Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro.

PubMed

Lowe, Henry I C; Watson, Charah T; Badal, Simone; Toyang, Ngeh J; Bryant, Joseph

2012-11-14

Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation. Kinase inhibition was investigated using competition binding (to the ATP sites) assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay. Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd50 of 0.26 μM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC50 values of 2.226 ± 0.28 μM and 1.67 ± 0.18 μM respectively. These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer.

Estrogen modulates sexually dimorphic contextual fear extinction in rats through estrogen receptor beta.

PubMed

Chang, Yao-Ju; Yang, Chih-Hao; Liang, Ying-Ching; Yeh, Che-Ming; Huang, Chiung-Chun; Hsu, Kuei-Sen

2009-11-01

Females and males are different in brain and behavior. These sex differences occur early during development due to a combination of genetic and hormonal factors and continue throughout the lifespan. Previous studies revealed that male rats exhibited significantly higher levels of contextual fear memory than female rats. However, it remains unknown whether a sex difference exists in the contextual fear extinction. To address this issue, male, normally cycling female, and ovariectomized (OVX) female Sprague-Dawley rats were subjected to contextual fear conditioning and extinction trials. Here we report that although male rats exhibited higher levels of freezing than cycling female rats after contextual fear conditioning, female rats subjected to conditioning in the proestrus and estrus stage exhibited an enhancement of fear extinction than male rats. An estrogen receptor (ER) beta agonist diarylpropionitrile but not an ERalpha agonist propyl-pyrazole-triol administration also enhanced extinction of contextual fear in OVX female rats, suggesting that estrogen-mediated facilitation of extinction involves the activation of ERbeta. Intrahippocampal injection of estradiol or diarylpropionitrile before extinction training in OVX female rats remarkably reduced the levels of freezing response during extinction trials. In addition, the locomotion or anxiety state of female rats does not vary across the ovarian cycle. These results reveal a crucial role for estrogen in mediating sexually dimorphic contextual fear extinction, and that estrogen-mediated enhancement of fear extinction involves the activation of ERbeta.

Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro

PubMed Central

2012-01-01

Background Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation. Methods Kinase inhibition was investigated using competition binding (to the ATP sites) assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay. Results Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd50 of 0.26 μM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC50 values of 2.226 ± 0.28 μM and 1.67 ± 0.18 μM respectively. Conclusions These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer. PMID:23151005

Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents.

PubMed

Liu, Jia-Jia; Zhao, Meng-Yue; Zhang, Xin; Zhao, Xin; Zhu, Hai-Liang

2013-11-01

Within the past years, many researches on the synthesis, structure-activity relationships (SAR), antitumor, antiinflammatory and anti-bacterial activities of the pyrazole derivatives have been reported. Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents because of their good inhibitory activity against BRAF(V600E), EGFR, telomerase, ROS Receptor Tyrosine Kinase and Aurora-A kinase. In addition, pyrazole derivatives also show good antiinflammatory and anti-bacterial activities. In this review, the bioactivities of the pyrazole derivatives mentioned above will be summarized in detail. We sincerely hope that increasing knowledge of the SAR and cellular processes underlying the bioactivity of pyrazole derivatives will be beneficial to the rational design of new generation of small molecule drugs.

Antioxidant and Antimicrobial Activity of 5-methyl-2-(5-methyl-1,3-diphenyl-1H-pyrazole-4-carbonyl)-2,4-dihydro-pyrazol-3-one

PubMed Central

Umesha, K. B.; Rai, K. M. L.; Harish Nayaka, M. A.

2009-01-01

Cycloaddition of nitrile imines 4 generated in situ by the catalytic dehydrogenation of diphenyl hydrazones 3 using Chloramine-T (CAT) as oxidant in glacial acetic acid with enolic form of ethyl acetoacetate 5 afforded Ethyl 3-aryl-5-methyl-1-phenyl-1H-pyrazol-4-carboxylate 6 in 80% yield. The said pyrazoles 6 refluxed with 80% hydrazine hydrate using absolute alcohol as solvent for about 2–3 hours to produce the respective 5-methyl-1,3-diphenyl-1H-pyrazole-4-carboxylic acid hydrazide 7. The alcoholic solution of pyrazole acid hydrazides on heating with ethyl acetoacetate 5 to give the 5-methyl-2-(5-methyl-1,3-diphenyl-1H-pyrazole-4-carbonyl)-2,4-dihydro-pyrazol-3-one 8. The synthesized compounds were found to exhibit good antimicrobial and antioxidant activity as evaluated by 1,1-diphenyl-2-picryl Hydrazyl (DPPH) radical scavenging, reducing power and DNA protection assays. PMID:23675159

Synthesis and antifungal activity of the derivatives of novel pyrazole carboxamide and isoxazolol pyrazole carboxylate.

PubMed

Sun, Jialong; Zhou, Yuanming

2015-03-09

A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma[S

PubMed Central

Jiang, Xuntian; Sidhu, Rohini; Porter, Forbes D.; Yanjanin, Nicole M.; Speak, Anneliese O.; te Vruchte, Danielle Taylor; Platt, Frances M.; Fujiwara, Hideji; Scherrer, David E.; Zhang, Jessie; Dietzen, Dennis J.; Schaffer, Jean E.; Ory, Daniel S.

2011-01-01

Niemann-Pick type C1 (NPC1) disease is a rare, progressively fatal neurodegenerative disease for which there are no FDA-approved therapies. A major barrier to developing new therapies for this disorder has been the lack of a sensitive and noninvasive diagnostic test. Recently, we demonstrated that two cholesterol oxidation products, specifically cholestane-3β,5α,6β-triol (3β,5α,6β-triol) and 7-ketocholesterol (7-KC), were markedly increased in the plasma of human NPC1 subjects, suggesting a role for these oxysterols in diagnosis of NPC1 disease and evaluation of therapeutics in clinical trials. In the present study, we describe the development of a sensitive and specific LC-MS/MS method for quantifying 3β,5α,6β-triol and 7-KC human plasma after derivatization with N,N-dimethylglycine. We show that dimethylglycine derivatization successfully enhanced the ionization and fragmentation of 3β,5α,6β-triol and 7-KC for mass spectrometric detection of the oxysterol species in human plasma. The oxysterol dimethylglycinates were resolved with high sensitivity and selectivity, and enabled accurate quantification of 3β,5α,6β-triol and 7-KC concentrations in human plasma. The LC-MS/MS assay was able to discriminate with high sensitivity and specificity between control and NPC1 subjects, and offers for the first time a noninvasive, rapid, and highly sensitive method for diagnosis of NPC1 disease. PMID:21518695

Synergistic effect of pyrazoles derivatives and doxorubicin in claudin-low breast cancer subtype.

PubMed

Saueressig, Silvia; Tessmann, Josiane; Mastelari, Rosiane; da Silva, Liziane Pereira; Buss, Julieti; Segatto, Natalia Vieira; Begnini, Karine Rech; Pacheco, Bruna; de Pereira, Cláudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

2018-02-01

Breast cancer is a global public health problem. For some subtypes, such as Claudin-low, the prognosis is poorer and the treatment is still a challenge. Pyrazoles are an important class of heterocyclic compounds and are promising anticancer agents based on their chemical properties. The present study was aimed not only at testing pyrazoles previously prepared by our research group in two breast cancer cell lines characterized by intermediated response to conventional chemotherapy but also at analyzing the possible synergistic effect of these pyrazoles associated with doxorubicin. Four 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H pyrazoles were tested for the first time in MCF-7 and MDA-MB-231 culture cells. The pyrazoles with best results in cytotoxicity were used in combination with doxorubicin and compared with this drug alone as standard. The synergic effect was analyzed using Combination Index method. In addition, cell death and apoptosis assays were carried out. Two pyrazoles with cytotoxic effect in MCF-7 and especially in MDA-MB-231 were identified. This activity was markedly higher in pyrazoles containing bromine and chlorine substituents. The combination of these pyrazoles with doxorubicin had a significant synergic effect in both cells tested and mainly in MDA-MB-231. These data were confirmed with apoptosis and cell death analysis. The synergic effect observed with combination of these pyrazoles and doxorubicin deserves special attention in Claudin-low breast cancer subtype. This should be explored in order to improve treatment results and minimize side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Molecular and biochemical biomarkers for diagnosis and therapy monitorization of Niemann-Pick type C patients.

PubMed

Hammerschmidt, Tatiane Grazieli; de Oliveira Schmitt Ribas, Graziela; Saraiva-Pereira, Maria Luiza; Bonatto, Márcia Polese; Kessler, Rejane Gus; Souza, Fernanda Timm Seabra; Trapp, Franciele; Michelin-Tirelli, Kristiane; Burin, Maira Graeff; Giugliani, Roberto; Vargas, Carmen Regla

2018-05-01

Niemann-Pick type C (NP-C), one of 50 inherited lysosomal storage disorders, is caused by NPC protein impairment that leads to unesterified cholesterol accumulation in late endosomal/lysosomal compartments. The clinical manifestations of NP-C include hepatosplenomegaly, neurological and psychiatric symptoms. Current diagnosis for NP-C is based on observation of the accumulated cholesterol in fibroblasts of affected individuals, using an invasive and time expensive test, called Filipin staining. Lately, two metabolites that are markedly increased in NP-C patients are arising as biomarkers for this disease screening: 7-ketocholesterol and cholestane-3β,5α,6β-triol, both oxidized cholesterol products. In this work, we aimed to evaluate the performance of cholestane-3β,5α,6β-triol analysis for the screening and monitoring of NPC patients, correlating it with chitotriosidase levels, Filipin staining and molecular analysis. It was investigated 76 non-treated individuals with NP-C suspicion and also 7 patients with previous NP-C diagnosis under treatment with miglustat, in order to verify the cholestane-3β,5α,6β-triol value as a tool for therapy monitoring. Considering molecular assay as golden standard, it was verified that cholestane-3β,5α,6β-triol analysis presented 88% of sensitivity, 96.08% of specificity, a positive and negative predictive value calculated in 91.67% and 94.23%, respectively, for the diagnosis of NP-C. Chitotriosidase levels were increased in patients with positive molecular analysis for NP-C. For Filipin staining, it was found 1 false positive, 7 false negative and 24 inconclusive cases, showing that this assay has important limitations for NP-C diagnosis. Besides, we found a significant decrease in cholestane-3β,5α,6β-triol concentrations in NP-C patients under therapy with miglustat when compared to non-treated patients. Taken together, the present data show that cholestane-3β,5α,6β-triol analysis has a high potential to be an important NP-C screening assay, and also can be used for therapy monitorization with miglustat in NP-C patients. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Pyrazole and imidazo[1,2-b]pyrazole derivatives as new potential anti-tuberculosis agents.

PubMed

Meta, Elda; Brullo, Chiara; Tonelli, Michele; Franzblau, Scott G; Wang, Yuehong; Ma, Rui; Baojie, Wan; Orena, Beatrice Silvia; Pasca, Maria Rosalia; Bruno, Olga

2018-05-23

We screened a large library of differently decorated imidazo-pyrazole and pyrazole derivatives as possible new antitubercular agents and this preliminary screening showed that many compounds are able to totally inhibit Mycobacterium growth (>90 %). Among the most active compounds, we selected some new possible hits based on their similarities and, at the same time, their novelty respect to the pipeline drugs. In order to increase the potency and obtain more information about structure activity relationship (SAR), we design and synthesized three new series of compounds (2a-e, 3a-e, and 4a-l). Performed tests confirmed that both new pyrazoles and imidazo-pyrazoles could represent a new starting point to obtain more potent compounds and further work is now underway to identify the protein targets of this new class of anti-TB agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synthesis, crystal structure, characterization and antifungal activity of 3,4-diaryl-1H-Pyrazoles derivatives

NASA Astrophysics Data System (ADS)

Zhang, Jin; Tan, Da-Jin; Wang, Tao; Jing, Si-Si; Kang, Yang; Zhang, Zun-Ting

2017-12-01

A series of 3,4-diaryl-1H-pyrazoles derivatives were designed and synthesized by the reaction of 3-heteroarylchromones and 3-phenylchromones with hydrazine hydrate in good yields. All of those compounds were characterized by 1H NMR, 13C NMR, IR, and HRMS. Moreover, 3-(2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-1H-pyrazole and 3-(2,4-dihydroxy phenyl)-4-(4-methoxyphenyl)-1H-pyrazole were further conformed by the single crystal X-ray diffraction. In addition, the antifungal activity against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani and Fusarium solani) of 3,4-diaryl-1H-pyrazoles were evaluated. 3-(2-Hydroxy-4-isopropoxyphenyl)-4-phenyl-1H-pyrazole was more better and broader inhibitory effect on Cytospora sp., C. gloeosporioides, A. solani and Fusarium solani with IC50 values of 26.96, 28.84, 16.77 and 22.10 μg/mL, respectively. 4-(4-Fluorophenyl)-3-(2-hydroxy-4-methoxyphenyl)-1H-pyrazole exhibited fairly effective antifungal activity against Cytospora sp., C. gloeosporioides and A. solani with IC50 values of 11.91, 14.92 and 16.98 μg/mL, respectively.

Synthesis of spiro-4H-pyrazole-oxindoles and fused 1H-pyrazoles via divergent, thermally induced tandem cyclization/migration of alkyne-tethered diazo compounds.

PubMed

Zhang, Cheng; Dong, Shanliang; Zheng, Yang; He, Ciwang; Chen, Jiaolong; Zhen, Jingsen; Qiu, Lihua; Xu, Xinfang

2018-01-31

A thermally induced, substrate-dependent reaction of alkynyl diazo compounds has been developed. This transformation produces spiro-4H-pyrazole-oxindoles and fused 1H-pyrazoles in good to high yields from the corresponding alpha-cyano and alpha-sulfonyl diazo compounds. The salient features of this reaction include excellent chemoselectivity and atom-economy, mild reaction conditions, simple purification and potential for large scale production.

Tricyclic Pyrazoles. Part 5. Novel 1,4-Dihydroindeno[1,2-c]pyrazole CB2 Ligands Using Molecular Hybridization Based on Scaffold Hopping

PubMed Central

Murineddu, Gabriele; Asproni, Battistina; Ruiu, Stefania; Deligia, Francesco; Falzoi, Matteo; Pau, Amedeo; Thomas, Brian F; Zhang, Yanan; Pinna, Gérard A; Pani, Luca; Lazzari, Paolo

2012-01-01

In search of new selective CB2 ligands, the synthesis and preliminary biological evaluation of novel 1,4-dihydroindeno[1,2-c]pyrazole hybrids of the highly potent prototypicals 5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-N-fenchyl-1H-pyrazole-3-carboxamide 1 and 1-(2,4-dichlorophenyl)-6-methyl-N-(piperidin-1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide 2 are detailed. We postulated that the introduction of those pharmacophoric elements essential for activity of 1 in the tricyclic core of 2 might provide CB2 ligands with further improved receptor selectivity and biological activity. Among the compounds, 6-chloro-7-methyl-1-(2,4-dichlorophenyl)-N-fenchyl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide (22) exhibited low two digit nanomolar affinity for the cannabinoid CB2R and maintained a high level of CB2-selectivity. PMID:22876271

Synthesis of diverse pyrazole-4-sulfonyl chlorides starting from 2-(benzylthio)malonaldehyde.

PubMed

Sokolyuk, Pavlo A; Kondratov, Ivan S; Gavrylenko, Olexiy V; Tolmachov, Andrey A

2016-02-01

A series of pyrazole-4-sulfonyl chlorides was obtained by a convenient 2-step method starting from synthetically available 2-(benzylthio)malonaldehyde. The method can be applied for the effective multi-gram synthesis of diverse pyrazole-containing sulfonyl chlorides which are mostly not available by other methods.

Selective oxidation of steroidal allylic alcohols using pyrazole and pyridinium chlorochoromate.

PubMed

Parish, E J; Chitrakorn, S; Lowery, S

1984-07-01

ABASTRACT: This paper presents a modified method for the selective oxidation of allylic alchols. Pyrazole, when used with pyridinium chlorochromate, is a mild and useful reagent system for the rapid and selective oxidation of steroidal allylic alcohols to the corresponding α, β-unsaturated ketones. The reaction of each substrate was carried out by adding the oxidant to a dry methylene chloride solution containing pyrazole and an allylic alchol. This report is the first on the use of pyrazole to augment selective oxidation by a chronium (VI) reagent.

Thermal decomposition of pyrazole to vinylcarbene + N 2: A first principles/RRKM study

NASA Astrophysics Data System (ADS)

da Silva, Gabriel

2009-05-01

Thermal decomposition of pyrazole, a five-membered nitrogen-containing heterocycle, has been studied using ab initio G3X theory and RRKM rate theory. The decomposition mechanism involves an intramolecular hydrogen shift to 3 H-pyrazole, followed by ring opening to 3-diazo-1-propene and dissociation to vinylcarbene (CH 2CHCH) + N 2. At 1 atm the calculated rate equation k [s -1] = 1.26 × 10 50T-10.699e -41200/T is obtained, which agrees with the results of flash vacuum pyrolysis experiments. The pyrazole decomposition product vinylcarbene is expected to rearrange to propyne, making pyrazole decomposition essentially thermoneutral. It is hypothesized that at high concentrations vinylcarbene could undergo a self-reaction to 1,3- and 1,4-cyclohexadiene.

Evaluation of plasma cholestane-3β,5α,6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism[S

PubMed Central

Boenzi, Sara; Deodato, Federica; Taurisano, Roberta; Goffredo, Bianca Maria; Rizzo, Cristiano; Dionisi-Vici, Carlo

2016-01-01

Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient’s age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C. PMID:26733147

Regio-selective lipase catalyzed hydrolysis of oxanorbornane-based sugar-like amphiphiles at air-water interface: A polarized FT-IRRAS study.

PubMed

Sarangi, Nirod Kumar; Ganesan, M; Muraleedharan, K M; Patnaik, Archita

2017-04-01

Interfacial hydrolysis of oxanorbornane-based amphiphile (Triol C16) by Candida rugosa lipase was investigated using real-time polarized Fourier transform-infrared reflection absorption spectroscopy (FT-IRRAS). The kinetics of hydrolysis was studied by analyzing the ester carbonyl ν(CO) stretching vibration band across the two dimensional (2D) array of molecules at the confined interface. In particular, we demonstrate Triol C16 to form Michaelis-Menten type complex, like that of lipid-substrate analogues, where the Triol C16 head group remained accessible to the catalytic triad of the lipase. The enzyme-induced selective cleavage of the ester bond was spectroscopically monitored by the disappearance of the intense ν(CO) resonance at 1736cm -1 . Consequently, the in situ spectroscopic measurements evidenced selective ester hydrolysis of Triol C16 yielding Tetrol C 2 OH and Palmitic acid, which remained predominantly in the undissociated form at the interface. The conformation sensitive amide I (majorly ν(CO)) and the interfacial water reorganization suggested 2D ordering of the enzyme molecules following which interfacial reactions were employed towards probing the enzyme kinetics at the air/water interface. The investigation demonstrated further the potential of IRRAS spectroscopy for real-time monitoring the hydrolytic product formation and selectivity at biomimetic interfaces. Copyright © 2017 Elsevier B.V. All rights reserved.

40 CFR 180.517 - Fipronil; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

...)-(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile) and its metabolites 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfonyl]-1H-pyrazole-3-carbonitrile and 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile and its photodegradate 5-amino-1-(2...

Two new steroidal saponins from Tribulus terrestris L.

PubMed

Liu, Tao; Lu, Xuan; Wu, Biao; Chen, Gang; Hua, Hui-Ming; Pei, Yue-Hu

2010-01-01

Two new steroidal saponins were isolated from the fruits of Tribulus terrestris L. Their structures were elucidated by spectroscopic and chemical analysis as (23S,24R,25R)-5alpha-spirostane-3beta,23,24-triol-3-O-{alpha-L-rhamnopyranosyl-(1 --> 2)-[beta-D-glucopyranosyl-(1 --> 4)]-beta-D-galactopyranoside} (1) and (23S,24R,25S)-5alpha-spirostane-3beta,23,24-triol-3-O-{alpha-L-rhamnopyranosyl-(1 --> 2)-[beta-D-glucopyranosyl-(1 --> 4)]-beta-D-galactopyranoside} (2).

Self-assembly of 3,5-bis(ethoxycarbonyl)pyrazolate anions and ammonium cations of beta-phenylethylamine or homoveratrylamine into hetero-double-stranded helical structures.

PubMed

Reviriego, Felipe; Sanz, Ana; Navarro, Pilar; Latorre, Julio; García-España, Enrique; Liu-Gonzalez, Malva

2009-08-21

Hydrogen-bonded double-stranded hetero-helices are formed when reacting sodium 3,5-bis(ethoxycarbonyl)pyrazolate with beta-phenethylammonium or homoveratrylammonium chloride, in which one of the strands is defined by the ammonium cations and the other one by the pyrazolate anions.

Three new labdane-type diterpene glycosides from fruits of Rubus chingii and their cytotoxic activities against five humor cell lines.

PubMed

Zhong, Ruijian; Guo, Qing; Zhou, Guoping; Fu, Huizheng; Wan, Kaihua

2015-04-01

Three new labdane-type diterpene glycosides, 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-7(8),13(14)-diene-3β,15,18-triol (1), 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (2), and 15-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranosyl-18-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (3), were isolated from the fruits of Rubus chingii. Their structures were elucidated on the basis of spectroscopic data and chemical methods. The cytotoxic activities of compounds 1-3 were evaluated against five human tumor cell lines (HCT-8, BGC-823, A549, and A2780). Compounds 3 showed cytotoxic activity against A549 with an IC50 value of 2.32μM. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Modeling intercalated PAH metabolites: Explanation for the stereochemical and shape selectivity of B-DNA for bay-region carcinogens

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

Szentpaly, L.V.; Shamovsky, I.L.

1996-12-31

The equilibrium structures of 22 intercalation complexes of different metabolites of polycyclic aromatic hydrocarbons (PAH) with the dG{sub 2}{lg_bullet}dC{sub 2} dinucleotide are obtained by AMBER and FLEX molecular modeling. The triol carbocations of highly potent carcinogens are stereochemically compatible with the dinucleotide and B-DNA. Their intercalation complexes are found (1) to be stabilized by two hydrogen bonds between DH groups of the triol cation and the N(3) atoms of the adjacent guanine residues, (2) to be {open_quotes}preorganized{close_quotes} for covalent bonding to the N(2) amino group of quanine, (3) to display only minor conformational changes with respect to the uncomplexed dinucleotidemore » in B-DNA. A new explanation for the stereochemical and shape selectivity in the initiation of cancer by PAHa is presented. The molecular mechanics study is sugmented by HF/6-31G{sup I} calculations on the conformations of phenanthrene triol carbocation.« less

17Beta-estradiol signaling and regulation of proliferation and apoptosis of rat Sertoli cells.

PubMed

Royer, Carine; Lucas, Thaís F G; Lazari, Maria F M; Porto, Catarina S

2012-04-01

The aim of the present study was to investigate the intracellular signaling events downstream of the classical estrogen receptors (ESRs) and G protein-coupled estrogen receptor 1 (GPER) involved in regulation of proliferation and apoptosis of rat Sertoli cells, in which we have previously described ESR1, ESR2, and GPER. ESRs play a role in Sertoli cell proliferation, and GPER, but not ESRs, plays a role modulating gene expression involved with apoptosis. The present study shows that 17beta-estradiol (E2) and the GPER-selective agonist G-1 rapidly activate phosphatidylinositol 3-kinase (PIK3)/serine threonine protein kinase (AKT) and cyclic AMP response element-binding (CREB) phosphorylation. E2 and the ESR1-selective agonist 4,4',4″-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT) increase the expression of cyclin D1 (CCND1), whereas the ESR2-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and G-1 do not change the expression of this protein, suggesting that ESR1 is the upstream receptor regulating Sertoli cell proliferation. E2- or PPT-ESR1, through activation of epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase 3/1 (MAPK3/1) and PIK3 pathways, induces upregulation of CCND1. KG-501, the compound that disrupts the phospho-CREB/CREB binding protein (CBP) complex, does not change E2- or PPT-ESR1-mediated CCND1 expression, suggesting that phospho-CREB/cyclic AMP response element/CBP is not involved in the expression of this protein. E2- or G-1-GPER, through activation of EGFR/MAPK3/1 and PIK3 pathways, may be involved in the upregulation of antiapoptotic proteins BCL2 and BCL2L2. E2- or G-1-GPER/EGFR/MAPK3/1/phospho-CREB decreases BAX expression. Taken together, these results show a differential effect of E2-GPER on the CREB-mediated transcription of proapoptotic and antiapoptotic genes of the same BCL2 gene family. ESR1 and GPER can mediate the rapid E2 actions in the Sertoli cells, which in turn can modulate nuclear transcriptional events important for Sertoli cell function and maintenance of normal testis development and homeostasis. Our findings are important to clarify the role of estrogen in a critical period of testicular development, and to direct further studies, which may contribute to better understanding of the causes of male infertility.

One step synthesis of 6-oxo-cholestan-3β,5α-diol

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

Voisin, Maud; Silvente-Poirot, Sandrine; Poirot, Marc, E-mail: marc.poirot@inserm.fr

Highlights: • Cholesterol-5,6-epoxides are metabolized into cholestane-3β,5α,6β-triol (CT) in cancer cells. • 6-Oxo-cholestan-3β,5α-diol (OCDO) is a putative metabolite of CT. • The one step syntheses of CT and OCDO from cholesterol are reported. • The one step syntheses of labelled CT and OCDO are reported. - Abstract: Cholesterol metabolism has been recently linked to cancer, highlighting the importance of the characterization of new metabolic pathways in the sterol series. One of these pathways is centered on cholesterol-5,6-epoxides (5,6-ECs). 5,6-ECs can either generate dendrogenin A, a tumor suppressor present in healthy mammalian tissues, or the carcinogenic cholestane-3β,5α,6β-triol (CT) and its putativemore » metabolite 6-oxo-cholestan-3β,5α-diol (OCDO) in tumor cells. We are currently investigating the identification of the enzyme involved in OCDO biosynthesis, which would be highly facilitated by the use of commercially unavailable [{sup 14}C]-cholestane-3β,5α,6β-triol and [{sup 14}C]-6-oxo-cholestan-3β,5α-diol. In the present study we report the one-step synthesis of [{sup 14}C]-cholestane-3β,5α,6β-triol and [{sup 14}C]-6-oxo-cholestan-3β,5α-diol by oxidation of [{sup 14}C]-cholesterol with iodide metaperiodate (HIO{sub 4})« less

Evaluation of plasma cholestane-3β,5α,6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism.

PubMed

Boenzi, Sara; Deodato, Federica; Taurisano, Roberta; Goffredo, Bianca Maria; Rizzo, Cristiano; Dionisi-Vici, Carlo

2016-03-01

Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient's age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Copper-catalyzed aerobic C(sp2)-H functionalization for C-N bond formation: synthesis of pyrazoles and indazoles.

PubMed

Li, Xianwei; He, Li; Chen, Huoji; Wu, Wanqing; Jiang, Huanfeng

2013-04-19

A simple, practical, and highly efficient synthesis of pyrazoles and indazoles via copper-catalyzed direct aerobic oxidative C(sp(2))-H amination has been reported herein. This process tolerated a variety of functional groups under mild conditions. Further diversification of pyrazoles was also investigated, which provided its potential for drug discovery.

(1H-pyrazole-κN2)(2,2':6',2''-terpyridine-κ3N,N',N'')platinum(II) bis(perchlorate) nitromethane monosolvate.

PubMed

Akerman, Matthew; Akerman, Kate; Jaganyi, Deogratius; Reddy, Desigan

2011-09-01

The reaction between [PtCl(terpy)]·2H(2)O (terpy is 2,2':6',2''-terpyridine) and pyrazole in the presence of two equivalents of AgClO(4) in nitromethane yields the title compound, [Pt(C(3)H(4)N(2))(C(15)H(11)N(3))](ClO(4))(2)·CH(3)NO(2), as a yellow crystalline solid. Single-crystal X-ray diffraction shows that the dicationic platinum(II) chelate is square planar with the terpyridine ligand occupying three sites and the pyrazole ligand occupying the fourth. The torsion angle subtended by the pyrazole ring relative to the terpyridine chelate is 62.4 (6)°. Density functional theory calculations at the LANL2DZ/PBE1PBE level of theory show that in vacuo the lowest-energy conformation has the pyrazole ligand in an orientation perpendicular to the terpyridine ligand (i.e. 90°). Seemingly, the stability gained by the formation of hydrogen bonds between the pyrazole NH group and the perchlorate anion in the solid-state structure is sufficient for the chelate to adopt a higher-energy conformation.

Partial deletion of argininosuccinate synthase protects from pyrazole plus lipopolysaccharide-induced liver injury by decreasing nitrosative stress

PubMed Central

Lu, Yongke; Leung, Tung Ming; Ward, Stephen C.

2012-01-01

Argininosuccinate synthase (ASS) is the rate-limiting enzyme in the urea cycle. Along with nitric oxide synthase (NOS)-2, ASS endows cells with the l-citrulline/nitric oxide (NO·) salvage pathway to continually supply l-arginine from l-citrulline for sustained NO· generation. Because of the relevant role of NOS in liver injury, we hypothesized that downregulation of ASS could decrease the availability of intracellular substrate for NO· synthesis by NOS-2 and, hence, decrease liver damage. Previous work demonstrated that pyrazole plus LPS caused significant liver injury involving NO· generation and formation of 3-nitrotyrosine protein adducts; thus, wild-type (WT) and Ass+/− mice (Ass−/− mice are lethal) were treated with pyrazole plus LPS, and markers of nitrosative stress, as well as liver injury, were analyzed. Partial ablation of Ass protected from pyrazole plus LPS-induced liver injury by decreasing nitrosative stress and hepatic and circulating TNFα. Moreover, apoptosis was prevented, since pyrazole plus LPS-treated Ass+/− mice showed decreased phosphorylation of JNK; increased MAPK phosphatase-1, which is known to deactivate JNK signaling; and lower cleaved caspase-3 than treated WT mice, and this was accompanied by less TdT-mediated dUTP nick end labeling-positive staining. Lastly, hepatic neutrophil accumulation was almost absent in pyrazole plus LPS-treated Ass+/− compared with WT mice. Partial Ass ablation prevents pyrazole plus LPS-mediated liver injury by reducing nitrosative stress, TNFα, apoptosis, and neutrophil infiltration. PMID:22052013

The motility and motion duration of jatimbulan tilapia (Oreochromis niloticus) spermatozoa in different salinity

NASA Astrophysics Data System (ADS)

Triastuti, J.; Kintani, D.; Luqman, E. M.; Pujiastuti, D. Y.

2018-04-01

Tilapia hatchery is still conducted in freshwater and seeds are death simultaneousy when cultivated in high salinity due to the acclimatization process. An alternative method to implement hatchery at high salinity is required. This study aims to determine the salinity of activation medium that provides the best Jatimbulan Tilapia sperm motility and motion duration at high salinity. The study applies completely randomized design (CRD), which consists of 5 treatments (0 ppt, 4 ppt, 9 ppt, 14 ppt and 19 ppt) and 4 repetitions. The parameters consists of sperm motility, motion duration, fresh sperm data (volume, color, odor, pH, consistency, and the concentration of sperm) and sperm abnormalities. The results exhibited that salinity significantly (p < 0.05). Influeneed the sperm motility and motion duration. Motility reaches its best at 0 ppt and 4 ppt (93.4 % and 87.8 %). For motion duration, best condition was in 0 ppt and 4 ppt treatments, totaling 2128 seconds and 1961.5 seconds. Meanwhile, sperm did not move when treated in waters with 9 ppt, 14 ppt and 19 ppt salinities.

21 CFR 74.2705 - FD&C Yellow No. 5.

Code of Federal Regulations, 2010 CFR

2010-04-01

... salt, not more than 0.2 percent. 4,5-Dihydro-5-oxo-1-(4-sulfophenyl)-1H-pyrazole-3-carboxylic acid, disodium salt, not more than 0.2 percent. Ethyl or methyl 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-1H-pyrazole-3...-sulfophenyl)azo]-1H-pyrazole-3-carboxylic acid (CAS Reg. No. 1934-21-0). To manufacture the additive, 4...

Furostanol saponins from the fruits of Tribulus terrestris.

PubMed

Chen, Gang; Su, Lan; Feng, Sheng-Guang; Lu, Xuan; Wang, Haifeng; Pei, Yue-Hu

2013-01-01

Two new steroidal saponins were isolated from the fruits of Tribulus terrestris. Their structures were assigned by spectroscopic analysis and colour reaction as 26-O-β-D-glucopyranosyl-(25R)-5α-furostane-12-one-3β,22α,26-triol-3-O-β-D-glucopyranosyl(1 → 4)-β-D-galactopyranoside (1); 26-O-β- D-glucopyranosyl-25(R)-5α-furostan-12-one-3β,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 4)]-β-D-galactopyranoside (2).

Synthesis and configuration of the nonadecenetriol isolated from seeds of Persea americana.

PubMed

Yan, Xin; Zhang, Shao-Min; Wu, Yikang; Gao, Po

2011-10-07

In an effort to establish the relative as well as absolute configuration of the trypanocidally active natural nonadec-6-en-1,2,4-triol isolated from Persea americana, the (2S,4R), (2S,4S), and (2R,4R) isomers were synthesized. The stereogenic centers taken from enantiopure chiral epoxy building blocks derived from inexpensive and readily available D-glucolactone. The (2R,4R) isomer gave (1)H and (13)C NMR as well as specific rotation in excellent consistence with those reported for the natural triol.

Synthesis of the first novel pyrazole thioglycosides as deaza ribavirin analogues.

PubMed

Abu-Zaied, Mamdouh A; Elgemeie, Galal H

2017-12-02

This study reports a novel and efficient method for the synthesis of the first reported novel class of thiopyrazoles and their corresponding thioglycosides. These series of compounds were designed through the reaction of hydrazine derivatives with sodium dithiolate salt 2 in EtOH at ambient temperature to give the corresponding sodium 5-amino-4-cyano-1H-pyrazole-3-thiolates 4a-d. The latter compounds were treated with α-acetobromoglucose 6a and α-acetobromogalactose 6b in DMF at ambient temperature to give in an excellent yields the corresponding pyrazole S-glycosides 7a-h. Ammonolysis of the pyrazole thioglycosides 7a-h afforded the corresponding free thioglycosides 8a-h.

Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice.

PubMed

Thammacharoen, Sumpun; Geary, Nori; Lutz, Thomas A; Ogawa, Sonoko; Asarian, Lori

2009-05-01

Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.

Synthesis of 3-Methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-One: How to Avoid O-Acylation

ERIC Educational Resources Information Center

Kurteva, Vanya B.; Petrova, Maria A.

2015-01-01

In this laboratory experiment, students synthesize 3-methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-one by selective C-acylation of 3-methyl-1-phenyl-1H-pyrazol-5-one. Calcium hydroxide is used to push the tautomeric equilibrium toward the enol form, to protect the hydroxyl functionality as a complex, to trap the liberated hydrogen chloride, and to…

Structure elucidation of the designer drug N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide and the relevance of predicted (13) C NMR shifts - a case study.

PubMed

Girreser, Ulrich; Rösner, Peter; Vasilev, Andrej

2016-07-01

The detailed structure elucidation process of the new cannabimimetic designer drug, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, with a highly substituted pyrazole skeleton, using nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric (MS) techniques is described. After a first analysis of the NMR spectra and comparison with 48 possible pyrazole and imidazole structures, a subset of six positional isomeric pyrazoles and six imidazoles remained conceivable. Four substituents of the heterocyclic skeleton were identified: a proton bound to a pyrazole ring carbon atom; a 5-fluoropentyl group; a 4-fluorophenyl substituent; and a carbamoyl group, which is N-substituted with a methyl residue carrying a tert.-butyl and a carbamoyl substituent. The 5-fluoropentyl residue is situated at the nitrogen ring atom. Additional NMR experiments like the (1) H,(13) C HMBC were performed, but due to the small number of signals based on long-range couplings, the comparison of predicted and observed (13) C chemical shifts became necessary. The open access Internet shift prediction programs NMRDB, NMRSHIFTDB2, and CSEARCH were employed for the prediction of (13) C shift values which allowed an efficient and unambiguous structure determination. For the identified N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, the best agreement between predicted (13) C shifts and the observed chemical shifts and long-range couplings for the pyrazole ring carbon atoms, with a standard error of about 2 ppm, was found with each of the predictions. For the comparison of measured and predicted chemical shifts model compounds with simple substituents proved helpful. The identified compound is a homologue of AZ-037 which is offered by Internet suppliers. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A new simple and rapid LC-ESI-MS/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease.

PubMed

Boenzi, Sara; Deodato, Federica; Taurisano, Roberta; Martinelli, Diego; Verrigni, Daniela; Carrozzo, Rosalba; Bertini, Enrico; Pastore, Anna; Dionisi-Vici, Carlo; Johnson, David W

2014-11-01

Two oxysterols, cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC), have been recently proposed as diagnostic markers of Niemann-Pick type C (NP-C) disease, representing a potential alternative diagnostic tool to the more invasive and time consuming filipin test in cultured fibroblasts. Usually, the oxysterols are detected and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using atmospheric pressure chemical ionization (APCI) or electro-spray-ionization (ESI) sources, after a variety of derivatization procedures to enhance sensitivity. We developed a sensitive LC-MS/MS method to quantify the oxysterols in plasma as dimethylaminobutyrate ester, suitable for ESI analysis. This method, with an easy liquid-phase extraction and a short derivatization procedure, has been validated to demonstrate specificity, linearity, recovery, lowest limit of quantification, accuracy and precision. The assay was linear over a concentration range of 0.5-200ng/mL for C-triol and 1.0-200ng/mL for 7-KC. Intra-day and inter-day coefficients of variation (CV%) were <15% for both metabolites. Receiver operating characteristic analysis estimates that the area under curve was 0.998 for C-triol, and 0.972 for 7-KC, implying a significant discriminatory power for the method in this patient population of both oxysterols. In summary, our method provides a simple, rapid and non-invasive diagnostic tool for the biochemical diagnosis of NP-C disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Ambient mixing ratios of atmospheric halogenated compounds at five background stations in China

NASA Astrophysics Data System (ADS)

Zhang, Gen; Yao, Bo; Vollmer, Martin K.; Montzka, Stephen A.; Mühle, Jens; Weiss, Ray F.; O'Doherty, Simon; Li, Yi; Fang, Shuangxi; Reimann, Stefan

2017-07-01

High precision measurements of three chlorofluorocarbons (CFCs), three hydrochlorofluorocarbons (HCFCs), six hydrofluorocarbons (HFCs), three perfluorocarbons (PFCs), and sulfur hexafluoride (SF6) were made at five Chinese background stations from January 2011 to December 2012. Their station means in the background air were 239.5 ± 0.69 parts-per-trillion dry-air mole fraction mixing ratios (ppt) for CFC-11, 536.5 ± 1.49 ppt for CFC-12, 74.66 ± 0.09 ppt for CFC-113, 232.1 ± 4.77 ppt for HCFC-22, 23.78 ± 0.29 ppt for HCFC-141b, 22.92 ± 0.42 ppt for HCFC-142b, 11.75 ± 0.43 ppt for HFC-125, 71.32 ± 1.35 ppt for HFC-134a, 13.62 ± 0.43 ppt for HFC-143a, 9.10 ± 1.26 ppt for HFC-152a, 25.45 ± 0.1 ppt for HFC-23, 7.28 ± 0.48 ppt for HFC-32, 4.32 ± 0.03 ppt for PFC-116, 0.63 ± 0.04 ppt for PFC-218, 1.36 ± 0.01 ppt for PFC-318, and 7.67 ± 0.03 ppt for SF6, respectively, which were comparable with those measured at the two Northern Hemisphere (NH) AGAGE stations: Mace Head, Ireland (MHD) and Trinidad Head, California, USA (THD). Compared with our results for earlier years from in-situ measurement at SDZ, background-air mixing ratios of CFCs are now declining, while those for HCFCs, HFCs, PFCs, and SF6 are still increasing. The ratios of the number of sampling events in which measured mixing ratios were elevated above background (pollution events) relative to the total sample frequency (POL/SUM) for CFCs, HCFCs, and HFCs were found to be station dependent, generally LAN > SDZ > LFS > XGL > WLG. The enhancement (△, polluted mixing ratios minus background mixing ratios) generally show distinct patterns, with HCFCs (40.7-175.4 ppt) > HFCs (15.8-66.3 ppt)> CFCs (15.8-33.8 ppt)> PFCs (0.1-0.9 ppt) at five stations, especially for HCFC-22 ranging from 36.9 ppt to 138.2 ppt. Combining with the molecular weights, our findings imply biggest emissions of HCFCs in the regions around these Chinese sites compared to HFCs and CFCs, while the smallest of PFCs, consistent with CFCs being phased out and replaced with HCFCs in China. In addition, relative emission strengths (emission was expressed by mole fractions) of these halocarbons in China were inferred as HCFC-22 > HCFC-141b > HFC-134a > HCFC-142b for the Yangtze River Delta (YRD) and as HCFC-22 > HCFC-142b > HCFC-141b ≈ HFC-134a in the North China Plain (NCP).

Synthetic routes to 3(5)-phosphonylated pyrazoles

NASA Astrophysics Data System (ADS)

Goulioukina, N. S.; Makukhin, N. N.; Beletskaya, I. P.

2016-07-01

This review comprehensively covers the currently available synthetic routes to 3(5)-phosphonylated pyrazoles. There are demonstrated significant advances in this field over the last 10-15 years caused by the use of the Bestmann-Ohira reagent [as well as (diazomethyl)phosphonates and phosphonylated hydrazonoyl halides] in reactions with diverse dipolarophiles. 1,3-Dipolar cycloaddition of diazo compounds to α,β-unsaturated phosphonates as well as intramolecular heterocyclization of (1-diazoallyl)phosphonates and (3--diazo-1-propenyl)phosphonates are discussed. Synthetic potential of cyclocondensation of organophosphorus 1,3-dielectrophilic compounds with hydrazines is shown. Ways to introduce a phosphonate group into the pyrazole ring are considered. Examples of chemical transformations of 3(5)-phosphonylated pyrazoles are reported. The bibliography includes 88 references.

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

PubMed

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

2016-05-04

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

Activation of the G protein-coupled estrogen receptor, but not estrogen receptor α or β, rapidly enhances social learning.

PubMed

Ervin, Kelsy Sharice Jean; Mulvale, Erin; Gallagher, Nicola; Roussel, Véronique; Choleris, Elena

2015-08-01

Social learning is a highly adaptive process by which an animal acquires information from a conspecific. While estrogens are known to modulate learning and memory, much of this research focuses on individual learning. Estrogens have been shown to enhance social learning on a long-term time scale, likely via genomic mechanisms. Estrogens have also been shown to affect individual learning on a rapid time scale through cell-signaling cascades, rather than via genomic effects, suggesting they may also rapidly influence social learning. We therefore investigated the effects of 17β-estradiol and involvement of the estrogen receptors (ERs) using the ERα agonist propyl pyrazole triol, the ERβ agonist diarylpropionitrile, and the G protein-coupled ER 1 (GPER1) agonist G1 on the social transmission of food preferences (STFP) task, within a time scale that focused on the rapid effects of estrogens. General ER activation with 17β-estradiol resulted in a modest facilitation of social learning, with mice showing a preference up to 30min of testing. Specific activation of the GPER1 also rapidly enhanced social learning, with mice showing a socially learned preference up to 2h of testing. ERα activation instead shortened the expression of a socially learned food preference, while ERβ activation had little to no effects. Thus, rapid estrogenic modulation of social learning in the STFP may be the outcome of competing action at the three main receptors. Hence, estrogens' rapid effects on social learning likely depend on the specific ERs present in brain regions recruited during social learning. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effects of salinity exposure on multiple life stages of a common freshwater mussel, Elliptio complanata

USGS Publications Warehouse

Blakeslee, Carrie J.; Galbraith, Heather S.; Robertson, Laura S.; St. John White, Barbara

2013-01-01

There is growing concern over the effects of increased salinization on freshwater organisms, which are largely unknown for unionid mussels. Adult and larval Elliptio complanata were exposed to low-level salt concentrations to determine the effects on mussel survival, physiology, and reproduction. Adults were exposed to salt concentrations of 0 parts per thousand (ppt), 2 ppt, 4 ppt, and 6 ppt NaCl and monitored over 7 d for mortality. Treatment groups exposed to 6 ppt and 4 ppt experienced 50% mortality at day 3 and day 4, respectively, with complete mortality by day 7. No mortality was observed in the other treatments. Adults were also exposed to sublethal salinity levels of 1 ppt and 2 ppt NaCl for 4 wk to determine physiological consequences of prolonged salinity exposure. Mussels exposed to 1 ppt and 2 ppt experienced reduced metabolic rates within the first 24 h of exposure that recovered to control levels in the 1-ppt treatment within 7 d. Metabolic recovery did not occur in the 2-ppt treatment by the end of 28 d. Glochidia exposed to 3-ppt NaCl during attachment to their host fish suffered a reduction in attachment success and metamorphosis, resulting in a 10-fold reduction in the number of juveniles produced per host fish. The present study demonstrates that low levels of salt can have a dramatic effect on the reproduction, physiology, and survival of freshwater mussels

Anle138b and related compounds are aggregation specific fluorescence markers and reveal high affinity binding to α-synuclein aggregates.

PubMed

Deeg, Andreas A; Reiner, Anne M; Schmidt, Felix; Schueder, Florian; Ryazanov, Sergey; Ruf, Viktoria C; Giller, Karin; Becker, Stefan; Leonov, Andrei; Griesinger, Christian; Giese, Armin; Zinth, Wolfgang

2015-09-01

Special diphenyl-pyrazole compounds and in particular anle138b were found to reduce the progression of prion and Parkinson's disease in animal models. The therapeutic impact of these compounds was attributed to the modulation of α-synuclein and prion-protein aggregation related to these diseases. Photophysical and photochemical properties of the diphenyl-pyrazole compounds anle138b, anle186b and sery313b and their interaction with monomeric and aggregated α-synuclein were studied by fluorescence techniques. The fluorescence emission of diphenyl-pyrazole is strongly increased upon incubation with α-synuclein fibrils, while no change in fluorescence emission is found when brought in contact with monomeric α-synuclein. This points to a distinct interaction between diphenyl-pyrazole and the fibrillar structure with a high binding affinity (Kd=190±120nM) for anle138b. Several α-synuclein proteins form a hydrophobic binding pocket for the diphenyl-pyrazole compound. A UV-induced dehalogenation reaction was observed for anle138b which is modulated by the hydrophobic environment of the fibrils. Fluorescence of the investigated diphenyl-pyrazole compounds strongly increases upon binding to fibrillar α-synuclein structures. Binding at high affinity occurs to hydrophobic pockets in the fibrils. The observed particular fluorescence properties of the diphenyl-pyrazole molecules open new possibilities for the investigation of the mode of action of these compounds in neurodegenerative diseases. The high binding affinity to aggregates and the strong increase in fluorescence upon binding make the compounds promising fluorescence markers for the analysis of aggregation-dependent epitopes. Copyright © 2015 Elsevier B.V. All rights reserved.

1,1'-Bis(pyrazol-3-yl)ferrocene: A Clip Ligand That Forms Supramolecular Aggregates and Prismatic Hexanuclear Coinage Metal Complexes.

PubMed

Veronelli, Mattia; Dechert, Sebastian; Demeshko, Serhiy; Meyer, Franc

2015-07-20

Two ferrocene derivatives with appended pyrazole substituents, namely, 1,1'-bis(5-methyl-1H-pyrazol-3-yl)ferrocene (H2LH) and 1,1'-bis(5-trifluoromethyl-1H-pyrazol-3-yl)ferrocene (H2LF), were synthesized. In solid state they form distinct H-bonded dimers with orthogonal (H2LH, C2 symmetry) or antiparallel (H2LF, C2h symmetry) arrangement of the two ferrocene/pyrazole hybrid molecules. Supramolecular dimerization was also detected in solution at low temperatures, though diffusion-ordered spectroscopy and variable-temperature NMR spectroscopy revealed several dynamic processes. Redox potentials of the ferrocene derivatives are affected by the nature of the pyrazole substituent (Me, CF3). In their deprotonated form [LR]2-, both ferrocene/pyrazole hybrids serve as ligands and form oligonuclear CuI, AgI, and AuI complexes that were identified by matrix-assisted laser desorption ionization mass spectrometry. X-ray crystallography revealed the structures of Cu6L3H and Ag6L3F, which both contain two parallel and eclipsed [M(μ-pz)]3 metallamacrocycles (M = Cu, Ag) linked by three ferrocene units. MI···MI distances between the two triangular M3N6 decks are shorter in Ag6L3F (3.28-3.30 vs 3.44-3.51 Å in the case of Cu6L3H), indicating substantial intramolecular closed-shell Ag(d10)-Ag(d10) interactions. However, Cu6L3H features close intermolecular Cu···Cu contacts as short as 3.37 Å. Mössbauer data for both the ligands and complexes were collected, and electrochemical properties were measured; preliminary luminescence data are reported.

Synthesis, Structure and Electrochemistry of Tetranuclear Oxygen-Centered Copper(II) Clusters with Acetylacetone and Benz-pyrazole Hydrolyzed Derivatives as Ligand.

PubMed

Vafazadeh, Rasoul; Willis, Anthony C

2016-01-01

Two copper(II) clusters Cu(4)OCl(6)(pyrazole)4, 1, and Cu(4)OBr(6)(Br-pyrazole)4, 2, have been synthesized by reacting acetylacetone and benzohydrazide (1:1 ratio) with CuX(2) (X = Cl for 1 and X= Br for 2) in methanol solutions. The structures of both clusters have been established by X-ray crystallography. The clusters contain four Cu, one O, six μ(2)-X atoms, and four pyrazole ligands. The pyrazoles was prepared in situ by the reaction of acetylacetone with benzohydrazide in methanol under reflux. In 2, the methine hydrogens of the pyrazole ligands have been replaced by bromine atoms. The four copper atoms encapsulate the central O atom in a tetrahedral arrangement. All copper atoms are five-coordinate and have similar coordination environments with slightly distorted trigonal bipyramidal geometry. The cyclic voltammogram of the clusters 1 and 2 show a one-electron quasi-reversible reduction wave in the region 0.485 to 0.731 V, and a one-electron quasi-reversible oxidation wave in the region 0.767 to 0.898 V. In 1, one irreversible oxidative response is observed on the positive of side of the voltammogram at 1.512 V and this can be assigned to Cu(II) to Cu(III) oxidation.

Molecular Modeling and Evaluation of Novel Dibenzopyrrole Derivatives as Telomerase Inhibitors and Potential Drug for Cancer Therapy.

PubMed

Kalathiya, Umesh; Padariya, Monikaben; Baginski, Maciej

2014-01-01

During previous years, many studies on synthesis, as well as on anti-tumor, anti-inflammatory and anti-bacterial activities of the pyrazole derivatives have been described. Certain pyrazole derivatives exhibit important pharmacological activities and have proved to be useful template in drug research. Considering importance of pyrazole template, in current work the series of novel inhibitors were designed by replacing central ring of acridine with pyrazole ring. These heterocyclic compounds were proposed as a new potential base for telomerase inhibitors. Obtained dibenzopyrrole structure was used as a novel scaffold structure and extension of inhibitors was done by different functional groups. Docking of newly designed compounds in the telomerase active site (telomerase catalytic subunit TERT) was carried out. All dibenzopyrrole derivatives were evaluated by three docking programs: CDOCKER, Ligandfit docking (Scoring Functions) and AutoDock. Compound C_9g, C_9k and C_9l performed best in comparison to all designed inhibitors during the docking in all methods and in interaction analysis. Introduction of pyrazole and extension of dibenzopyrrole in compounds confirm that such compound may act as potential telomerase inhibitors.

Mono azo dyes derived from 5-nitroanthranilic acid: Synthesis, absorption properties and DFT calculations

NASA Astrophysics Data System (ADS)

Karabacak Atay, Çiğdem; Gökalp, Merve; Kart, Sevgi Özdemir; Tilki, Tahir

2017-08-01

Four new azo dyes: 2-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]-5-nitrobenzoic acid (A), 2-[(3-hydroxy-5-methyl-1H-pyrazol-4-yl)diazenyl]-5-nitrobenzoic acid (B), 2-[(3,5-dimethyl-1H-pyrazol-4-yl)diazenyl]-5-nitrobenzoic acid (C) and 2-[(5-amino-3-methyl-1H-pyrazol-4-yl)diazenyl]-5-nitrobenzoic acid (D) which have the same 4-nitrobenzene/azo/pyrazole skeleton and different substituted groups are synthesized in this work. The structures and spectroscopic properties of these new azo dyes are characterized by using spectroscopic methods such as FT-IR, 1H NMR, 13C NMR and UV-vis. Their solvatochromic properties in chloroform, acetic acid, methanol, dimethylformamide (DMF) and dimethylsulphoxide (DMSO) are studied. Moreover, molecular structures and some spectroscopic properties of azo dyes are investigated by utilizing the quantum computational chemistry method based on Density Functional Theory (DFT) employing B3LYP hybrid functional level with 6-31G(d) basis set. It is seen that experimental and theoretical results are compatible with each other.

Design of the EO-1 Pulsed Plasma Thruster Attitude Control Experiment

NASA Technical Reports Server (NTRS)

Zakrzwski, Charles; Sanneman, Paul; Hunt, Teresa; Blackman, Kathie; Bauer, Frank H. (Technical Monitor)

2001-01-01

The Pulsed Plasma Thruster (PPT) Experiment on the Earth Observing 1 (EO-1) spacecraft has been designed to demonstrate the capability of a new generation PPT to perform spacecraft attitude control. The PPT is a small, self-contained pulsed electromagnetic Propulsion system capable of delivering high specific impulse (900-1200 s), very small impulse bits (10-1000 micro N-s) at low average power (less than 1 to 100 W). EO-1 has a single PPT that can produce torque in either the positive or negative pitch direction. For the PPT in-flight experiment, the pitch reaction wheel will be replaced by the PPT during nominal EO-1 nadir pointing. A PPT specific proportional-integral-derivative (PID) control algorithm was developed for the experiment. High fidelity simulations of the spacecraft attitude control capability using the PPT were conducted. The simulations, which showed PPT control performance within acceptable mission limits, will be used as the benchmark for on-orbit performance. The flight validation will demonstrate the ability of the PPT to provide precision pointing resolution. response and stability as an attitude control actuator.

Antimalarial activity of 4-(5-trifluoromethyl-1H-pyrazol-1-yl)-chloroquine analogues.

PubMed

Cunico, Wilson; Cechinel, Cleber A; Bonacorso, Helio G; Martins, Marcos A P; Zanatta, Nilo; de Souza, Marcus V N; Freitas, Isabela O; Soares, Rodrigo P P; Krettli, Antoniana U

2006-02-01

The antimalarial activity of chloroquine-pyrazole analogues, synthesized from the reaction of 1,1,1-trifluoro-4-methoxy-3-alken-2-ones with 4-hydrazino-7-chloroquinoline, has been evaluated in vitro against a chloroquine resistant Plasmodium falciparum clone. Parasite growth in the presence of the test drugs was measured by incorporation of [(3)H]hypoxanthine in comparison to controls with no drugs. All but one of the eight (4,5-dihydropyrazol-1-yl) chloroquine 2 derivatives tested showed a significant activity in vitro, thus, are a promising new class of antimalarials. The three most active ones were also tested in vivo against Plasmodium berghei in mice. However, the (pyrazol-1-yl) chloroquine 3 derivatives were mostly inactive, suggesting that the aromatic functionality of the pyrazole ring was critical.

Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice

PubMed Central

Kroeger, Daniel; Ferrari, Loris L.; Mahoney, Carrie E.; Arrigoni, Elda

2017-01-01

The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states. SIGNIFICANCE STATEMENT More than 40 million Americans suffer from chronic sleep disruption, and the development of effective treatments requires a more detailed understanding of the neuronal mechanisms controlling sleep and arousal. The pedunculopontine tegmental (PPT) nucleus has long been considered a key site for regulating wakefulness and REM sleep. This is mainly because of the cholinergic neurons contained in the PPT nucleus. However, the PPT nucleus also contains glutamatergic and GABAergic neurons that likely contribute to the regulation of cortical activity and sleep–wake states. The chemogenetic experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons each have distinct effects on sleep/wake behavior, improving our understanding of how the PPT nucleus regulates cortical activity and behavioral states. PMID:28039375

Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice.

PubMed

Kroeger, Daniel; Ferrari, Loris L; Petit, Gaetan; Mahoney, Carrie E; Fuller, Patrick M; Arrigoni, Elda; Scammell, Thomas E

2017-02-01

The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states. More than 40 million Americans suffer from chronic sleep disruption, and the development of effective treatments requires a more detailed understanding of the neuronal mechanisms controlling sleep and arousal. The pedunculopontine tegmental (PPT) nucleus has long been considered a key site for regulating wakefulness and REM sleep. This is mainly because of the cholinergic neurons contained in the PPT nucleus. However, the PPT nucleus also contains glutamatergic and GABAergic neurons that likely contribute to the regulation of cortical activity and sleep-wake states. The chemogenetic experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons each have distinct effects on sleep/wake behavior, improving our understanding of how the PPT nucleus regulates cortical activity and behavioral states. Copyright © 2017 the authors 0270-6474/17/371352-15$15.00/0.

Simple assembly of polysubstituted pyrazoles and isoxazoles via ring closure-ring opening domino reaction of 3-acyl-4,5-dihydrofurans with hydrazines and hydroxylamine.

PubMed

Chagarovskiy, Alexey O; Budynina, Ekaterina M; Ivanova, Olga A; Rybakov, Victor B; Trushkov, Igor V; Melnikov, Mikhail Ya

2016-03-14

A convenient general approach to 2-(pyrazol-4-yl)- and 2-(isoxazol-4-yl)ethanols based on the Brønsted acid-initiated reaction of 3-acyl-4,5-dihydrofurans with hydrazines or hydroxylamine was developed. Further transformation of the alcohol moiety in 2-(pyrazolyl)ethanols affording 2-(pyrazolyl)ethylamine as potent bioactive compounds as well as pyrazole-substituted derivatives of antitumor alkaloid crispine A was elaborated.

Visible-Light-Mediated Nickel(II)-Catalyzed C-N Cross-Coupling in Water: Green and Regioselective Access for the Synthesis of Pyrazole-Containing Compounds.

PubMed

You, Guirong; Wang, Kai; Wang, Xiaodan; Wang, Guodong; Sun, Jian; Duan, Guiyun; Xia, Chengcai

2018-06-26

A regioselective green approach for the nickel(II)-catalyzed C-N cross-coupling between arylamines and pyrazoles through a photoredox process is reported. Moderate to good yield was observed for this reaction, performed in water under air at room temperature. This strategy provides a powerful tool for the green synthesis of pyrazole-containing bioactive molecules. In addition, a single-electron-transfer mechanism is proposed in this report.

Regio- and enantioselective synthesis of N-substituted pyrazoles by rhodium-catalyzed asymmetric addition to allenes.

PubMed

Haydl, Alexander M; Xu, Kun; Breit, Bernhard

2015-06-08

The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labelling experiments gave insights into the reaction mechanism. This new methodology was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)-ruxolitinib. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical communication in tilapia: a comparison of Oreochromis mossambicus with O. niloticus.

PubMed

Hubbard, Peter C; Mota, Vasco C; Keller-Costa, Tina; da Silva, José Paulo; Canário, Adelino V M

2014-10-01

In allopatric speciation species differentiation generally results from different selective pressures in different environments, and identifying the traits responsible helps to understand the isolation mechanism(s) involved. Male Mozambique tilapia (Oreochromis mossambicus) use urine to signal dominance; furthermore, 5β-pregnane-3α,17,20β-triol-3α-glucuronide (and its α-epimer, 5β-pregnane-3α,17,20α-triol-3α-glucuronide), in their urine is a potent pheromone, the concentration of which is correlated with social status. The Nile tilapia (Oreochromisniloticus) is a close relative; species divergence probably resulted from geographical separation around 6 million years ago. This raises the question of whether the two species use similar urinary chemical cues during reproduction. The olfactory potency of urine, and crude extracts, from either species was assessed by the electro-olfactogram and the presence of the steroid glucuronides in urine from the Nile tilapia by liquid-chromatography/mass-spectrometry. Both species showed similar olfactory sensitivity to urine and respective extracts from either species, and similar sensitivity to the steroid glucuronides. 5β-Pregnan-3α,17α,20β-triol-3α-glucuronide was present at high concentrations (approaching 0.5mM) in urine from Nile tilapia, with 5β-pregnan-3α,17α,20α-triol-3α-glucuronide present at lower concentrations, similar to the Mozambique tilapia. Both species also had similar olfactory sensitivity to estradiol-3-glucuronide, a putative urinary cue from females. Together, these results support the idea that reproductive chemical cues have not been subjected to differing selective pressure. Whether these chemical cues have the same physiological and behavioural roles in O. niloticus as O. mossambicus remains to be investigated. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification and quantification of metabolites common to 17alpha-methyltestosterone and mestanolone in horse urine.

PubMed

Yamada, Masayuki; Aramaki, Sugako; Okayasu, Toshimasa; Hosoe, Tomoo; Kurosawa, Masahiko; Kijima-Suda, Isao; Saito, Koichi; Nakazawa, Hiroyuki

2007-09-21

Anabolic steroids with the 17alpha-methyl,17beta-hydroxyl group, which were developed as oral formulations for therapeutic purposes, have been abused in the field of human sports. These anabolic steroids are also used to enhance racing performance in racehorses. In humans, structurally related 17alpha-methyltestosterone (MTS) and mestanolone (MSL), which are anabolic steroids with the 17alpha-methyl,17beta-hydroxyl group, have metabolites in common. The purpose of this study was to determine metabolites common to these two steroids in horses, which may serve as readily available screening targets for the doping test of these steroids in racehorses. Urine sample collected after administering MTS and MSL to horses was treated to obtain unconjugated steroid, glucuronide, and sulfate fractions. The fractions were subjected to gas chromatography/mass spectrometry (GC/MS), and 17alpha-methyl-5alpha-androstan-3beta,17beta-diol, 17alpha-hydroxymethyl-5alpha-androstan-3beta,17beta-diol, 17alpha-methyl-5alpha-androstan-3beta,16beta,17beta-triol, and 17alpha-methyl-5alpha-androstan-3beta,16alpha,17beta-triol were detected as the common metabolites by comparison with synthesized reference standards. The urinary concentrations of these metabolites after dosing were determined by GC/MS. 17Alpha-methyl-5alpha-androstan-3beta,16beta,17beta-triol was mainly detected in the sulfate fractions of urine samples after administration. This compound was consistently detected for the longest time in the urine samples after dosing with both steroids. The results suggest that 17alpha-methyl-5alpha-androstan-3beta,16beta,17beta-triol is a very useful screening target for the doping test of MTS and MSL in racehorses.

Psychometric Properties of a Standardized Observation Protocol to Quantify Pediatric Physical Therapy Actions.

PubMed

Sonderer, Patrizia; Akhbari Ziegler, Schirin; Gressbach Oertle, Barbara; Meichtry, André; Hadders-Algra, Mijna

2017-07-01

Pediatric physical therapy (PPT) is characterized by heterogeneity. This blurs the evaluation of effective components of PPT. The Groningen Observation Protocol (GOP) was developed to quantify contents of PPT. This study assesses the reliability and completeness of the GOP. Sixty infant PPT sessions were video-taped. Two random samples of 10 videos were used to determine interrater and intrarater reliability using interclass correlation coefficients (ICCs) with 95% confidence intervals. Completeness of GOP 2.0 was based on 60 videos. Interrater reliability of quantifying PPT actions was excellent (ICC, 0.75-1.0) in 71% and sufficient to good (ICC, 0.4-0.74) in 24% of PPT actions. Intrarater reliability was excellent in 94% and sufficient to good in 6% of PPT actions. Completeness was good for greater than 90% of PPT actions. GOP 2.0 has good reliability and completeness. After appropriate training, it is a useful tool to quantify PPT for children with developmental disorders.

Addressing EO-1 Spacecraft Pulsed Plasma Thruster EMI Concerns

NASA Technical Reports Server (NTRS)

Zakrzwski, C. M.; Davis, Mitch; Sarmiento, Charles; Bauer, Frank H. (Technical Monitor)

2001-01-01

The Pulsed Plasma Thruster (PPT) Experiment on the Earth Observing One (EO-1) spacecraft has been designed to demonstrate the capability of a new generation PPT to perform spacecraft attitude control. Results from PPT unit level radiated electromagnetic interference (EMI) tests led to concerns about potential interference problems with other spacecraft subsystems. Initial plans to address these concerns included firing the PPT at the spacecraft level both in atmosphere, with special ground support equipment. and in vacuum. During the spacecraft level tests, additional concerns where raised about potential harm to the Advanced Land Imager (ALI). The inadequacy of standard radiated emission test protocol to address pulsed electromagnetic discharges and the lack of resources required to perform compatibility tests between the PPT and an ALI test unit led to changes in the spacecraft level validation plan. An EMI shield box for the PPT was constructed and validated for spacecraft level ambient testing. Spacecraft level vacuum tests of the PPT were deleted. Implementation of the shield box allowed for successful spacecraft level testing of the PPT while eliminating any risk to the ALI. The ALI demonstration will precede the PPT demonstration to eliminate any possible risk of damage of ALI from PPT operation.

Novel pyrazole derivatives with oxa/thiadiazolyl, pyrazolyl moieties and pyrazolo[4,3-d]-pyrimidine derivatives as potential antimicrobial and anticancer agents.

PubMed

Hafez, Hend N; El-Gazzar, Abdel-Rhman B A; Al-Hussain, Sami A

2016-05-15

A series of [4-amino-3-(4-chlorophenyl)-1H-pyrazol-5-yl](3,5-dimethyl-1H-pyrazol-1-yl)-methanone and 6-amino-3-(4-chlorophenyl)-5-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one have been synthesized from ethyl 4-amino-3-(4-chlorophenyl)-pyrazol-5-carboxylate. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)CNMR, Mass spectra and Elemental analysis. The compounds were evaluated for their in vitro antimicrobial and anticancer activity. Among the synthesized compounds, compounds 7a,b and 15 exhibited higher anticancer activity than the doxorubicin as reference drug. Most of the newly synthesized compounds have good to excellent antimicrobial activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis of Functionalized Pyrazoles via 1,3-Dipolar Cycloaddition of α-Diazo-β-ketophosphonates, Sufones and Esters with Electron-Deficient Alkenes.

PubMed

Baiju, T V; Namboothiri, Irishi N N

2017-10-01

1,3-Dipolar cycloaddition of diazo compounds with olefinic substrates is a promising atom-economic strategy for the construction of functionalized pyrazoles. Over the last few years, our group has been engaged in the synthesis of phosphonyl/sulfonylpyrazoles and pyrazole esters by employing Bestmann-Ohira Reagent (BOR) and its sulfur and ester analogs as 1,3-dipole precursors with various dipolarophiles. This account describes the novel synthetic methods developed in our laboratory, in the perspective of closely related work by others, for the synthesis of phosphonyl/sulfonylpyrazoles, pyrazole esters and the total synthesis of Withasomnine, a natural product, by using 1,3-dipolar cycloaddition as the key step. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolism of methyltestosterone in the greyhound.

PubMed

Biddle, S T B; O'Donnell, A; Houghton, E; Creaser, C

2009-03-01

Gas chromatography/mass spectrometry and selective derivatisation techniques have been used to identify urinary metabolites of methyltestosterone following oral administration to the greyhound. Several metabolites were identified including reduced, mono-, di- and trihydroxylated steroids. The major metabolites observed were 17alpha-methyl-5beta-androstane-3alpha-17beta-diol, 17alpha-methyl-5beta-androstane-3alpha,16alpha,17beta-triol, and a further compound tentatively identified as 17alpha-methyl-5z-androstane-6z,17beta-triol. The most abundant of these was the 17alpha-methyl-5beta-androstane-3alpha,16alpha,17beta-triol. This metabolite was identified by comparison with a reference standard synthesised using a Grignard procedure and characterised using trimethylsilyl (TMS) and acetonide-TMS derivatisation techniques. There did not appear to be any evidence for 16beta-hydroxylation as a phase I metabolic transformation in the greyhound. However, significant quantities of 16alpha-hydroxy metabolites were detected. Selective enzymatic hydrolysis procedures indicated that the major metabolites identified were excreted as glucuronic acid conjugates. Metabolic transformations observed in the greyhound have been compared with those of other mammalian species and are discussed here. John Wiley & Sons, Ltd

Preparation of 3,5-disubstituted pyrazoles and isoxazoles from terminal alkynes, aldehydes, hydrazines, and hydroxylamine.

PubMed

Harigae, Ryo; Moriyama, Katsuhiko; Togo, Hideo

2014-03-07

The reaction of terminal alkynes with n-BuLi, and then with aldehydes, followed by the treatment with molecular iodine, and subsequently hydrazines or hydroxylamine provided the corresponding 3,5-disubstituted pyrazoles or isoxazoles in good yields with high regioselectivity, through the formations of propargyl secondary alkoxides and α-alkynyl ketones. The present reactions are one-pot preparation of 3,5-disubstituted pyrazoles from terminal alkynes, aldehydes, molecular iodine, and hydrazines, and 3,5-disubstituted isoxazoles from terminal alkynes, aldehydes, molecular iodine, and hydroxylamine.

Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and biological investigations of pyrazole-appended quinolinyl chalcones

NASA Astrophysics Data System (ADS)

Prasath, R.; Bhavana, P.; Sarveswari, S.; Ng, Seik Weng; Tiekink, Edward R. T.

2015-02-01

Two series of new quinolinyl chalcones containing a pyrazole group, 3a-f and 4a-r, have been synthesized by Claisen-Schmidt condensation of the derivatives of 2-methyl-3-acetylquinoline with either substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde or 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde in 76-93% yield under ultrasonic method. The compounds were characterized using IR, 1H NMR and ESI-MS spectroscopic methods and, for representative compounds, by X-ray crystallography. An E-configuration about the Cdbnd C ethylene bond has been established via 1H NMR spectroscopy and X-ray crystallography. These compounds show promising anti-microbial properties, with 4a and 3e being the most potent against bacterial and fungal strains, respectively and the methoxy substituted compounds showed moderate anti-oxidant activity.

Peptide-nucleic acids (PNAs) with pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone (PPT) as a universal base: their synthesis and binding affinity for oligodeoxyribonucleotides.

PubMed

Hirano, Taisuke; Kuroda, Kenji; Kataoka, Masanori; Hayakawa, Yoshihiro

2009-07-21

Peptide-nucleic acids (PNAs) including pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone (PPT) as a nucleobase were synthesized, and their binding affinity for the complementary oligodeoxyribonucleotides was investigated. We found that PNAs with one or two PPT(s) and natural nucleobases (i.e., adenine, cytosine, guanine, or thymine) have excellent binding affinity for oligodeoxyribonucleotides with complementary bases at the positions facing the natural nucleobases, and with adenine, cytosine, guanine, and thymine at the positions opposite PPT in PNAs. The binding affinity of the PPT-containing PNA is higher than or comparable to that of a PNA consisting of all complementary natural nucleobases, viz. a PNA with a suitable natural nucleobase in place of PPT in the PPT-containing PNA. Consequently, it was concluded that PPT serves as a useful universal base that can recognize all natural nucleobases.

A simple hydrogen-bonded chain in (3Z)-3-{1-[(5-phenyl-1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one, and a hydrogen-bonded ribbon of centrosymmetric rings in the self-assembled adduct (3Z)-3-{1-[(5-methyl-1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one-6-(2-hydroxyethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7(4H)-one (1/1).

PubMed

Quiroga, Jairo; Portilla, Jaime; Cobo, Justo; Glidewell, Christopher

2010-01-01

(3Z)-3-{1-[(5-Phenyl-1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one, C(15)H(15)N(3)O(2), (I), and the stoichiometric adduct (3Z)-3-{1-[(5-methyl-1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one-6-(2-hydroxyethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7(4H)-one (1/1), C(10)H(13)N(3)O(2).C(10)H(13)N(3)O(2), (II), in which the two components have the same composition but different constitutions, are formed in the reactions of 2-acetyl-4-butyrolactone with 5-amino-3-phenyl-1H-pyrazole and 5-amino-3-methyl-1H-pyrazole, respectively. In each compound, the furanone component contains an intramolecular N-H...O hydrogen bond. The molecules of (I) are linked into a chain by a single intermolecular N-H...O hydrogen bond, while in (II), a combination of one O-H...N hydrogen bond, within the selected asymmetric unit, and two N-H...O hydrogen bonds link the molecular components into a ribbon containing alternating centrosymmetric R(4)(4)(20) and R(6)(6)(22) rings.

Synthesis and antifungal activity of novel pyrazolecarboxamide derivatives containing a hydrazone moiety

PubMed Central

2012-01-01

Background The plant pathogenic fungus (such as Gibberella zeae, Fusarium oxysporum and Cytospora mandshurica) causes devastating disease in agriculture. The pathogenic fungus is responsible for billions of dollars in economic losses worldwide each year. In order to discover new fungicidal molecule with good fungicidal activity against G. zeae, F. oxysporum, and C. mandshurica, we sought to combine the active sub-structure of hydrazone and pyrazole amide derivatives together to design and synthesize novel pyrazole amide derivatives containing a hydrazone moiety. Results A series of novel pyrazole amide derivatives bearing hydrazone moiety were synthesized. Their structures were characterized by 1 H-NMR, 13 C-NMR, IR, and elemental analysis. The preliminary biological assays revealed that most of the synthesized compounds exhibit favorable antifungal activities against G. zeae. The activity of compounds 7a, 7f, 7g, 7h, 7i, 7j, 7l and 7q were 40.82%, 47.78%, 50.32%, 40.82%, 49.05%, 48.73%, 40.19% and 45.89%, respectively, and the synthesized compounds showed certain antifungal activities against F. oxysporum and C.mandshurica. Conclusion A practical synthetic route to pyrazole amide derivatives containing a hydrazone moiety were synthesized by the condensation of intermediates 5-chloro-N-(4-subsititued-2-(hydrazinecarbonyl)-6-methylphenyl)-1,3-dimethyl-1 H-pyrazole-4-carboxamide with different aldehydes or ketones in ethanol at room temperature is presented, the results of the study suggested that the pyrazole amide derivatives containing hydrazone moieties could inhibit the growth of G. zeae, F. oxysporium and C. mandshurica to a certain extent. PMID:22647315

Synthesis, spectral, crystallography and thermal investigations of novel Schiff base complexes of manganese (III) derived from heterocyclic β-diketone with aromatic and aliphatic diamine

NASA Astrophysics Data System (ADS)

Surati, Kiran R.; Thaker, B. T.

2010-01-01

The Schiff base tetradentate ligands N,N-bis-(3,5-dimethyl-1-p-tolyl-1H-pyrazol-4-ylmethylene)-ethane-1,2-diamine (H 2L 1), N,N-bis-(3,5-dimethyl-1-p-sulfonyl-1H-pyrazol-4-ylmethylene)-ethane-1,2-diamine (H 2L 2), N,N-bis-(3,5-dimethyl-1-p-tolyl-1H-pyrazol-4-ylmethylene)-benzene-1,2-diamine (H 2L 3) and N,N-bis-(3,5-dimethyl-1-p-sulfonyl-1H-pyrazol-4-ylmethylene)-benzene-1,2-diamine (H 2L 4) were prepared from the reaction between 5-oxo-3-methyl-1-p-tolyl-1H-pyrazole-4-carbaldehyde or 4-(4-formyl-5-oxo-3-methyl-pyrazol-1-yl)-benzenesulfonic acid and o-phenylenediamine or ethylenediamine. And these are characterized by elemental analysis, FT-IR, 1H NMR and GC-MS. The corresponding Schiff base complexes of Mn(III) were prepared by condensation of [Mn 3(μ 3-O)(OAc) 6(H 2O) 3]·3H 2O with ligands H 2L 1, H 2L 2, H 2L 3 and H 2L 4. All these complexes have been characterized by elemental analysis, magnetic susceptibility, X-ray crystallography, conductometry measurement, FT-IR, electronic spectra and mass (FAB) spectrometry. Thermal behaviour of the complexes has been studied by TGA, DTA and DSC. Electronic spectra and magnetic susceptibility measurements indicate octahedral stereochemistry of manganese (III) complexes, while non-electrolytic behaviour complexes indicate the absence of counter ion.

Resistance to Phosphinothricin (Glufosinate) and Its Utilization as a Nitrogen Source by Chlamydomonas reinhardtii

PubMed Central

Franco, A. R.; Lopez-Siles, F. J.; Cardenas, J.

1996-01-01

Wild-type strain 21gr of the green alga Chlamydomonas reinhardtii was resistant to the ammonium salt of l-phosphinothricin (PPT, also called glufosinate), an irreversible inhibitor of glutamine synthetase activity and the main active component of the herbicide BASTA (AgrEvo, Frankfurt am Main, Germany). Under the same conditions, however, this strain was highly sensitive to l-methionine-S-sulfoximine, a structural analog of PPT which has been reported to be 5 to 10 times less effective than PPT as an inhibitor in plants. Moreover, this alga was able to grow with PPT as the sole nitrogen source when this compound was provided at low concentrations. This utilization of PPT was dependent upon the addition of acetate and light and did not take place in the presence of ammonium. Resistance was due neither to the presence of N-acetyltransferase or transaminase activity nor to the presence of glutamine synthetase isoforms resistant to PPT. By using l-[methyl-(sup14)C]PPT, we demonstrated that resistance is due to lack of PPT transport into the cells. This strongly suggests that PPT and l-methionine-S-sulfoximine enter the cells through different systems. Growth with PPT is supported by its deamination by an l-amino acid oxidase activity which has been previously described to be located at the periplasm. PMID:16535427

Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer's disease?

PubMed

Narlawar, Rajeshwar; Pickhardt, Marcus; Leuchtenberger, Stefanie; Baumann, Karlheinz; Krause, Sabine; Dyrks, Thomas; Weggen, Sascha; Mandelkow, Eckhard; Schmidt, Boris

2008-01-01

Curcumin binds to the amyloid beta peptide (Abeta) and inhibits or modulates amyloid precursor protein (APP) metabolism. Therefore, curcumin-derived isoxazoles and pyrazoles were synthesized to minimize the metal chelation properties of curcumin. The decreased rotational freedom and absence of stereoisomers was predicted to enhance affinity toward Abeta(42) aggregates. Accordingly, replacement of the 1,3-dicarbonyl moiety with isosteric heterocycles turned curcumin analogue isoxazoles and pyrazoles into potent ligands of fibrillar Abeta(42) aggregates. Additionally, several compounds are potent inhibitors of tau protein aggregation and depolymerized tau protein aggregates at low micromolar concentrations.

Microwave-assisted synthesis of N-pyrazole ureas and the p38alpha inhibitor BIRB 796 for study into accelerated cell ageing.

PubMed

Bagley, Mark C; Davis, Terence; Dix, Matthew C; Widdowson, Caroline S; Kipling, David

2006-11-21

Microwave irradiation of substituted hydrazines and beta-ketoesters gives 5-aminopyrazoles in excellent yield, which can be transformed to the corresponding N-carbonyl derivatives by treatment with an isocyanate or chloroformate. Derivatization of 4-nitronaphth-1-ol using predominantly microwave heating methods and reaction with an N-pyrazole carbamate provides a rapid route to the N-pyrazole urea BIRB 796 in high purity, as a potent and selective inhibitor of p38alpha mitogen-activated protein kinase for the study of accelerated ageing in Werner syndrome cells.

Mononuclear thiocyanate containing nickel(II) and binuclear azido bridged nickel(II) complexes of N4-coordinate pyrazole based ligand: Syntheses, structures and magnetic properties

NASA Astrophysics Data System (ADS)

Solanki, Ankita; Monfort, Montserrat; Kumar, Sujit Baran

2013-10-01

Two mononuclear nickel(II) complexes [NiL1(NCS)2] (1) and [NiL2(NCS)2] (2) and two azido bridged binuclear nickel(II) complexes [Ni(()2()2] (3) and [Ni(()2()2] (4), where L1, L2, L1‧ and L2‧ are N,N-diethyl-N‧,N‧-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)ethane-1,2-diamine (L1), N,N-bis((1H-pyrazol-1-yl)methyl)-N‧,N‧-diethylethane-1,2-diamine (L2), N,N-diethyl-N‧-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)ethane-1,2-diamine (L1‧) and N-((1H-pyrazol-1-yl)methyl)-N‧,N‧-diethylethane-1,2-diamine (L2‧) have been synthesized and characterized by microanalyses and physico-chemical methods. Single crystal X-ray diffraction analyses revealed that complexes 1 and 2 are mononuclear NCS- containing Ni(II) complex with octahedral geometry and complexes 3 and 4 are end-on (μ-1,1) azido bridged binuclear Ni(II) complexes with distorted octahedral geometry. Variable temperature magnetic studies of the complexes 3 and 4 display ferromagnetic interaction with J values 19 and 32 cm-1, respectively.

Earthquake-Induced Liquefaction of Confined Soil Zones: A Centrifuge Study

DTIC Science & Technology

1993-12-09

8217. 4.2 Pore pressure transducers (PPT) Pore pressures in the saturated soil were monitored by Druck PDCR 81 pore pressure transducers. This type of pore...PPT5406 -20 MTn-23.3 2 3 4 5 6 7 a 2 10 II 12 Mo, 34 .8 PPT6270 20~ Mlm=-I .2 1 2 3 4 5 6 8 a 1 0 II 12 4 M....7 0 PPT6263 A 3d Moa20.S PPT6260 7 -0 1 2 3

Could high salinity be used to control bullfrogs in small ponds?

USGS Publications Warehouse

Ward, David L.; Finch, Colton; Blasius, Heidi

2015-01-01

We examined survival of bullfrog (Rana catesbeiana) eggs and tadpoles at 3 ppt and 6 ppt salinity in the laboratory to determine if low-level salinity could be used to eradicate bullfrogs from small ponds that contain native fishes. Bullfrog eggs and tadpoles <10 days old experienced 100% mortality when held at 6 ppt salinity for 10 days. Bullfrog tadpoles 10–15 days old experienced significantly reduced survival when exposed to salinity of 6 ppt for 10 days. Older bullfrog tadpoles (>9 months old) appeared unaffected by 14 days of 6 ppt salinity. Salinity of 3 ppt did not impact survival of bullfrog tadpole eggs or tadpoles at any of the life stages we tested. Adding salt to ponds in the early spring to increase salinity to 6 ppt may be a cost effective way to eradicate bullfrogs from small ponds without harming native fishes.

Selection of Optimal Polypurine Tract Region Sequences during Moloney Murine Leukemia Virus Replication

PubMed Central

Robson, Nicole D.; Telesnitsky, Alice

2000-01-01

Retrovirus plus-strand synthesis is primed by a cleavage remnant of the polypurine tract (PPT) region of viral RNA. In this study, we tested replication properties for Moloney murine leukemia viruses with targeted mutations in the PPT and in conserved sequences upstream, as well as for pools of mutants with randomized sequences in these regions. The importance of maintaining some purine residues within the PPT was indicated both by examining the evolution of random PPT pools and from the replication properties of targeted mutants. Although many different PPT sequences could support efficient replication and one mutant that contained two differences in the core PPT was found to replicate as well as the wild type, some sequences in the core PPT clearly conferred advantages over others. Contributions of sequences upstream of the core PPT were examined with deletion mutants. A conserved T-stretch within the upstream sequence was examined in detail and found to be unimportant to helper functions. Evolution of virus pools containing randomized T-stretch sequences demonstrated marked preference for the wild-type sequence in six of its eight positions. These findings demonstrate that maintenance of the T-rich element is more important to viral replication than is maintenance of the core PPT. PMID:11044073

Salinity acclimation enhances salinity tolerance in tadpoles living in brackish water through increased Na⁺ , K⁺ -ATPase expression.

PubMed

Wu, Chi-Shiun; Yang, Wen-Kai; Lee, Tsung-Han; Gomez-Mestre, Ivan; Kam, Yeong-Choy

2014-01-01

Amphibians are highly susceptible to osmotic stress but, nonetheless, some species can adapt locally to withstand moderately high levels of salinity. Maintaining the homeostasis of body fluids by efficient osmoregulation is thus critical for larval survival in saline environments. We studied the role of acclimation in increased physiological tolerance to elevated water salinity in the Indian rice frog (Fejervarya limnocharis) tadpoles exposed to brackish water. We quantified the effects of salinity acclimation on tadpole survival, osmolality, water content, and gill Na⁺ , K⁺ -ATPase (NKA) expression. Tadpoles did not survive over 12 hr if directly transferred to 11 ppt (parts per thousand) whereas tadpoles previously acclimated for 48 hr in 7  ppt survived at least 48 hr. We reared tadpoles in 3 ppt and then we transferred them to one of (a) 3 ppt, (b) 11  ppt, and (c) 7  ppt for 48 hr and then 11 ppt. In the first 6 hr after transfer to 11 ppt, tadpole osmolality sharply increased and tadpole water content decreased. Tadpoles pre-acclimated for 48 hr in 7 ppt were able to maintain lower and more stable osmolality within the first 3 hr after transfer. These tadpoles initially lost water content, but over the next 6 hr gradually regained water and stabilized. In addition, they had a higher relative abundance of NKA proteins than tadpoles in other treatments. Pre-acclimation to 7 ppt for 48 hr was hence sufficient to activate NKA expression, resulting in increased survivorship and reduced dehydration upon later transfer to 11 ppt. J © 2013 Wiley Periodicals, Inc.

A role for tachykinins in female mouse and rat reproductive function.

PubMed

Pintado, C Oscar; Pinto, Francisco M; Pennefather, Jocelyn N; Hidalgo, Agustin; Baamonde, Ana; Sanchez, Teresa; Candenas, M Luz

2003-09-01

Tachykinins may be involved in reproduction. A reverse transcription-polymerase chain reaction assay was used to analyze the expression of tachykinins and tachykinin receptors in different types of reproductive cells from mice. The preprotachykinin (PPT) genes, PPT-A, PPT-B and PPT-C, that encode substance P/neurokinin A, neurokinin B, and hemokinin-1, respectively, and the genes that encode the tachykinin NK1, NK2, and NK3 receptors were all expressed, at different levels, in the uterus of superovulated, unfertilized mice. The mRNA of neprilysin (NEP), the main enzyme involved in tachykinin metabolism, was also expressed in the uterus. Isolated cumulus granulosa cells expressed PPT-A, PPT-B, PPT-C, and NEP and low levels of the tachykinin NK1 and NK2 receptors. Mouse oocytes expressed PPT-A and -B mRNA transcripts. A low expression of the three tachykinin receptors was observed but PPT-C and NEP were undetectable. Two- and 8- to 16-cell mouse embryos expressed only a low-abundance transcript corresponding to the NK1 receptor. However, the mRNAs of PPT-B, PPT-C and NEP appeared in blastocyst-stage embryos. A low-abundance transcript corresponding to the NK2 receptor was the only target gene detected in mice sperm. Female mice or rats treated neonatally with capsaicin showed a reduced fertility. A reduction in litter size was observed in female rats treated in vivo with the tachykinin NK3 receptor antagonist SR 142801. These data show that tachykinins of both neuronal and nonneuronal origin are differentially expressed in various types of reproductive cells and may play a role in female reproductive function.

Pain Threshold Tests in Patients With Heel Pain Syndrome.

PubMed

Saban, Bernice; Masharawi, Youssef

2016-07-01

Pressure pain threshold (PPT) is a useful tool for evaluating mechanical sensitivity in patients suffering from various musculoskeletal disorders. However, no previous study has investigated PPT in the heel of patients experiencing plantar heel pain syndrome (PHPS). The aim of this study was to compare PPT levels and topographic presentation of sensitivity in the heel of patients with PHPS and in healthy controls. The reliability of PPT testing in patients with PHPS was assessed for intra- and interrater recordings. The PPT levels of 40 feet in each group were then assessed on 5 predetermined sites in the heel using a standardized measurement protocol. Patient functional status (FS) as measured by the Foot & Ankle Computerized Adaptive Test was employed as an external reference. Multivariate analysis of covariance revealed no group differences for PPTs at all sites (P = .406). Age (P = .099) or BMI (P = .510) did not affect PPT values, although there was an effect on gender (P = .006). The analysis revealed significant differences between sites (P < .001) demonstrating a diverse topographic distribution. In the PHPS group, PPT levels at the anterior/medial, posterior/medial and central sites were significantly lower than at the posterior/lateral and anterior/lateral sites (P < .05). For the control group, PPT levels at the anterior/medial site were significantly lower than all other sites (P < .001). No significant differences were found between PPT of the PHPS patients and controls, therefore, PPT cannot be recommended as an assessment tool for these patients. The topographic distribution indicated low PPT levels at the anterior/medial area of the heel in patients with PHPS and controls. Level II, comparative study. © The Author(s) 2016.

Diet-derived phenols in plasma and tissues and their implications for health.

PubMed

Clifford, M N

2004-12-01

This paper seeks to catalyse a reappraisal of the nature, fate and biological significance in humans of phenols, polyphenols and tannins (PPT) consumed in normal diets, and in particular questions the primacy of PPT radical-scavenging mechanisms for the supposed health benefits of diets rich in fruits and vegetables. PPT are classified by structure and function. Arguments are presented to show that cinnamates and derived polyphenols make significantly larger contributions to the total PPT intake than the flavonols and flavones upon which the vast majority of attention has been focussed previously. Daily intakes of total PPT may range from less than 100 mg to in excess of 2 g, and the critical importance of coffee and black tea as the major dietary sources is shown. Only some 5% of the dietary PPT is absorbed in the duodenum, and of this only some 5%, mainly flavanols, reaches the plasma unchanged, the balance being mammalian conjugates. Over 95% of the intake passes to the colon and is fermented by the gut microflora. A fraction of the resulting microbial metabolites is absorbed and appears in the plasma primarily as mammalian conjugates. Even following high intakes of PPT, the plasma metabolites collectively make a very small (less than 5%) and transient contribution to the total concentration of redox active substances in plasma. This explains the failure of most studies that sought to detect an increase in plasma antioxidant power after consuming a PPT-rich meal or supplement. The powerfully antioxidant PPT aglycones, much used in in vitro studies, do not reach the plasma. The redox potential of those unchanged PPT and PPT metabolites that reach the plasma enables them to scavenge damaging radicals, but the endogenous plasma antioxidants, especially ascorbate, are required for disposal of the resultant phenoxyl radicals. Black tea and coffee, the major sources of PPT, are poor sources of ascorbate. It is suggested that if diets rich in fruits and vegetables are health-promoting, and if these effects are due to PPT, then alternatives to radical-scavenging mechanisms must be sought. Evidence is presented to show that some mammalian metabolites of PPT may indeed be able to protect the vascular endothelium and that diets rich in PPT may in humans at normal dietary levels have the ability to protect against Type II diabetes and the metabolic syndrome through effects on glucose absorption and associated hormones. Such effects are recommended for further investigation.

Synthesis, spectral, crystallography and thermal investigations of novel Schiff base complexes of manganese (III) derived from heterocyclic beta-diketone with aromatic and aliphatic diamine.

PubMed

Surati, Kiran R; Thaker, B T

2010-01-01

The Schiff base tetradentate ligands N,N-bis-(3,5-dimethyl-1-p-tolyl-1H-pyrazol-4-ylmethylene)-ethane-1,2-diamine (H(2)L(1)), N,N-bis-(3,5-dimethyl-1-p-sulfonyl-1H-pyrazol-4-ylmethylene)-ethane-1,2-diamine (H(2)L(2)), N,N-bis-(3,5-dimethyl-1-p-tolyl-1H-pyrazol-4-ylmethylene)-benzene-1,2-diamine (H(2)L(3)) and N,N-bis-(3,5-dimethyl-1-p-sulfonyl-1H-pyrazol-4-ylmethylene)-benzene-1,2-diamine (H(2)L(4)) were prepared from the reaction between 5-oxo-3-methyl-1-p-tolyl-1H-pyrazole-4-carbaldehyde or 4-(4-formyl-5-oxo-3-methyl-pyrazol-1-yl)-benzenesulfonic acid and o-phenylenediamine or ethylenediamine. And these are characterized by elemental analysis, FT-IR, (1)H NMR and GC-MS. The corresponding Schiff base complexes of Mn(III) were prepared by condensation of [Mn(3)(mu(3)-O)(OAc)(6)(H(2)O)(3)].3H(2)O with ligands H(2)L(1), H(2)L(2), H(2)L(3) and H(2)L(4). All these complexes have been characterized by elemental analysis, magnetic susceptibility, X-ray crystallography, conductometry measurement, FT-IR, electronic spectra and mass (FAB) spectrometry. Thermal behaviour of the complexes has been studied by TGA, DTA and DSC. Electronic spectra and magnetic susceptibility measurements indicate octahedral stereochemistry of manganese (III) complexes, while non-electrolytic behaviour complexes indicate the absence of counter ion. Copyright 2009. Published by Elsevier B.V.

Analogs of natural lipids. I. Synthesis and properties of tris-homoacyl derivatives of cyclopentane- 1,2,3-triols.

PubMed

Hancock, A J; Greenwald, S M; Sable, H Z

1975-07-01

A new series of analogs of triglycerides has been synthesized, in which the glycerol moiety is replaced by each of the three isomeric cyclopentanetriols. For each of the isomeric cyclopentane-1,2,3-triols (1,2,3/0; DL-1,2/3; and 1,3/2), the tris-homoacyl derivatives of octanoic, decanoic, lauric, myristic, palmitic, stearic, and dihydrosterculic acids were prepared by treatment of the respective triols with the appropriate acyl chloride in pyridine. The dihydrosterculates were prepared by fusing the triols with a mixture of the acyl anhydride and the corresponding potassium salt. It is proposed that because of restricted rotation of the carbon-carbon bonds the cyclopentanoid compounds are analogs of specific rotamers of triglycerides. Infrared spectra (KBr discs) obtained at room temperature show differences in crystal structure from series to series. A band near 720 cm-minus 1 (CH2 rock) is doubled in the 1,2,3/0 and 1,2/3 series and is single in the 1,3/2 series and the triglycerides. In each spectrum with a doublet at 720 cm-minus 1, a band near 1470 cm-minus 1 (CH2 bend) is doubled also. A strong band at 890 cm-minus 1 present in the triglyceride spectra is weak or missing from the spectra of the analogs. A band at 1418 cm-minus 1 (bending of CH2 adjacent to C equal to 0) present in the triglyceride spectra is demonstrable only in the 1,2,3/0 derivatives in comparison with the other three series. In all series the dihydrosterculates show a decrease in apparent polarity, relative to the stearates, significantly greater than expected from the introduction of an additional carbon atom. The potential utility of the analogs as probes of the effects of conformation on the physical properties and enzymatic susceptibility of glycerides is discussed.

C5 glycolipids of heterocystous cyanobacteria track symbiont abundance in the diatom Hemiaulus hauckii across the tropical North Atlantic

NASA Astrophysics Data System (ADS)

Bale, Nicole J.; Villareal, Tracy A.; Hopmans, Ellen C.; Brussaard, Corina P. D.; Besseling, Marc; Dorhout, Denise; Sinninghe Damsté, Jaap S.; Schouten, Stefan

2018-03-01

Diatom-diazotroph associations (DDAs) include marine heterocystous cyanobacteria found as exosymbionts and endosymbionts in multiple diatom species. Heterocysts are the site of N2 fixation and have thickened cell walls containing unique heterocyst glycolipids which maintain a low oxygen environment within the heterocyst. The endosymbiotic cyanobacterium Richelia intracellularis found in species of the diatom genus Hemiaulus and Rhizosolenia makes heterocyst glycolipids (HGs) which are composed of C30 and C32 diols and triols with pentose (C5) moieties that are distinct from limnetic cyanobacterial HGs with predominantly hexose (C6) moieties. Here we applied a method for analysis of intact polar lipids to the study of HGs in suspended particulate matter (SPM) and surface sediment from across the tropical North Atlantic. The study focused on the Amazon plume region, where DDAs are documented to form extensive surface blooms, in order to examine the utility of C5 HGs as markers for DDAs as well as their transportation to underlying sediments. C30 and C32 triols with C5 pentose moieties were detected in both marine SPM and surface sediments. We found a significant correlation between the water column concentration of these long-chain C5 HGs and DDA symbiont counts. In particular, the concentrations of both the C5 HGs (1-(O-ribose)-3,27,29-triacontanetriol (C5 HG30 triol) and 1-(O-ribose)-3,29,31-dotriacontanetriol (C5 HG32 triol)) in SPM exhibited a significant correlation with the number of Hemiaulus hauckii symbionts. This result strengthens the idea that long-chain C5 HGs can be applied as biomarkers for marine endosymbiotic heterocystous cyanobacteria. The presence of the same C5 HGs in surface sediment provides evidence that they are effectively transported to the sediment and hence have potential as biomarkers for studies of the contribution of DDAs to the paleo-marine N cycle.

Quinoline derivatives bearing pyrazole moiety: Synthesis and biological evaluation as possible antibacterial and antifungal agents.

PubMed

El Shehry, Mohamed F; Ghorab, Mostafa M; Abbas, Samir Y; Fayed, Eman A; Shedid, Said A; Ammar, Yousry A

2018-01-01

In an attempt for development of new antimicrobial agents, three series of quinoline derivatives bearing pyrazole moiety have been synthesized. The first series was synthesized through the synthesis of 4-(quinolin-2-yloxy)benzaldehyde and 4-(quinolin-2-yloxy)acetophenone and then treatment with ketone or aldehyde derivatives to afford the corresponding chalcones. Cyclization of the latter chalcones with hydrazine derivatives led to the formation of new pyrazoline derivatives. The second series was synthesized via the synthesis of 2-hydrazinylquinoline and then treatment with formylpyrazoles to afford the corresponding hydrazonyl pyrazole derivatives. The third series was synthesized through the treatment of 2-hydrazinylquinoline with ethoxyethylidene, dithioacetal and arylidene derivatives to afford the corresponding pyrazole derivatives. The synthesized compounds were evaluated for their expected antibacterial and antifungal activities; where, the majority of these compounds showed potent antibacterial and antifungal activities against the tested strains of bacteria and fungi. Pyrazole derivative 13b showed better results when compared with the reference drugs as revealed from their MIC values (0.12-0.98 μg/mL). The pyrazole derivative 13b showed fourfold potency of gentamycin in inhibiting the growth of S. flexneri (MIC 0.12 μg/mL). Also, compound 13b showed fourfold potency of amphotericin B in inhibiting the growth of A. clavatus (MIC 0.49 μg/mL) and C. albicans (MIC 0.12 μg/mL), respectively. The same compound showed twofold potency of gentamycin in inhibiting the growth of P. vulgaris (MIC 0.98 μg/mL), equipotent to the ampicillin and amphotericin B in inhibiting the growth of S. epidermidis (MIC 0.49 μg/mL), A. fumigatus (MIC 0.98 μg/mL), respectively. Thus, these studies suggest that quinoline derivatives bearing pyrazole moiety are interesting scaffolds for the development of novel antibacterial and antifungal agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Crystal structure of 1-meth-oxy-2,2,2-tris-(pyrazol-1-yl)ethane.

PubMed

Lyubartseva, Ganna; Parkin, Sean; Coleman, Morgan D; Mallik, Uma Prasad

2014-09-01

The title compound, C12H14N6O, consists of three pyrazole rings bound via nitro-gen to the distal ethane carbon of meth-oxy ethane. The dihedral angles between the three pyrazole rings are 67.62 (14), 73.74 (14), and 78.92 (12)°. In the crystal, mol-ecules are linked by bifurcated C-H,H⋯N hydrogen bonds, forming double-stranded chains along [001]. The chains are linked via C-H⋯O hydrogen bonds, forming a three-dimensional framework structure. The crystal was refined as a perfect (0.5:0.5) inversion twin.

Comparison of Occlusive and Open Application in a Psoriasis Plaque Test Design, Exemplarily Using Investigations of Mapracorat 0.1% Ointment versus Vehicle and Reference Drugs.

PubMed

Wigger-Alberti, Walter; Williams, Ragna; von Mackensen, Yi-Ling; Hoffman-Wecker, Maciej; Grossmann, Ulrike; Staedtler, Gerald; Nkulikiyinka, Richard; Shakery, Kaweh

2017-01-01

Psoriasis plaque tests (PPTs) are important tools in the early phases of antipsoriatic drug development. Two distinct PPT design variants (open vs. occluded drug application) are commonly used, but no previous work has aimed to directly compare and contrast their performance. We compared the antipsoriatic efficacy of mapracorat 0.1% ointment and reference drugs reported in 2 separate studies, representing open and occluded PPT designs. The drug effect size was measured by sonography (mean change in echo-poor band thickness), chromametry, and standardized clinical assessment. Antipsoriatic effects were detectable for the study drugs in both occluded and open PPTs. Differences between the potency of antipsoriatic drugs and vehicle were observable. The total antipsoriatic effect size appeared to be higher in the occluded PPT than the open PPT, despite the shorter treatment duration (2 vs. 4 weeks). Effect dynamics over time revealed greater differences between some study drugs in the open PPT compared to the occluded PPT. Taking the higher technical challenges for the open PPT into account, we recommend the occluded PPT as a standard screening setting in early drug development. In special cases, considering certain drug aspects or study objectives that would require procedural adaptations, an open PPT could be the better-suited design. Finally, both PPT models show clear advantages: classification as phase I studies, small number of psoriatic subjects, relatively short study duration, excellent discrimination between compounds and concentrations, parallel measurement of treatment response, and go/no go decisions very early in clinical development. © 2017 S. Karger AG, Basel.

Characterization of Panax ginseng UDP-Glycosyltransferases Catalyzing Protopanaxatriol and Biosyntheses of Bioactive Ginsenosides F1 and Rh1 in Metabolically Engineered Yeasts.

PubMed

Wei, Wei; Wang, Pingping; Wei, Yongjun; Liu, Qunfang; Yang, Chengshuai; Zhao, Guoping; Yue, Jianmin; Yan, Xing; Zhou, Zhihua

2015-09-01

Ginsenosides, the main pharmacologically active natural compounds in ginseng (Panax ginseng), are mostly the glycosylated products of protopanaxadiol (PPD) and protopanaxatriol (PPT). No uridine diphosphate glycosyltransferase (UGT), which catalyzes PPT to produce PPT-type ginsenosides, has yet been reported. Here, we show that UGTPg1, which has been demonstrated to regio-specifically glycosylate the C20-OH of PPD, also specifically glycosylates the C20-OH of PPT to produce bioactive ginsenoside F1. We report the characterization of four novel UGT genes isolated from P. ginseng, sharing high deduced amino acid identity (>84%) with UGTPg1. We demonstrate that UGTPg100 specifically glycosylates the C6-OH of PPT to produce bioactive ginsenoside Rh1, and UGTPg101 catalyzes PPT to produce F1, followed by the generation of ginsenoside Rg1 from F1. However, UGTPg102 and UGTPg103 were found to have no detectable activity on PPT. Through structural modeling and site-directed mutagenesis, we identified several key amino acids of these UGTs that may play important roles in determining their activities and substrate regio-specificities. Moreover, we constructed yeast recombinants to biosynthesize F1 and Rh1 by introducing the genetically engineered PPT-producing pathway and UGTPg1 or UGTPg100. Our study reveals the possible biosynthetic pathways of PPT-type ginsenosides in Panax plants, and provides a sound manufacturing approach for bioactive PPT-type ginsenosides in yeast via synthetic biology strategies. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Extremal states of positive partial transpose in a system of three qubits

NASA Astrophysics Data System (ADS)

Steensgaard Garberg, Øyvind; Irgens, Børge; Myrheim, Jan

2013-03-01

We have studied mixed states in the system of three qubits with the property that all their partial transposes are positive; these are called PPT states. We classify a PPT state by the ranks of the state itself and its three single partial transposes. In random numerical searches, we find entangled PPT states with a large variety of rank combinations. For ranks equal to five or higher, we find both extremal and nonextremal PPT states of nearly every rank combination, with the restriction that the square sum of the four ranks of an extremal PPT state can be at most 193. We have studied especially the rank-four entangled PPT states, which are found to have rank four for every partial transpose. These states are all extremal because of the previously known result that every PPT state of rank three or less is separable. We find two distinct classes of rank-4444 entangled PPT states, identified by a real valued quadratic expression invariant under local SL(2,C) transformations, mathematically equivalent to Lorentz transformations. This quadratic Lorentz invariant is nonzero for one class of states (type I in our terminology) and zero for the other class (type II). The previously known states based on unextendible product bases are a nongeneric subclass of the type-I states. We present analytical constructions of states of both types, general enough to reproduce all the rank-4444 PPT states we have found numerically. We can not exclude the possibility that there exist nongeneric rank-four PPT states that we do not find in our random numerical searches.

A common transport system for methionine, L-methionine-DL-sulfoximine (MSX), and phosphinothricin (PPT) in the diazotrophic cyanobacterium Nostoc muscorum.

PubMed

Singh, Arvind Kumar; Syiem, Mayashree B; Singh, Rajkumar S; Adhikari, Samrat; Rai, Amar Nath

2008-05-01

We present evidence, for the first time, of the occurrence of a transport system common for amino acid methionine, and methionine/glutamate analogues L-methionine-DL-sulfoximine (MSX) and phosphinothricin (PPT) in cyanobacterium Nostoc muscorum. Methionine, which is toxic to cyanobacterium, enhanced its nitrogenase activity at lower concentrations. The cyanobacterium showed a biphasic pattern of methionine uptake activity that was competitively inhibited by the amino acids alanine, isoleucine, leucine, phenylalanine, proline, valine, glutamine, and asparagine. The methionine/glutamate analogue-resistant N. muscorum strains (MSX-R and PPT-R strains) also showed methionine-resistant phenotype accompanied by a drastic decrease in 35S methionine uptake activity. Treatment of protein extracts from these mutant strains with MSX and PPT reduced biosynthetic glutamine synthetase (GS) activity only in vitro and not in vivo. This finding implicated that MSX- and PPT-R phenotypes may have arisen due to a defect in their MSX and PPT transport activity. The simultaneous decrease in methionine uptake activity and in vitro sensitivity toward MSX and PPT of GS protein in MSX- and PPT-R strains indicated that methionine, MSX, and PPT have a common transport system that is shared by other amino acids as well in N. muscorum. Such information can become useful for isolation of methionine-producing cyanobacterial strains.

A facile iodine(III)-mediated synthesis of 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines via oxidation of 2-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines and their antimicrobial evaluations

PubMed Central

2011-01-01

Background Fused heterocyclic 1,2,4-triazoles have acquired much importance because of their interesting biological properties. Although a number of methods have been reported in the literature which includes oxidation with phosphorus oxychloride, lead tetraacetate, bromine, etc., hypervalent iodine reagents have emerged as reagents of choice for various synthetically useful transformations due to their low toxicity, ready availability and ease of handling. Results A series of new 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines 4 has been conveniently synthesized by oxidative cyclization of 2-(3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines 3 promoted with iodobenzene diacetate under mild conditions (up to 90% isolated yields). All the new compounds were tested in vitro for their antimicrobial activity. Conclusions Iodine(III)-mediated oxidative approach has offered an easy access to new 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines 4. The antibacterial and antifungal activities of newly synthesized compounds have proved them potent antimicrobial agents. PMID:22373059

New steroidal glycosides from Tribulus terrestris L.

PubMed

Chen, Gang; Liu, Tao; Lu, Xuan; Wang, Hai-Feng; Hua, Hui-Ming; Pei, Yue-Hu

2012-01-01

Two new steroidal glycosides were isolated from Tribulus terrestris L. Their structures were elucidated as 26-O-β-D-glucopyranosyl-5α-furostan-12-one-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (1) and 26-O-β-D-glucopyranosyl-5α-furostan-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.

Combining silver- and organocatalysis: an enantioselective sequential catalytic approach towards pyrano-annulated pyrazoles.

PubMed

Hack, Daniel; Chauhan, Pankaj; Deckers, Kristina; Mizutani, Yusuke; Raabe, Gerhard; Enders, Dieter

2015-02-11

A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a silver salt, provides a new series of chiral pyrano-annulated pyrazole derivatives in excellent yields (up to 95%) and high enantioselectivities (up to 97% ee).

GREENER AND RAPID ACCESS TO BIO-ACTIVE HETEROCYCLES: ROOM TEMPERATURE SYNTHESIS OF PYRAZOLES AND DIAZEPINES IN AQUEOUS MEDIUM

EPA Science Inventory

An expeditious room temperature synthesis of pyrazoles and diazepines by condensation of hydrazines/hydrazides and diamines with various 1,3-diketones is described. This greener protocol was catalyzed by polystyrene supported sulfonic acid (PSSA) and proceeded efficiently in wate...

Mixing with microwaves: solvent-free and catalyst-free synthesis of pyrazoles and diazepines

EPA Science Inventory

A simple and facile condensation of hydrazines/hydrazides and diamines with 1,3-diketones/β-ketoester leads to the preparation of pyrazoles and diazepines in high yields. This eco-friendly protocol is accelerated by microwave heating and efficiently carried out without any r...

Effects of Artemisia annua extracts on sporulation of Eimeria oocysts.

PubMed

Fatemi, Ahmadreza; Razavi, Seyyed Mostafa; Asasi, Keramat; Goudarzi, Majid Torabi

2015-03-01

The present study aimed to compare the effect of different Artemisia annua extracts on sporulation rate of mixed oocysts of Eimeria acervulina, Eimeria necatrix, and Eimeria tenella. Three types of A. annua extracts including petroleum ether (PE), ethanol 96° (E), and water (W) extracts were prepared. Artemisinin, a sesquiterpene lactone endoperoxide derived from the A. annua analysis of each extract was done by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Fresh fecal samples containing three Eimeria species were floated and counted, and the oocysts were transferred into 50 tubes, each containing 10(5) oocysts per milliliter. Five tubes were control. Each of the other 45 tubes contained one of three doses (1 part per thousand (ppt), 2 ppt, and 5 ppt) and one of three extracts (PE, E, and W extracts) with five replications. The tubes were incubated for 48 h at 25-29 °C and aerated. Sporulation inhibition assay was used to evaluate the activity of extracts. The results showed that the E and PE extracts inhibit sporulation in 2 and 5 ppt concentrations, but the W extract stimulates it in all concentrations. The proportions of oocyst inhibition relative to control were 31 % (5 ppt) and 29 % (2 ppt) for PE and 34 % (5 ppt) and 46 % (2 ppt) for E extract. Furthermore, many oocysts in PE and E groups were wrinkled and contained abnormal sporocysts. The proportions of sporulation stimulation relative to control were 22 % (5 ppt), 24 % (2 ppt), and 27 % (1 ppt) in W extract. Our study is the first to demonstrate that all types of A. annua extracts do not necessarily have a similar activity, and the interaction of all contents and their relative concentrations is an important factor for sporulation stimulation or inhibition. It seems, some parts of unmetabolized excreted PE and E extracts could inhibit oocyst sporulation and eventually affect infection transmission.

Diazatetraester 1H-pyrazole crowns as fluorescent chemosensors for AMPH, METH, MDMA (ecstasy), and dopamine.

PubMed

Reviriego, Felipe; Navarro, Pilar; García-España, Enrique; Albelda, M Teresa; Frías, Juan C; Domènech, Antonio; Yunta, Maria J R; Costa, Rubén; Ortí, Enrique

2008-11-20

The synthesis and steady-state fluorescence studies on the interaction with AMPH, METH, MDMA, and DA of two diazatetraester pyrazole crowns containing appended N-(9H-fluoren-9-yl) and N-(naphth-2-ylmethyl) functions, in a water/ethanol 70:30 mixture at physiological pH, are described.

Pulsed Plasma Thruster Technology for Small Satellite Missions

NASA Technical Reports Server (NTRS)

Myers, Roger M.; Oleson, Steven R.; Mcguire, Melissa; Meckel, Nicole J.; Cassady, R. Joseph

1995-01-01

Pulsed plasma thrusters (PPT's) offer the combined benefits of extremely low average electric power requirements (1 to 150 W), high specific impulse (approximately 1000 s), and system simplicity derived from the use of an inert solid propellant. Potential applications range from orbit insertion and maintenance of small satellites to attitude control for large geostationary communications satellites. While PPT's have been used operationally on several spacecraft, there has been no new PPT technology development since the early 1970's. As result of the rapid growth in the small satellite community and the broad range of PPT applications, NASA has initiated a development program with the objective of dramatically reducing the PPT dry mass, increasing PPT performance, and demonstrating a flight ready system by October 1997. This paper presents the results of a series of near-Earth mission studies including both primary and auxiliary propulsion and attitude control functions and reviews the status of NASA's on-going development program.

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

Shardin, Rosidah; Pui, Law Kung; Yamin, Bohari M.

A simple mononuclear octahedral copper(II) complex was attempted from the reaction of three moles of 1-benzoyl-3-(pyridin-2-yl)-1H-pyrazole and one mole of copper(II) perchlorate hexahydrate in methanol. However, the product of the reaction was confirmed to be a dinuclear copper(II) complex with μ-(3-(pyridin-2-yl)-pyrazolato) and 3-(pyridin-2-yl)-1H-pyrazole ligands attached to each of the Cu(II) centre atom. The copper(II) ion assisted the cleavage of the C{sub benzoyl}N bond afforded a 3-(pyridin-2-yl)-1H-pyrazole molecule. Deprotonation of the 3-(pyridin-2-yl)-1H-pyrazole gave a 3-(pyridin-2-yl)-pyrazolato, which subsequently reacted with the Cu(II) ion to give the (3-(pyridin-2-yl)-pyrazolato)(3-(pyridin-2-yl)-1H-pyrazole)Cu(II) product moiety. The structure of the dinuclear complex was confirmed by x-ray crystallography. The complexmore » crystallized in a monoclinic crystal system with P2(1)/n space group and cell dimensions of a = 12.2029(8) Å, b = 11.4010(7) Å, c = 14.4052(9) Å and β = 102.414(2)°. The compound was further characterized by mass spectrometry, CHN elemental analysis, infrared and UV-visible spectroscopy and the results concurred with the x-ray structure. The presence of d-d transition at 671 nm (ε = 116 dm{sup 3} mol{sup −1} cm{sup −1}) supports the presence of Cu(II) centres.« less

Prevention and control of sexually transmissible infections among hotel-based female sex workers in Dhaka, Bangladesh.

PubMed

McCormick, Duncan F; Rahman, Motiur; Zadrozny, Sabrina; Alam, Anadil; Ashraf, Lutfa; Neilsen, Graham A; Kelly, Robert; Menezes, Prema; Miller, William C; Hoffman, Irving F

2013-12-01

Hotel-based sex workers in Bangladesh have high rates of sexually transmissible infections (STIs), high client turnover and low condom use. Two monthly clinic-based strategies were compared: periodic presumptive treatment (PPT) and enhanced syndromic management (ESM) - one round of presumptive treatment followed by treatment based on assessment and laboratory tests. A randomised controlled trial compared PPT and ESM by prevalence and incidence, behaviour, retention, cost and STI incidence and prevalence. Demographic, behavioural and clinical data were collected from women at two clinics in Dhaka. All women received presumptive treatment and were randomised to receive PPT or ESM at nine monthly visits. In total, 549 women (median age: <20 years) were enrolled. At baseline, the prevalence of chlamydia (Chlamydia trachomatis) and gonorrhoea (Neisseria gonorrhoeae) was 41% (ESM: 41%; PPT: 42%). After 9 months, chlamydia and gonorrhoea decreased to 7% overall, (ESM: 7.4%; PPT: 6.8%). At each visit, 98% of women receiving ESM met the therapy criteria and were treated. Retention was low (50%). Total costs were 50% lower per visit for each woman for PPT (ESM: $11.62 v. PPT: $5.80). The number of sex work sessions was reduced from 3.3 to 2.5 (P<0.001), but income did not change. Coercion was reduced but condom use at last sex did not change significantly. Monthly PPT and ESM were effective approaches for STI control. PPT offered a feasible, low-cost alternative to ESM. Educational aspects led to a reduction in coercion and fewer sessions. Implementation studies are needed to improve condom use and retention.

Relative and absolute test-retest reliabilities of pressure pain threshold in patients with knee osteoarthritis.

PubMed

Srimurugan Pratheep, Neeraja; Madeleine, Pascal; Arendt-Nielsen, Lars

2018-04-25

Pressure pain threshold (PPT) and PPT maps are commonly used to quantify and visualize mechanical pain sensitivity. Although PPT's have frequently been reported from patients with knee osteoarthritis (KOA), the absolute and relative reliability of PPT assessments remain to be determined. Thus, the purpose of this study was to evaluate the test-retest relative and absolute reliability of PPT in KOA. For that purpose, intra- and interclass correlation coefficient (ICC) as well as the standard error of measurement (SEM) and the minimal detectable change (MDC) values within eight anatomical locations covering the most painful knee of KOA patients was measured. Twenty KOA patients participated in two sessions with a period of 2 weeks±3 days apart. PPT's were assessed over eight anatomical locations covering the knee and two remote locations over tibialis anterior and brachioradialis. The patients rated their maximum pain intensity during the past 24 h and prior to the recordings on a visual analog scale (VAS), and completed The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and PainDetect surveys. The ICC, SEM and MDC between the sessions were assessed. The ICC for the individual variability was expressed with coefficient of variance (CV). Bland-Altman plots were used to assess potential bias in the dataset. The ICC ranged from 0.85 to 0.96 for all the anatomical locations which is considered "almost perfect". CV was lowest in session 1 and ranged from 44.2 to 57.6%. SEM for comparison ranged between 34 and 71 kPa and MDC ranged between 93 and 197 kPa with a mean PPT ranged from 273.5 to 367.7 kPa in session 1 and 268.1-331.3 kPa in session 2. The analysis of Bland-Altman plot showed no systematic bias. PPT maps showed that the patients had lower thresholds in session 2, but no significant difference was observed for the comparison between the sessions for PPT or VAS. No correlations were seen between PainDetect and PPT and PainDetect and WOMAC. Almost perfect relative and absolute reliabilities were found for the assessment of PPT's for KOA patients. The present investigation implicates that PPT's is reliable for assessing pain sensitivity and sensitization in KOA patients.

Ligand effects on the structure and magnetic properties of alternating copper(II) chains with 2,2'-bipyrimidine- and polymethyl-substituted pyrazolates as bridging ligands.

PubMed

Castro, Isabel; Calatayud, M Luisa; Barros, Wdeson P; Carranza, José; Julve, Miguel; Lloret, Francesc; Marino, Nadia; De Munno, Giovanni

2014-06-02

A novel series of heteroleptic copper(II) compounds of formulas {[Cu2(μ-H2O)(μ-pz)2(μ-bpm)(ClO4)(H2O)]ClO4·2H2O}n (1), {[Cu2(μ-H2O)(μ-3-Mepz)2(μ-bpm)](ClO4)2·2H2O}n (2), and {[Cu2(μ-OH)(μ-3,5-Me2pz)(μ-bpm)(H-3,5-Me2pz)2](ClO4)2}n (3) [bpm = 2,2'-bipyrimidine, Hpz = pyrazole, H-3-Mepz = 3-methylpyrazole, and H-3,5-Me2pz = 3,5-dimethylpyrazole] have been synthesized and structurally characterized by X-ray diffraction methods. The crystal structures of 1 and 2 consist of copper(II) chains with regular alternating bpm and bis(pyrazolate)(aqua) bridges, whereas that of 3 is made up of copper(II) chains with regular alternating bpm and (pyrazolate)(hydroxo) bridges. The copper centers are six- (1) or five-coordinate (2) in axially elongated, octahedral (1) or square-pyramidal (2) environments in 1 and 2, whereas they are five-coordinate in distorted trigonal-bipyramidal surroundings in 3. The values of the copper-copper separations across the bpm/pyrazolate bridges are 5.5442(7)/3.3131(6) (1), 5.538(1)/3.235(1) (2), and 5.7673(7)/3.3220(6) Å (3). The magnetic properties of 1-3 have been investigated in the temperature range of 25-300 K. The analysis of their magnetic susceptibility data through the isotropic Hamiltonian for an alternating antiferromagnetic copper(II) chain model [H = -J∑i=1-n/2 (S2i·S2i-1 + αS2i·S2i+1), with α = J'/J and Si = SCu = 1/2] reveals the presence of a strong to moderate antiferromagnetic coupling through the bis(pyrazolate)(aqua) [-J = 217 (1) and 215 cm(-1) (2)] and (pyrazolate)(hydroxo) bridges [-J = 153 cm(-1) (3)], respectively, whereas a strong to weak antiferromagnetic coupling occurs through the bis-bidentate bpm [-J' = 211 (1), 213 (2), and 44 cm(-1) (3)]. A simple orbital analysis of the magnetic exchange interaction within the bpm- and pyrazolate-bridged dicopper(II) fragments of 1-3 visualizes the σ-type pathways involving the (dx(2)-y(2)) (1 and 2) or d(z(2)) (3) magnetic orbitals on each metal ion, which account for the variation of the magnetic properties in these three novel examples of one-dimensional copper(II) compounds with regular alternating intrachain antiferromagnetic interactions.

miR-7-1 POTENTIATED ESTROGEN RECEPTOR AGONISTS FOR FUNCTIONAL NEUROPROTECTION IN VSC4.1 MOTONEURONS

PubMed Central

CHAKRABARTI, M.; BANIK, N. L.; RAY, S. K.

2013-01-01

Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI) insulted VSC4.1 motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using miRDB indicated that miR-7-1 could inhibit expression of L-type Ca2+ channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca2+/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future to attenuate apoptosis of motoneurons in SCI. PMID:24157932

MiR-7-1 potentiated estrogen receptor agonists for functional neuroprotection in VSC4.1 motoneurons.

PubMed

Chakrabarti, M; Banik, N L; Ray, S K

2014-01-03

Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI)-insulted ventral spinal cord 4.1 (VSC4.1) motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI-insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI-insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using microRNA database (miRDB) indicated that miR-7-1 could inhibit the expression of L-type Ca(2+) channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca(2+)/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI-insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future to attenuate apoptosis of motoneurons in SCI. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Gper and ESRs are expressed in rat round spermatids and mediate oestrogen-dependent rapid pathways modulating expression of cyclin B1 and Bax.

PubMed

Chimento, A; Sirianni, R; Zolea, F; Bois, C; Delalande, C; Andò, S; Maggiolini, M; Aquila, S; Carreau, S; Pezzi, V

2011-10-01

Spermatogenesis is a precisely controlled and timed process, comprising mitotic divisions of spermatogonia, meiotic divisions of spermatocytes, maturation and differentiation of haploid spermatids giving rise to spermatozoa. It is well known that the maintenance of spermatogenesis is controlled by gonadotrophins and testosterone, the effects of which are modulated by a complex network of locally produced factors, including oestrogens. However, it remains uncertain whether oestrogens are able to activate rapid signalling pathways directly in male germ cells. Classically, oestrogens act by binding to oestrogen receptors (ESRs) 1 and 2. Recently, it has been demonstrated that rapid oestrogen action can also be mediated by the G-protein-coupled oestrogen receptor 1 (Gper). The aim of the present study was to investigate ESRs and Gper expression in primary cultures of adult rat round spermatids (RS) and define if oestradiol (E2) is able to activate, through these receptors, pathways involved in the regulation of genes controlling rat RS apoptosis and/or maturation. In this study, we demonstrated that rat RS express ESR1, ESR2 and Gper. Short-time treatment of RS with E2, the selective Gper agonist G1 and the selective ESR1 and ERβ agonists, 4,4',4"-(4-propyl-[1H]pyrazole-1,3,5-triyl) trisphenol (PPT) and 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), respectively, determined activation of Extra-cellular signal-regulated kinase (ERK1/2) through the involvement of epidermal growth factor receptor transactivation. In addition, we investigated the effects of ESRs and Gper pathway activation on factors involved in RS maturation. Expression of cyclin B1 mRNA was downregulated by E2, G1 and PPT, but not by DPN. A concomitant and inverse regulation of the pro-apoptotic factor Bax mRNA expression was observed in the same conditions, with DPN being the only one determining an increase in this factor expression. Collectively, these data demonstrate that E2 activates, through ESRs and Gper, pathways involved in the regulation of genes controlling rat RS apoptosis and differentiation such as cyclin B1 and Bax. © 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors.

PubMed

Zhang, Xuqing; Song, Fengbing; Kuo, Gee-Hong; Xiang, Amy; Gibbs, Alan C; Abad, Marta C; Sun, Weimei; Kuo, Lawrence C; Sui, Zhihua

2011-08-15

A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

Iron Oxide-Supported Copper Oxide Nanoparticles (Nanocat-Fe-CuO): Magnetically Recyclable Catalysts for the Synthesis of Pyrazole Derivatives, 4-Methoxyaniline, and Ullmann-type Condensation Reactions

EPA Science Inventory

An efficient and benign protocol is reported for the synthesis of 4-methoxyaniline, medicinally important pyrazole derivatives, and Ullmann-type condensation reaction using magnetically separable and reusable magnetite-supported copper (nanocat-Fe-CuO) nanoparticles under mild co...

Development of Enabling Chemical Technologies for Power from Green Sources

DTIC Science & Technology

2013-11-18

structurally analogous polymers based on N-heterocycles (triazole, imidazole and pyrazole) and benz-N-heterocycles (benzotriazole, benzimidazole ...found that triazole (benzotriazole) and imidazole ( benzimidazole ) containing polymers exhibit similar proton conductivities, about 4 orders of...magnitude higher than those with pyrazole (benzopyrazole) (Figure 6b). The similar behavior of triazole and imidazole (benzotriazole and benzimidazole

40 CFR 180.585 - Pyraflufen-ethyl; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... residues of the herbicide, pyraflufen-ethyl, ethyl 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1H-pyrazol-3-yl)-4-fluorophenoxyacetate, and its acid metabolite, E-1, 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1H-pyrazol-3-yl)-4-fluorophenoxyacetic acid, expressed in terms of the parent in or on the...

Nucleophilic ortho-Allylation of Pyrroles and Pyrazoles: An Accelerated Pummerer/Thio-Claisen Rearrangement Sequence

PubMed Central

2013-01-01

Arylsulfinyl groups direct the metal-free, regiospecific, nucleophilic ortho-allylation of pyrroles and pyrazoles. Mechanistic studies support the intermediacy of allylsulfonium salts that undergo facile thio-Claisen rearrangement onto the heterocyclic ring, giving products of coupling. The strategy has been adapted to allow regiospecific propargylation of the heterocyclic substrates. PMID:23855635

A vanadium(IV) pyrazolate metal-organic polyhedron with permanent porosity and adsorption selectivity.

PubMed

Augustyniak, A W; Fandzloch, M; Domingo, M; Łakomska, I; Navarro, J A R

2015-10-11

A vanadium(IV) pyrazolate-based open metal-organic polyhedron of [V3(μ3-O)O(OH)2(μ4-BPD)1.5(μ-HCOO)3] (BDP = benzene-1,4-bipyrazolate) formulation gives rise to a porous crystal structure exhibiting micro and mesoporosity which is useful for selective adsorption of gases.

Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety.

PubMed

Karrouchi, K; Chemlal, L; Taoufik, J; Cherrah, Y; Radi, S; El Abbes Faouzi, M; Ansar, M

2016-11-01

A series of Schiff bases of 4-amino-1,2,4-triazole derivatives containing pyrazole (5a-h) were synthesized from condensation of 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (3) derivative with various aromatic aldehydes (4a-h). The structures of the synthesized compounds were elucidated by IR, 1 H NMR, 13 C NMR, and mass spectrometry. All the synthesized compounds (5a-h) were screened for their in vivo analgesic and in vitro antioxidant activities revealing significant analgesic and antioxidant properties. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Effects of salinity on chloride cells and Na+ K+-ATPase activity in the teleost Gillchthys mirabilis

USGS Publications Warehouse

Yoshikawa, J.S.M.; McCormick, S.D.; Young, G.; Bern, H.A.

1993-01-01

1. Longjawed mudsuckers, Gillichthys mirabilis, in 30ppt seawater (SW) were transferred to 1.5, 30 and 60ppt SW.2. In the first 1–3 days after transfer, plasma chloride level and plasma osmolarity rose in the 60ppt SW fish, and decreased in the 1.5ppt SW fish.3. By day 21, however, plasma chloride and osmolarity were at or near the levels seen in the controls (30ppt).4. Branchial and jawskin Na+, K+-ATPase activities were high in all salinities, and did not differ significantly among treatments.5. The vital fluorescent stains DASPEI and anthroylouabain were used to detect mitochondria and Na+, K+-ATPase, respectively, in chloride cells.6. Both stains indicated that jawskin chloride cell density did not differ among treatment groups.7. In contrast, chloride cell size increased significantly with increasing salinity.8. The chloride cells of fish in 60 ppt SW were noticeably angular in outline, whereas those of both the 1.5 and 30ppt SW fish were circular.9. The results are discussed in relation to the ion transport requirements encountered in the intertidal habitat of the mudsucker.

Demonstration of Regenerable, Large-scale Ion Exchange System Using WBA Resin in Rialto, CA

DTIC Science & Technology

2008-03-01

Saturation Index MCL – Maximum Contaminant Level NaOH – Sodium hydroxide NDBA – N-nitrosodi-n-butylamine NDEA – N-nitrosodiethylamine NDMA ...analyzed using EPA Method 521. NDMA was 2.6 ppt with a detection limit of 2 ppt. All other nitrosamines analyzed (including NDEA, NDBA, NDPA, NMEA...using IC/MS/MS. Nitrosamines were analyzed using EPA Method 521. NDMA was 2.6 ppt with a detection limit of 2 ppt. All other nitrosamines

Demonstration of Regenerable, Large-Scale Ion Exchange System Using WBA Resin in Rialto, CA

DTIC Science & Technology

2008-03-05

NDMA – N-nitrosodimethylamine NDPA – N-nitrosodi-n-propylamine NMEA – N-nitrosomethylethylamine NMOR – N-nitrosomorpholine NPDES – National Pollutant...were analyzed using EPA Method 521. NDMA was 2.6 ppt with a detection limit of 2 ppt. All other nitrosamines analyzed (including NDEA, NDBA, NDPA...ppb) using IC/MS/MS. Nitrosamines were analyzed using EPA Method 521. NDMA was 2.6 ppt with a detection limit of 2 ppt. All other nitrosamines

Preprotachykinin A mRNA expression in the rat brain during development.

PubMed

Brené, S; Lindefors, N; Friedman, W J; Persson, H

1990-12-15

Expression of preprotachykinin A (PPT-A) mRNA was analyzed by northern blots using mRNA prepared from rat brain at 12 different developmental stages ranging from embryonic day 15 (E15) to adult. A single PPT-A mRNA of 1.3 kb was detected throughout development. PPT-A mRNA was detected as early as E15 and an approximately 3-fold increase occurred at birth. This amount remained until 3 weeks of age when the level increased, reaching a peak at 5 weeks of age. Adult amounts were approximately 3-fold higher than the levels at birth. The distribution of PPT-A mRNA-expressing cells in rat brain was studied by in situ hybridization on sections from embryonic day 20, postnatal days 4 and 7 as well as adult. Cells expressing PPT-A mRNA were detected in the forebrain at all 4 ages analyzed. However, the hybridization pattern and the labeling intensity varied in different brain regions during development. In cingulate cortex, intense labeling was seen in numerous cells at embryonic day 20 and postnatal days 4 and 7, whereas in the adult cingulate cortex only a few scattered labeled cells were observed. In frontoparietal cortex labeled cells were found from postnatal day 4 to adult, with the highest density of labeled cells at P7. Developmental differences in both the distribution of PPT-A mRNA-expressing cells and the level of PPT-A mRNA expression were also found in caudate-putamen, lateral hypothalamus and amygdala. Thus, our results show several changes in PPT-A mRNA expression during ontogeny, indicating a region and time-specific regulation of PPT-A mRNA expression during brain maturation.

Parecoxib increases muscle pain threshold and relieves shoulder pain after gynecologic laparoscopy: a randomized controlled trial.

PubMed

Zhang, Hufei; Liu, Xinhe; Jiang, Hongye; Liu, Zimeng; Zhang, Xu-Yu; Xie, Hong-Zhe

2016-01-01

Postlaparoscopic shoulder pain (PLSP) remains a common problem after laparoscopies. The aim of this study was to investigate the correlation between pressure pain threshold (PPT) of different muscles and PLSP after gynecologic laparoscopy, and to explore the effect of parecoxib, a cyclooxygenase-2 inhibitor, on the changes of PPT. The patients were randomly allocated into two groups; group P and group C. In group P, parecoxib 40 mg was intravenously infused at 30 minutes before surgery and 8 and 20 hours after surgery. In group C, normal saline was infused at the corresponding time point. PPT assessment was performed 1 day before surgery and at postoperative 24 hours by using a pressure algometer at bilateral shoulder muscles (levator scapulae and supraspinatus) and forearm (flexor carpi ulnaris). Meanwhile, bilateral shoulder pain was evaluated through visual analog scale score at 24 hours after surgery. Preoperative PPT level of the shoulder, but not of the forearm, was significantly and negatively correlated with the intensity of ipsilateral PLSP. In group C, PPT levels of shoulder muscles, but not of forearm muscles, decreased after laparoscopy at postoperative 24 hours. The use of parecoxib significantly improved the decline of PPT levels of bilateral shoulder muscles (all P <0.01). Meanwhile, parecoxib reduced the incidence of PLSP (group P: 45% vs group C: 83.3%; odds ratio: 0.164; 95% confidence interval: 0.07-0.382; P <0.001) and the intensity of bilateral shoulder pain (both P <0.01). Preoperative PPT levels of shoulder muscles are closely associated with the severity of shoulder pain after gynecologic laparoscopy. PPT levels of shoulder muscles, but not of forearm muscles, significantly decreased after surgery. Parecoxib improved the decrease of PPT and relieved PLSP.

Pressure pain threshold with and without iontophoretic anesthesia of the masseter muscle in asymptomatic males.

PubMed

Fujisawa, M; Shoji, S; Ishibashi, K; Clark, G T

1999-01-01

The pressure pain threshold (PPT) in the superficial masseter muscle was measured with and without cutaneous anesthesia to determine whether there would be a difference in PPT scores. In 14 healthy male subjects, cutaneous tissues in the target areas were anesthetized with lidocaine with the help of an iontophoretic device. As a control, physiologic saline solution was applied iontophoretically to the contralateral masseter site. The subject and the PPT examiner did not know which side contained anesthesia, and the selection of which side to anesthetize was done in a random fashion. Multiple PPT measurements were made in the target sites before and immediately after the iontophoretic anesthesia. The PPT level on the lidocaine side was not statistically different from the PPT level recorded on the control side (339.0 +/- 87.6 kPa and 337.5 +/- 77.7 kPa, respectively). Pressure pain sensation in the human masseter is not derived predominantly from the cutaneous tissues, but from the muscle itself.

Osmoregulation and muscle water control in vitro facing salinity stress of the Amazon fish Oscar Astronotus ocellatus (Cichlidae)

USGS Publications Warehouse

Gutierre, Silvia M. M.; Schulte, Jessica M.; Schofield, Pam; Prodocimo, Viviane

2017-01-01

Specimens of Oscar Astronotus ocellatus from a fish farm were abruptly submitted to salt stress of 14 ppt and 20 ppt, for 3 and 8 h to determine their plasma osmolality. Muscle wet body mass change in vitro was analyzed from control freshwater animals. Fish in 14 ppt presented no osmolality distress even after 8 h. In 20 ppt, a slight increase (10%) in plasma osmolality was observed for both times of exposure when compared to control fish. Muscle slices submitted in vitro to hyper-osmotic saline displayed decreased body mass after 75 min, and slices submitted to hypo-osmotic saline displayed increased body mass after 45 min when compared to control (isosmotic saline). These results reinforce A. ocellatus’s euryhalinity. The fish were able to regulate its internal medium and tolerate 14 ppt, but presented an intense osmotic challenge and low muscle hydration control when facing salinities of 20 ppt.

Effect of short-term cold-water immersion on muscle pain sensitivity in elite track cyclists.

PubMed

Klich, Sebastian; Krymski, Igor; Michalik, Kamil; Kawczyński, Adam

2018-05-01

To determine the effect of short-term cold-water immersion (CWI) on muscle pain sensitivity after maximal anaerobic power training in track cyclists. Repeated measures. University Laboratory. 12 elite sprint track cyclists (age 24,75 ± 4,23 years). PPT measurements were made on dominant lower extremity (right) in 20 reference points, including anterior thigh muscles, posterior thigh muscles and posterior cuff muscles. PPT levels were measured: 1) before workout, 2) immediately after workout, but before CWI 3) 1 h after CWI and 4) 12 h after CWI. Mean PPT values for each muscle group per participant were calculated for further statistical analysis. The average PPT for anterior thigh muscles decreased significantly after effort (p = 0.001) and increased significantly 1 h after CWI (p = 0.048). In posterior thigh muscles PPT decreased significantly after effort (p = 0.014) and increased significantly 1 h and 12 h after CWI (p = 0.045 and p = 0.25 respectively). However, in posterior cuff muscles PPT decreased only after effort (p = 0.001). Short-term repeated sprint exercise appears to affect PPT in track cyclists. This study have reported that CWI in 5 °C for 5 min have had a beneficial effect in minimizing PPT 1 h post repeated maximal sprint training. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Effect of Pyrazolyl Substituents on the Photophysical and Photochemical Properties of Pyrazine Derivatives.

PubMed

Pizarro, Nancy; Prado, Gaspar; Saldías, Marianela; Sandoval-Altamirano, Catalina; Vega, Andrés

2018-02-15

The reaction of 2,5-dibromopyrazine with N-Lithium pyrazolate in a 1:2 ratio leads to a mixture of 2-bromo-5-(1H-pyrazol-1-yl)pyrazine (I) and 2,5-di(1H-pyrazol-1-yl)pyrazine (II). The structures of I and II are highly planar. Two absorption bands can be observed for the compounds in the UV-Vis region, having ε in the order of 10 4  m -1  cm -1 . TD-DFT computed results support the nature of the lower energy absorptions as π pyrazine →π* pyrazine transitions, including an additional intraligand charge transfer transition for I (π pyrazol →π* pyrazine ). Upon excitation at 280 or 320 nm, the emission of both compounds is almost not affected by solvent polarity or oxygen presence, showing two bands for I and one for II in the 350-450 nm region. Emission of II follows a mono-exponential decay, while I decays following a bi-exponential law, hypothesized from π pyrazine →π* pyrazine and π pyrazol →π* pyrazine transitions. Photodegradation of I and II follows a first-order kinetic with constants of 1.18 × 10 -2  min -1 and 0.13 × 10 -2  min -1 , respectively. Results suggest that photodegradation of I starts with the loose of bromide followed by intermolecular pyrazolyl subtraction and ring opening. This path is not available for II, which is reflected in its enhanced photostability. © 2018 The American Society of Photobiology.

Pyrazole amino acids: hydrogen bonding directed conformations of 3-amino-1H-pyrazole-5-carboxylic acid residue.

PubMed

Kusakiewicz-Dawid, Anna; Porada, Monika; Ochędzan-Siodłak, Wioletta; Broda, Małgorzata A; Bujak, Maciej; Siodłak, Dawid

2017-09-01

A series of model compounds containing 3-amino-1H-pyrazole-5-carboxylic acid residue with N-terminal amide/urethane and C-terminal amide/hydrazide/ester groups were investigated by using NMR, Fourier transform infrared, and single-crystal X-ray diffraction methods, additionally supported by theoretical calculations. The studies demonstrate that the most preferred is the extended conformation with torsion angles ϕ and ψ close to ±180°. The studied 1H-pyrazole with N-terminal amide/urethane and C-terminal amide/hydrazide groups solely adopts this energetically favored conformation confirming rigidity of that structural motif. However, when the C-terminal ester group is present, the second conformation with torsion angles ϕ and ψ close to ±180° and 0°, respectively, is accessible. The conformational equilibrium is observed in NMR and Fourier transform infrared studies in solution in polar environment as well as in the crystal structures of other related compounds. The observed conformational preferences are clearly related to the presence of intramolecular interactions formed within the studied residue. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Entanglement cost under positive-partial-transpose-preserving operations.

PubMed

Audenaert, K; Plenio, M B; Eisert, J

2003-01-17

We study the entanglement cost under quantum operations preserving the positivity of the partial transpose (PPT operations). We demonstrate that this cost is directly related to the logarithmic negativity, thereby providing the operational interpretation for this entanglement measure. As examples we discuss general Werner states and arbitrary bipartite Gaussian states. Then we prove that for the antisymmetric Werner state PPT cost and PPT entanglement of distillation coincide. This is the first example of a truly mixed state for which entanglement manipulation is asymptotically reversible, which points towards a unique entanglement measure under PPT operations.

Wear behavior of AISI 1090 steel modified by pulse plasma technique

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

Ayday, Aysun; Durman, Mehmet

2012-09-06

AISI 1090 steel was pulse plasma treated (PPT) using a Molybdenum electrode. Two different pulse numbers were chosen to obtain modified layers of 20{+-}5 {mu}m thickness. The dry sliding wear studies performed on this steel with and without PPT against an alumina ball counterpart showed that the PPT improved the wear resistance. The pulse number of the PPT modified layer was found to be highly influential in imparting the wear resistance to this steel, due to enhancement of surface hardness depending on treatment time.

Autoimmune Abnormalities of Postpartum Thyroid Diseases

PubMed Central

Di Bari, Flavia; Granese, Roberta; Le Donne, Maria; Vita, Roberto; Benvenga, Salvatore

2017-01-01

The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT) and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium) or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels) of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid. PMID:28751877

Midbrain dopamine neurons regulate preprotachykinin-A mRNA expression in the rat forebrain during development.

PubMed

Brené, S; Lindefors, N; Persson, H

1992-06-01

Intracerebroventricular 6-hydroxydopamine injections were performed at postnatal days 3 and 6 in animals pretreated with the norepinephrine uptakeblocker desimipramine in order to generate a selective lesion of dopamine neurons. In situ hybridization was then used to analyze preprotachykinin-A (PPT-A) mRNA expression in the lesioned as well as in saline-injected control animals. The midbrain dopaminergic lesion caused a 22-25% increase in the level of PPT-A mRNA in cingulate cortex and frontoparietal cortex when analysed at 2 weeks of age, compared to saline-injected control animals. In contrast, the lesion caused no change in PPT-A mRNA expression in the neonatal caudate-putamen. These results indicate that dopamine neurons downregulate the expression of PPT-A mRNA specifically in cingulate cortex and frontoparietal cortex during early postnatal brain development. In the adult rat forebrain, lesioned at P3 and P6, no change in the level of PPT-A mRNA was seen in cingulate cortex and frontoparietal cortex. However, a 29% decrease in PPT-A mRNA was seen in the lateral caudate-putamen with no significant change in neurons of medial caudate-putamen. Thus, dopamine neurons appears to exert a region specific influence on PPT-A mRNA expression during brain development.

Experience with perioperative pirfenidone for lung cancer surgery in patients with idiopathic pulmonary fibrosis.

PubMed

Iwata, Takekazu; Yoshida, Shigetoshi; Nagato, Kaoru; Nakajima, Takahiro; Suzuki, Hidemi; Tagawa, Tetsuzo; Mizobuchi, Teruaki; Ota, Satoshi; Nakatani, Yukio; Yoshino, Ichiro

2015-10-01

Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse lung disease associated with an increased risk of lung cancer. Patients with IPF sometimes develop a life-threatening acute exacerbation of IPF (AE-IPF) after lung cancer surgery. In this retrospective study, pirfenidone, an antifibrotic agent, was perioperatively administered to IPF patients with lung cancer with the aim of preventing postoperative AE-IPF, and the feasibility and clinical outcomes were investigated. Twelve IPF patients with concomitant lung cancer who received perioperative pirfenidone treatment (PPT) for lung cancer surgery were retrospectively investigated. Sixteen IPF patients undergoing lung cancer surgery without PPT were analyzed as historical controls. Compared to the controls, the PPT patients had a more severely impaired preoperative pulmonary function and a larger number of limited pulmonary resections. There was a significant preoperative decrease in the serum KL-6 levels of the PPT patients. No severe pirfenidone-related complications or IPF-related events occurred in the PPT patients, while six control patients developed AE-IPF (P = 0.0167). A quantitative histopathological evaluation of resected lung specimens found that tissue changes associated with IPF were significantly fewer in the PPT patients (P = 0.021). PPT is a feasible perioperative treatment for IPF patients with lung cancer. Its effectiveness in preventing postoperative AE-IPF thus warrants prospective verification.

Ethyl 5-amino-1-[(4-methyl­phen­yl)sulfon­yl]-1H-pyrazole-4-carboxyl­ate

PubMed Central

Elgazwy, Abdel-Sattar S. Hamad; Nassar, Ibrahim F.; Jones, Peter G.

2013-01-01

In the title mol­ecule, C13H15N3O4S, the benzene and pyrazole rings are inclined to each other at 77.48 (3)°. Two amino H atoms are involved in bifurcated hydrogen bonds, viz. intra­molecular N—H⋯O and inter­molecular N—H⋯O(N). The inter­molecular hydrogen bonds link the mol­ecules related by translation in [100] into chains. A short distance of 3.680 (3) Å between the centroids of benzene and pyrazole rings from neighbouring mol­ecules shows the presence of π–π inter­actions, which link the hydrogen-bonded chains into layers parallel to the ab plane. PMID:24427020

Discovery of 5-Amino- N -(1 H -pyrazol-4-yl)pyrazolo[1,5- a ]pyrimidine-3-carboxamide Inhibitors of IRAK4

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

Lim, Jongwon; Altman, Michael D.; Baker, James

2015-06-11

Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential signal transducer downstream of the IL-1R and TLR superfamily, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of 5-amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamides was developed via sequential modifications to the 5-position of the pyrazolopyrimidine ring and the 3-position of the pyrazole ring. Replacement of substituents responsible for poor permeability and improvement of physical properties guided by cLogD led to the identification of IRAK4 inhibitors with excellent potency, kinase selectivity, and pharmacokinetic properties suitable for oral dosing.

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides.

PubMed

Du, Shijie; Tian, Zaimin; Yang, Dongyan; Li, Xiuyun; Li, Hong; Jia, Changqing; Che, Chuanliang; Wang, Mian; Qin, Zhaohai

2015-05-08

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

Metal-Organic Frameworks of Pyrazolate Derivatives: Synthesis and Applications for Chemical Sensing, Gas Separation, and Catalysis

NASA Astrophysics Data System (ADS)

Kivi, Charlie Eric William

In this work we examine the structure and applications of metal-organic frameworks (MOFs) synthesized from pyrazolate derivatives. In total, six pyrazolate ligands were examined: 4-(4-(3,5-dimethyl-1H-pyrazol-4-yl)phenyl)pyridine (HL), 1,1'-methylenebis(3,5-dimethyl-1H-pyrazolyl-4-carboxylic acid) (H2BPM), triethyl-1,1',1''-methanetriyltris(3,5-dimethyl-1H-pyrazole-4-carboxylate) (TPM-1), triethyl-4,4',4''-(methanetriyltris[3,5-dimethyl-1H-pyrazole-1,4-diyl])tribenzoate (TPM-2), 1,1',1'',1'''-(propane-1,1,3,3-tetrayl)tetrakis(3,5-dimethyl-1H-pyrazole-4-carboxylic acid) (H4TPP), tetraethyl-1,1',1'',1'''-(1,4-phenylenebis[methanetriyl]) tetrakis(3,5-dimethyl-1H-pyrazole-4-carboxylate)pyridinephenylpyrazole ( TPX). These ligands were used to synthesize a variety of MOFs that were subsequently investigated for luminescent sensing, gas storage, and catalytic performance. In Chapter 2, three MOFs synthesized from the reaction of HL and CuX (X = Br, I) were investigated. These materials were found to form MOFs which contained the luminescent trinuclear Cu(I) pyrazolate unit. Only CuBr and HL alone resulted in a MOF of sufficient purity and stability to permit evaluation as a luminescent sensor. Experiments with various volatile organic compounds revealed turn-on (luminescence enhancement) behaviour for ethyl acetate, pentane, and benzene and turn-off (luminescence quenching) behaviour for diethyl ether and chloroform for this material. In Chapters 3 and 4, ten MOFs are described. These were synthesized from H2BPM and metal-acetate salts. Chapter 3 encompassed two MOFs: [Ni(BPM)]n·xDMSO and [Cd(BPM)]n·xDMSO. These MOFs are isostructural, microporous materials. Evacuation of the pores led to collapse of the [Cd(BPM)]n·xDMSO material but [Ni(BPM)]n·xDMSO proved to be permanently porous. Further investigations revealed [Ni(BPM)] n·xDMSO selectively adsorbed methane over nitrogen indicating it may serve as a porous material for coal mine methane capture. Chapter 4 investigated the many other structures H2BPM can assume in the presence of manganese, cobalt, iron, copper, and europium. Cobalt in particular proved highly tunable with 4 separate structures being synthesized such as [Co2(BPM)2(H2 O)4(Bpy)0.5]n·2DMF·2(H 2O). This was achieved through varying the synthetic conditions. [Co 2(BPM)2(H2O)4(Bpy) 0.5]n·2DMF·2(H2O)and [Eu( BPM)(OAc)]n were further investigated for the oxidation of olefins and luminescence respectively. In Chapter 5, metal complexes Mo(TPM-1)(CO)3, Mo(TPM-2)(CO)3, Pd2(H4TPP )Cl4, and Pd2(TPX)Cl4 were synthesized. The catalytic performance of Mo(TPM-1)(CO) 3 was evaluated and found to be effective for the oxidation of olefins. MOF synthesis was attempted with all four compounds but was ultimately unsuccessful. Although one MOF was produced from Mo(TPM-1)(CO)3, large scale synthesis was not possible preventing full investigation of its properties.

Evaluation of Pressure Pain Threshold as a Measure of Perceived Stress and High Job Strain.

PubMed

Hven, Lisbeth; Frost, Poul; Bonde, Jens Peter Ellekilde

2017-01-01

To investigate whether pressure pain threshold (PPT), determined by pressure algometry, can be used as an objective measure of perceived stress and job strain. We used cross-sectional base line data collected during 1994 to 1995 within the Project on Research and Intervention in Monotonous work (PRIM), which included 3123 employees from a variety of Danish companies. Questionnaire data included 18 items on stress symptoms, 23 items from the Karasek scale on job strain, and information on discomfort in specified anatomical regions was also collected. Clinical examinations included pressure pain algometry measurements of PPT on the trapezius and supraspinatus muscles and the tibia. Associations of stress symptoms and job strain with PPT of each site was analyzed for men and women separately with adjustment for age body mass index, and discomfort in the anatomical region closest to the point of pressure algometry using multivariable linear regression. We found significant inverse associations between perceived stress and PPT in both genders in models adjusting for age and body mass index: the higher level of perceived stress, the lower the threshold. For job strain, associations were weaker and only present in men. In men all associations were attenuated when adjusting for reported discomfort in regions close to the site of pressure algometry. The distributions of PPT among stressed and non-stressed persons were strongly overlapping. Despite significant associations between perceived stress and PPT, the discriminative capability of PPT to distinguish individuals with and without stress is low. PPT measured by pressure algometry seems not applicable as a diagnostic tool of a state of mental stress.

Effectiveness of PowerPoint-Based Lectures across Different Business Disciplines: An Investigation and Implications

ERIC Educational Resources Information Center

Burke, Lisa A.; James, Karen; Ahmadi, Mohammad

2009-01-01

The authors investigated business faculty members' degree of Power-Point (PPT) use across different functional areas in a business program and their use of specific PPT features. The authors also examined students' perceptions of PPT's effectiveness across different business courses (e.g., accounting, economics, management, business law,…

Irreversibility of Asymptotic Entanglement Manipulation Under Quantum Operations Completely Preserving Positivity of Partial Transpose.

PubMed

Wang, Xin; Duan, Runyao

2017-11-03

We demonstrate the irreversibility of asymptotic entanglement manipulation under quantum operations that completely preserve the positivity of partial transpose (PPT), resolving a major open problem in quantum information theory. Our key tool is a new efficiently computable additive lower bound for the asymptotic relative entropy of entanglement with respect to PPT states, which can be used to evaluate the entanglement cost under local operations and classical communication (LOCC). We find that for any rank-two mixed state supporting on the 3⊗3 antisymmetric subspace, the amount of distillable entanglement by PPT operations is strictly smaller than one entanglement bit (ebit) while its entanglement cost under PPT operations is exactly one ebit. As a by-product, we find that for this class of states, both the Rains's bound and its regularization are strictly less than the asymptotic relative entropy of entanglement. So, in general, there is no unique entanglement measure for the manipulation of entanglement by PPT operations. We further show a computable sufficient condition for the irreversibility of entanglement distillation by LOCC (or PPT) operations.

Pulsed Plasma Thrusters for Small Spacecraft Attitude Control

NASA Technical Reports Server (NTRS)

McGuire, Melissa L.; Myers, Roger M.

1996-01-01

Pulsed plasma thrusters (PPT's) are a new option for attitude control of a small spacecraft and may result in reduced attitude control system (ACS) mass and cost. The primary purpose of an ACS is to orient the spacecraft configuration to the desired accuracy in inertial space. The ACS functions for which the PPT system will be analyzed include disturbance torque compensation and slewing maneuvers such as sun acquisition for which the small impulse bit and high specific impulse of the PPT offers unique advantages. The NASA Lewis Reserach Center (LeRC) currently has a contracted flight PPT system development program in place with Olin Aerospace and a delivery date of October 1997. The PPT system in this study are based upon the work being done under the NASA LeRC program. Analysis of the use of PPT's for ACS showed that the replacement of the standard momentum wheels and torque rods systems with a PTT system to perform the altitude control maneuvers on a small low Earth orbiting spacecraft reduced the ACS mass by 50 to 75 percent with no increase in required power level over comparable wheel-based systems.

Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation.

PubMed

Chavolla-Calderón, Mara; Bayer, Meggan K; Fontán, J Julio Pérez

2003-04-01

Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex-mediated and stretch-mediated injuries. Reconstitution of PPT-A gene-deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene-deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract.

Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation

PubMed Central

Chavolla-Calderón, Mara; Bayer, Meggan K.; Fontán, J. Julio Pérez

2003-01-01

Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex–mediated and stretch-mediated injuries. Reconstitution of PPT-A gene–deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene–deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract. PMID:12671046

Concentrated sodium chloride brine solutions as an additional treatment for preventing the introduction of nonindigenous species in the ballast tanks of ships declaring no ballast on board.

PubMed

Santagata, Scott; Bacela, Karolina; Reid, David F; Mclean, Kevin A; Cohen, Jill S; Cordell, Jeffery R; Brown, Christopher W; Johengen, Thomas H; Ruiz, Gregory M

2009-02-01

Currently, seawater flushing is the only management strategy for reducing the number of viable organisms in residual sediments and water of ballast tanks of vessels declaring no ballast on board (NOBOB) that traffic ports of the eastern United States. Previously, we identified several species of freshwater and brackish-water peracarid crustaceans able to survive the osmotic shock that occurs during open-ocean ballast water exchange and, potentially, to disperse over long distances via ballasted ships and NOBOB vessels. We tested the efficacy of concentrated sodium chloride brine solutions as an additional treatment for eradicating the halotolerant taxa often present in the ballast tanks of NOBOB ships. The lowest brine treatments (30 ppt for 1 h) caused 100% mortality in several species of cladocerans and copepods collected from oligohaline habitats. Several brackish-water peracarid crustaceans, however, including some that can survive in freshwater as well, required higher brine concentrations and longer exposure durations (45-60 ppt for 3-24 h). The most resilient animals were widely introduced peracarid crustaceans that generally prefer mesohaline habitats but do not tolerate freshwater (required brine treatments of 60-110 ppt for 3-24 h). Brine treatments (30 ppt) also required less time to cause 100% mortality for eight taxa compared with treatments using 34 ppt seawater. Based on these experiments and published data, we present treatment strategies for the ballast tank biota often associated with NOBOB vessels entering the Great Lakes region. We estimate the lethal dosage of brine for 95% of the species in our experiments to be 110 ppt (95% confidence interval, 85-192 ppt) when the exposure time is 1 h and 60 ppt (95% confidence interval, 48-98 ppt) when the exposure duration is 6 h or longer.

Gene encoding prolactin in cinnamon clownfish Amphiprion melanopus and its expression upon acclimation to low salinities

PubMed Central

2013-01-01

Background Prolactin (PRL) is a key hormone for osmoregulation in fish. Levels of PRL in the pituitary gland and plasma ion composition of clownfish seem to change to regulate their hydromineral balance during adaptation to waters of different salinities. In order to understand osmoregulatory mechanism and its association with growth performance and PRL in fish, the gene encoding PRL and its expression level in cinnamon clownfish Amphiprion melanopus upon acclimation to low salinity was analyzed. Results The PRL gene of A. melanopus encoded a protein of 212 amino acid residues comprised of a putative signal peptide of 24 amino acids and a mature protein of 188 amino acids. Analysis of growth performance under different salinities of 34, 25, 15, and 10 ppt indicated that cinnamon clownfish could survive under salinities as low as 10 ppt. A higher rate of growth was observed at the lower salinities as compared to that of 34 ppt. Upon shifting the salinity of the surrounding water from 34 ppt to 15 ppt, the level of the PRL transcripts gradually increased to reach the peak level until 24 h of acclimation at 15 ppt, but decreased back as adaptation continued to 144 h. In contrast, levels of plasma Na+, Cl-, and osmolality decreased at the initial stage (4–8 h) of acclimation at 15 pt but increased back as adaptation continued till 144 h. Conclusion Cinnamon clownfish could survive under salinities as low as 10 ppt. Upon shifting the salinity of the surrounding water from 34 ppt to 15 ppt, the level of the PRL transcripts gradually increased during the initial stage of acclimation but decreased back to the normal level as adaptation continued. An opposite pattern of changes - decrease at the beginning followed by an increase - in the levels of plasma Na+, Cl-, and osmolality was found upon acclimation to low salinity. The results suggest an involvement of PRL in the processes of osmoregulation and homeostasis in A. melanopus. PMID:23276106

Gene encoding prolactin in cinnamon clownfish Amphiprion melanopus and its expression upon acclimation to low salinities.

PubMed

Noh, Gyeong Eon; Rho, Sum; Chang, Yong Jin; Min, Byung Hwa; Kim, Jong-Myoung

2013-01-01

Prolactin (PRL) is a key hormone for osmoregulation in fish. Levels of PRL in the pituitary gland and plasma ion composition of clownfish seem to change to regulate their hydromineral balance during adaptation to waters of different salinities. In order to understand osmoregulatory mechanism and its association with growth performance and PRL in fish, the gene encoding PRL and its expression level in cinnamon clownfish Amphiprion melanopus upon acclimation to low salinity was analyzed. The PRL gene of A. melanopus encoded a protein of 212 amino acid residues comprised of a putative signal peptide of 24 amino acids and a mature protein of 188 amino acids. Analysis of growth performance under different salinities of 34, 25, 15, and 10 ppt indicated that cinnamon clownfish could survive under salinities as low as 10 ppt. A higher rate of growth was observed at the lower salinities as compared to that of 34 ppt. Upon shifting the salinity of the surrounding water from 34 ppt to 15 ppt, the level of the PRL transcripts gradually increased to reach the peak level until 24 h of acclimation at 15 ppt, but decreased back as adaptation continued to 144 h. In contrast, levels of plasma Na+, Cl-, and osmolality decreased at the initial stage (4-8 h) of acclimation at 15 pt but increased back as adaptation continued till 144 h. Cinnamon clownfish could survive under salinities as low as 10 ppt. Upon shifting the salinity of the surrounding water from 34 ppt to 15 ppt, the level of the PRL transcripts gradually increased during the initial stage of acclimation but decreased back to the normal level as adaptation continued. An opposite pattern of changes - decrease at the beginning followed by an increase - in the levels of plasma Na+, Cl-, and osmolality was found upon acclimation to low salinity. The results suggest an involvement of PRL in the processes of osmoregulation and homeostasis in A. melanopus.

Variation in salinity tolerance among larval anurans: implications for community composition and the spread of an invasive, non-native species

USGS Publications Warehouse

Brown, Mary E.; Walls, Susan C.

2013-01-01

Amphibians in freshwater coastal wetlands periodically experience acute exposure to salinity from hurricane-related overwash events, as well as chronic exposure associated with rising sea levels. In a comparative experimental approach, we examined whether seven species of anuran amphibians vary in their tolerance to changes in salinity. In a laboratory study, we exposed larval Hyla cinerea (Green Treefrog), H. squirella (Squirrel Treefrog), Lithobates catesbeianus (American Bullfrog), L. sphenocephalus (Southern Leopard Frog), Anaxyrus terrestris (Southern Toad), and Gastrophryne carolinensis (Eastern Narrow-mouthed Toad) from an inland population in north central Florida, USA, and Osteopilus septentrionalis (Cuban Treefrog) tadpoles from an inland population in southwest Florida, to acute salinity for 72 h. For each species, we replicated trials in which tadpoles were exposed to salinities of 0.2 (control), 5, 10, 12, 14, and 16 ppt. For all species, tadpoles reared in the control and 5 ppt treatments had 96.7–100% survival. No individuals of G. carolinensis survived at salinities exceeding 5 ppt and no individuals of any species survived in the 14 or 16 ppt treatments. For all other native species, survival at 10 ppt ranged from 46.7 to 80%, but declined to 0% at 12 ppt (except for H. cinerea, of which only 3.3% survived at 12 ppt). In contrast, all individuals of the invasive, non-native O. septentrionalis survived exposure to a salinity of 10 ppt, and survival in this species remained relatively high at 12 ppt. Our results illustrate that the non-native O. septentrionalis has a higher salinity tolerance than the native species tested, which may contribute to its invasion potential. Moreover, species commonly associated with coastal freshwater wetlands differ in their salinity tolerances, suggesting that salt water intrusion due to storm surges and sea level rise may affect the species composition of these ecosystems.

Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy

PubMed Central

Wang, Tianqi; Zhang, Bo; Liu, Chunxi; Zhang, Na

2017-01-01

Gene therapy combined with chemotherapy to achieve synergistic therapeutic effects has been a hot topic in recent years. In this project, the human tumor necrosis factor-related apoptosis-inducing ligand-encoding plasmid gene (TRAIL) and doxorubicin (Dox)-coloaded multi-functional nanocarrier was constructed based on the theory of circulation, accumulation, internalization, and release. Briefly, polyethyleneimine (PEI) was selected as skeleton material to synthesize PEI–polyethylene glycol (PEG)–TAT (PPT). Dox was conjugated to PEI using C6-succinimidyl 6-hydrazinonicotinate acetone hydrazone (C6-SANH), and a pH-sensitive Dox-PEI (DP) conjugate was obtained. Then, intracellular cationic pH-sensitive cellular assistant PPT and DP were mixed to condense TRAIL, and TRAIL–Dox coloaded PPT/DP/TRAIL (PDT) nanocarriers were obtained by one-step assembly. TRAIL was completely condensed by DP or PPT when mass ratios (DP/PPT to TRAIL) were up to 100:64, which indicated that DP and PPT could be mixed at any ratio for TRAIL condensation. The intracellular uptake rate of PDT was enhanced (P<0.05) when the contents of PPT in PPT+DP increased from 0 to 30%. Free Dox and TRAIL-loaded nanocarriers (PPT/C6-SANH-PEI/TRAIL [PCT]) were selected as controls to verify the synergistic antitumor effects of PDT. Compared with free TRAIL, TRAIL-protein expression was upregulated by PDT and PCT on Western blotting assays. The in vitro cytotoxicity of PDT was significantly enhanced compared to free Dox and PCT (P<0.01). Furthermore, murine PDT nanocarriers showed higher in vivo antitumor ability than both the Dox group (P<0.05) and the murine PCT group (P<0.05). These results indicated that the TRAIL + Dox synergistic antitumor effect could be achieved by PDT, which paves the way to gene–drug combination therapy for cancer. PMID:29263663

Physiological short-term response to sudden salinity change in the Senegalese sole (Solea senegalensis).

PubMed

Herrera, Marcelino; Aragão, Cláudia; Hachero, Ismael; Ruiz-Jarabo, Ignacio; Vargas-Chacoff, Luis; Mancera, Juan Miguel; Conceição, Luis E C

2012-12-01

The physiological responses of Senegalese sole to a sudden salinity change were investigated. The fish were first acclimated to an initial salinity of 37.5 ppt for 4 h. Then, one group was subjected to increased salinity (55 ppt) while another group was subjected to decreased salinity (5 ppt). The third group (control group) remained at 37.5 ppt. We measured the oxygen consumption rate, osmoregulatory (plasma osmolality, gill and kidney Na(+),K(+)-ATPase activities) and stress (plasma cortisol and metabolites) parameters 0.5 and 3 h after transfer. Oxygen consumption at both salinities was higher than for the control at both sampling times. Gill Na(+),K(+)-ATPase activity was significantly higher for the 55 ppt salinity at 0.5 h. Plasma osmolality decreased in the fish exposed to 5 ppt at the two sampling times but no changes were detected for high salinities. Plasma cortisol levels significantly increased at both salinities, although these values declined in the low-salinity group 3 h after transfer. Plasma glucose at 5 ppt salinity did not vary significantly at 0.5 h but decreased at 3 h, while lactate increased for both treatments at the first sampling time and returned to the control levels at 3 h. Overall, the physiological response of S. senegalensis was immediate and involved a rise in oxygen consumption and plasma cortisol values as well as greater metabolite mobilization at both salinities.

The combined influence of sub-optimal temperature and salinity on the in vitro viability of Perkinsus marinus, a protistan parasite of the eastern oyster Crassostrea virginica

USGS Publications Warehouse

La Peyre, M.K.; Casas, S.M.; Gayle, W.; La Peyre, Jerome F.

2010-01-01

Perkinsus marinus is a major cause of mortality in eastern oysters along the Gulf of Mexico and Atlantic coasts. It is also well documented that temperature and salinity are the primary environmental factors affecting P. marinus viability and proliferation. However, little is known about the effects of combined sub-optimal temperatures and salinities on P. marinus viability. This in vitro study examined those effects by acclimating P. marinus at three salinities (7, 15, 25. ppt) to 10 ??C to represent the lowest temperatures generally reached in the Gulf of Mexico, and to 2 ??C to represent the lowest temperatures reached along the mid-Atlantic coasts and by measuring changes in cell viability and density on days 1, 30, 60 and 90 following acclimation. Cell viability and density were also measured in 7. ppt cultures acclimated to each temperature and then transferred to 3.5. ppt. The largest decreases in cell viability occurred only with combined low temperature and salinity, indicating that there is clearly a synergistic effect. The largest decreases in cell viability occurred only with both low temperature and salinity after 30. days (3.5. ppt, 2 ??C: 0% viability), 60. days (3.5. ppt, 10 ??C: 0% viability) and 90. days (7. ppt, 2 ??C: 0.6 ?? 0.7%; 7. ppt, 10 ??C: 0.2 ?? 0.2%). ?? 2010 .

Insights from the docking and molecular dynamics simulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis.

PubMed

Rohini, Karunakaran; Srikumar, Padmalayam Sadanandan

2013-01-01

A great challenge is posed to the treatment of tuberculosis due to the evolution of multidrug-resistant (MDR) and extensively drugresistant (XDR) strains of Mycobacterium tuberculosis in recent times. The complex cell envelope of the bacterium contains unusual structures of lipids which protects the bacterium from host enzymes and escape immune response. To overcome the drug resistance, targeting "drug targets" which have a critical role in growth and virulence factor is a novel approach for better tuberculosis treatment. The enzyme Phosphopantetheinyl transferase (PptT) is an attractive drug target as it is primarily involved in post translational modification of various types-I polyketide synthases and assembly of mycobactin, which is required for lipid virulence factors. Our in silico studies reported that the structural model of M.tuberculosis PptT characterizes the structure-function activity. The refinement of the model was carried out with molecular dynamics simulations and was analyzed with root mean square deviation (RMSD), and radius of gyration (Rg). This confirmed the structural behavior of PptT in dynamic system. Molecular docking with substrate coenzyme A (CoA) identified the binding pocket and key residues His93, Asp114 and Arg169 involved in PptT-CoA binding. In conclusion, our results show that the M.tuberculosis PptT model and critical CoA binding pocket initiate the inhibitor design of PptT towards tuberculosis treatment.

21 CFR 73.3122 - 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one. 73.3122 Section 73.3122 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical...

21 CFR 73.3122 - 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one. 73.3122 Section 73.3122 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical...

21 CFR 73.3122 - 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one. 73.3122 Section 73.3122 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical...

21 CFR 73.3122 - 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one. 73.3122 Section 73.3122 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical...

21 CFR 73.3122 - 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false 4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one. 73.3122 Section 73.3122 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical...

Hit-to-lead optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as a novel class of EP1 receptor antagonists.

PubMed

Atobe, Masakazu; Naganuma, Kenji; Kawanishi, Masashi; Morimoto, Akifumi; Kasahara, Ken-ichi; Ohashi, Shigeki; Suzuki, Hiroko; Hayashi, Takahiko; Miyoshi, Shiro

2013-11-15

We describe a medicinal chemistry approach to generate a series of 2-(1H-pyrazol-1-yl)thiazole compounds that act as selective EP1 receptor antagonists. The obtained results suggest that compound 12 provides the best EP1 receptor antagonist activity and demonstrates good oral pharmacokinetics. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of Pressure Pain Threshold as a Measure of Perceived Stress and High Job Strain

PubMed Central

Hven, Lisbeth; Frost, Poul

2017-01-01

Objective To investigate whether pressure pain threshold (PPT), determined by pressure algometry, can be used as an objective measure of perceived stress and job strain. Methods We used cross-sectional base line data collected during 1994 to 1995 within the Project on Research and Intervention in Monotonous work (PRIM), which included 3123 employees from a variety of Danish companies. Questionnaire data included 18 items on stress symptoms, 23 items from the Karasek scale on job strain, and information on discomfort in specified anatomical regions was also collected. Clinical examinations included pressure pain algometry measurements of PPT on the trapezius and supraspinatus muscles and the tibia. Associations of stress symptoms and job strain with PPT of each site was analyzed for men and women separately with adjustment for age body mass index, and discomfort in the anatomical region closest to the point of pressure algometry using multivariable linear regression. Results We found significant inverse associations between perceived stress and PPT in both genders in models adjusting for age and body mass index: the higher level of perceived stress, the lower the threshold. For job strain, associations were weaker and only present in men. In men all associations were attenuated when adjusting for reported discomfort in regions close to the site of pressure algometry. The distributions of PPT among stressed and non-stressed persons were strongly overlapping. Conclusions Despite significant associations between perceived stress and PPT, the discriminative capability of PPT to distinguish individuals with and without stress is low. PPT measured by pressure algometry seems not applicable as a diagnostic tool of a state of mental stress. PMID:28052089

An objective measure of physical function of elderly outpatients. The Physical Performance Test.

PubMed

Reuben, D B; Siu, A L

1990-10-01

Direct observation of physical function has the advantage of providing an objective, quantifiable measure of functional capabilities. We have developed the Physical Performance Test (PPT), which assesses multiple domains of physical function using observed performance of tasks that simulate activities of daily living of various degrees of difficulty. Two versions are presented: a nine-item scale that includes writing a sentence, simulated eating, turning 360 degrees, putting on and removing a jacket, lifting a book and putting it on a shelf, picking up a penny from the floor, a 50-foot walk test, and climbing stairs (scored as two items); and a seven-item scale that does not include stairs. The PPT can be completed in less than 10 minutes and requires only a few simple props. We then tested the validity of PPT using 183 subjects (mean age, 79 years) in six settings including four clinical practices (one of Parkinson's disease patients), a board-and-care home, and a senior citizens' apartment. The PPT was reliable (Cronbach's alpha = 0.87 and 0.79, interrater reliability = 0.99 and 0.93 for the nine-item and seven-item tests, respectively) and demonstrated concurrent validity with self-reported measures of physical function. Scores on the PPT for both scales were highly correlated (.50 to .80) with modified Rosow-Breslau, Instrumental and Basic Activities of Daily Living scales, and Tinetti gait score. Scores on the PPT were more moderately correlated with self-reported health status, cognitive status, and mental health (.24 to .47), and negatively with age (-.24 and -.18). Thus, the PPT also demonstrated construct validity. The PPT is a promising objective measurement of physical function, but its clinical and research value for screening, monitoring, and prediction will have to be determined.

Evapotranspiration Dynamics and Effects on Groundwater Recharge and Discharge at the Tuba City, Arizona, Disposal Site

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

None, None

The U.S. Department of Energy Office of Legacy Management is evaluating groundwater flow and contaminant transport at a former uranium mill site near Tuba City, Arizona. We estimated effects of temporal and spatial variability in evapotranspiration (ET) on recharge and discharge within a groundwater model domain (GMD) as part of this evaluation. We used remote sensing algorithms and precipitation (PPT) data to estimate ET and the ET/PPT ratios within the 3531 hectare GMD. For the period from 2000 to 2012, ET and PPT were nearly balanced (129 millimeters per year [mm yr -1] and 130 mm yr -1, respectively; ET/PPTmore » = 0.99). However, seasonal and annual variability in ET and PPT were out of phase, and spatial variability in vegetation differentiated discharge and recharge areas within the GMD. Half of ET occurred during spring and early summer when PPT was low, and about 70% of PPT arriving in fall and winter was discharged as plant transpiration in the spring and summer period. Vegetation type and health had a significant effect on the site water balance. Plant cover and ET were significantly higher (1) during years of lighter compared to years of heavier grazing pressure, and (2) on rangeland protected from grazing compared to rangeland grazed by livestock. Heavy grazing increased groundwater recharge (PPT > ET over the 13-year period). Groundwater discharge (ET > PPT over the 13-year period) was highest in riparian phreatophyte communities but insignificant in desert phreatophyte communities impacted by heavy grazing. Grazing management in desert upland and phreatophyte communities may result in reduced groundwater recharge, increased groundwater discharge, and could be used to influence local groundwater flow.« less

Interaction of dopamine beta-mono-oxygenase with substituted imidazoles and pyrazoles. Catalysis and inhibition.

PubMed Central

Sirimanne, S R; Herman, H H; May, S W

1987-01-01

The interaction of dopamine beta-mono-oxygenase (DBM) with substrate analogues possessing either imidazole or pyrazole functionalities at the alkyl chain terminus was investigated. 1-(4-Hydroxybenzyl)imidazole (4-HOBI) is an active substrate for DBM, and it exhibits the expected ascorbate- and fumarate-dependencies and normal kinetic behaviour at concentrations up to 10 mM. 4-Hydroxybenzaldehyde was identified as the product formed from 4-HOBI on the basis of h.p.l.c. and g.c.-m.s. analysis, and its formation exhibits the expected 1:1 stoichiometry with O2 consumption. The 4-HOBI/DBM reaction is kinetically comparable with other DBM activities, and 4-HOBI is the first substrate analogue yet reported that exhibits substantial activity though lacking a terminal amino group. Introduction of a methyl substituent at the 2-position of the imidazole ring abolishes substrate activity, probably through a steric effect. 1-(4-Hydroxybenzyl)pyrazole, where imidazole is replaced by the isomeric pyrazole moiety, is a potent DBM inhibitor, and not a substrate. These results represent the first report of an active heterocyclic substrate or inhibitor for this enzyme, and establish the basis for the design of new classes of DBM substrates and inhibitors. PMID:3593236

Computational study of antimalarial pyrazole alkaloids from Newbouldia laevis.

PubMed

Mammino, Liliana; Bilonda, Mireille K

2014-11-01

Six pyrazole alkaloids of natural origin (isolated from Newbouldia laevis in DR Congo) that exhibit antimalarial activity-namely withasomnine, newbouldine, and their para-hydroxy and -methoxy derivatives-were investigated theoretically. The nitro derivatives of withasomnine and para-hydroxywithasomnine, which show enhanced antimalarial activity, were also studied in this manner. A thorough conformational study was performed in vacuo and in three solvents (chloroform, acetonitrile, and water) at different levels of theory (HF, DFT/B3LYP, and MP2) using different basis sets. Adducts with explicit water molecules were calculated at the HF level. Due to the rigidity of the pyrazole system and the benzene ring, the only factor that influences the energies of withasomnine and newbouldine is the relative orientation of the two ring systems; two orientations are equally preferred. The para-hydroxy and -methoxy derivatives show a preference for a planar orientation of the OH and OC bonds. The main stabilizing influence on the nitro derivative of para-hydroxywithasomnine is the intramolecular hydrogen bond between the two consecutive functional groups. The calculated adducts show the preferred arrangements of water molecules in the vicinity of the N atoms of the pyrazole system and, for the derivatives, also in the vicinity of the substituents on the benzene ring.

Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

PubMed Central

Gajanan Khanage, Shantaram; Raju, Appala; Baban Mohite, Popat; Bhanudas Pandhare, Ramdas

2013-01-01

Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. Conclusion: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported. PMID:24312806

(Citric acid–co–polycaprolactone triol) polyester

PubMed Central

Thomas, Lynda V.; Nair, Prabha D.

2011-01-01

Tissue engineering holds enormous challenges for materials science, wherein the ideal scaffold to be used is expected to be biocompatible, biodegradable and possess mechanical and physical properties that are suitable for target application. In this context, we have prepared degradable polyesters in different ratios by a simple polycondensation technique with citric acid and polycaprolactone triol. Differential scanning calorimetry indicated that the materials were amorphous based the absence of a crystalline melting peak and the presence of a glass transition temperature below 37°C. These polyesters were found to be hydrophilic and could be tailor-made into tubes and films. Porosity could also be introduced by addition of porogens. All the materials were non-cytotoxic in an in vitro cytotoxicity assay and may degrade via hydrolysis to non-toxic degradation products. These polyesters have potential implications in the field of soft tissue engineering on account of their similarity of properties. PMID:23507730

Methyl-3,4-dihydroxybenzoate and 9-10-dihydrophenanthrene-2,4,7-triol two phenolic compounds from Dioscorea alata L. and their antioxidant activity

NASA Astrophysics Data System (ADS)

Aminah, N. S.; Yulvia, A.; Tanjung, M.

2017-09-01

Two phenolic compounds namely: methyl-3,4-dihydroxybenzoate (1) and 9,10-dihydrophenanthrene-2,4,7-triol (2) had been isolated for the first time from the tuber of Dioscorea alata L. The extraction of two compounds were done by maceration method using methanol as solvent, followed by partition with n-hexane and ethyl acetate. The ethyl acetate extract was separated and purified using various chromatographic techniques yielded pure compounds. The structure of isolated compounds were determined based on spectroscopic data, including UV-Vis, 1D and 2D NMR spectra. Compounds (1), (2) and ascorbic acid as a comparator were evaluated for their antioxidant properties against DPPH, showing their IC50 were 9,41 ± 0,08; 23,52 ± 0,05; and 10,95 ± 0,08 ppm, respectively.

17β-Estradiol inhibits TNF-α-induced proliferation and migration of vascular smooth muscle cells via suppression of TRAIL.

PubMed

Li, Hengchang; Cheng, Yang; Simoncini, Tommaso; Xu, Shiyuan

2016-07-01

Atherosclerosis is an inflammatory disease and involves migration of vascular smooth muscle cells (VSMCs). Estrogen inhibits VSMCs migration, while the underlying mechanism remains to be revealed. Recent years, there is emerging evidence showing that TNF-related apoptosis-inducing ligand (TRAIL) increases proliferation and migration of VSMCs. In this study, we investigated the regulatory effect of estrogen on TRAIL expression in VSMCs. TNF-α greatly enhanced TRAIL protein expression and stimulated VSMCs proliferation and migration. This effect was partially inhibited by the addition of TRAIL neutralizing antibody, suggesting that TRAIL is important in TNF-α-induced migration. 17β-estradiol (E2) inhibited TRAIL expression under TNF-α stimulation in a time- and concentration-dependent manner. This effect was was mimicked by ERα agonist 4',4″,4‴-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT), but not ERβ agonist 2,3-bis-(4-hydroxyphenyl)-propionitrile (DPN), indicating that ERα is involved in this action. TNF-α led to nuclear factor kappa B (NF-κB) p65 phosphorylation and the inhibitor pyrrolidine dithiocarbama (PDTC) inhibited TRAIL expression, suggesting that NF-κB signaling is crucial for TARIL production. E2 suppressed p65 phosphorylation in VSMCs and the overexpression of p65 subunit reversed the inhibitory effect of E2 on TRAIL expression and cell proliferation and migration. Taken together, our results indicate that E2 inhibits VSMCs proliferation and migration by downregulation of TRAIL expression via suppression of NF-κB pathway.

Plume Characterization of a One-Millipound Solid Teflon Pulsed Plasma Thruster, Phase 2

NASA Technical Reports Server (NTRS)

Rudolph, L. K.; Harstad, K. G.; Pless, L. C.; Jones, R. M.

1979-01-01

Measurements of the pulsed plasma thruster (PPT) plume upstream mass flux were made in the Molecular Sink (MOLSINK) vacuum facility in order to minimize the plume-tank wall reflected mass flux. Using specially designed collimators on 4 rows of Quartz Crystal Microbalanced (QCMs) mounted on a support extending radially away from the plume axis, measurements were made of the mass flux originating in a thin slice of the PPT primary plume at an arbitrary dip angle with respect to the thruster axis. The measured and analytically corrected mass flux from particles reflected from the MOLSINK walls was substracted from the collimated QCM measurements to improve their accuracy. These data were then analytically summed over dip angle to estimate the total plume backflow upstream of the thruster nozzle. The results indicate that the PPT backflow is of order 10 to the minus 10th power g/square cm/pulse in the region from 38 to 86 cm from the PPT axis in the nozzle exit plane. This flux drops with the square of the radial distance from the PPT axis and is comparable to the backflow of an 8 cm ion thruster, which has performance characteristics similar to those of the PPT.

Comparison of bile salt/phosphatidylcholine mixed micelles in solubilization to sterols and stability.

PubMed

Guo, Qin; Cai, Jie; Li, Pengyu; Xu, Dongling; Ni, Xiaomin; Wen, Hui; Liu, Dan; Lin, Suizhen; Hu, Haiyan

2016-01-01

Androst-3β,5α,6β-triol (Triol) is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC) after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of drug-loaded mixed micelles.

Clinical manifestations of postpartum thyroid disease.

PubMed

Lazarus, J H

1999-07-01

Postpartum thyroiditis (PPT) occurs in 5%-9% of unselected postpartum women; hyperthyroidism and hypothyroidism develop, the latter being permanent, in up to 25 %-30% of women. PPT is strongly associated with antithyroid peroxidase (anti-TPO) antibodies, but 50% of anti-TPO positive women do not develop thyroid dysfunction. Symptom analysis has shown that lack of energy and irritability were the most frequent hyperthyroid symptoms whereas lack of energy, aches and pains, poor memory, dry skin, and cold intolerance were the significant hypothyroid features. Some of these symptoms were more frequently observed than in antibody-negative controls even when these patients were euthyroid and in anti-TPOAb positive women who did not develop PPT at all. The diagnosis of PPT is based on the observation of abnormal thyroid function tests in a postpartum anti-TPOAb-positive woman: transient hyperthyroidism occurs at 14 weeks and hypothyroidism at 19 weeks postpartum. Diffuse or multifocal hypoechogenicity of the thyroid is seen on echography and a thyroid destructive process is evidenced by an increase in serum thyroglobulin and urinary iodine excretion. In addition to the 25%-30% of women who develop permanent hypothyroidism at 3 years, recent data indicate that 50% of women who have developed PPT will be hypothyroid 7-9 years later. The long-term risk is only 5% for those anti-TPOAb positive women not developing thyroid dysfunction postpartum. The risk of recurrent PPT is 70% if previous PPT was experienced and 25% if the patient was euthyroid after the first pregnancy.

Determination of 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and -furans at the part per trillion level in United States beef fat using high-resolution gas chromatography/high-resolution mass spectrometry

NASA Technical Reports Server (NTRS)

Ferrario, J.; Byrne, C.; McDaniel, D.; Dupuy, A. Jr; Harless, R.

1996-01-01

As part of the U.S. EPA Dioxin Reassessment Program, the 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and furans were measured at part per trillion (ppt) levels in beef fat collected from slaughter facilities in the United States. This is the first statistically designed national survey of these compounds in the U.S. beef supply. Analyte concentrations were determined by high-resolution gas chromatography/high-resolution mass spectrometry, using isotope dilution methodology. Method limits of detection on a whole weight basis were 0.05 ppt for TCDD and 0.10 ppt for TCDF, 0.50 ppt for the pentas (PeCDDs/PeCDFs)/hexas (HxCDDs/HxCDFs)/heptas (HpCDDs/HpCDFs), and 3.00 ppt for the octas (OCDD/OCDF). Method detection and quantitation limits were established on the basis of demonstrated performance criteria utilizing fortified samples rather than by conventional signal-to-noise or variability of response methods. The background subtraction procedures developed for this study minimized the likelihood of false positives and increased the confidence associated with reported values near the detection limits. Mean and median values for each of the 2,3,7,8-Cl-substituted dioxins and furans are reported, along with the supporting information required for their interpretation. The mean toxic equivalence values for the samples are 0.35 ppt (nondetects = 0) and 0.89 ppt (nondetects = 1/2 LOD).

Mesohaline submerged aquatic vegetation survey along the U.S. gulf of Mexico coast, 2000: A stratified random approach

USGS Publications Warehouse

Carter, J.; Merino, J.H.; Merino, S.L.

2009-01-01

Estimates of submerged aquatic vegetative (SAV) along the U.S. Gulf of Mexico (Gulf) generally focus on seagrasses. In 2000, we attempted a synoptic survey of SAV in the mesohaline (5-20 ppt) zone of estuarine and nearshore areas of the northeastern Gulf. Areas with SAV were identified from existing aerial 1992 photography, and a literature review was used to select those areas that were likely to experience mesohaline conditions during the growing season. In 2000, a drought year, we visited 217 randomly selected SAV beds and collected data on species composition and environmental conditions. In general, sites were either clearly polyhaline (2: 20 ppt) or oligohaline (S 5 ppt), with only five sites measuring between 5 and 20 ppt. Ruppia maritima L. (13-35 ppt, n = 28) was the only species that occurred in mesohaline salinities. Halodule wrightii Asch. occurred in 73% of the beds. The nonindigenous Myriophyllum spicatum L. was present in four locations with salinities below 3 ppt. No nonindigenous macroalgae were identified, and no nonindigenous angiosperms occurred in salinities above 3 ppt. Selecting sample locations based on historical salinity data was not a successful strategy for surveying SAV in mesohaline systems, particularly during a drought year. Our ability to locate SAV beds within 50 m of their aerially located position 8 yr later demonstrates some SAV stability in the highly variable conditions of the study area. ?? 2009 by the Marine Environmental Silences Consortium of Alabama.

A napthelene-pyrazol conjugate: Al(III) ion-selective blue shifting chemosensor applicable as biomarker in aqueous solution.

PubMed

Mukherjee, Manjira; Pal, Siddhartha; Lohar, Somenath; Sen, Buddhadeb; Sen, Supriti; Banerjee, Samya; Banerjee, Snehasis; Chattopadhyay, Pabitra

2014-10-07

A newly synthesized and crystalographically characterized napthelene–pyrazol conjugate, 1-[(5-phenyl-1H-pyrazole-3-ylimino)-methyl]-naphthalen-2-ol (HL) behaves as an Al(III) ion-selective chemosensor through internal charge transfer (ICT)-chelation-enhanced fluorescence (CHEF) processes in 100 mM HEPES buffer (water–DMSO 5:1, v/v) at biological pH with almost no interference of other competitive ions. This mechanism is readily studied from electronic, fluorimetric and (1)H NMR titration. The probe (HL) behaved as a highly selective fluorescent sensor for Al(III) ions as low as 31.78 nM within a very short response time (15–20 s). The sensor (HL), which has no cytotoxicity, is also efficient in detecting the distribution of Al(III) ions in HeLa cells via image development under fluorescence microscope.

A trisubstituted pyrazole derivative reduces DMBA-induced mammary tumor growth in rats by inhibiting estrogen receptor-α expression.

PubMed

Ananda, Hanumappa; Sharath Kumar, Kothanahally S; Sudhanva, Muddenahalli S; Rangappa, Shobith; Rangappa, Kanchugarakoppal S

2018-05-18

Aberrant expression of estrogen receptor alpha (ER-α) is observed in many pathological complications like breast cancer, endometrial cancer, and in osteoporosis. ER-α plays a vital role in the initiation and progression of breast cancer and confers chemo and radioresistance to the cancer cells by upregulating expression of anti-apoptotic proteins. The synthetic pyrazole derivative 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl)pyridine (compound 5d) displays significant cytotoxicity against mammary carcinoma cells. Molecular docking studies revealed that compound 5d binds to ligand binding domain of (ER-α). In vivo studies were carried out to investigate ER-α expression by immunohistochemistry and quantitative RT-PCR, which revealed reduction of ER-α in tumor cells upon treatment with compound 5d indicating its ER-α antagonistic effect. Our study ascertains compound 5d as a potent inhibitor of mammary carcinoma cells.

A Base-Resistant Metalloporphyrin Metal–Organic Framework for C–H Bond Halogenation

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

Lv, Xiu-Liang; Wang, Kecheng; Wang, Bin

A base-resistant porphyrin metal–organic framework (MOF), namely PCN-602 has been constructed with 12-connected [Ni 8(OH) 4(H 2O) 2Pz 12] (Pz = pyrazolate) cluster and a newly designed pyrazolate-based porphyrin ligand, 5,10,15,20-tetrakis(4-(pyrazolate-4-yl)phenyl)porphyrin under the guidance of the reticular synthesis strategy. Besides its robustness in hydroxide solution, PCN-602 also shows excellent stability in aqueous solutions of F –, CO 3 2–, and PO 4 3– ions. Interestingly, the Mn 3+-porphyrinic PCN-602, as a recyclable MOF catalyst, presents high catalytic activity for the C–H bond halogenation reaction in a basic system, significantly outperforming its homogeneous counterpart. For the first time, a porphyrinic MOFmore » was thus used as an efficient catalyst in a basic solution with coordinating anions, to the best of our knowledge.« less

Synthesis, crystal structures, fluorescence and xanthine oxidase inhibitory activity of pyrazole-based 1,3,4-oxadiazole derivatives

NASA Astrophysics Data System (ADS)

Qi, De-Qiang; Yu, Chuan-Ming; You, Jin-Zong; Yang, Guang-Hui; Wang, Xue-Jie; Zhang, Yi-Ping

2015-11-01

A series of pyrazole-based 1,3,4-oxadiazole derivatives were rationally designed and synthesized in good yields by following a convenient route. All the newly synthesized molecules were fully characterized by IR, 1H NMR and elemental analysis. Eight compounds were structurally determined by single crystal X-ray diffraction analysis. The fluorescence properties of all the compounds were investigated in dimethyl sulfoxide media. In addition, these newly synthesized compounds were evaluated for in vitro inhibitory activity against commercial enzyme xanthine oxidase (XO) by measuring the formation of uric acid from xanthine. Among the compounds synthesized and tested, 3d and 3e were found to be moderate inhibitory activity against commercial XO with IC50 = 72.4 μM and 75.6 μM. The studies gave a new insight in further optimization of pyrazole-based 1,3,4-oxadiazole derivatives with excellent fluorescence properties and XO inhibitory activity.

Pyrazole bridged dinuclear Cu(II) and Zn(II) complexes as phosphatase models: Synthesis and activity

NASA Astrophysics Data System (ADS)

Naik, Krishna; Nevrekar, Anupama; Kokare, Dhoolesh Gangaram; Kotian, Avinash; Kamat, Vinayak; Revankar, Vidyanand K.

2016-12-01

Present work describes synthesis of dibridged dinuclear [Cu2L2(μ2-NN pyr)(NO3)2(H2O)2] and [Zn2L(μ-OH)(μ-NNpyr)(H2O)2] complexes derived from a pyrazole based ligand bis(2-hydroxy-3-methoxybenzylidene)-1H-pyrazole-3,5-dicarbohydrazide. The ligand shows dimeric chelate behaviour towards copper against monomeric for zinc counterpart. Spectroscopic evidences affirm octahedral environment around the metal ions in solution state and non-electrolytic nature of the complexes. Both the complexes are active catalysts towards phosphomonoester hydrolysis with first order kcat values in the range of 2 × 10-3s-1. Zinc complex exhibited promising catalytic efficiency for the hydrolysis. The dinuclear complexes hydrolyse via Lewis acid activation, whereby the phosphate esters are preferentially bound in a bidentate bridging fashion and subsequent nucleophilic attack to release phosphate group.

Novel pyrazolyl-s-triazine derivatives, molecular structure and antimicrobial activity

NASA Astrophysics Data System (ADS)

Sharma, Anamika; Ghabbour, Hazem; Khan, Shams Tabrez; de la Torre, Beatriz G.; Albericio, Fernando; El-Faham, Ayman

2017-10-01

A new series of pyrazole-containing s-triazine derivatives were synthesized by reaction of the corresponding s-triazinyl hydrazine derivatives with acetylacetone in the presence of HClO4 or DMF/TEA. The former method allowed the preparation of the target products with higher yields. All compounds were fully characterized. X-ray single crystal diffraction for two representative compounds (4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine and N-benzyl-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine) was studied and the molecular structures were optimized using the DFT/B3LYP method. The structures were found to be in agreement with X-ray structures. The antimicrobial and antifungal activity of the prepared compounds were tested against the growth of several microorganisms.

Experimental and calculated structural parameters of 5-trihalomethyl-4,5-dihydro-1 H-pyrazole derivatives, novel analgesic agents

NASA Astrophysics Data System (ADS)

Machado, Pablo; Campos, Patrick T.; Lima, Glauber R.; Rosa, Fernanda A.; Flores, Alex F. C.; Bonacorso, Helio G.; Zanatta, Nilo; Martins, Marcos A. P.

2009-01-01

The crystal structures of four novel analgesic agents, methyl 5-hydroxy-3- or 4-methyl-5-trichloro[trifluoro]methyl-4,5-dihydro-1 H-pyrazole-1-carboxylate, have been determined by X-ray diffractometry. The data demonstrated that the molecular packing was stabilized mainly by O sbnd H⋯O hydrogen bonds of the 5-hydroxy and 1-carboxymethyl groups. The 4,5-dihydro-1 H-pyrazole rings were obtained as almost planar structures showing RMS deviation at a range of 0.0052-0.0805 Å. Additionally, computational investigation using semi-empirical AM1 and PM3 methods were performed to find a correlation between experimental and calculated geometrical parameters. The data obtained suggest that the structural data furnished by the AM1 method is in better agreement with those experimentally determined for the above compounds.

Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep.

PubMed

Shouse, M N; Siegel, J M

1992-01-31

Transection, lesion and unit recording studies have localized rapid eye movement (REM) sleep mechanisms to the pons. Recent work has emphasized the role of pontine cholinergic cells, especially those of the pedunculopontine tegmentum (PPT). The present study differentiated REM sleep deficits associated with lesions of the PPT from other pontine regions implicated in REM sleep generation, including those with predominantly cholinergic vs non-cholinergic cells. Twelve hour polygraphic recordings were obtained in 18 cats before and 1-2 weeks after bilateral electrolytic or radio frequency lesions of either: (1) PPT, which contains the dorsolateral pontine cholinergic cell column; (2) laterodorsal tegmental nucleus (LDT), which contains the dorsomedial pontine cholinergic cell column; (3) locus ceruleus (LC), which contains mostly noradrenergic cells; or (4) subceruleus (LC alpha, peri-LC alpha and the lateral tegmental field), which also contains predominantly noncholinergic cells. There were three main findings: (i) Only lesions of PPT and subceruleus significantly affected REM sleep time. These lesions produced comparable reductions in REM sleep time but influenced REM sleep components quite differently: (ii) PPT lesions, estimated to damage 90 +/- 4% of cholinergic cells, reduced the number of REM sleep entrances and phasic events, including ponto-geniculooccipital (PGO) spikes and rapid eye movements (REMs), but did not prevent complete atonia during REM sleep: (iii) Subceruleus lesions eliminated atonia during REM sleep. Mobility appeared to arouse the cat prematurely from REM sleep and may explain the brief duration of REM sleep epochs seen exclusively in this group. Despite the reduced amount of REM sleep, the total number of PGO spikes and REM sleep entrances increased over baseline values. Collectively, the results distinguish pontine loci regulating phasic events vs atonia. PPT lesions reduced phasic events, whereas subceruleus lesions created REM sleep without atonia. Severe REM sleep deficits after large pontine lesions, including PPT and subceruleus, might be explained by simultaneous production of both REM sleep syndromes. However, extensive loss of ACh neurons in the PPT does not disrupt REM sleep atonia.

Integration and Test Flight Validation Plans for the Pulsed Plasma Thruster Experiment on EO- 1

NASA Technical Reports Server (NTRS)

Zakrzwski, Charles; Benson, Scott; Sanneman, Paul; Hoskins, Andy; Bauer, Frank H. (Technical Monitor)

2002-01-01

The Pulsed Plasma Thruster (PPT) Experiment on the Earth Observing One (EO-1) spacecraft has been designed to demonstrate the capability of a new generation PPT to perform spacecraft attitude control. The PPT is a small, self-contained pulsed electromagnetic propulsion system capable of delivering high specific impulse (900-1200 s), very small impulse bits (10-1000 uN-s) at low average power (less than 1 to 100 W). Teflon fuel is ablated and slightly ionized by means of a capacitative discharge. The discharge also generates electromagnetic fields that accelerate the plasma by means of the Lorentz Force. EO-1 has a single PPT that can produce thrust in either the positive or negative pitch direction. The flight validation has been designed to demonstrate of the ability of the PPT to provide precision pointing accuracy, response and stability, and confirmation of benign plume and EMI effects. This paper will document the success of the flight validation.

A spin-crossover complex based on a 2,6-bis(pyrazol-1-yl)pyridine (1-bpp) ligand functionalized with a carboxylate group.

PubMed

Abhervé, Alexandre; Clemente-León, Miguel; Coronado, Eugenio; Gómez-García, Carlos J; López-Jordà, Maurici

2014-07-07

Combining Fe(ii) with the carboxylate-functionalized 2,6-bis(pyrazol-1-yl)pyridine (bppCOOH) ligand results in the spin-crossover compound [Fe(bppCOOH)2](ClO4)2 which shows an abrupt spin transition with a T1/2 of ca. 380 K and a TLIESST of 60 K due to the presence of a hydrogen-bonded linear network of complexes.

Molecular Self-Assembly of Group 11 Pyrazolate Complexes as Phosphorescent Chemosensors for Detection of Benzene

NASA Astrophysics Data System (ADS)

Ghazalli, N. F.; Yuliati, L.; Lintang, H. O.

2018-01-01

We highlight the systematic study on vapochromic sensing of aromatic vapors such as benzene using phosphorescent trinuclear pyrazolate complexes (2) with supramolecular assembly of a weak intermolecular metal-metal interaction consisting of 4-(3,5-dimethoxybenzyl)-3,5-dimethyl pyrazole ligand (1) and group 11 metal ions (Cu(I), Ag(I), Au(I)). The resulting chemosensor 2(Cu) revealed positive response to benzene vapors in 5 mins by blue-shifting its emission band in 44 nm (from 616 to 572 nm) and emitted bright orange to green, where this change cannot be recovered even with external stimuli. Comparing to 2(Ag) with longer metal-metal distance (473 nm) with same sensing time and quenching in 37%, 2(Au) gave quenching in 81% from its original intensity at 612 nm with reusability in 82% without external stimuli and emitted less emissive of red-orange from its original color. The shifting phenomenon in 2(Cu) suggests diffusion of benzene vapors to inside molecules for formation of intermolecular interaction with Cu(I)-Cu(I) interaction while quenching phenomenon in 2(Au) suggests diffusion of benzene vapors to between the Au(I)-Au(I) interaction. These results indicate that suitable molecular structure of ligand and metal ion in pyrazolate complex is important for designing chemosensor in the detection of benzene vapors.

Original 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH)

PubMed Central

2016-01-01

Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. As in our previous report, the structure–activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biological evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine. Inhibition of DHODH by this compound was confirmed in an array of in vitro assays, including enzymatic tests and cell-based assays for viral replication and cellular growth. This molecule was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH. PMID:26079043

New anticancer drug candidates sulfonamides as selective hCA IX or hCA XII inhibitors.

PubMed

Gul, Halise Inci; Yamali, Cem; Sakagami, Hiroshi; Angeli, Andrea; Leitans, Janis; Kazaks, Andris; Tars, Kaspars; Ozgun, Dilan Ozmen; Supuran, Claudiu T

2018-04-01

In this study, new 4-[3-(aryl)-5-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamides (19-36) were synthesized and evaluated their cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 34 (4-[5-(2,3,4-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl] benzensulfonamide, Potency-Selectivity Expression (PSE) = 141) and 36 (4-[5-(3,4,5-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide, PSE = 54.5) were found the leader anticancer compounds with the highest PSE values. In CA inhibitory studies, the compounds 36 and 24 (4-[5-(3,4,5-trimethoxyphenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide) were found the leader CA inhibitors depending on selectivity ratios. The compound 36 was a selective inhibitor of hCA XII isoenzyme (hCA I/hCA XII = 1250 and hCA II/hCA XII = 224) while the compound 24 was a selective inhibitor of hCA IX isoenzyme (hCA I/hCA IX = 161 and hCA II/hCA IX = 177). The compounds 24, 34, and 36 can be considered to develop new anticancer drug candidates. Copyright © 2018 Elsevier Inc. All rights reserved.

Electromagnetic propulsion for spacecraft

NASA Technical Reports Server (NTRS)

Myers, Roger M.

1993-01-01

Three electromagnetic propulsion technologies, solid propellant pulsed plasma thrusters (PPT), magnetoplasmadynamic (MPD) thrusters, and pulsed inductive thrusters (PIT), were developed for application to auxiliary and primary spacecraft propulsion. Both the PPT and MPD thrusters were flown in space, though only PPT's were used on operational satellites. The performance of operational PPT's is quite poor, providing only approximately 8 percent efficiency at approximately 1000 s specific impulse. However, laboratory PPT's yielding 34 percent efficiency at 2000 s specific impulse were extensively tested, and peak performance levels of 53 percent efficiency at 5170 s specific impulse were demonstrated. MPD thrusters were flown as experiments on the Japanese MS-T4 spacecraft and the Space Shuttle and were qualified for a flight in 1994. The flight MPD thrusters were pulsed, with a peak performance of 22 percent efficiency at 2500 s specific impulse using ammonia propellant. Laboratory MPD thrusters were demonstrated with up to 70 percent efficiency and 700 s specific impulse using lithium propellant. While the PIT thruster has never been flown, recent performance measurements using ammonia and hydrazine propellants are extremely encouraging, reaching 50 percent efficiency for specific impulses between 4000 to 8000 s. The fundamental operating principles, performance measurements, and system level design for the three types of electromagnetic thrusters are reviewed, and available data on flight tests are discussed for the PPT and MPD thrusters.

The assesment of effectiveness of plasmonic resonance photothermal therapy in tumor-bearing rats after multiple intravenous administration of gold nanorods

NASA Astrophysics Data System (ADS)

Bucharskaya, Alla B.; Maslyakova, Galina N.; Navolokin, Nikita A.; Terentyuk, Georgy S.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, V. V.

2017-03-01

To assess the effectiveness of plasmonic photothermal therapy (PPT) multiple intravenous strategy of gold nanorods (GNRs) administration was used before laser exposure. The model of alveolar liver cancer PC-1 was used in male outbred albino rats, which were intravenously administrated by single and multiple injections of GNRs and then were treated by PPT. The gold dosage was 400 μg (single injection group), 800 μg (double injection group), 1200 μg (triple injection group), and absorption maximum of gold nanorods suspension was at the wavelength of 808 nm. 24 hours after last injection the tumors were irradiated by the 808-nm diode laser during 15 min at power density 2.3 W/cm2. Temperature control of the tumor heating was provided by IR imager. 24 hours after the PPT the half of animals from each group was withdrawn from the experiments and the sampling tumor tissue for morphological study was performed. In survived animals the growth of tumors was evaluated during 21 days after the PPT. The antitumor effects of PPT after triple intravenous injection were comparable with those obtained at direct intratumoral administration of similar total dose of GNRs. The effectiveness of PPT depended on gold accumulation in tumor, probably, due to sufficient vascularization of tumor tissue.

Survival and development of horseshoe crab (Limulus polyphemus) embryos and larvae in hypersaline conditions.

PubMed

Ehlinger, Gretchen S; Tankersley, Richard A

2004-04-01

The horseshoe crab Limulus polyphemus spawns in the mid- to upper intertidal zone where females deposit eggs in nests below the sediment surface. Although adult crabs generally inhabit subtidal regions of estuaries with salinities from 5 to 34 ppt, developing embryos and larvae within nests are often exposed to more extreme conditions of salinity and temperature during summer spawning periods. To test whether these conditions have a negative impact on early development and survival, we determined development time, survival, and molt cycle duration for L. polyphemus embryos and larvae raised at 20 combinations of salinity (range: 30-60 ppt) and temperature (range: 25-40 degrees C). Additionally, the effect of hyperosmotic and hypoosmotic shock on the osmolarity of the perivitelline fluid of embryos was determined at salinities between 5 and 90 ppt. The embryos completed their development and molted at salinities below 60 ppt, yet failed to develop at temperatures of 35 degrees C or higher. Larval survival was high at salinities of 10-70 ppt but declined significantly at more extreme salinities (i.e., 5, 80, and 90 ppt). Perivitelline fluid remained nearly isoosmotic over the range of salinities tested. Results indicate that temperature and salinity influence the rate of crab development, but only the extremes of these conditions have an effect on survival.

A Pulsed Plasma Thruster Using Dimethyl Ether as Propellant

NASA Astrophysics Data System (ADS)

Masui, Souichi; Okada, Terumasa; Kitatomi, Makoto; Kakami, Akira; Tachibana, Takeshi

The pulsed plasma thruster (PPT), has attracted attention again as a micro-thruster because of its compactness, light weight, and comparatively low power consumption. On the other hand, the propellant utilization efficiency of a conventinal Teflon PPT is relatively low among electric propulsion devices because a propellant that originates from late-time ablation produces negligible thrust. The liquid propellant PPT (LP-PPT), in which water or ethanol is fed with an injector, was proposed to overcome these difficulties. Thrust measurements show that a LP-PPT provides higher specific impulses than a conventional PPT. However, water requires temperature management for propellant storage due to its relatively high freezing point. Moreover, even if ethanol, which has a sufficiently low freezing point, is used as propellant, a pressurant is necessary, as well as water, because the vapor pressures are insufficient for self-pressurization. In this study, we propose to use dimethyl ether (DME) as the propellant. DME, which has a freezing point of 131 K at 1 atm and a vapor pressure of 6 atm at 298 K, can be stored in tanks as a liquid, and requires no feeding pressurant. We designed a DME pulsed plasma thruster to evaluate performance. Thrust measurement yielded a specific impulse of 430 s for a coaxial type at a capacitor-stored energy of 13 J.

Transcutaneous Electrical Nerve Stimulation and Conditioned Pain Modulation Influence the Perception of Pain in Humans

PubMed Central

Liebano, Richard E.; Vance, Carol G.T.; Rakel, Barbara; Lee, Jennifer E.; Cooper, Nicholas A.; Marchand, Serge; Walsh, Deirdre M.; Sluka, Kathleen A.

2013-01-01

Background Research in animal models suggest that transcutaneous electrical nerve stimulation (TENS) and conditioned pain modulation (CPM) produce analgesia via two different supraspinal pathways. No known studies have examined whether TENS and CPM applied simultaneously in human subjects will enhance the analgesic effect of either treatment alone. The purpose of the current study was to investigate whether the simultaneous application of TENS and CPM will enhance the analgesic effect of that produced by either treatment alone. Methods Sixty healthy adults were randomly allocated into 2 groups: 1) CPM plus Active TENS; 2) CPM plus Placebo TENS. Pain threshold for heat (HPT) and pressure (PPT) was recorded from subject’s left forearm at baseline, during CPM, during Active or Placebo TENS, and during CPM plus Active or Placebo TENS. CPM was induced by placing the subjects’ contralateral arm in a hot water bath (46.5°C) for two minutes. TENS (100µs, 100Hz) was applied to the forearm for 20 minutes at a strong but comfortable intensity. Results Active TENS alone increased PPT (but not HPT) more than Placebo TENS alone (p=0.011). Combining CPM and Active TENS did not significantly increase PPT (p=0.232) or HPT (p=0.423) beyond CPM plus Placebo TENS. There was a significant positive association between PPT during CPM and during Active TENS (r2=0.46, p=0.003). Conclusions TENS application increases PPT, however combining CPM and TENS does not increase the CPM’s hypoalgesic response. CPM effect on PPT is associated with effects of TENS on PPT. PMID:23650092

Do downscaled general circulation models reliably simulate historical climatic conditions?

USGS Publications Warehouse

Bock, Andrew R.; Hay, Lauren E.; McCabe, Gregory J.; Markstrom, Steven L.; Atkinson, R. Dwight

2018-01-01

The accuracy of statistically downscaled (SD) general circulation model (GCM) simulations of monthly surface climate for historical conditions (1950–2005) was assessed for the conterminous United States (CONUS). The SD monthly precipitation (PPT) and temperature (TAVE) from 95 GCMs from phases 3 and 5 of the Coupled Model Intercomparison Project (CMIP3 and CMIP5) were used as inputs to a monthly water balance model (MWBM). Distributions of MWBM input (PPT and TAVE) and output [runoff (RUN)] variables derived from gridded station data (GSD) and historical SD climate were compared using the Kolmogorov–Smirnov (KS) test For all three variables considered, the KS test results showed that variables simulated using CMIP5 generally are more reliable than those derived from CMIP3, likely due to improvements in PPT simulations. At most locations across the CONUS, the largest differences between GSD and SD PPT and RUN occurred in the lowest part of the distributions (i.e., low-flow RUN and low-magnitude PPT). Results indicate that for the majority of the CONUS, there are downscaled GCMs that can reliably simulate historical climatic conditions. But, in some geographic locations, none of the SD GCMs replicated historical conditions for two of the three variables (PPT and RUN) based on the KS test, with a significance level of 0.05. In these locations, improved GCM simulations of PPT are needed to more reliably estimate components of the hydrologic cycle. Simple metrics and statistical tests, such as those described here, can provide an initial set of criteria to help simplify GCM selection.

Parallel trade of pharmaceuticals: a review of legal, economic, and political aspects.

PubMed

Bart, Thomas N

2008-01-01

An overview of the status quo of parallel trade of pharmaceuticals (pharmaceutical parallel trade [PPT]) was performed. The different economic, political, and legal viewpoints as well as the public health perspective are being taken into consideration. Analysis is being undertaken on a worldwide level, focusing on the situation of Switzerland in the context of current developments in the United States as well as in the European Union (EU). Desktop analysis using publicly available information (e.g., scientific literature, congress reports, official statistical databases) was performed during the years 2006 through 2007. Such gathered information was compiled and systematically structured to allow a crude overview of the development of intellectual property law in the last 100 years (as a prerequisite under which PPT legally can exist) as well as a description of the health economic and political context in which PPT is set currently. It could be shown that PPT is an ubiquitous phenomenon, appearing in industrialized countries as well as in the developing world. Economically, it has gained a significant weight in substantial parts of the EU in the last decade. This has to be seen in the context of EU efforts of enhanced economic and political integration. The worldwide constant growth of health-care expenditures, with its strain on national health-care budgets, has led to increased discussions about the necessity and consequences including possible dangers of PPT, namely, in the United States and in Switzerland, where up to now PPT has been only of marginal importance. The analysis of the value of PPT depends strongly on the importance that is given to different perspectives by the individual analyst. It is clear that an item-centered view of PPT is not able to analyze this phenomenon in an equitable way. Further attempts have to be made to standardize evaluation as well as to increase available information to empower science and decision-makers to perform objective analyses and informed decisions.

Effects of pond salinization on survival rate of amphibian hosts infected with the chytrid fungus.

PubMed

Stockwell, Michelle Pirrie; Storrie, Lachlan James; Pollard, Carla Jean; Clulow, John; Mahony, Michael Joseph

2015-04-01

The chytrid fungus Batrachochytrium dendrobatidis has been implicated in the decline and extinction of amphibian populations worldwide, but management options are limited. Recent studies show that sodium chloride (NaCl) has fungicidal properties that reduce the mortality rates of infected hosts in captivity. We investigated whether similar results can be obtained by adding salt to water bodies in the field. We increased the salinity of 8 water bodies to 2 or 4 ppt and left an additional 4 water bodies with close to 0 ppt and monitored salinity for 18 months. Captively bred tadpoles of green and golden bell frog (Litoria aurea) were released into each water body and their development, levels of B. dendrobatidis infection, and survival were monitored at 1, 4, and 12 months. The effect of salt on the abundance of nontarget organisms was also investigated in before and after style analyses. Salinities remained constant over time with little intervention. Hosts in water bodies with 4 ppt salt had a significantly lower prevalence of chytrid infection and higher survival, following metamorphosis, than hosts in 0 ppt salt. Tadpoles in the 4 ppt group were smaller in length after 1 month in the release site than those in the 0 and 2 ppt groups, but after metamorphosis body size in all water bodies was similar . In water bodies with 4 ppt salt, the abundance of dwarf tree frogs (Litoria fallax), dragonfly larvae, and damselfly larvae was lower than in water bodies with 0 and 2 ppt salt, which could have knock-on effects for community structure. Based on our results, salt may be an effective field-based B. dendrobatidis mitigation tool for lentic amphibians that could contribute to the conservation of numerous susceptible species. However, as in all conservation efforts, these benefits need to be weighed against negative effects on both target and nontarget organisms. © 2014 Society for Conservation Biology.

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo.

PubMed

Zhang, Li; Wang, Tengteng; Li, Qiang; Huang, Jing; Xu, Hao; Li, Jinlong; Wang, Yongjun; Liang, Qianqian

2016-01-01

Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is -35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment.

Phosphinothricin Acetyltransferases Identified Using In Vivo, In Vitro, and Bioinformatic Analyses

PubMed Central

VanDrisse, Chelsey M.; Hentchel, Kristy L.

2016-01-01

ABSTRACT Acetylation of small molecules is widespread in nature, and in some cases, cells use this process to detoxify harmful chemicals. Streptomyces species utilize a Gcn5 N-acetyltransferase (GNAT), known as Bar, to acetylate and detoxify a self-produced toxin, phosphinothricin (PPT), a glutamate analogue. Bar homologues, such as MddA from Salmonella enterica, acetylate methionine analogues such as methionine sulfoximine (MSX) and methionine sulfone (MSO), but not PPT, even though Bar homologues are annotated as PPT acetyltransferases. S. enterica was used as a heterologous host to determine whether or not putative PPT acetyltransferases from various sources could acetylate PPT, MSX, and MSO. In vitro and in vivo analyses identified substrates acetylated by putative PPT acetyltransferases from Deinococcus radiodurans (DR_1057 and DR_1182) and Geobacillus kaustophilus (GK0593 and GK2920). In vivo, synthesis of DR_1182, GK0593, and GK2920 blocked the inhibitory effects of PPT, MSX, and MSO. In contrast, DR_1057 did not detoxify any of the above substrates. Results of in vitro studies were consistent with the in vivo results. In addition, phylogenetic analyses were used to predict the functionality of annotated PPT acetyltransferases in Burkholderia xenovorans, Bacillus subtilis, Staphylococcus aureus, Acinetobacter baylyi, and Escherichia coli. IMPORTANCE The work reported here provides an example of the use of a heterologous system for the identification of enzyme function. Many members of this superfamily of proteins do not have a known function, or it has been annotated solely on the basis of sequence homology to previously characterized enzymes. The critical role of Gcn5 N-acetyltransferases (GNATs) in the modulation of central metabolic processes, and in controlling metabolic stress, necessitates approaches that can reveal their physiological role. The combination of in vivo, in vitro, and bioinformatics approaches reported here identified GNATs that can acetylate and detoxify phosphinothricin. PMID:27694229

Induction of hypoxia-inducible factor-1alpha and activation of caspase-3 in hypoxia-reoxygenated bone marrow stroma is negatively regulated by the delayed production of substance P.

PubMed

Qian, J; Ramroop, K; McLeod, A; Bandari, P; Livingston, D H; Harrison, J S; Rameshwar, P

2001-10-15

The bone marrow (BM), which is the major site of immune cell development in the adult, responds to different stimuli such as inflammation and hemorrhagic shock. Substance P (SP) is the major peptide encoded by the immune/hemopoietic modulator gene, preprotachykinin-1 (PPT-I). Differential gene expression using a microarray showed that SP reduced hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA levels in BM stroma. Because long-term hypoxia induced the expression of PPT-I in BM mononuclear cells, we used timeline studies to determine whether PPT-I is central to the biologic responses of BM stroma subjected to 30-min hypoxia (pO(2) = 35 mm Hg) followed by reoxygenation. HIF-1alpha mRNA and protein levels were increased up to 12 h. At this time, beta-PPT-I mRNA was detected with the release of SP at 16 h. SP release correlated with down-regulation of HIF-1alpha to baseline. A direct role for SP in HIF-1alpha expression was demonstrated as follows: 1) transient knockout of beta-PPT-I showed an increase in HIF-1alpha expression up to 48 h of reoxygenation; and 2) HIF-1alpha expression remained baseline during reoxygenation when stroma was subjected to hypoxia in the presence of SP. Reoxygenation activated the PPT-I promoter with concomitant nuclear translocation of HIF-1alpha that can bind to the respective consensus sequences within the PPT-I promoter. SP reversed active caspase-3, an indicator of apoptosis and erythropoiesis, to homeostasis level after reoxygenation of hypoxic stroma. The results show that during reoxgenation the PPT-I gene acts as a negative regulator on the expression of HIF-1alpha and active caspase-3 in BM stroma subjected to reoxygenation.

Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

PubMed

Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

2016-09-01

4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif.

Synthesis of New Thiazolyl Coupled Pyrazoles Bearing 2,4-Thiazolidinedionyl Pharmacophore and Their Anti-Inflammatory and Antibacterial Evaluation.

PubMed

Khillare, Lalit; Bhosle, Manisha; Bhalerao, Mahendra; Kharat, Kiran; Mane, Ramrao

2017-01-01

2, 4-Thiazolidinedione (TZD), pyrazole and thiazole heterocyclic rings exhibit a wide range of pharmacological activities. Medicinal chemists use these heterocyclic moieties as scaffolds in drug designing and discovery. The existing medicaments, celecoxib and meloxicam, used for treating inflammation and pain are having, pyrazole and thiazole, respectively as key scaffolds. Pyrazoles coupled with 2, 4-thiazolidinediones may display enhanced anti-inflammatory activity. With this hope the bench work was carried out. Heterocyclic aldehydes, 3-(4-methyl-2-substituted thiazol-5-yl)-1-phenyl-1Hpyrazole- 4- carbaldehydes (4a-b) have been allowed to undergo Knoevenagel condensation with N-substituted 2,4-thiazolidinediones (5a-e) in PEG-400 in the presence of L-proline at 110°C and obtained the condensed products (6a-j). COX-2 evaluation of the titled product has been carried out using in vitro COX-2 ELISA Kit. Antibacterial activity of these compounds (6a-j) has also been determined. On the basis of 1H NMR, 13C NMR and Mass spectral data of the condensed products the structures have been assigned to (Z)-5-((3-(4-methyl-2-substituted thiazol-5-yl)-1- phenyl-1H-pyrazol-4-yl)methylene) 3-substituted thiazolidine-2,4-diones (6a-j). Among the evaluated compounds (6a-j), 6f, 6g, 6h, 6i and 6j have shown notable COX-2 inhibitory activity. Compounds, 6a, 6b, 6c, 6d, 6e and 6f have inhibited the growth of the Bacillus cereus NCIM 2106, Bacillus subtilis NCIM 2063, Pseudomonas aeruginosa NCIM 2074, Salmonella typhimurium NCIM 2501 and Staphylococcus aureus NCIM 2079. However, compound 6f has emerged as a suitable candidate with dual properties i.e. COX-2 inhibitory and antibacterial in the present study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Supernova Cosmology Project

Science.gov Websites

in Presentations Ωm-ΩΛ with CMB, BAO, and SCP Union2 SN Constraints pdf | ppt Description Ωm-ΩΠ› with CMB, BAO, and SCP Union2 SN Constraints, including SN systematics pdf | ppt Description Ωm-w with CMB, BAO, and SCP Union2 SN Constraints pdf | ppt Description Ωm-w with CMB, BAO, and SCP Union2 SN

Studies of the pharmacology of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol, a synthetic anti-inflammatory androstene

PubMed Central

Ahlem, Clarence N; Kennedy, Michael R; Page, Theodore M; Reading, Christopher L; White, Steven K; McKenzie, John J; Cole, Phaedra I; Stickney, Dwight R; Frincke, James M

2011-01-01

17α-Ethynyl-androst-5ene-3β, 7β, 17β-triol (HE3286) is an orally bioavailable analogue of androst-5-ene-3β,7β,17β-triol, a non-glucocorticoid anti-inflammatory metabolite of the adrenal steroid, dehydroepiandrosterone. The pharmacology of HE3286 was characterized in preparation for clinical trials in type 2 diabetes mellitus and other diseases of inflammation. Interactions with nuclear hormone receptors and P450 enzymes were measured in vitro. Drug metabolism was studied preclinically in mice, rats, dogs, and monkeys. Neurological and cardiopulmonary safety and dose-ranging and chronic toxicity studies were conducted in rats and dogs in accordance with FDA guidelines. Pharmacokinetics and metabolites were measured in Phase I clinical trials. HE3286 was differentially metabolized between species. HE3286 and metabolites did not bind or transactivate steroid binding nuclear hormone receptors or inhibit P450 enzymes. There were no adverse effects in safety pharmacology and canine toxicology studies. Although HE3286 did not elicit systemic toxicity in rats, mild estrogenic effects were observed, but without apparent association to hormonal changes. Safety margins were greater than 20-fold in rats and dogs with respect to the most commonly used clinical dose of 10 mg/day. The terminal half-life in humans was 8 hours in males and 5.5 hours in females. HE3286 is the first derivative of the DHEA metabolome to undergo a comprehensive pharmacological and safety evaluation. The results of these investigations have shown that HE3286 has a low potential for toxicity and possesses pharmacological properties generally suitable for use in human medicine. The favorable profile of HE3286 warrants further exploration of this new class of anti-inflammatory agents. PMID:21686136

5-(1-Aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles: Synthesis, structural characterization, Hirshfeld analysis, anti-inflammatory and anti-bacterial studies

NASA Astrophysics Data System (ADS)

Kumbar, Mahadev N.; Kamble, Ravindra R.; Dasappa, Jagadeesh Prasad; Bayannavar, Praveen K.; Khamees, Hussien Ahmed; Mahendra, M.; Joshi, Shrinivas D.; Dodamani, Suneel; Rasal, V. P.; Jalalpure, Sunil

2018-05-01

A series of novel 5-(1-aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles 7(h-s) were designed and synthesized. Structural characterization was done by spectral and single crystal X-ray studies. The intermolecular interactions of compound 7n were quantified and visualized using Hirshfeld surface analysis. Structures of newly synthesized compounds were docked into active site of COX-2 enzyme PDB:

Curcumin derivatives inhibit or modulate beta-amyloid precursor protein metabolism.

PubMed

Narlawar, Rajeshwar; Baumann, Karlheinz; Schubenel, Robert; Schmidt, Boris

2007-01-01

Curcumin-derived oxazoles and pyrazoles were synthesized in order to minimize the metal chelation properties of curcumin. The reduced rotational freedom and the absence of stereoisomers was anticipated to enhance the inhibition of gamma-secretase. Accordingly, the replacement of the 1,3-dicarbonyl moiety by isosteric heterocycles turned curcumin analogue oxazoles and pyrazoles into potent gamma-secretase inhibitors. Compounds 4a-i were found to be potent inhibitors of gamma-secretase and displayed activity in the low micromolar range. 2007 S. Karger AG, Basel

Effectiveness of Pelvic Physiotherapy in Children With Functional Constipation Compared With Standard Medical Care.

PubMed

van Engelenburg-van Lonkhuyzen, Marieke L; Bols, Esther M J; Benninga, Marc A; Verwijs, Wim A; de Bie, Rob A

2017-01-01

Functional constipation (FC) is a common childhood problem often related to pelvic floor muscle dysfunction. We compared the effectiveness of pelvic physiotherapy (PPT) vs standard medical care (SMC) in children with FC. We performed a multicenter randomized controlled trial of 53 children (age, 5-16 y) with FC according to the Rome III criteria, at hospitals in The Netherlands from December 2009 to May 2014. Group allocation was concealed using a central computer system. SMC consisted of education, toilet training, and laxatives (n = 26), whereas PPT included SMC plus specific physiotherapeutic interventions (n = 27). Results were obtained from written reports from the subjects' pediatricians and parents. The primary outcome was absence of FC, according to Rome III criteria, after a 6-month follow-up period. Secondary outcomes were global perceived effect (range, 1-9; success was defined as a score ≥ 8), numeric rating scales assessing quality of life (parent and child; scale, 1-10), and the strengths and difficulties questionnaire (SDQ). Treatment was effective for 92.3% of the children receiving PPT and for 63.0% of the children receiving SMC (adjusted odds ratio for success of PPT, 11.7; 95% confidence interval, 1.8-78.3) (P = .011). Significantly more children undergoing PPT stopped using laxatives (adjusted odds ratio, 6.5; 95% confidence interval, 1.6-26.4) (P = .009). Treatment success (based on global perceived effect) was achieved for 88.5% of subjects receiving PPT vs 33.3% of subjects receiving SMC) (P < .001). PPT also produced larger adjusted mean differences, before vs after treatment, in numeric rating scales to assess quality of life: an increase of 1.8 points for parents (P = .047) and 2.0 points for children (P = .028). Results from the SDQ did not differ significantly between groups (P = .78). In a randomized controlled trial of children with FC, PPT was more effective than SMC on all outcomes measured, with the exception of findings from the SDQ. PPT should be considered as a treatment option for FC in children 5-16 years old. Dutch Clinical Trial Registration no: NL30551.068.09. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Positive Psychotherapy for Smoking Cessation: A Pilot Randomized Controlled Trial.

PubMed

Kahler, Christopher W; Spillane, Nichea S; Day, Anne M; Cioe, Patricia A; Parks, Acacia; Leventhal, Adam M; Brown, Richard A

2015-11-01

Greater depressive symptoms and low positive affect (PA) are associated with poor smoking cessation outcomes. Smoking cessation approaches that incorporate a focus on PA may benefit smokers trying to quit. The purpose of this study was to conduct a pilot randomized clinical trial to compare standard smoking cessation treatment (ST) with smoking cessation treatment that targets positive affect, termed positive psychotherapy for smoking cessation (PPT-S). Smokers who were seeking smoking cessation treatment were assigned by urn randomization to receive, along with 8 weeks of nicotine replacement therapy, either ST (n = 31) or PPT-S (n = 35). Seven-day point prevalence smoking abstinence was biochemically confirmed at 8, 16, and 26 weeks. Compared to ST, a greater percentage of participants in PPT-S were abstinent at 8 weeks, 16 weeks, and 26 weeks, but these differences were nonsignificant. In a more statistically powerful longitudinal model, participants in PPT-S had a significantly higher odds of abstinence (adjusted odds ratio [AOR] = 2.75; 95% CI = 1.02, 7.42; p = .046) across follow-ups compared to those in ST. The positive effect of PPT-S was stronger for those higher in PA (OR = 6.69, 95% CI = 1.16, 38.47, p = .03). Greater use of PPT-S strategies during the initial 8 weeks of quitting was associated with a less steep decline in smoking abstinence rates over time (OR = 2.64, 95% CI = 1.06, 6.56, p =.04). This trial suggests substantial promise for incorporating PPT into smoking cessation treatment. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase partitioning.

PubMed

Hashimoto, Masahito; Takashige, Katsuhiro; Furuyashiki, Maiko; Yoshidome, Keitaro; Sano, Ryoko; Kawamura, Yutaka; Ijichi, Shinji; Morioka, Hirofumi; Koide, Hiroyuki; Oku, Naoto; Moriya, Yoichiro; Kusumoto, Shoich; Suda, Yasuo

2008-01-01

OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of contaminants from OK-432 using Triton X-114 (TX-114)-water phase partitioning and examined an antitumor effect of the resulting preparation. OK-432 was subjected to TX-114 partitioning to give residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher and IL-10 production was lower than that of OK-432. In tumor-bearing mice model, administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN-gamma in mouse spleen cells in vitro. These results indicated that TX-114 partitioning removed some contaminants, which attenuates the antitumor effect, from OK-432 and increase the immunotherapeutic effects of OK-432.

Inverted electro-mechanical behaviour induced by the irreversible domain configuration transformation in (K,Na)NbO3-based ceramics

PubMed Central

Huan, Yu; Wang, Xiaohui; Koruza, Jurij; Wang, Ke; Webber, Kyle G.; Hao, Yanan; Li, Longtu

2016-01-01

Miniaturization of domains to the nanometer scale has been previously reported in many piezoelectrics with two-phase coexistence. Despite the observation of nanoscale domain configuration near the polymorphic phase transition (PPT) regionin virgin (K0.5Na0.5)NbO3 (KNN) based ceramics, it remains unclear how this domain state responds to external loads and influences the macroscopic electro-mechanical properties. To this end, the electric-field-induced and stress-induced strain curves of KNN-based ceramics over a wide compositional range across PPT were characterized. It was found that the coercive field of the virgin samples was highest in PPT region, which was related to the inhibited domain wall motion due to the presence of nanodomains. However, the coercive field was found to be the lowest in the PPT region after electrical poling. This was related to the irreversible transformation of the nanodomains into micron-sized domains during the poling process. With the similar micron-sized domain configuration for all poled ceramics, the domains in the PPT region move more easily due to the additional polarization vectors. The results demonstrate that the poling process can give rise to the irreversible domain configuration transformation and then account for the inverted macroscopic piezoelectricity in the PPT region of KNN-based ceramics. PMID:26915972

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

Schriner, J.E.; Yi, W.; Hofmann, S.L.

Palmitoyl-protein thioesterase (PPT) is a small glycoprotein that removes palmitate groups from cysteine residues in lipid-modified proteins. We recently reported mutations in PPT in patients with infantile neuronal ceroid lipofuscinosis (INCL), a severe neurodegenerative disorder. INCL is characterized by the accumulation of proteolipid storage material in brain and other tissues, suggesting that the disease is a consequence of abnormal catabolism of acylated proteins. In the current paper, we report the sequence of the human PPT cDNA and the structure of the human PPT gene. The cDNA predicts a protein of 306 amino acids that contains a 25-amino-acid signal peptide, threemore » N-linked glycosylation sites, and consensus motifs characteristic of thioesterases. Northern analysis of a human tissue blot revealed ubiquitous expression of a single 2.5-kb mRNA, with highest expression in lung, brain, and heart. The human PPT gene spans 25 kb and is composed of seven coding exons and a large eighth exon, containing the entire 3{prime}-untranslated region of 1388 bp. An Alu repeat and promoter elements corresponding to putative binding sites for several general transcription factors were identified in the 1060 nucleotides upstream of the transcription start site. The human PPT cDNA sequence and gene structure will provide the means for the identification of further causative mutations in INCL and facilitate genetic screening in selected high-risk populations. 31 refs., 5 figs., 1 tab.« less

Six new ergostane-type steroids from king trumpet mushroom (Pleurotus eryngii) and their inhibitory effects on nitric oxide production.

PubMed

Kikuchi, Takashi; Maekawa, Yukina; Tomio, Arisa; Masumoto, Yuki; Yamamoto, Taishi; In, Yasuko; Yamada, Takeshi; Tanaka, Reiko

2016-11-01

Six new ergostane-type steroids; (22E)-3β,5α,6α,11-tetrahydroxy-9(11)-seco-ergosta-7,22-dien-9-one (1), (22E)-8,14-epoxyergosta-6,22-diene-3β,5α,9α-triol (2), (22E)-4α,5α-epoxyergosta-7,22-diene-3β,6β-diol (3), (22E)-3β,4β,5α-trihydroxyergosta-7,22-dien-6-one (4), (22E)-ergosta-7,22-diene-3β,5β,6α-triol (5), and (22E)-6β-methoxyergosta-7,22-diene-3β,5α-diol 3-O-β-d-glucopyranoside (6) were isolated from the fruiting bodies of king trumpet mushroom (Pleurotus eryngii), along with fourteen known compounds (7-20). All isolated compounds were evaluated for their inhibitory effects on macrophage activation using a nitric oxide production inhibition assay. Copyright © 2016. Published by Elsevier Inc.

Recent Progress on C-4-Modified Podophyllotoxin Analogs as Potent Antitumor Agents

PubMed Central

Liu, Ying-Qian; Tian, Jing; Qian, Keduo; Zhao, Xiao-Bo; Morris-Natschke, Susan L.; Yang, Liu; Nan, Xiang; Tian, Xuan; Lee, Kuo-Hsiung

2015-01-01

Podophyllotoxin (PPT), as well as its congeners and derivatives, exhibits pronounced biological activities, especially antineoplastic effects. Its strong inhibitory effect on tumor cell growth led to the development of three of the most highly prescribed anticancer drugs in the world, etoposide, teniposide, and the water-soluble prodrug etoposide phosphate. Their clinical success as well as intriguing mechanism of action stimulated great interest in further modification of PPT for better antitumor activity. The C-4 position has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug resistance. Accordingly, numerous PPT derivatives have been prepared via hemisynthesis and important structure–activity relationship (SAR) correlations have been identified. Several resulting compounds, including GL-331, TOP-53, and NK611, reached clinical trials. Some excellent reviews on the distribution, sources, applications, synthesis, and SAR of PPT have been published. This review focuses on a second generation of new etoposide-related drugs and provides detailed coverage of the current status and recent development of C-4-modified PPT analogs as anticancer clinical trial candidates. PMID:24827545

(Z)-3-Methyl-4-[1-(4-methyl­anilino)propyl­idene]-1-phenyl-1H-pyrazol-5(4H)-one

PubMed Central

Sharma, Naresh; Vyas, Komal M.; Jadeja, R. N.; Kant, Rajni; Gupta, Vivek K.

2013-01-01

In the title mol­ecule, C20H21N3O, the central pyrazole ring forms dihedral angles of 4.75 (9) and 49.11 (9)°, respectively, with the phenyl and methyl-substituted benzene rings. The dihedral angle between the phenyl and benzene rings is 51.76 (8)°. The amino group and carbonyl O atom are involved in an intra­molecular N—H⋯O hydrogen bond. In the crystal, π–π inter­actions are observed between benzene rings [centroid–centroid seperation = 3.892 (2) Å] and pyrazole rings [centroid–centroid seperation = 3.626 (2) Å], forming chains along [111]. The H atoms of the methyl group on the p-tolyl substituent were refined as disordered over two sets of sites in a 0.60 (4):0.40 (4) ratio. PMID:24109353

trans-Bis(thio­cyanato-κN)tetra­kis­(3,4,5-trimethyl-1H-pyrazole-κN 2)nickel(II)–3,4,5-trimethyl-1H-pyrazole (1/1)

PubMed Central

Hossaini Sadr, Moayad; Engle, James T.; Ziegler, Christopher J.; Soltani, Behzad; Mousavi, Zahra

2011-01-01

In the title compound, [Ni(NCS)2(C6H10N2)4]·C6H10N2, the asymmetric unit comprises a NiII complex and a co-crystallised mol­ecule of 3,4,5-trimethyl-1H-pyrazole (PzMe3). The NiII atom is coordinated by four PzMe3 mol­ecules and two thio­cyanate anions to define a trans N4S2 distorted octa­hedral geometry. A number of intra­molecular N—H⋯N, N—H⋯S and C—H⋯N inter­actions contribute to the stability of the complex. The crystal structure is stabilized by inter­molecular N—H⋯S inter­actions, which link neighbouring mol­ecules into chains along the a axis. PMID:22219831

Fabrication of zinc-dicarboxylate- and zinc-pyrazolate-carboxylate-framework thin films through vapour-solid deposition.

PubMed

Medishetty, Raghavender; Zhang, Zongji; Sadlo, Alexander; Cwik, Stefan; Peeters, Daniel; Henke, Sebastian; Mangayarkarasi, Nagarathinam; Devi, Anjana

2018-05-17

Fabrication of three-dimensional metal-organic framework (MOF) thin films has been investigated for the first time through the conversion of a ZnO layer via a pure vapour-solid deposition reaction at ambient pressure. The fabrication of MOF thin films with a dicarboxylate linker, (DMA)2[Zn3(bdc)4] (1) (bdc = 1,4-benzenedicarboxylate), and a carboxy-pyrazolate linker, [Zn4O(dmcapz)6] (2) (dmcapz = 3,5-dimethyl-4-carboxypyrazole), involves the deposition of the linker and/or the preparation of a composite film preliminarily and its subsequent conversion into a MOF film using closed cell thermal treatment. Furthermore, it was possible to isolate thin films with a MOF-5 isotype structure grown along the [110] direction, using a carboxy-pyrazolate linker. This was achieved just by the direct reaction of the ZnO film and the organic linker vapors, employing a simple route that demonstrates the feasibility of MOF thin film fabrication using inexpensive routes at ambient pressure.

Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation

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

McElroy, William T.; Tan, Zheng; Ho, Ginny

IRAK4 is a critical upstream kinase in the IL-1R/TLR signaling pathway. Inhibition of IRAK4 is hypothesized to be beneficial in the treatment of autoimmune related disorders. A screening campaign identified a pyrazole class of IRAK4 inhibitors that were determined by X-ray crystallography to exhibit an unusual binding mode. SAR efforts focused on the identification of a potent and selective inhibitor with good aqueous solubility and rodent pharmacokinetics. Pyrazole C-3 piperidines were well tolerated, with N-sulfonyl analogues generally having good rodent oral exposure but poor solubility. N-Alkyl piperidines exhibited excellent solubility and reduced exposure. Pyrazoles possessing N-1 pyridine and fluorophenyl substituentsmore » were among the most active. Piperazine 32 was a potent enzyme inhibitor with good cellular activity. Compound 32 reduced the in vivo production of proinflammatory cytokines and was orally efficacious in a mouse antibody induced arthritis disease model of inflammation.« less

Design and environmentally benign synthesis of novel thiophene appended pyrazole analogues as anti-inflammatory and radical scavenging agents: Crystallographic, in silico modeling, docking and SAR characterization.

PubMed

Prabhudeva, Malledevarapura Gurumurthy; Bharath, Srinivasan; Kumar, Achutha Dileep; Naveen, Shivalingegowda; Lokanath, Neratur Krishnappagowda; Mylarappa, Bantaganahalli Ningappa; Kumar, Kariyappa Ajay

2017-08-01

Oxidative-stress induces inflammatory diseases and infections caused by drug-resistant microbial strains are on the rise necessitating the discovery of novel small-molecules for intervention therapy. The current study presents an effective and new green protocol for the synthesis of thiophene-appended pyrazoles through 3+2 annulations method. Chalcones 3(a-g) were prepared from 5-chloro-2-acetylthiophene and aromatic aldehydes by Claisen-Schmidt approach. The reaction of chalcones 3(a-g) with phenylhydrazine hydrochlorides 4(a-b) in acetic acid (30%) medium and also with freshly prepared citrus extract medium under reflux conditions produced the thiophene appended pyrazoles 5(a-l) in moderate yields. Structures of synthesized new pyrazoles were confirmed by spectral studies, elemental analysis and single crystal X-ray diffraction studies. Further, preliminary assessment of the anti-inflammatory properties of the compounds showed that, amongst the series, compounds 5d, 5e and 5l have excellent anti-inflammatory activities. Further, compounds 5c, 5d, 5g, and 5i exhibited excellent DPPH radical scavenging abilities in comparison with the standard ascorbic acid. Furthermore, using detailed structural modeling and docking efforts, combined with preliminary SAR, we show possible structural and chemical features on both the small-molecules and the protein that might contribute to the binding and inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

Infrared spectrum, structural and optical properties and molecular docking study of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde.

PubMed

Mary, Y Sheena; Panicker, C Yohannan; Sapnakumari, M; Narayana, B; Sarojini, B K; Al-Saadi, Abdulaziz A; Van Alsenoy, C; War, Javeed Ahmad; Fun, H K

2015-03-05

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde have been investigated experimentally and theoretically. The title compound was optimized using at HF and DFT levels of calculations. The B3LYP/6-311++G(d,p) (5D,7F) results and in agreement with experimental infrared bands. The normal modes are assigned using potential energy distribution. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using natural bonding orbital analysis. The frontier molecular orbital analysis is used to determine the charge transfer within the molecule. From molecular electrostatic potential map, it is evident that the negative electrostatic potential regions are mainly localized over the carbonyl group and mono substituted phenyl ring and are possible sites for electrophilic attack and, positive regions are localized around all para substituted phenyl and pyrazole ring, indicating possible sites for nucleophilic attack. First hyperpolarizability is calculated in order to find its role in nonlinear optics. The geometrical parameters are in agreement with experimental data. From the molecular docking studies, it is evident that the fluorine atom attached to phenyl ring and the carbonyl group attached to pyrazole ring are crucial for binding and the results draw us to the conclusion that the compound might exhibit phosphodiesterase inhibitory activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis, X-ray structure and cytotoxic effect of nickel(II) complexes with pyrazole ligands.

PubMed

Sobiesiak, Marta; Lorenz, Ingo-Peter; Mayer, Peter; Woźniczka, Magdalena; Kufelnicki, Aleksander; Krajewska, Urszula; Rozalski, Marek; Budzisz, Elzbieta

2011-12-01

Here we present the synthesis of the new Ni(II) complexes with chelating ligands 1-benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (a), 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (b) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (c). These ligands a-c create solid complexes with Ni(II). The crystal and molecular structures of two complexes were determined by X-ray diffraction method. Thermal stability of two complexes with ligand c by TG/DTG and DSC methods were also shown. Cytotoxic activity of all the complexes against three tumour cell lines and to normal endothelial cells (HUVEC) was also estimated. Complexes with ligand c exhibited relatively high cytotoxic activity towards HL-60 and NALM-6 leukaemia cells and WM-115 melanoma cells. Cytotoxic effectiveness of one of these complexes against melanoma WM-115 cells was two times higher than that of cisplatin. The protonation constant log K=9.63 of ligand b corresponding to the phenol 2-hydroxy group has been determined in 10% (v/v) DMSO/water solution (25°C). The coordination modes (formation of two monomeric species: NiL and NiL(2)) in the complexes with Ni(II) are discussed for b on the basis of the potentiometric and UV/Vis data. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Discovery and development of pyrazole-scaffold Hsp90 inhibitors.

PubMed

McDonald, Edward; Jones, Keith; Brough, Paul A; Drysdale, Martin J; Workman, Paul

2006-01-01

This review explains why the chaperone Hsp90 is an exciting protein target for the discovery of new drugs to treat cancer in the clinic, and summarises the properties of natural product derived inhibitors before relating the discovery and current state of development of synthetic pyrazole compounds. Blockade of Hsp90 results in reduced cellular levels of several proteins implicated in cancer including CDK4, ERBB2 and C-RAF, and causes simultaneous inhibition of cancer cell proliferation in culture and of tumor xenograft growth in vivo. Hsp90 has an ATPase domain that is necessary for its Hsp chaperone function, and X-ray crystallography has shown that natural product inhibitors (geldanamycin, radicicol) of Hsp90 function bind to this domain. High throughput assays focusing on the ATPase activity of Hsp90 were developed and used to discover novel chemical starting points for cancer drug discovery. The discovery, synthesis and SAR of 3,4-diaryl pyrazoles is described. X-Ray crystallography of protein-inhibitor complexes revealed important interactions involving the resorcinol substituent at C-3, and these X-ray structures strongly influenced subsequent medicinal chemistry research that has resulted in highly potent inhibitors with sub-micromolar activity in cells. SAR and X-ray data are summarised for analogues in which the 4-phenyl substituent is replaced by amides or piperazine derivatives. Prospects for the pyrazoles as they progress towards clinical development are discussed in relation to current Phase I trials with derivatives of geldanamycin.

Characterizing the Exhaust Plume of the Three-Electrode Micro Pulsed Plasma Thrusters

DTIC Science & Technology

2009-03-01

Plasma Thruster “, J Prop Power 1998;14:716-35 3 W. Andrew Hoskins, Christopher Rayburn, and Charles Sarmiento ” Pulsed Plasma Thruster...plasma thrusters are based on the previous PPT-4 and PPT-7 thruster designs. These thrusters used energy levels between 40 and 80 J generating several...PPT Programs 3 Program Year Energy Voltage Program Year Energy Voltage Zond-2 1964 50 J 1000 V TIP-III 1976 20 J 1630 V LES-6 1968 1.85 J 1360 V NOVA

Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease

PubMed Central

Jones, Melanie A.; Amr, Sami; Ferebee, Aerial; Huynh, Phung; Rosenfeld, Jill A.; Miles, Michael F.; Davies, Andrew G.; Korey, Christopher A.; Warrick, John M.; Shiang, Rita; Elsea, Sarah H.; Girirajan, Santhosh; Grotewiel, Mike

2014-01-01

ABSTRACT Wolfram syndrome (WFS) is a progressive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. WFS1 and WFS2 are caused by recessive mutations in the genes Wolfram Syndrome 1 (WFS1) and CDGSH iron sulfur domain 2 (CISD2), respectively. To explore the function of CISD2, we performed genetic studies in flies with altered expression of its Drosophila orthologue, cisd2. Surprisingly, flies with strong ubiquitous RNAi-mediated knockdown of cisd2 had no obvious signs of altered life span, stress resistance, locomotor behavior or several other phenotypes. We subsequently found in a targeted genetic screen, however, that altered function of cisd2 modified the effects of overexpressing the fly orthologues of two lysosomal storage disease genes, palmitoyl-protein thioesterase 1 (PPT1 in humans, Ppt1 in flies) and ceroid-lipofuscinosis, neuronal 3 (CLN3 in humans, cln3 in flies), on eye morphology in flies. We also found that cln3 modified the effects of overexpressing Ppt1 in the eye and that overexpression of cln3 interacted with a loss of function mutation in cisd2 to disrupt locomotor ability in flies. Follow-up multi-species bioinformatic analyses suggested that a gene network centered on CISD2, PPT1 and CLN3 might impact disease through altered carbohydrate metabolism, protein folding and endopeptidase activity. Human genetic studies indicated that copy number variants (duplications and deletions) including CLN3, and possibly another gene in the CISD2/PPT1/CLN3 network, are over-represented in individuals with developmental delay. Our studies indicate that cisd2, Ppt1 and cln3 function in concert in flies, suggesting that CISD2, PPT1 and CLN3 might also function coordinately in humans. Further, our studies raise the possibility that WFS2 and some lysosomal storage disorders might be influenced by common mechanisms and that the underlying genes might have previously unappreciated effects on developmental delay. PMID:24705017

Impact of the Central Polypurine Tract on the Kinetics of Human Immunodeficiency Virus Type 1 Vector Transduction

PubMed Central

Van Maele, Bénédicte; De Rijck, Jan; De Clercq, Erik; Debyser, Zeger

2003-01-01

Lentiviral vectors derived from human immunodeficiency virus type 1 (HIV-1) show great promise as gene carriers for future gene therapy. Insertion of a fragment containing the central polypurine tract (cPPT) in HIV-1 vector constructs is known to enhance transduction efficiency drastically, reportedly by facilitating the nuclear import of HIV-1 cDNA through a central DNA flap. We have studied the impact of the cPPT on the kinetics of HIV-1 vector transduction by real-time PCR. The kinetics of total HIV-1 DNA, two-long-terminal-repeat (2-LTR) circles, and, by an Alu-PCR, integrated proviral DNA were monitored. About 6 to 12 h after transduction, the total HIV-1 DNA reached a maximum level, followed by a steep decrease. The 2-LTR circles peaked after 24 to 48 h and were diluted upon cell division. Integration of HIV-1 DNA was first detected at 12 h postinfection. When HIV-1 vectors that contained the cPPT were used, DNA synthesis was similar but a threefold higher amount of 2-LTR circles was detected, confirming the impact on nuclear import. Moreover, a 10-fold increase in the amount of integrated DNA was observed in the presence of the cPPT. Only in the absence of the cPPT was a saturation in 2-LTR circle formation seen at a high multiplicity of infection, suggesting a role for the cPPT in overcoming a barrier to the nuclear import of HIV-1 DNA. A major effect of the central DNA flap on the juxtaposition of both LTRs is unlikely, since transduction with HIV-1 vectors containing ectopic cPPT fragments resulted in increased amounts of 2-LTR circles as well as integrated DNA. Inhibitors of transduction by cPPT-containing HIV vectors were also studied by real-time PCR. The reverse transcriptase inhibitor azidothymidine (AZT) and the nonnucleoside reverse transcriptase inhibitor α-APA clearly inhibited viral DNA synthesis, whereas integrase inhibitors such as the diketo acid L-708,906 and the pyranodipyrimidine V-165 specifically inhibited integration. PMID:12663775

Assessment of corrosion fatigue damage by acoustic emission and periodic proof tests

NASA Astrophysics Data System (ADS)

Mehdizadeh, P.

1976-03-01

The development of a better nondestructive inspection method for detecting corrosion fatigue damage based on acoustic emission (AE) and periodic proof testing (PPT) is studied for corrosion fatigue tests in salt water solution under tension-tension loading. It is shown that PPT combined with AE monitoring can be a sensitive method for assessing the progress of corrosion fatigue damage as the continuous AE monitoring method. The AE-PPT technique is shown to be dependent on the geometry and size of the crack relative to the test specimen. A qualitative method based on plateauing of acoustic emission counts during proof tests due to changes in the fracture mode is used to predict the remaining fatigue life up to 70% of the actual values. PPT is shown to have no adverse effect on fatigue performance in salt water.

[Effect of temperature and salinity on intrinsic increasing rate of Moina mongolica Daddy (Cladocera: Moinidae) population].

PubMed

Wang, Y; He, Z

2001-02-01

The intrinsic increasing rate of Moina mongolica Daddy, a euryhaline cladocera species isolated from inland brackish lakes of northwestern China, was studied at 20 degrees C-33 degrees C and 5-40 ppt, respectively. The results showed that its intrinsic increasing rate (rm) increased with increasing temperature from 20 degrees C-30 degrees C, and sharply dropped with further increasing temperature up to 33 degrees C. The rm of M. mongolica was relatively high at low salinity, the highest at 10 ppt, but no significant difference at 20-40 ppt. Therefore, 25 degrees C-30 degrees C and 10 ppt could be optimal for the development of M. mongolica population, and its increasing potential would not be affected significantly by rearing this cladocera species in seawater for a long period.

Involvement of Bim in Photofrin-mediated photodynamically induced apoptosis.

PubMed

Wang, Xianwang; He, Xiaobing; Hu, Shujuan; Sun, Anbang; Lu, Chengbiao

2015-01-01

Photodynamic therapy (PDT) is a promising noninvasive technique, which has been successfully applied to the treatment of human cancers. Studies have shown that the Bcl-2 family proteins play important roles in PDT-induced apoptosis. However, whether Bcl-2-interacting mediator of cell death (Bim) is involved in photodynamic treatment remains unknown. In this study, we attempt to determine the effect of Bim on Photofrin photodynamic treatment (PPT)-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells. The translocation of Bim/Bax of the cells were monitored by laser confocal scanning microscope. The levels of Bim protein and activated caspase-3 in cells were detected by western blot assay. Caspase-3 activities were measured by Caspase-3 Fluorogenic Substrate (Ac-DEVD-AFC) analysis. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. The effect of Bim on PPT-induced apoptosis was determined by RNAi. BimL translocated to mitochondria in response to PPT, similar to the downstream pro-apoptotic protein Bax activation. PPT increased the level of Bim and activated caspase-3 in cells and that knockdown of Bim by RNAi significantly protected against caspase-3 activity. PPT-induced apoptosis were suppressed in cells transfected with shRNA-Bim. We demonstrated the involvement of Bim in PPT-induced apoptosis in human ASTC-a-1 lung adenocarcinoma cells and suggested that enhancing Bim activity might be a potential strategy for treating human cancers. © 2015 S. Karger AG, Basel.

Impact of Periodic Presumptive Treatment for Bacterial Vaginosis on the Vaginal Microbiome among Women Participating in the Preventing Vaginal Infections Trial

PubMed Central

Srinivasan, Sujatha; Anzala, Omu; Kimani, Joshua; Andac, Chloe; Schwebke, Jane; Fredricks, David N.; McClelland, R. Scott

2017-01-01

Abstract Background. Evidence suggests that specific vaginal bacteria associated with bacterial vaginosis (BV) may increase the risk of adverse health outcomes in women. Among women participating in a randomized, double-blinded trial, we assessed the effect of periodic presumptive treatment (PPT) on detection of select vaginal bacteria. Methods. High-risk women from the United States and Kenya with a recent vaginal infection received intravaginal metronidazole 750 mg plus miconazole 200 mg or placebo for 5 consecutive nights each month for 12 months. Vaginal fluid specimens were collected via polyester/polyethylene terephthalate swabs every other month and tested for bacteria, using quantitative polymerase chain reaction (PCR) assays targeting the 16S ribosomal RNA gene. The effect of PPT on bacterium detection was assessed among all participants and stratified by country. Results. Of 234 women enrolled, 221 had specimens available for analysis. The proportion of follow-up visits with detectable quantities was lower in the PPT arm versus the placebo arm for the following bacteria: BVAB1, BVAB2, Atopobium vaginae, Leptotrichia/Sneathia, and Megasphaera. The magnitude of reductions was greater among Kenyan participants as compared to US participants. Conclusions. Use of monthly PPT for 1 year reduced colonization with several bacteria strongly associated with BV. The role of PPT to improve vaginal health should be considered, and efforts to improve the impact of PPT regimens are warranted. PMID:28007924

Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements

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

Ameriks, Michael K.; Axe, Frank U.; Bembenek, Scott D.

A crystal structure of 1 bound to a Cys25Ser mutant of cathepsin S helped to elucidate the binding mode of a previously disclosed series of pyrazole-based CatS inhibitors and facilitated the design of a new class of arylalkyne analogs. Optimization of the alkyne and tetrahydropyridine portions of the pharmacophore provided potent CatS inhibitors (IC{sub 50} = 40-300 nM), and an X-ray structure of 32 revealed that the arylalkyne moiety binds in the S1 pocket of the enzyme.

Spacer type mediated tunable spin crossover (SCO) characteristics of pyrene decorated 2,6-bis(pyrazol-1-yl)pyridine (bpp) based Fe(ii) molecular spintronic modules.

PubMed

Kumar, Kuppusamy Senthil; Šalitroš, Ivan; Moreno-Pineda, Eufemio; Ruben, Mario

2017-08-14

A simple "isomer-like" variation of the spacer group in a set of Fe(ii) spin crossover (SCO) complexes designed to probe spin state dependence of electrical conductivity in graphene-based molecular spintronic junctions led to the observation of remarkable variations in the thermal- and light-induced magnetic characteristics, paving a simple route for the design of functional SCO complexes with different temperature switching regimes based on a 2,6-bis(pyrazol-1-yl)pyridine ligand skeleton.

1-[(3,5-Dimethyl-1H-pyrazol-1-yl)carbon­yl]-5-methyl­indolizine-3-carbo­nitrile

PubMed Central

Gu, Wei-Jin; Xie, Wen-Li; Wang, Ting-Ting

2012-01-01

In the title mol­ecule, C16H14N4O, the indolizine ring system is essentially planar, with a maximum deviation of 0.013 (3) Å, and forms a dihedral angle of 7.52 (12)° with the pyrazole ring. In the crystal, weak C—H⋯O hydrogen bonds and π–π stacking inter­actions, with a centroid–centroid distance of 3.6378 (16) Å, link mol­ecules along [001]. PMID:23476226

Interactive effect of high environmental ammonia and nutritional status on ecophysiological performance of European sea bass (Dicentrarchus labrax) acclimated to reduced seawater salinities.

PubMed

Sinha, Amit Kumar; Rasoloniriana, Rindra; Dasan, Antony Franklin; Pipralia, Nitin; Blust, Ronny; De Boeck, Gudrun

2015-03-01

We investigated the interactive effect of ammonia toxicity, salinity challenge and nutritional status on the ecophysiological performance of European sea bass (Dicentrarchus labrax). Fish were progressively acclimated to normal seawater (32ppt), to brackish water (20ppt and 10ppt) and to hyposaline water (2.5ppt). Following acclimation to different salinities for two weeks, fish were exposed to high environmental ammonia (HEA, 20mg/L ∼1.18mM representing 50% of 96h LC50 value for ammonia) for 12h, 48h, 84h and 180h, and were either fed (2% body weight) or fasted (unfed for 7 days prior to HEA exposure). Biochemical responses such as ammonia (Jamm) and urea excretion rate, plasma ammonia, urea and lactate, plasma ions (Na(+), Cl(-) and K(+)) and osmolality, muscle water content (MWC) and liver and muscle energy budget (glycogen, lipid and protein), as well as branchial Na(+)/K(+)-ATPase (NKA) and H(+)-ATPase activity, and branchial mRNA expression of NKA and Na(+)/K(+)/2Cl(-) co-transporter (NKCC1) were investigated in order to understand metabolic and ion- osmoregulatory consequences of the experimental conditions. During HEA, Jamm was inhibited in fasted fish at 10ppt, while fed fish were still able to excrete efficiently. At 2.5ppt, both feeding groups subjected to HEA experienced severe reductions and eventually a reversion in Jamm. Overall, the build-up of plasma ammonia in HEA exposed fed fish was much lower than fasted ones. Unlike fasted fish, fed fish acclimated to lower salinities (10ppt-2.5ppt) could maintain plasma osmolality, [Na(+)], [Cl(-)] and MWC during HEA exposure. Thus fed fish were able to sustain ion-osmotic homeostasis which was associated with a more pronounced up-regulation in NKA expression and activity. At 2.5ppt both feeding groups activated H(+)-ATPase. The expression of NKCC1 was down-regulated at lower salinities in both fed and fasted fish, but was upregulated within each salinity after a few days of HEA exposure. Though an increment in plasma lactate content and a decline in energy stores were noted for both feeding regimes, the effect was more severe in feed deprived fish. Overall, several different physiological processes were disturbed in fasted sea bass during HEA exposure while feeding alleviated adverse effects of high ammonia and salinity challenge. This suggests that low food availability can render fish more vulnerable to external ammonia, especially at reduced seawater salinities. Copyright © 2015 Elsevier B.V. All rights reserved.

Control of La-doped Pb(Zr,Ti)O3 crystalline orientation and its influence on the properties of ferroelectric random access memory

NASA Astrophysics Data System (ADS)

Wang, Wensheng; Nomura, Kenji; Yamaguchi, Hideshi; Nakamura, Ko; Eshita, Takashi; Ozawa, Soichiro; Takai, Kazuaki; Mihara, Satoru; Hikosaka, Yukinobu; Hamada, Makoto; Kataoka, Yuji

2017-10-01

We investigated the crystallization mechanisms of sputter-deposited La-doped Pb(Zr,Ti)O3 (PLZT) on a Pt/Ti metal stack in the postdeposition annealing (PDA) at 600 °C in O2-mixed Ar ambient. As-deposited amorphous PLZT generally transforms to a perovskite phase over 550 °C through a metastable pyrochlore phase during the PDA. We found that the O2 content of the PDA ambient crucially affects the pyrochlore-perovskite transformation (PPT) speed. While an O2 content much higher than 2% of the PDA ambient suppresses PPT, an O2 content much lower than 2% enhances PPT. An O2 content around of 2% of the PDA suppresses PPT near the surface of PLZT and simultaneously keeps PPT fast in the inner regions of PLZT in the pyrochlore phase because of the O2 diffusion limit from the PLZT surface, eventually resulting in almost only the growth of highly {111} oriented columnar PLZT on Pt, which reveals better electric properties than those obtained by the PDA with the ambient of O2 contents much higher or lower than 2%.

Photo-pharmaceutical therapy: features and prospects

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Potapenko, Alexander Y.; Minenkov, Alexander A.

2001-07-01

This article is an attempt to analyze the concept, distinguishing features and possible application of photo- pharmaceutical therapy (PPT). Besides photopheresis, PUVA, and photodynamic therapy, PPT also embraces a broad spectrum of various combinations of light and drugs. PPT techniques can be classified according to the role of light in drug therapy into several groups: 1) Light activation of drugs before, during or after their administration, 2) light activation of cells of biotissue to potentiate the pharmaceutical effect of drugs, 3) light assisted drug delivery, 4) optical sensing of drug action at cellular and subcellular levels, and 5) selective photochemistry of drugs during their manufacturing. PPT seeks to describe the mechanisms of light-drug interaction, to time and sequence light-drug action, and to verify their synergetic effect. This article yields the results of developing new PPT modifications created in collaboration with some Russian scientific institutes and medical centers. The developed modifications are as follows: 1) drug pre-administration photoactivation, 2) antibody-photoconformation photoimmunotherapy, 3) photophonophoresis with a blend of photosensitizers and antibiotics, 4) photoelectrophoresis, 5) drug effect enhancement due to laser-induced blood circulation activation, 6) photoimmunization with alpha- fetoprotein, 7) photo-pharmaceutical dosimetry, and 8) a rapid drug toxicity photoassay.

gamma. -Preprotachykinin-(72-92)-peptide amide: An endogenous preprotachykinin I gene-derived peptide that preferentially binds to neurokinin-2 receptors

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

Dam, T.V.; Takeda, Y.; Krause, J.E.

1990-01-01

The presence of N-terminally extended forms of neurokinin A has recently been reported in the mammalian brain. Among them, gamma-preprotachykinin-(72-92)-peptide amide (gamma-PPT-(72-92)-NH2), a peptide derived by posttranslational processing of gamma-preprotachykinin, is most prominent. We report here that this peptide most likely acts on neurokinin-2 receptor sites since neurokinin A (a putative neurokinin-2 agonist) and gamma-PPT-(72-92)-NH2 are potent competitors of 125I-labeled gamma-PPT-(72-92)-NH2 binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of 125I-labeled gamma-PPT-(72-92)-NH2 and 125I-labeled neurokinin A binding sites are very similar in rat brain. On the other hand, 125I-labeled Bolton-Hunter-substance P (a neurokinin-1 ligand) and 125I-labeledmore » Bolton-Hunter-eledoisin (a neurokinin-3 ligand) binding sites are differentially located in this tissue. Thus, it appears that gamma-PPT-(72-92)-NH2 binds to neurokinin-2 receptors and should be considered as a putative endogenous ligand for this receptor class.« less

Pulsed plasma thrusters for small spacecraft attitude control

NASA Technical Reports Server (NTRS)

McGuire, Melissa L.; Myers, Roger M.

1996-01-01

Pulsed Plasma Thrusters (PPTS) are a new option for attitude control of a small spacecraft and may result in reduced attitude control system (ACS) mass and cost. The primary purpose of an ACS is to orient the spacecraft to the desired accuracy in inertial space. The ACS functions for which the PPT system will be analyzed include disturbance torque compensation, and slewing maneuvers such as sun acquisition for which the small impulse bit and high specific impulse of the PPT offers unique advantages. The NASA Lewis Research Center (LERC) currently has a contracted flight PPT system development program in place with Olin Aerospace with a delivery date of October 1997. The PPT systems in this study are based upon the work being done under the NASA LERC program. Analysis of the use of PPTs for ACS showed that the replacement of the standard momentum wheels and torque rods with a PPT system to perform the attitude control maneuvers on a small low Earth orbiting spacecraft reduced the ACS mass by 50 to 75% with no increase in required power level over comparable wheel-based systems, though rapid slewing power requirements may present an issue.

Reduced 3,4'-bipyrazoles from a simple pyrazole precursor: synthetic sequence, molecular structures and supramolecular assembly.

PubMed

Cuartas, Viviana; Insuasty, Braulio; Cobo, Justo; Glidewell, Christopher

2017-10-01

The reaction of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde and N-benzylmethylamine under microwave irradiation gives 5-[benzyl(methyl)amino]-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, C 19 H 19 N 3 O, (I). Subsequent reactions under basic conditions, between (I) and a range of acetophenones, yield the corresponding chalcones. These undergo cyclocondensation reactions with hydrazine to produce reduced bipyrazoles which can be N-formylated with formic acid or N-acetylated with acetic anhydride. The structures of (I) and of representative examples from this reaction sequence are reported, namely the chalcone (E)-3-{5-[benzyl(methyl)amino]-3-methyl-1-phenyl-1H-pyrazol-4-yl}-1-(4-bromophenyl)prop-2-en-1-one, C 27 H 24 BrN 3 O, (II), the N-formyl derivative (3RS)-5'-[benzyl(methyl)amino]-3'-methyl-1',5-diphenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole]-2-carbaldehyde, C 28 H 27 N 5 O, (III), and the N-acetyl derivative (3RS)-2-acetyl-5'-[benzyl(methyl)amino]-5-(4-methoxyphenyl)-3'-methyl-1'-phenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole], which crystallizes as the ethanol 0.945-solvate, C 30 H 31 N 5 O 2 ·0.945C 2 H 6 O, (IV). There is significant delocalization of charge from the benzyl(methyl)amino substituent onto the carbonyl group in (I), but not in (II). In each of (III) and (IV), the reduced pyrazole ring is modestly puckered into an envelope conformation. The molecules of (I) are linked by a combination of C-H...N and C-H...π(arene) hydrogen bonds to form a simple chain of rings; those of (III) are linked by a combination of C-H...O and C-H...N hydrogen bonds to form sheets of R 2 2 (8) and R 6 6 (42) rings, and those of (IV) are linked by a combination of O-H...N and C-H...O hydrogen bonds to form a ribbon of edge-fused R 2 4 (16) and R 4 4 (24) rings.

Regional grassland productivity responses to precipitation during multiyear above- and below-average rainfall periods.

PubMed

Petrie, Matthew D; Peters, Debra P C; Yao, Jin; Blair, John M; Burruss, Nathan D; Collins, Scott L; Derner, Justin D; Gherardi, Laureano A; Hendrickson, John R; Sala, Osvaldo E; Starks, Patrick J; Steiner, Jean L

2018-05-01

There is considerable uncertainty in the magnitude and direction of changes in precipitation associated with climate change, and ecosystem responses are also uncertain. Multiyear periods of above- and below-average rainfall may foretell consequences of changes in rainfall regime. We compiled long-term aboveground net primary productivity (ANPP) and precipitation (PPT) data for eight North American grasslands, and quantified relationships between ANPP and PPT at each site, and in 1-3 year periods of above- and below-average rainfall for mesic, semiarid cool, and semiarid warm grassland types. Our objective was to improve understanding of ANPP dynamics associated with changing climatic conditions by contrasting PPT-ANPP relationships in above- and below-average PPT years to those that occurred during sequences of multiple above- and below-average years. We found differences in PPT-ANPP relationships in above- and below-average years compared to long-term site averages, and variation in ANPP not explained by PPT totals that likely are attributed to legacy effects. The correlation between ANPP and current- and prior-year conditions changed from year to year throughout multiyear periods, with some legacy effects declining, and new responses emerging. Thus, ANPP in a given year was influenced by sequences of conditions that varied across grassland types and climates. Most importantly, the influence of prior-year ANPP often increased with the length of multiyear periods, whereas the influence of the amount of current-year PPT declined. Although the mechanisms by which a directional change in the frequency of above- and below-average years imposes a persistent change in grassland ANPP require further investigation, our results emphasize the importance of legacy effects on productivity for sequences of above- vs. below-average years, and illustrate the utility of long-term data to examine these patterns. © 2018 John Wiley & Sons Ltd.

REM sleep modulation by perifornical orexinergic inputs to the pedunculo-pontine tegmental neurons in rats.

PubMed

Khanday, M A; Mallick, B N

2015-11-12

Rapid eye movement sleep (REMS) is regulated by the interaction of the REM-ON and REM-OFF neurons located in the pedunculo-pontine-tegmentum (PPT) and the locus coeruleus (LC), respectively. Many other brain areas, particularly those controlling non-REMS (NREMS) and waking, modulate REMS by modulating these REMS-related neurons. Perifornical (PeF) orexin (Ox)-ergic neurons are reported to increase waking and reduce NREMS as well as REMS; dysfunction of the PeF neurons are related to REMS loss-associated disorders. Hence, we were interested in understanding the neural mechanism of PeF-induced REMS modulation. As a first step we have recently reported that PeF Ox-ergic neurons modulate REMS by influencing the LC neurons (site for REM-OFF neurons). Thereafter, in this in vivo study we have explored the role of PeF inputs on the PPT neurons (site for REM-ON neurons) for the regulation of REMS. Chronic male rats were surgically prepared with implanted bilateral cannulae in PeF and PPT and electrodes for recording sleep-waking patterns. After post-surgical recovery sleep-waking-REMS were recorded when bilateral PeF neurons were stimulated by glutamate and simultaneously bilateral PPT neurons were infused with either saline or orexin receptor1 (OX1R) antagonist. It was observed that PeF stimulation increased waking and decreased NREMS as well as REMS, which were prevented by OX1R antagonist into the PPT. We conclude that the PeF stimulation-induced reduction in REMS was likely to be due to inhibition of REM-ON neurons in the PPT. As waking and NREMS are inversely related, subject to confirmation, the reduction in NREMS could be due to increased waking or vice versa. Based on our findings from this and earlier studies we have proposed a model showing connections between PeF- and PPT-neurons for REMS regulation. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.

PubMed

Butler, Michael J; Hildebrandt, Ryan P; Eckel, Lisa A

2018-05-25

Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect. Copyright © 2017. Published by Elsevier Inc.

Synthesis, Photophysical and Computational Study of Novel Coumarin-based Organic Dyes.

PubMed

Kumbar, Mahadev N; Sannaikar, Madivalagouda S; Shaikh, Saba Kauser J; Kamble, Atulkumar A; Wari, Manjunath N; Inamdar, Sanjeev R; Qiao, Qiquan; Revanna, Bhavya N; Madegowda, Mahendra; Dasappa, Jagadeesh P; Kamble, Ravindra R

2018-03-01

A series of novel coumarin pyrazoline moieties combined with tetrazoles, 3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one, 6-chloro-3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one, 6-bromo-3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one and 6-bromo-3-(1-(4-bromophenyl)-4-(1H-tetrazol-5-yl)-1H pyrazol-3-yl)-2H-chromen-2-one7(a-d), were designed and synthesized. Single crystal X-ray diffraction and their interactions were studied by Hirshfeld surface analysis. Thermal stabilities and electrochemical properties of these compounds were examined from differential scanning calorimetry (DSC), thermogravimetric (TGA) and cyclic voltammetric (CV) studies. Their spectroscopic properties were analyzed in various alcohols and general solvents by UV-Vis absorption, fluorescence and time-resolved spectroscopy. In addition, the ground and excited state electronic properties were investigated using density functional theory (DFT). The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and energy band gap (E g ) values have revealed the effect of substitution of halogens. The substitution has equally affected the ground and excited states of 7(a-d) compounds. The solvatochromism on absorption, fluorescence spectra and fluorescence lifetimes of these compounds was investigated. All these results showed the chromen-2-one of pyrazoline tetrazole derivatives could play an important role in photonic and electronic devices. © 2017 The American Society of Photobiology.

Reconciling inconsistencies in precipitation-productivity relationships: implications for climate change.

PubMed

Knapp, Alan K; Ciais, Philippe; Smith, Melinda D

2017-04-01

Contents 41 I. 41 II. 42 III. 43 IV. 44 V. 45 Acknowledgements 46 References 46 SUMMARY: Precipitation (PPT) is a primary climatic determinant of plant growth and aboveground net primary production (ANPP) over much of the globe. Thus, PPT-ANPP relationships are important both ecologically and to land-atmosphere models that couple terrestrial vegetation to the global carbon cycle. Empirical PPT-ANPP relationships derived from long-term site-based data are almost always portrayed as linear, but recent evidence has accumulated that is inconsistent with an underlying linear relationship. We review, and then reconcile, these inconsistencies with a nonlinear model that incorporates observed asymmetries in PPT-ANPP relationships. Although data are currently lacking for parameterization, this new model highlights research needs that, when met, will improve our understanding of carbon cycle dynamics, as well as forecasts of ecosystem responses to climate change. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Similarity of SABRE field dependence in chemically different substrates

NASA Astrophysics Data System (ADS)

Dücker, Eibe B.; Kuhn, Lars T.; Münnemann, Kerstin; Griesinger, Christian

2012-01-01

The Non-Hydrogenative Parahydrogen-Induced Polarization (NH-PHIP) technique, which is referred to as Signal Amplification by Reversible Exchange (SABRE), has been reported to be applicable to various substrates and catalysts. For more detailed studies, pyridine was mainly examined in the past. Here, we examined several pyrazole derivatives towards their amenability to this method using Crabtree's Catalyst, which is the polarization transfer catalyst that is best documented. Additionally, the dependence of the signal enhancement on the field strength, at which the polarization step takes place, was examined for pyridine and four different pyrazoles. To achieve this, the polarization step was performed at numerous previously determined magnetic fields in the stray field of the NMR spectrometer. The substrate dependence of the field dependence proved to be relatively small for the different pyrazoles and a strong correlation to the field dependence for pyridine was observed. Reducing the number of spins in the catalyst by deuteration leads to increased enhancement. This indicates that more work has to be invested in order to be able to reproduce the SABRE field dependence by simulations.

Ru-bis(pyridine)pyrazolate (bpp)-Based Water-Oxidation Catalysts Anchored on TiO2: The Importance of the Nature and Position of the Anchoring Group.

PubMed

Francàs, Laia; Richmond, Craig; Garrido-Barros, Pablo; Planas, Nora; Roeser, Stephan; Benet-Buchholz, Jordi; Escriche, Lluís; Sala, Xavier; Llobet, Antoni

2016-04-04

Three distinct functionalisation strategies have been applied to the in,in-[{Ru(II)(trpy)}2(μ-bpp)(H2O)2](3+) (trpy=2,2':6',2''-terpyridine, bpp=bis(pyridine)pyrazolate) water-oxidation catalyst framework to form new derivatives that can adsorb onto titania substrates. Modifications included the addition of sulfonate, carboxylate, and phosphonate anchoring groups to the terpyridine and bis(pyridyl)pyrazolate ligands. The complexes were characterised in solution by using 1D NMR, 2D NMR, and UV/Vis spectroscopic analysis and electrochemical techniques. The complexes were then anchored on TiO2-coated fluorinated tin oxide (FTO) films, and the reactivity of these new materials as water-oxidation catalysts was tested electrochemically through controlled-potential electrolysis (CPE) with oxygen evolution detected by headspace analysis with a Clark electrode. The results obtained highlight the importance of the catalyst orientation with respect to the titania surface in regard to its capacity to catalytically oxidize water to dioxygen. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin.

PubMed

Nieto, Carla I; Cabildo, María Pilar; Cornago, María Pilar; Sanz, Dionisia; Claramunt, Rosa M; Torralba, María Carmen; Torres, María Rosario; Elguero, José; García, José A; López, Ana; Acuña-Castroviejo, Darío

2015-08-28

A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (¹H, (13)C, (19)F and (15)N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure-activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms.

A study of the vaporization enthalpies of some 1-substituted imidazoles and pyrazoles by correlation-gas chromatography.

PubMed

Lipkind, Dmitry; Plienrasri, Chatchawat; Chickos, James S

2010-12-23

The vaporization enthalpies of 1-methyl-, 1-ethyl-, 1-phenyl-, and 1-benzylimidazole, 1-methyl- and 1-phenylpyrazole, and trans-azobenzene are evaluated by correlation-gas chromatography (C-GC) using a variety of azines and diazines as standards. The vaporization enthalpies obtained by C-GC when compared to literature values are approximately 14 kJ·mol(-1) smaller for the imidazoles and 6 kJ·mol(-1) smaller for the pyrazoles. The literature vaporization enthalpies of 1-methylpyrrole and 1-methylindole, two closely related compounds with one less nitrogen, are reproduced by C-GC. These results suggest that the magnitude of the intermolecular interactions present in 1-substituted imidazoles and pyrazoles are significantly larger than the those present in the reference compounds and greater than or equal in magnitude to the enhanced intermolecular interactions observed previously in aromatic 1,2-diazines. The vaporization enthalpy and vapor pressure of a trans-1,2-diazine, trans-azobenzene, measured by C-GC using similar standards reproduced the literature values within experimental error.

Evaluation of Household Bleach as an Ovicide for the Control of Aedes Aegypti

PubMed Central

Mackay, Andrew J.; Amador, Manuel; Felix, Gilberto; Acevedo, Veronica; Barrera, Roberto

2015-01-01

Accumulations of dormant eggs in container habitats allow Aedes aegypti populations to survive harsh environmental conditions and may frustrate control interventions directed at larval and adult life stages. While sodium hypochlorite solutions (NaOCl) have long been recognized as ovicides for use against dengue vectors, the susceptibility of eggs to spray applications has not been robustly evaluated on substrate materials representative of the most frequently utilized artificial container habitats. Experiments were performed under controlled and natural conditions by applying dilutions of household bleach (52.5 ppt NaOCl) as a spray to eggs on plastic, rubber, and concrete surfaces, with and without a smectite clay thickener. Laboratory assays identified the minimum NaOCl concentrations required to eliminate eggs on plastic (10 ppt), rubber (20 ppt) and concrete (20 ppt) surfaces. Addition of smectite clay reduced the minimum effective concentration to 10 ppt NaOCl for all 3 substrates. A minimum exposure period of 24 h was required to completely eliminate egg viability on concrete surfaces, even at the highest NaOCl concentration (52.5 ppt). Field experiments verified that spray application of a 1:3 dilution of household bleach mixed with smectite clay can reduce egg hatching by ≥ 99% in shaded and sun-exposed plastic containers. Similarly, 4:1 dilution of household bleach (with or without smectite clay) eliminated ≥ 98% of eggs from concrete surfaces in outdoor, water-filled drums. In this study, we propose a practical, effective and safe strategy for using household bleach to eliminate Ae. aegypti eggs in a range of artificial container habitats. PMID:25843179

Impact of Periodic Presumptive Treatment for Bacterial Vaginosis on the Vaginal Microbiome among Women Participating in the Preventing Vaginal Infections Trial.

PubMed

Balkus, Jennifer E; Srinivasan, Sujatha; Anzala, Omu; Kimani, Joshua; Andac, Chloe; Schwebke, Jane; Fredricks, David N; McClelland, R Scott

2017-03-01

Evidence suggests that specific vaginal bacteria associated with bacterial vaginosis (BV) may increase the risk of adverse health outcomes in women. Among women participating in a randomized, double-blinded trial, we assessed the effect of periodic presumptive treatment (PPT) on detection of select vaginal bacteria. High-risk women from the United States and Kenya with a recent vaginal infection received intravaginal metronidazole 750 mg plus miconazole 200 mg or placebo for 5 consecutive nights each month for 12 months. Vaginal fluid specimens were collected via polyester/polyethylene terephthalate swabs every other month and tested for bacteria, using quantitative polymerase chain reaction (PCR) assays targeting the 16S ribosomal RNA gene. The effect of PPT on bacterium detection was assessed among all participants and stratified by country. Of 234 women enrolled, 221 had specimens available for analysis. The proportion of follow-up visits with detectable quantities was lower in the PPT arm versus the placebo arm for the following bacteria: BVAB1, BVAB2, Atopobium vaginae, Leptotrichia/Sneathia, and Megasphaera. The magnitude of reductions was greater among Kenyan participants as compared to US participants. Use of monthly PPT for 1 year reduced colonization with several bacteria strongly associated with BV. The role of PPT to improve vaginal health should be considered, and efforts to improve the impact of PPT regimens are warranted. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Validation of percutaneous puncture trajectory during renal access using 4D ultrasound reconstruction

NASA Astrophysics Data System (ADS)

Rodrigues, Pedro L.; Rodrigues, Nuno F.; Fonseca, Jaime C.; Vilaça, João. L.

2015-03-01

An accurate percutaneous puncture is essential for disintegration and removal of renal stones. Although this procedure has proven to be safe, some organs surrounding the renal target might be accidentally perforated. This work describes a new intraoperative framework where tracked surgical tools are superimposed within 4D ultrasound imaging for security assessment of the percutaneous puncture trajectory (PPT). A PPT is first generated from the skin puncture site towards an anatomical target, using the information retrieved by electromagnetic motion tracking sensors coupled to surgical tools. Then, 2D ultrasound images acquired with a tracked probe are used to reconstruct a 4D ultrasound around the PPT under GPU processing. Volume hole-filling was performed in different processing time intervals by a tri-linear interpolation method. At spaced time intervals, the volume of the anatomical structures was segmented to ascertain if any vital structure is in between PPT and might compromise the surgical success. To enhance the volume visualization of the reconstructed structures, different render transfer functions were used. Results: Real-time US volume reconstruction and rendering with more than 25 frames/s was only possible when rendering only three orthogonal slice views. When using the whole reconstructed volume one achieved 8-15 frames/s. 3 frames/s were reached when one introduce the segmentation and detection if some structure intersected the PPT. The proposed framework creates a virtual and intuitive platform that can be used to identify and validate a PPT to safely and accurately perform the puncture in percutaneous nephrolithotomy.

Acetylcholine from the mesopontine tegmental nuclei differentially affects methamphetamine induced locomotor activity and neurotransmitter levels in the mesolimbic pathway

PubMed Central

Dobbs, Lauren K.; Mark, Gregory P.

2012-01-01

Methamphetamine (MA) increases dopamine (DA) levels within the mesolimbic pathway and acetylcholine (ACh), a neurotransmitter known to increase DA cell firing and release and mediate reinforcement, within the ventral tegmental area (VTA). The laterodorsal tegmental (LDT) and pedunculopontine tegmental (PPT) nuclei provide cholinergic input to the VTA; however, the contribution of LDT- and PPT-derived ACh to MA-induced DA and ACh levels and locomotor activation remains unknown. The first experiment examined the role of LDT-derived ACh in MA locomotor activation by reversibly inhibiting these neurons with bilateral intra-LDT microinjections of the M2 receptor agonist oxotremorine (OXO). Male C57BL/6 J mice were given a bilateral 0.1 µl OXO (0, 1, or 10 nM/side) microinjection immediately prior to IP saline or MA (2 mg/kg). The highest OXO concentration significantly inhibited both saline-and MA-primed locomotor activity. In a second set of experiments we characterized the individual contributions of ACh originating in the LDT or pedunculopontine tegmental nucleus (PPT) to MA-induced levels of ACh and DA by administering intra-LDT or PPT OXO and performing in vivo microdialysis in the VTA and NAc. Intra-LDT OXO dose-dependently attenuated the MA-induced increase in ACh within the VTA but had no effect on DA in NAc. Intra-PPT OXO had no effect on ACh or DA levels within the VTA or NAc, respectively. We conclude that LDT, but not PPT, ACh is important in locomotor behavior and the cholinergic, but not dopaminergic, response to systemic MA. PMID:21945297

Pyranopterin Coordination Controls Molybdenum Electrochemistry in Escherichia coli Nitrate Reductase*

PubMed Central

Wu, Sheng-Yi; Rothery, Richard A.; Weiner, Joel H.

2015-01-01

We test the hypothesis that pyranopterin (PPT) coordination plays a critical role in defining molybdenum active site redox chemistry and reactivity in the mononuclear molybdoenzymes. The molybdenum atom of Escherichia coli nitrate reductase A (NarGHI) is coordinated by two PPT-dithiolene chelates that are defined as proximal and distal based on their proximity to a [4Fe-4S] cluster known as FS0. We examined variants of two sets of residues involved in PPT coordination: (i) those interacting directly or indirectly with the pyran oxygen of the bicyclic distal PPT (NarG-Ser719, NarG-His1163, and NarG-His1184); and (ii) those involved in bridging the two PPTs and stabilizing the oxidation state of the proximal PPT (NarG-His1092 and NarG-His1098). A S719A variant has essentially no effect on the overall Mo(VI/IV) reduction potential, whereas the H1163A and H1184A variants elicit large effects (ΔEm values of −88 and −36 mV, respectively). Ala variants of His1092 and His1098 also elicit large ΔEm values of −143 and −101 mV, respectively. An Arg variant of His1092 elicits a small ΔEm of +18 mV on the Mo(VI/IV) reduction potential. There is a linear correlation between the molybdenum Em value and both enzyme activity and the ability to support anaerobic respiratory growth on nitrate. These data support a non-innocent role for the PPT moieties in controlling active site metal redox chemistry and catalysis. PMID:26297003

Metformin increases pressure pain threshold in lean women with polycystic ovary syndrome.

PubMed

Kiałka, Marta; Milewicz, Tomasz; Sztefko, Krystyna; Rogatko, Iwona; Majewska, Renata

2016-01-01

Despite the strong preclinical rationale, there are only very few data considering the utility of metformin as a potential pain therapeutic in humans. The aim of this study was to determine the association between metformin therapy and pressure pain threshold (PPT) in lean women with polycystic ovary syndrome (PCOS). We hypothesized that metformin therapy in lean PCOS women increases PPT. Twenty-seven lean PCOS women with free androgen index phenotype >5 and 18 lean healthy controls were enrolled in the study. Fifteen of the PCOS women were randomly assigned to be treated with metformin 1,500 mg daily for 6 months. PPT and plasma β-endorphin levels were measured in all women at the beginning of the study and after 6 months of observation. We observed an increase in PPT values measured on deltoid and trapezius muscle in the PCOS with metformin group after 6 months of metformin administration (4.81±0.88 kg/cm(2), P<0.001 on deltoid muscle, and 5.71±1.16 kg/cm(2) on trapezius muscle). We did not observe any significant changes in PPT values in the PCOS without treatment group and in controls. We did not observe any significant changes in serum β-endorphin levels in any studied groups during the 6-month observation. We conclude that metformin therapy increases PPT in lean PCOS women, without affecting plasma β-endorphin concentration. Our results may suggest the potential role of metformin in pain therapy. We propose that larger, randomized studies on metformin impact on pain perception should be performed.

Smoking, inflammatory patterns, and postprandial hypertriglyceridemia

USDA-ARS?s Scientific Manuscript database

Background: Smoking is associated with increased postprandial hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential "drivers" for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPT. Methods: Men and women i...

Is One Trial Sufficient to Obtain Excellent Pressure Pain Threshold Reliability in the Low Back of Asymptomatic Individuals? A Test-Retest Study.

PubMed

Balaguier, Romain; Madeleine, Pascal; Vuillerme, Nicolas

2016-01-01

The assessment of pressure pain threshold (PPT) provides a quantitative value related to the mechanical sensitivity to pain of deep structures. Although excellent reliability of PPT has been reported in numerous anatomical locations, its absolute and relative reliability in the lower back region remains to be determined. Because of the high prevalence of low back pain in the general population and because low back pain is one of the leading causes of disability in industrialized countries, assessing pressure pain thresholds over the low back is particularly of interest. The purpose of this study study was (1) to evaluate the intra- and inter- absolute and relative reliability of PPT within 14 locations covering the low back region of asymptomatic individuals and (2) to determine the number of trial required to ensure reliable PPT measurements. Fifteen asymptomatic subjects were included in this study. PPTs were assessed among 14 anatomical locations in the low back region over two sessions separated by one hour interval. For the two sessions, three PPT assessments were performed on each location. Reliability was assessed computing intraclass correlation coefficients (ICC), standard error of measurement (SEM) and minimum detectable change (MDC) for all possible combinations between trials and sessions. Bland-Altman plots were also generated to assess potential bias in the dataset. Relative reliability for both intra- and inter- session was almost perfect with ICC ranged from 0.85 to 0.99. With respect to the intra-session, no statistical difference was reported for ICCs and SEM regardless of the conducted comparisons between trials. Conversely, for inter-session, ICCs and SEM values were significantly larger when two consecutive PPT measurements were used for data analysis. No significant difference was observed for the comparison between two consecutive measurements and three measurements. Excellent relative and absolute reliabilities were reported for both intra- and inter-session. Reliable measurements can be equally achieved when using the mean of two or three consecutive PPT measurements, as usually proposed in the literature, or with only the first one. Although reliability was almost perfect regardless of the conducted comparison between PPT assessments, our results suggest using two consecutive measurements to obtain higher short term absolute reliability.

Seasonal measurements of organic acid fluxes over a ponderosa pine forest

NASA Astrophysics Data System (ADS)

Fulgham, S. R.; Brophy, P.; Link, M.; Ortega, J. V.; Farmer, D.

2016-12-01

The biosphere acts as both a source and a sink of oxidized organic compounds. Ignoring dry deposition leads to overestimation of secondary organic aerosols by aerosol models, while ignoring emission sources underestimates the budget of organic acids. Developing parameterizations for oxidized organic dry deposition and emission requires observational constraints. Although biosphere parameters are impacted by seasonal variability, most reactive, trace-gas exchange measurements are made for only short periods of time in the main growing season. Here we make fast (5 - 10 Hz) and sensitive (e.g. 0.73 ppt mean limit of detection for formic acid with 10 s averaging) eddy covariance measurements of gas-phase organic acids and other oxidized organic species with a high resolution Time-of-Flight Chemical Ionization Mass Spectrometer with acetate and iodide reagent ions. Measurements were made in 4 - 6 week campaigns over five seasons from summer 2015 to fall 2016 as part of the Seasonal Particles in Forests Flux studY (SPIFFY) at the Manitou Experimental Forest Observatory near Woodland Park, Colorado. Permeation tubes were used for online calibration of carboxylic acids including formic (C1), propionic (C3), butyric (C4), methacrylic (CH2C(CH3)COOH), valeric (C5), and heptanoic (C7) acids. Average daytime mixing ratios for formic acid were 100 ± 100 ppt in winter and 1500 ± 1000 ppt in summer 2016. Upward fluxes of formic acid were observed throughout the experiment, daytime averages and standard deviations ranging from 1900 ± 1000 ppt cm s-1 in winter to 170 ± 130 ppt cm s-1 in spring. Propionic (22 ± 22 ppt cm s-1), butyric (17 ± 16 ppt cm s-1), and methacrylic (3.5 ± 6.1 ppt cm s-1) acids exhibit a mix of upward, near-zero, and downward fluxes. Fluxes were exponentially correlated to temperature, suggesting an ecosystem-scale source of these acids. We also measure exchange velocities of a broad suite of other oxidized organic compounds (31.99 m/z to 311.523 m/z in acetate and 31.99 m/z to 474.97 m/z in iodide) and investigate the role of elemental composition as a predictor of exchange velocity for these molecules.

Identification of cholinergic and non-cholinergic neurons in the pons expressing phosphorylated cyclic adenosine monophosphate response element-binding protein as a function of rapid eye movement sleep.

PubMed

Datta, S; Siwek, D F; Stack, E C

2009-09-29

Recent studies have shown that in the pedunculopontine tegmental nucleus (PPT), increased neuronal activity and kainate receptor-mediated activation of intracellular protein kinase A (PKA) are important physiological and molecular steps for the generation of rapid eye movement (REM) sleep. In the present study performed on rats, phosphorylated cyclic AMP response element-binding protein (pCREB) immunostaining was used as a marker for increased intracellular PKA activation and as a reflection of increased neuronal activity. To identify whether activated cells were either cholinergic or noncholinergic, the PPT and laterodorsal tegmental nucleus (LDT) cells were immunostained for choline acetyltransferase (ChAT) in combination with pCREB or c-Fos. The results demonstrated that during high rapid eye movement sleep (HR, approximately 27%), significantly higher numbers of cells expressed pCREB and c-Fos in the PPT, of which 95% of pCREB-expressing cells were ChAT-positive. With HR, the numbers of pCREB-positive cells were also significantly higher in the medial pontine reticular formation (mPRF), pontine reticular nucleus oral (PnO), and dorsal subcoeruleus nucleus (SubCD) but very few in the locus coeruleus (LC) and dorsal raphe nucleus (DRN). Conversely, with low rapid eye movement sleep (LR, approximately 2%), the numbers of pCREB expressing cells were very few in the PPT, mPRF, PnO, and SubCD but significantly higher in the LC and DRN. The results of regression analyses revealed significant positive relationships between the total percentages of REM sleep and numbers of ChAT+/pCREB+ (Rsqr=0.98) cells in the PPT and pCREB+ cells in the mPRF (Rsqr=0.88), PnO (Rsqr=0.87), and SubCD (Rsqr=0.84); whereas significantly negative relationships were associated with the pCREB+ cells in the LC (Rsqr=0.70) and DRN (Rsqr=0.60). These results provide evidence supporting the hypothesis that during REM sleep, the PPT cholinergic neurons are active, whereas the LC and DRN neurons are inactive. More importantly, the regression analysis indicated that pCREB activation in approximately 98% of PPT cholinergic neurons, was caused by REM sleep. Moreover the results indicate that during REM sleep, PPT intracellular PKA activation and a transcriptional cascade involving pCREB occur exclusively in the cholinergic neurons.

7-Chloro-5-(2-ethoxy­phen­yl)-1-methyl-3-propyl-2,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine

PubMed Central

Zhou, Ming-Qiu; Zhu, Kai; Lv, Xiao-Ping; Han, Ping-Fang; Wei, Ping

2009-01-01

In the title compound, C17H21ClN4O, the benzene ring is oriented at dihedral angles of 1.59 (3) and 1.27 (3)° with respect to the pyrimidine and pyrazole rings, while the dihedral angle between the pyrimidine and pyrazole rings is 0.83 (3)°. An intra­molecular N—H⋯O hydrogen bond results in the formation of a planar (r.m.s. deviation 0.004 Å) six-membered ring. PMID:21577789

Synthesis and antitumor screening of new 1,7-diphenyl-3-(1,3-disubstituted-1H-pyrazole-4-carbonyl)-[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones.

PubMed

Shawali, Ahmad S; Sherif, Sherif M; Darwish, Manal A A; El-merzabani, Mahmoud M

2010-01-01

A new series of 3-(1,3-disubstituted-1H-pyrazole-4-carbonyl)-1,7-diphenyl-[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones 4 was prepared by reaction of the enaminone 2 with hydrazonoyl halides 3. The preliminary screening for antitumor activity of the synthesized compounds was carried out against Ehrlich Ascites Carcinoma tumor cells. The results revealed that the studied compounds 4 have low or no antitumor activity towards EAC tumor cells.

Poly(meth)acrylates obtained by cascade reaction.

PubMed

Popescu, Dragos; Keul, Helmut; Moeller, Martin

2011-04-04

Preparation, purification, and stabilization of functional (meth)acrylates with a high dipole moment are complex, laborious, and expensive processes. In order to avoid purification and stabilization of the highly reactive functional monomers, a concept of cascade reactions was developed comprising enzymatic monomer synthesis and radical polymerization. Transacylation of methyl acrylate (MA) and methyl methacrylate (MMA) with different functional alcohols, diols, and triols (1,2,6-hexanetriol and glycerol) in the presence of Novozyme 435 led to functional (meth)acrylates. After the removal of the enzyme by means of filtration, removal of excess (meth)acrylate and/or addition of a new monomer, e.g., 2-hydroxyethyl (meth)acrylate the (co)polymerization via free radical (FRP) or nitroxide mediated radical polymerization (NMP) resulted in poly[(meth)acrylate]s with predefined functionalities. Hydrophilic, hydrophobic as well as ionic repeating units were assembled within the copolymer. The transacylation of MA and MMA with diols and triols carried out under mild conditions is an easy and rapid process and is suitable for the preparation of sensitive monomers. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microbial transformations of diosgenin by the white-rot basidiomycete Coriolus versicolor.

PubMed

Wu, Guang-Wei; Gao, Jin-Ming; Shi, Xin-Wei; Zhang, Qiang; Wei, Shao-Peng; Ding, Kan

2011-10-28

Microbial transformation of diosgenin (3β-hydroxy-5-spirostene) using white-rot fungus Coriolus versicolor afforded four previously unreported polyhydroxylated steroids, 25(R)-spirost-5-en-3β,7α,15α,21-tetraol (5), 25(R)-spirost-5-en-3β,7β,12β,21-tetrol (6), (25R)-spirost-5-en-3β,7α,12β,21-tetraol (7), and (25R)-spirost-5-en-3β,7β,11α,21-tetraol (8), along with three known congeners, 25(R)-spirost-5-en-3β,7β-diol (2), 25(R)-spirost-5-en-3β,7β,21-triol (3), and 25(R)-spirost-5-en-3β,7β,12β-triol (4). These structures were elucidated by 1D and 2D NMR as well as HR-ESIMS analysis. In addition, we provide evidence for two new microbial hydroxylations of diosgenin: C-21 primary carbon hydroxylation and C-15 hydroxylation. The 3β-hydroxyl group and double bond in the B-ring of diosgenin were found to be important structural determinants for their activity.

Failure of juice or juice extract from the noni plant (Morinda citrifolia) to protect rats against oxygen toxicity.

PubMed

Berg, John T; Furusawa, Eiichi

2007-02-01

Noni juice possesses antioxidant activity and prevents superoxide-mediated tissue injury in laboratory animals. A polysaccharide-rich precipitate of noni juice (noni-ppt) also stimulates tumor necrosis factor (TNF) and interleukin 1 (IL-1) in mice. Endotoxin (lipopolysaccharide) stimulates TNF and IL-1 in rats and protects against superoxide-mediated oxygen toxicity. Accordingly, we hypothesized that noni juice, or noni-ppt, would protect rats against pulmonary oxygen toxicity. Rats were divided into four groups; one received noni-ppt to test for cytokine-induced protection; another received noni juice to test for antioxidant activity; a third received saline as hyperoxia control; a fourth received no treatment in air. Rats were then exposed to either hyperoxia (> 97% oxygen at sea level for 52 or 60 hours) or air and lung injury assessed. Rats receiving saline, noni-ppt or noni juice exhibited typical signs of oxygen toxicity with hemorrhagic lungs, large pleural effusions and increases in protein concentration in bronchoalveolar lavage fluid. They also developed heavy lungs with increases in wet/dry weight ratios, hematocrit values and ratios of effusion protein to plasma protein concentration. These results show that Noni juice and Noni-ppt do not prevent oxygen toxicity in rats when administered according to the protocols used in this study.

Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in cultured neurons and neuronal progenitor cells from mice lacking PPT1.

PubMed

Kim, Sung-Jo; Zhang, Zhongjian; Saha, Arjun; Sarkar, Chinmoy; Zhao, Zhenwen; Xu, Yan; Mukherjee, Anil B

2010-08-02

Reactive oxygen species (ROS) damage brain lipids, carbohydrates, proteins, as well as DNA and may contribute to neurodegeneration. We previously reported that ER- and oxidative stress cause neuronal apoptosis in infantile neuronal ceroid lipofuscinosis (INCL), a lethal neurodegenerative storage disease, caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. Polyunsaturated fatty acids (PUFA) are essential components of cell membrane phospholipids in the brain and excessive ROS may cause oxidative damage of PUFA leading to neuronal death. Using cultured neurons and neuroprogenitor cells from mice lacking Ppt1, which mimic INCL, we demonstrate that Ppt1-deficient neurons and neuroprogenitor cells contain high levels of ROS, which may cause peroxidation of PUFA and render them incapable of providing protection against oxidative stress. We tested whether treatment of these cells with omega-3 or omega-6 PUFA protects the neurons and neuroprogenitor cells from oxidative stress and suppress apoptosis. We report here that both omega-3 and omega-6 fatty acids protect the Ppt1-deficient cells from ER- as well as oxidative stress and suppress apoptosis. Our results suggest that PUFA supplementation may have neuroprotective effects in INCL. Published by Elsevier Ireland Ltd.

Measurements of atmospheric carbonyl sulfide during the NASA Chemical Instrumentation Test and Evaluation Project: Implications for the global COS budget

NASA Technical Reports Server (NTRS)

Johnson, James E.; Bandy, Alan R.; Thornton, Donald C.; Bates, Timothy S.

1993-01-01

Atmospheric carbonyl sulfide COS concentrations were measured by three analytical systems during the Chemical Instrumentation Test and Evaluation (CITE 3) project. The three systems all used cryogenic sample preconcentration and gas chromatographic (GC) separation but differed in the method of detection. The FPD system used a flame photometric detector, the MS system used a mass selective detector, and the ECD-S system used a fluorinating catalyst followed by an electron capture detector. With the FPD system, we found a mean COS concentration of 510 ppt over the North Atlantic and 442 ppt over the Tropical Atlantic. With the ECD-S system, we found a mean COS concentration of 489 ppt over the North Atlantic and 419 ppt over the Tropical Atlantic. All three systems registered a latitudinal gradient in atmospheric COS of between 1.6 and 2.0 ppt per degree of latitude, with increasing COS concentrations northward which was similar to the gradient measured by Bingemer et al. (1990). It is difficult to reconcile the measured latitudinal concentration gradient with present theories of the global COS budget since the largest sink of COS is thought to be a flux to land plants, most of which are in the northern hemisphere.

Whole air canister sampling coupled with preconcentration GC/MS analysis of part-per-trillion levels of trimethylsilanol in semiconductor cleanroom air.

PubMed

Herrington, Jason S

2013-08-20

The costly damage airborne trimethylsilanol (TMS) exacts on optics in the semiconductor industry has resulted in the demand for accurate and reliable methods for measuring TMS at trace levels (i.e., parts per trillion, volume per volume of air [ppt(v)] [~ng/m(3)]). In this study I developed a whole air canister-based approach for field sampling trimethylsilanol in air, as well as a preconcentration gas chromatography/mass spectrometry laboratory method for analysis. The results demonstrate clean canister blanks (0.06 ppt(v) [0.24 ng/m(3)], which is below the detection limit), excellent linearity (a calibration relative response factor relative standard deviation [RSD] of 9.8%) over a wide dynamic mass range (1-100 ppt(v)), recovery/accuracy of 93%, a low selected ion monitoring method detection limit of 0.12 ppt(v) (0.48 ng/m(3)), replicate precision of 6.8% RSD, and stability (84% recovery) out to four days of storage at room temperature. Samples collected at two silicon wafer fabrication facilities ranged from 10.0 to 9120 ppt(v) TMS and appear to be associated with the use of hexamethyldisilazane priming agent. This method will enable semiconductor cleanroom managers to monitor and control for trace levels of trimethylsilanol.

Numerical Modeling and Testing of an Inductively-Driven and High-Energy Pulsed Plasma Thrusters

NASA Technical Reports Server (NTRS)

Parma, Brian

2004-01-01

Pulsed Plasma Thrusters (PPTs) are advanced electric space propulsion devices that are characterized by simplicity and robustness. They suffer, however, from low thrust efficiencies. This summer, two approaches to improve the thrust efficiency of PPTs will be investigated through both numerical modeling and experimental testing. The first approach, an inductively-driven PPT, uses a double-ignition circuit to fire two PPTs in succession. This effectively changes the PPTs configuration from an LRC circuit to an LR circuit. The LR circuit is expected to provide better impedance matching and improving the efficiency of the energy transfer to the plasma. An added benefit of the LR circuit is an exponential decay of the current, whereas a traditional PPT s under damped LRC circuit experiences the characteristic "ringing" of its current. The exponential decay may provide improved lifetime and sustained electromagnetic acceleration. The second approach, a high-energy PPT, is a traditional PPT with a variable size capacitor bank. This PPT will be simulated and tested at energy levels between 100 and 450 joules in order to investigate the relationship between efficiency and energy level. Arbitrary Coordinate Hydromagnetic (MACH2) code is used. The MACH2 code, designed by the Center for Plasma Theory and Computation at the Air Force Research Laboratory, has been used to gain insight into a variety of plasma problems, including electric plasma thrusters. The goals for this summer include numerical predictions of performance for both the inductively-driven PPT and high-energy PFT, experimental validation of the numerical models, and numerical optimization of the designs. These goals will be met through numerical and experimental investigation of the PPTs current waveforms, mass loss (or ablation), and impulse bit characteristics.

Effect of Progressive Volume-Based Overload During Plyometric Training on Explosive and Endurance Performance in Young Soccer Players.

PubMed

Ramírez-Campillo, Rodrigo; Henríquez-Olguín, Carlos; Burgos, Carlos; Andrade, David C; Zapata, Daniel; Martínez, Cristian; Álvarez, Cristian; Baez, Eduardo I; Castro-Sepúlveda, Mauricio; Peñailillo, Luis; Izquierdo, Mikel

2015-07-01

The purpose of the study was to compare the effects of progressive volume-based overload with constant volume-based overload on muscle explosive and endurance performance adaptations during a biweekly short-term (i.e., 6 weeks) plyometric training intervention in young soccer players. Three groups of young soccer players (age 13.0 ± 2.3 years) were divided into: control (CG; n = 8) and plyometric training with (PPT; n = 8) and without (NPPT; n = 8) a progressive increase in volume (i.e., 16 jumps per leg per week, with an initial volume of 80 jumps per leg each session). Bilateral and unilateral horizontal and vertical countermovement jump with arms (CMJA), 20-cm drop jump reactive strength index (RSI20), maximal kicking velocity (MKV), 10-m sprint, change of direction speed (CODS), and Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1) were measured. Although both experimental groups significantly increased CMJA, RSI20, CODS, and endurance performance, only PPT showed a significant improvement in MKV and 10-m sprint time. In addition, only PPT showed a significantly higher performance improvement in jumping, MKV, and Yo-Yo IR1 compared with CG. Also, PPT showed higher meaningful improvement compared with NPPT in all (except 1) jump performance measures. Furthermore, although PPT involved a higher total volume compared with NPPT, training efficiency (i.e., percentage change in performance/total jump volume) was similar between groups. Our results show that PPT and NPPT ensured significant improvement in muscle explosive and endurance performance measures. However, a progressive increase in plyometric training volume seems more advantageous to induce soccer-specific performance improvements.

Pyranopterin Coordination Controls Molybdenum Electrochemistry in Escherichia coli Nitrate Reductase.

PubMed

Wu, Sheng-Yi; Rothery, Richard A; Weiner, Joel H

2015-10-09

We test the hypothesis that pyranopterin (PPT) coordination plays a critical role in defining molybdenum active site redox chemistry and reactivity in the mononuclear molybdoenzymes. The molybdenum atom of Escherichia coli nitrate reductase A (NarGHI) is coordinated by two PPT-dithiolene chelates that are defined as proximal and distal based on their proximity to a [4Fe-4S] cluster known as FS0. We examined variants of two sets of residues involved in PPT coordination: (i) those interacting directly or indirectly with the pyran oxygen of the bicyclic distal PPT (NarG-Ser(719), NarG-His(1163), and NarG-His(1184)); and (ii) those involved in bridging the two PPTs and stabilizing the oxidation state of the proximal PPT (NarG-His(1092) and NarG-His(1098)). A S719A variant has essentially no effect on the overall Mo(VI/IV) reduction potential, whereas the H1163A and H1184A variants elicit large effects (ΔEm values of -88 and -36 mV, respectively). Ala variants of His(1092) and His(1098) also elicit large ΔEm values of -143 and -101 mV, respectively. An Arg variant of His(1092) elicits a small ΔEm of +18 mV on the Mo(VI/IV) reduction potential. There is a linear correlation between the molybdenum Em value and both enzyme activity and the ability to support anaerobic respiratory growth on nitrate. These data support a non-innocent role for the PPT moieties in controlling active site metal redox chemistry and catalysis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparative Developmental Toxicity of Desalination Brine and Sulfate-Dominated Saltwater in a Euryhaline Fish.

PubMed

Kupsco, Allison; Sikder, Rafid; Schlenk, Daniel

2017-02-01

Desalination is a promising sustainable solution to meet growing water needs of cities across the United States. However, the environmental impacts of the resulting filtrate (brine) discharged to surface water need to be evaluated before large-scale desalination can be successful in the United States. Developing fish are especially sensitive to changes in salinity and varying ionic composition. Limited research is available on the impacts of hypersalinity on chronic vertebrate embryonic development, particularly on sublethal effects. To investigate this, Japanese medaka (Oryzias latipes) embryos were treated with: (1) graphite filtered freshwater; (2) artificial seawater [17, 35, 42, 56, and 70 parts per thousand (ppt)]; (3) effluent from a desalination facility at Monterey Bay Aquarium, CA, diluted to 75, 50, and 25% with 35 ppt artificial seawater to simulate mixing (39, 42, 46, and 50 ppt); (4) artificial San Joaquin River water (CA, USA) (9, 13, and 17 ppt); and (5) artificial San Joaquin River water diluted to 75, 50, and 25% with artificial seawater to simulate estuarine mixing in the San Francisco Bay (13, 19, 24, and 30 ppt). Percent hatch, survival post hatch, deformities, swim bladder inflation, and median day to hatch were recorded to calculate EC 50 (50% effect concentration) and NOEC (no observable effect concentration) values. No significant difference was observed between artificial seawater and Monterey Bay aquarium effluent (EC 50  = 45-55 ppt). However, San Joaquin River water decreased survival post hatch and increased deformities in comparison to artificial seawater and San Joaquin River water mixed with seawater, suggesting that unique ion compositions may play a role in embryo and larval toxicity.

Pressure pain threshold and β-endorphins plasma level are higher in lean polycystic ovary syndrome women.

PubMed

Kiałka, Marta; Milewicz, Tomasz; Mrozińska, Sandra; Rogatko, Iwona; Sztefko, Krystyna; Majewska, Renata

2017-12-01

Despite some evidence that indicates that the evolution of polycystic ovary syndrome (PCOS) is related to the activity of the endogenous opioid system, and that concentration of plasma β-endorphin levels can increase pain threshold, there are no studies which evaluate pressure pain threshold in the PCOS women population. In 48 lean women with PCOS and 38 lean women without this disorder plasma β-endorphins and PPT were measured. The β-endorphins level was higher in the PCOS group compared to the controls (15.28±2.49 pg/mL vs. 6.33±1.71 pg/mL, P<0.001). In PCOS group PPTs measured on deltoid and trapezius muscles were higher compared to the controls (9.33±1.3 kg/cm² vs. 5.19±0.57 kg/cm², P<0.001; 8.23±1.04 kg/cm² vs. 4.79±0.55 kg/cm², P<0.001). The β-endorphin levels positively correlated with PPTs in PCOS group. Increase in β-endorphin level of 1 pg/mL was associated with increase of PPT value on deltoid muscle of 0.23 kg/cm² (R=0.632, P=0.011) and of 0.18 kg/cm² on trapezius muscle (R=0.588, P=0.037). There were no correlations between testosterone level and PPT in PCOS group. β-endorphin serum level as well as PPT are higher in lean PCOS group than in controls. We found correlations between β-endorphin levels and PPT in the PCOS group. It may suggest the role of endogenous opioids in the pathogenesis of PCOS and also that the increases in circulating plasma β-endorphins concentration can increases PPT in this group.

A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives.

PubMed

Lazzari, Paolo; Distinto, Rita; Manca, Ilaria; Baillie, Gemma; Murineddu, Gabriele; Pira, Marilena; Falzoi, Matteo; Sani, Monica; Morales, Paula; Ross, Ruth; Zanda, Matteo; Jagerovic, Nadine; Pinna, Gérard Aimè

2016-10-04

8-Chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide 9a was discovered as potent and selective CB1 antagonist by part of our group few years ago. In particular it was reported to have an affinity towards the CB1 cannabinoid receptor (CB1R), expressed as Ki, of 0.00035 nM. Nevertheless significantly divergent data were reported for the same compound from other laboratories. To unequivocally define the receptor profile of 9a, we have critically reviewed both its synthesis approach and binding data. Here we report that, in contrast to our previously reported data, 9a showed a Ki value for CB1R in the order of nanomolar rather than of fentomolar range. The new determined receptor profile of 9a was also ascertained for analogue derivatives 9b-i, as well as for 12. Moreover, the structural features of the synthesized compounds necessary for CB1R were investigated. Amongst the novel series, effects on CB1R intrinsic activity was highlighted due to the substituents at the position 3 of the pyrazole ring of the 1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole scaffold. Although the cannabinoid receptor profile of 9a was reviewed in this work, the relevance of this compound in CB1R antagonist based drug discovery is confirmed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Toxicological evaluation of two novel bitter modifying flavour compounds: 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)imidazolidine-2,4-dione and 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)-5,5-dimethylimidazolidine-2,4-dione.

PubMed

Karanewsky, Donald S; Arthur, Amy J; Liu, Hanghui; Chi, Bert; Ida, Lily; Markison, Stacy

2016-01-01

A toxicological evaluation of two novel bitter modifying flavour compounds, 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1 H -pyrazol-4-yl)-1-(3-hydroxybenzyl)imidazolidine-2,4-dione (S6821, CAS 1119831-25-2) and 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1 H -pyrazol-4-yl)-1-(3-hydroxybenzyl)-5,5-dimethylimidazolidine-2,4-dione (S7958, CAS 1217341-48-4), were completed for the purpose of assessing their safety for use in food and beverage applications. S6821 undergoes oxidative metabolism in vitro , and in rat pharmacokinetic studies both S6821 and S7958 are rapidly converted to the corresponding O-sulfate and O-glucuronide conjugates. S6821 was not found to be mutagenic or clastogenic in vitro , and did not induce micronuclei in bone marrow polychromatic erythrocytes in vivo . S7958, a close structural analog of S6821, was also found to be non-mutagenic in vitro . In short term and subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL) for both S7958 and S6821 was 100 mg/kg bw/day (highest dose tested) when administered as a food ad-mix for either 28 or 90 consecutive days, respectively. Furthermore, S6821 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

Synthesis, crystal structures and theoretical calculations of new 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles

NASA Astrophysics Data System (ADS)

Gökşen, Umut Salgın; Alpaslan, Yelda Bingöl; Kelekçi, Nesrin Gökhan; Işık, Şamil; Ekizoğlu, Melike

2013-05-01

1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3-methoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5a), 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5b) and 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-(4-methylphenyl)-5-(2,3-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5c) were synthesized. The crystal and molecular structures of the compounds 5a, 5b and 5c were determined by elemental analyses, IR, 1H NMR, ESI-MS and single-crystal X-ray diffraction. DFT method with 6-31G(d,p) basis set was used to calculate the optimized geometrical parameters, vibrational frequencies and chemical shift values. The calculated vibrational frequencies and chemical shift values were compared with experimental IR and 1H NMR values. The results represented that there was a good agreement between experimental and calculated values of the compounds 5a-5c. In addition, DFT calculations of the compounds, molecular electrostatic potentials (MEPs) and frontier molecular orbitals were performed at B3LYP/6-31G(d,p) level of theory. Furthermore, compounds were tested against three Gram-positive bacteria: Staphylococcus aureus ATCC 29213 (American Type Culture Collection), methicillin resistant S. aureus (MRSA) ATCC 43300 and Enterococcus faecalis ATCC 29212; two Gram negative bacteria: Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853; and three fungi: Candida albicans ATCC 90028, Candida krusei ATCC 6258 and Candida parapsilosis ATCC 90018. In general, all of the compounds were found to be slightly active against tested microorganisms.

Differences in hepatic microsomal cytochrome P-450 isoenzyme induction by pyrazole, chronic ethanol, 3-methylcholanthrene, and phenobarbital in high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats.

PubMed

Lucas, D; Ménez, J F; Berthou, F; Cauvin, J M; Deitrich, R A

1992-10-01

High and low alcohol sensitivity (HAS and LAS) rats have been selected for their differences in ethanol-induced sleep time. Liver monooxygenase activities were studied in HAS and LAS rats before and after treatments with known inducers such as chronic ethanol, pyrazole, 3-methylcholanthrene (3-MC) and phenobarbital (PB) to determine whether the selection procedure also selected for differences in the cytochrome P-450 (P-450) inducibility. This previously has been shown with long sleep (LS) and short sleep (SS) mice, which were selected using a similar criterion. 3-MC and PB, in conjunction with chronic ethanol treatment, were used in order to evaluate the interactions of ethanol with these inducers. Prior to treatment, total P-450 content was slightly lower in LAS than in HAS rats. However, both lines displayed the same microsomal monooxygenase activities related to different P-450 isozymes. This was demonstrated by ethoxyresorufin deethylation (EROD) for cytochrome P-450 1A1 (CYP1A1), acetanilide hydroxylation (ACET) for CYP1A2, pentoxyresorufin dealkylation (PROD) for CYP2B, 1-butanol oxidation (BUTAN) and N-nitrosodimethylamine demethylation (NDMA) for CYP2E1. After the different treatments, HAS rats did not differ from LAS rats in their CYP2E1 inducibility. However, pyrazole, PB and 3-MC treatment led to differences in CYP1A and CYP2B monooxygenase activities between the two lines. The enhancement of PROD by pyrazole treatment was less prominent in LAS (1.7-fold of the control value) than in HAS rats (3.8-fold).(ABSTRACT TRUNCATED AT 250 WORDS)

76 FR 76716 - Draft National Pollutant Discharge Elimination System (NPDES) General Permits for Discharges...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

...) the vessel has taken on ballast water that has a salinity of less than 18 ppt from a coastal... has not taken on ballast water with a salinity of less than 18 ppt in the previous month, the master...

[Postpartum thyroiditis. A review].

PubMed

Hurtado-Hernández, Z; Segura-Domínguez, A

2013-01-01

Postpartum thyroiditis (PPT) is a transient thyroid dysfunction of autoimmune origin that can occur in the first year postpartum in women who have not been previously diagnosed with thyroid disease. It may start with clinical thyrotoxicosis followed by hypothyroidism and the subsequent recovery of thyroid function, or may just appear as isolated thyrotoxicosis or hypothyroidism. PPT recurs in high percentage of patients after subsequent pregnancies. Many women develop permanent hypothyroidism sometime during the 3 to 10 year period after an episode of PPT. It is important for family physicians to be familiar with this disease, due to its high prevalence in order to make a correct diagnosis and therapeutic intervention. Family doctors also play a crucial role in the monitoring of these patients, given the negative implications of established hypothyroidism on reproduction in the female population during their reproductive years. This article reviews the principle characteristics of PPT along with its diagnosis and treatment. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis.

PubMed

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis

PubMed Central

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1-deficient mice (Ppt1−/−) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression, but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1−/− mice, revealing the thalamus as an important early focus of INCL pathogenesis. PMID:17046272

Changes in Disparity in County-Level Diagnosed Diabetes Prevalence and Incidence in the United States, between 2004 and 2012

PubMed Central

Gregg, Edward W.; Beckles, Gloria L.; Luman, Elizabeth T.; Barker, Lawrence E.; Geiss, Linda S.

2016-01-01

Background In recent decades, the United States experienced increasing prevalence and incidence of diabetes, accompanied by large disparities in county-level diabetes prevalence and incidence. However, whether these disparities are widening, narrowing, or staying the same has not been studied. We examined changes in disparity among U.S. counties in diagnosed diabetes prevalence and incidence between 2004 and 2012. Methods We used 2004 and 2012 county-level diabetes (type 1 and type 2) prevalence and incidence data, along with demographic, socio-economic, and risk factor data from various sources. To determine whether disparities widened or narrowed over the time period, we used a regression-based β-convergence approach, accounting for spatial autocorrelation. We calculated diabetes prevalence/incidence percentage point (ppt) changes between 2004 and 2012 and modeled these changes as a function of baseline diabetes prevalence/incidence in 2004. Covariates included county-level demographic and, socio-economic data, and known type 2 diabetes risk factors (obesity and leisure-time physical inactivity). Results For each county-level ppt increase in diabetes prevalence in 2004 there was an annual average increase of 0.02 ppt (p<0.001) in diabetes prevalence between 2004 and 2012, indicating a widening of disparities. However, after accounting for covariates, diabetes prevalence decreased by an annual average of 0.04 ppt (p<0.001). In contrast, changes in diabetes incidence decreased by an average of 0.04 ppt (unadjusted) and 0.09 ppt (adjusted) for each ppt increase in diabetes incidence in 2004, indicating a narrowing of county-level disparities. Conclusions County-level disparities in diagnosed diabetes prevalence in the United States widened between 2004 and 2012, while disparities in incidence narrowed. Accounting for demographic and, socio-economic characteristics and risk factors for type 2 diabetes narrowed the disparities, suggesting that these factors are strongly associated with changes in disparities. Public health interventions that target modifiable risk factors, such as obesity and physical inactivity, in high burden counties might further reduce disparities in incidence and, over time, in prevalence. PMID:27487006

Endogenous Pain Modulation Induced by Extrinsic and Intrinsic Psychological Threat in Healthy Individuals.

PubMed

Gibson, William; Moss, Penny; Cheng, Tak Ho; Garnier, Alexandre; Wright, Anthony; Wand, Benedict M

2018-03-01

Many factors interact to influence threat perception and the subsequent experience of pain. This study investigated the effect of observing pain (extrinsic threat) and intrinsic threat of pain to oneself on pressure pain threshold (PPT). Forty socially connected pairs of healthy volunteers were threat-primed and randomly allocated to experimental or control roles. An experimental pain modulation paradigm was applied, with non-nociceptive threat cues used as conditioning stimuli. In substudy 1, the extrinsic threat to the experimental participant was observation of the control partner in pain. The control participant underwent hand immersion in noxious and non-noxious water baths in randomized order. Change in the observing participant's PPT from baseline to mid- and postimmersion was calculated. A significant interaction was found for PPT between conditions and test time (F 2,78  = 24.9, P < .005). PPT increased by 23.6% ± 19.3% between baseline and during hand immersion (F 1,39  = 43.7, P < .005). Substudy 2 investigated threat of imminent pain to self. After a 15-minute break, the experimental participant's PPT was retested ("baseline 2"). Threat was primed by suggestion of whole arm immersion in an icier, larger water bath. PPT was tested immediately before anticipated arm immersion, after which the experiment ended. A significant increase in PPT between "baseline 2" and "pre-immersion" was seen (t = -7.6, P = .005), a pain modulatory effect of 25.8 ± 20.7%. Extrinsic and intrinsic threat of pain, in the absence of any afferent input therefore influences pain modulation. This may need to be considered in studies that use noxious afferent input with populations who show dysfunctional pain modulation. The effect on endogenous analgesia of observing another's pain and of threat of pain to oneself was investigated. Extrinsic as well as intrinsic threat cues, in the absence of any afferent input, increased pain thresholds, suggesting that mere threat of pain may initiate analgesic effects in traditional noxious experimental paradigms. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

The appropriateness of core group interventions using presumptive periodic treatment among rural Zimbabwean women who exchange sex for gifts or money.

PubMed

Cowan, Frances M; Hargrove, John W; Langhaug, Lisa F; Jaffar, Shabbar; Mhuriyengwe, Lovemore; Swarthout, Todd D; Peeling, Rosanna; Latif, Ahmed; Bassett, Mary T; Brown, David W G; Mabey, David; Hayes, Richard J; Wilson, David

2005-02-01

To map the characteristics of rural based sex workers in Zimbabwe with regard to demographics, mobility, behavior, HIV and sexually transmitted infection (STI) prevalence, to explore the appropriateness and feasibility of presumptive periodic treatment (PPT) for bacterial STIs as an HIV prevention intervention among these women, and to compare tolerability of 2 PPT regimens (1 g of azithromycin and 2 g of metronidazole+/-500 mg of ciprofloxacin). Five commercial farms and 2 mines in Mashonaland West, Zimbabwe. Three hundred sixty-three sex workers were recruited and completed a structured interviewer-administered questionnaire. Each participant had blood tested for antibody to HIV, herpes simplex virus 2 (HSV-2), and syphilis; urine tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and a vaginal swab tested for Trichomonas vaginalis (TV). Women were randomly assigned to receive a single dose of 1 of 2 PPT regimens and then followed to assess rates of side effects and reinfection. The overall prevalence of antibody to HIV was 55.7% (95% confidence interval [CI]: 50.6-60.9) and that of HSV-2 was 80.8% (95% CI: 76.7-84.9). The prevalence of CT and NG was low (CT=1.7%, 95% CI: 0.3-3.0); (NG=1.9%, 95% CI: 0.5-3.4), with a much higher prevalence of TV (TV=19.3%, 95% CI: 15.2-23.4). Prevalence of CT, NG, and TV was appreciably reduced 1 month after PPT but rose to pretreatment levels at the 2- and 3-month visits. The rate of moderate or severe side effects after PPT was low, but it was higher in the women who received ciprofloxacin in addition to azithromycin and metronidazole (P=0.007). It was feasible to access women who reported exchanging money or gifts for sex in rural communities, although many of these women engaged in sex work only infrequently. The prevalence of bacterial STIs was low, suggesting that PPT may not be an appropriate intervention in this setting. Rapid reinfection after PPT suggests that this needs to be given at monthly intervals to reduce prevalence of STIs.

Molecular characterization and transcriptional regulation of the Na +/K+ ATPase α subunit isoforms during development and salinity challenge in a teleost fish, the Senegalese sole (Solea senegalensis).

PubMed

Armesto, Paula; Campinho, Marco A; Rodríguez-Rúa, Ana; Cousin, Xavier; Power, Deborah M; Manchado, Manuel; Infante, Carlos

2014-09-01

In the present work, five genes encoding different Na(+),K(+) ATPase (NKA) α-isoforms in the teleost Solea senegalensis are described for the first time. Sequence analysis of predicted polypeptides revealed a high degree of conservation across teleosts and mammals. Phylogenetic analysis clustered the five genes into three main clades: α1 (designated atp1a1a and atp1a1b), α2 (designated atp1a2) and α3 (designated atp1a3a and atp1a3b) isoforms. Transcriptional analysis in larvae showed distinct expression profiles during development. In juvenile tissues, the atp1a1a gene was highly expressed in osmoregulatory organs, atp1a2 in skeletal muscle, atp1a1b in brain and heart and atp1a3a and atp1a3b mainly in brain. Quantification of mRNA abundance after a salinity challenge showed that atp1a1a transcript levels increased significantly in the gill of soles transferred to high salinity water (60 ppt). In contrast, atp1a3a transcripts increased at low salinity (5 ppt). In situ hybridization (ISH) analysis revealed that the number of ionocytes expressing atp1a1a transcripts in the primary gill filaments was higher at 35 and 60 ppt than at 5 ppt and remained undetectable or at very low levels in the lamellae at 5 and 35 ppt but increased at 60 ppt. Immunohistochemistry showed a higher number of positive cells in the lamellae. Whole-mount analysis of atp1a1a mRNA in young sole larvae revealed that it was localized in gut, pronephric tubule, gill, otic vesicle, yolk sac ionocytes and chordacentrum. Moreover, atp1a1a mRNAs increased at mouth opening (3 DPH) in larvae incubated at 36 ppt with a greater signal in gills. Copyright © 2014 Elsevier Inc. All rights reserved.

TA-3-38 Metals Fab SWPPP Rev 2 Jan 2017-Final

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

Burgin, Jillian Elizabeth

The TA-3-38 MFS is part of LANL’s Utilities and Infrastructures (UI) Facilities Operations Directorate (FOD) with day-to-day management provided by the Logistics Division Central Shops (LOG-CS); which has established a Stormwater Pollution Prevention Team (PPT) whose members are responsible for assisting the facility manager in developing and revising the facility’s SWPPP as well as maintaining control measures and taking corrective actions when required. All PPT members will have access to either a hard copy or an electronic version of this SWPPP. A list of PPT members along with duties and contact information is provided in Appendix A of this SWPPP.

TA-3-38 Carpenter's Shop SWPPP Rev 2 Jan 2017-Final

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

Burgin, Jillian Elizabeth

The TA-3-38 CS is part of LANL’s Utilities and Infrastructure (UI) Facilities Operations Directorate (FOD) with day-to-day management provided by the Logistics Division Central Shops (LOG-CS); which has established a Stormwater Pollution Prevention Team (PPT) whose members are responsible for assisting the facility manager in developing and revising the facility’s SWPPP as well as maintaining control measures and taking corrective actions when required. All PPT members will have access to either a hard copy or an electronic version of this SWPPP. A list of PPT members along with duties and contact information is provided in Appendix A of this SWPPP

Assessment of salinity intrusion in the James and Chickahominy Rivers as a result of simulated sea-level rise in Chesapeake Bay, East Coast, USA.

PubMed

Rice, Karen C; Hong, Bo; Shen, Jian

2012-11-30

Global sea level is rising, and the relative rate in the Chesapeake Bay region of the East Coast of the United States is greater than the worldwide rate. Sea-level rise can cause saline water to migrate upstream in estuaries and rivers, threatening freshwater habitat and drinking-water supplies. The effects of future sea-level rise on two tributaries of Chesapeake Bay, the James and Chickahominy (CHK) Rivers, were evaluated in order to quantify the salinity change with respect to the magnitude of sea-level rise. Such changes are critical to: 1) local floral and faunal habitats that have limited tolerance ranges to salinity; and 2) a drinking-water supply for the City of Newport News, Virginia. By using the three-dimensional Hydrodynamic-Eutrophication Model (HEM-3D), sea-level rise scenarios of 30, 50, and 100 cm, based on the U.S. Climate Change Science Program for the mid-Atlantic region for the 21st century, were evaluated. The model results indicate that salinity increases in the entire river as sea level rises and that the salinity increase in a dry year is greater than that in a typical year. In the James River, the salinity increase in the middle-to-upper river (from 25 to 50 km upstream of the mouth) is larger than that in the lower and upper parts of the river. The maximum mean salinity increase would be 2 and 4 ppt for a sea-level rise of 50 and 100 cm, respectively. The upstream movement of the 10 ppt isohaline is much larger than the 5 and 20 ppt isohalines. The volume of water with salinity between 10 and 20 ppt would increase greatly if sea level rises 100 cm. In the CHK River, with a sea-level rise of 100 cm, the mean salinity at the drinking-water intake 34 km upstream of the mouth would be about 3 ppt in a typical year and greater than 5 ppt in a dry year, both far in excess of the U.S. Environmental Protection Agency's secondary standard for total dissolved solids for drinking water. At the drinking-water intake, the number of days of salinity greater than 0.1 ppt increases with increasing sea-level rise; during a dry year, 0.1 ppt would be exceeded for more than 100 days with as small a rise as 30 cm. Copyright © 2012 Elsevier Ltd. All rights reserved.

Assessment of salinity intrusion in the James and Chickahominy Rivers as a result of simulated sea-level rise in Chesapeake Bay, East Coast, USA

USGS Publications Warehouse

Rice, Karen; Bo Hong,; Jian Shen,

2012-01-01

Global sea level is rising, and the relative rate in the Chesapeake Bay region of the East Coast of the United States is greater than the worldwide rate. Sea-level rise can cause saline water to migrate upstream in estuaries and rivers, threatening freshwater habitat and drinking-water supplies. The effects of future sea-level rise on two tributaries of Chesapeake Bay, the James and Chickahominy (CHK) Rivers, were evaluated in order to quantify the salinity change with respect to the magnitude of sea-level rise. Such changes are critical to: 1) local floral and faunal habitats that have limited tolerance ranges to salinity; and 2) a drinking-water supply for the City of Newport News, Virginia. By using the three-dimensional Hydrodynamic-Eutrophication Model (HEM-3D), sea-level rise scenarios of 30, 50, and 100 cm, based on the U.S. Climate Change Science Program for the mid-Atlantic region for the 21st century, were evaluated. The model results indicate that salinity increases in the entire river as sea level rises and that the salinity increase in a dry year is greater than that in a typical year. In the James River, the salinity increase in the middle-to-upper river (from 25 to 50 km upstream of the mouth) is larger than that in the lower and upper parts of the river. The maximum mean salinity increase would be 2 and 4 ppt for a sea-level rise of 50 and 100 cm, respectively. The upstream movement of the 10 ppt isohaline is much larger than the 5 and 20 ppt isohalines. The volume of water with salinity between 10 and 20 ppt would increase greatly if sea level rises 100 cm. In the CHK River, with a sea-level rise of 100 cm, the mean salinity at the drinking-water intake 34 km upstream of the mouth would be about 3 ppt in a typical year and greater than 5 ppt in a dry year, both far in excess of the U.S. Environmental Protection Agency's secondary standard for total dissolved solids for drinking water. At the drinking-water intake, the number of days of salinity greater than 0.1 ppt increases with increasing sea-level rise; during a dry year, 0.1 ppt would be exceeded for more than 100 days with as small a rise as 30 cm.

Assessment of free fetal DNA concentration in maternal plasma during the first trimester of pregnancy: comparative study between EDTA and PPT tubes - pilot study.

PubMed

Chadud, Carolina Schneider; Araujo Júnior, Edward; Martinhago, Ciro Dresh; Andari, Viviane Cristina Mello; Tedesco, Giselle Darahem; Bussamra, Luiz Claudio Silva; Aoki, Tsutomu

2015-01-01

To compare ethylenediamine tetraacetic acid (EDTA) tubes and plasma preparation tubes (PPT) for evaluating maternal plasma during the first trimester of pregnancy. A cross-sectional study was conducted on 24 male fetuses in women between 6 and 14 weeks of pregnancy. Blood samples (10 mL) were collected and stored in EDTA and PPT tubes. Subsequently, the samples were centrifuged and sent for free fetal DNA extraction by means of the polymerase chain reaction (PCR) technique. The reactions were performed in a real time PCR machine for detecting the amplification products. The genome region chosen for performing the PCR reactions was a target specific for the Y chromosome, in which the DYS-14 marker was amplified only when the DNA was of male sex. The free fetal DNA concentration was given by the threshold cycle (TC). To compare the tubes, the paired Student t-test was used. The mean gestational age was 11.08 ± 2.30 weeks (range: 6-14). The mean TC for PPT was 30.08 ± 1.05 (range: 27.08-32.61) and for EDTA, 30.23 ± 0.96 (range: 28.01-32.09), but without statistical significance (p=0.357). We did not observe any statistically significant difference in free fetal DNA concentration between the EDTA and PPT tubes.

Does Roller Massage With a Foam Roll Change Pressure Pain Threshold of the Ipsilateral Lower Extremity Antagonist and Contralateral Muscle Groups? An Exploratory Study.

PubMed

Cheatham, Scott W; Kolber, Morey J

2018-03-01

Foam rolling is a popular intervention used by allied health professionals and the general population. Current research suggests that foam rolling may have an effect on the ipsilateral antagonist muscle group and produce a cross-over effect in the muscles of the contralateral limb. The purpose of this study was to examine the acute effects of foam rolling to the left quadriceps on ipsilateral antagonist hamstrings and contralateral quadriceps muscle group pressure pain threshold (PPT). Through this research, we sought to gather data to further develop the methodology for future studies of this intervention. A pretest-posttest exploratory study. University kinesiology laboratory. 21 healthy adults (age = 27.52 ± 8.9 y). Video-guided foam roll intervention on the left quadriceps musculature. Ipsilateral hamstring (antagonist) and contralateral quadriceps muscle PPT. A significant difference was found between pretest to posttest measures for the ipsilateral hamstrings (t[20] = -6.2, P < 0.001) and contralateral quadriceps (t[20] = -9.1, P < 0.001) suggesting an increase in PPT. These findings suggest that foam rolling of the quadriceps musculature may have an acute effect on the PPT of the ipsilateral hamstrings and contralateral quadriceps muscles. Clinicians should consider these results to be exploratory and future investigations examining this intervention on PPT is warranted.

Effects of perturbation or plyometric training on core control and knee joint loading in women during lateral movements.

PubMed

Weltin, E; Gollhofer, A; Mornieux, G

2017-03-01

Deficits in trunk control are argued to increase the risk of knee injuries. However, no existing training program effectively addresses trunk control during lateral movements, such as cutting maneuvers. The purpose of this study was to investigate whether a combination of perturbation and plyometric training (PPT) would reduce trunk excursions against the new movement direction and reduce knee joint moments during lateral movements. Twenty-four active women participated in a RCT, where trunk and pelvis kinematics and knee joint moments were measured during lateral reactive jumps (LRJ) and unanticipated cutting maneuvers before and after a 4-week PPT program and compared to a control group. During LRJ, trunk rotation away from the new movement direction was reduced (P < 0.001), while pelvis rotation toward the new direction was increased (P = 0.006) after PPT. Moreover, decreased knee extension moments (P = 0.028) and knee internal rotation moments (P < 0.001) were reported after both trainings. Additionally, PPT reduced trunk rotation by 7.2° during unanticipated cuttings. A 4-week PPT improved core control by reducing trunk rotation and reduced knee joint moments during LRJ. During training, perturbations should be introduced to improve core control during dynamic athletic movements, possibly reducing the risk of ACL injuries. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Density and distribution of water boatmen and brine shrimp at a major shorebird wintering area in Puerto Rico

USGS Publications Warehouse

Tripp, K.J.; Collazo, J.A.

2003-01-01

The Cabo Rojo salt flats are an important wintering area for migratory shorebirds. Their quality is intimately related to prey availability, as prey are needed to meet energetic requirements. Understanding prey dynamics is, therefore, a key element of shorebird conservation plans. To this end, we monitored the density and distribution of water-boatmen (Trichocorixa spp.) and brine shrimp (Artemia spp.) in relation to water salinity from September to November of 1994 and 1995. Salinity ranged from 4 to 292 ppt, and gradients were related to hydrological alterations (e.g., salt extraction) and connection to the ocean. Brine shrimp were restricted to areas of highest salinity (??? 106 ppt), whereas water-boatmen to areas of lowest salinity ( 100 ppt. Lowering water salinity did not result in osmolal related mortality. Results underscored the sensitivity of water boatmen to high salinity, particularly when the difference in salinity between the 'source' and 'destination' localities widened. Water boatmen density increased in one lagoon as salinity decreased from 65 to 47 ppt. On the basis of our experiments, local adult survivorship improved and immigration and subsequent survival of adults, if any, was not hindered. The density of nymphs also suggested that hatching occurred concurrently. The foraging value of the salt flats can be enhanced by maintaining salinity at < 65 ppt in selected management units and minimizing differences in salinity concentrations among them.

Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns.

PubMed

Luise, Nicola; Wyatt, Paul

2018-05-07

Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. This communication highlights the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cascade multicomponent synthesis of indoles, pyrazoles, and pyridazinones by functionalization of alkenes.

PubMed

Matcha, Kiran; Antonchick, Andrey P

2014-10-27

The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

3,4-Dimethyl-1-phenyl­pyrano[2,3-c]pyrazol-6(1H)-one

PubMed Central

Ahmad, Neman; Tahir, M. Nawaz; Khan, Misbahul Ain; Ather, Abdul Qayyum; Khan, Muhammad Naeem

2011-01-01

In the title compound, C14H12N2O2, the dihedral angle between the phenyl ring and the 3,4-dimethyl­pyrano[2,3-c]pyrazol-6(1H)-one system is 7.28 (6)°. An intra­molecular C—H⋯O inter­action generates an S(6) ring. In the crystal, the mol­ecules are linked by C—H⋯O hydrogen bonds, forming C(8) chains. C–H⋯π and π–π inter­actions [centroid–centroid separation = 3.6374 (12) Å] further consolidate the packing. PMID:21754037

Multiple biological activities and molecular docking studies of newly synthesized 3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide chalcone hybrids.

PubMed

Sribalan, Rajendran; Banuppriya, Govindharasu; Kirubavathi, Maruthan; Jayachitra, A; Padmini, Vediappen

2016-12-01

A series of fifteen new chemical entities, 3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide chalcones (6a-o), were synthesized as new hybrids with enriched biological activities compared to their parent molecules. The compounds were characterized by 1 H NMR, 13 C NMR, Mass and IR spectral studies. Their antibacterial, anti-inflammatory and antioxidant activities have been evaluated. These compounds showed moderate to good antibacterial, anti-inflammatory and antioxidant activities. The molecular docking analysis was performed with cyclooxygenase enzyme to ascertain the probable binding model. Copyright © 2016 Elsevier Ltd. All rights reserved.

SAR and X-ray Structures of Enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and Cyclohexyldiamine Derivativies as Inhibitors of Coagulation Factor Xa

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

Qiao,J.; Chang, C.; Cheney, D.

In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties.

Experimental and computational approaches to the analysis of the molecular structure of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile

NASA Astrophysics Data System (ADS)

Al-Azmi, Amal; Shalaby, Mona Abbas

2018-03-01

A green, fast and straightforward procedure for the synthesis of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile is described in this paper. The method uses a coupling reaction between 4- nitrophenyl diazonium chloride and 5-aminopyrazole-4-carbonitrile. The structure is confirmed by different spectroscopic studies such as IR, NMR, HRMS and UV-vis spectroscopy in addition to X-ray single-crystal determination. The molecular geometry, vibrational frequencies and gauge-invariant atomic orbital (GIAO) 1H and 13C NMR chemical shift values of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile are calculated in the ground state using the Hartree-Fock (HF) method and density functional theory (DFT) with the 6-31G(d) basis set, and are compared with the experimental data. The natural bond orbital (NBO) analysis is performed so as to discuss the stability of the molecule that arises from hyper conjugative interactions and charge delocalization. The electronic properties, such as HOMO and LUMO energies, were calculated using time dependent density functional theory (TD-DFT) approach.

4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type I receptor kinase.

PubMed

Jin, Cheng Hua; Krishnaiah, Maddeboina; Sreenu, Domalapally; Subrahmanyam, Vura Bala; Park, Hyun-Ju; Park, So-Jung; Sheen, Yhun Yhong; Kim, Dae-Kee

2014-05-01

A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 μM and showed 95% inhibition at 0.03 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38α MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bis[1-meth­oxy-2,2,2-tris­(pyrazol-1-yl-κN 2)ethane]­nickel(II) bis­(tri­fluoro­methane­sulfonate) dihydrate

PubMed Central

Lyubartseva, Ganna; Parkin, Sean; Mallik, Uma Prasad

2013-01-01

In the title salt, [Ni(C12H14N6O)2](CF3SO3)2·2H2O, the NiII cation is located on an inversion centre and is coordinated by six N atoms from two tridentate 1-meth­oxy-2,2,2-tris­(pyrazol-1-yl)ethane ligands in a distorted octa­hedral geometry. The Ni—N distances range from 2.0594 (12) to 2.0664 (12) Å, intra-ligand N—Ni—N angles range from 84.59 (5) to 86.06 (5)°, and adjacent inter-ligand N—Ni—N angles range between 93.94 (5) and 95.41 (5)°. In the crystal, inversion-related pyrazole rings are π–π stacked, with an inter­planar spacing of 3.4494 (18) Å, forming chains that propagate parallel to the a-axis direction. Inter­molecular O—H⋯O hydrogen bonds are present between water mol­ecules and tri­fluoro­methane­sulfonate anions. PMID:24098167

Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid.

PubMed

Channar, Pervaiz Ali; Saeed, Aamer; Larik, Fayaz Ali; Batool, Bakhtawar; Kalsoom, Saima; Hasan, M M; Erben, Mauricio F; El-Seedi, Hesham R; Ali, Musrat; Ashraf, Zaman

2018-04-30

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC 50  = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC 50  = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid. Copyright © 2018 Elsevier Inc. All rights reserved.

Synthesis, spectral characterization and X-ray crystal structure studies of 3-(benzo[d][1,3]dioxol-5-yl)-5-(3-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carboxamide: Hirshfeld surface, DFT and thermal analysis

NASA Astrophysics Data System (ADS)

Kumara, Karthik; Dileep Kumar, A.; Naveen, S.; Ajay Kumar, K.; Lokanath, N. K.

2018-06-01

A novel pyrazole derivative, 3-(benzo[d][1,3]dioxol-5-yl)-5-(3-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carboxamide was synthesized and characterized by elemental analysis, FT-IR, NMR (1H and 13C), MS, UV-visible spectra and finally the structure was confirmed by the single crystal X-ray diffraction studies. The title compound (C16H15N3O3S) crystallized in the triclinic crystal system, with the space group Pī. A dihedral angle of 65.84(1)° between the pyrazole and the thiophene rings confirms the twisted conformation between them. The X-ray structure revealed that the pyrazole ring adopts an E-form and an envelope conformation on C7 atom. The crystal and molecular structure of the title compound is stabilized by inter molecular hydrogen bonds. The compound possesses three dimensional supramolecular self-assembly, in which Csbnd H⋯O and Nsbnd H⋯O chains build up two dimensional arrays, which are extended to 3D network through Csbnd H···Cg and Csbnd O···Cg interactions. The structure also exhibits intramolecular hydrogen bonds of the type Nsbnd H⋯N and π···π stacking interactions, which contributes to the crystal packing. Further, Hirshfeld surface analysis was carried out for the graphical visualization of several short intermolecular interactions on the molecular surface while the 2D finger-print plot provides percentage contribution of each individual atom-to-atom interactions. The thermal decomposition of the compound has been studied by thermogravimetric analysis. The molecular geometries and electronic structures of the compounds were fully optimized, calculated with ab-initio methods by HF, DFT/B3LYP functional in combination of different basis set with different solvent environment and the structural parameters were compared with the experimental data. The Mulliken atomic charges and molecular electrostatic potential on molecular van der Waals (vdW) surface were calculated to know the electrophilic and nucleophilic regions of the molecular surface. Nonlinear optical properties of the title compound were also discussed based on the polarizability and hyperpolarizability values.

Physiological characteristics and stress resistance of great sturgeon (Huso huso) juveniles fed with vitamins C, E, and HUFA-enriched Artemia urmiana nauplii.

PubMed

Jalali, Mohammad Ali; Hosseini, Seyed Abbas; Imanpour, Mohammad Reza

2010-09-01

This study was carried out to examine the effect of Artemia urmiana nauplii enriched with HUFA, and vitamins C and E on stress tolerance, hematocrit, and biochemical parameters of great sturgeon, Huso huso juveniles. Cod liver oil (EPA 18% and DHA 12%), ascorbyl-6-palmitate and alpha-tocopherol acetate were used as lipid, and vitamin C and E sources, respectively. Beluga juveniles at the stage of first feeding (69.7 +/- 5.9 mg body weight) were randomly divided into five treatments and three tanks were assigned to each diet. All fish groups were fed non-enriched Artemia for the initial 5 days and then fed enriched Artemia for 7 days. Juveniles were fed with Artemia enriched with HUFA + 20% vitamin C (C group); HUFA + 20% vitamin E-enriched Artemia nauplii (E group); HUFA + 20% vitamin C + 20% vitamin E (C and E group); HUFA without vitamins (HUFA) and non-enriched Artemia (control). After the period of enrichment, Juveniles were fed with Daphnia sp. from the 13th to the 40th day. At day 40, the fish were transferred directly from fresh water (0.5 ppt) to brackish water (6 ppt for 4 days and 12 ppt for 2 days) and warm water (from 27 to 33 degrees C) to evaluate juvenile resistance to salinity and thermal shocks. Moreover, all treatments were separately exposed to freshwater in tanks with the same capacity as used for osmotic and thermal tests (as fresh water control). The addition of vitamins C, E, and C + E to HUFA significantly increased fish resistance to 12 ppt salinity and temperature stress tests, whereas survival was not significantly different among challenges at 6 ppt. There was no significant difference in the hematocrit index under stress conditions. Enrichment had significant influence on plasma Na(+) level in the C group on the 4th day at 6 ppt. Na(+) and Ca(2+) concentrations in C, E, and C and E groups on the 1st day at 12 ppt, and Ca(2+) level in E group on the 2nd day at 12 ppt were lower than the other groups. The glucose level in the C and C and E groups was lower than the other treatments on the 1st day at 12 ppt and the 2nd day at 33 degrees C. Regardless of Artemia enrichment, plasma ions (Na(+), K(+), Ca(2+), and Mg(2+)) and glucose concentrations in fish exposed to salinity stress tests were higher than fish in fresh water. Glucose concentration in plasma also increased after 2 days at 33 degrees C. Although most of our results were not significantly different, the use of vitamins C, E, and HUFA in Artemia enrichment can improve Juveniles tolerance under stress conditions, and regardless of enrichment, these data show that beluga juveniles are partly sensitive to high salinity and temperature.

Nutritional Status as the Key Modulator of Antioxidant Responses Induced by High Environmental Ammonia and Salinity Stress in European Sea Bass (Dicentrarchus labrax).

PubMed

Sinha, Amit Kumar; AbdElgawad, Hamada; Zinta, Gaurav; Dasan, Antony Franklin; Rasoloniriana, Rindra; Asard, Han; Blust, Ronny; De Boeck, Gudrun

2015-01-01

Salinity fluctuation is one of the main factors affecting the overall fitness of marine fish. In addition, water borne ammonia may occur simultaneously with salinity stress. Additionally, under such stressful circumstances, fish may encounter food deprivation. The physiological and ion-osmo regulatory adaptive capacities to cope with all these stressors alone or in combination are extensively addressed in fish. To date, studies revealing the modulation of antioxidant potential as compensatory response to multiple stressors are rather lacking. Therefore, the present work evaluated the individual and combined effects of salinity challenge, ammonia toxicity and nutritional status on oxidative stress and antioxidant status in a marine teleost, European sea bass (Dicentrarchus labrax). Fish were acclimated to normal seawater (32 ppt), to brackish water (20 ppt and 10 ppt) and to hypo-saline water (2.5 ppt). Following acclimation to different salinities for two weeks, fish were exposed to high environmental ammonia (HEA, 20 mg/L representing 50% of 96h LC50 value for ammonia) for 12 h, 48 h, 84 h and 180 h, and were either fed (2% body weight) or fasted (unfed for 7 days prior to HEA exposure). Results show that in response to decreasing salinities, oxidative stress indices such as xanthine oxidase activity, levels of hydrogen peroxide (H2O2) and lipid peroxidation (malondialdehyde, MDA) increased in the hepatic tissue of fasted fish but remained unaffected in fed fish. HEA exposure at normal salinity (32 ppt) and at reduced salinities (20 ppt and 10 ppt) increased ammonia accumulation significantly (84 h-180 h) in both feeding regimes which was associated with an increment of H2O2 and MDA contents. Unlike in fasted fish, H2O2 and MDA levels in fed fish were restored to control levels (84 h-180 h); with a concomitant increase in superoxide dismutase (SOD), catalase (CAT), components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase), ascorbate peroxidase (APX) activity and reduced ascorbate (ASC) content. On the contrary, fasted fish could not activate many of these protective systems and rely mainly on CAT and ASC dependent pathways as antioxidative sentinels. The present findings exemplify that in fed fish single factors and a combination of HEA exposure and reduced seawater salinities (upto 10 ppt) were insufficient to cause oxidative damage due to the highly competent antioxidant system compared to fasted fish. However, the impact of HEA exposure at a hypo-saline environment (2.5 ppt) also defied antioxidant defence system in fed fish, suggesting this combined factor is beyond the tolerance range for both feeding groups. Overall, our results indicate that the oxidative stress mediated by the experimental conditions were exacerbated during starvation, and also suggest that feed deprivation particularly at reduced seawater salinities can instigate fish more susceptible to ammonia toxicity.

Nutritional Status as the Key Modulator of Antioxidant Responses Induced by High Environmental Ammonia and Salinity Stress in European Sea Bass (Dicentrarchus labrax)

PubMed Central

Zinta, Gaurav; Dasan, Antony Franklin; Rasoloniriana, Rindra; Asard, Han; Blust, Ronny; De Boeck, Gudrun

2015-01-01

Salinity fluctuation is one of the main factors affecting the overall fitness of marine fish. In addition, water borne ammonia may occur simultaneously with salinity stress. Additionally, under such stressful circumstances, fish may encounter food deprivation. The physiological and ion-osmo regulatory adaptive capacities to cope with all these stressors alone or in combination are extensively addressed in fish. To date, studies revealing the modulation of antioxidant potential as compensatory response to multiple stressors are rather lacking. Therefore, the present work evaluated the individual and combined effects of salinity challenge, ammonia toxicity and nutritional status on oxidative stress and antioxidant status in a marine teleost, European sea bass (Dicentrarchus labrax). Fish were acclimated to normal seawater (32 ppt), to brackish water (20 ppt and 10 ppt) and to hypo-saline water (2.5 ppt). Following acclimation to different salinities for two weeks, fish were exposed to high environmental ammonia (HEA, 20 mg/L representing 50% of 96h LC50 value for ammonia) for 12 h, 48 h, 84 h and 180 h, and were either fed (2% body weight) or fasted (unfed for 7 days prior to HEA exposure). Results show that in response to decreasing salinities, oxidative stress indices such as xanthine oxidase activity, levels of hydrogen peroxide (H2O2) and lipid peroxidation (malondialdehyde, MDA) increased in the hepatic tissue of fasted fish but remained unaffected in fed fish. HEA exposure at normal salinity (32 ppt) and at reduced salinities (20 ppt and 10 ppt) increased ammonia accumulation significantly (84 h–180 h) in both feeding regimes which was associated with an increment of H2O2 and MDA contents. Unlike in fasted fish, H2O2 and MDA levels in fed fish were restored to control levels (84 h–180 h); with a concomitant increase in superoxide dismutase (SOD), catalase (CAT), components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase), ascorbate peroxidase (APX) activity and reduced ascorbate (ASC) content. On the contrary, fasted fish could not activate many of these protective systems and rely mainly on CAT and ASC dependent pathways as antioxidative sentinels. The present findings exemplify that in fed fish single factors and a combination of HEA exposure and reduced seawater salinities (upto 10 ppt) were insufficient to cause oxidative damage due to the highly competent antioxidant system compared to fasted fish. However, the impact of HEA exposure at a hypo-saline environment (2.5 ppt) also defied antioxidant defence system in fed fish, suggesting this combined factor is beyond the tolerance range for both feeding groups. Overall, our results indicate that the oxidative stress mediated by the experimental conditions were exacerbated during starvation, and also suggest that feed deprivation particularly at reduced seawater salinities can instigate fish more susceptible to ammonia toxicity. PMID:26241315

SW-846 Test Method 4025: Screening for Polychlorinated Dibenzodioxins and Polychlorinated Dibenzofurans (PCDD/PCDFs) by Immunoassay

EPA Pesticide Factsheets

a procedure for the analysis of (PCDDs/PCDFs) in soil at 500 ppt (pg/g) using a simple onestep liquid phase oxidative cleanup or, at mid to low ppt levels, using a two step coupled column cleanup (oxidation and activated carbon binding)

Precipitation legacy effects on dryland ecosystem carbon fluxes: direction, magnitude and biogeochemical carryovers

USDA-ARS?s Scientific Manuscript database

The precipitation legacy effect, defined as the impact of historical precipitation (PPT) on extant ecosystem dynamics, has been recognized as an important driver in shaping the temporal variability of dryland aboveground net primary production (ANPP) and soil respiration. How the PPT legacy influenc...

Polynuclear Aromatic Hydrocarbons and Toxicity of Sediments from the Elizabeth River, Hampton Roads, Virginia

DTIC Science & Technology

1984-10-01

solid phase experiment, the shrimp were exposed to high (35 ppt) or law (10 ppt) salinities for 24 hours to test osmoregulation capacities. The...of sediments from these stations are rather low. Significant osmoregulation and, to a lesser degree, respiration effects were observed during the tests

Wide-area ratios of evapotranspiration to precipitation in monsoon dependent semiarid vegetation communities

USDA-ARS?s Scientific Manuscript database

Aims. E vapotranspiration (ET) and ratios of ET to precipitation (PPT) are important factors in the water budget of semiarid rangelands and are in part determined by the dominant plant communities. We determined ET and ET/PPT for shrublands, grasslands and mesquite savannas in southern Arizona and d...

Development of a PPT for the EO-1 Spacecraft

NASA Technical Reports Server (NTRS)

Benson, Scott W.; Arrington, Lynn A.; Hoskins, W. Andrew; Meckel, Nicole J.

2000-01-01

A Pulsed Plasma Thruster (PPT) has been developed for use in a technology demonstration flight experiment on the Earth Observing 1 (EO-1) New Millennium Program mission. The thruster replaces the spacecraft pitch axis momentum wheel for control and momentum management during an experiment of a minimum three-day duration. The EO-1 PPT configuration is a combination of new technology and design heritage from similar systems flown in the 1970's and 1980's. Acceptance testing of the protoflight unit has validated readiness for flight, and integration with the spacecraft, including initial combined testing, has been completed. The thruster provides a range of capability from 90 microN-sec impulse bit at 650 sec specific impulse for 12 W input power, through 860 microN-sec impulse bit at 1400 see specific impulse for 70 W input power. Development of this thruster reinitiates technology research and development and re-establishes an industry base for production of flight hardware. This paper reviews the EO-1 PPT development, including technology selection, design and fabrication, acceptance testing, and initial spacecraft integration and test.

Wide-area ratios of evapotranspiration to precipitation in monsoon-dependent semiarid vegetation communities

USGS Publications Warehouse

Glenn, Edward P.; Scott, Russell L.; Nguyen, Uyen; Nagler, Pamela L.

2015-01-01

Evapotranspiration (ET) and the ratio of ET to precipitation (PPT) are important factors in the water budget of semiarid rangelands and are in part determined by the dominant plant communities. Our goal was to see if landscape changes such as tree or shrub encroachment and replacement of native grasses by invasive grasses impacted ET and ET/PPT and therefore watershed hydrology in this biome. We determined ET and ET/PPT for shrublands, grasslands and mesquite savannas in southern Arizona at five moisture flux towers and determined the environmental factors controlling ET in each plant community. We then scaled ET over areas of 4–36 km2, representing homogeneous patches of each plant community, using the Enhanced Vegetation Index (EVI) from MODIS sensors on the Terra satellite. Over wide areas, estimated ET/PPT projected from MODIS EVI ranged from 0.71 for a sparsely-vegetated shrub site to 1.00 for grasslands and mesquite savannas. The results did not support hypotheses that encroachment of mesquites into grasslands or that replacement of native grasses with introduced Eragrostis lehmanniana (lehmann lovegrass) have increased rangeland ET.

Neuroprotection and lifespan extension in Ppt1−/− mice by NtBuHA: therapeutic implications for INCL

PubMed Central

Sarkar, Chinmoy; Chandra, Goutam; Peng, Shyiong; Zhang, Zhongjian; Liu, Aiyi; Mukherjee, Anil B.

2013-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disease (LSD) that has no effective treatment. It is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1-deficiency impairs the cleavage of thioester linkage in palmitoylated proteins (constituents of ceroid), preventing degradation by lysosomal hydrolases. Consequently, accumulation of lysosomal ceroid leads to INCL. Thioester linkage is cleaved by nucleophilic attack. Hydroxylamine, a potent nucleophilic cellular metabolite, may have therapeutic potential for INCL but its toxicity precludes clinical application. Here we report that a hydroxylamine-derivative, N-(tert-Butyl) hydroxylamine (NtBuHA), is non-toxic, cleaves thioester linkage in palmitoylated proteins and mediates lysosomal ceroid depletion in cultured cells from INCL patients. Importantly, in Ppt1−/− mice, which mimic INCL, NtBuHA crossed the blood-brain-barrier, depleted lysosomal ceroid, suppressed neuronal apoptosis, slowed neurological deterioration and extended lifespan. Our findings provide the proof of concept that thioesterase-mimetic and antioxidant small molecules like NtBuHA are potential drug-targets for thioesterase deficiency diseases like INCL. PMID:24056696

Beneficial Use of Drilling Waste - A Wetland Restoration Technology

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

Pioneer Natural Resources

1999-07-01

The results obtained thus far are promising with regard to the low toxicity of restored drill cuttings (particularly the Cameron substrate) with increasing levels of salinity. Water extraction, acid digestion, and interstitial water samples from the restored drill cuttings, as well as redox potential, soil pH and interstitial nitrate/ammonium concentrations, and the photosynthetic response, have been determined for the baseline fresh water condition (June-August 1998), at 9ppt (September-November 1998), at 18ppt (December-February 1998,1999), and at 27ppt (currently underway). Salinities will be brought to full-strength seawater (36ppt) on May 24, 1999. The Cameron drill cuttings are remarkably similar to dredge spoil,more » which is currently being used as a wetland creation substrate. The few elements that were extracted into the interstitial water were primarily cations (Ca, K, Mg) and were not elevated to a level that would pose a threat to wetlands productivity. Swaco drill cuttings remained high in aluminum with concomitant high pH, which likely resulted in limited plant productivity through hindered nutrient uptake.« less

Durable Hybrid Coatings

DTIC Science & Technology

2007-10-01

Freeman 1998). The concept of molecular FV and its relationship to a multiplicity of properties in materials has been discussed for decades. For...importance of FV and developed theoretical relationships without being able to accurately and directly measure it. Dilatometry, diffusion studies with an...found to decrease with increase oligomeric triol molecular weight . PAS was conducted on free films. In order to assess reproducibility, measurements

Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression.

PubMed

Bellanti, Francesco; Villani, Rosanna; Tamborra, Rosanna; Blonda, Maria; Iannelli, Giuseppina; di Bello, Giorgia; Facciorusso, Antonio; Poli, Giuseppe; Iuliano, Luigi; Avolio, Carlo; Vendemiale, Gianluigi; Serviddio, Gaetano

2018-05-01

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury. Copyright © 2017. Published by Elsevier B.V.

Decomposition of 2-((2-methoxyphenyl)diazenyl)benzene-1,3,5-triol molecule by an argon plasma jet

NASA Astrophysics Data System (ADS)

Tanışlı, Murat; Taşal, Erol

2018-05-01

In this study, we have presented the effects of the argon plasma on a 2-((2-methoxyphenyl)diazenyl)benzene-1,3,5-triol molecule—AZO compound (abbreviated as 2MDB)—under atmospheric pressure. In order to do this, the validated molecule has been considered and plasma has been used to modify it. The atmospheric pressure plasma jet system was specially designed for performing decomposing processes of the 2MDB molecule. The characterizations before and after the application of plasma—which takes only 3 minutes under atmospheric pressure conditions, to dissolve the 2MDB molecule in ethanol and methanol solutions—were examined using the Fourier transform infrared and Ultraviolet-Visible (UV-Vis) spectroscopies. After the plasma treatment, the molecule was broken at -C-N=N-C-C bond. Accurate and important changes are seen clearly from the results. In addition, according to UV-Vis spectra, π-π* electronic transitions related to -N=N- AZO bridge for the 2MDB molecule in polar-aprotic solvents such as ethanol and methanol were recorded as strong transitions. The new photoproducts such as -C-N-N=C and C=O were obtained from the 2MDB molecule.

Adjuvant-induced joint inflammation causes very rapid transcription of beta-preprotachykinin and alpha-CGRP genes in innervating sensory ganglia.

PubMed

Bulling, D G; Kelly, D; Bond, S; McQueen, D S; Seckl, J R

2001-04-01

Neuropeptides synthesized in dorsal root ganglia (DRG) have been implicated in neurogenic inflammation and nociception in experimental and clinical inflammatory arthritis. We examined the very early changes in response to adjuvant injection in a rat model of unilateral tibio-tarsal joint inflammation and subsequent monoarthritis. Within 30 min of adjuvant injection ipsilateral swelling and hyperalgesia were apparent, and marked increases in beta-preprotachykinin-A (beta-PPT-A) and alpha-calcitonin gene-related peptide (CGRP)-encoding mRNAs were observed in small-diameter L5 DRG neurones innervating the affected joint. This response was augmented by recruitment of additional small-diameter DRG neurones expressing beta-PPT-A and CGRP transcripts. The increased mRNA was paralleled by initial increases in L5 DRG content of the protein products, substance P and calcitonin gene-related peptide. Within 15 min of adjuvant injection there were increases in electrical activity in sensory nerves innervating a joint. Blockade of this activity prevented the rapid induction in beta-PPT-A and CGRP mRNA expression in DRG neurones. Increased expression of heteronuclear (intron E) beta-PPT-A RNA suggests that increases in beta-PPT-A mRNA levels were, at least in part, due to transcription. Pre-treatment with the protein synthesis inhibitor cycloheximide had no effect upon the early rise in neuropeptide mRNAS: This and the rapid time course of these changes suggest that increased sensory neural discharge and activation of a latent modulator of transcription are involved.

Amortized entanglement of a quantum channel and approximately teleportation-simulable channels

NASA Astrophysics Data System (ADS)

Kaur, Eneet; Wilde, Mark M.

2018-01-01

This paper defines the amortized entanglement of a quantum channel as the largest difference in entanglement between the output and the input of the channel, where entanglement is quantified by an arbitrary entanglement measure. We prove that the amortized entanglement of a channel obeys several desirable properties, and we also consider special cases such as the amortized relative entropy of entanglement and the amortized Rains relative entropy. These latter quantities are shown to be single-letter upper bounds on the secret-key-agreement and PPT-assisted quantum capacities of a quantum channel, respectively. Of especial interest is a uniform continuity bound for these latter two special cases of amortized entanglement, in which the deviation between the amortized entanglement of two channels is bounded from above by a simple function of the diamond norm of their difference and the output dimension of the channels. We then define approximately teleportation- and positive-partial-transpose-simulable (PPT-simulable) channels as those that are close in diamond norm to a channel which is either exactly teleportation- or PPT-simulable, respectively. These results then lead to single-letter upper bounds on the secret-key-agreement and PPT-assisted quantum capacities of channels that are approximately teleportation- or PPT-simulable, respectively. Finally, we generalize many of the concepts in the paper to the setting of general resource theories, defining the amortized resourcefulness of a channel and the notion of ν-freely-simulable channels, connecting these concepts in an operational way as well.

Acute food deprivation reverses morphine-induced locomotion deficits in M5 muscarinic receptor knockout mice.

PubMed

Steidl, Stephan; Lee, Esther; Wasserman, David; Yeomans, John S

2013-09-01

Lesions of the pedunculopontine tegmental nucleus (PPT), one of two sources of cholinergic input to the ventral tegmental area (VTA), block conditioned place preference (CPP) for morphine in drug-naïve rats. M5 muscarinic cholinergic receptors, expressed by midbrain dopamine neurons, are critical for the ability of morphine to increase nucleus accumbens dopamine levels and locomotion, and for morphine CPP. This suggests that M5-mediated PPT cholinergic inputs to VTA dopamine neurons critically contribute to morphine-induced dopamine activation, reward and locomotion. In the current study we tested whether food deprivation, which reduces PPT contribution to morphine CPP in rats, could also reduce M5 contributions to morphine-induced locomotion in mice. Acute 18-h food deprivation reversed the phenotypic differences usually seen between non-deprived wild-type and M5 knockout mice. That is, food deprivation increased morphine-induced locomotion in M5 knockout mice but reduced morphine-induced locomotion in wild-type mice. Food deprivation increased saline-induced locomotion equally in wild-type and M5 knockout mice. Based on these findings, we suggest that food deprivation reduces the contribution of M5-mediated PPT cholinergic inputs to the VTA in morphine-induced locomotion and increases the contribution of a PPT-independent pathway. The contributions of cholinergic, dopaminergic and GABAergic neurons to the effects of acute food deprivation are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Volatile Organic Compounds (VOCs) measurements onboard the HALO research aircraft during OMO-ASIA

NASA Astrophysics Data System (ADS)

Safadi, Layal; Neumaier, Marco; Fischbeck, Garlich; Geiger, Felix; Förster, Eric; Tomsche, Laura; Zahn, Andreas

2017-04-01

The objective of the OMO-Asia campaign that took place in summer 2015 was to study the free-radical chemistry at higher altitudes during the Asian summer monsoon taken over a wide area of Asia. VOC measurements (e.g. acetone, acetonitrile, benzene, and toluene) were conducted using a strongly modified instrument based on a commercial Proton-Transfer-Reaction Mass Spectrometer (PTRMS) from Ionicon. The PTRMS data are generally in good agreement with VOC measurements taken by the GC instrument from Max Planck Institute for Chemistry. In the outflow of the Monsoon plume acetone and acetonitrile volume mixing ratios (VMR) up to 1500 pptV and 180 pptV have been measured, respectively, pointing to a small contribution from biomass burning sources of which acetonitrile is an important tracer. Comparison with VOCs simulated in the atmospheric chemistry model EMAC model exhibits an underestimation (factor of 3 for acetone). The measured data were analyzed with the help of 10 days back trajectories to distinguish air mass origins. For air masses originating from North America (NA) an enhancement of 500 pptV acetone relative to the atmospheric background ( 500 pptV) can be traced back to active biogenic acetone sources in the NA boreal summer. An average enhancement of 400 pptV acetone comes from the Asian summer monsoon. Acetone - CO correlations in the monsoon relative to background air is being analyzed for further characterization and estimation of the sources.

Cellular and Molecular Mechanisms of REM Sleep Homeostatic Drive: A Plausible Component for Behavioral Plasticity

PubMed Central

Datta, Subimal; Oliver, Michael D.

2017-01-01

Homeostatic regulation of REM sleep drive, as measured by an increase in the number of REM sleep transitions, plays a key role in neuronal and behavioral plasticity (i.e., learning and memory). Deficits in REM sleep homeostatic drive (RSHD) are implicated in the development of many neuropsychiatric disorders. Yet, the cellular and molecular mechanisms underlying this RSHD remain to be incomplete. To further our understanding of this mechanism, the current study was performed on freely moving rats to test a hypothesis that a positive interaction between extracellular-signal-regulated kinase 1 and 2 (ERK1/2) activity and brain-derived neurotrophic factor (BDNF) signaling in the pedunculopontine tegmentum (PPT) is a causal factor for the development of RSHD. Behavioral results of this study demonstrated that a short period (<90 min) of selective REM sleep restriction (RSR) exhibited a strong RSHD. Molecular analyses revealed that this increased RSHD increased phosphorylation and activation of ERK1/2 and BDNF expression in the PPT. Additionally, pharmacological results demonstrated that the application of the ERK1/2 activation inhibitor U0126 into the PPT prevented RSHD and suppressed BDNF expression in the PPT. These results, for the first time, suggest that the positive interaction between ERK1/2 and BDNF in the PPT is a casual factor for the development of RSHD. These findings provide a novel direction in understanding how RSHD-associated specific molecular changes can facilitate neuronal plasticity and memory processing. PMID:28959190

Pressure pain threshold is higher in hypertensive compared with normotensive older adults: A case-control study.

PubMed

Nascimento Rebelatto, Marcelo; Alburquerque-Sendín, Francisco; Guimarães, João Flavio; Salvini, Tania Fatima

2017-06-01

To establish whether there are differences in pain sensitivity between hypertensive and normotensive older adults. A cross-sectional case control study was carried out. A total of 72 older adults, 36 normotensive and 36 hypertensive, participated in the study. The pressure pain threshold (PPT) was assessed on seven points bilaterally in both groups by means of pressure algometry. Two-factor analysis of variance (anova) - group and sex - was carried out, and the magnitude of the differences was calculated using Cohen's index. The PPT values were higher in the group of hypertensive older adults compared with the normotensive older adults; that difference was significant (P < 0.05) for the following points: right and left trochanters, left trapezium, left L3/L4 and left anterior tibialis muscle, with both trochanter and left L3/L4 PPT showing moderate magnitude of the differences. The correlations shown among the PPT were stronger in the group of hypertensive older adults. Thus, hypoalgesia was more generalized among the hypertensive older adults compared with the normotensive older adults. Sex did not influence that difference, although the magnitude of the difference was greater among men compared with women. Hypoalgesia, as assessed by means of PPT, showed a relationship with arterial hypertension in older adults. The influence of sex on hypoalgesia shown by hypertensive individuals is controversial. Geriatr Gerontol Int 2017; 17: 967-972. © 2016 Japan Geriatrics Society.

Pressure hyperalgesia in hind limb suspended rats.

PubMed

Chowdhury, Parimal; Soulsby, Michael E; Jayroe, John; Akel, Nisreen S; Gaddy, Dana; Dobretsov, Maxim

2011-10-01

Spaceflight and simulated microgravity often associate with pain and prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models of prediabetes result in pressure hyperalgesia. The current study was designed to determine whether or not simulated microgravity induced by hind limb suspension (HLS) in rats lead to insulinopenia and pressure hyperalgesia. Adult male rats were divided into HLS (N = 20) and control, non-suspended (N = 16) groups, respectively. Bodyweight and hind limb pressure-pain withdrawal threshold (PPT) were measured at regular 2-5 d intervals for 7 d before and 12-13 d after HLS. Bodyweights and PPT of control and HLS animals measured on the day of suspension were not different. During the experiment, control rats gained 61 +/- 5 g, but maintained their PPT at the baseline level. Suspended rats gained 26 +/- 3 g of weight during the same time period and their PPT declined from 105 +/- 6 g to 84 +/- 6 g. Neither blood glucose nor pancreatic islet density and area were affected by HLS. However, the random plasma insulin of HLS rats was significantly lower than that of control animals (1.6 +/- 0.2 vs. 2.7 +/- 0.2 ng ml(-1)). The observed relationship between insulin and PPT levels in the HLS rats was similar to that observed in rats with STZ-induced insulinopenia. These data suggest that moderate insulinopenia may affect the rat's sensitivity to deep pressure directly, without affecting glucose homeostasis. In addition, our data suggest that HLS rats may develop peripheral neuropathy.

Pain pressure threshold of a muscle tender spot increases following local and non-local rolling massage.

PubMed

Aboodarda, S J; Spence, A J; Button, Duane C

2015-09-28

The aim of the present study was to determine the acute effect of rolling massage on pressure pain threshold (PPT) in individuals with tender spots in their plantar flexor muscles. In a randomized control trial and single blinded study, tender spots were identified in 150 participants' plantar flexor muscles (gastrocnemius or soleus). Then participants were randomly assigned to one of five intervention groups (n = 30): 1) heavy rolling massage on the calf that exhibited the higher tenderness (Ipsi-R), 2) heavy rolling massage on the contralateral calf (Contra-R), 3) light stroking of the skin with roller massager on the calf that exhibited the higher tenderness (Sham), 4) manual massage on the calf that exhibited the higher tenderness (Ipsi-M) and 5) no intervention (Control). PPT was measured at 30 s and up to 15 min post-intervention via a pressure algometer. At 30 s post-intervention, the Ipsi-R (24 %) and Contra-R (21 %) demonstrated higher (p < 0.03) PPT values compared with Control and Sham. During 15 min post-intervention, PPT was higher (p < 0.05) following Ipsi-R (19.2 %), Contra-R (15.9 %) and Ipsi-M (10.9 %) compared with Control. There was no difference between the effects of three deep tissue massages (Ipsi-R, Ipsi-M and Contra-R) on PPT. Whereas the increased PPT following ipsilateral massage (Ipsi-R and Ipsi-M) might be attributed to the release of fibrous adhesions; the non-localized effect of rolling massage on the contralateral limb suggests that other mechanisms such as a central pain-modulatory system play a role in mediation of perceived pain following brief tissue massage. Overall, rolling massage over a tender spot reduces pain perception. ClinicalTrials.gov ( NCT02528812 ), August 19(th), 2015.

Observations of 1,1-difluoroethane (HFC-152a) at AGAGE and SOGE monitoring stations in 1994-2004 and derived global and regional emission estimates

NASA Astrophysics Data System (ADS)

Greally, B. R.; Manning, A. J.; Reimann, S.; McCulloch, A.; Huang, J.; Dunse, B. L.; Simmonds, P. G.; Prinn, R. G.; Fraser, P. J.; Cunnold, D. M.; O'Doherty, S.; Porter, L. W.; Stemmler, K.; Vollmer, M. K.; Lunder, C. R.; Schmidbauer, N.; Hermansen, O.; Arduini, J.; Salameh, P. K.; Krummel, P. B.; Wang, R. H. J.; Folini, D.; Weiss, R. F.; Maione, M.; Nickless, G.; Stordal, F.; Derwent, R. G.

2007-03-01

Ground-based in situ measurements of 1,1-difluoroethane (HFC-152a, CH3CHF2) which is regulated under the Kyoto Protocol are reported under the auspices of the AGAGE (Advanced Global Atmospheric Gases Experiment) and SOGE (System of Observation of halogenated Greenhouse gases in Europe) programs. Observations of HFC-152a at five locations (four European and one Australian) over a 10 year period were recorded. The annual average growth rate of HFC-152a in the midlatitude Northern Hemisphere has risen from 0.11 ppt/yr to 0.6 ppt/yr from 1994 to 2004. The Southern Hemisphere annual average growth rate has risen from 0.09 ppt/yr to 0.4 ppt/yr from 1998 to 2004. The 2004 average mixing ratio for HFC-152a was 5.0 ppt and 1.8 ppt in the Northern and Southern hemispheres, respectively. The annual cycle observed for this species in both hemispheres is approximately consistent with measured annual cycles at the same locations in other gases which are destroyed by OH. Yearly global emissions of HFC-152a from 1994 to 2004 are derived using the global mean HFC-152a observations and a 12-box 2-D model. The global emission of HFC-152a has risen from 7 Kt/yr to 28 Kt/yr from 1995 to 2004. On the basis of observations of above-baseline elevations in the HFC-152a record and a consumption model, regional emission estimates for Europe and Australia are calculated, indicating accelerating emissions from Europe since 2000. The overall European emission in 2004 ranges from 1.5 to 4.0 Kt/year, 5-15% of global emissions for 1,1-difluoroethane, while the Australian contribution is negligible at 5-10 tonnes/year, <0.05% of global emissions.

The Drosophila protein palmitoylome: Characterizing palmitoyl-thioesterases and DHHC palmitoyl-transferases

PubMed Central

Bannan, Barbra A.; Van Etten, Jamie; Kohler, John A.; Tsoi, Yui; Hansen, Nicole M.; Sigmon, Stacey; Fowler, Elizabeth; Buff, Haley; Williams, Tiffany S.; Ault, Jeffrey G.; Glaser, Robert L.; Korey, Christopher A.

2010-01-01

Palmitoylation is the post-translational addition of a palmitate moiety to a cysteine residue through a covalent thioester bond. The addition and removal of this modification is controlled by both palmitoyl acyl-transferases and thioesterases. Using bioinformatic analysis, we identified 22 DHHC family palmitoyl acyl-transferase homologs in the Drosophila genome. We used in situ hybridization, RT-PCR, and published FlyAtlas microarray data to characterize the expression patterns of all 22 fly homologs. Our results indicate that all are expressed genes, but several, including CG1407, CG4676, CG5620, CG6017/dHIP14, CG6618, CG6627, and CG17257 appear to be enriched in neural tissues suggesting that they are important for neural function. Furthermore, we have found that several may be expressed in a sex-specific manner with adult male-specific expression of CG4483 and CG17195. Using tagged versions of the DHHC genes, we demonstrate that fly DHHC proteins are primarily located in either the Golgi Apparatus or Endoplasmic Reticulum in S2 cells, except for CG1407, which was found on the plasma membrane. We also characterized the subcellular localization and expression of the three known thioesterases: Palmitoyl-protein Thioesterase 1 (Ppt1), Palmitoyl-protein Thioesterase 2 (Ppt2), and Acyl-protein Thioesterase 1 (APT1). Our results indicate that Ppt1 and Ppt2 are the major lysosomal thioesterases while APT1 is the likely cytoplasmic thioesterase. Finally, in vivo rescue experiments show that Ppt2 expression cannot rescue the neural inclusion phenotypes associated with loss of Ppt1, further supporting distinct functions and substrates for these two thioesterases. These results will serve as the basis for a more complete understanding of the protein palmitoylome's normal cellular functions in the fly and will lead to further insights into the molecular etiology of diseases associated with the mis-regulation of palmitoylation. PMID:18719403

Observations of Nitrogen Oxides Diurnal Variations and Eddy Covariance Fluxes above a Mixed Hardwood Forest during the 2016 PROPHET-AMOS Campaign

NASA Astrophysics Data System (ADS)

Shi, Q.; Kavassalis, S.; Moravek, A.; Steiner, A.; Murphy, J. G.

2017-12-01

Nitrogen oxides (NOx = NO + NO2) are important constituents in the atmosphere because they can control ozone production and undergo oxidation reactions with other species. Deposition and emission of NOx can impact the ecosystem by influencing the nitrogen cycle, vegetation health and forest carbon storage. Exchange of NOx between the atmosphere and biosphere is poorly understood due to a lack of direct observations. Here, we present results of nitrogen oxides observations and eddy covariance fluxes above a forest from the 2016 PROPHET-AMOS summer field campaign using a custom built AQD NOxy instrument. This field site is in a mixed deciduous and coniferous forest located in northern Michigan, with a research tower available for above-canopy measurements. Observations made at 29 m show the mixing ratio of NO and NO2 ranges from 0 to 640 ppt and 68 to 3600 ppt respectively. The night-time NO mixing ratio is close to zero, while NO2 builds up to a median of around 700 ppt. A maximum mixing ratio of NO resulting from photolysis of NO2 is frequently observed in the early morning. Median midday NO and NO2 mixing ratios are 50 ppt and 500 ppt. Fluxes calculated by eddy covariance showed an upward flux of NO2 and a downward flux of NO, which is an example of chemical flux divergence due to fast chemistry and diminished solar radiation below the canopy. Daytime fluxes of NO and NO2 peak at similar times in the morning, resulting in a net downward NOx flux with a maximum around 2.5 ppt m/s. To better explain NOx flux observations in this forest, results are compared to previous measurements of the total deposition budget of reactive nitrogen oxides, as well as results from 1-D canopy model FORCAsT.

Nongeneric positive partial transpose states of rank five in 3×3 dimensions

NASA Astrophysics Data System (ADS)

Hansen, Leif Ove; Myrheim, Jan

In 3×3 dimensions, entangled mixed states that are positive under partial transposition (PPT states) must have rank at least four. These rank four states are completely understood. We say that they have rank (4,4) since both a state ρ and its partial transpose ρP have rank four. The next problem is to understand the extremal PPT states of rank (5,5). We call two states SL⊗SL-equivalent if they are related by a product transformation. A generic rank (5,5) PPT state ρ is extremal, and both ρ and ρP have six product vectors in their ranges, and no product vectors in their kernels. The three numbers {6,6;0} are SL⊗SL-invariants that help us classify the state. There is no analytical understanding of such states. We have studied numerically a few types of nongeneric rank five PPT states, in particular, states with one or more product vectors in their kernels. We find an interesting new analytical construction of all rank four extremal PPT states, up to SL⊗SL-equivalence, where they appear as boundary states on one single five-dimensional face on the set of normalized PPT states. The interior of the face consists of rank (5,5) states with four common product vectors in their kernels, it is a simplex of separable states surrounded by entangled PPT states. We say that a state ρ is SL⊗SL-symmetric if ρ and ρP are SL⊗SL-equivalent, and is genuinely SL⊗SL-symmetric if it is SL⊗SL-equivalent to a state τ with τ=τP. Genuine SL⊗SL-symmetry implies a special form of SL⊗SL-symmetry. We have produced numerically, by a special method, a random sample of rank (5,5) SL⊗SL-symmetric states. About 50 of these are of type {6,6;0}, among those all are extremal and about half are genuinely SL⊗SL-symmetric. All these genuinely SL⊗SL-symmetric states can be transformed to have a circulant form. We find however that this is not a generic property of genuinely SL⊗SL-symmetric states. The remaining SL⊗SL-symmetric states found in the search have product vectors in their kernels, and they inspired us to study such states without regard to SL⊗SL-symmetry.

Characterization of a chemical artifact in the liquid chromatographic determination of 3-butyn-2-one using the 2,4-dinitrophenylhydrazine method.

PubMed

Vogel, M; Pötter, W; Karst, U

2000-07-21

This study reports the identification of a chemical artifact occurring in the liquid chromatographic analysis of 3-butyn-2-one by means of the 2,4-dinitrophenylhydrazine (DNPH) method. Besides the expected derivatization reaction to the corresponding butynone DNPhydrazone, a rearrangement was observed, thus leading to the formation of 3-methyl-1-(2',4'-dinitrophenyl)pyrazol (DNPP). Although the rearrangement product and the hydrazone can easily be separated by means of liquid chromatography, problems arise from coelution of the pyrazol with the formaldehyde DNPhydrazone. Identification of the artifact by means of UV-Vis spectroscopy using dual wavelength or diode array detection is discussed.

Two-photon absorption resonance in 3-(1,1-dicyanoethenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (DCNP)

NASA Astrophysics Data System (ADS)

Miniewicz, Andrzej; Delysse, Stéphane; Nunzi, Jean-Michel; Kajzar, François

1998-04-01

A two-photon absorption spectrum of 3-(1,1-dicyanoethenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (DCNP) in tetrahydrofuran solution has been studied by the Kerr ellipsometry technique. The spectral shape and amplitude of the imaginary part of the dominant molecular hyperpolarizability term Im( γXXXX) is compared with the relevant linear absorption spectrum within a simple two-level model. Agreement between the measured γXXXX=2.0×10 -48 m 5 V -2 and calculated γXXXX=(1.2-1.5)×10 -48 m 5 V -2 two-photon absorption molecular hyperpolarizabilties in the vicinity of the two-photon resonance transition is satisfactory.

BrO and inferred Bry profiles over the western Pacific: relevance of inorganic bromine sources and a Bry minimum in the aged tropical tropopause layer

NASA Astrophysics Data System (ADS)

Koenig, Theodore K.; Volkamer, Rainer; Baidar, Sunil; Dix, Barbara; Wang, Siyuan; Anderson, Daniel C.; Salawitch, Ross J.; Wales, Pamela A.; Cuevas, Carlos A.; Fernandez, Rafael P.; Saiz-Lopez, Alfonso; Evans, Mathew J.; Sherwen, Tomás; Jacob, Daniel J.; Schmidt, Johan; Kinnison, Douglas; Lamarque, Jean-François; Apel, Eric C.; Bresch, James C.; Campos, Teresa; Flocke, Frank M.; Hall, Samuel R.; Honomichl, Shawn B.; Hornbrook, Rebecca; Jensen, Jørgen B.; Lueb, Richard; Montzka, Denise D.; Pan, Laura L.; Reeves, J. Michael; Schauffler, Sue M.; Ullmann, Kirk; Weinheimer, Andrew J.; Atlas, Elliot L.; Donets, Valeria; Navarro, Maria A.; Riemer, Daniel; Blake, Nicola J.; Chen, Dexian; Huey, L. Gregory; Tanner, David J.; Hanisco, Thomas F.; Wolfe, Glenn M.

2017-12-01

We report measurements of bromine monoxide (BrO) and use an observationally constrained chemical box model to infer total gas-phase inorganic bromine (Bry) over the tropical western Pacific Ocean (tWPO) during the CONTRAST field campaign (January-February 2014). The observed BrO and inferred Bry profiles peak in the marine boundary layer (MBL), suggesting the need for a bromine source from sea-salt aerosol (SSA), in addition to organic bromine (CBry). Both profiles are found to be C-shaped with local maxima in the upper free troposphere (FT). The median tropospheric BrO vertical column density (VCD) was measured as 1.6×1013 molec cm-2, compared to model predictions of 0.9×1013 molec cm-2 in GEOS-Chem (CBry but no SSA source), 0.4×1013 molec cm-2 in CAM-Chem (CBry and SSA), and 2.1×1013 molec cm-2 in GEOS-Chem (CBry and SSA). Neither global model fully captures the C-shape of the Bry profile. A local Bry maximum of 3.6 ppt (2.9-4.4 ppt; 95 % confidence interval, CI) is inferred between 9.5 and 13.5 km in air masses influenced by recent convective outflow. Unlike BrO, which increases from the convective tropical tropopause layer (TTL) to the aged TTL, gas-phase Bry decreases from the convective TTL to the aged TTL. Analysis of gas-phase Bry against multiple tracers (CFC-11, H2O / O3 ratio, and potential temperature) reveals a Bry minimum of 2.7 ppt (2.3-3.1 ppt; 95 % CI) in the aged TTL, which agrees closely with a stratospheric injection of 2.6 ± 0.6 ppt of inorganic Bry (estimated from CFC-11 correlations), and is remarkably insensitive to assumptions about heterogeneous chemistry. Bry increases to 6.3 ppt (5.6-7.0 ppt; 95 % CI) in the stratospheric "middleworld" and 6.9 ppt (6.5-7.3 ppt; 95 % CI) in the stratospheric "overworld". The local Bry minimum in the aged TTL is qualitatively (but not quantitatively) captured by CAM-Chem, and suggests a more complex partitioning of gas-phase and aerosol Bry species than previously recognized. Our data provide corroborating evidence that inorganic bromine sources (e.g., SSA-derived gas-phase Bry) are needed to explain the gas-phase Bry budget in the upper free troposphere and TTL. They are also consistent with observations of significant bromide in Upper Troposphere-Lower Stratosphere aerosols. The total Bry budget in the TTL is currently not closed, because of the lack of concurrent quantitative measurements of gas-phase Bry species (i.e., BrO, HOBr, HBr, etc.) and aerosol bromide. Such simultaneous measurements are needed to (1) quantify SSA-derived Bry in the upper FT, (2) test Bry partitioning, and possibly explain the gas-phase Bry minimum in the aged TTL, (3) constrain heterogeneous reaction rates of bromine, and (4) account for all of the sources of Bry to the lower stratosphere.

Environmental Projects for Aerospace Applications

DTIC Science & Technology

2012-05-23

following for missile systems as part of a total hexavalent chromium free coating system:  1-Evaluate trivalent chromium pretreatment (TCP) for use on...Yourfilename.ppt Hexavalent Chromium Free Coating System for Magnesium Housings on Aviation Systems UNCLASSIFIED UNCLASSIFIED 12 Yourfilename.ppt...Sulfur Dioxide (SO2) testing complete. Hexavalent Chromium Free Coating System for Magnesium Housings on Aviation Systems Description If

Integrating a Digital Concept Mapping into a PPT Slide Writing Project

ERIC Educational Resources Information Center

Yen, Ai Chun; Yang, Pei Yi

2013-01-01

Carried out during a semester-long EFL (English as a foreign language) drama class, this research aimed to scrutinize the effects of digital concept mapping via LMS on English majors' (N = 38) PowerPoint (PPT) slide writing skills in Taiwan. Students were instructed to follow the concept mapping agenda via university learning management system…

Pyrazole derived ultra-short antimicrobial peptidomimetics with potent anti-biofilm activity.

PubMed

Ahn, Mija; Gunasekaran, Pethaiah; Rajasekaran, Ganesan; Kim, Eun Young; Lee, Soo-Jae; Bang, Geul; Cho, Kun; Hyun, Jae-Kyung; Lee, Hyun-Ju; Jeon, Young Ho; Kim, Nam-Hyung; Ryu, Eun Kyoung; Shin, Song Yub; Bang, Jeong Kyu

2017-01-05

In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin. Besides its higher selectivity (therapeutic index) toward bacterial cells than LL-37, Py11 showed highly increased proteolytic stability against trypsin digestion and maintained its antimicrobial activity in the presence of physiological salts. Interestingly, Py11 exhibited higher anti-biofilm activity against MDRPA compared to LL-37. The results from fluorescence spectroscopy and transmission electron microscopy (TEM) suggested that Py11 kills bacterial cells possibly by integrity disruption damaging the cell membrane, leading to the cytosol leakage and eventual cell lysis. Furthermore, Py11 displayed significant anti-inflammatory (endotoxin-neutralizing) activity by inhibiting LPS-induced production of nitric oxide (NO) and TNF-α. Collectively, our results suggest that Py11 may serve as a model compound for the design of antimicrobial and antisepsis agents. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant α-Synuclein

PubMed Central

Ahsan, Nuzhat; Mishra, Satyendra; Jain, Manish Kumar; Surolia, Avadhesha; Gupta, Sarika

2015-01-01

Accumulating evidence suggests that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson’s disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against α-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of α-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of α-synuclein amyloidosis and toxicity in Parkinson’s disease and other synucleinopathies. PMID:25985292

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.

Oxorhenium complexes bearing the water-soluble tris(pyrazol-1-yl)methanesulfonate, 1,3,5-triaza-7-phosphaadamantane, or related ligands, as catalysts for Baeyer-Villiger oxidation of ketones.

PubMed

Martins, Luísa M D R S; Alegria, Elisabete C B A; Smoleński, Piotr; Kuznetsov, Maxim L; Pombeiro, Armando J L

2013-04-15

New rhenium(VII or III) complexes [ReO3(PTA)2][ReO4] (1) (PTA = 1,3,5-triaza-7-phosphaadamantane), [ReO3(mPTA)][ReO4]I (2) (mPTA = N-methyl-1,3,5-triaza-7-phosphaadamantane cation), [ReO3(HMT)2][ReO4] (3) (HMT = hexamethylenetetramine), [ReO3(η(2)-Tpm)(PTA)][ReO4] (4) [Tpm = hydrotris(pyrazol-1-yl)methane, HC(pz)3, pz = pyrazolyl], [ReO3(Hpz)(HMT)][ReO4] (5) (Hpz = pyrazole), [ReO(Tpms)(HMT)] (6) [Tpms = tris(pyrazol-1-yl)methanesulfonate, O3SC(pz)3(-)] and [ReCl2{N2C(O)Ph}(PTA)3] (7) have been prepared from the Re(VII) oxide Re2O7 (1-6) or, in the case of 7, by ligand exchange from the benzoyldiazenido complex [ReCl2{N2C(O)Ph}(Hpz)(PPh3)2], and characterized by IR and NMR spectroscopies, elemental analysis and electrochemical properties. Theoretical calculations at the density functional theory (DFT) level of theory indicated that the coordination of PTA to both Re(III) and Re(VII) centers by the P atom is preferable compared to the coordination by the N atom. This is interpreted in terms of the Re-PTA bond energy and hard-soft acid-base theory. The oxo-rhenium complexes 1-6 act as selective catalysts for the Baeyer-Villiger oxidation of cyclic and linear ketones (e.g., 2-methylcyclohexanone, 2-methylcyclopentanone, cyclohexanone, cyclopentanone, cyclobutanone, and 3,3-dimethyl-2-butanone or pinacolone) to the corresponding lactones or esters, in the presence of aqueous H2O2. The effects of a variety of factors are studied toward the optimization of the process.

New antimycobacterial triterpenoids from Rhus taitensis.

PubMed

Jadulco, Raquel C; Koch, Michael; Van Wagoner, Ryan M; Pond, Christopher; Gideon, Osia G; Matainaho, Teatulohi; Piskaut, Pius; Barrows, Louis R

2011-09-01

Two new triterpenoids were isolated from the leaves and twigs of Rhus taitensis. Their structures were elucidated by 1D and 2D NMR spectroscopic studies as 1,10,24,25,30-pentahydroxysqualene and dammar-20(22),24-diene-3 β,26,27-triol. Both compounds exhibited moderate antimycobacterial activities with an MIC of 45 µg/mL. © Georg Thieme Verlag KG Stuttgart · New York.

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EPA Pesticide Factsheets

Empirical evidence suggests that exposure of Americans to dioxin-like compounds was low during the early decades of the 20th century, then increased during the 1940s and 1950s reaching a peak in the 1960s and 1970s, and progressively decreased to lower levels in the 1980s and 1990s. Such evidence includes dioxin analysis of carbon-dated sediment cores of lakes and rivers, preserved meat samples from different decades of the 20th century, and limited body burden measurements of dioxin-like compounds. Pinsky and Lorber (1998) summarized studies measuring 2,3,7,8-TCDD in blood and adipose tissue finding a range of 10-20 pg/g (ppt) lipid during the 1970s, and 2-10 ppt lipid during the 1980s. This study reviews body burdens of dioxin toxic equivalents, TEQs, to find a range from about 50-80 ppt lipid during the 1970s, 30-50 ppt lipid during the 1980s, and 10-20 ppt lipid during the 1990s (TEQs comprised of the 17 dioxin and furan congeners only). Pinsky and Lorber (1998) investigated historical exposure trends for 2,3,7,8-TCDD by using a single-compartment, first-order pharmacokinetic model. The current study extends this prior effort by modeling dioxin TEQs instead of the single compound, 2,3,7,8-TCDD. TEQs are modeled as though they are a single compound, in contrast to an approach where the individual dioxin and furan congeners are modeled separately. It was found that body burdens of TEQs during the 1970s, 80s, and 90s could be modeled by assuming a histor

Methyl farnesoate couples environmental changes to testicular development in the crab Carcinus maenas.

PubMed

Nagaraju, G P C; Borst, D W

2008-09-01

Carcinus maenas males have two major color phases. Green-phase males molt frequently and tend to live in brackish estuaries during the summer. After becoming red-phase males, they molt infrequently, have higher mating success, and live in cooler, deeper water. We found profound differences between these two phases in the way salinity and temperature affect hemolymph levels of methyl farnesoate (MF), a hormone that affects crustacean reproduction. Few green-phase males (<10%) had detectable MF in 33 ppt seawater (SW) at 11 or 18 degrees C. By contrast, about 30% of the red-phase males had detectable MF at either temperature. After transfer to 5 ppt SW, none of the green-phase males had detectable MF at 11 degrees C whereas 100% of green-phase males did at 18 degrees C. By contrast, 100% of the red-phase males had detectable MF in 5 ppt SW at either temperature. At 11 degrees C, green-phase males had detectable MF after eyestalk ablation (ESA), showing that they can produce MF. There was no additional increase in MF levels when ESA animals of either color phase were transferred to 5 ppt SW, suggesting that the eyestalk is the primary regulator of the MF response to low salinity. MF levels of green-phase males were increased by injecting MF, by ESA, or by exposure to 5 ppt SW at 18 degrees C. The testicular index of these treated animals nearly doubled after two weeks. Our results strongly suggest that environmental conditions such as temperature and salinity, affect testicular development in this crab by changing its MF levels.

Calculated trends and the atmospheric abundance of 1,1,1,2-tetrafluoroethane, 1,1-dichloro-1-fluoroethane, and 1-chloro-1,1-difluoroethane using automated in-situ gas chromatography-mass spectrometry measurements recorded at Mace Head, Ireland, from October 1994 to March 1997

NASA Astrophysics Data System (ADS)

Simmonds, P. G.; O'Doherty, S.; Huang, J.; Prinn, R.; Derwent, R. G.; Ryall, D.; Nickless, G.; Cunnold, D.

1998-01-01

The first in-situ measurements by automated gas chromatograph-mass spectrometer are reported for 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1-dichloro-1-fluoroethane, (HCFC-141b), and 1-chloro-1,1-difluoroethane, (HCFC-142b). These compounds are steadily replacing the chlorofluorocarbons (CFCs) as refrigerants, foam-blowing agents, and solvents. The concentrations of all three compounds are shown to be rapidly increasing in the atmosphere, with 134a increasing at a rate of 2.05±0.02 ppt yr-1 over the 30 months of observations. Similarly, 141b and 142b increased at rates of 2.49±0.03 and 1.24±0.02 ppt yr-1, respectively, over the same period. The concentrations recorded at the atmospheric research station at Mace Head, Ireland, on January 1, 1996, the midpoint of the time series, were 3.67 ppt (134a), 7.38 ppt (141b), and 8.78 ppt (142b). From these observations we optimally estimate the HCFC and HFC emissions using a 12-box global model and OH concentrations derived from global 1,1,1-trichloroethane (CCl3CH3) measurements. Comparing two methods of estimating emissions with independent industry estimates shows satisfactory agreement for 134a and 141b, while for 142b, industry estimates are less than half those required to explain our observations.

Two years of combined high-intensity physical training and heat acclimatization affect lymphocyte and serum HSP70 in purebred military working dogs.

PubMed

Bruchim, Yaron; Aroch, Itamar; Eliav, Ady; Abbas, Atallah; Frank, Ilan; Kelmer, Efrat; Codner, Carolina; Segev, Gilad; Epstein, Yoram; Horowitz, Michal

2014-07-15

Military working dogs in hot countries undergo exercise training at high ambient temperatures for at least 9 mo annually. Physiological adaptations to these harsh conditions have been extensively studied; however, studies focusing on the underlying molecular adaptations are limited. In the current study, military working dogs were chosen as a model to examine the effects of superimposing endurance exercise on seasonal acclimatization to environmental heat stress. The lymphocyte HSP70 profile and extracellular HSP70 were studied in tandem with physiological performance in the dogs from their recruitment for the following 2 yr. Aerobic power and heat shock proteins were measured at the end of each summer, with physical performance tests (PPTs) in an acclimatized room (22°C). The study shows that together with a profound enhancement of aerobic power and physical performance, hsp72 mRNA induction immediately post-PPT and 45 min later, progressively increased throughout the study period (relative change in median lymphocyte hsp72 mRNA first PPT, 4.22 and 12.82; second PPT, 17.19 and 109.05, respectively), whereas induction of HSP72 protein was stable. These responses suggest that cellular/molecular adaptive tools for maintaining HSP72 homeostasis exist. There was also a significant rise in basal and peak median optical density extracellular HSP at the end of each exercise test (first PPT, 0.13 and 0.15; second PPT, 1.04 and 1.52, respectively). The relationship between these enhancements and improved aerobic power capacity is not yet fully understood. Copyright © 2014 the American Physiological Society.

Growth evaluation of Atlantic Salmon (Salmo salar) raised in seawater or freshwater and fed either fishmeal based or marine-free diets

USDA-ARS?s Scientific Manuscript database

A forty week feeding study was conducted with Atlantic salmon (Salmo salar) smolts in two recirculating aquaculture systems. Two identical systems were used and contained either freshwater (0 ppt) or seawater (about 30 ppt). Fish were fed one of two diets, a control diet containing fishmeal and fi...

Post-fire tree regeneration in lowland Bolivia: implications for fire management

Treesearch

K.A. Gould; T.S. Fredericksen; F. Morales; D. Kennard; F.E. Putz; B. Mostacedo; M. Toldeo

2002-01-01

Tree regeneration was compared in burned and unburned portions of a tropical dry forest (1110 mm ppt/year) and a tropical humid forest (1542 mm ppt/year) in southeastern Bolivia. Both forests burned 5 years prior to our study, and both forests were also lightly selectively logged (intensity 3/ha)-the dry forest during the 1970 and 1980s...

Exploring the Role of Music in Secondary English and History Classrooms through Personal Practical Theory

ERIC Educational Resources Information Center

Goering, Christian Z.; Burenheide, Bradley J.

2010-01-01

This article explores the development of utilizing music as a Personal Practical Theory (PPT) in the teaching of English and history. Specifically, the authors explore the nature of PPT's, the benefits of utilizing music, and the process through which teachers begin using a new approach in their pedagogy. Unique contributions are the application…

40 CFR 261.35 - Deletion of certain hazardous waste codes following equipment cleaning and replacement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... cleaning and replacement. (a) Wastes from wood preserving processes at plants that do not resume or... parts per trillion (ppt), sample weight of 1000 g, IS spiking level of 1 ppt, final extraction volume of... previously used and the date on which their use ceased in each process at the plant; (3) Formulations...

40 CFR 261.35 - Deletion of certain hazardous waste codes following equipment cleaning and replacement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... cleaning and replacement. (a) Wastes from wood preserving processes at plants that do not resume or... parts per trillion (ppt), sample weight of 1000 g, IS spiking level of 1 ppt, final extraction volume of... previously used and the date on which their use ceased in each process at the plant; (3) Formulations...

Preschool Preposition Test and Classroom Behavior Description: Eighth Grade Follow-Up of Head Start Program.

ERIC Educational Resources Information Center

Aaronson, May; And Others

Head Start children tested at 4 years of age on the Preschool Preposition Test (PPT) and the Classroom Behavior Description checklist (CBD) were assessed for academic achievement and scholastic aptitude at the third- and eighth-grade levels. The PPT is a receptive language test which examines the comprehension of verbal directions by using spatial…

Counting Primitive Pythagorean Triples

ERIC Educational Resources Information Center

Ayoub, Ayoub B.

2005-01-01

A triple (x,y,z) of natural numbers is called a Primitive Pythagorean Triple (PPT) if it satisfies two conditions: (1) x[squared] + y[squared] = z[squared]; and (2) x, y, and z have no common factor other than one. All the PPT's are given by the parametric equations: (1) x = m[squared] - n[squared]; (2) y = 2mn; and (3) z = m[squared] +…

A study of parabens and bisphenol A in surface water and fish brain tissue from the Greater Pittsburgh Area.

PubMed

Renz, Lara; Volz, Conrad; Michanowicz, Drew; Ferrar, Kyle; Christian, Charles; Lenzner, Diana; El-Hefnawy, Talal

2013-05-01

Pollution from xenoestrogens has been discovered in the aquatic environment of the Greater Pittsburgh Area and is suspected to be caused by the failing sewer system. Personal care products and plasticizers have the potential to enter the water supply though treated and untreated sewage. Many of these compounds are suspected xenoestrogens. Paraben detection in surface waters was as follows: methyl paraben ranged between 2.2 to 17.3 ppt; ethyl paraben was not detectable; propyl paraben was detected at 9.2 and 12.0 ppt; butyl paraben was detected at 0.2 ppt. BPA was detected between 0.6 and 15.4 ppt. Estrogenic potential of extracts from fish brain tissue was tested via Bromodeoxyuridine MCF-7 analysis and paired with HPLC-MS to investigate the presence of xenoestrogens. All samples were non-detectable for parabens. BPA was detected in 44 of the 58 samples, with a range from non-detectable to 120 pg/g. BCFs were calculated. Results were statistically significant for location of capture (p < 0.05) and correlation existed between estrogenicity and BPA.

Early trends in the global tropospheric abundance of hydrochlorofluorocarbon-141b and 142b

NASA Astrophysics Data System (ADS)

Montzka, S. A.; Myers, R. C.; Butler, J. H.; Elkins, J. W.

1994-11-01

Hydrochlorofluorocarbons (HCFCs) are rapidly replacing chlorofluorocarbons (CFCs) as foam-blowing agents, solvents, and refrigerants. These substitutes, however, still contain chlorine and have the potential to deplete stratospheric ozone. Although the ozone destruction capacity of HCFCs is believed to be significantly less than that for CFCs, concern over unrestricted chlorine input to the atmosphere from HCFC use has prompted proposals for future limits on production. Here we report the first global time-series for mixing ratios of HCFC-141b (1,1-dichloro-1-fluoroethane) and HCFC-142b (1-chloro-1,1-difluoroethane) in air collected at seven remote sampling stations. Global mean mixing ratios in mid-1993 were 0.7 parts per 1012 (ppt) for HCFC-141b and 4.3 ppt for HCFC-142b. The global atmospheric abundance of HCFC-141b increased by 0.9 ppt, or a factor of ˜3, in 1993. Global abundance of HCFC-142b increased by 1.1 ppt yr-1 during 1992-1993. The results suggest that HCFCs are currently used extensively for replacing CFCs in selected applications. Furthermore, measured levels are significantly higher than expected based on available emission estimates and consumption predictions.

Effects of salinity on gastric emptying time in hybrid grouper, Epinephelus fuscoguttatus x E. lanceolattus juveniles

NASA Astrophysics Data System (ADS)

Noor, Noorashikin Md.; Das, Simon Kumar; Cob, Zaidi Che; Ghaffar, Mazlan Abd.

2018-04-01

The newly developed hybrid grouper: tiger grouper (Epinephelus fuscoguttatus) × giant grouper (Epinephelus fuscoguttatus) (TG×GG), has a high resistance towards different environmental condition (eg. in euryhaline environment) due to its genetic improvement. This study aims to investigate the effects of different salinities (10, 15, 20, 25 and 30 ppt) on the gastric emptying time (GET) of the TG×GG hybrid grouper juveniles. The fish were fed with commercial pellet over a 30 days experimental period under controlled laboratory conditions. The GET was determined by X-radiographic method, using barium sulfate (BaSO4) as an inert food marker. The X-radiography images showed that the shortest GET (12 h) was observed in the 15 ppt group, whereas the longest GET (18 h) in 30 ppt group. The results suggests to culture TG×GG hybrid grouper juveniles in 15 ppt with commercial pellet diet as this salinity proliferates faster digestion process which may contribute faster growth rate of this important fish species. Overall, these findings would be useful for the betterment of TG×GG hybrid grouper aquaculture which will eventually boost up the production of this newly developed hybrid grouper species.

Summertime Minimum Streamflow Elasticity to Antecendent Winter Precipitation, Peak Snow Water Equivalent and Summertime Evaporative Demand in the Western US Maritime Mountains

NASA Astrophysics Data System (ADS)

Schaperow, J.; Cooper, M. G.; Cooley, S. W.; Alam, S.; Smith, L. C.; Lettenmaier, D. P.

2017-12-01

As climate regimes shift, streamflows and our ability to predict them will change, as well. Elasticity of summer minimum streamflow is estimated for 138 unimpaired headwater river basins across the maritime western US mountains to better understand how climatologic variables and geologic characteristics interact to determine the response of summer low flows to winter precipitation (PPT), spring snow water equivalent (SWE), and summertime potential evapotranspiration (PET). Elasticities are calculated using log log linear regression, and linear reservoir storage coefficients are used to represent basin geology. Storage coefficients are estimated using baseflow recession analysis. On average, SWE, PET, and PPT explain about 1/3 of the summertime low flow variance. Snow-dominated basins with long timescales of baseflow recession are least sensitive to changes in SWE, PPT, and PET, while rainfall-dominated, faster draining basins are most sensitive. There are also implications for the predictability of summer low flows. The R2 between streamflow and SWE drops from 0.62 to 0.47 from snow-dominated to rain-dominated basins, while there is no corresponding increase in R2 between streamflow and PPT.

Unextendible product bases and extremal density matrices with positive partial transpose

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

Oyvind Sollid, Per; Magne Leinaas, Jon; Myrheim, Jan

2011-10-15

In bipartite quantum systems of dimension 3x3, entangled states that are positive under partial transposition (PPT) can be constructed with the use of unextendible product bases (UPBs). As discussed in a previous publication, all the lowest rank entangled PPT states of this system seem to be equivalent, under SL x SL transformations, to states that are constructed in this way. Here we consider a possible generalization of the UPB constuction to low-rank entangled PPT states in higher dimensions. The idea is to give up the condition of orthogonality of the product vectors, while keeping the relation between the density matrixmore » and the projection on the subspace defined by the UPB. We examine first this generalization for the 3x3 system where numerical studies indicate that one-parameter families of such generalized states can be found. Similar numerical searches in higher dimensional systems show the presence of extremal PPT states of similar form. Based on these results we suggest that the UPB construction of the lowest rank entangled states in the 3x3 system can be generalized to higher dimensions, with the use of nonorthogonal UPBs.« less

The effects of salinity and temperature shock on Kappaphycus alvarezii seaweed spores release

NASA Astrophysics Data System (ADS)

Harwinda, F. K.; Satyantini, W. H.; Masithah, E. W.

2018-04-01

One of the reproductive aspects of development step that is considered as the solution of this issue is seaweed sporulation technique through which is induced through salinity and temperature shock. This study aims to determine the effect of combination and interaction of salinity and temperature shock on the release of K. alvarezii spores in order to produce superior seeds. This research was conducted using Complete Randomized Design Factorial which consists of nine combinations of treatments and three replications. The used treatment in this study is the combination of different environmental factors such as salinity shock and temperature shock. The data were analyzed using ANOVA (Analysis of Variance) followed by Duncan Multiple Range Test. The results showed that salinity (31 ppt, 33 ppt, and 35 ppt) and temperature (30°C, 32°C, and 34°C). shock affected the osmoregulation system and the release of K. alvarezii spores. The salinity shock and temperature shock had interaction with K. alvarezii spore release on the sixth and seventh day with the best treatment at 32°C temperature and 31 ppt salinity and released 5413 cells/ml spores on the seventh day.

Aqueous phase synthesis, crystal structure and biological study of isoxazole extensions of pyrazole-4-carbaldehyde derivatives

NASA Astrophysics Data System (ADS)

Wazalwar, Sachin S.; Banpurkar, Anita R.; Perdih, Franc

2017-12-01

A series of novel isoxazol derivatives was synthesized by green route in aqueous phase at room temperature by the reaction of 3-methyl-4H-isoxazol-5-one with 3-(substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde by one-pot Knoevenagel condensation method using sodium benzoate as a catalyst. Compounds were characterized on the basis of IR, 1H NMR, mass spectroscopy and melting point determination. Crystal structures of five compounds were determined by X-ray diffraction. The compounds formed were screened for antibacterial and antifungal activity. Some compounds showed activity close to ampicillin against E. coli, S. aureus, and S. pyogenus. Two compounds showed antifungal activity against C. albicans close to standard greseofulvin.

One step N-glycosylation by filamentous fungi biofilm in bioreactor of a new phosphodiesterase-3 inhibitor tetrazole.

PubMed

de Melo Souza, Paula L; Arruda, Evilanna L; Pazini, Francine; Menegatti, Ricardo; Vaz, Boniek G; Lião, Luciano M; de Oliveira, Valéria

2016-07-01

An efficient and rapid process for N-glycosylation of 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole-LQFM 021 (1), a new synthetic derivative of pyrazole with phosphodiesterase-3 (PDE-3) inhibitory action, vasorelaxant activity and low toxicity catalyzed by filamentous fungi biofilm in bioreactor was successfully developed. A maximum N-glycosyl yield of 68% was obtained with Cunninghamella echinulata ATCC 9244 biofilm in bioreactor with conditions of 25mgml(-1) of 1 in PDSM medium at 28°C for 96h. After extraction with ethyl acetate, the derivative was identified by Ultrahigh Resolution Mass Spectrometry and (1)H-(13)C HSQC/HMBC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental and theoretical studies of a pyrazole-thiazolidin-2,4-di-one hybrid

NASA Astrophysics Data System (ADS)

Mushtaque, Md.; Avecilla, Fernando; Haque, Ashanul; Perwez, Ahmad; Khan, Md. Shahzad; Rizvi, M. Moshahid Alam

2017-08-01

The present work describes synthesis, characterization and biological evaluations of a hybrid compound 10 composed of two intriguing scaffolds pyrazole and thiazolidin-2,4-di-one. The title compound was obtained via multi-step reaction and characterized by a number of techniques (viz. IR, UV-Visible, 1H-NMR, 13C-NMR and MS) including X-ray crystallography. The structural and photophysical data of compound 10 were well supported by theoretical calculations performed at density functional (DFT) level. In-vitro anticancer studies on different human cancer cell lines indicated moderate to low activity of the compounds. The molecular target of the compound was predicted through in-silico studies. Finding of the studies are presented herein.

A highly sensitive and selective off-on fluorescent chemosensor for hydrazine based on coumarin β-diketone

NASA Astrophysics Data System (ADS)

Wu, Wei-Na; Wu, Hao; Wang, Yuan; Mao, Xian-Jie; Zhao, Xiao-Lei; Xu, Zhou-Qing; Fan, Yun-Chang; Xu, Zhi-Hong

2018-01-01

A coumarin-based sensor C1, namely 3-acetoacetylcoumarin was designed, synthesized and applied for hydrazine detection. Hydrazinolysis of the chemosensor gives a fluorescent coumarin-pyrazole product C1 - N2H4 [3-(3-methyl-1H-pyrazol-5-yl)coumarin], and thus resulting in a prominent fluorescence off-on response toward hydrazine under physiological conditions. The probe is highly selective toward hydrazine over cations, anions and other biologically/environmentally abundant analytes. The detection limit of the probe is 3.2 ppb. The sensing mechanism was supported by 1H NMR, IR, MS and DFT calculation. The application of the fluorescent probe in monitoring intracellular hydrazine in glioma cell line U251 was also demonstrated.

Enantiomeric-Enriched Ferrocenes: Synthesis, Chiral Resolution, and Mathematic Evaluation of CD-chiral Selector Energies with Ferrocene-Conjugates.

PubMed

Snegur, Lubov V; Borisov, Yurii A; Kuzmenko, Yuliya V; Davankov, Vadim A; Ilyin, Mikhail M; Ilyin, Mikhail M; Arhipov, Dmitry E; Korlyukov, Alexander A; Kiselev, Sergey S; Simenel, Alexander A

2017-08-25

Enantiomeric-enriched ferrocene-modified pyrazoles were synthesized via the reaction of the ferrocene alcohol, ( S )-FcCH(OH)CH₃ (Fc = ferrocenyl), with various pyrazoles in acidic conditions at room temperature within several minutes. X-ray structural data for racemic ( R , S )-1 N -(3,5-dimethyl pyrazolyl)ethyl ferrocene ( 1 ) and its ( S )-enantiomer ( S )- 1 were determined. A series of racemic pyrazolylalkyl ferrocenes was separated into enantiomers by analytical HPLC on β- and γ-cyclodextrins (CD) chiral stationary phases. The quantum chemical calculations of interaction energies of β-CD were carried out for both ( R )- and ( S )-enantiomers. A high correlation between experimental HPLC data and calculated interaction energies values was obtained.

BrO and Inferred Bry Profiles over the Western Pacific: Relevance of Inorganic Bromine Sources and a Bry Minimum in the Aged Tropical Tropopause Layer

NASA Technical Reports Server (NTRS)

Koenig, Theodore K.; Volkamer, Rainer; Baidar, Sunil; Dix, Barbara; Wang, Siyuan; Anderson, Daniel C.; Salawitch, Ross J.; Wales, Pamela A.; Cuevas, Carlos A.; Fernandez, Rafael P.;

Reverse right ventricular structural and extracellular matrix remodeling by estrogen in severe pulmonary hypertension

PubMed Central

Nadadur, Rangarajan D.; Umar, Soban; Wong, Gabriel; Eghbali, Mansour; Iorga, Andrea; Matori, Humann; Partow-Navid, Rod

2012-01-01

Chronic pulmonary hypertension (PH) leads to right-ventricular failure (RVF) characterized by RV remodeling. Ventricular remodeling is emerging as an important process during heart failure and recovery. Remodeling in RVF induced by PH is not fully understood. Recently we discovered that estrogen (E2) therapy can rescue severe preexisting PH. Here, we focused on whether E2 (42.5 μg·kg−1·day−1, 10 days) can reverse adverse RV structural and extracellular matrix (ECM) remodeling induced by PH using monocrotaline (MCT, 60 mg/kg). RV fibrosis was evident in RVF males. Intact females developed less severe RV remodeling compared with males and ovariectomized (OVX) females. Novel ECM-degrading disintegrin-metalloproteinases ADAM15 and ADAM17 transcripts were elevated ∼2-fold in all RVF animals. E2 therapy reversed RV remodeling in all groups. In vitro, E2 directly inhibited ANG II-induced expression of fibrosis markers as well as the metalloproteinases in cultured cardiac fibroblasts. Estrogen receptor-β agonist diarylpropionitrile (DPN) but not estrogen receptor-α agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) was as effective as E2 in inhibiting expression of these genes. Expression of ECM-interacting cardiac fetal-gene osteopontin (OPN) also increased ∼9-fold in RVF males. Intact females were partially protected from OPN upregulation (∼2-fold) but OVX females were not. E2 reversed OPN upregulation in all groups. Upregulation of OPN was also reversed in vitro by E2. Plasma OPN was elevated in RVF (∼1.5-fold) and decreased to control levels in the E2 group. RVF resulted in elevated Akt phosphorylation, but not ERK, in the RV, and E2 therapy restored Akt phosphorylation. In conclusion, E2 therapy reverses adverse RV remodeling associated with PH by reversing fibrosis and upregulation of novel ECM enzymes ADAM15, ADAM17, and OPN. These effects are likely mediated through estrogen receptor-β. PMID:22628376

Vision Integrating Strategies in Ophthalmology and Neurochemistry (VISION)

DTIC Science & Technology

2012-02-01

23, PPT and DPN (Table 1). The most potent of these compounds, ZYC-3, ZYC-26 and G1 are non- feminizing compared to the inactive compounds; PPT, an...induced cytotoxicity. Although these agents are estrogen analogs, they lack feminizing activity. • Discovered progressive quantitative changes in...Abstract #4619 Nixon ES, Simpkins JW. Neuroprotective effects of non- feminizing estrogen analogues in retinal neurons. 2011 Society for Neuroscience

Cross-Mode Comparability of Computer-Based Testing (CBT) versus Paper-Pencil Based Testing (PPT): An Investigation of Testing Administration Mode among Iranian Intermediate EFL Learners

ERIC Educational Resources Information Center

Khoshsima, Hooshang; Hosseini, Monirosadat; Toroujeni, Seyyed Morteza Hashemi

2017-01-01

Advent of technology has caused growing interest in using computers to convert conventional paper and pencil-based testing (Henceforth PPT) into Computer-based testing (Henceforth CBT) in the field of education during last decades. This constant promulgation of computers to reshape the conventional tests into computerized format permeated the…

Future Directions in Tactical Vertical Lift

DTIC Science & Technology

2010-04-29

The Aviation Science and Technology Challenge • OSD Future Vertical Lift • Transition to the Future AGENDA UNCLASSIFIED UNCLASSIFIED 4 Yourfilename.ppt...distributed, non-contiguous operations Joint Future Operational Environment The S&T Challenge Increased reliance on force projection by Aviation...UNCLASSIFIED UNCLASSIFIED 7 Yourfilename.ppt The S&T Challenge • “Army Aviation is the service’s most requested asset around the globe, ….. some units

WELLFOCUS PPT – modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial

PubMed Central

2014-01-01

Background The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. Methods/Design This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18–65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. Discussion This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. Trial registration Current Controlled Trials ISRCTN04199273 – WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013. PMID:24888479

Mechanistic experimental pain assessment in computer users with and without chronic musculoskeletal pain.

PubMed

Ge, Hong-You; Vangsgaard, Steffen; Omland, Øyvind; Madeleine, Pascal; Arendt-Nielsen, Lars

2014-12-06

Musculoskeletal pain from the upper extremity and shoulder region is commonly reported by computer users. However, the functional status of central pain mechanisms, i.e., central sensitization and conditioned pain modulation (CPM), has not been investigated in this population. The aim was to evaluate sensitization and CPM in computer users with and without chronic musculoskeletal pain. Pressure pain threshold (PPT) mapping in the neck-shoulder (15 points) and the elbow (12 points) was assessed together with PPT measurement at mid-point in the tibialis anterior (TA) muscle among 47 computer users with chronic pain in the upper extremity and/or neck-shoulder pain (pain group) and 17 pain-free computer users (control group). Induced pain intensities and profiles over time were recorded using a 0-10 cm electronic visual analogue scale (VAS) in response to different levels of pressure stimuli on the forearm with a new technique of dynamic pressure algometry. The efficiency of CPM was assessed using cuff-induced pain as conditioning pain stimulus and PPT at TA as test stimulus. The demographics, job seniority and number of working hours/week using a computer were similar between groups. The PPTs measured at all 15 points in the neck-shoulder region were not significantly different between groups. There were no significant differences between groups neither in PPTs nor pain intensity induced by dynamic pressure algometry. No significant difference in PPT was observed in TA between groups. During CPM, a significant increase in PPT at TA was observed in both groups (P < 0.05) without significant differences between groups. For the chronic pain group, higher clinical pain intensity, lower PPT values from the neck-shoulder and higher pain intensity evoked by the roller were all correlated with less efficient descending pain modulation (P < 0.05). This suggests that the excitability of the central pain system is normal in a large group of computer users with low pain intensity chronic upper extremity and/or neck-shoulder pain and that increased excitability of the pain system cannot explain the reported pain. However, computer users with higher pain intensity and lower PPTs were found to have decreased efficiency in descending pain modulation.

Adsorption of 1,2,3-Trichloropropane (TCP) to meet a MCL of 5 ppt.

PubMed

Babcock, Roger W; Harada, Bryce K; Lamichhane, Krishna M; Tsubota, Korey T

2018-02-01

1,2,3-Trichloropropane (TCP) is a groundwater contaminant in the drinking water aquifers in Hawaii and some other states. Granular activated carbon (GAC) has been used for 30 years to treat approximately 60 million gallons per day of TCP-contaminated groundwater in Hawaii. The State of Hawaii's current maximum contaminant level (MCL) for TCP is 600 ng/L (ppt), and consideration is being given to lower the MCL to 5 ppt. There is no EPA MCL for TCP. A study was conducted to determine if any GAC could meet a 5 ppt MCL for TCP, and if so, how many bedvolumes (BVs) could be treated prior to breakthrough. Constant Diffusivity-Rapid Small-Scale Column Tests (CD-RSSCTs) were performed to evaluate GAC adsorption of TCP. Three different groundwaters and six different GACs were utilized. The RSSCTs with the currently-utilized GAC were predictive of the performance of the GAC contactors (50,000 BVs to breakthrough). Any of the six GACs could meet a MCL of 5 ppt and some could do so for 150,000 or more BVs. No single GAC was optimal for all three well sites, indicating effects of subtle undefined differences in the water matrix and/or GAC physiochemical properties. The coal-based direct-activated carbon currently being used is the least optimal for all three well sites with respect to meeting a potential new TCP MCL of 5 ppt. The most effective GACs for Kunia were the Calgon coal-based GAC and the Siemens enhanced coconut shell GAC, while the most effective for Waipahu were the Siemens regular and enhanced coconut shell GACs, and the most effective for Mililani was the Calgon coal-based GAC. Choosing just one GAC for use at all three well sites (rather than the optimal for each site) would result in a reduction of treatment run time of 1 year at one well site (63% reduction). Copyright © 2017 Elsevier Ltd. All rights reserved.

WELLFOCUS PPT - modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial.

PubMed

Schrank, Beate; Riches, Simon; Coggins, Tony; Rashid, Tayyab; Tylee, Andre; Slade, Mike

2014-06-03

The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18-65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. Current Controlled Trials ISRCTN04199273 - WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013.

Salinity tolerance of non-native suckermouth armoured catfish (Loricariidae: Pterygoplichthys) in south-eastern Mexico: implications for invasion and dispersal

USGS Publications Warehouse

Capps, Krista A.; Nico, Leo G.; Mendoza-Carranza, Manuel; Arevalo-Frias, Wendi; Ropicki, Andrew J.; Heilpern, Sebastian A.; Rodiles-Hernandez, Rocio

2011-01-01

1. Salinity tolerance is one of several important physiological attributes that determine invasion success and the pattern of dispersal of introduced aquatic organisms. Introduced freshwater fishes able to tolerate elevated salinities have the potential to invade and exploit brackish-water (mixohaline) environments and use estuaries and coastal waters as 'bridges' for dispersing from one coastal river system to another. 2. Several members of the neotropical suckermouth armoured catfish genus Pterygoplichthys (Siluriformes: Loricariidae) have established non-native populations in inland waters of North and Central America, Asia and islands in the Caribbean, and Pacific and Indian oceans. Loricariids are generally considered to be strictly freshwater; but a few naturally occur in mesohaline habitats. 3.Catch and habitat data from 2004–2005 and 2009–2011 fish surveys in the Grijalva–Usumacinta River delta region (south-eastern Mexico) confirmed that introduced Pterygoplichthys populations established in upstream freshwater sites (where these catfish are abundant) have recently dispersed into downstream oligohaline and mesohaline estuarine habitats. During 2009–2011 surveys, these non-native catfish — tentatively identified as P. pardalis or its hybrids — were found in sites with salinities ranging from 1 to 8 ppt (mean 5.2 ppt). 4.Acute-salinity experiments were conducted with Pterygoplichthys (110–302 mm standard length, N=140) captured in the Grijalva–Usumacinta Basin to determine upper salinity tolerance levels. Tests demonstrated that individuals maintained in salinities of 0.2 ppt were able to survive abrupt (acute) exposure to salinities up to 10 ppt with little mortality over 10 days (240 h experimental endpoint). A few individuals survived abrupt exposure to 11 and 12 ppt for 20 or more hours, although none survived more than a few hours at 16 ppt or greater. 5.These field and experimental results provide quantitative evidence that non-native Pterygoplichthys are physiologically capable of surviving mesohaline conditions for extended periods and that non-native populations in Mexico are invading and presumably exploiting estuarine and other coastal environments, perhaps as feeding areas and potentially as dispersal routes.

Steroidal saponins from Tribulus terrestris.

PubMed

Kang, Li-Ping; Wu, Ke-Lei; Yu, He-Shui; Pang, Xu; Liu, Jie; Han, Li-Feng; Zhang, Jie; Zhao, Yang; Xiong, Cheng-Qi; Song, Xin-Bo; Liu, Chao; Cong, Yu-Wen; Ma, Bai-Ping

2014-11-01

Sixteen steroidal saponins, including seven previously unreported compounds, were isolated from Tribulus terrestris. The structures of the saponins were established using 1D and 2D NMR spectroscopy, mass spectrometry, and chemical methods. They were identified as: 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-2α,3β,22α,26-tetrol-12-one (terrestrinin C), 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-22α,26-diol-3,12-dione (terrestrinin D), 26-O-β-d-glucopyranosyl-(25S)-furost-4-en-22α,26-diol-3,6,12-trione (terrestrinin E), 26-O-β-d-glucopyranosyl-(25R)-5α-furostan-3β,22α,26-triol-12-one (terrestrinin F), 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-12β,22α,26-triol-3-one (terrestrinin G), 26-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(25R)-furost-4-en-22α,26-diol-3,12-dione (terrestrinin H), and 24-O-β-d-glucopyranosyl-(25S)-5α-spirostan-3β,24β-diol-12-one-3-O-β-d-glucopyranosyl-(1→4)-β-d-galactopyranoside (terrestrinin I). The isolated compounds were evaluated for their platelet aggregation activities. Three of the known saponins exhibited strong effects on the induction of platelet aggregation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Green engineering: Green composite material, biodiesel from waste coffee grounds, and polyurethane bio-foam

NASA Astrophysics Data System (ADS)

Cheng, Hsiang-Fu

In this thesis we developed several ways of producing green materials and energy resources. First, we developed a method to fabricate natural fibers composites, with the purpose to develop green textile/woven composites that could potentially serve as an alternative to materials derived from non-renewable sources. Flax and hemp fabrics were chosen because of their lightweight and exceptional mechanical properties. To make these textile/woven composites withstand moist environments, a commercially available marine resin was utilized as a matrix. The tensile, three-point bending, and edgewise compression strengths of these green textile/woven composites were measured using ASTM protocols. Secondly, we developed a chemical procedure to obtain oil from waste coffee grounds; we did leaching and liquid extractions to get liquid oil from the solid coffee. This coffee oil was used to produce bio-diesel that could be used as a substitute for petroleum-based diesel. Finally, polyurethane Bio-foam formation utilized glycerol that is the by-product from the biodiesel synthesis. A chemical synthesis procedure from the literature was used as the reference system: a triol and isocynate are mixed to produce polyurethane foam. Moreover, we use a similar triol, a by-product from bio-diesel synthesis, to reproduce polyurethane foam.

Sphingosines Derived from Marine Sponge as Potential Multi-Target Drug Related to Disorders in Cancer Development

PubMed Central

Biegelmeyer, Renata; Schröder, Rafael; Rambo, Douglas F.; Dresch, Roger R.; Carraro, João L. F.; Mothes, Beatriz; Moreira, José Cláudio F.; da Frota Junior, Mário L. C.; Henriques, Amélia T.

2015-01-01

Haliclona tubifera, marine sponge species abundant in Brazilian coastline, presents only a few papers published in the literature. Recently, we have reported the isolation of two modified C18 sphingoid bases: (2R,3R,6R,7Z)-2-aminooctadec-7-ene-1,3,6-triol and and (2R,3R,6R)-2-aminooctadec-1,3,6-triol. In order to continue our research, in this work aimed at the biological investigation of fractions that led to the isolation of these compounds. We evaluated the cytotoxic effect of marine sponge H. tubifera fractions in glioma (U87) and neuroblastoma (SH-SY5Y) human cell lines. In addition, considering the link between cancer, imbalance of reactive oxygen species and coagulation disorders, we also investigated the in vitro effects on blood coagulation and their redox properties. We showed that the ethyl acetate (EtOAc) fraction, rich in sphingoid bases, had important cytotoxic effects in both cancer cell lines with an IC50 < 15 μg/mL and also can inhibit the production of peroxyl radicals. Interestingly, this fraction increased the recalcification time of human blood, showing anticoagulant properties. The present study indicates the sphingosines fraction as a promising source of chemical prototypes, especially multifunctional drugs in cancer therapy. PMID:26308014

Partition of some key regulating services in terrestrial ecosystems: Meta-analysis and review.

PubMed

Viglizzo, E F; Jobbágy, E G; Ricard, M F; Paruelo, J M

2016-08-15

Our knowledge about the functional foundations of ecosystem service (ES) provision is still limited and more research is needed to elucidate key functional mechanisms. Using a simplified eco-hydrological scheme, in this work we analyzed how land-use decisions modify the partition of some essential regulatory ES by altering basic relationships between biomass stocks and water flows. A comprehensive meta-analysis and review was conducted based on global, regional and local data from peer-reviewed publications. We analyzed five datasets comprising 1348 studies and 3948 records on precipitation (PPT), aboveground biomass (AGB), AGB change, evapotranspiration (ET), water yield (WY), WY change, runoff (R) and infiltration (I). The conceptual framework was focused on ES that are associated with the ecological functions (e.g., intermediate ES) of ET, WY, R and I. ES included soil protection, carbon sequestration, local climate regulation, water-flow regulation and water recharge. To address the problem of data normality, the analysis included both parametric and non-parametric regression analysis. Results demonstrate that PPT is a first-order biophysical factor that controls ES release at the broader scales. At decreasing scales, ES are partitioned as result of PPT interactions with other biophysical and anthropogenic factors. At intermediate scales, land-use change interacts with PPT modifying ES partition as it the case of afforestation in dry regions, where ET and climate regulation may be enhanced at the expense of R and water-flow regulation. At smaller scales, site-specific conditions such as topography interact with PPT and AGB displaying different ES partition formats. The probable implications of future land-use and climate change on some key ES production and partition are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Convective Transport of Very-short-lived Bromocarbons to the Stratosphere

NASA Technical Reports Server (NTRS)

Liang, Qing; Atlas, Elliot Leonard; Blake, Donald Ray; Dorf, Marcel; Pfeilsticker, Klaus August; Schauffler, Sue Myhre

2014-01-01

We use the NASA GEOS Chemistry Climate Model (GEOSCCM) to quantify the contribution of two most important brominated very short-lived substances (VSLS), bromoform (CHBr3) and dibromomethane (CH2Br2), to stratospheric bromine and its sensitivity to convection strength. Model simulations suggest that the most active transport of VSLS from the marine boundary layer through the tropopause occurs over the tropical Indian Ocean, the Western Pacific warm pool, and off the Pacific coast of Mexico. Together, convective lofting of CHBr3 and CH2Br2 and their degradation products supplies 8 ppt total bromine to the base of the Tropical Tropopause Layer (TTL, 150 hPa), similar to the amount of VSLS organic bromine available in the marine boundary layer (7.8-8.4 ppt) in the above active convective lofting regions. Of the total 8 ppt VSLS-originated bromine that enters the base of TTL at 150 hPa, half is in the form of source gas injection (SGI) and half as product gas injection (PGI). Only a small portion (< 10%) the VSLS-originated bromine is removed via wet scavenging in the TTL before reaching the lower stratosphere. On global and annual average, CHBr3 and CH2Br2, together, contribute 7.7 pptv to the present-day inorganic bromine in the stratosphere. However, varying model deep convection strength between maximum and minimum convection conditions can introduce a 2.6 pptv uncertainty in the contribution of VSLS to inorganic bromine in the stratosphere (BryVSLS). Contrary to the conventional wisdom, minimum convection condition leads to a larger BryVSLS as the reduced scavenging in soluble product gases, thus a significant increase in PGI (2-3 ppt), greatly exceeds the relative minor decrease in SGI (a few 10ths ppt.

Influence of intramuscular granisetron on experimentally induced muscle pain by acidic saline.

PubMed

Louca, S; Ernberg, M; Christidis, N

2013-06-01

The aim of this study was to investigate whether intramuscular administration of the 5-HT(3) receptor antagonist granisetron reduces experimental muscle pain induced by repeated intramuscular injections of acidic saline into the masseter muscles. Twenty-eight healthy and pain-free volunteers, fourteen women and fourteen men participated in this randomized, double-blind and placebo-controlled study. After a screening examination and registration of the baseline pressure-pain threshold (PPT), the first simultaneous bilateral injections of 0·5 mL acidic saline (9 mg mL(-1) , pH 3·3) into the masseter muscles were performed. Two days later, PPT and pain (VAS) were re-assessed. The masseter muscle was then pre-treated with 0·5 mL granisetron (Kytril(®) 1 mg mL(-1) pH 5·3) on one side and control substance (isotonic saline, 9 mg mL(-1) pH 6) on the contralateral side. Two minutes thereafter a bilateral simultaneous injection of 0·5 mL acidic saline followed. The evoked pain intensity, pain duration, pain area and PPT were assessed. The volunteers returned 1 week later to re-assess VAS and PPT. On the side pre-treated with granisetron, the induced pain had significantly lower intensity and shorter duration (P < 0·05) compared with the side pre-treated with control. A subgroup analysis showed that the effect of granisetron on pain duration was significant only in women (P < 0·001), while the effect on peak pain and pain area were significant in both sexes. The results showed no significant change in PPT. In conclusion, these results indicate that granisetron has a pain-reducing effect on experimentally induced muscle pain by repeated acidic saline injection. © 2013 John Wiley & Sons Ltd.

The effect of culture on pain sensitivity.

PubMed

Al-Harthy, M; Ohrbach, R; Michelotti, A; List, T

2016-02-01

Cross-cultural differences in pain sensitivity have been identified in pain-free subjects as well as in chronic pain patients. The aim was to assess the impact of culture on psychophysical measures using mechanical and electrical stimuli in patients with temporomandibular disorder (TMD) pain and pain-free matched controls in three cultures. This case-control study compared 122 female cases of chronic TMD pain (39 Saudis, 41 Swedes and 42 Italians) with equal numbers of age- and gender-matched TMD-free controls. Pressure pain threshold (PPT) and tolerance (PPTo) were measured over one hand and two masticatory muscles. Electrical perception threshold and electrical pain threshold (EPT) and tolerance (EPTo) were recorded between the thumb and index fingers. Italian females reported significantly lower PPT in the masseter muscle than other cultures (P < 0.001) and in the temporalis muscle than Saudis (P = 0.003). Swedes reported significantly higher PPT in the thenar muscle than other cultures (P = 0.017). Italians reported significantly lower PPTo in all muscles than Swedes (P ≤ 0.006) and in the masseter muscle than Saudis (P < 0.001). Italians reported significantly lower EPTo than other cultures (P = 0.01). Temporomandibular disorder cases, compared to TMD-free controls, reported lower PPT and PPTo in all the three muscles (P < 0.001). This study found cultural differences between groups in the PPT, PPTo and EPTo. Overall, Italian females reported the highest sensitivity to both mechanical and electrical stimulation, while Swedes reported the lowest sensitivity. Mechanical pain thresholds differed more across cultures than did electrical pain thresholds. Cultural factors may influence response to type of pain test. © 2015 John Wiley & Sons Ltd.

Long-term tropospheric trend of octafluorocyclobutane (c-C4F8 or PFC-318)

NASA Astrophysics Data System (ADS)

Oram, D. E.; Mani, F. S.; Laube, J. C.; Newland, M. J.; Reeves, C. E.; Sturges, W. T.; Penkett, S. A.; Brenninkmeijer, C. A. M.; Röckmann, T.; Fraser, P. J.

2012-01-01

Air samples collected at Cape Grim, Tasmania between 1978 and 2008 and during a series of more recent aircraft sampling programmes have been analysed to determine the atmospheric abundance and trend of octafluorocyclobutane (c-C4F8 or PFC-318). c-C4F8 has an atmospheric lifetime in excess of 3000 yr and a global warming potential (GWP) of 10 300 (100 yr time horizon), making it one of the most potent greenhouse gases detected in the atmosphere to date. The abundance of c-C4F8 in the Southern Hemisphere has risen from 0.35 ppt in 1978 to 1.2 ppt in 2010, and is currently increasing at a rate of around 0.03 ppt yr-1. It is the third most abundant perfluorocarbon (PFC) in the present day atmosphere, behind CF4 (~75 ppt) and C2F6 (~4 ppt). Although a number of potential sources of c-C4F8 have been reported, including the electronics and semi-conductor industries, there remains a large discrepancy in the atmospheric budget. Using a 2-D global model to derive top-down global emissions based on the Cape Grim measurements yields a recent (2007) emission rate of around 1.1 Gg yr-1 and a cumulative emission up to and including 2007 of 38.1 Gg. Emissions reported on the EDGAR emissions database for the period 1986-2005 represent less than 1% of the top-down emissions for the same period, which suggests there is a large unaccounted for source of this compound. It is also apparent that the magnitude of this source has varied considerably over the past 30 yr, declining sharply in the late 1980s before increasing again in the mid-1990s.

Long-term tropospheric trend of octafluorocyclobutane (c-C4F8 or PFC-318)

NASA Astrophysics Data System (ADS)

Oram, D. E.; Mani, F. S.; Laube, J. C.; Newland, M. J.; Reeves, C. E.; Sturges, W. T.; Penkett, S. A.; Brenninkmeijer, C. A. M.; Röckmann, T.; Fraser, P. J.

2011-07-01

Air samples collected at Cape Grim, Tasmania between 1978 and 2008 and during a series of more recent aircraft sampling programmes have been analysed to determine the atmospheric abundance and trend of octafluorocyclobutane (-C4F8 or PFC-318). c-C4F8 has an atmospheric lifetime in excess of 3000 yr and a global warming potential (GWP) of 10 300 (100 yr time horizon), making it one of the most potent greenhouse gases detected in the atmosphere to date. The abundance of c-C4F8 in the Southern Hemisphere has risen from 0.35 ppt in 1978 to 1.2 ppt in 2010, and is currently increasing at a rate of around 0.03 ppt yr-1. It is the third most abundant perfluorocarbon (PFC) in the present day atmosphere, behind CF4 (~75 ppt) and C2F6 (~4 ppt). The origin of c-C4F8 is unclear. Using a 2-D global model to derive top-down global emissions based on the Cape Grim measurements yields a recent (2007) emission rate of around 1.1 Gg yr-1 and a cumulative emission up to and including 2007 of 38.1 Gg. Emissions reported on the EDGAR emissions database for the period 1986-2005 represent less than 1 % of the top-down emissions for the same period, which suggests there is a large unaccounted for source of this compound. It is also apparent that the magnitude of this source has varied considerably over the past 30 yr, declining sharply in the late 1980s before increasing again in the mid-1990s.

Association of Constitutive Hyperphosphorylation of Hsf1p with a Defective Ethanol Stress Response in Saccharomyces cerevisiae Sake Yeast Strains

PubMed Central

Noguchi, Chiemi; Watanabe, Daisuke; Zhou, Yan; Akao, Takeshi

2012-01-01

Modern sake yeast strains, which produce high concentrations of ethanol, are unexpectedly sensitive to environmental stress during sake brewing. To reveal the underlying mechanism, we investigated a well-characterized yeast stress response mediated by a heat shock element (HSE) and heat shock transcription factor Hsf1p in Saccharomyces cerevisiae sake yeast. The HSE-lacZ activity of sake yeast during sake fermentation and under acute ethanol stress was severely impaired compared to that of laboratory yeast. Moreover, the Hsf1p of modern sake yeast was highly and constitutively hyperphosphorylated, irrespective of the extracellular stress. Since HSF1 allele replacement did not significantly affect the HSE-mediated ethanol stress response or Hsf1p phosphorylation patterns in either sake or laboratory yeast, the regulatory machinery of Hsf1p is presumed to function differently between these types of yeast. To identify phosphatases whose loss affected the control of Hsf1p, we screened a series of phosphatase gene deletion mutants in a laboratory strain background. Among the 29 mutants, a Δppt1 mutant exhibited constitutive hyperphosphorylation of Hsf1p, similarly to the modern sake yeast strains, which lack the entire PPT1 gene locus. We confirmed that the expression of laboratory yeast-derived functional PPT1 recovered the HSE-mediated stress response of sake yeast. In addition, deletion of PPT1 in laboratory yeast resulted in enhanced fermentation ability. Taken together, these data demonstrate that hyperphosphorylation of Hsf1p caused by loss of the PPT1 gene at least partly accounts for the defective stress response and high ethanol productivity of modern sake yeast strains. PMID:22057870

Molecular characterization and transcriptional regulation of the renin-angiotensin system genes in Senegalese sole (Solea senegalensis Kaup, 1858): differential gene regulation by salinity.

PubMed

Armesto, Paula; Cousin, Xavier; Salas-Leiton, Emilio; Asensio, Esther; Manchado, Manuel; Infante, Carlos

2015-06-01

In this work, the complete cDNA sequence encoding angiotensinogen (agt) in the euryhaline flatfish Senegalese sole was obtained. Additionally, putative coding sequences belonging to other renin-angiotensin system (RAS) genes including renin (ren), angiotensin-converting enzyme (ace), angiotensin-converting enzyme 2 (ace2), as well as angiotensin II receptor type I (agtr1) and type II (agtr2), were also identified. In juvenile tissues, agt transcripts were mainly detected in liver, ren in kidney, ace and ace2 in intestine, agtr1 in kidney and brain, and agtr2 in liver and kidney. Expression analysis of the six RAS genes after a salinity shift revealed a clear increase of agt mRNA abundance in liver just after transferring soles to high salinity water (60 ppt) with a peak at 48 h. Moreover, gene expression analysis in gills showed transcriptional regulation of ace and agtr1 at 48 h and agtr2 at 96 h after transferring soles to 60 ppt. Incubation of larvae before mouth opening (until 3 days post hatch; dph) at low salinity (10 ppt) resulted in a coordinated transcriptional up-regulation of RAS genes. Nevertheless, no differences in mRNA abundance between salinities were observed when larvae were cultivated to low salinity after mouth opening. Whole-mount in situ hybridization (WISH) signal for agt and ace in 3 dph larvae incubated at 10 ppt and 35 ppt confirmed that the former gene was mainly expressed in liver whereas the later gene was mainly located in pharynx and posterior gut, without pronounced differences in intensity between salinities. Possible physiological significance of all these results is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Fall risk assessment among older adults with mild Alzheimer disease.

PubMed

Ryan, John J; McCloy, Constance; Rundquist, Peter; Srinivasan, Visalakshi; Laird, Rosemary

2011-01-01

Older adults with Alzheimer disease (AD) fall more than twice as often as those without dementia, yet few studies have assessed fall risk in this population. The purpose of the study was to determine whether a fall assessment, the Physical Performance Test 7-item (PPT 7-item), could accurately identify subjects with history of falls in a group of community-dwelling elders with mild AD. An additional purpose was to determine whether the PPT 7-item, a cognitive screen, and/or nonperformance data could predict falling in this population. Forty-three community-dwelling elders diagnosed with mild AD completed the fall risk assessment. In addition, the following data were collected: Mini-Mental State Examination (MMSE) score, age, gender, education, gait aid use, number of falls in the past 6 months, and history of fall-related injury. There was a significant difference in the PPT 7-item total score between subjects with history of falls and subjects without history of falls (z = -2.04, P = .042), with items related to turning (z = -2.56, P = .01) and walking (z = -2.89, P = .004) accounting for most of the difference. However, only gait aid usage predicted falling (45.8% of the variance). While the PPT 7-item was able to detect differences in mobility between subjects with history of falls and subjects without history of falls in subjects with mild AD, total PPT 7-item score did not predict falling. Gait aid usage was more strongly related to falling in these subjects. Early detection of fall risk in individuals with mild AD is important to prevent injuries and moderate costs of care.

The influence of cranio-cervical posture on maximal mouth opening and pressure pain threshold in patients with myofascial temporomandibular pain disorders.

PubMed

La Touche, Roy; París-Alemany, Alba; von Piekartz, Harry; Mannheimer, Jeffrey S; Fernández-Carnero, Josue; Rocabado, Mariano

2011-01-01

The aim of this study was to assess the influence of cranio-cervical posture on the maximal mouth opening (MMO) and pressure pain threshold (PPT) in patients with myofascial temporomandibular pain disorders. A total of 29 patients (19 females and 10 males) with myofascial temporomandibular pain disorders, aged 19 to 59 years participated in the study (mean years±SD; 34.69±10.83 y). MMO and the PPT (on the right side) of patients in neutral, retracted, and forward head postures were measured. A 1-way repeated measures analysis of variance followed by 3 pair-wise comparisons were used to determine differences. Comparisons indicated significant differences in PPT at 3 points within the trigeminal innervated musculature [masseter (M1 and M2) and anterior temporalis (T1)] among the 3 head postures [M1 (F=117.78; P<0.001), M2 (F=129.04; P<0.001), and T1 (F=195.44; P<0.001)]. There were also significant differences in MMO among the 3 head postures (F=208.06; P<0.001). The intrarater reliability on a given day-to-day basis was good with the interclass correlation coefficient ranging from 0.89 to 0.94 and 0.92 to 0.94 for PPT and MMO, respectively, among the different head postures. The results of this study shows that the experimental induction of different cranio-cervical postures influences the MMO and PPT values of the temporomandibular joint and muscles of mastication that receive motor and sensory innervation by the trigeminal nerve. Our results provide data that supports the biomechanical relationship between the cranio-cervical region and the dynamics of the temporomandibular joint, as well as trigeminal nociceptive processing in different cranio-cervical postures.

Sodium chloride inhibits the growth and infective capacity of the amphibian chytrid fungus and increases host survival rates.

PubMed

Stockwell, Michelle Pirrie; Clulow, John; Mahony, Michael Joseph

2012-01-01

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0-5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1-4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation.

Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

PubMed Central

Stockwell, Michelle Pirrie; Clulow, John; Mahony, Michael Joseph

2012-01-01

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation. PMID:22590639

Association of constitutive hyperphosphorylation of Hsf1p with a defective ethanol stress response in Saccharomyces cerevisiae sake yeast strains.

PubMed

Noguchi, Chiemi; Watanabe, Daisuke; Zhou, Yan; Akao, Takeshi; Shimoi, Hitoshi

2012-01-01

Modern sake yeast strains, which produce high concentrations of ethanol, are unexpectedly sensitive to environmental stress during sake brewing. To reveal the underlying mechanism, we investigated a well-characterized yeast stress response mediated by a heat shock element (HSE) and heat shock transcription factor Hsf1p in Saccharomyces cerevisiae sake yeast. The HSE-lacZ activity of sake yeast during sake fermentation and under acute ethanol stress was severely impaired compared to that of laboratory yeast. Moreover, the Hsf1p of modern sake yeast was highly and constitutively hyperphosphorylated, irrespective of the extracellular stress. Since HSF1 allele replacement did not significantly affect the HSE-mediated ethanol stress response or Hsf1p phosphorylation patterns in either sake or laboratory yeast, the regulatory machinery of Hsf1p is presumed to function differently between these types of yeast. To identify phosphatases whose loss affected the control of Hsf1p, we screened a series of phosphatase gene deletion mutants in a laboratory strain background. Among the 29 mutants, a Δppt1 mutant exhibited constitutive hyperphosphorylation of Hsf1p, similarly to the modern sake yeast strains, which lack the entire PPT1 gene locus. We confirmed that the expression of laboratory yeast-derived functional PPT1 recovered the HSE-mediated stress response of sake yeast. In addition, deletion of PPT1 in laboratory yeast resulted in enhanced fermentation ability. Taken together, these data demonstrate that hyperphosphorylation of Hsf1p caused by loss of the PPT1 gene at least partly accounts for the defective stress response and high ethanol productivity of modern sake yeast strains.

Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAF(V600E) inhibitors.

PubMed

Dong, Jing-Jun; Li, Qing-Shan; Wang, Shu-Fu; Li, Cui-Yun; Zhao, Xin; Qiu, Han-Yue; Zhao, Meng-Yue; Zhu, Hai-Liang

2013-10-07

The RAF-MEK-ERK cascade appears to be intimately involved in the regulation of cell cycle progression and apoptosis. The BRAF(V600E) mutant results in constitutive activation of the ERK pathway, which can lead to cellular growth dysregulation. A series of 5-phenyl-1H-pyrazol derivatives (3a-5e) have been designed and synthesized, and their biological activities were evaluated as potential BRAF(V600E) inhibitors. All the compounds were reported for the first time except 3e, and compound 1-(4-bromo-2-hydroxybenzyl)-3-phenyl-1-(5-phenyl-1H-pyrazol-3-yl)urea (5c) displayed the most potent inhibitory activity (BRAF(V600E) IC50 = 0.19 μM). Antiproliferative assay results indicated that compound 5c possessed high antiproliferative activity against cell lines WM266.4 and A375 in vitro, with IC50 values of 1.50 and 1.32 μM, respectively, which were comparable with the positive control vemurafenib. Docking simulations showed that compound 5c binds tightly to the BRAF(V600E) active site and acts as BRAF(V600E) inhibitor. A 3D-QSAR model was also built to provide more pharmacophore understanding towards designing new agents with more potent BRAF(V600E) inhibitory activity.

Determination of pyrazole and pyrrole pesticides in environmental water samples by solid-phase extraction using multi-walled carbon nanotubes as adsorbent coupled with high-performance liquid chromatography.

PubMed

Ma, Jiping; Lu, Xi; Xia, Yan; Yan, Fengli

2015-02-01

A solid-phase extraction (SPE) method using multi-walled carbon nanotubes as adsorbent coupled with high-performance liquid chromatography was developed for the determination of four pyrazole and pyrrole pesticides (fenpyroximate, chlorfenapyr, fipronil and flusilazole) in environmental water samples. Several parameters, such as extraction adsorbent, elution solvent and volume and sample loading flow rate were optimized to obtain high SPE recoveries and extraction efficiency. The calibration curves for the pesticides extracted were linear in the range of 0.05-10 μg L(-1) for chlorfenapyr and fenpyroximate and 0.05-20 μg L(-1) for fipronil and flusilazole, with the correlation coefficients (r(2)) between 0.9966 and 0.9990. The method gave good precisions (relative standard deviation %) from 2.9 to 10.1% for real spiked samples from reservoir water and seawater; method recoveries ranged 92.2-105.9 and 98.5-103.9% for real spiked samples from reservoir water and seawater, respectively. Limits of detection (S/N = 3) for the method were determined to be 8-19 ng L(-1). The optimized method was successfully applied to the determination of four pesticides of pyrazoles and pyrroles in real environmental water samples. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Novel fragment-based QSAR modeling and combinatorial design of pyrazole-derived CRK3 inhibitors as potent antileishmanials.

PubMed

Goyal, Sukriti; Dhanjal, Jaspreet K; Tyagi, Chetna; Goyal, Manisha; Grover, Abhinav

2014-07-01

The CRK3 cyclin-dependent kinase of Leishmania plays an important role in regulating the cell-cycle progression at the G2/M phase checkpoint transition, proliferation, and viability inside the host macrophage. In this study, a novel fragment-based QSAR model has been developed using 22 pyrazole-derived compounds exhibiting inhibitory activity against Leishmanial CRK3. Unlike other QSAR methods, this fragment-based method gives flexibility to study the relationship between molecular fragments of interest and their contribution for the variation in the biological response by evaluating cross-term fragment descriptors. Based on the fragment-based QSAR model, a combinatorial library was generated, and top two compounds were reported after predicting their activity. The QSAR model showed satisfactory statistical parameters for the data set (r(2) = 0.8752, q(2) = 0.6690, F-ratio = 30.37, and pred_r(2) = 0.8632) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution at R1 position improves the inhibitory activity, while decline in inhibitory activity was observed in presence of nitrogen at R2 position. The analysis carried out in this study provides a substantial basis for consideration of the designed pyrazole-based leads as potent antileishmanial drugs. © 2014 John Wiley & Sons A/S.

One-pot synthesis, biological evaluation, and docking study of new chromeno-annulated thiopyrano[2,3-c]pyrazoles.

PubMed

Parmar, Bhagyashri D; Sutariya, Tushar R; Brahmbhatt, Gaurangkumar C; Parmar, Narsidas J; Kant, Rajni; Gupta, Vivek K; Murumkar, Prashant R; Sharma, Mayank Kumar; Yadav, Mange Ram

2016-08-01

A one-pot synthesis of new chromeno-annulated thiopyrano[2,3-c]pyrazoles has been achieved through a domino-Knoevenagel-hetero-Diels-Alder reaction after combining various pyrazol-5-thiones with O-alkenyloxy/alkynyloxy-salicylaldehydes/naphthaldehydes in a Brønsted acidic ionic liquid, [Hmim]HSO[Formula: see text], methylimidazolium hydrogen sulphate, under microwave irradiation. The method is simple and in many cases the isolated products did not require further purification. The central pyranothiopyranyl cis-fusion was confirmed by 2D NMR NOESY and single-crystal X-ray analysis suggesting that the endo-E-Syn transition state would be the most favored pathway of the reaction. Many heterocycles of this new series were found active against six bacterial and two fungal strains. In addition, all the compounds possess good anti-oxidant activity with the ferric reducing anti-oxidant power value [Formula: see text]. All new structures were docked into active site of angiotensin I converting enzyme (ACE), assuming that the compounds possessed the anti-hypertensive activity potential on the basis of prediction of activity spectra of substances prediction results. Pyranyl ring oxygen in compound 9a forms two hydrogen bonds with HIS353 and HIS513 residues in the active site of the ACE having good G score ([Formula: see text]) of this compound, comparable to that of the reference drug captopril ([Formula: see text]).

Polarization IR spectra of hydrogen bonded pyrazole crystals: self-organization effects in proton and deuteron mixture systems. Long-range H/D isotopic effects

NASA Astrophysics Data System (ADS)

Flakus, Henryk T.; Machelska, Aleksandra

2002-02-01

This paper deals with experimental studies of the polarization IR spectra of solid-state pyrazole H1345, as well as of its H1D345, D1H345 and D1345 deuterium derivatives. Spectra were measured for the νNH and νND band frequency ranges at temperatures of 298 and 77 K. The spectra were found to strongly change their intensity distribution and their polarization properties with the decrease of temperature. These effects were ascribed to some temperature-induced conformational changes in the hydrogen bond lattices. The studies reported allowed the finding of new kind of isotopic effects H/D in the open-chain hydrogen bond systems, i.e. the self-organization effects. It was found that the spectrally active aggregates of hydrogen bonds remain unchanged despite the growing isotope H/D exchange rate. This statement was supported by analysis of the residual polarized νNH and νND band properties, measured for the isotopically diluted crystalline samples. Analysis of the band shapes of the four hydrogen isotope derivative crystals proved the existence of another kind of H/D isotopic effect, i.e. the long-range isotopic effect. It depends on an influence of the pyrazole ring hydrogen atoms onto the νNH and νND band widths and onto the band fine structures.

Estuarine River Data for the Ten Thousand Islands Area, Florida, Water Year 2005

USGS Publications Warehouse

Byrne, Michael J.; Patino, Eduardo

2008-01-01

The U.S. Geological Survey collected stream discharge, stage, salinity, and water-temperature data near the mouths of 11 tributaries flowing into the Ten Thousand Islands area of Florida from October 2004 to June 2005. Maximum positive discharge from Barron River and Faka Union River was 6,000 and 3,200 ft3/s, respectively; no other tributary exceeded 2,600 ft3/s. Salinity variation was greatest at Barron River and Faka Union River, ranging from 2 to 37 ppt, and from 3 to 34 ppt, respectively. Salinity maximums were greatest at Wood River and Little Wood River, each exceeding 40 ppt. All data were collected prior to the commencement of the Picayune Strand Restoration Project, which is designed to establish a more natural flow regime to the tributaries of the Ten Thousand Islands area.

Association of serum total antioxidant capacity and total oxidant status with pain perception in patients with myofacial pain dysfunction.

PubMed

Etoz, Osman A; Ataoglu, Hanife; Erel, Ozcan; Celik, Hakim; Herken, Emine Nur; Bayazit, Yildirim Ahmet

2009-01-01

We aimed to find out the association of total antioxidant capacity (TAC) and total oxidant status (TOS) with generalized pressure pain thresholds (PPT) of patients with myofacial pain dysfunction (MPD). PPT scores of patients with MPD (n = 37) and healthy individuals (n = 43) were measured on the hypothenar region of the hand using a mechanical algometer. Serum samples were collected and TAC and TOS were measured by novel methods. The TAC of patients was significantly lower than that of the control subjects. The difference between the TOS measurements of patients and control subjects was not significant. The PPT scores of the patients were significantly lower than that of control subjects. There may be an association between serum antioxidant capacity and MPD. Low serum TAC might also be related with pain perception.

Site condition, structure, and growth of baldcypress along tidal/non-tidal salinity gradients

USGS Publications Warehouse

Krauss, K.W.; Duberstein, J.A.; Doyle, T.W.; Conner, W.H.; Day, Richard H.; Inabinette, L.W.; Whitbeck, J.L.

2009-01-01

This report documents changes in forest structure and growth potential of dominant trees in salt-impacted tidal and non-tidal baldcypress wetlands of the southeastern United States. We inventoried basal area and tree height, and monitored incremental growth (in basal area) of codominant baldcypress (Taxodium distichum) trees monthly, for over four years, to examine the inter-relationships among growth, site fertility, and soil physico-chemical characteristics. We found that salinity, soil total nitrogen (TN), flood duration, and flood frequency affected forest structure and growth the greatest. While mean annual site salinity ranged from 0.1 to 3.4 ppt, sites with salinity concentrations of 1.3 ppt or greater supported a basal area of less than 40 m2/ha. Where salinity was < 0.7 ppt, basal area was as high as 87 m2/ha. Stand height was also negatively affected by higher salinity. However, salinity related only to soil TN concentrations or to the relative balance between soil TN and total phosphorus (TP), which reached a maximum concentration between 1.2 and 2.0 ppt salinity. As estuarine influence shifts inland with sea-level rise, forest growth may become more strongly linked to salinity, not only due to salt effects but also as a consequence of site nitrogen imbalance.

The influence of Positional Release Therapy on the myofascial trigger points of the upper trapezius muscle in computer users.

PubMed

Mohammadi Kojidi, M; Okhovatian, F; Rahimi, A; Baghban, A A; Azimi, H

2016-10-01

The purpose of the present study was to investigate the effect of Positional Release Therapy (PRT) in computer users via latent trigger points (LTrPs) of the upper trapezius muscle. Twenty-eight women with the upper trapezius MTrPs participated in this study. Subjects were randomly classified into two groups (14 in each group): the subjects in the Group 1 received PRT in shortened position while those in the group 2 received sham control in the neutral position of the upper trapezius muscle. They received three therapy sessions every other day for one week. The local pain intensity and Pressure pain threshold (PPT) were measured via Visual Analogue Scale (VAS) and algometry, respectively, before interventions and repeated 5 min after the first and third treatment sessions in each group. One-way ANOVA was used for data analysis. After treatment, between groups comparison revealed that for PPT and VAS, there were significant differences between the two groups (VAS and PPT; P < 0.05). Both groups (PRT and sham control) showed alleviation of pain and increase in PPT during three sessions of therapy although PRT showed to be more effective in these patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Infant positioning in daily life may mediate associations between physiotherapy and child development-video-analysis of an early intervention RCT.

PubMed

Dirks, Tineke; Hielkema, Tjitske; Hamer, Elisa G; Reinders-Messelink, Heleen A; Hadders-Algra, Mijna

2016-01-01

Paediatric physiotherapy (PPT) in high-risk infants comprises family involvement, but it is unclear whether parents mediate the intervention effect. We demonstrated in a randomized controlled trial in high-risk infants comparing the family centred programme Coping and Caring for infants with special needs (COPCA) and Traditional Infant Physiotherapy (TIP) that process evaluation revealed associations between COPCA-characteristics and outcome. To assess whether PPT affects how parents position their infant during bathing and whether this is associated with child outcome. 21 infants received COPCA and 25 TIP between 3 and 6 months corrected age. Bathing sessions were videotaped at 3, 6 and 18 months. Time spent with specific infant positions was correlated with quantified PPT-actions and functional mobility at 18 months measured with the Paediatric Evaluation of Disability Inventory (PEDI). At 3 and 18 months bathing position was similar in both groups, but differed at 6 months (time spent on sitting: COPCA 77.7%, TIP 39.2%; median difference 32.0% (95% CI: 10.6-50.5%). Sitting-time at 6 months was associated with higher PEDI functional mobility scores. Early PPT may affect parental behaviour, such as infant positioning during bathing, which, in turn, may affect child development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early trends in the global tropospheric abundance of hydrochlorofluorocarbon-141b and 142b

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

Montzka, S.A.; Myers, R.C.; Butler, J.H.

1994-11-15

Hydrochlorofluorocarbons (HCFCs) are rapidly replacing chlorofluorocarbons (CFCs) as foam-blowing agents, solvents, and refrigerants. These substitutes, however, still contain chlorine and have the potential to deplete stratospheric ozone. Although the ozone destruction capacity of HCFCs is believed to be significantly less than that for CFCs, concern over unrestricted chlorine input to the atmosphere from HCFC use has prompted proposals for future limits on production. The authors report the first global time-series for mixing ratios of HCFC-141b (1,1-dichloro-1-fluoroethane) and HCFC-142b (1-chloro-1,1-difluoroethane) in air collected at seven remote sampling stations. Global mean mixing ratios in mid-1993 were 0.7 parts per 10{sup 12} (ppt)more » for HCFC-141b and 4.3 ppt for HCFC-142b. The global atmospheric abundance of HCFC-141b increased by 0.9 ppt, or a factor of {approximately} 3, in 1993. Global abundance of HCFC-142b increased by 1.1 ppt yr{sup {minus}1} during 1992-1993. The results suggest that HCFCs are currently used extensively for replacing CFCs in selected applications. Furthermore, measured levels are significantly higher than expected based on available emission estimates and consumption predictions. 24 refs., 4 figs.« less

Analysis of N-Nitrosodimethylamine and N-Nitrodimethylamine in Groundwater

NASA Technical Reports Server (NTRS)

Greene, Ben; Mast, Dion; Baker, David L.

2006-01-01

A method for the analytical determination of N-nitrosodimethylamine (NDMA) and N-nitrodimethylamine (DMN) at parts-per-trillion (ppt) concentrations in groundwater is reported. The method uses a solid phase extraction (SPE) cartridge containing 2 g of activated coconut charcoal to extract a 500-mL water sample. NDMA and DMN are eluted from the SPE cartridge using acetone. The acetone is concentrated and brought to a final volume of 1.0 mL, which results in a theoretical 500-fold concentration of the analytes. The extracts are analyzed by gas chromatography (GC) with a nitrogenphosphorous detector (NPD), which is a highly sensitive and relatively inexpensive technique. The measured extraction efficiencies averaged 61 percent for NDMA and 74 percent for DMN. Extraction efficiencies were independent of NDMA and DMN concentrations from 40 to 2000 ppt. Several samples could be extracted then analyzed in a single day with the use of an extraction manifold and GC autosampler. A reporting limit of 10 ppt for NDMA and DMN was achieved. The MDLs for NDMA and DMN were 6.4 and 5.8 ppt, respectively. A typical turn-around time from beginning of extraction to reporting was 4 h. The method avoids the use of halogenated solvents, such as dichloromethane, and subsequent solvent exchange procedures necessary for use of the NPD detector.

Low-temperature chemotaxis, halotaxis and chemohalotaxis by the psychrophilic marine bacterium Colwellia psychrerythraea 34H.

PubMed

Showalter, G M; Deming, J W

2018-02-01

A variety of ecologically important processes are driven by bacterial motility and taxis, yet these basic bacterial behaviours remain understudied in cold habitats. Here, we present a series of experiments designed to test the chemotactic ability of the model marine psychrophilic bacterium Colwellia psychrerythraea 34H, when grown at optimal temperature and salinity (8°C, 35 ppt) or its original isolation conditions (-1°C, 35 ppt), towards serine and mannose at temperatures from -8°C to 27°C (above its upper growth temperature of 18°C), and at salinities of 15, 35 and 55 ppt (at 8°C and -1°C). Results indicate that C. psychrerythraea 34H is capable of chemotaxis at all temperatures tested, with strongest chemotaxis at the temperature at which it was first grown, whether 8°C or -1°C. This model marine psychrophile also showed significant halotaxis towards 15 and 55 ppt solutions, as well as strong substrate-specific chemohalotaxis. We suggest that such patterns of taxis may enable bacteria to colonize sea ice, position themselves optimally within its extremely cold, hypersaline and temporally fluctuating microenvironments, and respond to various chemical signals therein. © 2017 The Authors. Environmental Microbiology published by Society for Applied Microbiology and JohnWiley & Sons Ltd.

Factors Associated with Performance-based Physical Function of Older Veterans of the PLAAF: A Pilot Study

PubMed Central

Chen, Da-Wei; Jin, Yan-Bin; Liu, Wei; Du, Wen-Jin; Li, Hua-Jun; Chen, Jin-Wen; Xu, Wei

2014-01-01

[Purpose] This study investigated the factors associated with performance-based physical function of older veterans of the People’s Liberation Army Air Force of China (PLAAF). [Subjects and Methods] A cross-sectional survey of 146 older veterans of the PLAAF was carried out. Their physical function was measured using the Chinese Mini-Physical Performance Testing (CM-PPT). The demographics and health status (including physical measures, blood chemical tests, chronic diseases, and number of morbidities) were collected from health examination reports and computer records of case history. Cognition was measured using the Mini-Mental Status Examination (MMSE). [Results] In multiple linear regressions, age, MMSE, Parkinsonism, and chronic obstructive pulmonary disease were independently associated with CM-PPT, while previous stroke and albumin level reached borderline statistical significance. The association between the number of morbidities and CM-PPT was significant after adjustment for MMSE and demographics. The CM-PPT of low (0 or 1), medium (2 to 4) and high count (5 or more) morbidities were 11.3±3.9, 10.2±4.1, 6.1±3.8 respectively, and the difference among these three groups was significant. [Conclusion] Some modified conditions and the number of chronic diseases might be associated with the physical function of older veterans of the PLAAF. PMID:24648625

Central administration of a 5-HT2 receptor agonist and antagonist: lack of effect on rapid eye movement sleep and pgo waves.

PubMed

Sanford, L D; Hunt, W K; Ross, R J; Pack, A I; Morrison, A R

1998-01-01

Serotonin (5-HT) has a role in regulating behavioral state and controlling the production of ponto-geniculo-occipital (PGO) waves, though the exact mechanism of action is not known. The most prevailing explanation is that 5-HT exerts its influence on behavioral state and PGO waves by inhibiting and disinhibiting cholinergic cells in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT), which have been implicated in their generation. Recent work in rats has demonstrated 5-HT2 receptors on most cholinergic cells in PPT/LDT. We microinfused the relatively specific 5-HT2 agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane), the relatively specific 5-HT2 antagonist, ketanserin, and the nonspecific 5-HT antagonist, methysergide, locally into the peribrachial region of PPT in cats and monitored behavioral state and PGO waves. Neither drug significantly affected behavioral state or PGO wave activity. These results suggest that 5-HT2 receptors associated with cholinergic cells are minimally involved in the control of behavioral state and, together with the recent findings of others, suggest that 5-HT may not modulate PGO wave generation via direct action on cholinergic neurons in PPT/LDT, a departure from the long-held but minimally-tested view.

Efficient synthesis and biological evaluation of new benzopyran-annulated pyrano[2,3-c]pyrazole derivatives.

PubMed

Labana, Balvantsingh M; Brahmbhatt, Gaurangkumar C; Sutariya, Tushar R; Parmar, Narsidas J; Padrón, José M; Kant, Rajni; Gupta, Vivek K

2017-05-01

A one-pot method has been described to synthesize benzopyran-annulated pyrano[2,3-c]pyrazoles, effectively by combining O-alkenyloxy/alkynyloxy-acetophenones with various pyrazolones in triethylammonium acetate (TEAA) under microwave irradiation. While combination of O-allyloxy- or O-prenyloxy-acetophenones with pyrazolones occurred efficiently, that of O-propargyloxy-acetophenones was found effective in the presence of ZnO catalyst, via a domino Knoevenagel-hetero-Diels-Alder (DKHDA) reaction. Aminobenzopyran frameworks were also synthesized, after nitro-containing products were reduced in tandem with iron(II) in an acidic medium. The in vitro antiproliferative activity of these compounds was measured and discussed against gram-positive, gram-negative and M. tuberculosis bacteria, fungi, and various representative human solid tumor cell lines, in addition to their ferric reducing antioxidant capability.

Synthesis, characterization and cholinesterase enzymes inhibitory activity of 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone

NASA Astrophysics Data System (ADS)

Mehdi, Sayed Hasan; Ghalib, Raza Murad; Hashim, Rokiah; da Silva, M. Fátima C. Guedes; Sulaiman, Othman; Murugaiyah, Vikneswaran; Marimuthu, Mani Maran; Naqvi, Mehnaz

2013-10-01

The crystal structure of the title compound, 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone has been determined by single crystal X-ray diffraction. It crystallizes in the orthorhombic space group P212121. The FTIR as well as the 1H and 13C NMR spectra of the compound were also recorded and briefly discussed. Compound 1 demonstrated good inhibitory activity against butyrylcholinesterase (BChE; IC50 = 46.42 μM) comparable to physostigmine. However it showed moderate inhibitory activity against acetylcholinesterase (AChE; IC50 = 157.31 μM). It showed moderate inhibitory activity against acetylcholinesterase and selective inhibitory activity towards butyrylcholinesterase enzyme.

Dimethyl 4-[3-(4-meth­oxy­phen­yl)-1-phenyl-1H-pyrazol-4-yl]-2,6-dimethyl-1,4-dihydro­pyridine-3,5-dicarboxyl­ate dihydrate

PubMed Central

Fun, Hoong-Kun; Ooi, Chin Wei; Garudachari, B.; Shivananda, Kammasandra Nanjunda; Isloor, Arun M.

2012-01-01

In the title compound, C27H27N3O5·2H2O, the dihydro­pyridine ring adopts a flattened boat conformation. The central pyrazole ring is essentially planar [maximum deviation of 0.003 (1) Å] and makes dihedral angles of 50.42 (6) and 26.44 (6)° with the benzene rings. In the crystal, mol­ecules are linked via N—H⋯O, O—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds into two-dimensional networks parallel to the bc plane. The crystal structure is further consolidated by weak C—H⋯π inter­actions. PMID:22798871

Synthesis, characterisation, and in vitro anticancer activity of curcumin analogues bearing pyrazole/pyrimidine ring targeting EGFR tyrosine kinase.

PubMed

Ahsan, Mohamed Jawed; Khalilullah, Habibullah; Yasmin, Sabina; Jadav, Surender Singh; Govindasamy, Jeyabalan

2013-01-01

In search of potential therapeutics for cancer, we described herein the synthesis, characterization, and in vitro anticancer activity of a novel series of curcumin analogues. The anticancer effects were evaluated on a panel of 60 cell lines, according to the National Cancer Institute (NCI) screening protocol. There were 10 tested compounds among 14 synthesized compounds, which showed potent anticancer activity in both one-dose and 5-dose assays. The most active compound of the series was 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-yl(phenyl)methanone which showed mean growth percent of -28.71 in one-dose assay and GI₅₀ values between 0.0079 and 1.86 µM in 5-dose assay.

The Performance-Perceptual Test (PPT) and its relationship to aided reported handicap and hearing aid satisfaction.

PubMed

Saunders, Gabrielle H; Forsline, Anna

2006-06-01

Results of objective clinical tests (e.g., measures of speech understanding in noise) often conflict with subjective reports of hearing aid benefit and satisfaction. The Performance-Perceptual Test (PPT) is an outcome measure in which objective and subjective evaluations are made by using the same test materials, testing format, and unit of measurement (signal-to-noise ratio, S/N), permitting a direct comparison between measured and perceived ability to hear. Two variables are measured: a Performance Speech Reception Threshold in Noise (SRTN) for 50% correct performance and a Perceptual SRTN, which is the S/N at which listeners perceive that they can understand the speech material. A third variable is computed: the Performance-Perceptual Discrepancy (PPDIS); it is the difference between the Performance and Perceptual SRTNs and measures the extent to which listeners "misjudge" their hearing ability. Saunders et al. in 2004 examined the relation between PPT scores and unaided hearing handicap. In this publication, the relations between the PPT, residual aided handicap, and hearing aid satisfaction are described. Ninety-four individuals between the ages of 47 and 86 yr participated. All had symmetrical sensorineural hearing loss and had worn binaural hearing aids for at least 6 wk before participating. All subjects underwent routine audiological examination and completed the PPT, the Hearing Handicap Inventory for the Elderly/Adults (HHIE/A), and the Satisfaction for Amplification in Daily Life questionnaire. Sixty-five subjects attended one research visit for participation in this study, and 29 attended a second visit to complete the PPT a second time. Performance and Perceptual SRTN and PPDIS scores were normally distributed and showed excellent test-retest reliability. Aided SRTNs were significantly better than unaided SRTNs; aided and unaided PPDIS values did not differ. Stepwise multiple linear regression showed that the PPDIS, the Performance SRTN, and age were significant predictors of scores on the HHIE/A such that greater reported handicap is associated with underestimating hearing ability, poorer aided ability to understand speech in noise, and being younger. Scores on the Satisfaction with Amplification in Daily Life were not well explained by the PPT, age, or audiometric thresholds. When individuals were grouped by their HHIE/A scores, it was seen that individuals who report more handicap than expected based on their audiometric thresholds, have a more negative PPDIS, i.e., underestimate their hearing ability, relative to individuals who report expected handicap, who in turn have a more negative PPDIS than individuals who report less handicap than expected. No such patterns were apparent for the Performance SRTN. The study showed the PPT to be a reliable outcome measure that can provide more information than a performance measure and/or a questionnaire measure alone, in that the PPDIS can provide the clinician with an explanation for discrepant objective and subjective reports of hearing difficulties. The finding that self-reported handicap is affected independently by both actual ability to hear and the (mis)perception of ability to hear underscores the difficulty clinicians encounter when trying to interpret outcomes questionnaires. We suggest that this variable should be measured and taken into account when interpreting questionnaires and counseling patients.

Probing the subtropical lowermost stratosphere and the tropical upper troposphere and tropopause layer for inorganic bromine

NASA Astrophysics Data System (ADS)

Werner, Bodo; Stutz, Jochen; Spolaor, Max; Scalone, Lisa; Raecke, Rasmus; Festa, James; Fedele Colosimo, Santo; Cheung, Ross; Tsai, Catalina; Hossaini, Ryan; Chipperfield, Martyn P.; Taverna, Giorgio S.; Feng, Wuhu; Elkins, James W.; Fahey, David W.; Gao, Ru-Shan; Hintsa, Erik J.; Thornberry, Troy D.; Moore, Free Lee; Navarro, Maria A.; Atlas, Elliot; Daube, Bruce C.; Pittman, Jasna; Wofsy, Steve; Pfeilsticker, Klaus

2017-01-01

We report measurements of CH4 (measured in situ by the Harvard University Picarro Cavity Ringdown Spectrometer (HUPCRS) and NOAA Unmanned Aircraft System Chromatograph for Atmospheric Trace Species (UCATS) instruments), O3 (measured in situ by the NOAA dual-beam ultraviolet (UV) photometer), NO2, BrO (remotely detected by spectroscopic UV-visible (UV-vis) limb observations; see the companion paper of Stutz et al., 2016), and of some key brominated source gases in whole-air samples of the Global Hawk Whole Air Sampler (GWAS) instrument within the subtropical lowermost stratosphere (LS) and the tropical upper troposphere (UT) and tropopause layer (TTL). The measurements were performed within the framework of the NASA-ATTREX (National Aeronautics and Space Administration - Airborne Tropical Tropopause Experiment) project from aboard the Global Hawk (GH) during six deployments over the eastern Pacific in early 2013. These measurements are compared with TOMCAT/SLIMCAT (Toulouse Off-line Model of Chemistry And Transport/Single Layer Isentropic Model of Chemistry And Transport) 3-D model simulations, aiming at improvements of our understanding of the bromine budget and photochemistry in the LS, UT, and TTL.Changes in local O3 (and NO2 and BrO) due to transport processes are separated from photochemical processes in intercomparisons of measured and modeled CH4 and O3. After excellent agreement is achieved among measured and simulated CH4 and O3, measured and modeled [NO2] are found to closely agree with ≤ 15 ppt in the TTL (which is the detection limit) and within a typical range of 70 to 170 ppt in the subtropical LS during the daytime. Measured [BrO] ranges between 3 and 9 ppt in the subtropical LS. In the TTL, [BrO] reaches 0.5 ± 0.5 ppt at the bottom (150 hPa/355 K/14 km) and up to about 5 ppt at the top (70 hPa/425 K/18.5 km; see Fueglistaler et al., 2009 for the definition of the TTL used), in overall good agreement with the model simulations. Depending on the photochemical regime, the TOMCAT/SLIMCAT simulations tend to slightly underpredict measured BrO for large BrO concentrations, i.e., in the upper TTL and LS. The measured BrO and modeled BrO / Bryinorg ratio is further used to calculate inorganic bromine, Bryinorg. For the TTL (i.e., when [CH4] ≥ 1790 ppb), [Bryinorg] is found to increase from a mean of 2.63 ± 1.04 ppt for potential temperatures (θ) in the range of 350-360 K to 5.11 ± 1.57 ppt for θ = 390 - 400 K, whereas in the subtropical LS (i.e., when [CH4] ≤ 1790 ppb), it reaches 7.66 ± 2.95 ppt for θ in the range of 390-400 K. Finally, for the eastern Pacific (170-90° W), the TOMCAT/SLIMCAT simulations indicate a net loss of ozone of -0.3 ppbv day-1 at the base of the TTL (θ = 355 K) and a net production of +1.8 ppbv day-1 in the upper part (θ = 383 K).

Synthesis of Primary-Alcohol-Terminated Polyepichlorohydrin with Molecular Weight of 4000 to 12000

DTIC Science & Technology

1989-03-30

of aliphatic triols and tetraols, where the alcohol groups are primary and not attached to a neopentyl carbon atcm, are best acoamplished by the...was attemated, but it was found that the neopentyl alkyl halide intermediates are very resistant to displacement by cyanide ion. The reaction was...Hexwmethylphcshoramide (HMPA) has been suggested as being an excellent solvent for displacement reactions involving neopentyl structures2 . his solvent was not

The Comparison of Accuracy Scores on the Paper and Pencil Testing vs. Computer-Based Testing

ERIC Educational Resources Information Center

Retnawati, Heri

2015-01-01

This study aimed to compare the accuracy of the test scores as results of Test of English Proficiency (TOEP) based on paper and pencil test (PPT) versus computer-based test (CBT). Using the participants' responses to the PPT documented from 2008-2010 and data of CBT TOEP documented in 2013-2014 on the sets of 1A, 2A, and 3A for the Listening and…

Species Profiles: Life Histories and Environmental Requirements of Coastal Fishes and Invertebrates (North and Mid-Atlantic)

DTIC Science & Technology

1989-06-01

completely, oceanic salinities (34 ppt) to mesohaline (5-18 and metabolic rate partly, to a sinusoidal ppt) estuarine conditions (Bayne et al. 1976a... salinity change is large Newfoundland acclimated neither their feeding enough (reviewed by Davenport 1982). It can rate nor their metabolic rate to...mediating their conditions, and energ, requirements are response to a salinity change. Although larvae supplied by anaerobic metabolic pathways from the

Large-Scale Demonstration of Perchlorate Removal Using Weak Base Anion Resin at Well No. 3 in Rialto, California

DTIC Science & Technology

2012-12-01

Nitrosodiethylamine NDMA N-Nitrosodimethylamine NDPA N-Nitrosodi-n-propylamine ng/L nanogram/liter NMEA N-Nitrosomethylethylamine NMOR N...using USEPA Method 521. N-nitrosodimethylamine ( NDMA ) was 2.6 parts per trillion (ppt) with a detection limit of 2 ppt. All other nitrosamines...was returned to service. All samples were analyzed by Weck Laboratories using USEPA Method 521. Analytes included NDEA, NDMA , NDBA, NDPA, NMEA

Positive Psychotherapy for Smoking Cessation: Treatment Development, Feasibility and Preliminary Results

PubMed Central

Kahler, Christopher W.; Spillane, Nichea S.; Day, Anne; Clerkin, Elise; Parks, Acacia; Leventhal, Adam M.; Brown, Richard A.

2013-01-01

Low positive and high negative affect predict low rates of smoking abstinence among smokers making a quit attempt. Positive Psychotherapy can both increase positive affect and decrease negative affect and therefore may be a useful adjunct to behavioral smoking counseling. The purpose of the present study was to assess the feasibility and acceptability of a Positive Psychotherapy for Smoking Cessation (PPT-S) intervention that integrates standard smoking cessation counseling with nicotine patch and a package of positive psychology interventions. We delivered PPT-S to 19 smokers who were low in positive affect at baseline. Rates of session attendance and satisfaction with treatment were high, and most participants reported using and benefiting from the positive psychology interventions. Almost one-third of participants (31.6%) sustained smoking abstinence for 6 months after their quit date. Future studies to assess the relative efficacy of PPT-S compared to standard smoking cessation treatment are warranted. PMID:24683417

Positive Psychotherapy for Smoking Cessation: Treatment Development, Feasibility and Preliminary Results.

PubMed

Kahler, Christopher W; Spillane, Nichea S; Day, Anne; Clerkin, Elise; Parks, Acacia; Leventhal, Adam M; Brown, Richard A

2014-01-01

Low positive and high negative affect predict low rates of smoking abstinence among smokers making a quit attempt. Positive Psychotherapy can both increase positive affect and decrease negative affect and therefore may be a useful adjunct to behavioral smoking counseling. The purpose of the present study was to assess the feasibility and acceptability of a Positive Psychotherapy for Smoking Cessation (PPT-S) intervention that integrates standard smoking cessation counseling with nicotine patch and a package of positive psychology interventions. We delivered PPT-S to 19 smokers who were low in positive affect at baseline. Rates of session attendance and satisfaction with treatment were high, and most participants reported using and benefiting from the positive psychology interventions. Almost one-third of participants (31.6%) sustained smoking abstinence for 6 months after their quit date. Future studies to assess the relative efficacy of PPT-S compared to standard smoking cessation treatment are warranted.

Measurements of the dielectric properties of sea water at 1.43 GHz

NASA Technical Reports Server (NTRS)

Ho, W. W.; Love, A. W.; Vanmelle, M. J.

1974-01-01

Salinity and temperature of water surfaces of estuaries and bay regions are determined to accuracies of 1 ppt salinity and 0.3 kelvin surface temperature. L-band and S-band radiometers are used in combination as brightness temperature detectors. The determination of the brightness temperature versus salinity, with the water surface temperature as a parameter for 1.4 GHz, is performed with a capillary tube inserted into a resonance cavity. Detailed analysis of the results indicates that the measured values are accurate to better than 0.2 percent in the electric property epsilon' and 0.4 percent in epsilon''. The calculated brightness temperature as a function of temperature and salinity is better than 0.2 kelvin. Thus it is possible to reduce the measured data obtained with the two-frequency radiometer system with 1 ppt accuracy to values in the salinity range 5 to 40 ppt.

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

Jardine, A. B.; Jardine, K. J.; Fuentes, J. D.

Despite orders of magnitude difference in atmospheric reactivity and great diversity in biological functioning, little is known about monoterpene speciation in tropical forests. Here we report vertically resolved ambient air mixing ratios for 12 monoterpenes in a central Amazon rainforest including observations of the highly reactive cis-β-ocimene (160 ppt), trans-β-ocimene (79 ppt), and terpinolene (32 ppt) which accounted for an estimated 21% of total monoterpene composition yet 55% of the upper canopy monoterpene ozonolysis rate. All 12 monoterpenes showed a mixing ratio peak in the upper canopy, with three demonstrating subcanopy peaks in 7 of 11 profiles. Leaf level emissionsmore » of highly reactive monoterpenes accounted for up to 1.9% of photosynthesis confirming light-dependent emissions across several Amazon tree genera. These results suggest that highly reactive monoterpenes play important antioxidant roles during photosynthesis in plants and serve as near-canopy sources of secondary organic aerosol precursors through atmospheric photooxidation via ozonolysis.« less

Highly reactive light-dependent monoterpenes in the Amazon

NASA Astrophysics Data System (ADS)

Jardine, A. B.; Jardine, K. J.; Fuentes, J. D.; Martin, S. T.; Martins, G.; Durgante, F.; Carneiro, V.; Higuchi, N.; Manzi, A. O.; Chambers, J. Q.

2015-03-01

Despite orders of magnitude difference in atmospheric reactivity and great diversity in biological functioning, little is known about monoterpene speciation in tropical forests. Here we report vertically resolved ambient air mixing ratios for 12 monoterpenes in a central Amazon rainforest including observations of the highly reactive cis-β-ocimene (160 ppt), trans-β-ocimene (79 ppt), and terpinolene (32 ppt) which accounted for an estimated 21% of total monoterpene composition yet 55% of the upper canopy monoterpene ozonolysis rate. All 12 monoterpenes showed a mixing ratio peak in the upper canopy, with three demonstrating subcanopy peaks in 7 of 11 profiles. Leaf level emissions of highly reactive monoterpenes accounted for up to 1.9% of photosynthesis confirming light-dependent emissions across several Amazon tree genera. These results suggest that highly reactive monoterpenes play important antioxidant roles during photosynthesis in plants and serve as near-canopy sources of secondary organic aerosol precursors through atmospheric photooxidation via ozonolysis.

Synthesis of ultra-nano-carbon composite materials with extremely high conductivity by plasma post-treatment process of ultrananocrystalline diamond films

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

Yeh, Chien-Jui; Leou, Keh-Chyang; Manoharan, Divinah

2015-08-24

Needle-like diamond grains encased in nano-graphitic layers are an ideal granular structure of diamond films to achieve high conductivity and superior electron field emission (EFE) properties. This paper describes the plasma post-treatment (ppt) of ultrananocrystalline diamond (UNCD) films at low substrate temperature to achieve such a unique granular structure. The CH{sub 4}/N{sub 2} plasma ppt-processed films exhibit high conductivity of σ = 1099 S/cm as well as excellent EFE properties with turn-on field of E{sub 0} = 2.48 V/μm (J{sub e} = 1.0 mA/cm{sup 2} at 6.5 V/μm). The ppt of UNCD film is simple and robust process that is especially useful for device applications.

Induction of Amyloid-β42 Production by Fipronil and Other Pyrazole Insecticides.

PubMed

Cam, Morgane; Durieu, Emilie; Bodin, Marion; Manousopoulou, Antigoni; Koslowski, Svenja; Vasylieva, Natalia; Barnych, Bogdan; Hammock, Bruce D; Bohl, Bettina; Koch, Philipp; Omori, Chiori; Yamamoto, Kazuo; Hata, Saori; Suzuki, Toshiharu; Karg, Frank; Gizzi, Patrick; Haber, Vesna Erakovic; Bencetic Mihaljevic, Vlatka; Tavcar, Branka; Portelius, Erik; Pannee, Josef; Blennow, Kaj; Zetterberg, Henrik; Garbis, Spiros D; Auvray, Pierrick; Gerber, Hermeto; Fraering, Jeremy; Fraering, Patrick C; Meijer, Laurent

2018-01-01

Generation of amyloid-β peptides (Aβs) by proteolytic cleavage of the amyloid-β protein precursor (AβPP), especially increased production of Aβ42/Aβ43 over Aβ40, and their aggregation as oligomers and plaques, represent a characteristic feature of Alzheimer's disease (AD). In familial AD (FAD), altered Aβ production originates from specific mutations of AβPP or presenilins 1/2 (PS1/PS2), the catalytic subunits of γ-secretase. In sporadic AD, the origin of altered production of Aβs remains unknown. We hypothesize that the 'human chemical exposome' contains products able to favor the production of Aβ42/Aβ43 over Aβ40 and shorter Aβs. To detect such products, we screened a library of 3500 + compounds in a cell-based assay for enhanced Aβ42/Aβ43 production. Nine pyrazole insecticides were found to induce a β- and γ-secretase-dependent, 3-10-fold increase in the production of extracellular Aβ42 in various cell lines and neurons differentiated from induced pluripotent stem cells derived from healthy and FAD patients. Immunoprecipitation/mass spectrometry analyses showed increased production of Aβs cleaved at positions 42/43, and reduced production of peptides cleaved at positions 38 and shorter. Strongly supporting a direct effect on γ-secretase activity, pyrazoles shifted the cleavage pattern of another γ-secretase substrate, alcadeinα, and shifted the cleavage of AβPP by highly purified γ-secretase toward Aβ42/Aβ43. Focusing on fipronil, we showed that some of its metabolites, in particular the persistent fipronil sulfone, also favor the production of Aβ42/Aβ43 in both cell-based and cell-free systems. Fipronil administered orally to mice and rats is known to be metabolized rapidly, mostly to fipronil sulfone, which stably accumulates in adipose tissue and brain. In conclusion, several widely used pyrazole insecticides enhance the production of toxic, aggregation prone Aβ42/Aβ43 peptides, suggesting the possible existence of environmental "Alzheimerogens" which may contribute to the initiation and propagation of the amyloidogenic process in sporadic AD.

Inorganic Iodine and Bromine in the Tropical Upper Troposphere/Lower Stratosphere Derived From Balloon Borne Observations

NASA Astrophysics Data System (ADS)

Dorf, M.; Butz, A.; Camy-Peyret, C.; Chipperfield, M.; Kreycy, S.; Kritten, L.; Prados-Roman, C.; Pfeilsticker, K.

2008-12-01

Due to the ozone destroying capabilities of bromine and iodine bearing compounds, the stratospheric budget of inorganic bromine and iodine is of major interest for modeling ozone depletion and assessing the future evolution of the ozone layer. In particular the contribution of very short lived substances (VSLS) to the bromine budget has recently been shown to enhance ozone depletion in mid-latitudes and polar regions. So far, iodine species have not been unambiguously detected in the stratosphere with upper limits for total inorganic iodine (Iy) of about 0.1 ppt. However, observations are sparse and mainly restricted to mid- and high-latitudes. Here, we assess the budget of iodine and bromine in the tropical Upper Troposphere/ Lower Stratosphere (UT/LS) where the halogen source gases enter the stratosphere and supply the stratosphere with halogen species. We report on two stratospheric balloon flights of the LPMA/DOAS (Limb Profile Monitor of the Atmosphere/Differential Optical Absorption Spectrometer) payload from a tropical station in northern Brazil (5°S, 43°W) in June 2005 and June 2008. There, the LPMA/DOAS payload conducted spectroscopic direct sun measurements in the UV/visible and infrared spectral range during balloon ascent and in solar occultation geometry. The LPMA/DOAS observations allow for the retrieval of IO and OIO from their absorption features in the visible spectral range. Neither species could be detected unambiguously with detection limits ranging between 0.01 and 0.2 ppt in the UT/LS. Constraining a stratospheric chemistry model by the inferred detection limits for IO and OIO, yields an upper limit for Iy of 0.1 to 0.3 ppt. Implications for stratospheric ozone are discussed on the basis of model studies. BrO is inferred from absorption bands in the UV spectral range yielding the first BrO vertical profile in the tropical UT/LS. For the balloon flight in June 2005, total inorganic bromine (Bry) is estimated to (21.5 ± 2.5) ppt in 4.5-year-old air using a stratospheric model constrained by measured BrO. We derive a total contribution of (5.2 ± 2.5) ppt from brominated VSLS and inorganic product gases to Bry. Tropospheric BrO was found to be < 1 ppt. Our results are compared to 3-D CTM SLIMCAT model runs.

Global and regional emissions estimates of 1,1-difluoroethane (HFC-152a, CH3CHF2) from in situ and air archive observations

NASA Astrophysics Data System (ADS)

Simmonds, P. G.; Rigby, M.; Manning, A. J.; Lunt, M. F.; O'Doherty, S.; Young, D.; McCulloch, A.; Fraser, P. J.; Henne, S.; Vollmer, M. K.; Reimann, S.; Wenger, A.; Mühle, J.; Harth, C. M.; Salameh, P. K.; Arnold, T.; Weiss, R. F.; Krummel, P. B.; Steele, L. P.; Dunse, B. L.; Miller, B. R.; Lunder, C. R.; Hermansen, O.; Schmidbauer, N.; Saito, T.; Yokouchi, Y.; Park, S.; Li, S.; Yao, B.; Zhou, L. X.; Arduini, J.; Maione, M.; Wang, R. H. J.; Prinn, R. G.

2015-08-01

High frequency, ground-based, in situ measurements from eleven globally-distributed sites covering 1994-2014, combined with measurements of archived air samples dating from 1978 onward and atmospheric transport models, have been used to estimate the growth of 1,1-difluoroethane (HFC-152a, CH3CHF2) mole fractions in the atmosphere and the global emissions required to derive the observed growth. HFC-152a is a significant greenhouse gas but since it does not contain chlorine or bromine, HFC-152a makes no direct contribution to the destruction of stratospheric ozone and is therefore used as a substitute for the ozone depleting chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs). HFC-152a has exhibited substantial atmospheric growth since the first measurements reaching a maximum annualised global growth rate of 0.81 ± 0.05 ppt yr-1 in 2006, implying a substantial increase in emissions up to 2006. However, since 2007, the annualised rate of growth has slowed to 0.38 ± 0.04 ppt yr-1 in 2010 with a further decline to an average rate of change in 2013-2014 of -0.06 ± 0.05 ppt yr-1. The average Northern Hemisphere (NH) mixing ratio in 1994 was 1.2 ppt rising to a mixing ratio of 10.2 ppt in December 2014. Average annual mixing ratios in the Southern Hemisphere (SH) in 1994 and 2014 were 0.34 and 4.4 ppt, respectively. We estimate global emissions of HFC-152a have risen from 7.3 ± 5.6 Gg yr-1 in 1994 to a maximum of 54.4 ± 17.1 Gg yr-1 in 2011, declining to 52.5 ± 20.1 Gg yr-1 in 2014 or 7.2 ± 2.8 Tg-CO2 eq yr-1. Analysis of mixing ratio enhancements above regional background atmospheric levels suggests substantial emissions from North America, Asia and Europe. Global HFC emissions (so called "bottom up" emissions) reported by the United Nations Framework Convention on Climate Change (UNFCCC) are based on cumulative national emission data reported to the UNFCCC, which in turn are based on national consumption data. There appears to be a significant underestimate of "bottom-up" global emissions of HFC-152a, possibly arising from largely underestimated USA emissions and undeclared Asian emissions.

Measurements of dimethyl sulfide and H2S over the western North Atlantic and the tropical Atlantic

NASA Technical Reports Server (NTRS)

Andreae, T. W.; Andreae, M. O.; Bingemer, H. G.; Leck, C.

1993-01-01

Airborne measurements of DMS and H2S were made off the east coast of the United States and over the tropical Atlantic off Brazil. Samples were collected through a fluorinated ethylene propylene Teflon inlet manifold. Dimethyl sulfide (DMS) was preconcentrated onto gold wool and analyzed by gas chromatography/flame photometric detection. H2S was collected on AgNO3-impregnated filters and determined by fluorescence quenching. Use of a new scrubber material (cotton) to remove negative interference on DMS measurements was investigated. Comparison with a Na2CO3/Anakrom scrubber gave good overall agreement. Only under extreme conditions, e.g., on flight 9 (continental air mass, low humidity, high O3, and low DMS values) did Na2CO3 show noticeable loss of DMS compared to cotton. On most flights, especially in marine air masses with high humidity and relatively low O3, the results from both scrubbers agreed well with each other and with other instruments used during the intercalibration. Off the U.S. East Coast, DMS levels showed strong dependence on air mass origin with high values (up to 83 ppt) in marine tropical air masses and low values (10-20 ppt) in continental and polar air. Over the tropical Atlantic, DMS ranged over 20-100 ppt in the mixed layer. Nighttime values were a factor of 1.6-2.3 higher than daytime levels. DMS decreased with altitude to less than 1 ppt at 4000 m. H2S in the mixed layer off the U.S. East Coast ranged from 10 to 200 ppt. Significant influence from terrestrial and pollution sources was evident. H2S in air masses originating over the eastern seaboard was much higher than in continental polar air or over the remote tropical continents. In contrast, over the tropical Atlantic, concentrations were very low (5-10 ppt), typical of truly marine air. Night/day ratios were about 1.4. No significant geographical variability was seen in H2S levels over the tropical Atlantic. The correlation of atmospheric Rn-222 and H2S was significant, with both being higher off the U.S. East Coast than over the tropical Atlantic.

Effects of salinity and flooding on seedlings of cabbage palm (Sabal palmetto).

PubMed

Perry, L; Williams, K

1996-03-01

Sabal palmetto (Walt.) Lodd. ex Schultes (cabbage palm) dominates the coastal limit of many forests in North Florida and Georgia, United States. Changes in saltwater flooding due to sea level rise have been credicted with pushing the coastal limit of cabbage palms inland, eliminating regeneration before causing death of mature trees. Localized freshwater discharge along the coast causes different forest stands to experience tidal flooding with waters that differ in salinity. To elucidate the effect of such variation on regeneration failure under tidal flooding, we examined relative effects of flooding and salinity on the performance of cabbage palm seedlings. We examined the relationship between seedling establishment and degree of tidal inundation in the field, compared the ability of seedlings to withstand tidal flooding at two coastal sites that differed in tidal water salinity, and investigated the physiological responses of cabbage palm seedlings to salinity and flooding in a factorial greenhouse experiment. Seedling survival was inversely correlated with depth and frequency of tidal flooding. Survival of seedlings at a coastal site flooded by waters low in salinity [c. 3 parts per thousand (ppt)] was greater than that at a site flooded by waters higher in salinity (up to 23 ppt). Greenhouse experiments revealed that leaves of seedlings in pots flushed twice daily with salt solutions of 0 ppt and 8 ppt exhibited little difference in midmorning net CO 2 assimilation rates; those flushed with solutions of 15 ppt and 22 ppt, in contrast, had such low rates that they could not be detected. Net CO 2 assimilation rates also declined with increasing salinity for seedlings in pots that were continuously inundated. Continuous root zone inundation appeared to ameliorate effects of salinity on photosynthesis, presumably due to increased salt concentrations and possibly water deficits in periodically flushed pots. Such problems associated with periodic flushing by salt water may play a role in the mortality of cabbage palm seedlings in the field. The salinity range in which plant performance plummeted in the greenhouse was consistent with the salinity difference found between our two coastal study sites, suggesting that variation in tidal water salinity along the coast plays an important role in the ability of cabbage palm seedlings to withstand tidal flooding.

Performance Prediction Toolkit

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

Chennupati, Gopinath; Santhi, Nanadakishore; Eidenbenz, Stephen

The Performance Prediction Toolkit (PPT), is a scalable co-design tool that contains the hardware and middle-ware models, which accept proxy applications as input in runtime prediction. PPT relies on Simian, a parallel discrete event simulation engine in Python or Lua, that uses the process concept, where each computing unit (host, node, core) is a Simian entity. Processes perform their task through message exchanges to remain active, sleep, wake-up, begin and end. The PPT hardware model of a compute core (such as a Haswell core) consists of a set of parameters, such as clock speed, memory hierarchy levels, their respective sizes,more » cache-lines, access times for different cache levels, average cycle counts of ALU operations, etc. These parameters are ideally read off a spec sheet or are learned using regression models learned from hardware counters (PAPI) data. The compute core model offers an API to the software model, a function called time_compute(), which takes as input a tasklist. A tasklist is an unordered set of ALU, and other CPU-type operations (in particular virtual memory loads and stores). The PPT application model mimics the loop structure of the application and replaces the computational kernels with a call to the hardware model's time_compute() function giving tasklists as input that model the compute kernel. A PPT application model thus consists of tasklists representing kernels and the high-er level loop structure that we like to think of as pseudo code. The key challenge for the hardware model's time_compute-function is to translate virtual memory accesses into actual cache hierarchy level hits and misses.PPT also contains another CPU core level hardware model, Analytical Memory Model (AMM). The AMM solves this challenge soundly, where our previous alternatives explicitly include the L1,L2,L3 hit-rates as inputs to the tasklists. Explicit hit-rates inevitably only reflect the application modeler's best guess, perhaps informed by a few small test problems using hardware counters; also, hard-coded hit-rates make the hardware model insensitive to changes in cache sizes. Alternatively, we use reuse distance distributions in the tasklists. In general, reuse profiles require the application modeler to run a very expensive trace analysis on the real code that realistically can be done at best for small examples.« less

Synthesis and evaluation of thiazolidinone-pyrazole conjugates as anticancer and antimicrobial agents.

PubMed

Bhat, Mahima; Poojary, Boja; Kalal, Bhuvanesh Sukhlal; Gurubasavaraja Swamy, Purawarga Matada; Kabilan, Senthamaraikannan; Kumar, Vasantha; Shruthi, Nooji; Alias Anand, Selvam Athavan; Pai, Vinitha Ramanath

2018-05-01

To synthesize a series of new thiazolidinone-pyrazole hybrids (5a-o) and assess their anticancer (in vitro and in vivo) and antimicrobial activities. The compounds 5h (against Ehrlich ascites carcinoma cells), 5e and 5i (against the human breast cancer [MDA-MB231] cell line) exhibited potent anticancer activity. All the compounds except 5g and 5e found to be less toxic for the human dermal fibroblast cells. The effective interactions of the compounds in silico with MDM2 exemplified their inhibitory potency. The derivatives also showed moderate antimicrobial activity. The halogen atoms on various positions of the N-arylamino ring played an advantageous role in elevating the potency of the molecules. Thus, these conjugates could be used as a lead for further optimization to achieve promising therapeutics.

5-(4-Bromo­phen­oxy)-1-methyl-3-methyl-1H-pyrazole-4-carbaldehyde-O-[(5-meth­oxy-1,3,4-thia­diazol-2-yl)-meth­yl]oxime

PubMed Central

Fan, Chong-Guang; Chen, Jian-Cun; Dai, Hong; Wei, Yun-Hua; Shi, Yu-Jun

2012-01-01

In the title mol­ecule, C16H16BrN5O3S, the 1,3,4-thia­diazole ring is situated under the benzene ring, forming a dihedral angle of 86.6 (2)°, and with an S⋯Cg (where Cg is the centroid of the benzene ring) distance of 3.312 (3) Å. The benzene and 1,3,4-thia­diazole rings form dihedral angles of 83.8 (3) and 57.7 (2)°, respectively, with the central pyrazole ring. In the absence of classical hydrogen bonds, the crystal packing is stabilized by a C—H⋯π inter­action.. PMID:23284447

1-[5-(4-Bromo­phen­yl)-3-(4-fluoro­phen­yl)-4,5-dihydro-1H-pyrazol-1-yl]butan-1-one

PubMed Central

Fun, Hoong-Kun; Loh, Wan-Sin; Sapnakumari, M.; Narayana, B.; Sarojini, B. K.

2012-01-01

In the title compound, C19H18BrFN2O, the benzene rings form dihedral angles of 5.38 (7) and 85.48 (7)° with the mean plane of the 4,5-dihydro-1H-pyrazole ring (r.m.s. deviation = 0.0849 Å), which approximates to an envelope conformation with the –CH2– group as the flap. The dihedral angle between the benzene rings is 82.86 (7)°. In the crystal, C—H⋯F and C—H⋯O hydrogen bonds link the mol­ecules to form inversion dimers and together these generate chains along [011]. The crystal packing also features C—H⋯π inter­actions. PMID:22969553

Synthesis and antimicrobial studies of novel derivatives of 4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)benzoic acid as potent anti-Acinetobacter baumanni agents

PubMed Central

Allison, Devin; Delancey, Evan; Ramey, Hunter; Williams, Conrad; Alsharif, Zakeyah Ali; Al-khattabi, Hessa; Ontko, Allyn; Gilmore, David

2017-01-01

Microbial resistance to antibiotics is a global concern. The World Health Organization (WHO) has identified antimicrobial resistance as one the three greatest threats for human beings in the 21st century. Without urgent and coordinated action, the world is moving toward a post-antibiotic era, in which normal infections or minor injuries may become fatal. In an effort to find new agents, we report the synthesis and antimicrobial activities of 40 novel 1,3-diphenyl pyrazole derivatives. These compounds have shown zones of growth inhibition up to 85 mm against Acinetobacter baumannii. We tested the active compounds against this Gram-negative bacterium in minimum inhibitory concentration (MIC) tests and found activity with concentration as low as 4 μg/mL. PMID:28065568

Synthesis and antimicrobial studies of novel derivatives of 4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)benzoic acid as potent anti-Acinetobacter baumannii agents.

PubMed

Allison, Devin; Delancey, Evan; Ramey, Hunter; Williams, Conrad; Alsharif, Zakeyah Ali; Al-Khattabi, Hessa; Ontko, Allyn; Gilmore, David; Alam, Mohammad A

2017-02-01

Microbial resistance to antibiotics is a global concern. The World Health Organization (WHO) has identified antimicrobial resistance as one the three greatest threats for human beings in the 21st century. Without urgent and coordinated action, the world is moving toward a post-antibiotic era, in which normal infections or minor injuries may become fatal. In an effort to find new agents, we report the synthesis and antimicrobial activities of 40 novel 1,3-diphenyl pyrazole derivatives. These compounds have shown zones of growth inhibition up to 85mm against Acinetobacter baumannii. We tested the active compounds against this Gram-negative bacterium in minimum inhibitory concentration (MIC) tests and found activity with concentration as low as 4μg/mL. Published by Elsevier Ltd.

Synthesis, optical properties and application of a set of novel pyrazole nopinone derivatives

NASA Astrophysics Data System (ADS)

Yang, Jinlai; Xu, Xu; Rui, Jian; Wang, Zhonglong; Zhang, Yan; Wang, Shifa; Wu, Liangru

2017-08-01

Pyrazole derivatives (4-6) were directly synthesized from β-pinene derivative nopinone, and they were characterized by Fourier transform infrared (FTIR) spectoscope, nuclear magnetic resonance (NMR), and mass spectrometry. Their optical properties were investigated by ultraviolet-visible spectroscopy and fluorescence spectroscopy. The three compounds emitted strong blue fluorescence in ethanol. Using a fluorescence quenching method, compound 4 could be used to detect the content (100.57%) of copper sulfate pentahydrate (≥ 99%) with a RSD of 1.98%, y = - 0.1127 × + 2.7148, R2 = 0.9703 (Cu2 +: 0.5-8.0 × 10- 5 mol/L), and compounds 4-6 also had utility of calculating the content of anhydrous ferric chloride at a wide range of concentration. Thus, compounds 4-6 are new functional fluorescents for detecting the content of some purchased products.

Synthesis and characterization of novel 2, 2'-bipyrimidine fluorescent derivative for protein binding

PubMed Central

2011-01-01

Background Fluorescent dyes with biocompatible functional group and good fluorescence behavior are used as biosensor for monitoring different biological processes as well as detection of protein assay. All reported fluorophore used as sensors are having high selectivity and sensitivity but till there is more demand to synthesized new fluorophore which have improved fluorescence properties and good biocompatibility. Results Novel 4, 4'-(1, 1'-(5-(2-methoxyphenoxy)-[2, 2'-bipyrimidine]-4, 6-diyl)bis(1H-pyrazol-3, 1-diyl)) dianiline fluorescent dye was synthesized by multistep synthesis from 2-phenylacetonitrile, 2-chloropyrimidine and 2-methoxyphenol. This dye has absorption at 379 nm with intense single emission at 497 nm having fairly good quantum yield (0.375) and Stokes shift. The intermediates and dye were characterized by FT-IR, 1H NMR, 13C NMR and Mass spectral analysis. The pyrazole bipyrimidine based fluorescent dye possessing two amino groups suitable for binding with protein is reported. Its utility as a biocompatible conjugate was explained by conjugation with bovine serum albumin. The method is based on direct fluorescence detection of fluorophore-labelled protein before and after conjugation. Purified fluorescent conjugate was subsequently analyzed by fluorimetry. The analysis showed that the tested conjugation reaction yielded fluorescent conjugates of the dye through carbodiimide chemistry. Conclusion In summery synthesized fluorophore pyrazole-bipyrimidine has very good interaction towards protein bovine serum albumin and it acts as good candidate for protein assay. PMID:22067202

Evaluation of weed control efficacy and crop safety of the new HPPD-inhibiting herbicide-QYR301.

PubMed

Wang, Hengzhi; Liu, Weitang; Zhao, Kongping; Yu, Hui; Zhang, Jia; Wang, Jinxin

2018-05-21

QYR301, 1,3-Dimethyl-1H-pyrazole-4-carboxylic acid 4-[2-chloro-3-(3,5-dimethyl-pyrazol-1-ylmethyl)-4-methanesulfonyl-benzoyl]-2,5-dimethyl-2H-pyrazol-3-yl ester, is a novel HPPD-inhibiting herbicide and was evaluated to provide a reference for post-emergence (POST) application under greenhouse and field conditions. The crop safety (180 and 360 g active ingredient (a.i.) ha -1 treatments) experiment revealed that wheat, paddy, garlic and corn were the only four crops without injury at both examined herbicide rates. The weed control efficacy (60 and 120 g a.i. ha -1 ) experiment showed that QYR301 exhibited high efficacy against many weeds, especially weeds infesting paddy fields. Furthermore, it is interesting that both susceptible and multiple herbicide resistant Echinochloa crus-galli (L.) Beauv. and Echinochloa phyllopogon (Stapf) Koss, two notorious weed species in paddy field, remained susceptible to QYR301. Further crop tolerance results indicated that 20 tested paddy hybrids displayed different levels of tolerance to QYR301, with the japonica paddy hybrids having more tolerance than indica paddy hybrids under greenhouse conditions. Results obtained from field experiments showed that QYR301 POST at 135 to 180 g a.i. ha -1 was recommended to provide satisfactory full-season control of E. crus-galli and Leptochloa chinensis (L.) Nees and to maximize rice yields. These findings indicate that QYR301 possesses great potential for the management of weeds in paddy fields.

Synthesis, spectroscopic and theoretical studies of ethyl (2E)-3-amino-2-({[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]amino}carbonothioyl)but-2-enoate butanol solvate

NASA Astrophysics Data System (ADS)

Koca, İrfan; Sert, Yusuf; Gümüş, Mehmet; Kani, İbrahim; Çırak, Çağrı

2014-01-01

We have synthesized ethyl (2E)-3-amino-2-({[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]amino}carbonothioyl)but-2-enoate (2) by the reaction of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonyl chloride (1), ammonium thiocyanate and ethyl 3-aminobut-2-enoate and then characterized by elemental analyses, IR, Raman, 1H NMR, 13C NMR and X-ray diffraction methods. The experimental and theoretical vibrational spectra of 2 were investigated. The experimental FT-IR (4000-400 cm-1) and Laser-Raman spectra (4000-100 cm-1) of the molecule in the solid phase were recorded. Theoretical vibrational frequencies and geometric parameters (bond lengths, bond angles) were calculated using Ab Initio Hartree Fock (HF), Density Functional Theory (B3LYP) methods with 6-311++G(d,p) basis set by Gaussian 09W program. The computed values of frequencies are scaled using a suitable scale factor to yield good coherence with the observed values. The assignments of the vibrational frequencies were performed by potential energy distribution (PED) analysis by using VEDA 4 program. The theoretical optimized geometric parameters and vibrational frequencies were compared with the corresponding experimental X-ray diffraction data, and they were seen to be in a good agreement with each other. Also, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were calculated.

Canaveral National Seashore Water Quality and Aquatic Resource Inventory

NASA Technical Reports Server (NTRS)

Hall, C. R.; Provancha, J. A.; Oddy, D. M.; Lowers, R. L.; Drese, J. D.

2001-01-01

Mosquito Lagoon is a shallow, bar-built estuary located on the east central Florida Coast, primarily within the KSC boundary. The lagoon and watershed cover approximately 327 sq km (79422 acres) .The Lagoon occupies 159 sq km (37853 acres). Water depths average approximately 1m. The lagoon volume is approximately 1.6 x 10(exp 8)cu m. Water quality in Mosquito Lagoon is good. Salinity data typically range between 20 ppt and 35 ppt. The lowest value recorded was 4.5 ppt and the highest value was 37 ppt. Water temperatures fluctuate 2 - 3 C over a 24 h period. Cold front passage can rapidly alter water temperatures by 5 - 10 C or more in a short period of time. The highest temperature was 33.4 C and the lowest temperature was 8.8 C after a winter storm. Dissolved oxygen concentrations ranged from a low of 0.4 mg/l to a high of 15.3 mg/l. Extended periods of measurements below the Florida Department of Environmental Protection criteria of 4.0 mg/l were observed in fall and spring months suggesting high system respiration and oxygen demand. Metals such as antimony, arsenic, molybdenum and mercury were report as below detection limits for all samples. Cadmium, copper, chromium, silver, and zinc were found to be periodically above the Florida Department of Environmental Protection criteria for Class II and Class III surface waters.

Effect of salinity on the upper lethal temperature tolerance of early-juvenile red drum.

PubMed

McDonald, Dusty; Bumguardner, Britt; Cason, Paul

2015-10-01

Previous work investigating the temperature tolerance of juvenile red drum ranging 18-50mm TL found evidence for positive size dependence (smaller fish less tolerant to higher temperatures) suggesting smaller size classes (<18mm TL) potentially may succumb to extreme summer water temperatures. Here, we explored the upper lethal temperature tolerance (ULT) in smaller-sized red drum which ranged from 10 to 20mm TL across multiple salinities to further understand the thermal limitations of this propagated game fish. In order to investigate the combined effect of temperature and salinity on ULT, temperature trials were conducted under three levels of salinity which commonly occur along the coast of Texas (25, 35, and 45ppt). The rate of temperature increase (+0.25°C/h) was designed to mimic a natural temperature increase of a summer day in Texas. We determined that the lethal temperature at 50% (LT50) did not differ between the three salinities examined statistically; median lethal temperature for individuals exposed to 25ppt ranged from 36.4 to 37.7°C, 35ppt ranged from 36.4 to 37.7°C, and 45ppt ranged from 36.1 to 37.4°C. Further, LT50 data obtained here for early-juvenile red drum did not differ from data of a similar experiment examining 25mm TL sized fish. Published by Elsevier Ltd.

Changes in the vibration sensitivity and pressure pain thresholds in patients with burning mouth syndrome.

PubMed

Moura, Brenda de Souza; Ferreira, Natália Dos Reis; DosSantos, Marcos F; Janini, Maria Elisa Rangel

2018-01-01

To investigate the presence of changes in vibration detection and pressure pain threshold in patients with burning-mouth syndrome (BMS). Case-control study. The sample was composed of 30 volunteers, 15 with BMS and 15 in the control group. The pressure-pain threshold (PPT) and vibration-detection threshold (VDT) were examined. The clinical evaluation was complemented with the McGill Pain Questionnaire (MPQ), Douleur Neuropathique 4 (DN4) and Beck Depression and Anxiety Inventories (BDI and BAI, respectively). BMS subjects showed a statistically significant higher PPT in the tongue (p = 0.002), right (p = 0.001) and left (p = 0.004) face, and a significant reduction of the VDT in the tongue (p = 0.013) and right face (p = 0.030). Significant differences were also found when comparing the PPT and the VDT of distinct anatomical areas. However, a significant interaction (group × location) was only for the PPT. BMS subjects also showed significantly higher levels of depression (p = 0.01), as measured by the BDI, compared to controls; and a significant inverse correlation between the VDT in the left face and anxiety levels was detected. The study of somatosensory changes in BMS and its correlations with the clinical features as well as the levels of anxiety and depression expands current understanding of the neuropathic origin and the possible contribution of psychogenic factors related to this disease.

Patients with chronic tension-type headache demonstrate increased mechano-sensitivity of the supra-orbital nerve.

PubMed

Fernández-de-Las-Peñas, César; Coppieters, Michel W; Cuadrado, María Luz; Pareja, Juan A

2008-04-01

This study aimed to establish whether increased sensitivity to mechanical stimuli is present in neural tissues in chronic tension-type headache (CTTH). Muscle hyperalgesia is a common finding in CTTH. No previous studies have investigated the sensitivity of peripheral nerves in patients with CTTH. A blinded controlled study. Pressure pain thresholds (PPT) and pain intensity following palpation of the supra-orbital nerve (V1) were compared between 20 patients with CTTH and 20 healthy matched subjects. A pressure algometer and numerical pain rate scale were used to quantify PPT and pain to palpation. A headache diary was kept for 4 weeks to substantiate the diagnosis and record the pain history. The analysis of variance demonstrated significantly lower PPT for patients (0.86+/-0.13 kg/cm2) than controls (1.50+/-0.19 kg/cm2) (P<.001). Pain to palpation was also higher for patients (2.73+/-1.58) than controls (0.15+/-0.28) (P<.001). Within the CTTH group, intensity, frequency, and duration of the headaches were negatively correlated with PPT (rsor=0.72; P<.001). These findings reveal that mechanical hypersensitivity is not limited to muscles but also occurs in cranial nerves, and that the level of sensitization, either due to peripheral or central processes, is related to the severity of the primary headache.

Einstein-Podolsky-Rosen-like separability indicators for two-mode Gaussian states

NASA Astrophysics Data System (ADS)

Marian, Paulina; Marian, Tudor A.

2018-02-01

We investigate the separability of the two-mode Gaussian states (TMGSs) by using the variances of a pair of Einstein-Podolsky-Rosen (EPR)-like observables. Our starting point is inspired by the general necessary condition of separability introduced by Duan et al (2000 Phys. Rev. Lett. 84 2722). We evaluate the minima of the normalized forms of both the product and sum of such variances, as well as that of a regularized sum. Making use of Simon’s separability criterion, which is based on the condition of positivity of the partial transpose (PPT) of the density matrix (Simon 2000 Phys. Rev. Lett. 84 2726), we prove that these minima are separability indicators in their own right. They appear to quantify the greatest amount of EPR-like correlations that can be created in a TMGS by means of local operations. Furthermore, we reconsider the EPR-like approach to the separability of TMGSs which was developed by Duan et al with no reference to the PPT condition. By optimizing the regularized form of their EPR-like uncertainty sum, we derive a separability indicator for any TMGS. We prove that the corresponding EPR-like condition of separability is manifestly equivalent to Simon’s PPT one. The consistency of these two distinct approaches (EPR-like and PPT) affords a better understanding of the examined separability problem, whose explicit solution found long ago by Simon covers all situations of interest.

In Vitro Metabolism of 20(R)-25-Methoxyl-Dammarane-3, 12, 20-Triol from Panax notoginseng in Human, Monkey, Dog, Rat, and Mouse Liver Microsomes

PubMed Central

Li, Wei; Liu, Li; Sun, Baoshan; Guo, Zhenghong; Shi, Caihong; Zhao, Yuqing

2014-01-01

The present study characterized in vitro metabolites of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol (20(R)-25-OCH3-PPD) in mouse, rat, dog, monkey and human liver microsomes. 20(R)-25-OCH3-PPD was incubated with liver microsomes in the presence of NADPH. The reaction mixtures and the metabolites were identified on the basis of their mass profiles using LC-Q/TOF and were quantified using triple quadrupole instrument by multiple reaction monitoring. A total of 7 metabolites (M1–M7) of the phase I metabolites were detected in all species. 25(R)-OCH3-PPD was metabolized by hydroxylation, dehydrogenation, and O-demethylation. Enzyme kinetic of 20(R)-25-OCH3-PPD metabolism was evaluated in rat and human hepatic microsomes. Incubations studies with selective chemical inhibitors demonstrated that the metabolism of 20(R)-25-OCH3-PPD was primarily mediated by CYP3A4. We conclude that 20(R)-25-OCH3-PPD was metabolized extensively in mammalian species of mouse, rat, dog, monkey, and human. CYP3A4-catalyzed oxygenation metabolism played an important role in the disposition of 25(R)-OCH3-PPD, especially at the C-20 hydroxyl group. PMID:24736630

A physiologically based pharmacokinetic model to predict disposition of CYP2D6 and CYP1A2 metabolized drugs in pregnant women.

PubMed

Ke, Alice Ban; Nallani, Srikanth C; Zhao, Ping; Rostami-Hodjegan, Amin; Isoherranen, Nina; Unadkat, Jashvant D

2013-04-01

Conducting pharmacokinetic (PK) studies in pregnant women is challenging. Therefore, we asked if a physiologically based pharmacokinetic (PBPK) model could be used to evaluate different dosing regimens for pregnant women. We refined and verified our previously published pregnancy PBPK model by incorporating cytochrome P450 CYP1A2 suppression (based on caffeine PK) and CYP2D6 induction (based on metoprolol PK) into the model. This model accounts for gestational age-dependent changes in maternal physiology and hepatic CYP3A activity. For verification, the disposition of CYP1A2-metabolized drug theophylline (THEO) and CYP2D6-metabolized drugs paroxetine (PAR), dextromethorphan (DEX), and clonidine (CLO) during pregnancy was predicted. Our PBPK model successfully predicted THEO disposition during the third trimester (T3). Predicted mean postpartum to third trimester (PP:T3) ratios of THEO area under the curve (AUC), maximum plasma concentration, and minimum plasma concentration were 0.76, 0.95, and 0.66 versus observed values 0.75, 0.89, and 0.72, respectively. The predicted mean PAR steady-state plasma concentration (Css) ratio (PP:T3) was 7.1 versus the observed value 3.7. Predicted mean DEX urinary ratio (UR) (PP:T3) was 2.9 versus the observed value 1.9. Predicted mean CLO AUC ratio (PP:T3) was 2.2 versus the observed value 1.7. Sensitivity analysis suggested that a 100% induction of CYP2D6 during T3 was required to recover the observed PP:T3 ratios of PAR Css, DEX UR, and CLO AUC. Based on these data, it is prudent to conclude that the magnitude of hepatic CYP2D6 induction during T3 ranges from 100 to 200%. Our PBPK model can predict the disposition of CYP1A2, 2D6, and 3A drugs during pregnancy.

A Physiologically Based Pharmacokinetic Model to Predict Disposition of CYP2D6 and CYP1A2 Metabolized Drugs in Pregnant Women

PubMed Central

Ke, Alice Ban; Nallani, Srikanth C.; Zhao, Ping; Rostami-Hodjegan, Amin; Isoherranen, Nina

2013-01-01

Conducting pharmacokinetic (PK) studies in pregnant women is challenging. Therefore, we asked if a physiologically based pharmacokinetic (PBPK) model could be used to evaluate different dosing regimens for pregnant women. We refined and verified our previously published pregnancy PBPK model by incorporating cytochrome P450 CYP1A2 suppression (based on caffeine PK) and CYP2D6 induction (based on metoprolol PK) into the model. This model accounts for gestational age–dependent changes in maternal physiology and hepatic CYP3A activity. For verification, the disposition of CYP1A2–metabolized drug theophylline (THEO) and CYP2D6–metabolized drugs paroxetine (PAR), dextromethorphan (DEX), and clonidine (CLO) during pregnancy was predicted. Our PBPK model successfully predicted THEO disposition during the third trimester (T3). Predicted mean postpartum to third trimester (PP:T3) ratios of THEO area under the curve (AUC), maximum plasma concentration, and minimum plasma concentration were 0.76, 0.95, and 0.66 versus observed values 0.75, 0.89, and 0.72, respectively. The predicted mean PAR steady-state plasma concentration (Css) ratio (PP:T3) was 7.1 versus the observed value 3.7. Predicted mean DEX urinary ratio (UR) (PP:T3) was 2.9 versus the observed value 1.9. Predicted mean CLO AUC ratio (PP:T3) was 2.2 versus the observed value 1.7. Sensitivity analysis suggested that a 100% induction of CYP2D6 during T3 was required to recover the observed PP:T3 ratios of PAR Css, DEX UR, and CLO AUC. Based on these data, it is prudent to conclude that the magnitude of hepatic CYP2D6 induction during T3 ranges from 100 to 200%. Our PBPK model can predict the disposition of CYP1A2, 2D6, and 3A drugs during pregnancy. PMID:23355638

Differences in salinity tolerance of genetically distinct Phragmites australis clones

PubMed Central

Achenbach, Luciana; Eller, Franziska; Nguyen, Loc Xuan; Brix, Hans

2013-01-01

Different clones of the wetland grass Phragmites australis differ in their morphology and physiology, and hence in their ability to cope with environmental stress. We analysed the responses of 15 P. australis clones with distinct ploidy levels (PLs) (4n, 6n, 8n, 10n, 12n) and geographic origins (Romania, Russia, Japan, Czech Republic, Australia) to step-wise increased salinity (8, 16, 24, 32, 40, 56 and 72 ppt). Shoot elongation rate, photosynthesis and plant part-specific ion accumulation were studied in order to assess if traits associated with salinity tolerance can be related to the genetic background and the geographic origin of the clones. Salt stress affected all clones, but at different rates. The maximum height was reduced from 1860 mm in control plants to 660 mm at 40 ppt salinity. The shoot elongation rate of salt-exposed plants varied significantly between clones until 40 ppt salinity. The light-saturated photosynthesis rate (Pmax) was stimulated by a salinity of 8 ppt, but decreased significantly at higher salinities. The stomatal conductance (gs) and the transpiration rate (E) decreased with increasing salinity. Only three clones survived at 72 ppt salinity, although their rates of photosynthesis were strongly inhibited. The roots and basal leaves of the salt-exposed plants accumulated high concentrations of water-extractable Na+ (1646 and 1004 µmol g−1 dry mass (DM), respectively) and Cl− (1876 and 1400 µmol g−1 DM, respectively). The concentrations of water-extractable Mg2+ and Ca2+ were reduced in salt-exposed plants compared with controls. The variation of all the measured parameters was higher among clones than among PLs. We conclude that the salinity tolerance of distinct P. australis clones varies widely and can be partially attributed to their longitudinal geographic origin, but not to PL. Further investigation will help in improving the understanding of this species' salt tolerance mechanisms and their connection to genetic factors.

Shared Roles of Halobacteriovorax and Viruses in Bacterial Mortality: The Environment Dictates the Winner

NASA Astrophysics Data System (ADS)

Chen, H.; Laws, E. A.; Gulig, P. A.; Berhane, T. K.; Martin, J. L.; Williams, H.

2016-02-01

Bacteriophages (phages) are considered to be a major contributor to bacterial mortality. Although recent evidence shows a similar role for the predatory bacterium, Halobacteriovorax (HBx), this organism has been largely ignored. We designed controlled laboratory microcosm studies to examine and compare the predation of a virus and an HBx strain on Vibrio vulnificus (Vv), under a range of environmental conditions. Predator-prey models were used to simulate the results and interpolated using Matlab software. The results show that although the HBx and virus both preyed on Vv, the magnitudes of their respective responses were different and were largely driven by environmental conditions. In low nutrient seawater, HBx was highly active in preying on Vv, resulting in a 4.4 log reduction of prey within 40 hours, whereas phage contributed little to bacterial mortality. However, when nutrients were added to the seawater, phage was the more active predator. At moderate levels of nutrient concentrations (DNB 1:10 and DNB 1:100) both predators were active. Both virus and HBx grew well at salt concentrations ranging from 9 to 30 ppt. Phage reproduction was optimized at 30 ppt and also occurred at higher levels at 40 and 45 ppt. HBx, on the other hand, grew best at 9 ppt and did not grow at 40 and 45 ppt. At temperatures between 15 and 37˚C both predators grew well. The impact of predation on Vv was positively correlated with temperature. The collective results of this study suggest that both HBx and phages can play significant roles in bacterial mortality and hence in shaping microbial communities and cycling nutrients. However, whether HBx or phages play the larger role in any circumstance may be orchestrated by environmental conditions. These results warrant reconsideration of the roles of different biological agents and the environment in bacteria mortality.

Post-traumatic growth in adult survivors of brain injury: a qualitative study of participants completing a pilot trial of brief positive psychotherapy.

PubMed

Karagiorgou, Olga; Evans, Jonathan J; Cullen, Breda

2018-03-01

Post-traumatic growth (PTG) can occur following acquired brain injury (ABI). It has been proposed that people experiencing psychological distress following ABI may benefit from a positive psychotherapy intervention (PPT) aimed at increasing well-being; PPT may also influence PTG. We aimed to investigate PTG experiences in participants of a positive psychotherapy pilot trial. ABI survivors who had received PPT or treatment as usual (TAU) were interviewed individually after the end of the trial. Thematic analysis was conducted, to code transcripts for known themes from PTG literature as well as newly emerging themes. Four participants (age = 46-62; n = 3 male; months since injury = 11-20) from the PPT group and three (age = 58-74; n = 2 male; months since injury = 9-22) from the TAU group were interviewed. Six themes were shared across both groups: personal strength, appreciation of life, relating to others, optimism/positive attitude, feeling fortunate compared to others, and positive emotional/behavioral changes. Two themes were expressed by PPT participants only: lifestyle improvements and new possibilities. One TAU participant reported spiritual change. A greater understanding of the development of PTG following ABI may help rehabilitation clinicians to promote better adjustment by focusing on clients' potential for positive change and enhancing their capacity for growth. Implications for Rehabilitation Post-traumatic growth is "positive psychological change experienced as the result of the struggle with highly challenging life circumstances." This is the first qualitative investigation of post-traumatic growth in participants in a positive psychotherapy trial following acquired brain injury. Several post-traumatic growth themes were shared by participants from the positive psychotherapy and treatment as usual study arms, with additional themes evident only in positive psychotherapy participants. A greater understanding of post-traumatic growth among rehabilitation professionals may help to promote adjustment following brain injury.

Control of Wilt and Rot Pathogens of Tomato by Antagonistic Pink Pigmented Facultative Methylotrophic Delftia lacustris and Bacillus spp.

PubMed

Janahiraman, Veeranan; Anandham, Rangasamy; Kwon, Soon W; Sundaram, Subbiah; Karthik Pandi, Veeranan; Krishnamoorthy, Ramasamy; Kim, Kiyoon; Samaddar, Sandipan; Sa, Tongmin

2016-01-01

The studies on the biocontrol potential of pink pigmented facultative methylotrophic (PPFM) bacteria other than the genus Methylobacterium are scarce. In the present study, we report three facultative methylotrophic isolates; PPO-1, PPT-1, and PPB-1, respectively, identified as Delftia lacustris, Bacillus subtilis , and Bacillus cereus by 16S rRNA gene sequence analysis. Hemolytic activity was tested to investigate the potential pathogenicity of isolates to plants and humans, the results indicates that the isolates PPO-1, PPT-1, and PPB-1 are not pathogenic strains. Under in vitro conditions, D. lacustris PPO-1, B . subtilis PPT-1, and B . cereus PPB-1 showed direct antagonistic effect by inhibiting the mycelial growth of fungal pathogens; Fusarium oxysporum f. sp. lycopersici (2.15, 2.05, and 1.95 cm), Sclerotium rolfsii (2.14, 2.04, and 1.94 cm), Pythium ultimum (2.12, 2.02, and 1.92 cm), and Rhizoctonia solani (2.18, 2.08, and 1.98 cm) and also produced volatile inhibitory compounds. Under plant growth chamber condition methylotrophic bacterial isolates; D . lacustris PPO-1, B . subtilis PPT-1, and B. cereus PPB-1 significantly reduced the disease incidence of tomato. Under greenhouse condition, D . lacustris PPO-1, B . subtilis PPT-1, and B . cereus PPB-1 inoculated tomato plants, when challenged with F . oxysporum f. sp. lycopersici, S . rolfsii, P . ultimum , and R . solani , increased the pathogenesis related proteins (β-1,3-glucanase and chitinase) and defense enzymes (phenylalanine ammonia lyase, peroxidase, polyphenol oxidase, and catalase) on day 5 after inoculation. In the current study, we first report the facultative methylotrophy in pink pigmented D. lacustris, B . subtilis , and B . cereus and their antagonistic potential against fungal pathogens. Direct antagonistic and ISR effects of these isolates against fungal pathogens of tomato evidenced their possible use as a biocontrol agent.

Simple Test of Manual Dexterity Can Help to Identify Persons at High Risk for Neurodegenerative Diseases in the Community.

PubMed

Darweesh, Sirwan K L; Wolters, Frank J; Hofman, Albert; Stricker, Bruno H; Koudstaal, Peter J; Ikram, M Arfan

2017-01-01

Early identification of individuals at high risk of developing neurodegenerative diseases is essential for timely preventive intervention. However, simple methods that can be used for risk assessment in general practice are lacking. Within the population-based Rotterdam Study, we used the Purdue Pegboard Test (PPT) to assess manual dexterity in 4,856 persons (median age 70 years, 58% women) free of parkinsonism and dementia between 2000 and 2004. We followed these persons until January 1, 2012 for the onset of neurodegenerative diseases (defined as first diagnosis of parkinsonism or dementia). We determined the association of PPT scores with incident neurodegenerative disease, adjusting for age, sex, study cohort, level of education, smoking, preferred hand, parental history, memory complaints, and Mini-Mental State Examination. Furthermore, we determined the incremental predictive value of PPT, expressed as change in risk classification and discrimination. During follow-up (median 9.2 years), 277 participants were diagnosed with a neurodegenerative disease (227 with dementia and 50 with parkinsonism). Lower PPT scores were associated with higher risk of incident neurodegenerative diseases (hazard ratio [HR] = 1.28, 95% confidence interval [CI]: 1.18-1.41) and improved discrimination of incident neurodegenerative diseases. We also observed significant associations of PPT scores separately with incident dementia (HR = 1.25; 95% CI: 1.14-1.39]) and incident parkinsonism (HR = 1.41; 95% CI: 1.19-1.67). A rapid, nonlaboratory test of manual dexterity may help to identify persons at high risk for neurodegenerative diseases. This highlights the importance of motor function in the preclinical phase of both dementia and parkinsonism and may aid in selecting individuals for refined screening and neuroprotective trials. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Abridged geriatric assessment is a better predictor of overall survival than the Karnofsky Performance Scale and Physical Performance Test in elderly patients with cancer.

PubMed

Ghosn, Marwan; Ibrahim, Tony; El Rassy, Elie; Nassani, Najib; Ghanem, Sassine; Assi, Tarek

2017-03-01

Comprehensive geriatric assessment (CGA) is a complex and interdisciplinary approach to evaluate the health status of elderly patients. The Karnofsky Performance Scale (KPS) and Physical Performance Test (PPT) are less time-consuming tools that measure functional status. This study was designed to assess and compare abridged geriatric assessment (GA), KPS and PPT as predictive tools of mortality in elderly patients with cancer. This prospective interventional study included all individuals aged >70years who were diagnosed with cancer during the study period. Subjects were interviewed directly using a procedure that included a clinical test and a questionnaire composed of the KPS, PPT and abridged GCA. Overall survival (OS) was the primary endpoint. The log rank test was used to compare survival curves, and Cox's regression model (forward procedure) was used for multivariate survival analysis. One hundred patients were included in this study. Abridged GA was the only tool found to predict mortality [median OS for unfit patients (at least two impairments) 467days vs 1030days for fit patients; p=0.04]. Patients defined as fit by mean PPT score (>20) had worse median OS (560 vs 721days); however, this difference was not significant (p=0.488 on log rank). Although median OS did not differ significantly between patients with low (≤80) and high (>80) KPS scores (467 and 795days, respectively; p=0.09), survival curves diverged after nearly 120days of follow-up. Visual and hearing impairments were the only components of abridged GA of prognostic value. Neither KPS nor PPT were shown to predict mortality in elderly patients with cancer whereas abridged GA was predictive. This study suggests a possible role for visual and hearing assessment as screening for patients requiring CGA. Copyright © 2016 Elsevier Ltd. All rights reserved.

US Geological Survey Toxic Substances Hydrology Program: Proceedings of the technical meeting, Phoenix, Arizona, September 26-30, 1988

USGS Publications Warehouse

Mallard, Gail E.; Ragone, Stephen E.

1989-01-01

Crude oil floating at the surface of a shallow aquifer of glacial outwash, near Bemidji, Minnesota, is altered by geochemical processes. Hydrocarbons from the oil are attenuated by several reactions that include aerobic and anaerobic microbial degradation. These degradation reactions result in the development of geochemical facies in the shallow groundwater system. Groundwater most affected by the presence of organic compounds is anoxic, and concentrations of methane, dissolved organic carbon, and total inorganic are high--0.76 millimole/L, 2.9 millimole/L, and 12.3 millimole/L, respectively. The concentrations of chemical species and delta-(13)C isotope values indicate that the plume near the oil lens has become progressively more reducing. Over a 4-year period (1984 through 1987), the concentrations of methane and iron have increased by a factor of > 25. The data suggest that sequential degradation occurs, as predicted by thermo-dynamics: manganese is reduced before iron is reduced, which occurs before methanogenesis. These data provide field evidence that reduction of iron and manganese is an important mechanism of decomposition of organic matter in aquifers. The delta-(13)C values of inorganic carbon of the native groundwater range from -12 ppt to -15 ppt as a result of mixing of soil CO2 with CO2 from the dissolution of carbonates. Non methanogenic biodegradation of oil constituents adds isotopically light CO2 to the groundwater because the oil has a delta-(13)C value of 28 ppt. The delta-(13)C value of inorganic carbon in the reducing zone have become progressively heavier from 1985 through 1987. The maximum change occurs 15 m downgradient from the oil lens, where the delta-(13)C values increased from -21.6 ppt to -5.35 ppt. This change indicates that the plume has become more reducing and methanogenic over time. 

Pressure pain thresholds and musculoskeletal morbidity in automobile manufacturing workers.

PubMed

Gold, Judith E; Punnett, Laura; Katz, Jeffrey N

2006-02-01

Reduced pressure pain thresholds (PPTs) have been reported in occupational groups with symptoms of upper extremity musculoskeletal disorders (UEMSDs). The purpose of this study was to determine whether automobile manufacturing workers (n=460) with signs and symptoms of UEMSDs had reduced PPTs (greater sensitivity to pain through pressure applied to the skin) when compared with unaffected members of the cohort, which served as the reference group. The association of PPTs with symptom severity and localization of PE findings was investigated, as was the hypothesis that reduced thresholds would be found on the affected side in those with unilateral physical examination (PE) findings. PPTs were measured during the workday at 12 upper extremity sites. A PE for signs of UEMSDs and symptom questionnaire was administered. After comparison of potential covariates using t tests, linear regression multivariable models were constructed with the average of 12 sites (avgPPT) as the outcome. Subjects with PE findings and/or symptoms had a statistically significant lower avgPPT than non-cases. AvgPPT was reduced in those with more widespread PE findings and in those with greater symptom severity (test for trend, P

Control of Wilt and Rot Pathogens of Tomato by Antagonistic Pink Pigmented Facultative Methylotrophic Delftia lacustris and Bacillus spp.

PubMed Central

Janahiraman, Veeranan; Anandham, Rangasamy; Kwon, Soon W.; Sundaram, Subbiah; Karthik Pandi, Veeranan; Krishnamoorthy, Ramasamy; Kim, Kiyoon; Samaddar, Sandipan; Sa, Tongmin

2016-01-01

The studies on the biocontrol potential of pink pigmented facultative methylotrophic (PPFM) bacteria other than the genus Methylobacterium are scarce. In the present study, we report three facultative methylotrophic isolates; PPO-1, PPT-1, and PPB-1, respectively, identified as Delftia lacustris, Bacillus subtilis, and Bacillus cereus by 16S rRNA gene sequence analysis. Hemolytic activity was tested to investigate the potential pathogenicity of isolates to plants and humans, the results indicates that the isolates PPO-1, PPT-1, and PPB-1 are not pathogenic strains. Under in vitro conditions, D. lacustris PPO-1, B. subtilis PPT-1, and B. cereus PPB-1 showed direct antagonistic effect by inhibiting the mycelial growth of fungal pathogens; Fusarium oxysporum f. sp. lycopersici (2.15, 2.05, and 1.95 cm), Sclerotium rolfsii (2.14, 2.04, and 1.94 cm), Pythium ultimum (2.12, 2.02, and 1.92 cm), and Rhizoctonia solani (2.18, 2.08, and 1.98 cm) and also produced volatile inhibitory compounds. Under plant growth chamber condition methylotrophic bacterial isolates; D. lacustris PPO-1, B. subtilis PPT-1, and B. cereus PPB-1 significantly reduced the disease incidence of tomato. Under greenhouse condition, D. lacustris PPO-1, B. subtilis PPT-1, and B. cereus PPB-1 inoculated tomato plants, when challenged with F. oxysporum f. sp. lycopersici, S. rolfsii, P. ultimum, and R. solani, increased the pathogenesis related proteins (β-1,3-glucanase and chitinase) and defense enzymes (phenylalanine ammonia lyase, peroxidase, polyphenol oxidase, and catalase) on day 5 after inoculation. In the current study, we first report the facultative methylotrophy in pink pigmented D. lacustris, B. subtilis, and B. cereus and their antagonistic potential against fungal pathogens. Direct antagonistic and ISR effects of these isolates against fungal pathogens of tomato evidenced their possible use as a biocontrol agent. PMID:27872630

Species Profiles. Life Histories and Environmental Requirements of Coastal Fishes and Invertebrates (Gulf of Mexico). COMMON RANGIA.

DTIC Science & Technology

1985-04-01

osmoconformer at salinities greater ENVIRONMENTAL REQUIREMENTS than 10 ppt, and an osmoregulator at lower salinities (Bedford and Anderson 1972a,b; Otto...1973, 1974) tested the combined effects of temperature (8 to 32°C) and salinity (0 to 20 ppt) on .. k6.. Temperature embryos and larvae of common...Bedford, W. B. , and J. W. Anderson. Allen, K. 1961. The effect of salin - 1972a. The physiological response ity on the amino acid concentra- of the

Long Range Spoil Disposal Study. Part I. General Data for the Delaware River,

DTIC Science & Technology

1969-01-01

estimated approximately four and a half miles off- annual saving of $2,400,000. shore in the vicinity of Big Stone Beach, The feasibility plan for the ter...portioned to the rates of inflow to assure a In the case of pipeline dredging, also long detention period and presumably good bucket or dipper dredging, the...District is in process owned pipeline, dipper , and bucket dredges, of reducing the 13 ppt limitation to 8 ppt in also specially designed plant for the

Environmental Impact Statement/Environmental Impact Report for the Disposal and Reuse of Mare Island Naval Shipyard Vallejo, California. Volume 2.

DTIC Science & Technology

1998-04-01

from estuarine waters F-12 12 up to 14 ppt salinity (Moyle et al. 1992). For a large part of its annual life span, this species is associated...with the freshwater edge of the mixing zone (saltwater-freshwater interface), where the salinity is approximately 2 ppt (Ganssle 1966, Moyle et al...1992, Sweetnam and Stevens 1993). The delta smelt is adapted to living in the highly productive Estuary where salinity varies spatially and

A Comparative Analysis of the Resources Required for Test and Evaluation on Army-Led Weapon System Programs, Based Upon Program Size and Acquisition Management Complexity

DTIC Science & Technology

2007-12-01

Program Manager PMO Program Manager Office POM Program Objective Memorandum PPE Personal Protective Equipment PPT Production Prove...test • Technical feasibility test • Engineering development test • Production prove-out test ( PPT ) • Software qualification test 22 • Live fire...improvement BIDS (P3I) system is equipped with a detection suite to include high volume samplers, a fluorescent particle counter/sizer, a flow

Crony Attack: Strategic Attack’s Silver Bullet

DTIC Science & Technology

2006-11-01

Politics. 1. Bueno de Mesquita et al ., “Policy Failure and Political Survival,” 14–1. 1. Ibid., 149. 19. Ibid., 0. 20. Kirschner, “Microfoundations of...fighting. Notes 1. See Bueno de Mesquita et al ., “Policy Failure and Political Survival,” 147–61. 2. For more discussion of leadership’s manipulation...accessed 2 April 2003). http://www.d-i.net/fcs/;ppt/ellis_ kosovo_aar.ppt#315,7,Short War Syndrome (accessed 14 July 2006). Bueno de Mesquita, Bruce, et al

Structure-based design synthesis of functionalized 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-2H-chromen-2-one motifs and indigenous plant extracts and their antimalarial potential

NASA Astrophysics Data System (ADS)

Olayinka, Ajani; Grace, Olasehinde; Titilope, Dokunmu; Ruth, Diji-Geske; Olabode, Onileere; John, Openibo; Oreoluwa, Oluseye; Tochukwu, Chileke; Ezekiel, Adebiyi

2018-04-01

Resistance of the malaria parasite to conventional therapeutic agents calls for increased efforts in antimalarial drug discovery. Current efforts should be targeted at developing safe and affordable new agents to counter the spread of malaria parasites that are resistant to existing therapy. In this study, toxicological and in vivo antiplasmodial properties of 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-42H-chromen-2, Mangifera indica and Tithonia diversifolia in swiss albino mice models, Musmusculus were investigated. 2H-Chromen-2-one also known as coumarin is highly privileged oxygen-containing heterocyclic entity which are present in plant kingdom as secondary metabolites. The maceration technique of crude drug extraction was employed using cold water extraction. Toxicological analysis was carried out using Lorke's method for acute toxicity testing while the chemosuppressive activity was carried out using Peter's four day test on early infection. We also report the synthesis of functionalized 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-2H-chromen-2-one motifs via microwave assisted synthetic approach and isolation of indigenous plant extract in order to investigate their antimalarial efficacy. The condensation reaction of 3-acetylcoumarin with various benzaldehyde derivatives resulted in the formation of 3-[3-acryloyl]-2H-chromen-2-one which was subsequently reaction the hydrazine hydrate via microwave assisted hydrazinolysis to afford the targeted 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-2H-chromen-2-one motifs. The chemical structures were confirmed by analytical data and spectroscopic means such as FT-IR, UV, 1H NMR, 13C NMR and DEPT-135. The microwave assisted reaction was remarkably successful and gave targeted 3-(5-(s-phenyl)-4H-pyrazol-3-yl)-2H-chromen-2-one motifs in higher yields at lesser reaction time compared to conventional heating method. The LD50 of the aqueous extracts of the leaves and stem bark Mangifera indica was established to be ± 707.11 mg/kg b.w., p.o. (body weight, administered orally) in mice. Tithonia diversifolia aqueous leaf extracts is non-toxic at doses as high as 1000 mg/kg while the LD50 of the ethanolic leaf extracts was established to be ± 707.11 mg/kg b.w., p.o. in mice. The in vivo antiplasmodial activity was studied in chloroquine-sensitive Plasmodium berghei berghei - NK65 infected mice. All the plant extracts, at the doses (100, 200 and 400 mg/kg b.w., p.o.) used, produced significant (p < 0.05), dose dependent activity (> 80% inhibition of parasitaemia at maximum dose) against the parasite in the suppressive tests. The in vitro antimalarial screening of the synthesized compounds is presently on-going and the finding will be reported in due course.

Pulsed Plasma Thruster Contamination

NASA Technical Reports Server (NTRS)

Myers, Roger M.; Arrington, Lynn A.; Pencil, Eric J.; Carter, Justin; Heminger, Jason; Gatsonis, Nicolas

1996-01-01

Pulsed Plasma Thrusters (PPT's) are currently baselined for the Air Force Mightysat II.1 flight in 1999 and are under consideration for a number of other missions for primary propulsion, precision positioning, and attitude control functions. In this work, PPT plumes were characterized to assess their contamination characteristics. Diagnostics included planar and cylindrical Langmuir probes and a large number of collimated quartz contamination sensors. Measurements were made using a LES 8/9 flight PPT at 0.24, 0.39, 0.55, and 1.2 m from the thruster, as well as in the backflow region behind the thruster. Plasma measurements revealed a peak centerline ion density and velocity of approx. 6 x 10(exp 12) cm(exp -3) and 42,000 m/s, respectively. Optical transmittance measurements of the quartz sensors after 2 x 10(exp 5) pulses showed a rapid decrease in plume contamination with increasing angle from the plume axis, with a barely measurable transmittance decrease in the ultraviolet at 90 deg. No change in optical properties was detected for sensors in the backflow region.

Potential use of the facultative halophyte Chenopodium quinoa Willd. as substrate for biogas production cultivated with different concentrations of sodium chloride under hydroponic conditions.

PubMed

Turcios, Ariel E; Weichgrebe, Dirk; Papenbrock, Jutta

2016-03-01

This project analyses the biogas potential of the halophyte Chenopodium quinoa Willd. In a first approach C. quinoa was grown with different concentrations of NaCl (0, 10 and 20 ppt NaCl) and the crop residues were used as substrate for biogas production. In a second approach, C. quinoa was grown with 0, 10, 20 and 30 ppt NaCl under hydroponic conditions and the fresh biomass was used as substrate. The more NaCl is in the culture medium, the higher the sodium, potassium, crude ash and hemicellulose content in the plant tissue whereas the calcium, sulfur, nitrogen and carbon content in the biomass decrease. According to this study, it is possible to produce high yields of methane using biomass of C. quinoa. The highest specific methane yields were obtained using the substrate from the plants cultivated at 10 and 20 ppt NaCl in both experiments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurophysiological and clinical effects of dry needling in patients with upper trapezius myofascial trigger points.

PubMed

Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

2017-01-01

Dry needling (DN) is a widely used in treatment of myofascial trigger points (MTrPs). The purpose of this pretest-posttest clinical trial was to investigate the neurophysiological and clinical effects of DN in patients with MTrPs. A sample of 20 patients (3 man, 17 women; mean age 31.7 ± 10.8) with upper trapezius MTrPs received one session of deep DN. The outcomes of neuromuscular junction response (NMJR), sympathetic skin response (SSR), pain intensity (PI) and pressure pain threshold (PPT) were measured at baseline and immediately after DN. There were significant improvements in SSR latency and amplitude, pain, and PPT after DN. The NMJR decreased and returned to normal after DN. A single session of DN to the active upper trapezius MTrP was effective in improving pain, PPT, NMJR, and SSR in patients with myofascial trigger points. Further studies are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Highly reactive light-dependent monoterpenes in the Amazon

DOE PAGES

Jardine, A. B.; Jardine, K. J.; Fuentes, J. D.; ...

2015-03-06

Despite orders of magnitude difference in atmospheric reactivity and great diversity in biological functioning, little is known about monoterpene speciation in tropical forests. Here we report vertically resolved ambient air mixing ratios for 12 monoterpenes in a central Amazon rainforest including observations of the highly reactive cis-β-ocimene (160 ppt), trans-β-ocimene (79 ppt), and terpinolene (32 ppt) which accounted for an estimated 21% of total monoterpene composition yet 55% of the upper canopy monoterpene ozonolysis rate. All 12 monoterpenes showed a mixing ratio peak in the upper canopy, with three demonstrating subcanopy peaks in 7 of 11 profiles. Leaf level emissionsmore » of highly reactive monoterpenes accounted for up to 1.9% of photosynthesis confirming light-dependent emissions across several Amazon tree genera. These results suggest that highly reactive monoterpenes play important antioxidant roles during photosynthesis in plants and serve as near-canopy sources of secondary organic aerosol precursors through atmospheric photooxidation via ozonolysis.« less

Dioxins and dibenzofurans in adipose tissue of U. S. Vietnam veterans and controls

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

Kang, H.K.; Watanabe, K.K.; Breen, J.

1990-08-01

Concern about the adverse effects of exposure to Agent Orange is for the most part attributable to its toxic contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A total of 40 Vietnam veterans, 80 non-Vietnam veterans and 80 civilian men were selected from males born between 1936 and 1954 and their adipose tissues were analyzed for 17 2,3,7,8-substituted dioxins and dibenzofurans. TCDD levels were log normally distributed and the mean level of 2,3,7,8-TCDD in adipose tissue of the Vietnam veterans (13.4 ppt) was not significantly different from that of the non-Vietnam veterans (12.5 ppt) or civilian men (15.8 ppt). Adjusting for demographic variables did notmore » change the conclusions. The study results suggest that heavy exposure to Agent Orange for most Vietnam veterans was very unlikely and that there is no readily available and reliable indirect method of assessing exposure to Agent Orange for Vietnam veterans.« less

Modern inhalation anesthetics: Potent greenhouse gases in the global atmosphere

NASA Astrophysics Data System (ADS)

Vollmer, Martin K.; Rhee, Tae Siek; Rigby, Matt; Hofstetter, Doris; Hill, Matthias; Schoenenberger, Fabian; Reimann, Stefan

2015-03-01

Modern halogenated inhalation anesthetics undergo little metabolization during clinical application and evaporate almost completely to the atmosphere. Based on their first measurements in a range of environments, from urban areas to the pristine Antarctic environment, we detect a rapid accumulation and ubiquitous presence of isoflurane, desflurane, and sevoflurane in the global atmosphere. Over the past decade, their abundances in the atmosphere have increased to global mean mole fractions in 2014 of 0.097ppt, 0.30ppt, and 0.13ppt (parts per trillion, 10-12, in dry air), respectively. Emissions of these long-lived greenhouse gases inferred from the observations suggest a global combined release to the atmosphere of 3.1 ± 0.6 million t CO2 equivalent in 2014 of which ≈80% stems from desflurane. We also report on halothane, a previously widely used anesthetic. Its global mean mole fraction has declined to 9.2ppq (parts per quadrillion, 10-15) by 2014. However, the inferred present usage is still 280 ±120t yr-1.

The effect of vitamin D on thyroid autoimmunity in non-lactating women with postpartum thyroiditis.

PubMed

Krysiak, R; Kowalcze, K; Okopien, B

2016-05-01

The study included 38 non-lactating l-thyroxine-treated women with postpartum thyroiditis (PPT) and 21 matched healthy postpartum women. Women with vitamin D deficiency were treated with oral vitamin D (4000 IU daily), whereas women with vitamin D insufficiency and women with normal 25-hydroxy vitamin levels were either treated with vitamin D (2000 IU daily) or left untreated. Serum hormone levels and thyroid antibody titers were measured at the beginning of the study and 3 months later. 25-hydroxy vitamin D levels were lower in women with PPT than in healthy women. Thyroid peroxidase and thyroglobulin antibody titers inversely correlated with vitamin D status. Apart from increasing serum levels of 25-hydroxy vitamin D and decreasing serum levels of parathyroid hormone, vitamin D reduced titers of thyroid peroxidase antibodies and this effect was stronger in women with vitamin D deficiency. The study's results suggest that vitamin D supplementation may bring benefits to l-thyroxine-treated women with PPT.

Synthesis, characterization and computational chemical study of novel pyrazole derivatives as anticorrosion and antiscalant agents

NASA Astrophysics Data System (ADS)

El-Taib Heakal, F.; Attia, S. K.; Rizk, S. A.; Abou Essa, M. A.; Elkholy, A. E.

2017-11-01

Metals corrosion and scales deposition are two serious problems of heavy burden in most industries. Both problems can be mitigated by adding special chemicals capable of being adsorbed on metallic surfaces as well as on scale growing crystal surfaces. Efficient materials should be rich in functional groups containing heteroatoms and/or π bonds for supporting their adsorbability on surfaces. In the present work, four novel pyrazole derivatives were synthesized and characterized for their structures using elemental analysis and spectroscopic tools. The tested compounds were fabricated by treating 2,3-diaryloxirane-2,3-dicarbonitriles with different nitrogen nucleophiles. The density functional theory (DFT) was then applied to explore the structural and electronic characteristics of these materials. Molecular dynamics simulation was also run to scrutinize the ability of the prepared compounds to act as corrosion inhibitors and antiscalant agents by adsorbing on Fe and CaSO4 surfaces.

Interactions between pyrazole derived enantiomers and Chiralcel OJ: Prediction of enantiomer absolute configurations and elution order by molecular dynamics simulations.

PubMed

Hu, Guixiang; Huang, Meilan; Luo, Chengcai; Wang, Qi; Zou, Jian-Wei

2016-05-01

The separation of enantiomers and confirmation of their absolute configurations is significant in the development of chiral drugs. The interactions between the enantiomers of chiral pyrazole derivative and polysaccharide-based chiral stationary phase cellulose tris(4-methylbenzoate) (Chiralcel OJ) in seven solvents and under different temperature were studied using molecular dynamics simulations. The results show that solvent effect has remarkable influence on the interactions. Structure analysis discloses that the different interactions between two isomers and chiral stationary phase are dependent on the nature of solvents, which may invert the elution order. The computational method in the present study can be used to predict the elution order and the absolute configurations of enantiomers in HPLC separations and therefore would be valuable in development of chiral drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel coumarin-pyrazole-triazine based fluorescence chemosensor for fluoride detection via deprotonation process: Experimental and theoretical studies

NASA Astrophysics Data System (ADS)

Yalçın, Ergin; Alkış, Meltem; Seferoğlu, Nurgül; Seferoğlu, Zeynel

2018-03-01

A novel fluorescence coumarin-pyrazole-triazine based chemosensor (CPT) bearing 5-hydroxypyrazole as a receptoric part was synthesized and characterized by using IR, 1H/13C NMR and HRMS for the purpose of recognition of anions in DMSO. The most stable tautomeric form of CPT was determined by experimental techniques and theoretical calculations. The selectivity and sensitivity of CPT towards anions (CN-, F-, Cl-, Br-, I-, AcO-, HSO4-, H2PO4- and ClO4-) were determined using spectrophotometric and 1H NMR titration techniques as the experimental approach, and the results were explained by employing theoretical calculations. It was found to be suitable for the selective detection of F- in the presence of CN- and AcO- as competing anions. In addition, CPT exhibits significant "light-up" effect after interaction with TFA in CH2Cl2.

N-Acetonitrile Functionalized Nitropyrazoles: Precursors to Insensitive Asymmetric N-Methylene-C Linked Azoles.

PubMed

Kumar, Dheeraj; Imler, Gregory H; Parrish, Damon A; Shreeve, Jean'ne M

2017-06-12

Properties of energetic compounds obtained by linking energetic pyrazoles to tetrazoles by means of N-methylene-C bridges can be fine-tuned. Reactions of pyrazole derivatives with chloroacetonitrile followed by conversion of the cyano group to tetrazole using click reactions in the presence of zinc chloride result in asymmetric N-methylene-C bridged azole-based energetic compounds. All the compounds were thoroughly characterized by IR and NMR [ 1 H, 13 C { 1 H}, 15 N] spectroscopy, elemental analysis, and differential scanning calorimetry (DSC), and for two compounds, further supported by single-crystal X-ray diffraction studies. Heats of formation and detonation performances were calculated using Gaussian 03 and EXPLO5 v6.01 programs, respectively. Initial studies show that this new approach is promising for synthesizing less sensitive energetic compounds with fine-tuned properties. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis, structural characterization and theoretical studies of a new Schiff base 4-(((3-(tert-Butyl)-(1-phenyl)pyrazol-5-yl) imino)methyl)phenol

NASA Astrophysics Data System (ADS)

Cuenú, Fernando; Londoño-Salazar, Jennifer; Torres, John Eduard; Abonia, Rodrigo; D'Vries, Richard F.

2018-01-01

4-(((3-(tert-Butyl)-(1-phenyl)pyrazol-5-yl)imino)methyl)phenol (4-OHFPz) was synthesized and characterized by FT-IR, MS, NMR, and single-crystal X-ray diffraction. Optimization of molecular geometry, vibrational frequencies, and chemical shifts were calculated by using the methods of density functional theory (DFT) with B3LYP and B3PW91 as functionals and Hartree-Fock with 6-311G++(d,p) as basis set using the GAUSSIAN 09 program package. With the VEDA 4 software, the vibrational frequencies were assigned in terms of the potential energy distribution (PED). The equilibrium geometries calculated by all methods were compared with X-ray diffraction results, indicating that the theoretical results matches well with the experimental ones. The data obtained from the vibrational analysis and the calculated NMR are consistent with the experimental spectra.

Synthesis, optical properties and application of a set of novel pyrazole nopinone derivatives.

PubMed

Yang, Jinlai; Xu, Xu; Rui, Jian; Wang, Zhonglong; Zhang, Yan; Wang, Shifa; Wu, Liangru

2017-08-05

Pyrazole derivatives (4-6) were directly synthesized from β-pinene derivative nopinone, and they were characterized by Fourier transform infrared (FTIR) spectoscope, nuclear magnetic resonance (NMR), and mass spectrometry. Their optical properties were investigated by ultraviolet-visible spectroscopy and fluorescence spectroscopy. The three compounds emitted strong blue fluorescence in ethanol. Using a fluorescence quenching method, compound 4 could be used to detect the content (100.57%) of copper sulfate pentahydrate (≥99%) with a RSD of 1.98%, y=-0.1127×+2.7148, R 2 =0.9703 (Cu 2+ : 0.5-8.0×10 -5 mol/L), and compounds 4-6 also had utility of calculating the content of anhydrous ferric chloride at a wide range of concentration. Thus, compounds 4-6 are new functional fluorescents for detecting the content of some purchased products. Copyright © 2017 Elsevier B.V. All rights reserved.

DFT, FT-IR, FT-Raman and NMR studies of 4-(substituted phenylazo)-3,5-diacetamido-1H-pyrazoles

NASA Astrophysics Data System (ADS)

Kınalı, Selin; Demirci, Serkan; Çalışır, Zühre; Kurt, Mustafa; Ataç, Ahmet

2011-05-01

We present a detailed analysis of the structural and vibrational spectra of some novel azo dyes. 2-(Substituted phenylazo)malononitriles were synthesized by the coupling reaction of the diazonium salts, which were prepared with the use of various aniline derivatives with malononitrile, and then 4-(substituted phenylazo)-3,5-diamino-1H-pyrazole azo dyes were obtained via the ring closure of the azo compounds with hydrazine monohydrate. The experimental and theoretical vibrational spectra of azo dyes were studied. The structural and spectroscopic analysis of the molecules were carried out by using Becke's three-parameters hybrid functional (B3LYP) and density functional harmonic calculations. The 1H nuclear magnetic resonance (NMR) chemical shifts of the azo dye molecules were calculated using the gauge-invariant-atomic orbital (GIAO) method. The calculated vibrational wavenumbers and chemical shifts were compared with the experimental data of the molecules.

Client attachment in a randomized clinical trial of psychoanalytic and cognitive-behavioral psychotherapy for bulimia nervosa: Outcome moderation and change.

PubMed

Daniel, Sarah Ingrid Franksdatter; Poulsen, Stig; Lunn, Susanne

2016-06-01

In the context of a randomized clinical trial of psychoanalytic psychotherapy (PPT) versus cognitive behavior therapy (CBT) for bulimia nervosa (BN), this study performed secondary analyses of (a) the relation between attachment and pretreatment symptom levels, (b) whether client pretreatment attachment moderated treatment outcome, (c) whether change in client attachment was associated with symptomatic change, and (d) whether client attachment changed differently in the 2 treatments. Sixty-nine women and 1 man of a mean age of 25.8 years diagnosed with BN were randomly assigned to either 2 years of weekly PPT or 5 months of CBT. Assessments at intake, after 5 months, and after 2 years included the Eating Disorder Examination to assess eating disorder symptoms, the Adult Attachment Interview to assess client attachment, and the Symptom Checklist 90-R to assess general psychiatric distress. Repeated measures were analyzed using multilevel analysis. Higher scores on attachment insecurity and attachment preoccupation were associated with more frequent binging pretreatment. Pretreatment attachment did not predict treatment outcome. In PPT, but not in CBT, reduction of binging was associated with an increase in attachment security. The 2 treatment types were not associated with significantly different patterns of attachment-related change. Degree and type of attachment insecurity is related to the frequency of binging in BN. Increase in attachment security may be a treatment-specific mechanism of change in PPT for BN. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

HIV-1 resistance dynamics in patients failing dolutegravir maintenance monotherapy.

PubMed

Wijting, Ingeborg E A; Lungu, Cynthia; Rijnders, Bart J A; van der Ende, Marchina E; Pham, Hanh T; Mesplede, Thibault; Pas, Suzan D; Voermans, Jolanda J C; Schuurman, Rob; van de Vijver, David A M C; Boers, Patrick H M; Gruters, Rob A; Boucher, Charles A B; van Kampen, Jeroen J A

2018-03-29

A high genetic resistance barrier to the integrase-strand-transfer-inhibitor (INSTI) dolutegravir has been reported in vitro and in vivo. We describe the dynamics of INSTI-resistance-associated-mutations (INSTI-RAMs) and mutations in the 3'-polypurine tract (3'-PPT) in relation to virological failure (VF) observed in the randomized dolutegravir maintenance monotherapy study (DOMONO, NCT02401828). From ten patients with VF plasma samples prior to start cART and during VF were used to generate Sanger sequences of integrase, the 5' terminal bases of the 3'- LTR, and the 3'-PPT. Median HIV-RNA (IQR) at VF was 3,490 (1,440-4,990) c/mL. INSTI-RAMs were detected in 4/10 patients (S230R, R263K, N155H, E92Q+N155H) and in 4/10 patients no INSTI-RAMs were detected (2/10 patients integrase sequencing was unsuccessful). The time-to-VF ranged from 4 weeks to 72 weeks. In one patient, mutations developed in the highly conserved 3'-PPT. No changes in the terminal bases of the 3'-LTR were observed. The genetic barrier to resistance is too low to justify dolutegravir maintenance monotherapy as single INSTI-RAMs are sufficient to cause VF. The large variation in time-to-VF suggests that stochastic reactivation of a pre-existing provirus containing a single INSTI-RAM is the mechanism for failure. Changes in the 3'-PPT point to a new dolutegravir resistance mechanism in vivo.

Profiling and multivariate statistical analysis of Panax ginseng based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

PubMed

Wu, Wei; Sun, Le; Zhang, Zhe; Guo, Yingying; Liu, Shuying

2015-03-25

An ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed for the detection and structural analysis of ginsenosides in white ginseng and related processed products (red ginseng). Original neutral, malonyl, and chemically transformed ginsenosides were identified in white and red ginseng samples. The aglycone types of ginsenosides were determined by MS/MS as PPD (m/z 459), PPT (m/z 475), C-24, -25 hydrated-PPD or PPT (m/z 477 or m/z 493), and Δ20(21)-or Δ20(22)-dehydrated-PPD or PPT (m/z 441 or m/z 457). Following the structural determination, the UHPLC-Q-TOF-MS-based chemical profiling coupled with multivariate statistical analysis method was applied for global analysis of white and processed ginseng samples. The chemical markers present between the processed products red ginseng and white ginseng could be assigned. Process-mediated chemical changes were recognized as the hydrolysis of ginsenosides with large molecular weight, chemical transformations of ginsenosides, changes in malonyl-ginsenosides, and generation of 20-(R)-ginsenoside enantiomers. The relative contents of compounds classified as PPD, PPT, malonyl, and transformed ginsenosides were calculated based on peak areas in ginseng before and after processing. This study provides possibility to monitor multiple components for the quality control and global evaluation of ginseng products during processing. Copyright © 2014 Elsevier B.V. All rights reserved.

RNA sequencing analysis of transcriptional change in the freshwater mussel Elliptio complanata after environmentally relevant sodium chloride exposure

USGS Publications Warehouse

Robertson, Laura S.; Galbraith, Heather S.; Iwanowicz, Deborah; Blakeslee, Carrie J.; Cornman, Robert S.

2017-01-01

To identify potential biomarkers of salt stress in a freshwater sentinel species, we examined transcriptional responses of the common mussel Elliptio complanata to controlled sodium chloride (NaCl) exposures. Ribonucleic acid sequencing (RNA-Seq) of mantle tissue identified 481 transcripts differentially expressed in adult mussels exposed to 2 ppt NaCl (1.2 ppt chloride) for 7 d, of which 290 had nonoverlapping intervals. Differentially expressed gene categories included ion and transmembrane transport, oxidoreductase activity, maintenance of protein folding, and amino acid metabolism. The rate-limiting enzyme for synthesis of taurine, an amino acid frequently linked to osmotic stress in aquatic species, was upregulated, as was the transmembrane ion pump sodium/potassium adenosine 5′-triphosphatase. These patterns confirm a primary transcriptional response to the experimental dose, albeit likely overlapping with nonspecific secondary stress responses. Substantial involvement of the heat shock protein 70 chaperone family and the water-transporting aquaporin family was not detected, however, in contrast to some studies in other bivalves. A subset of the most significantly regulated genes was confirmed by quantitative polymerase chain reaction in an independent sample. Cluster analysis showed separation of mussels exposed to 2 ppt NaCl from control mussels in multivariate space, but mussels exposed to 1 ppt NaCl were largely indistinguishable from controls. Transcriptome-scale analysis of salt exposure under laboratory conditions efficiently identified candidate biomarkers for further functional analysis and field validation

Changes in the vibration sensitivity and pressure pain thresholds in patients with burning mouth syndrome

PubMed Central

Ferreira, Natália dos Reis; Janini, Maria Elisa Rangel

2018-01-01

Objective To investigate the presence of changes in vibration detection and pressure pain threshold in patients with burning-mouth syndrome (BMS). Design of the study Case-control study. The sample was composed of 30 volunteers, 15 with BMS and 15 in the control group. The pressure-pain threshold (PPT) and vibration-detection threshold (VDT) were examined. The clinical evaluation was complemented with the McGill Pain Questionnaire (MPQ), Douleur Neuropathique 4 (DN4) and Beck Depression and Anxiety Inventories (BDI and BAI, respectively). Results BMS subjects showed a statistically significant higher PPT in the tongue (p = 0.002), right (p = 0.001) and left (p = 0.004) face, and a significant reduction of the VDT in the tongue (p = 0.013) and right face (p = 0.030). Significant differences were also found when comparing the PPT and the VDT of distinct anatomical areas. However, a significant interaction (group × location) was only for the PPT. BMS subjects also showed significantly higher levels of depression (p = 0.01), as measured by the BDI, compared to controls; and a significant inverse correlation between the VDT in the left face and anxiety levels was detected. Conclusions The study of somatosensory changes in BMS and its correlations with the clinical features as well as the levels of anxiety and depression expands current understanding of the neuropathic origin and the possible contribution of psychogenic factors related to this disease. PMID:29782537

Development of the quantitative indicator of abdominal examination for clinical application: a pilot study.

PubMed

Ko, Seok-Jae; Lee, Hyunju; Kim, Seul-Ki; Kim, Minji; Kim, Jinsung; Lee, Beom-Joon; Park, Jae-Woo

2015-06-01

Abdominal examination (AE) is the evaluation of the status of illness by examining the abdominal region in traditional Korean medicine (TKM). Although AE is currently considered an important diagnostic method in TKM, owing to its clinical usage, no studies have been conducted to objectively assess its accuracy and develop standards. Twelve healthy subjects and 21 patients with functional dyspepsia have participated in this study. The patients were classified into epigastric discomfort group (n=11) and epigastric discomfort with tenderness group (n=10) according to the clinical diagnosis by AE. After evaluating the subjective epigastric discomfort in all subjects, two independent clinicians measured the pressure pain threshold (PPT) two times at an acupoint (CV 14) using an algometer. We then assessed the interrater and intrarater reliability of the PPT measurements and evaluated the validity (sensitivity and specificity) via a receiver operating characteristic plot and optimal cutoff value. The results of the interrater reliability test showed a very strong correlation (correlation coefficient range: 0.82-0.91). The results of intrarater reliability test also showed a higher than average correlation (intraclass correlation coefficient: 0.58-0.70). The optimal cutoff value of PPT in the epigastric area was 1.8 kg/cm(2) with 100% sensitivity and 54.54% specificity. PPT measurements in the epigastric area with an algometer demonstrated high reliability and validity for AE, which makes this approach potentially useful in clinical applications as a new quantitative measurement in TKM.

Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis.

PubMed

Michalski, Christoph W; Shi, Xin; Reiser, Carolin; Fachinger, Patrick; Zimmermann, Arthur; Büchler, Markus W; Di Sebastiano, Pierluigi; Friess, Helmut

2007-11-01

Generation and maintenance of pain in chronic pancreatitis (CP) have been shown to be partially attributable to neuroimmune interactions, which involve neuropeptides such as substance P (SP). So far, expression of SP receptors NK-2R, NK-3R, the SP-encoding gene preprotachykinin A (PPT-A), and the SP degradation enzyme neutral endopeptidase (NEP) and their relation to pain in CP have not been determined. Tissue samples from patients with CP (n = 25) and from healthy donors (n = 20) were analyzed for PPT-A, NK-2R, NK-3R, and NEP expression using quantitative RT-PCR. NEP protein levels were examined by immunoblot analysis and its localization was determined using immunohistochemistry. A scoring system was used to grade the extent of fibrosis on hematoxylin and eosin- and Masson-Trichrome-stained sections. Messenger RNA levels and the extent of pain were analyzed for correlations. In CP tissues, NK-2R and PPT-A expression was increased, whereas NK-3R and NEP mRNA levels were comparable with normal pancreas. Overexpression of NK-2R was related to the intensity, frequency, and duration of pain in CP patients. NK-1R and NEP expression was significantly related to the extent of fibrosis. Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

Measurements of acetylene in air extracted from polar ice cores

NASA Astrophysics Data System (ADS)

Nicewonger, M. R.; Aydin, M.; Montzka, S. A.; Saltzman, E. S.

2016-12-01

Acetylene (ethyne) is a non-methane hydrocarbon emitted during combustion of fossil fuels, biofuels, and biomass. The major atmospheric loss pathway of acetylene is oxidation by hydroxyl radical with a lifetime estimated at roughly two weeks. The mean annual acetylene levels over Greenland and Antarctica are 250 ppt and 20 ppt, respectively. Firn air measurements suggest atmospheric acetylene is preserved unaltered in polar snow and firn. Atmospheric reconstructions based on firn air measurements indicate acetylene levels rose significantly during the twentieth century, peaked near 1980, then declined to modern day levels. This historical trend is similar to that of other fossil fuel-derived non-methane hydrocarbons. In the preindustrial atmosphere, acetylene levels should primarily reflect emissions from biomass burning. In this study, we present the first measurements of acetylene in preindustrial air extracted from polar ice cores. Air from fluid and dry-drilled ice cores from Summit, Greenland and WAIS-Divide Antarctica is extracted using a wet-extraction technique. The ice core air is analyzed using gas chromatography and high-resolution mass spectrometry. Between 1400 to 1800 C.E., acetylene levels over Greenland and Antarctica varied between roughly 70-120 ppt and 10-30 ppt, respectively. The preindustrial Greenland acetylene levels are significantly lower than modern levels, reflecting the importance of northern hemisphere fossil fuel sources today. The preindustrial Antarctic acetylene levels are comparable to modern day levels, indicating similar emissions in the preindustrial atmosphere, likely from biomass burning. The implications of the preindustrial atmospheric acetylene records from both hemispheres will be discussed.

Measuring ethane and acetylene in Antarctic ice cores to quantify long-term hydrocarbon emissions from tropical fires

NASA Astrophysics Data System (ADS)

Nicewonger, M. R.; Aydin, M.; Prather, M. J.; Saltzman, E. S.

2017-12-01

This study examines ethane (C2H6) and acetylene (C2H2) in polar ice cores in order to reconstruct variations in the atmospheric levels of these trace gases over the past 2,000 years. Both of these non-methane hydrocarbons are released from fossil fuel, biofuel, and biomass burning. Ethane, but not acetylene, is also emitted from natural geologic outgassing of hydrocarbons. In an earlier study, we reported ethane levels in Greenland and Antarctic ice cores showing roughly equal contributions from biomass burning and geologic emissions to preindustrial atmospheric ethane levels (Nicewonger et al., 2016). Here we introduce acetylene as an additional constraint to better quantify preindustrial variations in the emissions from these natural hydrocarbon sources. Here we present 30 new measurements of ethane and acetylene from the WDC-06A ice core from WAIS Divide and the newly drilled South Pole ice core (SPICECORE). Ethane results display a gradual decline from peak levels of 110 ppt at 1400 CE to a minimum of 60-80 ppt during 1700-1875 CE. Acetylene correlates with ethane (r2 > 0.4), dropping from peak levels of 35 ppt at 1400 CE to 15-20 ppt at 1875 CE. The covariance between the two trace gases implies that the observed changes are likely caused by decreasing emissions from low latitude biomass burning. We will discuss results from chemical transport modeling and sensitivity tests and the implications for the preindustrial ethane and acetylene budgets.

PowerPoint or chalk and talk: Perceptions of medical students versus dental students in a medical college in India.

PubMed

Seth, Vikas; Upadhyaya, Prerna; Ahmad, Mushtaq; Moghe, Vijay

2010-01-01

To assess students' perceptions of the impact of PowerPoint (PPT) presentations in lectures in comparison to the traditional chalk and talk method and lectures using transparencies and overhead projector (TOHP). The study analyzes the preferences for teaching aids of medical students versus dental students. Second year medical and dental undergraduates were asked to fill in a nine-item questionnaire about their perceptions of the three lecture delivery methods. Following analysis of the questionnaire the students were interviewed further. The results were analyzed separately for medical and dental students to see if there was any difference in their perceptions. The majority of the medical students (65.33%) preferred PPT presentations, while 15.16% of students preferred the lectures using chalkboard, and 19.51% preferred TOHP for teaching (P < 0.001). Of the dental students: 41.84% preferred chalkboard, 31.21% preferred TOHP, and 25.85% students preferred PPT presentations in the lectures (P < 0.05). Some important comments of the students were also recorded on interview which could be valuable for the medical teachers. The medical students clearly preferred the use of PPT presentations while the dental students did not. The study does not bring out evidence based superiority of any lecture delivery method. It appears that in the hands of a trained teacher any teaching aid would be appropriate and effective. This highlights the need for formal training in teaching technologies to develop good presentation skills and thus motivate the students.

High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial

PubMed Central

Lanza, Elaine; Hartman, Terryl J.; Albert, Paul S.; Shields, Rusty; Slattery, Martha; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Schatzkin, Arthur

2006-01-01

Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence. PMID:16772456

High Performance Composites Based on Polyurethanes Reinforced with Polydiacetylenes

DTIC Science & Technology

1989-04-04

Mv Niax triol LHT240 (ex. Union Carbide) is a polyoxypropylene adduct of 1,2,6- hexanetriol and after drying by rotary film evaporation had an...hompolyurethane hard segment material, HDD/MDI, which has been quench -cooled from 280 to -1000C: after DSC measurement on the same material giving the...feature in the DSC curves fig 15(c) for HDD/MDI is the development of a glass-transition at 8500 in curve B’ following quench -cooling. The ladder-like, hard

Phototransformation of the insecticide fipronil: identification of novel photoproducts and evidence for an alternative pathway of photodegradation.

PubMed

Raveton, Muriel; Aajoud, Asmae; Willison, John C; Aouadi, Heddia; Tissut, Michel; Ravanel, Patrick

2006-07-01

Fipronil is a recently discovered insecticide of the phenylpyrazole series. It has a highly selective biochemical mode of action, which has led to its use in a large number of important agronomical, household, and veterinary applications. Previous studies have shown that, during exposure to light, fipronil is converted into a desulfurated derivative (desulfinyl-fipronil), which has slightly reduced insecticidal activity. In this study, the photodegradation of fipronil was studied in solution at low light intensities (sunlight or UV lamp). In addition to desulfinyl-fipronil, a large number of minor photoproducts were observed, including diversely substituted phenylpyrazole derivatives and aniline derivatives that had lost the pyrazole ring. Desulfinylfipronil itself was shown to be relatively stable under both UV light and sunlight, with only limited changes occurring in the substitution of the aromatic ring. Since this compound accumulated to levels corresponding to only 30-55% of the amount of fipronil degraded, it was concluded that one or more alternative pathways of photodegradation must be operating. On the basis of the structurally identified photoproducts, it is proposed that fipronil photodegradation occurs via at least two distinct pathways, one of which involves desulfuration at the 4-position of the pyrazole ring giving the desulfinyl derivative and the other of which involves a different modification of the 4-substituent, leading to cleavage of the pyrazole ring and the formation of aniline derivatives. The latter compounds do not accumulate to high levels and may, therefore, be degraded further. The ecological significance of these results is discussed, particularly with regard to the insecticidal activity of the photoproducts.

Metal organic frameworks (MOFs) for magnetic solid-phase extraction of pyrazole/pyrrole pesticides in environmental water samples followed by HPLC-DAD determination.

PubMed

Ma, Jiping; Yao, Zhidan; Hou, Liwei; Lu, Wenhui; Yang, Qipeng; Li, Jinhua; Chen, Lingxin

2016-12-01

Magnetic metal-organic frameworks (MOFs, [MIL-101]) were prepared and used as magnetic solid-phase extraction (MSPE) adsorbents for preconcentration of four kinds of pyrazole/pyrrole pesticides (flusilazole, fipronil, chlorfenapyr, and fenpyroximate) in environmental water samples, followed by high-performance liquid chromatography-diode-array detector (HPLC-DAD) determination. Several variables affecting MSPE efficiency were systematically investigated, including amount of MIL-101, extraction time, sample pH, salt concentration, type of desorption solvent and desorption number of times. Under optimized conditions, excellent linearity was achieved in the range of 5.0-200.0μg/L for flusilazole and fipronil, and 2.0-200.0μg/L for chlorfenapyr and fenpyroximate, with correlation coefficients r>0.9911. Limits of detection and quantification were 0.3-1.5μg/L and 1.0-5.0μg/L, respectively. The intra-day and inter-day precision (relative standard deviation, n=6, %) at three spiked levels were 1.1-5.4% and 3.9-7.8% in terms of peak area, respectively. The method recoveries at three fortified concentration levels ranged from 81.8% to 107.5% for reservoir water samples, 81.0-99.5% for river water samples, and 80.2-106.5% for seawater samples. The developed MOFs based MSPE coupled with HPLC method proved to be a convenient, rapid and eco-friendly alternative to the sensitive determination of pyrazole/pyrrole pesticides with high repeatability and excellent practical applicability. Copyright © 2016 Elsevier B.V. All rights reserved.

Infrared, Raman and NMR spectra, conformational stability, normal coordinate analysis and B3LYP calculations of 5-Amino-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde

NASA Astrophysics Data System (ADS)

Bahgat, Khaled; EL-Emary, Talaat

2013-02-01

FT Raman and IR spectra of the crystallized biologically active molecule, 5-Amino-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (5-APHC, C11H11N3O) have been recorded and analyzed. The equilibrium geometry, bonding features and harmonic vibrational frequencies of 5-APHC have been investigated with the help of B3LYP density functional theory (DFT) method with 6-31G(d) and 6-311+G(d,p) as basis set. The calculated molecular geometry has been compared with the experimental data. The assignments of the vibrational spectra have been carried out with the help of normal coordinate analysis (NCA) following the scaled quantum mechanical force field (SQM) technique. The optimized geometry shows the co-planarity of the aldehyde group with pyrazole ring. Potential energy surface (PES) scan studies has also been carried out by ab initio calculations with B3LYP/6-311+G(d,p) basis set. The red shifting of NH2 stretching wavenumber indicates the formation of N-H⋯O hydrogen bonding. 1H and 13C NMR spectra were recorded and 1H and 13C nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. UV-Vis spectrum of the compound was recorded in the region 200-400 nm and the electronic properties HOMO and LUMO energies were calculated by time-dependent TD-DFT approach. Mulliken charges of the 5-APHC molecule was also calculated and interpreted.

Synthesis, spectroscopic and theoretical studies of ethyl (2E)-3-amino-2-({[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]amino}carbonothioyl)but-2-enoate butanol solvate.

PubMed

Koca, İrfan; Sert, Yusuf; Gümüş, Mehmet; Kani, İbrahim; Çırak, Çağrı

2014-01-24

We have synthesized ethyl (2E)-3-amino-2-({[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]amino}carbonothioyl)but-2-enoate (2) by the reaction of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonyl chloride (1), ammonium thiocyanate and ethyl 3-aminobut-2-enoate and then characterized by elemental analyses, IR, Raman, (1)H NMR, (13)C NMR and X-ray diffraction methods. The experimental and theoretical vibrational spectra of 2 were investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in the solid phase were recorded. Theoretical vibrational frequencies and geometric parameters (bond lengths, bond angles) were calculated using Ab Initio Hartree Fock (HF), Density Functional Theory (B3LYP) methods with 6-311++G(d,p) basis set by Gaussian 09W program. The computed values of frequencies are scaled using a suitable scale factor to yield good coherence with the observed values. The assignments of the vibrational frequencies were performed by potential energy distribution (PED) analysis by using VEDA 4 program. The theoretical optimized geometric parameters and vibrational frequencies were compared with the corresponding experimental X-ray diffraction data, and they were seen to be in a good agreement with each other. Also, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were calculated. Copyright © 2013 Elsevier B.V. All rights reserved.

Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells.

PubMed

Tessmann, Josiane Weber; Buss, Julieti; Begnini, Karine Rech; Berneira, Lucas Moraes; Paula, Favero Reisdorfer; de Pereira, Claudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

2017-10-01

Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effective Approach for Increasing the Heteroatom Doping Levels of Porous Carbons for Superior CO2 Capture and Separation Performance.

PubMed

Abdelmoaty, Yomna H; Tessema, Tsemre-Dingel; Norouzi, Nazgol; El-Kadri, Oussama M; Turner, Joseph B McGee; El-Kaderi, Hani M

2017-10-18

Development of efficient sorbents for carbon dioxide (CO 2 ) capture from flue gas or its removal from natural gas and landfill gas is very important for environmental protection. A new series of heteroatom-doped porous carbon was synthesized directly from pyrazole/KOH by thermolysis. The resulting pyrazole-derived carbons (PYDCs) are highly doped with nitrogen (14.9-15.5 wt %) as a result of the high nitrogen-to-carbon ratio in pyrazole (43 wt %) and also have a high oxygen content (16.4-18.4 wt %). PYDCs have a high surface area (SA BET = 1266-2013 m 2 g -1 ), high CO 2 Q st (33.2-37.1 kJ mol -1 ), and a combination of mesoporous and microporous pores. PYDCs exhibit significantly high CO 2 uptakes that reach 2.15 and 6.06 mmol g -1 at 0.15 and 1 bar, respectively, at 298 K. At 273 K, the CO 2 uptake improves to 3.7 and 8.59 mmol g -1 at 0.15 and 1 bar, respectively. The reported porous carbons also show significantly high adsorption selectivity for CO 2 /N 2 (128) and CO 2 /CH 4 (13.4) according to ideal adsorbed solution theory calculations at 298 K. Gas breakthrough studies of CO 2 /N 2 (10:90) at 298 K showed that PYDCs display excellent separation properties. The ability to tailor the physical properties of PYDCs as well as their chemical composition provides an effective strategy for designing efficient CO 2 sorbents.

Microwave Assisted Synthesis of 1-[5-(Substituted Aryl)-1H-Pyrazol-3-yl]-3,5-Diphenyl-1H-1,2,4-Triazole as Antinociceptive and Antimicrobial Agents

PubMed Central

Khanage, Shantaram Gajanan; Mohite, Popat Baban; Pandhare, Ramdas Bhanudas; Raju, S. Appala

2014-01-01

Purpose: An efficient technique has been developed for microwave assisted synthesis of 1-[5-(substituted aryl)-1H-pyrazol-3-yl]-3,5-diphenyl-1H-1,2,4-triazole as antinociceptive and antimicrobial agents. Methods: The desired compounds (S1-S10) were synthesized by the microwave irradiation via cyclization of formerly synthesized chalcones of 3,5-diphenyl-1H-1,2,4-triazole and hydrazine hydrate in mild acidic condition. All newly synthesized compounds were subjected to study their antinociceptive and antimicrobial activity. The analgesic potential of compounds was tested by acetic acid induced writhing response and hot plate method. The MIC values for antimicrobial activity were premeditated by liquid broth method. Results: The compounds S1, S2, S4, S6 and S10 were found to be excellent peripherally acting analgesic agents when tested on mice by acetic acid induced writhing method and compounds S3, S6 and S1 at dose level of 100 mg/kg were exhibited superior centrally acting antinociceptive activity when tested by Eddy’s hot plate method. In antimicrobial activity compound S10 found to be broad spectrum antibacterial agent at MIC value of 15.62 µg/ml and compound S6 was exhibited antifungal potential at 15.62 µg/mL on both fungal strains. Conclusion: Some novel pyrazoles clubbed with 1,2,4-triazole derivatives were synthesized and evaluated as possible antimicrobial, centrally and peripherally acting analgesics. PMID:24511473

The performance-perceptual test and its relationship to unaided reported handicap.

PubMed

Saunders, Gabrielle H; Forsline, Anna; Fausti, Stephen A

2004-04-01

Measurement of hearing aid outcomes is necessary for demonstration of treatment efficacy, third-party payment, and cost-benefit analysis. Outcomes are usually measured with hearing-related questionnaires and/or tests of speech recognition. However, results from these two types of test often conflict. In this paper, we provide data from a new test measure, known as the Performance-Perceptual Test (PPT), in which subjective and performance aspects of hearing in noise are measured using the same test materials and procedures. A Performance Speech Reception Threshold (SRTN) and a Perceptual SRTN are measured using the Hearing In Noise Test materials and adaptive procedure. A third variable, the discrepancy between these two SRTNs, is also computed. It measures the accuracy with which subjects assess their own hearing ability and is referred to as the Performance-Perceptual Discrepancy (PPDIS). One hundred seven subjects between 24 and 83 yr of age took part. Thirty-three subjects had normal hearing, while the remaining seventy-four had symmetrical sensorineural hearing loss. Of the subjects with impaired hearing, 24 wore hearing aids and 50 did not. All subjects underwent routine audiological examination and completed the PPT and the Hearing Handicap Inventory for the Elderly/Adults on two occasions, between 1 and 2 wk apart. The PPT was conducted for unaided listening with the masker level set to 50, 65, and 80 dB SPL. PPT data show that the subjects with normal hearing have significantly better Performance and Perceptual SRTNs at each test level than the subjects with impaired hearing but that PPDIS values do not differ between the groups. Test-retest reliability for the PPT is excellent (r-values > 0.93 for all conditions). Stepwise multiple regression analysis showed that the Performance SRTN, the PPDIS, and age explain 40% of the variance in reported handicap (Hearing Handicap Inventory for the Elderly/Adults scores). More specifically, poorer performance, underestimation of hearing ability and younger age result in greater reported handicap, and vice versa. Reported handicap consists of a performance component and a (mis)perception component, as measured by the Performance SRTN and the PPDIS respectively. The PPT should thus prove to be a valuable tool for better understanding why some individuals complain of hearing difficulties but have only a mild hearing loss or conversely report few difficulties in the presence of substantial impairment. The measure would thus seem to provide both an explanation and a counseling tool for patients for whom there is a mismatch between reported and measured hearing difficulties.

Global and regional emissions estimates of 1,1-difluoroethane (HFC-152a, CH3CHF2) from in situ and air archive observations

NASA Astrophysics Data System (ADS)

Simmonds, P. G.; Rigby, M.; Manning, A. J.; Lunt, M. F.; O'Doherty, S.; McCulloch, A.; Fraser, P. J.; Henne, S.; Vollmer, M. K.; Mühle, J.; Weiss, R. F.; Salameh, P. K.; Young, D.; Reimann, S.; Wenger, A.; Arnold, T.; Harth, C. M.; Krummel, P. B.; Steele, L. P.; Dunse, B. L.; Miller, B. R.; Lunder, C. R.; Hermansen, O.; Schmidbauer, N.; Saito, T.; Yokouchi, Y.; Park, S.; Li, S.; Yao, B.; Zhou, L. X.; Arduini, J.; Maione, M.; Wang, R. H. J.; Ivy, D.; Prinn, R. G.

2016-01-01

High frequency, in situ observations from 11 globally distributed sites for the period 1994-2014 and archived air measurements dating from 1978 onward have been used to determine the global growth rate of 1,1-difluoroethane (HFC-152a, CH3CHF2). These observations have been combined with a range of atmospheric transport models to derive global emission estimates in a top-down approach. HFC-152a is a greenhouse gas with a short atmospheric lifetime of about 1.5 years. Since it does not contain chlorine or bromine, HFC-152a makes no direct contribution to the destruction of stratospheric ozone and is therefore used as a substitute for the ozone depleting chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs). The concentration of HFC-152a has grown substantially since the first direct measurements in 1994, reaching a maximum annual global growth rate of 0.84 ± 0.05 ppt yr-1 in 2006, implying a substantial increase in emissions up to 2006. However, since 2007, the annual rate of growth has slowed to 0.38 ± 0.04 ppt yr-1 in 2010 with a further decline to an annual average rate of growth in 2013-2014 of -0.06 ± 0.05 ppt yr-1. The annual average Northern Hemisphere (NH) mole fraction in 1994 was 1.2 ppt rising to an annual average mole fraction of 10.1 ppt in 2014. Average annual mole fractions in the Southern Hemisphere (SH) in 1998 and 2014 were 0.84 and 4.5 ppt, respectively. We estimate global emissions of HFC-152a have risen from 7.3 ± 5.6 Gg yr-1 in 1994 to a maximum of 54.4 ± 17.1 Gg yr-1 in 2011, declining to 52.5 ± 20.1 Gg yr-1 in 2014 or 7.2 ± 2.8 Tg-CO2 eq yr-1. Analysis of mole fraction enhancements above regional background atmospheric levels suggests substantial emissions from North America, Asia, and Europe. Global HFC emissions (so called "bottom up" emissions) reported by the United Nations Framework Convention on Climate Change (UNFCCC) are based on cumulative national emission data reported to the UNFCCC, which in turn are based on national consumption data. There appears to be a significant underestimate ( > 20 Gg) of "bottom-up" reported emissions of HFC-152a, possibly arising from largely underestimated USA emissions and undeclared Asian emissions.

Comparison of the effects of local cryotherapy and passive cross-body stretch on extensibility in subjects with posterior shoulder tightness.

PubMed

Park, Kyue-Nam; Kwon, Oh-Yun; Weon, Jong-Hyuck; Choung, Sung-Dae; Kim, Si-Hyun

2014-01-01

The objective was to compare the immediate effects of local cryotherapy (LC) and passive cross-body stretch on the extensibility of the posterior shoulder muscle in individuals with posterior shoulder tightness. Eighty-seven healthy subjects with a between-shoulder difference in internal rotation (IR) range of motion (ROM) greater than 10° were randomly divided into three groups: LC group, stretching group, and control group (n = 29 in each group). Subjects in the LC group received LC on infraspinatus and posterior deltoid muscles and subjects in the stretching group performed passive cross-body stretch. Stretch sensation was measured at the end range of passive IR and horizontal adduction (HA) using numerical rating scale, and the pressure pain threshold (PPT) at the infraspinatus and posterior deltoid muscles was measured using pressure algometry. Passive and active ROM of IR and HA of the glenohumeral joint were measured using an inclinometer. All measurements were performed at pre-intervention, post- intervention, and 10-min follow-up. Stretch sensation was significantly decreased and PPT was significantly increased in the LC and stretching groups at post-intervention, and these effects were maintained at 10-min follow-up, compared to the control group. Both the LC group and stretching group had a significantly greater increase in passive and active ROM of IR and HA, compared to the control group at post-intervention and 10-min follow-up. However, there were no significant differences in stretch sensation, PPT, or ROM of IR and HA between the LC group and stretching group. LC can be used to decrease the stretch sensation and increase PPT and ROM of IR and HA as much as a stretching exercise. LC could be an alternative method for increasing the restricted ROM of glenohumeral IR and HA for individuals with posterior shoulder tightness, especially for patients and sports players who have severe stretching discomfort. Key PointsLocal cryotherapy (LC) decreased the uncomfortable stretch sensation, and increased the pressure pain threshold (PPT) of infraspinatus and posterior deltoid muscles in subjects with posterior shoulder tightness.Decreased stretch sensation by LC without passive stretching could improve the passive and active ROM of internal rotation and horizontal adduction in subjects with posterior shoulder tightness, similar to cross-body stretch.LC can be an alternative method to increase extensibility when individuals with posterior shoulder tightness have high stretch sensitivity and low PPT in the infraspinatus and posterior deltoid muscles.

Comparison of the Effects of Local Cryotherapy and Passive Cross-Body Stretch on Extensibility in Subjects with Posterior Shoulder Tightness

PubMed Central

Park, Kyue-nam; Kwon, Oh-yun; Weon, Jong-hyuck; Choung, Sung-dae; Kim, Si-hyun

2014-01-01

The objective was to compare the immediate effects of local cryotherapy (LC) and passive cross-body stretch on the extensibility of the posterior shoulder muscle in individuals with posterior shoulder tightness. Eighty-seven healthy subjects with a between-shoulder difference in internal rotation (IR) range of motion (ROM) greater than 10° were randomly divided into three groups: LC group, stretching group, and control group (n = 29 in each group). Subjects in the LC group received LC on infraspinatus and posterior deltoid muscles and subjects in the stretching group performed passive cross-body stretch. Stretch sensation was measured at the end range of passive IR and horizontal adduction (HA) using numerical rating scale, and the pressure pain threshold (PPT) at the infraspinatus and posterior deltoid muscles was measured using pressure algometry. Passive and active ROM of IR and HA of the glenohumeral joint were measured using an inclinometer. All measurements were performed at pre-intervention, post- intervention, and 10-min follow-up. Stretch sensation was significantly decreased and PPT was significantly increased in the LC and stretching groups at post-intervention, and these effects were maintained at 10-min follow-up, compared to the control group. Both the LC group and stretching group had a significantly greater increase in passive and active ROM of IR and HA, compared to the control group at post-intervention and 10-min follow-up. However, there were no significant differences in stretch sensation, PPT, or ROM of IR and HA between the LC group and stretching group. LC can be used to decrease the stretch sensation and increase PPT and ROM of IR and HA as much as a stretching exercise. LC could be an alternative method for increasing the restricted ROM of glenohumeral IR and HA for individuals with posterior shoulder tightness, especially for patients and sports players who have severe stretching discomfort. Key Points Local cryotherapy (LC) decreased the uncomfortable stretch sensation, and increased the pressure pain threshold (PPT) of infraspinatus and posterior deltoid muscles in subjects with posterior shoulder tightness. Decreased stretch sensation by LC without passive stretching could improve the passive and active ROM of internal rotation and horizontal adduction in subjects with posterior shoulder tightness, similar to cross-body stretch. LC can be an alternative method to increase extensibility when individuals with posterior shoulder tightness have high stretch sensitivity and low PPT in the infraspinatus and posterior deltoid muscles. PMID:24570610

Experimental investigation of strong-field-ionization theories for laser fields from visible to midinfrared frequencies

NASA Astrophysics Data System (ADS)

Lai, Yu Hang; Xu, Junliang; Szafruga, Urszula B.; Talbert, Bradford K.; Gong, Xiaowei; Zhang, Kaikai; Fuest, Harald; Kling, Matthias F.; Blaga, Cosmin I.; Agostini, Pierre; DiMauro, Louis F.

2017-12-01

Strong-field-ionization yield versus intensity is investigated for various atomic targets (Ne, Ar, Kr, Xe, Na, K, Zn, and Mg) and light polarization from visible to mid-infrared (0.4-4 μ m ), from multiphoton to tunneling regimes. The experimental findings (normalized yield vs intensity, ratio of circular to linear polarization and saturation intensities) are compared to the theoretical models of Perelomov-Popov-Terent'ev (PPT) and Ammosov-Delone-Krainov (ADK). While PPT is generally satisfactory, ADK validity is found, as expected, to be much more limited.

Five new cyotoxic steroidal glycosides from the fruits of Solanum torvum.

PubMed

Li, Jinsheng; Zhang, Lu; Huang, Cheng; Guo, Fujiang; Li, Yiming

2014-03-01

The fruits of Solanum torvum Swartz, commonly known as Turkey berry, are edible and commonly used as a vegetable in the South Indian population's diet and as an essential ingredient in Thai cuisine. Five new steroidal glycosides together with five known ones were isolated from the fruits of S. torvum Swartz. Based on chemical and spectral evidence, the five new compounds were identified to be 25(S)-26-O-β-D-glucopyranosyl-5α-furost-22(20)-en-3β,6α,26-triol-6-O-[α-L-rhamnopyranosyl-(1→3)-O-β-D-quinovopyranoside] (1), 25(S)-26-O-β-D-glucopyranosyl-5α-furost-22(20)-en-3-one-6α,26-diol-6-O-[α-L-rhamnopyranosyl-(1→3)-O-β-D-quinovopyranoside] (2), 25(S)-26-O-β-D-glucopyranosyl-5α-furost-22(20)-en-3β,6α,26-triol-6-O-β-D-quinovopyranoside (3), 5α-pregn-16-en-20-one-3β,6α-diol-6-O-[α-L-rhamnopyranosyl-(1→3)-β-D-quinovopyranoside] (4), and 5α-pregn-16-en-3,20-dione-6α-ol-6-O-[α-L-rhamnopyranosyl-(1→3)-β-D-quinovopyranoside] (5). These new compounds were assayed for cytotoxicities in vitro, and 1 to 4 showed cyotoxic activity against the human melanoma cell line A375, with IC50 values of 30 μM to 260 μM. Copyright © 2014 Elsevier B.V. All rights reserved.

UDP-Glucosyltransferases from Rice, Brachypodium, and Barley: Substrate Specificities and Synthesis of Type A and B Trichothecene-3-O-β-d-glucosides

PubMed Central

Malachová, Alexandra; Piątkowska, Marta; Hametner, Christian; Šofrová, Jana; Jaunecker, Günther; Häubl, Georg; Lemmens, Marc

2018-01-01

Trichothecene toxins are confirmed or suspected virulence factors of various plant-pathogenic Fusarium species. Plants can detoxify these to a variable extent by glucosylation, a reaction catalyzed by UDP-glucosyltransferases (UGTs). Due to the unavailability of analytical standards for many trichothecene-glucoconjugates, information on such compounds is limited. Here, the previously identified deoxynivalenol-conjugating UGTs HvUGT13248 (barley), OsUGT79 (rice) and Bradi5g03300 (Brachypodium), were expressed in E. coli, affinity purified, and characterized towards their abilities to glucosylate the most relevant type A and B trichothecenes. HvUGT13248, which prefers nivalenol over deoxynivalenol, is also able to conjugate C-4 acetylated trichothecenes (e.g., T-2 toxin) to some degree while OsUGT79 and Bradi5g03300 are completely inactive with C-4 acetylated derivatives. The type A trichothecenes HT-2 toxin and T-2 triol are the kinetically preferred substrates in the case of HvUGT13248 and Bradi5g03300. We glucosylated several trichothecenes with OsUGT79 (HT-2 toxin, T-2 triol) and HvUGT13248 (T-2 toxin, neosolaniol, 4,15-diacetoxyscirpenol, fusarenon X) in the preparative scale. NMR analysis of the purified glucosides showed that exclusively β-d-glucosides were formed regio-selectively at position C-3-OH of the trichothecenes. These synthesized standards can be used to investigate the occurrence and toxicological properties of these modified mycotoxins. PMID:29509722

Synthetic approach to the AB ring system of ouabain.

PubMed

Jung, Michael E; Piizzi, Grazia

2003-04-04

Several novel hydroxylated cis-decalin derivatives, potential intermediates for the synthesis of the AB ring system of the important cardiotonic steroid ouabain, have been synthesized from commercially available starting materials. The first step in the preparation of these highly functionalized intermediates is a Robinson annulation of the beta-keto ester 6 and the 4-silyl-3-buten-2-one 5 to furnish the octalone 4 with good diastereoselectivity in fair yield (due to competition with a novel silicon-to-carbon phenyl migration). Reduction of the epoxy alcohol 3 (derived from 4 in two high-yielding steps) with LiAlH(4) gave a mixture of the desired triol 11 along with the product of an unusual reductive opening at the tertiary carbon, namely the triol 12. A plausible mechanism for this unusual reduction is presented as are possible methods for avoiding it. In particular, reduction of the corrresponding epoxy ketone 15 with aluminum amalgam proceeded in good yield to give the hydroxy ketone 16. Also reduction of the epoxide ester having the inverted stereochemistry at C3 afforded the desired tertiary alcohol 33 in good yield. Another approach using the beta,gamma-unsaturated ketal 38 permitted the formation of the tertiary alcohol 40. Fleming oxidation of the related, very functionalized silane 39 afforded the desired 1beta-alcohol 41 in fair yield. Finally a novel rearrangement was observed when the epoxy alcohol 24 was treated with DIBAL to effect loss of the angular hydroxymethyl group to produce the tetrasubstitued alkene 29 in high yield.