agrochemical and pharmaceutical agents. However, methods for their rapid and general preparation from widely available starting materials are limited. Traditional approaches such as the Balz–Schiemann and Halex reactions require harsh conditions that limit functional group tolerance and substrate scope. The use of transition metals to affect C–F bond formation has provided some useful alternatives, but a broadly applicable method remains elusive. In contrast to the widespread use of Pd0/PdII catalysis for aryl–Z bond formation (Z = C, N, O), the analogous C–F cross-coupling process was unknown until fairly recently. In large part, this is due to the challenging Ar–F reductive elimination from Pd(II) intermediates. We have discovered that certain biaryl monophosphine ligands are uniquely capable of promoting this transformation. In this Account, we describe the discovery and development of a Pd-catalyzed C–F cross-coupling process and the systematic developments that made this once hypothetical reaction possible. Key to these developments was the discovery of an unusual in situ ligand modification process in which a molecule of substrate is incorporated into the ligand scaffold and the identity of the modifying group is crucial to the outcome of the reaction. This prompted the synthesis of a variety of “premodified” ligands and the identification of one that led to an expanded substrate scope, including (hetero)aryl triflates and bromides. Contemporaneously, a new Pd(0) precatalyst was also discovered that avoids the need to reduce Pd(II) in situ, a process that was often inefficient and led to the formation of byproducts. The use of inexpensive but hygroscopic sources of fluoride necessitates a reaction setup inside of a N2-filled glovebox, limiting the practicality of the method. Thus, a preformed wax capsule was designed to isolate the catalyst and reagents from the atmosphere and permit benchtop storage and setup. This new technology thus removes the requirement to employ a glovebox for the aromatic fluorination process and other air-sensitive protocols. In every catalyst system that we have studied to date, we observed the formation of regioisomeric fluoride side products. Through deuterium labeling studies it was found that they likely arise from a deprotonation event resulting in the formation of HF and a Pd–benzyne intermediate. Through an investigation of the mechanism of this undesired pathway, a new ligand was designed that substantially reduces the formation of the aryl fluoride regioisomer and even allows room-temperature Ar–F reductive elimination from a Pd(II) intermediate. PMID:27656765

Substrate specificity of human protein arginine methyltransferase 7 (PRMT7): the importance of acidic residues in the double E loop.

PubMed

Feng, You; Hadjikyriacou, Andrea; Clarke, Steven G

2014-11-21

Protein arginine methyltransferase 7 (PRMT7) methylates arginine residues on various protein substrates and is involved in DNA transcription, RNA splicing, DNA repair, cell differentiation, and metastasis. The substrate sequences it recognizes in vivo and the enzymatic mechanism behind it, however, remain to be explored. Here we characterize methylation catalyzed by a bacterially expressed GST-tagged human PRMT7 fusion protein with a broad range of peptide and protein substrates. After confirming its type III activity generating only ω-N(G)-monomethylarginine and its distinct substrate specificity for RXR motifs surrounded by basic residues, we performed site-directed mutagenesis studies on this enzyme, revealing that two acidic residues within the double E loop, Asp-147 and Glu-149, modulate the substrate preference. Furthermore, altering a single acidic residue, Glu-478, on the C-terminal domain to glutamine nearly abolished the activity of the enzyme. Additionally, we demonstrate that PRMT7 has unusual temperature dependence and salt tolerance. These results provide a biochemical foundation to understanding the broad biological functions of PRMT7 in health and disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Understanding the Broad Substrate Repertoire of Nitroreductase Based on Its Kinetic Mechanism*

PubMed Central

Pitsawong, Warintra; Hoben, John P.; Miller, Anne-Frances

2014-01-01

The oxygen-insensitive nitroreductase from Enterobacter cloacae (NR) catalyzes two-electron reduction of nitroaromatics to the corresponding nitroso compounds and, subsequently, to hydroxylamine products. NR has an unusually broad substrate repertoire, which may be related to protein dynamics (flexibility) and/or a simple non-selective kinetic mechanism. To investigate the possible role of mechanism in the broad substrate repertoire of NR, the kinetics of oxidation of NR by para-nitrobenzoic acid (p-NBA) were investigated using stopped-flow techniques at 4 °C. The results revealed a hyperbolic dependence on the p-NBA concentration with a limiting rate of 1.90 ± 0.09 s−1, indicating one-step binding before the flavin oxidation step. There is no evidence for a distinct binding step in which specificity might be enforced. The reduction of p-NBA is rate-limiting in steady-state turnover (1.7 ± 0.3 s−1). The pre-steady-state reduction kinetics of NR by NADH indicate that NADH reduces the enzyme with a rate constant of 700 ± 20 s−1 and a dissociation constant of 0.51 ± 0.04 mm. Thus, we demonstrate simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR. Finally, we tested the ability of NR to reduce para-hydroxylaminobenzoic acid, demonstrating that the corresponding amine does not accumulate to significant levels even under anaerobic conditions. Thus E. cloacae NR is not a good candidate for enzymatic production of aromatic amines. PMID:24706760

Catalytic mechanism of phenylacetone monooxygenases for non-native linear substrates.

PubMed

Carvalho, Alexandra T P; Dourado, Daniel F A R; Skvortsov, Timofey; de Abreu, Miguel; Ferguson, Lyndsey J; Quinn, Derek J; Moody, Thomas S; Huang, Meilan

2017-10-11

Phenylacetone monooxygenase (PAMO) is the most stable and thermo-tolerant member of the Baeyer-Villiger monooxygenase family, and therefore it is an ideal candidate for the synthesis of industrially relevant compounds. However, its limited substrate scope has largely limited its industrial applications. In the present work, we provide, for the first time, the catalytic mechanism of PAMO for the native substrate phenylacetone as well as for a linear non-native substrate 2-octanone, using molecular dynamics simulations, quantum mechanics and quantum mechanics/molecular mechanics calculations. We provide a theoretical basis for the preference of the enzyme for the native aromatic substrate over non-native linear substrates. Our study provides fundamental atomic-level insights that can be employed in the rational engineering of PAMO for wide applications in industrial biocatalysis, in particular, in the biotransformation of long-chain aliphatic oils into potential biodiesels.

Drugs and the Environment: Stewardship and Sustainability

EPA Science Inventory

This report represents the first-ever comprehensive examination of the broad scope of issues surrounding the topic of disposal of unwanted, unneeded, leftover medications from consumer use and the countless ways in which the introduction of active pharmaceutical ingredients (API...

Expedient Spall Repair Methods and Equipment for Airfield Pavements Preprint

DTIC Science & Technology

2009-08-01

placement (3). RESEACH OBJECTIVES AND SCOPE The objective of this research was to develop one or more methods that will allow field personnel to...cores were used to perform in-situ tensile pull-off tests to evaluate the bond between the repair material and the substrate. Also, a series of 4...inch diameters cores were cut, and direct shear tests were performed on the repair material/substrate interface. Finally, all spalls were trafficked for

Hyperpolarization of Nitrogen-15 Schiff Bases by Reversible Exchange Catalysis with para-Hydrogen.

PubMed

Logan, Angus W J; Theis, Thomas; Colell, Johannes F P; Warren, Warren S; Malcolmson, Steven J

2016-07-25

NMR with thermal polarization requires relatively concentrated samples, particularly for nuclei with low abundance and low gyromagnetic ratios, such as (15) N. We expand the substrate scope of SABRE, a recently introduced hyperpolarization method, to allow access to (15) N-enriched Schiff bases. These substrates show fractional (15) N polarization levels of up to 2 % while having only minimal (1) H enhancements. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of an aryl-alcohol oxidase from the plant saprophytic basidiomycete Coprinopsis cinerea with broad substrate specificity against aromatic alcohols.

PubMed

Tamaru, Yoshiaki; Umezawa, Kiwamu; Yoshida, Makoto

2018-07-01

The aim of the study was to obtain information about the enzymatic properties of aryl-alcohol oxidase from the plant saprophytic basidiomycete Coprinopsis cinerea (rCcAAO), which is classified into the auxiliary activities family 3 subfamily 2 (AA3_2). The gene encoding AAO from the plant saprophytic basidiomycete Coprinopsis cinerea (CcAAO) was cloned, and the recombinant CcAAO (rCcAAO) was heterologously expressed in the methylotrophic yeast Pichia pastoris. The purified rCcAAO showed significant activity not only against trans,trans-2,4-hexadien-1-ol but also against a broad range of aromatic alcohols including aromatic compounds that were reported to be poor substrates for known AAOs. Moreover, site-directed mutagenesis analysis demonstrated that mutants with substitutions from leucine to phenylalanine and tryptophan at position 416 exhibited decreases of activity for aromatic alcohols but still maintained the activity for trans,trans-2,4-hexadien-1-ol. Leucine 416 in CcAAO contributes to the broad substrate specificity against various aromatic alcohols, which is useful for the production of hydrogen peroxide using this enzyme.

Some Lactobacillus l-Lactate Dehydrogenases Exhibit Comparable Catalytic Activities for Pyruvate and Oxaloacetate

PubMed Central

Arai, Kazuhito; Kamata, Takeo; Uchikoba, Hiroyuki; Fushinobu, Shinya; Matsuzawa, Hiroshi; Taguchi, Hayao

2001-01-01

The nonallosteric and allosteric l-lactate dehydrogenases of Lactobacillus pentosus and L. casei, respectively, exhibited broad substrate specificities, giving virtually the same maximal reaction velocity and substrate Km values for pyruvate and oxaloacetate. Replacement of Pro101 with Asn reduced the activity of the L. pentosus enzyme toward these alternative substrates to a greater extent than the activity toward pyruvate. PMID:11114942

Breaking the Dogma of Aldolase Specificity: Simple Aliphatic Ketones and Aldehydes are Nucleophiles for Fructose-6-phosphate Aldolase.

PubMed

Roldán, Raquel; Sanchez-Moreno, Israel; Scheidt, Thomas; Hélaine, Virgil; Lemaire, Marielle; Parella, Teodor; Clapés, Pere; Fessner, Wolf-Dieter; Guérard-Hélaine, Christine

2017-04-11

d-Fructose-6-phosphate aldolase (FSA) was probed for extended nucleophile promiscuity by using a series of fluorogenic substrates to reveal retro-aldol activity. Four nucleophiles ethanal, propanone, butanone, and cyclopentanone were subsequently confirmed to be non-natural substrates in the synthesis direction using the wild-type enzyme and its D6H variant. This exceptional widening of the nucleophile substrate scope offers a rapid entry, in good yields and high stereoselectivity, to less oxygenated alkyl ketones and aldehydes, which was hitherto impossible. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper(II) carboxylate promoted intramolecular diamination of terminal alkenes: improved reaction conditions and expanded substrate scope.

PubMed

Zabawa, Thomas P; Chemler, Sherry R

2007-05-10

The copper(II) carboxylate promoted diamination reaction has been improved by the use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the less-polar solvent dichloroethane (DCE) to be used, and as a consequence, decomposition of less-reactive substrates could be avoided. High diastereoselectivity was observed in the synthesis of 2,5-disubstituted pyrrolidines. Ureas, bis(anilines), and alpha-amido pyrroles derived from 2-allylaniline could also participate in the diamination reaction.

Enantioselective functionalization of allylic C-H bonds following a strategy of functionalization and diversification.

PubMed

Sharma, Ankit; Hartwig, John F

2013-11-27

We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S, or C-C bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee ≤97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated.

A Taxonomy of Accountable Care Organizations for Policy and Practice

PubMed Central

Shortell, Stephen M; Wu, Frances M; Lewis, Valerie A; Colla, Carrie H; Fisher, Elliott S

2014-01-01

Objective To develop an exploratory taxonomy of Accountable Care Organizations (ACOs) to describe and understand early ACO development and to provide a basis for technical assistance and future evaluation of performance. Data Sources/Study Setting Data from the National Survey of Accountable Care Organizations, fielded between October 2012 and May 2013, of 173 Medicare, Medicaid, and commercial payer ACOs. Study Design Drawing on resource dependence and institutional theory, we develop measures of eight attributes of ACOs such as size, scope of services offered, and the use of performance accountability mechanisms. Data are analyzed using a two-step cluster analysis approach that accounts for both continuous and categorical data. Principal Findings We identified a reliable and internally valid three-cluster solution: larger, integrated systems that offer a broad scope of services and frequently include one or more postacute facilities; smaller, physician-led practices, centered in primary care, and that possess a relatively high degree of physician performance management; and moderately sized, joint hospital–physician and coalition-led groups that offer a moderately broad scope of services with some involvement of postacute facilities. Conclusions ACOs can be characterized into three distinct clusters. The taxonomy provides a framework for assessing performance, for targeting technical assistance, and for diagnosing potential antitrust violations. PMID:25251146

Homology modelling of Drosophila cytochrome P450 enzymes associated with insecticide resistance.

PubMed

Jones, Robert T; Bakker, Saskia E; Stone, Deborah; Shuttleworth, Sally N; Boundy, Sam; McCart, Caroline; Daborn, Phillip J; ffrench-Constant, Richard H; van den Elsen, Jean M H

2010-10-01

Overexpression of the cytochrome P450 gene Cyp6g1 confers resistance against DDT and a broad range of other insecticides in Drosophila melanogaster Meig. In the absence of crystal structures of CYP6G1 or complexes with its substrates, structural studies rely on homology modelling and ligand docking to understand P450-substrate interactions. Homology models are presented for CYP6G1, a P450 associated with resistance to DDT and neonicotinoids, and two other enzymes associated with insecticide resistance in D. melanogaster, CYP12D1 and CYP6A2. The models are based on a template of the X-ray structure of the phylogenetically related human CYP3A4, which is known for its broad substrate specificity. The model of CYP6G1 has a much smaller active site cavity than the template. The cavity is also 'V'-shaped and is lined with hydrophobic residues, showing high shape and chemical complementarity with the molecular characteristics of DDT. Comparison of the DDT-CYP6G1 complex and a non-resistant CYP6A2 homology model implies that tight-fit recognition of this insecticide is important in CYP6G1. The active site can accommodate differently shaped substrates ranging from imidacloprid to malathion but not the pyrethroids permethrin and cyfluthrin. The CYP6G1, CYP12D1 and CYP6A2 homology models can provide a structural insight into insecticide resistance in flies overexpressing P450 enzymes with broad substrate specificities.

12 CFR 368.100 - Obligations concerning institutional customers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... securities market, a market with a particularly broad institutional component. Accordingly, the FDIC believes it is appropriate to provide further guidance to banks on their suitability obligations when making... important considerations in determining the scope of a bank's suitability obligations in making...

12 CFR 368.100 - Obligations concerning institutional customers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... securities market, a market with a particularly broad institutional component. Accordingly, the FDIC believes it is appropriate to provide further guidance to banks on their suitability obligations when making... important considerations in determining the scope of a bank's suitability obligations in making...

Amphibian malformations

USGS Publications Warehouse

,

1998-01-01

Frog malformations have been reported from 42 states. The broad geographic distribution of these malformations warrants national attention. Scientists at the USGS National Wildlife Health Center in Madison, Wisconsin are studying this problem in an effort to document its scope and to determine the causes of the observed malformations.

The Opportunity for High-Performance Biomaterials from Methane

PubMed Central

Strong, Peter James; Laycock, Bronwyn; Mahamud, Syarifah Nuraqmar Syed; Jensen, Paul Douglas; Lant, Paul Andrew; Tyson, Gene; Pratt, Steven

2016-01-01

Polyhydroxyalkanoate (PHA) biopolymers are widely recognised as outstanding candidates to replace conventional petroleum-derived polymers. Their mechanical properties are good and can be tailored through copolymer composition, they are biodegradable, and unlike many alternatives, they do not rely on oil-based feedstocks. Further, they are the only commodity polymer that can be synthesised intracellularly, ensuring stereoregularity and high molecular weight. However, despite offering enormous potential for many years, they are still not making a significant impact. This is broadly because commercial uptake has been limited by variable performance (inconsistent polymer properties) and high production costs of the raw polymer. Additionally, the main type of PHA produced naturally is poly-3-hydroxybutyrate (PHB), which has limited scope due to its brittle nature and low thermal stability, as well as its tendency to embrittle over time. Production cost is strongly impacted by the type of the feedstock used. In this article we consider: the production of PHAs from methanotrophs using methane as a cost-effective substrate; the use of mixed cultures, as opposed to pure strains; and strategies to generate a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer (PHBV), which has more desirable qualities such as toughness and elasticity. PMID:27681905

The Opportunity for High-Performance Biomaterials from Methane.

PubMed

Strong, Peter James; Laycock, Bronwyn; Mahamud, Syarifah Nuraqmar Syed; Jensen, Paul Douglas; Lant, Paul Andrew; Tyson, Gene; Pratt, Steven

2016-02-03

Polyhydroxyalkanoate (PHA) biopolymers are widely recognised as outstanding candidates to replace conventional petroleum-derived polymers. Their mechanical properties are good and can be tailored through copolymer composition, they are biodegradable, and unlike many alternatives, they do not rely on oil-based feedstocks. Further, they are the only commodity polymer that can be synthesised intracellularly, ensuring stereoregularity and high molecular weight. However, despite offering enormous potential for many years, they are still not making a significant impact. This is broadly because commercial uptake has been limited by variable performance (inconsistent polymer properties) and high production costs of the raw polymer. Additionally, the main type of PHA produced naturally is poly-3-hydroxybutyrate (PHB), which has limited scope due to its brittle nature and low thermal stability, as well as its tendency to embrittle over time. Production cost is strongly impacted by the type of the feedstock used. In this article we consider: the production of PHAs from methanotrophs using methane as a cost-effective substrate; the use of mixed cultures, as opposed to pure strains; and strategies to generate a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer (PHBV), which has more desirable qualities such as toughness and elasticity.

Influence of Molecular Shape on Molecular Orientation and Stability of Vapor-Deposited Organic Semiconductors

NASA Astrophysics Data System (ADS)

Walters, Diane M.; Johnson, Noah D.; Ediger, M. D.

Physical vapor deposition is commonly used to prepare active layers in organic electronics. Recently, it has been shown that molecular orientation and packing can be tuned by changing the substrate temperature during deposition, while still producing macroscopically homogeneous films. These amorphous materials can be highly anisotropic when prepared with low substrate temperatures, and they can exhibit exceptional kinetic stability; films retain their favorable packing when heated to high temperatures. Here, we study the influence of molecular shape on molecular orientation and stability. We investigate disc-shaped molecules, such as TCTA and m-MTDATA, nearly spherical molecules, such as Alq3, and linear molecules covering a broad range of aspect ratios, such as p-TTP and BSB-Cz. Disc-shaped molecules have preferential horizontal orientation when deposited at low substrate temperatures, and their orientation can be tuned by changing the substrate temperature. Alq3 forms stable, amorphous films that are optically isotropic when vapor deposited over a broad range of substrate temperatures. This work may guide the choice of material and deposition conditions for vapor-deposited films used in organic electronics and allow for more efficient devices to be fabricated.

Incorporating pest management into the design of multiple goal-oriented cropping systems

USDA-ARS?s Scientific Manuscript database

Suggestions are offered to facilitate efforts to incorporate pest management goals into the design of crop production systems. The scope of research programs should be expanded to ensure broad multidisciplinary cooperation. Inclusion of farmers, production specialists and researchers from discipli...

Introduction to Special Issue on Education and Health.

ERIC Educational Resources Information Center

Kiker, B. F.

1998-01-01

Introduces a special issue devoted to education-health linkages. The scope of coverage is quite broad. Papers treat education's connections with specific health-related behaviors, full-time employees' health insurance coverage, medical care/lifestyle choices, nurses' wage profiles, low birthweight children's capabilities, smoking decisions,…

A Different Kind of Web-Based Knowledge Management: The DTRA Acquisition ToolBook

DTIC Science & Technology

2008-12-01

Reimbursement Order MIPR: Military Interdepartmental Purchase Request PWS: Performance Work Statement SOO: Statement of Objectives SOW: Scope of Work Figure 1...Competitive BAA: Broad Agency Announcement IACRO: Inter-Agency Cost Reimbur ement Order MIPR: Military Interdepartmental Purchas Request PWS

76 FR 44603 - Intent To Prepare an Environmental Assessment and Scoping for an Evaluation of Alternatives To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... Impact Statement (GMP/EIS) for the Memorial in October 2009 and the record of Decision (ROD) was signed.... The 2009 GMP/EIS provided a broad analysis of potential impacts of the expansion of programs and...

The Staphylococcus aureus leucine aminopeptidase LAP is localized to the bacterial cytosol and demonstrates a broad substrate range that extends beyond leucine

PubMed Central

Carroll, Ronan K.; Veillard, Florian; Gagne, Danielle T.; Lindenmuth, Jarrod M.; Poreba, Marcin; Drag, Marcin; Potempa, Jan; Shaw, Lindsey N.

2013-01-01

Staphylococcus aureus is a potent pathogen of humans exhibiting a broad disease range, in part, due to an extensive repertoire of secreted virulence factors, including proteases. Recently, we identified the first example of an intracellular protease (leucine aminopeptidase - LAP) that is required for virulence in S. aureus. Disruption of pepZ, the gene encoding LAP, had no affect on the growth rate of bacteria, however, in systemic and localized infection models the pepZ mutant was significantly attenuated in virulence. Recently, a contradictory report has been published, suggesting that LAP is an extracellular enzyme and it is required for growth in S. aureus. Here, we investigate these results and confirm our previous findings that LAP is localized to the bacterial cytosol and is not required for growth. In addition we conduct a biochemical investigation of purified recombinant LAP identifying optimal conditions for enzymatic activity and substrate preference for hydrolysis. Our results show that LAP has a broad substrate range, including activity against the dipeptide cysteine-glycine and that leucine is not the primary target of LAP. PMID:23241672

Biocatalytic site- and enantioselective oxidative dearomatization of phenols

NASA Astrophysics Data System (ADS)

Baker Dockrey, Summer A.; Lukowski, April L.; Becker, Marc R.; Narayan, Alison R. H.

2018-02-01

The biocatalytic transformations used by chemists are often restricted to simple functional-group interconversions. In contrast, nature has developed complexity-generating biocatalytic reactions within natural product pathways. These sophisticated catalysts are rarely employed by chemists, because the substrate scope, selectivity and robustness of these catalysts are unknown. Our strategy to bridge the gap between the biosynthesis and synthetic chemistry communities leverages the diversity of catalysts available within natural product pathways. Here we show that, starting from a suite of biosynthetic enzymes, catalysts with complementary substrate scope as well as selectivity can be identified. This strategy has been applied to the oxidative dearomatization of phenols, a chemical transformation that rapidly builds molecular complexity from simple starting materials and cannot be accomplished with high selectivity using existing catalytic methods. Using enzymes from biosynthetic pathways, we have successfully developed a method to produce ortho-quinol products with controlled site- and stereoselectivity. Furthermore, we have capitalized on the scalability and robustness of this method in gram-scale reactions as well as multi-enzyme and chemoenzymatic cascades.

Expanding the substrate scope of chitooligosaccharide oxidase from Fusarium graminearum by structure-inspired mutagenesis.

PubMed

Ferrari, Alessandro R; Lee, Misun; Fraaije, Marco W

2015-06-01

Chitooligosaccharide oxidase from Fusarium graminearum (ChitO) oxidizes N-acetyl-D-glucosamine (GlcNAc) and its oligomers with high efficiency at the C1-hydroxyl moiety while it shows poor or no activity with other carbohydrates. By sequence and structural comparison with other known carbohydrate oxidases (glucooligosaccharide oxidase from Acremonium strictum and lactose oxidase from Microdochium nivale) eleven mutants were designed to redirect the catalytic scope of ChitO for improved oxidation of lactose, cellobiose and maltose. The catalytic properties of the most interesting mutants were further improved by combining single mutations. This has resulted in the creation of a set of ChitO variants that display totally different substrate tolerances. One ChitO variant shows a dramatic improvement in catalytic efficiency towards oxidation of glucose, cellobiose, lactose, and maltose. We also describe a ChitO variant with the highest catalytic efficiency in GlcNAc oxidation so far reported in the literature. © 2015 Wiley Periodicals, Inc.

X-ray structures of the Pseudomonas cichorii D-tagatose 3-epimerase mutant form C66S recognizing deoxy sugars as substrates.

PubMed

Yoshida, Hiromi; Yoshihara, Akihide; Ishii, Tomohiko; Izumori, Ken; Kamitori, Shigehiro

2016-12-01

Pseudomonas cichorii D-tagatose 3-epimerase (PcDTE), which has a broad substrate specificity, efficiently catalyzes the epimerization of not only D-tagatose to D-sorbose but also D-fructose to D-psicose (D-allulose) and also recognizes the deoxy sugars as substrates. In an attempt to elucidate the substrate recognition and catalytic reaction mechanisms of PcDTE for deoxy sugars, the X-ray structures of the PcDTE mutant form with the replacement of Cys66 by Ser (PcDTE_C66S) in complexes with deoxy sugars were determined. These X-ray structures showed that substrate recognition by the enzyme at the 1-, 2-, and 3-positions is responsible for enzymatic activity and that substrate-enzyme interactions at the 4-, 5-, and 6-positions are not essential for the catalytic reaction of the enzyme leading to the broad substrate specificity of PcDTE. They also showed that the epimerization site of 1-deoxy 3-keto D-galactitol is shifted from C3 to C4 and that 1-deoxy sugars may bind to the catalytic site in the inhibitor-binding mode. The hydrophobic groove that acts as an accessible surface for substrate binding is formed through the dimerization of PcDTE. In PcDTE_C66S/deoxy sugar complex structures, bound ligand molecules in both the linear and ring forms were detected in the hydrophobic groove, while bound ligand molecules in the catalytic site were in the linear form. This result suggests that the sugar-ring opening of a substrate may occur in the hydrophobic groove and also that the narrow channel of the passageway to the catalytic site allows a substrate in the linear form to pass through.

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

Hung, Cheng-Hung

The main objective of this project was to develop a low-cost integrated substrate for rigid OLED solid-state lighting produced at a manufacturing scale. The integrated substrates could include combinations of soda lime glass substrate, light extraction layer, and an anode layer (i.e., Transparent Conductive Oxide, TCO). Over the 3 + year course of the project, the scope of work was revised to focus on the development of a glass substrates with an internal light extraction (IEL) layer. A manufacturing-scale float glass on-line particle embedding process capable of producing an IEL glass substrate having a thickness of less than 1.7mm andmore » an area larger than 500mm x 400mm was demonstrated. Substrates measuring 470mm x 370mm were used in the OLED manufacturing process for fabricating OLED lighting panels in single pixel devices as large as 120.5mm x 120.5mm. The measured light extraction efficiency (calculated as external quantum efficiency, EQE) for on-line produced IEL samples (>50%) met the project’s initial goal.« less

An Educational System for the Seventies.

ERIC Educational Resources Information Center

Shelly (E.F.) and Co., New York, NY.

An Educational System for the Seventies (ES '70) is a research and demonstration program representing a broad scope of activity that cuts across every aspect of education. Four main categories of activities comprise the substance of the current effort: staff development, instructional managment and career guidance, school management, and…

Science Facilities Bibliography.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC.

A bibliographic collection on science buildings and facilities is cited with many different reference sources for those concerned with the design, planning, and layout of science facilities. References are given covering a broad scope of information on--(1) physical plant planning, (2) management and safety, (3) building type studies, (4) design…

Learning Systems in Post-Statutory Education

ERIC Educational Resources Information Center

Catherall, Paul

2008-01-01

This article examines the broad scope of systemised learning (e-learning) in post-statutory education. Issues for discussion include the origins and forms of learning systems, including technical and educational concepts and approaches, such as distributed and collaborative learning. The VLE (Virtual Learning Environment) is defined as the…

Constructing Ideologies and Valuing Nature in Two Eco-Cities

EPA Science Inventory

Eco-city development is flourishing as the scale and scope of environmental damage becomes increasingly clear. While there are no standard criteria of what constitutes an eco-city, the term has been increasingly applied to a number of different projects that straddle a broad arra...

Polydiacetylenes: An Ideal Color System for Teaching Polymer Science.

ERIC Educational Resources Information Center

Patel, Gordhan N.; Yang, Nan-Loh

1983-01-01

Describes 14 experiments that illustrate, via color changes, a broad scope of fundamental phenomena in polymer science. The experiments, suitable for high school through graduate level, require only test tubes, filter paper, heat source (hot plate or hair drier), and ultra-violet light source. (JN)

36 CFR 1225.12 - How are records schedules developed?

Code of Federal Regulations, 2010 CFR

2010-07-01

... activity to identify records series, systems, and nonrecord materials. (c) Determine the appropriate scope of the records schedule items, e.g., individual series/system component, work process, group of related work processes, or broad program area. (d) Evaluate the period of time the agency needs each...

36 CFR 1225.12 - How are records schedules developed?

Code of Federal Regulations, 2011 CFR

2011-07-01

... activity to identify records series, systems, and nonrecord materials. (c) Determine the appropriate scope of the records schedule items, e.g., individual series/system component, work process, group of related work processes, or broad program area. (d) Evaluate the period of time the agency needs each...

36 CFR 1225.12 - How are records schedules developed?

Code of Federal Regulations, 2012 CFR

2012-07-01

... activity to identify records series, systems, and nonrecord materials. (c) Determine the appropriate scope of the records schedule items, e.g., individual series/system component, work process, group of related work processes, or broad program area. (d) Evaluate the period of time the agency needs each...

Science and Engineering Indicators 2010

ERIC Educational Resources Information Center

National Science Foundation, 2010

2010-01-01

The Science Indicators series was designed to provide a broad base of quantitative information about U.S. science, engineering, and technology for use by policymakers, researchers, and the general public. "Science and Engineering Indicators 2010" contains analyses of key aspects of the scope, quality, and vitality of the Nation's science…

Development of glycosynthases with broad glycan specificity for the efficient glyco-remodeling of antibodies.

PubMed

Shivatare, Sachin S; Huang, Lin-Ya; Zeng, Yi-Fang; Liao, Jung-Yu; You, Tsai-Hong; Wang, Shi-Yun; Cheng, Ting; Chiu, Chih-Wei; Chao, Ping; Chen, Li-Tzu; Tsai, Tsung-I; Huang, Chiu-Chen; Wu, Chung-Yi; Lin, Nan-Horng; Wong, Chi-Huey

2018-06-12

The first systematic investigation of the effect of high mannose, hybrid, and bi- and tri-antennary complex type glycans on the effector functions of antibodies was achieved by the discovery of novel Endo-S2 mutants generated by site-directed mutagenesis as glycosynthases with broad substrate specificity.

Highly effective copper-mediated gem-difluoromethylenation of arylboronic acids.

PubMed

Ma, Guobin; Wan, Wen; Hu, Qingyang; Jiang, Haizhen; Wang, Jing; Zhu, Shizheng; Hao, Jian

2014-07-18

A copper-mediated gem-difluoromethylenation of aryl, heteroaryl and vinyl boronic acids with bromodifluoromethylated oxazole or thiazole derivatives has been developed. This novel reaction showed an excellent functional group tolerance and wide substrate scope, providing facile access to practical application in drug discovery and development.

Synthesis of 2‐Alkynoates by Palladium(II)‐Catalyzed Oxidative Carbonylation of Terminal Alkynes and Alcohols

PubMed Central

Cao, Qun; Hughes, N. Louise

2016-01-01

Abstract A homogeneous PdII catalyst, utilizing a simple and inexpensive amine ligand (TMEDA), allows 2‐alkynoates to be prepared in high yields by an oxidative carbonylation of terminal alkynes and alcohols. The catalyst system overcomes many of the limitations of previous palladium carbonylation catalysts. It has an increased substrate scope, avoids large excesses of alcohol substrate and uses a desirable solvent. The catalyst employs oxygen as the terminal oxidant and can be operated under safer gas mixtures. PMID:27305489

Copper(II) Carboxylate Promoted Intramolecular Diamination of Terminal Alkenes: Improved Reaction Conditions and Expanded Substrate Scope

PubMed Central

Zabawa, Thomas P.

2008-01-01

The copper(II) carboxylate promoted diamination reaction has been improved by the use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the less polar solvent, dichloroethane (DCE) to be used, and as a consequence, decomposition of less reactive substrates could be avoided. High diastereoselectivity was observed in the synthesis of 2,5-disubstituted pyrrolidines. Ureas, bis(anilines) and α-amido pyrroles derived from 2-allylaniline could also participate in the diamination reaction. PMID:17447781

Voltage- and temperature- controlled LC:PDMS waveguide channels

NASA Astrophysics Data System (ADS)

Rutkowska, Katarzyna A.; Asquini, Rita; d'Alessandro, Antonio

2017-08-01

In this paper, we present our studies on electrical and thermal tuning of light propagation in waveguide channels, made for the scope from a polydimethylsiloxane (PDMS) substrate infiltrated with nematic liquid crystal (LC). We demonstrated, via numerical simulations, the changes of the waveguide optical parameters when solicited by temperature changes or electric fields. Moreover, the paper goes through the fabrication process of a waveguide channel sample and its characterization, as well as some preliminary experimental trials of sputtering indium tin oxide (ITO) and chromium layers on PDMS substrate to obtain flat electrodes.

C-431 B -- Scope document

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

Hollister, H.L.

1951-06-01

This document describes the scope of the C-431-B Reactor Production Facility. In dealing with the broad phases of the project, it includes the Sections ``A`` (Scope Modifications) of the approved Design Criteria, modified to ensure correctness to date. Location of the facility has been set as shown on the site map in HDC-2101, designated site number one. Included in Project C-431-B are the 105-C Building, including within that building facilities previously located in the 1608 Building, a contaminated effluent crib adjacent to 105-C, and gas facilities using the 115-B Building interconnected with 105-C. Also included are an oil shed, amore » thimble storage cave, a badge house, and an exclusion fence. Building services and process lines will be considered part of the project to a location nominally five feet outside of 105-C.« less

37 CFR 202.3 - Registration of copyright.

Code of Federal Regulations, 2010 CFR

2010-07-01

... separate continuation sheet, CON 2, must be used to list contents titles, i.e., titles of independent works... on current events, either local, national, or international in scope. A newspaper contains a broad... other copyright claimant of a work, or the owner of any exclusive right in a work, or the duly...

Science & Engineering Indicators. National Science Board. NSB 14-01

ERIC Educational Resources Information Center

National Science Foundation, 2014

2014-01-01

The "Science and Engineering Indicators" series was designed to provide a broad base of quantitative information about U.S. science, engineering, and technology for use by policymakers, researchers, and the general public. "Science and Engineering Indicators 2014" contains analyses of key aspects of the scope, quality, and…

Staffing UK University Campuses Overseas: Lessons from MNE Practice

ERIC Educational Resources Information Center

Salt, John; Wood, Peter

2014-01-01

This article suggests that as their internal labor markets become more multinational in scope, UK universities may acquire similar staffing characteristics to commercial multinational enterprises (MNEs). Comparing evidence from four UK universities with several surveys of MNEs it concludes that, although there are broad similarities in the…

28 CFR 13.2 - Policy.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Policy. 13.2 Section 13.2 Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS REGULATIONS § 13.2... material or atomic weapons. The broad scope of this program is to help guard against the loss or diversion...

28 CFR 13.2 - Policy.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Policy. 13.2 Section 13.2 Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS REGULATIONS § 13.2... material or atomic weapons. The broad scope of this program is to help guard against the loss or diversion...

28 CFR 13.2 - Policy.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Policy. 13.2 Section 13.2 Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS REGULATIONS § 13.2... material or atomic weapons. The broad scope of this program is to help guard against the loss or diversion...

28 CFR 13.2 - Policy.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Policy. 13.2 Section 13.2 Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS REGULATIONS § 13.2... material or atomic weapons. The broad scope of this program is to help guard against the loss or diversion...

28 CFR 13.2 - Policy.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Policy. 13.2 Section 13.2 Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS REGULATIONS § 13.2... material or atomic weapons. The broad scope of this program is to help guard against the loss or diversion...

Convergent surface water distributions in U.S. cities

Treesearch

M.K. Steele; J.B. Heffernan; N. Bettez; J. Cavender-Bares; P.M. Groffman; J.M. Grove; S. Hall; S.E. Hobbie; K. Larson; J.L. Morse; C. Neill; K.C. Nelson; J. O' Neil-Dunne; L. Ogden; D.E. Pataki; C. Polsky; R. Roy Chowdhury

2014-01-01

Earth's surface is rapidly urbanizing, resulting in dramatic changes in the abundance, distribution and character of surface water features in urban landscapes. However, the scope and consequences of surface water redistribution at broad spatial scales are not well understood. We hypothesized that urbanization would lead to convergent surface water abundance and...

Space transfer concepts and analyses for exploration missions: Technical directive 10

NASA Technical Reports Server (NTRS)

Woodcock, Gordon R.

1992-01-01

The current technical effort is part of the third phase of a broad-scoped and systematic study of space transfer concepts for human lunar and Mars missions. The study addressed issues that were raised during the previous phases but specifically on launch vehicle size trades and MEV options.

Air Age Education. Aviation Career Awareness Program.

ERIC Educational Resources Information Center

Petrie, Edwin T.

Described is a program designed to help introduce the broad scope of occupational careers available with general aviation. The program is designed to aid the teacher in presenting the basic principles of flight, essential facts about general aviation as well as its occupational opportunities. It replaces previous elementary student materials, and…

School, Work and Family Planning. Interim Impacts in Project Redirection.

ERIC Educational Resources Information Center

Polit, Denise F.; And Others

Project Redirection was designed to help pregnant and parenting adolescents progress toward eventual self-sufficiency by linking them with community agencies and volunteers at four geographically and ethnically diverse sites in the United States. Distinctive features of the program include: (1) a broad scope of services including employability…

Integrated bird conservation web site in the United States

Treesearch

Roxanne Bogart; Chris Eberly; Elizabeth Martin

2005-01-01

In working towards a vision of integrated bird conservation, scientists, conservationists, land managers, and administrators are faced with a variety of scientific, managerial, administrative, and logistical challenges and complexities. The broad scope of integrated bird conservation requires organizations to work together to conserve birds across taxonomic groups,...

Catalytic asymmetric conjugate addition of Grignard reagents to chromones.

PubMed

Vila, Carlos; Hornillos, Valentín; Fañanás-Mastral, Martín; Feringa, Ben L

2013-07-07

A highly regio- and enantioselective copper catalysed direct conjugate addition of Grignard reagents to chromones has been developed taking advantage of the reduced reactivity of the resulting magnesium enolates. This methodology tolerates a broad scope of alkyl Grignards including secondary alkyl magnesium reagents as well as functionalised chromones.

48 CFR 26.203 - Transition of work.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Transition of work. 26.203... PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Disaster or Emergency Assistance Activities 26.203 Transition of work... emergency response work to local firms (e.g., unnecessarily broad scopes of work or long periods of...

48 CFR 26.203 - Transition of work.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Transition of work. 26.203... PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Disaster or Emergency Assistance Activities 26.203 Transition of work... emergency response work to local firms (e.g., unnecessarily broad scopes of work or long periods of...

77 FR 50523 - Texas Mid-Coast National Wildlife Refuge Complex, Brazoria, Fort Bend, Matagorda, and Wharton...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... principles of fish and wildlife management, conservation, legal mandates, and our policies. In addition to outlining broad management direction on conserving wildlife and their habitats, CCPs identify wildlife... past management, future management, and issues common to both agencies. Additional public scoping for...

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... bachelor level, or equivalent training and experience, in the physical or biological sciences or in..., radiation detection instrumentation, and biological hazards of exposure to radiation appropriate to the type... controls and provisions relating to procurement of byproduct material, procedures, record keeping, material...

10 CFR 33.23 - Criminal penalties.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Criminal penalties. 33.23 Section 33.23 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.23 Criminal penalties. (a) Section 223 of the Atomic Energy Act of 1954, as amended, provides for criminal...

10 CFR 33.23 - Criminal penalties.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Criminal penalties. 33.23 Section 33.23 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.23 Criminal penalties. (a) Section 223 of the Atomic Energy Act of 1954, as amended, provides for criminal...

10 CFR 33.21 - Violations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Violations. 33.21 Section 33.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.21 Violations. (a) The Commission may obtain an injunction or other court order to prevent a violation of the provisions...

10 CFR 33.21 - Violations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Violations. 33.21 Section 33.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.21 Violations. (a) The Commission may obtain an injunction or other court order to prevent a violation of the provisions...

10 CFR 33.23 - Criminal penalties.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Criminal penalties. 33.23 Section 33.23 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.23 Criminal penalties. (a) Section 223 of the Atomic Energy Act of 1954, as amended, provides for criminal...

10 CFR 33.21 - Violations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Violations. 33.21 Section 33.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.21 Violations. (a) The Commission may obtain an injunction or other court order to prevent a violation of the provisions...

10 CFR 33.23 - Criminal penalties.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Criminal penalties. 33.23 Section 33.23 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.23 Criminal penalties. (a) Section 223 of the Atomic Energy Act of 1954, as amended, provides for criminal...

10 CFR 33.21 - Violations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Violations. 33.21 Section 33.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.21 Violations. (a) The Commission may obtain an injunction or other court order to prevent a violation of the provisions...

10 CFR 33.23 - Criminal penalties.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Criminal penalties. 33.23 Section 33.23 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.23 Criminal penalties. (a) Section 223 of the Atomic Energy Act of 1954, as amended, provides for criminal...

10 CFR 33.21 - Violations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Violations. 33.21 Section 33.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Violations § 33.21 Violations. (a) The Commission may obtain an injunction or other court order to prevent a violation of the provisions...

7 CFR 1955.65 - Management of inventory and/or custodial real property.

Code of Federal Regulations, 2014 CFR

2014-01-01

... arrangement contracts to obtain services for more than one property; to a broad-scope management contract with... 7 Agriculture 14 2014-01-01 2014-01-01 false Management of inventory and/or custodial real... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) PROPERTY MANAGEMENT...

7 CFR 1955.65 - Management of inventory and/or custodial real property.

Code of Federal Regulations, 2012 CFR

2012-01-01

... arrangement contracts to obtain services for more than one property; to a broad-scope management contract with... 7 Agriculture 14 2012-01-01 2012-01-01 false Management of inventory and/or custodial real... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) PROPERTY MANAGEMENT...

7 CFR 1955.65 - Management of inventory and/or custodial real property.

Code of Federal Regulations, 2010 CFR

2010-01-01

... for more than one property; to a broad-scope management contract with a real estate broker or... 7 Agriculture 14 2010-01-01 2009-01-01 true Management of inventory and/or custodial real property..., DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) PROPERTY MANAGEMENT Management of...

7 CFR 1955.65 - Management of inventory and/or custodial real property.

Code of Federal Regulations, 2011 CFR

2011-01-01

... arrangement contracts to obtain services for more than one property; to a broad-scope management contract with... 7 Agriculture 14 2011-01-01 2011-01-01 false Management of inventory and/or custodial real... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) PROPERTY MANAGEMENT...

7 CFR 1955.65 - Management of inventory and/or custodial real property.

Code of Federal Regulations, 2013 CFR

2013-01-01

... arrangement contracts to obtain services for more than one property; to a broad-scope management contract with... 7 Agriculture 14 2013-01-01 2013-01-01 false Management of inventory and/or custodial real... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) PROPERTY MANAGEMENT...

The Scope of Writing Assessment.

ERIC Educational Resources Information Center

Hamp-Lyons, Liz

2002-01-01

Attempts to put the field of writing assessment into a historical, linguistic, and geographical/cultural context, in order to stimulate work in writing assessment from across as broad a set of perspectives as possible. Presents a history of writing assessment, looks at writing assessment in the modern period, and considers the future of writing…

76 FR 61347 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... Sciences of the U.S. Department of Education, is a survey that focuses on children's early school... child assessments. Like its sister study, the Early Childhood Longitudinal Study, Kindergarten Class of 1998-99, the ECLS-K:2011 is exceptionally broad in its scope and coverage of child development, early...

Iodide-catalyzed synthesis of N-nitrosamines via C-N cleavage of nitromethane.

PubMed

Zhang, Jie; Jiang, Jiewen; Li, Yuling; Wan, Xiaobing

2013-11-15

An iodide-catalyzed process to synthesize N-nitrosamines has been developed using TBHP as the oxidant. The mild catalytic system succeeded in cleaving the carbon-nitrogen bond in nitromethane. This methodology uses commercially available, inexpensive catalysts and oxidants and has a wide substrate scope and operational simplicity.

Recent Advances in the Pauson-Khand Reaction.

PubMed

Ricker, J David; Geary, Laina M

2017-06-01

The Pauson-Khand [2+2+1] cycloaddition of alkynes, alkenes, and carbon monoxide has been a vibrant area of research for more than 40 years. This review highlights recent achievements in the Pauson-Khand reaction, particularly in catalytic and asymmetric variants. Discussion of regioselectivity and advances in substrate scope is also presented.

Photoluminescence enhancement of silicon quantum dot monolayer by plasmonic substrate fabricated by nano-imprint lithography

NASA Astrophysics Data System (ADS)

Yanagawa, Hiroto; Inoue, Asuka; Sugimoto, Hiroshi; Shioi, Masahiko; Fujii, Minoru

2017-12-01

Near-field coupling between a silicon quantum dot (Si-QD) monolayer and a plasmonic substrate fabricated by nano-imprint lithography and having broad multiple resonances in the near-infrared (NIR) window of biological substances was studied by precisely controlling the QDs-substrate distance. A strong enhancement of the NIR photoluminescence (PL) of Si-QDs was observed. Detailed analyses of the PL and PL excitation spectra, the PL decay dynamics, and the reflectance spectra revealed that both the excitation cross-sections and the emission rates are enhanced by the surface plasmon resonances, thanks to the broad multiple resonances of the plasmonic substrate, and that the relative contribution of the two enhancement processes depends strongly on the excitation wavelength. Under excitation by short wavelength photons (405 nm), where enhancement of the excitation cross-section is not expected, the maximum enhancement was obtained when the QDs-substrate distance was around 30 nm. On the other hand, under long wavelength excitation (641 nm), where strong excitation cross-section enhancement is expected, the largest enhancement was obtained when the distance was minimum (around 1 nm). The achievement of efficient excitation of NIR luminescence of Si-QDs by long wavelength photons paves the way for the development of Si-QD-based fluorescence bio-sensing devices with a high bound-to-free ratio.

Towards substrate engineering of graphene-silicon Schottky diode photodetectors.

PubMed

Selvi, Hakan; Unsuree, Nawapong; Whittaker, Eric; Halsall, Matthew P; Hill, Ernie W; Thomas, Andrew; Parkinson, Patrick; Echtermeyer, Tim J

2018-02-15

Graphene-silicon Schottky diode photodetectors possess beneficial properties such as high responsivities and detectivities, broad spectral wavelength operation and high operating speeds. Various routes and architectures have been employed in the past to fabricate devices. Devices are commonly based on the removal of the silicon-oxide layer on the surface of silicon by wet-etching before deposition of graphene on top of silicon to form the graphene-silicon Schottky junction. In this work, we systematically investigate the influence of the interfacial oxide layer, the fabrication technique employed and the silicon substrate on the light detection capabilities of graphene-silicon Schottky diode photodetectors. The properties of devices are investigated over a broad wavelength range from near-UV to short-/mid-infrared radiation, radiation intensities covering over five orders of magnitude as well as the suitability of devices for high speed operation. Results show that the interfacial layer, depending on the required application, is in fact beneficial to enhance the photodetection properties of such devices. Further, we demonstrate the influence of the silicon substrate on the spectral response and operating speed. Fabricated devices operate over a broad spectral wavelength range from the near-UV to the short-/mid-infrared (thermal) wavelength regime, exhibit high photovoltage responses approaching 10 6 V W -1 and short rise- and fall-times of tens of nanoseconds.

Rhodium(III)-Catalyzed Amidation of Unactivated C(sp(3) )-H Bonds.

PubMed

Wang, He; Tang, Guodong; Li, Xingwei

2015-10-26

Nitrogenation by direct functionalization of C-H bonds represents an important strategy for constructing C-N bonds. Rhodium(III)-catalyzed direct amidation of unactivated C(sp(3) )-H bonds is rare, especially under mild reaction conditions. Herein, a broad scope of C(sp(3) )-H bonds are amidated under rhodium catalysis in high efficiency using 3-substituted 1,4,2-dioxazol-5-ones as the amide source. The protocol broadens the scope of rhodium(III)-catalyzed C(sp(3) )-H activation chemistry, and is applicable to the late-stage functionalization of natural products. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rural Idaho family physicians' scope of practice.

PubMed

Baker, Ed; Schmitz, David; Epperly, Ted; Nukui, Ayaka; Miller, Carissa Moffat

2010-01-01

Scope of practice is an important factor in both training and recruiting rural family physicians. To assess rural Idaho family physicians' scope of practice and to examine variations in scope of practice across variables such as gender, age and employment status. A survey instrument was developed based on a literature review and was validated by physician educators, practicing family physicians and executives at the state hospital association. This survey was mailed to rural family physicians practicing in Idaho counties with populations of less than 50,000. Descriptive, bivariate and multivariate analyses were employed to describe and compare scope of practice patterns. Responses were obtained from 92 of 248 physicians (37.1% response rate). Idaho rural family physicians reported providing obstetrical services in the areas of prenatal care (57.6%), vaginal delivery (52.2%) and C-sections (37.0%); other operating room services (43.5%); esophagogastroduodenoscopy (EGD) or colonoscopy services (22.5%); emergency room coverage (48.9%); inpatient admissions (88.9%); mental health services (90.1%); nursing home services (88.0%); and supervision to midlevel care providers (72.5%). Bivariate analyses showed differences in scope of practice patterns across gender, age group and employment status. Binomial logistic regression models indicated that younger physicians were roughly 3 times more likely to provide prenatal care and perform vaginal deliveries than older physicians in rural areas. Idaho practicing rural family physicians report a broad scope of practice. Younger, employed and female rural family medicine physicians are important subgroups for further study.

Applications of organocatalytic asymmetric synthesis to drug prototypes--dual action and selective inhibitors of n-nitric oxide synthase with activity against the 5-HT1D/1B subreceptors.

PubMed

Hanessian, Stephen; Stoffman, Eli; Mi, Xueling; Renton, Paul

2011-03-04

The scope of MacMillan's organocatalytic asymmetric conjugate addition reaction of indoles and electron-rich aromatics to α,β-unsaturated aldehydes has been extended to the use of 3-amino crotonaldehydes as substrates. The aromatics used include indoles as well as an aniline and a furan. The scope and effect of the groups on nitrogen (R, R') has also been studied. The method has been applied to the concise synthesis of an advanced precursor to S-(+)-1, a drug prototype for the treatment of migraine headaches.

An Interdisciplinary Experiment: Azo-Dye Metabolism by "Staphylococcus Aureus"

ERIC Educational Resources Information Center

Brocklesby, Kayleigh; Smith, Robert; Sharp, Duncan

2012-01-01

An interdisciplinary and engaging practical is detailed which offers great versatility in the study of a qualitative and quantitative metabolism of azo-dyes by "Staphylococcus aureus". This practical has broad scope for adaptation in the number and depth of variables to allow a focused practical experiment or small research project. Azo-dyes are…

78 FR 62698 - Lannett Company, Inc.; Grant of Registration To Import Schedule I Substance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

....'' Under the CSA, the term ``manufacture'' is broad in scope and includes ``the production, preparation... manufacturers holding registrations for the bulk manufacture of the substances an opportunity for a hearing... who is presently, or is applying to be, registered with DEA to manufacture such basic classes of...

Space transfer concepts and analyses for exploration missions

NASA Technical Reports Server (NTRS)

Woodcock, Gordon R.

1992-01-01

The current technical effort is part of the third phase of a broad-scoped and systematic study of space transfer concepts for human lunar and Mars missions. The study addressed the technical issues relating to the First Lunar Outpost (FLO) habitation vehicle with emphasis in the structure, power, life support system, and radiation environment.

National Forum on Education Statistics History

ERIC Educational Resources Information Center

Hoffman, Lee

2004-01-01

The first task force meeting, co-organized by the Center for Education Statistics and CCSSO, was convened in Alexandria, Virginia, on March 13?15, 1988. The purpose of this meeting was to explore alternative strategies for a cooperative federal-state education statistics program that would be broad in scope, encompassing the Common Core of Data…

Ohio Marketing Management and Research. Technical Competency Profile (TCP).

ERIC Educational Resources Information Center

Ray, Gayl M.; Wilson, Nick; Mangini, Rick

This document provides a framework for a broad-based secondary and postsecondary curriculum to prepare students for employment in marketing management and research (MMR). The first part of the technical competency profile (TCP) contains the following items: an explanation of the purpose and scope of Ohio's TCPs; college tech prep program…

Life and Work in a Technological Society. ERIC Digest No. 147.

ERIC Educational Resources Information Center

Kerka, Sandra

Technology is more than applied science. It is the processes and products by which humans have coped with and changed their environment throughout history. People have always lived and worked in a "technological society." Never before, however, has technological change been so rapid or broad in scope. The concept of an "educated…

Ohio Medical Office Management. Technical Competency Profile (TCP).

ERIC Educational Resources Information Center

Ray, Gayl M.; Wilson, Nick; Mangini, Rick

This document provides a framework for a broad-based secondary and postsecondary curriculum to prepare students for employment in medical office management. The first part of the technical competency profile (TCP) contains the following items: an explanation of the purpose and scope of Ohio's TCPs; college tech prep program standards; an overview…

Analytics for Knowledge Creation: Towards Epistemic Agency and Design-Mode Thinking

ERIC Educational Resources Information Center

Chen, Bodong; Zhang, Jianwei

2016-01-01

Innovation and knowledge creation call for high-level epistemic agency and design-mode thinking, two competencies beyond the traditional scopes of schooling. In this paper, we discuss the need for learning analytics to support these two competencies, and more broadly, the demand for education for innovation. We ground these arguments on a…

Establishing Common Course Objectives for Undergraduate Exercise Physiology

ERIC Educational Resources Information Center

Simonson, Shawn R.

2015-01-01

Undergraduate exercise physiology is a ubiquitous course in undergraduate kinesiology/exercise science programs with a broad scope and depth of topics. It is valuable to explore what is taught within this course. The purpose of the present study was to facilitate an understanding of what instructors teach in undergraduate exercise physiology, how…

76 FR 38401 - National Institute of Child Health and Human Development; Revision to Proposed Collection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-30

... Methodology Studies for the National Children's Study SUMMARY: In compliance with the requirement of Section... comments expressed support for the broad scope of the study. The written comments were identical and questioned the cost and utility of the study specifically and of federally funded biomedical research overall...

Historically Black Colleges and Universities: Their Place in American Higher Education.

ERIC Educational Resources Information Center

Roebuck, Julian B.; Murty, Komanduri S.

Issues related to historically black colleges and universities (HBCUs) are addressed from a broad analytical perspective, including the history and development of HBCUs, and their current descriptions, structure, and functions. The first five chapters systematize the widely scattered literature on the subject of HBCUs by describing the scope of…

Chemical News Via Audio Tapes: Chemical Industry News

ERIC Educational Resources Information Center

Hanford, W. E.; And Others

1972-01-01

Tape coverage of internal R&D news now has a broader scope with improved features. A new tape series covering external news of broad interest has been initiated. The use of tape in a Continuing Education Program is discussed as the future plans for expanding the audio tape program. (1 reference) (Author)

CTIC Cablebooks. Volume 1: The Community Medium.

ERIC Educational Resources Information Center

Jesuale, Nancy, Ed.; Smith, Ralph Lee, Ed.

The first of a two-part series, this volume addresses the broad scope of questions and issues that confront local governments when formulating or reevaluating cable policy. In 11 chapters, 14 authors present an historical perspective and discuss cable technology and state-of-the-art options: (1) "Overview of Cable TV Services and…

Defining Quality in Undergraduate Education: Directions for Future Research Informed by a Literature Review

ERIC Educational Resources Information Center

Bowers, Alison W.; Ranganathan, Shyam; Simmons, Denise R.

2018-01-01

Objectives: This research brief explores the literature addressing quality in undergraduate education to identify what previous research has said about quality and to offer future directions for research on quality in undergraduate education. Method: We conducted a scoping review to provide a broad overview of existing research. Using targeted…

Learning-Centered Instruction of Engineering Graphics for Freshman Engineering Students

ERIC Educational Resources Information Center

Pucha, Raghuram V.; Utschig, Tristan T.

2012-01-01

Teaching "Engineering Graphics" to freshman engineering students poses challenges to instructors as well as to students. While the instructors are confronted with a lack of material / text book that covers the broad scope of the subject matter, the students struggle to correlate newly developed skills to real-world engineering design problems…

Basic Course in Highway Traffic Records. Instructor's Guide.

ERIC Educational Resources Information Center

National Highway Traffic Safety Administration (DOT), Washington, DC.

The scope and content of this traffic records course are outlined in a chart (Course Structure) and tabulation (Overview of Course Content). General course objectives follow the overview. These define for the instructor the broad objectives, module by module, which the course is designed to reach. The last part of this section gives a detailed…

Compendium of National Data Sources on Higher Education.

ERIC Educational Resources Information Center

Rodriguez, Esther M., Ed.; Lenth, Charles S., Ed.

This compendium provides a guide to data collections in higher education focusing on sources that are national in scope, and updated and made available on a regular or periodic basis including surveys, data bases, reports, and statistical digests. These sources are divided into nine broad categories, each category contains separate entries for…

Using Reflective Practice to Support Management Student Learning: Three Brief Assignments

ERIC Educational Resources Information Center

Reilly, Anne H.

2018-01-01

Reflective practice supports critical thinking and assessment skills through analyzing one's own life experiences, and the role of reflection in learning has been long recognized. However, drawbacks of many reflective practice assignments are their broad scope and lengthy written requirements. I propose that the reflection process is robust enough…

Hematopathology, 2nd Edition | Center for Cancer Research

Cancer.gov

The world's leading reference in hematopathology returns with this completely updated second edition. Authored by international experts in the field, it covers a broad range of hematologic disorders -- both benign and malignant -- with information on the pathogenesis, clinical and pathologic diagnosis, and treatment for each. Comprehensive in scope, it's a must-have resource

Teenage Pregnancy: A Theoretical Analysis of a Social Problem.

ERIC Educational Resources Information Center

Davis, Richard A.

1989-01-01

Broadly outlines scope of the problem of teenage pregnancy, some of its more obvious causes, and some of the long-term implications of not truly understanding the nature of the problem. Concludes with theoretical critique of social disorganizational, social definitional, and social organizational approaches to the problem of teenage pregnancy.…

76 FR 46280 - Notice of Proposed Information Collection Requests

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-02

... Institute of Education Sciences of the U.S. Department of Education, is a survey that focuses on children's..., as well as direct child assessments. Like its sister study, the Early Childhood Longitudinal Study, Kindergarten Class of 1998-99, the ECLS-K:2011 is exceptionally broad in its scope and coverage of child...

Report of the Office of Science and Technology Policy Working Group on Basic Research in the Department of Energy

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

Not Available

1978-06-01

The OSTP Working Group was commissioned to advise on the scope and quality of basic research conducted by and on behalf of DOE. The Group formed Subgroups in these areas: large-scale solar, fossil, fusion, small technology, and geothermal, environment and life sciences, social sciences, transportation, and fission. Work of the Subgroups forms the basis of much of this report, which has five sections. Following the introduction, preface, and executive summary (Section II), there is discussion of broad problem areas as they pertain to research (Section III). Section IV consists of general recommendations regarding policies for, as well as management andmore » scope of, research within the DOE: this section has four parts: Part A pertains to research in programmatic areas under the aegis of the Assistant Secretaries; Part B deals with the role and structure of the Office of Energy Research; Part C is concerned with broad research issues; and Part D addresses DOE Laboratories and Energy Research Centers. In Section V, research needs and opportunities for selected programs are discussed.« less

Self-assembled antireflection coatings for light trapping based on SiGe random metasurfaces

NASA Astrophysics Data System (ADS)

Bouabdellaoui, Mohammed; Checcucci, Simona; Wood, Thomas; Naffouti, Meher; Sena, Robert Paria; Liu, Kailang; Ruiz, Carmen M.; Duche, David; le Rouzo, Judikael; Escoubas, Ludovic; Berginc, Gerard; Bonod, Nicolas; Zazoui, Mimoun; Favre, Luc; Metayer, Leo; Ronda, Antoine; Berbezier, Isabelle; Grosso, David; Gurioli, Massimo; Abbarchi, Marco

2018-03-01

We demonstrate a simple self-assembly method based on solid state dewetting of ultrathin silicon films and germanium deposition for the fabrication of efficient antireflection coatings on silicon for light trapping. We fabricate SiGe islands with a high surface density, randomly positioned and broadly varied in size. This allows one to reduce the reflectance to low values in a broad spectral range (from 500 nm to 2500 nm) and a broad angle (up to 55°) and to trap within the wafer a large portion of the impinging light (˜40 % ) also below the band gap, where the Si substrate is nonabsorbing. Theoretical simulations agree with the experimental results, showing that the efficient light coupling into the substrate is mediated by Mie resonances formed within the SiGe islands. This lithography-free method can be implemented on arbitrarily thick or thin SiO2 layers and its duration only depends on the sample thickness and on the annealing temperature.

Copper- and copper–N-heterocyclic carbene-catalyzed C─H activating carboxylation of terminal alkynes with CO2 at ambient conditions

PubMed Central

Yu, Dingyi; Zhang, Yugen

2010-01-01

The use of carbon dioxide as a renewable and environmentally friendly source of carbon in organic synthesis is a highly attractive approach, but its real world applications remain a great challenge. The major obstacles for commercialization of most current protocols are their low catalytic performances, harsh reaction conditions, and limited substrate scope. It is important to develop new reactions and new protocols for CO2 transformations at mild conditions and in cost-efficient ways. Herein, a copper-catalyzed and copper–N-heterocyclic carbene-cocatalyzed transformation of CO2 to carboxylic acids via C─H bond activation of terminal alkynes with or without base additives is reported. Various propiolic acids were synthesized in good to excellent yields under ambient conditions without consumption of any organometallic or organic reagent additives. This system has a wide scope of substrates and functional group tolerances and provides a powerful tool for the synthesis of highly functionalized propiolic acids. This catalytic system is a simple and economically viable protocol with great potential in practical applications. PMID:21059950

Photometric Characterization of the Reductive Amination Scope of the Imine Reductases from Streptomyces tsukubaensis and Streptomyces ipomoeae.

PubMed

Matzel, Philipp; Krautschick, Lukas; Höhne, Matthias

2017-10-18

Imine reductases (IREDs) have emerged as promising enzymes for the asymmetric synthesis of secondary and tertiary amines starting from carbonyl substrates. Screening the substrate specificity of the reductive amination reaction is usually performed by time-consuming GC analytics. We found two highly active IREDs in our enzyme collection, IR-20 from Streptomyces tsukubaensis and IR-Sip from Streptomyces ipomoeae, that allowed a comprehensive substrate screening with a photometric NADPH assay. We screened 39 carbonyl substrates combined with 17 amines as nucleophiles. Activity data from 663 combinations provided a clear picture about substrate specificity and capabilities in the reductive amination of these enzymes. Besides aliphatic aldehydes, the IREDs accepted various cyclic (C 4 -C 8 ) and acyclic ketones, preferentially with methylamine. IR-Sip also accepted a range of primary and secondary amines as nucleophiles. In biocatalytic reactions, IR-Sip converted (R)-3-methylcyclohexanone with dimethylamine or pyrrolidine with high diastereoselectivity (>94-96 % de). The nucleophile acceptor spectrum depended on the carbonyl substrate employed. The conversion of well-accepted substrates could also be detected if crude lysates were employed as the enzyme source. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanistic insights into hydroacylation with non-chelating aldehydes†Electronic supplementary information (ESI) available: Materials and methods, reaction procedures, characterization data. CCDC 1012849. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4sc02026jClick here for additional data file.

PubMed

Murphy, Stephen K; Bruch, Achim; Dong, Vy M

2015-01-01

The combination of a small-bite-angle diphosphine bis(dicyclohexylphosphino)methane (dcpm) and [Rh(cod)OMe] 2 catalyses the hydroacylation of 2-vinylphenols with a wide range of non-chelating aldehydes. Here we present a detailed experimental study that elucidates the factors contributing to the broad aldehyde scope and high reactivity. A variety of catalytically relevant intermediates were isolated and a [Rh(dcpm)(vinylphenolate)] complex was identified as the major catalytically relevant species. A variety of off-cycle intermediates were also identified that can re-enter the catalytic cycle by substrate- or 1,5-cyclooctadiene-mediated pathways. Saturation kinetics with respect to the 2-vinylphenol were observed, and this may contribute to the high selectivity for hydroacylation over aldehyde decarbonylation. A series of deuterium labelling experiments and Hammett studies support the oxidative addition of Rh to the aldehyde C-H bond as an irreversible and turnover-limiting step. The small bite angle of dcpm is crucial for lowering the barrier of this step and providing excellent reactivity with a variety of aldehydes.

An Unconventional Redox Cross Claisen Condensation-Aromatization of 4-Hydroxyprolines with Ketones.

PubMed

Tang, Mi; Sun, Rengwei; Li, Hao; Yu, Xinhong; Wang, Wei

2017-08-18

Reaction of α-amino acids, particularly prolines and their derivatives with carbonyl compounds via decarboxylative redox process, is a viable strategy for synthesis of structurally diverse nitrogen centered heterocyclics. In these processes, the decarboxylation is the essential driving force for the processes. The realization of the redox process without decarboxylation may offer an opportunity to explore new reactions. Herein, we report the discovery of an unprecedented redox Claisen-type condensation aromatization cascade reaction of 4-substituted 4-hydroxyproline and its esters with unreactive ketones. We found that the use of propionic acid as a catalyst and a co-solvent can change the reaction course. The commonly observed redox decarboxylation and aldol condensation reactions are significantly minimized. Moreover, unreactive ketones can effectively participate in the Claisen condensation reaction. The new reactivity enables a redox cyclization via an unconventional Claisen-type condensation reaction of in situ formed enamine intermediates from ketone precursors with 4-substituted 4-hydroxyproline and its esters as electrophilic acylation partners. Under the reaction conditions, the cascade process proceeds highly regio- and stereoselectively to afford highly synthetically and biologically valued cis-2,3-dihydro-1H-pyrrolizin-1-ones with a broad substrate scope in efficient 'one-pot' operation, whereas such structures generally require multiple steps.

Scalable and sustainable electrochemical allylic C-H oxidation

NASA Astrophysics Data System (ADS)

Horn, Evan J.; Rosen, Brandon R.; Chen, Yong; Tang, Jiaze; Chen, Ke; Eastgate, Martin D.; Baran, Phil S.

2016-05-01

New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as “classics”. Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.

Hydrosoluble Cu(i)-DAPTA complexes: synthesis, characterization, luminescence thermochromism and catalytic activity for microwave-assisted three-component azide-alkyne cycloaddition click reaction.

PubMed

Mahmoud, Abdallah G; Guedes da Silva, M Fátima C; Sokolnicki, Jerzy; Smoleński, Piotr; Pombeiro, Armando J L

2018-05-16

New hydrosoluble and air-stable Cu(i) halide compounds, viz. [CuX(DAPTA)3] (1) and (2), and [Cu(μ-X)(DAPTA)2]2 (3) and (4) (X = Br or I, in this order), have been prepared by reacting Cu(i) halide (i.e., bromide or iodide) with 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) under mild conditions. They represent the first examples of Cu(i) halide complexes bearing the DAPTA ligand, which have been fully characterized by elemental analysis, IR, 1H, 13C{1H} and 31P{1H} NMR spectroscopies, ESI-MS+ and, for 4, also by single-crystal X-ray diffraction (SCXRD) analyses. Complexes 1-4 are efficient catalysts for the one-pot microwave assisted three-component (terminal alkyne, organic halide and NaN3) Huisgen cycloaddition reaction in aqueous media to afford the corresponding disubstituted triazoles. The catalysis proceeds with a broad alkyne substrate scope and according to "click rules". Photophysical studies of compound 4 showed an unusual reversible thermochromic behaviour exhibiting a blue emission at 298 K due to the halide-to-ligand charge transfer (3XLCT) and a red emission at 77 K because of the {Cu2I2} unit.

SBA-15/hydrotalcite nanocomposite as an efficient support for the immobilization of heteropolyacid: A triply-hybrid catalyst for the synthesis of 2-amino-4H-pyrans in water

NASA Astrophysics Data System (ADS)

Sadjadi, Samahe; Heravi, Majid M.; Zadsirjan, Vahideh; Farzaneh, Vahid

2017-12-01

To circumvent the high solubility and low surface area of heteropolyacid and in attempt to develop a bi-functional heterogeneous catalyst for promoting organic transformations, heteropolyacid was embedded in functionalized SBA-15 and subsequently hybridized with layered double hydroxide. The catalyst could be considered as a bi-functional catalyst with both acidic and basic properties. The acidic properties emerged from the SBA-15 and heteropolyacid component while layered double hydroxide render the catalyst basic. The catalyst was characterized by using SEM/EDX, FT-IR, XRD, ICP-AES, BET and elemental mapping analysis. The catalytic activity of the catalyst was studied for promoting one-pot three-component condensation of aromatic aldehydes, malononitrile or ethyl cyanoacetate and C-H activated acidic molecules in aqueous media for the synthesis of 2-amino-4H-pyran derivatives. The catalyst exhibited high catalytic activity, which was superior to the previously reported ones. Moreover, the reusability of the catalyst was excellent and the leaching of heteropolyacid was dramatically suppressed. High yields, short reaction times, eco-friendly conditions, simplicity of the procedure, reusability of the catalyst and broad substrate scope are the merits of this protocol.

A VCP inhibitor substrate trapping approach (VISTA) enables proteomic profiling of endogenous ERAD substrates.

PubMed

Huang, Edmond Y; To, Milton; Tran, Erica; Dionisio, Lorraine T Ador; Cho, Hyejin J; Baney, Katherine L M; Pataki, Camille I; Olzmann, James A

2018-05-01

Endoplasmic reticulum (ER)-associated degradation (ERAD) mediates the proteasomal clearance of proteins from the early secretory pathway. In this process, ubiquitinated substrates are extracted from membrane-embedded dislocation complexes by the AAA ATPase VCP and targeted to the cytosolic 26S proteasome. In addition to its well-established role in the degradation of misfolded proteins, ERAD also regulates the abundance of key proteins such as enzymes involved in cholesterol synthesis. However, due to the lack of generalizable methods, our understanding of the scope of proteins targeted by ERAD remains limited. To overcome this obstacle, we developed a VCP inhibitor substrate trapping approach (VISTA) to identify endogenous ERAD substrates. VISTA exploits the small-molecule VCP inhibitor CB5083 to trap ERAD substrates in a membrane-associated, ubiquitinated form. This strategy, coupled with quantitative ubiquitin proteomics, identified previously validated (e.g., ApoB100, Insig2, and DHCR7) and novel (e.g., SCD1 and RNF5) ERAD substrates in cultured human hepatocellular carcinoma cells. Moreover, our results indicate that RNF5 autoubiquitination on multiple lysine residues targets it for ubiquitin and VCP--dependent clearance. Thus, VISTA provides a generalizable discovery method that expands the available toolbox of strategies to elucidate the ERAD substrate landscape.

Structural basis for the substrate specificity of PepA from Streptococcus pneumoniae, a dodecameric tetrahedral protease.

PubMed

Kim, Doyoun; San, Boi Hoa; Moh, Sang Hyun; Park, Hyejin; Kim, Dong Young; Lee, Sangho; Kim, Kyeong Kyu

2010-01-01

Regulated cytosolic proteolysis is one of the key cellular processes ensuring proper functioning of a cell. M42 family proteases show a broad spectrum of substrate specificities, but the structural basis for such diversity of the substrate specificities is lagging behind biochemical data. Here we report the crystal structure of PepA from Streptococcus pneumoniae, a glutamyl aminopeptidase belonging to M42 family (SpPepA). We found that Arg-257 in the substrate binding pocket is strategically positioned so that Arg-257 can make electrostatic interactions with the acidic residue of a substrate at its N-terminus. Structural comparison of the substrate binding pocket of the M42 family proteases, along with the structure-based multiple sequence alignment, argues that the appropriate electrostatic interactions contribute to the selective substrate specificity of SpPepA. Copyright 2009 Elsevier Inc. All rights reserved.

USArray Siting Outreach: Telling the EarthScope Story

NASA Astrophysics Data System (ADS)

Dorr, P. M.; Taber, J. J.; McQuillan, P.; Busby, R. W.; Woodward, R.

2013-12-01

USArray has engaged in a variety of activities that involve students in and inform the general public about EarthScope. Examples include the highly successful Transportable Array Student Siting Program that employed students and faculty from colleges and universities in the identification of sites for future Transportable Array stations in their region, and a range of informal education and media opportunities where information about EarthScope and its discoveries are shared with educators and the public. During the course of eight summers, more than 135 students from about 55 institutions conducted site reconnaissance for nearly 1375 sites from the West Coast to the East Coast, and from the Gulf of Mexico to the Great Lakes and southern Canada. While telling the EarthScope story, students who participated in the program increased their professional skills and deepened their personal growth. Other students had opportunities to engage in EarthScope-related research as part of the Research Experiences for Undergraduates program. Several EarthScope-focused outreach products for the public and educational audiences have been developed including Ground Motion Visualizations, EarthScope-centric and regional content sets for the IRIS Active Earth Monitor (AEM), and animations of earth processes. A kiosk loan program has helped to broadly disseminate the AEM displays. There have also been articles published in university, local and regional newspapers; stories appearing in national and international print and broadcast media; and documentaries produced by some of the world's most respected scientific and educational production companies that have included a segment about EarthScope and the Transportable Array. Over the next five years, USArray will be deploying and operating Transportable Array stations in Alaska and western Canada. This challenging environment will offer new opportunities to connect with communities throughout the region including native populations.

Functional and Structural Characterization of Purine Nucleoside Phosphorylase from Kluyveromyces lactis and Its Potential Applications in Reducing Purine Content in Food

PubMed Central

Mahor, Durga; Priyanka, Anu; Prasad, Gandham S; Thakur, Krishan Gopal

2016-01-01

Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway. We report a 1.97 Å resolution crystal structure of homotrimeric KlacPNP with an intrinsically bound hypoxanthine in the active site. KlacPNP belongs to the nucleoside phosphorylase-I (NP-I) family, and it specifically utilizes 6-oxopurine substrates in the following order: inosine > guanosine > xanthosine, but is inactive towards adenosine. To engineer enzymes with broad substrate specificity, we created two point variants, KlacPNPN256D and KlacPNPN256E, by replacing the catalytically active Asn256 with Asp and Glu, respectively, based on structural and comparative sequence analysis. KlacPNPN256D not only displayed broad substrate specificity by utilizing both 6-oxopurines and 6-aminopurines in the order adenosine > inosine > xanthosine > guanosine, but also displayed reversal of substrate specificity. In contrast, KlacPNPN256E was highly specific to inosine and could not utilize other tested substrates. Beer consumption is associated with increased risk of developing gout, owing to its high purine content. Here, we demonstrate that KlacPNP and KlacPNPN256D could be used to catalyze a key reaction involved in lowering beer purine content. Biochemical properties of these enzymes such as activity across a wide pH range, optimum activity at about 25°C, and stability for months at about 8°C, make them suitable candidates for food and beverage industries. Since KlacPNPN256D has broad substrate specificity, a combination of engineered KlacPNP and other enzymes involved in purine degradation could effectively lower the purine content in foods and beverages. PMID:27768715

Numerical analysis of high-power broad-area laser diode with improved heat sinking structure using epitaxial liftoff technique

NASA Astrophysics Data System (ADS)

Kim, Younghyun; Sung, Yunsu; Yang, Jung-Tack; Choi, Woo-Young

2018-02-01

The characteristics of high-power broad-area laser diodes with the improved heat sinking structure are numerically analyzed by a technology computer-aided design based self-consistent electro-thermal-optical simulation. The high-power laser diodes consist of a separate confinement heterostructure of a compressively strained InGaAsP quantum well and GaInP optical cavity layers, and a 100-μm-wide rib and a 2000-μm long cavity. In order to overcome the performance deteriorations of high-power laser diodes caused by self-heating such as thermal rollover and thermal blooming, we propose the high-power broad-area laser diode with improved heat-sinking structure, which another effective heat-sinking path toward the substrate side is added by removing a bulk substrate. It is possible to obtain by removing a 400-μm-thick GaAs substrate with an AlAs sacrificial layer utilizing well-known epitaxial liftoff techniques. In this study, we present the performance improvement of the high-power laser diode with the heat-sinking structure by suppressing thermal effects. It is found that the lateral far-field angle as well as quantum well temperature is expected to be improved by the proposed heat-sinking structure which is required for high beam quality and optical output power, respectively.

Cu-catalyzed aerobic oxidative esterification of acetophenones with alcohols to α-ketoesters.

PubMed

Xu, Xuezhao; Ding, Wen; Lin, Yuanguang; Song, Qiuling

2015-02-06

Copper-catalyzed aerobic oxidative esterification of acetophenones with alcohols using molecular oxygen has been developed to form a broad range of α-ketoesters in good yields. In addition to reporting scope and limitations of our new method, mechanism studies are reported that reveal that the carbonyl oxygen in the ester mainly originated from dioxygen.

Life in the Cosmic Context. An Astrobiology Course as an Experiment in Transdisciplinarity

NASA Astrophysics Data System (ADS)

Friaça, A. C. S.; Janot Pacheco, E.

2014-10-01

``Life in the Cosmic Context" (AGA0316) is the astrobiology course offered by University of São Paulo to undergraduate students of science and humanities majors. The variety of background of the population attending AGA0316 and the broad scope of the addresssed issues makes this course a laboratory of transdisciplinarity.

Economics and Comparative and International Education: Past, Present, Future

ERIC Educational Resources Information Center

Wolhuter, Charl

2017-01-01

The aim of this paper is to map this place of economics in the field of study of Comparative and International Education. Interrelationship between economy and education is concerned, two broad lines of enquiry lie within the scope of Comparative and International Education: economy as shaping force of education systems and the effect of education…

76 FR 41508 - Submission for OMB Review; Comment Request; Formative Research Methodology Studies for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

...; Comment Request; Formative Research Methodology Studies for the National Children's Study Summary: Under... support for the broad scope of the study. The written comments were identical and questioned the cost and utility of the study. The purpose of this notice is to allow an additional 30 days for public comment. The...

Mapping Research in Landscape Architecture: Balancing Supply of Academic Knowledge and Demand of Professional Practice

ERIC Educational Resources Information Center

Chen, Zheng; Miller, Patrick A.; Clements, Terry L.; Kim, Mintai

2017-01-01

With increasing academic research in the past few decades, the knowledge scope of landscape architecture has expanded from traditional focus on aesthetics to a broad range of ecological, cultural and psychological issues. In order to understand how academic research and knowledge expansion may have redefined the practice, two surveys were…

Who Is Conducting Educational Research in Australia and How Can Their Work Be Supported?

ERIC Educational Resources Information Center

Bennett, Dawn; Smith, Erica; Bennett, Sue; Chan, Philip; Bobis, Janette; Harrison, Neil; Seddon, Terri; Shore, Sue

2013-01-01

Educational research has long been the subject of lively and agitated debate, not least because of its diversity. Ranging in scope from academic development and broad-scale policy research through to student engagement and discipline-specific research, it includes methods of traditional academic inquiry and investigations and also less traditional…

Environmental Quality, the Fourth Annual Report of the Council on Environmental Quality.

ERIC Educational Resources Information Center

Council on Environmental Quality, Washington, DC.

The state of the environment and efforts to improve it are reported upon in this Fourth Annual Report of the Council on Environmental Quality. Broad in scope, the report covers federal and state activities during the past year, the urban environment, economics and environmental management, the law and land use regulation, environmental quality,…

Defense Threat Reduction Agency > Research > DTRIAC > Media Collection

Science.gov Websites

*Cover a broad scope of both the pre- and post-test activities of a test series or operation *Detonations FOIA Electronic Reading Room Privacy Impact Assessment DTRA No Fear Act Reporting Nuclear Test Personnel Review NTPR Fact Sheets NTPR Radiation Dose Assessment Documents US Atmospheric Nuclear Test

Sexualities in Education: A Reader. Counterpoints: Studies in the Postmodern Theory of Education. Volume 367

ERIC Educational Resources Information Center

Meiners, Erica R., Ed.; Quinn, Therese, Ed.

2012-01-01

With germinal texts, new writings, and related art, "Sexualities in Education: A Reader" illuminates a broad scope of analysis and organization. Composed of a framing essay and nine sections edited by established and emerging scholars and addressing critical topics for researchers and students of sexualities and education, the text…

Selective Guide to Literature on Engineering Geology. Engineering Literature Guides, Number 7.

ERIC Educational Resources Information Center

Mullen, Cecilia P., Comp.

This guide has been prepared for use by the undergraduate or graduate student in engineering geology. Because of the broad scope of the field, the major disciplines of soil mechanics, rock mechanics, and foundations are primarily emphasized. This document is a survey of information sources in engineering geology and is intended to identify those…

Environmental Quality, the Third Annual Report of the Council on Environmental Quality.

ERIC Educational Resources Information Center

Council on Environmental Quality, Washington, DC.

The state of the environment and efforts to improve it are reported upon in this Third Annual Report of the Council on Environmental Quality. Broad in scope, the report covers federal and state activities during the past year, the development of environmental indices, and legal implications of the National Environmental Policy Act. The chapter on…

California's Early Learning & Development System: A Review of Funding Streams and Programs

ERIC Educational Resources Information Center

Miller, Kate; Perez, Giannina S.

2010-01-01

California's public early learning and development programs and related services are funded through a range of federal, state and local sources. The purpose and scope of these funding streams vary broadly: some sources are dedicated primarily to serving children, birth to age five, and their families, while others can also be utilized for…

Space transfer concepts and analysis for exploration missions

NASA Technical Reports Server (NTRS)

1991-01-01

Covered here is the second phase of a broad scoped and systematic study of space transfer concepts for human lunar and Mars missions. The study addressed issues that were raised during Phase 1, developed generic Mars missions profile analysis data, and conducted preliminary analysis of the Mars in-space transportation requirements and implementation from the Stafford Committee Synthesis Report.

Why Academics Choose to Publish in a Mega-Journal

ERIC Educational Resources Information Center

Shopovski, Jovan; Marolov, Dejan

2017-01-01

With their broad scope, high publishing volume, a peer review process based on the scientific soundness of the content, and an open access model, mega journals have become an important part of scholarly publishing. The main aim of this paper is to determine the most important factor that influenced researchers' decisions to submit their academic…

The Wildland-Urban Interface: Increasing Significance, Complexity and Contribution

Treesearch

John F. Dwyer; Sarah M. McCaffrey

2002-01-01

During the past two decades, presentations at International Symposia on Society and Resource Management (ISSRM) have covered an increasingly broad scope of topics on natural resource issues. The wildland-urban interface (WUI) was a key topic of discussion at the ninth ISSRM in 2002: a reflection of the response by social scientists to increasing residential development...

Wood protection by commercial silver formulations against Eastern subterranean termites

Treesearch

Frederick Green; Rachel Ann Arango

2007-01-01

The scope of this paper is to compare commercial formulations of aqueous products containing silver for their ability to prevent termite damage by Eastern subterranean termites in a no-choice laboratory test. Five commercial products were tested in order to explore a broad range of formulation and silver forms: colloidal, ionic and nanoparticles. Southern pine wood...

State Plan for Technology for the State Board of Education of Ohio.

ERIC Educational Resources Information Center

Ohio State Dept. of Education, Columbus.

The state plan for educational technology in Ohio has been developed to facilitate a basic understanding of the broad scope of technology and how it can affect learning positively. It is also intended to provide a framework for policy and resource allocation decision making. Massive systemic changes in curriculum, professional development, and…

Differential growth responses of soil bacterial taxa to carbon substrates of varying chemical recalcitrance

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

Goldfarb, K.C.; Karaoz, U.; Hanson, C.A.

2011-04-18

Soils are immensely diverse microbial habitats with thousands of co-existing bacterial, archaeal, and fungal species. Across broad spatial scales, factors such as pH and soil moisture appear to determine the diversity and structure of soil bacterial communities. Within any one site however, bacterial taxon diversity is high and factors maintaining this diversity are poorly resolved. Candidate factors include organic substrate availability and chemical recalcitrance, and given that they appear to structure bacterial communities at the phylum level, we examine whether these factors might structure bacterial communities at finer levels of taxonomic resolution. Analyzing 16S rRNA gene composition of nucleotide analog-labeledmore » DNA by PhyloChip microarrays, we compare relative growth rates on organic substrates of increasing chemical recalcitrance of >2,200 bacterial taxa across 43 divisions/phyla. Taxa that increase in relative abundance with labile organic substrates (i.e., glycine, sucrose) are numerous (>500), phylogenetically clustered, and occur predominantly in two phyla (Proteobacteria and Actinobacteria) including orders Actinomycetales, Enterobacteriales, Burkholderiales, Rhodocyclales, Alteromonadales, and Pseudomonadales. Taxa increasing in relative abundance with more chemically recalcitrant substrates (i.e., cellulose, lignin, or tannin-protein) are fewer (168) but more phylogenetically dispersed, occurring across eight phyla and including Clostridiales, Sphingomonadalaes, Desulfovibrionales. Just over 6% of detected taxa, including many Burkholderiales increase in relative abundance with both labile and chemically recalcitrant substrates. Estimates of median rRNA copy number per genome of responding taxa demonstrate that these patterns are broadly consistent with bacterial growth strategies. Taken together, these data suggest that changes in availability of intrinsically labile substrates may result in predictable shifts in soil bacterial composition.« less

Environmentally Compliant Coating Remover Evaluation

DTIC Science & Technology

2012-08-30

22 9 Total of 491 products evaluated 7 Background • Many DoD depainting operations currently use environmentally compliant peroxide -assisted... benzyl alcohol strippers • These strippers have acceptable coating removal rates with minimal physical damage to metallic substrates • However, several...Coatings • Environmentally compliant benzyl alcohol product • Passed corrosion testing conducted by SMI in 2011 11 Laboratory Testing Scope

A General, Efficient and Functional-Group-Tolerant Catalyst System for the Palladium-Catalyzed Thioetherification of Aryl Bromides and Iodides

PubMed Central

Fernández-Rodríguez, Manuel A.; Hartwig, John F.

2010-01-01

The cross-coupling reaction of aryl bromides and iodides with aliphatic and aromatic thiols catalyzed by palladium complexes of the bisphosphine ligand CyPF-tBu (1) is reported. Reactions occur in excellent yields, broad scope, high tolerance of functional groups and with turnover numbers that exceed those of previous catalysts by two or three orders of magnitude. These couplings of bromo- and iodoarenes are more efficient than the corresponding reactions of chloroarenes and could be conducted with less catalyst loading and/or milder reaction conditions. Consequently, limitations regarding scope and functional group tolerance previously reported in the coupling of aryl chlorides are now overcome. PMID:19154131

Mapping the dark space of chemical reactions with extended nanomole synthesis and MALDI-TOF MS.

PubMed

Lin, Shishi; Dikler, Sergei; Blincoe, William D; Ferguson, Ronald D; Sheridan, Robert P; Peng, Zhengwei; Conway, Donald V; Zawatzky, Kerstin; Wang, Heather; Cernak, Tim; Davies, Ian W; DiRocco, Daniel A; Sheng, Huaming; Welch, Christopher J; Dreher, Spencer D

2018-05-24

Understanding the practical limitations of chemical reactions is critically important for efficiently planning the synthesis of compounds in pharmaceutical, agrochemical and specialty chemical research and development. However, literature reports of the scope of new reactions are often cursory and biased toward successful results, severely limiting the ability to predict reaction outcomes for untested substrates. We herein illustrate strategies for carrying out large scale surveys of chemical reactivity using a material-sparing nanomole-scale automated synthesis platform with greatly expanded synthetic scope combined with ultra-high throughput (uHT) matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Copyright © 2018, American Association for the Advancement of Science.

Efficient broad color luminescence from InGaN/GaN single quantum-well nanocolumn crystals on Si (111) substrate

NASA Astrophysics Data System (ADS)

Zhang, Wei; Zhang, Xuehua; Wang, Yongjin; Hu, Fangren

2017-10-01

Nanocolumn InGaN/GaN single quantum well crystals were deposited on Si (111) substrate with nitrified Ga dots as buffer layer. Transmission electron microscopy image shows the crystals' diameter of 100-130 nm and length of about 900 nm. Nanoscale spatial phase separation of cubic and hexagonal GaN was observed by selective area electron diffraction on the quantum well layer. Raman spectrum of the quantum well crystals proved that the crystals were fully relaxed. Room temperature photoluminescence from 450 to 750 nm and full width at half maximum of about 420 meV indicate broad color luminescence covering blue, green, yellow and red emission, which is helpful for the fabrication of tunable optoelectronic devices and colorful light emitting diodes.

Composite perfluorohydrocarbon membranes, their preparation and use

DOEpatents

Ding, Yong; Bikson, Benjamin

2017-04-04

Composite porous hydrophobic membranes are prepared by forming a perfluorohydrocarbon layer on the surface of a preformed porous polymeric substrate. The substrate can be formed from poly (aryl ether ketone) and a perfluorohydrocarbon layer can be chemically grafted to the surface of the substrate. The membranes can be utilized for a broad range of fluid separations, such as microfiltration, nanofiltration, ultrafiltration as membrane contactors for membrane distillation and for degassing and dewatering of fluids. The membranes can further contain a dense ultra-thin perfluorohydrocarbon layer superimposed on the porous poly (aryl ether ketone) substrate and can be utilized as membrane contactors or as gas separation. membranes for natural gas treatment and gas dehydration.

Electrically pumped 1.3 microm room-temperature InAs/GaAs quantum dot lasers on Si substrates by metal-mediated wafer bonding and layer transfer.

PubMed

Tanabe, Katsuaki; Guimard, Denis; Bordel, Damien; Iwamoto, Satoshi; Arakawa, Yasuhiko

2010-05-10

An electrically pumped InAs/GaAs quantum dot laser on a Si substrate has been demonstrated. The double-hetero laser structure was grown on a GaAs substrate by metal-organic chemical vapor deposition and layer-transferred onto a Si substrate by GaAs/Si wafer bonding mediated by a 380-nm-thick Au-Ge-Ni alloy layer. This broad-area Fabry-Perot laser exhibits InAs quantum dot ground state lasing at 1.31 microm at room temperature with a threshold current density of 600 A/cm(2). (c) 2010 Optical Society of America.

Hydrogenated amorphous carbon films on steel balls and Si substrates: Nanostructural evolutions and their trigging tribological behaviors

NASA Astrophysics Data System (ADS)

Wang, Yongfu; Wang, Yan; Zhang, Xingkai; Shi, Jing; Gao, Kaixiong; Zhang, Bin; Zhang, Junyan

2017-10-01

In this study, we prepared hydrogenated amorphous carbon films on steel balls and Si substrates (steel ball- and Si substrate-films) with different deposition time, and discussed their carbon nanostructural evolutions and tribological behaviors. The steel ball-film structure started to be graphite-like structure and then gradually transformed into fullerene-like (FL) structure. The Si substrate-film structure began in FL structure and kept it through the thickness. The difference may be result from the competition between high starting substrate temperature after additional nitriding applied on the steel balls (its supply power is higher than that in the film deposition), and relaxation of compressive stress from energized ion bombardment in film deposition process. The FL structural film friction couples could achieve ultra-low friction in open air. In particular, the Si substrate-film with 3 h, against the steel ball-film with 2 h and 3 h, exhibited super-low friction (∼0.009) and superlong wear life (∼5.5 × 105 cycles). Our result could widen the superlubricity scope from previously high load and velocity, to middle load and velocity.

What’s in a drop? Correlating observations and outcomes to guide macromolecular crystallization experiments

PubMed Central

Luft, Joseph R.; Wolfley, Jennifer R.; Snell, Edward H.

2011-01-01

Observations of crystallization experiments are classified as specific outcomes and integrated through a phase diagram to visualize solubility and thereby direct subsequent experiments. Specific examples are taken from our high-throughput crystallization laboratory which provided a broad scope of data from 20 million crystallization experiments on 12,500 different biological macromolecules. The methods and rationale are broadly and generally applicable in any crystallization laboratory. Through a combination of incomplete factorial sampling of crystallization cocktails, standard outcome classifications, visualization of outcomes as they relate chemically and application of a simple phase diagram approach we demonstrate how to logically design subsequent crystallization experiments. PMID:21643490

Extending the Scope of GTFR Glucosylation Reactions with Tosylated Substrates for Rare Sugars Synthesis.

PubMed

Görl, Julian; Possiel, Christian; Sotriffer, Christoph; Seibel, Jürgen

2017-10-18

Functionalized rare sugars were synthesized with 2-, 3-, and 6-tosylated glucose derivatives as acceptor substrates by transglucosylation with sucrose and the glucansucrase GTFR from Streptococcus oralis. The 2- and 3-tosylated glucose derivatives yielded the corresponding 1,6-linked disaccharides (isomaltose analogues), whereas the 6-tosylated glucose derivatives resulted in 1,3-linked disaccharides (nigerose analogue) with high regioselectivity in up to 95 % yield. Docking studies provided insight into the binding mode of the acceptors and suggested two different orientations that were responsible for the change in regioselectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Refining of plant oils to chemicals by olefin metathesis.

PubMed

Chikkali, Samir; Mecking, Stefan

2012-06-11

Plant oils are attractive substrates for the chemical industry. Their scope for the production of chemicals can be expanded by sophisticated catalytic conversions. Olefin metathesis is an example, which also illustrates generic issues of "biorefining" to chemicals. Utilization on a large scale requires high catalyst activities, which influences the choice of the metathesis reaction. The mixture of different fatty acids composing a technical-grade plant oil substrate gives rise to a range of products. This decisively determines possible process schemes, and potentially provides novel chemicals and intermediates not employed to date. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantiocomplementary Yarrowia lipolytica Oxidoreductases: Alcohol Dehydrogenase 2 and Short Chain Dehydrogenase/Reductase

PubMed Central

Napora-Wijata, Kamila; Strohmeier, Gernot A.; Sonavane, Manoj N.; Avi, Manuela; Robins, Karen; Winkler, Margit

2013-01-01

Enzymes of the non-conventional yeast Yarrowia lipolytica seem to be tailor-made for the conversion of lipophilic substrates. Herein, we cloned and overexpressed the Zn-dependent alcohol dehydrogenase ADH2 from Yarrowia lipolytica in Escherichia coli. The purified enzyme was characterized in vitro. The substrate scope for YlADH2 mediated oxidation and reduction was investigated spectrophotometrically and the enzyme showed a broader substrate range than its homolog from Saccharomyces cerevisiae. A preference for secondary compared to primary alcohols in oxidation direction was observed for YlADH2. 2-Octanone was investigated in reduction mode in detail. Remarkably, YlADH2 displays perfect (S)-selectivity and together with a highly (R)-selective short chain dehydrogenase/ reductase from Yarrowia lipolytica it is possible to access both enantiomers of 2-octanol in >99% ee with Yarrowia lipolytica oxidoreductases. PMID:24970175

Enantiocomplementary Yarrowia lipolytica Oxidoreductases: Alcohol Dehydrogenase 2 and Short Chain Dehydrogenase/Reductase.

PubMed

Napora-Wijata, Kamila; Strohmeier, Gernot A; Sonavane, Manoj N; Avi, Manuela; Robins, Karen; Winkler, Margit

2013-08-12

Enzymes of the non-conventional yeast Yarrowia lipolytica seem to be tailor-made for the conversion of lipophilic substrates. Herein, we cloned and overexpressed the Zn-dependent alcohol dehydrogenase ADH2 from Yarrowia lipolytica in Escherichia coli. The purified enzyme was characterized in vitro. The substrate scope for YlADH2 mediated oxidation and reduction was investigated spectrophotometrically and the enzyme showed a broader substrate range than its homolog from Saccharomyces cerevisiae. A preference for secondary compared to primary alcohols in oxidation direction was observed for YlADH2. 2-Octanone was investigated in reduction mode in detail. Remarkably, YlADH2 displays perfect (S)-selectivity and together with a highly (R)-selective short chain dehydrogenase/ reductase from Yarrowia lipolytica it is possible to access both enantiomers of 2-octanol in >99% ee with Yarrowia lipolytica oxidoreductases.

Amine oxidation by d-arginine dehydrogenase in Pseudomonas aeruginosa.

PubMed

Ouedraogo, Daniel; Ball, Jacob; Iyer, Archana; Reis, Renata A G; Vodovoz, Maria; Gadda, Giovanni

2017-10-15

d-Arginine dehydrogenase from Pseudomonas aeruginosa (PaDADH) is a flavin-dependent oxidoreductase, which is part of a novel two-enzyme racemization system that functions to convert d-arginine to l-arginine. PaDADH contains a noncovalently linked FAD that shows the highest activity with d-arginine. The enzyme exhibits broad substrate specificity towards d-amino acids, particularly with cationic and hydrophobic d-amino acids. Biochemical studies have established the structure and the mechanistic properties of the enzyme. The enzyme is a true dehydrogenase because it displays no reactivity towards molecular oxygen. As established through solvent and multiple kinetic isotope studies, PaDADH catalyzes an asynchronous CH and NH bond cleavage via a hydride transfer mechanism. Steady-state kinetic studies with d-arginine and d-histidine are consistent with the enzyme following a ping-pong bi-bi mechanism. As shown by a combination of crystallography, kinetic and computational data, the shape and flexibility of loop L1 in the active site of PaDADH are important for substrate capture and broad substrate specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

Supervisors' experiences of workplace supervision of nursing and paramedic students in rural settings: a scoping review.

PubMed

Trede, Franziska; McEwen, Celina; Kenny, Amanda; O'Meara, Peter

2014-05-01

We present our findings from a scoping review that sought to identify what is known about nursing and paramedic clinical supervisors' experiences of their supervision practices in rural settings. Our interest in these two groups is based on the central role that nurses and paramedics play in rural health care. Scoping reviews support identification of a broad range of literature, including all types of study designs. We adopted Arksey and O'Malley's five-stage approach: identifying the research question; identifying relevant studies; study selection; charting the data; and collating, summarising and reporting results. Databases searched included Academic Search Complete, Springer, Factiva, ProQuest, Ebsco, Informit, VOCEDplus and Scopus. Based on our research question and inclusion and exclusion criteria we selected relevant literature and summarised and reported it using Arksey and O'Malley's framework. The review yielded five articles from four countries: Sweden, Belgium, Malaysia and Australia. From this scoping review, we identified key themes related to supervisors' experiences, including clarification of expectations, support from managers and colleagues, the need for shared understanding between university, students and supervisors and required skills and competence in supervising students. © 2013.

Fabrication of nanopore and nanoparticle arrays with high aspect ratio AAO masks.

PubMed

Li, Z P; Xu, Z M; Qu, X P; Wang, S B; Peng, J; Mei, L H

2017-03-03

How to use high aspect ratio anodic aluminum oxide (AAO) membranes as an etching and evaporation mask is one of the unsolved problems in the application of nanostructured arrays. Here we describe the versatile utilizations of the highly ordered AAO membranes with a high aspect ratio of more than 20 used as universal masks for the formation of various nanostructure arrays on various substrates. The result shows that the fabricated nanopore and nanoparticle arrays of substrates inherit the regularity of the AAO membranes completely. The flat AAO substrates and uneven AAO frontages were attached to the Si substrates respectively as an etching mask, which demonstrates that the two kinds of replication, positive and negative, represent the replication of the mirroring of Si substrates relative to the flat AAO substrates and uneven AAO frontages. Our work is a breakthrough for the broad research field of surface nano-masking.

Fabrication of nanopore and nanoparticle arrays with high aspect ratio AAO masks

NASA Astrophysics Data System (ADS)

Li, Z. P.; Xu, Z. M.; Qu, X. P.; Wang, S. B.; Peng, J.; Mei, L. H.

2017-03-01

How to use high aspect ratio anodic aluminum oxide (AAO) membranes as an etching and evaporation mask is one of the unsolved problems in the application of nanostructured arrays. Here we describe the versatile utilizations of the highly ordered AAO membranes with a high aspect ratio of more than 20 used as universal masks for the formation of various nanostructure arrays on various substrates. The result shows that the fabricated nanopore and nanoparticle arrays of substrates inherit the regularity of the AAO membranes completely. The flat AAO substrates and uneven AAO frontages were attached to the Si substrates respectively as an etching mask, which demonstrates that the two kinds of replication, positive and negative, represent the replication of the mirroring of Si substrates relative to the flat AAO substrates and uneven AAO frontages. Our work is a breakthrough for the broad research field of surface nano-masking.

Large-Scale, Lineage-Specific Expansion of a Bric-a-Brac/Tramtrack/Broad Complex Ubiquitin-Ligase Gene Family in Rice[W

PubMed Central

Gingerich, Derek J.; Hanada, Kousuke; Shiu, Shin-Han; Vierstra, Richard D.

2007-01-01

Selective ubiquitination of proteins is directed by diverse families of ubiquitin-protein ligases (or E3s) in plants. One important type uses Cullin-3 as a scaffold to assemble multisubunit E3 complexes containing one of a multitude of bric-a-brac/tramtrack/broad complex (BTB) proteins that function as substrate recognition factors. We previously described the 80-member BTB gene superfamily in Arabidopsis thaliana. Here, we describe the complete BTB superfamily in rice (Oryza sativa spp japonica cv Nipponbare) that contains 149 BTB domain–encoding genes and 43 putative pseudogenes. Amino acid sequence comparisons of the rice and Arabidopsis superfamilies revealed a near equal repertoire of putative substrate recognition module types. However, phylogenetic comparisons detected numerous gene duplication and/or loss events since the rice and Arabidopsis BTB lineages split, suggesting possible functional specialization within individual BTB families. In particular, a major expansion and diversification of a subset of BTB proteins containing Meprin and TRAF homology (MATH) substrate recognition sites was evident in rice and other monocots that likely occurred following the monocot/dicot split. The MATH domain of a subset appears to have evolved significantly faster than those in a smaller core subset that predates flowering plants, suggesting that the substrate recognition module in many monocot MATH-BTB E3s are diversifying to ubiquitinate a set of substrates that are themselves rapidly changing. Intriguing possibilities include pathogen proteins attempting to avoid inactivation by the monocot host. PMID:17720868

Understanding Patenting Decisions: A Classroom Exercise

ERIC Educational Resources Information Center

Bernard, John C.; Yiannaka, Amalia

2010-01-01

Although many students have some knowledge of patents, it can be difficult for them to understand the components of an innovator's decision-making process. Key issues, such as whether to patent or to use trade secrecy, how broad a scope to claim, and what to do in the event of patent infringement, can be difficult to grasp from a standard lecture.…

The Pacific Northwest Research Station biodiversity initiative: scooping out the challenges in managing for biodiversity.

Treesearch

Rachel White; Randy Molina

2006-01-01

The USDA Forest Service Pacific Northwest Research Station's Biodiversity Initiative seeks to determine the types of science tools needed by natural resource professionals to meet diverse and complex biodiversity goals. During the scoping phase of this Initiative, we asked a broad cross-section of people whose work involves managing for biodiversity, from state...

Broad-Based Participatory Inquiry into the Definition and Scope of Disaster

ERIC Educational Resources Information Center

Ozturk Tasci, Fulya; Oguz Unver, Ayse

2017-01-01

Understanding what disaster means will not only raise our awareness but will also bring us closer to knowing how to protect ourselves in the face of their destructive effects. The aim of this study is to understand how the concept of disaster is perceived in different demographics/subgroups of the population and by defining the term, to determine…

Regioselective 5-exo-dig oxy-cyclization of 2-alkynylbenzamide for the synthesis of isobenzofuran-1-imines and isobenzofuran.

PubMed

Wang, Rui-Xiang; Yuan, Si-Tian; Liu, Jin-Biao; Wu, Jie; Qiu, Guanyinsheng

2018-06-06

A TBAB-mediated brominative 5-exo-dig oxy-cyclization of 2-alkynylbenzamide is described here for the synthesis of isobenzofuran-1-imines and isobenzofuran derivatives at room temperature with a high efficiency and a broad reaction scope. The resulting isobenzofuran derivatives are also applied for synthesising various substituted isobenzofuran derivatives.

Iron-catalyzed electrochemical C-H perfluoroalkylation of arenes.

PubMed

Khrizanforov, Mikhail; Strekalova, Sofia; Khrizanforova, Vera; Grinenko, Valeriya; Kholin, Kirill; Kadirov, Marsil; Burganov, Timur; Gubaidullin, Aidar; Gryaznova, Tatyana; Sinyashin, Oleg; Xu, Long; Vicic, David A; Budnikova, Yulia

2015-12-07

A new iron-catalyzed reaction for the coupling of perfluoroalkyl iodides (RFI) with aromatic substrates is described. The perfluoroalkylated arene products are obtained in good to excellent yields in the presence of a [(bpy)Fe(ii)] catalyst (10%) electrochemically regenerated or generated from [(bpy)Fe(iii)] at room temperature. The development, scope, and preliminary mechanistic studies of these transformations are reported.

Decarboxylative Arylation of α-Amino Acids via Photoredox Catalysis: A One-Step Conversion of Biomass to Drug Pharmacophore

PubMed Central

2015-01-01

The direct decarboxylative arylation of α-amino acids has been achieved via visible light-mediated photoredox catalysis. This method offers rapid entry to prevalent benzylic amine architectures from an abundant biomass, specifically α-amino acid precursors. Significant substrate scope is observed with respect to both the amino acid and arene components. PMID:24712922

LIDAR technology developments in support of ESA Earth observation missions

NASA Astrophysics Data System (ADS)

Durand, Yannig; Caron, Jérôme; Hélière, Arnaud; Bézy, Jean-Loup; Meynart, Roland

2017-11-01

Critical lidar technology developments have been ongoing at the European Space Agency (ESA) in support of EarthCARE (Earth Clouds, Aerosols, and Radiation Explorer), the 6th Earth Explorer mission, and A-SCOPE (Advanced Space Carbon and Climate Observation of Planet Earth), one of the candidates for the 7th Earth Explorer mission. EarthCARE is embarking an Atmospheric backscatter Lidar (ATLID) while A-SCOPE is based on a Total Column Differential Absorption Lidar. As EarthCARE phase B has just started, the pre-development activities, aiming at validating the technologies used in the flight design and at verifying the overall instrument performance, are almost completed. On the other hand, A-SCOPE pre-phase A has just finished. Therefore technology developments are in progress, addressing critical subsystems or components with the lowest TRL, selected in the proposed instrument concepts. The activities described in this paper span over a broad range, addressing all critical elements of a lidar from the transmitter to the receiver.

Defining food literacy: A scoping review.

PubMed

Truman, Emily; Lane, Daniel; Elliott, Charlene

2017-09-01

The term "food literacy" describes the idea of proficiency in food related skills and knowledge. This prevalent term is broadly applied, although its core elements vary from initiative to initiative. In light of its ubiquitous use-but varying definitions-this article establishes the scope of food literacy research by identifying all articles that define 'food literacy', analysing its key conceptualizations, and reporting outcomes/measures of this concept. A scoping review was conducted to identify all articles (academic and grey literature) using the term "food literacy". Databases included Medline, Pubmed, Embase, CAB Abstracts, CINAHL, Scopus, JSTOR, and Web of Science, and Google Scholar. Of 1049 abstracts, 67 studies were included. From these, data was extracted on country of origin, study type (methodological approach), primary target population, and the primary outcomes relating to food literacy. The majority of definitions of food literacy emphasize the acquisition of critical knowledge (information and understanding) (55%) over functional knowledge (skills, abilities and choices) (8%), although some incorporate both (37%). Thematic analysis of 38 novel definitions of food literacy reveals the prevalence of six themes: skills and behaviours, food/health choices, culture, knowledge, emotions, and food systems. Study outcomes largely focus on knowledge generating measures, with very few focusing on health related outcome measures. Current definitions of food literacy incorporate components of six key themes or domains and attributes of both critical and functional knowledge. Despite this broad definition of the term, most studies aiming to improve food literacy focus on knowledge related outcomes. Few articles address health outcomes, leaving an important gap (and opportunity) for future research in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Medical practice in rural Saskatchewan: factors in physician recruitment and retention.

PubMed

Wasko, Kevin; Jenkins, Jacqueline; Meili, Ryan

2014-01-01

The recruitment and retention of physicians in rural communities is a challenge throughout Canada and across the globe. In 1976, a group of medical students profiled rural communities with medical practices and produced a summary report entitled Medical Practice in Saskatchewan. Our objective was to repeat the 1976 study and to identify factors that motivate physicians to select rural locations for practice. Physicians practising in rural Saskatchewan were interviewed in 2011 and 2012. Through qualitative, inductive analysis, we identified themes that drove the recruitment and retention of physicians. Sixty-two physicians were interviewed and 105 communities profiled. Of the physicians interviewed, 21 noted that the ability to practise full-scope family medicine and having the freedom to practise as they desire was important for recruitment, and 43 reported that these factors influenced their decision to remain in a community. Attraction to a rural lifestyle (cited by 17 physicians), having a rural background (13) and having ties to a specific community (12) were important for recruitment. Feeling appreciated by patients (45), one's spouse and/or family enjoying the community (41), and integration into the community (38) were important factors for retention. The decision to practise in a rural location correlates with a desire for a broad and varied scope of practice, being attracted to a rural lifestyle and having rural roots. Once physicians establish a rural practice, they are more likely to stay if they can continue a broad scope of practice, if they feel appreciated by their patients, and if their spouses and family are happy in the community.

Palladium-Catalyzed α-Arylation of Zinc Enolates of Esters: Reaction Conditions and Substrate Scope

PubMed Central

Hama, Takuo; Ge, Shaozhong; Hartwig, John F.

2013-01-01

The intermolecular α-arylation of esters by palladium-catalyzed coupling of aryl bromides with zinc enolates of esters is reported. Reactions of three different types of zinc enolates have been developed. α-Arylation of esters occurs in high yields with isolated Reformatsky reagents, with Reformatsky reagents generated from α-bromo esters and activated zinc, and with zinc enolates generated by quenching lithium enolates of esters with zinc chloride. The use of zinc enolates, instead of alkali metal enolates, greatly expands the scope of the arylation of esters. The reactions occur at room temperature or at 70 °C with bromoarenes containing cyano, nitro, ester, keto, fluoro, enolizable hydrogen, hydroxyl or amino functionality and with bromopyridines. The scope of esters encompasses acyclic acetates, propionates, and isobutyrates, α-alkoxyesters, and lactones. The arylation of zinc enolates of esters was conducted with catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) or the highly reactive dimeric Pd(I) complex {[P(t-Bu)3]PdBr}2. PMID:23931445

Cell stiffness, contractile stress and the role of extracellular matrix

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

An, Steven S., E-mail: san@jhsph.edu; Kim, Jina; Ahn, Kwangmi

Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genesmore » in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.« less

Direct transfer of graphene onto flexible substrates.

PubMed

Martins, Luiz G P; Song, Yi; Zeng, Tingying; Dresselhaus, Mildred S; Kong, Jing; Araujo, Paulo T

2013-10-29

In this paper we explore the direct transfer via lamination of chemical vapor deposition graphene onto different flexible substrates. The transfer method investigated here is fast, simple, and does not require an intermediate transfer membrane, such as polymethylmethacrylate, which needs to be removed afterward. Various substrates of general interest in research and industry were studied in this work, including polytetrafluoroethylene filter membranes, PVC, cellulose nitrate/cellulose acetate filter membranes, polycarbonate, paraffin, polyethylene terephthalate, paper, and cloth. By comparing the properties of these substrates, two critical factors to ensure a successful transfer on bare substrates were identified: the substrate's hydrophobicity and good contact between the substrate and graphene. For substrates that do not satisfy those requirements, polymethylmethacrylate can be used as a surface modifier or glue to ensure successful transfer. Our results can be applied to facilitate current processes and open up directions for applications of chemical vapor deposition graphene on flexible substrates. A broad range of applications can be envisioned, including fabrication of graphene devices for opto/organic electronics, graphene membranes for gas/liquid separation, and ubiquitous electronics with graphene.

Characterization of a new oligoalginate lyase from marine bacterium Vibrio sp.

PubMed

Yu, Zuochen; Zhu, Benwei; Wang, Wenxia; Tan, Haidong; Yin, Heng

2018-06-01

A new oligoalginate lyase encoding gene, designed oal17A, was cloned from marine bacterium Vibrio sp. W13, and then expressed in Escherichia coli. The recombinant Oal17A was purified by NTA-Ni resin with maximal activity at 30°C and pH7.0. Oal17A exhibited broad substrate specificity, and preferred to degrade alginate than polyM or polyG into monosaccharide acid. The specific activity of Oal17A toward alginate, polyM and polyG was 21.14U/mg, 12.31U/mg and 7.43U/mg, respectively. With features of high-level expression and broad substrate specificity, Oal17A would be a potential tool for alginate monomer production process of alginate utilizing for biofuels and bioethanol production. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis and characterization of InN nanocrystals on glass substrate by plasma assisted reactive evaporation

NASA Astrophysics Data System (ADS)

Ganesh, V.; Alizadeh, M.; Shuhaimi, A.; Sundaram, S.; Hakim, K. M.; Goh, B. T.; Rahman, S. A.

2017-07-01

InN nanocrystals were grown on glass substrate by plasma assisted reactive evaporation technique and the quality was compared with InN on Si (111) substrate. Single phase InN was confirmed by X-ray diffraction and micro Raman analysis on both the substrates. Agglomerated and Hexagonal faceting nanocrystals observed by field emission scanning electron microscopy. Energy dispersive X-ray analysis shows InN nanocrystals are nearly stochiometric. Photoluminescence reveals a broad emission near bandedge at 2 .04 eV and defect band at 1.07 eV. The Hall measurement on both the substrates reveals high electron carrier concentration. These encouraging results obtained suggested that high quality single crystalline InN can be obtained on glass substrate further optimizing the growth parameters. This novel growth of InN nanocrystals on glass substrate is an important step towards the development of monolithic, high efficiency low-cost InGaN-based renewable energy sources.

Catalytic bismetallative multicomponent coupling reactions: scope, applications, and mechanisms

PubMed Central

Cho, Hee Yeon

2014-01-01

Catalytic reactions have played an indispensable role in organic chemistry for the last several decades. In particular, catalytic multicomponent reactions have attracted a lot of attention due to their efficiency and expediency towards complex molecule synthesis. The presence of bismetallic reagents (e.g. B–B, Si–Si, B–Si, Si–Sn, etc.) in this process renders the products enriched with various functional groups and multiple stereocenters. For this reason, catalytic bismetallative coupling is considered an effective method to generate the functional and stereochemical complexity of simple hydrocarbon substrates. This review highlights key developments of transition-metal catalyzed bismetallative reactions involving multiple π components. Specifically, it will highlight the scope, synthetic applications, and proposed mechanistic pathways of this process. PMID:24736839

Novel SiO2-deposited CaF2 substrate for vibrational sum-frequency generation (SFG) measurements of chemisorbed monolayers in an aqueous environment.

PubMed

Padermshoke, Adchara; Konishi, Shouta; Ara, Masato; Tada, Hirokazu; Ishibashi, Taka-Aki

2012-06-01

A novel SiO(2)-deposited CaF(2) (SiO(2)/CaF(2)) substrate for measuring vibrational sum-frequency generation (SFG) spectra of silane-based chemisorbed monolayers in aqueous media has been developed. The substrate is suitable for silanization and transparent over a broad range of the infrared (IR) probe. The present work demonstrates the practical application of the SiO(2)/CaF(2) substrate and, to our knowledge, the first SFG spectrum at the solid/water interface of a silanized monolayer observed over the IR fingerprint region (1780-1400 cm(-1)) using a back-side probing geometry. This new substrate can be very useful for SFG studies of various chemisorbed organic molecules, particularly biological compounds, in aqueous environments.

[Substrate specifity in Amoeba proteus].

PubMed

Sopina, V A

2006-01-01

Three different phosphatases ("slow", "middle" and "fast") were found in Amoeba proteus (strain B) after PAGE and a subsequent gel staining in 1-naphthyl phosphate containing incubation mixture (pH 9.0). Substrate specificity of these phosphatases was determined in supernatants of homogenates using inhibitors of phosphatase activity. All phosphatases showed a broad substrate specificity. Of 10 tested compounds, p-nitrophenyl phosphate was a preferable substrate for all 3 phosphatases. All phosphatases were able to hydrolyse bis-p-nitrophenyl phosphate and, hence, displayed phosphodiesterase activity. All phosphatases hydrolysed O-phospho-L-tyrosine to a greater or lesser degree. Only little differences in substrate specificity of phosphatases were noticed: 1) "fast" and "middle" phosphatases hydrolysed naphthyl phosphates and O-phospho-L-tyrosine less efficiently than did "slow" phosphatase; 2) "fast" and "middle" phosphatases hydrolysed 2- naphthyl phosphate to a lesser degree than 1-naphthyl phosphate 3) "fast" and "middle" phosphatases hydrolysed O-phospho-L-serine and O-phospho-L-threonine with lower intensity as compared with "slow" phosphatase; 4) as distinct from "middle" and "slow" phosphatases, the "fast" phosphatase hydrolysed glucose-6-phosphate very poorly. The revealed broad substrate specificity of "slow" phosphatase together with data of inhibitory analysis and results of experiments with reactivation of this phosphatase by Zn2+-ions after its inactivation by EDTA strongly suggest that only the "slow" phosphatase is a true alkaline phosphatase (EC 3.1.3.1). The alkaline phosphatase of A. proteus is secreted into culture medium where its activity is low. The enzyme displays both phosphomono- and phosphodiesterase activities, in addition to supposed protein phosphatase activity. It still remains unknown, to which particular phosphatase class the amoeban "middle" and "fast" phosphatases (pH 9.0) may be assigned.

Predicting the scope of practice of family physicians.

PubMed

Wong, Eric; Stewart, Moira

2010-06-01

To identify factors that are associated with the scope of practice of FPs and GPs who have office-based practices. Secondary univariable and multivariable analyses of cross-sectional data from the 2001 National Family Physician Workforce Survey conducted by the College of Family Physicians of Canada. Canada. General community of FPs and GPs who spent most of their clinical time in office settings. Demographic characteristics and scope of practice score (SPS), which was the number of 12 selected medical services provided by office-based FPs and GPs. The multivariable model explained 35.1% of the variation in the SPS among participants. Geographic factors of provincial division and whether or not the population served was rural explained 30.5% of the variation in the SPS. Male physician sex, younger physician age, being in group practice, greater access to hospital beds, less access to specialists, main practice setting of an academic teaching unit, mixed method physician payment, additional structured postresidency training, and greater number of different types of allied health professionals in the main practice setting were also associated with higher SPSs. Geographic factors were the strongest determinants of scope of practice; physician-related factors, availability of health care resources to the main practice setting, and practice organization factors were weaker determinants. It is important to understand how and why geographic factors influence scope of practice, and whether a broad scope of practice independent of population needs benefits the population. This study supports primary care renewal efforts that use mixed payment systems, incorporate allied health care professionals into family and general practices, and foster group practices.

Near-infrared–driven decomposition of metal precursors yields amorphous electrocatalytic films

PubMed Central

Salvatore, Danielle A.; Dettelbach, Kevan E.; Hudkins, Jesse R.; Berlinguette, Curtis P.

2015-01-01

Amorphous metal-based films lacking long-range atomic order have found utility in applications ranging from electronics applications to heterogeneous catalysis. Notwithstanding, there is a limited set of fabrication methods available for making amorphous films, particularly in the absence of a conducting substrate. We introduce herein a scalable preparative method for accessing oxidized and reduced phases of amorphous films that involves the efficient decomposition of molecular precursors, including simple metal salts, by exposure to near-infrared (NIR) radiation. The NIR-driven decomposition process provides sufficient localized heating to trigger the liberation of the ligand from solution-deposited precursors on substrates, but insufficient thermal energy to form crystalline phases. This method provides access to state-of-the-art electrocatalyst films, as demonstrated herein for the electrolysis of water, and extends the scope of usable substrates to include nonconducting and temperature-sensitive platforms. PMID:26601148

Cooperative catalysis by tertiary amino-thioureas: mechanism and basis for enantioselectivity of ketone cyanosilylation.

PubMed

Zuend, Stephan J; Jacobsen, Eric N

2007-12-26

The mechanism of the enantioselective cyanosilylation of ketones catalyzed by tertiary amino-thiourea derivatives was investigated using a combination of experimental and theoretical methods. The kinetic analysis is consistent with a cooperative mechanism in which both the thiourea and the tertiary amine of the catalyst are involved productively in the rate-limiting cyanide addition step. Density functional theory calculations were used to distinguish between mechanisms involving thiourea activation of ketone or of cyanide in the enantioselectivity-determining step. The strong correlation obtained between experimental and calculated ee's for a range of substrates and catalysts provides support for the most favorable calculated transition structures involving amine-bound HCN adding to thiourea-bound ketone. The calculations suggest that enantioselectivity arises from direct interactions between the ketone substrate and the amino-acid derived portion of the catalyst. On the basis of this insight, more enantioselective catalysts with broader substrate scope were prepared and evaluated experimentally.

Direct transfer of graphene onto flexible substrates

PubMed Central

Martins, Luiz G. P.; Song, Yi; Zeng, Tingying; Dresselhaus, Mildred S.; Kong, Jing; Araujo, Paulo T.

2013-01-01

In this paper we explore the direct transfer via lamination of chemical vapor deposition graphene onto different flexible substrates. The transfer method investigated here is fast, simple, and does not require an intermediate transfer membrane, such as polymethylmethacrylate, which needs to be removed afterward. Various substrates of general interest in research and industry were studied in this work, including polytetrafluoroethylene filter membranes, PVC, cellulose nitrate/cellulose acetate filter membranes, polycarbonate, paraffin, polyethylene terephthalate, paper, and cloth. By comparing the properties of these substrates, two critical factors to ensure a successful transfer on bare substrates were identified: the substrate’s hydrophobicity and good contact between the substrate and graphene. For substrates that do not satisfy those requirements, polymethylmethacrylate can be used as a surface modifier or glue to ensure successful transfer. Our results can be applied to facilitate current processes and open up directions for applications of chemical vapor deposition graphene on flexible substrates. A broad range of applications can be envisioned, including fabrication of graphene devices for opto/organic electronics, graphene membranes for gas/liquid separation, and ubiquitous electronics with graphene. PMID:24127582

Space transfer concepts and analysis for exploration missions

NASA Technical Reports Server (NTRS)

Woodcock, Gordon R.

1992-01-01

The current technical effort is part of the third phase of a broad-scoped and systematic study of space transfer concepts for human lunar and Mars missions. The study addressed the technical issues relating to the First Lunar Outpost (FLO) habitation vehicle with emphasis on the structure, power, life support system, and radiation environment for a baseline habitat with specific alternatives for the baseline.

Radiation -- A Cosmic Hazard to Human Habitation in Space

NASA Technical Reports Server (NTRS)

Lewis, Ruthan; Pellish, Jonathan

2017-01-01

Radiation exposure is one of the greatest environmental threats to the performance and success of human and robotic space missions. Radiation permeates all space and aeronautical systems, challenges optimal and reliable performance, and tests survival and survivability. We will discuss the broad scope of research, technological, and operational considerations to forecast and mitigate the effects of the radiation environment for deep space and planetary exploration.

["The eco-nurse is an expert in environmental health"].

PubMed

Biard, Nicolas

2018-03-01

Eco-nurses are trained in environmental health in order to act as a resource person with the public and health professionals. Experts in the field, their scope of action is broad, both targeted and on a more global scale. Philippe Perrin is an eco-nurse and the director of the Environmental Health Training Institute in France. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Substrate-Controlled Product Divergence: Conversion of CO2 into Heterocyclic Products.

PubMed

Rintjema, Jeroen; Epping, Roel; Fiorani, Giulia; Martín, Eddy; Escudero-Adán, Eduardo C; Kleij, Arjan W

2016-03-14

Substituted epoxy alcohols and amines allow substrate-controlled conversion of CO2 into a wide range of heterocyclic structures through different mechanistic manifolds. This new approach results in an unusual scope of CO2-derived products by initial activation of CO2 through either the amine or alcohol unit, thus providing nucleophiles for intramolecular epoxy ring opening under mild reaction conditions. Control experiments support the crucial role of the amine/alcohol fragment in this process with the nucleophile-assisted ring-opening step following an SN i pathway, and a 5-exo-tet cyclization, thus leading to heterocyclic scaffolds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding and Improving the Activity of Flavin Dependent Halogenases via Random and Targeted Mutagenesis

PubMed Central

Andorfer, Mary C.

2018-01-01

Flavin dependent halogenases (FDHs) catalyze the halogenation of organic substrates by coordinating reactions of reduced flavin, molecular oxygen, and chloride. Targeted and random mutagenesis of these enzymes has been used to both understand and alter their reactivity. These studies have led to insights into residues essential for catalysis and FDH variants with improved stability, expanded substrate scope, and altered site selectivity. Mutations throughout FDH structures have contributed to all of these advances. More recent studies have sought to rationalize the impact of these mutations on FDH function and to identify new FDHs to deepen our understanding of this enzyme class and to expand their utility for biocatalytic applications. PMID:29589959

Copper-Catalyzed Electrophilic Amination of Organoaluminum Nucleophiles with O-Benzoyl Hydroxylamines.

PubMed

Zhou, Shuangliu; Yang, Zhiyong; Chen, Xu; Li, Yimei; Zhang, Lijun; Fang, Hong; Wang, Wei; Zhu, Xiancui; Wang, Shaowu

2015-06-19

A copper-catalyzed electrophilic amination of aryl and heteroaryl aluminums with N,N-dialkyl-O-benzoyl hydroxylamines that affords the corresponding anilines in good yields has been developed. The catalytic reaction proceeds very smoothly under mild conditions and exhibits good substrate scope. Moreover, the developed catalytic system is also well suited for heteroaryl aluminum nucleophiles, providing facile access to heteroaryl amines.

The first mammalian aldehyde oxidase crystal structure: insights into substrate specificity.

PubMed

Coelho, Catarina; Mahro, Martin; Trincão, José; Carvalho, Alexandra T P; Ramos, Maria João; Terao, Mineko; Garattini, Enrico; Leimkühler, Silke; Romão, Maria João

2012-11-23

Aldehyde oxidases have pharmacological relevance, and AOX3 is the major drug-metabolizing enzyme in rodents. The crystal structure of mouse AOX3 with kinetics and molecular docking studies provides insights into its enzymatic characteristics. Differences in substrate and inhibitor specificities can be rationalized by comparing the AOX3 and xanthine oxidase structures. The first aldehyde oxidase structure represents a major advance for drug design and mechanistic studies. Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 Å. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity.

Growth and characterization of V2O5 nanorods deposited by spray pyrolysis at low temperatures

NASA Astrophysics Data System (ADS)

Abd-Alghafour, N. M.; Ahmed, Naser M.; Hassan, Zai.; Mohammad, Sabah M.; Bououdina, M.

2016-07-01

Vanadium pentoxide (V2O5) nanorods were deposited by spray pyrolysis on preheated glass substrates at low temperatures. The influence of substrate temperature on the crystallization of V2O5 has been investigated. X-ray diffraction analysis (XRD) revealed that the films deposited at Tsub = 300°C were orthorhombic structures with preferential along (001) direction. Formation of nanorods from substrate surface which led to the formation of films with small-sized and rod-shaped nanostructure is observed by field scanning electron microscopy. Optical transmittance in the visible range increases to reach a maximum value of about 80% for a substrate temperature of 350°C. PL spectra reveal one main broad peak centered around 540 nm with high intensity.

Allosteric regulation of rhomboid intramembrane proteolysis.

PubMed

Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

2014-09-01

Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases. © 2014 The Authors.

Allosteric regulation of rhomboid intramembrane proteolysis

PubMed Central

Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

2014-01-01

Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases. PMID:25009246

WOR5, a Novel Tungsten-Containing Aldehyde Oxidoreductase from Pyrococcus furiosus with a Broad Substrate Specificity

PubMed Central

Bevers, Loes E.; Bol, Emile; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

2005-01-01

WOR5 is the fifth and last member of the family of tungsten-containing oxidoreductases purified from the hyperthermophilic archaeon Pyrococcus furiosus. It is a homodimeric protein (subunit, 65 kDa) that contains one [4Fe-4S] cluster and one tungstobispterin cofactor per subunit. It has a broad substrate specificity with a high affinity for several substituted and nonsubstituted aliphatic and aromatic aldehydes with various chain lengths. The highest catalytic efficiency of WOR5 is found for the oxidation of hexanal (Vmax = 15.6 U/mg, Km = 0.18 mM at 60°C). Hexanal-incubated enzyme exhibits S = 1/2 electron paramagnetic resonance signals from [4Fe-4S]1+ (g values of 2.08, 1.93, and 1.87) and W5+ (g values of 1.977, 1.906, and 1.855). Cyclic voltammetry of ferredoxin and WOR5 on an activated glassy carbon electrode shows a catalytic wave upon addition of hexanal, suggesting that ferredoxin can be a physiological redox partner. The combination of WOR5, formaldehyde oxidoreductase, and aldehyde oxidoreductase forms an efficient catalyst for the oxidation of a broad range of aldehydes in P. furiosus. PMID:16199576

Enzyme specificity under dynamic control

NASA Astrophysics Data System (ADS)

Ota, Nobuyuki; Agard, David A.

2002-03-01

The contributions of conformational dynamics to substrate specificity have been examined by the application of principal component analysis to molecular dynamics trajectories of alpha-lytic protease. The wild-type alpha-lytic protease is highly specific for substrates with small hydrophobic side chains at the specificity pocket, while the Met190Ala binding pocket mutant has a much broader specificity, actively hydrolyzing substrates ranging from Ala to Phe. We performed a principal component analysis using 1-nanosecond molecular dynamics simulations using solvent boundary condition. We found that the walls of the wild-type substrate binding pocket move in tandem with one another, causing the pocket size to remain fixed so that only small substrates are recognized. In contrast, the M190A mutant shows uncoupled movement of the binding pocket walls, allowing the pocket to sample both smaller and larger sizes, which appears to be the cause of the observed broad specificity. The results suggest that the protein dynamics of alpha-lytic protease may play a significant role in defining the patterns of substrate specificity.

Structural insights into the cofactor-assisted substrate recognition of yeast methylglyoxal/isovaleraldehyde reductase Gre2.

PubMed

Guo, Peng-Chao; Bao, Zhang-Zhi; Ma, Xiao-Xiao; Xia, Qingyou; Li, Wei-Fang

2014-09-01

Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that catalyzes the stereoselective reduction of a broad range of substrates including aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae in an apo-form at 2.00Å and NADPH-complexed form at 2.40Å resolution. Gre2 forms a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain and a variable C-terminal domain, which participates in substrate recognition. The induced fit upon binding to the cofactor NADPH makes the two domains shift toward each other, producing an interdomain cleft that better fits the substrate. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis enabled us to define a potential substrate-binding pocket that determines the stringent substrate stereoselectivity for catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated gold ellipse nanoantenna dimers as sensitive and tunable surface enhanced Raman spectroscopy substrates

DOE PAGES

Jubb, A. M.; Jiao, Y.; Eres, Gyula; ...

2016-02-15

Here we demonstrate large area arrays of elevated gold ellipse dimers with precisely controlled gaps for use as sensitive and highly controllable surface enhanced Raman scattering (SERS) substrates. The significantly enhanced Raman signal observed with SERS arises from both localized and long range plasmonic effects. By controlling the geometry of a SERS substrate, in this case the size and aspect ratio of individual ellipses, the plasmon resonance can be tuned in a broad wavelength range, providing a method for designing the response of SERS substrates at different excitation wavelengths. Plasmon effects exhibited by the elevated gold ellipse dimer substrates aremore » also demonstrated and confirmed through finite difference time domain (FDTD) simulations. A plasmon resonance red shift with an increase of the ellipse aspect ratio is observed, allowing systematic control of the resulting SERS signal intensity. Optimized elevated ellipse dimer substrates with 10±2 nm gaps exhibit uniform SERS enhancement factors on the order of 10 9 for adsorbed p-mercaptoaniline molecules.« less

The research contributions of predominantly North American Family Medicine educators to medical learner feedback: a descriptive analysis following a scoping review.

PubMed

Hayes, Victoria; Bing-You, Robert; Varaklis, Kalli; Trowbridge, Robert; Kemp, Heather; McKelvy, Dina

2018-05-01

In 2016, we performed a scoping review as a means of mapping what is known in the literature about feedback to medical learners. In this descriptive analysis, we explore a subset of the results to assess the contributions of predominantly North American family medicine educators to the feedback literature. Nineteen articles extracted from our original scoping review plus six articles identified from an additional search of the journal Family Medicine are described in-depth. The proportion of articles involving family medicine educators identified in our scoping review is small (n=19/650, 3%) and the total remains low (25) after including additional articles (n=6) from a Family Medicine search. They encompass a broad range of feedback methods and content areas. They primarily originated in the United States (n=19) and Canada (n=3) within Family Medicine Departments (n=20) and encompass a variety of scientific and educational research methodologies. The contributions of predominantly North American Family Medicine educators to the literature on feedback to learners are sparse in number and employ a variety of focus areas and methodological approaches. More studies are needed to assess for areas of education research where family physicians could make valuable contributions.

Children, biobanks and the scope of parental consent

PubMed Central

Hens, Kristien; Cassiman, Jean-Jacques; Nys, Herman; Dierickx, Kris

2011-01-01

The use of stored tissue samples from children for genetic research raises specific ethical questions that are not all analogous to those raised when adult participants are concerned. These include issues with regard to consent, as it is typically a parent who consents to the use of samples from children. In this paper, we discuss the scope of parental consent. This scope has a temporal dimension and one related to the content of consent. It is not questioned that the temporal scope of parental consent is limited and that young adults have the right to decide on the fate of their samples when they reach the age of maturity. With regard to the content of consent, the question remains whether parents are allowed to give full broad consent to any possible future research on the samples of their children. We argue that they should not be allowed to do so, based on two premises. First, it is generally acknowledged that children have a right to express their own values and that they should be given the opportunity to develop their own autonomy as they grow older. Second, research and science are not completely value-free and some types of research may be more sensitive than other types. Children should be given the opportunity to express their values also in this respect. PMID:21386873

A broad-scale comparison of aerobic activity levels in vertebrates: endotherms versus ectotherms

PubMed Central

Gomez, Juan Pablo; Mavrodiev, Evgeny V.

2017-01-01

Differences in the limits and range of aerobic activity levels between endotherms and ectotherms remain poorly understood, though such differences help explain basic differences in species' lifestyles (e.g. movement patterns, feeding modes, and interaction rates). We compare the limits and range of aerobic activity in endotherms (birds and mammals) and ectotherms (fishes, reptiles, and amphibians) by evaluating the body mass-dependence of VO2 max, aerobic scope, and heart mass in a phylogenetic context based on a newly constructed vertebrate supertree. Contrary to previous work, results show no significant differences in the body mass scaling of minimum and maximum oxygen consumption rates with body mass within endotherms or ectotherms. For a given body mass, resting rates and maximum rates were 24-fold and 30-fold lower, respectively, in ectotherms than endotherms. Factorial aerobic scope ranged from five to eight in both groups, with scope in endotherms showing a modest body mass-dependence. Finally, maximum consumption rates and aerobic scope were positively correlated with residual heart mass. Together, these results quantify similarities and differences in the potential for aerobic activity among ectotherms and endotherms from diverse environments. They provide insights into the models and mechanisms that may underlie the body mass-dependence of oxygen consumption. PMID:28202808

Paediatric gastrostomy stoma complications and treatments: A rapid scoping review.

PubMed

Townley, Ashleigh; Wincentak, Joanne; Krog, Kim; Schippke, Julia; Kingsnorth, Shauna

2018-04-01

To provide a scoping review of the types of treatments used to address paediatric skin-related stoma complications specific to infection, hypergranulation and gastric leakage, and explore their effectiveness and indications for use. Stoma-related complications can be a common occurrence for children with gastrostomy (G) and gastrojejunostomy (GJ) tubes. Nurses require guidance to inform decision-making of the broad spectrum of treatments used in clinical practice. A scoping review using a rapid review approach. Working with a multidisciplinary health professional team, search terms were generated. A systematic search of CINAHL, MEDLINE and EMBASE databases was completed, coupled with an Internet search to identify relevant clinical practice guidelines and hand searching of citation lists. Eligible articles were peer-reviewed English publications, focused on paediatric populations aged 18 years and under, dating from 2002-2016 and described complications and treatment approaches related to G- and GJ-tube stomas. Pertinent information was extracted using a standardised template, and a narrative synthesis approach was used to analyse the data. Twenty-five articles were included in this review. Study designs varied, and complication management was often a secondary focus. A broad spectrum of treatments was used to manage each complication type. There was a lack of consensus on lines of therapy; however, a stepwise approach was often used for complication management, particularly for infections. The evidence on the comparative effectiveness of different treatment strategies of skin-related gastrostomy stoma complications in paediatric practice is sparse. Current evidence is generally limited to expert opinions. Future studies examining efficacy of treatments and their indications for use with children are warranted. Effective management of skin-related stoma complications is important to maintain health and wellness among children who rely on G- and GJ-tubes for nutrition support. © 2017 John Wiley & Sons Ltd.

Biodiversity and industry ecosystem management

NASA Astrophysics Data System (ADS)

Coleman, William G.

1996-11-01

The term biodiversity describes the array of interacting, genetically distinct populations and species in a region, the communities they comprise, and the variety of ecosystems of which they are functioning parts. Ecosystem health, a closely related concept, is described in terms of a process identifying biological indicators, end points, and values. The decline of populations or species, an accelerating trend worldwide, can lead to simplification of ecosystem processes, thus threatening the stability and sustainability of ecosystem services directly relevant to human welfare in the chain of economic and ecological relationships. The challenge of addressing issues of such enormous scope and complexity has highlighted the limitations of ecology-as-science. Additionally, biosphere-scale conflicts seem to lie beyond the scope of conventional economics, leading to differences of opinion about the commodity value of biodiversity and of the services that intact ecosystems provide. In the face of these uncertainties, many scientists and economists have adopted principles that clearly assign burdens of proof to those who would promote the loss of biodiversity and that also establish “near-trump” (preeminent) status for ecological integrity. Electric utility facilities and operations impact biodiversity whenever construction, operation, or maintenance of generation, delivery, and support facilities alters landscapes and habitats and thereby impacts species. Although industry is accustomed to dealing with broad environmental concerns (such as global warming or acid rain), the biodiversity issue invokes hemisphere-wide, regional, local, and site-specific concerns all at the same time. Industry can proactively address these issues of scope and scale in two main ways: first, by aligning strategically with the broad research agenda put forth by informed scientists and institutions; and second, by supporting focused management processes whose results will contribute incrementally to the broader agenda of rebuilding or maintaining biodiversity.

Biodiversity and industry ecosystem management

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

Coleman, W.G.

1996-11-01

Biodiversity describes the array of interacting, genetically distinct populations and species in a region, the communities they are functioning parts. Ecosystem health is a process identifying biological indicators, end points, and values. The decline of populations or species, an accelerating trend worldwide, can lead to simplification of ecosystem processes, thus threatening the stability an sustainability of ecosystem services directly relevant to human welfare in the chain of economic and ecological relationships. The challenge of addressing issues of such enormous scope and complexity has highlighted the limitations of ecology-as-science. Additionally, biosphere-scale conflicts seem to lie beyond the scope of conventional economics,more » leading to differences of opinion about the commodity value of biodiversity and of the services that intact ecosystems provide. In the fact of these uncertainties, many scientists and economists have adopted principles that clearly assign burdens of proof to those who would promote the loss of biodiversity and that also establish {open_quotes}near-trump{close_quotes} (preeminent) status for ecological integrity. Electric utility facilities and operations impact biodiversity whenever construction, operation, or maintenance of generation, delivery, and support facilities alters landscapes and habitats and thereby impacts species. Although industry is accustomed to dealing with broad environmental concerns (such as global warming or acid rain), the biodiversity issue invokes hemisphere-side, regional, local, and site-specific concerns all at the same time. Industry can proactively address these issues of scope and scale in two main ways: first, by aligning strategically with the broad research agenda put forth by informed scientists and institutions; and second, by supporting focused management processes whose results will contribute incrementally to the broader agenda of rebuilding or maintaining biodiversity. 40 refs., 8 figs.« less

Kitchen chemistry: A scoping review of the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions.

PubMed

Van Hout, Marie Claire

2014-01-01

Misuse of pharmaceuticals is of increasing drug policy and public health concern. A scoping review was conducted on the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions. The research question was broad: What is known from the existing literature about the diversion of pharmaceuticals for non-medicinal use and for home production of drug solutions? The scoping process centred on the systematic selection, collection, and summarization of extant knowledge within this broad thematic remit. One hundred and thirty-four records were grouped into discrete thematic categories namely: non medicinal use and tampering with pharmaceuticals, oral misuse of codeine cough syrups, homemade drug solutions, and home-produced drug-related harms in the narrative review design. Forms of abuse of codeine cough syrup include mixtures with alcohol or soft drinks ('Purple Drank'), with kratom leaves ('Kratom cocktails'), or chemically altered to extract dextromorphan ('Lemon Drop'). Production of homemade opiates ('Cheornaya', 'Kolyosa', Himiya', 'Braun', 'Krokodil'), methamphetamine ('Vint', 'Pervitin'), methcathinone ('Jeff'), and cathinone ('Boltushka') are described. Displacement patterns between the non-medical use of pharmaceuticals, commercial, and homemade drugs appear dependent on availability of opiates, prescribing practices, supervision of substitution drug dosing, availability of cheap ingredients, policing, and awareness of harms. Adverse health and social consequences relate to the use of unknown and contaminated (end) substances, injecting practices, redosing, medical complications, and death. The review highlights a public health imperative requiring a multidisciplinary approach to quantify potential impact and required integrated policy responses incorporating international regulation, enforcement, health surveillance and service delivery. Copyright © 2014 John Wiley & Sons, Ltd.

Temporal orientation.

PubMed

Maglio, Sam J; Trope, Yaacov

2018-05-18

Time in the mind orients people in one of two directions. An inward orientation points to the present, contracting the scope of thought to immediate concerns. An outward orientation, in contrast, points away from the present to the past or the future, expanding the scope of thought to a wider consideration set. These oriented arrows need not solely be used for mental time travel, as a similar inward/outward orientation can apply to social distance, spatial distance, and probability. We review recent findings illuminated by this broad form distancing, as illustrated in how people learn from and compare themselves to others, before concluding with a discussion of how change necessarily transpires over time, providing opportunities for future research at the intersection of future thought and present behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

Engineering substrate promiscuity in halophilic alcohol dehydrogenase (HvADH2) by in silico design.

PubMed

Cassidy, Jennifer; Bruen, Larah; Rosini, Elena; Molla, Gianluca; Pollegioni, Loredano; Paradisi, Francesca

2017-01-01

An alcohol dehydrogenase from the halophilic archaeon Haloferax volcanii (HvADH2) has been engineered by rational design to broaden its substrate scope towards the conversion of a range of aromatic substrates, including flurbiprofenol, that is an intermediate of the non-steroidal anti-inflammatory drug, flurbiprofen. Wild-type HvADH2 showed minimal activity with flurbiprofenol (11.1 mU/mg). A homology model of HvADH2 was built and docking experiments with this substrate revealed that the biphenyl rings of flurbiprofenol formed strong interactions with residues F85 and F108, preventing its optimal binding in the active site. Mutations at position 85 however did not increase activity. Site directed mutagenesis at position F108 allowed the identification of three variants showing a significant (up to 2.3-fold) enhancement of activity towards flurbiprofenol, when compared to wild-type HvADH2. Interestingly, F108G variant did not show the classic inhibition in the presence of (R)-enantiomer when tested with rac-1-phenylethanol, underling its potential in racemic resolution of secondary alcohols.

Finger millet (Eleusine coracana) - an economically viable source for antihypercholesterolemic metabolites production by Monascus purpureus.

PubMed

Venkateswaran, V; Vijayalakshmi, G

2010-08-01

Rice, parboiled rice, finger millet, germinated finger millet, broken wheat, njavara (medicinal rice), sorghum and maize were used as substrates for solid state fermentation of Monascus purpureus at 28°C for 7 days using 2% seed medium as inoculum for the production of its metabolites. The fungus exhibited good growth in all the substrates. The fermented substrates were dried at 45°C and analysed for antihypercholesterolemic metabolite statins by standardized HPLC method and dietary sterol contents by spectrophotometric method using reference standards of statin (pravastatin and lovastatin) and cholesterol, respectively. Germinated finger millet yielded higher total statin production of 5.2 g/kg dry wt with pravastatin and lovastatin content of 4.9 and 0.37 g/kg dry wt respectively than other substrates which range from 1.04-4.41 g/kg. In addition to statin, monascus fermented germinated finger millet yielded dietary sterol of 0.053 g/kg dry wt which is 7.6 folds higher than the control. The value addition of finger millet by germination and fermentation with Monascus purpureus provides scope for development of functional food.

Heavy Ion Current Transients in SiGe HBTs

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.; Reed, Robert A.; Vizkelethy, Gyorgy; McMorrow, Dale; Ferlet-Cavrois, Veronique; Baggio, Jacques; Paillet, Philipe; Duhanel, Olivier; Phillips, Stanley D.; Sutton, Akil K.;

Validation of automated supervised segmentation of multibeam backscatter data from the Chatham Rise, New Zealand

NASA Astrophysics Data System (ADS)

Hillman, Jess I. T.; Lamarche, Geoffroy; Pallentin, Arne; Pecher, Ingo A.; Gorman, Andrew R.; Schneider von Deimling, Jens

2018-06-01

Using automated supervised segmentation of multibeam backscatter data to delineate seafloor substrates is a relatively novel technique. Low-frequency multibeam echosounders (MBES), such as the 12-kHz EM120, present particular difficulties since the signal can penetrate several metres into the seafloor, depending on substrate type. We present a case study illustrating how a non-targeted dataset may be used to derive information from multibeam backscatter data regarding distribution of substrate types. The results allow us to assess limitations associated with low frequency MBES where sub-bottom layering is present, and test the accuracy of automated supervised segmentation performed using SonarScope® software. This is done through comparison of predicted and observed substrate from backscatter facies-derived classes and substrate data, reinforced using quantitative statistical analysis based on a confusion matrix. We use sediment samples, video transects and sub-bottom profiles acquired on the Chatham Rise, east of New Zealand. Inferences on the substrate types are made using the Generic Seafloor Acoustic Backscatter (GSAB) model, and the extents of the backscatter classes are delineated by automated supervised segmentation. Correlating substrate data to backscatter classes revealed that backscatter amplitude may correspond to lithologies up to 4 m below the seafloor. Our results emphasise several issues related to substrate characterisation using backscatter classification, primarily because the GSAB model does not only relate to grain size and roughness properties of substrate, but also accounts for other parameters that influence backscatter. Better understanding these limitations allows us to derive first-order interpretations of sediment properties from automated supervised segmentation.

2011 Year in review - Earth Resources Observation and Science Center

USGS Publications Warehouse

Johnson, Rebecca L.

2012-01-01

The USGS Earth Resources Observation and Science (EROS) Center's 2011 Year in Review is an annual report recounting the broad scope of the Center's 2011 accomplishments. The report covers preparations for the Landsat Data Continuity Mission (LDCM) launch, the ever-increasing use of free Landsat data, monitoring the effects of natural hazards, and more to emphasize the importance of innovation in using satellite data to study change over time.

Theoretical Underpinnings of the Other Social Effects Account

DTIC Science & Technology

2007-09-01

and to help focus on areas where capacity building is needed. The Civic Index focuses on 12 key themes of civic health and provides 363 example...be used in the emerging collaborative planning framework (also termed the four-account framework to stress the importance of all accounts), discusses ...conducting scoping workshops, generally as part of the EIS process Four-account framework defines problems more broadly and focuses on the full

Learning Over Time: Using Rapid Prototyping Generative Analysis Experts and Reduction of Scope to Operationalize Design

DTIC Science & Technology

2010-05-04

during the Vietnam Conflict. 67 David A. Kolb , Experiential Learning : Experience as the Source of Learning and Development. (Upper Saddle River, NJ...Essentials for Military Applications. Newport Paper #10. Newport: Newport War College Press. 1996. Kolb , David A. Experiential Learning : Experience... learning over analysis. A broad review of design theory suggests that four techniques - rapid prototyping, generative analysis, use of experts, and

Secure Multiparty Computation for Cooperative Cyber Risk Assessment

DTIC Science & Technology

2016-11-01

the scope of data available; the more attacks that are represented in the dataset the easier it will be to determine which vulnerabilities are most...assessments by pooling their data, as a dataset that covers the infrastructure of multiple institutions would allow each of them to account for...attacks that others had experienced [4]. Sharing information to produce a broad dataset would greatly improve the ability of each organization involved to

Comprehensive School Health Education National Programs. Abstracts of the 1989 Awards and Key Contact Directory. Presented at the National Conference (1st, December 10-12, Washington, D.C., 1989).

ERIC Educational Resources Information Center

Musick, Cindy, Ed.

This collection of abstracts describes in broad terms the scope and objectives of the 1989 Fund for the Improvement and Reform of Schools and Teaching (FIRST) Program in Comprehensive School Health Education and includes names and addresses of recipients. Key groups conducting these innovative programs include five state agencies, seven…

The Young Child and Music: Contemporary Principles in Child Development and Music Education. Proceedings of the Music in Early Childhood Conference (Provo, Utah, June 28-30, 1984).

ERIC Educational Resources Information Center

Boswell, Jacquelyn, Ed.

Proceedings of the 1984 Music in Early Childhood Conference held at Brigham Young University are presented in this document. Part I contains keynote addresses; Parts II through IV, respectively, consist of reports by research teams, synopses of workshops, and abstracts of research sessions. Keynote speakers addressed a broad scope of issues…

Educational Psychology in Scotland: Making a Difference. An Aspect Report on the Findings of Inspections of Local Authority Educational Psychology Services 2006-10

ERIC Educational Resources Information Center

Her Majesty's Inspectorate of Education, 2011

2011-01-01

This report provides, for the first time, an overview based on inspections of all 32 local authority educational psychology services. The picture it presents is broadly a very positive one although it also points to areas in which there is certainly scope for further improvement. The report shows that services are making a positive difference to…

Design of N-acyl homoserine lactonase with high substrate specificity by a rational approach.

PubMed

Kyeong, Hyun-Ho; Kim, Jin-Hyun; Kim, Hak-Sung

2015-06-01

N-Acyl homoserine lactone (AHL) is a major quorum-sensing signaling molecule in many bacterial species. Quorum-quenching (QQ) enzymes, which degrade such signaling molecules, have attracted much attention as an approach to controlling and preventing bacterial virulence and pathogenesis. However, naturally occurring QQ enzymes show a broad substrate spectrum, raising the concern of unintentionally attenuating beneficial effects by symbiotic bacteria. Here we report the rational design of acyl homoserine lactonase with high substrate specificity. Through docking analysis, we identified three key residues which play a key role in the substrate preference of the enzyme. The key residues were changed in a way that increases hydrophobic contact with a substrate having a short acyl chain (C4-AHL) while generating steric clashes with that containing a long acyl chain (C12-AHL). The resulting mutants exhibited a significantly shifted preference toward a substrate with a short acyl chain. Molecular dynamics simulations suggested that the mutations affect the behavior of a flexible loop, allowing tighter binding of a substrate with a short acyl chain.

Metal–Organic Frameworks Stabilize Solution-Inaccessible Cobalt Catalysts for Highly Efficient Broad-Scope Organic Transformations

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

Zhang, Teng; Manna, Kuntal; Lin, Wenbin

New and active earth-abundant metal catalysts are critically needed to replace precious metal-based catalysts for sustainable production of commodity and fine chemicals. We report here the design of highly robust, active, and reusable cobalt-bipyridine- and cobalt-phenanthroline-based metal–organic framework (MOF) catalysts for alkene hydrogenation and hydroboration, aldehyde/ketone hydroboration, and arene C–H borylation. In alkene hydrogenation, the MOF catalysts tolerated a variety of functional groups and displayed unprecedentedly high turnover numbers of ~2.5 × 10 6 and turnover frequencies of ~1.1 × 10 5 h –1. Structural, computational, and spectroscopic studies show that site isolation of the highly reactive (bpy)Co(THF) 2 speciesmore » in the MOFs prevents intermolecular deactivation and stabilizes solution-inaccessible catalysts for broad-scope organic transformations. Computational, spectroscopic, and kinetic evidence further support a hitherto unknown (bpy•–)CoI(THF) 2 ground state that coordinates to alkene and dihydrogen and then undergoing σ-complex-assisted metathesis to form (bpy)Co(alkyl)(H). Reductive elimination of alkane followed by alkene binding completes the catalytic cycle. MOFs thus provide a novel platform for discovering new base-metal molecular catalysts and exhibit enormous potential in sustainable chemical catalysis.« less

Enantioselective Synthesis of Aminodiols by Sequential Rhodium-Catalysed Oxyamination/Kinetic Resolution: Expanding the Substrate Scope of Amidine-Based Catalysis.

PubMed

Guasch, Joan; Giménez-Nueno, Irene; Funes-Ardoiz, Ignacio; Bernús, Miguel; Matheu, M Isabel; Maseras, Feliu; Castillón, Sergio; Díaz, Yolanda

2018-03-26

Regio- and stereoselective oxyamination of dienes through a tandem rhodium-catalysed aziridination-nucleophilic opening affords racemic oxazolidinone derivatives, which undergo a kinetic resolution acylation process with amidine-based catalysts (ABCs) to achieve s values of up to 117. This protocol was applied to the enantioselective synthesis of sphingosine. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Direct asymmetric aldol reactions between aldehydes and ketones catalyzed by L-tryptophan in the presence of water.

PubMed

Jiang, Zhaoqin; Yang, Hui; Han, Xiao; Luo, Jie; Wong, Ming Wah; Lu, Yixin

2010-03-21

Primary amino acids and their derivatives were investigated as catalysts for the direct asymmetric aldol reactions between ketones and aldehydes in the presence of water, and L-tryptophan was shown to be the best catalyst. Solvent effects, substrate scope and the influence of water on the reactions were investigated. Quantum chemical calculations were performed to understand the origin of the observed stereoselectivity.

Experimental and Theoretical Studies on the Nazarov Cyclization/Wagner-Meerwein Rearrangement Sequence

PubMed Central

Lebœuf, David; Ciesielski, Jennifer

2012-01-01

Highly functionalized cyclopentenones can be generated stereospecifically by a chemoselective copper(II)-mediated Nazarov/Wagner-Meerwein rearrangement sequence of divinyl ketones. A detailed investigation of this sequence is described including a study of substrate scope and limitations. After the initial 4π electrocyclization, this reaction proceeds via two different sequential [1,2]-shifts, with selectivity that depends upon either migratory ability or the steric bulkiness of the substituents at C1 and C5. This methodology allows the creation of vicinal stereogenic centers, including adjacent quaternary centers. This sequence can also be achieved by using a catalytic amount of copper(II) in combination with NaBAr4f, a weak Lewis acid. During the study of the scope of the reaction, a partial or complete E / Z isomerization of the enone moiety was observed in some cases prior to the cyclization, which resulted in a mixture of diastereomeric products. Use of a Cu(II)-bisoxazoline complex prevented the isomerization, allowing high diastereoselectivity to be obtained in all substrate types. In addition, the reaction sequence was studied by DFT computations at the UB3LYP/6-31G(d,p) level, which are consistent with the proposed sequences observed, including E / Z isomerizations and chemoselective Wagner-Meerwein shifts. PMID:22471833

Gold Redox Catalysis through Base-Initiated Diazonium Decomposition toward Alkene, Alkyne, and Allene Activation.

PubMed

Dong, Boliang; Peng, Haihui; Motika, Stephen E; Shi, Xiaodong

2017-08-16

The discovery of photoassisted diazonium activation toward gold(I) oxidation greatly extended the scope of gold redox catalysis by avoiding the use of a strong oxidant. Some practical issues that limit the application of this new type of chemistry are the relative low efficiency (long reaction time and low conversion) and the strict reaction condition control that is necessary (degassing and inert reaction environment). Herein, an alternative photofree condition has been developed through Lewis base induced diazonium activation. With this method, an unreactive Au I catalyst was used in combination with Na 2 CO 3 and diazonium salts to produce a Au III intermediate. The efficient activation of various substrates, including alkyne, alkene and allene was achieved, followed by rapid Au III reductive elimination, which yielded the C-C coupling products with good to excellent yields. Relative to the previously reported photoactivation method, our approach offered greater efficiency and versatility through faster reaction rates and broader reaction scope. Challenging substrates such as electron rich/neutral allenes, which could not be activated under the photoinitiation conditions (<5 % yield), could be activated to subsequently yield the desired coupling products in good to excellent yield. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cellulosic ethanol production via consolidated bioprocessing by a novel thermophilic anaerobic bacterium isolated from a Himalayan hot spring.

PubMed

Singh, Nisha; Mathur, Anshu S; Tuli, Deepak K; Gupta, Ravi P; Barrow, Colin J; Puri, Munish

2017-01-01

Cellulose-degrading thermophilic anaerobic bacterium as a suitable host for consolidated bioprocessing (CBP) has been proposed as an economically suited platform for the production of second-generation biofuels. To recognize the overall objective of CBP, fermentation using co-culture of different cellulolytic and sugar-fermenting thermophilic anaerobic bacteria has been widely studied as an approach to achieving improved ethanol production. We assessed monoculture and co-culture fermentation of novel thermophilic anaerobic bacterium for ethanol production from real substrates under controlled conditions. In this study, Clostridium sp. DBT-IOC-C19, a cellulose-degrading thermophilic anaerobic bacterium, was isolated from the cellulolytic enrichment cultures obtained from a Himalayan hot spring. Strain DBT-IOC-C19 exhibited a broad substrate spectrum and presented single-step conversion of various cellulosic and hemicellulosic substrates to ethanol, acetate, and lactate with ethanol being the major fermentation product. Additionally, the effect of varying cellulose concentrations on the fermentation performance of the strain was studied, indicating a maximum cellulose utilization ability of 10 g L -1 cellulose. Avicel degradation kinetics of the strain DBT-IOC-C19 displayed 94.6% degradation at 5 g L -1 and 82.74% degradation at 10 g L -1 avicel concentration within 96 h of fermentation. In a comparative study with Clostridium thermocellum DSM 1313, the ethanol and total product concentrations were higher by the newly isolated strain on pretreated rice straw at an equivalent substrate loading. Three different co-culture combinations were used on various substrates that presented two-fold yield improvement than the monoculture during batch fermentation. This study demonstrated the direct fermentation ability of the novel thermophilic anaerobic bacteria on various cellulosic and hemicellulosic substrates into ethanol without the aid of any exogenous enzymes, representing CBP-based fermentation approach. Here, the broad substrate utilization spectrum of isolated cellulolytic thermophilic anaerobic bacterium was shown to be of potential utility. We demonstrated that the co-culture strategy involving novel strains is efficient in improving ethanol production from real substrate.

Burnout and Scope of Practice in New Family Physicians.

PubMed

Weidner, Amanda K H; Phillips, Robert L; Fang, Bo; Peterson, Lars E

2018-05-01

Family physicians report some of the highest levels of burnout, but no published work has considered whether burnout is correlated with the broad scope of care that family physicians may provide. We examined the associations between family physician scope of practice and self-reported burnout. Secondary analysis of the 2016 National Family Medicine Graduate Survey respondents who provided outpatient continuity care (N = 1,617). We used bivariate analyses and logistic regression to compare self-report of burnout and measures of scope of practice including: inpatient medicine, obstetrics, pediatric ambulatory care, number of procedures and/or clinical content areas, and providing care outside the principal practice site. Forty-two percent of respondents reported feeling burned out from their work once a week or more. In bivariate analysis, elements of scope of practice associated with higher burnout rates included providing more procedures/clinical content areas (mean procedures/clinical areas: 7.49 vs 7.02; P = .02) and working in more settings than the principal practice site (1+ additional settings: 57.6% vs 48.4%: P = .001); specifically in the hospital (31.4% vs 24.2%; P = .002) and patient homes (3.3% vs 1.5%; P = .02). In adjusted analysis, practice characteristics significantly associated with lower odds of burnout were practicing inpatient medicine (OR = 0.70; 95% CI, 0.56-0.87; P = .0017) and obstetrics (OR = 0.64; 95% CI, 0.47-0.88; P = .0058). Early career family physicians who provide a broader scope of practice, specifically, inpatient medicine, obstetrics, or home visits, reported significantly lower rates of burnout. Our findings suggest that comprehensiveness is associated with less burnout, which is critical in the context of improving access to good quality, affordable care while maintaining physician wellness. © 2018 Annals of Family Medicine, Inc.

National Ice Center Visiting Scientist Program

NASA Technical Reports Server (NTRS)

Austin, Meg

2002-01-01

The long-term goal of the University Corporation for Atmospheric Research (UCAR) Visiting Scientist Program at the National Ice Center (NIC) is to recruit the highest quality visiting scientists in the ice research community for the broad purpose of strengthening the relationship between the operational and research communities in the atmospheric and oceanic sciences. The University Corporation for Atmospheric Research supports the scientific community by creating, conducting, and coordinating projects that strengthen education and research in the atmospheric, oceanic and earth sciences. UCAR accomplishes this mission by building partnerships that are national or global in scope. The goal of UCAR is to enable researchers and educators to take on issues and activities that require the combined and collaborative capabilities of a broadly engaged scientific community.

Unrequited: neurochemical enhancement of love.

PubMed

Bamford, Rebecca

2015-07-01

I raise several concerns with Earp and colleagues' analysis of enhancement through neurochemical modulation of love as a key issue in contemporary neuroethics. These include: (i) strengthening their deflation of medicalization concerns by showing how the objection that love should be left outside of the scope of medicine would directly undermine the goal of medicine; (ii) developing stronger analysis of the social and political concerns relevant to neurochemical modulation of love, by exploring and suggesting possible counters to ways in which 'wellbeing' may be used as a tool of oppression; (iii) providing reasons to support a broad need for ecological investigation of, and indeed ecological education concerning, neurotechnology; (iv) suggesting ways in which philosophy, and the humanities more broadly, remain directly relevant to responding effectively to issues in contemporary neuroethics.

On the levels of enzymatic substrate specificity: Implications for the early evolution of metabolic pathways

NASA Technical Reports Server (NTRS)

Lazcano, A.; Diaz-Villagomez, E.; Mills, T.; Oro, J.

1995-01-01

The most frequently invoked explanation for the origin of metabolic pathways is the retrograde evolution hypothesis. In contrast, according to the so-called 'patchwork' theory, metabolism evolved by the recruitment of relatively inefficient small enzymes of broad specificity that could react with a wide range of chemically related substrates. In this paper it is argued that both sequence comparisons and experimental results on enzyme substrate specificity support the patchwork assembly theory. The available evidence supports previous suggestions that gene duplication events followed by a gradual neoDarwinian accumulation of mutations and other minute genetic changes lead to the narrowing and modification of enzyme function in at least some primordial metabolic pathways.

Printable semiconductor structures and related methods of making and assembling

DOEpatents

Nuzzo, Ralph G.; Rogers, John A.; Menard, Etienne; Lee, Keon Jae; Khang; , Dahl-Young; Sun, Yugang; Meitl, Matthew; Zhu, Zhengtao; Ko, Heung Cho; Mack, Shawn

2013-03-12

The present invention provides a high yield pathway for the fabrication, transfer and assembly of high quality printable semiconductor elements having selected physical dimensions, shapes, compositions and spatial orientations. The compositions and methods of the present invention provide high precision registered transfer and integration of arrays of microsized and/or nanosized semiconductor structures onto substrates, including large area substrates and/or flexible substrates. In addition, the present invention provides methods of making printable semiconductor elements from low cost bulk materials, such as bulk silicon wafers, and smart-materials processing strategies that enable a versatile and commercially attractive printing-based fabrication platform for making a broad range of functional semiconductor devices.

Printable semiconductor structures and related methods of making and assembling

DOEpatents

Nuzzo, Ralph G [Champaign, IL; Rogers, John A [Champaign, IL; Menard, Etienne [Durham, NC; Lee, Keon Jae [Tokyo, JP; Khang, Dahl-Young [Urbana, IL; Sun, Yugang [Westmont, IL; Meitl, Matthew [Raleigh, NC; Zhu, Zhengtao [Rapid City, SD; Ko, Heung Cho [Urbana, IL; Mack, Shawn [Goleta, CA

2011-10-18

The present invention provides a high yield pathway for the fabrication, transfer and assembly of high quality printable semiconductor elements having selected physical dimensions, shapes, compositions and spatial orientations. The compositions and methods of the present invention provide high precision registered transfer and integration of arrays of microsized and/or nanosized semiconductor structures onto substrates, including large area substrates and/or flexible substrates. In addition, the present invention provides methods of making printable semiconductor elements from low cost bulk materials, such as bulk silicon wafers, and smart-materials processing strategies that enable a versatile and commercially attractive printing-based fabrication platform for making a broad range of functional semiconductor devices.

Printable semiconductor structures and related methods of making and assembling

DOEpatents

Nuzzo, Ralph G.; Rogers, John A.; Menard, Etienne; Lee, Keon Jae; Khang, Dahl-Young; Sun, Yugang; Meitl, Matthew; Zhu, Zhengtao; Ko, Heung Cho; Mack, Shawn

2010-09-21

The present invention provides a high yield pathway for the fabrication, transfer and assembly of high quality printable semiconductor elements having selected physical dimensions, shapes, compositions and spatial orientations. The compositions and methods of the present invention provide high precision registered transfer and integration of arrays of microsized and/or nanosized semiconductor structures onto substrates, including large area substrates and/or flexible substrates. In addition, the present invention provides methods of making printable semiconductor elements from low cost bulk materials, such as bulk silicon wafers, and smart-materials processing strategies that enable a versatile and commercially attractive printing-based fabrication platform for making a broad range of functional semiconductor devices.

ZnO buffer layer for metal films on silicon substrates

DOEpatents

Ihlefeld, Jon

2014-09-16

Dramatic improvements in metallization integrity and electroceramic thin film performance can be achieved by the use of the ZnO buffer layer to minimize interfacial energy between metallization and adhesion layers. In particular, the invention provides a substrate metallization method utilizing a ZnO adhesion layer that has a high work of adhesion, which in turn enables processing under thermal budgets typically reserved for more exotic ceramic, single-crystal, or metal foil substrates. Embodiments of the present invention can be used in a broad range of applications beyond ferroelectric capacitors, including microelectromechanical systems, micro-printed heaters and sensors, and electrochemical energy storage, where integrity of metallized silicon to high temperatures is necessary.

Improved measurement of extracellular enzymatic activities in subsurface sediments using competitive desorption treatment

NASA Astrophysics Data System (ADS)

Hoarfrost, Adrienne; Snider, Rachel; Arnosti, Carol

2017-02-01

Extracellular enzymatic activities initiate microbially-driven heterotrophic carbon cycling in subsurface sediments. While measurement of hydrolytic activities in sediments is fundamental to our understanding of carbon cycling, these measurements are often technically difficult due to sorption of organic substrates to the sediment matrix. Most methods that measure hydrolysis of organic substrates in sediments rely on recovery of a fluorophore or fluorescently-labeled target substrate from a sediment incubation. The tendency for substrates to sorb to sediments results in lower recovery of an added substrate, and can result in data that are unusable or difficult to interpret. We developed a treatment using competitive desorption of a fluorescently-labeled, high molecular weight organic substrate that improves recovery of the labeled substrate from sediment subsamples. Competitive desorption treatment improved recovery of the fluorescent substrate by a median of 66%, expanded the range of sediments for which activity measurements could be made, and was effective in sediments from a broad range of geochemical contexts. More reliable measurements of hydrolytic activities in sediments will yield usable and more easily interpretable data from a wider range of sedimentary environments, enabling better understanding of microbially-catalyzed carbon cycling in subsurface environments.

Application Of Optical Processing For Growth Of Silicon Dioxide

DOEpatents

Sopori, Bhushan L.

1997-06-17

A process for producing a silicon dioxide film on a surface of a silicon substrate. The process comprises illuminating a silicon substrate in a substantially pure oxygen atmosphere with a broad spectrum of visible and infrared light at an optical power density of from about 3 watts/cm.sup.2 to about 6 watts/cm.sup.2 for a time period sufficient to produce a silicon dioxide film on the surface of the silicon substrate. An optimum optical power density is about 4 watts/cm.sup.2 for growth of a 100.ANG.-300.ANG. film at a resultant temperature of about 400.degree. C. Deep level transient spectroscopy analysis detects no measurable impurities introduced into the silicon substrate during silicon oxide production and shows the interface state density at the SiO.sub.2 /Si interface to be very low.

CVD diamond substrate for microelectronics. Final report

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

Burden, J.; Gat, R.

1996-11-01

Chemical Vapor Deposition (CVD) of diamond films has evolved dramatically in recent years, and commercial opportunities for diamond substrates in thermal management applications are promising. The objective of this technology transfer initiative (TTI) is for Applied Science and Technology, Inc. (ASTEX) and AlliedSignal Federal Manufacturing and Technologies (FM&T) to jointly develop and document the manufacturing processes and procedures required for the fabrication of multichip module circuits using CVD diamond substrates, with the major emphasis of the project concentrating on lapping/polishing prior to metallization. ASTEX would provide diamond films for the study, and FM&T would use its experience in lapping, polishing,more » and substrate metallization to perform secondary processing on the parts. The primary goal of the project was to establish manufacturing processes that lower the manufacturing cost sufficiently to enable broad commercialization of the technology.« less

Size effect model on kinetics of interfacial reaction between Sn-xAg-yCu solders and Cu substrate

PubMed Central

Huang, M. L.; Yang, F.

2014-01-01

The downsizing of solder balls results in larger interfacial intermetallic compound (IMC) grains and less Cu substrate consumption in lead-free soldering on Cu substrates. This size effect on the interfacial reaction is experimentally demonstrated and theoretically analyzed using Sn-3.0Ag-0.5Cu and Sn-3.5Ag solder balls. The interfacial reaction between the Sn-xAg-yCu solders and Cu substrates is a dynamic response to a combination of effects of interfacial IMC growth, Cu substrate consumption and composition variation in the interface zone. A concentration gradient controlled (CGC) kinetics model is proposed to explain the combined effects. The concentration gradient of Cu at the interface, which is a function of solder volume, initial Cu concentration and reaction time, is the root cause of the size effect. We found that a larger Cu concentration gradient results in smaller Cu6Sn5 grains and more consumption of Cu substrate. According to our model, the growth kinetics of interfacial Cu6Sn5 obeys a t1/3 law when the molten solder has approached the solution saturation, and will be slower otherwise due to the interfering dissolution mechanism. The size effect introduced in this model is supported by a good agreement between theoretical and experimental results. Finally, the scope of application of this model is discussed. PMID:25408359

Collaborative research networks in health: a pragmatic scoping study for the development of an imaging network.

PubMed

Robinson, Tracy Elizabeth; Rankin, Nicole; Janssen, Anna; Mcgregor, Deborah; Grieve, Stuart; Shaw, Timothy

2015-12-09

Collaborative research networks are often touted as a solution for enhancing the translation of knowledge, but questions remain about how to evaluate their impact on health service delivery. This pragmatic scoping study explored the enabling factors for developing and supporting a collaborative imaging network in a metropolitan university in Australia. An advisory group was established to provide governance and to identify key informants and participants. Focus group discussions (n = 2) and semi-structured interviews (n = 22) were facilitated with representatives from a broad range of disciplines. In addition, a survey, a review of relevant websites (n = 15) and a broad review of the literature were undertaken to elicit information on collaborative research networks and perceived needs and factors that would support their involvement in a multi-disciplinary collaborative research network. Findings were de-identified and broad themes were identified. Participants identified human factors as having priority for developing and sustaining a collaborative research network. In particular, leadership, a shared vision and a communication plan that includes social media were identified as crucial for sustaining an imaging network in health research. It is important to develop metrics that map relationships between network members and the role that communication tools can contribute to this process. This study confirms that human factors remain significant across a range of collaborative endeavours. The use of focus group discussions, interviews, and literature and website reviews means we can now strongly recommend the primacy of human factors. More work is needed to identify how the network operates and what specific indicators or metrics help build the capacity of clinicians and scientists to participate in translational research.

An Investigation into the Meaning of the Term Commitment in Sino Foreign Higher Educational Alliances--An Adventure into the Heart and Soul of Successful Alliances

ERIC Educational Resources Information Center

Willis, Mike

2005-01-01

There is now a substantial body of research evaluating various aspects of educational alliances between Chinese and foreign universities, and one of the key aspects of success seems to be the degree of commitment made by the two sides. Yet the term commitment continues to remain elusive and very broad in scope. This paper attempts to identify what…

Analysis of Production Constraints at NADEP Alameda; A TQL Approach

DTIC Science & Technology

1993-06-01

they will be worth. B. RESEARCH QUESTIONS Can production systems currently using TQL theory and Theory of Constraints (TOC) be improved strategically ...This thesis will have a broad scope in following a systems approach to TQL. Any element of the system that is strategically important to improve...point in time. Since time and money are finite, focusing on those issues that are strategically important, first, is the most successful way of employing

α-Carbamoylsulfides as N-Carbamoylimine Precursors in the Visible Light Photoredox-Catalyzed Synthesis of α,α-Disubstituted Amines.

PubMed

Lebée, Clément; Languet, Morgan; Allain, Clémence; Masson, Géraldine

2016-03-18

A general and practical photoredox-promoted addition of nucleophiles to N-acylimines generated in situ from α-amidosulfides using Ru(bpy)3(PF6)2 as the photocatalyst is reported. The broad scope of the reaction toward various nucleophiles and amidosulfide derivatives was explored. This novel protocol provides a rapid, mild, and efficient access to valuable α,α-disubstituted amines in respectable yields.

The Pd-Catalyzed Conversion of Aryl Chlorides, Triflates, and Nonaflates to Nitroaromatics

PubMed Central

Fors, Brett P.; Buchwald, Stephen L.

2009-01-01

An efficient Pd-catalyst for the transformation of aryl chlorides, triflates and nonaflates to nitroaromatics has been developed. This reaction proceeds under weekly basic conditions and displays a broad scope and excellent functional group compatibility. Moreover, this method allows for the synthesis of aromatic nitro compounds that cannot be accessed efficiently via other nitration protocols. Mechanistic insight into the trasmetallation step of the catalytic process is also reported. PMID:19737014

Practical synthesis of phthalimides and benzamides by a multicomponent reaction involving arynes, isocyanides, and CO2/H2O.

PubMed

Kaicharla, Trinadh; Thangaraj, Manikandan; Biju, Akkattu T

2014-03-21

Transition-metal-free multicomponent reactions involving arynes and isocyanides with either CO2 or H2O have been reported. With CO2 as the third component, the reactions resulted in the formation of N-substituted phthalimides. The utility of water as the third component furnished benzamide derivatives in moderate to good yields. These reactions took place under mild conditions with broad scope.

Studio in Drawing and Painting; Graphics, Photography; Advanced Electric Courses in Art for Grades 10, 11, and 12, Volume 1.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

This is the first volume in a series that includes the syllabi for advanced elective courses in art education for grades 10, 11, and 12. The course objective is to provide a multiplicity of visual experiences in the drawing and painting areas of the graphic arts and photography that are broad in scope and that will challenge the student's ability…

The NASA Scientific and Technical Information System: Its scope and coverage

NASA Technical Reports Server (NTRS)

1978-01-01

Subjects of scientific and technical documents considered for inclusion in NASA's information bank are broadly summarized under the various categories used in Scientific and Technical Aerospace Reports and International Aerospace Abstracts. A general definition of each category is followed by a list of the aspects of each subject which are of exhaustive, selective, or negative interest because of their relevance to aerospace science and technology and to other NASA projects.

Using the Theory of Mind Inventory to Detect a Broad Range of Theory of Mind Challenges in Children with Hearing Loss: A Pilot Study

ERIC Educational Resources Information Center

Hutchins, Tiffany L.; Allen, Lyndsey; Schefer, Maggie

2017-01-01

Traditional child-performance measures of theory of mind (ToM) are associated with several limitations. The Theory of Mind Inventory-2 (ToMI-2) is a new broadband caregiver-informant measure designed to tap children's ToM competence. The purposes of this pilot study were to (1) gather preliminary data to explore the scope of the ToM challenges…

Preventive Medicine in World War II. Volume 2. Environmental Hygiene

DTIC Science & Technology

1955-01-01

in principle of future problems. This volume is concerned with environmental hygiene and its impact upon the health, well-being, and morale of United...theater. The scope of the problem was global. Therefore, emphasis has been placed upon principles and practices peculiar to areas of the world and the...the broad application of the principles of disease preven- tion to military conditions. In such a program, one of the prime factors is environmental

Improved Schmidt Conversion of Aldehydes to Nitriles Using Azidotrimethylsilane in 1,1,1,3,3,3-Hexafluoro-2-propanol.

PubMed

Motiwala, Hashim F; Yin, Qin; Aubé, Jeffrey

2015-12-29

The Schmidt reaction of aromatic aldehydes using a substoichiometric amount (40 mol %) of triflic acid is described. Low catalyst loading was enabled by a strong hydrogen-bond-donating solvent hexafluoro-2-propanol (HFIP). This improved protocol tolerates a broad scope of aldehydes with diverse functional groups and the corresponding nitriles were obtained in good to high yields without the need for aqueous work up.

Alkene metathesis: the search for better catalysts.

PubMed

Deshmukh, Prashant H; Blechert, Siegfried

2007-06-28

Alkene metathesis catalyst development has made significant progress over recent years. Research in metathesis catalyst design has endeavoured to tackle three key issues: those of (i) catalyst efficiency and activity, (ii) substrate scope and selectivity--particularly stereoselective metathesis reactions--and (iii) the minimization of metal impurities and catalyst recycling. This article describes a brief history of metathesis catalyst development, followed by a survey of more recent research, with a particular emphasis on ruthenium catalysts.

Synthesis of α,β-unsaturated aldehydes as potential substrates for bacterial luciferases.

PubMed

Brodl, Eveline; Ivkovic, Jakov; Tabib, Chaitanya R; Breinbauer, Rolf; Macheroux, Peter

2017-02-15

Bacterial luciferase catalyzes the monooxygenation of long-chain aldehydes such as tetradecanal to the corresponding acid accompanied by light emission with a maximum at 490nm. In this study even numbered aldehydes with eight, ten, twelve and fourteen carbon atoms were compared with analogs having a double bond at the α,β-position. These α,β-unsaturated aldehydes were synthesized in three steps and were examined as potential substrates in vitro. The luciferase of Photobacterium leiognathi was found to convert these analogs and showed a reduced but significant bioluminescence activity compared to tetradecanal. This study showed the trend that aldehydes, both saturated and unsaturated, with longer chain lengths had higher activity in terms of bioluminescence than shorter chain lengths. The maximal light intensity of (E)-tetradec-2-enal was approximately half with luciferase of P. leiognathi, compared to tetradecanal. Luciferases of Vibrio harveyi and Aliivibrio fisheri accepted these newly synthesized substrates but light emission dropped drastically compared to saturated aldehydes. The onset and the decay rate of bioluminescence were much slower, when using unsaturated substrates, indicating a kinetic effect. As a result the duration of the light emission is doubled. These results suggest that the substrate scope of bacterial luciferases is broader than previously reported. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Early chiropractic education in Oregon

PubMed Central

Keating, Joseph C

2002-01-01

Chiropractic education in the northwestern United States has its origins in the Marsh School & Cure in 1904. Most of the early schools were located in Portland, Oregon, including the D.D. Palmer College of Chiropractic (1908-1910), and several of these had merged by 1912 or 1913 to form the Pacific Chiropractic College, forerunner of today's Western States College. The latter was organized as a non-profit institution during the Great Depression, and struggled not only to survive but to create a higher standard. The early broad-scope of chiropractic training in the state probably encouraged the liberal scope of practice enjoyed in Oregon to this day. ImagesFigure 2Figure 3Figure 4Figure 6Figure 7Figure 8Figure 9Figure 11Figure 12Figure 13Figure 14Figure 15Figure 16Figure 18Figure 19Figure 20Figure 21Figure 22Figure 24

What are the Limitations of Enzymes in Synthetic Organic Chemistry?

PubMed

Reetz, Manfred T

2016-12-01

Enzymes have been used in organic chemistry and biotechnology for 100 years, but their widespread application has been prevented by a number of limitations, including the often-observed limited thermostability, narrow substrate scope, and low or wrong stereo- and/or regioselectivity. Directed evolution provides a means to address and generally solve these problems, especially since recent methodology development has made this protein engineering method faster, more efficient, and more reliable than in the past. This Darwinian approach to asymmetric catalysis has led to a number of industrial applications. Metabolic-pathway engineering, mutasynthesis, and fermentation are likewise enzyme-based techniques that enrich chemistry. This account outlines the scope, and particularly, the limitations, of biocatalysis. The complementary nature of enzymes and man-made catalysts is emphasized. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Suzuki-miyaura cross-coupling in acylation reactions, scope and recent developments.

PubMed

Blangetti, Marco; Rosso, Heléna; Prandi, Cristina; Deagostino, Annamaria; Venturello, Paolo

2013-01-17

Since the first report and due to its handiness and wide scope, the Suzuki-Miyaura (SM) cross coupling reaction has become a routine methodology in many laboratories worldwide. With respect to other common transition metal catalyzed cross couplings, the SM reaction has been so far less exploited as a tool to introduce an acyl function into a specific substrate. In this review, the various approaches found in the literature will be considered, starting from the direct SM acylative coupling to the recent developments of cross coupling between boronates and acyl chlorides or anhydrides. Special attention will be dedicated to the use of masked acyl boronates, alkoxy styryl and alkoxy dienyl boronates as coupling partners. A final section will be then focused on the acyl SM reaction as key synthetic step in the framework of natural products synthesis.

Studies on the Himbert Intramolecular Arene/ Allene Diels – Alder Cycloaddition. Mechanistic Studies and Expansion of Scope to All-Carbon Tethers

PubMed Central

Schmidt, Yvonne; Lam, Jonathan K.; Pham, Hung V.; Houk, K. N.; Vanderwal, Christopher D.

2013-01-01

The unusual intramolecular arene/allene cycloaddition described thirty years ago by Himbert permits rapid access to strained polycyclic compounds that offer great potential for the synthesis of complex scaffolds. To more fully understand the mechanism of this cycloaddition reaction, and to guide efforts to extend its scope to new substrates, quantum mechanical computational methods were employed in concert with laboratory experiments. These studies indicated that the cycloadditions likely proceed via concerted processes; a stepwise biradical mechanism was shown to be higher in energy in the cases studied. The original Himbert cycloaddition chemistry is also extended from heterocyclic to carbocyclic systems, with computational guidance used to predict thermodynamically favorable cases. Complex polycyclic scaffolds result from the combination of the cycloaddition and subsequent ring-rearrangement metathesis reactions. PMID:23634642

Repositioning the substrate activity screening (SAS) approach as a fragment-based method for identification of weak binders.

PubMed

Gladysz, Rafaela; Cleenewerck, Matthias; Joossens, Jurgen; Lambeir, Anne-Marie; Augustyns, Koen; Van der Veken, Pieter

2014-10-13

Fragment-based drug discovery (FBDD) has evolved into an established approach for "hit" identification. Typically, most applications of FBDD depend on specialised cost- and time-intensive biophysical techniques. The substrate activity screening (SAS) approach has been proposed as a relatively cheap and straightforward alternative for identification of fragments for enzyme inhibitors. We have investigated SAS for the discovery of inhibitors of oncology target urokinase (uPA). Although our results support the key hypotheses of SAS, we also encountered a number of unreported limitations. In response, we propose an efficient modified methodology: "MSAS" (modified substrate activity screening). MSAS circumvents the limitations of SAS and broadens its scope by providing additional fragments and more coherent SAR data. As well as presenting and validating MSAS, this study expands existing SAR knowledge for the S1 pocket of uPA and reports new reversible and irreversible uPA inhibitor scaffolds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermal Writing 1987

NASA Astrophysics Data System (ADS)

Peckham, Robert F.

1987-04-01

The creating of intelligent marks on a substrate by means of thermal energy has been in use for thousands of years, e.g., branding of livestock and burning images onto wood. During the past 30 years, this type of imaging has been significantly refined. Recent advances allow the creation of color images, 16 shades of gray and letter quality printing on white substrates. Permanent images are now being written with direct thermal processes. The foregoing make thermal writing very attractive for numerous applications. The general technology of how thermal writing is accomplished today, its applications, and why society should use thermal writing are the topics of this paper. To attempt to cover in great technical detail all of the current advancements in thermal writing is beyond our scope here. What is intended is the proposition that THERMAL WRITING is a superior form of creating images on paper substrates for Society's on demand hard copy requirements. First let's look at how thermal writing is being accomplished with today's technologies.

Lewis acid-Lewis acid heterobimetallic cooperative catalysis: mechanistic studies and application in enantioselective aza-Michael reaction.

PubMed

Yamagiwa, Noriyuki; Qin, Hongbo; Matsunaga, Shigeki; Shibasaki, Masakatsu

2005-09-28

The full details of a catalytic asymmetric aza-Michael reaction of methoxylamine promoted by rare earth-alkali metal heterobimetallic complexes are described, demonstrating the effectiveness of Lewis acid-Lewis acid cooperative catalysis. First, enones were used as substrates, and the 1,4-adducts were obtained in good yield (57-98%) and high ee (81-96%). Catalyst loading was successfully reduced to 0.3-3 mol % with enones. To broaden the substrate scope of the reaction to carboxylic acid derivatives, alpha,beta-unsaturated N-acylpyrroles were used as monodentate, carboxylic acid derivatives. With beta-alkyl-substituted N-acylpyrroles, the reaction proceeded smoothly and the products were obtained in high yield and good ee. Transformation of the 1,4-adducts from enones and alpha,beta-unsaturated N-acylpyrroles afforded corresponding chiral aziridines and beta-amino acids. Detailed mechanistic studies, including kinetics, NMR analysis, nonlinear effects, and rare earth metal effects, are also described. The Lewis acid-Lewis acid cooperative mechanism, including the substrate coordination mode, is discussed in detail.

Engineered jadomycin analogues with altered sugar moieties revealing JadS as a substrate flexible O-glycosyltransferase.

PubMed

Li, Liyuan; Pan, Guohui; Zhu, Xifen; Fan, Keqiang; Gao, Wubin; Ai, Guomin; Ren, Jinwei; Shi, Mingxin; Olano, Carlos; Salas, José A; Yang, Keqian

2017-07-01

Glycosyltransferases (GTs)-mediated glycodiversification studies have drawn significant attention recently, with the goal of generating bioactive compounds with improved pharmacological properties by diversifying the appended sugars. The key to achieving glycodiversification is to identify natural and/or engineered flexible GTs capable of acting upon a broad range of substrates. Here, we report the use of a combinatorial biosynthetic approach to probe the substrate flexibility of JadS, the GT in jadomycin biosynthesis, towards different non-native NDP-sugar substrates, enabling us to identify six jadomycin B analogues with different sugar moieties. Further structural engineering by precursor-directed biosynthesis allowed us to obtain 11 new jadomycin analogues. Our results for the first time show that JadS is a flexible O-GT that can utilize both L- and D- sugars as donor substrates, and tolerate structural changes at the C2, C4 and C6 positions of the sugar moiety. JadS may be further exploited to generate novel glycosylated jadomycin molecules in future glycodiversification studies.

Substrate specificity and pH dependence of homogeneous wheat germ acid phosphatase.

PubMed

Van Etten, R L; Waymack, P P

1991-08-01

The broad substrate specificity of a homogeneous isoenzyme of wheat germ acid phosphatase (WGAP) was extensively investigated by chromatographic, electrophoretic, NMR, and kinetic procedures. WGAP exhibited no divalent metal ion requirement and was unaffected upon incubation with EDTA or o-phenanthroline. A comparison of two catalytically homogeneous isoenzymes revealed little difference in substrate specificity. The specificity of WGAP was established by determining the Michaelis constants for a wide variety of substrates. p-Nitrophenyl phosphate, pyrophosphate, tripolyphosphate, and ATP were preferred substrates while lesser activities were seen toward sugar phosphates, trimetaphosphate, phosphoproteins, and (much less) phosphodiesters. An extensive table of Km and Vmax values is given. The pathway for the hydrolysis of trimetaphosphate was examined by colorimetric and 31P NMR methods and it was found that linear tripolyphosphate is not a free intermediate in the enzymatic reaction. In contrast to literature reports, homogeneous wheat germ acid phosphatase exhibits no measurable carboxylesterase activity, nor does it hydrolyze phenyl phosphonothioate esters or phytic acid at significant rates.

Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C.

PubMed

Poreba, Marcin; Mihelic, Marko; Krai, Priscilla; Rajkovic, Jelena; Krezel, Artur; Pawelczak, Malgorzata; Klemba, Michael; Turk, Dusan; Turk, Boris; Latajka, Rafal; Drag, Marcin

2014-04-01

Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad range of unnatural amino acids. Our approach identified very efficiently hydrolyzed substrates containing unnatural amino acids, which resulted in the design of significantly better substrates than those previously known. Additionally, in this study significant differences in terms of the structures of optimal substrates for human and malarial orthologs are important from the therapeutic point of view. These data can be also used for the design of specific inhibitors or activity-based probes.

Mid-infrared tunable metamaterials

DOEpatents

Brener, Igal; Miao, Xiaoyu; Shaner, Eric A.; Passmore, Brandon Scott

2017-07-11

A mid-infrared tunable metamaterial comprises an array of resonators on a semiconductor substrate having a large dependence of dielectric function on carrier concentration and a semiconductor plasma resonance that lies below the operating range, such as indium antimonide. Voltage biasing of the substrate generates a resonance shift in the metamaterial response that is tunable over a broad operating range. The mid-infrared tunable metamaterials have the potential to become the building blocks of chip based active optical devices in mid-infrared ranges, which can be used for many applications, such as thermal imaging, remote sensing, and environmental monitoring.

Mid-infrared tunable metamaterials

DOEpatents

Brener, Igal; Miao, Xiaoyu; Shaner, Eric A; Passmore, Brandon Scott; Jun, Young Chul

2015-04-28

A mid-infrared tunable metamaterial comprises an array of resonators on a semiconductor substrate having a large dependence of dielectric function on carrier concentration and a semiconductor plasma resonance that lies below the operating range, such as indium antimonide. Voltage biasing of the substrate generates a resonance shift in the metamaterial response that is tunable over a broad operating range. The mid-infrared tunable metamaterials have the potential to become the building blocks of chip based active optical devices in mid-infrared ranges, which can be used for many applications, such as thermal imaging, remote sensing, and environmental monitoring.

Xpo7 is a broad-spectrum exportin and a nuclear import receptor.

PubMed

Aksu, Metin; Pleiner, Tino; Karaca, Samir; Kappert, Christin; Dehne, Heinz-Jürgen; Seibel, Katharina; Urlaub, Henning; Bohnsack, Markus T; Görlich, Dirk

2018-05-10

Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future. © 2018 Aksu et al.

The First Mammalian Aldehyde Oxidase Crystal Structure

PubMed Central

Coelho, Catarina; Mahro, Martin; Trincão, José; Carvalho, Alexandra T. P.; Ramos, Maria João; Terao, Mineko; Garattini, Enrico; Leimkühler, Silke; Romão, Maria João

2012-01-01

Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 Å. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity. PMID:23019336

Effective cleaning of hexagonal boron nitride for graphene devices.

PubMed

Garcia, Andrei G F; Neumann, Michael; Amet, François; Williams, James R; Watanabe, Kenji; Taniguchi, Takashi; Goldhaber-Gordon, David

2012-09-12

Hexagonal boron nitride (h-BN) films have attracted considerable interest as substrates for graphene. ( Dean, C. R. et al. Nat. Nanotechnol. 2010 , 5 , 722 - 6 ; Wang, H. et al. Electron Device Lett. 2011 , 32 , 1209 - 1211 ; Sanchez-Yamagishi, J. et al. Phys. Rev. Lett. 2012 , 108 , 1 - 5 .) We study the presence of organic contaminants introduced by standard lithography and substrate transfer processing on h-BN films exfoliated on silicon oxide substrates. Exposure to photoresist processing adds a large broad luminescence peak to the Raman spectrum of the h-BN flake. This signal persists through typical furnace annealing recipes (Ar/H(2)). A recipe that successfully removes organic contaminants and results in clean h-BN flakes involves treatment in Ar/O(2) at 500 °C.

Application of optical processing for growth of silicon dioxide

DOEpatents

Sopori, B.L.

1997-06-17

A process for producing a silicon dioxide film on a surface of a silicon substrate is disclosed. The process comprises illuminating a silicon substrate in a substantially pure oxygen atmosphere with a broad spectrum of visible and infrared light at an optical power density of from about 3 watts/cm{sup 2} to about 6 watts/cm{sup 2} for a time period sufficient to produce a silicon dioxide film on the surface of the silicon substrate. An optimum optical power density is about 4 watts/cm{sup 2} for growth of a 100{angstrom}-300{angstrom} film at a resultant temperature of about 400 C. Deep level transient spectroscopy analysis detects no measurable impurities introduced into the silicon substrate during silicon oxide production and shows the interface state density at the SiO{sub 2}/Si interface to be very low. 1 fig.

[Biogas production from cellulose-containing substrates: a review].

PubMed

Tsavkelova, E A; Netrusov, A I

2012-01-01

Anaerobic microbial conversion of organic substrates to various biofuels is one of the alternative energy sources attracting the greatest attention of scientists. The advantages of biogas production over other technologies are the ability of methanogenic communities to degrade a broad range of substrates and concomitant benefits: neutralization of organic waste, reduction of greenhouse gas emission, and fertilizer production. Cellulose-containing materials are a good substrate, but their full-scale utilization encounters a number of problems, including improvement of the quality and amount ofbiogas produced and maintenance of the stability and high efficiency of microbial communities. We review data on microorganisms that form methanogenic cellulolytic communities, enzyme complexes of anaerobes essential for cellulose fiber degradation, and feedstock pretreatment, as biodegradation is hindered in the presence of lignin. Methods for improving biogas production by optimization of microbial growth conditions are considered on the examples of biogas formation from various types of plant and paper materials: writing paper and cardboard.

In situ functionalization and PEO coating of iron oxide nanocrystals using seeded emulsion polymerization.

PubMed

Kloust, Hauke; Schmidtke, Christian; Feld, Artur; Schotten, Theo; Eggers, Robin; Fittschen, Ursula E A; Schulz, Florian; Pöselt, Elmar; Ostermann, Johannes; Bastús, Neus G; Weller, Horst

2013-04-16

Herein we demonstrate that seeded emulsion polymerization is a powerful tool to produce multiply functionalized PEO coated iron oxide nanocrystals. Advantageously, by simple addition of functional surfactants, functional monomers, or functional polymerizable linkers-solely or in combinations thereof-during the seeded emulsion polymerization process, a broad range of in situ functionalized polymer-coated iron oxide nanocrystals were obtained. This was demonstrated by purposeful modulation of the zeta potential of encapsulated iron oxide nanocrystals and conjugation of a dyestuff. Successful functionalization was unequivocally proven by TXRF. Furthermore, the spatial position of the functional groups can be controlled by choosing the appropriate spacers. In conclusion, this methodology is highly amenable for combinatorial strategies and will spur rapid expedited synthesis and purposeful optimization of a broad scope of nanocrystals.

Connections of the Lateral Hypothalamic Area Juxtadorsomedial Region in the Male Rat

PubMed Central

Hahn, Joel D.; Swanson, Larry W.

2014-01-01

The connections of the lateral hypothalamic area juxtadorsomedial region (LHAjd) were investigated in a series of pathway-tracing experiments involving iontophoretic co-injection of the tracers Phaseolus vulgaris-leucoagglutinin (PHA-L; for outputs) and cholera toxin B subunit (CTB; for inputs). Results revealed that the LHAjd has connections with some 318 distinct gray matter regions encompassing all four subsystems—motor, sensory, cognitive, and behavioral state—included in a basic structure–function network model of the nervous system. Integration of these subsystems is necessary for the coordination and control of emotion and behavior, and in that regard the connections of the LHAjd indicate that it may have a prominent role. Furthermore, the LHAjd connections, together with the connections of other LHA differentiations studied similarly to date, indicate a distinct topographic organization that suggests each LHA differentiation has specifically differing degrees of involvement in the control of multiple behaviors. For the LHAjd, its involvement to a high degree in the control of defensive behavior, and to a lesser degree in the control of other behaviors, including ingestive and reproductive, is suggested. Moreover, the connections of the LHAjd suggest that its possible role in the control of these behaviors may be very broad in scope because they involve the somatic, neuroendocrine, and autonomic divisions of the nervous system. In addition, we suggest that connections between LHA differentiations may provide, at the level of the hypothalamus, a neuronal substrate for the coordinated control of multiple themes in the behavioral repertoire. PMID:22488503

Scalable and Sustainable Electrochemical Allylic C–H Oxidation

PubMed Central

Chen, Yong; Tang, Jiaze; Chen, Ke; Eastgate, Martin D.; Baran, Phil S.

2016-01-01

New methods and strategies for the direct functionalization of C–H bonds are beginning to reshape the fabric of retrosynthetic analysis, impacting the synthesis of natural products, medicines, and even materials1. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C–H functionalization due to the utility of enones and allylic alcohols as versatile intermediates, along with their prevalence in natural and unnatural materials2. Allylic oxidations have been featured in hundreds of syntheses, including some natural product syntheses regarded as “classics”3. Despite many attempts to improve the efficiency and practicality of this powerful transformation, the vast majority of conditions still employ highly toxic reagents (based around toxic elements such as chromium, selenium, etc.) or expensive catalysts (palladium, rhodium, etc.)2. These requirements are highly problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. As such, this oxidation strategy is rarely embraced for large-scale synthetic applications, limiting the adoption of this important retrosynthetic strategy by industrial scientists. In this manuscript, we describe an electrochemical solution to this problem that exhibits broad substrate scope, operational simplicity, and high chemoselectivity. This method employs inexpensive and readily available materials, representing the first example of a scalable allylic C–H oxidation (demonstrated on 100 grams), finally opening the door for the adoption of this C–H oxidation strategy in large-scale industrial settings without significant environmental impact. PMID:27096371

Carbon Dioxide-Mediated C(sp3)-H Arylation of Amine Substrates.

PubMed

Kapoor, Mohit; Liu, Daniel; Young, Michael C

2018-05-25

Elaborating amines via C-H functionalization has been an important area of research over the past decade but has generally relied on an added directing group or sterically hindered amine approach. Since free-amine-directed C(sp 3 )-H activation is still primarily limited to cyclization reactions and to improve the sustainability and reaction scope of amine-based C-H activation, we present a strategy using CO 2 in the form of dry ice that facilitates intermolecular C-H arylation. This methodology has been used to enable an operationally simple procedure whereby 1° and 2° aliphatic amines can be arylated selectively at their γ-C-H positions. In addition to potentially serving as a directing group, CO 2 has also been demonstrated to curtail the oxidation of sensitive amine substrates.

N-Tosylhydrazone directed annulation via C-H/N-N bond activation in Ru(ii)/PEG-400 as homogeneous recyclable catalytic system: a green synthesis of isoquinolines.

PubMed

Deshmukh, Dewal S; Bhanage, Bhalchandra M

2018-06-21

A green and sustainable methodology for the synthesis of isoquinolines using Ru(ii)/PEG-400 as a homogeneous recyclable catalytic system has been demonstrated. N-Tosylhydrazone, a rarely explored directing group, has been successfully employed for an annulation type of reaction with alkynes via C-H/N-N activation. A short reaction time with a simple extraction procedure, a wide substrate scope with high yields of products, easily prepared substrates, biodegradable solvent, and scalability up to the gram level enhance the efficiency and sustainability of the proposed protocol. Further, the expensive ruthenium-based homogeneous catalytic system could be reused up to a fourth consecutive cycle without any loss in its activity.

The positioning of palliative care in acute care: A multiperspective qualitative study in the context of metastatic melanoma.

PubMed

Fox, Jennifer; Windsor, Carol; Connell, Shirley; Yates, Patsy

2016-06-01

The positioning and meaning of palliative care within the healthcare system lacks clarity which adds a level of complexity to the process of transition to palliative care. This study explores the transition to the palliative care process in the acute care context of metastatic melanoma. A theoretical framework drawing on interpretive and critical traditions informs this research. The pragmatism of symbolic interactionism and the critical theory of Habermas brought a broad orientation to the research. Integration of the theoretical framework and grounded-theory methods facilitated data generation and analysis of 29 interviews with patients, family carers, and healthcare professionals. The key analytical findings depict a scope of palliative care that was uncertain for users of the system and for those working within the system. Becoming "palliative" is not a defined event; nor is there unanimity around referral to a palliative care service. As such, ambiguity and tension contribute to the difficulties involved in negotiating the transition to palliative care. Our findings point to uncertainty around the scopes of practice in the transition to palliative care. The challenge in the transition process lies in achieving greater coherency of care within an increasingly specialized healthcare system. The findings may not only inform those within a metastatic melanoma context but may contribute more broadly to palliative practices within the acute care setting.

Marriage as a Risk Factor for Internalizing Disorders: Clarifying Scope and Specificity

PubMed Central

Brock, Rebecca L.; Lawrence, Erika

2011-01-01

Objective Marital discord has been linked to both depression and anxiety; however, our understanding of how marriage contributes to the development of internalizing symptoms is limited in scope and lacking specificity. First, it is unclear whether the marital relationship contributes to the broad dimension of internalizing symptoms as opposed to specific diagnoses. Second, it is unclear how the marital relationship contributes to internalizing symptoms: through global marital dissatisfaction or through specific relationship processes (and which processes). The purpose of the present study was to address these two issues and, more generally, to develop a comprehensive and refined framework within which to understand the role of marriage in the developmental course of internalizing symptoms. Method Questionnaire and interview data were collected from 102 husbands and wives 5 times over the first 7 years of marriage. Results Results indicated that marital discord during the transition into marriage was associated with the broad dimension of internalizing symptoms for husbands but not for wives. Further, both global marital dissatisfaction and an imbalance of power and control put husbands at significant risk for symptoms over the first 7 years of marriage, whereas low levels of emotional intimacy put wives at significant risk. Conclusions Results exemplify the need to routinely consider intimate relationship processes in etiological models of depression and anxiety, and identify specific clinical targets that can be prioritized in interventions aimed at preventing internalizing disorders. PMID:21823784

α-Amination of aldehydes catalyzed by in situ generated hypoiodite.

PubMed

Tian, Jie-Sheng; Ng, Kang Wai Jeffrey; Wong, Jiun-Ru; Loh, Teck-Peng

2012-09-03

The metal-free amination of different aldehydes is catalyzed by hypoiodite, which is generated by employing commercially available sodium percarbonate as the co-oxidant. This approach has several advantages: it is a metal-free oxidation that works under mild reaction conditions; furthermore, it has a wide substrate scope and does not give toxic by-products from the co-oxidant that is used. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A PdAg bimetallic nanocatalyst for selective reductive amination of nitroarenes.

PubMed

Li, Linsen; Niu, Zhiqiang; Cai, Shuangfei; Zhi, Yun; Li, Hao; Rong, Hongpan; Liu, Lichen; Liu, Lei; He, Wei; Li, Yadong

2013-08-07

Herein we have identified an optimal catalyst, Pd1Ag1.7, for the tandem reductive amination between nitroarenes and aldehydes (selectivity > 93%). Key to the success is the ability to control the compositions of the investigational Pd1-xAgx (x = 0-1) catalysts, as well as the clear composition dependent activity/selectivity trend observed in this study. This catalyst features a wide substrate scope, excellent recyclability, activity and selectivity under ambient conditions.

Mapping estuarine distributions of the non-indigenous Japanese Eelgrass Zostera japonica using Color Infrared Aerial Photography

EPA Science Inventory

This presentation describes a technique for mapping distributions of the nonindigenous Japanese eelgrass Zostera japonica in estuarine ecosystems of the Pacific Northwest. The relatively broad distribution of this intertidal plant, often on very soft substrate, makes classical g...

Regulator and enzyme specificities of the TOL plasmid-encoded upper pathway for degradation of aromatic hydrocarbons and expansion of the substrate range of the pathway.

PubMed Central

Abril, M A; Michan, C; Timmis, K N; Ramos, J L

1989-01-01

The TOL plasmid upper pathway operon encodes enzymes involved in the catabolism of aromatic hydrocarbons such as toluene and xylenes. The regulator of the gene pathway, the XylR protein, exhibits a very broad effector specificity, being able to recognize as effectors not only pathway substrates but also a wide variety of mono- and disubstituted methyl-, ethyl-, and chlorotoluenes, benzyl alcohols, and p-chlorobenzaldehyde. Benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase, two upper pathway enzymes, exhibit very broad substrate specificities and transform unsubstituted substrates and m- and p-methyl-, m- and p-ethyl-, and m- and p-chloro-substituted benzyl alcohols and benzaldehydes, respectively, at a high rate. In contrast, toluene oxidase only oxidizes toluene, m- and p-xylene, m-ethyltoluene, and 1,2,4-trimethylbenzene [corrected], also at a high rate. A biological test showed that toluene oxidase attacks m- and p-chlorotoluene, albeit at a low rate. No evidence for the transformation of p-ethyltoluene by toluene oxidase has been found. Hence, toluene oxidase acts as the bottleneck step for the catabolism of p-ethyl- and m- and p-chlorotoluene through the TOL upper pathway. A mutant toluene oxidase able to transform p-ethyltoluene was isolated, and a mutant strain capable of fully degrading p-ethyltoluene was constructed with a modified TOL plasmid meta-cleavage pathway able to mineralize p-ethylbenzoate. By transfer of a TOL plasmid into Pseudomonas sp. strain B13, a clone able to slowly degrade m-chlorotoluene was also obtained. PMID:2687253

The participatory vulnerability scoping diagram - deliberative risk ranking for community water systems

USGS Publications Warehouse

Howe, Peter D.; Yarnal, Brent; Coletti, Alex; Wood, Nathan J.

2013-01-01

Natural hazards and climate change present growing challenges to community water system (CWS) managers, who are increasingly turning to vulnerability assessments to identify, prioritize, and adapt to risks. Effectively assessing CWS vulnerability requires information and participation from various sources, one of which is stakeholders. In this article, we present a deliberative risk-ranking methodology, the participatory vulnerability scoping diagram (P-VSD), which allows rapid assessment and integration of multiple stakeholder perspectives of vulnerability. This technique is based on methods of deliberative risk evaluation and the vulnerability scoping diagram. The goal of the methodology is to engage CWS managers and stakeholders collectively to provide qualitative contextual risk rankings as a first step in a vulnerability assessment. We conduct an initial assessment using a case study of CWS in two U.S. counties, sites with broadly similar exposures but differences in population, land use, and other social sensitivity factors. Results demonstrate that CWS managers and stakeholders in the two case study communities all share the belief that their CWS are vulnerable to hazards but differ in how this vulnerability manifests itself in terms of the exposure, sensitivity, and adaptive capacity of the system.

The scope of Baker's law.

PubMed

Pannell, John R; Auld, Josh R; Brandvain, Yaniv; Burd, Martin; Busch, Jeremiah W; Cheptou, Pierre-Olivier; Conner, Jeffrey K; Goldberg, Emma E; Grant, Alannie-Grace; Grossenbacher, Dena L; Hovick, Stephen M; Igic, Boris; Kalisz, Susan; Petanidou, Theodora; Randle, April M; de Casas, Rafael Rubio; Pauw, Anton; Vamosi, Jana C; Winn, Alice A

2015-11-01

Baker's law refers to the tendency for species that establish on islands by long-distance dispersal to show an increased capacity for self-fertilization because of the advantage of self-compatibility when colonizing new habitat. Despite its intuitive appeal and broad empirical support, it has received substantial criticism over the years since it was proclaimed in the 1950s, not least because it seemed to be contradicted by the high frequency of dioecy on islands. Recent theoretical work has again questioned the generality and scope of Baker's law. Here, we attempt to discern where the idea is useful to apply and where it is not. We conclude that several of the perceived problems with Baker's law fall away when a narrower perspective is adopted on how it should be circumscribed. We emphasize that Baker's law should be read in terms of an enrichment of a capacity for uniparental reproduction in colonizing situations, rather than of high selfing rates. We suggest that Baker's law might be tested in four different contexts, which set the breadth of its scope: the colonization of oceanic islands, metapopulation dynamics with recurrent colonization, range expansions with recurrent colonization, and colonization through species invasions. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Evaluating Factor XIII Specificity for Glutamine-Containing Substrates Using a MALDI-TOF Mass Spectrometry Assay

PubMed Central

Doiphode, Prakash G.; Malovichko, Marina V.; Mouapi, Kelly Njine; Maurer, Muriel C.

2014-01-01

Activated Factor XIII (FXIIIa) catalyzes the formation of γ-glutamyl-ε-lysyl cross-links within the fibrin blood clot network. Although several cross-linking targets have been identified, the characteristic features that define FXIIIa substrate specificity are not well understood. To learn more about how FXIIIa selects its targets, a matrix-assisted laser desorption ionization – time of flight mass spectrometry (MALDI-TOF MS) based assay was developed that could directly follow the consumption of a glutamine-containing substrate and the formation of a cross-linked product with glycine ethylester. This FXIIIa kinetics assay is no longer reliant on a secondary coupled reaction, on substrate labeling, or on detecting the final deacylation portion of the transglutaminase reaction. With the MALDI-TOF MS assay, glutamine-containing peptides derived from α2-antiplasmin, S. Aureus fibronectin binding protein A, and thrombin activatable fibrinolysis inhibitor were examined directly. Results suggest that the FXIIIa active site surface responds to changes in substrate residues following the reactive glutamine. The P-1 substrate position is sensitive to charge character and the P-2 and P-3 to the broad FXIIIa substrate specificity pockets. The more distant P-8 to P-11 region serves as a secondary substrate anchoring point. New knowledge on FXIIIa specificity may be used to design better substrates or inhibitors of this transglutaminase. PMID:24751466

Palladium pincer complex catalyzed stannyl and silyl transfer to propargylic substrates: synthetic scope and mechanism.

PubMed

Kjellgren, Johan; Sundén, Henrik; Szabó, Kálmán J

2005-02-16

Pincer complex catalyzed substitution of various propargylic substrates could be achieved using tin- and silicon-based dimetallic reagents to obtain propargyl- and allenylstannanes and silanes. These reactions involving chloride, mesylate, and epoxide substrates could be carried out under mild conditions, and therefore many functionalities (such as COOEt, OR, OH, NR, and NAc) are tolerated. It was shown that pincer catalysts with electron-supplying ligands, such as NCN, SCS, and SeCSe complexes, display the highest catalytic activity. The catalytic substitution of secondary propargyl chlorides and primary propargyl chlorides with electron-withdrawing substituents proceeds with high regioselectivity providing the allenyl product. Opening of the propargyl epoxides takes place with an excellent stereo- and regioselectivity to give stereodefined allenylstannanes. Silylstannanes as dimetallic reagents undergo an exclusive silyl transfer to the propargylic substrate affording allenylsilanes with high regioselectivity. According to our mechanistic studies, the key intermediate of the reaction is an organostannane (or silane)-coordinated pincer complex, which is formed from the dimetallic reagent and the corresponding pincer complex catalyst. DFT modeling studies have shown that the trimethylstannyl functionality is transferred to the propargylic substrate in a single reaction step with high allenyl selectivity. Inspection of the TS structures reveals that the trimethylstannyl group transfer is initiated by the attack of the palladium-tin sigma-bond electrons on the propargylic substrate. This is a novel mechanism in palladium chemistry, which is based on the unique topology of the pincer complex catalysts.

Choosing between possible lives: legal and ethical issues in preimplantation genetic diagnosis.

PubMed

Scott, Rosamund

2006-01-01

This article critically appraises the current legal scope of the principal applications of preimplantation genetic diagnosis (PGD). This relatively new technique, which is available to some parents undergoing in vitro fertilization (IVF) treatment, aims to ensure that a child is not born with a seemingly undesirable genetic condition. The question addressed here is whether there should be serious reasons to test for genetic conditions in embryos in order to be able to select between them. The Human Fertilisation and Embryology Authority and the Human Genetics Commission have decided that there should be such reasons by broadly aligning the criteria for PGD with those for selective abortion. This stance is critically explored, as are its implications for the possible use of PGD to select either against or for marginal features or for significant traits. The government is currently reviewing the legal scope and regulation of PGD.

What is occupational therapy’s role in addressing sleep problems among older adults?

PubMed Central

Leland, Natalie E.; Marcione, Nicole; Niemiec, Stacey L. Schepens; Don Fogelberg, Kaivalya Kelkar

2014-01-01

Sleep problems, prevalent among older adults, are associated with poor outcomes and high healthcare costs. In 2008, rest and sleep became its own area of occupation in the AOTA Occupational Therapy Practice Framework. This scoping review examined a broad context of sleep research in order to highlight efficacious interventions for older adults that fall within the occupational therapy scope of practice and present an agenda for research and practice. Four sleep intervention areas clearly aligned with the Practice Framework, including cognitive behavioral therapy for insomnia, physical activity, and multi-component interventions. Occupational therapy is primed to address sleep problems by targeting the context and environment, performance patterns, and limited engagement in evening activities that may contribute to poor sleep. Occupational therapy researchers and clinicians need to work collaboratively to establish the evidence-base for occupation-centered sleep interventions in order to improve the health and quality of life of the older adult. PMID:24844879

Motivation of synthesis, with an example on groundwater quality sustainability

NASA Astrophysics Data System (ADS)

Fogg, G. E.; Labolle, E. M.

2007-12-01

Synthesis of ideas and theories from disparate disciplines is necessary for addressing the major problems faced by society. Such integration happens neither via edict nor via lofty declarations of what is needed or what is best. It happens mainly through two mechanisms: limited scope collaborations (e.g., ~2-3 investigators) in which the researchers believe deeply in their need for each other's expertise and much larger scope collaborations driven by the 'big idea.' Perhaps the strongest motivation for broad, effective synthesis is the 'big idea' that is sufficiently important and inspiring to marshal the appropriate collaborative efforts. Examples include the Manhattan Project, the quest for cancer cures, predicting effects of climate change, and groundwater quality sustainability. The latter is posed as an example of a 'big idea' that would potentially unify research efforts in both the sciences and social sciences toward a common, pressing objective.

Water-quality data-collection activities in Colorado and Ohio; Phase II, Evaluation of 1984 field and laboratory quality-assurance practices

USGS Publications Warehouse

Childress, Carolyn J. Oblinger; Chaney, Thomas H.; Myers, Donna; Norris, J. Michael; Hren, Janet

1987-01-01

Serious questions have been raised by Congress about the usefulness of water-quality data for addressing issues of regional and national scope and, especially, for characterizing the current quality of the Nation's streams and ground water. In response, the U.S. Geological Survey has undertaken a pilot study in Colorado and Ohio to (1) determine the characteristics of current (1984) water-quality data-collection activities of Federal, regional, State, and local agencies, and academic institutions; and (2) determine how well the data from these activities, collected for various purposes and using different procedures, can be used to improve our ability to answer major broad-scope questions, such as:A. What are (or were) natural or near-natural water-quality conditions?B. What are existing water-quality conditions?C. How has water quality changed, and how do the changes relate to human activities?Colorado and Ohio were chosen for the pilot study largely because they represent regions with different types of waterquality concerns and programs. The study has been divided into three phases, the objectives of which are: Phase I--Inventory water-quality data-collection programs, including costs, and identify those programs that met a set of broad criteria for producing data that are potentially appropriate for water-quality assessments of regional and national scope. Phase II--Evaluate the quality assurance of field and laboratory procedures used in producing the data from programs that met the broad criteria of Phase I. Phase III--Compile the qualifying data and evaluate the adequacy of this data base for addressing selected water-quality questions of regional and national scope.Water-quality data are collected by a large number of organizations for diverse purposes ranging from meeting statutory requirements to research on water chemistry. Combining these individual data bases is an appealing and potentially cost-effective way to attempt to develop a data base adequate for regional or national water-quality assessments. However, to combine data from diverse sources, field and laboratory procedures used to produce the data need to be equivalent and need to meet specific qualityassurance standards. It is these factors that are the focus of Phase II, which is described in this report. In the first phase of this study, an inventory was made of all public organizations and academic institutions that undertook water-quality data-collection activities in Colorado and Ohio in 1984. Water-quality programs identified in Phase I were tested against a set of broad screening criteria. A total of 44 waterquality programs in Colorado and 29 programs in Ohio passed the Phase-I screen and were examined in Phase II. These programs accounted for an estimated 165,000 analyses in Colorado and 76,300 analyses in Ohio for 20 selected constituents and properties. Although qualifying programs included both surface- and ground-water sampling, they emphasized surface waters and produced few groundwater analyses (3,660 for Colorado and 470 for Ohio). For Phase II, information about field and laboratory qualityassurance practices was provided by each organization and its supporting laboratories through questionnaires. This information was evaluated against a set of specific criteria for field and laboratory practices. The criteria were developed from guidelines published by public agencies and professional organizations such as the American Public Health Association, the U.Sc, Environmental Protection Agency, and the U.S. Geological Survey. Each of the eight criteria that comprise the Phase-II screen fall into one of two major categories--field practices or laboratory practices.

Beyond brown: polyphenol oxidases as enzymes of plant specialized metabolism

USDA-ARS?s Scientific Manuscript database

Most cloned and/or characterized plant polyphenol oxidases (PPOs) have catecholase activity (i.e., they oxidize o-diphenols to o-quinones) and are localized or predicted to be localized to plastids. As a class, they have broad substrate specificity and are associated with browning of produce and oth...

Linking earth science informatics resources into uninterrupted digital value chains

NASA Astrophysics Data System (ADS)

Woodcock, Robert; Angreani, Rini; Cox, Simon; Fraser, Ryan; Golodoniuc, Pavel; Klump, Jens; Rankine, Terry; Robertson, Jess; Vote, Josh

2015-04-01

The CSIRO Mineral Resources Flagship was established to tackle medium- to long-term challenges facing the Australian mineral industry across the value chain from exploration and mining through mineral processing within the framework of an economically, environmentally and socially sustainable minerals industry. This broad portfolio demands collaboration and data exchange with a broad range of participants and data providers across government, research and industry. It is an ideal environment to link geoscience informatics platforms to application across the resource extraction industry and to unlock the value of data integration between traditionally discrete parts of the minerals digital value chain. Despite the potential benefits, data integration remains an elusive goal within research and industry. Many projects use only a subset of available data types in an integrated manner, often maintaining the traditional discipline-based data 'silos'. Integrating data across the entire minerals digital value chain is an expensive proposition involving multiple disciplines and, significantly, multiple data sources both internal and external to any single organisation. Differing vocabularies and data formats, along with access regimes to appropriate analysis software and equipment all hamper the sharing and exchange of information. AuScope has addressed the challenge of data exchange across organisations nationally, and established a national geosciences information infrastructure using open standards-based web services. Federated across a wide variety of organisations, the resulting infrastructure contains a wide variety of live and updated data types. The community data standards and infrastructure platforms that underpin AuScope provide important new datasets and multi-agency links independent of software and hardware differences. AuScope has thus created an infrastructure, a platform of technologies and the opportunity for new ways of working with and integrating disparate data at much lower cost. An early example of this approach is the value generated by combining geological and metallurgical data sets as part of the rapidly growing field of geometallurgy. This not only provides a far better understanding of the impact of geological variability on ore processing but also leads to new thinking on the types and characteristics of data sets collected at various stages of the exploration and mining process. The Minerals Resources Flagship is linking its research activities to the AuScope infrastructure, exploiting the technology internally to create a platform for integrated research across the minerals value chain and improved interaction with industry. Referred to as the 'Early Access Virtual Lab', the system will be fully interoperable with AuScope and international infrastructures using open standards like GeosciML. Secured access is provided to allow confidential collaboration with industry when required. This presentation will discuss how the CSIRO Mineral Resources Flagship is building on the AuScope infrastructure to transform the way that data and data products are identified, shared, integrated, and reused, to unlock the benefits of true integration of research efforts across the minerals digital value chain.

Substrate Scope of O-Methyltransferase from Streptomyces peucetius for Biosynthesis of Diverse Natural Products Methoxides.

PubMed

Parajuli, Prakash; Pandey, Ramesh Prasad; Nguyen, Thi Huyen Trang; Dhakal, Dipesh; Sohng, Jae Kyung

2018-04-01

Methylation is a common post-modification reaction that is observed during the biosynthesis of secondary metabolites produced by plants and microorganisms. Based on the sequence information from Streptomyces peucetius ATCC27952, a putative O-methyltransferase (OMT) gene SpOMT7740 was polymerase chain reaction amplified and cloned into E. coli BL21 (DE3) host to test the substrate promiscuity and conduct functional characterization. In vitro and in vivo reaction assays were carried out over various classes of substrates: flavonoids (flavonol, flavones, and isoflavonoid), chalcones, anthraquinones, anthracyclines, and sterol molecules, and the applications in synthesizing diverse classes of O-methoxy natural products were also illustrated. SpOMT7740 catalyzed the O-methylation reaction to form various natural and non-natural O-methoxides, includes 7-hydroxy-8-O-methoxy flavone, 3-O-methoxy flavone, three mono-, di-, and tri-O-methoxy genistein, mono-O-methoxy phloretin, mono-O-methoxy luteolin, 3-O-methoxy β-sitosterol, and O-methoxy anthraquinones (emodin and aloe emodin) and O-methoxy anthracycline (daunorubicin) exhibiting diverse substrate flexibility. Daunorubicin is a native secondary metabolite of S. peucetius. Among the compounds tested, 7,8-dihydroxyflavone was the best substrate for bioconversion to 7-hydroxy-8-O-methoxy flavone, and it was structurally elucidated. This enzyme showed a flexible catalysis over the given ranges of temperature, pH, and divalent cationic conditions for O-methylation.

Investigation of antenna-coupled Nb5N6 microbolometer THz detector with substrate resonant cavity.

PubMed

Tu, Xuecou; Jiang, Chengtao; Xiao, Peng; Kang, Lin; Zhai, Shimin; Jiang, Zhou; Feng Su, Run; Jia, Xiaoqing; Zhang, Labao; Chen, Jian; Wu, Peiheng

2018-04-02

Fabricating resonant cavities with conventional methods to improve the coupling efficiency of a detector in the terahertz (THz) region is difficult for the wavelength is too long. Here, we propose a solution by using the substrate cavity effect given that the substrate wavelength and thickness of the preparation device are in the same order. The planar dipole antenna-coupled Nb 5 N 6 microbolometers with different substrate thicknesses were fabricated. The interference effect of the substrate cavity on the optical voltage response of the detector is analyzed experimentally and theoretically. The experimental results show that the optical response of the detector is determined by the length of the substrate cavity. Thus, the THz devices with different detection frequencies can be designed by changing the substrate cavity length. Furthermore, on the basis of this substrate cavity effect, an asymmetric coupled Fabry-Pérot (FP) cavity is constituted by simply placing a movable metallic planar mirror at the backside of the Si substrate. The incident THz radiation on the Nb 5 N 6 microbolometer can be effectively manipulated by changing the substrate-mirror distance to modulate the phase relation between the reflect wave and the incident wave. The distinct radiation control can be observed, and the experiments can be well explained by numerically analyzing the responsivity dynamics that highlights the role of the FP cavity effect during radiation. All of the results discussed here can be extended to a broad range of frequency and other type of THz detectors.

A miniature filter on a suspended substrate with a two-sided pattern of strip conductors

NASA Astrophysics Data System (ADS)

Belyaev, B. A.; Voloshin, A. S.; Bulavchuk, A. S.; Galeev, R. G.

2016-06-01

A miniature bandpass filter of new design with original stripline resonators on suspended substrate has been studied. The proposed filters of third to sixth order are distinguished for their high frequency-selective properties and mush smaller size in comparison to analogs. It is shown that a broad stopband extending above three-fold central bandpass frequency is determined by weak coupling of resonators at resonances of the second and third modes. A prototype sixth-order filter with a central frequency of 1 GHz, manufactured on a ceramic substrate with dielectric permittivity ɛ = 80, has contour dimensions of 36.6 × 4.8 × 0.5 mm3. Parametric synthesis of the filter, based on electrodynamic 3D model simulations, showed quite good agreement with the results of measurements.

Evolutionary dynamics of enzymes.

PubMed

Demetrius, L

1995-08-01

This paper codifies and rationalizes the large diversity in reaction rates and substrate specificity of enzymes in terms of a model which postulates that the kinetic properties of present-day enzymes are the consequence of the evolutionary force of mutation and selection acting on a class of primordial enzymes with poor catalytic activity and broad substrate specificity. Enzymes are classified in terms of their thermodynamic parameters, activation enthalpy delta H* and activation entropy delta S*, in their kinetically significant transition states as follows: type 1, delta H* > 0, delta S* < 0; type 2, delta H* < or = 0, delta S* < or = 0; type 3, delta H* > 0, delta S* > 0. We study the evolutionary dynamics of these three classes of enzymes subject to mutation, which acts at the level of the gene which codes for the enzyme and selection, which acts on the organism that contains the enzyme. Our model predicts the following evolutionary trends in the reaction rate and binding specificity for the three classes of molecules. In type 1 enzymes, evolution results in random, non-directional changes in the reaction rate and binding specificity. In type 2 and 3 enzymes, evolution results in a unidirectional increase in both the reaction rate and binding specificity. We exploit these results in order to codify the diversity in functional properties of present-day enzymes. Type 1 molecules will be described by intermediate reaction rates and broad substrate specificity. Type 2 enzymes will be characterized by diffusion-controlled rates and absolute substrate specificity. The type 3 catalysts can be further subdivided in terms of their activation enthalpy into two classes: type 3a (delta H* small) and type 3b (delta H* large). We show that type 3a will be represented by the same functional properties that identify type 2, namely, diffusion-controlled rates and absolute substrate specificity, whereas type 3b will be characterized by non-diffusion-controlled rates and absolute substrate specificity. We infer from this depiction of the three classes of enzymes, a general relation between the two functional properties, reaction rate and substrate specificity, namely, enzymes with diffusion-controlled rates have absolute substrate specificity. By appealing to energetic considerations, we furthermore show that enzymes with diffusion-controlled rates (types 2 and 3a) form a small subset of the class of all enzymes. This codification of present-day enzymes derived from an evolutionary model, essentially relates the structural properties of enzymes, as described by their thermodynamic parameters, to their functional properties, as represented by the reaction rate and substrate specificity.

Neuroimaging and Anxiety: the Neural Substrates of Pathological and Non-pathological Anxiety.

PubMed

Taylor, James M; Whalen, Paul J

2015-06-01

Advances in the use of noninvasive neuroimaging to study the neural correlates of pathological and non-pathological anxiety have shone new light on the underlying neural bases for both the development and manifestation of anxiety. This review summarizes the most commonly observed neural substrates of the phenotype of anxiety. We focus on the neuroimaging paradigms that have shown promise in exposing this relevant brain circuitry. In this way, we offer a broad overview of how anxiety is studied in the neuroimaging laboratory and the key findings that offer promise for future research and a clearer understanding of anxiety.

Optical properties of chitin: surface-enhanced Raman scattering substrates based on antireflection structures on cicada wings

NASA Astrophysics Data System (ADS)

Stoddart, P. R.; Cadusch, P. J.; Boyce, T. M.; Erasmus, R. M.; Comins, J. D.

2006-02-01

The transparent wings of some cicada species present ordered arrays of papillary structures with a spacing of approximately 200 nm. These structures serve an antireflection function, with optical transmission peaking at a value of approximately 98% and rising above 90% over a broad band from 450 to 2500 nm. The dimensions of the papillae are comparable to the roughness scale of surface-enhanced Raman scattering (SERS) substrates. SERS measurements performed on silver- and gold-coated wings display enhancement factors of approximately 106 with no apparent background contribution from the wing.

SEMICONDUCTOR MATERIALS: White light photoluminescence from ZnS films on porous Si substrates

NASA Astrophysics Data System (ADS)

Caifeng, Wang; Qingshan, Li; Bo, Hu; Weibing, Li

2010-03-01

ZnS films were deposited on porous Si (PS) substrates using a pulsed laser deposition (PLD) technique. White light emission is observed in photoluminescence (PL) spectra, and the white light is the combination of blue and green emission from ZnS and red emission from PS. The white PL spectra are broad, intense in a visible band ranging from 450 to 700 nm. The effects of the excitation wavelength, growth temperature of ZnS films, PS porosity and annealing temperature on the PL spectra of ZnS/PS were also investigated.

Bacterial Anabaena variabilis phenylalanine ammonia lyase: a biocatalyst with broad substrate specificity.

PubMed

Lovelock, Sarah L; Turner, Nicholas J

2014-10-15

Phenylalanine ammonia lyases (PALs) catalyse the regio- and stereoselective hydroamination of cinnamic acid analogues to yield optically enriched α-amino acids. Herein, we demonstrate that a bacterial PAL from Anabaena variabilis (AvPAL) displays significantly higher activity towards a series of non-natural substrates than previously described eukaryotic PALs. Biotransformations performed on a preparative scale led to the synthesis of the 2-chloro- and 4-trifluoromethyl-phenylalanine derivatives in excellent ee, highlighting the enormous potential of bacterial PALs as biocatalysts for the synthesis of high value, non-natural amino acids. Copyright © 2014 Elsevier Ltd. All rights reserved.

n-BuLi as a highly efficient precatalyst for hydrophosphonylation of aldehydes and unactivated ketones.

PubMed

Liu, Chengwei; Zhang, Yu; Qian, Qinqin; Yuan, Dan; Yao, Yingming

2014-12-05

It was found for the first time that organic alkali metal compounds serve as highly efficient precatalysts for the hydrophosphonylation reactions of aldehydes and unactivated ketones with dialkyl phosphite under mild conditions. For ketone substrates, a reversible reaction was observed, and the influence of catalyst loading and reaction temperature on the reaction equilibrium was studied in detail. Overall, the hydrophosphonylation reactions catalyzed by 0.1 mol % n-BuLi were completed within 5 min for a broad range of substrates and generated a series of α-hydroxy phosphonates in high yields.

Workshop on the evolution of the Martian atmosphere

NASA Technical Reports Server (NTRS)

Luhmann, J. G. (Editor); Jakosky, B. M. (Editor)

1992-01-01

Thirty-three papers based on the state of our knowledge prior to the anticipated new results from Mars Observer were presented at the workshop. Because of the nature of the subject, the scope of the papers covered a broad disciplinary range encompassing astronomy and solar physics, geology and geophysics, climatology, atmospheric science, aeronomy, and space physics. The 42 participants heard about topics from the evolution of solar-type stars to candidate instrumentation for measuring escape to space on yet-unscheduled future missions.

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

Mayr, Nina A., E-mail: ninamayr@uw.edu; Hu, Kenneth S.; Liao, Zhongxing

In this era of globalization and rapid advances in radiation oncology worldwide, the American Society for Radiation Oncology (ASTRO) is committed to help decrease profound regional disparities through the work of the International Education Subcommittee (IES). The IES has expanded its base, reach, and activities to foster educational advances through a variety of educational methods with broad scope, in addition to committing to the advancement of radiation oncology care for cancer patients around the world, through close collaboration with our sister radiation oncology societies and other educational, governmental, and organizational groups.

Publications of the exobiology program for 1990: A special bibliography

NASA Technical Reports Server (NTRS)

1992-01-01

The Exobiology Program is an integrated program designed to investigate and understand those processes related to the origin, evolution, and distribution of life in the universe. The Exobiology Program is broad in scope, covering the following subject areas: cosmic evolution of biogenic compounds; prebiotic evolution; early evolution of life; evolution of advanced life; solar system exploration; search for extraterrestrial intelligence; planetary protection; and advanced programs in biological systems research. A listing of the 1990 publications resulting from research supported by the Exobiology Program is presented.

Defense RDT and E Planning and Strategy Parameters: Methodological Considerations. Appendices

DTIC Science & Technology

1974-12-01

true in the case of Saudi Arabia , Kuwait, Qatar and Libya. The "unaligned Third World" is neither unaligned nor is it the entity the term connotes...Liberial Ethiopia, Morocco, Bahrain, Kuwait, Saudi Arabia , etc., which relate to bases and broad considerations of intention relating to defense. The scope...garner a trade surplus of $65 billion, from a base of only $7 billion 3 in 1973. While Italy verges on bankruptcy Saudi Arabia , Kuwait, tne United

Copper-facilitated Suzuki reactions: application to 2-heterocyclic boronates.

PubMed

Deng, James Z; Paone, Daniel V; Ginnetti, Anthony T; Kurihara, Hideki; Dreher, Spencer D; Weissman, Steven A; Stauffer, Shaun R; Burgey, Christopher S

2009-01-15

The palladium-catalyzed Suzuki-Miyaura reaction has been utilized as one of the most powerful methods for C-C bond formation. However, Suzuki reactions of electron-deficient 2-heterocyclic boronates generally give low conversions and remain challenging. The successful copper(I) facilitated Suzuki coupling of 2-heterocyclic boronates that is broad in scope is reported. Use of this methodology affords greatly enhanced yields of these notoriously difficult couplings. Furthermore, mechanistic investigations suggest a possible role of copper in the catalytic cycle.

One-Pot Two-Step Multicomponent Process of Indole and Other Nitrogenous Heterocycles or Amines toward α-Oxo-acetamidines.

PubMed

Martinez-Ariza, Guillermo; McConnell, Nicholas; Hulme, Christopher

2016-04-15

A cesium carbonate promoted three-component reaction of N-H containing heterocycles, primary or secondary amines, arylglyoxaldehydes, and anilines is reported. The key step involves a tandem sequence of N-1 addition of a heterocycle or an amine to preformed α-iminoketones, followed by an air- or oxygen-mediated oxidation to form α-oxo-acetamidines. The scope of the reaction is enticingly broad, and this novel methodology is applied toward the synthesis of various polycyclic heterocycles.

Development of novel entry inhibitors targeting emerging viruses

PubMed Central

Zhou, Yanchen; Simmons, Graham

2013-01-01

Emerging viral diseases pose a unique risk to public health, and thus there is a need to develop therapies. A current focus of funding agencies, and hence research, is the development of broad-spectrum antivirals, and in particular, those targeting common cellular pathways. The scope of this article is to review screening strategies and recent advances in this area, with a particular emphasis on antivirals targeting the step of viral entry for emerging lipid-enveloped viruses such as Ebola virus and SARS-coronavirus. PMID:23199399

HCE Research Coordination Directorate (ReCoorD Database)

DTIC Science & Technology

2016-04-27

portfolio management is often hidden within broader mission scopes and visibility into those portfolio is often limited at best. Current specialty...specific tracking databases do not exist. Current broad-sweeping portfolio management tools do not exist (not true--define terms?). The HCE receives...requests from a variety of oversight bodies for reports on the current state of project-through- portfolio efforts. Tools such as NIH’s Reporter, while still in development, do not yet appear to meet HCE element requirements.

Manganese-Catalyzed Carbonylative Annulations for Redox-Neutral Late-Stage Diversification.

PubMed

Liang, Yu-Feng; Steinbock, Ralf; Münch, Annika; Stalke, Dietmar; Ackermann, Lutz

2018-05-04

An inexpensive, nontoxic manganese catalyst enabled unprecedented redox-neutral carbonylative annulations under ambient pressure. The manganese catalyst outperformed all other typically used base and precious-metal catalysts. The outstanding versatility of the manganese catalysis manifold was reflected by ample substrate scope, setting the stage for effective late-stage manipulations under racemization-free conditions of a wealth of marketed drugs and natural products, including alkaloids, amino acids, steroids, and carbohydrates. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cross-Aldol Reaction of Activated Carbonyls with Nitrosocarbonyl Intermediates: Stereoselective Synthesis toward α-Hydroxy-β-amino Esters and Amides.

PubMed

Mallik, Sumitava; Bhajammanavar, Vinod; Ramakrishna, Isai; Baidya, Mahiuddin

2017-07-21

A practical and flexible strategy toward α-hydroxy-β-amino esters and amides, which are important biological motifs, based on an organocatalytic cross-aldol reaction of in situ-generated nitrosocarbonyl intermediates followed by hydrogenation is presented. The protocol features operational simplicity, high yields, a wide substrate scope, and high regio- and diastereoselectivity profiles. The utility of this method was showcased through the synthesis of bestatin analogues and indole formation.

Iron-catalyzed 1,2-addition of perfluoroalkyl iodides to alkynes and alkenes.

PubMed

Xu, Tao; Cheung, Chi Wai; Hu, Xile

2014-05-05

Iron catalysis has been developed for the intermolecular 1,2-addition of perfluoroalkyl iodides to alkynes and alkenes. The catalysis has a wide substrate scope and high functional-group tolerance. A variety of perfluoroalkyl iodides including CF3 I can be employed. The resulting perfluoroalkylated alkyl and alkenyl iodides can be further functionalized by cross-coupling reactions. This methodology provides a straightforward and streamlined access to perfluoroalkylated organic molecules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Virtually Instantaneous, Room-temperature [11C]-Cyanation Using Biaryl Phosphine Pd(0) Complexes

PubMed Central

Lee, Hong Geun; Milner, Phillip J.; Placzek, Michael S.; Buchwald, Stephen L.; Hooker, Jacob M.

2015-01-01

A new radiosynthetic protocol for the preparation of [11C]aryl nitriles has been developed. This process is based on the direct reaction of in situ prepared L•Pd(Ar)X complexes (L=biaryl phosphine) with [11C]HCN. The strategy is operationally simple, exhibits a remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity compared to previously reported systems. With this procedure, a variety of [11C]nitrile-containing pharmaceuticals were prepared with high radiochemical efficiency. PMID:25565277

2-Aminoquinazolin-4(3H)-one as an Organocatalyst for the Synthesis of Tertiary Amines.

PubMed

Thakur, Maheshwar S; Nayal, Onkar S; Upadhyay, Rahul; Kumar, Neeraj; Maurya, Sushil K

2018-03-02

The potential of 2-aminoquinazolin-4(3H)-one as an organocatalyst for the activation of aldehydes via noncovalent interaction for the synthesis of tertiary amines using formic acid as a reducing agent is reported for the first time. The developed protocol demonstrated a dilated substrate scope for aromatic and aliphatic amines with aromatic and aliphatic aldehydes. Furthermore, the current method was also fruitful for the derivatization of ciprofloxacin and its derivative in good to excellent yields.

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular SN2 reaction.

PubMed

Xiong, Yiwen; Qian, Ping; Cao, Chenhui; Mei, Haibo; Han, Jianlin; Li, Guigen; Pan, Yi

2014-01-01

We report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) .

Moving Closer to EarthScope: A Major New Initiative for the Earth Sciences*

NASA Astrophysics Data System (ADS)

Simpson, D.; Blewitt, G.; Ekstrom, G.; Henyey, T.; Hickman, S.; Prescott, W.; Zoback, M.

2002-12-01

EarthScope is a scientific research and infrastructure initiative designed to provide a suite of new observational facilities to address fundamental questions about the evolution of continents and the processes responsible for earthquakes and volcanic eruptions. The integrated observing systems that will comprise EarthScope capitalize on recent developments in sensor technology and communications to provide Earth scientists with synoptic and high-resolution data derived from a variety of geophysical sensors. An array of 400 broadband seismometers will spend more than ten years crossing the contiguous 48 states and Alaska to image features that make up the internal structure of the continent and underlying mantle. Additional seismic and electromagnetic instrumentation will be available for high resolution imaging of geological targets of special interest. A network of continuously recording Global Positioning System (GPS) receivers and sensitive borehole strainmeters will be installed along the western U.S. plate boundary. These sensors will measure how western North America is deforming, what motions occur along faults, how earthquakes start, and how magma flows beneath active volcanoes. A four-kilometer deep observatory bored directly into the San Andreas fault will provide the first opportunity to observe directly the conditions under which earthquakes occur, to collect fault rocks and fluids for laboratory study, and to monitor continuously an active fault zone at depth. All data from the EarthScope facilities will be openly available in real-time to maximize participation from the scientific community and to provide on-going educational outreach to students and the public. EarthScope's sensors will revolutionize observational Earth science in terms of the quantity, quality and spatial extent of the data they provide. Turning these data into exciting scientific discovery will require new modes of experimentation and interdisciplinary cooperation from the Earth science community. A broad sector of the university research community has joined with federal agencies to stimulate the development of facility plans and move EarthScope forward as a coordinated national initiative. With strong prospects for funding next year, the time is right for bold new ideas on how to maximize the use of these powerful new resources in the Earth scientist's toolkit. * On behalf of the EarthScope Working Group

Principles to guide sustainable implementation of extended-scope-of-practice physiotherapy workforce redesign initiatives in Australia: stakeholder perspectives, barriers, supports, and incentives

PubMed Central

Morris, Joanne; Grimmer, Karen; Gilmore, Lisa; Perera, Chandima; Waddington, Gordon; Kyle, Greg; Ashman, Bryan; Murphy, Karen

2014-01-01

Sustainable implementation of new workforce redesign initiatives requires strategies that minimize barriers and optimize supports. Such strategies could be provided by a set of guiding principles. A broad understanding of the concerns of all the key stakeholder groups is required before effective strategies and initiatives are developed. Many new workforce redesign initiatives are not underpinned by prior planning, and this threatens their uptake and sustainability. This study reports on a cross-sectional qualitative study that sought the perspectives of representatives of key stakeholders in a new workforce redesign initiative (extended-scope-of-practice physiotherapy) in one Australian tertiary hospital. The key stakeholder groups were those that had been involved in some way in the development, management, training, funding, and/or delivery of the initiative. Data were collected using semistructured questions, answered individually by interview or in writing. Responses were themed collaboratively, using descriptive analysis. Key identified themes comprised: the importance of service marketing; proactively addressing barriers; using readily understood nomenclature; demonstrating service quality and safety, monitoring adverse events, measuring health and cost outcomes; legislative issues; registration; promoting viable career pathways; developing, accrediting, and delivering a curriculum supporting physiotherapists to work outside of the usual scope; and progression from “a good idea” to established service. Health care facilities planning to implement new workforce initiatives that extend scope of usual practice should consider these issues before instigating workforce/model of care changes. PMID:25018637

Principles to guide sustainable implementation of extended-scope-of-practice physiotherapy workforce redesign initiatives in Australia: stakeholder perspectives, barriers, supports, and incentives.

PubMed

Morris, Joanne; Grimmer, Karen; Gilmore, Lisa; Perera, Chandima; Waddington, Gordon; Kyle, Greg; Ashman, Bryan; Murphy, Karen

2014-01-01

Sustainable implementation of new workforce redesign initiatives requires strategies that minimize barriers and optimize supports. Such strategies could be provided by a set of guiding principles. A broad understanding of the concerns of all the key stakeholder groups is required before effective strategies and initiatives are developed. Many new workforce redesign initiatives are not underpinned by prior planning, and this threatens their uptake and sustainability. This study reports on a cross-sectional qualitative study that sought the perspectives of representatives of key stakeholders in a new workforce redesign initiative (extended-scope-of-practice physiotherapy) in one Australian tertiary hospital. The key stakeholder groups were those that had been involved in some way in the development, management, training, funding, and/or delivery of the initiative. Data were collected using semistructured questions, answered individually by interview or in writing. Responses were themed collaboratively, using descriptive analysis. Key identified themes comprised: the importance of service marketing; proactively addressing barriers; using readily understood nomenclature; demonstrating service quality and safety, monitoring adverse events, measuring health and cost outcomes; legislative issues; registration; promoting viable career pathways; developing, accrediting, and delivering a curriculum supporting physiotherapists to work outside of the usual scope; and progression from "a good idea" to established service. Health care facilities planning to implement new workforce initiatives that extend scope of usual practice should consider these issues before instigating workforce/model of care changes.

Integrating EarthScope Data to Constrain the Long-Term Effects of Tectonism on Continental Lithosphere

NASA Astrophysics Data System (ADS)

Porter, R. C.; van der Lee, S.

2017-12-01

One of the most significant products of the EarthScope experiment has been the development of new seismic tomography models that take advantage of the consistent station design, regular 70-km station spacing, and wide aperture of the EarthScope Transportable Array (TA) network. These models have led to the discovery and interpretation of additional compositional, thermal, and density anomalies throughout the continental US, especially within tectonically stable regions. The goal of this work is use data from the EarthScope experiment to better elucidate the temporal relationship between tectonic activity and seismic velocities. To accomplish this, we compile several upper-mantle seismic velocity models from the Incorporated Research Institute for Seismology (IRIS) Earth Model Collaboration (EMC) and compare these to a tectonic age model we compiled using geochemical ages from the Interdisciplinary Earth Data Alliance: EarthChem Database. Results from this work confirms quantitatively that the time elapsed since the most recent tectonic event is a dominant influence on seismic velocities within the upper mantle across North America. To further understand this relationship, we apply mineral-physics models for peridotite to estimate upper-mantle temperatures for the continental US from tomographically imaged shear velocities. This work shows that the relationship between the estimated temperatures and the time elapsed since the most recent tectonic event is broadly consistent with plate cooling models, yet shows intriguing scatter. Ultimately, this work constrains the long-term thermal evolution of continental mantle lithosphere.

The environment shapes microbial enzymes: five cold-active and salt-resistant carboxylesterases from marine metagenomes.

PubMed

Tchigvintsev, Anatoli; Tran, Hai; Popovic, Ana; Kovacic, Filip; Brown, Greg; Flick, Robert; Hajighasemi, Mahbod; Egorova, Olga; Somody, Joseph C; Tchigvintsev, Dmitri; Khusnutdinova, Anna; Chernikova, Tatyana N; Golyshina, Olga V; Yakimov, Michail M; Savchenko, Alexei; Golyshin, Peter N; Jaeger, Karl-Erich; Yakunin, Alexander F

2015-03-01

Most of the Earth's biosphere is cold and is populated by cold-adapted microorganisms. To explore the natural enzyme diversity of these environments and identify new carboxylesterases, we have screened three marine metagenome gene libraries for esterase activity. The screens identified 23 unique active clones, from which five highly active esterases were selected for biochemical characterization. The purified metagenomic esterases exhibited high activity against α-naphthyl and p-nitrophenyl esters with different chain lengths. All five esterases retained high activity at 5 °C indicating that they are cold-adapted enzymes. The activity of MGS0010 increased more than two times in the presence of up to 3.5 M NaCl or KCl, whereas the other four metagenomic esterases were inhibited to various degrees by these salts. The purified enzymes showed different sensitivities to inhibition by solvents and detergents, and the activities of MGS0010, MGS0105 and MGS0109 were stimulated three to five times by the addition of glycerol. Screening of purified esterases against 89 monoester substrates revealed broad substrate profiles with a preference for different esters. The metagenomic esterases also hydrolyzed several polyester substrates including polylactic acid suggesting that they can be used for polyester depolymerization. Thus, esterases from marine metagenomes are cold-adapted enzymes exhibiting broad biochemical diversity reflecting the environmental conditions where they evolved.

Reversible Self-Assembly of 3D Architectures Actuated by Responsive Polymers.

PubMed

Zhang, Cheng; Su, Jheng-Wun; Deng, Heng; Xie, Yunchao; Yan, Zheng; Lin, Jian

2017-11-29

An assembly of three-dimensional (3D) architectures with defined configurations has important applications in broad areas. Among various approaches of constructing 3D structures, a stress-driven assembly provides the capabilities of creating 3D architectures in a broad range of functional materials with unique merits. However, 3D architectures built via previous methods are simple, irreversible, or not free-standing. Furthermore, the substrates employed for the assembly remain flat, thus not involved as parts of the final 3D architectures. Herein, we report a reversible self-assembly of various free-standing 3D architectures actuated by the self-folding of smart polymer substrates with programmed geometries. The strategically designed polymer substrates can respond to external stimuli, such as organic solvents, to initiate the 3D assembly process and subsequently become the parts of the final 3D architectures. The self-assembly process is highly controllable via origami and kirigami designs patterned by direct laser writing. Self-assembled geometries include 3D architectures such as "flower", "rainbow", "sunglasses", "box", "pyramid", "grating", and "armchair". The reported self-assembly also shows wide applicability to various materials including epoxy, polyimide, laser-induced graphene, and metal films. The device examples include 3D architectures integrated with a micro light-emitting diode and a flex sensor, indicting the potential applications in soft robotics, bioelectronics, microelectromechanical systems, and others.

Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation.

PubMed

Scott, Daniel C; Rhee, David Y; Duda, David M; Kelsall, Ian R; Olszewski, Jennifer L; Paulo, Joao A; de Jong, Annemieke; Ovaa, Huib; Alpi, Arno F; Harper, J Wade; Schulman, Brenda A

2016-08-25

Hundreds of human cullin-RING E3 ligases (CRLs) modify thousands of proteins with ubiquitin (UB) to achieve vast regulation. Current dogma posits that CRLs first catalyze UB transfer from an E2 to their client substrates and subsequent polyubiquitylation from various linkage-specific E2s. We report an alternative E3-E3 tagging cascade: many cellular NEDD8-modified CRLs associate with a mechanistically distinct thioester-forming RBR-type E3, ARIH1, and rely on ARIH1 to directly add the first UB and, in some cases, multiple additional individual monoubiquitin modifications onto CRL client substrates. Our data define ARIH1 as a component of the human CRL system, demonstrate that ARIH1 can efficiently and specifically mediate monoubiquitylation of several CRL substrates, and establish principles for how two distinctive E3s can reciprocally control each other for simultaneous and joint regulation of substrate ubiquitylation. These studies have broad implications for CRL-dependent proteostasis and mechanisms of E3-mediated UB ligation. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure of a [NiFe] hydrogenase maturation protease HycI provides insights into its substrate selectivity.

PubMed

Kwon, Sunghark; Nishitani, Yuichi; Hirao, Yoshinori; Kanai, Tamotsu; Atomi, Haruyuki; Miki, Kunio

2018-04-15

The immature large subunit of [NiFe] hydrogenases undergoes C-terminal cleavage by a specific protease in the final step of the post-translational process before assembly with other subunits. It has been reported that the [NiFe] hydrogenase maturation protease HycI from Thermococcus kodakarensis (TkHycI) has the catalytic ability to target the membrane-bound hydrogenase large subunit MbhL from T. kodakarensis. However, the detailed mechanism of its substrate recognition remains elusive. We determined the crystal structure of TkHycI at 1.59 Å resolution to clarify how TkHycI recognizes its own substrate MbhL. Although the overall structure of TkHycI is similar to that of its homologous protease TkHybD, TkHycI adopts a larger loop than TkHybD, thereby creating a broad and deep cleft. We analyzed the structural properties of the TkHycI cleft probably involved in its substrate recognition. Our findings provide novel and profound insights into the substrate selectivity of TkHycI. Copyright © 2018 Elsevier Inc. All rights reserved.

Probing the substrate specificity of the bacterial Pnkp/Hen1 RNA repair system using synthetic RNAs

PubMed Central

Zhang, Can; Chan, Chio Mui; Wang, Pei; Huang, Raven H.

2012-01-01

Ribotoxins cleave essential RNAs involved in protein synthesis as a strategy for cell killing. RNA repair systems exist in nature to counteract the lethal actions of ribotoxins, as first demonstrated by the RNA repair system from bacteriophage T4 25 yr ago. Recently, we found that two bacterial proteins, named Pnkp and Hen1, form a stable complex and are able to repair ribotoxin-cleaved tRNAs in vitro. However, unlike the well-studied T4 RNA repair system, the natural RNA substrates of the bacterial Pnkp/Hen1 RNA repair system are unknown. Here we present comprehensive RNA repair assays with the recombinant Pnkp/Hen1 proteins from Anabaena variabilis using a total of 33 different RNAs as substrates that might mimic various damaged forms of RNAs present in living cells. We found that unlike the RNA repair system from bacteriophage T4, the bacterial Pnkp/Hen1 RNA repair system exhibits broad substrate specificity. Based on the experimental data presented here, a model of preferred RNA substrates of the Pnkp/Hen1 repair system is proposed. PMID:22190744

TERSSE: Definition of the Total Earth Resources System for the Shuttle Era. Volume 8: User's Mission and System Requirements Data (appendix A of Volume 3)

NASA Technical Reports Server (NTRS)

1974-01-01

A computer printout is presented of the mission requirement for the TERSSE missions and their associated user tasks. The data included in the data base represents a broad-based attempt to define the amount, extent, and type of information needed for an earth resources management program in the era of the space shuttle. An effort was made to consider all aspects of remote sensing and resource management; because of its broad scope, it is not intended that the data be used without verification for in-depth studies of particular missions and/or users. The data base represents the quantitative structure necessary to define the TERSSE architecture and requirements, and to an overall integrated view of the earth resources technology requirements of the 1980's.

Geology, Geochronology, and EarthScope: The EarthScope AGeS Program and a new idea for a 4D Earth Initiative

NASA Astrophysics Data System (ADS)

Flowers, R. M.; Arrowsmith, R.; Metcalf, J. R.; Rittenour, T. M.; Schoene, B.; Hole, J. A.; Pavlis, T. L.; Wagner, L. S.; Whitmeyer, S. J.; Williams, M. L.

2015-12-01

The EarthScope AGeS (Awards for Geochronology Student Research) program is a multi-year educational initiative aimed at enhancing interdisciplinary, innovative, and high-impact science by promoting training and new interactions between students, scientists, and geochronology labs at different institutions. The program offers support of up to $10,000 for graduate students to collect and interpret geochronology data that contribute to EarthScope science targets through visits to participating geochronology labs (www.earthscope.org/geochronology). The program was launched by a 2-day short course held before the 2014 National GSA meeting in Vancouver, at which 16 geochronology experts introduced 43 participants to the basic theory and applications of geochronology methods. By the first proposal submission deadline in spring 2015, 33 labs representing a broad range of techniques had joined the program by submitting lab plans that were posted on the EarthScope website. The lab plans provide information about preparation, realistic time frames for visits, and analytical costs. In the first year of the program, students submitted 47 proposals from 32 different institutions. Proposals were ranked by an independent panel, 10 were funded, and research associated with these projects is currently underway. The next proposal deadline will be held in spring 2016. The 4D-Earth initiative is an idea for a natural successor to the EarthScope program aimed at expanding the primarily 3D geophysical focus that captured a snapshot of present day North America into the 4th dimension of time (hence the connection to the prototypical AGeS program), and illuminating the crustal component that was below the resolution of much of the USArray image. Like EarthScope, the notion is that this initiative would integrate new infrastructure and usher in a new way of doing science. The overarching scientific motivation is to develop a Community Geologic Model for the 4-D Evolution of the North American continent to firmly answer long-standing questions of how the time-integrated processes of plate tectonics and surface processes produce the mantle and crustal structures we see today. A breakout session on this topic was held at the 2015 EarthScope National Meeting, and efforts are underway to solicit feedback to shape these ideas.

Synthesis of fructooligosaccharides (FosA) and inulin (InuO) by GH68 fructosyltransferases from Bacillus agaradhaerens strain WDG185.

PubMed

Kralj, Slavko; Leeflang, Chris; Sierra, Estefanía Ibáñez; Kempiński, Błażej; Alkan, Veli; Kolkman, Marc

2018-01-01

Fructooligosaccharides (FOS) and inulin, composed of β-2-1 linked fructose units, have a broad range of industrial applications. They are known to have various beneficial health effects and therefore have broad application potential in nutrition. For (modified) inulin also for non-food purposes more applications are arising. Examples are carboxymethylated inulin as anti-scalant and carboymlated inulin as emulsifiers. Various plants synthesize FOS and/or inulin type of fructans. However, isolating of FOS and inulin from plants is challenging due to for instance varying chains length. There is an increasing demand for FOS and inulin oligosaccharides and alternative procedures for their synthesis are attractive. We identified and characterized two fructosyltransferases from Bacillus agaradhaerens WDG185. FosA, a β-fructofuranosidase, synthesises short chain fructooligosaccharides (GF2-GF4) at high sucrose concentration, whereas InuO, an inulosucrase, synthesises a broad range of inulooligosaccharides (GF2-GF24) from sucrose, very similar to plant derived inulin. FosA and InuO showed activity over a broad pH range from 6 to 10 and optimal temperature at 60°C. Calcium ions and EDTA were found to have no effect on the activity of both enzymes. Kinetic analysis showed that only at relatively low substrate concentrations both enzymes showed Michaelis-Menten type of kinetics for total and transglycosylation activity. Both enzymes showed increased transglycosylation upon increasing substrate concentrations. These are the first examples of the molecular and biochemical characterization of a β-fructofuranosidase (FosA) and an inulosucrase enzyme (InuO) and its product from a Bacillus agaradhaerens strain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design of 2.5 GHz broad bandwidth microwave bandpass filter at operating frequency of 10 GHz using HFSS

NASA Astrophysics Data System (ADS)

Jasim, S. E.; Jusoh, M. A.; Mahmud, S. N. S.; Zamani, A. H.

2018-04-01

Development of low losses, small size and broad bandwidth microwave bandpass filter operating at higher frequencies is an active area of research. This paper presents a new route used to design and simulate microwave bandpass filter using finite element modelling and realized broad bandwidth, low losses, small dimension microwave bandpass filter operating at 10 GHz frequency using return loss method. The filter circuit has been carried out using Computer Aid Design (CAD), Ansoft HFSS software and designed with four parallel couple line model and small dimension (10 × 10 mm2) using LaAlO3 substrate. The response of the microwave filter circuit showed high return loss -50 dB at operating frequency at 10.4 GHz and broad bandwidth of 2.5 GHz from 9.5 to 12 GHz. The results indicate the filter design and simulation using HFSS is reliable and have the opportunity to transfer from lab potential experiments to the industry.

Assaying Oxidative Coupling Activity of CYP450 Enzymes.

PubMed

Agarwal, Vinayak

2018-01-01

Cytochrome P450 (CYP450) enzymes are ubiquitous catalysts in natural product biosynthetic schemes where they catalyze numerous different transformations using radical intermediates. In this protocol, we describe procedures to assay the activity of a marine bacterial CYP450 enzyme Bmp7 which catalyzes the oxidative radical coupling of polyhalogenated aromatic substrates. The broad substrate tolerance of Bmp7, together with rearrangements of the aryl radical intermediates leads to a large number of products to be generated by the enzymatic action of Bmp7. The complexity of the product pool generated by Bmp7 thus presents an analytical challenge for structural elucidation. To address this challenge, we describe mass spectrometry-based procedures to provide structural insights into aryl crosslinked products generated by Bmp7, which can complement subsequent spectroscopic experiments. Using the procedures described here, for the first time, we show that Bmp7 can efficiently accept polychlorinated aryl substrates, in addition to the physiological polybrominated substrates for the biosynthesis of polyhalogenated marine natural products. © 2018 Elsevier Inc. All rights reserved.

Enzymatic Detoxication, Conformational Selection, and the Role of Molten Globule Active Sites*

PubMed Central

Honaker, Matthew T.; Acchione, Mauro; Zhang, Wei; Mannervik, Bengt; Atkins, William M.

2013-01-01

The role of conformational ensembles in enzymatic reactions remains unclear. Discussion concerning “induced fit” versus “conformational selection” has, however, ignored detoxication enzymes, which exhibit catalytic promiscuity. These enzymes dominate drug metabolism and determine drug-drug interactions. The detoxication enzyme glutathione transferase A1–1 (GSTA1–1), exploits a molten globule-like active site to achieve remarkable catalytic promiscuity wherein the substrate-free conformational ensemble is broad with barrierless transitions between states. A quantitative index of catalytic promiscuity is used to compare engineered variants of GSTA1–1 and the catalytic promiscuity correlates strongly with characteristics of the thermodynamic partition function, for the substrate-free enzymes. Access to chemically disparate transition states is encoded by the substrate-free conformational ensemble. Pre-steady state catalytic data confirm an extension of the conformational selection model, wherein different substrates select different starting conformations. The kinetic liability of the conformational breadth is minimized by a smooth landscape. We propose that “local” molten globule behavior optimizes detoxication enzymes. PMID:23649628

Substrate promiscuity of a rosmarinic acid synthase from lavender (Lavandula angustifolia L.).

PubMed

Landmann, Christian; Hücherig, Stefanie; Fink, Barbara; Hoffmann, Thomas; Dittlein, Daniela; Coiner, Heather A; Schwab, Wilfried

2011-08-01

One of the most common types of modification of secondary metabolites is the acylation of oxygen- and nitrogen-containing substrates to produce esters and amides, respectively. Among the known acyltransferases, the members of the plant BAHD family are capable of acylating a wide variety of substrates. Two full-length acyltransferase cDNAs (LaAT1 and 2) were isolated from lavender flowers (Lavandula angustifolia L.) by reverse transcriptase-PCR using degenerate primers based on BAHD sequences. Recombinant LaAT1 exhibited a broad substrate tolerance accepting (hydroxy)cinnamoyl-CoAs as acyl donors and not only tyramine, tryptamine, phenylethylamine and anthranilic acid but also shikimic acid and 4-hydroxyphenyllactic acid as acceptors. Thus, LaLT1 forms esters and amides like its phylogenetic neighbors. In planta LaAT1 might be involved in the biosynthesis of rosmarinic acid, the ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, a major constituent of lavender flowers. LaAT2 is one of three members of clade VI with unknown function.

Improved GaSb-based quantum well laser performance through metamorphic growth on GaAs substrates

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

Richardson, Christopher J. K., E-mail: richardson@lps.umd.edu; He, Lei; Apiratikul, Paveen

The promise of the metamorphic growth paradigm is to enable design freedom of the substrate selection criteria beyond current choices that are limited by lattice matching requirements. A demonstration of this emerging degree of freedom is reported here by directly comparing identical laser structures grown both pseudomorphically on a GaSb substrate and metamorphically on a GaAs substrate. Improved thermal performance of the metamorphic laser material enables a higher output power before thermal roll-over begins. These performance gains are demonstrated in minimally processed gain-guided broad-area type-I lasers emitting close to 2-μm wavelengths and mounted p-side up. Continuous wave measurements at roommore » temperature yield a T{sub 0} of 145 K and peak output power of 192 mW from metamorphic lasers, compared to a T{sub 0} of 96 K and peak output power of 164 mW from identical lasers grown pseudomorphically on GaSb.« less

Insights into Methyltransferase Specificity and Bioactivity of Derivatives of the Antibiotic Plantazolicin

DOE PAGES

Hao, Yue; Blair, Patricia M.; Sharma, Abhishek; ...

2015-01-30

Peptide antibiotics represent a class of conformationally-constrained natural products of growing pharmaceutical interest. Plantazolicin (PZN) is a linear, polyheterocyclic natural product with highly selective and potent activity against the anthrax-causing bacterium, Bacillus anthracis. The bioactivity of PZN is contingent on dimethylation of its N-terminal Arg residue by an S-adenosylmethionine-dependent methyltransferase. Here in this paper, we explore the substrate tolerances of two homologous PZN methyltransferases by carrying out kinetic analyses of the enzymes against a synthetic panel of truncated PZN analogs containing the N-terminal Arg residue. X-ray cocrystal structures of the PZN methyltransferases with each of these heterocycle-containing substrates provide amore » rationale for understanding the strict substrate specificity of these enzymes. Kinetic studies of structure-guided, site-specific variants allowed for the assignment of residues governing catalysis and substrate scope. Microbiological testing further revealed that upon dimethylation of the N-terminal Arg, a pentaheterocyclized PZN analog retained potent anti-B. anthracis activity, nearly equal to that of full-length PZN. These studies may be useful in the biosynthetic engineering of natural product analogs with different bioactivity profiles, as demonstrated by our identification of a truncated plantazolicin derivative that is active against methicillin-resistant Staphylococcus aureus (MRSA).« less

Insights into Methyltransferase Specificity and Bioactivity of Derivatives of the Antibiotic Plantazolicin

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

Hao, Yue; Blair, Patricia M.; Sharma, Abhishek

Peptide antibiotics represent a class of conformationally-constrained natural products of growing pharmaceutical interest. Plantazolicin (PZN) is a linear, polyheterocyclic natural product with highly selective and potent activity against the anthrax-causing bacterium, Bacillus anthracis. The bioactivity of PZN is contingent on dimethylation of its N-terminal Arg residue by an S-adenosylmethionine-dependent methyltransferase. Here in this paper, we explore the substrate tolerances of two homologous PZN methyltransferases by carrying out kinetic analyses of the enzymes against a synthetic panel of truncated PZN analogs containing the N-terminal Arg residue. X-ray cocrystal structures of the PZN methyltransferases with each of these heterocycle-containing substrates provide amore » rationale for understanding the strict substrate specificity of these enzymes. Kinetic studies of structure-guided, site-specific variants allowed for the assignment of residues governing catalysis and substrate scope. Microbiological testing further revealed that upon dimethylation of the N-terminal Arg, a pentaheterocyclized PZN analog retained potent anti-B. anthracis activity, nearly equal to that of full-length PZN. These studies may be useful in the biosynthetic engineering of natural product analogs with different bioactivity profiles, as demonstrated by our identification of a truncated plantazolicin derivative that is active against methicillin-resistant Staphylococcus aureus (MRSA).« less

Stabilization of magnetic skyrmions by RKKY interactions

NASA Astrophysics Data System (ADS)

Bezvershenko, Alla V.; Kolezhuk, Alexei K.; Ivanov, Boris A.

2018-02-01

We study the stabilization of an isolated magnetic skyrmion in a magnetic monolayer on a nonmagnetic conducting substrate via the Ruderman-Kittel-Kasuya-Yosida (RKKY) exchange interaction. Two different types of the substrate are considered, usual normal metal and single-layer graphene. While the full stability analysis for skyrmions in the presence of the RKKY coupling requires a separate effort that is outside the scope of this work, we are able to study the radial stability (stability of a skyrmion against collapse) using variational energy estimates obtained within first-order perturbation theory, with the unperturbed Hamiltonian describing the isotropic Heisenberg magnet, and the two perturbations being the RKKY exchange and the easy-axis anisotropy. We show that a proper treatment of the long-range nature of the RKKY interaction leads to a qualitatively different stabilization scenario compared to previous studies, where solitons were stabilized by the frustrated exchange coupling (leading to terms with the fourth power of the magnetization gradients) or by the Dzyaloshinskii-Moriya interaction (described by terms linear in the magnetization gradients). In the case of a metallic substrate, the skyrmion stabilization is possible under restrictive conditions on the Fermi surface parameters, while in the case of a graphene substrate the stabilization is naturally achieved in several geometries with a lattice-matching of graphene and magnetic layer.

Porous silicon-copper phthalocyanine heterostructure based photoelectrochemical cell

NASA Astrophysics Data System (ADS)

A. Betty, C.; N, Padma; Arora, Shalav; Survaiya, Parth; Bhattacharya, Debarati; Choudhury, Sipra; Roy, Mainak

2018-01-01

A hybrid solar cell consisting of nanostructured p-type porous silicon (PS) deposited with visible light absorbing dye, Copper Phthalocyanine (CuPc) has been prepared in the photoelectrochemical cell configuration. P-type PS with (100) and (111) orientations which have different porous structures were used for studying the effects of the substrate morphology on the cell efficiency. Heterostructures were prepared by depositing three different thicknesses of CuPc for optimizing the cell efficiency. Structural and surface characterizations were studied using XRD, Raman, SEM and AFM on the PS-CuPc heterostructure. XRD spectrum on both plane silicon and porous silicon indicates the π-π stacking of CuPc with increased disorder for CuPc film on porous silicon. Electrochemical characterizations under sun light type radiation have been carried out to evaluate the photosensitivity of the heterostructure. Between the two different substrates, (100) PS gives better photocurrent, possibly due to the higher surface area and lower series resistance of the structure. Among the (100) PS substrates, (100) PS with 15 nm CuPc film gives Voc more than 1 V resulting in higher efficiency for the cell. The study suggests the scope for optimization of solar cell efficiency using various combinations of the substrate structure and thickness of the sensitizing layer.

Long-lived thermal control materials for high temperature and deep space applications

NASA Technical Reports Server (NTRS)

Whitt, Robin; O'Donnell, Tim

1988-01-01

Considerable effort has been put into developing thermal-control materials for the Galileo space-craft. This paper presents a summary of these findings to date with emphasis on requirements, testing and results for the post-Challenger Galileo mission. Polyimide film (Kapton), due to its inherent stability in vacuum, UV, and radiation environments, combined with good mechanical properties over a large temperature range, has been the preferred substrate for spacecraft thermal control materials. Composite outer layers, using Kapton substrates, can be fabricated to meet the requirements of severe space environments. Included in the processing of Kapton-based composite outer layers can be the deposition of metal oxide, metallic and/or polymeric thin-film coatings to provide desirable electrical, optical and thermo-optical properties. In addition, reinforcement of Kapton substrates with fabrics and films is done to improve mechanical properties. Also these substrates can be filled with varying amounts of carbon to achieve particular electrical properties. The investigation and material development reported on here has led to improved thermo-gravimetric stability, surface conductivity, RF transparency, radiation and UV stability, flammability and handle-ability of outer layer thermal control materials for deep space and near-sun spacecraft. Designing, testing, and qualifying composite thermal-control film materials to meet the requirements of the Galileo spacecraft is the scope of this paper.

Oviposition Substrate of the Mountain Fly Drosophila nigrosparsa (Diptera: Drosophilidae)

PubMed Central

Tratter, Magdalena; Bächli, Gerhard; Kirchmair, Martin; Kaufmann, Rüdiger; Arthofer, Wolfgang; Schlick-Steiner, Birgit C.; Steiner, Florian M.

2016-01-01

The survival of insect larvae often depends on the mother’s choice of oviposition substrate, and thus, this choice is an essential part of an insect species’ ecology. Especially species with narrow substrate preferences may suffer from changes in substrate availability triggered by, for example, climate change. Recent climate warming is affecting species directly (e.g., physiology) but also indirectly (e.g., biological interactions) leading to mismatching phenologies and distributions. However, the preferred oviposition substrate is still unknown for many drosophilid species, especially for those at higher elevations. In this study, we investigated the oviposition-substrate preference of the montane-alpine fly Drosophila nigrosparsa in rearing and multiple-choice experiments using natural substrates in the laboratory. Insect emergence from field-collected substrates was tested. More than 650 insects were reared from natural substrates, among them 152 drosophilids but no individual of D. nigrosparsa. In the multiple-choice experiments, D. nigrosparsa preferred ovipositing on mushrooms (> 93% of eggs); additionally, a few eggs were laid on berries but none on other substrates such as cow faeces, rotten plant material, and soil. The flies laid 24 times more eggs per day when mushrooms were included in the substrates than when they were excluded. We infer that D. nigrosparsa is a mushroom breeder with some variation in oviposition choice. The flies favoured some mushrooms over others, but they were not specialised on a single fungal taxon. Although it is unclear if and how climate change will affect D. nigrosparsa, our results indicate that this species will not be threatened by oviposition-substrate limitations in the near future because of the broad altitudinal distribution of the mushrooms considered here, even if the flies will have to shift upwards to withstand increasing temperatures. PMID:27788257

A retrospective study of 51,781 adult oral and maxillofacial biopsies.

PubMed

Dovigi, Edwin A; Kwok, Elaine Y L; Eversole, Lewis R; Dovigi, Allan J

2016-03-01

Few studies have compared patient and anatomic characteristics across the broad scope of oral and maxillofacial disease seen in dental clinics. The authors conducted a study to make these comparisons by surveying a large sample of histologically diagnosed oral and maxillofacial lesions in a US adult population. A total of 51,781 specimens biopsied from 51,781 adult patients were received by an oral pathology service over 13 years (2001-2015) and analyzed. A description of patients' sex and age at diagnosis, as well as the anatomic site of biopsy was given for diagnoses of 10 oral disease types, including malignant neoplasm, benign neoplasm, infectious, reactive, potentially malignant, developmental, healthy tissue, immune dysfunction, physical trauma, and other. The authors reported reactive lesions were the most prevalent disease type found in the sample (74.9%). Malignant diagnoses comprised 1.97% of all biopsies. The 3 most prevalent diagnoses in this study included benign keratosis, chronic apical periodontitis, and radicular cyst. Different anatomic sites, patient age groups, and sexes show different distributions of disease. Certain disease types and diagnoses were found to have a higher prevalence by sex, among particular age groups, and in certain anatomic sites. This information provides clinicians with a detailed and broad scope of the variety of oral and maxillofacial lesions processed at an oral pathology service and may assist practitioners in forming clinical impressions and differential diagnoses. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Pyruvate transport in isolated cardiac mitochondria from two species of amphibian exhibiting dissimilar aerobic scope: Bufo marinus and Rana catesbeiana.

PubMed

Duerr, Jeffrey M; Tucker, Kristina

2007-08-01

Cardiac mitochondria were isolated from Bufo marinus and Rana catesbeiana, two species of amphibian whose cardiovascular systems are adapted to either predominantly aerobic or glycolytic modes of locomotion. Mitochondrial oxidative capacity was compared using VO2 max and respiratory control ratios in the presence of a variety of substrates including pyruvate, lactate, oxaloacetate, beta-hydroxybutyrate, and octanoyl-carnitine. B. marinus cardiac mitochondria exhibited VO2 max values twice that of R. catesbeiana cardiac mitochondria when oxidizing carbohydrate substrates. Pyruvate transport was measured via a radiolabeled-tracer assay in isolated B. marinus and R. catesbeiana cardiac mitochondria. Time-course experiments described both alpha-cyano-4-hydroxycinnamate-sensitive (MCT-like) and phenylsuccinate-sensitive pyruvate uptake mechanisms in both species. Pyruvate uptake by the MCT-like transporter was enhanced in the presence of a pH gradient, whereas the phenylsuccinate-sensitive transporter was inhibited. Notably, anuran cardiac mitochondria exhibited activities of lactate dehydrogenase and pyruvate carboxylase. The presence of both transporters on the inner mitochondrial membrane affords the net uptake of monocarboxylates including pyruvate, beta-hydroxybutyrate, and lactate; the latter potentially indicating the presence of a lactate/pyruvate shuttle allowing oxidation of extramitochondrial NADH. Intramitochondrial lactate dehydrogenase and pyruvate carboxylase enables lactate to be oxidized to pyruvate or converted to anaplerotic oxaloacetate. Kinetics of the MCT-like transporter differed significantly between the two species, suggesting differences in aerobic scope may be in part attributable to differences in mitochondrial carbohydrate utilization. (c) 2007 Wiley-Liss, Inc.

Temporal and spectral properties of the songs of the southern green stink bug Nezara viridula (L.) from Slovenia.

PubMed

Cokl, A; Virant-Doberlet, M; Stritih, N

2000-01-01

Substrate born songs of the southern green stinkbug Nezara viridula (L.) from Slovenia were recorded and analysed. The male calling song is composed of narrow-band regularly repeated single pulses and of broad-band frequency modulated pulses grouped into pulse trains. The female calling song is characterised by broad-band pulsed and narrow-band non-pulsed pulse trains. A frequency modulated pre-pulse precedes the narrow-band pulse train. A frequency-modulated post-pulse usually follows the pulse train of the male courtship song. The male calling song triggers broad-band pulse trains of the female courtship song. The female also produces a repelling low-frequency vibration that inhibits male calling and courtship. The male rival song is characterised by prolonged pulses with a typical frequency modulation.

Kinetic analysis of extension of substrate specificity with Xanthomonas maltophilia, Aeromonas hydrophila, and Bacillus cereus metallo-beta-lactamases.

PubMed Central

Felici, A; Amicosante, G

1995-01-01

Twenty beta-lactam molecules, including penicillins, cephalosporins, penems, carbapenems, and monobactams, were investigated as potential substrates for Xanthomonas maltophilia ULA-511, Aeromonas hydrophila AE036, and Bacillus cereus 5/B/6 metallo-beta-lactamases. A detailed analysis of the kinetic parameters examined confirmed these enzymes to be broad-spectrum beta-lactamases with different ranges of catalytic efficiency. Cefoxitin and moxalactam, substrates for the beta-lactamases from X. maltophilia ULA-511 and B. cereus 5/B/6, behaved as inactivators of the A. hydrophila AE036 metallo-beta-lactamase, which appeared to be unique among the enzymes tested in this study. In addition, we report a new, faster, and reliable purification procedure for the B. cereus 5/B/6 metallo-beta-lactamase, cloned in Escherichia coli HB101. PMID:7695305

Measurement of Nonribosomal Peptide Synthetase Adenylation Domain Activity Using a Continuous Hydroxylamine Release Assay.

PubMed

Duckworth, Benjamin P; Wilson, Daniel J; Aldrich, Courtney C

2016-01-01

Adenylation is a crucial enzymatic process in the biosynthesis of nonribosomal peptide synthetase (NRPS) derived natural products. Adenylation domains are considered the gatekeepers of NRPSs since they select, activate, and load the carboxylic acid substrate onto a downstream peptidyl carrier protein (PCP) domain of the NRPS. We describe a coupled continuous kinetic assay for NRPS adenylation domains that substitutes the PCP domain with hydroxylamine as the acceptor molecule. The pyrophosphate released from the first-half reaction is then measured using a two-enzyme coupling system, which detects conversion of the chromogenic substrate 7-methylthioguanosine (MesG) to 7-methylthioguanine. From profiling substrate specificity of unknown or engineered adenylation domains to studying chemical inhibition of adenylating enzymes, this robust assay will be of widespread utility in the broad field NRPS enzymology.

A scoping review and research synthesis on financing and regulating oral care in long-term care facilities.

PubMed

MacEntee, Michael I; Kazanjian, Arminee; Kozak, Jean-Francois; Hornby, Kathy; Thorne, Sally; Kettratad-Pruksapong, Matana

2012-06-01

Oral health care for frail elders is grossly inadequate almost everywhere, and our knowledge of regulating and financing oral care in this context is unclear. This scoping study examined and summarised the published literature available and the gaps in knowledge about regulating and financing oral care in long-term care (LTC) facilities. We limited the electronic search to reports on regulating and financing oral care, including reports, commentaries, reviews and policy statements on financing and regulating oral health-related services. The broad electronic search identified 1168 citations, which produced 42 references, including 26 pieces of grey literature for a total of 68 papers. Specific information was found on public and private funding of care and on difficulties regulating care because of professional segregation, difficulties assessing need for care, uncertainty on appropriateness of treatments and issues around scope of professional practice. A wide range of information along with 19 implications and 18 specific gaps in knowledge emerged relevant to financing and regulating oral healthcare services in LTC facilities. Effort has been given to enhancing oral care for frail elders, but there is little agreement on how the care should be regulated or financed within the LTC sector. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

A resonance-free nano-film airborne ultrasound emitter

NASA Astrophysics Data System (ADS)

Daschewski, Maxim; Harrer, Andrea; Prager, Jens; Kreutzbruck, Marc; Beck, Uwe; Lange, Thorid; Weise, Matthias

2013-01-01

In this contribution we present a novel thermo-acoustic approach for the generation of broad band airborne ultrasound and investigate the applicability of resonance-free thermo-acoustic emitters for very short high pressure airborne ultrasound pulses. We report on measurements of thermo-acoustic emitter consisting of a 30 nm thin metallic film on a usual soda-lime glass substrate, generating sound pressure values of more than 140 dB at 60 mm distance from the transducer and compare the results with conventional piezoelectric airborne ultrasound transducers. Our experimental investigations show that such thermo-acoustic devices can be used as broad band emitters using pulse excitation.

Broad Frequency LTCC Vertical Interconnect Transition for Multichip Modules and System on Package Applications

NASA Technical Reports Server (NTRS)

Decrossas, Emmanuel; Glover, Michael D.; Porter, Kaoru; Cannon, Tom; Mantooth, H. Alan; Hamilton, M. C.

2013-01-01

Various stripline structures and flip chip interconnect designs for high-speed digital communication systems implemented in low temperature co-fired ceramic (LTCC) substrates are studied in this paper. Specifically, two different transition designs from edge launch 2.4 millimeter connectors to stripline transmission lines embedded in LTCC are discussed. After characterizing the DuPont (sup trademark) 9K7 green tape, different designs are proposed to improve signal integrity for high-speed digital data. The full-wave simulations and experimental data validate the presented designs over a broad frequency band from Direct Current to 50 gigahertz and beyond.

Matrix metalloproteinase processing of signaling molecules to regulate inflammation.

PubMed

Butler, Georgina S; Overall, Christopher M

2013-10-01

Inflammation is a complex and highly regulated process that facilitates the clearance of pathogens and mediates tissue repair. Failure to resolve inflammation can lead to chronic inflammatory diseases such as periodontitis. Matrix metalloproteinases are generally thought to be detrimental in disease because degradation of extracellular matrix contributes to pathology. However, proteomic techniques (degradomics) are revealing that matrix metalloproteinases process a diverse array of substrates and therefore have a broad range of functions. Many matrix metalloproteinase substrates modulate inflammation and hence, by processing these proteins, matrix metalloproteinases can orchestrate the inflammatory response. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

PubMed Central

Barski, Oleg A.; Tipparaju, Srinivas M.; Bhatnagar, Aruni

2008-01-01

The Aldo-Keto Reductase (AKR) superfamily comprises of several enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism and detoxification. Substrates of the family include glucose, steroids, glycosylation end products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β/α)8 barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the Phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics. PMID:18949601

Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction

PubMed Central

Siegel, Justin B.; Zanghellini, Alexandre; Lovick, Helena M.; Kiss, Gert; Lambert, Abigail R.; St.Clair, Jennifer L.; Gallaher, Jasmine L.; Hilvert, Donald; Gelb, Michael H.; Stoddard, Barry L.; Houk, Kendall N.; Michael, Forrest E.; Baker, David

2011-01-01

The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond forming reactions should be broadly useful in synthetic chemistry. PMID:20647463

Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction.

PubMed

Siegel, Justin B; Zanghellini, Alexandre; Lovick, Helena M; Kiss, Gert; Lambert, Abigail R; St Clair, Jennifer L; Gallaher, Jasmine L; Hilvert, Donald; Gelb, Michael H; Stoddard, Barry L; Houk, Kendall N; Michael, Forrest E; Baker, David

2010-07-16

The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond-forming reactions should be broadly useful in synthetic chemistry.

Combustion-Assisted Photonic Annealing of Printable Graphene Inks via Exothermic Binders.

PubMed

Secor, Ethan B; Gao, Theodore Z; Dos Santos, Manuel H; Wallace, Shay G; Putz, Karl W; Hersam, Mark C

2017-09-06

High-throughput and low-temperature processing of high-performance nanomaterial inks is an important technical challenge for large-area, flexible printed electronics. In this report, we demonstrate nitrocellulose as an exothermic binder for photonic annealing of conductive graphene inks, leveraging the rapid decomposition kinetics and built-in energy of nitrocellulose to enable versatile process integration. This strategy results in superlative electrical properties that are comparable to extended thermal annealing at 350 °C, using a pulsed light process that is compatible with thermally sensitive substrates. The resulting porous microstructure and broad liquid-phase patterning compatibility are exploited for printed graphene microsupercapacitors on paper-based substrates.

Carbohydrates as efficient catalysts for the hydration of α-amino nitriles.

PubMed

Chitale, Sampada; Derasp, Joshua S; Hussain, Bashir; Tanveer, Kashif; Beauchemin, André M

2016-11-01

Directed hydration of α-amino nitriles was achieved under mild conditions using simple carbohydrates as catalysts exploiting temporary intramolecularity. A broadly applicable procedure using both formaldehyde and NaOH as catalysts efficiently hydrated a variety of primary and secondary susbtrates, and allowed the hydration of enantiopure substrates to proceed without racemization. This work also provides a rare comparison of the catalytic activity of carbohydrates, and shows that the simple aldehydes at the basis of chemical evolution are efficient organocatalysts mimicking the function of hydratase enzymes. Optimal catalytic efficiency was observed with destabilized aldehydes, and with difficult substrates only simple carbohydrates such as formaldehyde and glycolaldehyde proved reliable.

The Post-polyketide Synthase Steps in iso-Migrastatin Biosynthesis Featuring Tailoring Enzymes with Broad Substrate Specificity

PubMed Central

Ma, Ming; Kwong, Thomas; Lim, Si-Kyu; Ju, Jianhua; Lohman, Jeremy R.; Shen, Ben

2013-01-01

The iso-migrastatin (iso-MGS) biosynthetic gene cluster from Streptomyces platensis NRRL 18993 consists of 11 genes, featuring an acyltransferase (AT)-less type I polyketide synthase (PKS) and three tailoring enzymes MgsIJK. Systematic inactivation of mgsIJK in S. platensis enabled us to (i) identify two nascent products (10 and 13) of the iso-MGS AT-less type I PKS, establishing an unprecedented novel feature for AT-less type I PKSs, and (ii) account for the formation of all known post-PKS biosynthetic intermediates (10-17) generated by the three tailoring enzymes MgsIJK, which possessed significant substrate promiscuities. PMID:23394593