Synthesis, biological activities and SAR studies of new 3-substitutedphenyl-4-substitutedbenzylideneamino-1,2,4-triazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors.

PubMed

Wang, Bao-Lei; Zhang, Li-Yuan; Liu, Xing-Hai; Ma, Yi; Zhang, Yan; Li, Zheng-Ming; Zhang, Xiao

2017-12-15

A series of new 3-substitutedphenyl-4-substitutedbenzylideneamino-1,2,4-triazole Mannich bases and bis-Mannich bases were synthesized through Mannich reaction with high yields. Their structures were confirmed by means of IR, 1 H NMR, 13 C NMR and elemental analysis. The preliminary bioassay indicated that compounds 7g, 7h and 7l exhibited potent in vitro inhibitory activities against ketol-acid reductoisomerase (KARI) with K i value of (0.38 ± 0.25), (6.59 ± 2.75) and (8.46 ± 3.99) μmol/L, respectively, and were comparable with IpOHA. They could be new KARI inhibitors for follow-up research. Some of the title compounds also exhibited obvious herbicidal activities against Echinochloa crusgalli and remarkable in vitro fungicidal activities against Physalospora piricola and Rhizoctonia cerealis. The SAR of the compounds were analyzed, in which the molecular docking revealed the binding mode of 7g with the KARI, and the 3D-QSAR results provided useful information for guiding further optimization of this kind of structures to discover new fungicidal agents towards Rhizoctonia cerealis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activity of bis(7-hydroxycoumarin) Mannich bases against bovine viral diarrhoea virus.

PubMed

Ibrahim, Munjed M; Mazzei, Mauro; Delogu, Ilenia; Szabó, Róbert; Sanna, Giuseppina; Loddo, Roberta

2016-10-01

Some Mannich bases of 7-hydroxycoumarins (3-6) with piperazine or other amines bearing two secondary amine groups were prepared and tested against viruses representative of RNA families. All compounds were symmetrical and possessed two identical coumarin moieties with respect to one diamine. In the series of 7-hydroxy derivatives, 3a was endowed with a significant activity against BVDV. Then, some of these double Mannich bases were alkylated and acylated. Among the propyloxy derivatives, only 3f showed a modest activity against BVDV. Among the acyl derivatives, the p-nitrobenzoyl derivative 3i emerged as the most active compound; in this series, the p-nitrobenzoyl derivative 3j also exhibited good action against BVDV and modest activity against CVB-5. On the whole, the compounds presented here show some differences, with respect to previous studies in terms of SAR from similar Mannich bases of 7-hydroxycoumarin. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis of novel ferrocenyl Mannich bases and their antibacterial activities

NASA Astrophysics Data System (ADS)

Liu, Yuting; Xin, Hong; Yin, Jingyi; Yin, Dawei; Yang, Zijiang; Li, Jie

2018-04-01

In this work, a series of Mannich bases bearing ferrocenyl groups were synthesized via Mannich reactions. The effects of different conditions on the reaction were explored, and the newly synthesized compounds were well characterized by NMR and FT-IR. All compounds have been screened for in vitro antibacterial and antifungal, and the compounds 1-ferrocenyl-3-phenyl-3-(m-nitrophenylamino)-1-acetone (2f) and 1-ferrocenyl-3-phenyl-3-(p-nitrophenylamino)-1-acetone (2g) were shown to be significant activity against all the tested bacterial strains, such as Staphylococcus aureus, Streptococcus, Actinomycete, Escherichia coli, Saccharomyces cerevisiae.

Synthesis and antimicrobial studies of some Mannich bases carrying imidazole moiety.

PubMed

Frank, Priya V; Manjunatha Poojary, Mahesha; Damodara, Naral; Chikkanna, Chandrashekhar

2013-06-01

3 Starting from 2-methyl-4-nitro-imidazole, new 5-(2-methyl- 4-nitro-1-imidazomethyl)-1,3,4-oxadiazole-2-thione () was synthesized and was subjected to Mannich reaction with appropriate amines to yield a new series of 3-substituted aminomethyl-5-(2-methyl-4-nitro-1-imidazomethyl)- 1,3,4-oxadiazole-2-thiones (4a-j). The structure of the title compounds was elucidated by elemental analysis and spectral data. The newly synthesized Mannich bases were screened for their antibacterial and antifungal activity. Many of these compounds exhibited potent antifungal activity.

Antinociceptive effect and mechanism of action of isatin, N-methyl isatin and oxopropyl isatin in mice.

PubMed

Giorno, Thais Biondino Sardella; Silva, Bárbara Vasconcellos da; Pinto, Angelo da Cunha; Fernandes, Patricia Dias

2016-04-15

There has been growing interest in the synthesis of new derivatives from isatin, found in Isatis genus. Our objectives were to characterize the antinociceptive mechanism of action of isatin, N-methyl-isatin (MI) and N-methyl-3-(2-oxopropyl)-3-hydroxy-2-oxindole (MOI). Substances (0.1-10mg/kg, p.o.) were studied in chemical (paw licking induced by formalin, capsaicin or glutamate) or thermal (hot plate) models of nociception. The involvement of several systems was evaluated using different receptor antagonists. All three substances inhibit both phases of formalin-induced licking, increase the area under the curve and MI and MOI have a higher effect than that of morphine (in hot plate). Capsaicin and glutamate-induced licking were also reduced by all three substances. In the hot plate model, the antinociceptive effect of isatin was reduced by naloxone and atropine; naloxone, atropine and L-NAME reduced MI effect while naloxone, atropine, L-NAME, mecamylamine and ondansetron reduced MOI effect. Our results suggest that isatin, MI and MOI: 1) present activity in models of nociception; 2) capsaicin and glutamate receptors seems to participate in the mechanism of action; 3) opioid, cholinergic, serotoninergic, nitrergic and adrenergic systems may be involved, at least in part, in the mechanism of action of some of these substances. Copyright © 2016 Elsevier Inc. All rights reserved.

Regioselective reaction: synthesis, characterization and pharmacological activity of some new Mannich and Schiff bases containing sydnone.

PubMed

Nithinchandra; Kalluraya, B; Aamir, S; Shabaraya, A R

2012-08-01

A novel series of 1-substituted aminomethyl-3-[1-(4-isobutylphenyl)ethyl]-4-(3-aryl-4-sydnonylidene) amino-1,2,4-triazol-5-thiones (9), was prepared from the 3-[1-(4-isobutylphenyl)ethyl]-4-(3-aryl-4-sydnonylidene) amino 5-mercapto-1,2,4-triazoles (8) by aminomethylation with formaldehyde and secondary amine. The structures of Schiff bases (8) and Mannich bases (9) were characterized on the basis of IR, NMR, mass spectra1 data and elemental analysis. The newly synthesized compounds were screened for their anti-inflammatory and analgesic activities. Mannich bases (9) carrying piperidine and morpholine residues showed promising anti-inflammatory and analgesic activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Synthesis and biological activities of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors.

PubMed

Zhang, Yan; Liu, Xing-Hai; Zhan, Yi-Zhou; Zhang, Li-Yuan; Li, Zheng-Ming; Li, Yong-Hong; Zhang, Xiao; Wang, Bao-Lei

2016-10-01

A series of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases have been conveniently synthesized in good yields. Their structures were characterized by IR, (1)H NMR, (13)C NMR and elemental analysis. The preliminary bioassay results indicated that some of the compounds showed promising in vitro fungicidal activities towards several test plant fungi; some of them exhibited significant herbicidal activities against Brassica campestris and excellent in vitro inhibitory activities against rice ketol-acid reductoisomerase (KARI). Among 14 novel compounds, 8c, 8d and 8m showed potent KARI inhibitory activities with Ki value of (0.96±0.42), (3.86±0.49) and (3.10±0.71) μmol/L, respectively, and were comparable with IpOHA. These compounds could be novel KARI inhibitors for further investigation. The density functional theory (DFT) calculations and molecular docking were carried out to study the structure-activity relationship (SAR) of the active inhibitors in this Letter. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modular synthesis and in vitro and in vivo antimalarial assessment of C-10 pyrrole mannich base derivatives of artemisinin.

PubMed

Pacorel, Bénédicte; Leung, Suet C; Stachulski, Andrew V; Davies, Jill; Vivas, Livia; Lander, Hollie; Ward, Stephen A; Kaiser, Marcel; Brun, Reto; O'Neill, Paul M

2010-01-28

In two steps from dihydroartemisinin, a small array of 16 semisynthetic C-10 pyrrole Mannich artemisinin derivatives (7a-p) have been prepared in moderate to excellent yield. In vitro analysis against both chloroquine sensitive and resistant strains has demonstrated that these analogues have nanomolar antimalarial activity, with several compounds being more than 3 times more potent than the natural product artemisinin. In addition to a potent antimalarial profile, these molecules also have very high in vitro therapeutic indices. Analysis of the optimal Mannich side chain substitution for in vitro and in vivo activity reveals that the morpholine and N-methylpiperazine Mannich side chains provide analogues with the best activity profiles, both in vitro and in vivo in the Peter's 4 day test.

New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges.

PubMed

Naglah, Ahmed M; Ahmed, Atallah F; Wen, Zhi-Hong; Al-Omar, Mohamed A; Amr, Abd El-Galil E; Kalmouch, Atef

2016-04-15

A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a-c. The chemical structures of the new Schiff bases (5b and 5d-h) were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%-42.2% ± 19.6% compared to the effect on COX-2 expression (<56.4% ± 3.1% inhibition) at the same concentration (10 μM). The higher iNOS inhibition activity of the tested Schiff bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a-c), and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents.

Synthesis, SAR Study and Evaluation of Mannich and Schiff Bases of Pyrazol-5(4H)-one Moiety Containing 3-(Hydrazinyl)-2-phenylquinazolin-4(3H)-one

PubMed Central

Sivakumar, K. K.; Rajasekharan, A.; Rao, R.; Narasimhan, B.

2013-01-01

In the present investigation, a series of 12 Mannich bases (QP1-12) and 5 Schiff bases (QSP1-5) of pyrazol-5(4H)-one moiety containing 3-(hydrazinyl)-2-phenylquinazolin-4(3H)-one has been synthesized and characterized by physicochemical as well as spectral means. The synthesized Mannich and Schiff bases were screened for their preliminary antimicrobial activity against Gram-positive and Gram-negative bacterial as well as fungal strains by the determination of zone of inhibition. Mannich bases (QP1-12) were found to be more potent antibacterial agents against Gram-positive bacteria, whereas Schiff bases (QSP1-5) were more potent against Gram-negative bacteria and fungi. Minimum inhibitory concentration result demonstrated that Mannich base compound (QP7) having ortho -OH and para -COOH group showed some improvement in antibacterial activity (minimum inhibitory concentration of 48.88×10−3 μM/ml) among the tested Gram-positive organisms and it also exhibit minimum inhibitory concentration of value of 12.22×10−3 μM/ml for Klebsiella pneumoniae. The antitubercular activity of synthesized compounds against Mycobacterium tuberculosis (H37Rv) was determined using microplate alamar blue assay. Compound QP11 showed appreciable antitubercular activity (minimum inhibitory concentration of 6.49×10−3 μM/ml) which was more active than the standard drugs, ethambutol (minimum inhibitory concentration of 7.60×10−3 μM/ml) and ciprofloxacin (9.4×10−3 μM/ml). Compounds QP11, QP9, QSP1, QSP2, and QSP5 have good selective index and may be selected as a lead compound for the development of novel antitubercular agents. PMID:24302802

Design, synthesis and preliminary antimicrobial evaluation of n-alkyl chain tethered c-5 functionalized bis-isatins

USDA-ARS?s Scientific Manuscript database

A series of N-alkyl tethered C-5 functionalized bis-isatins were synthesized and evaluated for antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed the compound 4t, with an optimal combination of bromo-substituent at the C-5 position of isatin ring al...

Synthesis, biological evaluation and structure-activity relationship studies of isoflavene based Mannich bases with potent anti-cancer activity.

PubMed

Chen, Yilin; Cass, Shelley L; Kutty, Samuel K; Yee, Eugene M H; Chan, Daniel S H; Gardner, Christopher R; Vittorio, Orazio; Pasquier, Eddy; Black, David StC; Kumar, Naresh

2015-11-15

Phenoxodiol, an analogue of the isoflavone natural product daidzein, is a potent anti-cancer agent that has been investigated for the treatment of hormone dependent cancers. This molecular scaffold was reacted with different primary amines and secondary amines under different Mannich conditions to yield either benzoxazine or aminomethyl substituted analogues. These processes enabled the generation of a diverse range of analogues that were required for structure-activity relationship (SAR) studies. The resulting Mannich bases exhibited prominent anti-proliferative effects against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. Further cytotoxicity studies against MRC-5 normal lung fibroblast cells showed that the isoflavene analogues were selective towards cancer cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antioxidant & anticancer activities of isatin (1H-indole-2,3-dione), isolated from the flowers of Couroupita guianensis Aubl

PubMed Central

Premanathan, Mariappan; Radhakrishnan, Srinivasan; Kulangiappar, Kumarasamy; Singaravelu, Ganesan; Thirumalaiarasu, Velayutham; Sivakumar, Thangavel; Kathiresan, Kandasamy

2012-01-01

Background & objectives: Derivatives of isatin are known to have cytotoxicity against human carcinoma cell lines. This compound therefore, has a potential to be used as a chemotherapeutic agent against cancer. This study was done to investigate the antioxidant and anticancer activities of isatin, extracted from flower of a folklore medicinal plant Couroupita guianensis against human promylocytic leukemia (HL60) cells. Methods: Active fractions demonstrating anticancer and antioxidant activities were isolated from the extracts of shade-dried flowers of C. guianensis by bioassay guided fractionation. The free radical scavenging activity was determined using lipid peroxidation assay. Cytotoxicity against human promylocytic leukemia HL60 cells was determined by MTT assay. Apoptotic activity was analyzed by DNA fragmentation and flowcytometry. Results: Isatin isolated from the active fraction showed antioxidant activity with the EC50 value of 72.80 μg/ml. It also exhibited cytotoxicity against human promylocytic leukemia HL60 cells in dose-dependant manner with the CC50 value of 2.94 μg/ml. The isatin-treated cells underwent apoptosis and DNA fragmentation. Apoptosis was confirmed by the FACS analysis using FITC-annexin V markers. Interpretation & conclusions: Isatin showed antioxidant activity and was cytotoxic to the HL60 cells due to induction of apoptosis. The isatin can be further evaluated to be used as a prophylactic agent to prevent the free radical-induced cancer and as a chemotherapeutic agent to kill the cancer cells. PMID:23287130

Synthesis and anticancer evaluation of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles and Mannich bases.

PubMed

Megally Abdo, Nadia Youssef; Kamel, Mona Monir

2015-01-01

A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5-(pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4-yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic acid hydrazide. Aminoalkylation of compounds 5a-d with formaldehyde and various secondary amines furnished the Mannich bases 6a-p. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against six human cancer cell lines and normal fibroblast cells. Sixteen of the tested compounds exhibited significant cytotoxicity against most cell lines. Among these derivatives, the Mannich bases 6j, 6m and 6p were found to exhibit the most potent activity. The Mannich base 6m showed more potent cytotoxic activity against gastric cancer NUGC (IC50=0.021 µM) than the standard CHS 828 (IC50=0.025 µM). Normal fibroblast cells WI38 were affected to a much lesser extent (IC50>10 µM).

Synthesis of new 1,2,4-triazole compounds containing Schiff and Mannich bases (morpholine) with antioxidant and antimicrobial activities.

PubMed

Ünver, Yasemin; Deniz, Sadik; Çelik, Fatih; Akar, Zeynep; Küçük, Murat; Sancak, Kemal

2016-01-01

Compound 2 was synthesized by reacting CS 2 /KOH with compound 1. The treatment of compound 2 with hydrazine hydrate produced compound 3. Then, compound 3 was converted to Schiff bases (4a-d) by the handling with several aromatic aldehydes. The treatment of triazole compounds 4a-d containing Schiff base with morpholine gave compounds 5a-d. All compounds were tested for their antioxidant and antimicrobial activities. The antioxidant test results of DPPH• radical scavenging and ferric reducing/antioxidant power methods showed good antioxidant activity. The triazole-thiol (3) was the most active, and the effect of the substituent type of the thiophene ring on the activity was same for both Schiff bases (4a-d) and Mannich bases (5a-d). Among the newly synthesized triazole derivatives, the Schiff base 4d and the Mannich base 5d carrying nitro substituent on the thiophene ring showed promising antibacterial and antifungal activity, with lower MIC values than the standard antibacterial ampicillin.

Antimicrobial and hypoglycemic activities of novel N-Mannich bases derived from 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thiones.

PubMed

Al-Abdullah, Ebtehal S; Al-Tuwaijri, Hanaa M; Hassan, Hanan M; Haiba, Mogedda E; Habib, Elsayed E; El-Emam, Ali A

2014-12-11

The reaction of 5-(1-adamantyl)-4-ethyl or allyl-1,2,4-triazoline-3-thione with formaldehyde solution and various 1-substituted piperazines yielded the corresponding N-Mannich bases. The newly synthesized N-Mannich bases were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Six compounds showed potent antibacterial activity against one or more of the tested microorganisms, while two compounds exhibited moderate activity against the tested Gram-positive bacteria. None of the newly synthesized compounds were proved to possess marked activity against Candida albicans. The oral hypoglycemic activity of six compounds was determined in streptozotocin (STZ)-induced diabetic rats. Four compounds produced significant strong dose-dependent reduction of serum glucose levels, compared to gliclazide at 10 mg/kg dose level (potency ratio > 75%).

Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids.

PubMed

Sorochinsky, Alexander E; Aceña, José Luis; Moriwaki, Hiroki; Sato, Tatsunori; Soloshonok, Vadim

2013-11-01

This review provides a comprehensive treatment of literature data dealing with asymmetric synthesis of α-amino-β-hydroxy and α,β-diamino acids via homologation of chiral Ni(II) complexes of glycine Schiff bases using aldol and Mannich-type reactions. These reactions proceed with synthetically useful chemical yields and thermodynamically controlled stereoselectivity and allow direct introduction of two stereogenic centers in a single operation with predictable stereochemical outcome. Furthermore, new application of Ni(II) complexes of α-amino acids Schiff bases for deracemization of racemic α-amino acids and (S) to (R) interconversion providing additional synthetic opportunities for preparation of enantiomerically pure α-amino acids, is also reviewed. Origin of observed diastereo-/enantioselectivity in the aldol, Mannich-type and deracemization reactions, generality and limitations of these methodologies are critically discussed.

Conformational Properties, Spectroscopy and Structure of ISATIN-(WATER)_{n=1-3} Clusters

NASA Astrophysics Data System (ADS)

Singh, Milind K.; Upadhya, D. M.; Singh, Vipin B.

2009-06-01

The structure, stability and vibrational characteristics of Isatin-(Water)_n clusters with n=1=3 have been investigated using second order Moller-Plesset (MP2) perturbation tehory and Density Functional Theory (with B3LYP) methods employing the basis set 6-31+G(d). The vertical excitation energies for these complexes have been also computed using the time-dependent density functional theory. The three stable conformational isomers, each for Isatin-(Water)_1 and Isatin-(Water)_2 clusters were obtained. It is shown that in the most stable isomer of Isatin-(Water)_1 cluster hydrogen bond between amide hydrogen and oxygen of water is found stronger as compared to the H-bond in Indole-(Water)_1 cluster. For a particular position of complexation of water, between the carbonyl oxygen's, results an unusual increase in the dipole moment due to an electronic charge displacement from the N atom to the C atom of the neighboring carbonyl bond. This causes a large separation between the effective charges forming the dipole. The complexes involving this position of water are expected to show a small charge transfer character. The experimentally observed electronic absorption peaks are reasonably reproduced by the TD-DFT calculations and it is found that the longest wavelength absorption peak of isatin at 406 nm is significantly red shifted after addition of a water molecule.

Isatin as an auxin source favoring floral and vegetative shoot regeneration from calli produced by thin layer explants of tomato pedicel

NASA Technical Reports Server (NTRS)

Applewhite, P. B.; K-Sawhney, R.; Galston, A. W.

1994-01-01

Thin layer explants taken from the pedicels and peduncles of flowering tomato plants yielded calli with great organogenetic potential. Of the 15 cultivars tested, 7 regenerated roots, shoots and eventually entire fruit-bearing plants. Calli grown on modified Murashige-Skoog medium responded to varied auxins and cytokinins with different morphogenetic patterns. Thus, naphthaleneacetic acid yielded root-producing calli, while the auxin precursor isatin (indole 2,3-dione) caused the production of calli with vegetative and floral shoots, rarely yielding roots. This may be related to isatin's slow, steady conversion to an active auxin (Plant Physiol 41:1485-1488, 1966) in contrast with naphthaleneacetic acid's immediate presentation of a high level of active auxin. The highest incidence of vegetative shoot (100%) and flower (50%) formation was obtained with 10 micromoles isatin and 3 micromoles zeatin. A few of the flowers developed into ripe fruits. The high frequency of induction of vegetative shoots and flowers before roots with isatin suggests its utility in micropropagation from plant tissue cultures.

A Strategy for Nonmigrating Plasticized PVC Modified with Mannich base of Waste Cooking Oil Methyl Ester.

PubMed

Jia, Puyou; Zhang, Meng; Hu, Lihong; Song, Fei; Feng, Guodong; Zhou, Yonghong

2018-01-25

The waste cooking oil (WCO) production from the catering industry and food processing industry causes serious environmental, economic and social problems. However, WCO can be used for the preparation of fine chemicals such as internal plasticizer. With this aim, this work is focused on preparing internal plasticizer by using WCO and determining technical viability of non-migration poly (vinyl chloride) (PVC) materials. The mannich base of waste cooking oil methyl ester (WCOME) was synthesized from WCO via esterification, interesterification and mannich reaction, which was used to produce self-plasticization PVC materials as an internal plasticizer. The results showed that the PVC was plasticized effectively. Self-plasticization PVC films showed no migration in n-hexane, but 15.7% of dioctyl phthalate (DOP) leached from DOP/PVC(50/50) system into n-hexane. These findings transformed the traditional plastic processing technology and obtained cleaner production of no migration plasticizer from WCO.

The redox-Mannich reaction.

PubMed

Chen, Weijie; Seidel, Daniel

2014-06-06

A complement to the classic three-component Mannich reaction, the redox-Mannich reaction, utilizes the same starting materials but incorporates an isomerization step that enables the facile preparation of ring-substituted β-amino ketones. Reactions occur under relatively mild conditions and are facilitated by benzoic acid.

Synthesis and characterization of copper complexes of Schiff base derived from isatin and salicylic hydrazide

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

Lekshmy, R. K., E-mail: lekshmyulloor@gmail.com, E-mail: tharapradeepkumar@yahoo.com; Thara, G. S., E-mail: lekshmyulloor@gmail.com, E-mail: tharapradeepkumar@yahoo.com

A series of novel metal complexes of Schiff base have been prepared by the interaction of Cu(II) with isatin salicylic hydrazide. All the new compounds were characterized by elemental analysis, conductance measurement, magnetic moment determination, IR, UV, NMR, Mass and EPR spectral studies, thermal studies and microbial activities. The results indicate that the ligand acts as a tridentate chelating ligand coordinating through nitrogen and oxygen atoms. The ligand and complexes show inactive against Escherichia coli and active against Staphylococcus aureus and B.substilis. By analyzing the results of spectral, thermal and elemental analysis square planar geometry is proposed for all themore » complexes.« less

A new mild base-catalyzed Mannich reaction of hetero-arylamines in water: highly efficient stereoselective synthesis of beta-aminoketones under microwave heating.

PubMed

Hao, Wen-Juan; Jiang, Bo; Tu, Shu-Jiang; Cao, Xu-Dong; Wu, Shan-Shan; Yan, Shu; Zhang, Xiao-Hong; Han, Zheng-Guo; Shi, Feng

2009-04-07

A new mild base-catalyzed Mannich reaction of aromatic aldehydes with 1,2-diphenylethanone and hetero-arylamines including pyridin-2-amine and pyrimidin-2-amine is described. In this reaction, a series of new beta-aminoketones were stereoselectively synthesized in water by controlling the steric hindrance of the substrates under microwave heating. This method has the advantages of a short synthetic route, operational simplicity, increased safety for small-scale high-speed synthesis, and minimal environmental impact.

Fe3O4 Nanoparticles Mediated Synthesis of Novel Isatin-dihydropyrimidinone Hybrid Molecules as Antioxidant and Cytotoxic Agents.

PubMed

Maddela, Srinubabu; Makula, Ajitha; Jayarambabu, N

2017-01-01

The present study emphasizes on designing a new series of isatin-dihydropyrimidinone derivatives by adopting a hybrid pharmacophore approach. Fe3O4 nanoparticles (Fe3O4 NP) are magnetically recoverable and are effective catalysts adequately used to synthesize Isatin-dihydropyrimidinones. Individual derivatives of Isatin and dihydropyrimidinone are equipotent to treat cytotoxicity. The present work was planned to fuse two pharmacophores (Isatin, dihydropyrimidinone) and to examine any synergistic effect in the anticancer activity. The individual compounds are synthesized by adopting appropriate synthetic routes like sandmayers and biginellis reaction and are fused together by using glacial acetic acid and Methanolic KOH to form novel Isatindihydropyrimidinone hybrids. All the new series of hybrids 7a-l were characterized by FT-IR, 1H NMR, 13C NMR, elemental analysis and Mass spectroscopy. The antioxidant activity of the synthesized compounds was assessed by using two models: 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) and Hydrogen peroxide (H2O2) scavenging assay. From the results it can be inferred that nearly all the synthesized compounds have shown antioxidant activity at the tested dose as correlated with the standard ascorbic acid. The in vitro cytotoxic activity was assayed by using MTT assay. Compound 7l with IC50 values 22.13, 25.68 and 35.59 μM has significantly greater potency against MCF- 7, HeLa and IMR-32 cell lines. The compounds with halogen and electron withdrawing groups at the C-5 position of isatin ring exhibited significant antioxidant and cytotoxic activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation.

PubMed

El-Naggar, Mohamed; Eldehna, Wagdy M; Almahli, Hadia; Elgez, Amr; Fares, Mohamed; Elaasser, Mahmoud M; Abdel-Aziz, Hatem A

2018-06-12

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates ( 4a ⁻ n ) and thiazolo[3,2- a ]benzimidazolone-isatin conjugates ( 7a ⁻ d ), and in vitro evaluation of their antiproliferative activity towards two breast cancer cell lines; triple negative MDA-MB-231, and MCF-7. Compounds 4m and 7b emerged as the most active congeners against MDA-MB-231 cells (IC 50 = 7.6 ± 0.5 and 13.2 ± 1.1 µM, respectively). Compounds 4m and 7b were able to provoke apoptosis in MDA-MB-231 cells, evidenced by the up-regulation of Bax and down-regulation of Bcl-2, besides boosting caspase-3 levels. Hybrid 4m induced a fourfold increase in the percentage of cells at Sub-G₁, with concurrent arrest in G₂-M phase by 2.5-folds. Furthermore, hybrid 4m resulted in a sixfold increase in the percentage of annexin V-FITC positive apoptotic MDA-MB-231 cells as compared with the control. Moreover, the cytotoxic activities of the active conjugates were assessed towards two nontumorigenic cell lines (breast MCF-10A and lung WI-38) where both conjugates 4m and 7b displayed mean tumor selectivity index: 9.6 and 13.9, respectively. Finally, several ADME descriptors were predicted for the active conjugates via a theoretical kinetic study.

In situ generation of N-Boc-protected alkenyl imines: controlling the E/Z geometry of alkenyl moieties in the Mukaiyama-Mannich reaction.

PubMed

Bai, Jian-Fei; Sasagawa, Hajime; Yurino, Taiga; Kano, Taichi; Maruoka, Keiji

2017-07-18

Readily available Boc-protected Z-alkenyl aminals could be used as Z-alkenyl and E-alkenyl imine precursors under acidic conditions. In the Mukaiyama-Mannich reaction of Z-alkenyl Boc-aminals, the E/Z geometry of the products was controlled by the catalyst used. The present method was also applied to asymmetric Mukaiyama-Mannich reactions.

Protease-catalysed Direct Asymmetric Mannich Reaction in Organic Solvent

NASA Astrophysics Data System (ADS)

Xue, Yang; Li, Ling-Po; He, Yan-Hong; Guan, Zhi

2012-10-01

We reported the first enzyme-catalysed, direct, three-component asymmetric Mannich reaction using protease type XIV from Streptomyces griseus (SGP) in acetonitrile. Yields of up to 92% with enantioselectivities of up to 88% e.e. and diastereoselectivities of up to 92:8 (syn:anti) were achieved under the optimised conditions. This enzyme's catalytic promiscuity expands the application of this biocatalyst and provides a potential alternative method for asymmetric Mannich reactions.

Synthesis and antimalarial activity study of some new Mannich bases of 7-chloro-4-aminoquinoline.

PubMed

Roy, Susanta; Chetia, Dipak; Rudrapal, Mithun; Prakash, Anil

2013-05-01

New derivatives of 7-chloro-4-aminoquinoline Mannich base were prepared by selectively modifying the aliphatic diethyl amino function of isoquine with different aliphatic/aromatic heterocyclic primary amino moieties at Mannich side chain. The synthesized compounds were characterized by their analytical and spectral data, and screened for in-vitro antimalarial activity against a chloroquine-sensitive 3D7 strain of Plasmodium falciparum. All the compounds showed in-vitro antimalarial activity at the tested dose; which, however, was considerably less than that of the standard reference drug, chloroquine. Among synthesized compounds, compounds with cyclohexyl (2f), methyl (2c) substitutions showed better activity than compounds substituted with n-octyl (2a), propyl (2b), 3-aminopropyl (2d) and furan-2- ylmethyl (2e) moieties at aminomethyl side chain. The results clearly demonstrate that the compound substituted with saturated cycloalkyl moiety (cyclohexyl) exhibited to some extent increased activity as compared to the compound containing heterocyclic moiety (furan-2-ylmethyl), and compounds with short chain alkyl substitutions (methyl, propyl) were found to be more active than that of compounds with long chain alkyl substitution (n-octyl).

Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors.

PubMed

Gupta, Sayan Dutta; Bommaka, Manish Kumar; Mazaira, Gisela I; Galigniana, Mario D; Subrahmanyam, Chavali Venkata Satya; Gowrishankar, Naryanasamy Lachmana; Raghavendra, Nulgumnalli Manjunathaiah

2015-09-01

The ubiquitously expressed heat shock protein 90 is an encouraging target for the development of novel anticancer agents. In a program directed towards uncovering novel chemical scaffolds against Hsp90, we performed molecular docking studies using Tripos-Sybyl drug designing software by including the required conserved water molecules. The results of the docking studies predicted Mannich bases derived from 2,4-dihydroxy acetophenone/5-chloro 2,4-dihydroxy acetophenone as potential Hsp90 inhibitors. Subsequently, a few of them were synthesized (1-6) and characterized by IR, (1)H NMR, (13)C NMR and mass spectral analysis. The synthesized Mannich compounds were evaluated for their potential to suppress Hsp90 ATPase activity by the colorimetric Malachite green assay. Subsequently, the molecules were screened for their antiproilferative effect against PC3 pancreatic carcinoma cells by adopting the 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The activity profile of the identified derivatives correlated well with their docking results. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibitory effects of benzimidazole containing new phenolic Mannich bases on human carbonic anhydrase isoforms hCA I and II.

PubMed

Gul, Halise Inci; Yazici, Zehra; Tanc, Muhammet; Supuran, Claudiu T

2016-12-01

New phenolic mono and bis Mannich bases incorporating benzimidazole, such as 2-(aminomethyl)-4-(1H-benzimidazol-2-yl)phenol and 2,6-bis(aminomethyl)-4-(1H-benzimidazol-2-yl)phenol were synthesized starting from 4-(1H-benzimidazol-2-yl)phenol. Amines used for the synthesis included dimethylamine, pyrrolidine, piperidine, N-methylpiperazine and morpholine. The CA inhibitory properties of these compounds were tested on the human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I and hCA II. These new compounds, as many phenols show moderate CA inhibitory properties.

Heterobimetallic transition metal/rare earth metal bifunctional catalysis: a Cu/Sm/Schiff base complex for syn-selective catalytic asymmetric nitro-Mannich reaction.

PubMed

Handa, Shinya; Gnanadesikan, Vijay; Matsunaga, Shigeki; Shibasaki, Masakatsu

2010-04-07

The full details of a catalytic asymmetric syn-selective nitro-Mannich reaction promoted by heterobimetallic Cu/Sm/dinucleating Schiff base complexes are described, demonstrating the effectiveness of the heterobimetallic transition metal/rare earth metal bifunctional catalysis. The first-generation system prepared from Cu(OAc)(2)/Sm(O-iPr)(3)/Schiff base 1a = 1:1:1 with an achiral phenol additive was partially successful for achieving the syn-selective catalytic asymmetric nitro-Mannich reaction. The substrate scope and limitations of the first-generation system remained problematic. After mechanistic studies on the catalyst prepared from Sm(O-iPr)(3), we reoptimized the catalyst preparation method, and a catalyst derived from Sm(5)O(O-iPr)(13) showed broader substrate generality as well as higher reactivity and stereoselectivity compared to Sm(O-iPr)(3). The optimal system with Sm(5)O(O-iPr)(13) was applicable to various aromatic, heteroaromatic, and isomerizable aliphatic N-Boc imines, giving products in 66-99% ee and syn/anti = >20:1-13:1. Catalytic asymmetric synthesis of nemonapride is also demonstrated using the catalyst derived from Sm(5)O(O-iPr)(13).

Detergent-dispersant additives based on high-molecular-weight alkylphenols

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

Kulieva, K.N.; Namazova, I.I.; Ismailova, N.D.

1988-09-01

This article describes the synthesis and investigation of Mannich bases produced for alkylphenols, obtained in turn from ethylene oligomers. These oligomers are the still bottoms from distillation products of high-temperature oligomerization of ethylene in the presence of triethylaluminum. Two narrow cuts obtained from the distillation of oligomer fraction were used to study the influence of ethylene oligomer molecular weight on the properties of the additives. The additives were blended in DS-11 oil to evaluate their detergency-dispersancy and other properties. Comparison blends were made with succinimide additives based on the same ethylene oligomers. The Mannich bases give improvements in the oxidationmore » resistance, anticorrosion properties, and detergency-dispersancy of the DS-11 diesel oil.« less

A chiral Brønsted acid-catalyzed highly enantioselective Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines.

PubMed

Unhale, Rajshekhar A; Sadhu, Milon M; Ray, Sumit K; Biswas, Rayhan G; Singh, Vinod K

2018-04-03

A chiral phosphoric acid-catalyzed asymmetric Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines, derived from 3-hydroxyisoindolinones has been demonstrated in this communication. A variety of isoindolinone-based α-amino diazo esters bearing a quaternary stereogenic center were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the products has been depicted by the hydrogenation of the diazo moiety of adducts.

Enantioselective and Regioselective Indium(III)-Catalyzed Addition of Pyrroles to Isatins

PubMed Central

Gutierrez, Elisa G.; Wong, Casey J.; Sahin, Aziza H.

2011-01-01

The indium(III)-catalyzed enantioselective and regioselective addition of pyrroles to isatins is described. The effects of metal and solvent on the reactivity and selectivity are compared and discussed, demonstrating that the indium(III)-indapybox complex provides the most effective catalyst. A case of divergent reactivity between pyrroles and indoles is presented. PMID:21992567

N-Heterocyclic carbene-catalyzed chemoselective cross-aza-benzoin reaction of enals with isatin-derived ketimines: access to chiral quaternary aminooxindoles.

PubMed

Xu, Jianfeng; Mou, Chengli; Zhu, Tingshun; Song, Bao-An; Chi, Yonggui Robin

2014-06-20

A chemo- and enantioselective cross-aza-benzoin reaction between enals and isatin-derived ketimines is disclosed. The high chemoselectivity (of the acyl anion reaction over enal α- and β-carbon reactions) is enabled by the electronic and steric properties of the N-heterocyclic carbene organocatalyst.

Improved anticancer and antiparasitic activity of new lawsone Mannich bases.

PubMed

Mahal, Katharina; Ahmad, Aamir; Schmitt, Florian; Lockhauserbäumer, Julia; Starz, Kathrin; Pradhan, Rohan; Padhye, Subhash; Sarkar, Fazlul H; Koko, Waleed S; Schobert, Rainer; Ersfeld, Klaus; Biersack, Bernhard

2017-01-27

Substituted lawsone Mannich bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. The new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human cancer cell lines associated with ROS formation. In addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic Trypanosoma brucei brucei cells via deformation of the microtubule cytoskeleton. The N-hexadecyl compound 2c was also highly active against locally isolated Entamoeba histolytica parasite samples exceeding the activity of metronidazole. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Isatin based Schiff bases as inhibitors of α-glucosidase: Synthesis, characterization, in vitro evaluation and molecular docking studies.

PubMed

Rahim, Fazal; Malik, Fazal; Ullah, Hayat; Wadood, Abdul; Khan, Fahad; Javid, Muhammad Tariq; Taha, Muhammad; Rehman, Wajid; Ur Rehman, Ashfaq; Khan, Khalid Mohammed

2015-06-01

Isatin base Schiff bases (1-20) were synthesized, characterized by (1)H NMR and EI/MS and evaluated for α-glucosidase inhibitory potential. Out of these twenty (20) compounds only six analogs showed potent α-glucosidase inhibitory potential with IC50 value ranging in between 2.2±0.25 and 83.5±1.0μM when compared with the standard acarbose (IC50=840±1.73μM). Among the series compound 2 having IC50 value (18.3±0.56μM), 9 (83.5±1.0μM), 11 (3.3±0.25μM), 12 (2.2±0.25μM), 14 (11.8±0.15μM), and 20 (3.0±0.15μM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking. Copyright © 2015 Elsevier Inc. All rights reserved.

Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups.

PubMed

Gao, Shuai; Zang, Jie; Gao, Qianwen; Liang, Xuewu; Ding, Qinge; Li, Xiaoyang; Xu, Wenfang; Chou, C James; Zhang, Yingjie

2017-06-15

As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC 50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605µM, respectively), compound 9n with IC 50 values of 0.032, 0.256 and 0.311µM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity. Copyright © 2017. Published by Elsevier Ltd.

Asymmetric vinylogous Mukaiyama aldol reaction of isatins under bifunctional organocatalysis: enantioselective synthesis of substituted 3-hydroxy-2-oxindoles.

PubMed

Laina-Martín, Víctor; Humbrías-Martín, Jorge; Fernández-Salas, José A; Alemán, José

2018-03-13

A highly enantioselective organocatalytic vinylogous Mukaiyama aldol reaction of silyloxy dienes and isatins under bifunctional organocatalysis is presented. Substituted 3-hydroxy-2-oxindoles are synthesised in good yields and enantioselectivities. These synthetic intermediates are used for the construction of more complex molecules with biological properties such as the formal synthesis of a CB2 agonist presented.

Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.

PubMed

Eldehna, Wagdy M; Almahli, Hadia; Al-Ansary, Ghada H; Ghabbour, Hazem A; Aly, Mohamed H; Ismael, Omnia E; Al-Dhfyan, Abdullah; Abdel-Aziz, Hatem A

2017-12-01

Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC 50  = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC 50  = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

Gold (I)-Catalyzed Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition and Mannich Reactions of Azlactones

PubMed Central

Melhado, Asa D.; Amarante, Giovanni W.; Wang, Z. Jane; Luparia, Marco; Toste, F. Dean

2011-01-01

Azlactones participate in stereoselective reactions with electron-deficient alkenes and N-sulfonyl aldimines to give products of 1,3-dipolar cycloaddition and Mannich addition reactions respectively. Both of these reactions proceed with good to excellent diastereo- and enantioselectivity using a single class of gold-catalysts, namely C2-symmetric bis(phosphinegold(I) carboxylate)complexes. The development of the azlactone Mannich reaction to provide fully protected anti-α,β-diamino acid derivatives is described. 1,3-Dipolar cycloaddition reactions of several acyclic 1,2-disubstituted alkenes, and the chemistry of the resultant cycloadducts, are examined to probe the stereochemical course of this reaction. Reaction kinetics and tandem MS studies of both the cycloaddition and Mannich reactions are reported. These studies support a mechanism in which the gold complexes catalyze addition reactions through nucleophile activation rather than the more typical activation of the electrophilic reaction component. PMID:21341677

Metabolomics-Driven Discovery of a Prenylated Isatin Antibiotic Produced by Streptomyces Species MBT28.

PubMed

Wu, Changsheng; Du, Chao; Gubbens, Jacob; Choi, Young Hae; van Wezel, Gilles P

2015-10-23

Actinomycetes are a major source of antimicrobials, anticancer compounds, and other medically important products, and their genomes harbor extensive biosynthetic potential. Major challenges in the screening of these microorganisms are to activate the expression of cryptic biosynthetic gene clusters and the development of technologies for efficient dereplication of known molecules. Here we report the identification of a previously unidentified isatin-type antibiotic produced by Streptomyces sp. MBT28, following a strategy based on NMR-based metabolomics combined with the introduction of streptomycin resistance in the producer strain. NMR-guided isolation by tracking the target proton signal resulted in the characterization of 7-prenylisatin (1) with antimicrobial activity against Bacillus subtilis. The metabolite-guided genome mining of Streptomyces sp. MBT28 combined with proteomics identified a gene cluster with an indole prenyltransferase that catalyzes the conversion of tryptophan into 7-prenylisatin. This study underlines the applicability of NMR-based metabolomics in facilitating the discovery of novel antibiotics.

Single-step synthesis of a new series of meso di-Mannich bases from the cyclic aminal (2S,7R,11S,16R)-1,8,10,17-tetraazapentacyclo[8.8.1.1.8,170.2,7011,16]icosane and p-substituted phenols

PubMed Central

2013-01-01

Background The results presented herein show that the cyclic aminal (2S,7R,11S,16R)-1,8,10,17-tetraazapentacyclo[8.8.1.1.8,170.2,7011,16]icosane (6), derived from cis-(meso)-1,2-diaminocyclohexane and formaldehyde, is a suitable substrate for the preption of a series of cis-meso Mannich bases such as 8a-l by reaction with p-substituted phenols 7a-l in basic media. These compounds are valuable synthetic products and may find application in asymmetric catalysis. Results The products were characterized principally by NMR and IR spectroscopy. Both the benzylic and aminalic protons of the perhydrobenzimidazolidine moiety were diastereotopic due to the presence of stereogenic nitrogen centers. The occurrence of intramolecular hydrogen bonding interactions was confirmed by the broad OH stretching vibration band in the IR spectra. Vibrational spectra were calculated using B3LYP at 6-31G(d,p) level, and the calculated frequencies for the νOH vibrations were compared to those of the experimental spectra. Hydrogen bonding interactions in the solid state were observed through the X-ray crystallography of 8j. Additionally, Mulliken charges and Fukui indices for 6 were calculated as theoretical descriptors of electrophilicity. Conclusion A new series of meso Mannich bases called 4,4′-disubstituted-2,2′-{[(3aR,7aS)-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene)} diphenols (8a-l) which are derived from cis-(meso)-1,2-diaminocyclohexane, were obtained from cyclic aminal 6. These results confirmed the behavior of 6 as an electrophilic preformed reagent in Mannich reactions in basic media. PMID:23758899

Kinetic and thermodynamic control in β-phenylethylamines reaction with isatin

NASA Astrophysics Data System (ADS)

Vélez, Yormari; Díaz-Oviedo, Christian; Quevedo, Rodolfo

2017-04-01

In this work it was established that dopamine's reaction with isatin produces the respective spiroisoquinoline through a Pictet-Spengler reaction whilst phenylethylamines, having less activated aromatic rings (tyramine and phenylethylamine), produce the respective imine as a mixture of stereoisomers E and Z. This article analyses the spectroscopic and structural patterns of the stereoisomers (E/Z) obtained and proposes the experimental conditions necessary for obtaining each of them as major products.

Synthesis of isatin thiosemicarbazones derivatives: in vitro anti-cancer, DNA binding and cleavage activities.

PubMed

Ali, Amna Qasem; Teoh, Siang Guan; Salhin, Abdussalam; Eltayeb, Naser Eltaher; Khadeer Ahamed, Mohamed B; Abdul Majid, A M S

2014-05-05

New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency. Copyright © 2014 Elsevier B.V. All rights reserved.

Bifunctional Iminophosphorane Organocatalysts for Enantioselective Synthesis: Application to the Ketimine Nitro-Mannich Reaction

PubMed Central

2013-01-01

The design, synthesis, and development of a new class of modular, strongly basic, and tunable bifunctional Brønsted base/H-bond-donor organocatalysts are reported. These catalysts incorporate a triaryliminophosphorane as the Brønsted basic moiety and are readily synthesized via a last step Staudinger reaction of a chiral organoazide and a triarylphosphine. Their application to the first general enantioselective organocatalytic nitro-Mannich reaction of nitromethane to unactivated ketone-derived imines allows the enantioselective construction of β-nitroamines possessing a fully substituted carbon atom. The reaction is amenable to multigram scale-up, and the products are useful for the synthesis of enantiopure 1,2-diamine and α-amino acid derivatives. PMID:24107070

When Ethyl Isocyanoacetate Meets Isatins: A 1,3-Dipolar/Inverse 1,3-Dipolar/Olefination Reaction for Access to 3-Ylideneoxindoles.

PubMed

Yuan, Wen-Kui; Cui, Tao; Liu, Wei; Wen, Li-Rong; Li, Ming

2018-03-16

A new CuI/1,10-phen-catalyzed reaction for the synthesis of 3-ylideneoxindoles from readily available isatins and ethyl isocyanoacetate, in which ethyl isocyanoacetate acts as a latent two-carbon donor like the Wittig reagent, is reported. A tandem procedure including 1,3-dipolar cycloaddition/inverse 1,3-dipolar ring opening/olefination allows the preparation of 3-ylideneoxindoles with broad functional group tolerance.

Stereodivergent Mannich reaction of bis(trimethylsilyl)ketene acetals with N-tert-butanesulfinyl imines by Lewis acid or Lewis base activation, a one-pot protocol to obtain chiral β-amino acids.

PubMed

Cantú-Reyes, Margarita; Alvarado-Beltrán, Isabel; Ballinas-Indilí, Ricardo; Álvarez-Toledano, Cecilio; Hernández-Rodríguez, Marcos

2017-09-20

We report a one-pot synthesis of chiral β 2,2,3 -amino acids by the Mannich addition of bistrimethylsilyl ketene acetals to N-tert-butanesulfinyl imines followed by the removal of the chiral auxiliary. The synthesis and isolation of pure β-amino acid hydrochlorides were conducted under mild conditions, without strong bases and this method is operationally simple. The stereoselective reaction was promoted by two different activation methods that lead to different stereoisomers: (1) Lewis Acid (LA) catalysis with boron trifluoride diethyl etherate and (2) Lewis Base (LB) catalysis with tetrabutylammonium difluorotriphenylsilicate. The reaction presented good diastereoselectivity with LB activation and moderate to good dr with LA catalysis. The exceptions in both protocols were imines with electron donating groups in the aromatic ring.

Multitarget drug design strategy against Alzheimer's disease: Homoisoflavonoid Mannich base derivatives serve as acetylcholinesterase and monoamine oxidase B dual inhibitors with multifunctional properties.

PubMed

Li, Yan; Qiang, Xiaoming; Luo, Li; Yang, Xia; Xiao, Ganyuan; Zheng, Yunxiaozhu; Cao, Zhongcheng; Sang, Zhipei; Su, Fu; Deng, Yong

2017-01-15

A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC 50 =2.49±0.08nM and 1.74±0.0581μM, respectively), good self- and Cu 2+ -induced Aβ 1-42 aggregation inhibitory potency, antioxidant activity, biometal chelating ability and high BBB permeability. These multifunctional properties make 10d as an excellent candidate for the development of efficient drugs against AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conventional and microwave assisted synthesis of pyrazolone Mannich bases possessing anti-inflammatory, analgesic, ulcerogenic effect and antimicrobial properties.

PubMed

Sivakumar, Kullampalayam Krishnasamy; Rajasekaran, Aiyalu; Senthilkumar, Palaniappan; Wattamwar, Prasad P

2014-07-01

In the present study, an efficient synthesis of some Mannich base of 5-methyl-2-[(2-oxo-2H-chromen-3-yl)carbonyl]-2,4-dihydro-3H-pyrazol-3-one (4a-j) have been described by using conventional and non-conventional (microwave) techniques. Microwave assisted reactions showed that require shorter reaction time and good yield. The newly synthesized compounds were screened for their anti-inflammatory, analgesic activity, antioxidant, and antibacterial effects were compared with standard drug. Among the compounds studied, compound (4f) showing nearly equipotent anti-inflammatory and analgesic activity than the standard drug (indomethacin), along with minimum ulcerogenic index. Compounds (4b and 4i) showing 1.06 times more active than ciprofloxacin against tested Gram-negative bacteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigation of biological effects of some Mannich Bases containing Bis-1,2,4- Triazole.

PubMed

Parlak, A E; Celik, S; Karatepe, M; Turkoglu, S; Alayunt, N O; Dastan, S D; Ulas, M; Sandal, S; Tekin, S; Koparir, M

2016-06-30

In this study, the effects of Mannich bases containing bis-1,2,4-triazole on the levels of in vivo malondialdehyde (MDA) and antioxidant vitamins (A, E, C) were examined in serum, livers and kidneys of rats. DA and vitamin (A, E, C) levels were determined by high performance liquid chromatography (HPLC). Antioxidant effect was investigated by determining the MDA levels in Saccharomyces cerevisiae cells as in vitro. Furthermore, the antitumor effects of compounds were investigated against MCF-7 human breast cancer cells. Interrelations of results among control and compound groups were evaluated using SPSS statistical software package. As a result, some of the compounds showed effective biological activity when compared to control conditions. The test compounds used in this study may be effective for utilization in the selection and design of model compounds for further studies.

Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase (DAAO) inhibitors.

PubMed

Szilágyi, Bence; Kovács, Péter; Ferenczy, György G; Rácz, Anita; Németh, Krisztina; Visy, Júlia; Szabó, Pál; Ilas, Janez; Balogh, György T; Monostory, Katalin; Vincze, István; Tábi, Tamás; Szökő, Éva; Keserű, György M

2018-05-01

d-Amino acid oxidase (DAAO) is a potential target in the treatment of schizophrenia as its inhibition increases brain d-serine level and thus contributes to NMDA receptor activation. Inhibitors of DAAO were sought testing [6+5] type heterocycles and identified isatin derivatives as micromolar DAAO inhibitors. A pharmacophore and structure-activity relationship analysis of isatins and reported DAAO inhibitors led us to investigate 1H-indazol-3-ol derivatives and nanomolar inhibitors were identified. The series was further characterized by pK a and isothermal titration calorimetry measurements. Representative compounds exhibited beneficial properties in in vitro metabolic stability and PAMPA assays. 6-fluoro-1H-indazol-3-ol (37) significantly increased plasma d-serine level in an in vivo study on mice. These results show that the 1H-indazol-3-ol series represents a novel class of DAAO inhibitors with the potential to develop drug candidates. Copyright © 2018 Elsevier Ltd. All rights reserved.

ALDOL- AND MANNICH-TYPE REACTIONS VIA IN SITU OLEFIN MIGRATION IN IONIC LIQUID

EPA Science Inventory

An aldol-type and a Mannich-type reaction via the cross-coupling of aldehydes and imines with allylic alcohols catalyzed by RuCl2(PPh3)3 was developed with ionic liquid as the solvent. The solvent/catalyst system could be reused for at least five times with no loss of reactiv...

Kinetic studies of the impact of thiocyanate moiety on the catalytic properties of Cu(II) and Fe(III) complexes of a new Mannich base

NASA Astrophysics Data System (ADS)

Ayeni, Ayowole O.; Watkins, Gareth M.

2018-04-01

Four new metal complexes of a novel Mannich base 5-methyl-2-((4-(pyridin-2-yl)piperazin-1-yl)methyl)phenol (HL) have been prepared. The compounds were characterized by an array of analytical and spectroscopic methods including Nuclear Magnetic Resonance, Infra-red and UV-Visible spectroscopy. Compounds 1-4 behaved as effective catalysts towards the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to its corresponding quinone in the presence of molecular oxygen in DMF solution while compound 4 proved to be the best catalyst with a turnover rate of 17.93 ± 1.10 h-1 as other complexes showed lower rates of oxidation. Also with the exception of dinuclear iron complex (4); thiocyanate containing Cu(II) complex exhibited lower catecholase activity compared to the Cu(II) complex without it.

RUTHENIUM-CATALYZED TANDEM OLEFIN MIGRATION-ALDOL AND MANNICH-TYPE REACTIONS IN IONIC LIQUID.

EPA Science Inventory

In the presence of a catalytic amount of RuCl2(PPh3)3, a cross-coupling of 3-buten-2-ol with aldehydes and imines was developed via a tandem olefin migration--aldol--Mannich reaction in bmim[PF6]. With In(OAc)3 as a co-catalyst, a-vinylbenzyl alcohol and aldehydes underwent sim...

Design, synthesis and preliminary structure-activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives.

PubMed

Liu, Haoran; Fan, Haoqun; Gao, Xiaohui; Huang, Xueqing; Liu, Xianjun; Liu, Linbo; Zhou, Chao; Tang, Jingjing; Wang, Qiuan; Liu, Wukun

2016-08-01

In order to study the structure-activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a-8d) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro. The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound 6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 μmol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound 6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE.

Up-scaling of tannin-based coagulants for wastewater treatment: performance in a water treatment plant.

PubMed

Grenda, Kinga; Arnold, Julien; Gamelas, José A F; Rasteiro, Maria G

2018-06-21

Tannin extracts from the bark of Acacia mearnsii and wood of Schinopsis balansae, commonly known as Quebracho, were employed. These were modified at laboratory sale via the Mannich aminomethylation with formaldehyde and dimethylamine hydrochloride. Some reaction conditions were varied, namely the formaldehyde dosage and reaction time, while keeping the Mannich solution activation time constant, and their influence on the shear viscosity of the created bio-coagulants was evaluated. The effect of the final pH of the products on their shear viscosity was also analyzed. Up-scaling of the Mannich reaction for tannin from South Africa was performed and the procedure developed at 1-L scale was reproducible in upscaled conditions. One example of a modified South Africa tannin and the modified Quebracho tannin was subsequently selected for the treatment of an industrial wastewater and tested for color and turbidity reduction in jar tests. The effluent treatment was carried out in a single and dual system with cationic synthetic flocculation agents of different charge degree. Good turbidity and decoloration results (93 and 89% reduction, respectively) were obtained with the simultaneous introduction of a cationic, 40% charged polyacrylamide, with minimal dosage (5 ppm) of the latter additive. The tannin-based coagulant from Acacia mearnsii was successfully applied in dual system with cationic polyacrylamide flocculant for industrial wastewater treatment at pilot plant scale. It was shown to satisfactorily treat the water and generate less sludge.

Synthesis, activity and pharmacophore development for isatin-β-thiosemicarbazones with selective activity towards multidrug resistant cellsa

PubMed Central

Hall, Matthew D.; Salam, Noeris K.; Hellawell, Jennifer L.; Fales, Henry M.; Kensler, Caroline B.; Ludwig, Joseph A.; Szakacs, Gergely; Hibbs, David E.; Gottesman, Michael M.

2009-01-01

We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-β-thiosemicarbazones from our initial study have been validated, and a range of analogs synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1-selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone, and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicty of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity, and aid in directing the search for the mechanism of action of 1. PMID:19397322

Highly Enantioselective Three-Component Direct Mannich Reactions of Unfunctionalized Ketones Catalyzed by Bifunctional Organocatalysts

PubMed Central

Guo, Qunsheng; Zhao, John Cong-Gui

2013-01-01

A highly stereoselective three-component direct Mannich reaction between aromatic aldehydes, p-toluenesulfonamide, and unfunctionalized ketones was achieved through an enolate mechanism for the first time with a bifunctional quinidine thiourea catalyst. The corresponding N-tosylated β-aminoketones were obtained in high yields and excellent diastereo- and enantioselectivities (up to >99:1 dr and >99% ee). PMID:23343472

Optical monitoring of thin film electro-polymerization on surface of ITO-coated lossy-mode resonance sensor

NASA Astrophysics Data System (ADS)

Sobaszek, Michał; Dominik, Magdalena; Burnat, Dariusz; Bogdanowicz, Robert; Stranak, Viteszlav; Sezemsky, Petr; Śmietana, Mateusz

2017-04-01

This work presents an optical fiber sensors based on lossy-mode resonance (LMR) phenomenon supported by indium tin oxide (ITO) thin overlay for investigation of electro-polymerization effect on ITO's surface. The ITO overlays were deposited on core of polymer-clad silica (PCS) fibers using reactive magnetron sputtering (RMS) method. Since ITO is electrically conductive and electrochemically active it can be used as a working electrode in 3-electrode cyclic voltammetry setup. For fixed potential applied to the electrode current flow decrease with time what corresponds to polymer layer formation on the ITO surface. Since LMR phenomenon depends on optical properties in proximity of the ITO surface, polymer layer formation can be monitored optically in real time. The electrodeposition process has been performed with Isatin which is a strong endogenous neurochemical regulator in humans as it is a metabolic derivative of adrenaline. It was found that optical detection of Isatin is possible in the proposed configuration.

Sorption of certain isatins on various sorbents under RP-HPLC conditions

NASA Astrophysics Data System (ADS)

Konstantinov, A. V.; Shafigulin, R. V.; Il'in, M. M.; Davankov, V. A.; Bulanova, A. V.; Purygin, P. P.

2013-06-01

The results from chromatographic analysis of biologically active isatin derivatives on hyper-crosslinked polystyrene (HCLPS) and silica gel modified by octadecyl groups (SilC18) are presented. The constants of distribution of sorbates between a mobile phase and the investigated sorbents ( K x ) and the changes in the standard differential molar Gibbs energies of adsorption (Δ _a bar G^circ ) are calculated, along with the chromatographic retention-physicochemical property of sorbate dependences. It is found that the equations describing these dependences have high forecasting ability with respect to the values of retention factors of the investigated sorbates.

Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine Mannich bases.

PubMed

Jose, Gilish; Suresha Kumara, Tholappanavara H; Sowmya, Haliwana B V; Sriram, Dharmarajan; Guru Row, Tayur N; Hosamani, Amar A; More, Sunil S; Janardhan, Bhavya; Harish, B G; Telkar, Sandeep; Ravikumar, Yalegara Siddappa

2017-05-05

In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by 1 H NMR, 13 C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C 23 H 29 ClN 4 ] +2 , H 2 O). The in vitro antimicrobial activities of the compounds were evaluated against various bacterial and fungal strains using Agar diffusion method and Broth micro dilution method. Compounds 7e, 7f, 7r, 7t, and 7u were showed good Gram-positive antibacterial activity against S. aureus, B. flexus, C. sporogenes and S. mutans. Furthermore, in vitro antimycobacterial activity was evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) using MABA. Compounds 7r, 7t, and 7u were showed good antitubercular activity against Mtb (MIC ≥6.25 μg/mL). Among the tested compounds, 1-((4-chloro-2-(cyclohexylmethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)methyl)piperidine-3-carboxamide (7t) was showed excellent antimycobacterial activity against Mtb (MIC <0.78 μg/mL) and low cytotoxicity against the HEK-293T cell line (SI >25). Molecular docking of the active compounds against glutamate racemase (MurI) and Mtb glutamine synthetase were explained the structure-activity observed in vitro. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Identification of the anti‐mycobacterial functional properties of piperidinol derivatives

PubMed Central

Guy, Collette S; Tichauer, Esther; Kay, Gemma L; Phillips, Daniel J; Bailey, Trisha L; Harrison, James; Furze, Christopher M; Millard, Andrew D; Gibson, Matthew I; Pallen, Mark J

2017-01-01

Background and Purpose Tuberculosis (TB) remains a major global health threat and is now the leading cause of death from a single infectious agent worldwide. The current TB drug regimen is inadequate, and new anti‐tubercular agents are urgently required to be able to successfully combat the increasing prevalence of drug‐resistant TB. The purpose of this study was to investigate a piperidinol compound derivative that is highly active against the Mycobacterium tuberculosis bacillus. Experimental Approach The antibacterial properties of the piperidinol compound and its corresponding bis‐Mannich base analogue were evaluated against M. smegmatis and Gram‐negative organisms. Cytotoxicity studies were undertaken in order to determine the selectivity index for these compounds. Spontaneous resistant mutants of M. smegmatis were generated against the piperidinol and corresponding bis‐Mannich base lead derivatives and whole genome sequencing employed to determine the genetic modifications that lead to selection pressure in the presence of these compounds. Key Results The piperidinol and the bis‐Mannich base analogue were found to be selective for mycobacteria and rapidly kill this organism with a cytotoxicity selectivity index for mycobacteria of >30‐fold. Whole genome sequencing of M. smegmatis strains resistant to the lead compounds led to the identification of a number of single nucleotide polymorphisms indicating multiple targets. Conclusion and Implications Our results indicate that the piperidinol moiety represents an attractive compound class in the pursuit of novel anti‐tubercular agents. Linked Articles This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro‐organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc PMID:28195652

The Two Faces of Sulfinates: Illustrating Umpolung Reactivity

ERIC Educational Resources Information Center

Tapia-Pineda, Adabelia; Perez-Arrieta, Carlos; Silva-Cuevas, Carolina; Paleo, Ehecatl; Lujan-Montelongo, J. Armando

2016-01-01

A simple, microscale experiment was developed with the aim of demonstrating the concept of umpolung in synthetic organic chemistry. Starting from a common alkyl sulfinate, students perform a polarity inversion by performing a Grignard-based sulfoxide synthesis and a Mannich-type formamide synthesis. The products are purified without chromatography…

Post-Synthetic Mannich Chemistry on Metal-Organic Frameworks: System-Specific Reactivity and Functionality-Triggered Dissolution.

PubMed

Amer Hamzah, Harina; Gee, William J; Raithby, Paul R; Teat, Simon J; Mahon, Mary F; Burrows, Andrew D

2018-05-29

The Mannich reaction of the zirconium MOF [Zr 6 O 4 (OH) 4 (bdc-NH 2 ) 6 ] (UiO-66-NH 2 , bdc-NH 2 =2-amino-1,4-benzenedicarboxylate) with paraformaldehyde and pyrazole, imidazole or 2-mercaptoimidazole led to post-synthetic modification (PSM) through C-N bond formation. The reaction with imidazole (Him) goes to completion whereas those with pyrazole (Hpyz) and 2-mercaptoimidazole (HimSH) give up to 41 and 36 % conversion, respectively. The BET surface areas for the Mannich products are reduced from that of UiO-66-NH 2 , but the compounds show enhanced selectivity for adsorption of CO 2 over N 2 at 273 K. The thiol-containing MOFs adsorb mercury(II) ions from aqueous solution, removing up to 99 %. The Mannich reaction with pyrazole succeeds on [Zn 4 O(bdc-NH 2 ) 3 ] (IRMOF-3), but a similar reaction on [Zn 2 (bdc-NH 2 ) 2 (dabco)] (dabco=1,4-diazabicyclo[2.2.2]octane) gave [Zn 3 (bdc-NH 2 ) 1.32 (bdc-NHCH 2 pyz) 1.68 (dabco)]⋅2 C 7 H 8 5, whereas the reaction with imidazole gave the expected PSM product. Compound 5 forms via a dissolution-recrystallisation process that is triggered by the "free" pyrazolate nitrogen atom competing with dabco for coordination to the zinc(II) centre. In contrast, the "free" nitrogen atom on the imidazolate is too far away to compete in this way. Mannich reactions on [In(OH)(bdc-NH 2 )] (MIL-68(In)-NH 2 ) stop after the first step, and the product was identified as [In(OH)(bdc-NH 2 ) 0.41 (bdc-NHCH 2 OCH 3 ) 0.30 (bdc-N=CH 2 ) 0.29 ], with addition of the heterocycle prevented by steric interactions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexes.

PubMed

Neves, Amanda P; Pereira, Michelle X G; Peterson, Erica J; Kipping, Ralph; Vargas, Maria D; Silva, Floriano P; Carneiro, J Walkimar M; Farrell, Nicholas P

2013-02-01

Several chlorido and amino Pt(2+) complexes of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases HL exhibiting moderate to high cytotoxicity against cancer cell lines were studied in order to investigate their modes of DNA binding, in vitro DNA strand breaks, mechanism of topoisomerase (Topo I) inhibition and cellular accumulation. DNA model base studies have shown that complex 1a [Pt(HL1)Cl(2)] was capable of binding covalently to 9-ethylguanine (9-EtG) and 5'-GMP. (1)H NMR and mass spectrometry studies have shown that both chlorides were substituted by 9-EtG ligands, whereas 5'-GMP was able to replace only one chlorido ligand, due to steric hindrance. The chlorido Pt(2+) complexes [Pt(HL)Cl(2)] highly accumulate in prostate (PC-3) and melanoma (MDA-MB-435) cell lines, being able to induce DNA strand breaks in vitro and inhibit Topo I by a catalytic mode. On the other hand, the free 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones HL and the amino Pt(2+) complexes [Pt(L(-))(NH(3))(2)]NO(3) neither cause DNA strand breakage nor exhibit strong DNA interaction, nevertheless the latter were also found to be catalytic inhibitors of Topo I at 100μM. Thus, coordination of the Mannich bases HL to the "PtCl(2)" fragment substantially affects the chemical and biophysical properties of the pro-ligands, leading to an improvement of their DNA binding properties and generating compounds that cleave DNA and catalytically inhibit Topo I. Finally, the high cytotoxicity exhibited by the free (uncomplexed) 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones might be associated with their decomposition in solution, which is not observed for the Pt(2+) complexes. Copyright © 2012 Elsevier Inc. All rights reserved.

2-methyl-3-butyn-2-ol as an acetylene precursor in the Mannich reaction. A new synthesis of suicide inactivators of monoamine oxidase

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

Fowler, J.S.

A two-step reaction process is reported for the synthesis of /sup 11/C, /sup 13/C, or /sup 14/C-labelled propargylamines in moderate yields. The propargylamines were prepared by a modified Mannich scheme without the use of acetylene. The reaction scheme involved the use of 2-methyl-3-butyn-2-ol followed by KOH-catalyzed elimination of acetone from the acetylenic carbinols. (BLM)

Intramolecular Redox-Mannich Reactions: Facile Access to the Tetrahydroprotoberberine Core.

PubMed

Ma, Longle; Seidel, Daniel

2015-09-07

Cyclic amines such as pyrrolidine undergo redox-annulations with 2-formylaryl malonates. Concurrent oxidative amine α-CH bond functionalization and reductive N-alkylation render this transformation redox-neutral. This redox-Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)-thalictricavine and its epimer. An unusually mild amine-promoted dealkoxycarbonylation was discovered in the course of these studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design, synthesis and anticonvulsant properties of new N-Mannich bases derived from 3-phenylpyrrolidine-2,5-diones.

PubMed

Kamiński, Krzysztof; Obniska, Jolanta; Chlebek, Iwona; Wiklik, Beata; Rzepka, Sabina

2013-11-01

The synthesis and anticonvulsant properties of new N-Mannich bases of 3-phenyl- (9a-d), 3-(2-chlorophenyl)- (10a-d), 3-(3-chlorophenyl)- (11a-d) and 3-(4-chlorophenyl)-pyrrolidine-2,5-diones (12a-d) were described. The key synthetic strategies involve the formation of 3-substituted pyrrolidine-2,5-diones (5-8), and then aminoalkylation reaction (Mannich-type) with formaldehyde and corresponding secondary amines, which let to obtain the final compounds 9a-d, 10a-d, 11a-d and 12a-d in good yields. Initial anticonvulsant screening was performed in mice (ip) using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The most effective compounds in mice were tested after oral administration in rats. The acute neurological toxicity was determined applying the minimal motor impairment rotarod test. The in vivo results revealed that numerous compounds were effective especially in the MES test (model of human tonic-clonic seizures). The most active in the MES seizures in rats was 1-[(4-benzyl-1-piperidyl)methyl]-3-(2-chlorophenyl)pyrrolidine-2,5-dione (10c) which showed ED50 value of 37.64mg/kg. It should be stressed that this molecule along with 9a, 9d and 10d showed protection in the psychomotor seizure test (6-Hz), which is known as an animal model of therapy-resistant epilepsy. Furthermore compounds 9a, 9d and 10d were also tested in the pilocarpine-induced status prevention (PISP) test to assess their potential effectiveness in status epilepticus. For the most promising molecule 9d an influence on human CYP3A4 isoform of P-450 cytochrome was studied in vitro. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases.

PubMed

Yamali, Cem; Gul, Halise Inci; Sakagami, Hiroshi; Supuran, Claudiu T

2016-01-01

Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25-43%) and hCA II (6-25%) isoforms at 10 μM concentration of inhibitor, the compounds were more selective (1.5-5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.

5-(2-Carboxyethenyl) isatin derivative induces G{sub 2}/M cell cycle arrest and apoptosis in human leukemia K562 cells

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

Zhou, Yao; Zhao, Hong-Ye; Han, Kai-Lin

2014-08-08

Highlights: • 5-(2-Carboxyethenyl) isatin derivative (HKL 2H) inhibited K562’s proliferation. • HKL 2H caused the morphology change of G{sub 2}/M phase arrest and typical apoptosis. • HKL 2H induced G2/M cell cycle phase arrest in K562 cells. • HKL 2H induced apoptosis in K562 cells through the mitochondrial pathway. - Abstract: Our previous study successfully identified that the novel isatin derivative (E)-methyl 3-(1-(4-methoxybenzyl)-2,3-dioxoindolin-5-yl) acrylate (HKL 2H) acts as an anticancer agent at an inhibitory concentration (IC{sub 50}) level of 3 nM. In this study, the molecular mechanism how HKL 2H induces cytotoxic activity in the human chronic myelogenous leukemia K562more » cells was investigated. Flow cytometric analysis showed that the cells were arrested in the G{sub 2}/M phase and accumulated subsequently in the sub-G{sub 1} phase in the presence of HKL 2H. HKL 2H treatment down-regulated the expressions of CDK1 and cyclin B but up-regulated the level of phosphorylated CDK1. Annexin-V staining and the classic DNA ladder studies showed that HKL 2H induced the apoptosis of K562 cells. Our study further showed that HKL 2H treatment caused the dissipation of mitochondrial membrane potential, activated caspase-3 and lowered the Bcl-2/Bax ratio in K562 cells, suggesting that the HKL 2H-causing programmed cell death of K562 cells was caused via the mitochondrial apoptotic pathway. Taken together, our data demonstrated that HKL 2H, a 5-(2-carboxyethenyl) isatin derivative, notably induces G{sub 2}/M cell cycle arrest and mitochondrial-mediated apoptosis in K562 cells, indicating that this compound could be a promising anticancer candidate for further investigation.« less

Highly efficient and generalized asymmetric synthesis of quaternary stereogenic carbon-containing β-amino indanones/indanoles via Mannich-type additions between 1-indanones and N-tert-butanesulfinylketimines.

PubMed

Wu, Lingmin; Xie, Chen; Mei, Haibo; Soloshonok, Vadim A; Han, Jianlin; Pan, Yi

2014-07-14

Here we report that, unlike other ketones, 1-indanone and acetophenone derived enolates undergo Mannich-type addition reactions with N-tert-butanesulfinyl ketimines with excellent yields (up to 98%) and diastereoselectivity (>99/1). The resulting compounds represent a new type of biologically relevant β-aminoketone derivative bearing quaternary stereogenic carbon, which could be further converted into the corresponding β-amino ketones and β-amino alcohols, possessing three consecutive stereogenic centres.

Chemotherapy of Rodent Malaria. Part 1

DTIC Science & Technology

1987-10-01

to produce exaggerated resistance factors (I 90 values). For example, the ED of chloroquine against the artemisinin 90 resistant ART strain...primaquine, quinine, cinchonine, quinidine, mefloquine, halofantrine, artemisinin , pyronaridine, mepacrine and Mannich bases (such as WR 228258). It is...RC. It is markedly resistant to primaquine and possesses slight cross-resistance to quinidine, mefloquine, artemisinin . There is also a marked cross

Isatinphenylsemicarbazones as efficient colorimetric sensors for fluoride and acetate anions - anions induce tautomerism.

PubMed

Jakusová, Klaudia; Donovalová, Jana; Cigáň, Marek; Gáplovský, Martin; Garaj, Vladimír; Gáplovský, Anton

2014-04-05

The anion induced tautomerism of isatin-3-4-phenyl(semicarbazone) derivatives is studied herein. The interaction of F(-), AcO(-), H2PO4(-), Br(-) or HSO4(-) anions with E and Z isomers of isatin-3-4-phenyl(semicarbazone) and N-methylisatin-3-4-phenyl(semicarbazone) as sensors influences the tautomeric equilibrium of these sensors in the liquid phase. This tautomeric equilibrium is affected by (1) the inter- and intra-molecular interactions' modulation of isatinphenylsemicarbazone molecules due to the anion induced change in the solvation shell of receptor molecules and (2) the sensor-anion interaction with the urea hydrogens. The acid-base properties of anions and the difference in sensor structure influence the equilibrium ratio of the individual tautomeric forms. Here, the tautomeric equilibrium changes were indicated by "naked-eye" experiment, UV-VIS spectral and (1)H NMR titration, resulting in confirmation that appropriate selection of experimental conditions leads to a high degree of sensor selectivity for some investigated anions. Sensors' E and Z isomers differ in sensitivity, selectivity and sensing mechanism. Detection of F(-) or CH3COO(-) anions at high weakly basic anions' excess is possible. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti-Inflammatory Activity and Structure-Activity Relationships of Brominated Indoles from a Marine Mollusc

PubMed Central

Ahmad, Tarek B.; Rudd, David; Smith, Joshua; Kotiw, Michael; Mouatt, Peter; Seymour, Lisa M.; Liu, Lei; Benkendorff, Kirsten

2017-01-01

Marine molluscs are rich in biologically active natural products that provide new potential sources of anti-inflammatory agents. Here we used bioassay guided fractionation of extracts from the muricid Dicathais orbita to identify brominated indoles with anti-inflammatory activity, based on the inhibition of nitric oxide (NO) and tumour necrosis factor α (TNFα) in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and prostaglandin E2 (PGE2) in calcium ionophore-stimulated 3T3 ccl-92 fibroblasts. Muricid brominated indoles were then compared to a range of synthetic indoles to determine structure-activity relationships. Both hypobranchial gland and egg extracts inhibited the production of NO significantly with IC50 of 30.8 and 40 μg/mL, respectively. The hypobranchial gland extract also inhibited the production of TNFα and PGE2 with IC50 of 43.03 µg/mL and 34.24 µg/mL, respectively. The purified mono-brominated indole and isatin compounds showed significant inhibitory activity against NO, TNFα, and PGE2, and were more active than dimer indoles and non-brominated isatin. The position of the bromine atom on the isatin benzene ring significantly affected the activity, with 5Br > 6Br > 7Br. The mode of action for the active hypobranchial gland extract, 6-bromoindole, and 6-bromoisatin was further tested by the assessment of the translocation of nuclear factor kappa B (NFκB) in LPS-stimulated RAW264.7 mouse macrophage. The extract (40 µg/mL) significantly inhibited the translocation of NFκB in the LPS-stimulated RAW264.7 macrophages by 48.2%, whereas 40 µg/mL of 6-bromoindole and 6-bromoistain caused a 60.7% and 63.7% reduction in NFκB, respectively. These results identify simple brominated indoles as useful anti-inflammatory drug leads and support the development of extracts from the Australian muricid D. orbita, as a new potential natural remedy for the treatment of inflammation. PMID:28481239

Regio- and stereoselective synthesis of benzothiazolo-pyrimidinones via an NHC-catalyzed Mannich/lactamization domino reaction† †Electronic supplementary information (ESI) available. CCDC 1029497. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4cc08594a

PubMed Central

Ni, Qijian; Song, Xiaoxiao; Xiong, Jiawen; Raabe, Gerhard

2015-01-01

An NHC-catalyzed regio- and stereoselective Mannich/lactamization domino reaction of N-(benzothiazolyl)imines with α-chloroaldehydes has been developed. This new protocol provides a facile approach for the asymmetric synthesis of benzothiazolo-pyrimidinones and a pyrrolo[1,2-a]indolone in moderate to good yields (34–78%) and excellent stereoselectivities (87–99% ee, up to >20 : 1 d.r.). PMID:25476422

Enantioselective Organocatalytic Aminomethylation of Aldehydes: A Role for Ionic Interactions and Efficient Access to β2-Amino Acids

PubMed Central

Chi, Yonggui; Gellman, Samuel H.

2009-01-01

Organocatalytic Mannich addition of aldehydes to a formaldehyde-derived iminium species catalyzed by proline-derived chiral pyrrolidines provides β-amino aldehydes with ≥ 90% ee. Mechanistic analysis of the proline-catalyzed reactions suggests that non-hydrogen-bonded ionic interactions at the Mannich reaction transition state can influence stereochemical outcome. The β-amino aldehydes from our process bear a substituent adjacent to the carbonyl and can be efficiently converted to protected β2-amino acids, which are important building blocks for β-peptide foldamers that display useful biological activities. PMID:16719457

Achiral Mannich-Base Curcumin Analogs Induce Unfolded Protein Response and Mitochondrial Membrane Depolarization in PANC-1 Cells.

PubMed

Szebeni, Gábor J; Balázs, Árpád; Madarász, Ildikó; Pócz, Gábor; Ayaydin, Ferhan; Kanizsai, Iván; Fajka-Boja, Roberta; Alföldi, Róbert; Hackler, László; Puskás, László G

2017-10-07

Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549), hepatocellular carcinoma (HepG2) and pancreatic cancer cell line (PANC-1). Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells. Cytotoxic activity was accompanied by cytostatic effect since curcumin and analogs treatment led to G₀/G₁ cell cycle arrest. Moreover, cytotoxic effect could be also detected via the accumulation of curcuminoids in the endoplasmic reticulum (ER) and the up-regulation of ER stress-related unfolded protein response (UPR) genes: HSPA5 , ATF4, XBP1 , and DDIT3 . The activated UPR induced mitochondrial membrane depolarization, caspase-3 activation and subsequent DNA breakdown in PANC-1 cells. Achiral curcumin analogs, C509, C521 and C524 possessed superior, 40-times more potent cytotoxic activity compared to natural dihydroxy-dimetoxycurcumin in PANC-1 cells.

Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies.

PubMed

Milošev, Milorad Z; Jakovljević, Katarina; Joksović, Milan D; Stanojković, Tatjana; Matić, Ivana Z; Perović, Milka; Tešić, Vesna; Kanazir, Selma; Mladenović, Milan; Rodić, Marko V; Leovac, Vukadin M; Trifunović, Snežana; Marković, Violeta

2017-06-01

A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b, 5e, and 5j on the cell cycle were investigated by flow cytometric analysis. It was found that these compounds cause the accumulation of cells in the subG1 and G1 phases of the cell cycle and induce caspase-dependent apoptosis, while the anti-angiogenic effects of 5b, 5e, and 5j have been confirmed in EA.hy926 cells using a tube formation assay. Further, the interaction of Bax protein with compound 5b was investigated by means of molecular modeling, applying the combined molecular docking/molecular dynamics approach. © 2016 John Wiley & Sons A/S.

Synthesis, spectroscopic investigations, DFT studies, molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids: Experimental and theoretical approaches

NASA Astrophysics Data System (ADS)

Almutairi, Maha S.; Zakaria, Azza S.; Ignasius, P. Primsa; Al-Wabli, Reem I.; Joe, Isaac Hubert; Attia, Mohamed I.

2018-02-01

Indole-isatin molecular hybrids 5a-i have been synthesized and characterized by different spectroscopic methods to be evaluated as new antimicrobial agents against a panel of Gram positive bacteria, Gram negative bacteria, and moulds. Compound 5h was selected as a representative example of the prepared compounds 5a-i to perform computational investigations. Its vibrational properties have been studied using FT-IR and FT-Raman with the aid of density functional theory approach. The natural bond orbital analysis as well as HOMO and LUMO molecular orbitals investigations of compound 5h were carried out to explore its possible intermolecular delocalization or hyperconjugation and its possible interactions with the target protein. Molecular docking of compound 5h predicted its binding mode with the fungal target protein.

¹⁹F magnetic resonance probes for live-cell detection of peroxynitrite using an oxidative decarbonylation reaction.

PubMed

Bruemmer, Kevin J; Merrikhihaghi, Sara; Lollar, Christina T; Morris, Siti Nur Sarah; Bauer, Johannes H; Lippert, Alexander R

2014-10-21

We report a newly discovered oxidative decarbonylation reaction of isatins that is selectively mediated by peroxynitrite (ONOO(-)) to provide anthranilic acid derivatives. We have harnessed this rapid and selective transformation to develop two reaction-based probes, 5-fluoroisatin and 6-fluoroisatin, for the low-background readout of ONOO(-) using (19)F magnetic resonance spectroscopy. 5-fluoroisatin was used to non-invasively detect ONOO(-) formation in living lung epithelial cells stimulated with interferon-γ (IFN-γ).

Mannich-Benzimidazole Derivatives as Antioxidant and Anticholinesterase Inhibitors: Synthesis, Biological Evaluations, and Molecular Docking Study.

PubMed

Alpan, Ayşe Selcen; Sarıkaya, Görkem; Çoban, Güneş; Parlar, Sülünay; Armagan, Güliz; Alptüzün, Vildan

2017-07-01

A series of Mannich bases of benzimidazole derivatives having a phenolic group were designed to assess their anticholinesterase and antioxidant activities. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were evaluated in vitro by using Ellman's method. According to the activity results, all of the compounds exhibited moderate to good AChE inhibitory activity (except for 2a), with IC 50 values ranging from 0.93 to 10.85 μM, and generally displayed moderate BuChE inhibitory activity. Also, most of the compounds were selective against BuChE. Compound 4b was the most active molecule on the AChE enzyme and also selective. In addition, we investigated the antioxidant effects of the synthesized compounds against FeCl 2 /ascorbic acid-induced oxidative stress in the rat brain in vitro, and the activity results showed that most of the compounds are effective as radical scavengers. Molecular docking studies and molecular dynamics simulations were also carried out. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of a novel fused pyrrolodiazepine-based library with anti-cancer activity.

PubMed

Malik, Neha; Iyamu, Iredia D; Scheidt, Karl A; Schiltz, Gary E

2018-04-11

Development of drugs for new and persistent diseases will increasingly rely on the expansion of accessible chemical space to allow exploration of novel molecular targets. Here we report the synthesis of a library of novel fused heterobicyclic small molecules based on the 1,4-diazepine and 2,4-pyrrolidinedione scaffolds. Key chemical transformations included a Mannich-type condensation and chemoselective N-acylation reactions. Screening shows anti-cancer activity of several library compounds which suggests translational potential of this novel chemical scaffold.

Chemotherapy of Rodent Malaria.

DTIC Science & Technology

1981-09-01

floxacrine analogue WR* (BK 02771) which remained fully effective against P.y.nigeriensis challenge seven days after treatment and was still partially...In particular we note that the Mannich base WR 194965 is highly active sc against the N strain and the moderately chloroquine resistant RC strain. The...this line. Floxacrine and the two floxacrine analogues WR* (BK02771) and WR* (BK 02780) have been compared and, whilst both analogues are markedj

Ketopantoyl-lactone reductase from Candida parapsilosis: purification and characterization as a conjugated polyketone reductase.

PubMed

Hata, H; Shimizu, S; Hattori, S; Yamada, H

1989-02-24

Ketopantoyl-lactone reductase (2-dehydropantoyl-lactone reductase, EC 1.1.1.168) was purified and crystallized from cells of Candida parapsilosis IFO 0708. The enzyme was found to be homogeneous on ultracentrifugation, high-performance gel-permeation liquid chromatography and SDS-polyacrylamide gel electrophoresis. The relative molecular mass of the native and SDS-treated enzyme is approximately 40,000. The isoelectric point of the enzyme is 6.3. The enzyme was found to catalyze specifically the reduction of a variety of natural and unnatural polyketones and quinones other than ketopantoyl lactone in the presence of NADPH. Isatin and 5-methylisatin are rapidly reduced by the enzyme, the Km and Vmax values for isatin being 14 microM and 306 mumol/min per mg protein, respectively. Ketopantoyl lactone is also a good substrate (Km = 333 microM and Vmax = 481 mumol/min per mg protein). Reverse reaction was not detected with pantoyl lactone and NADP+. The enzyme is inhibited by quercetin, several polyketones and SH-reagents. 3,4-Dihydroxy-3-cyclobutene-1,2-dione, cyclohexenediol-1,2,3,4-tetraone and parabanic acid are uncompetitive inhibitors for the enzyme, the Ki values being 1.4, 0.2 and 3140 microM, respectively, with isatin as substrate. Comparison of the enzyme with the conjugated polyketone reductase of Mucor ambiguus (S. Shimizu, H. Hattori, H. Hata and H. Yamada (1988) Eur. J. Biochem. 174, 37-44) and ketopantoyl-lactone reductase of Saccharomyces cerevisiae suggested that ketopantoyl-lactone reductase is a kind of conjugated polyketone reductase.

Antifungal activity of fused Mannich ketones triggers an oxidative stress response and is Cap1-dependent in Candida albicans.

PubMed

Rossignol, Tristan; Kocsis, Béla; Bouquet, Orsolya; Kustos, Ildikó; Kilár, Ferenc; Nyul, Adrien; Jakus, Péter B; Rajbhandari, Kshitij; Prókai, László; d'Enfert, Christophe; Lóránd, Tamás

2013-01-01

We investigated the antifungal activity of fused Mannich ketone (FMK) congeners and two of their aminoalcohol derivatives. In particular, FMKs with five-membered saturated rings were shown to have minimum inhibitory concentration (MIC90s) ranging from 0.8 to 6 µg/mL toward C. albicans and the closely related C. parapsilosis and C. krusei while having reduced efficacy toward C. glabrata and almost no efficacy against Aspergillus sp. Transcript profiling of C. albicans cells exposed for 30 or 60 min to 2-(morpholinomethyl)-1-indanone, a representative FMK with a five-membered saturated ring, revealed a transcriptional response typical of oxidative stress and similar to that of a C. albicans Cap1 transcriptional activator. Consistently, C. albicans lacking the CAP1 gene was hypersensitive to this FMK, while C. albicans strains overexpressing CAP1 had decreased sensitivity to 2-(morpholinomethyl)-1-indanone. Quantitative structure-activity relationship studies revealed a correlation of antifungal potency and the energy of the lowest unoccupied molecular orbital of FMKs and unsaturated Mannich ketones thereby implicating redox cycling-mediated oxidative stress as a mechanism of action. This conclusion was further supported by the loss of antifungal activity upon conversion of representative FMKs to aminoalcohols that were unable to participate in redox cycles.

A New Highly Selective and Specific Anti-puerarin polyclonal Antibody for Determination of Puerarin Using a Mannich Reaction Hapten Conjugate

PubMed Central

Udomsin, Orapin; Krittanai, Supaluk; Kitisripanya, Tharita; Tanaka, Hiroyuki; Putalun, Waraporn

2017-01-01

Background: Puerarin (PUE) is a phytoestrogen found in Pueraria candollei and Pueraria lobata. These plants are substantial for traditional medicine in various Asian countries. PUE is a key marker that can be found only in the Pueraria species. Objective: To establish the method for determination of PUE content which is required for quality control of pharmaceutical products. Materials and Methods: PUE-cationized bovine serum albumin conjugate was created via Mannich reaction. After the rabbit immunization, the obtain anti-PUE polyclonal antibody (PAb) was used to develop an enzyme-linked immunosorbent assay (ELISA). Results: An anti-PUE PAb possess a great sensitivity and specificity. The cross-reactivity analysis shows no cross-reaction of an established antibody against other substances. In addition, we successfully developed an indirect competitive ELISA (icELISA) for the quantitative analysis of PUE. The result of method validation conforms to acceptance criteria and correlates with high-performance liquid chromatography, the reference method. The icELISA was applied to determine PUE content in Pueraria spp. plant samples and its derived pharmaceutical products. Conclusion: This highly specific immunogen was created from the Mannich reaction. An icELISA can also be applied to other research propose in the further studies. SUMMARY The new immunogen conjugated (puerarin-cBSA) via Mannich reaction was successfully in rising of antibody against puerarin (PUE)The obtained anti-PUE polyclonal antibody (PAb) was high sensitivity and specificity to PUEAn indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed and validated using anti-PUE PAbThe established icELISA was applied to determine PUE content in various tuberous root of Pueraria sppMoreover, icELISA method can be applicable in Pueraria spp. derived products. Abbreviations used: PUE: Puerarin; PAb: Polyclonal antibody; ELISA: Enzyme-linked immunosorbent assay; icELISA: Indirect competitive ELISA; cBSA: Cationized bovine serum albumin. PMID:29491643

Kinetic Evidence of an Apparent Negative Activation Enthalpy in an Organocatalytic Process

PubMed Central

Han, Xiao; Lee, Richmond; Chen, Tao; Luo, Jie; Lu, Yixin; Huang, Kuo-Wei

2013-01-01

A combined kinetic and computational study on our tryptophan-based bifunctional thiourea catalyzed asymmetric Mannich reactions reveals an apparent negative activation enthalpy. The formation of the pre-transition state complex has been unambiguously confirmed and these observations provide an experimental support for the formation of multiple hydrogen bonding network between the substrates and the catalyst. Such interactions allow the creation of a binding cavity, a key factor to install high enantioselectivity. PMID:23990028

Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as SARS-CoV 3C-like protease inhibitors.

PubMed

Liu, Wei; Zhu, He-Min; Niu, Guo-Jun; Shi, En-Zhi; Chen, Jie; Sun, Bo; Chen, Wei-Qiang; Zhou, Hong-Gang; Yang, Cheng

2014-01-01

The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains a chymotrypsin-like main protease analogous to that of the main picornavirus protease, 3CL(pro). 3CL(pro) plays a pivotal role in the viral replication cycle and is a potential target for SARS inhibitor development. A series of isatin derivatives as possible SARS-CoV 3CL(pro) inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CL(pro). Structure-activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k₁ showed most potent inhibitory activity against 3CL(pro) (IC₅₀=1.04 μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Degradation of N-heterocyclic indole by a novel endophytic fungus Phomopsis liquidambari.

PubMed

Chen, Yan; Xie, Xing-Guang; Ren, Cheng-Gang; Dai, Chuan-Chao

2013-02-01

A broad-spectrum endophytic Phomopsis liquidambari, was used to degrade environmental pollutant indole. In the condition of using indole as sole carbon and nitrogen source, the optimum concentration of indole supplied was determined to be 100 mg L(-1), with 41.7% ratio of indole degradation within 120 h. Exogenous addition of plant litter significantly increased indole degradation to 99.1% within 60 h. Indole oxidation to oxindole and isatin were the key steps limiting indole degradation. Plant litter addition induced fungus to produce laccase and LiP to non-specific oxidize indole. The results of fungal metabolites pathway through HPLC-MS and NMR analysis showed that indole was firstly oxidized to oxindole and isatin, and deoxidated to indolenie-2-dione, then hydroxylated to 2-dioxindole, which pyridine ring were cleaved through C-N position and changed to 2-aminobenzoic acid. Such metabolic pathway was similar with bacterial degradation of indole-3-acetic acid in plant. Copyright © 2012 Elsevier Ltd. All rights reserved.

Recent progress in asymmetric bifunctional catalysis using multimetallic systems.

PubMed

Shibasaki, Masakatsu; Kanai, Motomu; Matsunaga, Shigeki; Kumagai, Naoya

2009-08-18

The concept of bifunctional catalysis, wherein both partners of a bimolecular reaction are simultaneously activated, is very powerful for designing efficient asymmetric catalysts. Catalytic asymmetric processes are indispensable for producing enantiomerically enriched compounds in modern organic synthesis, providing more economical and environmentally benign results than methods requiring stoichiometric amounts of chiral reagents. Extensive efforts in this field have produced many asymmetric catalysts, and now a number of reactions can be rendered asymmetric. We have focused on the development of asymmetric catalysts that exhibit high activity, selectivity, and broad substrate generality under mild reaction conditions. Asymmetric catalysts based on the concept of bifunctional catalysis have emerged as a particularly effective class, enabling simultaneous activation of multiple reaction components. Compared with conventional catalysts, bifunctional catalysts generally exhibit enhanced catalytic activity and higher levels of stereodifferentiation under milder reaction conditions, attracting much attention as next-generation catalysts for prospective practical applications. In this Account, we describe recent advances in enantioselective catalysis with bifunctional catalysts. Since our identification of heterobimetallic rare earth-alkali metal-BINOL (REMB) complexes, we have developed various types of bifunctional multimetallic catalysts. The REMB catalytic system is effective for catalytic asymmetric Corey-Chaykovsky epoxidation and cyclopropanation. A dinucleating Schiff base has emerged as a suitable multidentate ligand for bimetallic catalysts, promoting catalytic syn-selective nitro-Mannich, anti-selective nitroaldol, and Mannich-type reactions. The sugar-based ligand GluCAPO provides a suitable platform for polymetallic catalysts; structural elucidation revealed that their higher order polymetallic structures are a determining factor for their function in the catalytic asymmetric Strecker reaction. Rational design identified a related ligand, FujiCAPO, which exhibits superior performance in catalytic asymmetric conjugate addition of cyanide to enones and a catalytic asymmetric Diels-Alder-type reaction. The combination of an amide-based ligand with a rare earth metal constitutes a unique catalytic system: the ligand-metal association is in equilibrium because of structural flexibility. These catalytic systems are effective for asymmetric amination of highly coordinative substrate as well as for Mannich-type reaction of alpha-cyanoketones, in which hydrogen bonding cooperatively contributes to substrate activation and stereodifferentiation. Most of the reactions described here generate stereogenic tetrasubstituted carbons or quaternary carbons, noteworthy accomplishments even with modern synthetic methods. Several reactions have been incorporated into the asymmetric synthesis of therapeutics (or their candidate molecules) such as Tamiflu, AS-3201 (ranirestat), GRL-06579A, and ritodrine, illustrating the usefulness of bifunctional asymmetric catalysis.

Annulation of o-Quinodimethanes through N-Heterocyclic Carbene Catalysis for the Synthesis of 1-Isochromanones.

PubMed

Janssen-Müller, Daniel; Singha, Santanu; Olyschläger, Theresa; Daniliuc, Constantin G; Glorius, Frank

2016-09-02

The activation of 2-(bromomethyl)benzaldehydes using N-heterocyclic carbenes represents a novel approach to the generation of o-quinodimethane (o-QDM) intermediates. Coupling with ketones such as phenylglyoxylates, isatins, or trifluoromethyl ketones via [4 + 2] annulation gives access to functionalized 1-isochromanones.

Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin.

PubMed

Liu, Hao-Ran; Men, Xue; Gao, Xiao-Hui; Liu, Lin-Bo; Fan, Hao-Qun; Xia, Xin-Hua; Wang, Qiu-An

2018-03-01

Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC 50 for AChE = 0.82 ± 0.08 μmol•L -1 , IC 50 for BuChE = 46.30 ± 3.26 μmol•L -1 ) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC 50 for AChE = 10.54 ± 0.86 μmol•L -1 , IC 50 for BuChE = 0.26 ± 0.08 μmol•L -1 ). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.

Structural characterization of analgesic isothiazolopyridines of Mannich base type; X-ray analysis of 2-[(4-phenylpiperazin-1-yl)ethyl]- and 2-[(4-methylpiperazin-1-yl)methyl]-4,6-dimethylisothiazolo[5,4- b]pyridin-3(2 H)-ones

NASA Astrophysics Data System (ADS)

Karczmarzyk, Zbigniew; Malinka, Wiesław

2008-10-01

The crystal and molecular structures of the title 2-[(4-phenylpiperazin-1-yl)ethyl], 6, and 2-[(4-methylpiperazin-1-yl)methyl], 7, derivatives of isothiazolo[5,4- b]pyridine were determined. The molecular packing in 6 is influenced by C-H…X (X = N, O) hydrogen bonds and π… π interactions of the pairs of isothiazolopyridine rings belonging to inversion related molecules. The crystal structure of 7 contains the net of O-H…N and C-H…O intermolecular hydrogen bonds. Moreover, isothiazole and pyridine rings show significant stacking with the shortest π… π distances of 3.453 Å. The conformations of the molecules 6 and 7 were compared with those observed in the crystals of related analgesic 4-arylpiperazine ( 2, 3) and 4-arylpiperidine ( 4, 5) derivatives of isothiazolopyridine of Mannich base type. Additionally, the computational investigations using semi-empirical AM1 and RHF/6-31G∗∗ ab initio methods are performed within series 2- 7 in order to find correlation between geometrical and electronic parameters of the molecules and their analgesic action. Results of the theoretical calculations show that the charge distribution on the piperazine N atoms is correlated with conformation of the (4-arylpiperazin-1-yl)methyl side chain and analgesic action of isothiazolopyridines analyzed.

SPR Biosensors in Direct Molecular Fishing: Implications for Protein Interactomics.

PubMed

Florinskaya, Anna; Ershov, Pavel; Mezentsev, Yuri; Kaluzhskiy, Leonid; Yablokov, Evgeniy; Medvedev, Alexei; Ivanov, Alexis

2018-05-18

We have developed an original experimental approach based on the use of surface plasmon resonance (SPR) biosensors, applicable for investigation of potential partners involved in protein⁻protein interactions (PPI) as well as protein⁻peptide or protein⁻small molecule interactions. It is based on combining a SPR biosensor, size exclusion chromatography (SEC), mass spectrometric identification of proteins (LC-MS/MS) and direct molecular fishing employing principles of affinity chromatography for isolation of potential partner proteins from the total lysate of biological samples using immobilized target proteins (or small non-peptide compounds) as ligands. Applicability of this approach has been demonstrated within the frame of the Human Proteome Project (HPP) and PPI regulation by a small non-peptide biologically active compound, isatin.

Synthesis of a new class of Betti bases by the Mannich-type reaction: efficient, facile, solvent-free and one-pot protocol.

PubMed

Shahrisa, Aziz; Teimuri-Mofrad, Reza; Gholamhosseini-Nazari, Mahdi

2015-02-01

A variety of organocatalysts has been screened for the synthesis of arylaminonaphthols. It has been shown that (N,N-dimethylethanolamine) is a highly efficient organocatalyst for the direct synthesis of a novel class of arylaminonaphthols via three-component condensation of 2-naphthol, aldehydes, and arylamines under solvent-free conditions. Mild, one-pot, and green reaction conditions, relatively short reaction times and good yields make this protocol highly significant. 25 new compounds have been synthesized by this method.

Green synthesis, biological and spectroscopic study on the interaction of multi-component Mannich bases of imidazo[2,1-b]benzothiazoles with human serum albumin.

PubMed

Maddili, Swetha K; Yandrati, Leela Prasad; Siddam, Shakuntala; Kannekanti, Vijaya Kumar; Gandham, Himabindu

2017-11-01

A series of Mannich bases of imidazo[2, l-b]benzothiazoles were prepared through one-pot multi-component reaction in the presence of water as an eco-friendly solvent. All the synthesized compounds were confirmed from IR, 1 HNMR, 13 CNMR, and Mass spectroscopy. Evaluation of in vitro anti-inflammatory and anti-microbial activities of all the synthesized derivatives was further accomplished. These results clearly displayed that compound 6d exhibited outstanding anti-inflammatory activity with a percentage inhibition of 70.23% by membrane stabilization method whereas 67.54% at 100μgmL -1 by the albumin denaturation method, which is comparable to the standard Diclofenac. Further screening against five fungal species (C. albicans ATCC 76615, C. mycoderma, C. utilis, A. flavus, and B. yeast) along with four gram positive (Methicillin-resistant S. aureus N315 (MRSA), Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 21216, and Micrococcus luteus ATCC 4698), and six Gram-negative bacterial strains (Escherichia coli DH52, Escherichia coli JM109, Salmonella dysenteriae, Pseudomonas aeruginosa ATCC 27853, Bacillus proteus ATCC13315 and Bacillus typhi) was carried out. These findings manifested that compound 7c displayed excellent antifungal efficacy while compound 7b revealed significant anti-microbial activity. In addition binding behaviour of compound 7b was investigated by binding study between calf thymus DNA and compound 7b by UV-Vis absorption spectroscopy and further research about HSA interactions was carried out. Copyright © 2017 Elsevier B.V. All rights reserved.

Substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase.

PubMed

Endo, Satoshi; Arai, Yuki; Hara, Akira; Kitade, Yukio; Bunai, Yasuo; El-Kabbani, Ossama; Matsunaga, Toshiyuki

2013-01-01

In this study, we examined the substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase (AKR1C5), which plays a role in the termination of pregnancy by progesterone inactivation. AKR1C5 moderately reduced the 3-keto group of only 5α-dihydrosteroids with 17β- or 20α/β-hydroxy group among 3-ketosteroids. In contrast, the enzyme reversibly and efficiently catalyzed the reduction of various 17- and 20-ketosteroids, including estrogen precursors (dehydroepiandrosterone, estrone and 5α-androstan-3β-ol-17-one) and tocolytic 5β-pregnane-3,20-dione. In addition to the progesterone inactivation, the formation of estrogens and metabolism of the tocolytic steroid by AKR1C5 may be related to its role in rabbit parturition. AKR1C5 also reduced various non-steroidal carbonyl compounds, including isatin, an antagonist of the C-type natriuretic peptide receptor, and 4-oxo-2-nonenal, suggesting its roles in controlling the bioactive isatin and detoxification of cytotoxic aldehydes. AKR1C5 was potently and competitively inhibited by flavonoids such as kaempferol and quercetin, suggesting that its activity is affected by ingested flavonoids.

Design, Synthesis and In Vitro Anti-microbial Evaluation of Ethylene/ Propylene-1H-1,2,3-Triazole-4-Methylene-tethered Isatin-coumarin Hybrids.

PubMed

Jin, Xiaohong; Xu, Yan; Yang, Xuhong; Chen, Xiuling; Wu, Minghu; Guan, Jianguo; Feng, Lianshun

2017-01-01

A new class of ethylene/propylene-1H-1,2,3-triazole-4-methylene-tethered isatincoumarin hybrids 8a-j, integrating three anti-tuberculosis pharmacophores coumarin, isatin and 1,2,3- triazole was designed and synthesized. These hybrids were assessed for their in vitro anti-TB activity against MTB H37Rv and MDRTB, as well as anti-bacterial activity against Gram-positive and Gram-negative strains, and cytotoxicity in VERO cell line. The results showed that all hybrids with acceptable cytotoxicity (CC50: 64-512 µg/mL) exhibited weak to moderate anti-microbial activity. The most active hybrid 8i with MIC of 50 µg/mL against MTB H37Rv and MDR-TB, also has excellent cytotoxicity profile (CC50: 128 µg/mL). The resistance index of hybrid 8i was 1, indicating that hybrid 8i has no cross-resistance with the first-line anti-TB agent. Thus, hybrid 8i could act as a lead for further optimization. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The relationship between surface tension and the industrial performance of water-soluble polymers prepared from acid hydrolysis lignin, a saccharification by-product from woody materials.

PubMed

Matsushita, Yasuyuki; Imai, Masanori; Iwatsuki, Ayuko; Fukushima, Kazuhiko

2008-05-01

In this study, water-soluble anionic and cationic polymers were prepared from sulfuric acid lignin (SAL), an acid hydrolysis lignin, and the relationship between the surface tension of these polymers and industrial performance was examined. The SAL was phenolized (P-SAL) to enhance its solubility and reactivity. Sulfonation and the Mannich reaction with aminocarboxylic acids produced water-soluble anionic polymers and high-dispersibility gypsum paste. The dispersing efficiency increased as the surface tension decreased, suggesting that the fluidity of the gypsum paste increased with the polymer adsorption on the gypsum particle surface. Water-soluble cationic polymers were prepared using the Mannich reaction with dimethylamine. The cationic polymers showed high sizing efficiency under neutral papermaking conditions; the sizing efficiency increased with the surface tension. This suggests that the polymer with high hydrophilicity spread in the water and readily adhered to the pulp surface and the rosin, showing good retention.

ALDOL- AND MANNICH-TYPE REACTIONS VIA IN SITU OLEFIN MIGRATION IN IONIC LIQUID. (R828129)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Synthesis of novel heterocycles through reaction of indolin-2-one derivatives with active methylene and amino reagents.

PubMed

Abdel-Latif, F F; Ahmed, E K; Mekheimer, R; Mashaly, M M

1997-10-01

Several new spiro compounds were synthesized via one-pot ternary condensation of isatin, malononitrile and each of thiobarbituric acid, barbituric acid, 3-methyl-pyrazolin-5-one, 1-phenyl-3-methyl-pyrazolin-5-one, acetylacetone, benzoylacetone, ethyl acetoacetate, phenacyl cyanide or ethyl-cyanoacetate dimer. Structures and reaction mechanism were reported and supported via a second synthetic route.

New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres.

PubMed

Attia, Mohamed I; Eldehna, Wagdy M; Afifi, Samar A; Keeton, Adam B; Piazza, Gary A; Abdel-Aziz, Hatem A

2017-01-01

The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC50 value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC50 value less than 0.8 μM.

Antinociceptive properties of N-Mannich bases derived from 3-substituted pyrrolidine-2,5-dione in the formalin model of persistent pain in mice.

PubMed

Obniska, Jolanta; Sałat, Kinga; Librowski, Tadeusz; Kamiński, Krzysztof; Lipkowska, Anna; Wiklik, Beata; Rybka, Sabina; Rapacz, Anna

2015-02-01

Accumulated data indicate that anticonvulsants possess antinociceptive properties in rodent pain models. In view of the anticonvulsant activity demonstrated previously among N-Mannich bases derived from 3-mono- (1-6) and 3,3-disubstituted pyrrolidine-2,5-diones (7-14) their analgesic activity has been investigated in the formalin model of tonic pain in mice. The compounds 1-14 were tested at doses equal to the respective ED50 values obtained earlier in the MES test. 0.5% formalin solution was given as intraplantar injections into the hind paw of the mouse and the duration of the nocifensive response was counted in drug-treated and vehicle-treated animals in the acute and the late phases of the test. A significant antinociceptive activity was observed for majority of the compounds. In the first phase of the test all the active compounds, except for 9-11, reduced the duration of the licking response up to 88% (compounds 2 and 6; p<0.001). In the late phase the 1-3, 5, 6, 9 and 14 were the most effective agents and their analgesic activities ranged from 92 to 100%. The results of the research indicate that some of the investigated compounds reduced effectively either both phases of the test or were able to attenuate pain during only the acute or late phase of the formalin test. These properties, which are particularly strong in case of the compounds 1-3, 5, 6, 9 and 14, might be relevant for the development of novel analgesic-active compounds and their possible use in neuropathic pain syndromes. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Some Novel Mannich Bases of 5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one and Their Anti-Inflammatory Activity.

PubMed

Koksal, Meric; Ozkan-Dagliyan, Irem; Ozyazici, Tugce; Kadioglu, Beril; Sipahi, Hande; Bozkurt, Ayhan; Bilge, Suleyman S

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1 H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively. © 2017 Deutsche Pharmazeutische Gesellschaft.

Concise total syntheses of (+/-)-strychnine and (+/-)-akuammicine.

PubMed

Sirasani, Gopal; Paul, Tapas; Dougherty, William; Kassel, Scott; Andrade, Rodrigo B

2010-05-21

Concise total syntheses of Strychnos alkaloids strychnine (1) and akuammicine (2) have been realized in 13 and 6 operations, respectively. Key steps include (1) the vinylogous Mannich reaction; (2) a novel, sequential one-pot spirocyclization/intramolecular aza-Baylis-Hillman reaction; and (3) a Heck cyclization. The synthesis of 1 proceeds via the Wieland-Gumlich aldehyde (26).

Direct 3D Printing of Catalytically Active Structures

DOE PAGES

Manzano, J. Sebastian; Weinstein, Zachary B.; Sadow, Aaron D.; ...

2017-09-22

3D printing of materials with active functional groups can provide custom-designed structures that promote chemical conversions. Catalytically active architectures were produced by photopolymerizing bifunctional molecules using a commercial stereolithographic 3D printer. Functionalities in the monomers included a polymerizable vinyl group to assemble the 3D structures and a secondary group to provide them with active sites. The 3D-printed architectures containing accessible carboxylic acid, amine, and copper carboxylate functionalities were catalytically active for the Mannich, aldol, and Huisgen cycloaddition reactions, respectively. The functional groups in the 3D-printed structures were also amenable to post-printing chemical modification. And as proof of principle, chemically activemore » cuvette adaptors were 3D printed and used to measure in situ the kinetics of a heterogeneously catalyzed Mannich reaction in a conventional solution spectrophotometer. In addition, 3D-printed millifluidic devices with catalytically active copper carboxylate complexes were used to promote azide-alkyne cycloaddition under flow conditions. The importance of controlling the 3D architecture of the millifluidic devices was evidenced by enhancing reaction conversion upon increasing the complexity of the 3D prints.« less

Direct 3D Printing of Catalytically Active Structures

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

Manzano, J. Sebastian; Weinstein, Zachary B.; Sadow, Aaron D.

3D printing of materials with active functional groups can provide custom-designed structures that promote chemical conversions. Catalytically active architectures were produced by photopolymerizing bifunctional molecules using a commercial stereolithographic 3D printer. Functionalities in the monomers included a polymerizable vinyl group to assemble the 3D structures and a secondary group to provide them with active sites. The 3D-printed architectures containing accessible carboxylic acid, amine, and copper carboxylate functionalities were catalytically active for the Mannich, aldol, and Huisgen cycloaddition reactions, respectively. The functional groups in the 3D-printed structures were also amenable to post-printing chemical modification. And as proof of principle, chemically activemore » cuvette adaptors were 3D printed and used to measure in situ the kinetics of a heterogeneously catalyzed Mannich reaction in a conventional solution spectrophotometer. In addition, 3D-printed millifluidic devices with catalytically active copper carboxylate complexes were used to promote azide-alkyne cycloaddition under flow conditions. The importance of controlling the 3D architecture of the millifluidic devices was evidenced by enhancing reaction conversion upon increasing the complexity of the 3D prints.« less

Quantum chemical calculations and molecular docking studies of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione(CTD) and its mannich product 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD)

NASA Astrophysics Data System (ADS)

Fatma, Shaheen; Bishnoi, Abha; Verma, Anil Kumar; Singh, Vineeta; Srivastava, Krishna

2018-04-01

This work presents the synthesis of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione (CTD) by Claisen condensation of thiazolidine-2,4-dione and mannich product of CTD, 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD). The static first hyperpolarizability values for thiazolidine-2,4-dione derivatives have been calculated as 10.28 × 10-30 esu for CTD and 19.42 × 10-30 esu for CMTD. The gradual increase in hyperpolarizability values of synthesized thiazolidine-2,4-dione derivatives from CTD to CMTD is due to the blockage of sbnd NH group on CTD by mannich reaction. The structures of these compounds have been derived by spectroscopic(IR, UV, Mass, 1H and 13C NMR) analysis as well as with the help of theoretical studies. The high values of first static hyperpolarizability indicate that the synthesized derivatives are suitable as non-linear optical (NLO) material. CTD with MIC value of 12.5 μg/mL can be developed as an alternative drug for the treatment of enteric fever. Calculated frontier orbital gap values suggest that the CMTD is a soft molecule with high chemical reactivity and is more polarizable as compared to the CTD. Molecular electrostatic potential is calculated for the optimized geometry of the molecules to estimate their chemical reactivity. The inhibitor CTD forms a stable complex with 3-dehydroquinase enzyme of Salmonella typhi. It is evident from the ligand receptor interactions and a binding affinity value of -5.88 kcal/mol and an inhibition constant of 49.22 μM. This is further confirmed by the experimental biological data. The molecular docking studies are supportive of the antibacterial activity of CTD exhibiting high inhibition constant and binding energy.

Synthesis and Metalation of a Ligand: An Interdisciplinary Laboratory Experiment for Second-Year Organic and Introductory Inorganic Chemistry Students

ERIC Educational Resources Information Center

Kasting, Benjamin J.; Bowser, Andrew K.; Anderson-Wile, Amelia M.; Wile, Bradley M.

2015-01-01

An interdisciplinary laboratory experiment involving second-year undergraduate organic chemistry and introductory inorganic chemistry undergraduate students is described. Organic chemistry students prepare a series of amine-bis(phenols) via a Mannich reaction, and characterize their products using melting point; FTIR; and [superscript 1]H,…

Multicomponent Synthesis of a N-Protected Alpha-Amino Ester: Ethyl 2-((4-Methoxyphenyl)Amino)-3-Phenylpropanoate

ERIC Educational Resources Information Center

Le Gall, Erwan; Pignon, Antoine

2012-01-01

This laboratory experiment describes the preparation of a N-protected phenylalanine ethyl ester by a zinc-mediated Mannich-like multicomponent reaction between benzyl bromide, "p"-anisidine, and ethyl glyoxylate. The one-step reaction involves the in situ metallation of benzyl bromide into a benzylzinc reagent and its addition onto imine (Barbier…

Bangalore India Bio 2010.

PubMed

Thammanabhatla, Pratibha; Pailla, Mamatha

2010-08-01

The Bangalore India Bio 2010 conference, held in Bangalore, India, included topics covering new developments in the biopharma industry. This conference report highlights selected presentations on novel therapeutics for the treatment of cancer, including identification of novel benzimidazole, N-subsituted isatin and azetidine derivatives, and an Wnt antagonist. In addition, presentations from several biopharma companies and universities are highlighted, including Proteomics International Pty Ltd, Oxford BioMedica plc, AnaptysBio Inc, SIOGEN Biotech, RV College of Engineering and Indian Institute of Science.

An in vitro study of the antimicrobial effects of indigo naturalis prepared from Strobilanthes formosanus Moore.

PubMed

Chiang, Yin-Ru; Li, Ann; Leu, Yann-Lii; Fang, Jia-You; Lin, Yin-Ku

2013-11-21

Indigo naturalis is effective in treating nail psoriasis coexisting with microorganism infections. This study examines the antimicrobial effects of indigo naturalis prepared from Strobilanthes formosanus Moore. Eight bacterial and seven fungal strains were assayed using the agar diffusion method to examine the effects of indigo naturalis and its bioactive compounds. The bioactive compounds of indigo naturalis were purified sequentially using GFC, TLC, and HPLC. Their structures were identified using mass spectrometry and NMR spectroscopy. UPLC-MS/MS was applied to compare the metabolome profiles of indigo naturalis ethyl-acetate (EA) extract and its source plant, Strobilanthes formosanus Moore. The results of in vitro antimicrobial assays showed that indigo naturalis EA-extract significantly (≥1 mg/disc) inhibits Gram-positive bacteria (Staphylococcus aureus, S. epidermis and methicillin-resistant S. aureus (MRSA)) and mildly inhibits non-dermatophytic onychomycosis pathogens (Aspergillus fumigates and Candida albicans), but has little effect on dermatophyes. Isatin and tryptanthrin were identified as the bioactive compounds of indigo naturalis using S. aureus and S. epidermis as the bioassay model. Both bioactive ingredients had no effect on all tested fungi. In summary, indigo naturalis prepared from Strobilanthes formosanus Moore exhibits antimicrobial effects on Staphylococcus and non-dermatophytic onychomycosis pathogens. Tryptanthrin and isatin may be its major bioactive ingredients against Staphylococcus and the inhibitory effect on MRSA may be due to other unidentified ingredients.

New lab-made coagulant based on Schinopsis balansae tannin extract: synthesis optimization and preliminary tests on refractory water pollutants

NASA Astrophysics Data System (ADS)

Sánchez-Martín, J.; Beltrán-Heredia, J.; Coco-Rivero, B.

2014-09-01

Quebracho colorado tannin extract was used as a coagulant raw material for water and wastewater treatment. The chemical synthesis follows a Mannich reaction mechanism and provides a fully working coagulant that can remove several pollutants from water. This paper addresses the optimization of such synthesis and confirms the feasibility of the coagulant by testing it in a preliminary screening for the elimination of dyes and detergents. The optimum combination of reagents was 6.81 g of diethanolamine (DEA) and 2.78 g of formaldehyde (F) per g of tannin extract. So obtained coagulant was succesfully tested on the removal of 9 dyes and 8 detergents.

Structural characterisation of some vanillic Mannich bases: Experimental and theoretical study

NASA Astrophysics Data System (ADS)

Petrović, Vladimir P.; Simijonović, Dušica; Novaković, Sladjana B.; Bogdanović, Goran A.; Marković, Svetlana; Petrović, Zorica D.

2015-10-01

In this paper, synthesis and structural determination of 2-[1-(N-4-fluorophenylamino)-1-(4-hydroxy-3-methoxyphenyl)]methylcyclohexanone (MB-F) is presented. To determine the structure of this new compound, IR and NMR spectral characterisation was performed experimentally and theoretically. Simulation of spectral data was carried out using three functionals: B3LYP, B3LYP-D2, and M06-2X. The results obtained for MB-F were compared to those attained for similar, known compound 2-[1-(N-phenylamino)-1-(4-hydroxy-3-methoxyphenyl)]methylcyclohexanone (MB-H), whose crystal structure is presented here. Taking into account all experimental and theoretical findings, the structure of MB-F was proposed.

Synthesis of new Schiff bases bearing 1,2,4-triazole, thiazolidine and chloroazetidine moieties and their pharmacological evaluation.

PubMed

Kandile, Nadia G; Mohamed, Mansoura I; Ismaeel, Hind M

2017-12-01

New compounds based on oxindole moiety were synthesized via the reaction of 5-substitued isatins 1a-e with different nucleophiles such as benzidine, 3,3'-dimethoxybenzidine 2a,b and 2,6-diaminopyridine 3 to afford three different classes of bis-Schiff bases 4a-e, 5a-e and 6a-e, respectively. The structures of the new compounds were elucidated on the basis of their FTIR, 1 H NMR, 13 C NMR, GC/MS spectral data and elemental analysis. The in vitro antimicrobial activity of the new compounds was evaluated using a broth dilution technique in terms of minimal inhibitory concentration (MIC) against four bacterial and two fungal pathogens and anticancer activities against HELA cervix. The revealed data showed that compound 9d has excellent activity against Gram + ve and Gram -ve bacteria, and compounds 11b presented promising anticancer activity against HELA cervix. [Formula: see text].

Identification of target cells by immunohistochemical detection of covalently rearranged estradiol in rehydrated paraffin sections.

PubMed

Jungblut, P W; Sierralta, W D

1998-04-01

Estradiol is released from the binding niche of the receptor and covalently arrested in the molecular vicinity by the Mannich reaction during target fixation in acetic acid/formaldehyde. The exposed steroid is freely accessible for appropriate antibodies. It can be visualized in sections by the second antibody/enzyme technique in high resolution and without enhancements.

Lighting up Protons with MorphFl, a Fluorescein-Morpholine Dyad: An Experiment for the Organic Laboratory

ERIC Educational Resources Information Center

Miller, Tyson A.; Spangler, Michael; Burdette, Shawn C.

2011-01-01

A two-period organic laboratory experiment that includes fluorescence sensing is presented. The pH-sensitive sensor MorphFl is prepared using a Mannich reaction between a fluorescein derivative and the iminium ion of morpholine. During the first laboratory, students prepare MorphFl. The second session begins with characterizing the sensor using…

Single-site labeling of lysine in proteins through a metal-free multicomponent approach.

PubMed

Chilamari, Maheshwerreddy; Kalra, Neetu; Shukla, Sanjeev; Rai, Vishal

2018-06-15

We report a chemoselective and site-selective approach that distinguishes one Lys from its multiple copies, N-terminus, and other competitors. The phospha-Mannich protocol works with multiple proteins and installs probes without structural and functional perturbations. It delivers an antibody-drug conjugate with selective anti-proliferative activity towards HER2 expressing SKBR3 breast cancer cells.

A Diastereoselective Multicomponent Reaction for Construction of Alkynylamide-Substituted α,β-Diamino Acid Derivatives To Hunt Hits.

PubMed

Lei, Ruirui; Wu, Yong; Dong, Suzhen; Jia, Kaili; Liu, Shunying; Hu, Wenhao

2017-03-17

A highly diasetereoselective Mannich-type multicomponent reaction was developed to rapidly construct alkynylamide-substituted α,β-diamino acid derivatives from simple starting materials under mild conditions in moderate to good yields for hit hunting. Most of the resulting products 4 exhibited good anticancer activity in HCT116, BEL7402, and SMMC7721 cells.

Quantum dynamics of nuclear spins and spin relaxation in organic semiconductors

DOE PAGES

Mkhitaryan, V. V.; Dobrovitski, V. V.

2017-06-12

3D printing of materials with active functional groups can provide custom-designed structures that promote chemical conversions. Herein, catalytically active architectures were produced by photopolymerizing bifunctional molecules using a commercial stereolithographic 3D printer. Functionalities in the monomers included a polymerizable vinyl group to assemble the 3D structures and a secondary group to provide them with active sites. The 3D-printed architectures containing accessible carboxylic acid, amine, and copper carboxylate functionalities were catalytically active for the Mannich, aldol, and Huisgen cycloaddition reactions, respectively. The functional groups in the 3D-printed structures were also amenable to post-printing chemical modification. As proof of principle, chemically activemore » cuvette adaptors were 3D printed and used to measure in situ the kinetics of a heterogeneously catalyzed Mannich reaction in a conventional solution spectrophotometer. In addition, 3D-printed millifluidic devices with catalytically active copper carboxylate complexes were used to promote azide-alkyne cycloaddition under flow conditions. The importance of controlling the 3D architecture of the millifluidic devices was evidenced by enhancing reaction conversion upon increasing the complexity of the 3D prints.« less

Search for new potential anticonvulsants with anxiolytic and antidepressant properties among derivatives of 4,4-diphenylpyrrolidin-2-one.

PubMed

Malawska, Katarzyna; Rak, Aleksandra; Gryzło, Beata; Sałat, Kinga; Michałowska, Małgorzata; Żmudzka, Elżbieta; Lodarski, Krzysztof; Malawska, Barbara; Kulig, Katarzyna

2017-02-01

The aim of this study was to synthesize a series of new N-Mannich bases derived from 4,4-diphenylpyrrolidin-2-one having differently substituted 4-phenylpiperazines as potential anticonvulsant agents with additional (beneficial) pharmacological properties. The target compounds 8-12 were prepared in one step from the 4-substituted phenylpiperazines, paraformaldehyde, and synthesized 4,4-diphenylpyrrolodin-2-one (7) by a Mannich-type reaction. The obtained compounds were assessed and tested for their anticonvulsant activity in two screening mouse models of seizures, i.e., the maximal electroshock (MES) test and in the subcutaneous pentylenetetrazole (scPTZ) test. The effect of these compounds on animals' motor coordination was measured in the rotarod test. A selected 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) was evaluated in vivo for its anxiolytic- and antidepressant-like properties. Its impact on animals' locomotor activity was also evaluated. Compound 8 showed protection (25%) in the MES and in the scPTZ tests at the dose of 100mg/kg and was not neurotoxic. In the four-plate test, compound 8 at the dose of 30mg/kg showed a statistically significant (p<0.05) anxiolytic-like activity. In the forced swim test, it reduced the immobility time by 24.3% (significant at p<0.05), which indicates its potential antidepressant-like properties. In the locomotor activity test, compound 8 significantly reduced animals' locomotor activity by 79.9%. The results obtained make a new derivative of 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) a promising lead structure for further development. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Optimization of tocotrienols as antiproliferative and antimigratory leads.

PubMed

Behery, Fathy A; Akl, Mohamed R; Ananthula, Suryatheja; Parajuli, Parash; Sylvester, Paul W; El Sayed, Khalid A

2013-01-01

The vitamin E family members γ- and δ-tocotrienols (2 and 3, respectively) are known natural products with documented anticancer activities. Redox-silent structural modifications, such as esterification, etherification and carbamoylation, of 2 and 3 significantly enhanced their anticancer activities. However, hit-to-lead optimization of tocotrienols and their analogs was yet to be reported at the outset of the project described herein. Subjecting the chroman ring of 2 and 3 to the electrophilic substitution reactions, namely, Mannich and Lederer-Manasse procedures, afforded 42 new products. These included the 3,4-dihydro-1,3-oxazines 3-29 and 35-44, Mannich bases 30-31, and the hydroxymethyl analogs 32-34. Of these, the δ-tocotrienol analogs 8, 11, 18, 24, 25, 27, and 40 inhibited the proliferation of the highly metastatic +SA mammary epithelial cancer cell line, with IC(50) values in the nanomolar (nM) range. In NCI's 60 human tumor cell line panel, 8, 17, 38, and 40 showed antiproliferative activity, with nM GI(50) values. The δ-tocotrienol analogs 10 and 38 inhibited the migration of the highly metastatic human breast cancer cell line MDA-MB-231 with IC(50) values of 1.3 and 1.5 μM, respectively, in the wound-healing assay. A dose of 0.5 mg/day for 14 days of one of the active analogs, 30, significantly slowed the growth of +SA mammary tumors in the syngeneic BALB/c mouse model, compared to the vehicle- and the parent γ-tocotrienol-treated control groups. Electrophilic substitution reactions promoted tocotrienols to lead level and can enable their future use to control metastatic breast malignancies. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Synthesis of the C(18) -norditerpenoid alkaloid neofinaconitine: a lesson in convergent synthesis planning.

PubMed

Liu, Xiao-Yu; Chen, David Y-K

2014-01-20

Hexacyclic framework: The total synthesis of the complex C18 -norditerpenoid alkaloid neofinaconitine has been achieved by a convergent approach. This remarkable synthesis featured two Diels-Alder cycloadditions and subsequent Mannich-type N-acyliminium and radical cyclizations to establish the unique hexacyclic core structure of the target molecule. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selecting of a cytochrome P450cam SeSaM library with 3-chloroindole and endosulfan - Identification of mutants that dehalogenate 3-chloroindole.

PubMed

Kammoonah, Shaima; Prasad, Brinda; Balaraman, Priyadarshini; Mundhada, Hemanshu; Schwaneberg, Ulrich; Plettner, Erika

2018-01-01

Cytochrome P450 cam (a camphor hydroxylase) from the soil bacterium Pseudomonas putida shows potential importance in environmental applications such as the degradation of chlorinated organic pollutants. Seven P450 cam mutants generated from Sequence Saturation Mutagenesis (SeSaM) and isolated by selection on minimal media with either 3-chloroindole or the insecticide endosulfan were studied for their ability to oxidize of 3-chloroindole to isatin. The wild-type enzyme did not accept 3-chloroindole as a substrate. Mutant (E156G/V247F/V253G/F256S) had the highest maximal velocity in the conversion of 3-chloroindole to isatin, whereas mutants (T56A/N116H/D297N) and (G60S/Y75H) had highest k cat /K M values. Six of the mutants had more than one mutation, and within this set, mutation of residues 297 and 179 was observed twice. Docking simulations were performed on models of the mutant enzymes; the wild-type did not accommodate 3-chloroindole in the active site, whereas all the mutants did. We propose two potential reaction pathways for dechlorination of 3-chloroindole. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone. Copyright © 2017 Elsevier B.V. All rights reserved.

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

PubMed Central

Lara-Castillo, Nuria; Zandi, Souska; Nakao, Shintaro; Ito, Yasuhiro; Noda, Kousuke; She, Haicheng; Ahmed, Muna; Frimmel, Sonja; Ablonczy, Zsolt; Hafezi-Moghadam, Ali

2009-01-01

Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 μmol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP’s effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP’s TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy. PMID:19910509

Synthesis, spectroscopic characterization and biological activities of N4O2 Schiff base ligand and its metal complexes of Co(II), Ni(II), Cu(II) and Zn(II)

NASA Astrophysics Data System (ADS)

Al-Resayes, Saud I.; Shakir, Mohammad; Abbasi, Ambreen; Amin, Kr. Mohammad Yusuf; Lateef, Abdul

The Schiff base ligand, bis(indoline-2-one)triethylenetetramine (L) obtained from condensation of triethylenetetramine and isatin was used to synthesize the complexes of type, [ML]Cl2 [M = Co(II), Ni(II), Cu(II) and Zn(II)]. L was characterized on the basis of the results of elemental analysis, FT-IR, 1H and 13C NMR, mass spectroscopic studies. The stoichiometry, bonding and stereochemistries of complexes were ascertained on the basis of results of elemental analysis, magnetic susceptibility values, molar conductance and various spectroscopic studies. EPR, UV-vis and magnetic moments revealed an octahedral geometry for complexes. L and its Cu(II) and Zn(II) complexes were screened for their antibacterial activity. Analgesic activity of Cu(II) and Zn(II) complexes was also tested in rats by tail flick method. Both complexes were found to possess good antibacterial and moderate analgesic activity.

Gold-catalyzed three-component annulation: efficient synthesis of highly functionalized dihydropyrazoles from alkynes, hydrazines, and aldehydes or ketones.

PubMed

Suzuki, Yamato; Naoe, Saori; Oishi, Shinya; Fujii, Nobutaka; Ohno, Hiroaki

2012-01-06

Polysubstituted dihydropyrazoles were directly obtained by a gold-catalyzed three-component annulation. This reaction consists of a Mannich-type coupling of alkynes with N,N'-disubstituted hydrazines and aldehydes/ketones followed by intramolecular hydroamination. Cascade cyclization using 1,2-dialkynylbenzene derivatives as the alkyne component was also performed producing fused tricyclic dihydropyrazoles in good yields. © 2011 American Chemical Society

Ketopantoyl lactone reductase is a conjugated polyketone reductase.

PubMed

Hata, H; Shimizu, S; Hattori, S; Yamada, H

1989-03-01

Ketopantoyl lactone reductase (EC 1.1.1.168) of Saccharomyces cerevisiae was found to catalyze the reduction of a variety of natural and unnatural conjugated polyketone compounds and quinones, such as isatin, ninhydrin, camphorquinone and beta-naphthoquinone in the presence of NADPH. 5-Bromoisatin is the best substrate for the enzyme (Km = 3.1 mM; Vmax = 650 mumol/min/mg). The enzyme is inhibited by quercetin, and several polyketones. These results suggest that ketopantoyl lactone reductase is a carbonyl reductase which specifically catalyzes the reduction of conjugated polyketones.

Facial Regioselective Synthesis of Novel Bioactive Spiropyrrolidine/Pyrrolizine-Oxindole Derivatives via a Three Components Reaction as Potential Antimicrobial Agents.

PubMed

Hassaneen, Huwaida M E; Eid, Elshimaa M; Eid, Hamid A; Farghaly, Thoraya A; Mabkhot, Yahia Nasser

2017-02-26

This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6a - j and spirooxindole-spiropiperidinone-pyrrolizines 8a - j, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4a - j . All of the newly synthesized compounds were evaluated for their antimicrobial activities and their minimum inhibitory concentration (MIC) against most of the test organisms. The tested compounds displayed excellent activity against all of the tested microorganisms.

An Expedient Regio- and Diastereoselective Synthesis of Hybrid Frameworks with Embedded Spiro[9,10]dihydroanthracene [9,3']-pyrrolidine and Spiro[oxindole-3,2'-pyrrolidine] Motifs via an Ionic Liquid-Mediated Multicomponent Reaction.

PubMed

Arumugam, Natarajan; Almansour, Abdulrahman I; Kumar, Raju Suresh; Menéndez, J Carlos; Sultan, Mujeeb A; Karama, Usama; Ghabbour, Hazem A; Fun, Hoong-Kun

2015-09-03

A series of hitherto unreported anthracene-embedded dispirooxindoles has been synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ from the reaction of isatin and sarcosine to 10-benzylideneanthracen-9(10H)-one as a dipolarophile in 1-butyl-3-methylimidazolium bromide([bmim]Br), an ionic liquid. This reaction proceeded regio- and diastereoselectively, in good to excellent yields.

Design, synthesis, in vitro Evaluation and docking studies on dihydropyrimidine-based urease inhibitors.

PubMed

Iftikhar, Fatima; Ali, Yousaf; Ahmad Kiani, Farooq; Fahad Hassan, Syed; Fatima, Tabeer; Khan, Ajmal; Niaz, Basit; Hassan, Abbas; Latif Ansari, Farzana; Rashid, Umer

2017-10-01

In our previous report, we have identified 3,4-dihydropyrimidine scaffold as promising class of urease inhibitor in a structure based virtual screen (SBVS) experiment. In present study, we attempted to optimize the scaffold by varying C-5 substituent. The elongation of the C-5 chain was achieved by the reaction of C-5 ester with hydrazine leading to C-5 carbohydrazides which were further used as building blocks for the synthesis of fifteen new compounds having diverse moieties. A significantly higher in vitro urease inhibitory activity with IC 50 values in submicromolar range was observed for semithiocarbazide derivatives (4a-c, 0.58-0.79µM) and isatin Schiff base derivative 5a (0.23µM). Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its key amino acid residues. The overall results of urease inhibition have shown that these compounds can be further optimized and developed as lead urease inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

New Trends in Research of Energetic Materials (5th Seminar) Held in Pardubice, Czech Republic on 24-25 Apr 2002

DTIC Science & Technology

2002-04-01

stearic acid, palmitic acid, octadecanol, zinc stearate, silicone grease, silicone oil, organosilicon resin , asphalt, and estane, as single or...small amount of urea was present. The product crystallized directly from the reaction mixture. The following reaction conditions were changed in the...triazacycloheptane (3) includes Mannich condensation of ethylenedinitramine with formaldehyde and monoethanolamine to give 3- ethanol- 1,5-dinitro-l1,3,5

Divergent chemo-, regio-, and diastereoselective normal electron-demand Povarov-type reactions with α-oxo-ketene dienophiles.

PubMed

Galvez, Jaime; Castillo, Juan-Carlos; Quiroga, Jairo; Rajzmann, Michel; Rodriguez, Jean; Coquerel, Yoann

2014-08-15

The reactions between electron-rich 2-aza-dienes and α-oxo-ketenes derived from the Wolff rearrangement of 2-diazocycloalkane-1,3-diones chemo- and regioselectively produced spiro hydropyrid-4-ones with good to excellent diastereoselectivities. These reactions are likely to proceed via a domino Wolff/Friedel-Crafts/intramolecular Mannich process. Prolonged domino sequences also allowed the expeditious preparation of a series of pyrazolopyridine and pyridopyrimidine heterocycles.

Reactive Uptake of Ammonia to Secondary Organic Aerosols: Kinetics of Organonitrogen Formation

NASA Astrophysics Data System (ADS)

Liu, Yongchun; Liggio, John; Staebler, Ralf; Li, Shao-Meng

2015-04-01

Organonitrogen compounds originating from the heterogeneous uptake of NH3 or amines by secondary organic aerosol (SOA) has received significant attention recently. This is primarily due to its potential contribution to brown carbon (BrC), which can absorb solar radiation and affect climate. In addition, particle phase Organonitrogen species may represent a means of altering regional nitrogen cycles and/or nitrogen deposition patterns though the sequestering of ambient ammonia which is ultimately deposited downwind. Several reduced nitrogen forming heterogeneous reactions have previously been proposed, including Schiff base and/or Mannich reactions between NH3, ammonium salts or amines and organic carbonyl functional groups in particles. In order to assess and model the possible impact of Schiff base, Mannich or other N-forming reactions (via NH3) on the radiative forcing ability of ambient SOA and/or its impact on N-deposition, the kinetics of such heterogeneous reactions are required, and yet remain largely unknown. In the current study, the uptake kinetics of NH3 to form organonitrogen compounds in SOA derived from the ozonolysis of α-pinene and the OH oxidation of m-xylene is reported for the first time from experiments performed in a 9 m3 smog chamber equipped with a High Resolution Time-of-Flight Aerosol Mass Spectrometer. The results demonstrate that particle bound organonitrogen compounds are mainly formed by NH3 uptake onto newly formed SOA (~1 hr), but relatively little onto more aged SOA. The uptake coefficients of NH3 to form organonitrogen compounds (between 0-150 min) are on the order of 10-4-10-3 and are prominently dependent upon particle acidity. Following 6 hours of reaction, the total organonitrogen mass contributed up to 10.0±1.5 wt% and 31.5±4.4 wt% to the total SOA mass from the ozonolysis of α-pinene and OH oxidation of m-xylene. The influence of VOC precursors, seed particle acidity and gaseous NH3 concentration on the obtained uptake coefficients is described. The implications of the kinetics on atmospheric BrC and N-deposition are also discussed.

Adsorption of Cu(II), Hg(II), and Ni(II) ions by modified natural wool chelating fibers.

PubMed

Monier, M; Ayad, D M; Sarhan, A A

2010-04-15

The graft copolymerization of ethyl acrylate (EA) onto natural wool fibers initiated by potassium persulphate and Mohr's salt redox initiator system in limited aqueous medium was carried out in heterogeneous media. Ester groups of the grafted copolymers were partially converted into hydrazide function groups followed by hydrazone formation through reaction with isatin. Also the application of the modified fibers for metal ion uptake was studied using Cu(II), Hg(II) and Ni(II). The modified chelating fibers were characterized using FTIR spectroscopy, SEM and X-ray diffraction. 2009 Elsevier B.V. All rights reserved.

B-type natriuretic peptide expression and cardioprotection is regulated by Akt dependent signaling at early reperfusion.

PubMed

Breivik, L; Jensen, A; Guvåg, S; Aarnes, E K; Aspevik, A; Helgeland, E; Hovland, S; Brattelid, T; Jonassen, A K

2015-04-01

Exogenously administered B-type natriuretic peptide (BNP) has been shown to offer cardioprotection through activation of particulate guanylyl cyclase (pGC), protein kinase G (PKG) and KATP channel opening. The current study explores if cardioprotection afforded by short intermittent BNP administration involves PI3K/Akt/p70s6k dependent signaling, and whether this signaling pathway may participate in regulation of BNP mRNA expression at early reperfusion. Isolated Langendorff perfused rat hearts were subjected to 30min of regional ischemia and 120min of reperfusion (IR). Applying intermittent 3×30s infusion of BNP peptide in a postconditioning like manner (BNPPost) reduced infarct size by >50% compared to controls (BNPPost 17±2% vs. control 42±4%, p<0.001). Co-treatment with inhibitors of the PI3K/Akt/p70s6k pathway (wortmannin, SH-6 and rapamycin) completely abolished the infarct-limiting effect of BNP postconditioning (BNPPost+Wi 36±5%, BNPPost+SH-6 41±4%, BNPPost+Rap 37±6% vs. BNPPost 17±2%, p<0.001). Inhibition of natriuretic peptide receptors (NPR) by isatin also abrogated BNPPost cardioprotection (BNPPost+isatin 46±2% vs. BNPPost 17±2%, p<0.001). BNPPost also significantly phosphorylated Akt and p70s6k at early reperfusion, and Akt phosphorylation was inhibited by SH-6 and isatin. Myocardial BNP mRNA levels in the area at risk (AA) were significantly elevated at early reperfusion as compared to the non-ischemic area (ANA) (Ctr(AA) 2.7±0.5 vs. Ctr(ANA) 1.2±0.2, p<0.05) and the ischemic control tissue (Ctr(AA) 2.7±0.5 vs. ischemia 1.0±0.1, p<0.05). Additional experiments also revealed a significant higher BNP mRNA level in ischemic postconditioned (IPost) hearts as compared to ischemic controls (IPost 6.7±1.3 vs. ischemia 1.0±0.2, p<0.05), but showed no difference from controls run in parallel (Ctr 5.4±0.8). Akt inhibition by SH-6 completely abrogated this elevation (IPost 6.7±1.3 vs. IPost+SH-6 1.8±0.7, p<0.05) (Ctr 5.4±0.8 vs. SH-6 1.5±0.9, p<0.05). In conclusion, Akt dependent signaling is involved in mediating the cardioprotection afforded by intermittent BNP infusion at early reperfusion, and may also participate in regulation of reperfusion induced BNP expression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Biogenetically inspired approach to the Strychnos alkaloids. Concise syntheses of (+/-)-akuammicine and (+/-)-strychnine.

PubMed

Ito, M; Clark, C W; Mortimore, M; Goh, J B; Martin, S F

2001-08-22

A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was completed by a novel sequence of reactions requiring only 10 steps from commercially available starting materials. The approach features a tandem vinylogous Mannich addition and an intramolecular hetero Diels-Alder reaction to rapidly assemble the pentacyclic heteroyohimboid derivative 8 from the readily available hydrocarboline 6. Oxidation of the E ring of 8 gave the lactone 9 that was converted into deformylgeissoschizine (11). The subsequent elaboration of 11 into 2 was effected by a biomimetically patterned transformation that involved sequential oxidation and base-induced skeletal reorganization. A variation of these tactics was then applied to the synthesis of the C(18) hydroxylated akuammicine derivative 36. Because 36 had previously been converted into strychnine (1) in four steps, its preparation constitutes a concise, formal synthesis of this complex alkaloid.

Tetraalkylammonium Salts as Hydrogen-Bonding Catalysts.

PubMed

Shirakawa, Seiji; Liu, Shiyao; Kaneko, Shiho; Kumatabara, Yusuke; Fukuda, Airi; Omagari, Yumi; Maruoka, Keiji

2015-12-21

Although the hydrogen-bonding ability of the α hydrogen atoms on tetraalkylammonium salts is often discussed with respect to phase-transfer catalysts, catalysis that utilizes the hydrogen-bond-donor properties of tetraalkylammonium salts remains unknown. Herein, we demonstrate hydrogen-bonding catalysis with newly designed tetraalkylammonium salt catalysts in Mannich-type reactions. The structure and the hydrogen-bonding ability of the new ammonium salts were investigated by X-ray diffraction analysis and NMR titration studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pyrrolidine-mediated direct preparation of (e)-monoarylidene derivatives of homo- and heterocyclic ketones with various aldehydes.

PubMed

Gu, Xin; Wang, Xiaoyan; Wang, Fengtian; Sun, Hongbao; Liu, Jie; Xie, Yongmei; Xiang, Mingli

2014-02-12

An efficient method for the facile synthesis of (E)-monoarylidene derivatives of homo- and heterocyclic ketones with various aldehydes in the presence of a pyrrolidine organocatalyst has been achieved. A range of α,β-unsaturated ketones were obtained in moderate to high yields (up to 99%). Unlike the Claisen-Schmidt condensation process, the formation of undesired bisarylidene byproducts is not observed. The possible reaction mechanism suggests that the reaction proceeds via a Mannich-elimination sequence.

Coronary response to diadenosine tetraphosphate after ischemia-reperfusion in the isolated rat heart.

PubMed

García-Villalón, Angel Luis; Fernández, Nuria; Monge, Luis; Diéguez, Godofredo

2011-06-25

Diadenosine tetraphosphate (AP4A) is a vasoactive mediator that may be released from platelet granules and that may reach higher plasma concentrations during coronary ischemia-reperfusion. The objective of this study was to analyze its coronary effects in such conditions. To this, rat hearts were perfused in a Langendorff preparation and the coronary response to Ap4A (10(-7)-10(-5) M) was recorded. In control hearts, Ap4A produced concentration-dependent vasodilatation both at the basal coronary resting tone and after precontracting coronary vasculature with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F2α (U46619), and this vasodilatation was reduced by reactive blue 2 (2×10(-6) M), glibenclamide (10(-5) M), H89 (10(-6) M), U73122 (5×10(-6) M) and endothelin-1 (10(-9) M), but not by L-NAME (10(-4) M), isatin (10(-4) M), GF109203x (5×10(-7) M), or wortmannin (5×10(-7) M). After ischemia-reperfusion, the vasodilatation to Ap4A diminished, both in hearts with basal or increased vascular tone, and in this case the relaxation to Ap4A was not modified by reactive blue 2, L-NAME, glibenclamide, isatin, H89, GF109203x or wortmannin, although it was reduced by U73122 and endothelin-1. UTP produced coronary relaxation that was also reduced after ischemia-reperfusion. These results suggest that the coronary relaxation to Ap4A is reduced after ischemia-reperfusion, and that this reduction may be due to impaired effects of KATP channels and to reduced response of purinergic P2Y receptors. Copyright © 2011 Elsevier B.V. All rights reserved.

Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors.

PubMed

Hubálek, Frantisek; Binda, Claudia; Khalil, Ashraf; Li, Min; Mattevi, Andrea; Castagnoli, Neal; Edmondson, Dale E

2005-04-22

Several reversible inhibitors selective for human monoamine oxidase B (MAO B) that do not inhibit MAO A have been described in the literature. The following compounds: 8-(3-chlorostyryl)caffeine, 1,4-diphenyl-2-butene, and trans,trans-farnesol are shown to inhibit competitively human, horse, rat, and mouse MAO B with K(i) values in the low micromolar range but are without effect on either bovine or sheep MAO B or human MAO A. In contrast, the reversible competitive inhibitor isatin binds to all known MAO B and MAO A with similar affinities. Sequence alignments and the crystal structures of human MAO B in complex with 1,4-diphenyl-2-butene or with trans,trans-farnesol provide molecular insights into these specificities. These inhibitors span the substrate and entrance cavities with the side chain of Ile-199 rotated out of its normal conformation suggesting that Ile-199 is gating the substrate cavity. Ile-199 is conserved in all known MAO B sequences except bovine MAO B, which has Phe in this position (the sequence of sheep MAO B is unknown). Phe is conserved in the analogous position in MAO A sequences. The human MAO B I199F mutant protein of MAO B binds to isatin (K(i) = 3 microM) but not to the three inhibitors listed above. The crystal structure of this mutant demonstrates that the side chain of Phe-199 interferes with the binding of those compounds. This suggests that the Ile-199 "gate" is a determinant for the specificity of these MAO B inhibitors and provides a molecular basis for the development of MAO B-specific reversible inhibitors without interference with MAO A function in neurotransmitter metabolism.

Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression.

PubMed

Fogaça, Manoela Viar; Cândido-Bacani, Priscila de Matos; Benicio, Lucas Milanez; Zapata, Lara Martinelli; Cardoso, Priscilla de Freitas; de Oliveira, Marcelo Tempesta; Calvo, Tamara Regina; Varanda, Eliana Aparecida; Vilegas, Wagner; de Syllos Cólus, Ilce Mara

2017-12-01

Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN- and ISA-induced expression of ERCC1 or BAX genes. HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 μM) or ISA (0.5 to 50 μM). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD 50 - 1 g/kg b.w.) and submitted to comet assay in vivo. IRN reduced the viability of CHO-K1 (24 h; 5 to 200 μM) and HeLa cells (10 to 200 μM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 μM; HeLa: 5 and 10 μM). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations.

Ammonium chloride catalyzed synthesis of novel Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles and evaluation of their antimicrobial and anti-breast cancer activities.

PubMed

Al-Shareef, Hossa F; Elhady, Heba A; Aboellil, Amany H; Hussein, Essam M

2016-01-01

Indolinone and spiro-indoline derivatives have been employed in the preparation of different important therapeutic compounds required for treatment of anticonvulsants, antibacterial, Antitubercular, and anticancer activities. Schiff bases have been found to possess various pharmacological activities such as antitubercular, plant growth inhibiting, insecticsidal, central nerve system depressant, antibacterial, anticancer, anti-inflammatory, and antimicrobial. Mannich bases have a variety of biological activities such as antibacterial and antifungal activities. In this study, a green, rapid and efficient protocol for the synthesis of a new series of Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitrile derivatives using ammonium chloride as a very inexpensive and readily available reagent. The prepared compounds were assessed in vitro for their antimicrobial activity. Also, the cytotoxic activity of the prepared compounds was assessed in vitro against human cells line MCF7 breast cancer. Good activity was distinguished for Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles, with some members recorded higher antimicrobial and anti-breast cancer activities.Graphical abstractNovel Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles.

A Highly Stereocontrolled, One-Pot Approach toward Pyrrolobenzoxazinones and Pyrroloquinazolinones through a Lewis Acid-Catalyzed [3 + 2]-Cycloannulation Process.

PubMed

Boomhoff, Michael; Ukis, Rostyslav; Schneider, Christoph

2015-08-21

We report herein a stereocontrolled [3 + 2]-cycloheteroannulation of bis-silyl dienediolate 1 with 2-aminobenzoic acid- and 2-aminobenzamide-derived imines to furnish highly substituted pyrrolo[1,2-a]benzoxazinones 3 and pyrrolo[1,2-a]quinazolinones 4, respectively, in good overall yields. This one-pot process rapidly generates molecular complexity and comprises a Lewis acid-catalyzed, vinylogous Mannich reaction of 1 followed by an intramolecular N,O-acetal- and N,N-aminal formation, respectively, which proceeds with good to excellent stereocontrol.

Synthetic versatility of 2-substituted-6-methyl 2,3-dihydropyridinones in the synthesis of polyfunctional piperidine-based compounds and related β amino acid derivatives.

PubMed

Yang, Yang; Hardman, Clayton

2017-10-18

Chiral 2-substituted-6-methyl 2,3-dihydropyidinones 9, which can be facilely obtained from an asymmetric vinylogous Mannich reaction (VMR) with 1,3-bis-trimethysily enol ether, were used as versatile intermediates in constructing chiral polyfunctional piperidine-based compounds. The 6-methyl group of such compounds can be conveniently functionalized via alkylation and acylation reactions to provide efficient entries to the synthesis of a variety of chiral multi-substituted piperidine-based compounds. Further elaboration of the corresponding intermediates also provided access to polyfunctional indolizidine-based compounds. These methods were showcased in an asymmetric synthesis of 2,6-di-substituted piperidine compound 13, reported as the key intermediate in the synthesis of (+)-calvine and a natural alkaloid (-)-indolizidine 209D. Furthermore, selective C5 iodination of compound 9 enabled the installation of additional functional groups at this position. Finally, we demonstrated that the oxidative cleavage of 2-substituted-6-methyl-2,3-dihydropyidinones is a practical and efficient method for the enantioselective synthesis of β-amino acids, which can undergo further intra-molecular cyclization to give the corresponding chiral four-membered β-lactam derivatives.

The molecular structure of 5-X-isatines where (X = F, Cl, and Br) determined by gas-phase electron diffraction with theoretical calculations

NASA Astrophysics Data System (ADS)

Belyakov, Alexander V.; Nikolaenko, Kirill O.; Davidovich, Pavel B.; Ivanov, Anatolii D.; Ponyaev, Alexander I.; Rykov, Anatolii N.; Shishkov, Igor F.

2018-01-01

The molecular structures of 5-X-isatines where X = F (1), Cl (2), and Br (3) were studied by gas-phase electron diffraction (GED) and theoretical calculations at M062X/aug-cc-pVTZ and MP2/aug-cc-pVTZ levels. The best fit of the experimental scattering intensities was obtained for a molecular model of Cs symmetry. The small differences between similar geometric parameters were constrained at the values calculated at the M062X level. The bond distances in the benzene ring are in agreement with their standard values. The (Odbnd)Csbnd C(dbnd O) carbon-carbon bonds of the pyrrole moiety in title compounds (1.581(11), 1.578(8), 1.574(12) Å, respectively) are remarkably lengthened in comparison with standard C(sp2)-C(sp2) value, 1.425(11) Å for N-methylpyrrole. According to NBO analysis this lengthening cannot be attributed to the electrostatic repulsion of oxygen lone pairs alone and is, mainly, due to the hyperconjugation, that is delocalization of oxygen lone pairs of π-type into the corresponding carbon-carbon antibonding orbital, nπ(O)→σ*(Csbnd C). Deletion of σ*(Csbnd C) orbital followed by subsequent geometry optimization led to shortening of the corresponding Csbnd C bond by 0.05-0.06 Å. Electronegative halogen atoms led to increase of Csbnd CXsbnd C endocyclic bond angles at ipso carbon atom as compared with the value of 120° in regular hexagon. According to different aromaticity descriptors, aromaticity of benzene moiety of title compounds is smaller in comparison with benzene molecule. External magnetic field induces diatropic ring current in benzene moiety. Local reactivity descriptors that indicate sites in a molecule that are susceptible to nucleophilic, electrophilic and radical attack are calculated.

Design, synthesis and fluorescence property evaluation of blue emitting triazole-linked chromene peptidomimetics.

PubMed

Mohan, T Jency; Bahulayan, D

2017-08-01

A highly efficient "Click with MCR" strategy for the three-step synthesis of two types of blue emitting chromene peptidomimetics is described. The peptidomimetics were synthesized via a copper-catalyzed [3[Formula: see text]2] azide-alkyne cycloaddition between chromene alkynes obtained from a three-component reaction and the peptide azides obtained from Ugi or Mannich type multicomponent reactions. The photophysical properties of the peptidomimetics are comparable with commercial fluorophores. Computational studies using drug property descriptors support the possibility of using these molecules for modulating difficult target classes having large, flat, and groove-shaped binding sites.

Detailed solvent, structural, quantum chemical study and antimicrobial activity of isatin Schiff base

NASA Astrophysics Data System (ADS)

Brkić, Dominik R.; Božić, Aleksandra R.; Marinković, Aleksandar D.; Milčić, Miloš K.; Prlainović, Nevena Ž.; Assaleh, Fathi H.; Cvijetić, Ilija N.; Nikolić, Jasmina B.; Drmanić, Saša Ž.

2018-05-01

The ratios of E/Z isomers of sixteen synthesized 1,3-dihydro-3-(substituted phenylimino)-2H-indol-2-one were studied using experimental and theoretical methodology. Linear solvation energy relationships (LSER) rationalized solvent influence of the solvent-solute interactions on the UV-Vis absorption maxima shifts (νmax) of both geometrical isomers using the Kamlet-Taft equation. Linear free energy relationships (LFER) in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on pKa, NMR chemical shifts and νmax values. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. The substituent and solvent effect on intramolecular charge transfer (ICT) were interpreted with the aid of time-dependent density functional (TD-DFT) method. Additionally, the results of TD-DFT calculations quantified the efficiency of ICT from the calculated charge-transfer distance (DCT) and amount of transferred charge (QCT). The antimicrobial activity was evaluated using broth microdilution method. 3D QSAR modeling was used to demonstrate the influence of substituents effect as well as molecule geometry on antimicrobial activity.

Biodegradation of indole at high concentration by persolvent fermentation with Pseudomonas sp. ST-200.

PubMed

Doukyu, N; Aono, R

1997-05-01

Pseudomonas sp. strain ST-200 grew on indole as a sole carbon source. The minimal inhibitory concentration of indole was 0.3 mg/ml for ST-200. However, ST-200 grew in a persolvent fermentation system containing a large amount of indole (a medium containing 20% by vol. diphenylmethane and 4 mg/ml indole), because most of the indole was partitioned in the organic solvent layer. When the organism was grown in the medium containing indole at 1 mg/ml in the presence of diphenylmethane, more than 98% of the indole was consumed after 48h. Isatic acid (0.4 mg/ml) and isatin (0.03 mg/ml) were produced as the metabolites in the aqueous medium layer.

Practical synthesis, anticonvulsant, and antimicrobial activity of N-allyl and N-propargyl di(indolyl)indolin-2-ones.

PubMed

Praveen, Chandrasekaran; Ayyanar, Asairajan; Perumal, Paramasivan Thirumalai

2011-07-01

An operation friendly protocol for the synthesis of novel di(indolyl)indolin-2-ones via Cu(OTf)(2) catalyzed bis-addition of N-allyl and N-propargyl indole with isatin was developed. This methodology allowed us to achieve the products in excellent yields without requiring purification technique like column chromatography. All the synthesized compounds were evaluated for their in vivo anticonvulsant activity against maximal electroshock test. Six compounds showed maximum activity compared to the standard drug phenytoin. The scope of the new molecules as antimicrobial agents were tested against two bacterial strains (Staphylococcus aureus and Escherichia coli) and one fungal strain (Candida albicans). Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthesis, spectroscopic characterization, DFT study and antimicrobial activity of novel alkylaminopyrazole derivatives

NASA Astrophysics Data System (ADS)

Zalaru, Christina; Dumitrascu, Florea; Draghici, Constantin; Tarcomnicu, Isabela; Tatia, Rodica; Moldovan, Lucia; Chifiriuc, Mariana-Carmen; Lazar, Veronica; Marinescu, Maria; Nitulescu, Mihai George; Ferbinteanu, Marilena

2018-03-01

A new series of substituted N,N-bis-[(1H-pyrazol-1-yl)methyl]-aminohexadecane Mannich bases were synthesized, characterized by IR, 1H NMR 13C NMR, UV-Vis, MS and elemental analysis, and tested for their biological activity. All the synthesized compounds were tested for in vitro antimicrobial activity against a panel of selected bacterial and fungal strains using erythromycin and clotrimazole as standards. Most of the synthesized compounds demonstrated very good activity at minimum inhibitory concentrations (MICs). Compound 3b with an halogen atom into the pharmacophore structure exhibited the most significant activity against Bacillus subtilis (MIC = 0.007 μgmLL-1) versus erythromycin as standard. In vitro cytotoxicity of the new compounds was studied using MTT assay. The analysis of the test cells showed that the newly synthesized alkylaminopyrazoles derivatives were biocompatible until a concentration of 5 μgmL-1; two compounds presented a high degree of biocompatibility on the studied concentration range.

Synthesis of NMP, a Fluoxetine (Prozac) Precursor, in the Introductory Organic Laboratory

NASA Astrophysics Data System (ADS)

Perrine, Daniel M.; Sabanayagam, Nathan R.; Reynolds, Kristy J.

1998-10-01

A synthesis of the immediate precursor of the widely used antidepressant fluoxetine (Prozac) is described. The procedure is short, safe, and simple enough to serve as a laboratory exercise for undergraduate students in the second semester of introductory organic chemistry and is one which will be particularly interesting to those planning a career in the health sciences. The compound synthesized is (°)-N,N-dimethyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine, or "N-methyl Prozac" (NMP). The synthesis of NMP requires one two-hour period and a second three-hour period. In the first period, a common Mannich base, 3-dimethylaminopropiophenone, is reduced with sodium borohydride to form (°)-3-dimethylamino-1-phenylpropanol. In the second period, potassium t-butoxide is used to couple (°)-3-dimethylamino-1-phenylpropanol with p-chlorotrifluoromethylbenzene to form NMP, which is isolated as its oxalate salt. All processes use equipment and materials that are inexpensive and readily available in most undergraduate laboratories. Detailed physical data are given on NMP, including high-field DEPT 13C NMR.

Enantioselective Synthesis of SNAP-7941

PubMed Central

Goss, Jennifer M.; Schaus, Scott E.

2009-01-01

An enantioselective synthesis of SNAP-7941, a potent melanin concentrating hormone receptor antagonist, was achieved using two organocatalytic methods. The first method utilized to synthesize the enantioenriched dihydropyrimidone core was the Cinchona alkaloid-catalyzed Mannich reaction of β-keto esters to acyl imines and the second was chiral phosphoric acid-catalyzed Biginelli reaction. Completion of the synthesis was accomplished via selective urea formation at the N3 position of the dihydropyrimidone with the 3-(4-phenylpiperidin-1-yl)propyl amine side chain fragment. The synthesis of SNAP-7921 highlights the utility of asymmetric organocatalytic methods in the construction of an important class of chiral heterocycles. PMID:18767801

Concise Syntheses of bis-Strychnos Alkaloids (-)-Sungucine, (-)-Isosungucine, and (-)-Strychnogucine B from (-)-Strychnine.

PubMed

Zhao, Senzhi; Teijaro, Christiana N; Chen, Heng; Sirasani, Gopal; Vaddypally, Shivaiah; Zdilla, Michael J; Dobereiner, Graham E; Andrade, Rodrigo B

2016-08-08

The first chemical syntheses of complex, bis-Strychnos alkaloids (-)-sungucine (1), (-)-isosungucine (2), and (-)-strychnogucine B (3) from (-)-strychnine (4) is reported. Key steps included (1) the Polonovski-Potier activation of strychnine N-oxide; (2) a biomimetic Mannich coupling to forge the signature C23-C5' bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH3 CN-mediated reduction to fashion the ethylidene moieties in 1-3. DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

α-Imino Esters in Organic Synthesis: Recent Advances.

PubMed

Eftekhari-Sis, Bagher; Zirak, Maryam

2017-06-28

α-Imino esters are useful precursors for the synthesis of a variety of types of natural and unnatural α-amino acid derivatives, with a wide range of biological activities. Due to the adjacent ester group, α-imino esters are more reactive relative to other types of imines and undergo different kinds of reactions, including organometallics addition, metal catalyzed vinylation and alkynylation, aza-Henry, aza-Morita-Baylis-Hillman, imino-ene, Mannich-type, and cycloaddition reactions, as well as hydrogenation and reduction. This review discusses the mechanism, scope, and applications of the reactions of α-imino esters and related compounds in organic synthesis, covering the literature from the last 12 years.

Synthesis of novel 16-spiro steroids: 7-(Aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo estrone hybrid heterocycles.

PubMed

Jeyachandran, Veerappan; Vivek Kumar, Sundaravel; Ranjith Kumar, Raju

2014-04-01

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of isatins or acenaphthylene-1,2-dione and 1,3-thiazolane-4-carboxylic acid to various exocyclic dipolarophiles synthesized from estrone afforded a library of novel C-16 spiro oxindole or acenaphthylene-1-one - 7-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole - estrone hybrid heterocycles. These reactions occur regio- and stereo-selectively affording a single isomer of the spiro estrones in excellent yields with the formation of two C-C and one C-N bonds along with the generation of four new contiguous stereo-centers in a single step. Copyright © 2014 Elsevier Inc. All rights reserved.

Photophysical study of some 3-benzoylmethyleneindol-2-ones and estimation of ground and excited states dipole moments from solvatochromic methods using solvent polarity parameters

NASA Astrophysics Data System (ADS)

Saroj, Manju K.; Sharma, Neera; Rastogi, Ramesh C.

2012-03-01

3-Benzoylmethyleneindol-2-ones, isatin based chalcones containing donor and acceptor moieties that exhibit excited-state intramolecular charge transfer, have been studied in different solvents by absorption and emission spectroscopy. The excited state behavior of these compounds is strongly dependent on the nature of substituents and the environment. These compounds show multiple emissions arising from a locally excited state and the two states due to intramolecular processes viz. intramolecular charge transfer (ICT) and excited state intramolecular proton transfer (ESIPT). Excited-state dipole moments have been calculated using Stoke-shifts of LE and ICT states using solvatochromic methods. The higher values of dipole moments obtained lead to support the formation of ICT state as one of the prominent species in the excited states of all 3-benzoylmethyleneindol-2-ones. The correlation of the solvatochromic Stokes-shifts with the microscopic solvent polarity parameter (ETN) was found to be superior to that obtained using bulk solvent polarity functions. The absorption and florescence spectral characteristics have been also investigated as a function of acidity and basicity (Ho/pH) in aqueous phase.

Enantioselective Bronsted Acid Catalysis with Chiral Pentacarboxycyclopentadienes

NASA Astrophysics Data System (ADS)

Gheewala, Chirag

This thesis details the design and development of pentacarboxycyclopentadienes (PCCPs) as a new platform for enantioselective Bronsted acid catalysis. Prior to this research, enantioselective Bronsted acid catalysis was limited to the BINOL (and variations thereof) framework. While this catalyst platform has paved the way for a myriad of novel asymmetric chemical transformations, the utility of this catalyst scaffold has suffered from its lengthy and expensive preparations. As an alternative, starting from readily available 1,2,3,4,5-pentacarbomethoxycyclopentadiene and various chiral alcohols and amines, the synthesis of a library of strongly acidic chiral catalysts is described. The utility of these novel acid catalysts is explored in various transformations. As a prelude to the heart of this work, Chapter 1 focuses on the advancements made in asymmetric Bronsted acid catalysis through BINOL-phosphate derived catalysts, focusing on the major accomplishments made by researchers since 2004. The provided review highlights the utility of these chiral acid catalysts but also reveals the need for a new scaffold that is more affordable and accessible. Chapter 2 discusses the background of PCCPs, including its initial discovery and subsequent applications. Our work in developing novel transesterified and amidated derivatives is discussed with accompanying crystal structures of achiral and chiral PCCPs. pKa measurements demonstrate the capacity of PCCPs to be used as strong Bronsted acid catalysts and are compared to literature values of known Bronsted acid catalysts. Chapter 3 focuses on the utility of PCCPs as enantioselective Bronsted acid catalysts in a variety of chemical transformations including the Mukaiyama-Mannich reaction, transfer hydrogenation, Pictet-Spengler reaction, diaryl alcohol substitution, Mukayaiama oxocarbenium aldol reaction, and [4+2]-cycloaddition. Catalyst loadings down to 0.01 mol% and reaction scale up to 25 grams in the Mukaiyama-Mannich reaction demonstrate the practical utility and robustness of PCCPs. Substrate scopes of these transformations show the breadth of accessible molecules that can be synthesized via PCCPs. Mechanistic rationales and transition state analyses are discussed in each of the transformations.

Immunoenzyme assay of nonylphenol: study of selectivity and detection of alkylphenolic non-ionic surfactants in water samples.

PubMed

Mart'ianov, Andrey A; Dzantiev, Boris B; Zherdev, Anatoly V; Eremin, Sergei A; Cespedes, Raquel; Petrovic, Mira; Barcelo, Damia

2005-01-30

Immunoenzyme assay (ELISA) is proposed and characterized for determination of alkylphenol ethoxylates, a primary class of manufactured non-ionic surfactants. The assay is based on the obtained polyclonal antibodies against nonylphenol (NP), the main stable intermediate of the decomposition of nonylphenol ethoxylates. A mixture of non-modified branched isomers of NP was applied as hapten coupled to protein carriers by Mannich reaction with the use of formaldehyde. The proposed ELISA format is based on immobilized NP-(soybean trypsin inhibitor) conjugate as a competitor of antigen molecules contained in the tested sample for binding with specific antibodies indirectly labeled via an anti-species immunoperoxidase conjugate. The developed ELISA allows to reveal NP with the limit of detection about 10ngml(-1) and NP-related compounds such as octylphenol, alkylphenoletoxylates, alkylphenolcarboxylates and their halogenated derivatives. The ELISA was applied for assaying polluted water samples, namely influents and effluents from different wastewater treatment plants (WWTP) and tap water. ELISA and chromatographic data demonstrate good correlation (r = 0.94), while ELISA gives higher values. Due to endocrine disrupting and other toxic activities of some metabolites of alkylphenolic non-ionic surfactants, the developed assay may be effectively used in ecological monitoring and sanitary control.

Radioimmunoassay of vinblastine and vincristine.

PubMed Central

Teale, J D; Clough, J M; Marks, V

1977-01-01

1 The cytotoxic agent, vinblastine, was conjugated to albumin, using the Mannich reaction. Rabbits immunized with two conjugates, containing differing amounts of hapten, produce antibodies which bound [3H]-vinblastine. 2 Antisera from one rabbit cross-reacted with both vinblastine and vincristine and were used to develop radioimmunoassays for measuring their concentration in plasma. 3 The antisera showed no cross-reactivity with other alkaloids or cytotoxic drugs and provided assays sensitive to a concentration of 2.1 ng vinblastine or 3.8 ng vincristine/ml of plasma added direct to the assay tubes. 4 This is sufficiently sensitive to permit the measurement of plasma vinblastine levels for up to 24 h after the intravenous administration of 15 mg of the drug. PMID:558786

Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates

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

Katz, Francine S.; Pecic, Stevan; Tran, Timothy H.

Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups—Mannich phenols and general bases—that are capable of reactivating OPC-inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data,more » significantly broaden the available approaches for reactivation of AChE.« less

Titanocene(III)-Catalyzed Three-Component Reaction of Secondary Amides, Aldehydes, and Electrophilic Alkenes.

PubMed

Zheng, Xiao; He, Jiang; Li, Heng-Hui; Wang, Ao; Dai, Xi-Jie; Wang, Ai-E; Huang, Pei-Qiang

2015-11-09

An umpolung Mannich-type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one-pot formation of C-N and C-C bonds by a titanocene-catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N-substituted γ-amido-acid derivatives and γ-amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α-amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SYNTHESIS AND BIOLOGICAL EVALUATION OF N-(SUBSTITUTED PHENYL)-2-(5H-[1,2,4]TRIAZINO[5,6-b]INDOL-3-YLSULFANYL)ACETAMIDES AS ANTIMICROBIAL, ANTIDEPRESSANT AND ANTICONVULSANT AGENTS.

PubMed

Shruthi, N; Poojary, Boja; Kumar, Vasantha; Prathibha, A; Hussain, Mumtaz Mohammed; Revanasiddappa, B C; Joshi, Himanshu

2015-01-01

A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtained by condensation of Isatin with thiosemicarbazide. Chloro N-phenylacetamides were obtained from different substituted anilines. Their structures were characterized by IR, 1H NMR, LC-MS and elemental analyses. Newly synthesized compounds were screened for antimicrobial, antidepressant and anticonvulsant activities. Preliminary results indicated that most of the compounds showed lesser MIC value than the standard drug used when tested for antimicrobial activity. Some of the compounds were endowed with very good antidepressant and anticonvulsant activity.

Chemical oxidation of a malodorous compound, indole, using iron entrapped in calcium alginate beads.

PubMed

Ben Hammouda, Samia; Adhoum, Nafaâ; Monser, Lotfi

2016-01-15

Iron-alginate beads (Fe-ABs) were successfully prepared by the ion-gelation method, and applied as heterogeneous Fenton catalysts for the removal of a malodorous compound 'indole'. Similarly, copper-enriched alginate beads (Cu-ABs) were synthesized and tested as like-Fenton catalyst, however, their application proved not to be effective for this purpose. Fe-ABs catalysts were characterized by FTIR, SEM, EDS and AAS spectroscopy. Results pointed out that the parameters affecting Fenton catalysis must be carefully chosen to avoid excessive iron release. Under optimal conditions, complete indole removal and considerably high reduction of TOC, without significant leaching was achieved. Indole decay followed a pseudo-first-order kinetics. The absolute rate constant for indole hydroxylation was 3.59×10(9) M(-1) s(-1), as determined by the competition kinetics method. Four reaction intermediates (Isatin, Dioxindole, Oxindole and Anthralinic acid) were identified by ULC/MS/MS analysis. Short-chain aliphatic carboxylic acids like formic, acetic, oxalic, maleic, oxamic and pyruvic acids were identified by ion exclusion chromatography and as end-products. Based on the identified by-products, a plausible mineralization pathway was proposed. Moreover, the catalyst was recovered quantitatively by simple filtration and reused for several times without significant loss of activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Indole, a Signaling Molecule Produced by the Gut Microbiota, Negatively Impacts Emotional Behaviors in Rats

PubMed Central

Jaglin, Mathilde; Rhimi, Moez; Philippe, Catherine; Pons, Nicolas; Bruneau, Aurélia; Goustard, Bénédicte; Daugé, Valérie; Maguin, Emmanuelle; Naudon, Laurent; Rabot, Sylvie

2018-01-01

Gut microbiota produces a wide and diverse array of metabolites that are an integral part of the host metabolome. The emergence of the gut microbiome-brain axis concept has prompted investigations on the role of gut microbiota dysbioses in the pathophysiology of brain diseases. Specifically, the search for microbe-related metabolomic signatures in human patients and animal models of psychiatric disorders has pointed out the importance of the microbial metabolism of aromatic amino acids. Here, we investigated the effect of indole on brain and behavior in rats. Indole is produced by gut microbiota from tryptophan, through the tryptophanase enzyme encoded by the tnaA gene. First, we mimicked an acute and high overproduction of indole by injecting this compound in the cecum of conventional rats. This treatment led to a dramatic decrease of motor activity. The neurodepressant oxidized derivatives of indole, oxindole and isatin, accumulated in the brain. In addition, increase in eye blinking frequency and in c-Fos protein expression in the dorsal vagal complex denoted a vagus nerve activation. Second, we mimicked a chronic and moderate overproduction of indole by colonizing germ-free rats with the indole-producing bacterial species Escherichia coli. We compared emotional behaviors of these rats with those of germ-free rats colonized with a genetically-engineered counterpart strain unable to produce indole. Rats overproducing indole displayed higher helplessness in the tail suspension test, and enhanced anxiety-like behavior in the novelty, elevated plus maze and open-field tests. Vagus nerve activation was suggested by an increase in eye blinking frequency. However, unlike the conventional rats dosed with a high amount of indole, the motor activity was not altered and neither oxindole nor isatin could be detected in the brain. Further studies are required for a comprehensive understanding of the mechanisms supporting indole effects on emotional behaviors. As our findings suggest that people whose gut microbiota is highly prone to produce indole could be more likely to develop anxiety and mood disorders, we addressed the issue of the inter-individual variability of indole producing potential in humans. An in silico investigation of metagenomic data focused on the tnaA gene products definitively proved this inter-individual variability. PMID:29686603

Modern Approaches for Asymmetric Construction of Carbon-Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs.

PubMed

Zhu, Yi; Han, Jianlin; Wang, Jiandong; Shibata, Norio; Sodeoka, Mikiko; Soloshonok, Vadim A; Coelho, Jaime A S; Toste, F Dean

2018-04-11

New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand in nearly every sector of chemical industry. The asymmetric construction of quaternary C-F stereogenic centers is the most synthetically challenging and, consequently, the least developed area of research. As a reflection of this apparent methodological deficit, pharmaceutical drugs featuring C-F stereogenic centers constitute less than 1% of all fluorine-containing medicines currently on the market or in clinical development. Here we provide a comprehensive review of current research activity in this area, including such general directions as asymmetric electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, asymmetric elaboration of fluorine-containing substrates via alkylations, Mannich, Michael, and aldol additions, cross-coupling reactions, and biocatalytic approaches.

Synthesis, Antiinflammatory and Antimicrobial Activity of Some New 1-(3-Phenyl-3,4-Dihydro-2H-1,3-Benzoxazin-6-yl)-Ethanone Derivatives.

PubMed

Akhter, Mymoona; Husain, A; Akhter, N; Khan, M S Y

2011-01-01

Synthesis of title compounds (4a-j) was carried out by following aminomethylation Mannich reaction. Test compounds were effective in inhibiting edema induced by carrageenan. The percent inhibition obseved was in the range of 25-83.3%. Compound (4c, e, h and j) were also tested for analgesic effect and showed percent protection ranging between 57-65%. All the synthesized compounds were active against E. coli and S. aureus but only compounds (4 b, c, e, i and j) were active against B. subtilis. All these compound were also found active against A. niger. Compound 4j was the most active compound with 83.3% inhibition of edema, 65.35% percent protection and inhibited all the three bacterial strains.

Enantioselective synthesis of pactamycin, a complex antitumor antibiotic.

PubMed

Malinowski, Justin T; Sharpe, Robert J; Johnson, Jeffrey S

2013-04-12

Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties across multiple phylogenetic domains, but it is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Here, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction and symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals 15 steps and is immediately amenable for structural analog synthesis.

Anthracycline-Formaldehyde Conjugates and Their Targeted Prodrugs

NASA Astrophysics Data System (ADS)

Koch, Tad H.; Barthel, Benjamin L.; Kalet, Brian T.; Rudnicki, Daniel L.; Post, Glen C.; Burkhart, David J.

The sequence of research leading to a proposal for anthracycline cross-linking of DNA is presented. The clinical anthracycline antitumor drugs are anthraquinones, and as such are redox active. Their redox chemistry leads to induction of oxidative stress and drug metabolites. An intermediate in reductive glycosidic cleavage is a quinone methide, once proposed as an alkylating agent of DNA. Subsequent research now implicates formaldehyde as a mediator of anthracycline-DNA cross-linking. The cross-link at 5'-GC-3' sites consists of a covalent linkage from the amino group of the anthracycline to the 2-amino group of the G-base through a methylene from formaldehyde, hydrogen bonding from the 9-OH to the G-base on the opposing strand, and hydrophobic interactions through intercalation of the anthraquinone. The combination of these interactions has been described as a virtual cross-link of DNA. The origin of the formaldehyde in vivo remains a mystery. In vitro, doxorubicin reacts with formaldehyde to give firstly a monomeric oxazolidine, doxazolidine, and secondly a dimeric oxazolidine, doxoform. Doxorubicin reacts with formaldehyde in the presence of salicylamide to give the N-Mannich base conjugate, doxsaliform. Doxsaliform is several fold more active in tumor cell growth inhibition than doxorubicin, but doxazolidine and doxoform are orders of magnitude more active than doxorubicin. Exploratory research on the potential for doxsaliform and doxazolidine as targeted cytotoxins is presented. A promising lead design is pentyl PABC-Doxaz, targeted to a carboxylesterase enzyme overexpressed in liver cancer cells and/or colon cancer cells.

Exploring the Chemistry of Bicyclic Isoxazolidines for the Multicomponent Synthesis of Glycomimetic Building Blocks.

PubMed

Hoogenboom, Jorin; Lutz, Martin; Zuilhof, Han; Wennekes, Tom

2016-10-07

Starting from a chiral furanone, the nitrone-olefin [3 + 2] cycloaddition can be used to obtain bicyclic isoxazolidines for which we report a set of reactions to selectively modify each functional position. These synthetically versatile bicyclic isoxazolidines allowed us to obtain complex glycomimetic building blocks, like iminosugars, via multicomponent chemistry. For example, a library of 20 pipecolic acid derivatives, a recurring motif in various prescription drugs, could be obtained via a one-pot Staudinger/aza-Wittig/Ugi three-component reaction of a bicyclic isoxazolidine-derived azido-hemiacetal. Notably, specific pipecolic acids in this library were obtained via hydrolysis of an unique tricyclic imidate side product of the Ugi reaction. The azido-hemiacetal was also converted into an aza-C-glycoside iminosugar via an unprecendented one-pot Staudinger/aza-Wittig/Mannich reaction.

The synthesis, antimalarial activity and CoMFA analysis of novel aminoalkylated quercetin analogs.

PubMed

Helgren, Travis R; Sciotti, Richard J; Lee, Patricia; Duffy, Sandra; Avery, Vicky M; Igbinoba, Osayawemwen; Akoto, Matthew; Hagen, Timothy J

2015-01-15

A series of novel aminoalkylated quercetin analogs, prepared via the Mannich reaction of various primary and secondary amines with formaldehyde, were tested for antimalarial activity. The compounds were screened against three drug resistant malarial strains (D6, C235 and W2) and were found to exhibit sub-micromolar activity across all three strains (0.065-13.0μM). The structure-activity relationship determined from the antimalarial activity data suggests the inclusion of phenethyl amine sidechains on the quercetin scaffolding is necessary for potent activity. Additionally, the most active compounds ((5) and (6)) were tested for both early and late stage anti-gametocytocidal activity. Finally, the antimalarial activity data were utilized to construct comparative molecular field analysis (CoMFA) models to be used for further compound refinement. Copyright © 2014 Elqsevier Ltd. All rights reserved.

Synthesis, Antiinflammatory and Antimicrobial Activity of Some New 1-(3-Phenyl-3,4-Dihydro-2H-1,3-Benzoxazin-6-yl)-Ethanone Derivatives

PubMed Central

Akhter, Mymoona; Husain, A.; Akhter, N.; Khan, M. S. Y

2011-01-01

Synthesis of title compounds (4a-j) was carried out by following aminomethylation Mannich reaction. Test compounds were effective in inhibiting edema induced by carrageenan. The percent inhibition obseved was in the range of 25-83.3%. Compound (4c, e, h and j) were also tested for analgesic effect and showed percent protection ranging between 57-65%. All the synthesized compounds were active against E. coli and S. aureus but only compounds (4 b, c, e, i and j) were active against B. subtilis. All these compound were also found active against A. niger. Compound 4j was the most active compound with 83.3% inhibition of edema, 65.35% percent protection and inhibited all the three bacterial strains. PMID:22131632

New spiro-oxindole constructed with pyrrolidine/thioxothiazolidin-4-one derivatives: Regioselective synthesis, X-ray crystal structures, Hirshfeld surface analysis, DFT, docking and antimicrobial studies

NASA Astrophysics Data System (ADS)

Barakat, Assem; Soliman, Saied M.; Al-Majid, Abdullah Mohammed; Ali, M.; Islam, Mohammad Shahidul; Elshaier, Yaseen A. M. M.; Ghabbour, Hazem A.

2018-01-01

In this work, polycyclic heterocycles containing spirooxindole, pyrrolidine, and thioxothiazolidin-4-one rings have been synthesized via the regioselective 1,3-dipolar cycloaddition of azomethine ylide, which is generated in situ by the condensation of the dicarbonyl compound isatin and the secondary amino acid (L-proline), with 5-arylidine-2-thioxothiazolidin-4-one as the dipolarophile. The structure of the synthesized compounds 4a and 4b were determined by using X-ray single crystal diffraction, and also, Hirshfeld surface analysis were reported. Their geometric parameters were calculated using density functional theory at the B3LYP/6-311G (d,p) level of theory. Both compounds showed antimicrobial and antifungal activity better than selected standards (ampicillin and gentamicin in case of antibacterial activity and Amphotericin A and fluconazole in case of antifungal activity). Molecular docking study of the synthesized compounds indicated that phenyl group plays an important role in determination of compound interaction inside the receptors.

Density functional theory molecular modeling, chemical synthesis, and antimicrobial behaviour of selected benzimidazole derivatives

NASA Astrophysics Data System (ADS)

Marinescu, Maria; Tudorache, Diana Gabriela; Marton, George Iuliu; Zalaru, Christina-Marie; Popa, Marcela; Chifiriuc, Mariana-Carmen; Stavarache, Cristina-Elena; Constantinescu, Catalin

2017-02-01

Eco-friendly, one-pot, solvent-free synthesis of biologically active 2-substituted benzimidazoles is presented and discussed herein. Novel N-Mannich bases are synthesized from benzimidazoles, secondary amines and formaldehyde, and their structures are confirmed by 1H nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), and elemental analysis. All benzimidazole derivatives are evaluated by qualitative and quantitative methods against 9 bacterial strains. The largest microbicide and anti-biofilm effect is observed for the 2-(1-hydroxyethyl)-compounds. Density functional theory (DFT) modeling of the molecular structure and frontier molecular orbitals, i.e. highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO/LUMO), is accomplished by using the GAMESS 2012 software. Antimicrobial activity is correlated with the electronic parameters (chemical hardness, electronic chemical potential, global electrophilicity index), Mullikan atomic charges and geometric parameters of the benzimidazole compounds. The planarity of the compound, symmetry of the molecule, and the presence of a nucleophilic group, are advantages for a high antimicrobial activity. Finally, we briefly show that further accurate processing of such compounds into thin films and hybrid structures, e.g. by laser ablation matrix-assisted pulsed laser evaporation and/or laser-induced forward transfer, may indeed provide simple and environmental friendly, state-of-the-art solutions for antimicrobial coatings.

Molecular docking and molecular dynamics simulation analyses of urea with ammoniated and ammoxidized lignin.

PubMed

Li, Wenzhuo; Zhang, Song; Zhao, Yingying; Huang, Shuaiyu; Zhao, Jiangshan

2017-01-01

Ammoniated lignin, prepared through the Mannich reaction of lignin, has more advantages as a slow-release carrier of urea molecules than ammoxidized lignin and lignin. The advantages of the ammoniated lignin include its amine groups added and its high molecular mass kept as similar as that of lignin. Three organic molecules including guaiacyl, 2-hydroxybenzylamine and 5-carbamoylpentanoic acid are monomers respectively in lignin, ammoniated lignin and ammoxidized lignin. We studied the difference between the interactions of lignin, ammoniated lignin and ammoxidized lignin with respect to urea, based on radial distribution functions (RDFs) results from molecular dynamics (MD) simulations. Glass transition temperature (T g ) and solubility parameter (δ) of ammoniated and ammoxidized lignin have been calculated by MD simulations in the constant-temperature and constant-pressure ensemble (NPT). Molecular docking results showed the interaction sites of the urea onto the ammoniated and ammoxidized lignin and three different interaction modes were identified. Root mean square deviation (RMSD) values could indicate the mobilities of the urea molecule affected by the three different interaction modes. A series of MD simulations in the constant-temperature and constant-volume ensemble (NVT) helped us to calculate the diffusivity of urea which was affected by the content of urea in ammoniated and ammoxidized lignin. Copyright © 2016 Elsevier Inc. All rights reserved.

The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo

PubMed Central

Hackler, László; Ózsvári, Béla; Gyuris, Márió; Sipos, Péter; Fábián, Gabriella; Molnár, Eszter; Marton, Annamária; Faragó, Nóra; Mihály, József; Nagy, Lajos István; Szénási, Tibor; Diron, Andrea; Párducz, Árpád; Kanizsai, Iván; Puskás, László G.

2016-01-01

C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis model. C-150 reduced the number of tumors in Drosophila with similar efficacy to mitoxantrone. In an in vivo orthotopic glioma model, C-150 significantly increased the median survival of treated nude rats compared to control animals. The multi-target action of C-150, and its preliminary in vivo efficacy would render this curcumin analogue as a potent clinical candidate against glioblastoma. PMID:26943907

The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo.

PubMed

Hackler, László; Ózsvári, Béla; Gyuris, Márió; Sipos, Péter; Fábián, Gabriella; Molnár, Eszter; Marton, Annamária; Faragó, Nóra; Mihály, József; Nagy, Lajos István; Szénási, Tibor; Diron, Andrea; Párducz, Árpád; Kanizsai, Iván; Puskás, László G

2016-01-01

C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis model. C-150 reduced the number of tumors in Drosophila with similar efficacy to mitoxantrone. In an in vivo orthotopic glioma model, C-150 significantly increased the median survival of treated nude rats compared to control animals. The multi-target action of C-150, and its preliminary in vivo efficacy would render this curcumin analogue as a potent clinical candidate against glioblastoma.

Amination of black liquor and the application in the ready-mixed wet mortar.

PubMed

Zheng, Dafeng; Zheng, Tao; Chen, Ran; Li, Xiaokang; Qiu, Xueqing

2018-01-01

In order to extend the application of black liquor (BL), amino group was introduced in lignin through Mannich reaction. The structure of the aminated black liquor (ABL) was characterized with FT-IR, elemental analysis, the zeta potential and the inherent viscosity. The foam generated by ABL was more stable, for the surface tension was lower. The results of the mortar test indicated that the water-retention rate of the fresh mortar incorporated with 0.3 wt% ABL was 89.1%; the consistency loss was about 39.7% after 4 h. When the dosage was less than 0.3 wt%, ABL could increase the bond strength of the hardened mortars. The results showed that ABL could be used as an effective ready-mixed wet mortar admixture. This study not only provided a new method to develop new mortar admixture, but also alleviated the pollution of BL.

Synthesis, spectral, thermal and antimicrobial studies on cobalt(II), nickel(II), copper(II), zinc(II) and palladium(II) complexes containing thiosemicarbazone ligand

NASA Astrophysics Data System (ADS)

El-Sawaf, Ayman K.; El-Essawy, Farag; Nassar, Amal A.; El-Samanody, El-Sayed A.

2018-04-01

The coordination characteristic of new N4-morpholinyl isatin-3-thiosemicarbazone (HL) towards Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) has been studies. The structures of the complexes were described by elemental analyses, molar conductivity, magnetic, thermal and spectral (IR, UV-Vis, 1H and 13C NMR and ESR) studies. On the basis of analytical and spectral studies the ligand behaves as monobasic tridentate ONS donor forming two five membered rings towards cobalt, copper and palladium and afforded complexes of the kind [M(L)X], (Mdbnd Co, Cu or Pd; Xdbnd Cl, Br or OAc). Whereas the ligand bound to NiCl2 as neutral tridentate ONS donor and with ZnCl2 as neutral bidentate NS donor. The newly synthesized thiosemicarbazone ligand and some of its complexes were examined for antimicrobial activity against 2 gram negative bacterial strains (Escherichia coli Pseudomonas and aeruginosa), 2 gram positive bacterial strains (Streptococcus pneumoniae and Staphylococcus aureus)} and two Pathogenic fungi (Aspergillus fumigatus and Candida albicans). All metal complexes possess higher antimicrobial activity comparing with the free thiosemicarbazone ligand. The high potent activities of the complexes may arise from the coordination and chelation, which tends to make metal complexes act as more controlling and potent antimicrobial agents, thus hindering the growing of the microorganisms. The antimicrobial results also show that copper bromide complex is better antimicrobial agent as compared to the Schiff base and its metal complexes.

Human NRDRB1, an alternatively spliced isoform of NADP(H)-dependent retinol dehydrogenase/reductase enhanced enzymatic activity of benzil.

PubMed

Yan, Yinxia; Song, Xuhong; Liu, Gefei; Su, Zhongjing; Du, Yongming; Sui, Xuxia; Chang, Xiaolan; Huang, Dongyang

2012-01-01

Human NRDRB1, a 226 amino acid alternatively spliced isoform of the NADP(H)- dependent retinol dehydrogenase/reductase (NRDR), lacks the complete coding region of exon 3, but preserves all the important functional motifs for NRDR catalytic activity. Nevertheless, its tissue distribution and physiological function remain to be elucidated. Expression of NRDRB1 and NRDR in cells and tissues was analyzed by semi-quantitative polymerase chain reaction (PCR) and western blot. NRDRB1 was expressed as a His(6) fusion protein and subjected to kinetics assays. Recombinant NRDRB1 had 1.2 to 8.6 fold higher k(cat)/K(m) values than recombinant NRDR, depending on the substrate. NRDRB1 catalyzed the NADPH-dependent reduction of α-dicarbonyl compounds, such as isatin, 9,10-phenanthrenequinone, and especially benzil. The significantly high catalytic activity and the relatively high expression in human liver of NRDRB1 conferred cellular resistance to benzil-induced cell toxicity and over-expression of NRDRB1 in low expressing Ec109 cells significantly enhanced cell tolerance toward benzil. Based on its substrate specificity, catalytic activity and relatively high expression in human liver tissue, our results suggest that NRDRB1, an alternatively spliced isoform of NRDR in vivo functions better than NRDR as a dicarbonyl reductase for xenobiotics containing reactive carbonyls. Our study is the first reporting this phenomenon of the enzymes involved in biochemical reactions. Copyright © 2012 S. Karger AG, Basel.

Gold catalyzed double condensation reaction: Synthesis, antimicrobial and cytotoxicity of spirooxindole derivatives.

PubMed

Parthasarathy, K; Praveen, Chandrasekar; Jeyaveeran, J C; Prince, A A M

2016-09-01

Microwave assisted synthesis of spirooxindoles via tandem double condensation between isatins and 4-hydroxycoumarin under gold catalysis is reported. The reaction is practical to perform, since the products can be isolated by simple filtration without requiring tedious column chromatography. The scope of this chemistry is exemplified by preparing structurally diverse spirooxindoles (22 examples) in excellent yields. Antimicrobial evaluation of the synthesized compounds revealed that three compounds (3a, 3f and 3s) exhibited significant MIC values in comparison to the standard drugs. Molecular docking studies of these compounds with AmpC-β-lactamase receptor revealed that 3a exhibited minimum binding energy (-117.819kcal/mol) indicating its strong affinity towards amino acid residues via strong hydrogen bond interaction. All compounds were also evaluated for their in vitro cytotoxicity against COLO320 cancer cells. Biological assay and molecular docking studies demonstrated that 3g is the most active compound in terms of its low IC50 value (50.0μM) and least free energy of binding (-8.99kcal/mol) towards CHK1 receptor, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.

PubMed

Han, Changho; Chatterjee, Arindam; Noetzel, Meredith J; Panarese, Joseph D; Smith, Emery; Chase, Peter; Hodder, Peter; Niswender, Colleen; Conn, P Jeffrey; Lindsley, Craig W; Stauffer, Shaun R

2015-01-15

Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for assessment of all three modes of pharmacology at M1, including agonist, positive allosteric modulator, and antagonist activities in a single screening platform. We disclose a dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one hit (DBPQ, CID 915409) and examine N-benzyl pharmacophore/SAR relationships versus previously reported quinolin-3(5H)-ones and isatins, including ML137. SAR and consideration of recently reported crystal structures, homology modeling, and structure-function relationships using point mutations suggests a shared binding mode orientation at the putative common allosteric binding site directed by the pendant N-benzyl substructure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis and discovery of novel piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors.

PubMed

Kia, Yalda; Osman, Hasnah; Kumar, Raju Suresh; Murugaiyah, Vikneswaran; Basiri, Alireza; Perumal, Subbu; Wahab, Habibah A; Bing, Choi Sy

2013-04-01

Three-component reaction of a series of 1-acryloyl-3,5-bisbenzylidenepiperidin-4-ones with isatin and L-proline in 1:1:1 and 1:2:2 molar ratios in methanol afforded, respectively the piperidone-grafted novel mono- and bisspiro heterocyclic hybrids comprising functionalized piperidine, pyrrolizine and oxindole ring systems in good yields. The in vitro evaluation of cholinesterase enzymes inhibitory activity of these cycloadducts disclosed that monospiripyrrolizines (8a-k), are more active with IC50 ranging from 3.36 to 20.07 μM than either the dipolarophiles (5a-k) or bisspiropyrrolizines (9a-k). The compounds, 8i and 8e with IC50 values of 3.36 and 3.50 μM, respectively showed the maximum inhibition of acethylcholinesterase (AChE) and butrylylcholinestrase (BuChE). Molecular modeling simulation, disclosed the binding interactions of the most active compounds to the active site residues of their respective enzymes. The docking results were in accordance with the IC50 values obtained from in vitro cholinesterase assay. Copyright © 2013 Elsevier Ltd. All rights reserved.

New 14-membered octaazamacrocyclic complexes of divalent transition metal ions with their antimicrobial and spectral studies

NASA Astrophysics Data System (ADS)

Singh, D. P.; Kumar, Krishan; Sharma, Chetan

2010-01-01

A novel series of macrocyclic complexes of the type [M(C 18H 14N 10S 2)X 2]; where M = Co(II), Ni(II), Cu(II), Zn(II) and Cd(II); X = Cl -, NO 3-, CH 3COO - has been synthesized by [2+2] condensation of thiocarbohydrazide and isatin in the presence of divalent metal salts in methanolic medium. The complexes have been characterized with the help of elemental analyses, conductance measurements, magnetic measurements, electronic, NMR and infrared spectral studies. The low value of molar conductance indicates them to be non-electrolytes. On the basis of various studies a distorted octahedral geometry may be proposed for all of these complexes. These metal complexes were also tested for their in vitro antimicrobial activities against some Gram-positive bacteria viz. Staphylococcus aureus, Bacillus subtilis, and some Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and some fungal strains Aspergillus niger, Aspergillus flavus (molds), Candida albicans, Saccharomyces cerevisiae (yeasts). The results obtained were compared with standard antibiotic: Ciprofloxacin and the standard antifungal drug: Amphotericin-B.

Rational design and synthesis of androgen receptor-targeted nonsteroidal anti-androgen ligands for the tumor-specific delivery of a doxorubicin-formaldehyde conjugate.

PubMed

Cogan, Peter S; Koch, Tad H

2003-11-20

The synthesis and preliminary evaluation of a doxorubicin-formaldehyde conjugate tethered to the nonsteroidal antiandrogen, cyanonilutamide (RU 56279), for the treatment of prostate cancer are reported. The relative ability of the targeting group to bind to the human androgen receptor was studied as a function of tether. The tether served to attach the antiandrogen to the doxorubicin-formaldehyde conjugate via an N-Mannich base of a salicylamide derivative. The salicylamide was selected to serve as a trigger release mechanism to separate the doxorubicin-formaldehyde conjugate from the targeting group after it has bound to the androgen receptor. The remaining part of the tether consisted of a linear group that spanned from the 5-position of the salicylamide to the 3'-position of cyanonilutamide. The structures explored for the linear region of the tether were derivatives of di(ethylene glycol), tri(ethylene glycol), N,N'-disubstituted-piperazine, and 2-butyne-1,4-diol. Relative binding affinity of the tethers bound to the targeting group for human androgen receptor were measured using a (3)H-Mibolerone competition assay and varied from 18% of nilutamide binding for the butynediol-based linear region to less than 1% for one of the piperazine derivatives. The complete targeted drug with the butynediol-based linear region has a relative binding affinity of 10%. This relative binding affinity is encouraging in light of the cocrystal structure of human androgen receptor ligand binding domain bound to the steroid Metribolone which predicts very limited space for a tether connecting the antiandrogen on the inside to the cytotoxin on the outside.

meso-4,4′-Dimeth­oxy-2,2′-{[(3aR,7aS)-2,3,3a,4,5,6,7,7a-octa­hydro-1H-benz­imidazole-1,3-di­yl]bis­(methyl­ene)}diphenol

PubMed Central

Rivera, Augusto; Quiroga, Diego; Ríos-Motta, Jaime; Kučeraková, Monika; Dušek, Michal

2013-01-01

The title compound, C23H30N2O4, a di-Mannich base derived from 4-meth­oxy­phenol and cis-1,2-di­amine­cyclo­hexane, has a perhydro­benzimidazolidine nucleus, in which the cyclo­hexane ring adopts a chair conformation and the heterocyclic ring has a half-chair conformation with a C—N—C—C torsion angles of −48.14 (15) and −14.57 (16)°. The mean plane of the heterocycle makes dihedral angles of 86.29 (6) and 78.92 (6)° with the pendant benzene rings. The mol­ecular structure of the title compound shows the presence of two inter­actions between the N atoms of the imidazolidine ring and the hydroxyl groups through intra­molecular O—H⋯N hydrogen bonds with graph-set motif S(6). The unobserved lone pairs of the N atoms are presumed to be disposed in a syn conformation, being only the second example of an exception to the typical ‘rabbit-ears’ effect in 1,2-di­amines. PMID:24046631

New indole, aminoindole and pyranoindole derivatives with anti-inflammatory activity.

PubMed

Nakkady, S S; Fathy, M M; Hishmat, O H; Mahmond, S S; Ebeid, M Y

2000-01-01

6-Methoxy-1-methyl-2,3-diphenyl indol-5-carboxaldehyde (2) was demethylated to give the 6-hydroxy derivative (3) which was cyclized to the pyrano[3,2-f]indole derivatives (4a-d) by the action of ethyl acetoacetate, diethyl malonate, malononitrile, ethyl cyanoacetate. When 4c was boiled in acetic acid, it gave 4d. Reduction of 4c by sodium borohydride yielded the orthoaminonitrile (5). Friedel Craft's acetylation of 1b yielded the 5-acetyl derivative (6), which reacted with hydrazine hydrate, o-toluidine and o-aminophenol to afford (7a-c). Demethylation of (1b) yielded the hydroxyl derivative (8), which differs from compound (9) obtained by demethylation of 6-methoxy-2,3-diphenyl-indole (1a). Friedel Craft's acetylation of 9 gave the 7-acetyl compound (10) which yielded the hydrazone (11). The reaction of primary aromatic amines, (i.e. p-nitroaniline, p-anisidine and p-bromo aniline) with 6-methoxy-1-methyl-2,3-diphenyl-indol-5-carboxaldehyde (2) gave the Schiff bases (12a-c). The latter compounds were reduced by sodium borohydride to yield the corresponding Mannich bases (13a-c). Treatment of 12a-c with thioglycolic acid led to the thiazolidin-4-one-derivatives (14a-c). When (12a-c) reacted with cyanoacetamide, the amino group was replaced by the active methylene to form the cyano compound (15). The structure was confirmed by reacting the carboxaldehyde (2) with cyanoacetamide to yield (15). Pharmacological screening was has been carried out to test the anti-inflammatory activity, ulcerogenecity, effect on the isolated rabbit intestine and the antispasmodic activity.

Synthesis, Amphiphilic Property and Thermal Stability of Novel Main-chain Poly(o-carborane-benzoxazines)

NASA Astrophysics Data System (ADS)

Yang, Xiaoxue; Han, Guo; Yang, Zhen; Zhang, Xiaoa; Jiang, Shengling; Lyu, Yafei

2017-10-01

Five poly(o-carborane-benzoxazines) were synthesized via Mannich reaction of o-carborane bisphenol, paraformaldehyde, and diamine, and their structures were well characterized. Light transmission and 1H NMR in D2O confirmed that poly(o-carborane-benzoxazines) with PEG segments showed excellent water solubility and amphiphilic property. TGA analyses were conducted under nitrogen and air, and the results showed that the polymers own high initial decomposition temperatures owing to the shielding effect of carborane moiety on its adjacent aromatic structures. Besides, poly(o-carborane-benzoxazines) own high char yield at elevated temperatures, for the boron atom could combine with oxygen from the polymer structure or/and the air and be oxidized to form boron oxide, and thus the polymer weight is retained to a large extent. PEG segments had an adverse effect on the initial decomposition and char yield, and thus their concentration should be adjusted to control the polymer’s thermal stability.

Preparation and characterization of monoclonal antibody against melatonin.

PubMed

Soukhtanloo, Mohammad; Ansari, Mohammad; Paknejad, Maliheh; Parizadeh, Mohammad Reza; Rasaee, Mohammad Javad

2008-06-01

Anti-melatonin monoclonal antibodies (MAb) were prepared following coupling melatonin to bovine serum albumin (BSA) by Mannich reaction. Balb/c mice were immunized via injection of the melatonin-BSA intraperitonally. The spleen cells producing high titer of antibody were fused with myeloma cells of SP2/0 origin. After two limiting dilutions, two stable clones (AS-H10 and AS-D26) exhibiting best properties were selected for further studies. The class and subclass of two MAbs were found to be IgG(1) and IgG(2a) with lambda and kappa light chains, respectively. Antibodies secreted by these two clones showed high affinity of about 10(9)M(1). Study of the specificity criteria showed that these clones had no cross reactivity with indolic, aromatic, and imidazole ring-containing compounds, and had high specificity towards melatonin. The calibration curve was constructed with a sensitivity range of 10 ng/mL to 10 microg/mL. In conclusion, these MAbs may be useful for immunoassay of melatonin.

Chemistry of withaferin-A: chemo, regio, and stereoselective synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A via one-pot three-component [3+2] azomethine ylide cycloaddition and their cytotoxicity evaluation.

PubMed

Bharitkar, Yogesh P; Kanhar, Satish; Suneel, Neradibilli; Mondal, Susanta Kumar; Hazra, Abhijit; Mondal, Nirup B

2015-05-01

Withaferin-A (WA) has attracted the attention of chemists as well as biologists due to its interesting structure and various bio-activities. In light of the promising biological importance of WA as well as pyrrolidine-2-spiro-3'-oxindole ring system, we became interested in the synthesis of a combined motif involving both the ring systems via the 1,3-dipolar cycloaddition of WA at Δ(2)-bond of the α,β-unsaturated carbonyl system. We now report a facile, atom-economic synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A (10 compounds) via the intermolecular cycloaddition of azomethine ylides generated in situ from proline and isatins/acenaphthoquinone. The reaction is highly chemo, regio, and stereoselective affording the cis-fused products with β-orienting hydrogen. The structures were determined by 1D/2D NMR spectroscopic data analysis and unequivocally confirmed by X-ray crystallographic analysis in some cases. Bioevaluation of the compounds against six cancer lines (e.g., CHO, HepG2, HeLa, HEK 293, MDCK-II, and Caco-2) identified 4 promising potential anticancer compounds.

Positioning of the carboxamide side chain in 11-oxo-11H-indeno[1,2-b]quinolinecarboxamide anticancer agents: effects on cytotoxicity.

PubMed

Deady, L W; Desneves, J; Kaye, A J; Finlay, G J; Baguley, B C; Denny, W A

2001-02-01

A series of 11-oxo-11H-indeno[1,2-b]quinolines bearing a carboxamide-linked cationic side chain at various positions on the chromophore was studied to determine structure-activity relationships between cytotoxicity and the position of the side chain. The compounds were prepared by Pfitzinger synthesis from an appropriate isatin and 1-indanone, followed by various oxidative steps, to generate the required carboxylic acids. The 4- and 6-carboxamides (with the side chain on a terminal ring, off the short axis of the chromophore) were effective cytotoxins. The dimeric 4- and 6-linked analogues were considerably more cytotoxic than the parent monomers, but had broadly similar activities. In contrast, analogues with side chains at the 8-position (on a terminal ring but off the long axis of the chromophore) or 10-position (off the short axis of the chromophore but in a central ring) were drastically less effective. The 4,10- and 6,10-biscarboxamides had activities between those of the corresponding parent monocarboxamides. The first of these showed good activity against advanced subcutaneous colon 38 tumours in mice.

Hybrid Elastin-like Polypeptide–Polyethylene Glycol (ELP-PEG) Hydrogels with Improved Transparency and Independent Control of Matrix Mechanics and Cell Ligand Density

PubMed Central

2015-01-01

Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin-like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP’s lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP-polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 °C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell–matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics. PMID:25111283

Hybrid elastin-like polypeptide-polyethylene glycol (ELP-PEG) hydrogels with improved transparency and independent control of matrix mechanics and cell ligand density.

PubMed

Wang, Huiyuan; Cai, Lei; Paul, Alexandra; Enejder, Annika; Heilshorn, Sarah C

2014-09-08

Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin-like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP's lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP-polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 °C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell-matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics.

Modern malaria chemoprophylaxis.

PubMed

Shanks, G Dennis; Edstein, Michael D

2005-01-01

Currently available medications for malaria chemoprophylaxis are efficacious but the problems of patient compliance, the advance of parasite drug resistance, and real or perceived serious adverse effects mean that new chemical compounds are needed.Primaquine, which has been widely used to treat relapsing malaria since the 1950s, has been shown to prevent malaria when taken daily. Tafenoquine is a new 8-aminoquinoline with a much longer half-life than primaquine. Field trials to date indicate that tafenoquine is efficacious and can be taken weekly or perhaps even less frequently. Both primaquine and tafenoquine require exact knowledge of a person's glucose 6-phosphate dehydrogenase status in order to prevent drug-induced haemolysis. Other potential malaria chemoprophylactic drugs such as third-generation antifol compounds and Mannich bases have reached advanced preclinical testing. Mefloquine has been seen to cause serious neuropsychiatric adverse effects on rare occasions. Recent public controversy regarding reputedly common serious adverse effects has made many Western travellers unwilling to take mefloquine. Special risk groups exposed to malaria, such as long-term travellers, children, pregnant women, aircrew and those requiring unimpeded psychomotor reactions, migrants returning to visit malarious countries of origin and febrile persons who have returned from malaria endemic areas, all require a nuanced approach to the use of drugs to prevent malaria. The carrying of therapeutic courses of antimalarial drugs to be taken only if febrile illness develops is indicated in very few travellers despite its appeal to some who fear adverse effects more than they fear potentially lethal malaria infection. Travellers with a significant exposure to malaria require a comprehensive plan for prevention that includes anti-mosquito measures but which is still primarily be based on the regular use of efficacious antimalarial medications.

A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology.

PubMed

Zhou, Chao; Liu, LiJuan; Zhuang, Jing; Wei, JunYu; Zhang, TingTing; Gao, ChunDi; Liu, Cun; Li, HuaYao; Si, HongZong; Sun, ChangGang

2018-06-23

BACKGROUND The method of multiple targets overall control is increasingly used to predict the main active ingredient and potential target group of Chinese traditional medicines and to determine the mechanisms involved in their curative effects. Qingdai is the main traditional Chinese medicine used in the treatment of chronic myelogenous leukemia (CML), but the complex active ingredients and antitumor targets in treatment of CML have not been clearly defined in previous studies. MATERIAL AND METHODS We constructed a protein-protein interaction network diagram of CML with 638 nodes (proteins) and 1830 edges, based on the biological function of chronic myelocytic leukemia by use of Cytoscape, and we determined 19 key gene nodes in the CML molecule by network topological properties analysis in a data bank. Then, we used the Surflex-dock plugin in SYBYL7.3 docking and acquired the protein crystal structures of key genes involved in CML from the chemical composition of the traditional Chinese medicine Qingdai with key proteins in CML networks. RESULTS According to the score and the spatial structure, the pharmacodynamically active ingredients of Qingdai are Isdirubin, Isoindigo, N-phenyl-2-naphthylamine, and Isatin, among which Isdirubin is the most important. We further screened the most effective activity key protein structures of CML to find the best pharmacodynamically active ingredients of Qingdai, according to the binding interactions of the inhibitors at the catalytic site performed in best docking combinations. CONCLUSIONS The results suggest that Isdirubin plays a role in resistance to CML by altering the expressions of PIK3CA, MYC, JAK2, and TP53 target proteins. Network pharmacology and molecular docking technology can be used to search for possible reactive molecules in traditional chinese medicines (TCM) and to elucidate their molecular mechanisms.

(E)-3-(2-Alkyl-10H-phenothiazin-3-yl)-1-arylprop-2-en-1-ones: Preparative, IR, NMR and DFT study on their substituent-dependent reactivity in hydrazinolysis and sonication-assisted oxidation with copper(II)nitrate.

PubMed

Găină, Luiza; Csámpai, Antal; Túrós, György; Lovász, Tamás; Zsoldos-Mády, Virág; Silberg, Ioan A; Sohár, Pál

2006-12-07

A series of novel 3(5)-aryl/ferrocenyl-5(3)-phenothiazinylpyrazoles and pyrazolines were obtained by substituent-dependent regioselective condensation of the corresponding (E)-3-(2-alkyl-10H-phenothiazin-3-yl)-1-aryl/ferrocenylprop-2-en-1-one with hydrazine or methylhydrazine in acetic acid. The different propensity of the primary formed beta-hydrazino adducts to undergo competitive retro-Mannich reaction was interpreted in terms of tautomerisation equilibrium constants calculated by DFT using a solvent model. The regioselectivity of the cyclisation reactions with methylhydrazine and the substituent-dependent redox properties of pyrazolines were also rationalized by comparative DFT calculations performed for simplified model molecules. On the effect of ultrasound-promoted oxidation with copper(II)nitrate phenothiazine-containing pyrazolines, enones and oxo-compounds were selectively transformed into sulfoxides. Only one sulfoxide enone was partially converted into an oxirane derivative. The structure of the novel products was determined by IR and NMR spectroscopy including COSY, HSQC, HMBC and DNOE measurements.

Imaging Caspase-3 Activation as a Marker of Apoptosis-Targeted Treatment Response in Cancer

PubMed Central

Chen, Delphine L.; Engle, Jacquelyn T.; Griffin, Elizabeth A.; Miller, J. Philip; Chu, Wenhua; Zhou, Dong; Mach, Robert H.

2016-01-01

Purpose We tested whether positron emission tomography (PET) with the caspase-3 targeted isatin analog [18F]WC-4-116 could image caspase-3 activation in response to an apoptosis-inducing anticancer therapy. Procedures [18F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. Biodistribution studies with [18F]WC-4-116 and [18F]ICMT-18, a non-caspase-3-targeted tracer, as well as [18F]WC-4-116 microPET imaging assessed responses in Colo205 tumor bearing mice treated with death receptor 5 (DR5) targeted agonist antibodies. Immunohistochemical staining and enzyme assays confirmed caspase-3 activation. Two-way analysis of variance or Student’s t-test assessed for treatment-related changes in tracer uptake. Results [18F]WC-4-116 increased 8 ± 2-fold in etoposide-treated cells. The [18F]WC-4-116 %ID/g also increased significantly in tumors with high caspase-3 enzyme activity (p < 0.05). [18F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 enzyme activity. Conclusions [18F]WC-4-116 uptake in vivo reflects increased caspase-3 activation and may be useful for detecting caspase-3 mediated apoptosis treatment responses in cancer. PMID:25344147

Tip-Enhanced Photoinduced Electron Transfer and Ionization on Vertical Silicon Nanowires.

PubMed

Chen, Xiaoming; Wang, Tao; Lin, Leimiao; Wo, Fangjie; Liu, Yaqin; Liang, Xiao; Ye, Hui; Wu, Jianmin

2018-05-02

Nanostructured semiconductors are one of the most potent candidates for matrix-free laser desorption/ionization mass spectrometric (LDI-MS) analysis of low-molecular-weight molecules. Herein, the enhanced photoinduced electron transfer and LDI on the tip of a vertical silicon nanowire (SiNW) array were investigated. Theoretical simulation and LDI detection of indigo and isatin molecules in negative ion mode revealed that the electric field can be enhanced on the tip end of SiNWs, thereby promoting the energy and electron transfer to the analytes adsorbed on the tip of SiNWs. On the basis of this finding, a tip-contact sampling method coupled with LDI-MS detection was established. In this strategy, the tip of SiNWs can be regarded as microextraction heads for the sampling of molecules when they come in contact with analytes. Impression of skin, tissue, and pericarp on the vertical SiNW array can effectively transfer endogenous metabolites or exogenous substances onto the tip. Upon laser irradiation, the adsorbed molecules on the SiNW tip can be efficiently ionized and detected in negative ion mode because of the tip-enhanced electron transfer and LDI effect. We believe this work may significantly expand the application of LDI-MS in various fields.

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphos Ph Complexes.

PubMed

Phanopoulos, Andreas; Long, Nicholas; Miller, Philip

2015-04-10

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphos(Ph)) (1) via a phosphorus based Mannich reaction of the hydroxylmethylene phosphine precursor with ammonia in methanol under a nitrogen atmosphere. The N-triphos(Ph) ligand precipitates from the solution after approximately 1 hr of reflux and can be isolated analytically pure via simple cannula filtration procedure under nitrogen. Reaction of the N-triphos(Ph) ligand with [Ru3(CO)12] under reflux affords a deep red solution that show evolution of CO gas on ligand complexation. Orange crystals of the complex [Ru(CO)2{N(CH2PPh2)3}-κ(3)P] (2) were isolated on cooling to RT. The (31)P{(1)H} NMR spectrum showed a characteristic single peak at lower frequency compared to the free ligand. Reaction of a toluene solution of complex 2 with oxygen resulted in the instantaneous precipitation of the carbonate complex [Ru(CO3)(CO){N(CH2PPh2)3}-κ(3)P] (3) as an air stable orange solid. Subsequent hydrogenation of 3 under 15 bar of hydrogen in a high-pressure reactor gave the dihydride complex [RuH2(CO){N(CH2PPh2)3}-κ(3)P] (4), which was fully characterized by X-ray crystallography and NMR spectroscopy. Complexes 3 and 4 are potentially useful catalyst precursors for a range of hydrogenation reactions, including biomass-derived products such as levulinic acid (LA). Complex 4 was found to cleanly react with LA in the presence of the proton source additive NH4PF6 to give [Ru(CO){N(CH2PPh2)3}-κ(3)P{CH3CO(CH2)2CO2H}-κ(2)O](PF6) (6).

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

PubMed Central

Phanopoulos, Andreas; Long, Nicholas; Miller, Philip

2015-01-01

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphosPh) (1) via a phosphorus based Mannich reaction of the hydroxylmethylene phosphine precursor with ammonia in methanol under a nitrogen atmosphere. The N-triphosPh ligand precipitates from the solution after approximately 1 hr of reflux and can be isolated analytically pure via simple cannula filtration procedure under nitrogen. Reaction of the N-triphosPh ligand with [Ru3(CO)12] under reflux affords a deep red solution that show evolution of CO gas on ligand complexation. Orange crystals of the complex [Ru(CO)2{N(CH2PPh2)3}-κ3P] (2) were isolated on cooling to RT. The 31P{1H} NMR spectrum showed a characteristic single peak at lower frequency compared to the free ligand. Reaction of a toluene solution of complex 2 with oxygen resulted in the instantaneous precipitation of the carbonate complex [Ru(CO3)(CO){N(CH2PPh2)3}-κ3P] (3) as an air stable orange solid. Subsequent hydrogenation of 3 under 15 bar of hydrogen in a high-pressure reactor gave the dihydride complex [RuH2(CO){N(CH2PPh2)3}-κ3P] (4), which was fully characterized by X-ray crystallography and NMR spectroscopy. Complexes 3 and 4 are potentially useful catalyst precursors for a range of hydrogenation reactions, including biomass-derived products such as levulinic acid (LA). Complex 4 was found to cleanly react with LA in the presence of the proton source additive NH4PF6 to give [Ru(CO){N(CH2PPh2)3}-κ3P{CH3CO(CH2)2CO2H}-κ2O](PF6) (6). PMID:25938678

The use of BMED for glyphosate recovery from glyphosate neutralization liquor in view of zero discharge.

PubMed

Shen, Jiangnan; Huang, Jie; Liu, Lifen; Ye, Wenyuan; Lin, Jiuyang; Van der Bruggen, Bart

2013-09-15

Alkaline glyphosate neutralization liquors containing a high salinity pose a severe environmental pollution problem by the pesticide industry. However, there is a high potential for glyphosate recovery due to the high concentration of glyphosate in the neutralization liquors. In the study, a three-compartment bipolar membrane electrodialysis (BMED) process was applied on pilot scale for the recovery of glyphosate and the production of base/acid with high concentration in view of zero discharge of wastewater. The experimental results demonstrate that BMED can remove 99.0% of NaCl from the feed solution and transform this fraction into HCl and NaOH with high concentration and purity. This is recycled for the hydrolysis reaction of the intermediate product generated by the means of the Mannich reaction of paraformaldehyde, glycine and dimethylphosphite catalyzed by triethylamine in the presence of HCl and reclamation of the triethylamine catalyst during the production process of glyphosate. The recovery of glyphosate in the feed solution was over 96%, which is acceptable for industrial production. The current efficiency for producing NaOH with a concentration of 2.0 mol L(-1) is above 67% and the corresponding energy consumption is 2.97 kWh kg(-1) at a current density of 60 mA cm(-2). The current efficiency increases and energy consumption decreases as the current density decreases, to 87.13% and 2.37 kWh kg(-1), respectively, at a current density of 30 mA cm(-2). Thus, BMED has a high potential for desalination of glyphosate neutralization liquor and glyphosate recovery, aiming at zero discharge and resource recycling in industrial application. Copyright © 2013 Elsevier B.V. All rights reserved.

The preparation and use of metal salen complexes derived from cyclobutane diamine

NASA Astrophysics Data System (ADS)

Patil, Smita

The helix is an important chiral motif in nature, there is increasing development in field of helical transition metal complexes and related supramolecular structures. Hence, the goals of this work are to apply the principles of helicity in order to produce metal complexes with predictable molecular shapes and to study their properties as asymmetric catalysts. Computational studies suggest that the (1R,2 R)-cyclobutyldiamine unit can produce highly twisted salen complexes with a large energy barrier between the M and P helical forms. To test this prediction, the tartrate salt of (1R,2R)-cyclobutyldiamine was synthesized and condensed with a series of saliclaldehydes to produce novel salen ligands. The salicylaldehydes chosen have extended phenanthryl or benz[a]anthryl sidearms to encourage formation of helical coordination complexes. These ligands were metallated with zinc, iron and manganese salts to produce salen metal complexes which were characterized by NMR analysis, high-resolution mass spectrometry, and IR spectroscopy. A second ligand type, neutral bis(pyridine-imine) has also been synthesized from (1R,2R)-cyclobutyldiamine and quinolylaldehydes. The synthesis of bis(pyridine-imine) ligands was conducted using greener method, solvent assisted grinding. These ligands, in-situ with nickel metal salts, showed good catalytic activity for asymmetric Diels-Alder reactions. The third ligand type studied was chiral acid-functionalized Schiff-base ligands. These were synthesized by the condensation of 3-formyl-5-methyl salicylic acid and (1R,2R)-cyclobutyldiamine. With this type of ligand, there is possibility of producing both mono and dinuclear metal complexes. In our studies, we were only able to synthesize mononuclear complexs. These were tested as catalysts for asymmetric direct Mannich-type reaction, but were found to be ineffective.

Carbon dioxide, oxygen, and pH detection in animal adipose tissue by means of extracorporeal microdialysis

NASA Astrophysics Data System (ADS)

Baldini, F.; Bizzarri, A.; Cajlakovic, M.; Feichtner, F.; Gianesello, L.; Giannetti, A.; Gori, G.; Konrad, C.; Mencaglia, A. A.; Mori, E.; Pavoni, V.; Perna, A. M.; Trono, C.

2007-05-01

Atypical physiological symptoms can be developed in healthy people under critically ill conditions. pH, pO II and pCO II are informative indicators of the conditions of a living system and can be valuable in determining the physiologic status of the critically ill patients. The continuous monitoring of these small molecules into the interstitial fluid (ISF) is a promising approach to reduce diagnostic blood loss and painful stress associated with blood sampling. Microdialysis is the approach followed for the extraction of the sample from the subcutaneous adipose tissue; the drawn interstitial fluid flows through a microfluidic circuit formed by the microdialysis catheter in series with a glass capillary on the internal wall of which the appropriate chemistry for sensing is immobilised. Absorption changes for pH sensor and modulation of the fluorescence lifetime for pO II and pCO II are the working principle. Phenol red covalently bound into the internal wall of a glass capillary by means of the Mannich reaction and platinum(II) tetrakis-pentafluorophenyl-porphyrine entrapped within a polymerised polystyrene layer are the chemical transducers used for pH and oxygen detection; the ion pair 8- hydroxypyrene-1,3,6-trisulfonic acid trisodium salt/ tetraoctylammonium hydroxide, dissolved in a silicon-based polymeric matrix, is used for the carbon dioxide detection. A suitable hemorrhagic shock model was developed in order to validate clinically the developed sensors in the condition of extreme stress and the obtained results show that the adipose tissue can become an alternative site for the continuous oitoring of pH, pO II and pCO II.

Hexanuclear, heterometallic, Ni₃Ln₃ complexes possessing O-capped homo- and heterometallic structural subunits: SMM behavior of the dysprosium analogue.

PubMed

Goura, Joydeb; Guillaume, Rogez; Rivière, Eric; Chandrasekhar, Vadapalli

2014-08-04

The reaction of hetero donor chelating mannich base ligand 6,6'-{(2-(dimethylamino)ethylazanediyl)bis(methylene)}bis(2-methoxy-4-methylphenol) with Ni(ClO4)2·6H2O and lanthanide(III) salts [Dy(III) (1); Tb(III) (2); Gd (III) (3); Ho(III) (4); and Er(III) (5)] in the presence of triethylamine and pivalic acid afforded a series of heterometallic hexanuclear Ni(II)-Ln(III) coordination compounds, [Ni3Ln3(μ3-O)(μ3-OH)3(L)3(μ-OOCCMe3)3]·(ClO4)·wCH3CN·xCH2Cl2·yCH3OH·zH2O [for 1, w = 8, x = 3, y = 0, z = 5.5; for 2, w = 0, x = 5, y = 0, z = 6.5; for 3, w = 15, x = 18, y = 3, z = 7.5; for 4, w = 15, x = 20, y = 6, z = 9.5; and for 5, w = 0, x = 3, y = 2, z = 3]. The molecular structure of these complexes reveals the presence of a monocationic hexanuclear derivative containing one perchlorate counteranion. The asymmetric unit of each of the hexanuclear derivatives comprises the dinuclear motif [NiLn(L)(μ3-O)(μ3-OH)(μ-Piv)]. The cation contains three interlinked O-capped clusters: one Ln(III)3O and three Ni(II)Ln(III)2O. Each of the lanthanide centers is eight- coordinated (distorted trigonal-dodecahedron), while the nickel centers are hexacoordinate (distorted octahedral). The study of the magnetic properties of all compounds are reported and suggests single molecule magnet behavior for the Dy(III) derivative (1).

Degradation of textile dyes by cyanobacteria.

PubMed

Dellamatrice, Priscila Maria; Silva-Stenico, Maria Estela; Moraes, Luiz Alberto Beraldo de; Fiore, Marli Fátima; Monteiro, Regina Teresa Rosim

Dyes are recalcitrant compounds that resist conventional biological treatments. The degradation of three textile dyes (Indigo, RBBR and Sulphur Black), and the dye-containing liquid effluent and solid waste from the Municipal Treatment Station, Americana, São Paulo, Brazil, by the cyanobacteria Anabaena flos-aquae UTCC64, Phormidium autumnale UTEX1580 and Synechococcus sp. PCC7942 was evaluated. The dye degradation efficiency of the cyanobacteria was compared with anaerobic and anaerobic-aerobic systems in terms of discolouration and toxicity evaluations. The discoloration was evaluated by absorption spectroscopy. Toxicity was measured using the organisms Hydra attenuata, the alga Selenastrum capricornutum and lettuce seeds. The three cyanobacteria showed the potential to remediate textile effluent by removing the colour and reducing the toxicity. However, the growth of cyanobacteria on sludge was slow and discoloration was not efficient. The cyanobacteria P. autumnale UTEX1580 was the only strain that completely degraded the indigo dye. An evaluation of the mutagenicity potential was performed by use of the micronucleus assay using Allium sp. No mutagenicity was observed after the treatment. Two metabolites were produced during the degradation, anthranilic acid and isatin, but toxicity did not increase after the treatment. The cyanobacteria showed the ability to degrade the dyes present in a textile effluent; therefore, they can be used in a tertiary treatment of effluents with recalcitrant compounds. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Characterization of a Novel Phenol Hydroxylase in Indoles Biotranformation from a Strain Arthrobacter sp. W1

PubMed Central

Li, Xinliang; Zhang, Xuwang; Zhou, Jiti

2012-01-01

Background Indigoids, as popular dyes, can be produced by microbial strains or enzymes catalysis. However, the new valuable products with their transformation mechanisms, especially inter-conversion among the intermediates and products have not been clearly identified yet. Therefore, it is necessary to investigate novel microbial catalytic processes for indigoids production systematically. Findings A phenol hydroxylase gene cluster (4,606 bp) from Arthrobacter sp. W1 (PHw1) was obtained. This cluster contains six components in the order of KLMNOP, which exhibit relatively low sequence identities (37–72%) with known genes. It was suggested that indole and all the tested indole derivatives except for 3-methylindole were transformed to various substituted indigoid pigments, and the predominant color products derived from indoles were identified by spectrum analysis. One new purple product from indole, 2-(7-oxo-1H-indol-6(7H)-ylidene) indolin-3-one, should be proposed as the dimerization of isatin and 7-hydroxylindole at the C-2 and C-6 positions. Tunnel entrance and docking studies were used to predict the important amino acids for indoles biotransformation, which were further proved by site-directed mutagenesis. Conclusions/Significance We showed that the phenol hydroxylase from genus Arthrobacter could transform indoles to indigoids with new chemical compounds being produced. Our work should show high insights into understanding the mechanism of indigoids bio-production. PMID:23028517

Ionic liquid mediated synthesis of mono- and bis-spirooxindole-hexahydropyrrolidines as cholinesterase inhibitors and their molecular docking studies.

PubMed

Kia, Yalda; Osman, Hasnah; Kumar, Raju Suresh; Basiri, Alireza; Murugaiyah, Vikneswaran

2014-02-15

One pot, three-component reaction of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with isatin and sarcosine in molar ratios of 1:1:1 and 1:2:2 furnished to mono- and bis-spiropyrrolidine heterocyclic hybrids comprising functionalized piperidine, pyrrolidine and oxindole structural motifs. Both mono and bis-spiropyrrolidines displayed good inhibitory activity against acetylcholinesterase (AChE) with IC₅₀ values of 2.36-9.43 μM. For butyrylcholinesterase (BChE), mono-cycloadducts in series 8 with IC₅₀ values of lower than 10 μM displayed better inhibitory activities than their bis-cycloadduct analogs in series 9 with IC₅₀ values of 7.44-19.12 μM. The cycloadducts 9j and 8e were found to be the most potent AChE and BChE inhibitors with IC₅₀ values of 2.35 and 3.21 μM, respectively. Compound 9j was found to be competitive inhibitor of AChE while compound 8e was a mixed-mode inhibitor of BChE with calculated Ki values of 2.01 and 6.76 μM, respectively. Molecular docking on Torpedo californica AChE and human BChE showed good correlation between IC₅₀ values and free binding energy values of the synthesized compounds docked into the active site of the enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis, Biological Activity, and Docking Study of Novel Isatin Coupled Thiazolidin-4-one Derivatives as Anticonvulsants.

PubMed

Nikalje, Anna P; Ansari, Altamash; Bari, Sanjay; Ugale, Vinod

2015-06-01

A series of 2-(substituted-phenyl)-3-(2-oxoindolin-3-ylidene)amino)-thiazolidin-4-one derivatives were designed and synthesized under microwave irradiation, using an eco-friendly, efficient, microwave-assisted synthetic protocol that involves cyclocondensation of 3-substituted benzylidine-hydrazono-indolin-2-one 3a-j with thioglycolic acid in dimethyl formamide (DMF) as solvent and anhydrous zinc chloride as a catalyst, keeping in view the structural requirement of the pharmacophore. The intermediate compounds 3a-j were obtained by condensation of the hydrazone of indoline-2,3-dione with aromatic aldehydes. The synthesized derivatives were evaluated for CNS depressant activity and anticonvulsant activity in mice using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) induced seizure tests. All the derivatives showed good CNS depressant activity and showed protection in the MES test, indicative of their ability to inhibit the seizure spread. A histopathological study was performed to evaluate liver toxicity caused by the synthesized compounds. The compounds were nontoxic. A computational study was performed, in which log P values were calculated experimentally. Virtual screening was performed by molecular docking of the designed compounds into the ATP binding sites of the NMDA and AMPA receptors, to predict if these compounds have analogous binding modes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

d-PET-controlled “off-on” Polarity-sensitive Probes for Reporting Local Hydrophilicity within Lysosomes

NASA Astrophysics Data System (ADS)

Zhu, Hao; Fan, Jiangli; Mu, Huiying; Zhu, Tao; Zhang, Zhen; Du, Jianjun; Peng, Xiaojun

2016-10-01

Polarity-sensitive fluorescent probes are powerful chemical tools for studying biomolecular structures and activities both in vitro and in vivo. However, the lack of “off-on” polarity-sensing probes has limited the accurate monitoring of biological processes that involve an increase in local hydrophilicity. Here, we design and synthesize a series of “off-on” polarity-sensitive fluorescent probes BP series consisting of the difluoroboron dippyomethene (BODIPY) fluorophore connected to a quaternary ammonium moiety via different carbon linkers. All these probes showed low fluorescence quantum yields in nonpolar solution but became highly fluorescent in polar media. BP-2, which contains a two-carbon linker and a trimethyl quaternary ammonium, displayed a fluorescence intensity and quantum yield that were both linearly correlated with solvent polarity. In addition, BP-2 exhibited high sensitivity and selectivity for polarity over other environmental factors and a variety of biologically relevant species. BP-2 can be synthesized readily via an unusual Mannich reaction followed by methylation. Using electrochemistry combined with theoretical calculations, we demonstrated that the “off-on” sensing behavior of BP-2 is primarily due to the polarity-dependent donor-excited photoinduced electron transfer (d-PET) effect. Live-cell imaging established that BP-2 enables the detection of local hydrophilicity within lysosomes under conditions of lysosomal dysfunction.

Microwave: An Important and Efficient Tool for the Synthesis of Biological Potent Organic Compounds.

PubMed

Kumari, Kamlesh; Vishvakarma, Vijay K; Singh, Prashant; Patel, Rajan; Chandra, Ramesh

2017-01-01

Green Chemistry is an interdisciplinary science or it can also be explained as a branch of chemistry. It is generally described as the chemistry to aim to synthesize chemical compounds to trim down the utilization of harmful chemicals proposed by the Environmental Protection Agency (EPA). Recently, the plan of academicians, researchers, industrialists is to generate greener and more efficient methodologies to carry out various organic syntheses. In the present scenario, green chemistry utilizes the raw materials economically, minimizes the waste and prevents the uses of harmful or hazardous chemicals to make the organic reactions simple and efficient. Microwave technique is a new, simple and efficient technology which opens new prospects to the chemists to carry out various organic and inorganic reactions, which are difficult via conventional methodology. It is used to decrease the duration of time to carry various organic transformation along with maximum yield, minimum by-products, minimum energy utilization, less manpower etc. e.g. various famous organic reactions have been carried out by various research groups like Aldol condensation, Knoevenagel condensation, Beckmann rearrangement, Vilsmeier reaction, Perkin reaction, Benzil-Benzilic acid rearrangement, Fischer cyclization, Mannich reaction, Claisen-Schmidt condensation, etc. Further, reduction, oxidation, coupling, condensation reaction were also performed using microwave technology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

TiO2 Immobilized on Manihot Carbon: Optimal Preparation and Evaluation of Its Activity in the Decomposition of Indigo Carmine

PubMed Central

Antonio-Cisneros, Cynthia M.; Dávila-Jiménez, Martín M.; Elizalde-González, María P.; García-Díaz, Esmeralda

2015-01-01

Applications of carbon-TiO2 materials have attracted attention in nanotechnology due to their synergic effects. We report the immobilization of TiO2 on carbon prepared from residues of the plant Manihot, commercial TiO2 and glycerol. The objective was to obtain a moderate loading of the anatase phase by preserving the carbonaceous external surface and micropores of the composite. Two preparation methods were compared, including mixing dry precursors and immobilization using a glycerol slurry. The evaluation of the micropore blocking was performed using nitrogen adsorption isotherms. The results indicated that it was possible to use Manihot residues and glycerol to prepare an anatase-containing material with a basic surface and a significant SBET value. The activities of the prepared materials were tested in a decomposition assay of indigo carmine. The TiO2/carbon eliminated nearly 100% of the dye under UV irradiation using the optimal conditions found by a Taguchi L4 orthogonal array considering the specific surface, temperature and initial concentration. The reaction was monitored by UV-Vis spectrophotometry and LC-ESI-(Qq)-TOF-MS, enabling the identification of some intermediates. No isatin-5-sulfonic acid was detected after a 60 min photocatalytic reaction, and three sulfonated aromatic amines, including 4-amino-3-hydroxybenzenesulfonic acid, 2-(2-amino-5-sulfophenyl)-2-oxoacetic acid and 2-amino-5-sulfobenzoic acid, were present in the reaction mixture. PMID:25588214

N-nitrosodimethylamine formation upon ozonation and identification of precursors source in a municipal wastewater treatment plant.

PubMed

Sgroi, Massimiliano; Roccaro, Paolo; Oelker, Gregg L; Snyder, Shane A

2014-09-02

Ozone doses normalized to the dissolved organic carbon concentration were applied to the primary influent, primary effluent, and secondary effluent of a wastewater treatment plant producing water destined for potable reuse. Results showed the most N-Nitrosodimethylamine (NDMA) production from primary effluent, and the recycle streams entering the primary clarifiers were identified as the main source of NDMA precursors. The degradation of aminomethylated polyacrylamide (Mannich) polymer used for sludge treatment was a significant cause of precursor occurrence. A strong correlation between NDMA formation and ammonia concentration was found suggesting an important role of ammonia oxidation on NDMA production. During ozonation tests in DI water using dimethylamine (DMA) as model precursor, the NDMA yield significantly increased in the presence of ammonia and bromide due to the formation of hydroxylamine and brominated nitrogenous oxidants. In addition, NDMA formation during ozonation of dimethylformamide (DMF), the other model precursor used in this study, occurred only in the presence of ammonia, and it was attributable to the oxidation of DMF by hydroxyl radicals. Filtered wastewater samples (0.7 μm) produced more NDMA than unfiltered samples, suggesting that ozone reacted with dissolved precursors and supporting the hypothesis of polymer degradation. Particularly, the total suspended solids content similarly affected NDMA formation and the UV absorbance decrease during ozonation due to the different ozone demand created in filtered and unfiltered samples.

Vanadate complexes bearing an imidazolidine-bridged bis(aryloxido) ligand: synthesis and solid state and solution structure.

PubMed

Kober, Ewa; Nerkowski, Tomasz; Janas, Zofia; Jerzykiewicz, Lucjan B

2012-05-07

A new imidazolidine-bridged bis(aryloxido) ligand precursor (H(2)L) [H(2)L = 2,2'-(imidazolidine-1,3-diylbis(methylene))bis(4-(1,1,3,3-tetramethylbutyl-2-yl)phenol)] was prepared in a relatively high yield (∼60%) via a single-step Mannich condensation of 4-(1,1,3,3-tetramethylbutyl)phenol, ethylenediamine and paraformaldehyde at 2:1:3 molar ratio and characterized by chemical and physical techniques including X-ray crystallography. Reactions of H(2)L with [VO(OEt)(3)] at 1:1 and 1:2 molar ratios in toluene afforded [V(L-κ(3)O,N,N,O)(O)(OEt)] (1) and [V(2)(μ-L-κ(4)O,N,N,O)(μ-OEt)(2)(O)(2)(OEt)(2)] (2), respectively. Alcoholysis of 1 with EtOH enables elimination of one molecule of H(2)L and the formation of 2. Compounds 1 and 2 were characterized by IR and NMR spectroscopy as well as ES-MS experiments. The definitive molecular structure of 2 was provided by a single-crystal analysis and revealed its dinuclear nature, featuring two octahedral vanadium centres bridged by both OEt groups and the L ligand. The (51)V, (1)H and (13)C NMR spectra as well as ES-MS showed that 2 does not stay intact in solution and undergoes dissociation to give 1 and [VO(OEt)(3)].

Heterometallic Zn3 Ln3 Ensembles Containing (μ6 -CO3 ) Ligand and Triangular Disposition of Ln3+ ions: Analysis of Single-Molecule Toroic (SMT) and Single-Molecule Magnet (SMM) Behavior.

PubMed

Goura, Joydeb; Colacio, Enrique; Herrera, Juan Manuel; Suturina, Elizaveta A; Kuprov, Ilya; Lan, Yanhua; Wernsdorfer, Wolfgang; Chandrasekhar, Vadapalli

2017-11-21

Two new heterometallic Zn 3 Ln 3 (Ln 3+ =Dy, Tb) complexes, with a double triangular topology of the metal ions, have been assembled from the polytopic Mannich base ligand 6,6'-{[2-(dimethylamino)ethylazanediyl]bis(methylene)}bis(2-methoxy-4-methylphenol) (H 2 L) with the aid of an in situ generated carbonate ligand from atmospheric CO 2 fixation. Theoretical calculations indicate axial ground states for the Ln 3+ ions in these complexes, with their local magnetic moments being almost coplanar and tangential to the Ln 3+ atoms that define the equilateral triangle. Therefore, they can be considered as single-molecule toroics (SMTs) with almost zero total magnetic moment. Micro-SQUID measurements on the Dy 3+ counterpart show hysteresis loops below 3 K that have an S-shape, with large coercive fields opening upon cooling. This behavior is typical of a single molecule magnet (SMM) with very slow zero-field relaxation. At around ±0.35 T, the loops have a broad step, which is due to a direct relaxation process and corresponds to an acceleration of the relaxation of the magnetization, also observed at this magnetic field from ac susceptibility measurements. Simulations suggest that the broad step corresponds to two level avoidance of crossing points where the spin chiral Kramers doublet meets excited states of the coupled manifold, whose position is defined by exchange and dipole interactions. The Tb 3+ counterpart does not exhibit SMM behavior, which is due to the fact that the degeneracy of the ground state of the exchange coupled system is lifted at zero field, thus favoring quantum tunneling of magnetization (QTM). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mutations of Toluene-4-Monooxygenase That Alter Regiospecificity of Indole Oxidation and Lead to Production of Novel Indigoid Pigments

PubMed Central

McClay, Kevin; Boss, Corinne; Keresztes, Ivan; Steffan, Robert J.

2005-01-01

Broad-substrate-range monooygenase enzymes, including toluene-4-monooxygenase (T4MO), can catalyze the oxidation of indole. The indole oxidation products can then condense to form the industrially important dye indigo. Site-directed mutagenesis of T4MO resulted in the creation of T4MO isoforms with altered pigment production phenotypes. High-pressure liquid chromatography, thin-layer chromatography, and nuclear magnetic resonance analysis of the indole oxidation products generated by the mutant T4MO isoforms revealed that the phenotypic differences were primarily due to changes in the regiospecificity of indole oxidation. Most of the mutations described in this study changed the ratio of the primary indole oxidation products formed (indoxyl, 2-oxindole, and isatin), but some mutations, particularly those involving amino acid G103 of tmoA, allowed for the formation of additional products, including 7-hydroxyindole and novel indigoid pigments. For example, mutant G103L converted 17% of added indole to 7-hydroxyindole and 29% to indigoid pigments including indigo and indirubin and two other structurally related pigments. The double mutant G103L:A107G converted 47% of indole to 7-hydroxyindole, but no detectable indigoid pigments were formed, similar to the product distribution observed with the toluene-2-monooxygenase (T2MO) of Burkholderia cepacia G4. These results demonstrate that modification of the tmoA active site can change the products produced by the enzyme and lead to the production of novel pigments and other indole oxidation products with potential commercial and medicinal utility. PMID:16151140

Spectra analysis of coating antigen: A possible explanation for difference in anti-AFB1 polyclonal antibody sensitivity

NASA Astrophysics Data System (ADS)

Ye, Yang; Liu, Aiping; Wang, Xiaohong; Chen, Fusheng

2016-10-01

For the detection of small hapten molecules, indirect competitive enzyme-linked immunosorbent assay (icELISA) is a preferred method. However, diverse coating antigen might bring different antiserum titer and sensitivity for the identical antiserum. In the present study, four AFB1-protein (aflatoxin B1-carrier protein) conjugates were prepared by activated ester method (AFB1O-BSA/AFB1O-OVA) and mannich method (AFB1-cBSA/AFB1-cOVA), and then applied as coating antigen for titer and sensitivity detection of the identical antiserum obtained from rabbit immunized by AFB1-KLH. Afterwards, the ultraviolet-visible, fluorescence and far-ultraviolet circular dichroism (far-UV CD) spectra were recorded for understanding the difference in titer and sensitivity obtained. Results revealed that AFB1O-BSA/AFB1O-OVA showed a strong intrinsic fluorescence band centered at 450 nm that originated from the emission of AFB1, which differed from AFB1-cBSA/AFB1-cOVA, while the decrease of α-helical and increase of β-sheet in AFB1-cBSA was the most remarkable. This indicated that the better sensitivity obtained by using AFB1O-BSA as coating antigen might be caused by its extended structure, because such structure affect the binding between AFB1 and antibody. The study might offer structural information for understanding the titer and sensitivity difference caused by coating antigen.

The syntheses, characterization and in vitro metabolism of nitracaine, methoxypiperamide and mephtetramine.

PubMed

Power, John D; Scott, Kenneth R; Gardner, Elizabeth A; Curran McAteer, Bronagh M; O'Brien, John E; Brehon, Margaret; Talbot, Brian; Kavanagh, Pierce V

2014-01-01

Three legal highs; nitracaine (3-(diethylamino)-2,2-dimethylpropyl 4-nitrobenzoate), methoxypiperamide (MEOP, (4-methoxyphenyl)(4-methylpiperazin-1-yl)methanone) and mephtetramine (MTTA, 2-((methylamino)methyl)-3,4-dihydronaphthalen-1(2H)-one) appeared in 2013 as new psychoactive substances (NPS) on Internet websites selling 'research chemicals'. These compounds were synthesized and analyzed via our synthesize, analyze, and metabolize (SAM) protocol. Nitracaine was synthesized by the transesterification of methyl 4-nitrobenzoate with 3-(diethylamino)-2,2-dimethylpropan-1-ol. Methoxypiperamide was synthesized by the reaction of 4-methoxybenzoyl chloride with 1-methylpiperazine, and mephtetramine through the Mannich reaction of 1-tetralone with paraformaldehyde and methylamine hydrochloride. Each compound was characterized by nuclear magnetic resonance (NMR), gas chromatography with electron impact mass spectrometry (GC-EIMS), liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), and high resolution electrospray ionization mass spectrometry (HR-ESI-MS). A sample of nitracaine was also test-purchased from an Internet vendor and its structure confirmed by GC-EIMS and LC-ESI-MS. Finally, the in vitro metabolism of the nitracaine, mephtetramine, and methoxypiperamide was investigated, using a human microsomal liver extract, in order to tentatively identify potential metabolites that may be encountered in the analysis of biological samples in clinical or toxicology labs. The use of our SAM protocol highlights the ability of academic research labs to quickly respond to and disseminate information about emerging NPS. Copyright © 2014 John Wiley & Sons, Ltd.

Degradation of Ciprofloxacin by Basidiomycetes and Identification of Metabolites Generated by the Brown Rot Fungus Gloeophyllum striatum

PubMed Central

Wetzstein, Heinz-Georg; Stadler, Marc; Tichy, Hans-Volker; Dalhoff, Axel; Karl, Wolfgang

1999-01-01

Ciprofloxacin (CIP), a fluoroquinolone antibacterial drug, is widely used in the treatment of serious infections in humans. Its degradation by basidiomycetous fungi was studied by monitoring 14CO2 production from [14C]CIP in liquid cultures. Sixteen species inhabiting wood, soil, humus, or animal dung produced up to 35% 14CO2 during 8 weeks of incubation. Despite some low rates of 14CO2 formation, all species tested had reduced the antibacterial activity of CIP in supernatants to between 0 and 33% after 13 weeks. Gloeophyllum striatum was used to identify the metabolites formed from CIP. After 8 weeks, mycelia had produced 17 and 10% 14CO2 from C-4 and the piperazinyl moiety, respectively, although more than half of CIP (applied at 10 ppm) had been transformed into metabolites already after 90 h. The structures of 11 metabolites were elucidated by high-performance liquid chromatography combined with electrospray ionization mass spectrometry and 1H nuclear magnetic resonance spectroscopy. They fell into four categories as follows: (i) monohydroxylated congeners, (ii) dihydroxylated congeners, (iii) an isatin-type compound, proving elimination of C-2, and (iv) metabolites indicating both elimination and degradation of the piperazinyl moiety. A metabolic scheme previously described for enrofloxacin degradation could be confirmed and extended. A new type of metabolite, 6-defluoro-6-hydroxy-deethylene-CIP, provided confirmatory evidence for the proposed network of congeners. This may result from sequential hydroxylation of CIP and its congeners by hydroxyl radicals. Our findings reveal for the first time the widespread potential for CIP degradation among basidiomycetes inhabiting various environments, including agricultural soils and animal dung. PMID:10103250

A freshwater bacterial strain, Shewanella sp. Lzh-2, isolated from Lake Taihu and its two algicidal active substances, hexahydropyrrolo[1,2-a]pyrazine-1,4-dione and 2, 3-indolinedione.

PubMed

Li, Zhenghua; Lin, Shengqin; Liu, Xianglong; Tan, Jing; Pan, Jianliang; Yang, Hong

2014-05-01

Cyanobacterial blooms have become a serious problem in Lake Taihu during the last 20 years, and Microcystis aeruginosa and Synechococcus sp. are the two dominant species in cyanobacterial blooms of Lake Taihu. A freshwater bacterial strain, Shewanella sp. Lzh-2, with strong algicidal properties against harmful cyanobacteria was isolated from Lake Taihu. Two substances with algicidal activity secreted extracellularly by Shewanella sp. Lzh-2, S-2A and S-2B, were purified from the bacterial culture of strain Lzh-2 using ethyl acetate extraction, column chromatography, and high performance liquid chromatography (HPLC) in turn. The substances S-2A and S-2B were identified as hexahydropyrrolo[1,2-a]pyrazine-1,4-dione and 2, 3-indolinedione (isatin), respectively, based on liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and hydrogen-nuclear magnetic resonance (H-NMR) analyses, making this the first report of their algicidal activity toward cyanobacteria. S-2A (hexahydropyrrolo[1,2-a]pyrazine-1,4-dione) had no algicidal effects against Synechococcus sp. BN60, but had a high level of algicidal activity against M. aeruginosa 9110. The LD50 value of S-2A against M. aeruginosa 9110 was 5.7 μg/ml. S-2B (2, 3-indolinedione) showed a potent algicidal effect against both M. aeruginosa 9110 and Synechococcus sp. BN60, and the LD50 value of S-2B against M. aeruginosa 9110 and Synechococcus sp. BN60 was 12.5 and 34.2 μg/ml, respectively. Obvious morphological changes in M. aeruginosa 9110 and Synechococcus sp. BN60 were observed after they were exposed to S-2A (or S-2B) for 24 h. Approximately, the algicidal activity, the concentration of S-2A and S-2B, and the cell density of Lzh-2 were positively related to each other during the cocultivation process. Overall, these findings increase our knowledge about algicidal substances secreted by algicidal bacteria and indicate that strain Lzh-2 and its two algicidal substances have the potential for use as a bio-agent in controlling cyanobacterial blooms in Lake Taihu.

A Series of F-Element Chelators; Diaza Crown Ethers Functionalized with Catecholate Binding Substituents

DOE PAGES

Stein, Benjamin W.; Cary, Samantha K.; Berg, John M.; ...

2017-12-06

Here, we report on the preparation of azacrown ethers functionalized with catechol groups. The synthetic approach was (1st) novel in that it made use of the Mannich reaction and (2nd) valuable in that it provided an improved synthesis (in terms of practical deployment) of the known N,N'-bis(2,3-dihydroxybenzyl)-4,13-diaza-18-crown-6, H 4ChaCha. Moreover, it demonstrated potential application of the synthetic method for accommodating a wide range of catecholate functionalities by using the synthetic strategy to prepare N,N'-bis(2,3-dihydroxy-5-tert-butylbenzyl)-4,13-diaza-18-crown-6 (H 4 tBu 2ChaCha) for the first time. These H 4ChaCha and H 4 tBu2ChaCha macrocycles offer exciting opportunity to expand redox chemistry for the f-elements.more » As “proof-of-principle,” we isolated the unusual tetrameric cluster [La 2( tBuChaCha) 2] 2 from reactions between H 4 tBu 2ChaCha and La[N(SiMe 3) 2] 3. Characterization of [La 2( tBuChaCha) 2] 2 by elemental analysis, single crystal X-ray diffraction, IR, and UV–vis–NIR spectroscopy suggested that the complex represented a rare example of an f-element semiquinone. It further demonstrated that the combination of La 3+ and H 4 tBu 2ChaCha provided access to one-electron oxidation chemistry within redox potential windows that were amenable to mild reaction conditions.« less

A Series of F-Element Chelators; Diaza Crown Ethers Functionalized with Catecholate Binding Substituents

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

Stein, Benjamin W.; Cary, Samantha K.; Berg, John M.

Here, we report on the preparation of azacrown ethers functionalized with catechol groups. The synthetic approach was (1st) novel in that it made use of the Mannich reaction and (2nd) valuable in that it provided an improved synthesis (in terms of practical deployment) of the known N,N'-bis(2,3-dihydroxybenzyl)-4,13-diaza-18-crown-6, H 4ChaCha. Moreover, it demonstrated potential application of the synthetic method for accommodating a wide range of catecholate functionalities by using the synthetic strategy to prepare N,N'-bis(2,3-dihydroxy-5-tert-butylbenzyl)-4,13-diaza-18-crown-6 (H 4 tBu 2ChaCha) for the first time. These H 4ChaCha and H 4 tBu2ChaCha macrocycles offer exciting opportunity to expand redox chemistry for the f-elements.more » As “proof-of-principle,” we isolated the unusual tetrameric cluster [La 2( tBuChaCha) 2] 2 from reactions between H 4 tBu 2ChaCha and La[N(SiMe 3) 2] 3. Characterization of [La 2( tBuChaCha) 2] 2 by elemental analysis, single crystal X-ray diffraction, IR, and UV–vis–NIR spectroscopy suggested that the complex represented a rare example of an f-element semiquinone. It further demonstrated that the combination of La 3+ and H 4 tBu 2ChaCha provided access to one-electron oxidation chemistry within redox potential windows that were amenable to mild reaction conditions.« less

Supercritical fluid chromatography for separation and preparation of tautomeric 7-epimeric spiro oxindole alkaloids from Uncaria macrophylla.

PubMed

Yang, Wenzhi; Zhang, Yibei; Pan, Huiqin; Yao, Changliang; Hou, Jinjun; Yao, Shuai; Cai, Luying; Feng, Ruihong; Wu, Wanying; Guo, Dean

2017-02-05

Increasing challenge arising from configurational interconversion in aqueous solvent renders it rather difficult to isolate high-purity tautomeric reference standards and thus largely hinders the holistic quality control of traditional Chinese medicine (TCM). Spiro oxindole alkaloids (SOAs), as the markers for the medicinal Uncaria herbs, can easily isomerize in polar or aqueous solvent via a retro-Mannich reaction. In the present study, supercritical fluid chromatography (SFC) is utilized to separate and isolate two pairs of 7-epimeric SOAs, including rhynchophylline (R) and isorhynchophylline (IR), corynoxine (C) and corynoxine B (CB), from Uncaria macrophylla. Initially, the solvent that can stabilize SOA epimers was systematically screened, and acetonitrile was used to dissolve and as the modifier in SFC. Then, key parameters of ultra-high performance SFC (ultra-performance convergence chromatography, UPC 2 ), comprising stationary phase, additive in modifier, column temperature, ABPR pressure, and flow rate, were optimized in sequence. Two isocratic UPC 2 methods were developed on the achiral Torus 1-AA and Torus Diol columns, suitable for UV and MS detection, respectively. MCI gel column chromatography fractionated the U. macrophylla extract into two mixtures (R/IR and C/CB). Preparative SFC, using a Viridis Prep Silica 2-EP OBD column and acetonitrile-0.2% diethylamine in CO 2 as the mobile phase, was finally employed for compound purification. As a result, the purity of four SOA compounds was all higher than 95%. Different from reversed-phase HPLC, SFC, by use of water-free mobile phase (inert CO 2 and aprotic modifier), provides a solution to rapid analysis and isolation of tautomeric reference standards for quality control of TCM. Copyright © 2016 Elsevier B.V. All rights reserved.

Riccardin D-N induces lysosomal membrane permeabilization by inhibiting acid sphingomyelinase and interfering with sphingomyelin metabolism in vivo

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

Li, Lin

Lysosomes are important targets for anticancer drug discovery. Our previous study showed that Riccardin D-N (RD-N), a natural macrocylic bisbibenzyl derivative produced by Mannich reaction, induced cell death by accumulating in lysosomes. Experiments were performed on human lung squamous cell carcinoma tissue from left inferior lobar bronchus of patient xenografts and H460 cells. RD-N was administrated for 25 days. The specimens of xenografts in Balb/c athymic (nu +/nu +) male mice were removed for immunohistochemistry, subcellular fractionation, enzyme activities and Western blotting analysis. mRFP-GFP-LC3 reporter was used to examine autophagy in H460 cells. Sphingomyelin assay was evaluated by thin-layer chromatographymore » and assay kit. Lysosomal membrane permeabilization (LMP) caused by acid sphingomyelinase (ASM) inhibition and subsequent changes of sphingomyelin (SM) metabolism selectively destabilized the cancer cell lysosomes in RD-N-treated H460 cells in vitro and tumor xenograft model in vivo. The destabilized lysosomes induced the release of cathepsins from the lysosomes into the cytosol and further triggered cell death. These results explain the underlying mechanism of RD-N induced LMP. It can be concluded that a more lysosomotropic derivative was synthesized by introduction of an amine group, which could have more potential applications in cancer therapy. - Highlights: • Riccardin D-N (RD-N) significantly downregulated LAMP1 expressions. • RD-N inhibited the acid sphingomyelinase activity. • RD-N induced lysosomal membrane permeabilization in vivo. • RD-N induced SM accumulation in the lysosomal membranes. • RD-N also induced the release of cathepsins from destabilized lysosomes.« less

Synthesis of specifically deuterated S-benzylcysteines and of oxytocin and related diastereomers deuterated in the half-cystine positions

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

Upson, D.A.; Hruby, V.J.

1976-04-16

S-Benzylcysteine derivatives specifically deuterated at the ..cap alpha.. carbon only, the ..beta.. carbon only, and at both the ..cap alpha.. and ..beta.. carbons have been synthesized. These labeled compounds have been enzymatically resolved and the enantiomers and reacemates have been converted to the N-tert-butyloxycarbonyl derivatives. The deuterium labels were not exchanged under the conditions of the syntheses. Condensation of the sodium salt of diethyl ..cap alpha..-acetami-domalonate with benzyl chloromethyl sulfide followed by hydrolysis with DCl afforded S-benzyl-DL-(..cap alpha..-/sup 2/H/sub 1/) cysteine. Acetylation followed by treatment with hog renal acylase separated the stereoisomers. A Mannich reaction with (/sup 2/H/sub 2/) methylenemore » diacetate, diethyl ..cap alpha..-acetamido-..cap alpha..-dimethylamino(/sup 2/H/sub 2/)methylmalonate methiodide (15). Treatment of 15 with sodium benzylmercaptide gave diethyl ..cap alpha..-acetamido-..cap alpha..-benzylthio(/sup 2/H/sub 2/)methylmalonate, which was hydrolyzed with HCl to yield S-benzyl-DL-(..beta..,..beta..-/sup 2/H/sub 2/)cysteine or with DCl to afford S-benzyl-DL-(..cap alpha..,..beta..,..beta..,-/sup 2/H/sub 3/)cysteine. These compounds were resolved as before. The preparation of S-benzyl-DL-(..cap alpha..,..beta..,..beta..-/sup 2/H/sub 3/)cysteine required an efficient source of ethanol-d. This deuterated solvent was prepared in quantitative yield in 2 h from tetraethoxysilane, D/sub 2/O, and a catalytic amount of thionyl chloride. The protected deuterated amino acids were used in the preparation of several oxytocin analogues in which the specific deuteration appears in either the 1-hemicystine or the 6-hemicystine residues.« less

Atrial natriuretic peptide administered just prior to reperfusion limits infarction in rabbit hearts.

PubMed

Yang, Xi-Ming; Philipp, Sebastian; Downey, James M; Cohen, Michael V

2006-07-01

We investigated whether atrial natriuretic peptide (ANP) given just prior to reperfusion reduces infarction in rabbit hearts and whether protection is related to activation of protein kinase G (PKG). Isolated rabbit hearts were subjected to a 30-min period of regional ischemia; treated hearts received a 20-min infusion of ANP (0.1 microM) starting 5 min before 2 h of reperfusion. ANP infusion decreased infarction from 31.5+/-2.4% of the risk zone in untreated hearts to 12.5+/-2.0% (P<0.001). To explore mechanisms of protection ischemic hearts were treated simultaneously with ANP and isatin, a blocker of the natriuretic peptide receptor, shortly before reperfusion. ANP's protective effect was aborted (36.8+/-2.9% infarction). There is no acceptable blocker of protein kinase G that can be used in intact organs. However, 8-(4-chlorophenylthio)-guanosine 3', 5'-cyclic monophosphate (10 microM), a cell-permeable cGMP analog that directly activates PKG, was infused from 5 min before to 15 min after reperfusion. The PKG activator mimicked ANP's protection with only 18.2+/-3.6% infarction (P<0.001). 5-Hydroxyde-canoate (5-HD), a putative mitochondrial KATP channel (mKATP) inhibitor, abrogated ANP's protection (34.4+/-2.6% infarction). Unexpectedly, 1H-[1,2,4]oxadiazole- [4,3-a]quinoxalin-1-one (ODQ), a blocker of soluble guanylyl cyclase also prevented ANP's infarct-sparing effect. It is unclear whether this observation implicated participation of soluble guanylyl cyclase in the mechanism or simply a lack of selectivity of ODQ. Finally the reperfusion injury salvage kinases (RISK), phosphatidylinositol 3-kinase and extracellular signal-regulated kinase, were implicated in ANP's mechanism since either wortmannin or PD98059 infused at reperfusion prevented ANP's infarct-sparing effect. ANP administered just prior to reperfusion protects hearts against infarction, likely by activation of PKG, opening of mKATP, and stimulation of downstream kinases.

Characterization of supramolecular (H2O)18 water morphology and water-methanol (H2O)15(CH3OH)3 clusters in a novel phosphorus functionalized trimeric amino acid host.

PubMed

Raghuraman, Kannan; Katti, Kavita K; Barbour, Leonard J; Pillarsetty, Nagavarakishore; Barnes, Charles L; Katti, Kattesh V

2003-06-11

Phosphorus functionalized trimeric alanine compounds (l)- and (d)-P(CH(2)NHCH(CH(3))COOH)(3) 2 are prepared in 90% yields by the Mannich reaction of Tris(hydroxymethyl)phosphine 1 with (l)- or (d)- Alanine in aqueous media. The hydration properties of (l)-2 and (d)-2 in water and water-methanol mixtures are described. The crystal structure analysis of (l)-2.4H(2)O, reveals that the alanine molecules pack to form two-dimensional bilayers running parallel to (001). The layered structural motif depicts two closely packed monolayers of 2 each oriented with its phosphorus atoms projected at the center of the bilayer and adjacent monolayers are held together by hydrogen bonds between amine and carboxylate groups. The water bilayers are juxtaposed with the H-bonded alanine trimers leading to 18-membered (H(2)O)(18) water rings. Exposure of aqueous solution of (l)-2 and (d)-2 to methanol vapors resulted in closely packed (l)-2 and (d)-2 solvated with mixed water-methanol (H(2)O)(15)(CH(3)OH)(3) clusters. The O-O distances in the mixed methanol-water clusters of (l)-2.3H(2)O.CH(3)OH and (d)-2.3H(2)O.CH(3)OH (O-O(average) = 2.857 A) are nearly identical to the O-O distance observed in the supramolecular (H(2)O)(18) water structure (O-O(average) = 2.859 A) implying the retention of the hydrogen bonded structure in water despite the accommodation of hydrophobic methanol groups within the supramolecular (H(2)O)(15)(CH(3)OH)(3) framework. The O-O distances in (l)-2.3H(2)O.CH(3)OH and (d)-2.3H(2)O.CH(3)OH and in (H(2)O)(18) are very close to the O-O distance reported for liquid water (2.85 A).

Elucidation of Mechanisms and Selectivities of Metal-Catalyzed Reactions using Quantum Chemical Methodology.

PubMed

Santoro, Stefano; Kalek, Marcin; Huang, Genping; Himo, Fahmi

2016-05-17

Quantum chemical techniques today are indispensable for the detailed mechanistic understanding of catalytic reactions. The development of modern density functional theory approaches combined with the enormous growth in computer power have made it possible to treat quite large systems at a reasonable level of accuracy. Accordingly, quantum chemistry has been applied extensively to a wide variety of catalytic systems. A huge number of problems have been solved successfully, and vast amounts of chemical insights have been gained. In this Account, we summarize some of our recent work in this field. A number of examples concerned with transition metal-catalyzed reactions are selected, with emphasis on reactions with various kinds of selectivities. The discussed cases are (1) copper-catalyzed C-H bond amidation of indoles, (2) iridium-catalyzed C(sp(3))-H borylation of chlorosilanes, (3) vanadium-catalyzed Meyer-Schuster rearrangement and its combination with aldol- and Mannich-type additions, (4) palladium-catalyzed propargylic substitution with phosphorus nucleophiles, (5) rhodium-catalyzed 1:2 coupling of aldehydes and allenes, and finally (6) copper-catalyzed coupling of nitrones and alkynes to produce β-lactams (Kinugasa reaction). First, the methodology adopted in these studies is presented briefly. The electronic structure method in the great majority of these kinds of mechanistic investigations has for the last two decades been based on density functional theory. In the cases discussed here, mainly the B3LYP functional has been employed in conjunction with Grimme's empirical dispersion correction, which has been shown to improve the calculated energies significantly. The effect of the surrounding solvent is described by implicit solvation techniques, and the thermochemical corrections are included using the rigid-rotor harmonic oscillator approximation. The reviewed examples are chosen to illustrate the usefulness and versatility of the adopted methodology in solving complex problems and proposing new detailed reaction mechanisms that rationalize the experimental findings. For each of the considered reactions, a consistent mechanism is presented, the experimentally observed selectivities are reproduced, and their sources are identified. Reproducing selectivities requires high accuracy in computing relative transition state energies. As demonstrated by the results summarized in this Account, this accuracy is possible with the use of the presented methodology, benefiting of course from a large extent of cancellation of systematic errors. It is argued that as the employed models become larger, the number of rotamers and isomers that have to be considered for every stationary point increases and a careful assessment of their energies is therefore necessary in order to ensure that the lowest energy conformation is located. This issue constitutes a bottleneck of the investigation in some cases and is particularly important when analyzing selectivities, since small energy differences need to be reproduced.

Physical Fitness and Body Composition in 8-10-Year-Old Danish Children Are Associated With Sports Club Participation.

PubMed

Larsen, Malte N; Nielsen, Claus M; Ørntoft, Christina Ø; Randers, Morten B; Manniche, Vibeke; Hansen, Lone; Hansen, Peter R; Bangsbo, Jens; Krustrup, Peter

2017-12-01

Larsen, MN, Nielsen, CM, Ørntoft, CØ, Randers, M, Manniche, V, Hansen, L, Hansen, PR, Bangsbo, J, and Krustrup, P. Physical fitness and body composition in 8-10-year-old Danish children are associated with sports club participation. J Strength Cond Res 31(12): 3425-3434, 2017-We investigated whether physical fitness and body composition in 8-10-year-old Danish children are associated with sports club participation. The study included 423 schoolchildren, comprising 209 girls and 214 boys, of whom 67 and 74%, respectively, were active in sports clubs. Yo-Yo intermittent recovery level 1 for children (YYIR1C), balance, jump and coordination tests, together with dual-energy X-ray absorptiometry, were used to determine exercise capacity and body composition. Children active in sports clubs had better (p < 0.05) YYIR1C (33%, 767 ± 26 vs. 575 ± 29 m), 20-m sprint (3%, 4.33 ± 0.03 vs. 4.48 ± 0.04 seconds), coordination (6%, 68 ± 1 vs. 72 ± 1 second), and balance test performances (9%, 19.3 ± 0.5 vs. 21.2 ± 0.7 falls·min) and lower fat mass index (16%, 3.8 ± 0.1 vs. 4.5 ± 0.2 kg[fat]·m) than children not active in sports clubs. Ball game players had better (p < 0.05) YYIR1C (38%, 925 ± 39 vs. 671 ± 28 m), 20-m sprint (4%, 4.25 ± 0.03 vs. 4.42 ± 0.04 seconds), and coordination test performances (5%, 65 ± 1 vs. 69 ± 1 second), along with higher (p < 0.05) lean body mass (5%, 24.00 ± 0.22 vs. 22.83 ± 0.25 kg) and whole-body BMD (2%, 0.90 ± < 0.01 vs. 0.88 ± <0.01 g·cm) compared with children active in other sports. The study showed that 8[FIGURE DASH]10-year-old Danish children engaged in sports-club activity, especially ball game players, have better exercise capacity and superior body composition compared with children not active in sports clubs.

Steering Asymmetric Lewis Acid Catalysis Exclusively with Octahedral Metal-Centered Chirality.

PubMed

Zhang, Lilu; Meggers, Eric

2017-02-21

Catalysts for asymmetric synthesis must be chiral. Metal-based asymmetric catalysts are typically constructed by assembling chiral ligands around a central metal. In this Account, a new class of effective chiral Lewis acid catalysts is introduced in which the octahedral metal center constitutes the exclusive source of chirality. Specifically, the here discussed class of catalysts are composed of configurationally stable, chiral-at-metal Λ-configured (left-handed propeller) or Δ-configured (right-handed propeller) iridium(III) or rhodium(III) complexes containing two bidentate cyclometalating 5-tert-butyl-2-phenylbenzoxazole (dubbed IrO and RhO) or 5-tert-butyl-2-phenylbenzothiazole (dubbed IrS and RhS) ligands in addition to two exchange-labile acetonitriles. They are synthetically accessible in an enantiomerically pure fashion through a convenient auxiliary-mediated synthesis. Such catalysts are of interest due to their intrinsic structural simplicity (only achiral ligands) and the prospect of an especially effective asymmetric induction due to the intimate contact between the chiral metal center and the metal-coordinated substrates or reagents. With respect to chiral Lewis acid catalysis, the bis-cyclometalated iridium and rhodium complexes provide excellent catalytic activities and asymmetric inductions for a variety of reactions including Michael additions, Friedel-Crafts reactions, cycloadditions, α-aminations, α-fluorinations, Mannich reactions, and a cross-dehydrogenative coupling. Mechanistically, substrates such as 2-acyl imidazoles are usually activated by two-point binding. Exceptions exist as for example for an efficient iridium-catalyzed enantioselective transfer hydrogenation of arylketones with ammonium formate, which putatively proceeds through an iridium-hydride intermediate. The bis-cyclometalated iridium complexes catalyze visible-light-induced asymmetric reactions by intertwining asymmetric catalysis and photoredox catalysis in a unique fashion. This has been applied to the visible-light-induced α-alkylation of 2-acyl imidazoles (and in some instances 2-acylpyridines) with acceptor-substituted benzyl, phenacyl, trifluoromethyl, perfluoroalkyl, and trichloromethyl groups, in addition to photoinduced oxidative α-aminoalkylations and a photoinduced stereocontrolled radical-radical coupling, each employing a single iridium complex. In all photoinduced reaction schemes, the iridium complex serves as a chiral Lewis acid catalyst and at the same time as precursor of in situ assembled photoactive species. The nature of these photoactive intermediates then determines their photochemical properties and thereby the course of the asymmetric photoredox reactions. The bis-cyclometalated rhodium complexes are also very useful for asymmetric photoredox catalysis. Less efficient photochemical properties are compensated with a more rapid ligand exchange kinetics, which permits higher turnover frequencies of the catalytic cycle. This has been applied to a visible-light-induced enantioselective radical α-amination of 2-acyl imidazoles. In this reaction, an intermediate rhodium enolate is supposed to function as a photoactivatable smart initiator to initiate and reinitiate an efficient radical chain process. If a more efficient photoactivation is required, a rhodium-based Lewis acid can be complemented with a photoredox cocatalyst, and this has been applied to efficient catalytic asymmetric alkyl radical additions to acceptor-substituted alkenes. We believe that this class of chiral-only-at-metal Lewis acid catalysts will be of significant value in the field of asymmetric synthesis, in particular in combination with visible-light-induced redox chemistry, which has already resulted in novel strategies for asymmetric synthesis of chiral molecules. Hopefully, this work will also pave the way for the development of other asymmetric catalysts featuring exclusively octahedral centrochirality.

Physical Fitness and Body Composition in 8–10-Year-Old Danish Children Are Associated With Sports Club Participation

PubMed Central

Nielsen, Claus M.; Ørntoft, Christina Ø.; Randers, Morten B.; Manniche, Vibeke; Hansen, Lone; Hansen, Peter R.; Bangsbo, Jens; Krustrup, Peter

2017-01-01

Abstract Larsen, MN, Nielsen, CM, Ørntoft, CØ, Randers, M, Manniche, V, Hansen, L, Hansen, PR, Bangsbo, J, and Krustrup, P. Physical fitness and body composition in 8–10-year-old Danish children are associated with sports club participation. J Strength Cond Res 31(12): 3425–3434, 2017—We investigated whether physical fitness and body composition in 8–10-year-old Danish children are associated with sports club participation. The study included 423 schoolchildren, comprising 209 girls and 214 boys, of whom 67 and 74%, respectively, were active in sports clubs. Yo-Yo intermittent recovery level 1 for children (YYIR1C), balance, jump and coordination tests, together with dual-energy X-ray absorptiometry, were used to determine exercise capacity and body composition. Children active in sports clubs had better (p < 0.05) YYIR1C (33%, 767 ± 26 vs. 575 ± 29 m), 20-m sprint (3%, 4.33 ± 0.03 vs. 4.48 ± 0.04 seconds), coordination (6%, 68 ± 1 vs. 72 ± 1 second), and balance test performances (9%, 19.3 ± 0.5 vs. 21.2 ± 0.7 falls·min−1) and lower fat mass index (16%, 3.8 ± 0.1 vs. 4.5 ± 0.2 kg[fat]·m−2) than children not active in sports clubs. Ball game players had better (p < 0.05) YYIR1C (38%, 925 ± 39 vs. 671 ± 28 m), 20-m sprint (4%, 4.25 ± 0.03 vs. 4.42 ± 0.04 seconds), and coordination test performances (5%, 65 ± 1 vs. 69 ± 1 second), along with higher (p < 0.05) lean body mass (5%, 24.00 ± 0.22 vs. 22.83 ± 0.25 kg) and whole-body BMD (2%, 0.90 ± < 0.01 vs. 0.88 ± <0.01 g·cm−2) compared with children active in other sports. The study showed that 8‒10-year-old Danish children engaged in sports-club activity, especially ball game players, have better exercise capacity and superior body composition compared with children not active in sports clubs. PMID:28445225

Depicting changes in tumor biology in response to cetuximab mono- or combination therapy by apoptosis and proliferation imaging using 18F-ICMT-11 and 3'-Deoxy-3'-[18F]Fluorothymidine (18F-FLT) PET.

PubMed

Heinzmann, Kathrin; Nguyen, Quang-De; Honess, Davina Jean; Smith, Donna-Michelle; Stribbling, Stephen; Brickute, Diana; Barnes, Christopher; Griffiths, John Richard; Aboagye, Eric Ofori

2018-05-24

Imaging biomarkers must demonstrate their value in monitoring treatment. Two PET tracers, the caspase-3/7-specific isatin-5-sulfonamide 18 F-ICMT-11 and 3'-Deoxy-3'-[ 18 F]Fluorothymidine ( 18 F-FLT), were employed to detect early treatment-induced changes in tumor biology and whether any changes indicate response to cetuximab, administered as mono- or combination therapy with gemcitabine. Methods: Effects of single or repeated doses of the anti-Epidermal Growth Factor Receptor (EGFR) antibody cetuximab (10mg/kg on day 1 only or day 1 and 2) and/or a single dose of gemcitabine (125mg/kg; day 2) were investigated in mice bearing cetuximab-sensitive H1975 tumors (non-small cell lung cancer) by 18 F-ICMT-11 or 18 F-FLT-PET (day 3). Imaging was also performed in mice bearing cetuximab-insensitive HCT116 tumors (colorectal cancer) after two doses of cetuximab (day 1 and 2). For imaging/histology comparison, tumors were evaluated for proliferation (Ki67; thymidine kinase 1, TK1), cell death (cleaved caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)) and target engagement (EGFR expression) by immunohistochemistry, immunofluorescence and immunoblot, respectively. Tumor and plasma were analysed for thymidine and gemcitabine metabolites by liquid chromatography-mass spectrometry. Results: Retention of both tracers was sensitive to cetuximab in H1975 tumors. 18 F-ICMT-11 uptake and ex vivo cleaved caspase-3 staining notably increased in tumors treated with repeated doses of cetuximab- (75%) and combination-treatment (46%). While one dose of cetuximab was insufficient to induce apoptosis it did affect proliferation. Significant reduction in tumor 18 F-FLT uptake (44 to 50%; P < 0.001) induced by cetuximab mono- and combination-therapy were paralleled with a clear decrease in proliferation (%Ki67 decrease: 72 to 95%; P < 0.0001) and followed by marked tumor growth delay. TK1 expression and tumor thymidine concentrations were profoundly reduced. Neither imaging tracer depicted the gemcitabine-induced tumor changes. However, cleaved caspase-3 and Ki67 staining were not significantly different while TK1 expression and thymidine concentrations increased after gemcitabine-treatment. No cetuximab-induced modulation of the imaging tracers or other response markers was detected in the insensitive model HCT116. Conclusion: 18 F-ICMT-11 and 18 F-FLT are valuable tools to assess cetuximab-sensitivity depicting distinct and time-variant aspects of treatment response. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The Azomethine Ylide Route to Amine C–H Functionalization: Redox-Versions of Classic Reactions and a Pathway to New Transformations

PubMed Central

2016-01-01

Conspectus Redox-neutral methods for the functionalization of amine α-C–H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C–H bond functionalization are oxidative in nature. While the most efficient variants utilize atmospheric oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramolecular hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic organic transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet–Spengler, and Kabachnik–Fields reactions, Friedel–Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C–H bond functionalization. Intramolecular versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloadditions and other pericyclic processes, have been identified as common intermediates. Extension of this chemistry to amine α,β-difunctionalization has been shown to be possible by way of converting the intermediate azomethine ylides into transient enamines. This Account details the evolution of this general strategy and the progress made to date. Further included is a discussion of related decarboxylative reactions and transformations that result in the redox-neutral aromatization of (partially) saturated cyclic amines. These processes also involve azomethine ylides, reactive intermediates that appear to be far more prevalent in condensation chemistry of amines and carbonyl compounds than previously considered. In contrast, as exemplified by some redox transformations that have been studied in greater detail, iminium ions are not necessarily involved in all amine/aldehyde condensation reactions. PMID:25560649

The azomethine ylide route to amine C-H functionalization: redox-versions of classic reactions and a pathway to new transformations.

PubMed

Seidel, Daniel

2015-02-17

Conspectus Redox-neutral methods for the functionalization of amine α-C-H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C-H bond functionalization are oxidative in nature. While the most efficient variants utilize atmospheric oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramolecular hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic organic transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet-Spengler, and Kabachnik-Fields reactions, Friedel-Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C-H bond functionalization. Intramolecular versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloadditions and other pericyclic processes, have been identified as common intermediates. Extension of this chemistry to amine α,β-difunctionalization has been shown to be possible by way of converting the intermediate azomethine ylides into transient enamines. This Account details the evolution of this general strategy and the progress made to date. Further included is a discussion of related decarboxylative reactions and transformations that result in the redox-neutral aromatization of (partially) saturated cyclic amines. These processes also involve azomethine ylides, reactive intermediates that appear to be far more prevalent in condensation chemistry of amines and carbonyl compounds than previously considered. In contrast, as exemplified by some redox transformations that have been studied in greater detail, iminium ions are not necessarily involved in all amine/aldehyde condensation reactions.

[Progress in bio-based polyamides].

PubMed

Huang, Zhengqiang; Cui, Zhe; Zhang, Heming; Fu, Peng; Zhao, Qingxiang; Liu, Minying

2016-06-25

Bio-based polyamides are environment-friendly polymers. The precursors of bio-based polyamides come from bio-based materials such as castor oil, glucose and animal oil. Bio-based polyamides precursors include bio-based amino acids, bio-based lactams, bio-based diprotic acid and bio-based diamines. In this paper, we discussed the route of the precursors of bio-based polyamides that come from bio-based materials. We discussed the properties of bio-based polyamides. Bio-based PA11and bio-based PA1010 are well-known bio-based polyamides; we discussed the origin materials of the precursors, the route of manufacturing bio-based PA11 and PA1010, and their modifications status. The variety, classification and commercial production of bio-based polyamides were described in details, as well as bio-based polyamides development in China.

[Current status of bio-based materials industry in China].

PubMed

Diao, Xiaoqian; Weng, Yunxuan; Huang, Zhigang; Yang, Nan; Wang, Xiyuan; Zhang, Min; Jin, Yujuan

2016-06-25

In recent years, bio-based materials are becoming a new dominant industry leading the scientific and technological innovation, and economic development of the world. We reviewed the new development of bio-based materials industry in China, analyzed the entire market of bio-based materials products comprehensively, and also stated the industry status of bio-based chemicals, such as lactic acid, 1,3-propanediol, and succinic acid; biodegradable bio-based polymers, such as co-polyester of diacid and diol, polylactic acid, carbon dioxide based copolymer, polyhydroxyalknoates, polycaprolactone, and thermoplastic bio-based plastics; non-biodegradable bio-based polymers, such as bio-based polyamide, polytrimethylene terephthalate, bio-based polyurethane, and bio-based fibers.

48 CFR 32.1002 - Bases for performance-based payments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Bases for performance... REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Performance-Based Payments 32.1002 Bases for performance-based payments. Performance-based payments may be made on any of the following bases: (a...

48 CFR 32.1002 - Bases for performance-based payments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Bases for performance... REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Performance-Based Payments 32.1002 Bases for performance-based payments. Performance-based payments may be made on any of the following bases: (a...

48 CFR 32.1002 - Bases for performance-based payments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Bases for performance... REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Performance-Based Payments 32.1002 Bases for performance-based payments. Performance-based payments may be made on any of the following bases: (a...

48 CFR 32.1002 - Bases for performance-based payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Bases for performance... REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Performance-Based Payments 32.1002 Bases for performance-based payments. Performance-based payments may be made on any of the following bases: (a...

24 CFR 1000.103 - How may IHBG funds be used for tenant-based or project-based rental assistance?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Housing Activities § 1000.103 How may IHBG funds be used for tenant-based or project-based rental assistance? (a) IHBG funds may be used for project-based or tenant-based rental assistance. (b) IHBG funds may be used for project-based or tenant-based rental assistance that is provided in a manner...

Entanglement bases and general structures of orthogonal complete bases

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

Zhong Zaizhe

2004-10-01

In quantum mechanics and quantum information, to establish the orthogonal bases is a useful means. The existence of unextendible product bases impels us to study the 'entanglement bases' problems. In this paper, the concepts of entanglement bases and exact-entanglement bases are defined, and a theorem about exact-entanglement bases is given. We discuss the general structures of the orthogonal complete bases. Two examples of applications are given. At last, we discuss the problem of transformation of the general structure forms.

Net-centric ACT-R-Based Cognitive Architecture with DEVS Unified Process

DTIC Science & Technology

2011-04-01

effort has been spent in analyzing various forms of requirement specifications, viz, state-based, Natural Language based, UML-based, Rule- based, BPMN ...requirement specifications in one of the chosen formats such as BPMN , DoDAF, Natural Language Processing (NLP) based, UML- based, DSL or simply

Is questionnaire-based sitting time inaccurate and can it be improved? A cross-sectional investigation using accelerometer-based sitting time

PubMed Central

Gupta, Nidhi; Christiansen, Caroline Stordal; Hanisch, Christiana; Bay, Hans; Burr, Hermann; Holtermann, Andreas

2017-01-01

Objectives To investigate the differences between a questionnaire-based and accelerometer-based sitting time, and develop a model for improving the accuracy of questionnaire-based sitting time for predicting accelerometer-based sitting time. Methods 183 workers in a cross-sectional study reported sitting time per day using a single question during the measurement period, and wore 2 Actigraph GT3X+ accelerometers on the thigh and trunk for 1–4 working days to determine their actual sitting time per day using the validated Acti4 software. Least squares regression models were fitted with questionnaire-based siting time and other self-reported predictors to predict accelerometer-based sitting time. Results Questionnaire-based and accelerometer-based average sitting times were ≈272 and ≈476 min/day, respectively. A low Pearson correlation (r=0.32), high mean bias (204.1 min) and wide limits of agreement (549.8 to −139.7 min) between questionnaire-based and accelerometer-based sitting time were found. The prediction model based on questionnaire-based sitting explained 10% of the variance in accelerometer-based sitting time. Inclusion of 9 self-reported predictors in the model increased the explained variance to 41%, with 10% optimism using a resampling bootstrap validation. Based on a split validation analysis, the developed prediction model on ≈75% of the workers (n=132) reduced the mean and the SD of the difference between questionnaire-based and accelerometer-based sitting time by 64% and 42%, respectively, in the remaining 25% of the workers. Conclusions This study indicates that questionnaire-based sitting time has low validity and that a prediction model can be one solution to materially improve the precision of questionnaire-based sitting time. PMID:28093433

Influence of base modifications on in-flight base drag in the presence of jet exhaust for Mach numbers from 0.7 to 1.5

NASA Technical Reports Server (NTRS)

Powers, Sheryll Goecke

1988-01-01

The use of external modifications in the base region to reduce the base drag of a blunt-base body in the presence of jet engine exhaust was investigated in flight. Base pressure data were obtained for the following configurations: (1) blunt base; (2) blunt base modified with splitter plate; and (3) blunt base modified with two variations of a vented cavity. Reynolds number based on the length of the aircraft ranged from 1.2 to 3.1 x 10 to the 8th. Mach number M ranges were 0.71 less than or = M less than or = 0.95 and 1.10 less than or = M less than or = 1.51. The data were analyzed using the blunt base for a reference, or baseline condition. For 1.10 less than or = M less than or = 1.51, the reduction in base drag coefficient provided by the vented cavity configuration ranged from 0.07 to 0.05. These increments in base drag coefficient at M = 1.31 and 1.51 result in base drag reductions of 27 and 24 percent, respectively, when compared to the blunt base drag. For M less than 1, the drag increment between the blunt base and the modification is not significant.

Computer-based simulation training to improve learning outcomes in mannequin-based simulation exercises.

PubMed

Curtin, Lindsay B; Finn, Laura A; Czosnowski, Quinn A; Whitman, Craig B; Cawley, Michael J

2011-08-10

To assess the impact of computer-based simulation on the achievement of student learning outcomes during mannequin-based simulation. Participants were randomly assigned to rapid response teams of 5-6 students and then teams were randomly assigned to either a group that completed either computer-based or mannequin-based simulation cases first. In both simulations, students used their critical thinking skills and selected interventions independent of facilitator input. A predetermined rubric was used to record and assess students' performance in the mannequin-based simulations. Feedback and student performance scores were generated by the software in the computer-based simulations. More of the teams in the group that completed the computer-based simulation before completing the mannequin-based simulation achieved the primary outcome for the exercise, which was survival of the simulated patient (41.2% vs. 5.6%). The majority of students (>90%) recommended the continuation of simulation exercises in the course. Students in both groups felt the computer-based simulation should be completed prior to the mannequin-based simulation. The use of computer-based simulation prior to mannequin-based simulation improved the achievement of learning goals and outcomes. In addition to improving participants' skills, completing the computer-based simulation first may improve participants' confidence during the more real-life setting achieved in the mannequin-based simulation.

Foundation: Transforming data bases into knowledge bases

NASA Technical Reports Server (NTRS)

Purves, R. B.; Carnes, James R.; Cutts, Dannie E.

1987-01-01

One approach to transforming information stored in relational data bases into knowledge based representations and back again is described. This system, called Foundation, allows knowledge bases to take advantage of vast amounts of pre-existing data. A benefit of this approach is inspection, and even population, of data bases through an intelligent knowledge-based front-end.

36 CFR 1237.30 - How do agencies manage records on nitrocellulose-base and cellulose-acetate base film?

Code of Federal Regulations, 2010 CFR

2010-07-01

... records on nitrocellulose-base and cellulose-acetate base film? 1237.30 Section 1237.30 Parks, Forests... and cellulose-acetate base film? (a) The nitrocellulose base, a substance akin to gun cotton, is chemically unstable and highly flammable. Agencies must handle nitrocellulose-base film (used in the...

10 CFR 429.40 - Candelabra base incandescent lamps and intermediate base incandescent lamps.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 3 2013-01-01 2013-01-01 false Candelabra base incandescent lamps and intermediate base....40 Candelabra base incandescent lamps and intermediate base incandescent lamps. (a) Sampling plan for selection of units for testing. (1) The requirements of § 429.11 are applicable to candelabra base...

10 CFR 429.40 - Candelabra base incandescent lamps and intermediate base incandescent lamps.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 3 2012-01-01 2012-01-01 false Candelabra base incandescent lamps and intermediate base....40 Candelabra base incandescent lamps and intermediate base incandescent lamps. (a) Sampling plan for selection of units for testing. (1) The requirements of § 429.11 are applicable to candelabra base...

Introducing Computer-Based Testing in High-Stakes Exams in Higher Education: Results of a Field Experiment.

PubMed

Boevé, Anja J; Meijer, Rob R; Albers, Casper J; Beetsma, Yta; Bosker, Roel J

2015-01-01

The introduction of computer-based testing in high-stakes examining in higher education is developing rather slowly due to institutional barriers (the need of extra facilities, ensuring test security) and teacher and student acceptance. From the existing literature it is unclear whether computer-based exams will result in similar results as paper-based exams and whether student acceptance can change as a result of administering computer-based exams. In this study, we compared results from a computer-based and paper-based exam in a sample of psychology students and found no differences in total scores across the two modes. Furthermore, we investigated student acceptance and change in acceptance of computer-based examining. After taking the computer-based exam, fifty percent of the students preferred paper-and-pencil exams over computer-based exams and about a quarter preferred a computer-based exam. We conclude that computer-based exam total scores are similar as paper-based exam scores, but that for the acceptance of high-stakes computer-based exams it is important that students practice and get familiar with this new mode of test administration.

An Alternative Collaborative Supervision Practice between University-Based Teachers and School-Based Teachers

ERIC Educational Resources Information Center

Steele, Annfrid R.

2017-01-01

There is an increased focus in teacher education on research-based teaching as a means to develop a more research-based professional knowledge. However, research from several Western countries shows that neither school-based nor university-based teachers are familiar with how to integrate research-based knowledge in professional teacher practice.…

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

Concept and practice of evidence-based psychiatry and its application in Nigerian psychiatry: a critical review.

PubMed

Onifade, P O; Oluwole, L O

2006-01-01

The practice of Evidence-Based Psychiatry started in the 1990's, however prior to this time the practice of psychiatry did have an evidenced base though not structured and systematically spelt out. This study aimed to review the development of the concept and practice of Evidence-Based Psychiatry and to identify position of Nigerian psychiatry in it. Narrative reviews were made from information obtained from scientific publications i.e. (books and journals) and internet-based electronic articles. Evidence-Based Psychiatry emerged from Evidence-Based Medicine in the 1990's and aims to base practice on the best available evidence. The evidence is graded into A, B, and C, depending on the study design. Also critical to the practice of Evidence-Based Psychiatry is the availability of high-grade evidence and an efficient means of storing and retrieving it. Evidence-Based Psychiatry uses a systematic approach and involves five steps. Its scope covers aetiology, diagnosis, intervention, and prognosis. A comprehensive definition of Evidence-Based Psychiatry is given. There is a suggestion to change the term 'Evidence-Based' to 'Systematic Evidence-Based'. The right way to determine if a therapeutic intervention is evidence-based is to consider if the process that led to it is systematic in terms of the five steps of Evidence-Based Psychiatry. Nigeria is yet to develop structures required for Systematic Evidence-Based Psychiatry.

Is questionnaire-based sitting time inaccurate and can it be improved? A cross-sectional investigation using accelerometer-based sitting time.

PubMed

Gupta, Nidhi; Christiansen, Caroline Stordal; Hanisch, Christiana; Bay, Hans; Burr, Hermann; Holtermann, Andreas

2017-01-16

To investigate the differences between a questionnaire-based and accelerometer-based sitting time, and develop a model for improving the accuracy of questionnaire-based sitting time for predicting accelerometer-based sitting time. 183 workers in a cross-sectional study reported sitting time per day using a single question during the measurement period, and wore 2 Actigraph GT3X+ accelerometers on the thigh and trunk for 1-4 working days to determine their actual sitting time per day using the validated Acti4 software. Least squares regression models were fitted with questionnaire-based siting time and other self-reported predictors to predict accelerometer-based sitting time. Questionnaire-based and accelerometer-based average sitting times were ≈272 and ≈476 min/day, respectively. A low Pearson correlation (r=0.32), high mean bias (204.1 min) and wide limits of agreement (549.8 to -139.7 min) between questionnaire-based and accelerometer-based sitting time were found. The prediction model based on questionnaire-based sitting explained 10% of the variance in accelerometer-based sitting time. Inclusion of 9 self-reported predictors in the model increased the explained variance to 41%, with 10% optimism using a resampling bootstrap validation. Based on a split validation analysis, the developed prediction model on ≈75% of the workers (n=132) reduced the mean and the SD of the difference between questionnaire-based and accelerometer-based sitting time by 64% and 42%, respectively, in the remaining 25% of the workers. This study indicates that questionnaire-based sitting time has low validity and that a prediction model can be one solution to materially improve the precision of questionnaire-based sitting time. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

BEAT: A Web-Based Boolean Expression Fault-Based Test Case Generation Tool

ERIC Educational Resources Information Center

Chen, T. Y.; Grant, D. D.; Lau, M. F.; Ng, S. P.; Vasa, V. R.

2006-01-01

BEAT is a Web-based system that generates fault-based test cases from Boolean expressions. It is based on the integration of our several fault-based test case selection strategies. The generated test cases are considered to be fault-based, because they are aiming at the detection of particular faults. For example, when the Boolean expression is in…

Lessons to be Learned from Evidence-based Medicine: Practice and Promise of Evidence-based Medicine and Evidence-based Education.

ERIC Educational Resources Information Center

Wolf, Fredric M.

2000-01-01

Presents statistics of deaths caused by medical errors and argues the effects of misconceptions in diagnosis and treatment. Suggests evidence-based medicine to enhance the quality of practice and minimize error rates. Presents 10 evidence-based lessons and discusses the possible benefits of evidence-based medicine to evidence-based education and…

14 CFR 119.47 - Maintaining a principal base of operations, main operations base, and main maintenance base...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Maintaining a principal base of operations, main operations base, and main maintenance base; change of address. 119.47 Section 119.47 Aeronautics... Under Part 121 or Part 135 of This Chapter § 119.47 Maintaining a principal base of operations, main...

14 CFR 119.47 - Maintaining a principal base of operations, main operations base, and main maintenance base...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Maintaining a principal base of operations, main operations base, and main maintenance base; change of address. 119.47 Section 119.47 Aeronautics... Under Part 121 or Part 135 of This Chapter § 119.47 Maintaining a principal base of operations, main...

14 CFR 119.47 - Maintaining a principal base of operations, main operations base, and main maintenance base...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Maintaining a principal base of operations, main operations base, and main maintenance base; change of address. 119.47 Section 119.47 Aeronautics... Under Part 121 or Part 135 of This Chapter § 119.47 Maintaining a principal base of operations, main...

14 CFR 119.47 - Maintaining a principal base of operations, main operations base, and main maintenance base...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Maintaining a principal base of operations, main operations base, and main maintenance base; change of address. 119.47 Section 119.47 Aeronautics... Under Part 121 or Part 135 of This Chapter § 119.47 Maintaining a principal base of operations, main...

Online Learning: A Comparison of Web-Based and Land-Based Courses

ERIC Educational Resources Information Center

Brown, Joy L. M.

2012-01-01

Distance learning has become more popular in recent years. Due to concern about the quality of web-based courses, the purpose of this study was to explore the differences in web-based versus land-based courses. In this study, the researcher compares web-based and land-based education courses to explore the strengths and weaknesses of each type of…

High-Resolution Crystal Structure of a Silver(I)-RNA Hybrid Duplex Containing Watson-Crick-like C-Silver(I)-C Metallo-Base Pairs.

PubMed

Kondo, Jiro; Tada, Yoshinari; Dairaku, Takenori; Saneyoshi, Hisao; Okamoto, Itaru; Tanaka, Yoshiyuki; Ono, Akira

2015-11-02

Metallo-base pairs have been extensively studied for applications in nucleic acid-based nanodevices and genetic code expansion. Metallo-base pairs composed of natural nucleobases are attractive because nanodevices containing natural metallo-base pairs can be easily prepared from commercially available sources. Previously, we have reported a crystal structure of a DNA duplex containing T-Hg(II)-T base pairs. Herein, we have determined a high-resolution crystal structure of the second natural metallo-base pair between pyrimidine bases C-Ag(I)-C formed in an RNA duplex. One Ag(I) occupies the center between two cytosines and forms a C-Ag(I)-C base pair through N3-Ag(I)-N3 linear coordination. The C-Ag(I)-C base pair formation does not disturb the standard A-form conformation of RNA. Since the C-Ag(I)-C base pair is structurally similar to the canonical Watson-Crick base pairs, it can be a useful building block for structure-based design and fabrication of nucleic acid-based nanodevices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The influence of affective and cognitive arguments on message judgement and attitude change: The moderating effects of meta-bases and structural bases.

PubMed

Keer, Mario; van den Putte, Bas; Neijens, Peter; de Wit, John

2013-01-01

This study investigated whether the efficacy of affective vs. cognitive persuasive messages was moderated by (1) individuals' subjective assessments of whether their attitudes were based on affect or cognition (i.e. meta-bases) and (2) the degree individuals' attitudes were correlated with affect and cognition (i.e. structural bases). Participants (N = 97) were randomly exposed to a message containing either affective or cognitive arguments discouraging binge drinking. The results demonstrated that meta-bases and not structural bases moderated the influence of argument type on message judgement. Affective (cognitive) messages were judged more positively when individuals' meta-bases were more affective (cognitive). In contrast, structural bases and not meta-bases moderated the influence of argument type on attitude and intention change following exposure to the message. Surprisingly, change was greater among individuals who read a message that mismatched their structural attitude base. Affective messages were more effective as attitudes were more cognition-based, and vice versa. Thus, although individuals prefer messages that match their meta-base, attitude and intention change regarding binge drinking are best established by mismatching their structural base.

Introducing Computer-Based Testing in High-Stakes Exams in Higher Education: Results of a Field Experiment

PubMed Central

Boevé, Anja J.; Meijer, Rob R.; Albers, Casper J.; Beetsma, Yta; Bosker, Roel J.

2015-01-01

The introduction of computer-based testing in high-stakes examining in higher education is developing rather slowly due to institutional barriers (the need of extra facilities, ensuring test security) and teacher and student acceptance. From the existing literature it is unclear whether computer-based exams will result in similar results as paper-based exams and whether student acceptance can change as a result of administering computer-based exams. In this study, we compared results from a computer-based and paper-based exam in a sample of psychology students and found no differences in total scores across the two modes. Furthermore, we investigated student acceptance and change in acceptance of computer-based examining. After taking the computer-based exam, fifty percent of the students preferred paper-and-pencil exams over computer-based exams and about a quarter preferred a computer-based exam. We conclude that computer-based exam total scores are similar as paper-based exam scores, but that for the acceptance of high-stakes computer-based exams it is important that students practice and get familiar with this new mode of test administration. PMID:26641632

24 CFR 35.700 - Purpose and applicability.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... practicable lead-based paint hazards in residential properties receiving project-based assistance under a HUD... Program project-based rental assistance and sponsor-based rental assistance components (42 U.S.C. 11402...

24 CFR 35.700 - Purpose and applicability.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... practicable lead-based paint hazards in residential properties receiving project-based assistance under a HUD... Program project-based rental assistance and sponsor-based rental assistance components (42 U.S.C. 11402...

24 CFR 35.700 - Purpose and applicability.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... practicable lead-based paint hazards in residential properties receiving project-based assistance under a HUD... Program project-based rental assistance and sponsor-based rental assistance components (42 U.S.C. 11402...

24 CFR 35.700 - Purpose and applicability.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... practicable lead-based paint hazards in residential properties receiving project-based assistance under a HUD... Program project-based rental assistance and sponsor-based rental assistance components (42 U.S.C. 11402...

24 CFR 35.700 - Purpose and applicability.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... practicable lead-based paint hazards in residential properties receiving project-based assistance under a HUD... Program project-based rental assistance and sponsor-based rental assistance components (42 U.S.C. 11402...

Identification of Synthetic Fluids Utilizing Pyrolysis Gas Liquid Chromatographic Techniques

DTIC Science & Technology

1981-09-01

Base Stock No. 6327 Di-isodecyl Azelate II 7 Synthetic Base Stock No. 6318 Di-2-ethylhexyl Azelate I 8 Synthetic Base Stock No. 6323 l)i-2-ethylhexyl...Adipatc 13 9 Synthetic Base Stock No. 6321 Di-2-cthylhexyl Sebacattk 14 10 Synthetic Base Stock No. 6326 Di-tridecyl Azelate 15 11 Synthetic Base...Stock No. 6319 Di-tridecyl Adipate 16 12 Synthetic Base Stock No. 6320 Di-iso-octyl Azelate 17 13 Synthetic Base Stock No. 6516 TMP Triheptanoate 18 14

Construction of Silica-Based Micro/Nanoplatforms for Ultrasound Theranostic Biomedicine.

PubMed

Zhou, Yang; Han, Xiaoxia; Jing, Xiangxiang; Chen, Yu

2017-09-01

Ultrasound (US)-based biomedicine has been extensively explored for its applications in both diagnostic imaging and disease therapy. The fast development of theranostic nanomedicine significantly promotes the development of US-based biomedicine. This progress report summarizes and discusses the recent developments of rational design and fabrication of silica-based micro/nanoparticles for versatile US-based biomedical applications. The synthetic strategies and surface-engineering approaches of silica-based micro/nanoparticles are initially discussed, followed by detailed introduction on their US-based theranostic applications. They have been extensively explored in contrast-enhanced US imaging, US-based multi-modality imaging, synergistic high-intensity focused US (HIFU) ablation, sonosensitizer-enhanced sonodynamic therapy (SDT), as well as US-triggered chemotherapy. Their biological effects and biosafety have been briefly discussed to guarantee further clinical translation. Based on the high biocompatibility, versatile composition/structure and high performance in US-based theranostic biomedicine, these silica-based theranostic agents are expected to pave a new way for achieving efficient US-based theranostics of disease by taking the specific advantages of material science, nanotechnology and US-based biomedicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of diet on titratable acid-base excretion in grasshoppers.

PubMed

Frazier, M R; Harrison, J F; Behmer, S T

2000-01-01

Despite the potential for diet to affect organismal acid-base status, especially in herbivores, little is known about the effects of diet on acid-base loading and excretion. We tested the effects of diet on acid-base loading and excretion in grasshoppers by (a) comparing the fecal acid-base content of 15 grasshopper species collected from the field and (b) comparing fecal acid-base excretion rates of Schistocerca americana grasshoppers fed vegetable diets that differed in their ashed and raw acid-base contents. The field experiments indicated that grass-feeding species excrete fairly neutral fecal pellets, while forb/mixed-feeding species vary widely in their fecal acid-base contents. In the laboratory experiment, acid-base excretion rates were positively correlated with dietary ashed base intake rates but were not correlated with the acid-base content of raw, unashed diet or feeding rate. These experiments suggest that some diets could strongly challenge the acid-base homeostasis of herbivores; in some grasshoppers, dietary acid-base loads could produce certainly lethal 1-unit changes in average body pH within 6 h if they were not excreted.

A demonstrative model of a lunar base simulation on a personal computer

NASA Technical Reports Server (NTRS)

1985-01-01

The initial demonstration model of a lunar base simulation is described. This initial model was developed on the personal computer level to demonstrate feasibility and technique before proceeding to a larger computer-based model. Lotus Symphony Version 1.1 software was used to base the demonstration model on an personal computer with an MS-DOS operating system. The personal computer-based model determined the applicability of lunar base modeling techniques developed at an LSPI/NASA workshop. In addition, the personnal computer-based demonstration model defined a modeling structure that could be employed on a larger, more comprehensive VAX-based lunar base simulation. Refinement of this personal computer model and the development of a VAX-based model is planned in the near future.

Investigation of contrast-enhanced subtracted breast CT images with MAP-EM based on projection-based weighting imaging.

PubMed

Zhou, Zhengdong; Guan, Shaolin; Xin, Runchao; Li, Jianbo

2018-06-01

Contrast-enhanced subtracted breast computer tomography (CESBCT) images acquired using energy-resolved photon counting detector can be helpful to enhance the visibility of breast tumors. In such technology, one challenge is the limited number of photons in each energy bin, thereby possibly leading to high noise in separate images from each energy bin, the projection-based weighted image, and the subtracted image. In conventional low-dose CT imaging, iterative image reconstruction provides a superior signal-to-noise compared with the filtered back projection (FBP) algorithm. In this paper, maximum a posteriori expectation maximization (MAP-EM) based on projection-based weighting imaging for reconstruction of CESBCT images acquired using an energy-resolving photon counting detector is proposed, and its performance was investigated in terms of contrast-to-noise ratio (CNR). The simulation study shows that MAP-EM based on projection-based weighting imaging can improve the CNR in CESBCT images by 117.7%-121.2% compared with FBP based on projection-based weighting imaging method. When compared with the energy-integrating imaging that uses the MAP-EM algorithm, projection-based weighting imaging that uses the MAP-EM algorithm can improve the CNR of CESBCT images by 10.5%-13.3%. In conclusion, MAP-EM based on projection-based weighting imaging shows significant improvement the CNR of the CESBCT image compared with FBP based on projection-based weighting imaging, and MAP-EM based on projection-based weighting imaging outperforms MAP-EM based on energy-integrating imaging for CESBCT imaging.

40 CFR 745.233 - Lead-based paint activities requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.233 Lead-based paint activities requirements. Lead-based paint... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Lead-based paint activities...

40 CFR 745.233 - Lead-based paint activities requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.233 Lead-based paint activities requirements. Lead-based paint... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Lead-based paint activities...

40 CFR 745.233 - Lead-based paint activities requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.233 Lead-based paint activities requirements. Lead-based paint... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Lead-based paint activities...

40 CFR 745.233 - Lead-based paint activities requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.233 Lead-based paint activities requirements. Lead-based paint... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Lead-based paint activities...

40 CFR 745.233 - Lead-based paint activities requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.233 Lead-based paint activities requirements. Lead-based paint... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Lead-based paint activities...

[A Study of the Evidence-Based Nursing Practice Competence of Nurses and Its Clinical Applications].

PubMed

Hsu, Li-Ling; Hsieh, Suh-Ing; Huang, Ya-Hsuan

2015-10-01

Nurses must develop competence in evidence-based nursing in order to provide the best practice medical care to patients. Evidence-based nursing uses issue identification, data mining, and information consolidation from the related medical literature to help nurses find the best evidence. Therefore, for medical institutions to provide quality clinical care, it is necessary for nurses to develop competence in evidence-based nursing. This study aims to explore the effect of a fundamental evidence-based nursing course, as a form of educational intervention, on the development of evidence-based nursing knowledge, self-efficacy in evidence-based practice activities, and outcome expectations of evidence-based practice in nurse participants. Further the competence of these nurses in overcoming obstacles in evidence-based nursing practice. This quasi-experimental study used a pre-post test design with a single group of participants. A convenience sample of 34 nurses from a municipal hospital in northern Taiwan received 8 hours of a fundamental evidence-based nursing course over a two-week period. Participants were asked to complete four questionnaires before and after the intervention. The questionnaires measured the participants' basic demographics, experience in mining the medical literature, evidence-based nursing knowledge, self-efficacy in evidence-based practice activities, outcome expectations of evidence-based practice, competence in overcoming obstacles in evidence-based nursing practice, and learning satisfaction. Collected data was analyzed using paired t, Wilcoxon Signed Rank, and McNemar tests to measure the differences among participants' evidence-based nursing knowledge and practice activities before and after the workshop. The nurses demonstrated significantly higher scores from pre-test to post-test in evidence-based nursing knowledge II, self-efficacy in evidence-based nursing practice activities, and outcome expectations of evidence-based practice. Although the differences did not reach statistical significance, the post-test scores were significantly lower than pre-test scores in terms of the measurement of the nurses' obstacles in evidence-based nursing practice, which indicates significant improvements from pre-test to post-test in terms of the competence of participants in overcoming obstacles in evidence-based nursing practice. The intervention was found to be effective in improving the evidence-based nursing knowledge, self-efficacy in evidence-based nursing practice activities, and outcome expectations of evidence-based practice of participants and effective in reducing their obstacles in evidence-based nursing practice. Medical institutions should provide evidence-based nursing courses on a regular basis as a part of in-service education for nurses in order to help nurses develop the evidence-based nursing knowledge and practical competence required to provide quality clinical care.

Case-based reasoning for space applications: Utilization of prior experience in knowledge-based systems

NASA Technical Reports Server (NTRS)

King, James A.

1987-01-01

The goal is to explain Case-Based Reasoning as a vehicle to establish knowledge-based systems based on experimental reasoning for possible space applications. This goal will be accomplished through an examination of reasoning based on prior experience in a sample domain, and also through a presentation of proposed space applications which could utilize Case-Based Reasoning techniques.

Moral empiricism and the bias for act-based rules.

PubMed

Ayars, Alisabeth; Nichols, Shaun

2017-10-01

Previous studies on rule learning show a bias in favor of act-based rules, which prohibit intentionally producing an outcome but not merely allowing the outcome. Nichols, Kumar, Lopez, Ayars, and Chan (2016) found that exposure to a single sample violation in which an agent intentionally causes the outcome was sufficient for participants to infer that the rule was act-based. One explanation is that people have an innate bias to think rules are act-based. We suggest an alternative empiricist account: since most rules that people learn are act-based, people form an overhypothesis (Goodman, 1955) that rules are typically act-based. We report three studies that indicate that people can use information about violations to form overhypotheses about rules. In study 1, participants learned either three "consequence-based" rules that prohibited allowing an outcome or three "act-based" rules that prohibiting producing the outcome; in a subsequent learning task, we found that participants who had learned three consequence-based rules were more likely to think that the new rule prohibited allowing an outcome. In study 2, we presented participants with either 1 consequence-based rule or 3 consequence-based rules, and we found that those exposed to 3 such rules were more likely to think that a new rule was also consequence based. Thus, in both studies, it seems that learning 3 consequence-based rules generates an overhypothesis to expect new rules to be consequence-based. In a final study, we used a more subtle manipulation. We exposed participants to examples act-based or accident-based (strict liability) laws and then had them learn a novel rule. We found that participants who were exposed to the accident-based laws were more likely to think a new rule was accident-based. The fact that participants' bias for act-based rules can be shaped by evidence from other rules supports the idea that the bias for act-based rules might be acquired as an overhypothesis from the preponderance of act-based rules. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Evaluation of Rice Bran Wax as an Ointment Base with Standard Base

PubMed Central

Sabale, Vidya; Sabale, P. M.; Lakhotiya, C. L.

2009-01-01

Waxes have been used in many cosmetic preparations and pharmaceuticals as formulation aids. Rice bran wax is a byproduct of rice bran oil industry. Present investigation has been aimed to explore the possible utility of rice bran wax as ointment base compared to standard base. The rice bran wax obtained, purified and its physicochemical characteristics were determined. Ointment base acts as a carrier for medicaments. The ointment base composition determines not only the extent of penetration but also controls the transfer of medicaments from the base to the body tissues. Rice bran wax base was compared with standard base for appearance, spreadability, water number, wash ability and diffusibility. The results show that rice bran wax acts as an ointment base as far as its pharmaceutical properties are concerned and it could effectively replace comparatively costlier available ointment bases. PMID:20177466

Recent Progress in Optical Biosensors Based on Smartphone Platforms

PubMed Central

Geng, Zhaoxin; Zhang, Xiong; Fan, Zhiyuan; Lv, Xiaoqing; Su, Yue; Chen, Hongda

2017-01-01

With a rapid improvement of smartphone hardware and software, especially complementary metal oxide semiconductor (CMOS) cameras, many optical biosensors based on smartphone platforms have been presented, which have pushed the development of the point-of-care testing (POCT). Imaging-based and spectrometry-based detection techniques have been widely explored via different approaches. Combined with the smartphone, imaging-based and spectrometry-based methods are currently used to investigate a wide range of molecular properties in chemical and biological science for biosensing and diagnostics. Imaging techniques based on smartphone-based microscopes are utilized to capture microscale analysts, while spectrometry-based techniques are used to probe reactions or changes of molecules. Here, we critically review the most recent progress in imaging-based and spectrometry-based smartphone-integrated platforms that have been developed for chemical experiments and biological diagnosis. We focus on the analytical performance and the complexity for implementation of the platforms. PMID:29068375

The effects of performance-based assessment criteria on student performance and self-assessment skills

PubMed Central

van der Klink, Marcel R.; van Merriënboer, Jeroen J. G.

2010-01-01

This study investigated the effect of performance-based versus competence-based assessment criteria on task performance and self-assessment skills among 39 novice secondary vocational education students in the domain of nursing and care. In a performance-based assessment group students are provided with a preset list of performance-based assessment criteria, describing what students should do, for the task at hand. The performance-based group is compared to a competence-based assessment group in which students receive a preset list of competence-based assessment criteria, describing what students should be able to do. The test phase revealed that the performance-based group outperformed the competence-based group on test task performance. In addition, higher performance of the performance-based group was reached with lower reported mental effort during training, indicating a higher instructional efficiency for novice students. PMID:20054648

Recent Progress in Optical Biosensors Based on Smartphone Platforms.

PubMed

Geng, Zhaoxin; Zhang, Xiong; Fan, Zhiyuan; Lv, Xiaoqing; Su, Yue; Chen, Hongda

2017-10-25

With a rapid improvement of smartphone hardware and software, especially complementary metal oxide semiconductor (CMOS) cameras, many optical biosensors based on smartphone platforms have been presented, which have pushed the development of the point-of-care testing (POCT). Imaging-based and spectrometry-based detection techniques have been widely explored via different approaches. Combined with the smartphone, imaging-based and spectrometry-based methods are currently used to investigate a wide range of molecular properties in chemical and biological science for biosensing and diagnostics. Imaging techniques based on smartphone-based microscopes are utilized to capture microscale analysts, while spectrometry-based techniques are used to probe reactions or changes of molecules. Here, we critically review the most recent progress in imaging-based and spectrometry-based smartphone-integrated platforms that have been developed for chemical experiments and biological diagnosis. We focus on the analytical performance and the complexity for implementation of the platforms.

Web-based interventions for menopause: A systematic integrated literature review.

PubMed

Im, Eun-Ok; Lee, Yaelim; Chee, Eunice; Chee, Wonshik

2017-01-01

Advances in computer and Internet technologies have allowed health care providers to develop, use, and test various types of Web-based interventions for their practice and research. Indeed, an increasing number of Web-based interventions have recently been developed and tested in health care fields. Despite the great potential for Web-based interventions to improve practice and research, little is known about the current status of Web-based interventions, especially those related to menopause. To identify the current status of Web-based interventions used in the field of menopause, a literature review was conducted using multiple databases, with the keywords "online," "Internet," "Web," "intervention," and "menopause." Using these keywords, a total of 18 eligible articles were analyzed to identify the current status of Web-based interventions for menopause. Six themes reflecting the current status of Web-based interventions for menopause were identified: (a) there existed few Web-based intervention studies on menopause; (b) Web-based decision support systems were mainly used; (c) there was a lack of detail on the interventions; (d) there was a lack of guidance on the use of Web-based interventions; (e) counselling was frequently combined with Web-based interventions; and (f) the pros and cons were similar to those of Web-based methods in general. Based on these findings, directions for future Web-based interventions for menopause are provided. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nonlinear dynamic modeling of a simple flexible rotor system subjected to time-variable base motions

NASA Astrophysics Data System (ADS)

Chen, Liqiang; Wang, Jianjun; Han, Qinkai; Chu, Fulei

2017-09-01

Rotor systems carried in transportation system or under seismic excitations are considered to have a moving base. To study the dynamic behavior of flexible rotor systems subjected to time-variable base motions, a general model is developed based on finite element method and Lagrange's equation. Two groups of Euler angles are defined to describe the rotation of the rotor with respect to the base and that of the base with respect to the ground. It is found that the base rotations would cause nonlinearities in the model. To verify the proposed model, a novel test rig which could simulate the base angular-movement is designed. Dynamic experiments on a flexible rotor-bearing system with base angular motions are carried out. Based upon these, numerical simulations are conducted to further study the dynamic response of the flexible rotor under harmonic angular base motions. The effects of base angular amplitude, rotating speed and base frequency on response behaviors are discussed by means of FFT, waterfall, frequency response curve and orbits of the rotor. The FFT and waterfall plots of the disk horizontal and vertical vibrations are marked with multiplications of the base frequency and sum and difference tones of the rotating frequency and the base frequency. Their amplitudes will increase remarkably when they meet the whirling frequencies of the rotor system.

Design of Composite Structures Using Knowledge-Based and Case Based Reasoning

NASA Technical Reports Server (NTRS)

Lambright, Jonathan Paul

1996-01-01

A method of using knowledge based and case based reasoning to assist designers during conceptual design tasks of composite structures was proposed. The cooperative use of heuristics, procedural knowledge, and previous similar design cases suggests a potential reduction in design cycle time and ultimately product lead time. The hypothesis of this work is that the design process of composite structures can be improved by using Case-Based Reasoning (CBR) and Knowledge-Based (KB) reasoning in the early design stages. The technique of using knowledge-based and case-based reasoning facilitates the gathering of disparate information into one location that is easily and readily available. The method suggests that the inclusion of downstream life-cycle issues into the conceptual design phase reduces potential of defective, and sub-optimal composite structures. Three industry experts were interviewed extensively. The experts provided design rules, previous design cases, and test problems. A Knowledge Based Reasoning system was developed using the CLIPS (C Language Interpretive Procedural System) environment and a Case Based Reasoning System was developed using the Design Memory Utility For Sharing Experiences (MUSE) xviii environment. A Design Characteristic State (DCS) was used to document the design specifications, constraints, and problem areas using attribute-value pair relationships. The DCS provided consistent design information between the knowledge base and case base. Results indicated that the use of knowledge based and case based reasoning provided a robust design environment for composite structures. The knowledge base provided design guidance from well defined rules and procedural knowledge. The case base provided suggestions on design and manufacturing techniques based on previous similar designs and warnings of potential problems and pitfalls. The case base complemented the knowledge base and extended the problem solving capability beyond the existence of limited well defined rules. The findings indicated that the technique is most effective when used as a design aid and not as a tool to totally automate the composites design process. Other areas of application and implications for future research are discussed.

Literature-Based Instruction: Reshaping the Curriculum.

ERIC Educational Resources Information Center

Raphael, Taffy E., Ed.; Au, Kathryn H., Ed.

Making a case for the value of literature-based instruction, this book presents an overview of the extensive knowledge base supporting literature-based approaches to literacy instruction. It notes that literature-based instruction goes beyond simply changing the kinds of texts children read--also required in literature-based instruction are an…

Environmental Assessment: General Plan-Based Environmental Impact Analysis Process, Laughlin Air Force Base

DTIC Science & Technology

2007-05-01

BASED ENVIROMENTAL IMPACT ANALYSIS PROCESS LAUGHLIN AIR FORCE BASE, TEXAS AGENCY: 47th Flying Training Wing (FTW), Laughlin Air Force Base (AFB), Texas...8217\\ \\ \\ \\ \\\\ \\ ~ >(- \\ , ~ AOC01 \\ PS018 / WP002 \\ DP008 // WP006 \\ ~ ,/ ’----- -----·-------------~--/·/ LAUGHLIN AIR FORCE BASE ENVIROMENTAL RESTORATION

10 CFR 429.40 - Candelabra base incandescent lamps and intermediate base incandescent lamps.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 3 2014-01-01 2014-01-01 false Candelabra base incandescent lamps and intermediate base incandescent lamps. 429.40 Section 429.40 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION CERTIFICATION....40 Candelabra base incandescent lamps and intermediate base incandescent lamps. (a) Sampling plan for...

Starting Strong: Evidence-­Based Early Literacy Practices

ERIC Educational Resources Information Center

Blamey, Katrin; Beauchat, Katherine

2016-01-01

Four evidence-based instructional approaches create an essential resource for any early literacy teacher or coach. Improve your teaching practices in all areas of early literacy. Use four proven instructional approaches--standards based, evidenced based, assessment based, and student based--to improve their teaching practice in all areas of early…

Quantitative Analyses about Market- and Prevalence-Based Needs for Adapted Physical Education Teachers in the Public Schools in the United States

ERIC Educational Resources Information Center

Zhang, Jiabei

2011-01-01

The purpose of this study was to analyze quantitative needs for more adapted physical education (APE) teachers based on both market- and prevalence-based models. The market-based need for more APE teachers was examined based on APE teacher positions funded, while the prevalence-based need for additional APE teachers was analyzed based on students…

Systematic Differences in HIV, Syphilis and Risk Behaviors among Street Based and Establishment Based Female Sex Workers in Kathmandu Valley of Nepal.

PubMed

Kakchapati, Sampurna; Paudel, Tarun; Maharjan, Manju; Lim, Apiradee

2016-12-01

Female Sex Workers (FSWs) are main drivers of the HIV epidemic in Nepal. The work environment of sex work in Nepal is differentiated into establishment based (e.g. massage parlors, dance restaurants, hotels and lodges) and street based (e.g. streets, parks and markets). The study compares HIV, syphilis and risk behaviours among establishment-based FSWs and street-based FSWs in Kathmandu Valley of Nepal. Cross-sectional bio-behavioral surveys in 2006, 2008, 2011 and 2015 aimed to sample 2093 FSWs using two stage cluster sampling in the Kathmandu valley. Statistical analysis used chi-squared tests and logistic regression models to assess differences of HIV, syphilis and risk behaviors among street-based FSWs and establishment-based FSWs. The study included 39.7% street-based FSWs and 60.3% establishment-based FSWs. The street-based FSWs had lower education levels, older age groups, separated, longer duration of sex work and inconsistent condom used with clients than establishment-based FSWs (p<0.05). Establishment-based FSWs were lower exposure to HIV intervention programs and pervasive alcohol consumption and use of drugs (p<0.05). The multivariate analysis showed that street-based FSWs were more likely of HIV test (aOR=1.25, 95%CI=1.04, 1.49), HIV (aOR=4.72, 95%CI=2.19, 10.15) and syphilis (aOR=7.96, 95%CI=3.49, 18.15) than establishment-based FSWs. Street-based FSWs possessed higher risk behaviour and have higher HIV and syphilis prevalence. HIV prevention interventions targeting FSWs should consider risks and vulnerability of street-based FSWs. .

Systematic Differences in HIV, Syphilis and Risk Behaviors among Street Based and Establishment Based Female Sex Workers in Kathmandu Valley of Nepal

PubMed Central

Paudel, Tarun; Maharjan, Manju; Lim, Apiradee

2016-01-01

Background: Female Sex Workers (FSWs) are main drivers of the HIV epidemic in Nepal. The work environment of sex work in Nepal is differentiated into establishment based (e.g. massage parlors, dance restaurants, hotels and lodges) and street based (e.g. streets, parks and markets). The study compares HIV, syphilis and risk behaviours among establishment-based FSWs and street-based FSWs in Kathmandu Valley of Nepal. Materials and Methods: Cross-sectional bio-behavioral surveys in 2006, 2008, 2011 and 2015 aimed to sample 2093 FSWs using two stage cluster sampling in the Kathmandu valley. Statistical analysis used chi-squared tests and logistic regression models to assess differences of HIV, syphilis and risk behaviors among street-based FSWs and establishment-based FSWs. Results: The study included 39.7% street-based FSWs and 60.3% establishment-based FSWs. The street-based FSWs had lower education levels, older age groups, separated, longer duration of sex work and inconsistent condom used with clients than establishment-based FSWs (p<0.05). Establishment-based FSWs were lower exposure to HIV intervention programs and pervasive alcohol consumption and use of drugs (p<0.05). The multivariate analysis showed that street-based FSWs were more likely of HIV test (aOR=1.25, 95%CI=1.04, 1.49), HIV (aOR=4.72, 95%CI=2.19, 10.15) and syphilis (aOR=7.96, 95%CI=3.49, 18.15) than establishment-based FSWs. Conclusion: Street-based FSWs possessed higher risk behaviour and have higher HIV and syphilis prevalence. HIV prevention interventions targeting FSWs should consider risks and vulnerability of street-based FSWs. . PMID:28804674

Nurses' readiness for evidence-based practice at Finnish university hospitals: a national survey.

PubMed

Saunders, Hannele; Stevens, Kathleen R; Vehviläinen-Julkunen, Katri

2016-08-01

The aim of this study was to determine nurses' readiness for evidence-based practice at Finnish university hospitals. Although systematic implementation of evidence-based practice is essential to effectively improving patient outcomes and value of care, nurses do not consistently use evidence in practice. Uptake is hampered by lack of nurses' individual and organizational readiness for evidence-based practice. Although nurses' evidence-based practice competencies have been widely studied in countries leading the evidence-based practice movement, less is known about nurses' readiness for evidence-based practice in the non-English-speaking world. A cross-sectional descriptive survey design. The study was conducted in November-December 2014 in every university hospital in Finland with a convenience sample (n = 943) of practicing nurses. The electronic survey data were collected using the Stevens' Evidence-Based Practice Readiness Inventory, which was translated into Finnish according to standardized guidelines for translation of research instruments. The data were analysed using descriptive and inferential statistics. Nurses reported low to moderate levels of self-efficacy and low levels of evidence-based practice knowledge. A statistically significant, direct correlation was found between nurses' self-efficacy in employing evidence-based practice and their actual evidence-based practice knowledge level. Several statistically significant differences were found between nurses' socio-demographic variables and nurses' self-efficacy in employing evidence-based practice, and actual and perceived evidence-based practice knowledge. Finnish nurses at university hospitals are not ready for evidence-based practice. Although nurses are familiar with the concept of evidence-based practice, they lack the evidence-based practice knowledge and self-efficacy in employing evidence-based practice required for integrating best evidence into clinical care delivery. © 2016 John Wiley & Sons Ltd.

Marker-based or model-based RSA for evaluation of hip resurfacing arthroplasty? A clinical validation and 5-year follow-up.

PubMed

Lorenzen, Nina Dyrberg; Stilling, Maiken; Jakobsen, Stig Storgaard; Gustafson, Klas; Søballe, Kjeld; Baad-Hansen, Thomas

2013-11-01

The stability of implants is vital to ensure a long-term survival. RSA determines micro-motions of implants as a predictor of early implant failure. RSA can be performed as a marker- or model-based analysis. So far, CAD and RE model-based RSA have not been validated for use in hip resurfacing arthroplasty (HRA). A phantom study determined the precision of marker-based and CAD and RE model-based RSA on a HRA implant. In a clinical study, 19 patients were followed with stereoradiographs until 5 years after surgery. Analysis of double-examination migration results determined the clinical precision of marker-based and CAD model-based RSA, and at the 5-year follow-up, results of the total translation (TT) and the total rotation (TR) for marker- and CAD model-based RSA were compared. The phantom study showed that comparison of the precision (SDdiff) in marker-based RSA analysis was more precise than model-based RSA analysis in TT (p CAD < 0.001; p RE = 0.04) and TR (p CAD = 0.01; p RE < 0.001). The clinical precision (double examination in 8 patients) comparing the precision SDdiff was better evaluating the TT using the marker-based RSA analysis (p = 0.002), but showed no difference between the marker- and CAD model-based RSA analysis regarding the TR (p = 0.91). Comparing the mean signed values regarding the TT and the TR at the 5-year follow-up in 13 patients, the TT was lower (p = 0.03) and the TR higher (p = 0.04) in the marker-based RSA compared to CAD model-based RSA. The precision of marker-based RSA was significantly better than model-based RSA. However, problems with occluded markers lead to exclusion of many patients which was not a problem with model-based RSA. HRA were stable at the 5-year follow-up. The detection limit was 0.2 mm TT and 1° TR for marker-based and 0.5 mm TT and 1° TR for CAD model-based RSA for HRA.

Advanced membrane electrode assemblies for fuel cells

DOEpatents

Kim, Yu Seung; Pivovar, Bryan S.

2012-07-24

A method of preparing advanced membrane electrode assemblies (MEA) for use in fuel cells. A base polymer is selected for a base membrane. An electrode composition is selected to optimize properties exhibited by the membrane electrode assembly based on the selection of the base polymer. A property-tuning coating layer composition is selected based on compatibility with the base polymer and the electrode composition. A solvent is selected based on the interaction of the solvent with the base polymer and the property-tuning coating layer composition. The MEA is assembled by preparing the base membrane and then applying the property-tuning coating layer to form a composite membrane. Finally, a catalyst is applied to the composite membrane.

Theoretical determination of one-electron redox potentials for DNA bases, base pairs, and stacks.

PubMed

Paukku, Y; Hill, G

2011-05-12

Electron affinities, ionization potentials, and redox potentials for DNA bases, base pairs, and N-methylated derivatives are computed at the DFT/M06-2X/6-31++G(d,p) level of theory. Redox properties of a guanine-guanine stack model are explored as well. Reduction and oxidation potentials are in good agreement with the experimental ones. Electron affinities of base pairs were found to be negative. Methylation of canonical bases affects the ionization potentials the most. Base pair formation and base stacking lower ionization potentials by 0.3 eV. Pairing of guanine with the 5-methylcytosine does not seem to influence the redox properties of this base pair much.

Method for rapid base sequencing in DNA and RNA

DOEpatents

Jett, J.H.; Keller, R.A.; Martin, J.C.; Moyzis, R.K.; Ratliff, R.L.; Shera, E.B.; Stewart, C.C.

1987-10-07

A method is provided for the rapid base sequencing of DNA or RNA fragments wherein a single fragment of DNA or RNA is provided with identifiable bases and suspended in a moving flow stream. An exonuclease sequentially cleaves individual bases from the end of the suspended fragment. The moving flow stream maintains the cleaved bases in an orderly train for subsequent detection and identification. In a particular embodiment, individual bases forming the DNA or RNA fragments are individually tagged with a characteristic fluorescent dye. The train of bases is then excited to fluorescence with an output spectrum characteristic of the individual bases. Accordingly, the base sequence of the original DNA or RNA fragment can be reconstructed. 2 figs.

Mutually unbiased bases in six dimensions: The four most distant bases

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

Raynal, Philippe; Lue Xin; Englert, Berthold-Georg

2011-06-15

We consider the average distance between four bases in six dimensions. The distance between two orthonormal bases vanishes when the bases are the same, and the distance reaches its maximal value of unity when the bases are unbiased. We perform a numerical search for the maximum average distance and find it to be strictly smaller than unity. This is strong evidence that no four mutually unbiased bases exist in six dimensions. We also provide a two-parameter family of three bases which, together with the canonical basis, reach the numerically found maximum of the average distance, and we conduct a detailedmore » study of the structure of the extremal set of bases.« less

Advanced membrane electrode assemblies for fuel cells

DOEpatents

Kim, Yu Seung; Pivovar, Bryan S

2014-02-25

A method of preparing advanced membrane electrode assemblies (MEA) for use in fuel cells. A base polymer is selected for a base membrane. An electrode composition is selected to optimize properties exhibited by the membrane electrode assembly based on the selection of the base polymer. A property-tuning coating layer composition is selected based on compatibility with the base polymer and the electrode composition. A solvent is selected based on the interaction of the solvent with the base polymer and the property-tuning coating layer composition. The MEA is assembled by preparing the base membrane and then applying the property-tuning coating layer to form a composite membrane. Finally, a catalyst is applied to the composite membrane.

Method for rapid base sequencing in DNA and RNA

DOEpatents

Jett, J.H.; Keller, R.A.; Martin, J.C.; Moyzis, R.K.; Ratliff, R.L.; Shera, E.B.; Stewart, C.C.

1990-10-09

A method is provided for the rapid base sequencing of DNA or RNA fragments wherein a single fragment of DNA or RNA is provided with identifiable bases and suspended in a moving flow stream. An exonuclease sequentially cleaves individual bases from the end of the suspended fragment. The moving flow stream maintains the cleaved bases in an orderly train for subsequent detection and identification. In a particular embodiment, individual bases forming the DNA or RNA fragments are individually tagged with a characteristic fluorescent dye. The train of bases is then excited to fluorescence with an output spectrum characteristic of the individual bases. Accordingly, the base sequence of the original DNA or RNA fragment can be reconstructed. 2 figs.

Method for rapid base sequencing in DNA and RNA

DOEpatents

Jett, James H.; Keller, Richard A.; Martin, John C.; Moyzis, Robert K.; Ratliff, Robert L.; Shera, E. Brooks; Stewart, Carleton C.

1990-01-01

A method is provided for the rapid base sequencing of DNA or RNA fragments wherein a single fragment of DNA or RNA is provided with identifiable bases and suspended in a moving flow stream. An exonuclease sequentially cleaves individual bases from the end of the suspended fragment. The moving flow stream maintains the cleaved bases in an orderly train for subsequent detection and identification. In a particular embodiment, individual bases forming the DNA or RNA fragments are individually tagged with a characteristic fluorescent dye. The train of bases is then excited to fluorescence with an output spectrum characteristic of the individual bases. Accordingly, the base sequence of the original DNA or RNA fragment can be reconstructed.

23. Photographic copy of an asconstructed site plan for North ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

23. Photographic copy of an as-constructed site plan for North Base: Air Force Flight Test Center, Edwards Air Force Base, Edwards, California: North Base Site Plan, February 1970. This drawing shows the North Base building distribution substantially as it appears in 1995. Records on file at AFFTC/CE-CECC-B (Design/Construction Flight/RPMC), Edwards AFB, California. - Edwards Air Force Base, North Base, North Base Road, Boron, Kern County, CA

Comparability of a Paper-Based Language Test and a Computer-Based Language Test.

ERIC Educational Resources Information Center

Choi, Inn-Chull; Kim, Kyoung Sung; Boo, Jaeyool

2003-01-01

Utilizing the Test of English Proficiency, developed by Seoul National University (TEPS), examined comparability between the paper-based language test and the computer-based language test based on content and construct validation employing content analyses based on corpus linguistic techniques in addition to such statistical analyses as…

24 CFR 200.800 - Lead-based paint.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Lead-based paint. 200.800 Section... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Lead-Based Paint Poisoning Prevention § 200.800 Lead-based paint. The Lead-Based Paint Poisoning Prevention Act (42 U.S.C. 4821-4846), the Residential Lead-Based...

24 CFR 200.800 - Lead-based paint.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Lead-based paint. 200.800 Section... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Lead-Based Paint Poisoning Prevention § 200.800 Lead-based paint. The Lead-Based Paint Poisoning Prevention Act (42 U.S.C. 4821-4846), the Residential Lead-Based...

24 CFR 200.800 - Lead-based paint.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Lead-based paint. 200.800 Section... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Lead-Based Paint Poisoning Prevention § 200.800 Lead-based paint. The Lead-Based Paint Poisoning Prevention Act (42 U.S.C. 4821-4846), the Residential Lead-Based...

24 CFR 200.800 - Lead-based paint.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Lead-based paint. 200.800 Section... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Lead-Based Paint Poisoning Prevention § 200.800 Lead-based paint. The Lead-Based Paint Poisoning Prevention Act (42 U.S.C. 4821-4846), the Residential Lead-Based...

24 CFR 200.800 - Lead-based paint.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Lead-based paint. 200.800 Section... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Lead-Based Paint Poisoning Prevention § 200.800 Lead-based paint. The Lead-Based Paint Poisoning Prevention Act (42 U.S.C. 4821-4846), the Residential Lead-Based...

77 FR 26229 - Meloy Channel, U.S. Coast Guard Base Miami Beach, FL; Restricted Area

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

....S. Coast Guard Base Miami Beach, FL; Restricted Area AGENCY: United States Army Corps of Engineers... the waters surrounding the U.S. Coast Guard Base Miami Beach, Florida (Base Miami Beach). Base Miami... corridors encompassing the waters immediately contiguous to Base Miami Beach. The amendment will also serve...

40 CFR 1066.610 - Mass-based and molar-based exhaust emission calculations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Mass-based and molar-based exhaust... (CONTINUED) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Calculations § 1066.610 Mass-based and molar-based exhaust emission calculations. (a) Calculate your total mass of emissions over a test cycle as...

40 CFR 1066.610 - Mass-based and molar-based exhaust emission calculations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Mass-based and molar-based exhaust... (CONTINUED) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Calculations § 1066.610 Mass-based and molar-based exhaust emission calculations. (a) Calculate your total mass of emissions over a test cycle as...

Model-based RSA of a femoral hip stem using surface and geometrical shape models.

PubMed

Kaptein, Bart L; Valstar, Edward R; Spoor, Cees W; Stoel, Berend C; Rozing, Piet M

2006-07-01

Roentgen stereophotogrammetry (RSA) is a highly accurate three-dimensional measuring technique for assessing micromotion of orthopaedic implants. A drawback is that markers have to be attached to the implant. Model-based techniques have been developed to prevent using special marked implants. We compared two model-based RSA methods with standard marker-based RSA techniques. The first model-based RSA method used surface models, and the second method used elementary geometrical shape (EGS) models. We used a commercially available stem to perform experiments with a phantom as well as reanalysis of patient RSA radiographs. The data from the phantom experiment indicated the accuracy and precision of the elementary geometrical shape model-based RSA method is equal to marker-based RSA. For model-based RSA using surface models, the accuracy is equal to the accuracy of marker-based RSA, but its precision is worse. We found no difference in accuracy and precision between the two model-based RSA techniques in clinical data. For this particular hip stem, EGS model-based RSA is a good alternative for marker-based RSA.

A narrative review of undergraduate peer-based healthcare ethics teaching.

PubMed

Hindmarch, Thomas; Allikmets, Silvia; Knights, Felicity

2015-12-12

This study explores the literature in establishing the value of undergraduate peer-based healthcare ethics teaching as an educational methodology. A narrative review of the literature concerning peer-based ethics teaching was conducted. MEDLINE, EMBASE, CINAHL, SCOPUS databases, and the Cochrane Library, were systematically searched for studies of peer-based ethics or professionalism teaching. Selected studies related peer-based teaching to ethics education outcomes. Ten publications were identified. Selected studies were varied in their chosen intervention methodology and analysis. Collectively, the identified studies suggest peer-based ethics education is an effective and valued educational methodology in training healthcare professionals. One paper suggests peer-based ethics teaching has advantages over traditional didactic methods. Peer-based ethics teaching also receives positive feedback from student participants. However, the limited literature base demonstrates a clear need for more evaluation of this pedagogy. The current literature base suggests that undergraduate peer based healthcare ethics teaching is valuable in terms of efficacy and student satisfaction. We conclude that the medical community should invest in further study in order to capitalise upon the potential of peer-based ethics teaching in undergraduate healthcare education.

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

Stoiber, Marcus H.; Brown, James B.

This software implements the first base caller for nanopore data that calls bases directly from raw data. The basecRAWller algorithm has two major advantages over current nanopore base calling software: (1) streaming base calling and (2) base calling from information rich raw signal. The ability to perform truly streaming base calling as signal is received from the sequencer can be very powerful as this is one of the major advantages of this technology as compared to other sequencing technologies. As such enabling as much streaming potential as possible will be incredibly important as this technology continues to become more widelymore » applied in biosciences. All other base callers currently employ the Viterbi algorithm which requires the whole sequence to employ the complete base calling procedure and thus precludes a natural streaming base calling procedure. The other major advantage of the basecRAWller algorithm is the prediction of bases from raw signal which contains much richer information than the segmented chunks that current algorithms employ. This leads to the potential for much more accurate base calls which would make this technology much more valuable to all of the growing user base for this technology.« less

The roles of constraint-based and dedication-based influences on user's continued online shopping behavior.

PubMed

Chang, Su-Chao; Chou, Chi-Min

2012-11-01

The objective of this study was to determine empirically the role of constraint-based and dedication-based influences as drivers of the intention to continue using online shopping websites. Constraint-based influences consist of two variables: trust and perceived switching costs. Dedication-based influences consist of three variables: satisfaction, perceived usefulness, and trust. The current results indicate that both constraint-based and dedication-based influences are important drivers of the intention to continue using online shopping websites. The data also shows that trust has the strongest total effect on online shoppers' intention to continue using online shopping websites. In addition, the results indicate that the antecedents of constraint-based influences, technical bonds (e.g., perceived operational competence and perceived website interactivity) and social bonds (e.g., perceived relationship investment, community building, and intimacy) have indirect positive effects on the intention to continue using online shopping websites. Based on these findings, this research suggests that online shopping websites should build constraint-based and dedication-based influences to enhance user's continued online shopping behaviors simultaneously.

Household-based trip survey procedure

DOT National Transportation Integrated Search

1993-02-22

This memorandum describes the development of interim trip production cross-classification models for four home-based trip purposes: home-based work (HBW), home-based shopping and personal business (HBPB), home-based social and recreational (HBSR), an...

Overheating Anomalies during Flight Test Due to the Base Bleeding

NASA Technical Reports Server (NTRS)

Luchinsky, Dmitry; Hafiychuck, Halyna; Osipov, Slava; Ponizhovskaya, Ekaterina; Smelyanskiy, Vadim; Dagostino, Mark; Canabal, Francisco; Mobley, Brandon L.

2012-01-01

In this paper we present the results of the analytical and numerical studies of the plume interaction with the base flow in the presence of base out-gassing. The physics-based analysis and CFD modeling of the base heating for single solid rocket motor performed in this research addressed the following questions: what are the key factors making base flow so different from that in the Shuttle [1]; why CFD analysis of this problem reveals small plume recirculation; what major factors influence base temperature; and why overheating was initiated at a given time in the flight. To answer these questions topological analysis of the base flow was performed and Korst theory was used to estimate relative contributions of radiation, plume recirculation, and chemically reactive out-gassing to the base heating. It was shown that base bleeding and small base volume are the key factors contributing to the overheating, while plume recirculation is effectively suppressed by asymmetric configuration of the flow formed earlier in the flight. These findings are further verified using CFD simulations that include multi-species gas environment both in the plume and in the base. Solid particles in the exhaust plume (Al2O3) and char particles in the base bleeding were also included into the simulations and their relative contributions into the base temperature rise were estimated. The results of simulations are in good agreement with the temperature and pressure in the base measured during the test.

Evaluation of medical students of teacher-based and student-based teaching methods in Infectious diseases course.

PubMed

Ghasemzadeh, I; Aghamolaei, T; Hosseini-Parandar, F

2015-01-01

Introduction: In recent years, medical education has changed dramatically and many medical schools in the world have been trying for expand modern training methods. Purpose of the research is to appraise the medical students of teacher-based and student-based teaching methods in Infectious diseases course, in the Medical School of Hormozgan Medical Sciences University. Methods: In this interventional study, a total of 52 medical scholars that used Section in this Infectious diseases course were included. About 50% of this course was presented by a teacher-based teaching method (lecture) and 50% by a student-based teaching method (problem-based learning). The satisfaction of students regarding these methods was assessed by a questionnaire and a test was used to measure their learning. information are examined with using SPSS 19 and paired t-test. Results: The satisfaction of students of student-based teaching method (problem-based learning) was more positive than their satisfaction of teacher-based teaching method (lecture).The mean score of students in teacher-based teaching method was 12.03 (SD=4.08) and in the student-based teaching method it was 15.50 (SD=4.26) and where is a considerable variation among them (p<0.001). Conclusion: The use of the student-based teaching method (problem-based learning) in comparison with the teacher-based teaching method (lecture) to present the Infectious diseases course led to the student satisfaction and provided additional learning opportunities.

Performance analysis of a potassium-base AMTEC cell

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

Huang, C.; Hendricks, T.J.; Hunt, T.K.

1998-07-01

Sodium-BASE Alkali-Metal-Thermal-to-Electric-Conversion (AMTEC) cells have been receiving increased attention and funding from the Department of Energy, NASA and the United States Air Force. Recently, sodium-BASE (Na-BASE) AMTEC cells were selected for the Advanced Radioisotope Power System (ARPS) program for the next generation of deep-space missions and spacecraft. Potassium-BASE (K-BASE) AMTEC cells have not received as much attention to date, even though the vapor pressure of potassium is higher than that of sodium at the same temperature. So that, K-BASE AMTEC cells with potentially higher open circuit voltage and higher power output than Na-BASE AMTEC cells are possible. Because the surfacemore » tension of potassium is about half of the surface tension of sodium at the same temperature, the artery and evaporator design in a potassium AMTEC cell has much more challenging pore size requirements than designs using sodium. This paper uses a flexible thermal/fluid/electrical model to predict the performance of a K-BASE AMTEC cell. Pore sizes in the artery of K-BASE AMTEC cells must be smaller by an order of magnitude than in Na-BASE AMTEC cells. The performance of a K-BASE AMTEC cell was higher than a Na-BASE AMTEC cell at low voltages/high currents. K-BASE AMTEC cells also have the potential of much better electrode performance, thereby creating another avenue for potentially better performance in K-BASE AMTEC cells.« less

Disturbance of DNA conformation by the binding of testosterone-based platinum drugs via groove-face and intercalative interactions: a molecular dynamics simulation study

PubMed Central

2013-01-01

Background To explore novel platinum-based anticancer agents that are distinct from the structure and interaction mode of the traditional cisplatin by forming the bifunctional intrastrand 1,2 GpG adduct, the monofunctional platinum + DNA adducts with extensive non-covalent interactions had been studied. It was reported that the monofunctional testosterone-based platinum(II) agents present the high anticancer activity. Moreover, it was also found that the testosterone-based platinum agents could cause the DNA helix to undergo significant unwinding and bending over the non-testosterone-based platinum agents. However, the interaction mechanisms of these platinum agents with DNA at the atomic level are not yet clear so far. Results In the present work, we used molecular dynamics (MD) simulations and DNA conformational dynamics calculations to study the DNA distortion properties of the testosterone-based platinum + DNA, the improved testosterone-based platinum + DNA and the non-testosterone-based platinum + DNA adducts. The results show that the intercalative interaction of the improved flexible testosterone-based platinum agent with DNA molecule could cause larger DNA conformational distortion than the groove-face interaction of the rigid testosterone-based platinum agent with DNA molecule. Further investigations for the non-testosterone-based platinum agent reveal the occurrence of insignificant change of DNA conformation due to the absence of testosterone ligand in such agent. Based on the DNA dynamics analysis, the DNA base motions relating to DNA groove parameter changes and hydrogen bond destruction of DNA base pairs were also discussed in this work. Conclusions The flexible linker in the improved testosterone-based platinum agent causes an intercalative interaction with DNA in the improved testosterone-based platinum + DNA adduct, which is different from the groove-face interaction caused by a rigid linker in the testosterone-based platinum agent. The present investigations provide useful information of DNA conformation affected by a testosterone-based platinum complex at the atomic level. PMID:23517640

Compatibility of pedigree-based and marker-based relationship matrices for single-step genetic evaluation.

PubMed

Christensen, Ole F

2012-12-03

Single-step methods provide a coherent and conceptually simple approach to incorporate genomic information into genetic evaluations. An issue with single-step methods is compatibility between the marker-based relationship matrix for genotyped animals and the pedigree-based relationship matrix. Therefore, it is necessary to adjust the marker-based relationship matrix to the pedigree-based relationship matrix. Moreover, with data from routine evaluations, this adjustment should in principle be based on both observed marker genotypes and observed phenotypes, but until now this has been overlooked. In this paper, I propose a new method to address this issue by 1) adjusting the pedigree-based relationship matrix to be compatible with the marker-based relationship matrix instead of the reverse and 2) extending the single-step genetic evaluation using a joint likelihood of observed phenotypes and observed marker genotypes. The performance of this method is then evaluated using two simulated datasets. The method derived here is a single-step method in which the marker-based relationship matrix is constructed assuming all allele frequencies equal to 0.5 and the pedigree-based relationship matrix is constructed using the unusual assumption that animals in the base population are related and inbred with a relationship coefficient γ and an inbreeding coefficient γ / 2. Taken together, this γ parameter and a parameter that scales the marker-based relationship matrix can handle the issue of compatibility between marker-based and pedigree-based relationship matrices. The full log-likelihood function used for parameter inference contains two terms. The first term is the REML-log-likelihood for the phenotypes conditional on the observed marker genotypes, whereas the second term is the log-likelihood for the observed marker genotypes. Analyses of the two simulated datasets with this new method showed that 1) the parameters involved in adjusting marker-based and pedigree-based relationship matrices can depend on both observed phenotypes and observed marker genotypes and 2) a strong association between these two parameters exists. Finally, this method performed at least as well as a method based on adjusting the marker-based relationship matrix. Using the full log-likelihood and adjusting the pedigree-based relationship matrix to be compatible with the marker-based relationship matrix provides a new and interesting approach to handle the issue of compatibility between the two matrices in single-step genetic evaluation.

Research on the comparison of performance-based concept and force-based concept

NASA Astrophysics Data System (ADS)

Wu, Zeyu; Wang, Dongwei

2011-03-01

There are two ideologies about structure design: force-based concept and performance-based concept. Generally, if the structure operates during elastic stage, the two philosophies usually attain the same results. But beyond that stage, the shortage of force-based method is exposed, and the merit of performance-based is displayed. Pros and cons of each strategy are listed herein, and then which structure is best suitable to each method analyzed. At last, a real structure is evaluated by adaptive pushover method to verify that performance-based method is better than force-based method.

Accuracy and Reliability of Eye-Based vs Quadrant-Based Diagnosis of Plus Disease in Retinopathy of Prematurity.

PubMed

Kim, Sang Jin; Campbell, J Peter; Kalpathy-Cramer, Jayashree; Ostmo, Susan; Jonas, Karyn E; Choi, Dongseok; Chan, R V Paul; Chiang, Michael F

2018-06-01

Presence of plus disease in retinopathy of prematurity is the most critical element in identifying treatment-requiring disease. However, there is significant variability in plus disease diagnosis. In particular, plus disease has been defined as 2 or more quadrants of vascular abnormality, and it is not clear whether it is more reliably and accurately diagnosed by eye-based assessment of overall retinal appearance or by quadrant-based assessment combining grades of 4 individual quadrants. To compare eye-based vs quadrant-based diagnosis of plus disease and to provide insight for ophthalmologists about the diagnostic process. In this multicenter cohort study, we developed a database of 197 wide-angle retinal images from 141 preterm infants from neonatal intensive care units at 9 academic institutions (enrolled from July 2011 to December 2016). Each image was assigned a reference standard diagnosis based on consensus image-based and clinical diagnosis. Data analysis was performed from February 2017 to September 2017. Six graders independently diagnosed each of the 4 quadrants (cropped images) of the 197 eyes (quadrant-based diagnosis) as well as the entire image (eye-based diagnosis). Images were displayed individually, in random order. Quadrant-based diagnosis of plus disease was made when 2 or more quadrants were diagnosed as indicating plus disease by combining grades of individual quadrants post hoc. Intragrader and intergrader reliability (absolute agreement and κ statistic) and accuracy compared with the reference standard diagnosis. Of the 141 included preterm infants, 65 (46.1%) were female and 116 (82.3%) white, and the mean (SD) gestational age was 27.0 (2.6) weeks. There was variable agreement between eye-based and quadrant-based diagnosis among the 6 graders (Cohen κ range, 0.32-0.75). Four graders showed underdiagnosis of plus disease with quadrant-based diagnosis compared with eye-based diagnosis (by McNemar test). Intergrader agreement of quadrant-based diagnosis was lower than that of eye-based diagnosis (Fleiss κ, 0.75 [95% CI, 0.71-0.78] vs 0.55 [95% CI, 0.51-0.59]). The accuracy of eye-based diagnosis compared with the reference standard diagnosis was substantial to near-perfect, whereas that of quadrant-based plus disease diagnosis was only moderate to substantial for each grader. Graders had lower reliability and accuracy using quadrant-based diagnosis combining grades of individual quadrants than with eye-based diagnosis, suggesting that eye-based diagnosis has advantages over quadrant-based diagnosis. This has implications for more precise definitions of plus disease regarding the criterion of 2 or more quadrants, clinical care, computer-based image analysis, and education for all ophthalmologists who manage retinopathy of prematurity.

Construction of dynamic stochastic simulation models using knowledge-based techniques

NASA Technical Reports Server (NTRS)

Williams, M. Douglas; Shiva, Sajjan G.

1990-01-01

Over the past three decades, computer-based simulation models have proven themselves to be cost-effective alternatives to the more structured deterministic methods of systems analysis. During this time, many techniques, tools and languages for constructing computer-based simulation models have been developed. More recently, advances in knowledge-based system technology have led many researchers to note the similarities between knowledge-based programming and simulation technologies and to investigate the potential application of knowledge-based programming techniques to simulation modeling. The integration of conventional simulation techniques with knowledge-based programming techniques is discussed to provide a development environment for constructing knowledge-based simulation models. A comparison of the techniques used in the construction of dynamic stochastic simulation models and those used in the construction of knowledge-based systems provides the requirements for the environment. This leads to the design and implementation of a knowledge-based simulation development environment. These techniques were used in the construction of several knowledge-based simulation models including the Advanced Launch System Model (ALSYM).

Contests versus Norms: Implications of Contest-Based and Norm-Based Intervention Techniques

PubMed Central

Bergquist, Magnus; Nilsson, Andreas; Hansla, André

2017-01-01

Interventions using either contests or norms can promote environmental behavioral change. Yet research on the implications of contest-based and norm-based interventions is lacking. Based on Goal-framing theory, we suggest that a contest-based intervention frames a gain goal promoting intensive but instrumental behavioral engagement. In contrast, the norm-based intervention was expected to frame a normative goal activating normative obligations for targeted and non-targeted behavior and motivation to engage in pro-environmental behaviors in the future. In two studies participants (n = 347) were randomly assigned to either a contest- or a norm-based intervention technique. Participants in the contest showed more intensive engagement in both studies. Participants in the norm-based intervention tended to report higher intentions for future energy conservation (Study 1) and higher personal norms for non-targeted pro-environmental behaviors (Study 2). These findings suggest that contest-based intervention technique frames a gain goal, while norm-based intervention frames a normative goal. PMID:29218026

Contests versus Norms: Implications of Contest-Based and Norm-Based Intervention Techniques.

PubMed

Bergquist, Magnus; Nilsson, Andreas; Hansla, André

2017-01-01

Interventions using either contests or norms can promote environmental behavioral change. Yet research on the implications of contest-based and norm-based interventions is lacking. Based on Goal-framing theory, we suggest that a contest-based intervention frames a gain goal promoting intensive but instrumental behavioral engagement. In contrast, the norm-based intervention was expected to frame a normative goal activating normative obligations for targeted and non-targeted behavior and motivation to engage in pro-environmental behaviors in the future. In two studies participants ( n = 347) were randomly assigned to either a contest- or a norm-based intervention technique. Participants in the contest showed more intensive engagement in both studies. Participants in the norm-based intervention tended to report higher intentions for future energy conservation (Study 1) and higher personal norms for non-targeted pro-environmental behaviors (Study 2). These findings suggest that contest-based intervention technique frames a gain goal, while norm-based intervention frames a normative goal.

Widespread Transient Hoogsteen Base-Pairs in Canonical Duplex DNA with Variable Energetics

PubMed Central

Alvey, Heidi S.; Gottardo, Federico L.; Nikolova, Evgenia N.; Al-Hashimi, Hashim M.

2015-01-01

Hoogsteen base-pairing involves a 180 degree rotation of the purine base relative to Watson-Crick base-pairing within DNA duplexes, creating alternative DNA conformations that can play roles in recognition, damage induction, and replication. Here, using Nuclear Magnetic Resonance R1ρ relaxation dispersion, we show that transient Hoogsteen base-pairs occur across more diverse sequence and positional contexts than previously anticipated. We observe sequence-specific variations in Hoogsteen base-pair energetic stabilities that are comparable to variations in Watson-Crick base-pair stability, with Hoogsteen base-pairs being more abundant for energetically less favorable Watson-Crick base-pairs. Our results suggest that the variations in Hoogsteen stabilities and rates of formation are dominated by variations in Watson-Crick base pair stability, suggesting a late transition state for the Watson-Crick to Hoogsteen conformational switch. The occurrence of sequence and position-dependent Hoogsteen base-pairs provide a new potential mechanism for achieving sequence-dependent DNA transactions. PMID:25185517

Asymmetric Base-Bleed Effect on Aerospike Plume-Induced Base-Heating Environment

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Droege, Alan; DAgostino, Mark; Lee, Young-Ching; Williams, Robert

2004-01-01

A computational heat transfer design methodology was developed to study the dual-engine linear aerospike plume-induced base-heating environment during one power-pack out, in ascent flight. It includes a three-dimensional, finite volume, viscous, chemically reacting, and pressure-based computational fluid dynamics formulation, a special base-bleed boundary condition, and a three-dimensional, finite volume, and spectral-line-based weighted-sum-of-gray-gases absorption computational radiation heat transfer formulation. A separate radiation model was used for diagnostic purposes. The computational methodology was systematically benchmarked. In this study, near-base radiative heat fluxes were computed, and they compared well with those measured during static linear aerospike engine tests. The base-heating environment of 18 trajectory points selected from three power-pack out scenarios was computed. The computed asymmetric base-heating physics were analyzed. The power-pack out condition has the most impact on convective base heating when it happens early in flight. The source of its impact comes from the asymmetric and reduced base bleed.

The Consistencies and Vagaries of the Washington State Inventory of Evidence-Based Practice: The Definition of "Evidence-Based" in a Policy Context.

PubMed

Walker, Sarah Cusworth; Lyon, Aaron R; Aos, Steve; Trupin, Eric W

2017-01-01

As states increasingly establish the importance of evidence-based practice through policy and funding mandates, the definition of evidence-based practice can have a significant impact on investment decisions. Not meeting established criteria can mean a loss of funding for established programs and the implementation disruption of programs without a strong research base. Whether the definition of "evidence-based" is influenced by these high stakes contexts is an interesting question that can inform the larger field about the value and utility of evidence-based practice lists/inventories for disseminating knowledge. In this paper we review the development of the Washington State Inventory of Evidence-Based, Research-Based and Promising Practices as a case study for the process of defining evidence-based practice in a policy context. As part of this study we also present a comparison of other well-known evidence-based practice inventories and examine consistencies and differences in the process of identifying and developing program ratings.

Does a pre-intervention functional assessment increase intervention effectiveness? A meta-analysis of within-subject interrupted time-series studies.

PubMed

Hurl, Kylee; Wightman, Jade; Haynes, Stephen N; Virues-Ortega, Javier

2016-07-01

This study examined the relative effectiveness of interventions based on a pre-intervention functional behavioral assessment (FBA), compared to interventions not based on a pre-intervention FBA. We examined 19 studies that included a direct comparison between the effects of FBA- and non-FBA-based interventions with the same participants. A random effects meta-analysis of effect sizes indicated that FBA-based interventions were associated with large reductions in problem behaviors when using non-FBA-based interventions as a reference intervention (Effect size=0.85, 95% CI [0.42, 1.27], p<0.001). In addition, non-FBA based interventions had no effect on problem behavior when compared to no intervention (0.06, 95% CI [-0.21, 0.33], p=0.664). Interestingly, both FBA-based and non-FBA-based interventions had significant effects on appropriate behavior relative to no intervention, albeit the overall effect size was much larger for FBA-based interventions (FBA-based: 1.27, 95% CI [0.89, 1.66], p<0.001 vs. non-FBA-based: 0.35, 95% CI [0.14, 0.56], p=0.001). In spite of the evidence in favor of FBA-based interventions, the limited number of comparative studies with high methodological standards underlines the need for further comparisons of FBA-based versus non-FBA-based interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

An investigation of care-based vs. rule-based morality in frontotemporal dementia, Alzheimer's disease, and healthy controls.

PubMed

Carr, Andrew R; Paholpak, Pongsatorn; Daianu, Madelaine; Fong, Sylvia S; Mather, Michelle; Jimenez, Elvira E; Thompson, Paul; Mendez, Mario F

2015-11-01

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer's disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules. Published by Elsevier Ltd.

An Investigation of Care-Based vs. Rule-Based Morality in Frontotemporal Dementia, Alzheimer’s Disease, and Healthy Controls

PubMed Central

Carr, Andrew R.; Paholpak, Pongsatorn; Daianu, Madelaine; Fong, Sylvia S.; Mather, Michelle; Jimenez, Elvira E.; Thompson, Paul; Mendez, Mario F.

2015-01-01

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer’s disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules. PMID:26432341

Does Solving Insight-Based Problems Differ from Solving Learning-Based Problems? Some Evidence from an ERP Study

ERIC Educational Resources Information Center

Leikin, Roza; Waisman, Ilana; Leikin, Mark

2016-01-01

We asked: "What are the similarities and differences in mathematical processing associated with solving learning-based and insight-based problems?" To answer this question, the ERP research procedure was employed with 69 male adolescent subjects who solved specially designed insight-based and learning-based tests. Solutions of…

Representing Micro-Macro Linkages by Actor-Based Dynamic Network Models

ERIC Educational Resources Information Center

Snijders, Tom A. B.; Steglich, Christian E. G.

2015-01-01

Stochastic actor-based models for network dynamics have the primary aim of statistical inference about processes of network change, but may be regarded as a kind of agent-based models. Similar to many other agent-based models, they are based on local rules for actor behavior. Different from many other agent-based models, by including elements of…

Innovate and Evaluate: Expanding the Research Base for Competency-Based Education. AEI Series on Competency-Based Higher Education

ERIC Educational Resources Information Center

Kelly, Andrew P.; Columbus, Rooney

2016-01-01

Competency-based education (CBE) has garnered significant attention lately from reformers and policymakers. Put simply, CBE awards credit based on what students have learned rather than how much time they spend in class. Competency-based programs identify specific competencies, develop assessments to measure mastery of those competencies, and then…

77 FR 42652 - Meloy Channel, U.S. Coast Guard Base Miami Beach, FL; Restricted Area

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

....S. Coast Guard Base Miami Beach, FL; Restricted Area AGENCY: United States Army Corps of Engineers... Guard Base Miami Beach, Florida (Base Miami Beach). Base Miami Beach is composed of multiple U.S. Coast... contiguous to Base Miami Beach. The amendment will also serve to protect the general public from injury or...

Evidence-based policy as reflexive practice. What can we learn from evidence-based medicine?

PubMed

Bal, Roland

2017-04-01

The call for evidence-based policy is often accompanied by rather uncritical references to the success of evidence-based medicine, leading to often unsuccessful translation attempts. In this paper, I reflect on the practice of evidence-based medicine in an attempt to sketch a more productive approach to translating evidence into the practice of policy making. Discussing three episodes in the history of evidence-based medicine - clinical trials, and the production and use of clinical guidelines - I conclude that the success of evidence-based medicine is based on the creation of reflexive practices in which evidence and practice can be combined productively. In the conclusion, I discuss the prospects of such a practice for evidence-based policy.

Evidence based practice beliefs and implementation among nurses: a cross-sectional study

PubMed Central

2014-01-01

Background Having a positive attitude towards evidence-based practice and being able to see the value of evidence-based practice for patients have been reported as important for the implementation of evidence-based practice among nurses. The aim of this study was to map self-reported beliefs towards EBP and EBP implementation among nurses, and to investigate whether there was a positive correlation between EBP beliefs and EBP implementation. Method We carried out a cross-sectional study among 356 nurses at a specialist hospital for the treatment of cancer in Norway. The Norwegian translations of the Evidence-based Practice Belief Scale and the Evidence-based Practice Implementation Scale were used. Results In total, 185 nurses participated in the study (response rate 52%). The results showed that nurses were positive towards evidence-based practice, but only practised it to a small extent. There was a positive correlation (r) between beliefs towards evidence-based practice and implementation of evidence-based practice (r = 0.59, p = 0.001). There was a statistical significant positive, but moderate correlation between all the four subscales of the EBP Beliefs Scale (beliefs related to: 1) knowledge, 2) resources, 3) the value of EBP and 4) difficulty and time) and the EBP Implementation Scale, with the highest correlation observed for beliefs related to knowledge (r = 0.38, p < .0001). Participants who had learned about evidence-based practice had significantly higher scores on the Evidence-based Practice Belief Scale than participants who were unfamiliar with evidence-based practice. Those involved in evidence-based practice working groups also reported significantly higher scores on the Evidence-based Practice Belief Scale than participants not involved in these groups. Conclusion This study shows that nurses have a positive attitude towards evidence-based practice, but practise it to a lesser extent. There was a positive correlation between beliefs about evidence-based practice and implementation of evidence-based practice. Beliefs related to knowledge appear to have the greatest effect on implementation of evidence-based practice. Having knowledge and taking part in evidence-based practice working groups seem important. PMID:24661602

Patch-based generation of a pseudo CT from conventional MRI sequences for MRI-only radiotherapy of the brain

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

Andreasen, Daniel, E-mail: dana@dtu.dk; Van Leemput, Koen; Hansen, Rasmus H.

Purpose: In radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality, the information on electron density must be derived from the MRI scan by creating a so-called pseudo computed tomography (pCT). This is a nontrivial task, since the voxel-intensities in an MRI scan are not uniquely related to electron density. To solve the task, voxel-based or atlas-based models have typically been used. The voxel-based models require a specialized dual ultrashort echo time MRI sequence for bone visualization and the atlas-based models require deformable registrations of conventional MRI scans. In this study, we investigate the potential of amore » patch-based method for creating a pCT based on conventional T{sub 1}-weighted MRI scans without using deformable registrations. We compare this method against two state-of-the-art methods within the voxel-based and atlas-based categories. Methods: The data consisted of CT and MRI scans of five cranial RT patients. To compare the performance of the different methods, a nested cross validation was done to find optimal model parameters for all the methods. Voxel-wise and geometric evaluations of the pCTs were done. Furthermore, a radiologic evaluation based on water equivalent path lengths was carried out, comparing the upper hemisphere of the head in the pCT and the real CT. Finally, the dosimetric accuracy was tested and compared for a photon treatment plan. Results: The pCTs produced with the patch-based method had the best voxel-wise, geometric, and radiologic agreement with the real CT, closely followed by the atlas-based method. In terms of the dosimetric accuracy, the patch-based method had average deviations of less than 0.5% in measures related to target coverage. Conclusions: We showed that a patch-based method could generate an accurate pCT based on conventional T{sub 1}-weighted MRI sequences and without deformable registrations. In our evaluations, the method performed better than existing voxel-based and atlas-based methods and showed a promising potential for RT of the brain based only on MRI.« less

Quantum structures for recombination control in the light-emitting transistor

NASA Astrophysics Data System (ADS)

Chen, Kanuo; Hsiao, Fu-Chen; Joy, Brittany; Dallesasse, John M.

2017-02-01

Recombination of carriers in the direct-bandgap base of a transistor-injected quantum cascade laser (TI-QCL) is shown to be controllable through the field applied across the quantum cascade region located in the transistor's base-collector junction. The influence of the electric field on the quantum states in the cascade region's superlattice allows free flow of electrons out of the transistor base only for field values near the design field that provides optimal QCL gain. Quantum modulation of base recombination in the light-emitting transistor is therefore observed. In a GaAs-based light-emitting transistor, a periodic superlattice is grown between the p-type base and the n-type collector. Under different base-collector biasing conditions the distribution of quantum states, and as a consequence transition probabilities through the wells and barriers forming the cascade region, leads to strong field-dependent mobility for electrons in transit through the base-collector junction. The radiative base recombination, which is influenced by minority carrier transition lifetime, can be modulated through the quantum states alignment in the superlattice. A GaAs-based transistor-injected quantum cascade laser with AlGaAs/GaAs superlattice is designed and fabricated. Radiative base recombination is measured under both common-emitter and common-base configuration. In both configurations the optical output from the base is proportional to the emitter injection. When the quantum states in the superlattice are aligned the optical output in the base is reduced as electrons encounter less impedance entering the collector; when the quantum states are misaligned electrons have longer lifetime in the base and the radiative base recombination process is enhanced.

Data Bases in Writing: Method, Practice, and Metaphor.

ERIC Educational Resources Information Center

Schwartz, Helen J.

1985-01-01

Points out the need for informed and experienced users of data bases. Discusses the definition of a data base, creating a data base for research, comparison use, and checking written text as a data base. (EL)

Refining Automatically Extracted Knowledge Bases Using Crowdsourcing.

PubMed

Li, Chunhua; Zhao, Pengpeng; Sheng, Victor S; Xian, Xuefeng; Wu, Jian; Cui, Zhiming

2017-01-01

Machine-constructed knowledge bases often contain noisy and inaccurate facts. There exists significant work in developing automated algorithms for knowledge base refinement. Automated approaches improve the quality of knowledge bases but are far from perfect. In this paper, we leverage crowdsourcing to improve the quality of automatically extracted knowledge bases. As human labelling is costly, an important research challenge is how we can use limited human resources to maximize the quality improvement for a knowledge base. To address this problem, we first introduce a concept of semantic constraints that can be used to detect potential errors and do inference among candidate facts. Then, based on semantic constraints, we propose rank-based and graph-based algorithms for crowdsourced knowledge refining, which judiciously select the most beneficial candidate facts to conduct crowdsourcing and prune unnecessary questions. Our experiments show that our method improves the quality of knowledge bases significantly and outperforms state-of-the-art automatic methods under a reasonable crowdsourcing cost.

Sustainability of meat-based and plant-based diets and the environment.

PubMed

Pimentel, David; Pimentel, Marcia

2003-09-01

Worldwide, an estimated 2 billion people live primarily on a meat-based diet, while an estimated 4 billion live primarily on a plant-based diet. The US food production system uses about 50% of the total US land area, 80% of the fresh water, and 17% of the fossil energy used in the country. The heavy dependence on fossil energy suggests that the US food system, whether meat-based or plant-based, is not sustainable. The use of land and energy resources devoted to an average meat-based diet compared with a lactoovovegetarian (plant-based) diet is analyzed in this report. In both diets, the daily quantity of calories consumed are kept constant at about 3533 kcal per person. The meat-based food system requires more energy, land, and water resources than the lactoovovegetarian diet. In this limited sense, the lactoovovegetarian diet is more sustainable than the average American meat-based diet.

Method for rapid base sequencing in DNA and RNA with two base labeling

DOEpatents

Jett, J.H.; Keller, R.A.; Martin, J.C.; Posner, R.G.; Marrone, B.L.; Hammond, M.L.; Simpson, D.J.

1995-04-11

A method is described for rapid-base sequencing in DNA and RNA with two-base labeling and employing fluorescent detection of single molecules at two wavelengths. Bases modified to accept fluorescent labels are used to replicate a single DNA or RNA strand to be sequenced. The bases are then sequentially cleaved from the replicated strand, excited with a chosen spectrum of electromagnetic radiation, and the fluorescence from individual, tagged bases detected in the order of cleavage from the strand. 4 figures.

A Fundamental Approach to Developing Aluminium based Bulk Amorphous Alloys based on Stable Liquid Metal Structures and Electronic Equilibrium - 154041

DTIC Science & Technology

2017-03-28

AFRL-AFOSR-JP-TR-2017-0027 A Fundamental Approach to Developing Aluminium-based Bulk Amorphous Alloys based on Stable Liquid -Metal Structures and...to 16 Dec 2016 4.  TITLE AND SUBTITLE A Fundamental Approach to Developing Aluminium-based Bulk Amorphous Alloys based on Stable Liquid -Metal...including Al, Cu, Ni, Zr, Mg, Pd, Ga , Ca. Many new Al-based amorphous alloys were found within the numerous alloy systems studied in this project, and

Method for rapid base sequencing in DNA and RNA with two base labeling

DOEpatents

Jett, James H.; Keller, Richard A.; Martin, John C.; Posner, Richard G.; Marrone, Babetta L.; Hammond, Mark L.; Simpson, Daniel J.

1995-01-01

Method for rapid-base sequencing in DNA and RNA with two-base labeling and employing fluorescent detection of single molecules at two wavelengths. Bases modified to accept fluorescent labels are used to replicate a single DNA or RNA strand to be sequenced. The bases are then sequentially cleaved from the replicated strand, excited with a chosen spectrum of electromagnetic radiation, and the fluorescence from individual, tagged bases detected in the order of cleavage from the strand.

A systematic review of surgical skills transfer after simulation-based training: laparoscopic cholecystectomy and endoscopy.

PubMed

Dawe, Susan R; Windsor, John A; Broeders, Joris A J L; Cregan, Patrick C; Hewett, Peter J; Maddern, Guy J

2014-02-01

A systematic review to determine whether skills acquired through simulation-based training transfer to the operating room for the procedures of laparoscopic cholecystectomy and endoscopy. Simulation-based training assumes that skills are directly transferable to the operation room, but only a few studies have investigated the effect of simulation-based training on surgical performance. A systematic search strategy that was used in 2006 was updated to retrieve relevant studies. Inclusion of articles was determined using a predetermined protocol, independent assessment by 2 reviewers, and a final consensus decision. Seventeen randomized controlled trials and 3 nonrandomized comparative studies were included in this review. In most cases, simulation-based training was in addition to patient-based training programs. Only 2 studies directly compared simulation-based training in isolation with patient-based training. For laparoscopic cholecystectomy (n = 10 studies) and endoscopy (n = 10 studies), participants who reached simulation-based skills proficiency before undergoing patient-based assessment performed with higher global assessment scores and fewer errors in the operating room than their counterparts who did not receive simulation training. Not all parameters measured were improved. Two of the endoscopic studies compared simulation-based training in isolation with patient-based training with different results: for sigmoidoscopy, patient-based training was more effective, whereas for colonoscopy, simulation-based training was equally effective. Skills acquired by simulation-based training seem to be transferable to the operative setting for laparoscopic cholecystectomy and endoscopy. Future research will strengthen these conclusions by evaluating predetermined competency levels on the same simulators and using objective validated global rating scales to measure operative performance.

Effectiveness of an education intervention to strengthen nurses' readiness for evidence-based practice: A single-blind randomized controlled study.

PubMed

Saunders, Hannele; Vehviläinen-Julkunen, Katri; Stevens, Kathleen R

2016-08-01

Nurses' lack of readiness for evidence-based practice slows down the uptake, adoption, and implementation of evidence-based practice which is of international concern as it impedes attainment of the highest quality of care and best patient outcomes. There is limited evidence about the most effective approaches to strengthen nurses' readiness for evidence-based practice. To evaluate the effectiveness of an Advanced Practice Nurse-delivered education program to strengthen nurses' readiness for evidence-based practice at a university hospital. A single-blind randomized controlled trial with repeated measures design, with measures completed during spring and fall 2015, before the education program (T0), within 1week after (T1), 8weeks after (T2), and 4months after completion of education interventions (T3). One large university hospital system in Finland, consisting of 15 acute care hospitals. The required sample size, calculated by a priori power analysis and including a 20% estimated attrition rate, called for 85 nurse participants to be recruited. Nurses working in different professional nursing roles and care settings were randomly allocated into two groups: intervention (evidence-based practice education, N=43) and control (research utilization education, N=34). The nurse participants received live 4-h education sessions on the basic principles of evidence-based practice (intervention group) and on the principles of research utilization (control group). The intervention group also received a web-based interactive evidence-based practice education module with a booster mentoring intervention. Readiness for evidence-based practice data, previous experience with evidence-based practice, and participant demographics were collected using the Stevens' EBP Readiness Inventory. Nurses' confidence in employing evidence-based practice and actual evidence-based practice knowledge were lower at T0, compared with the post-education scores, specifically at T1. The improvement in the confidence or actual evidence-based practice knowledge levels did not differ between the intervention and control groups. Confidence in employing evidence-based practice was directly correlated with level of education and inversely correlated with age. Actual evidence-based practice knowledge was lowest among nurses who had no previous knowledge or experience of evidence-based practice. Both the evidence-based practice and research utilization education interventions improved nurses' confidence in employing evidence-based practice and actual evidence-based practice knowledge, strengthening their evidence-based practice readiness at least in the short-term. Most of the variation in the confidence in employing evidence-based practice and actual evidence-based practice knowledge levels was due to background factors, such as primary role and education level, which emphasize differences in educational needs between nurses with diverse backgrounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Text-Based and Visual-Based Programming Input Methods for First-Time Learners

ERIC Educational Resources Information Center

Saito, Daisuke; Washizaki, Hironori; Fukazawa, Yoshiaki

2017-01-01

Aim/Purpose: When learning to program, both text-based and visual-based input methods are common. However, it is unclear which method is more appropriate for first-time learners (first learners). Background: The differences in the learning effect between text-based and visual-based input methods for first learners are compared the using a…

78 FR 44424 - Revisions to Page 700 of FERC Form No. 6

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... original cost (TOC) rate base information provided on line 5 of page 700 by requiring the reporting of the three subparts of the TOC rate base: (1) Rate Base--Original Cost (proposed line 5a); (2) Rate Base... oil pipeline's TOC Rate Base. Consequently, the NOPR proposed to move the TOC rate base from line 5 to...

NetWeaver for EMDS user guide (version 1.1): a knowledge base development system.

Treesearch

Keith M. Reynolds

1999-01-01

The guide describes use of the NetWeaver knowledge base development system. Knowledge representation in NetWeaver is based on object-oriented fuzzy-logic networks that offer several significant advantages over the more traditional rulebased representation. Compared to rule-based knowledge bases, NetWeaver knowledge bases are easier to build, test, and maintain because...

Model Documentation of Base Case Data | Regional Energy Deployment System

Science.gov Websites

Model | Energy Analysis | NREL Documentation of Base Case Data Model Documentation of Base Case base case of the model. The base case was developed simply as a point of departure for other analyses Base Case derives many of its inputs from the Energy Information Administration's (EIA's) Annual Energy

Creating Stimulating Learning and Thinking Using New Models of Activity-Based Learning and Metacognitive-Based Activities

ERIC Educational Resources Information Center

Pang, Katherine

2010-01-01

The purpose of this paper is to present a novel way to stimulate learning, creativity, and thinking based on a new understanding of activity-based learning (ABL) and two methods for developing metacognitive-based activities for the classroom. ABL, in this model, is based on the premise that teachers are distillers and facilitators of information…

Overview of Selected State Policies and Supports Related to K-12 Competency-Based Education. REL 2017-249

ERIC Educational Resources Information Center

Brodersen, R. Marc; Yanoski, David; Mason, Katie; Apthorp, Helen; Piscatelli, Jennifer

2017-01-01

Competency-based education--also known as proficiency-based, mastery-based, and performance-based education--has received increased attention in recent years as an education approach that may help ensure that students graduate from high school with the knowledge and skills necessary for college and their careers. In competency-based education,…

On Decision-Making Among Multiple Rule-Bases in Fuzzy Control Systems

NASA Technical Reports Server (NTRS)

Tunstel, Edward; Jamshidi, Mo

1997-01-01

Intelligent control of complex multi-variable systems can be a challenge for single fuzzy rule-based controllers. This class of problems cam often be managed with less difficulty by distributing intelligent decision-making amongst a collection of rule-bases. Such an approach requires that a mechanism be chosen to ensure goal-oriented interaction between the multiple rule-bases. In this paper, a hierarchical rule-based approach is described. Decision-making mechanisms based on generalized concepts from single-rule-based fuzzy control are described. Finally, the effects of different aggregation operators on multi-rule-base decision-making are examined in a navigation control problem for mobile robots.

A narrative review of undergraduate peer-based healthcare ethics teaching

PubMed Central

Allikmets, Silvia; Knights, Felicity

2015-01-01

Objectives This study explores the literature in establishing the value of undergraduate peer-based healthcare ethics teaching as an educational methodology. Methods A narrative review of the literature concerning peer-based ethics teaching was conducted. MEDLINE, EMBASE, CINAHL, SCOPUS databases, and the Cochrane Library, were systematically searched for studies of peer-based ethics or professionalism teaching. Selected studies related peer-based teaching to ethics education outcomes. Results Ten publications were identified. Selected studies were varied in their chosen intervention methodology and analysis. Collectively, the identified studies suggest peer-based ethics education is an effective and valued educational methodology in training healthcare professionals. One paper suggests peer-based ethics teaching has advantages over traditional didactic methods. Peer-based ethics teaching also receives positive feedback from student participants. However, the limited literature base demonstrates a clear need for more evaluation of this pedagogy. Conclusions The current literature base suggests that undergraduate peer based healthcare ethics teaching is valuable in terms of efficacy and student satisfaction. We conclude that the medical community should invest in further study in order to capitalise upon the potential of peer-based ethics teaching in undergraduate healthcare education. PMID:26668050

Boron nitride nanotube-based biosensing of various bacterium/viruses: continuum modelling-based simulation approach.

PubMed

Panchal, Mitesh B; Upadhyay, Sanjay H

2014-09-01

In this study, the feasibility of single walled boron nitride nanotube (SWBNNT)-based biosensors has been ensured considering the continuum modelling-based simulation approach, for mass-based detection of various bacterium/viruses. Various types of bacterium or viruses have been taken into consideration at the free-end of the cantilevered configuration of the SWBNNT, as a biosensor. Resonant frequency shift-based analysis has been performed with the adsorption of various bacterium/viruses considered as additional mass to the SWBNNT-based sensor system. The continuum mechanics-based analytical approach, considering effective wall thickness has been considered to validate the finite element method (FEM)-based simulation results, based on continuum volume-based modelling of the SWBNNT. As a systematic analysis approach, the FEM-based simulation results are found in excellent agreement with the analytical results, to analyse the SWBNNTs for their wide range of applications such as nanoresonators, biosensors, gas-sensors, transducers and so on. The obtained results suggest that by using the SWBNNT of smaller size the sensitivity of the sensor system can be enhanced and detection of the bacterium/virus having mass of 4.28 × 10⁻²⁴ kg can be effectively performed.

Control of radiative base recombination in the quantum cascade light-emitting transistor using quantum state overlap

NASA Astrophysics Data System (ADS)

Chen, Kanuo; Hsiao, Fu-Chen; Joy, Brittany; Dallesasse, John M.

2018-07-01

The concept of the quantum cascade light-emitting transistor (QCLET) is proposed by incorporating periodic stages of quantum wells and barriers in the completely depleted base-collector junction of a heterojunction bipolar transistor. The radiative band-to-band base recombination in the QCLET is shown to be controllable using the base-collector voltage bias for a given emitter-base biasing condition. A self-consistent Schrödinger-Poisson Equation model is built to validate the idea of the QCLET. A GaAs-based QCLET is designed and fabricated. Control of radiative band-to-band base recombination is observed and characterized. By changing the voltage across the quantum cascade region in the QCLET, the alignment of quantum states in the cascade region creates a tunable barrier for electrons that allows or suppresses emitter-injected electron flow from the p-type base through the quantum cascade region into the collector. The field-dependent electron barrier in the base-collector junction manipulates the effective minority carrier lifetime in the base and controls the radiative base recombination process. Under different quantum cascade region biasing conditions, the radiative base recombination is measured and analyzed.

Comparison of Physician-, Biomarker-, and Symptom-Based Strategies for Adjustment of Inhaled Corticosteroid Therapy in Adults With Asthma

PubMed Central

Calhoun, William J.; Ameredes, Bill T.; King, Tonya S.; Icitovic, Nikolina; Bleecker, Eugene R.; Castro, Mario; Cherniack, Reuben M.; Chinchilli, Vernon M.; Craig, Timothy; Denlinger, Loren; DiMango, Emily A.; Engle, Linda L.; Fahy, John V.; Grant, J. Andrew; Israel, Elliot; Jarjour, Nizar; Kazani, Shamsah D.; Kraft, Monica; Kunselman, Susan J.; Lazarus, Stephen C.; Lemanske, Robert F.; Lugogo, Njira; Martin, Richard J.; Meyers, Deborah A.; Moore, Wendy C.; Pascual, Rodolfo; Peters, Stephen P.; Ramsdell, Joe; Sorkness, Christine A.; Sutherland, E. Rand; Szefler, Stanley J.; Wasserman, Stephen I.; Walter, Michael J.; Wechsler, Michael E.; Boushey, Homer A.

2013-01-01

Context No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms. Objective To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessment–based adjustment in preventing treatment failure in adults with mild to moderate asthma. Design, Setting, and Participants A randomized, parallel, 3-group, placebo-controlled, multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy (n=114 assigned to physician assessment–based adjustment [101 completed], n=115 to biomarker-based [exhaled nitric oxide] adjustment [92 completed], and n=113 to symptom-based adjustment [97 completed]), the Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010. Interventions For physician assessment–based adjustment and biomarker-based (exhaled nitric oxide) adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for symptom-based adjustment, inhaled corticosteroids were taken with each albuterol rescue use. Main Outcome Measure The primary outcome was time to treatment failure. Results There were no significant differences in time to treatment failure. The 9-month Kaplan-Meier failure rates were 22% (97.5% CI, 14%-33%; 24 events) for physician assessment–based adjustment, 20% (97.5% CI, 13%-30%; 21 events) for biomarker-based adjustment, and 15% (97.5% CI, 9%-25%; 16 events) for symptom-based adjustment. The hazard ratio for physician assessment–based adjustment vs biomarker-based adjustment was 1.2 (97.5% CI, 0.6-2.3). The hazard ratio for physician assessment–based adjustment vs symptom-based adjustment was 1.6 (97.5% CI, 0.8-3.3). Conclusion Among adults with mild to moderate persistent asthma controlled with low-dose inhaled corticosteroid therapy, the use of either biomarker-based or symptom-based adjustment of inhaled corticosteroids was not superior to physician assessment–based adjustment of inhaled corticosteroids in time to treatment failure. Trial Registration clinicaltrials.gov Identifier: NCT00495157 PMID:22968888

An Empirical Assessment and Comparison of Species-Based and Habitat-Based Surrogates: A Case Study of Forest Vertebrates and Large Old Trees

PubMed Central

Lindenmayer, David B.; Barton, Philip S.; Lane, Peter W.; Westgate, Martin J.; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E.

2014-01-01

A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely to be superior. PMID:24587050

An empirical assessment and comparison of species-based and habitat-based surrogates: a case study of forest vertebrates and large old trees.

PubMed

Lindenmayer, David B; Barton, Philip S; Lane, Peter W; Westgate, Martin J; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E

2014-01-01

A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely to be superior.

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

Tanabe, S; Utsunomiya, S; Abe, E

Purpose: To assess an accuracy of fiducial maker-based setup using ExacTrac (ExT-based setup) as compared with soft tissue-based setup using Cone-beam CT (CBCT-based setup) for patients with prostate cancer receiving intensity-modulated radiation therapy (IMRT) for the purpose of investigating whether ExT-based setup can be an alternative to CBCT-based setup. Methods: The setup accuracy was analyzed prospectively for 7 prostate cancer patients with implanted three fiducial markers received IMRT. All patients were treated after CBCT-based setup was performed and corresponding shifts were recorded. ExacTrac images were obtained before and after CBCT-based setup. The fiducial marker-based shifts were calculated based on thosemore » two images and recorded on the assumption that the setup correction was carried out by fiducial marker-based auto correction. Mean and standard deviation of absolute differences and the correlation between CBCT and ExT shifts were estimated. Results: A total of 178 image dataset were analyzed. On the differences between CBCT and ExT shifts, 133 (75%) of 178 image dataset resulted in smaller differences than 3 mm in all dimensions. Mean differences in the anterior-posterior (AP), superior-inferior (SI), and left-right (LR) dimensions were 1.8 ± 1.9 mm, 0.7 ± 1.9 mm, and 0.6 ± 0.8 mm, respectively. The percentages of shift agreements within ±3 mm were 76% for AP, 90% for SI, and 100% for LR. The Pearson coefficient of correlation for CBCT and ExT shifts were 0.80 for AP, 0.80 for SI, and 0.65 for LR. Conclusion: This work showed that the accuracy of ExT-based setup was correlated with that of CBCT-based setup, implying that ExT-based setup has a potential ability to be an alternative to CBCT-based setup. The further work is to specify the conditions that ExT-based setup can provide the accuracy comparable to CBCT-based setup.« less

Study on Hybrid Image Search Technology Based on Texts and Contents

NASA Astrophysics Data System (ADS)

Wang, H. T.; Ma, F. L.; Yan, C.; Pan, H.

2018-05-01

Image search was studied first here based on texts and contents, respectively. The text-based image feature extraction was put forward by integrating the statistical and topic features in view of the limitation of extraction of keywords only by means of statistical features of words. On the other hand, a search-by-image method was put forward based on multi-feature fusion in view of the imprecision of the content-based image search by means of a single feature. The layered-searching method depended on primarily the text-based image search method and additionally the content-based image search was then put forward in view of differences between the text-based and content-based methods and their difficult direct fusion. The feasibility and effectiveness of the hybrid search algorithm were experimentally verified.

CIRSS vertical data integration, San Bernardino County study phases 1-A, 1-B

NASA Technical Reports Server (NTRS)

Christenson, J.; Michel, R. (Principal Investigator)

1981-01-01

User needs, data types, data automation, and preliminary applications are described for an effort to assemble a single data base for San Bernardino County from data bases which exist at several administrative levels. Each of the data bases used was registered and converted to a grid-based data file at a resolution of 4 acres and used to create a multivariable data base for the entire study area. To this data base were added classified LANDSAT data from 1976 and 1979. The resulting data base thus integrated in a uniform format all of the separately automated data within the study area. Several possible interactions between existing geocoded data bases and LANDSAT data were tested. The use of LANDSAT to update existing data base is to be tested.

Comparison of clinical knowledge bases for summarization of electronic health records.

PubMed

McCoy, Allison B; Sittig, Dean F; Wright, Adam

2013-01-01

Automated summarization tools that create condition-specific displays may improve clinician efficiency. These tools require new kinds of knowledge that is difficult to obtain. We compared five problem-medication pair knowledge bases generated using four previously described knowledge base development approaches. The number of pairs in the resulting mapped knowledge bases varied widely due to differing mapping techniques from the source terminologies, ranging from 2,873 to 63,977,738 pairs. The number of overlapping pairs across knowledge bases was low, with one knowledge base having half of the pairs overlapping with another knowledge base, and most having less than a third overlapping. Further research is necessary to better evaluate the knowledge bases independently in additional settings, and to identify methods to integrate the knowledge bases.

Expert system for web based collaborative CAE

NASA Astrophysics Data System (ADS)

Hou, Liang; Lin, Zusheng

2006-11-01

An expert system for web based collaborative CAE was developed based on knowledge engineering, relational database and commercial FEA (Finite element analysis) software. The architecture of the system was illustrated. In this system, the experts' experiences, theories and typical examples and other related knowledge, which will be used in the stage of pre-process in FEA, were categorized into analysis process and object knowledge. Then, the integrated knowledge model based on object-oriented method and rule based method was described. The integrated reasoning process based on CBR (case based reasoning) and rule based reasoning was presented. Finally, the analysis process of this expert system in web based CAE application was illustrated, and an analysis example of a machine tool's column was illustrated to prove the validity of the system.

Participant satisfaction with appearance-based versus health-based educational videos promoting sunscreen use: a randomized controlled trial.

PubMed

Tuong, William; Armstrong, April W

2015-02-16

Increasing participant satisfaction with health interventions can improve compliance with recommended health behaviors and lead to better health outcomes. However, factors that influence participant satisfaction have not been well studied in dermatology-specific behavioral health interventions. We sought to assess participant satisfaction of either an appearance-based educational video or a health-based educational video promoting sunscreen use along dimensions of usefulness of educational content, message appeal, and presentation quality. In a randomized controlled trial, participants were randomized 1:1 to view an appearance-based video or a health-based video. After six weeks, participant satisfaction with the educational videos was assessed. Fifty high school students were enrolled and completed the study. Participant satisfaction ratings were assessed using a pre-tested 10-point assessment scale. The participants rated the usefulness of the appearance-based video (8.1 ± 1.2) significantly higher than the health-based video (6.4 ± 1.4, p<0.001). The message appeal of the appearance-based video (8.3 ± 1.0) was also significantly higher than the health-based video (6.6 ± 1.6, p<0.001). The presentation quality rating was similar between the appearance-based video (7.8 ± 1.3) and the health-based video (8.1 ± 1.3), p=0.676. Adolescents rated the appearance-based video higher than the health-based video in terms of usefulness of educational content and message appeal.

Structural parameter study on polymer-based ultrasonic motor

NASA Astrophysics Data System (ADS)

Wu, Jiang; Mizuno, Yosuke; Nakamura, Kentaro

2017-11-01

Our previous study has shown that traveling-wave rotary ultrasonic motors using polymer-based vibrators can work in the same way as conventional motors with metal-based vibrators. It is feasible to enhance the performance, particularly output torques, of polymer-based motors by adjusting several key dimensions of their vibrators. In this study, poly phenylene sulfide, a functional polymer exhibiting low attenuation at ultrasonic frequency, is selected as the vibrating body, which is activated with a piezoelectric ceramic element bonded on its back surface. The optimal thicknesses of the polymer-based motors are higher than those of metal-based motors. When the same voltages were applied, the maximum torques and output powers available with the polymer-based motors were lower than the values of the metal-based motors with the same structures. The reasons for the lower torque were explained on the basis of vibration modes. First, the force factors of the polymer-based vibrators are lower than those of metal-based vibrators owing to the great difference in the mechanical constants between polymers and piezoelectric ceramics. Subsequently, though the force factors of polymer-based vibrators can be slightly enhanced by increasing their thicknesses, the unavoidable radial vibrations become higher and cause undesirable friction loss, which reduces the output torques. Though the polymer-based motors have rotation speeds comparable to those of metal-based motors, their output power are lower due to the low electromechanical coupling factors of the polymer-based vibrators.

0-6621 : developing a mixture-based specification for flexible base.

DOT National Transportation Integrated Search

2012-08-01

The Texas Department of Transportation : (TxDOT) currently utilizes Item 247, Flexible : Base, to specify a foundation course of flexible : base utilized in a pavement. Base materials are : not allowed to be used by the contractors until : the ...

Surveillance Among Men Who have Sex with Men in the United States: A Comparison of Web-Based and Venue-Based Samples.

PubMed

Chen, Yen-Tyng; Bowles, Kristina; An, Qian; DiNenno, Elizabeth; Finlayson, Teresa; Hoots, Brooke; Paz-Bailey, Gabriela; Wejnert, Cyprian

2018-07-01

Although men who have sex with men (MSM) recruited through web-based and venue-based sampling methods have been compared, no large web-based and venue-based samples using similar survey instruments have been examined in the U.S. This study describes the differences in sociodemographic characteristics and risk behaviors between the 2012 Web-based HIV Behavioral Survey (n = 3221) and 2011 National HIV Behavioral Surveillance (n = 9256). Compared with participants in the venue-based sample, participants in the web-based sample were older, less likely to be black or Hispanic, more likely to have higher socioeconomic status, and more likely to have anal sex without a condom with their last male sex partner. Web-based participants were less likely to have multiple male sex partners, ever injected drugs, been tested for HIV in the past 12 months, and received free condoms than venue-based participants. The method for sampling MSM into a behavioral survey should consider the sub-population of MSM to be reached.

Active contour-based visual tracking by integrating colors, shapes, and motions.

PubMed

Hu, Weiming; Zhou, Xue; Li, Wei; Luo, Wenhan; Zhang, Xiaoqin; Maybank, Stephen

2013-05-01

In this paper, we present a framework for active contour-based visual tracking using level sets. The main components of our framework include contour-based tracking initialization, color-based contour evolution, adaptive shape-based contour evolution for non-periodic motions, dynamic shape-based contour evolution for periodic motions, and the handling of abrupt motions. For the initialization of contour-based tracking, we develop an optical flow-based algorithm for automatically initializing contours at the first frame. For the color-based contour evolution, Markov random field theory is used to measure correlations between values of neighboring pixels for posterior probability estimation. For adaptive shape-based contour evolution, the global shape information and the local color information are combined to hierarchically evolve the contour, and a flexible shape updating model is constructed. For the dynamic shape-based contour evolution, a shape mode transition matrix is learnt to characterize the temporal correlations of object shapes. For the handling of abrupt motions, particle swarm optimization is adopted to capture the global motion which is applied to the contour in the current frame to produce an initial contour in the next frame.

Comparing team-based and mixed active-learning methods in an ambulatory care elective course.

PubMed

Zingone, Michelle M; Franks, Andrea S; Guirguis, Alexander B; George, Christa M; Howard-Thompson, Amanda; Heidel, Robert E

2010-11-10

To assess students' performance and perceptions of team-based and mixed active-learning methods in 2 ambulatory care elective courses, and to describe faculty members' perceptions of team-based learning. Using the 2 teaching methods, students' grades were compared. Students' perceptions were assessed through 2 anonymous course evaluation instruments. Faculty members who taught courses using the team-based learning method were surveyed regarding their impressions of team-based learning. The ambulatory care course was offered to 64 students using team-based learning (n = 37) and mixed active learning (n = 27) formats. The mean quality points earned were 3.7 (team-based learning) and 3.3 (mixed active learning), p < 0.001. Course evaluations for both courses were favorable. All faculty members who used the team-based learning method reported that they would consider using team-based learning in another course. Students were satisfied with both teaching methods; however, student grades were significantly higher in the team-based learning course. Faculty members recognized team-based learning as an effective teaching strategy for small-group active learning.

Dynamics of spontaneous flipping of a mismatched base in DNA duplex.

PubMed

Yin, Yandong; Yang, Lijiang; Zheng, Guanqun; Gu, Chan; Yi, Chengqi; He, Chuan; Gao, Yi Qin; Zhao, Xin Sheng

2014-06-03

DNA base flipping is a fundamental theme in DNA biophysics. The dynamics for a B-DNA base to spontaneously flip out of the double helix has significant implications in various DNA-protein interactions but are still poorly understood. The spontaneous base-flipping rate obtained previously via the imino proton exchange assay is most likely the rate of base wobbling instead of flipping. Using the diffusion-decelerated fluorescence correlation spectroscopy together with molecular dynamics simulations, we show that a base of a single mismatched base pair (T-G, T-T, or T-C) in a double-stranded DNA can spontaneously flip out of the DNA duplex. The extrahelical lifetimes are on the order of 10 ms, whereas the intrahelical lifetimes range from 0.3 to 20 s depending on the stability of the base pairs. These findings provide detailed understanding on the dynamics of DNA base flipping and lay down foundation to fully understand how exactly the repair proteins search and locate the target mismatched base among a vast excess of matched DNA bases.

17 CFR 240.3a68-2 - Requests for interpretation of swaps, security-based swaps, and mixed swaps.

Code of Federal Regulations, 2014 CFR

2014-04-01

... swaps, security-based swaps, and mixed swaps. 240.3a68-2 Section 240.3a68-2 Commodity and Securities..., Security-Based Swap, and Security-Based Swap Agreement; Mixed Swaps; Security-Based Swap Agreement Recordkeeping § 240.3a68-2 Requests for interpretation of swaps, security-based swaps, and mixed swaps. (a) In...

17 CFR 240.3a68-2 - Requests for interpretation of swaps, security-based swaps, and mixed swaps.

Code of Federal Regulations, 2013 CFR

2013-04-01

... swaps, security-based swaps, and mixed swaps. 240.3a68-2 Section 240.3a68-2 Commodity and Securities..., Security-Based Swap, and Security-Based Swap Agreement; Mixed Swaps; Security-Based Swap Agreement Recordkeeping § 240.3a68-2 Requests for interpretation of swaps, security-based swaps, and mixed swaps. (a) In...

Graphene-based field-effect transistor biosensors

DOEpatents

Chen; , Junhong; Mao, Shun; Lu, Ganhua

2017-06-14

The disclosure provides a field-effect transistor (FET)-based biosensor and uses thereof. In particular, to FET-based biosensors using thermally reduced graphene-based sheets as a conducting channel decorated with nanoparticle-biomolecule conjugates. The present disclosure also relates to FET-based biosensors using metal nitride/graphene hybrid sheets. The disclosure provides a method for detecting a target biomolecule in a sample using the FET-based biosensor described herein.

Transitioning Client Based NALCOMIS to a Multi Function Web Based Application

DTIC Science & Technology

2016-09-23

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS TRANSITIONING CLIENT- BASED NALCOMIS TO A MULTI-FUNCTION WEB- BASED APPLICATION by Aaron P...TITLE AND SUBTITLE TRANSITIONING CLIENT- BASED NALCOMIS TO A MULTI-FUNCTION WEB- BASED APPLICATION 5. FUNDING NUMBERS 6. AUTHOR(S) Aaron P. Schnetzler 7...NALCOMIS. NALCOMIS has two configurations that are used by organizational and intermediate level maintenance activi- ties, Optimized Organizational

Case-based reasoning: The marriage of knowledge base and data base

NASA Technical Reports Server (NTRS)

Pulaski, Kirt; Casadaban, Cyprian

1988-01-01

The coupling of data and knowledge has a synergistic effect when building an intelligent data base. The goal is to integrate the data and knowledge almost to the point of indistinguishability, permitting them to be used interchangeably. Examples given in this paper suggest that Case-Based Reasoning is a more integrated way to link data and knowledge than pure rule-based reasoning.

Clinical and cost-effectiveness of home-based cardiac rehabilitation compared to conventional, centre-based cardiac rehabilitation: Results of the FIT@Home study.

PubMed

Kraal, Jos J; Van den Akker-Van Marle, M Elske; Abu-Hanna, Ameen; Stut, Wim; Peek, Niels; Kemps, Hareld Mc

2017-08-01

Aim Although cardiac rehabilitation improves physical fitness after a cardiac event, many eligible patients do not participate in cardiac rehabilitation and the beneficial effects of cardiac rehabilitation are often not maintained over time. Home-based training with telemonitoring guidance could improve participation rates and enhance long-term effectiveness. Methods and results We randomised 90 low-to-moderate cardiac risk patients entering cardiac rehabilitation to three months of either home-based training with telemonitoring guidance or centre-based training. Although training adherence was similar between groups, satisfaction was higher in the home-based group ( p = 0.02). Physical fitness improved at discharge ( p < 0.01) and at one-year follow-up ( p < 0.01) in both groups, without differences between groups (home-based p = 0.31 and centre-based p = 0.87). Physical activity levels did not change during the one-year study period (centre-based p = 0.38, home-based p = 0.80). Healthcare costs were statistically non-significantly lower in the home-based group (€437 per patient, 95% confidence interval -562 to 1436, p = 0.39). From a societal perspective, a statistically non-significant difference of €3160 per patient in favour of the home-based group was found (95% confidence interval -460 to 6780, p = 0.09) and the probability that it was more cost-effective varied between 97% and 75% (willingness-to-pay of €0 and €100,000 per quality-adjusted life-years, respectively). Conclusion We found no differences between home-based training with telemonitoring guidance and centre-based training on physical fitness, physical activity level or health-related quality of life. However, home-based training was associated with a higher patient satisfaction and appears to be more cost-effective than centre-based training. We conclude that home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients entering cardiac rehabilitation.

Complexity in Acid–Base Titrations: Multimer Formation Between Phosphoric Acids and Imines

PubMed Central

Malm, Christian; Kim, Heejae; Wagner, Manfred

2017-01-01

Abstract Solutions of Brønsted acids with bases in aprotic solvents are not only common model systems to study the fundamentals of proton transfer pathways but are also highly relevant to Brønsted acid catalysis. Despite their importance the light nature of the proton makes characterization of acid–base aggregates challenging. Here, we track such acid–base interactions over a broad range of relative compositions between diphenyl phosphoric acid and the base quinaldine in dichloromethane, by using a combination of dielectric relaxation and NMR spectroscopy. In contrast to what one would expect for an acid–base titration, we find strong deviations from quantitative proton transfer from the acid to the base. Even for an excess of the base, multimers consisting of one base and at least two acid molecules are formed, in addition to the occurrence of proton transfer from the acid to the base and simultaneous formation of ion pairs. For equimolar mixtures such multimers constitute about one third of all intermolecular aggregates. Quantitative analysis of our results shows that the acid‐base association constant is only around six times larger than that for the acid binding to an acid‐base dimer, that is, to an already protonated base. Our findings have implications for the interpretation of previous studies of reactive intermediates in organocatalysis and provide a rationale for previously observed nonlinear effects in phosphoric acid catalysis. PMID:28597513

A Flexible Base Electrode Array for Intraspinal Microstimulation

PubMed Central

Khaled, I.; Elmallah, S.; Cheng, C.; Moussa, W.A.; Mushahwar, V.K.; Elias, A.L.

2013-01-01

In this paper, we report the development of a flexible base array of penetrating electrodes which can be used to interface with the spinal cord. A customizable and feasible fabrication protocol is described. The flexible base arrays were fabricated and implanted into surrogate cords which were elongated by 12%. The resulting strains were optically measured across the cord and compared to those associated with two types of electrodes arrays (one without a base and one with a rigid base connecting the electrodes). The deformation behavior of cords implanted with the flexible base arrays resembled the behavior of cords implanted with individual microwires that were not connected through a base. The results of the strain test were used to validate a 2D finite element model. The validated model was used to assess the stresses induced by the electrodes of the 3 types of arrays on the cord, and to examine how various design parameters (thickness, base modulus, etc.) impact the mechanical behavior of the electrode array. Rigid base arrays induced higher stresses on the cord than the flexible base arrays which in turn imposed higher stresses than the individual microwire implants. The developed flexible base array showed improvement over the rigid base array; however, its stiffness needs to be further reduced to emulate the mechanical behavior of individual microwire arrays without a base. PMID:23744656

24 CFR 35.1200 - Purpose and applicability.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental... procedures to eliminate as far as practicable lead-based paint hazards in housing occupied by families receiving tenant-based rental assistance. Such assistance includes tenant-based rental assistance under the...

24 CFR 35.1200 - Purpose and applicability.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental... procedures to eliminate as far as practicable lead-based paint hazards in housing occupied by families receiving tenant-based rental assistance. Such assistance includes tenant-based rental assistance under the...

24 CFR 35.1200 - Purpose and applicability.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental... procedures to eliminate as far as practicable lead-based paint hazards in housing occupied by families receiving tenant-based rental assistance. Such assistance includes tenant-based rental assistance under the...

24 CFR 35.1200 - Purpose and applicability.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental... procedures to eliminate as far as practicable lead-based paint hazards in housing occupied by families receiving tenant-based rental assistance. Such assistance includes tenant-based rental assistance under the...

24 CFR 35.1200 - Purpose and applicability.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental... procedures to eliminate as far as practicable lead-based paint hazards in housing occupied by families receiving tenant-based rental assistance. Such assistance includes tenant-based rental assistance under the...

47 CFR 65.800 - Rate base.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Rate base. 65.800 Section 65.800 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERSTATE RATE OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Rate Base § 65.800 Rate base. The rate base shall...

47 CFR 65.800 - Rate base.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Rate base. 65.800 Section 65.800 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERSTATE RATE OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Rate Base § 65.800 Rate base. The rate base shall...

47 CFR 65.800 - Rate base.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Rate base. 65.800 Section 65.800 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERSTATE RATE OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Rate Base § 65.800 Rate base. The rate base shall...

17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.

Code of Federal Regulations, 2014 CFR

2014-04-01

... day tolerance provision. An index that is a narrow-based security index that becomes a broad-based... than forty-five days. An index that is a narrow-based security index that becomes a broad-based...

47 CFR 65.800 - Rate base.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Rate base. 65.800 Section 65.800 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERSTATE RATE OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Rate Base § 65.800 Rate base. The rate base shall...

US Air Force Air Base Ground Defense Doctrine. Are The Issues Which Arose Concerning Air Base Ground Defense During the Vietnam Conflict Recognized in Current US Air Force Doctrine

DTIC Science & Technology

1984-05-01

Conflict; US efforts to overcome these difficulties_ statistics concerning hostile attacks against air bases and the results thereof (8]; and, a...buses. During the period from � through 1973 the threat to ,air bacses iontinued, as reflected in the air base attack statistics provided ,at...advantage of aI r base vulnerabi lities to gather detailed intelligenrci concerning the air bases. C1 48 -STANDOFF ATTACKS- Based upon the statistics in

How Prevalent Is Object-Based Attention?

PubMed Central

Pilz, Karin S.; Roggeveen, Alexa B.; Creighton, Sarah E.; Bennett, Patrick J.; Sekuler, Allison B.

2012-01-01

Previous research suggests that visual attention can be allocated to locations in space (space-based attention) and to objects (object-based attention). The cueing effects associated with space-based attention tend to be large and are found consistently across experiments. Object-based attention effects, however, are small and found less consistently across experiments. In three experiments we address the possibility that variability in object-based attention effects across studies reflects low incidence of such effects at the level of individual subjects. Experiment 1 measured space-based and object-based cueing effects for horizontal and vertical rectangles in 60 subjects comparing commonly used target detection and discrimination tasks. In Experiment 2 we ran another 120 subjects in a target discrimination task in which rectangle orientation varied between subjects. Using parametric statistical methods, we found object-based effects only for horizontal rectangles. Bootstrapping methods were used to measure effects in individual subjects. Significant space-based cueing effects were found in nearly all subjects in both experiments, across tasks and rectangle orientations. However, only a small number of subjects exhibited significant object-based cueing effects. Experiment 3 measured only object-based attention effects using another common paradigm and again, using bootstrapping, we found only a small number of subjects that exhibited significant object-based cueing effects. Our results show that object-based effects are more prevalent for horizontal rectangles, which is in accordance with the theory that attention may be allocated more easily along the horizontal meridian. The fact that so few individuals exhibit a significant object-based cueing effect presumably is why previous studies of this effect might have yielded inconsistent results. The results from the current study highlight the importance of considering individual subject data in addition to commonly used statistical methods. PMID:22348018

Validating the WHO Maternal Near Miss Tool in a high-income country.

PubMed

Witteveen, Tom; de Koning, Ilona; Bezstarosti, Hans; van den Akker, Thomas; van Roosmalen, Jos; Bloemenkamp, Kitty W

2016-01-01

This study was performed to assess the applicability of the WHO Maternal Near Miss Tool (MNM Tool) and the organ dysfunction criteria in a high-income country. The MNM tool was applied to 2552 women who died of pregnancy-related causes or sustained severe acute maternal morbidity between August 2004 and August 2006 in one of the 98 hospitals with a maternity unit in the Netherlands. Fourteen (0.6%) cases had insufficient data for application. Each case was assessed according to the three main "MNM categories" specified in the MNM tool and their subcategory criteria: five disease-, four intervention- and seven organ dysfunction-based criteria. Potentially life-threatening conditions (disease-based inclusions) and life-threatening cases (organ dysfunction-based inclusions) were differentiated according to WHO methodology. Outcomes were incidence of all (sub)categories and case-fatality rates. Of the 2538 cases, 2308 (90.9%) women fulfilled disease-based, 2116 (83.4%) intervention-based and 1024 (40.3%) organ dysfunction-based criteria. Maternal death occurred in 48 women, of whom 23 (47.9%) fulfilled disease-based, 33 (68.8%) intervention-based and 31 (64.6%) organ dysfunction-based criteria. Case-fatality rates were 23/2308 (1.0%) for cases fulfilling the disease-based criteria, 33/2116 (1.6%) for intervention-based criteria and 31/1024 (3.0%) for women fulfilling the organ dysfunction-based criteria. In the Netherlands, where advanced laboratory and clinical monitoring are available, organ dysfunction-based criteria of the MNM tool failed to identify nearly two-thirds of sustained severe acute maternal morbidity cases and more than one-third of maternal deaths. Disease-based criteria remain important, and using only organ dysfunction-based criteria would lead to underestimating severe acute maternal morbidity. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Availability, price and promotions for cigarettes and non-cigarette tobacco products: an observational comparison of US Air Force bases with nearby tobacco retailers, 2016.

PubMed

Kong, Amanda Y; Golden, Shelley D; Myers, Allison E; Little, Melissa A; Klesges, Robert; Talcott, Wayne; Vandegrift, Sara M; Cassidy, Daniel G; Ribisl, Kurt M

2018-04-28

Active duty military personnel have higher cigarette and smokeless tobacco use rates than civilian populations. Although US Airmen (called Airmen regardless of gender or rank) are required to be tobacco-free during initial training, many resume use once this period ends, perhaps as a result of easy access to cheap tobacco products. Between July and September 2016, we collected tobacco product, price and promotion information by visiting on-base (n=28) and off-base (n=80) tobacco retailers near the eight technical training bases where approximately 99% of Airmen attend training. We conducted mixed linear effects models to examine on-base versus off-base differences. Cigarette packs were 11%-12% cheaper at on-base retailers compared with off-base retailers. Newport Menthol and Marlboro Red cigarette packs were $0.87 and $0.80 lower on-base (p<0.001) while the cheapest pack available was $0.54 lower on-base (p<0.01). Copenhagen smokeless tobacco was also significantly cheaper on-base (B=-0.65, p<0.01). Interior price promotions were more common on-base. Retail stores located on Air Force bases sell cigarettes and smokeless tobacco products at prices well below those in nearby off-base retailers: the vast majority of these retailers feature interior price promotions for these products. Federal policies regulating prices of on-base tobacco sales, if implemented more effectively, have the potential to protect the health of Airmen by helping them remain tobacco-free after technical training. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Knowledge information management toolkit and method

DOEpatents

Hempstead, Antoinette R.; Brown, Kenneth L.

2006-08-15

A system is provided for managing user entry and/or modification of knowledge information into a knowledge base file having an integrator support component and a data source access support component. The system includes processing circuitry, memory, a user interface, and a knowledge base toolkit. The memory communicates with the processing circuitry and is configured to store at least one knowledge base. The user interface communicates with the processing circuitry and is configured for user entry and/or modification of knowledge pieces within a knowledge base. The knowledge base toolkit is configured for converting knowledge in at least one knowledge base from a first knowledge base form into a second knowledge base form. A method is also provided.

Skull base, orbits, temporal bone, and cranial nerves: anatomy on MR imaging.

PubMed

Morani, Ajaykumar C; Ramani, Nisha S; Wesolowski, Jeffrey R

2011-08-01

Accurate delineation, diagnosis, and treatment planning of skull base lesions require knowledge of the complex anatomy of the skull base. Because the skull base cannot be directly evaluated, imaging is critical for the diagnosis and management of skull base diseases. Although computed tomography (CT) is excellent for outlining the bony detail, magnetic resonance (MR) imaging provides better soft tissue detail and is helpful for evaluating the adjacent meninges, brain parenchyma, and bone marrow of the skull base. Thus, CT and MR imaging are often used together for evaluating skull base lesions. This article focuses on the radiologic anatomy of the skull base pertinent to MR imaging evaluation. Copyright © 2011 Elsevier Inc. All rights reserved.

Differentiating location- and distance-based processes in memory for time: an ERP study.

PubMed

Curran, Tim; Friedman, William J

2003-09-01

Memory for the time of events may benefit from reconstructive, location-based, and distance-based processes, but these processes are difficult to dissociate with behavioral methods. Neuropsychological research has emphasized the contribution of prefrontal brain mechanisms to memory for time but has not clearly differentiated location- from distance-based processing. The present experiment recorded event-related brain potentials (ERPs) while subjects completed two different temporal memory tests, designed to emphasize either location- or distance-based processing. The subjects' reports of location-based versus distance-based strategies and the reaction time pattern validated our experimental manipulation. Late (800-1,800 msec) frontal ERP effects were related to location-based processing. The results provide support for a two-process theory of memory for time and suggest that frontal memory mechanisms are specifically related to reconstructive, location-based processing.

Score-Level Fusion of Phase-Based and Feature-Based Fingerprint Matching Algorithms

NASA Astrophysics Data System (ADS)

Ito, Koichi; Morita, Ayumi; Aoki, Takafumi; Nakajima, Hiroshi; Kobayashi, Koji; Higuchi, Tatsuo

This paper proposes an efficient fingerprint recognition algorithm combining phase-based image matching and feature-based matching. In our previous work, we have already proposed an efficient fingerprint recognition algorithm using Phase-Only Correlation (POC), and developed commercial fingerprint verification units for access control applications. The use of Fourier phase information of fingerprint images makes it possible to achieve robust recognition for weakly impressed, low-quality fingerprint images. This paper presents an idea of improving the performance of POC-based fingerprint matching by combining it with feature-based matching, where feature-based matching is introduced in order to improve recognition efficiency for images with nonlinear distortion. Experimental evaluation using two different types of fingerprint image databases demonstrates efficient recognition performance of the combination of the POC-based algorithm and the feature-based algorithm.

Students' attitudes and perceptions of teaching and assessment of evidence-based practice in an occupational therapy professional Master's curriculum: a mixed methods study.

PubMed

Thomas, Aliki; Han, Lu; Osler, Brittony P; Turnbull, Emily A; Douglas, Erin

2017-03-27

Most health professions, including occupational therapy, have made the application of evidence-based practice a desired competency and professional responsibility. Despite the increasing emphasis on evidence-based practice for improving patient outcomes, there are numerous research-practice gaps in the health professions. In addition to efforts aimed at promoting evidence-based practice with clinicians, there is a strong impetus for university programs to design curricula that will support the development of the knowledge, attitudes, skills and behaviours associated with evidence-based practice. Though occupational therapy curricula in North America are becoming increasingly focused on evidence-based practice, research on students' attitudes towards evidence-based practice, their perceptions regarding the integration and impact of this content within the curricula, and the impact of the curriculum on their readiness for evidence-based practice is scarce. The present study examined occupational therapy students' perceptions towards the teaching and assessment of evidence-based practice within a professional master's curriculum and their self-efficacy for evidence-based practice. The study used a mixed methods explanatory sequential design. The quantitative phase included a cross-sectional questionnaire exploring attitudes towards evidence-based practice, perceptions of the teaching and assessment of evidence-based practice and evidence-based practice self-efficacy for four cohorts of students enrolled in the program and a cohort of new graduates. The questionnaire was followed by a focus group of senior students aimed at further exploring the quantitative findings. All student cohorts held favourable attitudes towards evidence-based practice; there was no difference across cohorts. There were significant differences with regards to perceptions of the teaching and assessment of evidence-based practice within the curriculum; junior cohorts and students with previous education had less favourable perceptions. Students' self-efficacy for evidence-based practice was significantly higher across cohorts. Four main themes emerged from the focus group data: (a) Having mixed feelings about the value of evidence-based practice (b) Barriers to the application of evidence-based practice; (c) Opposing worlds and (d) Vital and imperfect role of the curriculum. This study provides important data to support the design and revision of evidence-based practice curricula within professional rehabilitation programs.

17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.

Code of Federal Regulations, 2011 CFR

2011-04-01

... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...

17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...

17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.

Code of Federal Regulations, 2013 CFR

2013-04-01

... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...

17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.

Code of Federal Regulations, 2012 CFR

2012-04-01

... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...

Intrusion-based reasoning and depression: cross-sectional and prospective relationships.

PubMed

Berle, David; Moulds, Michelle L

2014-01-01

Intrusion-based reasoning refers to the tendency to form interpretations about oneself or a situation based on the occurrence of a negative intrusive autobiographical memory. Intrusion-based reasoning characterises post-traumatic stress disorder, but has not yet been investigated in depression. We report two studies that aimed to investigate this. In Study 1 both high (n = 42) and low (n = 28) dysphoric participants demonstrated intrusion-based reasoning. High-dysphoric individuals engaged in self-referent intrusion-based reasoning to a greater extent than did low-dysphoric participants. In Study 2 there were no significant differences in intrusion-based reasoning between currently depressed (n = 27) and non-depressed (n = 51) participants, and intrusion-based reasoning did not predict depressive symptoms at 6-month follow-up. Interestingly, previously (n = 26) but not currently (n = 27) depressed participants engaged in intrusion-based reasoning to a greater extent than never-depressed participants (n = 25), indicating the possibility that intrusion-based reasoning may serve as a "scar" from previous episodes. The implications of these findings are discussed.

A knowledge-based object recognition system for applications in the space station

NASA Technical Reports Server (NTRS)

Dhawan, Atam P.

1988-01-01

A knowledge-based three-dimensional (3D) object recognition system is being developed. The system uses primitive-based hierarchical relational and structural matching for the recognition of 3D objects in the two-dimensional (2D) image for interpretation of the 3D scene. At present, the pre-processing, low-level preliminary segmentation, rule-based segmentation, and the feature extraction are completed. The data structure of the primitive viewing knowledge-base (PVKB) is also completed. Algorithms and programs based on attribute-trees matching for decomposing the segmented data into valid primitives were developed. The frame-based structural and relational descriptions of some objects were created and stored in a knowledge-base. This knowledge-base of the frame-based descriptions were developed on the MICROVAX-AI microcomputer in LISP environment. The simulated 3D scene of simple non-overlapping objects as well as real camera data of images of 3D objects of low-complexity have been successfully interpreted.

Refining Automatically Extracted Knowledge Bases Using Crowdsourcing

PubMed Central

Xian, Xuefeng; Cui, Zhiming

2017-01-01

Machine-constructed knowledge bases often contain noisy and inaccurate facts. There exists significant work in developing automated algorithms for knowledge base refinement. Automated approaches improve the quality of knowledge bases but are far from perfect. In this paper, we leverage crowdsourcing to improve the quality of automatically extracted knowledge bases. As human labelling is costly, an important research challenge is how we can use limited human resources to maximize the quality improvement for a knowledge base. To address this problem, we first introduce a concept of semantic constraints that can be used to detect potential errors and do inference among candidate facts. Then, based on semantic constraints, we propose rank-based and graph-based algorithms for crowdsourced knowledge refining, which judiciously select the most beneficial candidate facts to conduct crowdsourcing and prune unnecessary questions. Our experiments show that our method improves the quality of knowledge bases significantly and outperforms state-of-the-art automatic methods under a reasonable crowdsourcing cost. PMID:28588611

Value-based medicine: evidence-based medicine and beyond.

PubMed

Brown, Gary C; Brown, Melissa M; Sharma, Sanjay

2003-09-01

Value-based medicine is the practice of medicine emphasizing the value received from an intervention. Value is measured by objectively quantifying: 1) the improvement in quality of life and/or 2) the improvement in length of life conferred by an intervention. Evidence-based medicine often measures the improvement gained in length of life, but generally ignores the importance of quality of life improvement or loss. Value-based medicine incorporates the best features of evidence-based medicine and takes evidence-based data to a higher level by incorporating the quality of life perceptions of patients with a disease in concerning the value of an intervention. Inherent in value-based medicine are the costs associated with an intervention. The resources expended for the value gained in value-based medicine is measured with cost-utility analysis in terms of the US dollars/QALY (money spent per quality-adjusted life-year gained). A review of the current status and the likely future of value-based medicine is addressed herein.

Lunar bases and space activities of the 21st century

NASA Technical Reports Server (NTRS)

Mendell, W. W. (Editor)

1985-01-01

The present conference gives attention to such major aspects of lunar colonization as lunar base concepts, lunar transportation, lunar science research activities, moon-based astronomical researches, lunar architectural construction, lunar materials and processes, lunar oxygen production, life support and health maintenance in lunar bases, societal aspects of lunar colonization, and the prospects for Mars colonization. Specific discussions are presented concerning the role of nuclear energy in lunar development, achromatic trajectories and the industrial scale transport of lunar resources, advanced geologic exploration from a lunar base, geophysical investigations of the moon, moon-based astronomical interferometry, the irradiation of the moon by particles, cement-based composites for lunar base construction, electrostatic concentration of lunar soil minerals, microwave processing of lunar materials, a parametric analysis of lunar oxygen production, hydrogen from lunar regolith fines, metabolic support for a lunar base, past and future Soviet lunar exploration, and the use of the moons of Mars as sources of water for lunar bases.

Rule-based reasoning is fast and belief-based reasoning can be slow: Challenging current explanations of belief-bias and base-rate neglect.

PubMed

Newman, Ian R; Gibb, Maia; Thompson, Valerie A

2017-07-01

It is commonly assumed that belief-based reasoning is fast and automatic, whereas rule-based reasoning is slower and more effortful. Dual-Process theories of reasoning rely on this speed-asymmetry explanation to account for a number of reasoning phenomena, such as base-rate neglect and belief-bias. The goal of the current study was to test this hypothesis about the relative speed of belief-based and rule-based processes. Participants solved base-rate problems (Experiment 1) and conditional inferences (Experiment 2) under a challenging deadline; they then gave a second response in free time. We found that fast responses were informed by rules of probability and logical validity, and that slow responses incorporated belief-based information. Implications for Dual-Process theories and future research options for dissociating Type I and Type II processes are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

How Affectively-Based and Cognitively-Based Attitudes Drive Intergroup Behaviours: The Moderating Role of Affective-Cognitive Consistency

PubMed Central

Zhou, Jie; Dovidio, John; Wang, Erping

2013-01-01

The moderating role of affective-cognitive consistency in the effects of affectively-based and cognitively-based attitudes on consummatory and instrumental behaviors was explored using two experimental studies in the intergroup context. Study 1 revealed that affectively-based attitudes were better predictors than cognitively-based attitudes regardless of affective-cognitive consistency for consummatory behaviors (e.g., undergraduates’ supportive behaviors toward government officials). Study 2, which investigated task groups’ supportive behaviors toward an immediate supervisory group, found that for these instrumental behaviors cognitively-based attitudes were better predictors than affectively-based attitudes only when affective-cognitive consistency was high. The present research also examined the mechanism by which affective-cognitive consistency moderates the relative roles of affectively-based and cognitively-based attitudes in attitude-behavior consistency. Results indicated that attitude-behavior consistency is eroded primarily because of the weaker relationship of affective or cognitive components to behaviors than to general attitudes. The reciprocal implications of research on attitudes and work on intergroup relations are considered. PMID:24244751

Preparation of non-metals properties for data base

NASA Technical Reports Server (NTRS)

1988-01-01

The development of non-metallic material properties data bases is discussed. The data bases consist of the non-metallic material classes of adhesives, adhesive/sealants, plastics, and elastomers. A specifications data base was also developed to incorporate material specifications data as a supplement to the Elastomers Data Base. Examples of the forms used are provided to show the properties of the materials which appear in the data base.

2010 Defense Industrial Base Critical Infrastructure Protection Conference (DIBCIP) Risk Reduction and Mitigation in the Defense Industrial Base

DTIC Science & Technology

2010-04-28

Base Critical Infrastructure Protection Conference (DIBCIP) “Risk Reduction & Mitigation in the Defense Industrial Base ” April 26-28, 2010...Philadelphia, PA Agenda Tuesday, April 27, 2010 Keynote Address: The Economic Crisis and Its Impact on the DIB: Defense Industrial Base Forecasts 2010...Ms. Nancy Pomerleau, Exercise Director, Partnership Outreach Division, DHS-IP DIB 2010 DIB CIP DEFENSE INDUSTRIAL BASE CRITICAL

The Research of New Environment-Friendly Oil-based Drilling Fluid Base Oil

NASA Astrophysics Data System (ADS)

Sui, Dianjie; Sun, Yuxue; Zhao, Jingyuan; Zhao, Fulei; Zhu, Xiuyu; Xu, Jianjun

2018-01-01

In this paper, the heavy hydrocarbon of Daqing is used, and the desulfurization and de-aromatization experiments and refining process are carried out, A base oil suitable for oil-based drilling fluid was developed, and the performance of base oil was evaluated, we can know the aromatics content of oil base is low, less toxic, less pollution and it can meet the requirement of environmental protection.

Scanning the skeleton of the 4D F-theory landscape

NASA Astrophysics Data System (ADS)

Taylor, Washington; Wang, Yi-Nan

2018-01-01

Using a one-way Monte Carlo algorithm from several different starting points, we get an approximation to the distribution of toric threefold bases that can be used in four-dimensional F-theory compactification. We separate the threefold bases into "resolvable" ones where the Weierstrass polynomials ( f, g) can vanish to order (4 , 6) or higher on codimension-two loci and the "good" bases where these (4 , 6) loci are not allowed. A simple estimate suggests that the number of distinct resolvable base geometries exceeds 103000, with over 10250 "good" bases, though the actual numbers are likely much larger. We find that the good bases are concentrated at specific "end points" with special isolated values of h 1,1 that are bigger than 1,000. These end point bases give Calabi-Yau fourfolds with specific Hodge numbers mirror to elliptic fibrations over simple threefolds. The non-Higgsable gauge groups on the end point bases are almost entirely made of products of E 8, F 4, G 2 and SU(2). Nonetheless, we find a large class of good bases with a single non-Higgsable SU(3). Moreover, by randomly contracting the end point bases, we find many resolvable bases with h 1,1( B) ˜ 50-200 that cannot be contracted to another smooth threefold base.

Computer-based teaching is as good as face to face lecture-based teaching of evidence based medicine: a randomised controlled trial

PubMed Central

2007-01-01

Background At postgraduate level evidence based medicine (EBM) is currently taught through tutor based lectures. Computer based sessions fit around doctors' workloads, and standardise the quality of educational provision. There have been no randomized controlled trials comparing computer based sessions with traditional lectures at postgraduate level within medicine. Methods This was a randomised controlled trial involving six postgraduate education centres in the West Midlands, U.K. Fifty five newly qualified foundation year one doctors (U.S internship equivalent) were randomised to either computer based sessions or an equivalent lecture in EBM and systematic reviews. The change from pre to post-intervention score was measured using a validated questionnaire assessing knowledge (primary outcome) and attitudes (secondary outcome). Results Both groups were similar at baseline. Participants' improvement in knowledge in the computer based group was equivalent to the lecture based group (gain in score: 2.1 [S.D = 2.0] versus 1.9 [S.D = 2.4]; ANCOVA p = 0.078). Attitudinal gains were similar in both groups. Conclusion On the basis of our findings we feel computer based teaching and learning is as effective as typical lecture based teaching sessions for educating postgraduates in EBM and systematic reviews. PMID:17659076

Evidence based practice readiness: A concept analysis.

PubMed

Schaefer, Jessica D; Welton, John M

2018-01-15

To analyse and define the concept "evidence based practice readiness" in nurses. Evidence based practice readiness is a term commonly used in health literature, but without a clear understanding of what readiness means. Concept analysis is needed to define the meaning of evidence based practice readiness. A concept analysis was conducted using Walker and Avant's method to clarify the defining attributes of evidence based practice readiness as well as antecedents and consequences. A Boolean search of PubMed and Cumulative Index for Nursing and Allied Health Literature was conducted and limited to those published after the year 2000. Eleven articles met the inclusion criteria for this analysis. Evidence based practice readiness incorporates personal and organisational readiness. Antecedents include the ability to recognize the need for evidence based practice, ability to access and interpret evidence based practice, and a supportive environment. The concept analysis demonstrates the complexity of the concept and its implications for nursing practice. The four pillars of evidence based practice readiness: nursing, training, equipping and leadership support are necessary to achieve evidence based practice readiness. Nurse managers are in the position to address all elements of evidence based practice readiness. Creating an environment that fosters evidence based practice can improve patient outcomes, decreased health care cost, increase nurses' job satisfaction and decrease nursing turnover. © 2018 John Wiley & Sons Ltd.

Biochemical behavior of N-oxidized cytosine and adenine bases in DNA polymerase-mediated primer extension reactions

PubMed Central

Tsunoda, Hirosuke; Kudo, Tomomi; Masaki, Yoshiaki; Ohkubo, Akihiro; Seio, Kohji; Sekine, Mitsuo

2011-01-01

To clarify the biochemical behavior of 2′-deoxyribonucleoside 5′-triphosphates and oligodeoxyribonucleotides (ODNs) containing cytosine N-oxide (Co) and adenine N-oxide (Ao), we examined their base recognition ability in DNA duplex formation using melting temperature (Tm) experiments and their substrate specificity in DNA polymerase-mediated replication. As the result, it was found that the Tm values of modified DNA–DNA duplexes incorporating 2′-deoxyribonucleoside N-oxide derivatives significantly decreased compared with those of the unmodified duplexes. However, single insertion reactions by DNA polymerases of Klenow fragment (KF) (exo−) and Vent (exo−) suggested that Co and Ao selectively recognized G and T, respectively. Meanwhile, the kinetic study showed that the incorporation efficiencies of the modified bases were lower than those of natural bases. Ab initio calculations suggest that these modified bases can form the stable base pairs with the original complementary bases. These results indicate that the modified bases usually recognize the original bases as partners for base pairing, except for misrecognition of dATP by the action of KF (exo−) toward Ao on the template, and the primers could be extended on the template DNA. When they misrecognized wrong bases, the chain could not be elongated so that the modified base served as the chain terminator. PMID:21300642

Biochemical behavior of N-oxidized cytosine and adenine bases in DNA polymerase-mediated primer extension reactions.

PubMed

Tsunoda, Hirosuke; Kudo, Tomomi; Masaki, Yoshiaki; Ohkubo, Akihiro; Seio, Kohji; Sekine, Mitsuo

2011-04-01

To clarify the biochemical behavior of 2'-deoxyribonucleoside 5'-triphosphates and oligodeoxyribonucleotides (ODNs) containing cytosine N-oxide (C(o)) and adenine N-oxide (A(o)), we examined their base recognition ability in DNA duplex formation using melting temperature (T(m)) experiments and their substrate specificity in DNA polymerase-mediated replication. As the result, it was found that the T(m) values of modified DNA-DNA duplexes incorporating 2'-deoxyribonucleoside N-oxide derivatives significantly decreased compared with those of the unmodified duplexes. However, single insertion reactions by DNA polymerases of Klenow fragment (KF) (exo(-)) and Vent (exo(-)) suggested that C(o) and A(o) selectively recognized G and T, respectively. Meanwhile, the kinetic study showed that the incorporation efficiencies of the modified bases were lower than those of natural bases. Ab initio calculations suggest that these modified bases can form the stable base pairs with the original complementary bases. These results indicate that the modified bases usually recognize the original bases as partners for base pairing, except for misrecognition of dATP by the action of KF (exo(-)) toward A(o) on the template, and the primers could be extended on the template DNA. When they misrecognized wrong bases, the chain could not be elongated so that the modified base served as the chain terminator.

Family vs Village-Based: Intangible View on the Sustainable of Seaweed Farming

NASA Astrophysics Data System (ADS)

Teniwut, Wellem A.; Teniwut, Yuliana K.; Teniwut, Roberto M. K.; Hasyim, Cawalinya L.

2017-10-01

Compare to other fishery activities for instance fish mariculture and catching fisheries, seaweed farming is considered easier. Also, the market for seaweed is wider and will keep growing. Thus, makes seaweed farming as one of the fastest commodity to improve the welfare of a coastal community. There are technical and non-technical factors in seaweed farming management, for non-technical on this intangible factors vary between family-based and village-based management, therefore aimed of this study was to simulate farmers decision to choose between family-based and village-based on seaweed managing system trigger by intangible factors. We conducted our study in Southeast Maluku, data collecting conducted from October to December 2016 by depth interview and questionnaires on seaweed farmers. We used logistic regression to compare each intangible factors on family and village-based seaweed farming management. The result showed that for family-based management farmers were willing to transfer their knowledge among each member in the household. For village-based revealed that farmers with higher education background tend to work on village-based, also, the result also stated that in village-based management member were those who have better capability and skill, at the same time village-based management had a small probability for conflict to occur compared to family-based.

Event- and time-triggered remembering: the impact of attention deficit hyperactivity disorder on prospective memory performance in children.

PubMed

Talbot, Karley-Dale S; Kerns, Kimberly A

2014-11-01

The current study examined prospective memory (PM, both time-based and event-based) and time estimation (TR, a time reproduction task) in children with and without attention deficit hyperactivity disorder (ADHD). This study also investigated the influence of task performance and TR on time-based PM in children with ADHD relative to controls. A sample of 69 children, aged 8 to 13 years, completed the CyberCruiser-II time-based PM task, a TR task, and the Super Little Fisherman event-based PM task. PM performance was compared with children's TR abilities, parental reports of daily prospective memory disturbances (Prospective and Retrospective Memory Questionnaire for Children, PRMQC), and ADHD symptomatology (Conner's rating scales). Children with ADHD scored more poorly on event-based PM, time-based PM, and TR; interestingly, TR did not appear related to performance on time-based PM. In addition, it was found that PRMQC scores and ADHD symptom severity were related to performance on the time-based PM task but not to performance on the event-based PM task. These results provide some limited support for theories that propose a distinction between event-based PM and time-based PM. Copyright © 2014 Elsevier Inc. All rights reserved.

Systematic review of skills transfer after surgical simulation-based training.

PubMed

Dawe, S R; Pena, G N; Windsor, J A; Broeders, J A J L; Cregan, P C; Hewett, P J; Maddern, G J

2014-08-01

Simulation-based training assumes that skills are directly transferable to the patient-based setting, but few studies have correlated simulated performance with surgical performance. A systematic search strategy was undertaken to find studies published since the last systematic review, published in 2007. Inclusion of articles was determined using a predetermined protocol, independent assessment by two reviewers and a final consensus decision. Studies that reported on the use of surgical simulation-based training and assessed the transferability of the acquired skills to a patient-based setting were included. Twenty-seven randomized clinical trials and seven non-randomized comparative studies were included. Fourteen studies investigated laparoscopic procedures, 13 endoscopic procedures and seven other procedures. These studies provided strong evidence that participants who reached proficiency in simulation-based training performed better in the patient-based setting than their counterparts who did not have simulation-based training. Simulation-based training was equally as effective as patient-based training for colonoscopy, laparoscopic camera navigation and endoscopic sinus surgery in the patient-based setting. These studies strengthen the evidence that simulation-based training, as part of a structured programme and incorporating predetermined proficiency levels, results in skills transfer to the operative setting. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Greater fruit selection following an appearance-based compared with a health-based health promotion poster

PubMed Central

2016-01-01

Abstract Background This study investigated the impact of an appearance-based compared with a traditional health-based public health message for healthy eating. Methods A total of 166 British University students (41 males; aged 20.6 ± 1.9 years) were randomized to view either an appearance-based (n = 82) or a health-based (n = 84) fruit promotion poster. Intentions to consume fruit and immediate fruit selection (laboratory observation) were assessed immediately after poster viewing, and subsequent self-report fruit consumption was assessed 3 days later. Results Intentions to consume fruit were not predicted by poster type (largest β = 0.03, P = 0.68) but were associated with fruit-based liking, past consumption, attitudes and social norms (smallest β = 0.16, P = 0.04). Immediate fruit selection was greater following the appearance-based compared with the health-based poster (β = −0.24, P < 0.01), and this effect remained when controlling for participant characteristics (β = −0.21, P < 0.01). Subsequent fruit consumption was greater following the appearance-based compared with the health-based poster (β = −0.22, P = 0.03), but this effect became non-significant on consideration of participant characteristics (β = −0.15, P = 0.13), and was instead associated with fruit-based liking and past consumption (smallest β = 0.24, P = 0.03). Conclusions These findings demonstrate the clear value of an appearance-based compared with a health-based health promotion poster for increasing fruit selection. A distinction between outcome measures and the value of a behavioural measure is also demonstrated. PMID:28158693

Base pairing and base mis-pairing in nucleic acids

NASA Technical Reports Server (NTRS)

Wang, A. H. J.; Rich, A.

1986-01-01

In recent years we have learned that DNA is conformationally active. It can exist in a number of different stable conformations including both right-handed and left-handed forms. Using single crystal X-ray diffraction analysis we are able to discover not only additional conformations of the nucleic acids but also different types of hydrogen bonded base-base interactions. Although Watson-Crick base pairings are the predominant type of interaction in double helical DNA, they are not the only types. Recently, we have been able to examine mismatching of guanine-thymine base pairs in left-handed Z-DNA at atomic resolution (1A). A minimum amount of distortion of the sugar phosphate backbone is found in the G x T pairing in which the bases are held together by two hydrogen bonds in the wobble pairing interaction. Because of the high resolution of the analysis we can visualize water molecules which fill in to accommodate the other hydrogen bonding positions in the bases which are not used in the base-base interactions. Studies on other DNA oligomers have revealed that other types of non-Watson-Crick hydrogen bonding interactions can occur. In the structure of a DNA octamer with the sequence d(GCGTACGC) complexed to an antibiotic triostin A, it was found that the two central AT base pairs are held together by Hoogsteen rather than Watson-Crick base pairs. Similarly, the G x C base pairs at the ends are also Hoogsteen rather than Watson-Crick pairing. Hoogsteen base pairs make a modified helix which is distinct from the Watson-Crick double helix.

Effects of a fish oil-based emulsion on rat hepatoma cell invasion in culture.

PubMed

Hagi, Akifumi; Nakayama, Mitsuo; Miura, Yutaka; Yagasaki, Kazumi

2007-01-01

Total parenteral nutrition containing a lipid emulsion is often employed after surgical tumor resection. This study investigated the effects of a fish oil-based infusion on rat hepatoma cell invasion. Rat ascites hepatoma cell line AH109A was precultured with a fish oil-based or safflower oil-based emulsion for 48 h. Changes in membranous fatty acid composition were evaluated by gas chromatography. The invasiveness of hepatoma cells was assessed by coculturing with mesentery-derived mesothelial cells. To examine ex vivo effects of the fish oil-based infusion on hepatoma invasion, sera were prepared from rats infused with fish oil- or safflower oil-based emulsion and the effects of these sera were assessed. To clarify the mechanism of inhibition of invasion by the fish oil-based emulsion, the effects of prostaglandin (PG) E(2) and PGE(3) on invasion were examined. Pretreatment with the fish oil-based emulsion reduced invasiveness without affecting growth compared with the safflower oil-based emulsion. Pretreatment with the sera from rats infused with the fish oil-based emulsion also reduced invasiveness compared with the sera from rats infused with the safflower oil-based emulsion. The addition of PGE(2) eliminated the inhibitory effect of the fish oil-based emulsion, and the addition of PGE(3) reduced the invasiveness of hepatoma cells pretreated with the safflower oil-based emulsion. These results suggest that the fish oil-based emulsion may have anti-invasive effects. Changes in the membranous fatty acid composition and consequent changes in the prostaglandins produced may be involved in this inhibitory effect.

Financial Management Reforms in the Health Sector: A Comparative Study Between Cash-based and Accrual-based Accounting Systems.

PubMed

Abolhallaje, Masoud; Jafari, Mehdi; Seyedin, Hesam; Salehi, Masoud

2014-10-01

Financial management and accounting reform in the public sectors was started in 2000. Moving from cash-based to accrual-based is considered as the key component of these reforms and adjustments in the public sector. Performing this reform in the health system is a part of a bigger reform under the new public management. The current study aimed to analyze the movement from cash-based to accrual-based accounting in the health sector in Iran. This comparative study was conducted in 2013 to compare financial management and movement from cash-based to accrual-based accounting in health sector in the countries such as the United States, Britain, Canada, Australia, New Zealand, and Iran. Library resources and reputable databases such as Medline, Elsevier, Index Copernicus, DOAJ, EBSCO-CINAHL and SID, and Iranmedex were searched. Fish cards were used to collect the data. Data were compared and analyzed using comparative tables. Developed countries have implemented accrual-based accounting and utilized the valid, reliable and practical information in accrual-based reporting in different areas such as price and tariffs setting, operational budgeting, public accounting, performance evaluation and comparison and evidence based decision making. In Iran, however, only a few public organizations such as the municipalities and the universities of medical sciences use accrual-based accounting, but despite what is required by law, the other public organizations do not use accrual-based accounting. There are advantages in applying accrual-based accounting in the public sector which certainly depends on how this system is implemented in the sector.

Detecting the Presence of Bacterial DNA and RNA by Polymerase Chain Reaction to Diagnose Suspected Periprosthetic Joint Infection after Antibiotic Therapy.

PubMed

Fang, Xin-Yu; Li, Wen-Bo; Zhang, Chao-Fan; Huang, Zi-da; Zeng, Hui-Yi; Dong, Zheng; Zhang, Wen-Ming

2018-02-01

To explore the diagnostic efficiency of DNA-based and RNA-based quantitative polymerase chain reaction (qPCR) analyses for periprosthetic joint infection (PJI). To determine the detection limit of DNA-based and RNA-based qPCR in vitro, Staphylococcus aureus and Escherichia coli strains were added to sterile synovial fluid obtained from a patient with knee osteoarthritis. Serial dilutions of samples were analyzed by DNA-based and RNA-based qPCR. Clinically, patients who were suspected of having PJI and eventually underwent revision arthroplasty in our hospital from July 2014 to December 2016 were screened. Preoperative puncture or intraoperative collection was performed on patients who met the inclusion and exclusion criteria to obtain synovial fluid. DNA-based and RNA-based PCR analyses and culture were performed on each synovial fluid sample. The patients' demographic characteristics, medical history, and laboratory test results were recorded. The diagnostic efficiency of both PCR assays was compared with culture methods. The in vitro analysis demonstrated that DNA-based qPCR assay was highly sensitive, with the detection limit being 1200 colony forming units (CFU)/mL of S. aureus and 3200 CFU/mL of E. coli. Meanwhile, The RNA-based qPCR assay could detect 2300 CFU/mL of S. aureus and 11 000 CFU/mL of E. coli. Clinically, the sensitivity, specificity, and accuracy were 65.7%, 100%, and 81.6%, respectively, for the culture method; 81.5%, 84.8%, and 83.1%, respectively, for DNA-based qPCR; and 73.6%, 100%, and 85.9%, respectively, for RNA-based qPCR. DNA-based qPCR could detect suspected PJI with high sensitivity after antibiotic therapy. RNA-based qPCR could reduce the false positive rates of DNA-based assays. qPCR-based methods could improve the efficiency of PJI diagnosis. © 2018 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Anthropometric measures in cardiovascular disease prediction: comparison of laboratory-based versus non-laboratory-based model.

PubMed

Dhana, Klodian; Ikram, M Arfan; Hofman, Albert; Franco, Oscar H; Kavousi, Maryam

2015-03-01

Body mass index (BMI) has been used to simplify cardiovascular risk prediction models by substituting total cholesterol and high-density lipoprotein cholesterol. In the elderly, the ability of BMI as a predictor of cardiovascular disease (CVD) declines. We aimed to find the most predictive anthropometric measure for CVD risk to construct a non-laboratory-based model and to compare it with the model including laboratory measurements. The study included 2675 women and 1902 men aged 55-79 years from the prospective population-based Rotterdam Study. We used Cox proportional hazard regression analysis to evaluate the association of BMI, waist circumference, waist-to-hip ratio and a body shape index (ABSI) with CVD, including coronary heart disease and stroke. The performance of the laboratory-based and non-laboratory-based models was evaluated by studying the discrimination, calibration, correlation and risk agreement. Among men, ABSI was the most informative measure associated with CVD, therefore ABSI was used to construct the non-laboratory-based model. Discrimination of the non-laboratory-based model was not different than laboratory-based model (c-statistic: 0.680-vs-0.683, p=0.71); both models were well calibrated (15.3% observed CVD risk vs 16.9% and 17.0% predicted CVD risks by the non-laboratory-based and laboratory-based models, respectively) and Spearman rank correlation and the agreement between non-laboratory-based and laboratory-based models were 0.89 and 91.7%, respectively. Among women, none of the anthropometric measures were independently associated with CVD. Among middle-aged and elderly where the ability of BMI to predict CVD declines, the non-laboratory-based model, based on ABSI, could predict CVD risk as accurately as the laboratory-based model among men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Adaptation and validation of the Evidence-Based Practice Belief and Implementation scales for French-speaking Swiss nurses and allied healthcare providers.

PubMed

Verloo, Henk; Desmedt, Mario; Morin, Diane

2017-09-01

To evaluate two psychometric properties of the French versions of the Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales, namely their internal consistency and construct validity. The Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales developed by Melnyk et al. are recognised as valid, reliable instruments in English. However, no psychometric validation for their French versions existed. Secondary analysis of a cross sectional survey. Source data came from a cross-sectional descriptive study sample of 382 nurses and other allied healthcare providers. Cronbach's alpha was used to evaluate internal consistency, and principal axis factor analysis and varimax rotation were computed to determine construct validity. The French Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales showed excellent reliability, with Cronbach's alphas close to the scores established by Melnyk et al.'s original versions. Principal axis factor analysis showed medium-to-high factor loading scores without obtaining collinearity. Principal axis factor analysis with varimax rotation of the 16-item Evidence-Based Practice Beliefs scale resulted in a four-factor loading structure. Principal axis factor analysis with varimax rotation of the 17-item Evidence-Based Practice Implementation scale revealed a two-factor loading structure. Further research should attempt to understand why the French Evidence-Based Practice Implementation scale showed a two-factor loading structure but Melnyk et al.'s original has only one. The French versions of the Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales can both be considered valid and reliable instruments for measuring Evidence-Based Practice beliefs and implementation. The results suggest that the French Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales are valid and reliable and can therefore be used to evaluate the effectiveness of organisational strategies aimed at increasing professionals' confidence in Evidence-Based Practice, supporting its use and implementation. © 2017 John Wiley & Sons Ltd.

Telling Active Learning Pedagogies Apart: From Theory to Practice

ERIC Educational Resources Information Center

Cattaneo, Kelsey Hood

2017-01-01

Designing learning environments to incorporate active learning pedagogies is difficult as definitions are often contested and intertwined. This article seeks to determine whether classification of active learning pedagogies (i.e., project-based, problem-based, inquiry-based, case-based, and discovery-based), through theoretical and practical…

13 CFR 120.1000 - Risk-Based Lender Oversight.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Risk-Based Lender Oversight. 120.1000 Section 120.1000 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Supervision § 120.1000 Risk-Based Lender Oversight. (a) Risk-Based Lender...

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications

USDA-ARS?s Scientific Manuscript database

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylat...

32 CFR 989.25 - Base closure and realignment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Base closure and realignment. 989.25 Section 989... PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.25 Base closure and realignment. Base closure or realignment may entail special requirements for environmental analysis. The permanent base closure...

32 CFR 989.25 - Base closure and realignment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Base closure and realignment. 989.25 Section 989... PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.25 Base closure and realignment. Base closure or realignment may entail special requirements for environmental analysis. The permanent base closure...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.90 - Opportunity to conduct an evaluation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Disclosure of Known Lead-Based Paint and/or Lead-Based Paint Hazards Upon Sale or Lease of Residential... inspection for the presence of lead-based paint and/or lead-based paint hazards. (b) Notwithstanding...

A Web-Based and Print-Based Computer-Tailored Physical Activity Intervention for Prostate and Colorectal Cancer Survivors: A Comparison of User Characteristics and Intervention Use

PubMed Central

Bolman, Catherine; Peels, Denise Astrid; Volders, Esmee; de Vries, Hein; Lechner, Lilian

2017-01-01

Background Physical activity (PA) is beneficial in improving negative physical and psychological effects of cancer. The rapidly increasing number of cancer survivors, resulting from aging and improved cancer care, emphasizes the importance to develop and provide low cost, easy accessible PA programs. Such programs could be provided through the Internet, but that could result in the exclusion of cancer survivors not familiar with the Internet. Therefore, we developed a computer-tailored PA intervention for prostate and colorectal cancer survivors in which both Web-based and print materials are provided, and participants can choose their own preferred delivery mode. Objective The aim of this study was to assess participants’ characteristics related to delivery mode and use of intervention materials. Methods We studied characteristics of participants using Web-based and printed intervention materials in a randomized controlled trial (RCT). Prostate and colorectal cancer survivors recruited from hospitals were randomized to OncoActive (computer-tailored PA intervention) or a usual-care control group. OncoActive participants received both Web-based and printed materials. Participants were classified into initial print- or Web-based participants based on their preferred mode of completion of the first questionnaire, which was needed for the computer-tailored PA advice. Intervention material use during the remainder of the intervention was compared for initial print- or Web-based participants. Additionally, participants were classified into those using only print materials and those using Web-based materials. Differences in participant characteristics and intervention material use were studied through analysis of variance (ANOVAs), chi-square tests, and logistic regressions. Results The majority of the participants in the intervention group were classified as initial Web-based participants (170/249, 68.3%), and 84.9% (191/249) used Web-based intervention materials. Dropout was low (15/249, 6.0%) and differed between initial Web-based (4/170, 2.4%) and print-based (11/79, 14%) participants. Participants were less likely to start Web-based with higher age (odds ratio [OR]=0.93), longer time since last treatment (OR=0.87), and higher fatigue (OR=0.96), and more likely with higher education (OR=4.08) and having completed treatments (OR=5.58). Those who were older (OR=0.93) and post treatment for a longer time (OR=0.86) were less likely to use Web-based intervention materials. Initial print-based participants predominantly used print-based materials, whereas initial Web-based participants used both print- and Web-based materials. Conclusions To our knowledge, this is one of the first studies that assessed participant characteristics related to delivery mode in an intervention in which participants had a free choice of delivery modes. Use of print-based materials among the initial Web-based participants was substantial, indicating the importance of print-based materials. According to our findings, it may be important to offer Web- and print-based materials alongside each other. Providing Web-based materials only may exclude older, less educated, more fatigued, or currently treated participants; these groups are especially more vulnerable and could benefit most from PA interventions. PMID:28835353

47 CFR 90.539 - Frequency stability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... base station signal. (b) The frequency stability of base transmitters operating in the narrowband... is locked to the base station. When AFC is not locked to the base station, the frequency stability... base station, and 5 parts per million or better when AFC is not locked. [63 FR 58651, Nov. 2, 1998, as...

Base Rates: Both Neglected and Intuitive

ERIC Educational Resources Information Center

Pennycook, Gordon; Trippas, Dries; Handley, Simon J.; Thompson, Valerie A.

2014-01-01

Base-rate neglect refers to the tendency for people to underweight base-rate probabilities in favor of diagnostic information. It is commonly held that base-rate neglect occurs because effortful (Type 2) reasoning is required to process base-rate information, whereas diagnostic information is accessible to fast, intuitive (Type 1) processing…

48 CFR 9904.418-50 - Techniques for application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... objective's allocation base data shall be excluded from the base used to allocate the pool. (g) Use of... which the pool relates. (c) Change in allocation base. No change in an existing indirect cost pool allocation base is required if the allocation resulting from the existing base does not differ materially...

Investigation of biobased and petroleum base oils in the entire spectrum of lubrication regimes

USDA-ARS?s Scientific Manuscript database

The tribological properties of biobased and petroleum-based base oils in the entire lubrication regime were investigated. High oleic sunflower oil (HOSuO) and commercially available polyalphaolefin (PAO-6) were selected to represent biobased and petroleum-based base oils, respectively. These two oil...

75 FR 64643 - Reporting of Security-Based Swap Transaction Data

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... information relating to pre-enactment security-based swaps to a registered security-based swap data repository... within 60 days after a registered security- based swap data repository commences operations to receive... repository,\\8\\ and security- based swap execution facility.\\9\\ The Commission has issued an advance notice of...

47 CFR 61.16 - Base documents.

Code of Federal Regulations, 2011 CFR

2011-10-01

... for Electronic Filing § 61.16 Base documents. (a) The Base Document is a complete tariff which incorporates all effective revisions, as of the last day of the preceding month. The Base Document should be... 47 Telecommunication 3 2011-10-01 2011-10-01 false Base documents. 61.16 Section 61.16...

Evidence-Based Practice for Outpatient Clinical Teams

ERIC Educational Resources Information Center

Hamilton, John D.

2006-01-01

This column focuses on evidence-based practice (EBP) within multidisciplinary outpatient settings, but first provides some definitions. Besides EBP (Burns and Hoagwood, 2005; Guyatt and Rennie, 2002), there are also evidence-based medicine (EBM; March et al., 2005), evidence-based service (EBS; Chorpita et al., 2002), and evidence-based treatment…

40 CFR 745.229 - Certification of individuals and firms engaged in lead-based paint activities: public and...

Code of Federal Regulations, 2012 CFR

2012-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.229 Certification of individuals and firms engaged in lead-based... engaged in lead-based paint activities: public and commercial buildings, bridges and superstructures...

24 CFR 965.701 - Lead-based paint poisoning prevention.

Code of Federal Regulations, 2010 CFR

2010-04-01

... URBAN DEVELOPMENT PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Lead-Based Paint Poisoning Prevention § 965.701 Lead-based paint poisoning prevention. The requirements of the Lead-Based Paint Poisoning... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Lead-based paint poisoning...

24 CFR 965.701 - Lead-based paint poisoning prevention.

Code of Federal Regulations, 2014 CFR

2014-04-01

... URBAN DEVELOPMENT PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Lead-Based Paint Poisoning Prevention § 965.701 Lead-based paint poisoning prevention. The requirements of the Lead-Based Paint Poisoning... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Lead-based paint poisoning...

24 CFR 965.701 - Lead-based paint poisoning prevention.

Code of Federal Regulations, 2012 CFR

2012-04-01

... URBAN DEVELOPMENT PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Lead-Based Paint Poisoning Prevention § 965.701 Lead-based paint poisoning prevention. The requirements of the Lead-Based Paint Poisoning... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Lead-based paint poisoning...

40 CFR 745.230 - Work practice standards for conducting lead-based paint activities: public and commercial...

Code of Federal Regulations, 2012 CFR

2012-07-01

... SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.230 Work practice standards for conducting lead-based paint activities: public... lead-based paint activities: public and commercial buildings, bridges and superstructures. [Reserved...

40 CFR 745.230 - Work practice standards for conducting lead-based paint activities: public and commercial...

Code of Federal Regulations, 2013 CFR

2013-07-01

... SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.230 Work practice standards for conducting lead-based paint activities: public... lead-based paint activities: public and commercial buildings, bridges and superstructures. [Reserved...

40 CFR 745.229 - Certification of individuals and firms engaged in lead-based paint activities: public and...

Code of Federal Regulations, 2013 CFR

2013-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.229 Certification of individuals and firms engaged in lead-based... engaged in lead-based paint activities: public and commercial buildings, bridges and superstructures...

40 CFR 745.229 - Certification of individuals and firms engaged in lead-based paint activities: public and...

Code of Federal Regulations, 2014 CFR

2014-07-01

...) TOXIC SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.229 Certification of individuals and firms engaged in lead-based... engaged in lead-based paint activities: public and commercial buildings, bridges and superstructures...

24 CFR 965.701 - Lead-based paint poisoning prevention.

Code of Federal Regulations, 2011 CFR

2011-04-01

... URBAN DEVELOPMENT PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Lead-Based Paint Poisoning Prevention § 965.701 Lead-based paint poisoning prevention. The requirements of the Lead-Based Paint Poisoning... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Lead-based paint poisoning...

24 CFR 965.701 - Lead-based paint poisoning prevention.

Code of Federal Regulations, 2013 CFR

2013-04-01

... URBAN DEVELOPMENT PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Lead-Based Paint Poisoning Prevention § 965.701 Lead-based paint poisoning prevention. The requirements of the Lead-Based Paint Poisoning... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Lead-based paint poisoning...

40 CFR 745.230 - Work practice standards for conducting lead-based paint activities: public and commercial...

Code of Federal Regulations, 2014 CFR

2014-07-01

... SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.230 Work practice standards for conducting lead-based paint activities: public... lead-based paint activities: public and commercial buildings, bridges and superstructures. [Reserved...

10 CFR 904.7 - Base charge.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Base charge. 904.7 Section 904.7 Energy DEPARTMENT OF... Marketing § 904.7 Base charge. (a) The Base Charge shall be developed by the Administrator and promulgated in accordance with appropriate DOE regulations. The Base Charge shall be composed of a capacity...

26 CFR 1.954-1 - Foreign base company income.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 10 2013-04-01 2013-04-01 false Foreign base company income. 1.954-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Controlled Foreign Corporations § 1.954-1 Foreign base company income... computing the foreign base company income of a controlled foreign corporation. Foreign base company income...

10 CFR 904.7 - Base charge.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Base charge. 904.7 Section 904.7 Energy DEPARTMENT OF... Marketing § 904.7 Base charge. (a) The Base Charge shall be developed by the Administrator and promulgated in accordance with appropriate DOE regulations. The Base Charge shall be composed of a capacity...

47 CFR 61.16 - Base documents.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Base documents. 61.16 Section 61.16... for Electronic Filing § 61.16 Base documents. (a) The Base Document is a complete tariff which incorporates all effective revisions, as of the last day of the preceding month. The Base Document should be...

25 CFR 39.102 - What is academic base funding?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false What is academic base funding? 39.102 Section 39.102... PROGRAM Indian School Equalization Formula Base and Supplemental Funding § 39.102 What is academic base funding? Academic base funding is the ADM times the weighted student unit. ...

26 CFR 1.954-1 - Foreign base company income.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 10 2011-04-01 2011-04-01 false Foreign base company income. 1.954-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Controlled Foreign Corporations § 1.954-1 Foreign base company income... computing the foreign base company income of a controlled foreign corporation. Foreign base company income...

25 CFR 39.102 - What is academic base funding?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false What is academic base funding? 39.102 Section 39.102... PROGRAM Indian School Equalization Formula Base and Supplemental Funding § 39.102 What is academic base funding? Academic base funding is the ADM times the weighted student unit. ...

25 CFR 39.102 - What is academic base funding?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true What is academic base funding? 39.102 Section 39.102... PROGRAM Indian School Equalization Formula Base and Supplemental Funding § 39.102 What is academic base funding? Academic base funding is the ADM times the weighted student unit. ...

26 CFR 1.954-1 - Foreign base company income.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 10 2012-04-01 2012-04-01 false Foreign base company income. 1.954-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Controlled Foreign Corporations § 1.954-1 Foreign base company income... computing the foreign base company income of a controlled foreign corporation. Foreign base company income...

47 CFR 61.16 - Base documents.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Base documents. 61.16 Section 61.16... for Electronic Filing § 61.16 Base documents. (a) The Base Document is a complete tariff which incorporates all effective revisions, as of the last day of the preceding month. The Base Document should be...

10 CFR 904.7 - Base charge.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Base charge. 904.7 Section 904.7 Energy DEPARTMENT OF... Marketing § 904.7 Base charge. (a) The Base Charge shall be developed by the Administrator and promulgated in accordance with appropriate DOE regulations. The Base Charge shall be composed of a capacity...

21. Photographic copy of a keyed site plan for North ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. Photographic copy of a keyed site plan for North Base: Military Construction, Muroc Flight Test Base, Muroc, California; General Layout Plan, December 1944. Reproduced from the holdings of the National Archives, Pacific Southwest Region - Edwards Air Force Base, North Base, North Base Road, Boron, Kern County, CA

Riding the Rapids of Classroom-Based Research

ERIC Educational Resources Information Center

Lonergan, Robyn; Cumming, Therese M.

2017-01-01

Conducting classroom-based research can be difficult, often fraught with challenges, analogous to riding a canoe down the rapids. The dynamics of classroom-based research often require flexibility on the parts of both the researcher and school personnel. Classroom-based research is viewed here through a framework of problem-based methodology as…